﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Frenkel, MPC
   Haji, SA
   Frenkel, REP
AF Frenkel, Max P. C.
   Haji, Shamim A.
   Frenkel, Ronald E. P.
TI Effect of Prophylactic Intraocular Pressure-Lowering Medication on
   Intraocular Pressure Spikes After Intravitreal Injections
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; TRIAMCINOLONE; PARACENTESIS; PEGAPTANIB;
   NECESSITY; TRENDS
AB Objective: To determine if prophylactic use of intraocular pressure (IOP)-lowering medication is effective in reducing the IOP spikes after intravitreal injections of pegaptanib, bevacizumab, and ranibizumab.
   Methods: Seventy-one patients with exudative age-related macular degeneration received intravitreal injections of 1 of 3 anti vascular endothelial growth factor medications: 30 patients received pegaptanib (0.09 mL), 47 patients received bevacizumab (0.05 mL), and 42 patients received ranibizumab (0.05 mL). Intraocular pressure lowering medication, 1 hour prior to the injection, was used 63%, 74%, and 66% of the time in eyes that received pegaptanib, ranibizumab, and bevacizumab, respectively. Intraocular pressure was measured prior to injection, within 1 minute after injection, and every 5 to 10 minutes until the pressure was reduced to a safe level.
   Results: All 3 intravitreal injections caused significant initial IOP spikes (mean [SD] IOP of 38.5 [11.56] mm Hg in the pegaptanib group, 37.75 [8.36] mm Hg in the ranibizumab group, and 34.88 [10.45] mm Hg in the bevacizumab group). The IOP reduced to less than 30 mm Hg in all 3 groups within 20 minutes. Prophylactic medication did not prevent postinjection IOP spikes. Patients with and without glaucoma showed a similar rate of IOP normalization over time in all 3 groups.
   Conclusion: Intraocular pressure spikes after intravitreal injection of pegaptanib, ranibizumab, and bevacizumab are common and in most cases transient. Routine prophylactic use of IOP-lowering medications is essentially ineffective in preventing IOP spikes after intravitreal injection of pegaptanib, ranibizumab, and bevacizumab and therefore not necessary before the injection.
RP Frenkel, MPC (通讯作者)，509 SE Riverside Dr,Ste 302, Stuart, FL 34994 USA.
EM efleye@aol.com
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NR 22
TC 42
Z9 45
U1 0
U2 0
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 DEC
PY 2010
VL 128
IS 12
BP 1523
EP 1527
DI 10.1001/archophthalmol.2010.297
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 693GL
UT WOS:000285212500003
PM 21149773
OA Bronze
DA 2022-11-30
ER

PT J
AU Pazos, MDC
   Nader, HB
AF Pazos, M. d. C.
   Nader, H. B.
TI Effect of photodynamic therapy on the extracellular matrix and
   associated components
SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
LA English
DT Review
DE photodynamic therapy; extracellular matrix; adhesion; chemical
   mediators; matrix metalloproteinases
ID EPITHELIUM-DERIVED FACTOR; VASCULAR CELL-MIGRATION; HUMAN CANCER-CELLS;
   GROWTH-FACTOR-BETA; IN-VITRO; TISSUE TRANSGLUTAMINASE; INTEGRIN
   EXPRESSION; ADHESION; INTERLEUKIN-6; INHIBITION
AB In many countries, photodynamic therapy (PDT) has been recognized as a standard treatment for malignant conditions (for example, esophageal and lung cancers) and non-malignant ones such as age-related macular degeneration and actinic keratoses. The administration of a non-toxic photosensitizer, its selective retention in highly proliferating cells and the later activation of this molecule by light to form reactive oxygen species that cause cell death is the principle of PDT. Three important mechanisms are responsible for the PDT effectiveness: a) direct tumor cell kill; b) damage of the tumor vasculature; c) post-treatment immunological response associated with the leukocyte stimulation and release of many inflammatory mediators like cytokines, growth factors, components of the complement system, acute phase proteins, and other immunoregulators. Due to the potential applications of this therapy, many studies have been reported regarding the effect of the treatment on cell survival/death, cell proliferation, matrix assembly, proteases and inhibitors, among others. Studies have demonstrated that PDT alters the extracellular matrix profoundly. For example, PDT induces collagen matrix changes, including cross-linking. The extracellular matrix is vital for tissue organization in multicellular organisms. In cooperation with growth factors and cytokines, it provides cells with key signals in a variety of physiological and pathological processes, for example, adhesion/migration and cell proliferation/differentiation/death. Thus, the focus of the present paper is related to the effects of PDT observed on the extracellular matrix and on the molecules associated with it, such as, adhesion molecules, matrix metalloproteinases, growth factors, and immunological mediators.
C1 Univ Fed Sao Paulo, EPM, Dept Bioquim, BR-04044020 Sao Paulo, Brazil.
C3 Universidade Federal de Sao Paulo (UNIFESP)
RP Pazos, MDC (通讯作者)，Univ Fed Sao Paulo, EPM, Dept Bioquim, Rua Tres Maio,100 4o Andar, BR-04044020 Sao Paulo, Brazil.
EM marcelo.pazos@gmail.com
RI Nader, Helena Bonciani/D-9253-2012
OI NADER, HELENA/0000-0002-7569-2166
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NR 59
TC 51
Z9 56
U1 1
U2 12
PU ASSOC BRAS DIVULG CIENTIFICA
PI SAO PAULO
PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL
SN 0100-879X
J9 BRAZ J MED BIOL RES
JI Brazilian J. Med. Biol. Res.
PD AUG
PY 2007
VL 40
IS 8
BP 1025
EP 1035
DI 10.1590/S0100-879X2006005000142
PG 11
WC Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Research & Experimental
   Medicine
GA 195LJ
UT WOS:000248413400002
PM 17665038
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Yang, P
   Peairs, JJ
   Tano, R
   Jaffe, GJ
AF Yang, Ping
   Peairs, James J.
   Tano, Ryotaro
   Jaffe, Glenn J.
TI Oxidant-mediated akt activation in human RPE cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; SYNTHASE KINASE 3-BETA; PROTEIN-KINASE;
   PHOSPHATIDYLINOSITOL 3-KINASE; OXIDATIVE STRESS; HEAT-SHOCK;
   PHOSPHOINOSITIDE 3-KINASE; MACULAR DEGENERATION; SURVIVAL; APOPTOSIS
AB PURPOSE. To determine whether a model oxidant, hydrogen peroxide (H2O2), influences Akt activation and, if so, whether Akt activation promotes retinal pigment epithelial (RPE) cell survival.
   METHODS. Cultured human RPE cells were pretreated with medium alone, with LY294002 (LY), an inhibitor of phosphatidylinositol-3 kinase (PI3K) and its downstream effector Akt, or with Akt/protein kinase B signaling inhibitor (API)-2, a specific Akt inhibitor, and then were stimulated with H2O2 at different doses for various times. Akt phosphorylation was evaluated by Western blot using antibody against phosphorylated Akt (Ser473). The effect of Akt blockade on RPE cell viability was assessed by tetrazolium salt (WST-1) assay and a lactate dehydrognease (LDH) release assay. Caspase-mediated cytokeratin cleavage, an early apoptosis marker, was assessed by M30 antibody staining. Caspase-independent apoptosis was determined by nuclear translocation of apoptosis-inducing factor (AIF). RPE cell morphology was evaluated by electron microscopy. The effect of H2O2 on downstream Akt targets was examined by Western blot using antibody against phosphorylated forkhead in rhabdomyosarcoma (FKHR) and phosphorylated glycogen synthase kinase (GSK)-3 beta.
   RESULTS. H2O2 induced Akt phosphorylation in a dose-dependent manner and also induced the phosphorylation of downstream effectors FKHR and GSK-3 beta. LY markedly inhibited H2O2-mediated Akt phosphorylation and significantly enhanced caspase-associated and caspase-independent RPE cell death.
   CONCLUSIONS. A model oxidant, H2O2, induces PI3K and thereby activates Akt. Akt activation enhances RPE cell survival and thus may protect RPE cells from oxidant-induced cell death under normal circumstances and in disease states such as age-related macular degeneration (AMD).
C1 Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
C3 Duke University
RP Jaffe, GJ (通讯作者)，Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
EM jaffe001@mc.duke.edu
FU NEI NIH HHS [R01 EY9106, 930EY05722] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R01EY009106, P30EY005722] Funding Source: NIH RePORTER
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NR 49
TC 78
Z9 83
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2006
VL 47
IS 10
BP 4598
EP 4606
DI 10.1167/iovs.06-0140
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 088AU
UT WOS:000240784700054
PM 17003457
DA 2022-11-30
ER

PT J
AU Schiefer, MA
   Grill, WM
AF Schiefer, MA
   Grill, WM
TI Sites of neuronal excitation by epiretinal electrical stimulation
SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
LA English
DT Article
DE neural stimulation; retinal ganglion cell; retinal prosthesis; visual
   prosthesis
ID RETINAL GANGLION-CELLS; VISUAL-PERCEPTION; THRESHOLDS; PRESERVATION;
   CONDUCTANCES; MORPHOLOGIES; ACTIVATION; PATTERN; MODEL
AB Action potentials arising from retinal ganglion cells ultimately create visual percepts. In persons blind from retinitis pigmentosa and age-related macular degeneration, viable retinal ganglion cells remain, and the retina can be stimulated electrically to restore partial sight. However, it is unclear what neuronal elements in the retina are activated by epiretinal electrical stimulation. This study investigated the effects of cellular geometry, electrode to neuron distance, stimulus duration, and stimulus polarity on excitation of a retinal ganglion cell with an epiretinal electrode. Computer-based compartmental models representing simplified retinal ganglion cell morphology provided evidence that the threshold for excitation was lower when an electrode was located in proximity to the characteristic 90 degrees bend in the axon of the retinal ganglion cell than when it was located over a passing axon of the nerve fiber layer. This electrode-position-dependent difference in threshold occurred with both cathodic and anodic monophasic stimuli, with point source and disk electrodes, at multiple electrode-to-neuron distances, and was robust to changes in the electrical properties of the model. This finding reveals that the physical geometry of the retinal ganglion cells produces stimulation thresholds that depend strongly on electrode position. The low excitation thresholds near the bend in the axon will result in activation of cells local to the electrode at lower currents than required to excite passing axons. This pattern of activation provides a potential explanation of how epiretinal electrical stimulation results in the production of punctuate, rather than diffuse or streaky phosphenes.
C1 Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
   Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
C3 Case Western Reserve University; Duke University
RP Schiefer, MA (通讯作者)，Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
EM matthew.schiefer@case.edu; warren.grill@duke.edu
RI Schiefer, Matthew/AAE-9275-2020; Schiefer, Matthew/G-4528-2010
OI Schiefer, Matthew/0000-0001-8490-088X
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NR 49
TC 52
Z9 55
U1 0
U2 6
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1534-4320
EI 1558-0210
J9 IEEE T NEUR SYS REH
JI IEEE Trans. Neural Syst. Rehabil. Eng.
PD MAR
PY 2006
VL 14
IS 1
BP 5
EP 13
DI 10.1109/TNSRE.2006.870488
PG 9
WC Engineering, Biomedical; Rehabilitation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Rehabilitation
GA 028WH
UT WOS:000236519000002
PM 16562626
DA 2022-11-30
ER

PT J
AU Mylona, I
   Papadopoulou, K
   Roumelis, S
   Floros, GD
AF Mylona, Ioanna
   Papadopoulou, Kalliopi
   Roumelis, Serafeim
   Floros, Georgios D.
TI Drop in well-being of ARMD patients under treatment with anti-VEGF
   injections during the COVID-19 pandemic
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE ARMD; COVID-19; Anti-VEGF
AB Purpose Patients with age-related macular degeneration (ARMD) are required to follow a treatment protocol that requires regular follow-ups. The COVID-19 pandemic has created an additional burden for patients with ARMD under treatment with anti-vascular endothelial growth factor (anti-VEGF) injections, since patients face a congestion of the health system and closing of the outpatient services. This study examines the impact of the uncertainty regarding patients' treatment on their sense of well-being. Methods This is a longitudinal cohort study of eighty patients who were followed during the year following the outbreak of the COVID pandemic. Patients reported their sense of well-being with the WHO-5 questionnaire and their perception and fears for the impact of the pandemic on their ongoing ARMD treatment. Results There was a significant drop in mental well-being during the pandemic that paralleled the self-reported impact of the pandemic on ARMD treatment. Patients who reported a higher impact of COVID-19 on their treatment had experienced a higher drop in mental wellbeing compared to those who hadn't, with female gender being an additional risk factor. Objective measurements of visual acuity did not factor in the drop of sense of well-being. Conclusions The high initial level of uncertainty regarding ARMD patients' long-term course was further exacerbated when exposed to additional uncertainties during the pandemic regarding their standard of care. Planning ahead for continuation of services and close contact with patients during similar health emergencies is of paramount importance.
C1 [Mylona, Ioanna] Gen Hosp Katerini, Dept Ophthalmol, Katerini, Greece.
   [Papadopoulou, Kalliopi] Hippokrat Gen Hosp Thessaloniki, Dept Ophthalmol, Thessaloniki, Greece.
   [Roumelis, Serafeim] Gen Hosp Serres, Dept Ophthalmol, Serres, Greece.
   [Floros, Georgios D.] Aristotle Univ Thessaloniki, Dept Psychiat 2, Thessaloniki, Greece.
C3 Aristotle University of Thessaloniki
RP Mylona, I (通讯作者)，Gen Hosp Katerini, Dept Ophthalmol, Katerini, Greece.
EM milona_ioanna@windowslive.com
OI Mylona, Ioanna/0000-0002-1032-3730
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NR 17
TC 0
Z9 0
U1 1
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 AUG
PY 2022
VL 42
IS 8
BP 2493
EP 2499
DI 10.1007/s10792-022-02296-4
EA APR 2022
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3E4YE
UT WOS:000777256900003
PM 35362811
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Jacobs, B
   Palmer, N
   Shetty, T
   Dimaras, H
   Hajrasouliha, A
   Jusufbegovic, D
   Corson, TW
AF Jacobs, Brandon
   Palmer, Nicholas
   Shetty, Trupti
   Dimaras, Helen
   Hajrasouliha, Amir
   Jusufbegovic, Denis
   Corson, Timothy W.
TI Patient preferences in retinal drug delivery
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ANTI-VEGF THERAPY; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; EFFICACY;
   DISEASE; MODELS
AB Retinal vascular diseases (RVDs) are often treated with intravitreally (IVT) injected drugs, with relatively low patient compliance and potential risks. Ongoing research explores alternative RVD treatments, including eye drops and oral tablets. This study surveyed RVD patients treated with IVT injections to establish factors influencing low compliance rates while gauging treatment delivery method preferences. Demographics, perspectives, and treatment preferences were collected via IRB-approved, self-administered survey sent to Glick Eye Institute patients treated via IVT injections. Demographics, diagnoses, and treatments were ascertained from respondents' medical records. Gender, age, and number of IVT injections received were used as stratifications. Five-level Likert-style scales and t-tests evaluated responses and stratification comparisons. The most common diagnoses in the respondent population (n = 54; response rate = 5%) were age-related macular degeneration, macular edema, and diabetic retinopathy. Respondents had varying levels of education, income, and age. Most (83%) admitted feeling anxious prior to their first IVT injection, but 80% reported willingness to receive IVT injections indefinitely, with a preference for ophthalmologist visits every 1-3 months. Eye drops would be preferred over IVT injections by 76% of respondents, while 65% preferred oral tablets, due to several perceived negative factors of IVT injections and positive factors for eye drops. Stratified groups did not differ in responses to survey questions. RVD patients will accept IVT injections for vision preservation, but alternative delivery methods like eye drops or oral tablets would be preferred. Thus, development of eye drop and oral therapeutics for RVD treatment is further emphasized by these findings.
C1 [Jacobs, Brandon; Palmer, Nicholas; Shetty, Trupti; Hajrasouliha, Amir; Jusufbegovic, Denis; Corson, Timothy W.] Indiana Univ Sch Med, Eugene & Marilyn Glick Eye Inst, 1160 West Michigan St, Indianapolis, IN 46202 USA.
   [Jacobs, Brandon; Palmer, Nicholas; Shetty, Trupti; Hajrasouliha, Amir; Jusufbegovic, Denis; Corson, Timothy W.] Indiana Univ Sch Med, Dept Ophthalmol, 1160 West Michigan St, Indianapolis, IN 46202 USA.
   [Dimaras, Helen] Hosp Sick Children, Toronto, ON, Canada.
   [Dimaras, Helen] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
   [Dimaras, Helen] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Div Clin Publ Hlth, Toronto, ON, Canada.
   [Shetty, Trupti] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
C3 Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington; University of
   Toronto; University Toronto Affiliates; Hospital for Sick Children
   (SickKids); University of Toronto; University of Toronto; National
   Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
RP Corson, TW (通讯作者)，Indiana Univ Sch Med, Eugene & Marilyn Glick Eye Inst, 1160 West Michigan St, Indianapolis, IN 46202 USA.; Corson, TW (通讯作者)，Indiana Univ Sch Med, Dept Ophthalmol, 1160 West Michigan St, Indianapolis, IN 46202 USA.
EM tcorson@iu.edu
OI Dimaras, Helen/0000-0003-1164-2001
FU National Institutes of Health [T35EY031282]; Research to Prevent
   Blindness
FX This work was supported by National Institutes of Health T35EY031282 and
   by a Challenge Grant from Research to Prevent Blindness.
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NR 37
TC 3
Z9 3
U1 2
U2 2
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 23
PY 2021
VL 11
IS 1
AR 18996
DI 10.1038/s41598-021-98568-7
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA UU4SG
UT WOS:000698791600027
PM 34556761
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Blasiak, J
   Koskela, A
   Pawlowska, E
   Liukkonen, M
   Ruuth, J
   Toropainen, E
   Hyttinen, JMT
   Viiri, J
   Eriksson, JE
   Xu, HP
   Chen, M
   Felszeghy, S
   Kaarniranta, K
AF Blasiak, Janusz
   Koskela, Ali
   Pawlowska, Elzbieta
   Liukkonen, Mikko
   Ruuth, Johanna
   Toropainen, Elisa
   Hyttinen, Juha M. T.
   Viiri, Johanna
   Eriksson, John E.
   Xu, Heping
   Chen, Mei
   Felszeghy, Szabolcs
   Kaarniranta, Kai
TI Epithelial-Mesenchymal Transition and Senescence in the Retinal Pigment
   Epithelium of NFE2L2/PGC-1 alpha Double Knock-Out Mice
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; AMD; epithelial-mesenchymal
   transition; senescence; NFE2L2/PGC-1 alpha dKO mice
AB Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. In our previous studies, we found that deficiencies in the nuclear factor, erythroid 2 like 2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) genes caused AMD-like pathological phenotypes in mice. In the present work, we show hijacked epithelial-mesenchymal transition (EMT) due to the common loss of PGC-1 alpha and NFE2L2 (double knock-out, dKO) genes in aged animals. The implanted area was assessed by histology, immunohistochemistry and transmission electron microscopy. Confocal microscopy revealed altered regions in the filamentous actin ring. This contrasted with hexagonal RPE morphology in wild-type mice. The ultrastructural RPE features here illustrated loss of apical microvilli, alteration of cell-cell contact, loss of basal in-folding with deposits on Bruch's membrane, and excessive lipofuscin deposition in dKO samples. We also found the expression of epithelial-mesenchymal transition transcription factors, such as Snail, Slug, collagen 1, vimentin and OB-cadherin, to be significantly different in dKO RPEs. An increased immunoreactivity of senescence markers p16, DEC1 and HMGB1 was also noted. These findings suggest that EMT and senescence pathways may intersect in the retinas of dKO mice. Both processes can be activated by damage to the RPE, which may be caused by increased oxidative stress resulting from the absence of NFE2L2 and PGC-1 alpha genes, important for antioxidant defense. This dKO model may provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease.
C1 [Blasiak, Janusz] Univ Lodz, Fac Biol & Environm Protect, Dept Mol Genet, Pomorska 141-143, PL-90236 Lodz, Poland.
   [Koskela, Ali; Liukkonen, Mikko; Ruuth, Johanna; Toropainen, Elisa; Hyttinen, Juha M. T.; Viiri, Johanna; Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Kuopio 70210, Finland.
   [Pawlowska, Elzbieta] Med Univ Lodz, Dept Orthodont, PL-92217 Lodz, Poland.
   [Eriksson, John E.] Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.
   [Eriksson, John E.] Abo Akad Univ, Turku 20520, Finland.
   [Eriksson, John E.] Abo Akad Univ, Fac Sci & Technol, Cell Biol, Turku 20500, Finland.
   [Xu, Heping; Chen, Mei] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
   [Felszeghy, Szabolcs] Univ Eastern Finland, Inst Biomed, Yliopistonranta 1 A, Kuopio 70211, Finland.
   [Felszeghy, Szabolcs] Univ Eastern Finland, Inst Dent, Yliopistonranta 1 C, Kuopio 70211, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70210, Finland.
C3 University of Lodz; University of Eastern Finland; Medical University
   Lodz; University of Turku; Abo Akademi University; Abo Akademi
   University; Queens University Belfast; University of Eastern Finland;
   University of Eastern Finland; Kuopio University Hospital; University of
   Eastern Finland
RP Kaarniranta, K (通讯作者)，Univ Eastern Finland, Dept Ophthalmol, Kuopio 70210, Finland.; Kaarniranta, K (通讯作者)，Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70210, Finland.
EM janusz.blasiak@biol.uni.lodz.pl; ali.koskela@uef.fi;
   elzbieta.pawlowska@umed.lodz.pl; mikko.liukkonen@uef.fi;
   johanna.ruuth@uef.fi; elisa.toropainen@uef.fi; Juha.Hyttinen@uef.fi;
   johanna.viiri@uef.fi; john.eriksson@utu.fi; heping.xu@qub.ac.uk;
   mei.chen@qub.ac.uk; szabolcs.felszeghy@uef.fi; kai.kaarniranta@uef.fi
RI Xu, Heping/A-4430-2008
OI Xu, Heping/0000-0003-4000-931X; Liukkonen, Mikko/0000-0002-4259-4041;
   Pawlowska, Elzbieta/0000-0002-5373-4783; Blasiak,
   Janusz/0000-0001-9539-9584; Hyttinen, Juha/0000-0002-3414-4032
FU Kuopio University Hospital [5503743]; Finnish Eye Foundation; Sigrid
   Juselius Foundation; Finnish Funding Agency for Technology and
   Innovation; Health Research Council of the Academy of Finland [296840,
   333302]; Paivikki and Sakari Sohlberg Foundation; National Science
   Centre, Poland [2017/27/B/NZ3/00872]
FX This research was f by the Kuopio University Hospital (K.K.) (Grant
   Number 5503743), the Finnish Eye Foundation, The Sigrid Juselius
   Foundation, The Finnish Funding Agency for Technology and Innovation,
   the Health Research Council of the Academy of Finland (Grant Numbers
   296840 and 333302), the Paivikki and Sakari Sohlberg Foundation,
   National Science Centre, Poland (J.B.) (Grant number
   2017/27/B/NZ3/00872).
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NR 38
TC 6
Z9 6
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 FEB
PY 2021
VL 22
IS 4
AR 1684
DI 10.3390/ijms22041684
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QP8CP
UT WOS:000624059000001
PM 33567500
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dekkers, G
   Brouwer, MC
   Jeremiasse, J
   Kamp, A
   Biggs, RM
   van Mierlo, G
   Lauder, S
   Katti, S
   Kuijpers, TW
   Rispens, T
   Jongerius, I
AF Dekkers, Gillian
   Brouwer, Mieke C.
   Jeremiasse, Jorn
   Kamp, Angela
   Biggs, Robyn M.
   van Mierlo, Gerard
   Lauder, Scott
   Katti, Suresh
   Kuijpers, Taco W.
   Rispens, Theo
   Jongerius, Ilse
TI Unraveling the Effect of a Potentiating Anti-Factor H Antibody on
   Atypical Hemolytic Uremic Syndrome-Associated Factor H Variants
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; ENDOTHELIAL-CELLS; MEMBRANOPROLIFERATIVE
   GLOMERULONEPHRITIS; ALTERNATIVE PATHWAY; HOST RECOGNITION;
   BINDING-SITES; C-TERMINUS; MUTATIONS; ACTIVATION; C3B
AB The complement system plays an important role in our innate immune system. Complement activation results in clearance of pathogens, immune complex, and apoptotic cells. The host is protected from complement-mediated damage by several complement regulators. Factor H (FH) is the most important fluid-phase regulator of the alternative pathway of the complement system. Heterozygous mutations in FH are associated with complement-related diseases such as atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration. We recently described an agonistic anti-FH mAb that can potentiate the regulatory function of FH. This Ab could serve as a potential new drug for aHUS patients and alternative to C5 blockade by eculizumab. However, it is unclear whether this Ab can potentiate FH mutant variants in addition to wild-type (WT) FH. In this study, the functionality and potential of the agonistic Ab in the context of pathogenic aHUS-related FH mutant proteins was investigated. The binding affinity of recombinant WT FH and the FH variants, W1183L, V1197A, R1210C, and G1194D to C3b was increased upon addition of the potentiating Ab and similarly, the decay-accelerating activity of all mutants is increased. The potentiating anti-FH Ab is able to restore the surface regulatory function of most of the tested FH mutants to WT FH levels on a human HAP-1 cell line and on sheep erythrocytes. In conclusion, our potentiating anti-FH is broadly active and able to enhance both WT FH function as well as most aHUS-associated FH variants tested in this study.
C1 [Dekkers, Gillian; Brouwer, Mieke C.; Jeremiasse, Jorn; Kamp, Angela; van Mierlo, Gerard; Rispens, Theo; Jongerius, Ilse] Univ Amsterdam, Dept Immunopathol, Landsteiner Lab, Amsterdam UMC,Sanquin Res, NL-1066 CX Amsterdam, Netherlands.
   [Biggs, Robyn M.; Lauder, Scott; Katti, Suresh] Gemini Therapeut Inc, Cambridge, MA 02139 USA.
   [Kuijpers, Taco W.; Jongerius, Ilse] Amsterdam UMC, Dept Pediat Immu Nol Rheumatol & Infect Dis, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands.
   [Kuijpers, Taco W.] Univ Amsterdam, Dept Blood Cell Res, Landsteiner Lab, Amsterdam UMC,Sanquin Res, NL-1066 CX Amsterdam, Netherlands.
C3 University of Amsterdam; Emma Children's Hospital; University of
   Amsterdam; University of Amsterdam
RP Jongerius, I (通讯作者)，Sanquin Res, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands.
EM I.jongerius@sanquin.nl
OI Dekkers, Gillian/0000-0002-9127-356X; Jongerius,
   Ilse/0000-0002-7759-9897
FU Gemini Therapeutics
FX This work was supported by a research grant from Gemini Therapeutics to
   G.D. and M.C.B.
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NR 39
TC 4
Z9 4
U1 0
U2 0
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 OCT 1
PY 2020
VL 205
IS 7
BP 1778
EP +
DI 10.4049/jimmunol.2000368
PG 13
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA NV6FP
UT WOS:000574415200006
PM 32848031
OA Bronze
DA 2022-11-30
ER

PT J
AU Bo, QY
   Shen, MX
   Xiao, MC
   Liang, J
   Zhai, YQ
   Zhu, H
   Jiang, M
   Wang, FH
   Luo, XT
   Sun, XD
AF Bo, Qiyu
   Shen, Mengxi
   Xiao, Meichun
   Liang, Jian
   Zhai, Yuanqi
   Zhu, Hong
   Jiang, Mei
   Wang, Fenghua
   Luo, Xueting
   Sun, Xiaodong
TI 3-Methyladenine Alleviates Experimental Subretinal Fibrosis by
   Inhibiting Macrophages and M2 Polarization Through the PI3K/Akt Pathway
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE subretinal fibrosis; macrophage polarization; 3-MA; PI3K; Akt signal
   pathway; age-related macular degeneration
ID INDUCED CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; ALTERNATIVE
   ACTIVATION; AUTOPHAGY; MONOCYTES; MODULATION; MANAGEMENT; INDUCTION;
   MECHANISM; OUTCOMES
AB Purpose:To explore the effects of 3-methyladenine (3-MA), a selective inhibitor of phosphatidylinositol-3-kinase (PI3K), on experimental subretinal fibrosis (SRF) in mice. Methods:The SRF mouse model was established by 532 nm laser photocoagulation at each fundus of mice on day 0. 3-MA was administered every 2 days from day 0 to 35. Immunofluorescence of choroidal flat mounts was performed to evaluate the size of SRF area, local macrophages, and polarization, respectively. Besides, Western blot analysis was carried out to assess the expression levels of macrophage polarization-related genes, Arg-1, Ym-1, and transforming growth factor-beta(2)(TGF-beta(2)). Co-culture and migration experiments were used to demonstrate the inhibitory effect of 3-MA on fibroblasts. The gene knockout and Western blot analysis were used to explore the signal pathways related to macrophage polarization. Results:Compared with the control group, the 3-MA-treated group showed significantly less size of SRF area. 3-MA treatment reduced both circulating and local macrophages, and counteracted M2 polarization. Moreover, 3-MA inhibited fibroblast recruitment. Mechanistically, we proved that 3-MA inhibits macrophage M2 polarization by suppressing PI3K/Akt signal pathway rather than the PI3K-autophagy-related signal pathway. Conclusions:3-MA exerts antifibrotic effects on experimental SRF by targeting circulating and local macrophages and M2 polarization, through PI3K/Akt signal pathway. These results support the potential use of 3-MA as a new therapeutic modality for SRF associated with neovascular age-related macular degeneration.
C1 [Bo, Qiyu; Shen, Mengxi; Xiao, Meichun; Liang, Jian; Zhai, Yuanqi; Zhu, Hong; Jiang, Mei; Wang, Fenghua; Luo, Xueting; Sun, Xiaodong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Shanghai Gen Hosp,Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
   [Liang, Jian; Zhai, Yuanqi; Zhu, Hong; Jiang, Mei; Wang, Fenghua; Luo, Xueting; Sun, Xiaodong] Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Zhu, Hong; Wang, Fenghua; Sun, Xiaodong] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
   [Wang, Fenghua; Sun, Xiaodong] Natl Clin Res Ctr Eye Dis, Shanghai, Peoples R China.
   [Wang, Fenghua; Sun, Xiaodong] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University
RP Luo, XT; Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Shanghai Gen Hosp,Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
EM xtluo@sjtu.edu.cn; xdsun@sjtu.edu.cn
RI Shen, Mengxi/ABC-6941-2021
OI Shen, Mengxi/0000-0002-1336-1695
FU National Natural Science Foundation of China [81730026]; National
   Science and Technology Major Project of China [2017ZX09304010]; Project
   of Shanghai Hospital Development Center [SHDC12016105]; Science and
   Technology Commission of Shanghai Municipality [17411953000,
   16140900800, 0303N17001]; National New Drugs Program [2018
   ZX09301029001]; National Key RD Program [2016YFC 0904800,
   2017YFA0105301]; Eastern Young Program [QD2016003]
FX This study was supported by the National Natural Science Foundation of
   China (81730026); National Science and Technology Major Project of China
   (2017ZX09304010); Project of Shanghai Hospital Development Center
   (SHDC12016105); Science and Technology Commission of Shanghai
   Municipality (17411953000, 16140900800, and 0303N17001); National New
   Drugs Program (2018 ZX09301029001); National Key R&D Program (2016YFC
   0904800 and 2017YFA0105301), and Eastern Young Program (QD2016003).
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NR 47
TC 8
Z9 8
U1 1
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD OCT 1
PY 2020
VL 36
IS 8
BP 618
EP 628
DI 10.1089/jop.2019.0112
EA JUN 2020
PG 11
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA NZ0LA
UT WOS:000541856100001
PM 32552228
DA 2022-11-30
ER

PT J
AU Pilotti, C
   Greenwood, J
   Moss, SE
AF Pilotti, Camilla
   Greenwood, John
   Moss, Stephen E.
TI Functional Evaluation of AMD-Associated Risk Variants of Complement
   Factor B
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retina; complement; angiogenesis; AMD; CFB
ID ALTERNATIVE PATHWAY; ACTIVATION; ANGIOGENESIS; POLYMORPHISM; MACROPHAGE;
   SPECTRUM; C3
AB PURPOSE. The 32W and 32Q variants of complement factor B (CFB) are associated with reduced risk of developing neovascular age-related macular degeneration (AMD) compared with the common 32R allele. The objective of this study was to determine if the most protective R32Q variant affects the neovascular process in a manner consistent with the reported reduced disease association.
   METHODS. The 32R, 32W, and 32Q human CFB variants were expressed in human embryonic kidney 293T cells and purified from culture supernatant. The ex vivo mouse fetal metatarsal explant model was used to investigate the effect of these three human CFB variants on angiogenesis. Metatarsal bones were isolated from mouse embryos and cultured in the presence of the three CFB variants, and angiogenesis was measured following immunostaining of fixed samples. ELISAs were used to quantify C3 and VEGF protein levels in metatarsal culture and quantitative PCR to measure Cfb, C3, and Vegf expression.
   RESULTS. We show here that the three CFB variants have different biological activities in the mouse metatarsal assay, with CFBR32 exhibiting significantly greater angiogenic activity than CFBQ32 or CFBW32, which were broadly similar. We also observed differences in macrophage phenotype with these two variants that may contribute to their activities in this experimental model.
   CONCLUSIONS. We have demonstrated that the biological activities of CFBR32, CFBW32, and CFBQ32 are consistent with their AMD risk association, and we provide functional evidence of roles for these variants in angiogenesis that may be relevant to the pathogenesis of the neovascular form of AMD.
C1 [Pilotti, Camilla; Greenwood, John; Moss, Stephen E.] UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
C3 University of London; University College London
RP Moss, SE (通讯作者)，UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM s.moss@ucl.ac.uk
FU GSK
FX Supported by a GSK PhD studentship award (CP).
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NR 34
TC 2
Z9 2
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 MAY
PY 2020
VL 61
IS 5
AR 19
DI 10.1167/iovs.61.5.19
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LZ0ET
UT WOS:000540905500020
PM 32407521
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Falavarjani, KG
   Au, A
   Anvari, P
   Molaei, S
   Ghasemizadeh, S
   Verma, A
   Tsui, I
   Sadda, S
   Sarraf, D
AF Falavarjani, Khalil Ghasemi
   Au, Adrian
   Anvari, Pasha
   Molaei, Saber
   Ghasemizadeh, Shahriar
   Verma, Aditya
   Tsui, Irena
   Sadda, Srinivas
   Sarraf, David
TI En Face OCT of Type 2 Neovascularization: A Reappraisal of the Pitchfork
   Sign
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; MACULAR DEGENERATION; SPECTRUM
AB BACKGROUND AND OBJECTIVES: To describe a new en face optical coherence tomography (OCT) imaging feature of type 2 choroidal neovascularization (CNV) and illustrate the OCT angiographic (OCTA) findings in these eyes.
   PATIENTS AND METHODS: Multimodal images of patients with type 2 CNV who displayed the typical "pitchfork" sign with cross-sectional OCT were reviewed. Corresponding en face structural OCT and OCTA images were analyzed to correlate the finding before and after anti-vascular endothelial growth factor (VEGF) therapy.
   RESULTS: Five eyes of five patients, including two females and three males with a median age of 13 years (range: 8 years to 84 years), were studied. The etiology for type 2 CNV was laser-induced maculopathy in two eyes, idiopathic in two eyes, and age-related macular degeneration in one eye. None of the eyes had evidence of inflammatory ocular disease. En face OCT displayed a characteristic wreath-like pattern of hyperreflective spikes surrounding the type 2 neovascular membrane that originated from the ellipsoid zone and extended into the outer nuclear layer. Wreath-like spikes resolved with intravitreal anti-VEGF injection with good visual outcomes and transformation of the neovascular lesion from a type 2 to type 1 morphology.
   CONCLUSIONS: Type 2 CNV associated with the pitchfork sign with cross-sectional OCT displayed a characteristic wreath-like pattern of hyperreflective spikes with en face OCT that resolved with anti-VEGF therapy. This form of type 2 neovascularization may occur in eyes with different underlying etiologies and without signs of intraocular inflammation and is not limited to pediatric patients.
C1 [Falavarjani, Khalil Ghasemi; Anvari, Pasha; Molaei, Saber; Ghasemizadeh, Shahriar] Iran Univ Med Sci, Rassoul Akram Hosp, Eye Res Ctr, Tehran, Iran.
   [Au, Adrian; Tsui, Irena; Sadda, Srinivas; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Verma, Aditya; Sadda, Srinivas] Univ Calif Los Angeles, Doheny Eye Inst, Los Angeles, CA USA.
   [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
C3 Iran University of Medical Sciences; University of California System;
   University of California Los Angeles; University of California Los
   Angeles Medical Center; David Geffen School of Medicine at UCLA; Doheny
   Eye Institute; University of California System; University of California
   Los Angeles; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); VA Greater Los Angeles Healthcare System
RP Sarraf, D (通讯作者)，100 Stein Plaza, Los Angeles, CA 90095 USA.
EM sarraf@jsei.ucla.edu
RI Falavarjani, Khalil Ghasemi/I-4029-2019; Anvari, Pasha/AAI-2626-2019;
   Verma, Aditya/AGK-6502-2022; Ghasemizadeh, Shahriar/ABH-3115-2021
OI Anvari, Pasha/0000-0002-3765-4206; Ghasemizadeh,
   Shahriar/0000-0003-1567-1280; Ghasemi Falavarjani,
   Khalil/0000-0001-5221-1844
FU Research To Prevent Blindness, New York; Macula Foundation, New York
FX Supported by Research To Prevent Blindness, New York (DS), and the
   Macula Foundation, New York (DS).
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NR 14
TC 2
Z9 2
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD NOV
PY 2019
VL 50
IS 11
BP 719
EP 725
DI 10.3928/23258160-20191031-07
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA JQ3VF
UT WOS:000498876000017
PM 31755971
DA 2022-11-30
ER

PT J
AU Nakamura, S
   Noguchi, T
   Inoue, Y
   Sakurai, S
   Nishinaka, A
   Hida, Y
   Masuda, T
   Nakagami, Y
   Horai, N
   Tsusaki, H
   Hara, H
   Shimazawa, M
AF Nakamura, Shinsuke
   Noguchi, Tetsuro
   Inoue, Yuki
   Sakurai, Shuji
   Nishinaka, Ann
   Hida, Yoshifumi
   Masuda, Tomomi
   Nakagami, Yasuhiro
   Horai, Naoto
   Tsusaki, Hideshi
   Hara, Hideaki
   Shimazawa, Masamitsu
TI Nrf2 Activator RS9 Suppresses Pathological Ocular Angiogenesis and
   Hyperpermeability
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE Nrf2; VEGF; hyperpermeability; neovascularization
ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; OXIDATIVE
   STRESS; CHOROIDAL NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION;
   ISCHEMIA-REPERFUSION; DIABETIC-RETINOPATHY; INFLAMMATION; MECHANISMS;
   CELLS
AB PURPOSE. Ocular angiogenesis, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration, are closely related to oxidative stress. Many reports have shown that the cellular protective mechanism against oxidative stress and inflammatory response has nuclear factor-erythroid 2-related factor-2 (Nrf2) activity. The aim of this study was to investigate the effectiveness and mechanism of Nrf2 activation in treating the ocular diseases with abnormal vessels.
   METHODS. The effects of Nrf2 activators, bardoxolone methyl (BARD) and RS9, were evaluated against vascular endothelial growth factor (VEGF)-induced cell migration in human retinal microvascular endothelial cells (HRMECs). We measured the expression of the Nrf2 target genes, Ho-1 and Nqo-1 mRNA, in mouse retinas after a single injection of BARD and RS9. The effects and mechanisms of RS9 against retinal angiogenesis were evaluated using an oxygen-induced retinopathy (OIR) model in mice. Moreover, the effect of RS9 against choroidal neovascularization (CNV) was evaluated in a laser-induced CNV monkey model.
   RESULTS. Both BARD and RS9 decreased VEGF-induced cell migration, and significantly increased Ho-1 mRNA expression; however, only RS9 significantly increased Nqo-1 mRNA. RS9 decreased retinal neovascularization through suppressing VEGF expression and increasing Nrf2, HO-1, platelet-derived growth factor receptor (PDGFR)-beta, and tight junction proteins in OIR murine retinas. Furthermore, RS9 showed a tendency toward decreasing CNV lesions, and improved vascular leakage in a CNV monkey model.
   CONCLUSIONS. These data indicate that a Nrf2 activator might be a candidate for treatment of ocular diseases characterized by pathophysiological angiogenesis and hyperpermeability.
C1 [Nakamura, Shinsuke; Inoue, Yuki; Sakurai, Shuji; Nishinaka, Ann; Hida, Yoshifumi; Masuda, Tomomi; Hara, Hideaki; Shimazawa, Masamitsu] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
   [Noguchi, Tetsuro; Horai, Naoto; Tsusaki, Hideshi; Hara, Hideaki; Shimazawa, Masamitsu] Gifu Pharmaceut Univ, Biomed Res, Gifu, Japan.
   [Noguchi, Tetsuro; Horai, Naoto] Shin Nippon Biomed Labs Ltd, Safety Res Labs SNBL DSR, Kagoshima, Japan.
   [Nakagami, Yasuhiro; Tsusaki, Hideshi] Daiichi Sankyo Co Ltd, Tokyo, Japan.
C3 Gifu Pharmaceutical University; Gifu Pharmaceutical University; Shin
   Nippon Biomedical Laboratories Ltd.; Daiichi Sankyo Company Limited
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; Nakagami,
   Yasuhiro/0000-0003-3618-1715
FU Daiichi Sankyo Co., Ltd.
FX Supported by Daiichi Sankyo Co., Ltd., Yasuhiro Nakagami and Shin Nippon
   Biomedical Laboratories Ltd., Tetsuro Noguchi, Naoto Horai, and Hideshi
   Tsusaki.
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NR 63
TC 13
Z9 13
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 MAY
PY 2019
VL 60
IS 6
BP 1943
EP 1952
DI 10.1167/iovs.18-25745
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HZ6RS
UT WOS:000468980600016
PM 31050722
OA gold
DA 2022-11-30
ER

PT J
AU Parsons, N
   Annamalai, B
   Obert, E
   Schnabolk, G
   Tomlinson, S
   Rohrer, B
AF Parsons, Nathaniel
   Annamalai, Balasubramaniam
   Obert, Elisabeth
   Schnabolk, Gloriane
   Tomlinson, Stephen
   Rohrer, Barbel
TI Inhibition of the alternative complement pathway accelerates repair
   processes in the murine model of choroidal neovascularization
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Complement system; Choroidal neovascularization; Anaphylatoxin; Targeted
   alternative pathway inhibitor CR2-fH; Injury; Repair
ID TARGETED INHIBITOR; C3A RECEPTOR; MOUSE MODEL; ACTIVATION; CELLS
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the US. Polymorphisms in complement components are associated with increased AMD risk, and it has been hypothesized that an overactive complement system is partially responsible for AMD pathology. Choroidal neovascularization (CNV) has two phases, injury/angiogenesis and repair/fibrosis. Complement activation has been shown to be involved in the angiogenesis phase of murine CNV, but has not been investigated during repair. Anaphylatoxin (C3a and C5a) signaling in particular has been shown to be involved in both tissue injury and repair in other models. CNV was triggered by laser-induced photocoagulation in C57BL/6 J mice, and lesion sizes measured by optical coherence tomography. Alternative pathway (AP) activation or C3a-receptor (C3aR) and C5a-receptor (C5aR) engagement was inhibited during the repair phase only of CNV with the AP-inhibitor CR2-fH, a C3aR antagonist (N24(2,2diphenylethoxy)acetyli-L-arginine, TFA), or a C5a blocking antibody (CLS026), respectively. Repair after CNV was also investigated in C3aR/C5aR double knockout mice. CR2-fl-I treatment normalized anaphylatoxin levels in the eye and accelerated regression of CNV lesions. In contrast, blockade of anaphylatoxin-receptor signaling pharmacologically or genetically did not significantly alter the course of lesion repair. These results suggest that continued complement activation prevents fibrotic scar resolution, and emphasizes the importance of reducing anaphylatoxins to homeostatic levels. This duality of complement, playing a role in injury and repair, will need to be considered when selecting a complement inhibitory strategy for AMD.
C1 [Parsons, Nathaniel; Annamalai, Balasubramaniam; Obert, Elisabeth; Schnabolk, Gloriane; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol & Microbiol, Charleston, SC 29425 USA.
   [Tomlinson, Stephen] Med Univ South Carolina, Dept Immunol, Charleston, SC 29425 USA.
   [Tomlinson, Stephen; Rohrer, Barbel] Dept Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina
RP Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU Department of Veterans Affairs [RX000444, BX003050, RX001141, BX004256];
   National Institutes of Health [EY019320, DK102912]; SmartState Centers
   of Excellence Endowment; NIH [C06 RR015455]; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK102912] Funding Source:
   NIH RePORTER; Veterans Affairs [I01RX001141, I21RX002363, I01BX003050,
   I01RX000444] Funding Source: NIH RePORTER
FX The authors would like to thank Dr. P Heeger from Icahn School of
   Medicine at Mount Sinai (New York, USA) for providing us with
   C3aR<SUP>-/-</SUP> C5aR<SUP>-/-</SUP> mice for our experiments and Yi
   Wang at Alexion Pharmaceuticals for providing us with the anti-C5a
   blocking antibody. This work was sponsored in part by a Department of
   Veterans Affairs awards RX000444 (BR), BX003050 (BR), RX001141 (ST) and
   BX004256 (ST), National Institutes of Health grants EY019320 (BR) and
   DK102912 (ST), as well as the SmartState Centers of Excellence Endowment
   (BR). Animal studies were conducted in a facility constructed with
   support from the NIH (C06 RR015455).
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NR 32
TC 13
Z9 14
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD APR
PY 2019
VL 108
BP 8
EP 12
DI 10.1016/j.molimm.2019.02.001
PG 5
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA HQ4ZC
UT WOS:000462418800002
PM 30763805
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Rudolf, M
   Curcio, CA
   Schlotzer-Schrehardt, U
   Sefat, AMM
   Tura, A
   Aherrahrou, Z
   Brinkmann, M
   Grisanti, S
   Miura, Y
   Ranjbar, M
AF Rudolf, Martin
   Curcio, Christine A.
   Schloetzer-Schrehardt, Ursula
   Sefat, Armin Mir Mohi
   Tura, Ayseguel
   Aherrahrou, Zouhair
   Brinkmann, Max
   Grisanti, Salvatore
   Miura, Yoko
   Ranjbar, Mahdy
TI Apolipoprotein A-I Mimetic Peptide L-4F Removes Bruch's Membrane Lipids
   in Aged Nonhuman Primates
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; lipids; Bruch's membrane; retinal
   pigment epithelium; drusen; histochemistry; electron microscopy;
   lipoproteins; apolipoprotein mimetic; L-4F
ID COMPLEMENT FACTOR-H; MACULAR-DEGENERATION; RHESUS-MONKEYS; APOA-I;
   CHOROIDAL NEOVASCULARIZATION; ATTACK COMPLEX; ESTERIFIED CHOLESTEROL;
   DRUSENOID MACULOPATHY; GEOGRAPHIC ATROPHY; HUMAN-NEUTROPHILS
AB PURPOSE. Multiple evidence lines support Bruch's membrane lipid deposition as a major precursor of soft drusen and age-related macular degeneration as including a potentially treatable atherosclerosis-like progression in the subretinal pigment epithelium (RPE)-basal lamina space. We evaluated the effect of anti-inflammatory, antiatherogenic peptide L-4F on Bruch's membrane of aged nonhuman primates in a dose-escalating study.
   METHODS. Macaca fascicularis >= 20 years of age evaluated by color fundus photography and optical coherence tomography received monocular intravitreal injections of L-4F (n = 7) or a placebo-scrambled peptide (n = 2) in 6 doses of 25 to 175 mu g over 6 months. Eyes were processed for detection and masked semiquantitative assessment of macular Bruch's membrane neutral lipid (oil red O staining), esterified cholesterol (filipin histochemistry), membrane attack complex (immunofluorescence), and paramacular thickness (transmission electron microscopy).
   RESULTS. Bruch's membrane neutral lipid, esterified cholesterol, and membrane attack complex were cleared and ultrastructure was improved in L-4F-injected eyes, compared to placebo-injected eyes. Fellow eyes were also affected to the same degree as the injected eyes. Punctate yellow fundus lesions without corresponding RPE elevations on optical coherence tomography correlated to RPE lipoidal degeneration (engorgement with lipid droplets), which was unchanged by this treatment.
   CONCLUSIONS. Clinical-stage apolipoprotein A-I mimetic peptide L-4F, delivered intravitreally in repeated doses, produced a substantial pharmacologic reduction of Bruch's membrane lipid and restoration of ultrastructure in a nonhuman primate model that exhibits an important precursor of soft drusen, if not soft drusen themselves.
C1 [Rudolf, Martin; Sefat, Armin Mir Mohi; Tura, Ayseguel; Brinkmann, Max; Grisanti, Salvatore; Miura, Yoko; Ranjbar, Mahdy] Univ Lubeck, Dept Ophthalmol, Lubeck, Germany.
   [Rudolf, Martin; Sefat, Armin Mir Mohi; Miura, Yoko] Univ Lubeck, Translat AMD Res Grp Lubeck, Lubeck, Germany.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL 35294 USA.
   [Schloetzer-Schrehardt, Ursula] Univ Erlangen Nurnberg, Dept Ophthalmol, Erlangen, Germany.
   [Aherrahrou, Zouhair] Univ Lubeck, Inst Cardiogenet, Lubeck, Germany.
   [Aherrahrou, Zouhair] German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, Lubeck, Germany.
   [Aherrahrou, Zouhair] Univ Heart Ctr Lubeck, Lubeck, Germany.
   [Brinkmann, Max; Ranjbar, Mahdy] Univ Lubeck, Lab Angiogenesis & Ocular Cell Transplantat, Lubeck, Germany.
   [Miura, Yoko] Univ Lubeck, Inst Biomed Opt, Lubeck, Germany.
C3 University of Lubeck; University of Lubeck; University of Alabama
   System; University of Alabama Birmingham; University of Erlangen
   Nuremberg; University of Lubeck; German Centre for Cardiovascular
   Research; University of Lubeck; University of Lubeck
RP Curcio, CA (通讯作者)，Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL 35294 USA.
EM christinecurcio@uabmc.edu
RI Brinkmann, Max/AAA-1171-2021; Miura, Yoko/B-5588-2015
OI Aherrahrou, Zouhair/0000-0002-1241-8733
FU Novartis
FX The authors thank Christine Orun for technical assistance. This project
   was supported by Novartis investigator-initiated research.
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NR 121
TC 23
Z9 23
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2019
VL 60
IS 2
BP 461
EP 472
DI 10.1167/iovs.18-25786
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN0LZ
UT WOS:000459881100001
PM 30707219
OA gold
DA 2022-11-30
ER

PT J
AU Liu, P
   Thomson, BR
   Khalatyan, N
   Feng, L
   Liu, XR
   Savas, JN
   Quaggin, SE
   Jin, J
AF Liu, Pan
   Thomson, Benjamin R.
   Khalatyan, Natalia
   Feng, Liang
   Liu, Xiaorong
   Savas, Jeffrey N.
   Quaggin, Susan E.
   Jin, Jing
TI Selective permeability of mouse blood-aqueous barrier as determined by
   N-15-heavy isotope tracing and mass spectrometry
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE blood-aqueous barrier; blood-ocular barrier; proteomics; stable isotope
   labeling in mammals; complement system
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; PROTEOME ANALYSIS; OXIDATIVE
   STRESS; BRAIN-BARRIER; CELL BIOLOGY; HUMOR; EYE; PROTEINS; MODEL
AB The blood-aqueous barrier plays a key role in regulating aqueous humor homeostasis by selectively restricting passage of proteins into the eye. The kinetics of aqueous flow are traditionally measured using artificial markers; however, these marker molecules do not address the barrier's selective permeability to plasma proteins. Here we applied stable isotope labeling of all serum proteins with nitrogen-15 (N-15) atoms. Following systemic injection of this "heavy" serumin mice, the N-15-to-endogenous nitrogen-14 (N-14) ratio of each protein in aqueous was measured by mass spectrometry. By monitoring the kinetic changes in these ratios, we determined the permeability profiles of hundreds of serum proteins. Meanwhile, we subjected one of the eyes to neoangiogenic wound healing by inflicting injury to the corneal limbus and compared the N-15 proteomes between the normal eyes and the recovering eyes at 2 weeks after injury. In the injured eye, we detected markedly enhanced permeability to inhibitory complement regulator proteins, such as Cfh, Cfhr, Cfb, Cfi, Cfd, and Vtn. Many of the proteins in this group are implicated in age-related macular degeneration associated with leakage of the blood-retinal barrier due to inflammation. To rule out the possibility that the observed leakage was due simply to physical damage of the blood vessels, we separately created a neovascularization model using an alkali burn of the avascular cornea. In this latter model, elevated levels of Cfh and Cfb were evident. These findings suggest that ocular neovascularization is associated with enhanced permeability to serum complement regulators.
C1 [Liu, Pan; Thomson, Benjamin R.; Quaggin, Susan E.; Jin, Jing] Northwestern Univ, Feinberg Cardiovasc & Renal Res Inst, Feinberg Sch Med, Div Nephrol & Hypertens, Chicago, IL 60611 USA.
   [Khalatyan, Natalia; Savas, Jeffrey N.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
   [Feng, Liang; Liu, Xiaorong] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Liu, Xiaorong] Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA.
   [Liu, Xiaorong] Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern
   University; Feinberg School of Medicine; Northwestern University;
   Feinberg School of Medicine; University of Virginia; University of
   Virginia
RP Jin, J (通讯作者)，Northwestern Univ, Feinberg Cardiovasc & Renal Res Inst, Feinberg Sch Med, Div Nephrol & Hypertens, Chicago, IL 60611 USA.
EM jing.jin@northwestern.edu
RI Liu, Xiaorong/R-3787-2019
OI Liu, Xiaorong/0000-0002-7655-6342; Khalatyan,
   Natalia/0000-0002-2883-0589; Thomson, Benjamin/0000-0001-6565-5866
FU National Institutes of Health [R01 EY026286, R00 DC013805, R01
   EY025799]; NATIONAL EYE INSTITUTE [R01EY025799, R01EY026286] Funding
   Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [R01HL124120] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON
   DEAFNESS AND OTHER COMMUNICATION DISORDERS [R00DC013805] Funding Source:
   NIH RePORTER
FX This work was supported by the National Institutes of Health (Grants R01
   EY026286, to X.L.; R00 DC013805, to J.N.S.; and R01 EY025799, to
   S.E.Q.). We thank Qunfeng Dong (Loyola University) for advice on
   statistics and George Anagnos for assistance with data analysis. We also
   thank the Center for Advanced Microscopy for imaging services and the
   Center for Comparative Medicine of Northwestern University for animal
   care.
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NR 45
TC 8
Z9 8
U1 2
U2 10
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 SEP 4
PY 2018
VL 115
IS 36
BP 9032
EP 9037
DI 10.1073/pnas.1807982115
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GS3VY
UT WOS:000443555000066
PM 30127000
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Eldem, B
   Lai, TYY
   Ngah, NF
   Vote, B
   Yu, HG
   Fabre, A
   Backer, A
   Clunas, NJ
AF Eldem, Bora
   Lai, Timothy Y. Y.
   Ngah, Nor Fariza
   Vote, Brendan
   Yu, Hyeong Gon
   Fabre, Alban
   Backer, Arthur
   Clunas, Nathan J.
TI An analysis of ranibizumab treatment and visual outcomes in real-world
   settings: the UNCOVER study
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Observational study; Ranibizumab; Visual acuity; Tomography; Optical
   coherence
ID AGE-RELATED MACULOPATHY; 2.0 MG RANIBIZUMAB; MACULAR DEGENERATION;
   EXTEND PROTOCOL; EFFICACY; SAFETY; PREVALENCE; REGIMEN; TRIALS
AB To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia-Pacific region.
   Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed.
   More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 mu m. The greatest mean CRT change was observed in the self-paid group, with -92.6 mu m.
   UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.
C1 [Eldem, Bora] Hacettepe Univ, Dept Ophthalmol, Sch Med, TR-06100 Ankara, Samanpazari, Turkey.
   [Lai, Timothy Y. Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
   [Ngah, Nor Fariza] Hosp Selayang, Dept Ophthalmol, Selayang, Selangor, Malaysia.
   [Vote, Brendan] Launceston Eye Inst, South Launceston, Australia.
   [Yu, Hyeong Gon] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Fabre, Alban] IQVIA, Barcelona, Spain.
   [Backer, Arthur; Clunas, Nathan J.] Novartis Pharma AG, Basel, Switzerland.
C3 Hacettepe University; Chinese University of Hong Kong; Seoul National
   University (SNU); Novartis
RP Eldem, B (通讯作者)，Hacettepe Univ, Dept Ophthalmol, Sch Med, TR-06100 Ankara, Samanpazari, Turkey.
EM beldem@superonline.com
RI Lai, Timothy Y Y/AAC-2120-2020
OI Lai, Timothy Y Y/0000-0002-7832-6428
FU Novartis Pharma AG, Basel, Switzerland
FX This study was sponsored by Novartis Pharma AG, Basel, Switzerland, and
   its respective affiliates. A contract research organization, IQVIA
   (formerly Quintiles), was responsible for the conduct of the study, data
   management, quality review, statistical analysis, report, and scientific
   communications writing. Medical writing assistance to the authors was
   provided by Coralie Lecomte, PharmD MSc and Corey Joseph, MPH, from
   IQVIA. Neither honoraria nor payments were made for authorship.
CR Abedi F, 2014, RETINA-J RET VIT DIS, V34, P1531, DOI 10.1097/IAE.0000000000000134
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NR 24
TC 8
Z9 8
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAY
PY 2018
VL 256
IS 5
BP 963
EP 973
DI 10.1007/s00417-017-3890-8
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GD5XD
UT WOS:000430580300010
PM 29502232
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Frede, K
   Ebert, F
   Kipp, AP
   Schwerdtle, T
   Baldermann, S
AF Frede, Katja
   Ebert, Franziska
   Kipp, Anna P.
   Schwerdtle, Tanja
   Baldermann, Susanne
TI Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment
   Epithelial Cells
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE lutein; Nif2; ARPE-19 cells; AMD; Tween40 micelles
ID PHASE-II ENZYMES; OXIDATIVE STRESS; ARPE-19 CELLS; HEME OXYGENASE-1;
   BETA-CAROTENE; VITAMIN-A; GENES; EXPRESSION; ZEAXANTHIN; INDUCTION
AB The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were nontoxic in APRE-19 cells up to 0.04% Tween40 and led to a cellular lutein accumulation of 62 mu M +/- 14 mu M after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 +/- 0.4-fold compared to that of unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 +/- 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 +/- 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 +/- 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 +/- 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant but also activates Nrf 2 in ARPE-19 cells.
C1 [Frede, Katja; Baldermann, Susanne] Leibniz Inst Vegetable & Ornamental Crops Grossbe, Plant Qual & Food Secur, Theodor Echtermeyer Weg 1, D-14979 Grossbeeren, Germany.
   [Frede, Katja; Ebert, Franziska; Schwerdtle, Tanja; Baldermann, Susanne] Univ Potsdam, Inst Nutr Sci, Dept Food Chem, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany.
   [Kipp, Anna P.] Friedrich Schiller Univ Jena, Inst Nutr, Dornburger Str 24, D-07743 Jena, Germany.
C3 Leibniz Institut fur Gemuse- und Zierpflanzenbau (IGZ); University of
   Potsdam; Friedrich Schiller University of Jena
RP Frede, K (通讯作者)，Leibniz Inst Vegetable & Ornamental Crops Grossbe, Plant Qual & Food Secur, Theodor Echtermeyer Weg 1, D-14979 Grossbeeren, Germany.; Frede, K (通讯作者)，Univ Potsdam, Inst Nutr Sci, Dept Food Chem, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany.
EM frede@igzev.de
RI Baldermann, Susanne/C-4292-2014; Baldermann, Susanne/AAH-6303-2020
OI Baldermann, Susanne/0000-0002-1501-4320; Baldermann,
   Susanne/0000-0002-1501-4320; Kipp, Anna Patricia/0000-0002-3307-1038;
   Frede, Katja/0000-0002-7989-6983
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NR 59
TC 43
Z9 45
U1 3
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JUL 26
PY 2017
VL 65
IS 29
BP 5944
EP 5952
DI 10.1021/acs.jafc.7b01929
PG 9
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Chemistry; Food Science & Technology
GA FC2EF
UT WOS:000406649400011
PM 28665123
OA hybrid
DA 2022-11-30
ER

PT J
AU Jones, MK
   Lu, B
   Girman, S
   Wang, SM
AF Jones, Melissa K.
   Lu, Bin
   Girman, Sergey
   Wang, Shaomei
TI Cell-based therapeutic strategies for replacement and preservation in
   retinal degenerative diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Animal models; Retinitis pigmentosa;
   Stem cell therapy; Transplantation; Visual function
ID MESENCHYMAL STEM-CELLS; PIGMENT EPITHELIAL-CELLS; DOMINANT
   RETINITIS-PIGMENTOSA; FIBROBLAST-GROWTH-FACTOR; CILIARY NEUROTROPHIC
   FACTOR; AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; ONSET
   MACULAR DEGENERATION; IMPLANTABLE MINIATURE TELESCOPE; HUMAN NEURAL
   PROGENITORS
AB Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
   [Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei] Cedars Sinai Med Ctr, Dept Biomed Sci, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
   [Wang, Shaomei] Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA.
C3 Cedars Sinai Medical Center; Cedars Sinai Medical Center; University of
   California System; University of California Los Angeles; University of
   California Los Angeles Medical Center; David Geffen School of Medicine
   at UCLA
RP Wang, SM (通讯作者)，Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM shaomei.wang@cshs.org
FU National Institutes of Health [EY020488]; Board of Governors
   Regenerative Medicine Institute at the Cedars-Sinai Medical Center; 
   [CIRM-LSP1-08325]; NATIONAL EYE INSTITUTE [R01EY020488] Funding Source:
   NIH RePORTER
FX This work was supported by the National Institutes of Health [EY020488],
   CIRM-LSP1-08325 and Board of Governors Regenerative Medicine Institute
   at the Cedars-Sinai Medical Center.
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NR 511
TC 59
Z9 65
U1 0
U2 29
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 2017
VL 58
BP 1
EP 27
DI 10.1016/j.preteyeres.2017.01.004
PG 27
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EV3EH
UT WOS:000401640100001
PM 28111323
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Smith, JW
   Rogers, RB
   Jeon, S
   Rubakhin, SS
   Wang, L
   Sweedler, JV
   Neuringer, M
   Kuchan, MJ
   Erdman, JW
AF Smith, Joshua W.
   Rogers, Randy B.
   Jeon, Sookyoung
   Rubakhin, Stanislav S.
   Wang, Lin
   Sweedler, Jonathan V.
   Neuringer, Martha
   Kuchan, Matthew J.
   Erdman, John W., Jr.
TI Carrot solution culture bioproduction of uniformly labeled (13) C-lutein
   and in vivo dosing in non-human primates
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Lutein; phytochemicals; nutrition; isotopic tracer; mass spectrometry;
   non-human primate
ID CELL-SUSPENSION CULTURES; BETA-CAROTENE; PLASMA APPEARANCE;
   MASS-SPECTROMETRY; XANTHOPHYLL CYCLE; HIGHER-PLANTS; C-13 TRACER;
   GAS-PHASE; HUMANS; TISSUE
AB Lutein is a xanthophyll abundant in nature and most commonly present in the human diet through consumption of leafy green vegetables. With zeaxanthin and meso-zeaxanthin, lutein is a component of the macular pigment of the retina, where it protects against photooxidation and age-related macular degeneration. Recent studies have suggested that lutein may positively impact cognition throughout the lifespan, but outside of the retina, the deposition, metabolism, and function(s) of lutein are poorly understood. Using a novel botanical cell culture system (Daucus carota), the present study aimed to produce a stable isotope lutein tracer for use in future investigations of dietary lutein distribution and metabolism. Carrot cultivars were initiated into liquid solution culture, lutein production conditions optimized, and uniformly labeled (13) C-glucose was provided as the sole media carbon source for four serial growth cycles. Lutein yield was 2.58 +/- 0.24 mu g/g, and mass spectrometry confirmed high enrichment of (13) C: 64.9% of lutein was uniformly labeled and 100% of lutein was labeled on at least 37 of 40 possible carbons. Purification of carrot extracts yielded a lutein dose of 1.92mg with 96.0 +/- 0.60% purity. (13) C-lutein signals were detectable in hepatic extracts of an adult rhesus macaque monkey (Macaca mulatta) dosed with (13) C-lutein, but not in hepatic samples collected from control animals. This novel botanical biofactory approach can be used to produce sufficient quantities of highly enriched and pure (13) C-lutein doses for use in tracer studies investigating lutein distribution, metabolism, and function.
C1 [Smith, Joshua W.; Jeon, Sookyoung; Erdman, John W., Jr.] Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA.
   [Rogers, Randy B.; Erdman, John W., Jr.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA.
   [Rubakhin, Stanislav S.; Wang, Lin; Sweedler, Jonathan V.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Neuringer, Martha] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Kuchan, Matthew J.] Abbott Nutr, Columbus, OH 43219 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign;
   University of Illinois System; University of Illinois Urbana-Champaign;
   University of Illinois System; University of Illinois Urbana-Champaign;
   Oregon Health & Science University; Oregon National Primate Research
   Center
RP Erdman, JW (通讯作者)，Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA.; Erdman, JW (通讯作者)，Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA.
EM jwerdman@illinois.edu
RI Jeon, Sookyoung/AAL-8526-2021; Rubakhin, Stanislav S/E-6685-2017;
   Sweedler, Jonathan V/A-9405-2009
OI Jeon, Sookyoung/0000-0002-3620-0851; Rubakhin, Stanislav
   S/0000-0003-0437-1493; Sweedler, Jonathan V/0000-0003-3107-9922; Smith,
   Josh/0000-0002-8636-8097
FU Abbott Nutrition through the Center for Nutrition, Learning and Memory,
   University of Illinois, Urbana - Champaign; US Department of Agriculture
   [1950-51000-073-01]; NIH [P51OD011092]; OFFICE OF THE DIRECTOR, NATIONAL
   INSTITUTES OF HEALTH [P51OD011092] Funding Source: NIH RePORTER
FX Funding was provided by Abbott Nutrition through the Center for
   Nutrition, Learning and Memory, University of Illinois, Urbana -
   Champaign; US Department of Agriculture grant no. 1950-51000-073-01 and
   NIH grant no. P51OD011092 (MN).
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NR 55
TC 3
Z9 3
U1 0
U2 8
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 2017
VL 242
IS 3
BP 305
EP 315
DI 10.1177/1535370216675067
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EK9TI
UT WOS:000394266400010
PM 27798119
OA Green Published
DA 2022-11-30
ER

PT J
AU Kremlacek, J
   Jiraskova, N
   Nekolova, J
   Sikl, R
   Kuba, M
AF Kremlacek, Jan
   Jiraskova, Nad'a
   Nekolova, Jana
   Sikl, Radovan
   Kuba, Miroslav
TI Electrophysiological testing of visual function after mirror telescope
   implantation: a case report
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Intraocular mirror telescope; Agerelated macular degeneration;
   Motion-onset VEPs; Pattern-reversal VEPs; Oddball ERPs; P3b
ID LOW-VISION REHABILITATION; MOTION-ONSET VEPS; MACULAR DEGENERATION;
   MINIATURE TELESCOPE; EVOKED-POTENTIALS; INTRAOCULAR-LENS; ACUITY; TRIAL
AB The implantation of an intraocular telescope increases life quality in patients with end-stage age-related macular degeneration (AMD). The present study monitored changes in electrophysiological markers of visual processing before and during seventeen months after a novel mirror telescope implantation in two patients (OV-male 90 years, MZ-female 70 years) with the final-stage form of AMD.
   Visual evoked potentials were recorded to high-contrast pattern-reversal (PR-VEP for check size 40' and 10'), low-contrast motion-onset stimuli (in visual periphery M-VEP M20A degrees, and in central part M-VEP C8A degrees), and event-related potentials (ERPs) in the oddball visual paradigm.
   MZ's more systematic responses showed attenuation and prolongation of the M-VEP M20A degrees and the PR-VEP 40' immediately after the telescope implantation with a slow amplitude recovery with unchanged prolonged latency. The implantation completely eradicated the M-VEP C8A degrees without any restoration. The PR-VEP 10' were not readable. Only a part of OV's PR-VEP 40' and M-VEP M20' were of a repeatable and expected morphology. These OV's VEPs were consistent with MZ's findings. The ERPs did not show any effect of implantation in both patients. Post-implantation visual acuity and reaction time overcame the pre-implantation levels.
   The mirror telescope preserved peripheral vision in contrast to classic telescopes; however, the telescope concurrently reduced the luminance of the magnified retinal image, which was likely responsible for the prolongation of the VEP latencies.
C1 [Kremlacek, Jan; Kuba, Miroslav] Charles Univ Prague, Fac Med Hradec Kralove, Dept Pathol Physiol, Simkova 870, Hradec Kralove 50038, Czech Republic.
   [Jiraskova, Nad'a; Nekolova, Jana] Univ Hosp, Fac Med Hradec Kralove, Dept Ophthalmol, Prague, Czech Republic.
   [Jiraskova, Nad'a; Nekolova, Jana] Charles Univ Prague, Prague, Czech Republic.
   [Sikl, Radovan] Acad Sci, Inst Psychol, Brno, Czech Republic.
C3 Charles University Prague; Charles University Prague; General University
   Hospital Prague; Charles University Prague; Czech Academy of Sciences;
   Institute of Psychology of the Czech Academy of Sciences
RP Kremlacek, J (通讯作者)，Charles Univ Prague, Fac Med Hradec Kralove, Dept Pathol Physiol, Simkova 870, Hradec Kralove 50038, Czech Republic.
EM jan.kremlacek@lfhk.cuni.cz
RI Kremlacek, Jan/A-4313-2008; Kuba, Miroslav/D-8252-2017; Jirásková,
   Naďa/L-9198-2017; Nekolová, Jana/I-6031-2017; Nekolová,
   Jana/AAX-3663-2021
OI Kremlacek, Jan/0000-0001-8641-4287; Kuba, Miroslav/0000-0003-2525-0463;
   Jirásková, Naďa/0000-0002-2268-7400; Nekolová, Jana/0000-0002-0662-8662;
   Nekolová, Jana/0000-0002-0662-8662
FU Charles University [PRVOUK-P37/07]
FX This work was supported by the Charles University project
   [PRVOUK-P37/07] provided financial support in the form of salaries. The
   sponsor had no role in the design or conduct of this research.
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   Vottonen P, 2013, CLIN OPHTHALMOL, V7, P437, DOI 10.2147/OPTH.S40427
NR 36
TC 2
Z9 2
U1 0
U2 4
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 DEC
PY 2016
VL 133
IS 3
BP 171
EP 181
DI 10.1007/s10633-016-9563-9
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ED6OM
UT WOS:000388974900003
PM 27832406
DA 2022-11-30
ER

PT J
AU Tsui, I
   Havunjian, MA
   Davis, JA
   Giaconi, JA
AF Tsui, Irena
   Havunjian, Margaret A.
   Davis, John A.
   Giaconi, JoAnn A.
TI Snapshot of Teleretinal Screening for Diabetic Retinopathy at the West
   Los Angeles Medical Center
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE ophthalmology; telehealth; telemedicine; behavioral health
ID TELEMEDICINE; DIAGNOSIS; PROGRAM; PROGRESSION; QUALITY; AGE
AB Introduction:The West Los Angeles Veterans Affairs Medical Center is a large urban facility with a robust teleretinal screening program in primary care clinic, established in 2006. The purpose of this article is to provide a snapshot of teleretinal screening at this site.Methods:Diabetic patients from 2012 were analyzed with a prospective cohort study. Demographic information, results of teleretinal screening, referral to eye clinic, and loss to follow-up (defined as no eye care within 2 years) were collected.Results:Of 516 patients with diabetes screened with teleretinal imaging, 120 patient charts were reviewed for data analysis. Teleretinal imaging diagnosed 15% (18/120) of patients with varying stages of nonproliferative diabetic retinopathy (DR). Of patients screened, 55.8% (67/120) of the patients were referred to an eye clinic for further ophthalmic evaluation. Nondiabetic retinopathy reasons for eye clinic referral included glaucoma suspect (13.3%, 16/120) and age-related macular degeneration (10.0%, 12/120). Of all patients screened, 37.5% (45/120) of them were lost to follow-up, defined as no teleretinal screening or eye clinic appointment within 2 years. Patients who lived farther away from clinic had a higher risk of loss to follow-up (p=0.04).Discussion:We found, although only 15% of patients were diagnosed with DR from teleretinal screening, more than 50% of patients were referred to eye clinic. In addition, of all screened patients, there was a high rate of not returning to theVeterans Affairs (VA) for eye care.
C1 [Tsui, Irena; Havunjian, Margaret A.; Davis, John A.; Giaconi, JoAnn A.] Univ Calif Los Angeles, Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA.
   [Tsui, Irena] Univ Calif Los Angeles, Doheny Eye Inst, Los Angeles, CA USA.
   [Tsui, Irena; Giaconi, JoAnn A.] West Los Angeles Vet Affairs Med Ctr, Dept Ophthalmol, Los Angeles, CA USA.
C3 University of California System; University of California Los Angeles;
   Doheny Eye Institute; University of California System; University of
   California Los Angeles; US Department of Veterans Affairs; Veterans
   Health Administration (VHA); West Los Angeles VA Medical Center
RP Tsui, I (通讯作者)，Univ Calif Los Angeles, Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM itsui@jsei.ucla.edu
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NR 19
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 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD OCT
PY 2016
VL 22
IS 10
BP 843
EP 846
DI 10.1089/tmj.2015.0246
PG 4
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA DZ9PR
UT WOS:000386211100008
PM 26985625
DA 2022-11-30
ER

PT J
AU Ren, XY
   Li, J
   Xu, XX
   Wang, CM
   Cheng, YG
AF Ren, Xinyi
   Li, Jia
   Xu, Xianxing
   Wang, Chunming
   Cheng, Yuanguo
TI IBI302, a promising candidate for AMD treatment, targeting both the VEGF
   and complement system with high binding affinity in vitro and effective
   targeting of the ocular tissue in healthy rhesus monkeys
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE VEGF; Complement proteins; Bispecific; Binding affinity;
   Pharmacokinetics
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; ANGIOGENESIS; PATHWAY;
   RANIBIZUMAB; BEVACIZUMAB; INHIBITOR; DISEASE
AB Uncontrolled activation of complement and upregulation of vascular endothelial growth factor (VEGF) play fundamental roles in age-related macular degeneration (AMD). However, most drugs used to treat AMD focus on a single target, and the percentage of effectively treated patients in clinical practice needs to be improved. Therefore, novel AMD treatment approaches are needed. IBI302 is a novel bispecific decoy receptor fusion protein designed with both a VEGF inhibition domain and a complement cascade inhibition domain, which are connected by the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity between IBI302 and VEGF isoforms and complement proteins by using surface plasmon resonance (SPR) technology. Anti-VEGF blockers (aflibercept and bevacizumab) and complement receptor 1 were used as references. The SPR assay results indicated that IBI302 could bind different VEGF isoforms and complement proteins with high affinity. The biological activity of IBI302 was also studied. IBI302 showed an inhibitory effect on human primary umbilical vein endothelial cell proliferation and the activation of complement pathways in vitro. Finally, the pharmacokinetic (PK) properties of IBI302 were evaluated in rhesus monkeys. The PK results showed that after a 0.5 mg/eye intravitreal dosage, IBI302 became rapidly distributed from the vitreous humor into targeted tissues and remained active over 504 h. Overall, the favorable anti-angiogenic and anti-complement effects of IBI302 along with the good PK profiles in rhesus monkeys support the selection and development of IBI302 as a promising candidate for AMD treatment. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Ren, Xinyi; Cheng, Yuanguo] Beijing Inst Microbiol & Epidemiol, Dept Pharm, Beijing, Peoples R China.
   [Li, Jia; Wang, Chunming] Innovent Biol Inc, Dept Preclin Res, Suzhou, Peoples R China.
   [Xu, Xianxing] Beijing Chaoyang Hosp, Dept Pharm, Beijing, Peoples R China.
C3 Beijing Institute of Microbiology & Epidemiology
RP Cheng, YG (通讯作者)，Beijing Inst Microbiol & Epidemiol, Dept Pharm, Beijing, Peoples R China.
EM cheng_yg@163.com
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NR 21
TC 14
Z9 18
U1 0
U2 13
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 352
EP 358
DI 10.1016/j.exer.2016.02.004
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL1DL
UT WOS:000375372300039
PM 26919788
DA 2022-11-30
ER

PT J
AU Carido, M
   Zhu, Y
   Postel, K
   Benkner, B
   Cimalla, P
   Karl, MO
   Kurth, T
   Paquet-Durand, F
   Koch, E
   Munch, TA
   Tanaka, EM
   Ader, M
AF Carido, Madalena
   Zhu, Yu
   Postel, Kai
   Benkner, Boris
   Cimalla, Peter
   Karl, Mike O.
   Kurth, Thomas
   Paquet-Durand, Francois
   Koch, Edmund
   Muench, Thomas A.
   Tanaka, Elly M.
   Ader, Marius
TI Characterization of a Mouse Model With Complete RPE Loss and Its Use for
   RPE Cell Transplantation
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinal pigment epithelium; sodium iodate; age-related macular
   degeneration; transplantation; hESC-derived RPE
ID RETINAL-PIGMENT EPITHELIUM; INDEPENDENT PHOTORECEPTOR APOPTOSIS;
   EMBRYONIC STEM-CELLS; SODIUM IODATE; BRUCHS MEMBRANE; ROYAL-COLLEGE;
   HORSERADISH-PEROXIDASE; MACULAR DEGENERATION; RPE65(-/-) MOUSE; VISUAL
   FUNCTION
AB PURPOSE. Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the usefulness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells.
   METHODS. Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell-derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were analyzed 3 weeks later.
   RESULTS. Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abolished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments.
   CONCLUSIONS. Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.
C1 [Carido, Madalena; Zhu, Yu; Postel, Kai; Karl, Mike O.; Kurth, Thomas; Tanaka, Elly M.; Ader, Marius] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Dresden, Germany.
   [Benkner, Boris; Muench, Thomas A.] Univ Tubingen, Werner Reichardt Ctr Integrat Neurosci, Tubingen, Germany.
   [Benkner, Boris; Muench, Thomas A.] Univ Tubingen, Bernstein Ctr Computac Biol, Tubingen, Germany.
   [Cimalla, Peter; Koch, Edmund] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dresden, Germany.
   [Karl, Mike O.] DZNE, German Ctr Neurodegenerat Dis, Dresden, Germany.
   [Paquet-Durand, Francois] Univ Tubingen, Inst Ophthalm Res, Tubingen, Germany.
C3 Technische Universitat Dresden; Eberhard Karls University of Tubingen;
   Eberhard Karls University of Tubingen; Technische Universitat Dresden;
   Carl Gustav Carus University Hospital; Helmholtz Association; German
   Center for Neurodegenerative Diseases (DZNE); Technische Universitat
   Dresden; Eberhard Karls University of Tubingen; Eberhard Karls
   University Hospital
RP Ader, M (通讯作者)，CRTD DFG Ctr Regenerat Therapies Dresden Cluster, Fetscherstr 105, D-01307 Dresden, Germany.
EM marius.ader@crt-dresden.de
RI Tanaka, Elly M/F-8572-2010; Paquet-Durand, Francois/G-6709-2015; Ader,
   Marius/E-7535-2010; Karl, Mike O./E-7246-2010
OI Paquet-Durand, Francois/0000-0001-7355-5742; Ader,
   Marius/0000-0001-9467-7677; Karl, Mike O./0000-0002-0926-6556; Tanaka,
   Elly/0000-0003-4240-2158; Munch, Thomas/0000-0002-8884-6961; Kurth,
   Thomas/0000-0001-5624-1717; Carido, Madalena/0000-0001-8969-0877; Koch,
   Edmund/0000-0003-0554-2178
FU Deutsche Forschungsgemeinschaft (DFG) [FZT 111, EXC 307]; CRTD seed
   grant [043-261576]; Fundacao para a Ciencia e Tecnologia (FCT, Portugal)
   [SFRH/BD/69144/2010]; Bundesministerium fur Bildung und Forschung (BMBF;
   Berlin, Germany) [FKZ 01GQ1002]; ProRetina Stiftung (Frankfurt a. M.,
   Germany)
FX Supported by grants from the Deutsche Forschungsgemeinschaft (DFG) FZT
   111 (Center for Regenerative Therapies Dresden, Cluster of Excellence;
   Dresden, Germany) and EXC 307 (Center for Integrative Neuroscience
   Tubingen, Cluster of Excellence; Tubingen, Germany), CRTD seed grant
   (043-261576), Fundacao para a Ciencia e Tecnologia (FCT, Portugal) grant
   (SFRH/BD/69144/2010), the Bundesministerium fur Bildung und Forschung
   (BMBF; Berlin, Germany) FKZ 01GQ1002 (Bernstein Center Tubingen,
   Tubingen, Germany) and the ProRetina Stiftung (Frankfurt a. M.,
   Germany).
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NR 63
TC 44
Z9 47
U1 0
U2 22
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 2014
VL 55
IS 8
BP 5431
EP 5444
DI 10.1167/iovs.14-14325
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ9DV
UT WOS:000343145500101
PM 25103259
DA 2022-11-30
ER

PT J
AU Kim, KA
   Cha, KH
   Choi, SJ
   Pan, CH
   Jung, SH
AF Kim, Kyung-A
   Cha, Kwang Hyun
   Choi, Soon-Jung
   Pan, Cheol-Ho
   Jung, Sang Hoon
TI THE EXTRACT OF CHLORELLA VULGARIS PROTECTS TRANSFORMED RETINAL GANGLION
   CELLS FROM OXIDATIVE STRESS-INDUCED CELLS DEATH
SO JOURNAL OF FOOD BIOCHEMISTRY
LA English
DT Article
ID DIFFERENTIATED RGC-5 CELLS; WATER EXTRACT; IN-VITRO; LUTEIN;
   CAROTENOIDS; ANTIOXIDANT; GLUTAMATE; GLAUCOMA; DAMAGE; PROLIFERATION
AB This study investigated whether an extract of Chlorella vulgaris (ECV) could ameliorate the negative influence of N-methyl-d-aspartate (NMDA) on the retinas of rats and decrease oxidative stress-induced cell death in transformed retinal ganglion cells (RGC-5). The ECV was shown to attenuate the negative effect of l-buthionine-(S,R)-sulfoximine (BSO) and glutamate on RGC-5 cells. ECV also decreased the expression of apoptotic proteins induced by BSO and glutamate. NMDA affected the thickness of the retinal inner plexiform layer (IPL) and increased the number of TUNEL-positive RGCs. However, ECV treatment was protective against IPL thinning and reduced the number of TUNEL-positive cells in the ganglion cell layer. Our results clearly demonstrate the neuroprotective effect of ECV on retinal degeneration both in vitro and in vivo.
   Practical ApplicationsChlorella vulgaris is used in alternative medicine and traditional foods because of its high nutritional content and significant amounts of lutein, which may be beneficial in protecting against age-related eye diseases such as cataract, age-related macular degeneration (AMD), and glaucoma. However, its protective effect against glaucoma-related retinal ganglion cell degeneration has not been investigated. This study aimed to examine whether the extract of C.vulgaris (ECV) could be protective against retinal degeneration. Our results indicate that ECV can protect retinal cells from oxidative stress-induced damage both in vitro and in vivo. These effects may be due to the anti-apoptotic potencies of compounds contained in C.vulgaris. Thus, C.vulgaris may be a useful supplement to prevent retinal degeneration.
C1 [Kim, Kyung-A; Cha, Kwang Hyun; Choi, Soon-Jung; Pan, Cheol-Ho; Jung, Sang Hoon] Korea Inst Sci & Technol, Funct Food Ctr, Gangneung Inst, Kangnung 210340, South Korea.
C3 Korea Institute of Science & Technology (KIST)
RP Jung, SH (通讯作者)，Korea Inst Sci & Technol, Funct Food Ctr, Gangneung Inst, Kangnung 210340, South Korea.
EM shjung507@gmail.com
FU Korea Institute of Planning and Evaluation for Technology of Food,
   Agriculture, Forestry and Fisheries; Korea Institute of Science and
   Technology (KIST), Republic of Korea [2Z03850]
FX This study was supported by the Korea Institute of Planning and
   Evaluation for Technology of Food, Agriculture, Forestry and Fisheries,
   and by an intramural grant (2Z03850) from the Korea Institute of Science
   and Technology (KIST), Republic of Korea.
CR Artan M, 2008, BIOORGAN MED CHEM, V16, P7921, DOI 10.1016/j.bmc.2008.07.078
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NR 37
TC 4
Z9 4
U1 0
U2 12
PU WILEY-BLACKWELL
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 APR
PY 2014
VL 38
IS 2
BP 129
EP 139
DI 10.1111/jfbc.12030
PG 11
WC Biochemistry & Molecular Biology; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Food Science & Technology
GA AE6PR
UT WOS:000334116500001
DA 2022-11-30
ER

PT J
AU Owsley, C
   McGwin, G
   Searcey, K
AF Owsley, Cynthia
   McGwin, Gerald, Jr.
   Searcey, Karen
TI A Population-Based Examination of the Visual and Ophthalmological
   Characteristics of Licensed Drivers Aged 70 and Older
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Aging; Driving; Vision impairment; Eye disease
ID MOTOR-VEHICLE CRASH; UNITED-STATES; DIABETIC-RETINOPATHY; CONTRAST
   SENSITIVITY; ADULTS; RISK; IMPAIRMENT; PREVALENCE; CATARACT; PERFORMANCE
AB Background. Safe driving performance depends on visual skills yet little is known about the prevalence of vision impairments in older drivers and the eye conditions that cause them. This study is a population-based examination of the prevalence of vision impairment and major ophthalmological conditions among drivers aged 70 and older.
   Methods. The source population was a random sample of 2,000 licensed drivers aged 70 and older residing in north central Alabama. All had driven within the past 3 months. Binocular visual acuity and contrast sensitivity were assessed. The Useful Field of View subtest 2 and Trails B assessed visual processing speed. Ophthalmological diagnoses for cataract, intraocular lens placement, glaucoma, diabetic retinopathy, age-related macular degeneration, and diabetic retinopathy were obtained through medical records from the most recent eye examination.
   Results. Ninety-two percent of drivers had visual acuity of 20/40 or better; only two drivers (0.1%) had acuity worse than 20/100. Ninety-three percent had normal contrast sensitivity (>= 1.5). About 40% had slowed visual processing speed (44%, Useful Field of View; 38%, Trails B). The most common eye condition was cataract, with more than half having cataract in one or both eyes (56%); yet by the 80s and 90s, the prevalence was low, with most drivers having undergone cataract surgery and intraocular lens placement.
   Conclusions. This population-based study suggests that serious impairment in central vision visual acuity or contrast sensitivity is rather uncommon in older drivers; however, slowed visual processing speed is common.
C1 [Owsley, Cynthia; McGwin, Gerald, Jr.; Searcey, Karen] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Dept Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Sch Med, Sect Trauma Bums & Surg Crit Care, Dept Surg, Birmingham, AL 35294 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
RP Owsley, C (通讯作者)，Univ Alabama Birmingham, Dept Ophthalmol, 700 S 18th St,Suite 609, Birmingham, AL 35294 USA.
EM owsley@uab.edu
FU National Eye Institute of the National Institutes of Health; National
   Institute on Aging of the National Institutes of Health [R01EY18966,
   P30AG22838]; American Recovery and Reinvestment Act; EyeSight Foundation
   of Alabama; Able Trust; Research to Prevent Blindness, Inc.; NATIONAL
   EYE INSTITUTE [R01EY018966] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [P30AG022838] Funding Source: NIH RePORTER
FX This work was supported by the National Eye Institute and the National
   Institute on Aging of the National Institutes of Health (R01EY18966,
   P30AG22838); the American Recovery and Reinvestment Act of 2009; the
   EyeSight Foundation of Alabama; the Able Trust; and Research to Prevent
   Blindness, Inc.
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NR 42
TC 36
Z9 36
U1 0
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2013
VL 68
IS 5
BP 567
EP 573
DI 10.1093/gerona/gls185
PG 7
WC Geriatrics & Gerontology; Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA 125KO
UT WOS:000317538900009
PM 22982690
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Sugano, E
   Isago, H
   Murayama, N
   Tamai, M
   Tomita, H
AF Sugano, Eriko
   Isago, Hitomi
   Murayama, Namie
   Tamai, Makoto
   Tomita, Hiroshi
TI Different Anti-Oxidant Effects of Thioredoxin 1 and Thioredoxin 2 in
   Retinal Epithelial Cells
SO CELL STRUCTURE AND FUNCTION
LA English
DT Article
DE adeno-associated virus; age-related macular degeneration; oxidative
   stress; retinal epithelial cells; thioredoxin
ID FACTOR-KAPPA-B; OXIDATIVE STRESS; MACULAR DEGENERATION;
   ENDOTHELIAL-CELLS; GROWTH-FACTOR; CATHEPSIN-S; DAMAGE; EXPRESSION; RPE;
   PROTECTION
AB Age-related macular degeneration (AMD) affects the retina and is the most common cause of blindness in elderly persons in developed countries. The retina is constantly subjected to oxidative stress; to avoid the effects of oxidative stress, retinal pigment epithelial (RPE) cells possess potent anti-oxidant systems. Disruption of these systems leads to dysfunction of RPE cells, which then accelerates the development of AMD. Here, we investigated the role of thioredoxins (TRXs), scavengers of intracellular reactive oxygen species, by assessing the effect of TRX overexpression on cell viability, morphology, NF-kappa B expression, and mitochondrial membrane potential, in RPE cells. TRX-overexpressing cell lines were generated by infection of an established human RPE cell line (ARPE) with adeno-associated virus vectors encoding either TRX1 or TRX2. We showed that overexpression of TRXs reduced cell death caused by 4-hydroxynonenal (4-HNE)-induced oxidative stress; TRX2 was more effective than TRX1 in promoting cell survival. 4-HNE caused perinuclear NF-kappa B accumulation, which was absent in TRX-overexpressing cells. Moreover, overexpression of TRXs prevented depolarization of mitochondrial membranes; again, TRX2 was more effective than TRX1 in maintaining the membrane potential. The difference in the protective effects of these TRXs against oxidative stress may be due to their expression profile. TRX2 was expressed in the mitochondria, while TRX1 was expressed in the cytoplasm. Thus, TRX2 may directly protect mitochondria by preventing depolarization. These results demonstrate that TRXs are potent antioxidant proteins in RPE cells and their direct effect on mitochondria may be a key to prevent oxidative stress.
C1 [Sugano, Eriko; Isago, Hitomi; Murayama, Namie; Tomita, Hiroshi] Iwate Univ, Grad Sch Engn, Fac Engn, Dept Chem & Bioengn, Morioka, Iwate 0208551, Japan.
   [Tamai, Makoto] Tohoku Univ, Sch Med, Sendai, Miyagi 9808574, Japan.
   [Tomita, Hiroshi] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 9808574, Japan.
   [Tomita, Hiroshi] Tohoku Univ Hosp, Clin Res Innovat & Educ Ctr, Sendai, Miyagi 9808574, Japan.
C3 Iwate University; Tohoku University; Tohoku University; Tohoku
   University
RP Tomita, H (通讯作者)，Iwate Univ, Grad Sch Engn, Fac Engn, Lab Visual Neurosci,Dept Chem & Bioengn, 4-3-5 Ueda, Morioka, Iwate 0208551, Japan.
EM htomita@iwate-u.ac.jp
RI Tomita, Hiroshi/O-2135-2018
OI Tomita, Hiroshi/0000-0003-1051-2301
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
   [23791960, 24390393, 23659804]; Program for Promotion of Fundamental
   studies in Health Sciences of the National Institute of Biomedical
   Innovation (NIBIO)
FX This work was supported in part by Grants-in-Aid for Scientific Research
   from the Ministry of Education, Culture, Sports, Science and Technology
   of Japan (nos. 23791960, 24390393, and 23659804); Program for Promotion
   of Fundamental studies in Health Sciences of the National Institute of
   Biomedical Innovation (NIBIO).
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NR 30
TC 20
Z9 20
U1 0
U2 5
PU JAPAN SOC CELL BIOLOGY
PI KYOTO
PA C/O NAKANISHI PRINTING SHIMODACHIURI OGAWA HIGASHI, KAMIGYO-KU, KYOTO,
   602-8048, JAPAN
SN 0386-7196
EI 1347-3700
J9 CELL STRUCT FUNCT
JI Cell Struct. Funct.
PY 2013
VL 38
IS 1
BP 81
EP 88
DI 10.1247/csf.12025
PG 8
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 172WG
UT WOS:000321035700009
PM 23485938
OA Bronze
DA 2022-11-30
ER

PT J
AU Rohrer, B
   Coughlin, B
   Bandyopadhyay, M
   Holers, VM
AF Rohrer, Baerbel
   Coughlin, Beth
   Bandyopadhyay, Mausumi
   Holers, V. Michael
TI Systemic Human CR2-Targeted Complement Alternative Pathway Inhibitor
   Ameliorates Mouse Laser-Induced Choroidal Neovascularization
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID RETINAL VEIN OCCLUSION; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   TARGETED INHIBITOR; FACTOR-B; AGE; ACTIVATION; DRUSEN; RISK; BEVACIZUMAB
AB Purpose: Genetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted'' to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD.
   Methods: Choroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined.
   Results: CNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid.
   Conclusion: Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.
C1 [Rohrer, Baerbel; Coughlin, Beth] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Med Univ S Carolina, Neurosci Div Res, Charleston, SC 29425 USA.
   [Holers, V. Michael] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA.
   [Holers, V. Michael] Taligen Therapeut Inc, Cambridge, MA USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; University of Colorado System; University of Colorado Anschutz
   Medical Campus
RP Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU National Institutes of Health [EY019320, C06 RR015455]; Department for
   Veterans Affairs merit award [RX000444]; Taligen Therapeutics; Research
   to Prevent Blindness (RPB), New York, NY; NATIONAL CENTER FOR RESEARCH
   RESOURCES [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY019320] Funding Source: NIH RePORTER
FX The authors thank Kannan Kunchithapautham for his help with QRT-PCR and
   ELISA assays, and Luanna Bartholomew for critical review. This work was
   supported in part by a National Institutes of Health grant EY019320 (B.
   R.), a Department for Veterans Affairs merit award RX000444 (B.R.), a
   sponsored research agreement by Taligen Therapeutics (B.R.), and an
   unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New
   York, NY. B.R. is a RPB Olga Keith Wiess Scholar. Animal studies were
   conducted in a facility constructed with support from the NIH (C06
   RR015455).
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NR 47
TC 33
Z9 38
U1 0
U2 3
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 AUG
PY 2012
VL 28
IS 4
BP 402
EP 409
DI 10.1089/jop.2011.0212
PG 8
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 982DI
UT WOS:000307021500012
PM 22309197
OA Green Published
DA 2022-11-30
ER

PT J
AU Bai, YJ
   Huang, LZ
   Xu, XL
   Du, W
   Zhou, AY
   Yu, WZ
   Li, XX
AF Bai, Yu-Jing
   Huang, Lv-Zhen
   Xu, Xiao-Lei
   Du, Wei
   Zhou, Ai-Yi
   Yu, Wen-Zhen
   Li, Xiao-Xin
TI Polyethylene Glycol-Modified Pigment Epithelial-Derived Factor: New
   Prospects for Treatment of Retinal Neovascularization
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; GENE-TRANSFER;
   DELIVERY; ANGIOGENESIS; RETINOPATHY; PHARMACEUTICALS; PEGYLATION;
   PROTEINS; DRUGS
AB Pathological retinal neovascularization and choroidal neovascularization are major causes of vision loss in a variety of clinical conditions, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural, endogenous inhibitor of neovascularization, but its application is restricted because of its instability and short half-life. Polyethylene glycol (PEG) has been used as a drug carrier to slow clearance rate for decades. The present study investigated PEGylated-PEDF for the first time and evaluated its long-term effects on preventing angiogenesis in vitro and in vivo. PEG showed lower cytotoxicity to human umbilical vein endothelial cells (HUVECs). In vitro, PEGylated-PEDF inhibited HUVEC proliferation, migration, tube formation, and vascular endothelium growth factor secretion and induced HUVEC apoptosis in a dose-dependent manner, and it showed a statistically significant difference compared with the PEDF treatment group. In vivo, PEGylated-PEDF had a long-lasting effect in both plasma and retinal concentrations. In an oxygen-induced retinopathy model, one intravitreous injection of PEGylated-PEDF after mouse pups were moved into room air resulted in a significant difference in the inhibition of retinal neovascularization, which decreased the nonperfusion area, compared with the PEDF-treated group. Our present study demonstrated for the first time the long-term inhibitory effects of PEGylated-PEDF on the prevention of neovascularization in vitro and in vivo. These data suggest that PEGylated-PEDF could offer an innovative therapeutic strategy for preventing retinal neovascularization.
C1 [Bai, Yu-Jing; Huang, Lv-Zhen; Du, Wei; Zhou, Ai-Yi; Yu, Wen-Zhen; Li, Xiao-Xin] Peking Univ, Peoples Hosp, Dept Ophthalmol, Minist Educ,Key Lab Vis Loss & Restorat, Beijing 100044, Peoples R China.
   [Xu, Xiao-Lei] Dong Xiao Jiang Beijing Sci & Technol Co Ltd, Beijing, Peoples R China.
C3 Peking University
RP Li, XX (通讯作者)，Peking Univ, Peoples Hosp, Dept Ophthalmol, Minist Educ,Key Lab Vis Loss & Restorat, Xizhimen S St 11,Xi Cheng Dist, Beijing 100044, Peoples R China.
EM dr_lixiaoxin@163.com
FU National Basic Research Program of China's 973 Program [2011 CB510200]
FX This work was supported by the National Basic Research Program of
   China's 973 Program [Grant 2011 CB510200].
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NR 30
TC 30
Z9 31
U1 0
U2 11
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUL
PY 2012
VL 342
IS 1
BP 131
EP 139
DI 10.1124/jpet.112.192575
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 960NO
UT WOS:000305395400014
PM 22495066
DA 2022-11-30
ER

PT J
AU Ruiz-Moreno, JM
   Montero, JA
   Amat, P
   Lugo, F
AF Ruiz-Moreno, Jose M.
   Montero, Javier A.
   Amat, Pedro
   Lugo, Francisco
TI Macular atrophy after combined intravitreal triamcinolone and
   photodynamic therapy to treat choroidal neovascularization
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age related macular degeneration; choriocapillaris atrophy;
   intravitreous triamcinolone; photodynamic therapy; retinal pigment
   epithelium atrophy
ID ACETONIDE; DEGENERATION; INJECTION; RANIBIZUMAB; PDT
AB AIM: To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).
   METHODS: The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.4 +/- 2.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group.
   RESULTS: Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P =0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (5044 +/- 1666)mu m in the study group vs (4345 +/- 1550)mu m in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.87 +/- 0.33) in the cases with RPE atrophy vs (0.66 +/- 0.26) in the cases with no RPE atrophy in the study group (P =0.11, Mann-Whitney U test).
   CONCLUSION: The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy.
C1 [Montero, Javier A.] Pio del Rio Hortega Univ Hosp, Ophthalmol Unit, Valladolid 47012, Spain.
   [Ruiz-Moreno, Jose M.] Univ Castilla La Mancha, Albacete Med Sch, Dept Ophthalmol, E-13071 Ciudad Real, Spain.
   [Ruiz-Moreno, Jose M.; Montero, Javier A.; Amat, Pedro; Lugo, Francisco] Alicante Inst Ophthalmol, Vitreo Retinal Unit, Alicante, Spain.
C3 Universidad de Castilla-La Mancha
RP Montero, JA (通讯作者)，Pio del Rio Hortega Univ Hosp, Ophthalmol Unit, C Carraca S-N, Valladolid 47012, Spain.
EM javmonmor@hotmail.com
RI Ruiz-Moreno, José M/E-4644-2016
OI Ruiz-Moreno, Jose M/0000-0001-9636-0788
CR Augustin AJ, 2006, OPHTHALMOLOGY, V113, P14, DOI 10.1016/j.ophtha.2005.09.002
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NR 18
TC 3
Z9 3
U1 0
U2 0
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 2010
VL 3
IS 2
BP 161
EP 163
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 664BQ
UT WOS:000282934300016
PM 22553543
DA 2022-11-30
ER

PT J
AU Liu, ZB
   Sun, LJ
   Zhu, L
   Jia, X
   Li, XS
   Jia, HQ
   Wang, Y
   Weber, P
   Long, JG
   Liu, JK
AF Liu, Zhongbo
   Sun, Lijuan
   Zhu, Lu
   Jia, Xu
   Li, Xuesen
   Jia, Haiqun
   Wang, Ying
   Weber, Peter
   Long, Jiangang
   Liu, Jiankang
TI Hydroxytyrosol protects retinal pigment epithelial cells from
   acrolein-induced oxidative stress and mitochondrial dysfunction
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE DNA damage; hydroxytyrosol; macular degeneration; mitochondrial membrane
   potential; nuclear factor-E2-related factor 2; protein carbonyl
AB Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 mu mol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 mu mol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 mu mol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration.
C1 [Liu, Jiankang] Univ Calif Irvine, Inst Brain Aging & Dementia, Gillespie Neurosci Res Facil 1261, Irvine, CA 92697 USA.
   [Liu, Zhongbo; Sun, Lijuan; Zhu, Lu; Jia, Xu; Li, Xuesen; Jia, Haiqun] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
   [Liu, Zhongbo; Zhu, Lu; Li, Xuesen; Jia, Haiqun] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China.
   [Wang, Ying; Weber, Peter] R&D Human Nutr & Hlth, DSM Nutr Prod, Basel, Switzerland.
C3 University of California System; University of California Irvine;
   Chinese Academy of Sciences; Shanghai Institutes for Biological
   Sciences, CAS; Chinese Academy of Sciences; University of Chinese
   Academy of Sciences, CAS; DSM NV
RP Liu, JK (通讯作者)，Univ Calif Irvine, Inst Brain Aging & Dementia, Gillespie Neurosci Res Facil 1261, Irvine, CA 92697 USA.
EM j.liu@uci.edu
RI Jia, Haiqun/B-1305-2012; Zhu, Lu/N-1073-2017; Liu, Jiankang/A-1610-2011;
   Long, Jiangang/A-7835-2015; Liu, Zhongbo/U-3004-2017
OI Jia, Haiqun/0000-0003-1606-4861; Zhu, Lu/0000-0003-2716-4649; Long,
   Jiangang/0000-0002-6584-3880; Jiangang, Long/0000-0001-8074-957X
FU National Eye Institute, NIH [EY0160101]; Macular Degeneration Research
   [2005038]; Chinese Academy of Sciences [05PG14104]; DSM Nutritional
   Products Ltd; NATIONAL EYE INSTITUTE [R21EY016101] Funding Source: NIH
   RePORTER
FX We thank Zhihui Min and Chun Feng for the excellent technical assistance
   for flow cytometry and laser confocal microscope assays. This study was
   supported by National Eye Institute, NIH grant EY0160101, Macular
   Degeneration Research (MDR Grant 2005038), Chinese Academy of Sciences
   grant 05PG14104, and DSM Nutritional Products Ltd.
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NR 50
TC 70
Z9 86
U1 1
U2 16
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 DEC
PY 2007
VL 103
IS 6
BP 2690
EP 2700
DI 10.1111/j.1471-4159.2007.04954.x
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA V04MN
UT WOS:000207062600014
PM 20938484
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Winter, JO
   Cogan, SF
   Rizzo, JF
AF Winter, Jessica O.
   Cogan, Stuart F.
   Rizzo, Joseph F., III
TI Retinal prostheses: current challenges and future outlook
SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
LA English
DT Review
DE visual prosthesis; retina; biocompatibility; electrode
ID SUBRETINAL ELECTRICAL-STIMULATION; SEMICONDUCTOR-BASED PHOTODIODES;
   CHARGE INJECTION LIMITS; HIGH STIMULUS RATES; VISUAL-PERCEPTION;
   OPTIC-NERVE; AUDITORY-NERVE; MICROELECTRODE ARRAY; RETINITIS-PIGMENTOSA;
   PERFORATED MEMBRANE
AB Blindness from retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), usually causes a significant decline in quality of life for affected patients. Currently there is no cure for these conditions. However, over the last decade, several groups have been developing retinal prostheses which hopefully will provide some degree of improved visual function to these patients. Several such devices are now in clinical trials. Unfortunately, the possibility of electrode or tissue damage limits excitation schemes to those that may be employed with electrodes that have relatively low charge densities. Further, the excitation thresholds that have been required to achieve vision to date, in general, are relatively high. This may result in part from poor apposition between neurons and the stimulating electrodes and is confounded by the effects of the photoreceptor loss, which initiates other pathology in the surviving retinal tissue. The combination of these and other factors imposes a restriction on the pixel density that can be used for devices that actively deliver electrical stimulation to the retina. The resultant use of devices with relatively low pixel densities presumably will limit the degree of visual resolution that can be obtained with these devices. Further increases in pixel density, and therefore increased visual acuity, will necessitate either improved electrode-tissue biocompatibility or lower stimulation thresholds. To meet this challenge, innovations in materials and devices have been proposed. Here, we review the types of retinal prostheses investigated, the extent of their current biocompatibility and future improvements designed to surmount these limitations.
C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA.
   Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
   Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA.
   EIC Labs, Norwood, MA 02062 USA.
   Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
C3 University System of Ohio; Ohio State University; University System of
   Ohio; Ohio State University; Harvard University; Harvard Medical School;
   Harvard University; Massachusetts Eye & Ear Infirmary
RP Winter, JO (通讯作者)，VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA.
EM winter.63@osu.edu
RI Winter, Jessica O./AAO-5773-2020
OI Winter, Jessica O./0000-0002-5370-0137
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NR 138
TC 81
Z9 93
U1 1
U2 34
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0920-5063
EI 1568-5624
J9 J BIOMAT SCI-POLYM E
JI J. Biomater. Sci.-Polym. Ed.
PD AUG
PY 2007
VL 18
IS 8
BP 1031
EP 1055
DI 10.1163/156856207781494403
PG 25
WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer
   Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science; Polymer Science
GA 203WS
UT WOS:000249005300007
PM 17705997
DA 2022-11-30
ER

PT J
AU Kadomoto, S
   Nanegrungsunk, O
   Nittala, MG
   Karamat, A
   Sadda, SR
AF Kadomoto, Shin
   Nanegrungsunk, Onisa
   Nittala, Muneeswar Gupta
   Karamat, Ayesha
   Sadda, SriniVas R.
TI Enhanced Detection of Reticular Pseudodrusen on Color Fundus Photos by
   Image Embossing
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; reticular pseudodrusen; image
   processing; embossing
ID MACULAR DEGENERATION; SENSITIVITY; DRUSEN; SPECIFICITY; EYES
AB Purpose To evaluate whether processing a color fundus photo (CFP) using an image embossing technique can improve the detection of reticular pseudodrusen (RPD). Methods This post-hoc analysis included the eyes of subjects enrolled in the Amish Eye Study with early or intermediate age-related macular degeneration and evidence of RPD. All patients underwent CFP, near-infrared reflectance (NIR), and fundus autofluorescence (FAF) imaging. The ground-truth presence of RPD was established with a combination of NIR and FAF imaging. An embossing processed (EP) image was created by replacing each pixel of the CFP image with a highlight or a shadow representing light and dark boundaries in the original CFP image. The presence of RPD in CFP and EP images was assessed by two graders in a masked fashion and the sensitivity of CFP and EP for detection of RPD was evaluated. Cohen's kappa (k) was used to test inter-grader agreement for CFP and EP. Results A total of 106 eyes from 62 patients with RPDs were analyzed. The sensitivity for detection of RPD on CFP and EP was 63.2% (95%CI: 52.0%-74.4%) and 91.5% (95%CI: 85.0%-98.0%), respectively. The inter-rater reliabilities of CFP and EP for RPD detection were 0.81 and 0.84, respectively. Conclusions Embossing of CFP can improve the sensitivity for detection of RPD. The embossing technique can be a useful tool for better assessment of the true frequency of RPD in datasets where only CFP images are available.
C1 [Kadomoto, Shin; Nanegrungsunk, Onisa; Nittala, Muneeswar Gupta; Karamat, Ayesha; Sadda, SriniVas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 150 N Orange Grove Blvd,Suite 232, Los Angeles, CA 91103 USA.
   [Kadomoto, Shin; Nanegrungsunk, Onisa; Nittala, Muneeswar Gupta; Karamat, Ayesha; Sadda, SriniVas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 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
RP Sadda, SR (通讯作者)，Doheny Eye Inst, Doheny Image Reading Ctr, 150 N Orange Grove Blvd,Suite 232, Los Angeles, CA 91103 USA.
EM ssadda@doheny.org
FU National Eye Institute of the National Institute of Health [R01EY023164,
   R01EY030614]
FX This study was supported by National Eye Institute of the National
   Institute of Health under Award Number R01EY023164 and R01EY030614. The
   content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Institutes of
   health. 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 22
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD NOV 2
PY 2022
VL 47
IS 11
BP 1547
EP 1552
DI 10.1080/02713683.2022.2126860
EA SEP 2022
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5H1JD
UT WOS:000863414800001
PM 36183241
DA 2022-11-30
ER

PT J
AU Ren, CD
   Hu, CY
   Wu, Y
   Li, TT
   Zou, AQ
   Yu, DH
   Shen, TY
   Cai, WT
   Yu, J
AF Ren, Chengda
   Hu, Chengyu
   Wu, Yan
   Li, Tingting
   Zou, Aiqi
   Yu, Donghui
   Shen, Tianyi
   Cai, Wenting
   Yu, Jing
TI Nicotinamide Mononucleotide Ameliorates Cellular Senescence and
   Inflammation Caused by Sodium Iodate in RPE
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID OXIDATIVE STRESS; NAD(+); DEGENERATION; EXPRESSION; SRT1720; SIR2
AB Senescent cells have been demonstrated to have lower cellular NAD(+) levels and are involved in the development of various age-related diseases, including age-related macular degeneration (AMD). Sodium iodate (NaIO3) has been primarily used as an oxidant to establish a model of dry AMD. Results of previous studies have showed that NaIO3 induced retinal tissue senescence in vivo. However, the role of NaIO3 and the mechanism by which it induces retinal pigment epithelium (RPE) senescence remains unknown. In this study, RPE cell senescence was confirmed to be potentially induced by NaIO3. The results showed that the number of senescence-associated-beta-galactosidase (SA-beta-gal-)-positive cells and the protein levels of p16 and p21 increased after NaIO3 treatment. Additionally, the senescent RPE cells underwent oxidative stress and NAD(+) depletion. Furthermore, significant DNA damage and mitochondrial dysfunction were also detected in senescent RPE cells. The antioxidant N-acetylcysteine (NAC) could alleviate cellular senescence only by a minimal degree, whereas supplementation with nicotinamide mononucleotide (NMN) strongly ameliorated RPE senescence through the alleviation of DNA damage and the maintenance of mitochondrial function. The protective effects of NMN were demonstrated to rely on undisturbed Sirt1 signaling. Moreover, both the expression of senescence markers of RPE and subretinal inflammatory cell infiltration were decreased by NMN treatment in vivo. Our results indicate that RPE senescence induced by NaIO3 acquired several key features of AMD. More importantly, NMN may potentially be used to treat RPE senescence and senescence-associated pre-AMD changes by restoring the NAD(+) levels in cells and tissues.
C1 [Ren, Chengda; Hu, Chengyu; Wu, Yan; Li, Tingting; Zou, Aiqi; Yu, Donghui; Shen, Tianyi; Cai, Wenting; Yu, Jing] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.
C3 Tongji University
RP Yu, J (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.
EM schaish@tongji.edu.cn; 2111840@tongji.edu.cn; txwuyan@163.com;
   ltt_sylvia@163.com; andyzouaq@163.com; dhyu@tongji.edu.cn;
   1831263@tongji.edu.cn; caiwentingtj@163.com; dryujing@aliyun.com
RI Yu, Donghui/HCH-5897-2022
OI Yu, Donghui/0000-0001-5360-6186
FU NSFC [82101130]; Fundamental Research Funds for the Central Universities
   [22120180509]
FX AcknowledgmentsThis work was supported by NSFC (82000903) and NSFC
   (82101130) and Fundamental Research Funds for the Central Universities
   (22120180509).
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NR 43
TC 0
Z9 0
U1 4
U2 4
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD JUL 18
PY 2022
VL 2022
AR 5961123
DI 10.1155/2022/5961123
PG 23
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 3L9MA
UT WOS:000835083200002
PM 35898618
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Pujari, A
   Saluja, G
   Chawla, R
   Samdani, A
   Phuljhele, S
   Saxena, R
AF Pujari, Amar
   Saluja, Gunjan
   Chawla, Rohan
   Samdani, Asha
   Phuljhele, Swati
   Saxena, Rohit
TI Optical coherence tomography angiography in amblyopia: A critical update
   on current understandings and future perspectives
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE Optical coherence tomography angiography; amblyopia; OCTA and amblyopia
ID CHILDREN; DENSITY; EYES
AB Optical coherence tomography angiography (OCTA) is a non-invasive tool to assess the retino-choroidal vasculature in vivo. It tracks the red blood cell movement and maps the vasculature in quick succession. In routine, diabetic retinopathy, age related macular degeneration, central serous chorioretinopathy, and others are commonly being studied to unveil its clinic role. On the other hand, amblyopia is a condition where the visual acuity is subnormal due to non-organic causes in the eye. But the OCTA studies till now have shown variable changes along retino-choroidal vasculature. Hence, to comprehend the existing literature knowledge, a systematic literature search was carried out and the original works describing novel findings in amblyopic eyes on OCTA were included. Upon detailed assessment, firstly, the disturbed vasculature along superficial retinal plexus, deeper retinal plexus, and choroidal plexus were evident in most untreated amblyopic eyes. However, such changes were not uniform, which is due to noted heterogenic patient profile, small sample size, biometric biases, non-uniform algorithms, and other factors. And to note, even in presence of such diverse changes, almost all the authors stated a plausible explanation for their notable changes. Secondly, the utility of OCTA in identifying vascular changes with standard treatments and segregation of visual beneficiaries from non-beneficiaries were possible. Hence, to conclude, OCTA is a valuable tool which can provide valuable useful insights into the amblyopic eyes during pre and post treatment periods. However, to gather more concrete evidence for clinical benefits, systematic, homogenous, and better structured clinical studies are mandated.
C1 [Pujari, Amar; Saluja, Gunjan; Chawla, Rohan; Samdani, Asha; Phuljhele, Swati; Saxena, Rohit] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Room 212,RPC-1, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences
RP Pujari, A (通讯作者)，All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Room 212,RPC-1, New Delhi 110029, India.
EM dramarpujari@gmail.com
OI Chawla, Rohan/0000-0002-6791-4435
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NR 29
TC 0
Z9 0
U1 2
U2 5
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 MAY
PY 2022
VL 32
IS 3
BP 1324
EP 1332
AR 11206721211042554
DI 10.1177/11206721211042554
EA SEP 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1G7SZ
UT WOS:000691978200001
PM 34472984
DA 2022-11-30
ER

PT J
AU Kim, J
   Kim, JH
   Do, JY
   Lee, JY
   Yanai, R
   Lee, IK
   Suk, K
   Park, DH
AF Kim, Juhee
   Kim, Jong-Heon
   Do, Ji Yeon
   Lee, Jung Yi
   Yanai, Ryoji
   Lee, In-kyu
   Suk, Kyoungho
   Park, Dong Ho
TI Key Role of Microglial Matrix Metalloproteinases in Choroidal
   Neovascularization
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE age-related macular degeneration (AMD); choroidal neovascluarization;
   matrix metalloproteinase; microglia; aqueous humor
ID MACULAR DEGENERATION; RETINAL MICROGLIA; MINOCYCLINE; ACTIVATION; MOUSE;
   MATRIX-METALLOPROTEINASE-9; INFLAMMATION; CONTRIBUTES; METABOLITES;
   EXPRESSION
AB Age-related macular degeneration (AMD), especially neovascular AMD with choroidal neovascularization (CNV), is the leading cause of blindness in the elderly. Although matrix metalloproteinases (MMPs) are involved in pathological ocular angiogenesis, including CNV, the cellular origin of MMPs in AMD remains unknown. The present study investigated the role of microglial MMPs in CNV. MMP activities were analyzed by gelatin zymography in aqueous humor samples from patients with CNV and laser-induced CNV mice. Active MMP-9 was increased in the aqueous humor samples from neovascular AMD patients compared with control subjects. In the retinal pigment epithelium (RPE)/choroid from CNV mice, active MMP-9 increased, beginning 1 h post-CNV induction, and remained upregulated until Day 7. In RPE/choroid from CNV mice, active MMP-9 was suppressed by minocycline, a known microglial inhibitor, at 6 h and 1-day post-CNV induction. Flow cytometry revealed that the proportion of activated microglia increased very early, beginning at 1 h post-CNV induction, and was maintained until Day 7. Similarly, immunohistochemistry revealed increased microglial activation and MMP-9 expression on CNV lesions at 6 h and 1-day post-CNV induction. SB-3CT, an MMP inhibitor, decreased vascular leakage and lesion size in laser-induced CNV mice. These findings indicated nearly immediate recruitment of activated microglia and very early MMP-9 activation in the RPE/choroid. The present study newly identified a potential role for early microglial MMP-9 expression in CNV, and furthermore that modulating microglial MMP expression is a novel putative therapeutic for CNV.
C1 [Kim, Juhee; Do, Ji Yeon; Lee, Jung Yi; Lee, In-kyu; Park, Dong Ho] Kyungpook Natl Univ Hosp, Leading Edge Res Ctr Drug Discovery & Dev Diabet, Daegu, South Korea.
   [Kim, Jong-Heon; Suk, Kyoungho] Kyungpook Natl Univ, Brain Sci & Engn Inst, Daegu, South Korea.
   [Lee, Jung Yi] JD Bioscience Inc, R&D Ctr, Gwangju, South Korea.
   [Yanai, Ryoji] Yamaguchi Univ, Dept Ophthalmol, Grad Sch Med, Ube, Yamaguchi, Japan.
   [Lee, In-kyu] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu, South Korea.
   [Lee, In-kyu; Park, Dong Ho] Kyungpook Natl Univ, Res Inst Aging & Metab, Daegu, South Korea.
   [Suk, Kyoungho] Kyungpook Natl Univ, Sch Med, Dept Pharmacol, Daegu, South Korea.
   [Park, Dong Ho] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Ophthalmol, Daegu, South Korea.
C3 Kyungpook National University; Kyungpook National University Hospital;
   Kyungpook National University; Yamaguchi University; Kyungpook National
   University; Kyungpook National University Hospital; Kyungpook National
   University; Kyungpook National University; Kyungpook National
   University; Kyungpook National University Hospital
RP Park, DH (通讯作者)，Kyungpook Natl Univ Hosp, Leading Edge Res Ctr Drug Discovery & Dev Diabet, Daegu, South Korea.; Park, DH (通讯作者)，Kyungpook Natl Univ, Res Inst Aging & Metab, Daegu, South Korea.; Park, DH (通讯作者)，Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Ophthalmol, Daegu, South Korea.
EM dongho_park@knu.ac.kr
RI Lee, In-Kyu/AAR-6374-2021
FU Basic Science Research Program of the National Research Foundation of
   Korea (NRF) - Korean government (Ministry of Science and ICT)
   [2019R1A2C1084371]; Korea Health Technology R&D Project of the Korea
   Health Industry Development Institute (KHIDI) - Ministry of Health and
   Welfare, Republic of Korea [HI16C1501]; MSIT (Ministry of Science and
   ICT), Korea, under the ITRC (Information Technology Research Center)
   support program [IITP-2021-2020-0-01808]
FX DP was financially supported by the Basic Science Research Program of
   the National Research Foundation of Korea (NRF), funded by the Korean
   government (Ministry of Science and ICT; 2019R1A2C1084371) and the Korea
   Health Technology R&D Project of the Korea Health Industry Development
   Institute (KHIDI), funded by the Ministry of Health and Welfare,
   Republic of Korea (HI16C1501). DP was also supported by the MSIT
   (Ministry of Science and ICT), Korea, under the ITRC (Information
   Technology Research Center) support program (IITP-2021-2020-0-01808)
   supervised by the IITP (Institute of Information & Communications
   Technology Planning & Evaluation).
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NR 44
TC 2
Z9 2
U1 3
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD FEB 26
PY 2021
VL 15
AR 638098
DI 10.3389/fncel.2021.638098
PG 10
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA QV1XH
UT WOS:000627770600001
PM 33716674
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gliem, M
   Wieg, I
   Birtel, J
   Muller, PL
   Faust, I
   Hendig, D
   Holz, FG
   Finger, RP
   Issa, PC
AF Gliem, Martin
   Wieg, Isabel
   Birtel, Johannes
   Mueller, Philipp L.
   Faust, Isabel
   Hendig, Doris
   Holz, Frank G.
   Finger, Robert P.
   Issa, Peter Charbel
TI Retinal findings in carriers of monoallelic ABCC6 mutations
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE retina
ID PSEUDOXANTHOMA ELASTICUM; PHENOTYPIC CHARACTERISTICS; GENE; R1141X;
   MINERALIZATION; CALCIFICATION; INHIBITOR; DYSTROPHY; MEMBRANE; SPECTRUM
AB Aim
   Biallelic ABCC6 mutations cause pseudoxanthoma elasticum, a systemic disease characterised by calcification of elastic tissue and a specific retinal phenotype. In this study, we investigated if monoallelic ABCC6 mutations are also associated with retinal alterations.
   Methods
   In this prospective, cross-sectional, monocentre case-control study, carriers of monoallelic ABCC6 mutations were investigated and compared with age-matched controls. The retinal phenotype was characterised using fundus photography, fundus autofluorescence, confocal near-infrared reflectance imaging, spectral domain optical coherence tomography and in selected cases late-phase indocyanine green angiography.
   Results
   Thirty-eight subjects carrying monoallelic ABCC6 mutations (mean age 70.2 years, range 50-90, 26 female) were examined and compared with 77 age-matched controls (mean age 69.9 years, range 50-93, 43 female). Retinal alterations were more frequently found in carriers of monoallelic ABCC6 mutations compared with controls (50% vs 33.8%, p=0.107) with increasing prevalence at older age. Typical findings were peripapillary atrophy (37% vs 23%, p=0.184), pattern dystrophy-like changes (24% vs 12%, p=0.109), reticular pseudodrusen (21% vs 5%, p=0.019), small angioid streaks (8% vs 1%, p=0.105), choroidal neovascularisations and atrophic lesions (both 8% vs 0%, p=0.034). Late-phase indocyanine green angiography showed a reduced cyanescence centred to the posterior pole in 11 of 14 examined subjects with monoallelic ABCC6 mutations.
   Conclusion
   The findings of this study indicate a possible ocular ABCC6 haploinsufficiency phenotype. Due to its late-onset and phenotypic similarities, misinterpretation as age-related macular degeneration is possible.
C1 [Gliem, Martin; Wieg, Isabel; Birtel, Johannes; Mueller, Philipp L.; Holz, Frank G.; Finger, Robert P.; Issa, Peter Charbel] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Gliem, Martin; Birtel, Johannes; Mueller, Philipp L.; Holz, Frank G.; Issa, Peter Charbel] Univ Bonn, Ctr Rare Dis Bonn ZSEB, Bonn, Germany.
   [Gliem, Martin; Issa, Peter Charbel] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England.
   [Gliem, Martin; Issa, Peter Charbel] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England.
   [Faust, Isabel; Hendig, Doris] Ruhr Univ Bochum, Heart & Diabet Ctr North Rhine Westphalia, Inst Lab & Transfus Med, Univ Hosp, Bad Oeynhausen, Germany.
C3 University of Bonn; University of Bonn; Oxford University Hospitals NHS
   Foundation Trust; University of Oxford; Ruhr University Bochum
RP Issa, PC (通讯作者)，Oxford Eye Hosp, Oxford, England.
EM study-enquiry@outlook.com
RI Müller, Philipp L./P-3350-2019; Issa, Peter Charbel/O-2580-2019
OI Issa, Peter Charbel/0000-0002-0351-6673
FU ProRetina, Aachen, Germany; German Research Foundation [GL920/1-1];
   National Institute for Health Research (NIHR) Oxford Biomedical Research
   Centre (BRC), Oxford, UK
FX This work was supported by the ProRetina, Aachen, Germany; the German
   Research Foundation (MG, grant #GL920/1-1); and the National Institute
   for Health Research (NIHR) Oxford Biomedical Research Centre (BRC),
   Oxford, UK.
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NR 26
TC 4
Z9 4
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2020
VL 104
IS 8
BP 1089
EP 1092
DI 10.1136/bjophthalmol-2018-313448
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PK2OA
UT WOS:000602289600011
PM 30923132
DA 2022-11-30
ER

PT J
AU Augustin, M
   Harper, DJ
   Merkle, CW
   Glosmann, M
   Hitzenberger, CK
   Baumann, B
AF Augustin, Marco
   Harper, Danielle J.
   Merkle, Conrad W.
   Gloesmann, Martin
   Hitzenberger, Christoph K.
   Baumann, Bernhard
TI Optical Coherence Tomography Findings in the Retinas of SOD1 Knockout
   Mice
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE retinal pigment epithelium; imaging/image analysis; nonclinical; OCT/OCT
   angiography
ID SUPEROXIDE-DISMUTASE 1; GANGLION-CELL LOSS; MACULAR DEGENERATION;
   OXIDATIVE STRESS; AXIAL RESOLUTION; DRUSEN; OCT; NEOVASCULARIZATION;
   ACCUMULATION; DYSFUNCTION
AB Purpose: The retinal phenotype of popular mouse models mimicking ophthalmic diseases, such as the superoxide dismutase 1 (SOD1) knockout (KO) mouse model, has mainly been assessed by ex vivo histology and in vivo fundus photography. We used multifunctional optical coherence tomography (OCT) to characterize the retinas of SOD1 KO mice in vivo.
   Methods: The custom-made ophthalmoscope featured a combination of conventional OCT, polarization-sensitive OCT, and OCT angiography. Seven SOD1 KO mice and nine age-matched controls were imaged between 6 and 17 months of age. A postprocessing framework was used to analyze total and outer retinal thickness changes. Drusen-like lesions were segmented, and their sizes and the number of lesions were assessed quantitatively. Their appearance in the conventional reflectivity images, as well as in the corresponding polarization-sensitive images, was characterized qualitatively.
   Results: Drusenlike lesions increased in size and number with age for SOD1 KO mice. Exploiting the multiple contrast channels, the appearance of the lesions was found to resemble pseudodrusen observed in eyes of patients suffering from dry age-related macular degeneration. The total and outer retinal thicknesses were lower on average after 11 months and 7 months in SOD1 KO mice compared with age-matched controls. Neovascularizations were found in one out of seven KO animals.
   Conclusions: OCT imaging proved beneficial for a detailed in vivo characterization of the pathological changes in SOD1 KO mice.
   Translational Relevance: Phenotyping of animal models using modern imaging concepts can be conducted with more precision and might also ease the translation of conclusions between clinical and preclinical research.
C1 [Augustin, Marco; Harper, Danielle J.; Merkle, Conrad W.; Hitzenberger, Christoph K.; Baumann, Bernhard] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Waehringer Guertel 18-20,4L 1090, Vienna, Austria.
   [Gloesmann, Martin] Univ Vet Med Vienna, Imaging Unit, VetCore Facil Res, Vienna, Austria.
C3 Medical University of Vienna; University of Veterinary Medicine Vienna
RP Augustin, M (通讯作者)，Med Univ Vienna, Ctr Med Phys & Biomed Engn, Waehringer Guertel 18-20,4L 1090, Vienna, Austria.
EM marco.augustin@meduniwien.ac.at
RI Glösmann, Martin/F-9349-2019
OI Glösmann, Martin/0000-0002-2094-3247; Merkle,
   Conrad/0000-0002-2465-4100; Harper, Danielle J./0000-0003-2768-3684
FU Austrian Science Fund (FWF) [P25823-B24]; European Research Council [ERC
   StG 640396 OPTIMALZ]
FX Supported by the Austrian Science Fund (FWF Grant P25823-B24) and the
   European Research Council (ERC StG 640396 OPTIMALZ).
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NR 43
TC 2
Z9 2
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAR
PY 2020
VL 9
IS 4
AR 15
DI 10.1167/tvst.9.4.15
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LB9VX
UT WOS:000524980600015
PM 32818102
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Cho, HY
   Park, HS
   Ko, EJ
   Ryu, CS
   Kim, JO
   Kim, YR
   Ahn, EH
   Lee, WS
   Kim, NK
AF Cho, Hee Young
   Park, Han Sung
   Ko, Eun Ju
   Ryu, Chang Soo
   Kim, Jung Oh
   Kim, Young Ran
   Ahn, Eun Hee
   Lee, Woo Sik
   Kim, Nam Keun
TI Association of Complement Factor D and H Polymorphisms with Recurrent
   Pregnancy Loss
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE complement factor D; complement factor H; recurrent pregnancy loss;
   polymorphism
ID MACULAR DEGENERATION; Y402H POLYMORPHISM; BINDING; DEFICIENCY
AB Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation, and the incidence of RPL is estimated at 1% of all pregnancies. While the etiologies of RPL are diverse, immune function is considered to be an important cause of RPL. In particular, the complement system is essential for stable development of the placenta and fetus. Moreover, complement factor D (CFD) and complement factor H (CFH) are important regulators of the complement system and are associated with diseases, such as age-related macular degeneration. Therefore, we investigated whether polymorphisms of CFD and CFH are associated with RPL in 412 women with RPL and 384 control women. Genotyping of three polymorphisms (CFD rs2230216, CFH rs1065489, and CFH rs1061170) was performed by TaqMan probe real-time PCR and PCR-restriction fragment length polymorphism. Association of three polymorphisms with RPL was evaluated by statistical analysis. The GT/TC genotype combination of CFH rs1065489 G>T/CFH rs1061170 T>C was associated with a decreased risk of RPL occurrence compared with reference genotypes (adjusted odds ratio [AOR] = 0.439; 95% confidence interval [CI] = 0.238-0.810; p = 0.008), and this association remained significant after adjustment for multiple comparisons using false discovery rate (FDR) correction (p = 0.040). In addition, the CFH rs1065489G>T polymorphism is associated with homocysteine and prolactin level and CFH rs1061170 TC genotype is related to uric acid and triglycerides level in RPL patients. Therefore, those factors could be possible clinical risk factors in RPL patients.
C1 [Cho, Hee Young; Kim, Young Ran; Ahn, Eun Hee] CHA Univ, CHA Bundang Med Ctr, Dept Obstet & Gynecol, Seongnam 13496, South Korea.
   [Park, Han Sung; Ko, Eun Ju; Ryu, Chang Soo; Kim, Jung Oh; Kim, Nam Keun] CHA Univ, Coll Life Sci, Dept Biomed Sci, Seongnam 13496, South Korea.
   [Lee, Woo Sik] CHA Univ, CHA Gangnam Med Ctr, Fertil Ctr, Seoul 06125, South Korea.
C3 Pochon Cha University; Pochon Cha University; Pochon Cha University
RP Kim, NK (通讯作者)，CHA Univ, Coll Life Sci, Dept Biomed Sci, Seongnam 13496, South Korea.; Lee, WS (通讯作者)，CHA Univ, CHA Gangnam Med Ctr, Fertil Ctr, Seoul 06125, South Korea.
EM hycho.md@gmail.com; hahnsung@naver.com; ejko05@naver.com;
   regis2040@nate.com; jokim8505@gmail.com; happyiran@cha.ac.kr;
   bestob@chamc.co.kr; wooslee@cha.ac.kr; nkkim@cha.ac.kr
OI Cho, Hee Young/0000-0001-7064-5056; Kim, Jung Oh/0000-0002-4171-2034;
   Kim, Nam Keun/0000-0003-0541-3528
FU National Research Foundation of Korea (NRF) - Korean government (MSIT)
   [2017R1D1A1B03031542, 2018R1D1A1B07044096, 2018R1D1A1A09082764]; Korea
   Health Technology R&D Project through the Korea Health Industry
   Development Institute (KHIDI) - Ministry of Health andWelfare, Republic
   of Korea [HI18C19990200]
FX This research was supported by the National Research Foundation of Korea
   (NRF) grants funded by the Korean government (MSIT; grant numbers
   2017R1D1A1B03031542, 2018R1D1A1B07044096, and 2018R1D1A1A09082764). The
   research was also supported by a grant from the Korea Health Technology
   R&D Project through the Korea Health Industry Development Institute
   (KHIDI) and funded by the Ministry of Health andWelfare, Republic of
   Korea. (grant number HI18C19990200).
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NR 30
TC 6
Z9 6
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 JAN 1
PY 2020
VL 21
IS 1
AR 17
DI 10.3390/ijms21010017
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KO2KF
UT WOS:000515378000017
PM 31861421
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chai, F
   Zeng, L
   Li, CH
   Zhao, XQ
AF Chai, Fang
   Zeng, Lu
   Li, Chunhua
   Zhao, Xiquan
TI Spontaneous suprachoroidal hemorrhage in a high myopia patient with
   rhegmatogenous retinal detachment: a case report and literature review
SO BIOSCIENCE REPORTS
LA English
DT Review
ID PARS-PLANA VITRECTOMY; ANGLE-CLOSURE GLAUCOMA; MACULAR DEGENERATION;
   RISK-FACTORS; CHOROIDAL HEMORRHAGE; SECONDARY; MANAGEMENT; OUTCOMES
AB Purpose: To report a rare case of spontaneous suprachoroidal hemorrhage (SSCH) in a high myopia patient with rhegmatogenous retinal detachment (RRD) and successful treatment.
   Methods: We present a case of SSCH that occurred in a 73 woman with high myopia with RRD and discuss the results of a systemic review of the literature published from 1999 to 2017.
   Results: Phacoemulsification without intraocular lens implantation and vitrectomy combined with silicone oil injection was performed and retinal detachment and choroidal detachment were reattached after oil removed. In the literature review, we found that among a total of 36 patients (37 eyes), acute secondary glaucoma was a complication in 70.3% (26 eyes) of the cases, and over half of the cases (24 eyes, 64.9%) were treated with surgery. Eighteen cases (50%) were characterized by systemic hypertension and 21 cases (58.3%) had abnormal hemostasis. Age-related macular degeneration (ARMD) was the most common (12 eyes, 32.4%) ocular disease and was followed by glaucoma (7 cases, 18.9%). Visual acuity was classified as hand motion (HM) or worse in 25 eyes (out of 34 eyes, 73.5%) at initial presentation and in 25 eyes (out of 36 eyes, 69.4%) upon final examination. Nine cases experienced significant visual improvement, including six that underwent vitrectomy.
   Conclusion: Advanced age, systemic anticoagulation, and hypertension are strong risk factors. RRD associated with massive SSCH is an extremely rare event. Vitrectomy and choroidal blood drainage can effectively remove suprachoroidal hemorrhage (SCH) and promote retinal reattachment in these eyes. However, the final visual prognosis usually remains poor.
C1 [Chai, Fang; Zeng, Lu; Li, Chunhua; Zhao, Xiquan] Xi An Jiao Tong Univ, Sch Med, Affiliated Guangren Hosp, Shaanxi Ophthalm Med Ctr,Xian Hosp 4, Xian 710004, Shaanxi, Peoples R China.
C3 Xi'an Jiaotong University
RP Zhao, XQ (通讯作者)，Xi An Jiao Tong Univ, Sch Med, Affiliated Guangren Hosp, Shaanxi Ophthalm Med Ctr,Xian Hosp 4, Xian 710004, Shaanxi, Peoples R China.
EM zhaoxiquan1972@163.com
FU Project of Science and Technology of Social Development Funding
   [2016SF-100]; Bureau-level scientific reasearch projects [J201901013];
   Xi'an No. 4 Hospital Research Incubation Fund [2018LH-2]
FX This work was supported by the Project of Science and Technology of
   Social Development Funding [grant number 2016SF-100]; Bureau-level
   scientific reasearch projects [grant number J201901013]; and the Xi'an
   No. 4 Hospital Research Incubation Fund [grant number 2018LH-2].
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NR 42
TC 5
Z9 5
U1 0
U2 2
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.
PD JUN 25
PY 2019
VL 39
AR BSR20181454
DI 10.1042/BSR20181454
PN 6
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA IN7LD
UT WOS:000478862900001
PM 31160485
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Dodo, BI
   Li, YM
   Kaba, D
   Liu, XH
AF Dodo, Bashir Isa
   Li, Yongmin
   Kaba, Djibril
   Liu, Xiaohui
TI Retinal Layer Segmentation in Optical Coherence Tomography Images
SO IEEE ACCESS
LA English
DT Article
DE Image segmentation; Retina; Diseases; Blindness; Speckle; Image edge
   detection; Optical coherence tomography; Medical image analysis; optical
   coherence tomography; fuzzy image processing; graph-cut; continuous
   max-flow
ID AUTOMATIC SEGMENTATION; ENERGY MINIMIZATION; SPECKLE REDUCTION; GRAPH
   CUTS; OCT IMAGES; BOUNDARIES
AB The four major causes of blindness are age-related diseases, out of which three affects the retina. These diseases, i.e., glaucoma, diabetic retinopathy, and age-related macular degeneration, require life-long treatment and cause irreversible blindness. Conversely, early diagnosis has been shown to curtail or prevent blindness and visual impairments. A critical element of the clinical diagnosis is the analysis of individual retinal layer properties, as the manifestation of the dominant eye diseases has been shown to correlate with structural changes to the retinal layers. Regrettably, manual segmentation is dependent on the ophthalmologists level of expertise, and currently becoming impractical due to advancement in imaging modalities. Inherently, much research on computer-aided diagnostic methods is conducted to aid in extracting useful layer information from these images, which were inaccessible without these techniques. However, speckle noise and intensity inhomogeneity remain a challenge with a detrimental effect on the performance of automated methods. In this paper, we propose a method comprising of fuzzy image processing techniques and graph-cut methods to robustly segment optical coherence tomography (OCT) into five (5) distinct layers. Notably, the method establishes a specific region of interest to suppress the interference of speckle noise, while Fuzzy C-means is utilized to build data terms for better integration into the continuous max-flow to handle inhomogeneity. The method is evaluated on 225 OCT B-scan images, and promising experimental results were achieved. The method will allow for early diagnosis of major eye diseases by providing the basic, yet critical layer information necessary for an effective eye examination.
C1 [Dodo, Bashir Isa; Li, Yongmin; Liu, Xiaohui] Brunel Univ London, Dept Comp Sci, Uxbridge UB8 3PH, Middx, England.
   [Kaba, Djibril] Connected Pl Catapult, Alan Turing Inst, London NW1 2DB, England.
C3 Brunel University
RP Dodo, BI (通讯作者)，Brunel Univ London, Dept Comp Sci, Uxbridge UB8 3PH, Middx, England.
EM bashir.dodo@brunel.ac.uk
RI Liu, Xiaohui/B-5046-2013; Dodo, Bashir Isa/AAI-7448-2020
OI Liu, Xiaohui/0000-0003-1589-1267; Dodo, Bashir Isa/0000-0001-5467-4324
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NR 49
TC 8
Z9 8
U1 0
U2 2
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 2019
VL 7
BP 152388
EP 152398
DI 10.1109/ACCESS.2019.2947761
PG 11
WC Computer Science, Information Systems; Engineering, Electrical &
   Electronic; Telecommunications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Telecommunications
GA JN8TB
UT WOS:000497163000162
OA Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Thompson, IA
   Liu, BY
   Sen, HN
   Jiao, XD
   Katamay, R
   Li, ZY
   Hu, MJ
   Hejtmancik, F
   Nussenblatt, RB
AF Thompson, Ian A.
   Liu, Baoying
   Sen, H. Nida
   Jiao, Xiadong
   Katamay, Robert
   Li, Zhiyu
   Hu, Mengjun
   Hejtmancik, Fielding
   Nussenblatt, Robert B.
TI Association of Complement Factor H Tyrosine 402 Histidine Genotype with
   Posterior Involvement in Sarcoid-Related Uveitis
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID 1ST INTERNATIONAL WORKSHOP; MACULAR DEGENERATION; MULTIFOCAL
   CHOROIDITIS; OCULAR SARCOIDOSIS; S-ANTIGEN; AGE; CFH; POLYMORPHISM;
   GENE; DEFICIENCY
AB PURPOSE: To determine whether the complement factor H (CFH) tyrosine 402 histidine (Y402H) variant, recently shown to be associated with age-related macular degeneration (AMD) and multifocal choroiditis, is associated with specific ocular sarcoidosis clinical phenotypes in black and white persons.
   DESIGN: Case-control study.
   METHODS: The CFH Y402H polymorphism (rs1061170) was genotyped in 41 subjects with ocular sarcoidosis and 393 control subjects. Allele frequencies in the ocular sarcoidosis cases were compared with controls using chi-square score tests. Genotypic model-based (dominant, recessive, and additive) associations of the rs1061170 allele were tested using multivariate logistic regression. Bayesian information criteria were used to formalize model selection. Genotypes were correlated with disease characteristics and severity of ocular inflammation.
   RESULTS: The C allele (rs1061170) was found in 35% of controls, but occurred with a significantly higher frequency (48.7%) in ocular sarcoidosis cases (odds ratio, 1.72; 95% confidence interval, 1.09 to 2.78; P = .018). Logistic regression demonstrated an association between rs1061170 and ocular sarcoidosis in 2 of 3 genetic models (additive, P = .0078; recessive, P = .0018). Posterior uveitis and panuveitis were overrepresented significantly in cases with the homozygous variant genotype (CC, 91%; P = .047). The population-attributable risk related to this CFH risk variant was 20%.
   CONCLUSIONS: The Y402H polymorphism of CFH seems to be associated with ocular sarcoidosis in black and white persons. Carriage of the CFH Y402H polymorphism in both alleles is associated with an increased risk for posterior uveitis and panuveitis presentation. The prognostic importance of this genotype will require prolonged follow-up studies. Published by Elsevier Inc.
C1 [Thompson, Ian A.; Liu, Baoying; Sen, H. Nida; Katamay, Robert; Li, Zhiyu; Hu, Mengjun; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Jiao, Xiadong; Hejtmancik, Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI)
RP Nussenblatt, RB (通讯作者)，NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU National Eye Institute, National Institutes of Health, Bethesda,
   Maryland; NATIONAL EYE INSTITUTE [ZIEEY000482, ZIAEY000376, ZIAEY000356]
   Funding Source: NIH RePORTER
FX Publication of this article was supported by intramural funding from the
   National Eye Institute, National Institutes of Health, Bethesda,
   Maryland (R.B.N.). Involved in Design of study (I.A.T., B.L., H.N.S.,
   R.B.N.); Collection (I.A.T., B.L., H.N.S., X.J., R.K., Z.L., M.H., F.H.,
   R.B.N.) and analysis and interpretation (I.A.T., B.L., H.N.S., F.H.,
   R.B.N.) of data; and Preparation (I.A.T., B.L., H.N.S., R.B.N.), review
   (I.A.T., B.L., H.N.S., F.H., R.B.N.), and approval (I.A.T., B.L.,
   H.N.S., X.J., R.K., Z.L., M.H., F.H., R.B.N.) of manuscript. This study
   of patient data was approved by the Neuroscience Institutional Review
   Board of the National Institute of Health. The authors thank Ms Karen
   Weikel from the American Red Cross for her valuable service in the
   recruitment of subjects.
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NR 39
TC 21
Z9 21
U1 0
U2 7
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 JUN
PY 2013
VL 155
IS 6
BP 1068
EP 1074
DI 10.1016/j.ajo.2013.01.019
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 157JU
UT WOS:000319893200013
PM 23497844
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Handa, JT
AF Handa, James T.
TI How does the macula protect itself from oxidative stress?
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE Age-related macular degeneration; Innate immune response; Nrf2;
   Oxidative stress; Oxidation specific epitope; Retinal pigment epithelium
ID RETINAL-PIGMENT EPITHELIUM; COMPLEMENT FACTOR-H; AGE-RELATED
   MACULOPATHY; MITOCHONDRIAL-DNA DAMAGE; SMOKE-INDUCED EMPHYSEMA;
   GENE-EXPRESSION; BRUCHS MEMBRANE; VITAMIN-E; PHOTORECEPTOR DEGENERATION;
   ANTIOXIDANT SUPPLEMENTS
AB Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. (C) 2012 Elsevier Ltd. All rights reserved.
C1 Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，Johns Hopkins Sch Med, Wilmer Eye Inst, Smith Bldg,Room 3015,400 N Broadway, Baltimore, MD 21218 USA.
EM jthanda@jhmi.edu
FU NIH [EY14005, EY019904]; Edward N. and Della L. Thome Memorial
   Foundation; Beckmann Award in Age-related Macular Degeneration; Research
   to Prevent Blindness; NATIONAL EYE INSTITUTE [R01EY019904, R01EY014005]
   Funding Source: NIH RePORTER
FX This work was supported by NIH EY14005, EY019904, Edward N. and Della L.
   Thome Memorial Foundation Awards Program in AMD Research, Beckmann Award
   in Age-related Macular Degeneration, Senior Scientific Investigator
   Award from Research to Prevent Blindness, an unrestricted grant from
   Research to Prevent Blindness. Dr. Handa's lab has also received
   generous gifts from the Merlau family. Dr. Handa is the Robert Bond
   Welch Professor. I thank Katayoon Ebrahimi, MD, for supplying the
   photomicrographs.
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NR 175
TC 100
Z9 104
U1 3
U2 30
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0098-2997
EI 1872-9452
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 418
EP 435
DI 10.1016/j.mam.2012.03.006
PG 18
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 983WR
UT WOS:000307149900006
PM 22503691
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Fett, AL
   Hermann, MM
   Muether, PS
   Kirchhof, B
   Fauser, S
AF Fett, Anna L.
   Hermann, Manuel M.
   Muether, Philipp S.
   Kirchhof, Bernd
   Fauser, Sascha
TI Immunohistochemical localization of complement regulatory proteins in
   the human retina
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Article
DE Complement system; Age-related macular degeneration;
   Immunohistochemistry; Retina
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; SYSTEM; EYE; INFLAMMATION;
   GENES
AB Age-related macular degeneration (AMD) is a complex disease. Genetic studies have found strong associations between AMD and variants of several complement pathway-associated genes. The regulation of the complement cascade seems to be critical in the pathogenesis of AMD. In 45 human donor eyes immunohistochemistry was performed using antibodies directed against major regulators of the complement system: complement factor H (CFH), decay accelerating factor (DAF/CD55), complement receptor 1 (CR1/CD35), and membrane cofactor protein (MCP/CD46). All eyes were classified in AMD and controls. 11 eyes were graded as early AMD. 34 eyes were controls. In all eyes staining was found in intercapillary pillars of choroid adjacent to Bruch's membrane for CFH, at the basal surface of RPE cells for MCP, and at the apical side of the retinal pigment epithelium for CR1. DAF immunoreactivity was increased along the inner segments of rod and cone photoreceptor cells at the level of the external limiting membrane Labeling of soft drusen was found for CFH and CR1. In addition, DAF and CR1 showed staining of ganglion cells in all eyes. CFH and particularly MCP showed decreased or absent staining in eyes with early AMD adjacent to Bruch's membrane. The overlapping expression of regulators at the level of Bruch's membrane and the retinal pigment epithelium shows the importance of this site for control of the complement system. Decreased and therefore unbalanced expression of regulators, as shown in this study for CFH and MCP, may ultimately lead to AMD.
C1 [Fauser, Sascha] Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50924 Cologne, Germany.
C3 University of Cologne
RP Fauser, S (通讯作者)，Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Kerpener Str 62, D-50924 Cologne, Germany.
EM sfauser@gmx.net
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NR 23
TC 51
Z9 52
U1 0
U2 4
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
EI 1699-5848
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD MAR
PY 2012
VL 27
IS 3
BP 357
EP 364
PG 8
WC Cell Biology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Pathology
GA 879DE
UT WOS:000299309100011
PM 22237713
DA 2022-11-30
ER

PT J
AU Li, W
   Laird, JM
   Lu, L
   Roychowdhury, S
   Nagy, LE
   Zhou, R
   Crabb, JW
   Salomon, RG
AF Li, Wei
   Laird, James M.
   Lu, Liang
   Roychowdhury, Sanjoy
   Nagy, Laura E.
   Zhou, Rong
   Crabb, John W.
   Salomon, Robert G.
TI Isolevuglandins covalently modify phosphatidylethanolamines in vivo:
   Detection and quantitative analysis of hydroxylactam adducts
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Levuglandin; Isolevuglandin; Isoketal; Phosphatidylethanolamine;
   Oxidative stress; Biomarker; Free radical; Mass spectrometry; Protein
   adduct
ID LOW-DENSITY-LIPOPROTEIN; TANDEM MASS-SPECTROMETRY; GAMMA-KETOALDEHYDES
   ISOLEVUGLANDINS; PROTEIN ADDUCTS; MACULAR DEGENERATION; ISOPROSTANE
   PATHWAY; PROSTAGLANDIN ENDOPEROXIDES; OXIDIZED PHOSPHOLIPIDS;
   EICOSAPENTAENOIC ACID; HUMAN PLASMA
AB Levuglandins (LGs) and isolevuglandins (isoLGs, also called "isoketals" or "isoKs") are extraordinarily reactive products of cyclooxygenase- and free radical-induced oxidation of arachidonates. We now report the detection in vivo and quantitative analysis of LG/isoLG adducts that incorporate the amino group of phosphatidylethanolamines (PEs) into LG/isoLG-hydroxylactams. Notably, LC-MS/MS detection of these hydroxylactams is achieved with samples that are an order of magnitude smaller and sample processing is much simpler and less time consuming than required for measuring protein-derived LG/isoLG-lysyl lactams. A key feature of our protocol is treatment of biological phospholipid extracts with phospholipase A(2) to generate mainly 1-palmitoyl-2-lysoPE-hydroxylactams from heterogeneous mixtures of phospholipids with a variety of acyl groups on the 2 position. Over 160% higher mean levels of LG/isoLG-PE-hydroxylactam (P<0.001) were detected in liver from chronic ethanol-fed mice (32.4 +/- 6.3 ng/g, n = 6) compared to controls (12.1 +/- 1.5 ng/g, n = 4), and mean levels in plasma from patients with age-related macular degeneration (5.2 +/- 0.4 ng/ml, n = 15) were elevated similar to 53% (P<0.0001) compared to those of healthy volunteers (3.4 +/- 0.1 ng/ml, n = 15). just as LG/isoLG-protein adducts provide a dosimeter of oxidative injury, this study suggests that LG/isoLG-PE-hydroxylactams are potential biomarkers for assessing risk for oxidative stress-stimulated diseases. (C) 2009 Elsevier Inc. All rights reserved
C1 [Li, Wei; Laird, James M.; Lu, Liang; Zhou, Rong; Crabb, John W.; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Nagy, Laura E.] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA.
   [Crabb, John W.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
C3 Case Western Reserve University; Case Western Reserve University;
   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 LI, WEI/B-7946-2011; Salomon, Robert G/C-3463-2008
OI Salomon, Robert/0000-0001-9456-3557
FU NIH [AA013868, AA011975, GM021249, HL087018, EY014239]; State of Ohio
   [05-29]; NATIONAL EYE INSTITUTE [R01EY014239] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL087018]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [R01GM021249] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA013868, R56AA011975, R01AA011975]
   Funding Source: NIH RePORTER
FX This work was supported by NIH Grants AA013868 and AA011975 to L.E.
   Nagy, GM021249 and HL087018 to R.G. Salomon, and EY014239 to JW Crabb
   and by BRTT Grant 05-29 from the State of Ohio to J.W. Crabb and R.G.
   Salomon.
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NR 59
TC 36
Z9 37
U1 0
U2 7
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 DEC 1
PY 2009
VL 47
IS 11
BP 1539
EP 1552
DI 10.1016/j.freeradbiomed.2009.09.003
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 521PN
UT WOS:000271934300003
PM 19751823
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Andriolo, RB
   Puga, ME
   Belfort, R
   Atallah, AN
AF Andriolo, Regis Bruni
   Puga, Maria Eduarda
   Belfort Junior, Rubens
   Atallah, Alvaro Nagib
TI Bevacizumab for ocular neovascular diseases: a systematic review
SO SAO PAULO MEDICAL JOURNAL
LA English
DT Review
DE Angiogenesis inhibitors; Retinal neovascularization; Corneal
   angiogenesis; Macular degeneration; Review
ID DIABETIC MACULAR EDEMA; RANDOMIZED CLINICAL-TRIAL; INTRAVITREAL
   BEVACIZUMAB; CHOROIDAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY;
   DEGENERATION; TRIAMCINOLONE; VERTEPORFIN; PHOTOCOAGULATION; AVASTIN
AB CONTEXT AND OBJECTIVE: Many eye diseases involve increased local levels of vascular endothelial growth factor (VEGF), and there are several therapeutic strategies for them. Thus, the aim of this study was to evaluate the effectiveness and safety of bevacizumab for treating eye diseases involving increased local levels of VEGF, as the assumed pathophysiological mechanism.
   DATA SOURCES: The following databases were systematically searched for evidence: PubMed, CENTRAL (Cochrane Library), Literatura Latino-Americana e do Caribe em Ciencias da Sa de (Lilacs) and reference lists, without language restrictions. Only randomized controlled trials were included. The primary outcome of interest was visual acuity, irrespective of the evaluation method.
   DATA SYNTHESIS: A total of 667 eyes in nine randomized trials were included. Meta-analysis showed that the proportion of patients with age-related macular degeneration who presented improvements from baseline regarding best-corrected visual acuity was higher among those treated with bevacizumab than among those in the photodynamic therapy group (risk ratio, RR, 0.49; 95% confidence interval, CI, 0.31 to 0.78; P = 0.01).
   CONCLUSIONS: The evidence available demonstrates that bevacizumab alone or combined with other treatments is more effective than other options, including photodynamic therapy, focal photocoagulation and triamcinolone. The use of bevacizumab instead of photodynamic therapy could reduce treatment costs by more than 99% and could significantly increase access to treatment. However, long-term studies are still needed in order to reduce uncertainty concerning the safety of this medication for all ocular neovascular diseases in which bevacizumab has the potential to improve visual acuity.
C1 [Andriolo, Regis Bruni; Puga, Maria Eduarda; Belfort Junior, Rubens; Atallah, Alvaro Nagib] Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil.
C3 Universidade Federal de Sao Paulo (UNIFESP)
RP Atallah, AN (通讯作者)，Rua Borges Lagoa,564 Conjunto 63,Edificio Espaco, BR-04038000 Sao Paulo, Brazil.
EM atallahmbe@uol.com.br
RI Belfort, Rubens/E-2252-2012; Andriolo, Regis Bruni/A-2564-2014; Atallah,
   Álvaro N/K-7182-2013
OI Belfort, Rubens/0000-0002-8422-3898; Andriolo, Regis
   Bruni/0000-0003-0306-5750; Puga, Maria Eduarda dos
   Santos/0000-0001-8470-861X; Atallah, Alvaro Nagib/0000-0003-0890-594X
FU Brazilian Ministry of Health
FX Science and Technology Department of the Science Secretariat, Brazilian
   Ministry of Health. The sponsor had no role in the design and conduct of
   the study or in collection, management, analysis and interpretation of
   the data or in preparation, review or approval of the manuscript
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   2008, CAHABA GBA MEDICAR B, P11
NR 29
TC 14
Z9 17
U1 0
U2 4
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 MAR 5
PY 2009
VL 127
IS 2
BP 84
EP 91
DI 10.1590/S1516-31802009000200006
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 469LJ
UT WOS:000267899500006
PM 19597683
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Kaempf, S
   Johnen, S
   Salz, AK
   Weinberger, A
   Walter, P
   Thumann, G
AF Kaempf, Stefanie
   Johnen, Sandra
   Salz, Anna Katharina
   Weinberger, Andreas
   Walter, Peter
   Thumann, Gabriele
TI Effects of bevacizumab (Avastin) on retinal cells in organotypic culture
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULAR MEMBRANES; MACULAR
   DEGENERATION; INTRAVITREAL BEVACIZUMAB; GENE-TRANSFER; IN-VIVO;
   INJECTION; SAFETY; RANIBIZUMAB; THERAPY
AB PURPOSE. Repetitive intravitreal injections of bevacizumab are a successful treatment option for exudative age-related macular degeneration (AMD). The aim of this study was to evaluate the toxicity of bevacizumab in the adult mammalian neurosensory retina in culture.
   METHODS. Adult porcine neurosensory retinas were cultured adjoined to the retinal pigment epithelium-choroid layer (retina-RPE-choroid complex) in static culture for 3 days, whereas neural retinas alone were cultured in a perfusion chamber for 3 days. Bevacizumab was added to the culture and perfusion medium at three concentrations (0.25 mg/mL [n = 6], 0.5 mg/mL [n = 6], and 1.25 mg/mL [n = 6]). Retina-RPE-choroid complex and neural retinas alone cultured without bevacizumab were used as controls. After 3 days in culture, the neural retinas alone and the retina-RPE-choroid complexes were analyzed histologically and immunohistochemically for the expression of glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, rhodopsin, smooth muscle actin (SMA), and apoptosis.
   RESULTS. No toxic effects on ganglion or photoreceptor cells were observed at any concentration of bevacizumab. The expression of GFAP and vimentin was slightly increased in Muller cells, whereas glutamine synthetase and rhodopsin were unaffected by bevacizumab. However, significantly enhanced SMA expression in retina blood vessels was observed in retinas cultured in the presence of bevacizumab.
   CONCLUSIONS. Bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations fivefold higher than those used clinically. The increased expression of SMA is an indication of the loss of functional VEGF modulating smooth muscle cells in mature vessels.
C1 [Kaempf, Stefanie] Univ Aachen, Rhein Westfal TH Aachen, IZKF BIOMAT, D-52074 Aachen, Germany.
   Univ Aachen, Rhein Westfal TH Aachen, Dept Ophthalmol, D-52074 Aachen, Germany.
C3 RWTH Aachen University; RWTH Aachen University
RP Kaempf, S (通讯作者)，Univ Aachen, Rhein Westfal TH Aachen, IZKF BIOMAT, D-52074 Aachen, Germany.
EM smueller-kaempf@ukaachen.de
RI Johnen, Sandra/ABA-9955-2020; Walter, Peter/L-5982-2018
OI Johnen, Sandra/0000-0003-0028-2557; Walter, Peter/0000-0001-8745-6593
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NR 44
TC 34
Z9 35
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2008
VL 49
IS 7
BP 3164
EP 3171
DI 10.1167/iovs.07-1265
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 318WR
UT WOS:000257124000050
PM 18344448
DA 2022-11-30
ER

PT J
AU Takahashi, H
   Ishizaki, H
   Tahara, H
   Tamaki, Y
   Yanagi, Y
AF Takahashi, Hidenori
   Ishizaki, Hidenobu
   Tahara, Hideaki
   Tamaki, Yasuhiro
   Yanagi, Yasuo
TI Suppression of choroidal neovascularization by vaccination with epitope
   peptide derived from human VEGF receptor 2 in an animal model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; GROWTH; RECEPTOR-2
AB PURPOSE. It has been shown that vaccination with peptides derived from human vascular endothelial growth factor receptor 2 (VEGFR2) induces cytotoxic T lymphocytes (CTLs) with potent cytotoxicity against endothelial cells expressing VEGFR2 in a A2/Kb transgenic mice system expressing human HLA-A*0201. The present study examined the efficacy of this immunotherapy against age-related macular degeneration (AMD) using a choroidal neovascularization (CNV) model.
   METHODS. Seven-to 10- week-old A2/Kb transgenic mice expressing human HLA-A*0201 were used. The mice were divided into three groups of 15 animals each: phosphate-buffered saline (PBS) treatment ( control); immunity adjuvant ( incomplete Freund adjuvant [IFA]); and antigen peptide of human VEGFR 2 and IFA ( peptide vaccination group). Immunization was given on days 0 and 11. On day 20, six CNVs were induced in both eyes of each animal using a semiconductor laser set to 75 mu m, 200 mW, and 0.05 seconds. Leakage from the CNV was measured by fluorescein angiography 7 days after laser treatment. CNV volume was measured using a choroidal flatmount after perfusing the mice with fluorescein conjugate lectin.
   RESULTS. There were no significant differences in the leakage or the area of CNV in the IFA-treated group compared with controls. In contrast, the fluorescent leakage index in the peptide vaccination group was reduced to 80% and the CNV area to 18% compared with the control group (P < 0.0001 and P < 0.05, respectively).
   CONCLUSIONS. This model provides a rationale for immunotherapy using the epitope peptides derived from VEGFR2 for the treatment of CNV.
C1 [Takahashi, Hidenori; Tamaki, Yasuhiro; Yanagi, Yasuo] Univ Tokyo, Sch Med, Dept Ophthalmol, Inst Med Sci,Bunkyo Ku, Tokyo 1138655, Japan.
   [Ishizaki, Hidenobu; Tahara, Hideaki] Univ Tokyo, Inst Med Sci, Dept Surg & Bioengn, Tokyo 1138655, Japan.
C3 University of Tokyo; University of Tokyo
RP Tamaki, Y (通讯作者)，Univ Tokyo, Sch Med, Dept Ophthalmol, Inst Med Sci,Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM tamaki-tky@umin.ac.jp
RI Yanagi, Yasuo/AAA-5441-2022; Yanagi, Yasuo/AAF-2670-2020; Takahashi,
   Hidenori/H-2945-2019
OI Takahashi, Hidenori/0000-0001-5331-4730; Yanagi,
   Yasuo/0000-0002-0362-7285
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   2005, RETINA, V25, P119
NR 13
TC 8
Z9 10
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 MAY
PY 2008
VL 49
IS 5
BP 2143
EP 2147
DI 10.1167/iovs.07-0523
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 292UH
UT WOS:000255291100052
PM 18436847
DA 2022-11-30
ER

PT J
AU Lee, SJ
   Kim, JH
   Kim, JH
   Chung, MJ
   Wen, Q
   Chung, H
   Kim, KW
   Yu, YS
AF Lee, Sung-Joon
   Kim, Jeong Hun
   Kim, Jin Hyoung
   Chung, Mi Ja
   Wen, Qingcheng
   Chung, Hum
   Kim, Kyu-Won
   Yu, Young Suk
TI Human apolipoprotein E2 transgenic mice show lipid accumulation in
   retinal pigment epithelium and altered expression of VEGF and bFGF in
   the eyes
SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
LA English
DT Article
DE age-related rnacular degeneration; apolipoprotein E2; VEGF; bFGF
ID III HYPERLIPOPROTEINEMIA; MACULAR DEGENERATION; BRUCHS MEMBRANE; DRUSEN;
   MODEL; DYSBETALIPOPROTEINEMIA; NEOVASCULARIZATION; ATHEROSCLEROSIS;
   PATHOGENESIS; E3-LEIDEN
AB We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet (8 +/- 2 per 50 mu m(2) for normal chow and 11 +/- 2 per 50 mu m(2), p<0.05). ApoE expression was similar in the apoE2 and control mice: however, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes of apoE2 mice develop typical lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.
C1 Korea Univ, Div Food Biosci & Technol, Coll Life Sci & Biotechnol, Inst Biomed Sci & Safety, Seoul 136713, South Korea.
   Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110744, South Korea.
   Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea.
   Seoul Natl Univ, Coll Pharm, Div Pharmaceut Biosci, Seoul 151742, South Korea.
   Seoul Natl Univ, Inst Pharmaceut Sci, Seoul 151742, South Korea.
C3 Korea University; Seoul National University (SNU); Seoul National
   University (SNU); Seoul National University Hospital; Seoul National
   University (SNU); Seoul National University (SNU)
RP Yu, YS (通讯作者)，Korea Univ, Div Food Biosci & Technol, Coll Life Sci & Biotechnol, Inst Biomed Sci & Safety, Seoul 136713, South Korea.
EM ysyu@snu.ac.kr
RI Yu, Young Suk/J-5551-2012; Lee, Sung-Joon/F-2435-2013; Kim, Kyu
   Won/AAJ-7213-2020; Chung, Hum/J-5657-2012; Kim, Jeong Hun/J-2748-2012
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NR 43
TC 26
Z9 28
U1 0
U2 2
PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
PI SEOUL
PA KOREA SCI TECHNOL CENTER #507,  635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL
   135-703, SOUTH KOREA
SN 1017-7825
EI 1738-8872
J9 J MICROBIOL BIOTECHN
JI J. Microbiol. Biotechnol.
PD JUN
PY 2007
VL 17
IS 6
BP 1024
EP 1030
PG 7
WC Biotechnology & Applied Microbiology; Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Microbiology
GA 185IB
UT WOS:000247703500019
PM 18050922
DA 2022-11-30
ER

PT J
AU Donati, MC
   Carifi, G
   Virgili, G
   Menchini, U
AF Donati, MC
   Carifi, G
   Virgili, G
   Menchini, U
TI Retinal angiomatous proliferation: Association with clinical and
   angiographic features
SO OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; retinal angiomatous proliferation;
   fluorescein angiography; indocyanine green angiography
ID OCCULT CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; CHORIORETINAL
   ANASTOMOSIS; LASER PHOTOCOAGULATION; PHOTODYNAMIC THERAPY
AB Aim: It was the aim of this study to evaluate the frequency of retinal angiomatous proliferation (RAP) and its association with specific clinical and angiographic characteristics in age-related macular degeneration (AMD).
   Methods: A consecutive series of 126 newly diagnosed patients with exudative AMD was reviewed retrospectively. All underwent a complete ophthalmic examination, a red-free photograph and fluorescein angiography. Most patients (85/126) underwent indocyanine green choroidal angiography (ICGA). RAP was diagnosed when a connection between the retinal vasculature and the neovascular complex was recognized angiographically.
   Results: Out of 126 patients with recent neovascular AMD, 17 had RAP (13.5%; 95% Cl 8.1-20.7). The study eye of patients with RAP had more frequent hemorrhages (88.2 vs. 59.6%; p = 0.027), hard exudates (82.4 vs. 26.6%; p < 0.001), pigment epithelium detachment (64.7 vs. 23.8%; p = 0.001) and a hot spot in ICGA (70.6 vs. 22.1%; p < 0.001) with respect to the other forms of exudative AMD. Hemorrhages were more frequently superficial, multiple and within the edge of the lesion in the RAP group. Bilateral AMD was more common in the RAP group (70.6 vs. 38.0%; p = 0.011). No statistically significant differences were found regarding sex, age and visual acuity.
   Conclusion: RAP represents a common lesion in patients with neovascular AMD referred to a tertiary care clinic. The recognition of hemorrhages, hard exudates, pigment epithelium detachment or a hot spot in ICGA can assist a correct diagnosis. Copyright (c) 2006 S. Karger AG, Basel.
C1 Univ Florence, Eye Clin, Dept Oto Neuro Ophtalmol Surg Sci, I-50121 Florence, Italy.
C3 University of Florence
RP Donati, MC (通讯作者)，Univ Florence, Eye Clin, Dept Oto Neuro Ophtalmol Surg Sci, I-50121 Florence, Italy.
EM gianni.virgili@unifi.it
RI Virgili, Gianni/P-6607-2014
OI Virgili, Gianni/0000-0002-9960-2989
CR Axer-Siegel R, 2002, OPHTHALMOLOGY, V109, P1726, DOI 10.1016/S0161-6420(02)01149-1
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NR 14
TC 24
Z9 24
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2006
VL 220
IS 1
BP 31
EP 36
DI 10.1159/000089272
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 996JN
UT WOS:000234170300006
PM 16374046
DA 2022-11-30
ER

PT J
AU Nucci, C
   Cedrone, C
   Culasso, F
   Ricci, F
   Cesareo, M
   Corsi, A
   Cerulli, L
AF Nucci, C
   Cedrone, C
   Culasso, F
   Ricci, F
   Cesareo, M
   Corsi, A
   Cerulli, L
TI Incidence of visual loss in the Ponza Eye Study, Italy
SO EYE
LA English
DT Article
DE blindness; low vision; incidence; population-study
ID IMPAIRMENT; PREVALENCE; ACUITY
AB Aim To study the incidence of visual loss over a 12-year period in the survivors of an original cohort aged 40 years or older at baseline.
   Methods Visual acuity (VA) was measured by means of a standardized logMAR chart. World Health Organization definition of blindness and low vision was adopted ( respectively, best-corrected VA >1.3 logMAR or a visual field <10 degrees around central fixation, and best-corrected VA >0.5 - 1.3 logMAR or a visual field <20 degrees around central fixation). Moreover, binocular visual loss incidence (VA >0.5 logMAR) was calculated in a ` healthy' group who had uncorrected VA of 0.0 logMAR or better in both eyes at baseline and absence of eye diseases.
   Results Of the 584 eligible survivors, 411 (70.7%) had a 12-year follow-up visit. The overall incidence figures were as follows: best-corrected binocular blindness (0.7%), binocular low vision (3.9%), monocular blindness (2.7%), and monocular low vision (5.0%), respectively. The results for presenting VAs were 1.2, 9.5, 4.2, and 15.3%. Figures for uncorrected, best-corrected, and presenting binocular visual loss incidence in the ` healthy' group were respectively 12.7, 0.9, and 3.7%.
   Conclusion The discrepancy between the ideal and real situations that emerges from this study has important implications for health-care planning. Over a period of 12 years, a substantial percentage of ` healthy' subjects will have to seek medical care. Incident visual loss was caused mainly by untreated cataract, glaucoma, myopia, and age-related macular degeneration.
C1 Univ Roma Tor Vergata, Cattedra Ottica Fisiopatol, Dipartimento Biopatol & Diagnost Immagini, 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 Nucci, C (通讯作者)，Univ Roma Tor Vergata, Cattedra Ottica Fisiopatol, Dipartimento Biopatol & Diagnost Immagini, Via Montpellier 1, I-00133 Rome, Italy.
EM nucci@med.uniroma2.it
RI ricci, federico/AAC-3836-2020
OI ricci, federico/0000-0002-4224-9280; CORSI, ANDREA/0000-0002-3831-0659
CR Cedrone C, 1997, Ophthalmic Epidemiol, V4, P59
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NR 15
TC 17
Z9 19
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2005
VL 19
IS 2
BP 175
EP 182
DI 10.1038/sj.eye.6701444
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 893LE
UT WOS:000226719700010
PM 15218520
OA Bronze
DA 2022-11-30
ER

PT J
AU Pallikaris, IG
   Kymionis, GD
   Ginis, HS
   Kounis, GA
   Tsilimbaris, MK
AF Pallikaris, IG
   Kymionis, GD
   Ginis, HS
   Kounis, GA
   Tsilimbaris, MK
TI Ocular rigidity in living human eyes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID INTRAOCULAR-PRESSURE MEASUREMENTS; CORNEAL THICKNESS; ELASTICITY
AB PURPOSE. To measure the rigidity coefficient of a large number of subjects at clinically encountered intraocular pressures (IOPs) and to examine the possible correlation of ocular rigidity with other factors, such as the age of the patients, ocular parameters ( axial length and corneal thickness), and pathologic conditions affecting the eye.
   METHODS. The pressure - volume relationship and the ocular rigidity coefficient ( K) were determined in 79 eyes undergoing cataract surgery, by injecting 200 muL of saline solution ( in steps of 4.5 muL) through the limbus into the anterior chamber, while continually monitoring the IOP with a transducer, up to the limit of 60 mm Hg. Data within an IOP range of 10 to 35 mm Hg were used to calculate the scleral rigidity coefficient. All measurements were taken at the same time of day, to eliminate any possible diurnal variation.
   RESULTS. The mean ocular rigidity coefficient was 0.0126 mm Hg/muL (95% confidence interval [CI], 0.0112 - 0.0149). A statistically significant positive correlation between the rigidity coefficient and age of the patient was found ( P = 0.02), whereas similar findings were not observed for the examined ocular parameters ( axial length, P = 0.09; and corneal thickness, P = 0.12). No correlation was found for patients with diabetes mellitus ( P = 0.39), age-related macular degeneration ( P = 0.55), and hypertension ( P = 0.45).
   CONCLUSIONS. The present study provides quantitative data on the ocular rigidity coefficient based on measurements in a large series of living human eyes. A positive correlation between the ocular rigidity coefficient and the patient's age was documented.
C1 Univ Crete, Sch Med, Vardinoyann Eye Inst Crete, Dept Ophthalmol, Iraklion 71110, Crete, Greece.
C3 University of Crete
RP Kymionis, GD (通讯作者)，Univ Crete, Sch Med, Vardinoyann Eye Inst Crete, Dept Ophthalmol, Iraklion 71110, Crete, Greece.
EM kymionis@med.uoc.gr
OI Tsilimbaris, Miltiadis/0000-0002-0130-1150
CR Abbasoglu KE, 1998, OPHTHALMOLOGY, V105, P2193, DOI 10.1016/S0161-6420(98)91215-5
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NR 19
TC 210
Z9 226
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 FEB
PY 2005
VL 46
IS 2
BP 409
EP 414
DI 10.1167/iovs.04-0162
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 890WP
UT WOS:000226542100001
PM 15671262
DA 2022-11-30
ER

PT J
AU Taarnhoj, NCBB
   Kjeka, O
   Larsen, M
AF Taarnhoj, NCBB
   Kjeka, O
   Larsen, M
TI Kinetics of retinal lipoprotein precipitation and elimination after
   closure of subretinal new vessels
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VEIN OCCLUSION
AB PURPOSE. To study the kinetics of retinal precipitation and elimination of lipoprotein in relation to photodynamic therapy of subretinal new vessels.
   METHODS. This was a retrospective observational study of subretinal precipitate before and after photodynamic therapy for subfoveal new vessels secondary to age-related macular degeneration in 14 eyes demonstrating precipitate at one or more visits, using digital red-free gray-scale fundus photography, intravenous fluorescein angiography, optical coherence tomography, and morphometric mapping.
   RESULTS. In 14 eyes of 14 patients, the area covered by lipoprotein precipitate increased from a mean of 0.54 optic disc areas (range, 0-2.61) before treatment to a mean of 0.65 optic disc areas (range, 0.01-3.04) at 45 d after treatment (P = 0.18). Eyes with a serous detachment at baseline, before the initial treatment (n = 10) demonstrated more treatment-related precipitation than eyes without a serous detachment at baseline (n = 4; P = 0.034). Two eyes with a large amount of precipitate and a long follow-up demonstrated net elimination of precipitate from approximately 100 days after the initial treatment, with uniexponential precipitate half-fives of 43 and 32 days.
   CONCLUSIONS. Photodynamic therapy for subfoveal new vessels may be associated with retinal precipitation of lipoprotein, presumably because early extraction of water and salts from the subretinal fluid increases the concentration of leaked plasma proteins. Despite reperfusion of the subretinal vessels, macromolecular leakage appears to cease within 106 days, indicating that functional maturation of the new vessels has occurred, with an associated decrease in pore size.
C1 Univ Copenhagen, Herlev Hosp, Dept Ophthalmol, DK-2730 Herlev, Denmark.
   Univ Bergen, Haukeland Hosp, Dept Ophthalmol, N-5021 Bergen, Norway.
C3 University of Copenhagen; Herlev & Gentofte Hospital; University of
   Bergen; Haukeland University Hospital
RP Taarnhoj, NCBB (通讯作者)，Univ Copenhagen, Herlev Hosp, Dept Ophthalmol, DK-2730 Herlev, Denmark.
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NR 5
TC 8
Z9 8
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2003
VL 44
IS 4
BP 1680
EP 1685
DI 10.1167/iovs.01-1132
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 660TG
UT WOS:000181848900042
PM 12657609
DA 2022-11-30
ER

PT J
AU Grant, A
   Aubin, MJ
   Buhrmann, R
   Kergoat, MJ
   Li, G
   Freeman, EE
AF Grant, Alyssa
   Aubin, Marie-Josee
   Buhrmann, Ralf
   Kergoat, Marie-Jeanne
   Li, Gisele
   Freeman, Ellen E.
TI Visual Impairment, Eye Disease, and 3-Year Cognitive Decline: The
   Canadian Longitudinal Study on Aging
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Visual impairment; cognitive decline; glaucoma; eye disease; CLSA
ID OPEN-ANGLE GLAUCOMA; ALZHEIMER-DISEASE; VISION IMPAIRMENT;
   PROCESSING-SPEED; AGE-DIFFERENCES; DEMENTIA; RISK; MEMORY; BRAIN;
   ASSOCIATION
AB Purpose To examine the longitudinal association between vision-related variables and the 3-year change in cognitive test scores in a community-dwelling sample of adults and to explore whether sex, education, or hearing loss act as effect modifiers. Methods Data came from two waves of a 3-year population-based prospective cohort study (Canadian Longitudinal Study on Aging), which consisted of 30,097 randomly selected people aged 45-85 years from 7 Canadian provinces. Visual impairment (VI) was defined as binocular presenting visual acuity worse than 20/40. Participants were asked if they had ever had a diagnosis of age-related macular degeneration (AMD), glaucoma, or cataract. Cognitive change over 3 years was examined by calculating the difference between baseline and follow-up scores for the Rey Auditory Verbal Learning Test (RAVLT) and the RAVLT delayed test (memory tests), the Controlled Oral Word Association Test (COWAT) and the Animal Naming Test (ANT) (verbal fluency tests), and the Mental Alternation Test (MAT) (processing speed test). Multiple linear regression was used. Results VI, AMD, and cataract were not associated with 3-year changes on any of the 5 cognitive tests after adjusting for age, sex, ethnicity, education, income, smoking, diabetes, stroke, heart disease, and province. A report of glaucoma was associated with greater declines in MAT scores (beta = -0.60, 95% CI -1.03, -0.18). No effect modification was detected. Conclusions Glaucoma was associated with worsening processing speed. Further research to confirm this finding and to understand the possible reason is necessary.
C1 [Grant, Alyssa; Freeman, Ellen E.] Univ Ottawa, Sch Epidemiol & Publ Hlth, 600 Peter Morand Crescent,Off 301H, Ottawa, ON, Canada.
   [Aubin, Marie-Josee; Li, Gisele] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Aubin, Marie-Josee; Li, Gisele] Ctr Univ Ophtalmol Hop Maisonneuve Rosemont, Montreal, PQ, Canada.
   [Aubin, Marie-Josee] Univ Montreal, Espum, Dept Social & Prevent Med, Montreal, PQ, Canada.
   [Buhrmann, Ralf] Univ Ottawa, Dept Ophthalmol, Ottawa, ON, Canada.
   [Kergoat, Marie-Jeanne] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Kergoat, Marie-Jeanne] Univ Montreal, Dept Med, Montreal, PQ, Canada.
   [Freeman, Ellen E.] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
C3 University of Ottawa; Universite de Montreal; Universite de Montreal;
   University of Ottawa; 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, 600 Peter Morand Crescent,Off 301H, Ottawa, ON, Canada.
EM efreeman@gmail.com
FU Canadian Institutes of Health Research [ACD-170303, LSA 94473]; Canada
   Foundation for Innovation
FX This work was supported by the Canadian Institutes of Health Research
   under grants ACD-170303 and LSA 94473 and the Canada Foundation for
   Innovation.
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NR 63
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 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD SEP 3
PY 2022
VL 29
IS 5
BP 545
EP 553
DI 10.1080/09286586.2021.1974494
EA SEP 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4S0HV
UT WOS:000693066500001
PM 34486480
OA hybrid
DA 2022-11-30
ER

PT J
AU Sun, HJ
   Zhang, FF
   Xiao, Q
   Xu, J
   Zhu, LJ
AF Sun, Hong-Jing
   Zhang, Fang-Fang
   Xiao, Qing
   Xu, Jia
   Zhu, Li-Jin
TI lncRNA MEG3, Acting as a ceRNA, Modulates RPE Differentiation Through
   the miR-7-5p/Pax6 Axis
SO BIOCHEMICAL GENETICS
LA English
DT Article
DE AMD; RPE dedifferentiation; MEG3; MiR-7-5p; Pax6
ID RETINAL-PIGMENT EPITHELIUM; LONG NONCODING RNAS; MACULAR DEGENERATION;
   CANCER CELLS; PROLIFERATION; EXPRESSION; PAX6
AB Accumulated evidence indicated that long non-coding RNAs (lncRNAs) involves in numerous biological and pathological processes, including age-related macular degeneration (AMD). Dysfunction and dedifferentiation of retinal pigment epithelium (RPE) cells have been demonstrated to be one of the crucial factor in AMD etiology. Herein, we aim to investigate the essential role of lncRNA maternally expressed gene 3 (MEG3) in AMD progression. Expression patterns of MEG3 were measured in dysfunctional REP cells exposed with H2O2 or TNF-alpha using qRT-PCR assay. Specifically, the intercellular distribution of MEG3 in REP cells was further explored using the subcellular fraction detection. Relative expression of RPE markers or RPE dedifferentiation-related markers was determined using qRT-PCR and western blot analysis, respectively. Immunofluorescence staining was performed to examine the expressions of RPE markers ZO-1 and beta-catenin. Concentration of vascular endothelial growth factor (VEGFA) in the supernatant was detected using ELISA kit. Luciferase reporter assay was performed to verify the MEG3/miR-7-5p/Pax6 regulatory network, which was further determined in in vitro studies. MEG3 expression was significantly decreased in H2O2 or TNF-alpha-treated REP cells, and it was upregulated along with RPE differentiation. Reduced MEG3 expression resulted in RPE dedifferentiation, which was indicated by decreased expressions of RPE markers, accumulated mitochondrial reactive oxygen species, and reduced VEGFA. Mechanistically, MEG3 functioned as a sponge for miR-7-5p to restore the expression of Pax6. Our study demonstrated that MEG3 exerts a protective role against AMD by maintaining RPE differentiation via miR-7-5p/Pax6 axis, suggesting a protective therapeutic target in AMD treatment.
C1 [Sun, Hong-Jing; Xiao, Qing; Xu, Jia] Zhejiang Univ, Affiliated Hosp 2, Dept Ophthalmol, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China.
   [Zhang, Fang-Fang; Zhu, Li-Jin] Hangzhou Med Coll, Sch Publ Hlth, 182 Tianmushan Rd, Hangzhou 310013, Zhejiang, Peoples R China.
C3 Zhejiang University; Hangzhou Medical College
RP Zhu, LJ (通讯作者)，Hangzhou Med Coll, Sch Publ Hlth, 182 Tianmushan Rd, Hangzhou 310013, Zhejiang, Peoples R China.
EM lijinzhu@hmc.edu.cn
OI Zhu, Li-Jin/0000-0002-7589-9415
FU Zhejiang Provincial Medical and Health Science and Technology Project
   [2020KY150, 2020KY528, 2020KY578, 2021KY128]; Zhejiang Provincial
   Science and Technology Program of Traditional Chinese Medicine
   [2019ZA072]
FX This work was supported by Zhejiang Provincial Medical and Health
   Science and Technology Project (Nos. 2020KY150, 2020KY528, 2020KY578,
   2021KY128) and Zhejiang Provincial Science and Technology Program of
   Traditional Chinese Medicine (No. 2019ZA072).
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NR 24
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0006-2928
EI 1573-4927
J9 BIOCHEM GENET
JI Biochem. Genet.
PD DEC
PY 2021
VL 59
IS 6
BP 1617
EP 1630
DI 10.1007/s10528-021-10072-9
EA MAY 2021
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA WO6TP
UT WOS:000652570000001
PM 34018078
DA 2022-11-30
ER

PT J
AU Truong, V
   Viken, K
   Geng, ZH
   Barkan, S
   Johnson, B
   Ebeling, MC
   Montezuma, SR
   Ferrington, DA
   Dutton, JR
AF Truong, Vincent
   Viken, Kevin
   Geng, Zhaohui
   Barkan, Samantha
   Johnson, Blake
   Ebeling, Mara C.
   Montezuma, Sandra R.
   Ferrington, Deborah A.
   Dutton, James R.
TI Automating Human Induced Pluripotent Stem Cell Culture and
   Differentiation of iPSC-Derived Retinal Pigment Epithelium for
   Personalized Drug Testing
SO SLAS TECHNOLOGY
LA English
DT Article
DE human induced pluripotent stem cells; automation; automated cell culture
   platform; retinal pigment epithelium; age-related macular degeneration;
   personalized drug screening; TECAN Fluent; liquid handling
ID MACULAR DEGENERATION; AGE; PATIENT; SYSTEM; MODEL
AB Derivation and differentiation of human induced pluripotent stem cells (hiPSCs) provide the opportunity to generate medically important cell types from individual patients and patient populations for research and the development of potential cell therapies. This technology allows disease modeling and drug screening to be carried out using diverse population cohorts and with more relevant cell phenotypes than can be accommodated using traditional immortalized cell lines. However, technical complexities in the culture and differentiation of hiPSCs, including lack of scale and standardization and prolonged experimental timelines, limit the adoption of this technology for many large-scale studies, including personalized drug screening. The entry of reproducible end-to-end automated workflows for hiPSC culture and differentiation, demonstrated on commercially available platforms, provides enhanced accessibility of this technology for both research laboratories and commercial pharmaceutical testing. Here we have utilized TECAN Fluent automated cell culture workstations to perform hiPSC culture and differentiation in a reproducible and scalable process to generate patient-derived retinal pigment epithelial cells for downstream use, including drug testing. hiPSCs derived from multiple donors with age-related macular degeneration (AMD) were introduced into our automated workflow, and cell lines were cultured and differentiated into retinal pigment epithelium (RPE). Donor hiPSC-RPE lines were subsequently entered in an automated drug testing workflow to measure mitochondrial function after exposure to "mitoactive" compounds. This work demonstrates scalable, reproducible culture and differentiation of hiPSC lines from individuals on the TECAN Fluent platform and illustrates the potential for end-to-end automation of hiPSC-based personalized drug testing.
C1 [Truong, Vincent; Viken, Kevin; Geng, Zhaohui; Barkan, Samantha; Johnson, Blake; Ferrington, Deborah A.; Dutton, James R.] Univ Minnesota, Stem Cell Inst, 2001 6th St SE, Minneapolis, MN 55455 USA.
   [Truong, Vincent; Viken, Kevin; Ebeling, Mara C.; Montezuma, Sandra R.; Ferrington, Deborah A.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN USA.
   [Geng, Zhaohui; Dutton, James R.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 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 Dutton, JR (通讯作者)，Univ Minnesota, Stem Cell Inst, 2001 6th St SE, Minneapolis, MN 55455 USA.
EM dutto015@umn.edu
OI Viken, Kevin/0000-0003-3822-2269; Ferrington,
   Deborah/0000-0003-2561-7464
FU National Institutes of Health/National Eye Institute [R01EY02855401];
   Regenerative Medicine Minnesota [091718 TR 009]; Department of
   Ophthalmology and Visual Neurosciences; Stem Cell Institute
FX The authors disclosed receipt of the following financial support for the
   research, authorship, and/or publication of this article: J.R.D. and
   D.A.F. acknowledge funding support from the National Institutes of
   Health/National Eye Institute (grant R01EY02855401), Regenerative
   Medicine Minnesota (Grant 091718 TR 009), the Department of
   Ophthalmology and Visual Neurosciences and the Stem Cell Institute. None
   of the funding agencies had a role in study design; the collection,
   analysis, and interpretation of data; writing the manuscript; or the
   decision to submit the manuscript for publication.
CR BOK D, 1993, J CELL SCI, P189
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NR 29
TC 5
Z9 5
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 2472-6303
EI 2472-6311
J9 SLAS TECHNOL
JI SLAS Technol.
PD JUN
PY 2021
VL 26
IS 3
SI SI
BP 287
EP 299
AR 2472630320972110
DI 10.1177/2472630320972110
EA DEC 2020
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA SF2WK
UT WOS:000630160700001
PM 33292045
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU El-Darzi, N
   Mast, N
   Petrov, AM
   Pikuleva, IA
AF El-Darzi, Nicole
   Mast, Natalia
   Petrov, Alexey M.
   Pikuleva, Irina A.
TI 2-Hydroxypropyl-beta-cyclodextrin reduces retinal cholesterol in
   wild-type and Cyp27a1(-/-)Cyp46a1(-/-) mice with deficiency in the
   oxysterol production
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE age-related macular degeneration; cholesterol; retina;
   2-hydroxypropyl-beta-cyclodextrin
ID STEROL-CARRIER PROTEIN-2; ORAL FLUORESCEIN ANGIOGRAPHY; GDP/GTP EXCHANGE
   PROTEIN; MACULAR DEGENERATION; BETA-CYCLODEXTRINS; AGE; METABOLISM;
   TRANSPORT; IDENTIFICATION; ACCUMULATION
AB Background and Purpose: 2-Hydroxypropyl-beta-cyclodextrin (HPCD) is an FDA approved vehicle for drug delivery and an efficient cholesterol-lowering agent. HPCD was proposed to lower tissue cholesterol via multiple mechanisms including those mediated by oxysterols. CYP27A1 and CYP46A1 are the major oxysterol-producing enzymes in the retina that convert cholesterol to 27- and 24-hydroxycholesterol, respectively. We investigated whether HPCD treatments affected the retina of wild-type andCyp27a1(-/-)Cyp46a1(-/-)mice that do not produce the major retinal oxysterols.
   Experimental Approach: HPCD administration was either by i.p., p.o. or s.c. Delivery to the retina was confirmed by angiography using the fluorescently labelled HPCD. Effects on the levels of retinal sterols, mRNA and proteins were evaluated by GC-MS, qRT-PCR and label-free approach, respectively.
   Key Results: In both wild-type andCyp27a1(-/-)Cyp46a1(-/-)mice, HPCD crossed the blood-retinal barrier when delivered i.p. and lowered the retinal cholesterol content when administered p.o. and s.c. In both genotypes, oral HPCD treatment affected the expression of cholesterol-related genes as well as the proteins involved in endocytosis, lysosomal function and lipid homeostasis. Mechanistically, liver X receptors and the altered expression ofLipe(hormone-sensitive lipase),Nceh1(neutral cholesterol ester hydrolase 1) and NLTP (non-specific lipid-transfer protein) could mediate some of the HPCD effects.
   Conclusions and Implications: HPCD treatment altered retinal cholesterol homeostasis and is a potential therapeutic approach for the reduction of drusen and subretinal drusenoid deposits, cholesterol-rich lesions and hallmarks of age-related macular degeneration.
C1 [El-Darzi, Nicole; Mast, Natalia; Petrov, Alexey M.; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 2085 Adelbert Rd,Room 303, Cleveland, OH 44106 USA.
   [Petrov, Alexey M.] RAS, Kazan Sci Ctr, Fed Res Ctr, Lab Biophys Synapt Proc,Kazan Inst Biochem & Biop, 2-31 Lobachevsky St,Box 30, Kazan 420111, Russia.
   [Petrov, Alexey M.] Kazan State Medial Univ, Inst Neurosci, 49 Butlerova St, Kazan 420012, Russia.
C3 Case Western Reserve University; Russian Academy of Sciences; Kazan
   Scientific Centre of the Russian Academy of Sciences; Kazan Institute of
   Biochemistry & Biophysics; Kazan State Medical University
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 2085 Adelbert Rd,Room 303, Cleveland, OH 44106 USA.
EM iap8@case.edu
RI Petrov, Alexey/O-4500-2017
OI Petrov, Alexey/0000-0002-1432-3455; Mast, Natalia/0000-0001-6427-640X;
   Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health; Cleveland Eye Bank Foundation; National
   Eye Institute [EY011373, EY018383, EY025383]
FX National Institutes of Health; Cleveland Eye Bank Foundation; National
   Eye Institute, Grant/Award Numbers: EY011373, EY018383, EY025383
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NR 79
TC 6
Z9 6
U1 5
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2021
VL 178
IS 16
BP 3220
EP 3234
DI 10.1111/bph.15209
EA AUG 2020
PG 15
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA TS9KU
UT WOS:000567294600001
PM 32698250
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Ho, E
   Boffa, J
   Palanker, D
AF Ho, Elton
   Boffa, Jack
   Palanker, Daniel
TI Performance of complex visual tasks using simulated prosthetic vision
   via augmented-reality glasses
SO JOURNAL OF VISION
LA English
DT Article
DE prosthetic vision; augmented reality; visual acuity; reading; face
   recognition
AB Photovoltaic subretinal prosthesis is designed for restoration of central vision in patients with age-related macular degeneration (AMD). We investigated the utility of prosthetic central vision for complex visual tasks using augmented-reality (AR) glasses simulating reduced acuity, contrast, and visual field. AR glasses with blocked central 20 degrees of visual field included an integrated video camera and software which adjusts the image quality according to three user-defined parameters: resolution, corresponding to the equivalent pixel size of an implant; field of view, corresponding to the implant size; and number of grayscale levels. The real-time processed video was streamed on a screen in front of the right eye. Nineteen healthy participants were recruited to complete visual tasks including vision charts, sentence reading, and face recognition. With vision charts, letter acuity exceeded the pixel-sampling limit by 0.2 logMAR. Reading speed decreased with increasing pixel size and with reduced field of view (7 degrees-12 degrees). In the face recognition task (four-way forced choice, 5 degrees angular size) participants identified faces at >75% accuracy, even with 100 mu m pixels and only two grayscale levels. With 60 mu m pixels and eight grayscale levels, the accuracy exceeded 97%. Subjects with simulated prosthetic vision performed slightly better than the sampling limit on the letter acuity tasks, and were highly accurate at recognizing faces, even with 100 mu m/pixel resolution. These results indicate feasibility of reading and face recognition using prosthetic central vision even with 100 mu m pixels, and performance improves further with smaller pixels.
C1 [Ho, Elton] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Ho, Elton; Boffa, Jack; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA USA.
C3 Stanford University; Stanford University; Stanford University
RP Ho, E (通讯作者)，Stanford Univ, Dept Phys, Stanford, CA 94305 USA.; Ho, E (通讯作者)，Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
EM eltonho@stanford.edu
OI Palanker, Daniel/0000-0002-0480-3025
FU National Institutes of Health [R01-EY-018608, R01-EY-027786]; Stanford
   Institute of Neuroscience; Research to Prevent Blindness; NSF [0339122];
   Department of Defense [W81XWH-15-10009]
FX This work was supported by the National Institutes of Health (Grants
   R01-EY-018608, R01-EY-027786), the Department of Defense (Grant
   W81XWH-15-10009), Stanford Institute of Neuroscience, and Research to
   Prevent Blindness.; Stimulus images courtesy of Michael J. Tarr, Center
   for the Neural Basis of Cognition and Department of Psychology, Carnegie
   Mellon University, http://www.tarrlab.org/.Funding provided by NSF award
   0339122.
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NR 44
TC 9
Z9 9
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 NOV
PY 2019
VL 19
IS 13
AR 22
DI 10.1167/19.13.22
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA VK0VX
UT WOS:000656719900017
PM 31770773
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Crowley, MA
   Delgado, O
   Will-Orrego, A
   Buchanan, NM
   Anderson, K
   Jaffee, BD
   Dryja, TP
   Liao, SM
AF Crowley, Maura A.
   Delgado, Omar
   Will-Orrego, Adrian
   Buchanan, Natasha M.
   Anderson, Karen
   Jaffee, Bruce D.
   Dryja, Thaddeus P.
   Liao, Sha-Mei
TI Induction of Ocular Complement Activation by Inflammatory Stimuli and
   Intraocular Inhibition of Complement Factor D in Animal Models
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE alternative complement pathway; animal model; complement factor D;
   toll-like receptor
ID ENDOTOXIN-INDUCED UVEITIS; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   COMPONENT C3; GEOGRAPHIC ATROPHY; CHOROIDAL NEOVASCULARIZATION;
   GENE-EXPRESSION; FACTOR-B; RETINAL DEGENERATION; CYNOMOLGUS MONKEYS
AB PURPOSE. Genome-wide association studies suggest a role for the complement system in age-related macular degeneration (AMD). We characterized ocular complement activation and evaluated a complement factor D (FD) neutralizing antibody.
   METHODS. Mice were treated with toll-like receptor (TLR) ligands, intravitreal injection (IVT), or corneal debridement. Levels of complement proteins and mRNA were measured. A FD neutralizing antibody was administered IVT into eyes of rabbits that were challenged with LPS (lipopolysaccharide) administered intravenously.
   RESULTS. Levels of C3 and factor B (FB) mRNA and protein in the eye were increased following intraperitoneal injection of TLR4 ligand LPS. Increased levels of C3 and FB breakdown products were observed in both eye tissues and plasma. Complement activation products were markedly reduced in C3(-/-) and Cfb(-/-) mice challenged with LPS. Ocular complement levels were also elevated in mice treated systemically with TLR2 and -3 ligands, injured by IVT injection or corneal debridement, or even in normal aging. IVT administration of a complement FD neutralizing antibody in rabbits inhibited LPS-induced complement activation in the posterior segment of the eye, but not in the anterior segment of the eye or in plasma.
   CONCLUSIONS. Systemic TLR stimulation and eye tissue injury induced time-dependent alternative complement pathway activation in the eye. Ocular complement levels were also gradually elevated during aging. An anti-FD antibody IVT potently inhibited LPS-induced complement activation in the posterior segment of the eye. This study provides insights into the dynamic profile of ocular complement activation, which is valuable for complement research in eye diseases and for developing complement therapeutics for AMD.
C1 [Crowley, Maura A.; Delgado, Omar; Will-Orrego, Adrian; Buchanan, Natasha M.; Anderson, Karen; Jaffee, Bruce D.; Dryja, Thaddeus P.; Liao, Sha-Mei] Novartis Inst Biomed Res, Cambridge, MA USA.
C3 Novartis
RP Liao, SM (通讯作者)，Novartis Inst Biomed Res, Dept Ophthalmol, 22 Windsor St, Cambridge, MA 02139 USA.
EM sha-mei.liao@novartis.com
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NR 86
TC 10
Z9 10
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2018
VL 59
IS 2
BP 940
EP 951
DI 10.1167/iovs.17-22605
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FX8LO
UT WOS:000426346300038
PM 29450541
OA gold
DA 2022-11-30
ER

PT J
AU Kivinen, N
   Felszeghy, S
   Kinnunen, AI
   Setala, N
   Aikio, M
   Kinnunen, K
   Sironen, R
   Pihlajaniemi, T
   Kauppinen, A
   Kaarniranta, K
AF Kivinen, Niko
   Felszeghy, Szabolcs
   Kinnunen, Aino I.
   Setala, Niko
   Aikio, Mari
   Kinnunen, Kati
   Sironen, Reijo
   Pihlajaniemi, Taina
   Kauppinen, Anu
   Kaarniranta, Kai
TI Absence of collagen XVIII in mice causes age-related insufficiency in
   retinal pigment epithelium proteostasis
SO BIOGERONTOLOGY
LA English
DT Article
DE Aging; Autophagy; Collagen XVIII; Macula; Retina; Animal model
ID MACULAR DEGENERATION AMD; ALZHEIMERS-DISEASE; OXIDATIVE STRESS;
   DEFICIENT MICE; BECLIN 1; AUTOPHAGY; CELLS; ENDOSTATIN; EYE; P62
AB Collagen XVIII has the structural properties of both collagen and proteoglycan. It has been found at the basement membrane/stromal interface where it is thought to mediate their attachment. Endostatin, a proteolytic fragment from collagen XVIII C-terminal end has been reported to possess anti-angiogenic properties. Age-related vision loss in collagen XVIII mutant mice has been accompanied with a pathological accumulation of deposits under the retinal pigment epithelium (RPE). We have recently demonstrated that impaired proteasomal and autophagy clearance are associated with the pathogenesis of age-related macular degeneration. This study examined the staining levels of proteasomal and autophagy markers in the RPE of different ages of the Col18a1 (-/-) mice. Eyes from 3, 6-7, 10-13 and 18 months old mice were enucleated and embedded in paraffin according to the routine protocol. Sequential 5 mu m-thick parasagittal samples were immunostained for proteasome and autophagy markers ubiquitin (ub), SQSTM1/p62 and beclin-1. The levels of immunopositivity in the RPE cells were evaluated by confocal microscopy. Collagen XVIII knock-out mice had undergone age-related RPE degeneration accompanied by an accumulation of drusen-like deposits. Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space whereas SQSTM1/p62 and beclin-1 stainings were clearly present in the basal part of RPE cell cytoplasm in the Col18a1 (-/-) mice. SQSTM1/p62 displayed mild extracellular space staining. Disturbed proteostasis regulated by collagen XVIII might be responsible for the RPE degeneration, increased protein aggregation, ultimately leading to choroidal neovascularization.
C1 [Kivinen, Niko; Kinnunen, Kati; Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
   [Kivinen, Niko; Kinnunen, Kati; Kaarniranta, Kai] Univ Eastern Finland, Kuopio, Finland.
   [Felszeghy, Szabolcs] Univ Debrecen, Fac Dent, Dept Anat Histol & Embryol, Debrecen, Hungary.
   [Kinnunen, Aino I.; Aikio, Mari; Pihlajaniemi, Taina] Univ Oulu, Bioctr Oulu, Oulu, Finland.
   [Kinnunen, Aino I.; Aikio, Mari; Pihlajaniemi, Taina] Univ Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Oulu, Finland.
   [Kinnunen, Aino I.] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Neurobiol, Bioctr Kuopio, Kuopio, Finland.
   [Setala, Niko] Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
   [Sironen, Reijo] Univ Eastern Finland, Pathol & Forens Med, Kuopio, Finland.
   [Sironen, Reijo] Univ Eastern Finland, Bioctr Kuopio, Kuopio, Finland.
   [Sironen, Reijo] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland.
   [Sironen, Reijo] Kuopio Univ Hosp, Inst Clin Med, Clin Pathol, Imaging Ctr, Kuopio, Finland.
   [Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, Kuopio, Finland.
C3 Kuopio University Hospital; University of Eastern Finland; University of
   Eastern Finland; University of Debrecen; University of Oulu; University
   of Oulu; University of Eastern Finland; Central Finland Central
   Hospital; University of Eastern Finland; University of Eastern Finland;
   University of Eastern Finland; Kuopio University Hospital; University of
   Eastern Finland; University of Eastern Finland
RP Kivinen, N (通讯作者)，Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.; Kivinen, N (通讯作者)，Univ Eastern Finland, Kuopio, Finland.
EM niko.kivinen@uef.fi
OI Kaarniranta, Kai/0000-0003-2600-8679; Pihlajaniemi,
   Taina/0000-0002-1664-9045
FU VTR grand of Kuopio University Hospital; Finnish Eye Foundation; Evald
   and Hilda Nissi Foundation; Janos Bolyai fellowship of the Hungarian
   Academy of Science
FX This research was supported by VTR grand of Kuopio University Hospital,
   The Finnish Eye Foundation, Evald and Hilda Nissi Foundation and Janos
   Bolyai fellowship of the Hungarian Academy of Science (Sz. F.). We thank
   Ewen McDonald for checking the language and warmly acknowledge the
   importance of the critical technical help from Anne Seppanen, Tunde
   Palne Terdik and Zoltan Hegyi.
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NR 64
TC 8
Z9 8
U1 1
U2 8
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 AUG
PY 2016
VL 17
IS 4
BP 749
EP 761
DI 10.1007/s10522-016-9647-7
PG 13
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA DQ6MR
UT WOS:000379319700007
PM 27125427
DA 2022-11-30
ER

PT J
AU Woodell, A
   Jones, BW
   Williamson, T
   Schnabolk, G
   Tomlinson, S
   Atkinson, C
   Rohrer, B
AF Woodell, Alex
   Jones, Bryan W.
   Williamson, Tucker
   Schnabolk, Gloriane
   Tomlinson, Stephen
   Atkinson, Carl
   Rohrer, Baerbel
TI A Targeted Inhibitor of the Alternative Complement Pathway Accelerates
   Recovery From Smoke-Induced Ocular Injury
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE alternative complement pathway; CR2-fH; knockout mouse; smoke exposure;
   mitochondria; Bruch's membrane deposits; dry age-related macular
   degeneration
ID RETINAL-PIGMENT EPITHELIUM; CAUSES OXIDATIVE DAMAGE; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; CIGARETTE-SMOKE; CHOROIDAL
   NEOVASCULARIZATION; MEDIATED INJURY; RPE CELLS; STRESS; ACTIVATION
AB PURPOSE. Morphologic and genetic evidence exists that an overactive complement system driven by the complement alternative pathway (AP) is involved in pathogenesis of age-related macular degeneration (AMD). Smoking is the only modifiable risk factor for AMD. As we have shown that smoke-related ocular pathology can be prevented in mice that lack an essential activator of AP, we ask here whether this pathology can be reversed by increasing inhibition in AP.
   METHODS. Mice were exposed to either cigarette smoke (CS) or filtered air (6 hours/day, 5 days/week, 6 months). Smoke-exposed animals were then treated with the AP inhibitor (CR2-fH) or vehicle control (PBS) for the following 3 months. Spatial frequency and contrast sensitivity were assessed by optokinetic response paradigms at 6 and 9 months; additional readouts included assessment of retinal morphology by electron microscopy (EM) and gene expression analysis by quantitative RT-PCR.
   RESULTS. The CS mice treated with CR2-fH showed significant improvement in contrast threshold compared to PBS-treated mice, whereas spatial frequency was unaffected by CS or pharmacologic intervention. Treatment with CR2-fH in CS animals reversed thinning of the retina observed in PBS-treated mice as analyzed by spectral-domain optical coherence tomography, and reversed most morphologic changes in RPE and Bruch's membrane seen in CS animals by EM.
   CONCLUSIONS. Taken together, these findings suggest that AP inhibitors not only prevent, but have the potential to accelerate the clearance of complement-mediated ocular injury. Improving our understanding of the regulation of the AP is paramount to developing novel treatment approaches for AMD.
C1 [Woodell, Alex; Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
   [Jones, Bryan W.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA.
   [Williamson, Tucker; Tomlinson, Stephen; Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA.
   [Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.
   [Atkinson, Carl] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
C3 Medical University of South Carolina; Utah System of Higher Education;
   University of Utah; Medical University of South Carolina; US Department
   of Veterans Affairs; Veterans Health Administration (VHA); Ralph H
   Johnson VA Medical Center; Medical University of South Carolina; Medical
   University of South Carolina
RP Atkinson, C (通讯作者)，Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM atkinsoc@musc.edu; rohrer@musc.edu
OI Jones, Bryan/0000-0001-5527-6643
FU National Institutes of Health (NIH) [R01EY019320, R01 NHLBI 091944, NIH
   EY015128, NIH EY02576, EY014800]; Department of Veterans Affairs [I01
   RX000444]; Research to Prevent Blindness (RPB), Inc., New York, New
   York, United States; Vision Core from Research to Prevent Blindness;
   Edward N. and Della L. Thome Memorial Foundation; NIH [C06 RR015455];
   NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY019320, R01EY015128, P30EY014800,
   R01EY024581, R01EY002576] Funding Source: NIH RePORTER; Veterans Affairs
   [I01BX003050, I01RX000444] Funding Source: NIH RePORTER
FX Supported in part by National Institutes of Health (NIH) Grants
   R01EY019320, R01 NHLBI 091944, NIH EY015128, NIH EY02576, and EY014800;
   Department of Veterans Affairs I01 RX000444; an unrestricted grant to
   the Medical University of South Carolina from Research to Prevent
   Blindness (RPB), Inc., New York, New York, United States; Vision Core,
   an unrestricted grant from Research to Prevent Blindness to the Moran
   Eye Center; Edward N. and Della L. Thome Memorial Foundation grant for
   Age-Related Macular Degeneration Research. Animal studies were conducted
   in a facility constructed with support from the NIH (C06 RR015455). CA,
   ST, and BR are patent holders for the use of CR2-fH in
   complement-dependent diseases. This patent is licensed to Alexion
   Therapeutics.
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NR 46
TC 20
Z9 20
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2016
VL 57
IS 4
BP 1728
EP 1737
DI 10.1167/iovs.15-18471
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL8XY
UT WOS:000375926700027
PM 27064393
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Miyake, M
   Tsujikawa, A
   Yamashiro, K
   Ooto, S
   Oishi, A
   Tamura, H
   Nakata, I
   Matsuda, F
   Yoshimura, N
AF Miyake, Masahiro
   Tsujikawa, Akitaka
   Yamashiro, Kenji
   Ooto, Sotaro
   Oishi, Akio
   Tamura, Hiroshi
   Nakata, Isao
   Matsuda, Fumihiko
   Yoshimura, Nagahisa
TI Choroidal Neovascularization in Eyes With Choroidal Vascular
   Hyperpermeability
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE CSC; type 1 CNV; choroidal vascular hyperpermeability; AMD; genetics
ID CENTRAL SEROUS CHORIORETINOPATHY; INDOCYANINE GREEN VIDEOANGIOGRAPHY;
   COMPLEMENT FACTOR-H; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY;
   VASCULOPATHY; THICKNESS; GENE; ANGIOGRAPHY; ASSOCIATION
AB PURPOSE. We describe the clinical and genetic characteristics of choroidal neovascularization (CNV) in eyes with choroidal vascular hyperpermeability (CVH).
   METHODS. This cross-sectional study consisted of 438 consecutive patients who underwent fluorescein and indocyanine green angiography for macular disease. We used the genotypes of 1576 age-related macular degeneration (AMD) cases and 3248 general population controls as reference groups for genetic association analyses.
   RESULTS. Of 871 eyes (438 patients) examined, CVH was found in 227 eyes (26.1%). Of these 227 eyes, 52 (22.6%) had CNV in the macular area. The proportion of patients with drusen and the choroidal thickness were not different between eyes with and without CNV, after adjusting for age (P = 0.21 and 0.95). Of the 52 eyes with CNV, 51 had type 1 CNV and only one eye had pure type 2 CNV. Of the 51 eyes with type 1 CNV, polypoidal lesions were observed in 17 eyes (33.3%). Genotype distributions of ARMS2 (A69S) and CFH (I62V) in patients with CVH and type 1 CNV significantly differed from those of AMD cases (P = 0.0014 and 0.0098, respectively), but not from general population controls (P = 0.33 and 0.82, statistical power of 88.5% and 72.9%, respectively).
   CONCLUSIONS. In patients with CVH, type 1 CNV may occur frequently and sometimes accompanies type 2 CNV or polypoidal lesions. In terms of ARMS2 and CFH, genetic background of patients with CVH and type 1 CNV was different from those with AMD, but rather similar to the general Japanese population.
C1 [Miyake, Masahiro; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Oishi, Akio; Tamura, Hiroshi; Nakata, Isao; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan.
   [Miyake, Masahiro; Nakata, Isao; Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Inserm U852, Ctr Genom Med, Kyoto 6068507, Japan.
C3 Kyoto University; Kyoto University
RP Tsujikawa, A (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Kyoto 6068507, Japan.
EM tujikawa@kuhp.kyoto-u.ac.jp
RI Oishi, Akio/AAE-9996-2020; TAMURA, Hiroshi/H-1855-2011; Miyake,
   Masahiro/V-1261-2019
OI Oishi, Akio/0000-0002-0977-9458; TAMURA, Hiroshi/0000-0002-7740-2732;
   Miyake, Masahiro/0000-0001-7410-3764; Yamashiro,
   Kenji/0000-0001-9354-8558; Tsujikawa, Akitaka/0000-0003-0779-7799
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NR 40
TC 31
Z9 33
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 MAY
PY 2014
VL 55
IS 5
BP 3223
EP 3230
DI 10.1167/iovs.14-14059
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AL9TP
UT WOS:000339484800054
PM 24781946
DA 2022-11-30
ER

PT J
AU Golbaz, I
   Ahlers, C
   Stock, G
   Schutze, C
   Schriefl, S
   Schlanitz, F
   Simader, C
   Prunte, C
   Schmidt-Erfurth, UM
AF Golbaz, Isabelle
   Ahlers, Christian
   Stock, Geraldine
   Schuetze, Christopher
   Schriefl, Sabine
   Schlanitz, Ferdinand
   Simader, Christian
   Pruente, Christian
   Schmidt-Erfurth, Ursula Margarethe
TI Quantification of the Therapeutic Response of Intraretinal, Subretinal,
   and Subpigment Epithelial Compartments in Exudative AMD during Anti-VEGF
   Therapy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; INTRAVITREAL RANIBIZUMAB; DENSITY
AB PURPOSE. To analyze the functional and morphologic effects of different ranibizumab treatment regimens on retinal and sub-retinal as well as sub-RPE compartments in neovascular age-related macular degeneration (nAMD) using spectral-domain optical coherence tomography (SD-OCT) and manual segmentation software.
   METHODS. Twenty-seven eyes of 27 patients with nAMD were examined over a 12-month period. Two treatment arms received either monthly or quarterly administered intravitreal ranibizumab. Intraretinal, subretinal, and sub-RPE volume equivalents were delineated using manual segmentation software over a defined series of B-scans obtained by SD-OCT. The mean area in pixels was calculated for each compartment at each time interval.
   RESULTS. SD-OCT and manual segmentation allowed for exact identification of intraretinal, subretinal and sub-RPE compartments and their responses to different treatment regimens. The loading dose demonstrated a corresponding treatment effect on all anatomic parameters. In contrast to the sub-RPE compartment, intraretinal fluid accumulation and subretinal fluid accumulation (SRFA) demonstrated an immediate response to ranibizumab therapy. The overall plasticity of the morphologic response declined over time. In general, SRFA demonstrated greater sensitivity for therapeutic effects and was more frequently associated with recurrent disease.
   CONCLUSIONS. An exact quantification of fluid in different anatomic compartments based on SD-OCT imaging, using appropriate segmentation software systems, may be useful to determine optimal treatment and retreatment parameters and explains the Lack of correlation of best-corrected visual acuity and conventional OCT values. (Invest Ophthalmol Vis Sci. 2011;52:1599-1605) DOI:10.1167/iovs.09-5018
C1 [Golbaz, Isabelle; Ahlers, Christian; Stock, Geraldine; Schuetze, Christopher; Schriefl, Sabine; Schlanitz, Ferdinand; Simader, Christian; Pruente, Christian; Schmidt-Erfurth, Ursula Margarethe] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, UM (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Simader,
   Christian/0000-0002-1784-2883
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NR 19
TC 56
Z9 58
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 MAR
PY 2011
VL 52
IS 3
BP 1599
EP 1605
DI 10.1167/iovs.09-5018
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 742SR
UT WOS:000288965300048
PM 21051733
DA 2022-11-30
ER

PT J
AU Wang, MH
   Chen, X
   Zhang, HP
AF Wang, Minghui
   Chen, Xiang
   Zhang, Heping
TI Maximal conditional chi-square importance in random forests
SO BIOINFORMATICS
LA English
DT Article
ID GENETICALLY COMPLEX TRAITS; FACTOR-H POLYMORPHISM; ASSOCIATION ANALYSIS;
   LINKAGE STRATEGIES; GENE POLYMORPHISMS; CLASSIFICATION; RISK;
   HAPLOTYPES; EXPRESSION; SELECTION
AB Motivation: High-dimensional data are frequently generated in genome-wide association studies (GWAS) and other studies. It is important to identify features such as single nucleotide polymorphisms (SNPs) in GWAS that are associated with a disease. Random forests represent a very useful approach for this purpose, using a variable importance score. This importance score has several shortcomings. We propose an alternative importance measure to overcome those shortcomings.
   Results: We characterized the effect of multiple SNPs under various models using our proposed importance measure in random forests, which uses maximal conditional chi-square (MCC) as a measure of association between a SNP and the trait conditional on other SNPs. Based on this importance measure, we employed a permutation test to estimate empirical P-values of SNPs. Our method was compared to a univariate test and the permutation test using the Gini and permutation importance. In simulation, the proposed method performed consistently superior to the other methods in identifying of risk SNPs. In a GWAS of age-related macular degeneration, the proposed method confirmed two significant SNPs (at the genome-wide adjusted level of 0.05). Further analysis showed that these two SNPs conformed with a heterogeneity model. Compared with the existing importance measures, the MCC importance measure is more sensitive to complex effects of risk SNPs by utilizing conditional information on different SNPs. The permutation test with the MCC importance measure provides an efficient way to identify candidate SNPs in GWAS and facilitates the understanding of the etiology between genetic variants and complex diseases.
C1 [Wang, Minghui; Chen, Xiang; Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
C3 Yale University
RP Zhang, HP (通讯作者)，Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 333 Cedar St, New Haven, CT 06520 USA.
EM heping.zhang@yale.edu
RI Chen, Xiang/N-2524-2018; Zhang, He/GXN-0028-2022
OI Chen, Xiang/0000-0002-2499-8261; 
FU National Institutes of Health [R01DA016750]; NATIONAL INSTITUTE ON DRUG
   ABUSE [R01DA016750] Funding Source: NIH RePORTER
FX This research was supported in part by grant R01DA016750 from the
   National Institutes of Health.
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NR 32
TC 28
Z9 30
U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD MAR 15
PY 2010
VL 26
IS 6
BP 831
EP 837
DI 10.1093/bioinformatics/btq038
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Computer Science, Interdisciplinary Applications; Mathematical &
   Computational Biology; Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Computer Science; Mathematical & Computational Biology; Mathematics
GA 564UO
UT WOS:000275243500017
PM 20130032
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Damani, SB
   Topol, EJ
AF Damani, Samir B.
   Topol, Eric J.
TI Future use of genomics in coronary artery disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; PREMATURE MYOCARDIAL-INFARCTION; WIDE ASSOCIATION;
   MACULAR DEGENERATION; HEART-DISEASE; LINKAGE ANALYSIS; MEF2A MUTATIONS;
   CONFERS RISK; SUSCEPTIBILITY LOCUS; GENOMEWIDE LINKAGE
AB Coronary artery disease (CAD) remains the number one cause of death in industrialized countries despite our collective efforts to minimize attributable risk from known contributors to CAD such as hypertension, dyslipidemia, and smoking. In addition, clinical trials have consistently demonstrated a family history of coronary disease to be predictive for future cardiovascular events beyond that which would be explained by traditional risk factors. These findings support and have prompted widespread investigation into the genomic basis of CAD and myocardial infarction (MI). Recent advances in genotyping technology have allowed for easier identification and confirmation of susceptibility genes for complex traits across different cohorts via increased power of studies stemming from faster accrual of cases and control subjects and more precise genetic mapping. These technological advances have resulted in defining the genes contributing to a substantial or even majority of population-attributable risk for type 2 diabetes and age-related macular degeneration (AMD) cases. Similar progress in replicating novel susceptibility genes for CAD and specifically MI is now rapidly occurring, with a recent gene marker on chromosome 9p21 representing a highly significant and common variant susceptibility factor. With improved resequencing technology and better phenotypic characterization of our CAD cases and control subjects, we should achieve successes in gene identification and confirmation similar to diabetes and AMD, thereby allowing us to better quantify CAD risk earlier in life and institute more effective therapy reducing the individual propensity to develop CAD. (J Am Coll Cardiol 2007;50:1933-40) (c) 2007 by the American College of Cardiology Foundation.
C1 Scripps Res Inst, Scripps Genom Med, La Jolla, CA 92037 USA.
   Scripps Clin, Div Cardiovasc Dis, La Jolla, CA USA.
   Scripps Hlth, Scripps Genom Med, La Jolla, CA USA.
C3 Scripps Research Institute; Scripps Research Institute
RP Topol, EJ (通讯作者)，Scripps Res Inst, Scripps Genom Med, 10550 N Torey Pines Rd,MEM-275, La Jolla, CA 92037 USA.
EM etopol@scripps.edu
OI Topol, Eric/0000-0002-1478-4729
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NR 81
TC 47
Z9 48
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD NOV 13
PY 2007
VL 50
IS 20
BP 1933
EP 1940
DI 10.1016/j.jacc.2007.07.062
PG 8
WC Cardiac & Cardiovascular Systems
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 231GR
UT WOS:000250935100001
PM 17996556
OA Bronze
DA 2022-11-30
ER

PT J
AU Olivo, M
   Ali-Seyed, M
AF Olivo, Malini
   Ali-Seyed, Mohamed
TI Apoptosis signalling mechanisms in human cancer cells induced by
   Calphostin-PDT
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE photodynamic therapy; Calphostin C; caspases nasopharyngeal carcinoma;
   apoptosis
ID PROTEIN-KINASE-C; HYPERICIN-INDUCED APOPTOSIS; PHOTODYNAMIC THERAPY;
   CARCINOMA-CELLS; MEDIATED APOPTOSIS; ANTICANCER AGENTS; TUMOR-CELLS;
   IN-VITRO; DEATH; FAS
AB Photodynamic therapy (PDT) is a promising treatment that is approved by the US FDA for the treatment of oesophageal and lung cancer as well as for age-related macular degeneration. In this study, using standard tissue culture techniques, the photo cytotoxicity and apoptotic mechanisms of Calphostin C (Cal C), a perylenequinone microbial compound in combination with visible light dose was examined in different tumor cell lines. Our results demonstrated both a time and drug-light dose dependence in Cal-C-PDT induced photo toxicity and apoptotic cell death. The induction of apoptosis by Cal C-PDT was found to transit to necrotic cell death at higher drug and light doses. The detection of apoptosis in irradiated tumor cells was performed using various approaches including cell morphology analysis, flow cytometry [DNA fragmentation and phosphatidylserine (PS) externalization] and biochemical assays (activation of caspases). Time-course analysis of Cal C cellular uptake and distribution showed a rapid increase within the cellular compartments. The activation of caspases and nuclear fragmentation was evidenced at a maximum time point of 3 h after irradiation. By the use of specific caspase substrates, significant activation of caspase-8 and -3 was found. Mitochondrial involvement during Cal C-PDT-induced apoptosis was proven by a rapid reduction of the mitochondrial membrane potential. Furthermore, Cal C-PDT also enhanced FasL expression, which then induced Fas signalling-dependent cell death in NPC and colon cancer cell lines tested. Our results contribute to a deeper understanding of the processes involved in apoptotic cell death following photodynamic treatment with Cal C.
C1 Natl Canc Ctr, Div Med Sci, Singapore 169610, Singapore.
   Natl Univ Singapore, Dept Pharm, Singapore 117548, Singapore.
   Emory Univ, Dept Pathol, Atlanta, GA 30322 USA.
   Emory Univ, Lab Med, Atlanta, GA 30322 USA.
C3 National Cancer Centre Singapore (NCCS); National University of
   Singapore; Emory University; Emory University
RP Olivo, M (通讯作者)，Natl Canc Ctr, Div Med Sci, 11 Hosp Dr, Singapore 169610, Singapore.
EM dmsmcd@nccs.com.sg
OI Olivo, Malini/0000-0002-1795-8683; Seyed, Mohamed
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NR 46
TC 16
Z9 18
U1 0
U2 6
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAR
PY 2007
VL 30
IS 3
BP 537
EP 548
PG 12
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 136IO
UT WOS:000244216000001
PM 17273754
DA 2022-11-30
ER

PT J
AU Osborne, NN
   Wood, JPM
AF Osborne, Neville N.
   Wood, John P. M.
TI The beta-adrenergic receptor antagonist metipranolol blunts zinc-induced
   photoreceptor and RPE apoptosis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CORTICAL NEURONAL DEATH; PROTEIN-KINASE-C; LIPID-PEROXIDATION; OXIDATIVE
   STRESS; EPITHELIAL-CELLS; ORAL ZINC; RAT-BRAIN; ANTIOXIDANT; INDUCTION;
   LOCALIZATION
AB PURPOSE. To determine the effect of zinc on retinal cells at concentrations at which it is known to cause oxidative stress. Furthermore, the effects of metipranolol, known to prevent retinal damage, and of other antiglaucoma drugs were determined on zinc- injured retinal cells.
   METHODS. Lipid peroxidation assays were conducted on rat brain and bovine retina - retinal pigment epithelial ( RPE) membrane preparations. Immunohistochemistry, immunoblot analysis and the terminal- deoxynucleotidyl transferase dUTP- linked nick- end labeling ( TUNEL) procedure determined the effects of zinc with or without trolox or metipranolol on photoreceptor death in situ. The effect of treatments on cultured RPE cells was analyzed using cell viability assays, immunoblot analysis, and the TUNEL procedure.
   RESULTS. Zinc- induced lipid peroxidation of rat brain and bovine retina - RPE membranes, although the effect of the latter was of a ( twofold) greater magnitude. Both effects, however, were similarly attenuated by metipranolol, desacetylmetipranolol, and trolox. Antiglaucoma drugs other than metipranolol had no effect. Intraocular injection of 150 mu M zinc and treatment of cultured RPE cells with zinc led to mainly photoreceptor apoptosis and apoptotic death of RPE cells ( 50% death at 18 mu M rising to 10% at 50 mu M), respectively. Zinc- induced apoptosis of cultured RPE cells and photoreceptors were attenuated only by metipranolol and trolox.
   CONCLUSIONS. The combined data suggest that oxidative injury to RPE cells and photoreceptors may be caused by elevated levels of zinc in diseases such as age- related macular degeneration ( AMD) and that metipranolol may act as an efficacious antioxidant to blunt this process.
C1 Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England.
C3 University of Oxford
RP Osborne, NN (通讯作者)，Univ Oxford, Nuffield Lab Ophthalmol, Walton St, Oxford OX2 6AW, England.
EM neville.osborne@eye.ox.ac.uk
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NR 64
TC 15
Z9 16
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 2006
VL 47
IS 7
BP 3178
EP 3186
DI 10.1167/iovs.05-1370
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 058TX
UT WOS:000238688600057
PM 16799065
DA 2022-11-30
ER

PT J
AU Becker, S
   Wahl, HW
   Schilling, O
   Burmedi, D
AF Becker, S
   Wahl, HW
   Schilling, O
   Burmedi, D
TI Assistive device use in visually impaired older adults: Role of control
   beliefs
SO GERONTOLOGIST
LA English
DT Article
DE age-related low vision; age-reloted macular degeneration; assistive
   device use; control theory; psychological factors
ID MACULAR DEGENERATION; VISION LOSS
AB Purpose: We investigate whether psychological control, conceptually framed within the life-span theory of control by Heckhausen and Schulz, drives assistive device use in visually impaired elders. In particular, we expect the two primary control modes differentiated in the life-span theory of control (i.e., selective primary and compensatory primary control) to be positively related to assistive device use. We present cross-sectional as well as repeated measures analyses. Design and Methods: We assessed a sample of 71 participants (age, M = 79.5 years) suffering from age-related macular degeneration at two measurement occasions covering a 1-year interval. In addition to the application of a standardized control questionnaire based on the life-span theory of control distinctions of different control modes, we measured assistive device use as the reported number of devices used, based on a given list. Results: On the bivariate level, we could find the theoretically expected relation between selective primary control and selective compensatory control only for the analyses at Time 1. We used multiple regression models to acknowledge overlapping variance beneath the different control modes; we did this separately for both measurement occasions. Consistent with our expectation, we found selective primary control to be a significant predictor of assistive device use at Time 1, whereas after a 1-year period of disease progression, compensatory primary control took over at Time 2. Implications: Findings provide empirical support for the assumption that educational programs related to assistive device use in visually impaired elders also should take psychological control issues more strongly into consideration.
C1 Univ Heidelberg, German Ctr Res Ageing, D-69115 Heidelberg, Germany.
   Univ Heidelberg, Inst Gerontol, D-69115 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg; Ruprecht Karls University
   Heidelberg
RP Wahl, HW (通讯作者)，Univ Heidelberg, German Ctr Res Ageing, Bergheimer Str 20, D-69115 Heidelberg, Germany.
EM wahl@dzfa.uni-heidelberg.de
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NR 22
TC 13
Z9 13
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD DEC
PY 2005
VL 45
IS 6
BP 739
EP 746
DI 10.1093/geront/45.6.739
PG 8
WC Gerontology
WE Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA 989UN
UT WOS:000233699500003
PM 16326655
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Ratanasukon, M
   Kittantong, A
AF Ratanasukon, M
   Kittantong, A
TI Results of intravitreal tissue plasminogen activator and expansile gas
   injection for submacular haemorrhage in Thais
SO EYE
LA English
DT Article
DE age-related macular degeneration; submacular haemorrhage; tissue
   plasminogen activator; vitreous haemorrhage
ID EXPERIMENTAL SUBRETINAL HEMORRHAGE; POLYPOIDAL CHOROIDAL VASCULOPATHY;
   MACULAR DEGENERATION; NATURAL-HISTORY; MANAGEMENT
AB Purpose To study the results of intravitreal tissue plasminogen activator (tPA) and expansile gas injection for submacular haemorrhage in Thai patients.
   Methods The medical records of Thai patients who presented with submacular haemorrhage between January 1998 and December 2002 were reviewed. The inclusion criteria were acute onset of bleeding (< 1 month), treatment with intravitreal injection of tPA solution (50 - 100 mg in 0.1 ml) and expansile gas (0.3 - 0.4 ml of 100% perfluoropropane or sulphur hexafluoride), and at least 6 months of follow-up. Our main outcome measures were best final postoperative visual acuity and surgical complications.
   Results A total of 19 eyes of 19 patients completed the inclusion criteria with a mean duration of 13.1 days. The causes of haemorrhage were age-related macular degeneration in 15 eyes (78.9%), idiopathic choroidal neovascularization in two eyes (10.5%), and traumatic, and valsalva retinopathy in one eye each (5.2%). After a mean follow-up of 13 months (range 6 - 39 months), postoperative visual acuity improved two lines or greater in 12 eyes (63.2%), stabilized in six eyes (31.6%) and worsened in one (5.2%). The final visual acuity measured 20/63 or better in 10 eyes (52.6%). The surgical complications were breakthrough vitreous haemorrhage ( three eyes) and cataracts ( three eyes), and two had retinal detachments.
   Conclusion The treatment of submacular haemorrhage with intravitreal injection of tPA and expansile gas improved visual acuity in more than half of the patients. In all, 10 in 19 eyes demonstrated final visual acuity at a functional level.
C1 Prince Songkla Univ, Fac Med, Dept Ophthalmol, Hat Yai 90110, Thailand.
C3 Prince of Songkla University
RP Ratanasukon, M (通讯作者)，Prince Songkla Univ, Fac Med, Dept Ophthalmol, Hat Yai 90110, Thailand.
EM mratanasukon@yahoo.com
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NR 16
TC 11
Z9 11
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD DEC
PY 2005
VL 19
IS 12
BP 1328
EP 1332
DI 10.1038/sj.eye.6701769
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 992AX
UT WOS:000233857300016
PM 15565185
OA Bronze
DA 2022-11-30
ER

PT J
AU Sengupta, N
   Caballero, S
   Mames, RN
   Butler, JM
   Scott, EW
   Grant, MB
AF Sengupta, N
   Caballero, S
   Mames, RN
   Butler, JM
   Scott, EW
   Grant, MB
TI The role of adult bone marrow-derived stem cells in choroidal
   neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CD34(+) CELLS;
   MIGRATION; EXPRESSION; ADHESION; RETINOPATHY; BLOOD
AB PURPOSE. Age-related macular degeneration (ARMD) is the primary cause of blindness in people aged of 50 years or more. The wet form leads to severe loss of central vision. Recent evidence supports that adult hematopoietic stem cells (HSCs) contribute to preretinal neovascularization. In the current study, it was determined whether HSC, by producing both blood and blood, vessels, provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice.
   METHODS. Gfp chimeric mice were-developed by bone marrow ablation of C57BL/6J mice and reconstitution with donor tissue from gfp(+/+) transgenic mice. Up chimeric mice underwent laser rupture of Bruch's membrane and were killed and eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by confocal microscopy of retinal flatmounts. Because endothelial progenitor cells (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the EPC contribution to CNV.
   RESULTS. Laser injury alone was sufficient to induce stem cell recruitment and subsequent CNV. Gfp(+) cells formed part of the functional vasculature in the choroid as early as 1 week after injury and were present for, the. duration of the study. The relative EPC contribution to CNV remained fairly constant throughout the study and constituted almost 50% of the total vasculature.
   CONCLUSIONS. Adult stem cells are recruited to the choroid in a model of CNV, where they contribute to forming aberrant new vessels. This observation suggests that targeting stem cell recruitment to the eye may offer a novel therapeutic strategy for ARMD.
C1 Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
   Univ Florida, Program Stem Cell Biol, Gainesville, FL 32610 USA.
   Retina Ctr, Gainesville, FL USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida
RP Grant, MB (通讯作者)，Univ Florida, Dept Pharmacol & Therapeut, POB 100267, Gainesville, FL 32610 USA.
EM grantma@pharmacology.ufl.edu
FU NATIONAL EYE INSTITUTE [R29EY007739, R01EY012601, R01EY007739] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY007739, EY012601] Funding Source:
   Medline
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NR 33
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Z9 132
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2003
VL 44
IS 11
BP 4908
EP 4913
DI 10.1167/iovs.03-0342
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 737LL
UT WOS:000186231800043
PM 14578416
DA 2022-11-30
ER

PT J
AU Togacar, M
   Ergen, B
   Tumen, V
AF Togacar, Mesut
   Ergen, Burhan
   Tumen, Vedat
TI Use of dominant activations obtained by processing OCT images with the
   CNNs and slime mold method in retinal disease detection
SO BIOCYBERNETICS AND BIOMEDICAL ENGINEERING
LA English
DT Article
DE Retinal disease; Slime mold algorithm; Transfer learning; Selection of
   dominant activations; Optical coherence tomography
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; AUTOMATED DETECTION
AB Retinal disease is one of the diseases that cause visual symptoms or loss of vision in humans. This disease can affect the choroid, which severely affects vision. Optical coher-ence tomography (OCT) images are usually used to detect retinal disease. OCT is an imag-ing technique that takes high-resolution slices of retinal images. It takes time for experts to examine and interpret the OCT images. Experts need to take advantage of technological capabilities to make this process faster and more accurate. Three datasets were used in this study. Dataset #1 (UCSD dataset) consists of choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal OCT image types. Dataset #2 (Duke dataset) and Dataset #3 consist of age-related macular degeneration (AMD), DME, and normal OCT image types. An artificial intelligence based hybrid approach was proposed for retinal disease detection. In the proposed approach, class-based activations were extracted for each model with nine transfer learning models using the dataset. Next, the dominant acti-vations were selected from the model-based activations of each class using the slime mold algorithm (SMA) and the selected activations were classified using the softmax method. The overall accuracy obtained in classification is as follows: 99.60% for dataset 1, 99.89% for dataset #2 and 97.49% for dataset #3. In this study, it was found that the proposed approach contributes to the performance of transfer learning models.(c) 2022 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
C1 [Togacar, Mesut] Firat Univ, Tech Sci Vocat Sch, Comp Technol Dept, Elazig, Turkey.
   [Ergen, Burhan] Firat Univ, Fac Engn, Dept Comp Engn, Elazig, Turkey.
   [Tumen, Vedat] Bitlis Eren Univ, Fac Engn & Architecture, Dept Comp Engn, Bitlis, Turkey.
C3 Firat University; Firat University; Bitlis Eren University
RP Togacar, M (通讯作者)，Firat Univ, Tech Sci Vocat Sch, Comp Technol Dept, Elazig, Turkey.
EM mtogacar@firat.edu.tr; bergen@firat.edu.tr; vtumen@beu.edu.tr
RI TOĞAÇAR, Mesut/W-1628-2018
OI TOĞAÇAR, Mesut/0000-0002-8264-3899; TUMEN, VEDAT/0000-0003-0271-216X
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Z9 0
U1 3
U2 3
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0208-5216
J9 BIOCYBERN BIOMED ENG
JI Biocybern. Biomed. Eng.
PD APR-JUN
PY 2022
VL 42
IS 2
BP 646
EP 666
DI 10.1016/j.bbe.2022.05.005
PG 21
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 2H8BP
UT WOS:000814514700004
DA 2022-11-30
ER

PT J
AU Chuang, CJ
   Wang, ML
   Yeh, JH
   Chen, TC
   Tsou, SC
   Lee, YJ
   Chang, YY
   Lin, HW
AF Chuang, Chen-Ju
   Wang, Meilin
   Yeh, Jui-Hsuan
   Chen, Tzu-Chun
   Tsou, Shang-Chun
   Lee, Yi-Ju
   Chang, Yuan-Yen
   Lin, Hui-Wen
TI The Protective Effects of alpha-Mangostin Attenuate Sodium
   Iodate-Induced Cytotoxicity and Oxidative Injury via Mediating SIRT-3
   Inactivation via the PI3K/AKT/PGC-1 alpha Pathway
SO ANTIOXIDANTS
LA English
DT Article
DE age-related macular degeneration (AMD); oxidative stress; retinal
   pigment epithelial (RPE); alpha-mangostin (alpha-MG); antiapoptotic;
   antioxidant
ID PIGMENT EPITHELIAL-CELLS; HYDROGEN-PEROXIDE; XANTHONES; STRESS;
   ACTIVATION; DAMAGE
AB It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (alpha-mangostin, alpha-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with alpha-MG (0, 3.75, 7.5, and 15 mu M) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with alpha-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1 alpha-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that alpha-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that alpha-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.
C1 [Chuang, Chen-Ju] Kaohsiung Municipal United Hosp, Emergency Dept, Kaohsiung 80457, Taiwan.
   [Wang, Meilin; Chang, Yuan-Yen] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Sch Med, Dept Microbiol & Immunol,Clin Lab, Taichung 40201, Taiwan.
   [Yeh, Jui-Hsuan; Chen, Tzu-Chun] Chung Shan Med Univ, Inst Med, Taichung 40201, Taiwan.
   [Tsou, Shang-Chun] Chung Shan Med Univ, Dept Nutr, Taichung 40201, Taiwan.
   [Lee, Yi-Ju] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Pathol, 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 40402, Taiwan.
C3 Chung Shan Medical University; Chung Shan Medical University Hospital;
   Chung Shan Medical University; Chung Shan Medical University; Chung Shan
   Medical University; Chung Shan Medical University Hospital; Asia
   University Taiwan; China Medical University Taiwan; China Medical
   University Hospital - Taiwan
RP Chang, YY (通讯作者)，Chung Shan Med Univ, Chung Shan Med Univ Hosp, Sch Med, Dept Microbiol & Immunol,Clin Lab, 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 40402, Taiwan.
EM ilovespurs168@gmail.com; eq7bie5d@gmail.com; jasmine.lyl@gmail.com;
   cyy0709@csmu.edu.tw; d9138001@asia.edu.tw
OI Chang, Yuan-Yen/0000-0001-6395-4280
FU Chung Shan Medical University [NCHU-CSMU-10708, NCHU-CSMU-10910];
   Ministry of Science and Technology, Taiwan [MOST-108-2320-B-468-002,
   MOST-109-2320-B-040-019-MY3, MOST-109-2320-B-468-004-MY3]
FX FundingThe authors would like to thank the Chung Shan Medical University
   (project numbers: NCHU-CSMU-10708, and NCHU-CSMU-10910), and the
   Ministry of Science and Technology, Taiwan (project numbers:
   MOST-108-2320-B-468-002, MOST-109-2320-B-040-019-MY3, and
   MOST-109-2320-B-468-004-MY3) for financially supporting this research.
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NR 41
TC 3
Z9 3
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 DEC
PY 2021
VL 10
IS 12
AR 1870
DI 10.3390/antiox10121870
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 XW2UJ
UT WOS:000735480600001
PM 34942973
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kureshi, R
   Zhu, A
   Shen, JK
   Tzeng, SY
   Astrab, LR
   Sargunas, PR
   Green, JJ
   Campochiaro, PA
   Spangler, JB
AF Kureshi, Rakeeb
   Zhu, Angela
   Shen, Jikui
   Tzeng, Stephany Y.
   Astrab, Leilani R.
   Sargunas, Paul R.
   Green, Jordan J.
   Campochiaro, Peter A.
   Spangler, Jamie B.
TI Structure-Guided Molecular Engineering of a Vascular Endothelial Growth
   Factor Antagonist to Treat Retinal Diseases
SO CELLULAR AND MOLECULAR BIOENGINEERING
LA English
DT Article
DE Ocular neovascularization; Vascular endothelial growth factor receptor;
   Directed evolution; Affinity engineering; Nonviral gene therapy
ID MACULAR DEGENERATION; DRUG-DELIVERY; VEGF; RANIBIZUMAB; BINDING;
   NEUTRALIZATION; BEVACIZUMAB; ANTIBODIES; INJECTION; THERAPY
AB Background Ocular neovascularization is a hallmark of retinal diseases including neovascular age-related macular degeneration and diabetic retinopathy, two leading causes of blindness in adults. Neovascularization is driven by the interaction of soluble vascular endothelial growth factor (VEGF) ligands with transmembrane VEGF receptors (VEGFR), and inhibition of the VEGF pathway has shown tremendous clinical promise. However, anti-VEGF therapies require invasive intravitreal injections at frequent intervals and high doses, and many patients show incomplete responses to current drugs due to the lack of sustained VEGF signaling suppression. Methods We synthesized insights from structural biology with molecular engineering technologies to engineer an anti-VEGF antagonist protein. Starting from the clinically approved decoy receptor protein aflibercept, we strategically designed a yeast-displayed mutagenic library of variants and isolated clones with superior VEGF affinity compared to the clinical drug. Our lead engineered protein was expressed in the choroidal space of rat eyes via nonviral gene delivery. Results Using a structure-informed directed evolution approach, we identified multiple promising anti-VEGF antagonist proteins with improved target affinity. Improvements were primarily mediated through reduction in dissociation rate, and structurally significant convergent sequence mutations were identified. Nonviral gene transfer of our engineered antagonist protein demonstrated robust and durable expression in the choroid of treated rats one month post-injection. Conclusions We engineered a novel anti-VEGF protein as a new weapon against retinal diseases and demonstrated safe and noninvasive ocular delivery in rats. Furthermore, our structure-guided design approach presents a general strategy for discovery of targeted protein drugs for a vast array of applications.
C1 [Kureshi, Rakeeb; Tzeng, Stephany Y.; Astrab, Leilani R.; Green, Jordan J.; Spangler, Jamie B.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Zhu, Angela; Astrab, Leilani R.; Sargunas, Paul R.; Green, Jordan J.; Spangler, Jamie B.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
   [Shen, Jikui; Green, Jordan J.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Shen, Jikui; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Tzeng, Stephany Y.; Green, Jordan J.; Spangler, Jamie B.] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD USA.
   [Tzeng, Stephany Y.; Green, Jordan J.] Johns Hopkins Univ, Inst Nanobiotechnol, Baltimore, MD USA.
   [Green, Jordan J.] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21218 USA.
   [Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins Medicine; Johns Hopkins University; Johns
   Hopkins University; Johns Hopkins University; Johns Hopkins University;
   Johns Hopkins University
RP Spangler, JB (通讯作者)，Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
EM Jamie.spangler@jhu.edu
RI Green, Jordan/B-9001-2009
OI Green, Jordan/0000-0003-4176-3808; Sargunas, Paul/0000-0003-4455-9669;
   Spangler, Jamie/0000-0001-8187-3732
FU NIH [R01EY031097, R01CA228133]; E. Matilda Ziegler Foundation for the
   Blind; Louis B. Thalheimer Translational Fund; Research to Prevent
   Blindness
FX The authors thank Patrick James Krohl for technical assistance with the
   project. The authors also acknowledge the NIH (R01EY031097,
   R01CA228133), the E. Matilda Ziegler Foundation for the Blind, the Louis
   B. Thalheimer Translational Fund, and Research to Prevent Blindness (Dr.
   H. James and Carole Free Catalyst Award and unrestricted grant) for
   support.
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NR 52
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 1865-5025
EI 1865-5033
J9 CELL MOL BIOENG
JI Cell. Mol. Bioeng.
PD OCT
PY 2020
VL 13
IS 5
SI SI
BP 405
EP 418
DI 10.1007/s12195-020-00641-0
EA JUL 2020
PG 14
WC Cell & Tissue Engineering; Biophysics; Cell Biology; Engineering,
   Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biophysics; Engineering
GA OM6SD
UT WOS:000554317800001
PM 33184574
OA Green Published
DA 2022-11-30
ER

PT J
AU Terauchi, G
   Shinoda, K
   Sakai, H
   Kawashima, M
   Matsumoto, CS
   Mizota, A
   Miyake, Y
AF Terauchi, Gaku
   Shinoda, Kei
   Sakai, Hiroyuki
   Kawashima, Makoto
   Matsumoto, Celso Soiti
   Mizota, Atsushi
   Miyake, Yozo
TI Retinal function determined by flicker ERGs before and soon after
   intravitreal injection of anti-VEGF agents
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Age-related macular degeneration; Electroretinogram;
   Intravitreal injection; Macular edema; Ranibizumab; Retinal vein
   occlusion; Vascular endothelial growth factor
ID DIABETIC MACULAR EDEMA; TRAP-EYE; RANIBIZUMAB; AFLIBERCEPT; BEVACIZUMAB;
   THERAPY; TIME; ENDOPHTHALMITIS; VITRECTOMY; MORPHOLOGY
AB BackgroundTo evaluate the retinal function before and soon after an intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agents.MethodsSeventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval (R) system was used to record 28Hz flicker electroretinograms (ERGs) from the injected and non-injected eyes before (Phase 1, P1), within 2h after the injection (P2), and 2 to 24h after the injection (P3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests.ResultsThe amplitudes were not significantly different at the three phases. The implicit time of the injected eye was 31.23.2msec at P1, and it was not significantly different at P2 (31.7 +/- 3.1msec) but it was significantly longer at P3 (32.2 +/- 3.3msec, P<0.01, ANOVA for both). The implicit time in the non-injected fellow eye was 30.5 +/- 3.3msec at P1, and it was significantly longer at P2 (31.1 +/- 3.2msec) and phase 3 (31.3 +/- 3.4msec, P<0.01, ANOVA for both).Conclusions The results indicate that an intravitreal anti-VEGF injection will increase the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection.
C1 [Terauchi, Gaku; Shinoda, Kei; Sakai, Hiroyuki; Kawashima, Makoto; Matsumoto, Celso Soiti; Mizota, Atsushi] Teikyo Univ, Sch Med, Dept Ophthalmol, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan.
   [Shinoda, Kei] Saitama Med Univ, Fac Med, Dept Ophthalmol, 38 Moro Hongo, Moroyama, Saitama 3500495, Japan.
   [Matsumoto, Celso Soiti] Matsumoto Eye Clin, 50-2 Takagaki,Awa Cho, Awa, Tokushima 7711705, Japan.
   [Miyake, Yozo] Aichi Med Univ, Sch Med, Dept Ophthalmol, 1-1 Yazakokarimata, Nagakute, Aichi 4801195, Japan.
C3 Teikyo University; Saitama Medical University; Aichi Medical University
RP Shinoda, K (通讯作者)，Teikyo Univ, Sch Med, Dept Ophthalmol, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan.; Shinoda, K (通讯作者)，Saitama Med Univ, Fac Med, Dept Ophthalmol, 38 Moro Hongo, Moroyama, Saitama 3500495, Japan.
EM shinok@saitama-med.ac.jp
RI Shinoda, Kei/ABC-7993-2020
OI Shinoda, Kei/0000-0002-1543-9345
FU Research Grants on Sensory and Communicative Disorders from the Ministry
   of Health, Labor, and Welfare, Japan
FX Support of this study was provided by Research Grants on Sensory and
   Communicative Disorders from the Ministry of Health, Labor, and Welfare,
   Japan.
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NR 36
TC 4
Z9 5
U1 0
U2 4
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUN 17
PY 2019
VL 19
AR 129
DI 10.1186/s12886-019-1129-7
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ID7WA
UT WOS:000471892300003
PM 31208350
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Qin, J
   Rinella, N
   Zhang, QQ
   Zhou, H
   Wong, J
   Deiner, M
   Roorda, A
   Porco, TC
   Wang, RK
   Schwartz, DM
   Duncan, JL
AF Qin, Jia
   Rinella, Nicholas
   Zhang, Qinqin
   Zhou, Hao
   Wong, Jessica
   Deiner, Michael
   Roorda, Austin
   Porco, Travis C.
   Wang, Ruikang K.
   Schwartz, Daniel M.
   Duncan, Jacque L.
TI OCT Angiography and Cone Photoreceptor Imaging in Geographic Atrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE adaptive optics scanning laser ophthalmoscopy; geographic atrophy; swept
   source optical coherence tomography angiography
ID ADAPTIVE OPTICS; MACULAR DEGENERATION; EYES; FLOW
AB PURPOSE. To compare cone spacing and choriocapillaris (CC) perfusion adjacent to geographic atrophy (GA) in patients with age-related macular degeneration (AMD) and age-similar normal eyes.
   METHODS. Subjects were imaged using adaptive optics scanning laser ophthalmoscopy (AOSLO), fundus autofluorescence (FAF), and swept-source optical coherence tomography angiography. The GA border was identified using FAF images; CC flow void was analyzed in 18 regions extending from the GA border. A grader masked to CC perfusion selected regions of interest (ROIs) with unambiguous cone mosaics in AOSLO images. At each ROI, cone spacing and CC flow void were converted to Z-scores (standard deviations from the mean of 12 normal eyes aged 50 to 81 years for cone spacing, and 60 normal eyes age 51 to 88 years for CC flow void).
   RESULTS. Excluding regions of GA and drusen, CC flow void in eight eyes of six patients with AMD was significantly greater than in four age-similar normal eyes (exact permutation test, P = 0.024). CC flow void was negatively correlated with distance from the GA margin (r = -0.35; 95% confidence interval [CI], -0.53 to -0.12). Increased cone spacing was significantly correlated with CC flow void (r = 0.33; 95% CI, 0.12 to 0.59). Cone spacing was increased in 39% of ROIs, while CC flow void was increased in 96% of ROIs.
   CONCLUSIONS. In eyes with GA due to AMD, CC hypoperfusion was significantly correlated with, and more extensive than, cone photoreceptor loss. The results suggest that reduced CC perfusion contributes to the development of GA.
C1 [Qin, Jia; Rinella, Nicholas; Wong, Jessica; Deiner, Michael; Porco, Travis C.; Schwartz, Daniel M.; Duncan, Jacque L.] Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way K113, San Francisco, CA 94143 USA.
   [Zhang, Qinqin; Zhou, Hao; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
   [Roorda, Austin] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
   [Roorda, Austin] Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA.
   [Porco, Travis C.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco;
   University of Washington; University of Washington Seattle; University
   of California System; University of California Berkeley; University of
   California System; University of California Berkeley; University of
   California System; University of California San Francisco
RP Duncan, JL (通讯作者)，Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way K113, San Francisco, CA 94143 USA.
EM jacque.duncan@ucsf.edu
RI ; Zhou, Hao/U-7850-2017
OI Wang, Ruikang/0000-0001-5169-8822; Zhou, Hao/0000-0003-0068-5102
FU NIH [EY002162, EY 024239, EY024158, FDA R01-41001]; Research to Prevent
   Blindness; Bernard A. Newcomb Macular Degeneration Fund; That Man May
   See, Inc.; Hope for Vision; Foundation Fighting Blindness; Beckman
   Initiative for Macular Research Grant [1201]; Claire Giannini Fund; L.L.
   Hillblom Foundation Research Network Grant; Hedco Foundation; Pritzker
   Foundation; NEI ARVO; NATIONAL EYE INSTITUTE [R01EY024158, P30EY002162]
   Funding Source: NIH RePORTER
FX Supported by NIH Grants NIH EY002162, EY 024239, EY024158, and FDA
   R01-41001; Research to Prevent Blindness; The Bernard A. Newcomb Macular
   Degeneration Fund; That Man May See, Inc.; Hope for Vision; Foundation
   Fighting Blindness; Beckman Initiative for Macular Research Grant 1201;
   The Claire Giannini Fund; L.L. Hillblom Foundation Research Network
   Grant; The Hedco Foundation; and The Pritzker Foundation. An NEI ARVO
   Travel Award provided support to present some of the results at the
   annual ARVO meeting in Baltimore, MD.
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NR 36
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 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2018
VL 59
IS 15
BP 5985
EP 5992
DI 10.1167/iovs.18-25032
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HF5EU
UT WOS:000454256200019
PM 30572343
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cao, L
   Liu, J
   Pu, J
   Milne, G
   Chen, M
   Xu, HP
   Shipley, A
   Forrester, JV
   McCaig, CD
   Lois, N
AF Cao, Lin
   Liu, Jie
   Pu, Jin
   Milne, Gillian
   Chen, Mei
   Xu, Heping
   Shipley, Alan
   Forrester, John V.
   McCaig, Colin D.
   Lois, Noemi
TI Polarized retinal pigment epithelium generates electrical signals that
   diminish with age and regulate retinal pathology
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE ATP1B1; CCL2; CX3CR1 double knockout mice; cell-cell connection;
   extracellular electrical signalling
ID MACULAR DEGENERATION; CELL LINE; INTERPHOTORECEPTOR MATRIX;
   ISCHEMIC-INJURY; MOUSE MODELS; ANIMAL-MODEL; FACTOR PEDF; IN-VIVO;
   EXPRESSION; FIELDS
AB The transepithelial potential difference (TEP) across the retinal pigment epithelial (RPE) is dependent on ionic pumps and tight junction seals between epithelial cells. RPE cells release neurotrophic growth factors such as pigment epithelial derived factor (PEDF), which is reduced in age-related macular degeneration (AMD). The mechanisms that control the secretion of PEDF from RPE cells are not well understood. Using the CCL2/CX3CR1 double knockout mouse model (DKO), which demonstrates RPE damage and retinal degeneration, we uncovered an interaction between PEDF and the TEP which is likely to play an important role in retinal ageing and in the pathogenesis of AMD. We found that: (a) the expression of ATP1B1 (the Na+/K+-ATPase 1 subunit) was reduced significantly in RPE from aged mice, in patients with CNV (Choroidal Neovascularization) and in DKO mice; (b) the expression of PEDF also was decreased in aged persons and in DKO mice; (c) the TEP across RPE was reduced markedly in RPE cells from DKO mice and (d) an applied electric field (EF) of 50-100mV/mm, used to mimic the natural TEP, increased the expression and secretion of PEDF in primary RPE cells. In conclusion, the TEP across the RPE depends on the expression of ATP1B1 and this regulates the secretion of PEDF by RPE cells and so may regulate the onset of retinal disease. Increasing the expression of PEDF using an applied EF to replenish a disease or age-reduced TEP may offer a new way of preventing or reversing retinal dysfunction.
C1 [Cao, Lin; Pu, Jin; Milne, Gillian; Forrester, John V.; McCaig, Colin D.] Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Cao, Lin] Yizhou Int Proton Med Ctr & Canc Hosp, Shijiazhuang, Hebei, Peoples R China.
   [Liu, Jie] Chinese Peoples Liberat Army Gen Hosp, Hosp Affiliated 1, Dept Ophthalmol, Beijing, Peoples R China.
   [Chen, Mei; Xu, Heping; Lois, Noemi] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
   [Shipley, Alan] Univ New England, Biol Res & Dev, Biddeford, ME USA.
C3 University of Aberdeen; Chinese People's Liberation Army General
   Hospital; Queens University Belfast; University of New England - Maine
RP McCaig, CD (通讯作者)，Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.; Lois, N (通讯作者)，Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM c.mccaig@abdn.ac.uk; n.lois@qub.ac.uk
RI Xu, Heping/A-4430-2008
OI Xu, Heping/0000-0003-4000-931X; Milne, Gillian/0000-0003-1153-2646
FU Fight for Sight [1712/13, 1361/1362]; NHS Grampian Endowments, Friends
   of ANCHOR, Action Medical Research [GN2299]
FX Fight for Sight, Grant/Award Number: 1712/13, 1361/1362; NHS Grampian
   Endowments, Friends of ANCHOR, Action Medical Research, Grant/Award
   Number: GN2299
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NR 70
TC 5
Z9 5
U1 1
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD NOV
PY 2018
VL 22
IS 11
BP 5552
EP 5564
DI 10.1111/jcmm.13829
PG 13
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA GY1IF
UT WOS:000448279600034
PM 30160348
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Poddar, R
   Migacz, JV
   Schwartz, DM
   Werner, JS
   Gorczynska, I
AF Poddar, Raju
   Migacz, Justin V.
   Schwartz, Daniel M.
   Werner, John S.
   Gorczynska, Iwona
TI n Challenges and advantages in wide-field optical coherence tomography
   angiography imaging of the human retinal and choroidal vasculature at
   1.7-MHz A-scan rate
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE optical coherence tomography; retinal blood flow; choroidal blood flow;
   ophthalmic optics and devices; ophthalmology; medical and biological
   imaging; optical coherence tomographyangiography; swept-source optical
   coherence tomography; Fourier-domain mode-locked laser
ID SWEPT-SOURCE; AMPLITUDE-DECORRELATION; SPECKLE-VARIANCE; ANTERIOR
   SEGMENT; FLOW VELOCITY; AXIAL SCANS; BLOOD-FLOW; OCT; CHORIOCAPILLARIS
AB We present noninvasive, three-dimensional, depth-resolved imaging of human retinal and choroidal blood circulation with a swept-source optical coherence tomography (OCT) system at 1065-nm center wavelength. Motion contrast OCT imaging was performed with the phase-variance OCT angiography method. A Fourier-domain mode-locked light source was used to enable an imaging rate of 1.7 MHz. We experimentally demonstrate the challenges and advantages of wide-field OCT angiography (OCTA). In the discussion, we consider acquisition time, scanning area, scanning density, and their influence on visualization of selected features of the retinal and choroidal vascular networks. The OCTA imaging was performed with a field of view of 16 deg (5 mm x 5 mm) and 30 deg (9 mm x 9 mm). Data were presented in en face projections generated from single volumes and in en face projection mosaics generated from up to 4 datasets. OCTA imaging at 1.7 MHz A-scan rate was compared with results obtained from a commercial OCTA instrument and with conventional ophthalmic diagnostic methods: fundus photography, fluorescein, and indocyanine green angiography. Comparison of images obtained from all methods is demonstrated using the same eye of a healthy volunteer. For example, imaging of retinal pathology is presented in three cases of advanced age-related macular degeneration.(C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
C1 [Poddar, Raju; Migacz, Justin V.; Werner, John S.; Gorczynska, Iwona] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Vis Sci & Adv Retinal Imaging Lab VSRI, Sacramento, CA 95817 USA.
   [Poddar, Raju] Birla Inst Technol, Dept Bioengn, Ranchi, Jharkhand, India.
   [Schwartz, Daniel M.] Univ Calif San Francisco, Dept Ophthalmol & Vis Sci, San Francisco, CA 94143 USA.
   [Gorczynska, Iwona] Nicolaus Copernicus Univ, Inst Phys, Torun, Poland.
C3 University of California System; University of California Davis; Birla
   Institute of Technology Mesra; University of California System;
   University of California San Francisco; Nicolaus Copernicus University
RP Poddar, R (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Vis Sci, Vis Sci & Adv Retinal Imaging Lab VSRI, Sacramento, CA 95817 USA.; Poddar, R (通讯作者)，Birla Inst Technol, Dept Bioengn, Ranchi, Jharkhand, India.
EM rpoddar@bitmesra.ac.in
RI PODDAR, RAJU/R-1671-2018; Gorczynska, Iwona M./P-9367-2015
OI Gorczynska, Iwona M./0000-0002-6120-8791
FU National Eye Institute [R01EY024239]; Research to Prevent Blindness;
   Larry L. Hillblom Foundation
FX We gratefully acknowledge the contributions of VSRI UC Davis lab members
   especially, Susan Garcia (VSRI, UC Davis Medical Center) in subject
   recruitment, as well as Thomas Klein and Wolfgang Weiser (OptoRes GmbH)
   for technical advice on the FDML laser. This research was supported by
   the National Eye Institute (R01EY024239), Research to Prevent Blindness
   and the Larry L. Hillblom Foundation.
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NR 51
TC 21
Z9 22
U1 0
U2 6
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 OCT
PY 2017
VL 22
IS 10
AR 106018
DI 10.1117/1.JBO.22.10.106018
PG 14
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 FL5DF
UT WOS:000414251000031
PM 29090534
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Hossain, RF
   Deaguero, IG
   Boland, T
   Kaul, AB
AF Hossain, Ridwan F.
   Deaguero, Isaac G.
   Boland, Thomas
   Kaul, Anupama B.
TI Biocompatible, large-format, inkjet printed heterostructure
   MoS2-graphene photodetectors on conformable substrates
SO NPJ 2D MATERIALS AND APPLICATIONS
LA English
DT Article
ID IN-VIVO; MACULAR DEGENERATION; MOS2 NANOSHEETS; GRAPHENE; DEVICE;
   PHOTOTRANSISTORS; CYTOTOXICITY; OXIDE
AB An inkjet printed, biocompatible, heterostructure photodetector is described that was constructed using inks of photo-active molybdenum disulfide (MoS2) and electrically conducting graphene which facilitated charge collection of the photocarriers. The importance of such devices stems from their potential utility in age-related-macular degeneration, which is a condition where the photosensitive retinal tissue degrades with aging, eventually compromising vision. The absence of effective therapeutic remedies for patients with this disorder has motivated the development of such devices to restore some degree of visual function. Inkjet printed, flexible prosthetic devices offer design simplicity where additive manufacturing can enable large format, low-cost arrays. The biocompatible inkjet printed two-dimensional heterojunction devices were photoresponsive to broadband incoming radiation in the visible regime, and the photocurrent Iph scaled proportionally with the incident light intensity, exhibiting a photoresponsivity R similar to 0.30 A/W. This is 10(3) times higher compared to prior reports, and detectivity D was calculated to be similar to 3.6 x 10(10) Jones. Straindependent measurements were also conducted with bending, indicating the feasibility of such devices printed on flexible substrates. Drop cast and printed CT-MoS2 inks were characterized using techniques, such as Raman spectroscopy, photoluminescence measurements and scanning electron microscopy. Both mouse embryonic fibroblast and human esophageal fibroblast were used for the biocompatibility analysis for inks drop cast on two types of flexible substrates, polyethylene terephthalate and polyimide. The biocompatibility of inks formed using two-dimensional graphene and MoS2 on polyimide substrates was extremely high, in excess of 98% for mouse embryonic fibroblast.
C1 [Hossain, Ridwan F.; Kaul, Anupama B.] Univ Texas El Paso, Elect & Comp Engn, El Paso, TX 79968 USA.
   [Deaguero, Isaac G.; Boland, Thomas] Univ Texas El Paso, Met Mat & Biomed Engn, El Paso, TX 79968 USA.
   [Kaul, Anupama B.] Univ North Texas, Dept Mat Sci & Engn, Denton, TX 76207 USA.
   [Kaul, Anupama B.] Univ North Texas, Dept Elect Engn, Denton, TX 76207 USA.
C3 University of Texas System; University of Texas El Paso; University of
   Texas System; University of Texas El Paso; University of North Texas
   System; University of North Texas Denton; University of North Texas
   System; University of North Texas Denton
RP Kaul, AB (通讯作者)，Univ Texas El Paso, Elect & Comp Engn, El Paso, TX 79968 USA.; Kaul, AB (通讯作者)，Univ North Texas, Dept Mat Sci & Engn, Denton, TX 76207 USA.; Kaul, AB (通讯作者)，Univ North Texas, Dept Elect Engn, Denton, TX 76207 USA.
EM akaul@utep.edu
RI Boland, Thomas/AAN-7999-2021; Kaul, Anupama/AAJ-8312-2021
OI Boland, Thomas/0000-0003-2161-5699; Kaul, Anupama/0000-0003-4052-8064
FU University of Texas System Faculty Science and Technology Acquisition
   and Retention (STARS) award [EC284802]; Army Research Office (ARO)
   [W911NF-15-1-0425]
FX The authores would like to thank Julio Rincon from the Biomedical
   Device, Delivery, and Diagnostic Laboratory at the University of Texas
   at El Paso for help with the confocal microscopy. Support is
   acknowledged from the University of Texas System Faculty Science and
   Technology Acquisition and Retention (STARS) award (EC284802). We also
   greatly thank the Army Research Office (ARO) (grant number
   W911NF-15-1-0425) who provided funding that enabled us to pursue this
   work.
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NR 39
TC 66
Z9 66
U1 3
U2 52
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
EI 2397-7132
J9 NPJ 2D MATER APPL
JI npj 2D Mater. Appl.
PD SEP 7
PY 2017
VL 1
AR 28
DI 10.1038/s41699-017-0034-2
PG 10
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
   Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science; Physics
GA FG9ZJ
UT WOS:000410798400001
OA gold
DA 2022-11-30
ER

PT J
AU Sterling, J
   Guttha, S
   Song, Y
   Song, D
   Hadziahmetovic, M
   Dunaief, JL
AF Sterling, Jacob
   Guttha, Samyuktha
   Song, Ying
   Song, Delu
   Hadziahmetovic, Majda
   Dunaief, Joshua L.
TI Iron importers Zip8 and Zip14 are expressed in retina and regulated by
   retinal iron levels
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Zip8; Zip14; Retina; Iron; Age-related macular degeneration (AMD);
   Ceruloplasmin; Hephaestin; Hepcidin
ID HEPCIDIN KNOCKOUT MICE; TRANSPORTER ZIP14; ZINC TRANSPORTER;
   HEMOCHROMATOSIS; CERULOPLASMIN; TRANSFERRIN; DISRUPTION; OVERLOAD;
   DEGENERATION; HOMEOSTASIS
AB Intracellular retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness among individuals over the age of 50. Ceruloplasminihephaestin double knockout mice (Cp/Heph DKO) and hepcidin knockout mice (Hepc KO) accumulate retinal iron and model some features of AMD. Two canonical pathways govern cellular iron import transferrin-bound iron import and non-transferrin bound iron import. In Cp/Heph DKO and Hepc KO iron-loaded retinas, transferrin-bound iron import is downregulated. Despite this effort to reduce cellular iron burden, iron continues to accumulate in these retinas in an age-dependent manner. Quantitative RT-PCR and Western analysis were used to quantify the expression of three ferrous iron importers, Dmtl, Zip8, and Zip14, in wild-type (Wt), Cp/Heph DKO, and Hepc KO retinas. Zip8 and Zip14 protein levels were analyzed using Western analysis in mice injected intravitreally with either apo- or holo-transferrin to elucidate one possible mechanism of Zip14 regulation in the retina. Both zip8 and zip14 were expressed in the mouse retina. Paradoxically, protein levels of non-transferrin bound iron importers were upregulated in both Cp/fleph DKO and Hepc KO retinas. Intravitreal holo-transferrin injection decreased Zip 14 protein levels. These data indicate that Zip8 and Zip14 may take up increasing amounts of non-transferrin bound iron in these two mouse models of retinal iron accumulation. Their upregulation in these already iron-loaded retinas suggests a vicious cycle leading to toxicity.(C) 2017 Elsevier Ltd. All rights reserved.
C1 [Sterling, Jacob; Guttha, Samyuktha; Song, Ying; Song, Delu; Hadziahmetovic, Majda; Dunaief, Joshua L.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, Scheie Eye Inst,Stellar Chance Lab 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，Univ Penn, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, Scheie Eye Inst,Stellar Chance Lab 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jacobst@sas.upenn.edu; spg65@drexel.edu; yingsong@mail.med.upenn.edu;
   delusong@mail.med.upenn.edu; majdahadziahmetovic@gmail.com;
   jdunaief@upenn.edu
OI Sterling, Jacob/0000-0001-7535-1073
FU NIH/NEI [EY015240]; Research to Prevent Blindness; F. M. Kirby
   Foundation; Paul and Evanina Bell Mackall Foundation Trust; NATIONAL EYE
   INSTITUTE [R01EY015240, P30EY001583] Funding Source: NIH RePORTER
FX Funding from NIH/NEI EY015240, Research to Prevent Blindness, the F. M.
   Kirby Foundation, a gift in memory of Lee F. Mauger, MD, and the Paul
   and Evanina Bell Mackall Foundation Trust.
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NR 34
TC 25
Z9 26
U1 1
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2017
VL 155
BP 15
EP 23
DI 10.1016/j.exer.2016.12.008
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EQ4BF
UT WOS:000398017000002
PM 28057442
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Owen, LA
   Morrison, MA
   Ahn, J
   Woo, SJ
   Sato, H
   Robinson, R
   Morgan, DJ
   Zacharaki, F
   Simeonova, M
   Uehara, H
   Chakravarthy, U
   Hogg, RE
   Ambati, BK
   Kotoula, M
   Baehr, W
   Haider, NB
   Silvestri, G
   Miller, JW
   Tsironi, EE
   Farrer, LA
   Kim, IK
   Park, KH
   DeAngelis, MM
AF Owen, Leah A.
   Morrison, Margaux A.
   Ahn, Jeeyun
   Woo, Se Joon
   Sato, Hajime
   Robinson, Rosann
   Morgan, Denise J.
   Zacharaki, Fani
   Simeonova, Marina
   Uehara, Hironori
   Chakravarthy, Usha
   Hogg, Ruth E.
   Ambati, Balamurali K.
   Kotoula, Maria
   Baehr, Wolfgang
   Haider, Neena B.
   Silvestri, Giuliana
   Miller, Joan W.
   Tsironi, Evangelia E.
   Farrer, Lindsay A.
   Kim, Ivana K.
   Park, Kyu Hyung
   DeAngelis, Margaret M.
TI FLT1 Genetic Variation Predisposes to Neovascular AMD in Ethnically
   Diverse Populations and Alters Systemic FLT1 Expression
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; angiogenesis; FLT1; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; TUMOR ANGIOGENESIS; FACTOR RECEPTOR-1; NR2E3
   FUNCTIONS; VEGF; ASSOCIATION; RISK; POLYMORPHISMS
AB PURPOSE. Current understanding of the genetic risk factors for age-related macular degeneration (AMD) is not sufficiently predictive of the clinical course. The VEGF pathway is a key therapeutic target for treatment of neovascular AMD; however, risk attributable to genetic variation within pathway genes is unclear. We sought to identify single nucleotide polymorphisms (SNPs) associated with AMD within the VEGF pathway.
   METHODS. Using a tagSNP, direct sequencing and meta-analysis approach within four ethnically diverse cohorts, we identified genetic risk present in FLT1, though not within other VEGF pathway genes KDR, VEGFA, or VASH1. We used ChIP and ELISA in functional analysis.
   RESULTS. The FLT1 SNPs rs9943922, rs9508034, rs2281827, rs7324510, and rs9513115 were significantly associated with increased risk of neovascular AMD. Each association was more significant after meta-analysis than in any one of the four cohorts. All associations were novel, within noncoding regions of FLT1 that do not tag for coding variants in linkage disequilibrium. Analysis of soluble FLT1 demonstrated higher expression in unaffected individuals homozygous for the FLT1 risk alleles rs9943922 (P=0.0086) and rs7324510 (P=0.0057). In silico analysis suggests that these variants change predicted splice sites and RNA secondary structure, and have been identified in other neovascular pathologies. These data were supported further by murine chromatin immunoprecipitation demonstrating that FLT1 is a target of Nr2e3, a nuclear receptor gene implicated in regulating an AMD pathway.
   CONCLUSIONS. Although exact variant functions are not known, these data demonstrate relevancy across ethnically diverse genetic backgrounds within our study and, therefore, hold potential for global efficacy.
C1 [Owen, Leah A.; Morrison, Margaux A.; Robinson, Rosann; Morgan, Denise J.; Uehara, Hironori; Ambati, Balamurali K.; Baehr, Wolfgang; DeAngelis, Margaret M.] Univ Utah, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
   [Ahn, Jeeyun; Park, Kyu Hyung] Seoul Metropolitan Govt Seoul Natl Univ, Dept Ophthalmol, Boramae Med Ctr, Seoul, South Korea.
   [Woo, Se Joon] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seoungnam, South Korea.
   [Sato, Hajime] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, Sendai, Miyagi 980, Japan.
   [Zacharaki, Fani; Kotoula, Maria; Tsironi, Evangelia E.] Univ Thessaly, Sch Med, Dept Ophthalmol, Larisa, Greece.
   [Simeonova, Marina; Miller, Joan W.; Kim, Ivana K.] Harvard Univ, Sch Med, Dept Ophthalmol, Retina Serv,Massachusetts Eye & Ear, Boston, MA USA.
   [Chakravarthy, Usha; Hogg, Ruth E.; Silvestri, Giuliana] Queens Univ, Ctr Expt Med, Belfast, Antrim, North Ireland.
   [Haider, Neena B.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
C3 Utah System of Higher Education; University of Utah; Seoul National
   University (SNU); Seoul National University Hospital; Seoul National
   University (SNU); Tohoku University; University of Thessaly; Harvard
   University; Harvard Medical School; Massachusetts Eye & Ear Infirmary;
   Queens University Belfast; Harvard University; Harvard Medical School;
   Schepens Eye Research Institute; Boston University; Boston University;
   Boston University; Boston University; Boston University; Boston
   University; Boston University; Boston University; Boston University;
   Boston University
RP DeAngelis, MM (通讯作者)，Univ Utah, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM Margaret.deangelis@utah.edu
RI Farrer, Lindsay/AAS-1035-2020; DeAngelis, e/J-7863-2015; Hogg, Ruth
   E./ABC-9602-2020; Kotoula, Maria/Y-6539-2019
OI Hogg, Ruth E./0000-0001-9413-2669; Ahn, Jeeyun/0000-0001-9017-1652;
   Miller, Joan/0000-0003-2046-3996; Kim, Ivana/0000-0003-0310-6129;
   Chakravarthy, Usha/0000-0002-2606-3734; Farrer,
   Lindsay/0000-0001-5533-4225; Owen, Leah/0000-0003-3802-3868
FU NIH [EY-014458]; ALSAM Foundation; Edward N. & Della L. Thome Memorial
   Fund; Lincy Foundation; Bausch Lomb; National Research Foundation of
   Korea - Ministry of Education, Science and Technology
   [2012R1A1A2008943]; Research to Prevent Blindness Foundation; NATIONAL
   EYE INSTITUTE [P30EY014800, R01EY014458] Funding Source: NIH RePORTER;
   Fight for Sight [1376] Funding Source: researchfish
FX Supported by NIH Grant EY-014458, the ALSAM Foundation, the Edward N. &
   Della L. Thome Memorial Fund, the Lincy Foundation, Bausch & Lomb,
   National Research Foundation of Korea grants funded by the Ministry of
   Education, Science and Technology (2012R1A1A2008943), and an
   unrestricted grant from the Research to Prevent Blindness Foundation to
   the University of Utah Department of Ophthalmology and Visual Sciences.
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NR 75
TC 12
Z9 13
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2014
VL 55
IS 6
BP 3543
EP 3554
DI 10.1167/iovs.14-14047
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AL9TX
UT WOS:000339485800023
PM 24812550
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhang, J
   Tuo, JS
   Cao, XG
   Shen, DF
   Li, W
   Chan, CC
AF Zhang, Jun
   Tuo, Jingsheng
   Cao, Xiaoguan
   Shen, Defen
   Li, Wei
   Chan, Chi-Chao
TI Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient
   mice on Crb1rd8 background
SO SYNAPSE
LA English
DT Article
DE age-related macular degeneration; cone synapse degeneration; rod synapse
   plasticity; animal model
ID AGE-RELATED MACULOPATHY; ROD BIPOLAR CELLS; MACULAR DEGENERATION;
   RETINAL DEGENERATION; CONE PHOTORECEPTOR; MOUSE MODEL; CHEMOKINE
   RECEPTORS; SIGNALING PATHWAY; MAMMALIAN RETINA; HORIZONTAL CELLS
AB Photoreceptor ribbon synapse releases glutamate to postsynaptic targets. The synaptic ribbon may play multiple roles in ribbon synapse development, synaptic vesicle recycling, and synaptic transmission. Age-related macular degeneration (AMD) patients appear to have fewer or no detectable synaptic ribbons as well as abnormal swelling in the photoreceptor terminals in the macula. However, reports on changes of photoreceptor synapses in AMD are scarce and photoreceptor type and quantity affected in early AMD is still unclear. Here, we employed multiple anatomical techniques to investigate these questions in Ccl2-/-/Cx3cr1-/- mouse on Crb1rd8 background (DKO rd8) at one month of age. We found that approximately 17% of photoreceptors over the focal lesion were lost. Immunostaining for synapse-associated proteins (CtBP2, synaptophysin, and vesicular glutamate transporter 1) showed significantly reduced expression and ectopic localization. Cone opsins demonstrated dramatic reduction in expression (S-opsins) and extensive mislocalization (M-opsins). Quantitative ultrastructural analysis confirmed a significant decrease in the number of cone terminals and nuclei, numerous vacuoles in remaining cone terminals, reduction in the number of synaptic ribbons in photoreceptor terminals, and ectopic rod ribbon synapses. In addition, glutamate receptor immunoreactivity on aberrant sprouting of rod bipolar cells and horizontal cells were identified at the ectopic synapses. These results indicate that synaptic alterations occur at the early stages of disease and cones are likely more susceptible to damage caused by DKO rd8 mutation. They provide a new insight into potential mechanism of vision function lost due to synaptic degeneration before cell death in the early stages of AMD. Synapse 67:515-531, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Zhang, Jun; Chan, Chi-Chao] NEI, Histol Core, NIH, Bethesda, MD 20892 USA.
   [Tuo, Jingsheng; Cao, Xiaoguan; Shen, Defen; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Cao, Xiaoguan] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China.
   [Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); Peking University; National Institutes of Health (NIH)
   - USA; NIH National Eye Institute (NEI)
RP Chan, CC (通讯作者)，NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA.
EM junzhang@ninds.nih.gov; chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU National Eye Institute, NIH; NATIONAL EYE INSTITUTE [ZIAEY000222,
   ZICEY000461] Funding Source: NIH RePORTER
FX Contract grant sponsor: Intramural Research Program of National Eye
   Institute, NIH.
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NR 82
TC 18
Z9 18
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
EI 1098-2396
J9 SYNAPSE
JI Synapse
PD AUG
PY 2013
VL 67
IS 8
BP 515
EP 531
DI 10.1002/syn.21674
PG 17
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 169KB
UT WOS:000320777800006
PM 23592324
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Michalska-Malecka, K
   Nowak, M
   Gosciniewicz, P
   Karpe, J
   Slowinska-Lozynska, L
   Lypaczewska, A
   Romaniuk, D
AF Michalska-Malecka, Katarzyna
   Nowak, Mariusz
   Gosciniewicz, Piotr
   Karpe, Jacek
   Slowinska-Lozynska, Ludmila
   Lypaczewska, Agnieszka
   Romaniuk, Dorota
TI Results of cataract surgery in the very elderly population
SO CLINICAL INTERVENTIONS IN AGING
LA English
DT Article
DE very elderly patients; cataract surgery; postoperative best corrected
   visual acuity; intraocular pressure
ID QUALITY-OF-LIFE; RISK-FACTORS; VISUAL IMPAIRMENT; OLDER-PEOPLE;
   INTRAOPERATIVE COMPLICATIONS; INTRAOCULAR-PRESSURE; FALLS; VISION;
   IMPACT; WOMEN
AB Aim: The aim of our study was to retrospectively evaluate the effectiveness and safety of cataract surgery and intraocular lens implantation (IOL) for patients aged 90 years or older, whom we define as "very elderly."
   Methods: The study involved a total number of 122 patients (122 eyes) with senile cataracts. The mean age of patients was 91.2 +/- 2.3 years (range 90-100 years old). Phacoemulsification (phaco) was done on 113 of 122 eyes, and 9 of 122 eyes had extracapsular cataract extraction (ECCE). Postoperative visual acuity and intraocular pressure (IOP) were analyzed on the first postoperative day, 3 months after surgery, and 6 months after surgery.
   Results: Best corrected visual acuity (BCVA) improved in 100 of 122 eyes (82.0%). BCVA remained the same in 20 of 122 eyes (16.4%) and decreased in 2 of 122 eyes (1.6%), mainly because of coexisting age-related macular degeneration (AMD). The BCVA 3 months after surgery was >= 0.8 in 23 of 122 eyes (18.9%), between 0.5 and 0.7 in 28 of 122 eyes (22.3%), and between 0.2 and 0.4 in 33 of 122 eyes (27.1%). We found significant implications of cataract surgery on decreasing IOP in the studied group of patients suffering from glaucoma compared to the patients without glaucoma.
   Conclusion: Advanced age is not a contraindication for cataract surgery. The results of the study showed that when systemic conditions are stable, both phaco and ECCE with IOL for very elderly patients are effective and safe.
C1 [Michalska-Malecka, Katarzyna; Gosciniewicz, Piotr; Lypaczewska, Agnieszka; Romaniuk, Dorota] Med Univ Silesia, Univ Hosp 5, Dept Ophthalmol, Katowice, Poland.
   [Nowak, Mariusz] Med Univ Silesia, Dept Pathophysiol & Endocrinol, Div Pathophysiol, Zabrze, Poland.
   [Karpe, Jacek] Med Univ Silesia, Dept Anesthesiol & Intens Therapy, Zabrze, Poland.
   [Slowinska-Lozynska, Ludmila] Med Univ Silesia, Fac Med Zabrze, Dept Biophys, Katowice, Silesia, Poland.
C3 Medical University Silesia; Medical University Silesia; Medical
   University Silesia; Medical University Silesia
RP Michalska-Malecka, K (通讯作者)，Sybirakow St 18, PL-44203 Rybnik, Silesia, Poland.
EM kasia@marat.com.pl
OI Karpe, Jacek/0000-0003-0578-2497; MICHALSKA-MALECKA,
   KATARZYNA/0000-0002-0550-8386; Nowak, Mariusz/0000-0003-1754-9959
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NR 29
TC 14
Z9 14
U1 0
U2 8
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1176-9092
EI 1178-1998
J9 CLIN INTERV AGING
JI Clin. Interv. Aging
PY 2013
VL 8
BP 1041
EP 1046
DI 10.2147/CIA.S44834
PG 6
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 196GW
UT WOS:000322762900001
PM 23966774
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Fahed, DC
   Ghazi, NG
   Jabbour, NM
   Fahed, CD
   Fahed, JC
   Salti, HI
AF Fahed, Daoud C.
   Ghazi, Nicola G.
   Jabbour, Nabil M.
   Fahed, Charbel D.
   Fahed, John C.
   Salti, Haytham I.
TI Impact of AREDS in a developing country 5 years after publication of the
   study
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; AREDS; Developing country; Vitamin
   supplement
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RISK-FACTORS; CHOROIDAL
   NEOVASCULARIZATION; PREVALENCE; EYE; POPULATION; EXPOSURE; PROGRESSION;
   ZEAXANTHIN
AB PURPOSE. The Age-Related Eye Disease Study (AREDS) is the only large-scale study to demonstrate a reduction in the risk of progression to end-stage age-related macular degeneration (AMD) when vitamin supplementation was given to patients with advanced forms of the disease. Our study assesses the impact of this study on vitamin supplementation in patients with advanced AMD from 5 years before publication of the AREDS results until 5 years after.
   METHODS. Medical records of patients with AMD presenting between September 1996 and October 2006 were reviewed. Patients were subclassified according to AREDS categories. The proportion of advanced cases on vitamin replacement before October 2001 was compared to that after October 2001. Since October 2001, the different reasons for abstinence were investigated and analyzed.
   RESULTS. Only 2403 patients of the 40,000 medical records reviewed met the AREDS AMD criteria. Of these, 137 patients verifying categories 3 and 4 were diagnosed prior to October 2001. Fourteen were on supplements then. Fifty-three patients complied with the represcribed vitamins during subsequent visits after October 2001, raising the percentage significantly to 48.9% (p<0.001). Also, from October 2001 until October 2006, an additional 76 patients verified categories 3 and 4. Fifty-three (69.7%) of them were on vitamins (p=0.001). Financial burden was the principal reason for abstinence in 67.7% of patients prescribed vitamins after October 2001.
   CONCLUSION. The results of AREDS had an impressive impact on prescribing supplements in AREDS category 3 and 4 patients in Lebanon. The main reason for noncompliance is financial.
C1 [Fahed, Daoud C.; Salti, Haytham I.] Amer Univ Beirut, Dept Ophthalmol, Med Ctr, Beirut, Lebanon.
   [Ghazi, Nicola G.] Univ Virginia Hlth Sci Syst, Dept Ophthalmol, Charlottesville, VA USA.
   [Jabbour, Nabil M.] W Virginia Univ, Dept Ophthalmol, Charleston, WV 25304 USA.
   [Fahed, Charbel D.] Ophthalm Consultants Beirut, Beirut, Lebanon.
   [Fahed, Daoud C.; Jabbour, Nabil M.; Fahed, Charbel D.; Fahed, John C.] Foresight Fdn, Beirut, Lebanon.
C3 American University of Beirut; University of Virginia; West Virginia
   University
RP Salti, HI (通讯作者)，Amer Univ Beirut, Dept Ophthalmol, Med Ctr, Beirut, Lebanon.
EM hs06@aub.edu.lb
RI Ghazi, Nicola/AAH-4169-2020
OI Ghazi, Nicola/0000-0001-9255-8025
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NR 29
TC 7
Z9 7
U1 0
U2 4
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JAN-FEB
PY 2011
VL 21
IS 1
BP 67
EP 72
DI 10.5301/EJO.2010.4138
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 687MI
UT WOS:000284782200010
PM 20602323
DA 2022-11-30
ER

PT J
AU Szczotka-Flynn, L
   Ahmadian, R
   Diaz, M
AF Szczotka-Flynn, Loretta
   Ahmadian, Rouzbeh
   Diaz, Mireya
TI A Re-evaluation of the Risk of Microbial Keratitis From Overnight
   Contact Lens Wear Compared With Other Life Risks
SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE
LA English
DT Article
DE Contact lens; Extended wear; Case fatality; Silicone hydrogel; Microbial
   keratitis
ID IN-SITU KERATOMILEUSIS; ULCERATIVE KERATITIS; SILICONE HYDROGEL;
   CASE-FATALITY; OUTBREAK; KERATOCONUS; CATARACT; SURVIVAL; OUTCOMES;
   SURGERY
AB Purpose: In 1995, Myers and Weiss published in article comparing file risk of ulcerative keratitis related to low oxygen permeability (Dk) extended contact lens wear to other life risks. This article updates the risks associated with silicone hydrogel (SH) extended wear contact lens use and some comparative life risks, to provide a current perspective within the hierarchy of life risks.
   Methods: A comparative ratio was defined as the incidence of microbial keratitis in a population of SH extended wear contact lens users divided by the incidence of other disease or occurrence in a given population at risk.
   Results: The risk of SH lens-related microbial keratitis is about 1.5 to 16 times less risky than certain nonfatal disruptive Occurrences in the general population, and about the same as the risk of developing breast cancer. Compared with other ocular conditions, the risk of microbial keratitis with SH lenses is about the same as developing late-stage age-related macular degeneration or retinal detachment after cataract extraction on an annual basis; it is over 200 times greater than developing eye or orbit cancer; it is about 7, 20, or more than 30 times less than proceeding to penetrating keratoplasty in keratoconus, developing nuclear cataract, or experiencing a corneal inflammatory event during low-Dk extended wear, respectively.
   Conclusions: Although the risk of microbial keratitis with modern clay SH contact lens extended wear has not changed since the 1980s, when put in perspective with other life risks, it is a relatively rare occurrence.
C1 [Szczotka-Flynn, Loretta] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Szczotka-Flynn, Loretta] Univ Hosp Case Med Ctr, Cleveland, OH USA.
   [Ahmadian, Rouzbeh] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
   [Diaz, Mireya] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University Hospital; Case Western Reserve University;
   Henry Ford Health System; Henry Ford Hospital
RP Szczotka-Flynn, L (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 1100 Euclid Ave,Bolwell Bldg Suite 3200, Cleveland, OH 44106 USA.
EM loretta.szczotka@uhhospitals.org
FU Research to Prevent Blindness; Ohio Lion's Eye Research Foundation;
   National Eve Institute [K23EY015270-01, R21EY015145]; NATIONAL EYE
   INSTITUTE [R21EY015145, K23EY015270] Funding Source: NIH RePORTER
FX Supported by Research to Prevent Blindness (L.S.-F.), Ohio Lion's Eye
   Research Foundation (L.S.-F.), and National Eve Institute grants
   K23EY015270-01 (L.S.-F.) and R21EY015145 (L.S.-F., M.D.).
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NR 48
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1542-2321
EI 1542-233X
J9 EYE CONTACT LENS
JI Eye Contact Lens-Sci. Clin. Pra.
PD MAR
PY 2009
VL 35
IS 2
BP 69
EP 75
DI 10.1097/ICL.0b013e3181998dd3
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 420SA
UT WOS:000264308300006
PM 19265327
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Degenring, RF
   Kreissig, I
   Akkoyun, I
   Kamppeter, BA
AF Jonas, JB
   Degenring, RF
   Kreissig, I
   Akkoyun, I
   Kamppeter, BA
TI Intraocular pressure elevation after intravitreal triamcinolone
   acetonide injection
SO OPHTHALMOLOGY
LA English
DT Article
ID CYSTOID MACULAR EDEMA; CRYSTALLINE CORTISONE; ADJUNCTIVE TREATMENT;
   DEGENERATION; ENDOPHTHALMITIS; SECONDARY; GLAUCOMA; SAFETY
AB Purpose: To report on intraocular pressure (IOP) after intravitreal injections of triamcinolone acetonide.
   Design: Meta-analysis of previously reported data and case series studies.
   Participants: The study included 272 patients (305 eyes) receiving an intravitreal injection of approximately 20 mg triamcinolone acetonide as treatment for diffuse diabetic macular edema (n = 84 patients), exudative age-related macular degeneration (n = 181 patients), retinal vein occlusions (n = 20 patients), uveitis (n = 9), pseudophakic cystoid macular edema (n = 6), and other reasons (n = 5). Mean follow-up was 10.4 +/- 6.7 months (median, 7.9 months; range, 3.0-35.7 months). Intervention: Intravitreal injection of approximately 20 mg triamcinolone acetonide.
   Main Outcome Measure: Intraocular pressure.
   Results: Intraocular pressure readings higher than 21 mmHg, 30 mmHg, 35 mmHg, and 40 mmHg, respectively, were measured in 112 (41.2%) patients, 31 (11.4%) patients, 15 (5.5%) patients, and 5 (1.8%) patients, respectively. Triamcinolone-incluced IOP elevation was treated by antiglaucoma medication in all but 3 (1.0%) eyes, for which filtering surgery was performed. Mean IOP started to rise 1 week after injection and returned to baseline values approximately 8 to 9 months after injection. Younger age (P = 0.029) was significantly associated with triamcinolone-induced ocular hypertension. Triamcinolone responders and triamcinolone nonresponders did not vary significantly in gender (P = 0.42), refractive error (P = 0.86), diabetes mellitus status (P = 0.74), and reason for treatment.
   Conclusions: These findings may be useful for comparing risks and benefits of intravitreal triamcinolone acetonide therapy. (c) 2005 by the American Academy of Ophthalmology.
C1 Heidelberg Univ, Fac Clin Med Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Univ Mannheim, Augenklin, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM Jost.Jonas@augen.ma.uni-heidelberg.de
RI AKKOYUN, IMREN VARDARLI/AAK-7713-2021
OI AKKOYUN, IMREN VARDARLI/0000-0002-2860-7424
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NR 46
TC 251
Z9 268
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2005
VL 112
IS 4
BP 593
EP 598
DI 10.1016/j.ophtha.2004.10.042
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 910WF
UT WOS:000227962200011
PM 15808249
DA 2022-11-30
ER

PT J
AU Liang, FQ
   Green, L
   Wang, C
   Alssadi, R
   Godley, BF
AF Liang, FQ
   Green, L
   Wang, C
   Alssadi, R
   Godley, BF
TI Melatonin protects human retinal pigment epithelial (RPE) cells against
   oxidative stress
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE melatonin; retinal pigment epithelial cell; oxidative stress; DNA
   damage; mitochondria; age-related macular degeneration
ID MITOCHONDRIAL-DNA DAMAGE; INDUCED APOPTOSIS; GENE-EXPRESSION;
   PINEAL-GLAND; ANTIOXIDANT; GLUTATHIONE; MEMBRANES
AB Oxidative stress is involved in the pathogenesis of age-related macular degeneration (AMD). Administration of conventional antioxidants has been shown to slow the progression of AMD and vision loss. Melatonin, an endogenous neurohormone produced by the pineal gland and retina, has been reported to be a potent antioxidant and free radical scavenger. In this study we tested whether melatonin can protect retinal pigment epithelial (RPE) cells against hydrogen peroxide (H2O2)-induced cell death. Since mitochondrial DNA (mtDNA) is preferentially susceptible to oxidative damage, we tested whether melatonin can reduce H2O2-induced mtDNA lesions. A human RPE cell line (ARPE-19) was cultured and exposed to H2O2 (100 and 200 muM) for 1 hr to induce cell death. Prior to H2O2 treatment, cells were treated with various concentrations (0.1 - 200 muM) of melatonin for 2, 24 or 72 hr. Control cells received either melatonin or ethanol alone. Cell viability, as determined by MTT assay, showed no significant (P > 0.05) protection against H2O2 toxicity in cells receiving 2- and 24-hr pretreatment of melatonin at either concentration. However, when melatonin was administered diurnally for 3 consecutive days, this prolonged treatment markedly reduced H2O2-induced cell death (P < 0.05). MtDNA damage, as assessed with quantitative PCR, was significantly decreased (P = 0.031) in RPE cells pretreated with melatonin as compared to those without melatonin treatment. These results suggest that melatonin may play a role in protecting RPE cells from oxidative stress. (C) 2004 Elsevier Ltd. All rights reserved.
C1 Retina Fdn SW, Dallas, TX 75231 USA.
   Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX USA.
C3 Retina Foundation of the Southwest; University of Texas System;
   University of Texas Dallas; University of Texas Southwestern Medical
   Center Dallas
RP Godley, BF (通讯作者)，Retina Fdn SW, 9900 N Cent Expressway,Suite 400, Dallas, TX 75231 USA.
EM fliang@retinafoundation.org; bgodley@retinafoundation.org
FU NATIONAL EYE INSTITUTE [R01EY012850] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY 12850] Funding Source: Medline
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NR 47
TC 81
Z9 84
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 JUN
PY 2004
VL 78
IS 6
BP 1069
EP 1075
DI 10.1016/j.exer.2004.02.003
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 821AM
UT WOS:000221431600003
PM 15109913
DA 2022-11-30
ER

PT J
AU Deruaz, A
   Matter, M
   Whatham, AR
   Goldschmidt, M
   Duret, F
   Issenhuth, M
   Safran, AB
AF Deruaz, A
   Matter, M
   Whatham, AR
   Goldschmidt, M
   Duret, F
   Issenhuth, M
   Safran, AB
TI Can fixation instability improve text perception during eccentric
   fixation in patients with central scotomas?
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PREFERRED RETINAL LOCI; MACULAR SCOTOMA; SMALL SACCADES; ADAPTATION;
   LOCATION; PHOTORECEPTORS; STABILITY; DISORDERS; VISION; FOVEA
AB Background: Oculomotor behaviour was investigated in 14 patients with central scotomas from age related macular degeneration (AMD) or Stargardt's disease. A scanning laser ophthalmoscope (SLO) was used to project letters and words onto the retina and to assess fixation behaviour. Five patients reported while deciphering letters that they needed to "move their eye'' to prevent the image from vanishing. The observation of the SLO fundus images revealed that the gradual disappearance of the stimulus did not result from a transient projection of the word in the lesion. This prompted the authors to investigate, in an experimental setting, whether purposeful changes in fixation position could improve the perception of an eccentrically fixated text stimulus.
   Methods: Twenty normal subjects were asked to alternate fixation, every three to four seconds, between two vertically aligned dots, spaced 10degrees apart, and to report any changes in the perception of a laterally located letter, 1.5degrees in height, 7degrees apart and equidistant between the two fixation spots.
   Results: Nineteen subjects reported a transient refreshment of the letter image immediately after the realisation of a saccade. Improved perception lasted approximately a second. With persistent fixation, they noted a rapid fading effect that reduced letter recognition.
   Conclusion: These observations suggest that ocular instability during eccentric viewing can have a functional advantage, probably related to counteracting Troxler's phenomenon. In addition to alternating between PRLs, it appears that saccades related to fixation instability might be valuable and improve text perception in individuals with a central scotoma and eccentric fixation. This possibility should be taken into consideration when conducting visual rehabilitation procedures.
C1 Univ Hosp Geneva, Dept Clin Neurosci & Dermatol, Ophthalmol Clin, Neuroophthalmol Unit, CH-1211 Geneva 14, Switzerland.
   Catholic Univ Louvain, Dept Physiol & Pharmacol, B-3000 Louvain, Belgium.
C3 University of Geneva; Universite Catholique Louvain
RP Deruaz, A (通讯作者)，Univ Hosp Geneva, Dept Clin Neurosci & Dermatol, Ophthalmol Clin, Neuroophthalmol Unit, 22 Alcide Jentzer, CH-1211 Geneva 14, Switzerland.
EM anouk.deruaz@hcuge.ch
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   [No title captured]
NR 36
TC 20
Z9 22
U1 0
U2 8
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 APR 1
PY 2004
VL 88
IS 4
BP 461
EP 463
DI 10.1136/bjo.2003.025601
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 804MI
UT WOS:000220302400007
PM 15031154
OA Bronze, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Bellmann, C
   Miller, DW
   Mehltretter, K
   Schutt, F
   Jorzik, J
   Unnebrink, K
   Holz, FG
AF Bellmann, C
   Miller, DW
   Mehltretter, K
   Schutt, F
   Jorzik, J
   Unnebrink, K
   Holz, FG
TI Digital analysis of choroidal neovascularisation in consecutive
   fluorescein angiograms for use in longitudinal clinical trials
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; EYE; PHOTOCOAGULATION;
   LESIONS; FUNDUS; PHOTOGRAPHS; PREVALENCE; AGREEMENT
AB Background/aims: To document the natural history and to assess the efficacy of interventional therapies in neovascular age related macular degeneration (AMD), an accurate and reproducible method is required for analysis of consecutive fluorescence angiograms. The development and evaluation of an image analysis software for this purpose is described here. It allows for the quantitative analysis of changes in CNV and/or leakage area over time.
   Methods: In digitised angiograms, a mouse driven arrow was used to delineate the CNV border. The ratio of the CNV area to the square of the distance between two vessels was automatically calculated by pixel count to compensate for variation in image sizes at different examination times. These results were directly transferred and stored in a database. To assess reproducibility, CNV areas in 20 patients with occult and 20 patients with classic CNV were determined independently by two readers.
   Results: There was only marginal variability between observers with this method: the mean deviation was 0.01 pixels for classic CNV (95% CI -0.17 to +0.15, SD 0.35) and 0.55 pixels for occult CNV (95% CI -1.06 to -0.04, SD 1.14).
   Conclusions: This practical PC based method allows for quantification of angiographic features such as CNV size in early frames and area of leakage in late frames. Limitations include non-readily defined borders in angiograms of poor image quality or indistinct borders of the hyperfluorescent areas of interest. The software is applicable to future clinical trials where the analysis of neovascular complex changes is required, for example, following therapeutic intervention.
C1 Univ Heidelberg, Dept Ophthalmol, INF 400, D-69120 Heidelberg, Germany.
   Univ Heidelberg, Coordinat Ctr Clin Trials, Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg; Ruprecht Karls University
   Heidelberg
RP Holz, FG (通讯作者)，Univ Heidelberg, Dept Ophthalmol, INF 400, D-69120 Heidelberg, Germany.
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NR 20
TC 5
Z9 5
U1 0
U2 0
PU BRITISH MED JOURNAL PUBL 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 2003
VL 87
IS 7
BP 890
EP 892
DI 10.1136/bjo.87.7.890
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 690ZZ
UT WOS:000183581500022
PM 12812893
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Xu, ND
   Liu, Y
   Nai, SS
   Tao, Y
   Ding, YH
   Jia, LM
   Geng, QZ
   Li, J
   Bai, YJ
   Wei, GH
   Dong, MQ
   Luo, LY
   Zhao, MW
   Xu, XZ
   Li, XX
   Li, J
   Huang, LZ
AF Xu, Ningda
   Liu, Yue
   Nai, Shanshan
   Tao, Yong
   Ding, Yuehe
   Jia, Lemei
   Geng, Qizhi
   Li, Jie
   Bai, Yujing
   Wei, Gong-Hong
   Dong, Meng-Qiu
   Luo, Linyi
   Zhao, Mingwei
   Xu, Xingzhi
   Li, Xiao-Xin
   Li, Jing
   Huang, Lvzhen
TI UBE3D Is Involved in Blue Light-Induced Retinal Damage by Regulating
   Double-Strand Break Repair
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration (AMD); double-strand break repair
   (DSBR); KAP1; heterochromatin; methionine oxidation; ubiquitin-protein
   ligase E3D (UBE3D)
ID MACULAR DEGENERATION; DNA; PHOSPHORYLATION; PROTEIN; RECRUITMENT;
   PATHWAY; ATM
AB PURPOSE. Age-related macular degeneration (AMD) is currently the leading cause of blindness worldwide. Previously, we identified ubiquitin-protein ligase E3D (UBE3D) as an AMD-associated protein for East Asian populations, and here we further demonstrate that UBE3D could be associated with DNA damage response.
   METHODS. The established I-SceI-inducible GFP reporter system was used to explore the effect of UBE3D on homologous recombination. Immunoprecipitation-mass spectrometry (MS) was used to explore potential UBE3D-interacting proteins and validated with coimmunoprecipitation assays and the pulldown assays. Micrococcal nuclease (MNase) assays were used to investigate the function of UBE3D on heterochromatin de-condensation upon DNA damage. An aged mouse model of blue light-induced eye damage was constructed, and electroretinography (ERG) and optical coherence tomography (OCT) were performed to compare the differences between wild-type and UBE3D(+/-) mice.
   RESULTS. First, we show that GFP-UBE3D is recruited to damage sites by PCNA, through a PCNA-interacting protein (PIP) box. Furthermore, UBE3D interacts with KAP1 via R377R378 and oxidation of the AMD-associated V379M mutation abolishes KAP1-UBE3D binding. By MNase assays, UBE3D depletion reduces the chromatin relaxation levels upon DNA damage. In addition, UBE3D depletion renders less KAP1 recruitment. Compared with wild type, blue light induces less damage in UBE3D(+/-) mice as measured by ERG and OCT, consistent with our biochemical results.
   CONCLUSIONS. Hence, we propose that one potential mechanism that UBE3D-V379M contributes to AMD pathogenesis might be via defective DNA damage repair linked with oxidative stress and our results offered a potential direction for the treatment of AMD.
C1 [Xu, Ningda; Bai, Yujing; Zhao, Mingwei; Li, Xiao-Xin; Huang, Lvzhen] Peking Univ, Peoples Hosp, Eye Dis & Optometry Inst,Hlth Sci Ctr,Coll Optome, Dept Ophthalmol,Beijing Key Lab Diag & Therapy Re, Beijing, Peoples R China.
   [Liu, Yue; Geng, Qizhi; Li, Jie; Xu, Xingzhi; Li, Jing] Capital Normal Univ, Beijing Key Lab DNA Damage Response, Beijing, Peoples R China.
   [Liu, Yue; Nai, Shanshan; Geng, Qizhi; Li, Jie; Xu, Xingzhi; Li, Jing] Capital Normal Univ, Coll Life Sci, Beijing, Peoples R China.
   [Tao, Yong] Capital Med Univ, Beijing Chaoyang Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Ding, Yuehe; Jia, Lemei; Dong, Meng-Qiu] Natl Inst Biol Sci, Beijing, Peoples R China.
   [Wei, Gong-Hong] Univ Oulu, Fac Biochem & Mol Med, Bioctr Oulu, Oulu, Finland.
   [Wei, Gong-Hong] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai Med Coll,Shanghai Canc Ctr, Shanghai, Peoples R China.
   [Luo, Linyi] Southern Medical Univ, Affiliated Dongguan Hosp, Dept Ophthalmol & Visual Sci, Guangzhou, Guangdong, Peoples R China.
   [Xu, Xingzhi] Shenzhen Univ, Guangdong Key Lab Genome Stabil Dis Prevent, Sch Med, Shenzhen, Guangdong, Peoples R China.
   [Li, Xiao-Xin] Xiamen Univ, Dept Ophthalmol, Xiamen Eye Ctr, Xiamen, Peoples R China.
C3 Peking University; Capital Normal University; Capital Normal University;
   Capital Medical University; National Institute of Biological Sciences,
   Beijing; University of Oulu; Fudan University; Shenzhen University;
   Xiamen University
RP Li, XX; Huang, LZ (通讯作者)，Peking Univ, Peoples Hosp, Eye Dis & Optometry Inst,Hlth Sci Ctr,Coll Optome, Dept Ophthalmol,Beijing Key Lab Diag & Therapy Re, Beijing 100044, Peoples R China.; Li, J (通讯作者)，Capital Normal Univ, Beijing Key Lab DNA Damage Response, Coll Life Sci, Beijing 100048, Peoples R China.
EM drlixiaoxin@163.com; jing_li@mail.cnu.edu.cn; huanglvzhen@126.com
RI Li, Jing/C-2031-2013
OI Li, Jing/0000-0002-3977-1641
FU National Natural Science Foundation of China (NSFC) fund [31872720,
   81470649, 81670870, 32090031, 31761133012, 31530016]; R&D Program of
   Beijing Municipal Education Commission [KZ202210028043]; Science and
   technology innovation project of Chinese academy of medical sciences
   [2019-RC-HL-019]; National Key R&D Program of China [2020YFC2008200];
   National Basic Research Program of China [2017YFA0503900]; Shenzhen
   Science and Technology Innovation Commission [JCYJ20180507182213033,
   JCYJ20170412113009742]
FX Supported by the National Natural Science Foundation of China (NSFC)
   fund (31872720 to J. L., 81470649 and 81670870 to L.H., 32090031,
   31761133012, and 31530016 to X. X.); R&D Program of Beijing Municipal
   Education Commission (KZ202210028043) to J. L.; Science and technology
   innovation project of Chinese academy of medical sciences
   (2019-RC-HL-019) to L.H.; National Key R&D Program of China
   (2020YFC2008200) to M.Z.; the National Basic Research Program of China
   (2017YFA0503900), and the Shenzhen Science and Technology Innovation
   Commission (JCYJ20180507182213033 and JCYJ20170412113009742) to X.X.
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NR 39
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 SEP
PY 2022
VL 63
IS 10
AR 7
DI 10.1167/iovs.63.10.7
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5U4DV
UT WOS:000876500500006
PM 36094642
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Liu, JX
   Ma, DY
   Zhi, XY
   Wang, MW
   Zhao, JY
   Qin, Y
AF Liu, Jin-xia
   Ma, Dong-yue
   Zhi, Xin-yu
   Wang, Ming-wu
   Zhao, Jiang-yue
   Qin, Yu
TI MiR-125b attenuates retinal pigment epithelium oxidative damage via
   targeting Nrf2/HIF-1 alpha signal pathway
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Nrf2; HIF-1a; miR-125b; Oxidative stress; Age-related macular
   degeneration
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; STRESS; DEGENERATION; MECHANISMS;
   INDUCTION; PROTECTS; INJURY
AB The retinal pigment epithelium cells (RPE) are sensitive to oxidative stimuli due to long-term exposure to various environmental stimuli. Thus, the oxidative injury of RPE cells caused by the imbalance of redox homeostasis is one of the main pathogenic factors of age-related macular degeneration (AMD). But the sophisticated mechanisms linking AMD to oxidative stress are not fully elucidated. Activation of Nrf2 signal pathway can protect RPE cells from oxidative damage. The present study investigated the regulating mechanism of miR-125b in Nrf2 cascade and evaluated its antioxidant capacity. The in vitro studies indicated that overexpression of miR-125b substantially inhibited Keap1 expression, enhanced Nrf2 expression and induced Nrf2 nuclear translocation. Importantly, functional studies demonstrated that forced expression of miR-125b could significantly elevate cell proliferation and superoxide dismutase (SOD) levels while reduce reactive oxygen species (ROS) overproduction and malondialdehyde (MDA) formation. Further studies showed that miR-125b had no effect when Nrf2 was silenced in ARPE-19 cells. Additionally, the results identified that Nrf2 silence induced ROS accumulation enhances HIF-1 alpha protein expression, while miR-125b could offset this effect via promoting HIF-1 alpha protein degradation. Subsequent in vivo studies demonstrated that sodium iodate induced outer retina thinner was reversed with exogenous supplementation of miR-125b, which was cancelled in Nrf2 knockout mice. In conclusion, this study illustrated that miR-125b can protect RPE from oxidative damage via targeting Nrf2/HIF-1 alpha signal pathway and potentially may serve as a therapeutic agent of AMD.
C1 [Liu, Jin-xia; Ma, Dong-yue; Zhi, Xin-yu; Zhao, Jiang-yue; Qin, Yu] China Med Univ, Eye Hosp, Dept Ophthalmol, Key Lens Res Lab Liaoning Prov,Affiliated Hosp 4, Shenyang 110005, Liaoning, Peoples R China.
   [Wang, Ming-wu] Univ Arizona, Coll Med, Dept Ophthalmol & Vis Sci, Tucson, AZ 85710 USA.
   [Wang, Ming-wu] NeuVis Med Inst, Tucson, AZ 85718 USA.
C3 China Medical University; University of Arizona
RP Qin, Y (通讯作者)，China Med Univ, Eye Hosp, Dept Ophthalmol, Key Lens Res Lab Liaoning Prov,Affiliated Hosp 4, Shenyang 110005, Liaoning, Peoples R China.
EM yqin@cmu.edu.cn
RI zhao, zhaojiangyue/GQQ-2821-2022
OI Wang, Mingwu/0000-0003-0259-3607
FU Youth Project of National Natural Science Foundation of China
   [81600717]; National Natural Science Foundation of China (Nurture)
   [114-3111210504]; Natural Science Foundation of Liaoning Province,China
   [201602851, 2021-MS-200]
FX This study was supported by the Youth Project of National Natural
   Science Foundation of China (No. 81600717) , Double Tops: the National
   Natural Science Foundation of China (Nurture) (No. 114-3111210504) , and
   the Natural Science Foundation of Liaoning Province,China (No.
   201602851, No. 2021-MS-200) .
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NR 45
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD JAN 1
PY 2022
VL 410
IS 1
AR 112955
DI 10.1016/j.yexcr.2021.112955
PG 11
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA 0J2UM
UT WOS:000779961200004
PM 34875217
DA 2022-11-30
ER

PT J
AU Xie, LQ
   Ji, XY
   Tu, YY
   Wang, K
   Zhu, LL
   Zeng, XW
   Wang, X
   Zhang, J
   Zhu, MH
AF Xie, Laiqing
   Ji, Xiaoyan
   Tu, Yuanyuan
   Wang, Kun
   Zhu, Linling
   Zeng, Xinwei
   Wang, Xue
   Zhang, Ji
   Zhu, Manhui
TI MLN4924 inhibits hedgehog signaling pathway and activates autophagy to
   alleviate mouse laser-induced choroidal neovascularization lesion
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE Choroidal neovascularization (CNV); MLN4924; Hedgehog pathway;
   Autophagy; Choroidal endothelial cells
ID MACULAR DEGENERATION; MECHANISMS; APOPTOSIS; CI
AB Neovascular age-related macular degeneration (nAMD), featured as choroidal neovascularization (CNV), can cause blindness in the elderly population. MLN4924, a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally down-regulated protein 8)-activating enzyme (NAE), inhibits the proliferation, angiogenesis and inflammation of multiple cancers via up-regulating hedgehog pathway-regulated autophagy. MLN4924 intraperitoneal injection mitigated the leakage, area and volume of mouse laserinduced CNV lesion. Additionally, compared to CNV 7 d group, MLN4924 treated mouse retina-retinal pigment epithelium (RPE)-choroid complex showed decreased expression of hedgehog pathway-associated molecules patched 1 (PTCH1), smoothened (SMO), GLI family zinc finger 1 (GLI1) and GLI family zinc finger 2 (GLI2) with increased expression of autophagy-associated molecules sequestosome 1 (p62) and LC microtubule-associated protein 1 light chain 3 (LC3). Meanwhile, human choroidal endothelial cells (HCECs) exposed to hypoxia condition also showed decreased expression of hedgehog pathway-associated molecules and increased expression of autophagy-associated molecules. Compared to hypoxia + MLN4924 group, SMO agonist SAG up-regulated hedgehog pathway and down-regulated autophagy, whereas autophagy inhibitor PIK-III inhibited autophagy with no effect on hedgehog pathway, indicating that MLN4924 facilitated autophagy of HCECs via hindering hedgehog pathway under hypoxia condition. Finally, MLN4924 inhibited proliferation, migration and tube formation of HCECs via boosting hedgehog pathway-regulated autophagy. In summary, MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. The results provide a potential interfering strategy for nAMD targeting the autophagy of choroidal endothelial cells.
C1 [Xie, Laiqing; Ji, Xiaoyan; Zeng, Xinwei; Wang, Xue; Zhang, Ji] Soochow Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
   [Tu, Yuanyuan; Wang, Kun; Zhu, Linling; Zhu, Manhui] Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
C3 Soochow University - China; Soochow University - China
RP Zhang, J (通讯作者)，Soochow Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.; Zhu, MH (通讯作者)，Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
EM jizhang0068@sina.com; zhumanhuieye@126.com
RI 涂, 园园/AGE-3991-2022
FU Suzhou Science and Technology Bureau [SYS2018060, SYS2018005]; Suzhou
   Commission of Health and Family Planning [KJXW2018076]; Natural Science
   Foundation of China [SDFEYGJ1905]; Open subject of the State Key
   Laboratory of Radiation Medicine and Radiation Protection [GZK1201912]
FX The study was supported by the Suzhou Science and Technology Bureau (No.
   SYS2018060 & No. SYS2018005), the Suzhou Commission of Health and Family
   Planning (No. KJXW2018076), Natural Science Foundation of China (No.
   SDFEYGJ1905) and Open subject of the State Key Laboratory of Radiation
   Medicine and Radiation Protection (No. GZK1201912).
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NR 44
TC 0
Z9 1
U1 3
U2 5
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI ISSY-LES-MOULINEAUX
PA 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE
SN 0753-3322
EI 1950-6007
J9 BIOMED PHARMACOTHER
JI Biomed. Pharmacother.
PD OCT
PY 2020
VL 130
AR 110654
DI 10.1016/j.biopha.2020.110654
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA OH6JX
UT WOS:000582697900125
PM 34321162
OA gold
DA 2022-11-30
ER

PT J
AU Tsunoda, K
   Fujinami, K
   Yoshitake, K
   Iwata, T
AF Tsunoda, Kazushige
   Fujinami, Kaoru
   Yoshitake, Kazutoshi
   Iwata, Takeshi
TI Late-onset night blindness with peripheral flecks accompanied by
   progressive trickle-like macular degeneration
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Night blindness; White dot syndrome; Macular degeneration; Trickling AMD
ID MEDIATED DARK-ADAPTATION; FUNDUS-ALBIPUNCTATUS; SYMPTOMATIC
   ABNORMALITIES; RETINAL DEGENERATION; GEOGRAPHIC ATROPHY; JAPANESE
   FAMILY; RDH5 MUTATION; GENE; CONE; AUTOFLUORESCENCE
AB Purpose To report the clinical and genetic characteristics of 6 cases with late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration.
   Methods Clinical and genetic data were collected from 6 independent patients who complained of night blindness in their fifth to eighth decade of life. The ophthalmological examinations included ophthalmoscopy, fundus autofluorescence (FAF), and full-field electroretinography (ERG). Whole exome sequencing with target gene analysis was performed to determine the causative genes and variants.
   Results All of the patients first complained of night blindness at the ages of 40-71 years. Funduscopic examinations demonstrated white or atrophic flecks scattered in the posterior pole and peripheral retina bilaterally. FAF showed patchy hypo-autofluorescence spots in the posterior pole similar to that of the trickling type of age-related macular degeneration (AMD). The region of abnormal FAF rapidly expanded with age, and one eye developed a choroidal neovascularization. The full-field scotopic ERGs with 20 min of dark adaptation were severely reduced or extinguished in all cases. There was partial recovery of the ERGs after 180 min of dark adaptation. The cone ERGs were reduced in all cases. Whole exome sequencing revealed no pathogenic variants of 301 retinal disease-associated genes.
   Conclusions The six cases had some common features with the flecked retina syndrome, familial drusen, and late-onset retinal degeneration although none had pathogenic variants causative for these disorders. These cases may represent a subset of severe trickling AMD or a new clinical entity of acquired pan-retinal visual cycle deficiency of unknown etiology.
C1 [Tsunoda, Kazushige; Fujinami, Kaoru] Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Div Vision Res, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
   [Fujinami, Kaoru] UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
   [Yoshitake, Kazutoshi; Iwata, Takeshi] Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
C3 University of London; University College London
RP Tsunoda, K (通讯作者)，Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Div Vision Res, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
EM tsunodakazushige@kankakuki.go.jp
FU Japan Agency for Medical Research and Development (AMED); Ministry of
   Health, Labor and Welfare, and Japan [18ek0109282h0002]; Japan Society
   for the Promotion of Science [H26-26462674, 16H06269, 161(1(0193];
   National Hospital Organization Network Research Fund [H30-NHO-Sensory
   Organs-03]; Novartis; Foundation Fighting Blindness, USA; Great Britain
   Sasakawa Foundation Butterfield Awards, UK
FX This study is supported by research grants from the Japan Agency for
   Medical Research and Development (AMED), the Ministry of Health, Labor
   and Welfare, and Japan (18ek0109282h0002 to TI), Grants-in-Aid for
   Scientific Research, Japan Society for the Promotion of Science
   (H26-26462674 to KT, 16H06269, 161(1(0193 to KF), National Hospital
   Organization Network Research Fund (H30-NHO-Sensory Organs-03 to KF,
   KT), and Novartis Research Grant (2018 to KT). Kaoru Fujinami is
   supported by Foundation Fighting Blindness, USA, and Great Britain
   Sasakawa Foundation Butterfield Awards, UK.
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NR 51
TC 5
Z9 5
U1 1
U2 4
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 DEC
PY 2019
VL 139
IS 3
BP 171
EP 184
DI 10.1007/s10633-019-09705-7
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KS8EU
UT WOS:000518539500002
PM 31286363
DA 2022-11-30
ER

PT J
AU Aharony, O
   Gal-Or, O
   Polat, A
   Nahum, Y
   Weinberger, D
   Zimmer, Y
AF Aharony, Omer
   Gal-Or, Orly
   Polat, Asaf
   Nahum, Yoav
   Weinberger, Dov
   Zimmer, Yair
TI Automatic Characterization of Retinal Blood Flow Using OCT Angiograms
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE optical coherence tomography angiography; vascular quantification;
   vessel density; fractal dimension; foveal avascular zone
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; DIABETIC-RETINOPATHY; FUNDUS IMAGES;
   MICROVASCULATURE; FEATURES; DENSITY
AB Purpose: To quantitatively characterize the retinal vascular network in healthy and pathological cases using optical coherence tomography angiography (OCTA) images.
   Methods: The study included 56 eyes of 28 patients as follows: 26 healthy, 20 with diabetic retinopathy (DR), 6 with age-related macular degeneration (AMD), and 4 with retinal vein occlusion (RVO). For 33 eyes (16 healthy and 17 with DR), vessel density maps were provided by the OCTA machine. An automatic algorithm classified the image (as healthy, DR, AMD, or RVO) and provided quantitative information obtained from the angiograms, including global vessel density, global fractal dimension, and fovea avascular zone (FAZ) area. Classification results were compared with the diagnosis made by a retina specialist. The quantitative values were compared with the literature and to values provided by the OCTA machine.
   Results: The success rate of classification was 83.9%. Vessel densities obtained by our algorithm (in healthy and DR cases) were significantly lower than the values reported in previous studies using OCTA. Similarly, they were much lower than the values provided by the OCTA machine. However, vessel densities in the healthy cases were similar to or higher than (depending on the retinal layer) the recently published values that may be considered as gold standard. Our values of fractal dimension were similar to those previously reported.
   Conclusions: Our algorithm provides significantly improved vessel density values compared with previous studies. We believe our algorithm successfully omits false vessels.
   Translational Relevance: Accurately assessing retinal vessel density enables better evaluation of retinal disorders.
C1 [Aharony, Omer; Zimmer, Yair] Afeka Coll Engn, Sch Med Engn, 38 Mivtza Kadesh St, IL-6998812 Tel Aviv, Israel.
   [Gal-Or, Orly; Polat, Asaf; Nahum, Yoav; Weinberger, Dov] Rabin Med Ctr, Dept Ophthalmol, Petah Tiqwa, Israel.
   [Gal-Or, Orly; Polat, Asaf; Nahum, Yoav; Weinberger, Dov] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.
C3 Rabin Medical Center; Tel Aviv University; Sackler Faculty of Medicine
RP Zimmer, Y (通讯作者)，Afeka Coll Engn, Sch Med Engn, 38 Mivtza Kadesh St, IL-6998812 Tel Aviv, Israel.
EM yairz@afeka.ac.il
RI Nahum, Yoav/AAW-8327-2021
OI Nahum, Yoav/0000-0002-0246-4787
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NR 20
TC 4
Z9 4
U1 0
U2 5
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 JUL
PY 2019
VL 8
IS 4
AR 6
DI 10.1167/tvst.8.4.6
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IL8ZN
UT WOS:000477575100001
PM 31338254
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Khalid, S
   Akram, MU
   Hassan, T
   Jameel, A
   Khalil, T
AF Khalid, Samina
   Akram, M. Usman
   Hassan, Taimur
   Jameel, Amina
   Khalil, Tehmina
TI Automated Segmentation and Quantification of Drusen in Fundus and
   Optical Coherence Tomography Images for Detection of ARMD
SO JOURNAL OF DIGITAL IMAGING
LA English
DT Article
DE Optical coherence tomography (OCT); Fundus images; Age related macular
   degeneration (ARMD); RPE; Grading
ID DIABETIC MACULAR EDEMA; RETINAL LAYERS; SD-OCT; DEGENERATION; THICKNESS;
   EYES
AB Age-related macular degeneration (ARMD) is one of the most common retinal syndromes that occurs in elderly people. Different eye testing techniques such as fundus photography and optical coherence tomography (OCT) are used to clinically examine the ARMD-affected patients. Many researchers have worked on detecting ARMD from fundus images, few of them also worked on detecting ARMD from OCT images. However, there are only few systems that establish the correspondence between fundus and OCT images to give an accurate prediction of ARMD pathology. In this paper, we present fully automated decision support system that can automatically detect ARMD by establishing correspondence between OCT and fundus imagery. The proposed system also distinguishes between early, suspect and confirmed ARMD by correlating OCT B-scans with respective region of the fundus image. In first phase, proposed system uses different B-scan based features along with support vector machine (SVM) to detect the presence of drusens and classify it as ARMD or normal case. In case input OCT scan is classified as ARMD, region of interest from corresponding fundus image is considered for further evaluation. The analysis of fundus image is performed using contrast enhancement and adaptive thresholding to detect possible drusens from fundus image and proposed system finally classified it as early stage ARMD or advance stage ARMD. The proposed system is tested on local data set of 100 patients with 100 fundus images and 6800 OCT B-scans. Proposed system detects ARMD with the accuracy, sensitivity, and specificity ratings of 98.0, 100, and 97.14%, respectively.
C1 [Khalid, Samina; Khalil, Tehmina] Mirpur Univ Sci & Technol, Dept Comp Sci & Informat Technol, Mirpur, Pakistan.
   [Khalid, Samina; Khalil, Tehmina] Bahria Univ, Dept Software Engn, Islamabad, Pakistan.
   [Akram, M. Usman; Hassan, Taimur] Natl Univ Sci & Technol, Dept Comp Engn, Islamabad, Pakistan.
   [Hassan, Taimur] Bahria Univ, Dept Elect Engn, Islamabad, Pakistan.
   [Jameel, Amina] Bahria Univ, Dept Comp Engn, Islamabad, Pakistan.
C3 National University of Sciences & Technology - Pakistan
RP Akram, MU (通讯作者)，Natl Univ Sci & Technol, Dept Comp Engn, Islamabad, Pakistan.
EM usmakram@gmail.com
RI Hassan, Taimur/AAO-3928-2020; Akram, Muhammad Usman/AAD-7343-2020;
   Khalid, Samina/AAV-3527-2021
OI Hassan, Taimur/0000-0002-5896-8677; Akram, Muhammad
   Usman/0000-0002-6208-7231; Khalid, Samina/0000-0003-4771-6842
FU IGNITE formally known as National ICT RD fund
FX This study is sponsored by IGNITE formally known as National ICT R&D
   fund.
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NR 45
TC 13
Z9 13
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0897-1889
EI 1618-727X
J9 J DIGIT IMAGING
JI J. Digit. Imaging
PD AUG
PY 2018
VL 31
IS 4
BP 464
EP 476
DI 10.1007/s10278-017-0038-7
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA GR8RI
UT WOS:000442992300011
PM 29204763
OA Green Published
DA 2022-11-30
ER

PT J
AU Namitha, KK
   Negi, PS
AF Namitha, Kanakapura Krishnamurthy
   Negi, Pradeep Singh
TI Transformation of tomato cv. Arka Ahuti (Solanum lycopersicum L.) with
   phytoene desaturase (CrtI) and lycopene beta-cyclase (CrtY) genes
   increases carotenoid content and antioxidant potential
SO JOURNAL OF PLANT BIOCHEMISTRY AND BIOTECHNOLOGY
LA English
DT Article
DE Agroinjection; Carotenoid enhancement; Lycopene beta-cyclase; Phytoene
   desaturase; Tomato transformation
ID FRUIT-DEVELOPMENT; BIOSYNTHESIS; PLANTS; EXPRESSION; PROVITAMIN;
   SYNTHASE; CONVERSION; VARIETIES; PATHWAY; HEALTH
AB In recent years, there has been a considerable interest in the dietary carotenoids due to their pro-vitamin A activity, high antioxidant potential, ability to prevent onset of certain cancers and age related macular degeneration. To enhance the carotenoid content, agroinjection of tomato fruits was carried out with Agrobacterium tumefaciens GV 3101 containing binary vector pRI 101(I) (harbouring Phytoene desaturase (CrtI) gene), and pRI 101(Y) (harbouring Lycopene beta-cyclase (CrtY) gene) individually. The presence of transgenes was confirmed by PCR, and transgenes integration was seen in Southern blot analysis. The beta-carotene and lycopene content in pRI 101(I) agro-infiltrated tomato fruits showed up to 2.4- and 1.2-fold increase, respectively, over control fruits; whereas up to 2- and 1.2-fold increase was observed in pRI 101(Y) agro-infiltrated tomato fruits. The total antioxidant potential was also found to be higher (5-6-fold) for hydrophilic and lipophilic extracts from agro-infiltrated tomatoes when compared to extracts from control tomatoes, probably due to the combined effect of enhanced carotenoids, phenolics and ascorbic acid. A relatively new method of introducing transgenes directly into tomato fruits was carried out, and the levels of beta-carotene and lycopene were enhanced in comparison to control fruits. The present study indicated the usefulness of agroinfiltration in transformation of tomatoes for enhancement of carotenoid content, however, stability of transgenes in future generation needs to be ascertained. Once stable transformation is achieved, the fruits can be used to derive maximal health benefits associated with carotenoids.
C1 [Namitha, Kanakapura Krishnamurthy; Negi, Pradeep Singh] Cent Food Technol Res Inst, CSIR, Fruit & Vegetable Technol Dept, Mysore 570020, Karnataka, India.
C3 Council of Scientific & Industrial Research (CSIR) - India; CSIR -
   Central Food Technological Research Institute (CFTRI)
RP Negi, PS (通讯作者)，Cent Food Technol Res Inst, CSIR, Fruit & Vegetable Technol Dept, Mysore 570020, Karnataka, India.
EM psnegi@cftri.res.in
RI Negi, Pradeep S/J-7493-2015; Negi, Pradeep/ABF-1751-2020
OI Negi, Pradeep S/0000-0002-0458-6294; Negi, Pradeep/0000-0002-0458-6294
FU Council of Scientific and Industrial Research, New Delhi, India
FX We thank Director, CSIR-CFTRI for constant support and encouragement.
   KKN acknowledges Council of Scientific and Industrial Research, New
   Delhi, India, for the financial support in the form of a Senior Research
   Fellowship for pursuing Doctoral programme.
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NR 49
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Z9 3
U1 0
U2 21
PU SPRINGER INDIA
PI NEW DELHI
PA 7TH FLOOR, VIJAYA BUILDING, 17, BARAKHAMBA ROAD, NEW DELHI, 110 001,
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SN 0971-7811
EI 0974-1275
J9 J PLANT BIOCHEM BIOT
JI J. Plant Biochem. Biotechnol.
PD JAN
PY 2018
VL 27
IS 1
BP 68
EP 77
DI 10.1007/s13562-017-0417-7
PG 10
WC Biochemistry & Molecular Biology; Plant Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Plant Sciences
GA FS8XA
UT WOS:000422696800007
DA 2022-11-30
ER

PT J
AU Hashemi, H
   Khabazkhoob, M
   Nabovati, P
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   Shafaee, S
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AF Hashemi, Hassan
   Khabazkhoob, Mehdi
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   Ostadimoghaddam, Hadi
   Shafaee, Shokrolah
   Doostdar, Asgar
   Yekta, AbbasAli
TI The Prevalence of Age-Related Eye Disease in an Elderly Population
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Age-related maculopathy; cataract; diabetic retinopathy; epidemiology;
   glaucoma; prevalence
ID VISUAL IMPAIRMENT; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; INDIAN
   POPULATION; GLOBAL PREVALENCE; RURAL-POPULATION; OLDER POPULATION;
   RISK-FACTORS; BLINDNESS; GLAUCOMA
AB Purpose: To determine the prevalence of cataracts, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) in Iranians over the age of 54 years.
   Methods: Through a cross-sectional study using randomized cluster sampling, 60 clusters were selected in Sari, a city in the North of Iran. In each cluster, 20 people over 54 years of age were chosen systematically and were invited to participate in the study. After enrollment, all participants had optometric and ophthalmologic exams including slit lamp biomicroscopy and fundoscopy.
   Results: Of the 1185 selected persons, 937 (79.1%) participated in this study (age range 55-87 years). The prevalence of cataracts, AMD, glaucoma, and DR in at least one eye was 29.6% (95% confidence interval [CI] 26.6-32.5), 5.8% (95% CI: 4.3-7.3), 3.7% (95% CI: 2.5-5.0), and 2.7% (95% CI: 1.6-3.7), respectively. All prevalences significantly increased with aging. AMD was more prevalent in men (7.4%) than women (4.4%) (p = 0.054). Overall, 35.8% (95% CI: 32.7-38.8) of participants had at least one of the four conditions; this rate was 27.4% for the 55-59-year old age group and 52.4% for those over 75 years of age.
   Conclusion: Overall, 35.8% of the studied population had at least one of the four diseases. Cataracts, followed by AMD, are the most common age-related eye diseases in the Iranian population, and thus, precise planning along with enhanced diagnostic and therapeutic facilities are necessary.
C1 [Hashemi, Hassan; Nabovati, Payam] Noor Eye Hosp, Noor Res Ctr Ophthalm Epidemiol, Tehran, Iran.
   [Khabazkhoob, Mehdi] Shahid Beheshti Univ Med Sci, Sch Nursing & Midwifery, Dept Med Surg Nursing, Tehran, Iran.
   [Khabazkhoob, Mehdi] Noor Eye Hosp, Noor Ophthalmol Res Ctr, Tehran, Iran.
   [Ostadimoghaddam, Hadi; Shafaee, Shokrolah] Mashhad Univ Med Sci, Sch Paramed Sci, Refract Errors Res Ctr, Mashhad, Iran.
   [Doostdar, Asgar] Iran Univ Med Sci, Dept Optometry, Tehran, Iran.
   [Yekta, AbbasAli] Mashhad Univ Med Sci, Sch Paramed Sci, Dept Optometry, Mashhad, Iran.
C3 Shahid Beheshti University Medical Sciences; Mashhad University Medical
   Science; Iran University of Medical Sciences; Mashhad University Medical
   Science
RP Yekta, A (通讯作者)，Mashhad Univ Med Sci, Sch Paramed Sci, Dept Optometry, Mashhad, Iran.
EM yektaa@mums.ac.ir
RI Nabovati, Payam/AAP-6759-2021; Doostdar, Asgar/AAT-2487-2021; Yekta,
   Abbasali/A-7810-2017; ostadimoghaddam, hadi/P-3198-2018; Khabazkhoob,
   Mehdi/Q-4537-2017; Hashemi, Hassan/N-2293-2019
OI Doostdar, Asgar/0000-0002-7370-5437; Yekta,
   Abbasali/0000-0003-4356-9064; ostadimoghaddam, hadi/0000-0002-1210-2923;
   Hashemi, Hassan/0000-0002-6086-1537; Khabazkhoob,
   Mehdi/0000-0003-0801-8793
FU Mashhad University of Medical Sciences, Iran
FX This project was supported by Mashhad University of Medical Sciences,
   Iran.
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NR 39
TC 21
Z9 22
U1 0
U2 10
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 AUG
PY 2017
VL 24
IS 4
BP 222
EP 228
DI 10.1080/09286586.2016.1270335
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FA4FT
UT WOS:000405399900004
PM 28658589
DA 2022-11-30
ER

PT J
AU Natoli, R
   Fernando, N
   Jiao, HH
   Racic, T
   Madigan, M
   Barnett, NL
   Chu-Tan, JA
   Valter, K
   Provis, J
   Rutar, M
AF Natoli, Riccardo
   Fernando, Nilisha
   Jiao, Haihan
   Racic, Tanja
   Madigan, Michele
   Barnett, Nigel L.
   Chu-Tan, Joshua A.
   Valter, Krisztina
   Provis, Jan
   Rutar, Matt
TI Retinal Macrophages Synthesize C3 and Activate Complement in AMD and in
   Models of Focal Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; inflammation; macrophages; retinal
   degeneration; complement
ID C57BL/6J MOUSE RETINA; MACULAR DEGENERATION; PHOTORECEPTOR DEGENERATION;
   MEDIATED INFLAMMATION; OXIDATIVE DAMAGE; MULLER CELLS; 2 PARTS; DRUSEN;
   EXPRESSION; IMMUNOLOGY
AB PURPOSE. Complement system dysregulation is strongly linked to the progression of age-related macular degeneration (AMD). Deposition of complement including C3 within the lesions in atrophic AMD is thought to contribute to lesion growth, although the contribution of local cellular sources remains unclear. We investigated the role of retinal microglia and macrophages in complement activation within atrophic lesions, in AMD and in models of focal retinal degeneration.
   METHODS. Human AMD donor retinas were labeled for C3 expression via in situ hybridization. Rats were subject to photo-oxidative damage, and lesion expansion was tracked over a 2-month period using optical coherence tomography (OCT). Three strategies were used to determine the contribution of local and systemic C3 in mice: total C3 genetic ablation, local C3 inhibition using intravitreally injected small interfering RNA (siRNA), and depletion of serum C3 using cobra venom factor.
   RESULTS. Retinal C3 was expressed by microglia/macrophages located in the outer retina in AMD eyes. In rodent photo-oxidative damage, C3-expressing microglia/macrophages and complement activation were located in regions of lesion expansion in the outer retina over 2 months. Total genetic ablation of C3 ameliorated degeneration and complement activation in retinas following damage, although systemic depletion of serum complement had no effect. In contrast, local suppression of C3 expression using siRNA inhibited complement activation and deposition, and reduced cell death.
   CONCLUSIONS. These findings implicate C3, produced locally by retinal microglia/macrophages, as contributing causally to retinal degeneration. Consequently, this suggests that C3-targeted gene therapy may prove valuable in slowing the progression of AMD.
C1 [Natoli, Riccardo; Fernando, Nilisha; Jiao, Haihan; Racic, Tanja; Chu-Tan, Joshua A.; Valter, Krisztina; Provis, Jan; Rutar, Matt] Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
   [Natoli, Riccardo; Valter, Krisztina; Provis, Jan] Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
   [Madigan, Michele] Univ Sydney, Save Sight Inst, Discipline Clin Ophthalmol, Sydney, NSW, Australia.
   [Madigan, Michele] Univ New South Wales, Sch Optometry & Vis Sci, Kensington, NSW, Australia.
   [Barnett, Nigel L.] Queensland Eye Inst, South Brisbane, Qld, Australia.
   [Barnett, Nigel L.] Univ Queensland, Clin Res Ctr, Herston, Qld, Australia.
   [Barnett, Nigel L.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
   [Rutar, Matt] Univ Melbourne, Dept Anat & Neurosci, Victoria, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; University of Sydney; University of New
   South Wales Sydney; Queensland Eye Institute; University of Queensland;
   Queensland University of Technology (QUT); University of Melbourne
RP Provis, J (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
EM jan.provis@anu.edu.au
RI Provis, Jan/C-9529-2009; Chu-Tan, Joshua A/A-9728-2019; Valter,
   Krisztina/L-3015-2016; Barnett, Nigel L/F-1226-2010
OI Provis, Jan/0000-0002-6405-2868; Barnett, Nigel L/0000-0002-0704-2233;
   Rutar, Matthew/0000-0002-8893-5120; Jiao, Haihan/0000-0002-5404-9307;
   Natoli, Riccardo/0000-0002-9350-0439; Valter,
   Krisztina/0000-0002-2033-0408; Chu-Tan, Joshua/0000-0001-7936-8972;
   Fernando, Nilisha/0000-0002-8488-1348
FU Retina Australia; National Health and Medical Research Council (NHMRC)
   [APP1049990]; Australian Government Research Training Program (RTP)
   Scholarship
FX Supported by a grant from Retina Australia, as well as the National
   Health and Medical Research Council (NHMRC; APP1049990). Also supported
   by an Australian Government Research Training Program (RTP) Scholarship.
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NR 53
TC 58
Z9 61
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2017
VL 58
IS 7
BP 2977
EP 2990
DI 10.1167/iovs.17-21672
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EZ8FE
UT WOS:000404959300017
PM 28605809
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Jin, L
   Liu, WR
   Tian, MX
   Jiang, XF
   Wang, H
   Zhou, PY
   Ding, ZB
   Peng, YF
   Dai, Z
   Qiu, SJ
   Zhou, J
   Fan, J
   Shi, YH
AF Jin, Lei
   Liu, Wei-Ren
   Tian, Meng-Xin
   Jiang, Xi-Fei
   Wang, Han
   Zhou, Pei-Yun
   Ding, Zhen-Bin
   Peng, Yuan-Fei
   Dai, Zhi
   Qiu, Shuang-Jian
   Zhou, Jian
   Fan, Jia
   Shi, Ying-Hong
TI CCL24 contributes to HCC malignancy via RhoB- VEGFA-VEGFR2 angiogenesis
   pathway and indicates poor prognosis
SO ONCOTARGET
LA English
DT Article
DE CCL24; HCC; RhoB; VEGFA; prognosis
ID ENDOTHELIAL GROWTH-FACTOR; COLORECTAL-CANCER; T-CELLS; EXPRESSION;
   ACTIVATION; EOTAXIN-2; CHEMOKINES; RESISTANCE; MIGRATION; MECHANISM
AB CCL24 is one chemotactic factor extensively studied in airway inflammation and colorectal cancer but less studied in hepatocellular carcinoma (HCC) retrospectively. So HCC tissue microarray (TMA) was used to estimate relationship between CCL24 and prognosis, cell experiments were conducted to study its influence for HCC cell biological behavior. CCL24 was injected to nude mice to monitor tumor formation and pulmonary metastasis; qRT-PCR, western blot and Immunohistochemistry were used to explore potential mechanism. CCL24 plays roles in target cells via its downstream CCR3, or it is regulated by Type 2 helper T cells (Th2 cell) factors, so immune related experiments were conducted. Meanwhile, Rho GTPase family have close relation not only with T cell priming, but with neovascularization; CCL24 contributes to neovascularization in age-related macular degeneration via CCR3, so Rho GTPase family, Th2 cell factors, Human Umbilical Vein Endothelial Cells were used to uncover their trafficking. Ultimate validation was confirmed by small interfering RNA. Results showed CCL24 expression was higher in caner tissues than adjacent normal tissues, it could contribute to proliferation, migration, and invasion in HCCs, could accelerate pulmonary metastasis, promote HUVECs tube formation. Th2 cell factors were irrelevant with CCL24 in HCCs; and RhoB, VEGFA, and VEGFR2 correlated with CCL24 in both mRNA and protein level. Downstream RhoB-VEGFA signaling pathway was validated by siRhoB and siVEGFA inhibition. In a word, CCL24 contributes to HCC malignancy via RhoB-VEGFA-VEGFR2 angiogenesis pathway and indicates poor prognosis, which urges us to study further CCL24 effects on diagnosis and potential therapy for HCC.
C1 [Jin, Lei; Liu, Wei-Ren; Tian, Meng-Xin; Jiang, Xi-Fei; Wang, Han; Zhou, Pei-Yun; Ding, Zhen-Bin; Peng, Yuan-Fei; Dai, Zhi; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Shi, Ying-Hong] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Zhongshan Hosp, Dept Liver Surg,Liver Canc Inst,Minist Edu, Shanghai, Peoples R China.
   [Zhou, Jian; Fan, Jia] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China.
C3 Fudan University; Fudan University
RP Shi, YH (通讯作者)，Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Zhongshan Hosp, Dept Liver Surg,Liver Canc Inst,Minist Edu, Shanghai, Peoples R China.
EM shi.yinghong@zs-hospital.sh.cn
RI Shi, Yongyong/GSO-1627-2022
OI Shi, Yongyong/0000-0003-1710-1505; Zhou, Jian/0000-0002-7650-7540
FU National Natural Science Foundation of China [81272389, 81472674,
   81502486]
FX This work was supported by the grants from National Natural Science
   Foundation of China (No.81272389, 81472674, 81502486).
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NR 39
TC 25
Z9 26
U1 1
U2 9
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 JAN 17
PY 2017
VL 8
IS 3
BP 5135
EP 5148
DI 10.18632/oncotarget.14095
PG 14
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA EJ5AH
UT WOS:000393228400111
PM 28042950
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Koenig, P
   Sanowar, S
   Lee, CV
   Fuh, G
AF Koenig, Patrick
   Sanowar, Sarah
   Lee, Chingwei V.
   Fuh, Germaine
TI Tuning the specificity of a Two-in-One Fab against three angiogenic
   antigens by fully utilizing the information of deep mutational scanning
SO MABS
LA English
DT Article
DE Angiopoietin-1; Angiopoietin-2; deep mutational scanning; deep
   sequencing; dual action Fab; dual specificity antibody; drug discovery;
   phage; specificity engineering; vascular endothelial growth factor
ID VITRO AFFINITY MATURATION; CROSS-REACTIVITY; ANTIBODY; BINDING; PROTEIN;
   MUTAGENESIS; TARGET; STRATEGY
AB Monoclonal antibodies developed for therapeutic or diagnostic purposes need to demonstrate highly defined binding specificity profiles. Engineering of an antibody to enhance or reduce binding to related antigens is often needed to achieve the desired biologic activity without safety concern. Here, we describe a deep sequencing-aided engineering strategy to fine-tune the specificity of an angiopoietin-2 (Ang2)/vascular endothelial growth factor (VEGF) dual action Fab, 5A12.1 for the treatment of age-related macular degeneration. This antibody utilizes overlapping complementarity-determining region (CDR) sites for dual Ang2/VEGF interaction with K-D in the sub-nanomolar range. However, it also exhibits significant (KD of 4 nM) binding to angiopoietin-1, which has high sequence identity with Ang2. We generated a large phage-displayed library of 5A12.1 Fab variants with all possible single mutations in the 6 CDRs. By tracking the change of prevalence of each mutation during various selection conditions, we identified 35 mutations predicted to decrease the affinity for Ang1 while maintaining the affinity for Ang2 and VEGF. We confirmed the specificity profiles for 25 of these single mutations as Fab protein. Structural analysis showed that some of the Fab mutations cluster near a potential Ang1/2 epitope residue that differs in the 2 proteins, while others are up to 15 angstrom away from the antigen-binding site and likely influence the binding interaction remotely. The approach presented here provides a robust and efficient method for specificity engineering that does not require prior knowledge of the antigen antibody interaction and can be broadly applied to antibody specificity engineering projects.
C1 [Koenig, Patrick; Sanowar, Sarah; Lee, Chingwei V.; Fuh, Germaine] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech
RP Koenig, P; Fuh, G (通讯作者)，Genentech Inc, Antibody Engn, 1 DNA Way, San Francisco, CA 94080 USA.
EM koenig.patrick@gmail.com; germainefuh@gmail.com
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NR 47
TC 10
Z9 10
U1 2
U2 9
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PY 2017
VL 9
IS 6
BP 959
EP 967
DI 10.1080/19420862.2017.1337618
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA FC3UC
UT WOS:000406763900007
PM 28585908
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Croze, RH
   Thi, WJ
   Clegg, DO
AF Croze, Roxanne H.
   Thi, William J.
   Clegg, Dennis O.
TI ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in
   Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age related macular degeneration; retinal pigment epithelium; ROCK
   inhibition
ID TO-MESENCHYMAL TRANSITION; GROWTH-FACTOR-BETA; MACULAR DEGENERATION;
   KINASE INHIBITOR; MIGRATION; VITREORETINOPATHY; ACTIVATION; PATHWAY;
   PHOSPHORYLATION; DIFFERENTIATION
AB Purpose: Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell-derived RPE (hESC-RPE) attachment, proliferation, and wound closure.
   Methods: H9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined.
   Results: Pharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition.
   Conclusions: ROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing.
   Translational Relevance: Modulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies.
C1 [Croze, Roxanne H.; Thi, William J.; Clegg, Dennis O.] Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Stem Cell Biol & Engn, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Clegg, DO (通讯作者)，Univ Calif Santa Barbara, Neurores Inst, Bldg 571,Room 6131, Santa Barbara, CA 93106 USA.
EM dennis.clegg@lifesci.ucsb.edu
FU California Institute for Regenerative Medicine (CIRM) [DR1-01444,
   CL1-00521, TB1-01177, TG2-01151, FA1-00616]; Foundation Fighting
   Blindness Wynn-Gund Translational Research Acceleration Program; Garland
   Initiative for Vision at UC Santa Barbara; US Army Research Office
   [W911NF-09-0001]
FX Supported by the California Institute for Regenerative Medicine (CIRM;
   DR1-01444, CL1-00521, TB1-01177, TG2-01151 and FA1-00616), The
   Foundation Fighting Blindness Wynn-Gund Translational Research
   Acceleration Program, the Garland Initiative for Vision at UC Santa
   Barbara, and a grant to the University of California Santa Barbara
   Institute for Collaborative Biotechnologies from the US Army Research
   Office (W911NF-09-0001). The content within does not necessarily reflect
   the position or policy of the government, and endorsement should not be
   inferred. RHC was a fellow of the California Institute for Regenerative
   Medicine.
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NR 53
TC 15
Z9 15
U1 0
U2 10
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 NOV
PY 2016
VL 5
IS 6
AR 7
DI 10.1167/tvst.5.6.7
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EI7SW
UT WOS:000392704600007
PM 27917311
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Baek, SM
   Yu, SY
   Son, Y
   Hong, HS
AF Baek, Sang-Min
   Yu, Seung-Young
   Son, Youngsook
   Hong, Hyun Sook
TI Substance P promotes the recovery of oxidative stress-damaged retinal
   pigmented epithelial cells by modulating Akt/GSK-3 beta signaling
SO MOLECULAR VISION
LA English
DT Article
ID AKT ACTIVATION; STEM-CELLS; RECEPTOR; RPE; TRIAMCINOLONE; APOPTOSIS;
   RESVERATROL; BEVACIZUMAB; INVOLVEMENT; THERAPY
AB Purpose: Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress.
   Methods: To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3 beta activation in RPE cells in vitro.
   Results: H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3 beta signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells.
   Conclusions: SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3 beta signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.
C1 [Baek, Sang-Min] Kyung Hee Univ, Grad Sch, Dept Med, Seoul, South Korea.
   [Yu, Seung-Young] Kyung Hee Univ Hosp, Dept Ophthalmol, Seoul, South Korea.
   [Son, Youngsook] Kyung Hee Univ, Grad Sch Biotechnol, Coll Life Sci, Global Campus, Yongin, South Korea.
   [Son, Youngsook] Kyung Hee Univ, Dept Genet Engn, Coll Life Sci, Global Campus, Yongin, South Korea.
   [Hong, Hyun Sook] Kyung Hee Univ, Coll Med, East West Med Res Inst, 1 Hoegi Dong, Seoul 02447, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University
   Hospital; Kyung Hee University; Kyung Hee University; Kyung Hee
   University
RP Hong, HS (通讯作者)，Kyung Hee Univ, Coll Med, East West Med Res Inst, 1 Hoegi Dong, Seoul 02447, South Korea.
EM hshong@khu.ac.kr
RI HONG, HYUN SOOK/AAI-3017-2020
OI HONG, HYUN SOOK/0000-0003-3659-1386
FU Korean Health Technology R&D Project grant from the Ministry of Health
   and Welfare (Sejong, Republic of Korea) [HI13C1479]; Bio & Medical
   Technology Development Program of the National Research Foundation
   [NRF-2012M3A9C6050499]
FX This study was supported by a Korean Health Technology R&D Project grant
   (HI13C1479) from the Ministry of Health and Welfare (Sejong, Republic of
   Korea) and by the Bio & Medical Technology Development Program
   (NRF-2012M3A9C6050499) of the National Research Foundation.
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NR 43
TC 25
Z9 27
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD AUG 12
PY 2016
VL 22
BP 1015
EP 1023
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA DX7MG
UT WOS:000384571000001
PM 27582624
DA 2022-11-30
ER

PT J
AU Vessey, KA
   Greferath, U
   Aplin, FP
   Jobling, AI
   Phipps, JA
   Ho, T
   De Iongh, RU
   Fletcher, EL
AF Vessey, Kirstan A.
   Greferath, Ursula
   Aplin, Felix P.
   Jobling, Andrew I.
   Phipps, Joanna A.
   Ho, Tracy
   De Iongh, Robbert U.
   Fletcher, Erica L.
TI Adenosine Triphosphate-Induced Photoreceptor Death and Retinal
   Remodeling In Rats
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE retinitis pigmentosa (RP); age-related macular degeneration (AMD or
   ARMD); neural degeneration; retinal remodeling; rodent
ID OXYGEN-INDUCED RETINOPATHY; LIGHT DAMAGE; MOUSE MODEL; PURINERGIC
   RECEPTORS; MACULAR DEGENERATION; NEURAL REGENERATION; P2X(7) RECEPTORS;
   MAMMALIAN RETINA; IODOACETIC ACID; AMACRINE CELLS
AB Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Muller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision. (C) 2014 Wiley Periodicals, Inc.
C1 [Vessey, Kirstan A.; Greferath, Ursula; Aplin, Felix P.; Jobling, Andrew I.; Phipps, Joanna A.; Ho, Tracy; De Iongh, Robbert U.; Fletcher, Erica L.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia.
   [Aplin, Felix P.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.
   [Aplin, Felix P.] Bion Inst, East Melbourne, Vic 3002, Australia.
C3 University of Melbourne; Centre for Eye Research Australia; Royal
   Victorian Eye & Ear Hospital; Bionics Institute
RP Fletcher, EL (通讯作者)，Univ Melbourne, Dept Anat & Neurosci, Level 7,Med Bldg,Grattan St, Parkville, Vic 3010, Australia.
EM elf@unimelb.edu.au
RI De Iongh, Robb U/H-9646-2019; Fletcher, Erica/E-6364-2012; Jobling,
   Andrew/C-8221-2015
OI De Iongh, Robb U/0000-0001-7013-1610; Fletcher,
   Erica/0000-0001-9412-9523; Ho, Tracy/0000-0002-9277-7823; Vessey,
   Kirstan/0000-0003-1031-1964; Greferath, Ursula/0000-0003-1028-648X;
   Jobling, Andrew/0000-0002-7827-3135
FU Australian Research Council (ARC) Special Research Initiative (SRI) in
   Bionic Vision Science and Technology; National Health and Medical
   Research Council of Australia [1021042]
FX Grant sponsor: Australian Research Council (ARC) Special Research
   Initiative (SRI) in Bionic Vision Science and Technology (to Bionic
   Vision Australia); Grant sponsor: National Health and Medical Research
   Council of Australia; Grant number: 1021042.
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NR 93
TC 30
Z9 30
U1 0
U2 15
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
EI 1096-9861
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD SEP 1
PY 2014
VL 522
IS 13
BP 2928
EP 2950
DI 10.1002/cne.23558
PG 23
WC Neurosciences; Zoology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Zoology
GA AL9TM
UT WOS:000339484500002
PM 24639102
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Chew, EY
AF Chew, Emily Y.
TI Nutrition Effects on Ocular Diseases in the Aging Eye
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; cataract type; antioxidants
ID AGE-RELATED CATARACT; VITAMIN SUPPLEMENT USE; FATTY-ACID INTAKE; MACULAR
   DEGENERATION; RANDOMIZED-TRIAL; BETA-CAROTENE; FISH CONSUMPTION; 5-YEAR
   INCIDENCE; DIETARY-FAT; ANTIOXIDANT
AB PURPOSE. We reviewed the data from the clinical trials of nutritional supplements for the treatment of age-related cataract and age-related macular degeneration (AMD) to determine future directions of research and treatment.
   METHODS. Data from the controlled clinical trials are presented and reviewed for potential opportunities for further research into the treatment of cataracts and AMD.
   RESULTS. Two trials using daily multivitamins/minerals demonstrated a reduction in the progression of nuclear cataract, but increased the risk of posterior subcapsular cataract. For AMD, the Age-Related Eye Disease Study (AREDS) formulation (vitamins C, E, beta-carotene, zinc, and copper) reduced the risk of progression to advanced AMD by 25% at 5 years. Because beta-carotene is associated with increased lung cancer in former smokers, lutein/zeaxanthin could replace beta-carotene and provide an incremental increase in the beneficial effects beyond the effects of the AREDS formulation. In addition, a randomized clinical trial of B vitamins demonstrated a beneficial effect for AMD with the vitamin B complex.
   CONCLUSIONS. Future evaluation may include additional assessments of nutrients for the treatment of progression of cataract and AMD. A modest reduction would have significant impact as the numbers of persons affected with these two leading causes of blindness are projected to double in the next decade. An important step would be to develop surrogate outcomes to increase efficiency in clinical trials. More detailed phenotyping, especially of AMD, is required as it appears to be not one disease, but a group of diseases. Genotype-phenotype analyses may help to target pathways that are important in AMD.
C1 NEI, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Chew, EY (通讯作者)，NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
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NR 49
TC 29
Z9 29
U1 0
U2 20
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2013
VL 54
IS 14
SI SI
DI 10.1167/iovs.13-12914
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 278IX
UT WOS:000328884600009
DA 2022-11-30
ER

PT J
AU Barber, AC
   Hippert, C
   Duran, Y
   West, EL
   Bainbridge, JWB
   Warre-Cornish, K
   Luhmann, UFO
   Lakowski, J
   Sowden, JC
   Ali, RR
   Pearson, RA
AF Barber, Amanda C.
   Hippert, Claire
   Duran, Yanai
   West, Emma L.
   Bainbridge, James W. B.
   Warre-Cornish, Katherine
   Luhmann, Ulrich F. O.
   Lakowski, Jorn
   Sowden, Jane C.
   Ali, Robin R.
   Pearson, Rachael A.
TI Repair of the degenerate retina by photoreceptor transplantation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE gliosis; retinal degeneration; stem cells
ID STEM-CELLS; CONGENITAL AMAUROSIS; CHONDROITINASE ABC; VISUAL FUNCTION;
   INTEGRATION; PRECURSORS; MICE; ROD; DIFFERENTIATION; MORPHOGENESIS
AB Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, the loss of photoreceptors. There are few treatments and none reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration of vision following rod-photoreceptor transplantation into a mouse model of stationary night-blindness, raising the critical question of whether photoreceptor replacement is equally effective in different types and stages of degeneration. We present a comprehensive assessment of rod-photoreceptor transplantation across six murine models of inherited photoreceptor degeneration. Transplantation is feasible in all models examined but disease type has a major impact on outcome, as assessed both by the morphology and number of integrated rod-photoreceptors. Integration can increase (Prph2(+/Delta 307)), decrease (Crb1(rd8/rd8), Gnat1(-/-), Rho(-/-)), or remain constant (PDE6 beta(rd1/rd1), Prph2(rd2/rd2)) with disease progression, depending upon the gene defect, with no correlation with severity. Robust integration is possible even in late-stage disease. Glial scarring and outer limiting membrane integrity, features that change with degeneration, significantly affect transplanted photoreceptor integration. Combined breakdown of these barriers markedly increases integration in a model with an intact outer limiting membrane, strong gliotic response, and otherwise poor transplantation outcome (Rho(-/-)), leading to an eightfold increase in integration and restoration of visual function. Thus, it is possible to achieve robust integration across a broad range of inherited retinopathies. Moreover, transplantation outcome can be improved by administering appropriate, tailored manipulations of the recipient environment.
C1 [Barber, Amanda C.; Hippert, Claire; Duran, Yanai; West, Emma L.; Bainbridge, James W. B.; Warre-Cornish, Katherine; Luhmann, Ulrich F. O.; Ali, Robin R.; Pearson, Rachael A.] UCL, Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Lakowski, Jorn; Sowden, Jane C.] UCL, Inst Child Hlth, Dev Biol Unit, London WC1N 1EH, England.
   [Ali, Robin R.] UCL, Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England.
C3 University of London; University College London; University of London;
   University College London; University of London; University College
   London
RP Ali, RR (通讯作者)，UCL, Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
EM r.ali@ucl.ac.uk; rachael.pearson@ucl.ac.uk
RI West, Emma L/C-5252-2013; Pearson, Rachael/Y-3339-2018; Lakowski,
   Jorn/ABD-6613-2020
OI Pearson, Rachael/0000-0002-1107-1969; Lakowski,
   Jorn/0000-0003-4214-7580; Sowden, Jane/0000-0003-0937-2479; Ali,
   Robin/0000-0003-3126-6517; Warre Cornish, Katherine/0000-0001-7892-4295;
   Bainbridge, James/0000-0003-1318-8201; West, Emma/0000-0002-7006-3686
FU British Retinitis Pigmentosa Society [GR566]; Wellcome Trust [082217,
   086128]; Royal Society [RG080398]; Medical Research Council UK
   [G03000341, G0901550 mr/j004553/1]; Great Ormond Street Hospital
   Children's Charity; Department of Health's National Institute for Health
   Research Biomedical Research Centre; Moorfields Eye Hospital; Miller's
   Trust; Medical Research Council [G0700438, MR/J004553/1, G0901550]
   Funding Source: researchfish; National Institute for Health Research
   [NF-SI-0508-10130, NIHR-RP-011-003] Funding Source: researchfish; Great
   Ormond Street Hospital Childrens Charity [V1257] Funding Source:
   researchfish; MRC [G0700438, G0901550, MR/J004553/1] Funding Source:
   UKRI
FX We thank A. Eddaoudi for technical assistance. This work was supported
   by grants from the British Retinitis Pigmentosa Society (GR566),
   Wellcome Trust (082217; 086128), Royal Society (RG080398), and Medical
   Research Council UK (G03000341; G0901550 mr/j004553/1). R.A.P. is a
   Royal Society University Research Fellow; J.C.S. is supported by Great
   Ormond Street Hospital Children's Charity; and R.R.A. is partially
   funded by the Department of Health's National Institute for Health
   Research Biomedical Research Centre, Moorfields Eye Hospital, and the
   Miller's Trust.
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NR 23
TC 189
Z9 194
U1 2
U2 49
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 2
PY 2013
VL 110
IS 1
BP 354
EP 359
DI 10.1073/pnas.1212677110
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 071XI
UT WOS:000313630300076
PM 23248312
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Shang, JL
   Zhang, JY
   Lei, XJ
   Zhang, YY
   Chen, BD
AF Shang, Junliang
   Zhang, Junying
   Lei, Xiujuan
   Zhang, Yuanyuan
   Chen, Baodi
TI Incorporating heuristic information into ant colony optimization for
   epistasis detection
SO GENES & GENOMICS
LA English
DT Article
DE Epistasis detection; Heuristic information; Ant colony optimization;
   Single nucleotide polymorphisms; Genome-wide association study
ID ASSOCIATION
AB Epistasis has been receiving increasing attention in understanding the mechanism underlying susceptibility to complex diseases. Though many works have been done for epistasis detection, genome-wide association study remains a challenging task: it makes the search space excessively huge while solution quality is excessively demanded. In this study, we introduce an ant colony optimization based algorithm, AntMiner, by incorporating heuristic information into ant-decision rules. The heuristic information is used to direct ants in the search process for improving computational efficiency and solution accuracy. During iterations, chi-squared test is conducted to measure the association between an interaction and the phenotype. At the completion of the iteration process, statistically significant epistatic interactions are ordered and then screened by a post-procedure. Experiments of AntMiner and its comparison with existing algorithms epiMODE, TEAM and AntEpiSeeker are performed on both simulation data sets and real age-related macular degeneration data set, under the criteria of detection power and sensitivity. Results demonstrate that AntMiner is promising for epistasis detection. In terms of detection power, AntMiner performs best among all the other algorithms on all cases regardless of epistasis models and single nucleotide polymorphism size; compared with AntEpiSeeker, AntMiner can obtain better detection power but with less ants and iterations. In terms of sensitivity, AntMiner is better than AntEpiSeeker in detecting epistasis models displaying marginal effects but it has moderate sensitivity on epistasis models displaying no marginal effects. The study may provide clues on heuristics for further epistasis detection. The software package is available online at https://sourceforge.net/projects/antminer/files/.
C1 [Shang, Junliang; Zhang, Junying; Zhang, Yuanyuan; Chen, Baodi] Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Peoples R China.
   [Lei, Xiujuan] Shaanxi Normal Univ, Coll Comp Sci, Xian 710062, Peoples R China.
C3 Xidian University; Shaanxi Normal University
RP Shang, JL (通讯作者)，Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Peoples R China.
EM jlshang@mail.xidian.edu.cn; jyzhang@mail.xidian.edu.cn
FU National Natural Science Foundation of China [61070137, 91130006,
   60933009, 61100164]
FX We are grateful to the anonymous reviewers whose suggestions and
   comments contributed to the significant improvement of this paper. This
   work was supported by the National Natural Science Foundation of China
   (Grant No. 61070137); the Major Research Plan of the National Natural
   Science Foundation of China (Grant No. 91130006); the Key Program of the
   National Natural Science Foundation of China (Grant No. 60933009); the
   Young Scientists Fund of the National Natural Science Foundation of
   China (Grant No. 61100164).
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NR 30
TC 22
Z9 22
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1976-9571
EI 2092-9293
J9 GENES GENOM
JI Genes Genom.
PD JUN
PY 2012
VL 34
IS 3
BP 321
EP 327
DI 10.1007/s13258-012-0003-2
PG 7
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 964LA
UT WOS:000305695300010
DA 2022-11-30
ER

PT J
AU Velpandian, T
   Arora, B
   Senthilkumari, S
   Ravi, AK
   Gayathri, C
   Azad, R
   Ghose, S
AF Velpandian, Thirumurthy
   Arora, Beauty
   Senthilkumari, Srinivasan
   Ravi, Alok Kumar
   Gayathri, Chandrasekar
   Azad, Rajvardhan
   Ghose, Supriyo
TI Regional Variation in the Levels of Macular Xanthophylls and Carotenoids
   in Dietary Components: Comparing North and South India
SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY
LA English
DT Article
DE xanthophyll; carotenoid; macula; fruits and vegetables; India
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; VITAMIN-C; LUTEIN;
   PREVALENCE; VEGETABLES; ANTIOXIDANTS; DEGENERATION; ZEAXANTHIN; FRUIT
AB Multiple epidemiological studies have emphasized the intake of dark green leafy vegetables rich in xanthophylls in reducing the risk of developing age-related macular degeneration (AMD). Therefore, the present study was undertaken to quantify the levels of major carotenoids in commonly consumed fruits and vegetables of Indian origin and of xanthophylls in the macula of Indian human donor eyes. Fresh fruits (n=20) and vegetables (n=51) collected from two zones of India were tested for the estimation of xanthophyll, lycopene and beta-carotene by using HPLC with Photodiode Array Detection. Lutein and zeaxanthin were quantified from macula and in selected vegetables collected from both southern (SI) and northern (NI) regions of India. Xanthophylls, beta-carotene and lycopene were found in many affordable vegetables commonly available for consumption in India. Higher content of lutein and zeaxanthin was confirmed in many economical leafy vegetables and fruits. Surprisingly, the mean macular levels of lutein and zeaxanthin of SI donor eyes (n=13) were found to be significantly (p<0.001) four times less than in NI donor eyes (n=15) and the macular levels of Northern India were comparable with reported levels in western populations. The present study showed considerable levels of xanthophylls in many of the commonly consumed fruit and vegetable sources in both parts of India. However, SI donor eyes showed lower levels as compared to NI donors and this warrants further investigation about the bioavailability of xanthophylls in their blood and food intake. The relevance of these findings with prevalence of AMD in South India needs to be explored.
C1 [Velpandian, Thirumurthy; Arora, Beauty; Ravi, Alok Kumar; Gayathri, Chandrasekar] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pharmacol & Pharm, New Delhi 110029, India.
   [Azad, Rajvardhan] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Vitreoretinal Dis & Trauma, New Delhi 110029, India.
   [Ghose, Supriyo] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Pediat Ophthalmol & Oculoplasty, New Delhi 110029, India.
   [Senthilkumari, Srinivasan] Aravind Med Res Fdn, Dr G Venkataswamy Eye Res Inst, Madurai 625020, Tamil Nadu, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences; All India Institute of Medical
   Sciences (AIIMS) New Delhi; Dr. Rajendra Prasad Centre for Ophthalmic
   Sciences; All India Institute of Medical Sciences (AIIMS) New Delhi; Dr.
   Rajendra Prasad Centre for Ophthalmic Sciences
RP Velpandian, T (通讯作者)，All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pharmacol & Pharm, New Delhi 110029, India.
EM tvelpandian@hotmail.com
RI Velpandian, Thirumurthy/ABE-7016-2021
FU Department of Science and Technology [SR/FT/L-139/2004]
FX We acknowledge the Department of Science and Technology for the Young
   Scientist Grant SR/FT/L-139/2004. We thank National Eye Bank of Dr.
   Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi and Eye Bank
   of Aravind Eye Hospital. Madurai for providing human donor eyes for this
   study. We also thank the donors and their relatives for consenting to
   donate the unused portion of eyes from eye banks for research.
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NR 39
TC 3
Z9 3
U1 1
U2 5
PU CENTER ACADEMIC PUBL JAPAN
PI TOKYO
PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN
SN 0301-4800
EI 1881-7742
J9 J NUTR SCI VITAMINOL
JI J. Nutr. Sci. Vitaminol.
PD DEC
PY 2010
VL 56
IS 6
BP 411
EP 420
DI 10.3177/jnsv.56.411
PG 10
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 703XX
UT WOS:000286016400009
PM 21422710
OA gold
DA 2022-11-30
ER

PT J
AU Murdaugh, LS
   Wang, Z
   Del Priore, LV
   Dillon, J
   Gaillard, ER
AF Murdaugh, L. S.
   Wang, Z.
   Del Priore, L. V.
   Dillon, J.
   Gaillard, E. R.
TI Age-related accumulation of 3-nitrotyrosine and nitro-A2E in human
   Bruch's membrane
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Bruch's membrane; RPE; inflammation; macular dystrophy
ID COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; NITRIC-OXIDE; MACULAR
   DEGENERATION; TYROSINE NITRATION; DRUSEN; PROTEINS; INFLAMMATION;
   POLYMORPHISM; EXPRESSION
AB Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the elderly population. The pathophysiology of AMD is complex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. Recently four independent research groups have identified a commonly inherited variant (Y402H) of the complement factor H gene in the genome from different groups of AMD patients. The Y402H variant of CFH significantly increases the risk of AMD and links the genetics of the disease with inflammation. During inflammation there is activation of inducible nitric oxide synthase and release of nitric oxide, which in principal could lead to non-enzymatic nitration within extracellular deposits and/or intrinsic extracellular matrix protein components of human Bruch's membrane. We have identified two biomarkers for non-enzymatic nitration in aged human Bruch's membrane, indicative of inflammation, that include 3-nitrotyrosine identified in Bruch's membrane preparations and nitrated A2E from the lipid soluble extract of the Bruch's membrane preparation. Approximately 30-40 times more A2E is observed in samples of the organic soluble extract of lipofuscin compared to the extract of Bruch's membrane. It is of interest to note that although A2E is a major constituent of RPE lipofuscin, nitrated A2E could not be detected in RPE extracts. We show here that nitro-A2E is a specific biomarker of nitrosative stress in Bruch's membrane and its concentration correlates directly with tissue age. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Murdaugh, L. S.; Wang, Z.; Gaillard, E. R.] No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   [Del Priore, L. V.; Dillon, J.; Gaillard, E. R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
C3 Northern Illinois University; Columbia University
RP Gaillard, ER (通讯作者)，No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
EM Gaillard@niu.edu
RI Gaillard, Elizabeth/M-2627-2019
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NR 63
TC 40
Z9 40
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAY
PY 2010
VL 90
IS 5
BP 564
EP 571
DI 10.1016/j.exer.2010.01.014
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 587JQ
UT WOS:000276988200005
PM 20153746
DA 2022-11-30
ER

PT J
AU Karadimas, P
   Paleokastritis, GP
   Bouzas, EA
AF Karadimas, P.
   Paleokastritis, G. P.
   Bouzas, E. A.
TI Fundus autofluorescence imaging findings in retinal pigment epithelial
   tear
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; autofluorescence imaging; retinal
   pigment epithelial tear
ID MACULAR DEGENERATION
AB PURPOSE. Retinal pigment epithelial (RPE) tear is a clinical and angiographic entity, which usually occurs in association with pigment epithelial detachments (PED), in the context of neovascular age-related macular degeneration (ARMD). The recording of fundus autofluorescence (FAF) has been introduced as a technique of retinal imaging, allowing the in vivo assessment of the integrity of RPE The authors describe the FAF imaging findings in a patient with RPE tear.
   METHODS. Observational case report.
   RESULTS. A 70-year-old woman developed RPE tear after the application of photodynamic therapy for choroidal neovascularization associated with PED. The diagnosis of the RPE tear was confirmed by fluorescein angiography (FA) and indocyanine green angiography (ICGA). FAF imaging revealed absence of autofluorescence at the area which was denuded of RPE, while at the area where the RPE was rolled, a heterogeneous signal of FAF was recorded. The intensity of the signal in that area was, on average, not different from the normal background FAF signal expected in an unaffected RPE/photoreceptor complex.
   CONCLUSION. The authors report the FAF imaging findings in a patient with RPE tear These findings can be interpreted from the ability of FAF imaging to access in vivo the integrity of RPE, and correlate well with the histopathology of this clinical entity. FAF imaging, as a fast and noninvasive technique, may be a useful modality, alternative to FA and ICGA, in the diagnosis and evaluation of such cases. Moreover, it may contribute to a more detailed phenotyping of the various clinical pictures associated with neovascular ARMD.
C1 Henry Dunant Hosp, Dept Ophthalmol 1, Med Retina Unit, Athens 11526, Greece.
C3 Henry Dunant Hospital
RP Karadimas, P (通讯作者)，Henry Dunant Hosp, Dept Ophthalmol 1, Med Retina Unit, 107 Mesog Ave, Athens 11526, Greece.
EM t_karadimas@yahoo.com
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NR 5
TC 13
Z9 14
U1 0
U2 0
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP-OCT
PY 2006
VL 16
IS 5
BP 767
EP 769
DI 10.1177/112067210601600520
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 117TJ
UT WOS:000242895900022
PM 17061235
DA 2022-11-30
ER

PT J
AU Fryer, BH
   Wang, CH
   Vedantam, S
   Zhou, GL
   Jin, SH
   Fletcher, L
   Simon, MC
   Field, J
AF Fryer, BH
   Wang, CH
   Vedantam, S
   Zhou, GL
   Jin, SH
   Fletcher, L
   Simon, MC
   Field, J
TI CGMP-dependent protein kinase phosphorylates p21-activated kinase (Pak)
   1, inhibiting Pak/Nck binding and stimulating Pak/vasodilator-stimulated
   phosphoprotein association
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELL-MIGRATION; RHO-GTPASES; ACTIN CYTOSKELETON; ENA/VASP PROTEINS;
   PAK1; ANGIOGENESIS; NCK; SIGNALS; RAS; MECHANISMS
AB Endothelial cells are normally non-motile and quiescent; however, endothelial cells will become permeable and invade and proliferate to form new blood vessels ( angiogenesis) in response to wounding, cancer, diabetic retinopathy, age-related macular degeneration, or rheumatoid arthritis. p21-activated kinase ( Pak), an effector for the Rho GTPases Rac and Cdc42, is required for angiogenesis and regulates endothelial cell permeability and motility. Although Pak is primarily activated by Rac and Cdc42, there are additional proteins that regulate Pak activity and localization, including three AGC protein kinase family members, Akt-1, PDK-1, and cAMP-dependent protein kinase. We describe phosphorylation and regulation of Pak localization by a fourth AGC kinase family member, cGMP-dependent protein kinase ( PKG). Using in vitro mapping, a phosphospecific antibody, co-transfection assays, and untransfected bovine aortic endothelial cells we determined thatPKGphosphorylates Pak at serine 21. Phosphorylation was accompanied by changes in proteins associated with Pak. The adaptor protein Nck was released, whereas a novel complex with vasodilator-stimulated phosphoprotein was stimulated. Furthermore Ser-21 phosphorylation of Pak appears to be important for regulation of cell morphology. In both human umbilical vein endothelial cells and HeLa cells, activation of PKG in the presence of Pak stimulated tail retraction and cell polarization. However, in cells expressing S21A mutant Pak1, PKG activation or treatment with a peptide that blocks Nck/Pak binding caused aberrant cell morphology, blocked cell retraction, and mislocalized Pak, producing uropod ( tail-like) structures. These data suggest that PKG regulates Pak and that the interaction plays a role in tail retraction.
C1 Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
   Univ Penn, Howard Hughes Med Inst, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Howard Hughes Medical Institute; University
   of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania;
   Pennsylvania Medicine; Childrens Hospital of Philadelphia
RP Field, J (通讯作者)，Univ Penn, Sch Med, Dept Pharmacol, John Morgan Bldg,Rm 149, Philadelphia, PA 19104 USA.
EM field@pharm.med.upenn.edu
RI Simon, Celeste/AAG-3941-2021
FU NATIONAL CANCER INSTITUTE [T32CA009677] Funding Source: NIH RePORTER;
   NCI NIH HHS [CA09677] Funding Source: Medline; NIGMS NIH HHS [GM48241,
   R01 GM048241] Funding Source: Medline
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NR 37
TC 31
Z9 33
U1 1
U2 5
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 APR 28
PY 2006
VL 281
IS 17
BP 11487
EP 11495
DI 10.1074/jbc.M600279200
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 035GH
UT WOS:000236988100010
PM 16490784
OA hybrid
DA 2022-11-30
ER

PT J
AU Stanzel, BV
   Espana, EM
   Grueterich, M
   Kawakita, T
   Tseng, SCG
   Binder, S
AF Stanzel, BV
   Espana, EM
   Grueterich, M
   Kawakita, T
   Tseng, SCG
   Binder, S
TI Amniotic membrane maintains the phenotype of rabbit retinal pigment
   epithelial cells in culture
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; amniotic membrane; basement membrane;
   differentiation; epithelial cells; eye; in vitro; pigmentation; rabbit;
   retinal pigment epithelium; RPE65; tight junctions; transepithelial
   resistance
ID MACULAR DEGENERATION; MICROSOMAL PROTEIN; LIMBAL EPITHELIUM;
   TRANSPLANTATION; CORNEAL; RPE65; DIFFERENTIATION; EXPRESSION; GROWTH;
   CALCIUM
AB The success of surgical removal of choroidal neovascularisation followed by transplantation of autologous retinal pigment epithelial cells (RPE) for age-related macular degeneration (ARMD) may be limited by damage in Bruch's membrane. We investigated whether amniotic membrane (AM) might be used as an alternative basement membrane-containing matrix to support RPE growth and differentiation.
   Primary RPE plastic cultures were established from freshly enucleated Dutch belted rabbit eyes in DMEM/F12 containing 0.1 mm Ca++ and 10% dialysed FBS. Upon subconfluence, cells were subcultured at 5000-9000 cells cm(-2) in the above-mentioned culture medium on intact AM (iAM), epithelially denuded AM (dAM) or plastic. After confluence, the Ca++ concentration in the medium was increased to 1.8 mm for 4 weeks. Growth and morphology were monitored by phase contrast microscopy, and the phenotype by immunostaining with antibodies against cytokeratin 18, tight junction protein ZO-1, and RPE65 protein, and by transepithelial resistance (TER) measurement. Immunostaining to cytokeratin 18 confirmed the epithelial origin of isolated cells in both primary culture and subcultures. Compared to plastic cultures, RPE increased pigmentation within 24 hr after seeding on AM, with iAM being more pronounced than dAM. RPE adopted a hexagonal epithelial phenotype with more organised pigmentation, strong expression of ZO-1 and RPE65, and a significantly higher TER 4 weeks after Ca++ switch on dAM. Our results indicate that AM may be used as a basement membrane-containing matrix to maintain RPE phenotype in vitro, and may facilitate subsequent transplantation to treat ARMD. (C) 2004 Elsevier Ltd. All rights reserved.
C1 L Boltzmann Inst Retinol & Biomicroscop Lasersurg, A-1030 Vienna, Austria.
   Univ Miami, Sch Med, Bascom Palmer Eye Inst, Ophthalm Biophys Ctr, Miami, FL 33152 USA.
   TissueTech Inc, Miami, FL USA.
   Ocular Surface Res & Educ Fdn, Miami, FL USA.
   Univ Munich, Hosp Eye, D-8000 Munich, Germany.
C3 Ludwig Boltzmann Institute; Bascom Palmer Eye Institute; University of
   Miami; University of Munich
RP Binder, S (通讯作者)，L Boltzmann Inst Retinol & Biomicroscop Lasersurg, Juchgasse 25, A-1030 Vienna, Austria.
EM susanne.binder@wienkav.at
RI Stanzel, Boris/AAG-7010-2022; Stanzel, Boris/ADP-9221-2022
OI Stanzel, Boris/0000-0002-4316-1539; Stanzel, Boris/0000-0002-4316-1539
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NR 44
TC 44
Z9 48
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 JAN
PY 2005
VL 80
IS 1
BP 103
EP 112
DI 10.1016/j.exer.2004.06.032
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 899EG
UT WOS:000227127100012
PM 15652531
DA 2022-11-30
ER

PT J
AU Wang, F
   Rendahl, KG
   Manning, WC
   Quiroz, D
   Coyne, M
   Miller, SS
AF Wang, F
   Rendahl, KG
   Manning, WC
   Quiroz, D
   Coyne, M
   Miller, SS
TI AAV-mediated expression of vascular endothelial growth factor induces
   choroidal neovascularization in rat
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RECOMBINANT ADENOASSOCIATED VIRUS; PIGMENT EPITHELIAL-CELLS;
   BLOOD-RETINAL BARRIER; MACULAR DEGENERATION; GENE-TRANSFER; IN-VIVO;
   SUBRETINAL NEOVASCULARIZATION; TRANSGENIC MICE; HEMOPHILIA-B; VIRAL
   VECTOR
AB PURPOSE. To develop a small-animal model of choroidal neovascularization (CNV) by injecting adeno-associated virus (AAV)-VEGF into the subretinal space (SRS) of rats.
   METHODS. An adeno-associated viral vector encoding human VEGF,6, was injected into the subretinal space (SRS) of Sprague-Dawley or Long Evans rats. Expression of VEGF was identified by RT-PCR and immunohistochemistry. Physiological and pathologic changes in the retina and choroid were evaluated by electroretinography, fluorescein angiography, light microscopy, and three-dimensional reconstruction of serial sections.
   RESULTS. Green fluorescent protein (GFP) and VEGF were expressed for at least 20 months in the retina and retinal pigment epithelium (RPE). Histologic sections showed extensive subretinal neovascularization, degenerating photoreceptors, and proliferating RPE at 5 weeks to 20 months after injection of AAV-VEGF. At 2 to 12 months after injection, leaking blood vessels were detected by fluorescein angiography. Electroretinogram a- and b-wave amplitudes were significantly decreased during this time. Three-dimensional reconstruction of serial sections demonstrated that choroidal blood vessels penetrated Bruch's membrane, one of them splitting into three branches in the SRS. In the current model, CNV was produced in 95% of the animals tested (19/20). It persisted for more than 20 months, a necessary requirement for modeling the development of CNV in age-related macular degeneration (AMD).
   CONCLUSIONS. In this study, a highly reproducible animal model of long-lasting CNV was developed. This model is being used to test antiangiogenic molecules to reduce or inhibit CNV and could be extended to primates.
C1 Univ Calif Berkeley, Sch Optometry, Berkeley, CA USA.
   Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   Chiron Corp, Gene Therapy Grp, Emeryville, CA USA.
C3 University of California System; University of California Berkeley;
   University of California System; University of California Berkeley;
   Novartis
RP Miller, SS (通讯作者)，NEI, NIH, Bldg 31,Rm 6A20,9000 Rockville Pike, Bethesda, MD 20892 USA.
FU NATIONAL EYE INSTITUTE [P30EY003176, R01EY002205, R37EY002205] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY02205, EY03176] Funding Source:
   Medline
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NR 66
TC 75
Z9 92
U1 0
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2003
VL 44
IS 2
BP 781
EP 790
DI 10.1167/iovs.02-0281
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 645GA
UT WOS:000180966800047
PM 12556414
DA 2022-11-30
ER

PT J
AU Rincon, M
   Espinoza, LC
   Silva-Abreu, M
   Sosa, L
   Pesantez-Narvaez, J
   Abrego, G
   Calpena, AC
   Mallandrich, M
AF Rincon, Maria
   Carolina Espinoza, Lupe
   Silva-Abreu, Marcelle
   Sosa, Lilian
   Pesantez-Narvaez, Jessica
   Abrego, Guadalupe
   Cristina Calpena, Ana
   Mallandrich, Mireia
TI Quality by Design of Pranoprofen Loaded Nanostructured Lipid Carriers
   and Their Ex Vivo Evaluation in Different Mucosae and Ocular Tissues
SO PHARMACEUTICALS
LA English
DT Article
DE design of experiment; porcine mucous membrane; ophthalmic tissues;
   permeation; nanostructured lipid carriers
ID IN-VITRO; BIOPHARMACEUTICAL PROFILE; PLGA NANOPARTICLES; PORCINE;
   PERMEABILITY; PERMEATION; DELIVERY; OPTIMIZATION; HYDROGELS; SYSTEMS
AB Transmucosal delivery is commonly used to prevent or treat local diseases. Pranoprofen is an anti-inflammatory drug prescribed in postoperative cataract surgery, intraocular lens implantation, chorioretinopathy, uveitis, age-related macular degeneration or cystoid macular edema. Pranoprofen can also be used for acute and chronic management of osteoarthritis and rheumatoid arthritis. Quality by Design (QbD) provides a systematic approach to drug development and maps the influence of the formulation components. The aim of this work was to develop and optimize a nanostructured lipid carrier by means of the QbD and factorial design suitable for the topical management of inflammatory processes on mucosal tissues. To this end, the nanoparticles loading pranoprofen were prepared by a high-pressure homogenization technique with Tween 80 as stabilizer and Lanette (R) 18 as the solid lipid. From, the factorial design results, the PF-NLCs-N6 formulation showed the most suitable characteristics, which was selected for further studies. The permeability capacity of pranoprofen loaded in the lipid-based nanoparticles was evaluated by ex vivo transmucosal permeation tests, including buccal, sublingual, nasal, vaginal, corneal and scleral mucosae. The results revealed high permeation and retention of pranoprofen in all the tissues tested. According to the predicted plasma concentration at the steady-state, no systemic effects would be expected, any neither were any signs of ocular irritancy observed from the optimized formulation when tested by the HET-CAM technique. Hence, the optimized formulation (PF-NLCs-N6) may offer a safe and attractive nanotechnological tool in topical treatment of local inflammation on mucosal diseases.
C1 [Rincon, Maria] Univ Barcelona, Fac Chem, Dept Mat Sci & Phys Chem, C Marti & Franques 1-11, Barcelona 08028, Spain.
   [Carolina Espinoza, Lupe] Univ Tecn Particular Loja, Dept Quim, Loja 1101608, Ecuador.
   [Silva-Abreu, Marcelle; Cristina Calpena, Ana; Mallandrich, Mireia] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Av Joan XXIII 27-31, Barcelona 08028, Spain.
   [Silva-Abreu, Marcelle; Cristina Calpena, Ana; Mallandrich, Mireia] Univ Barcelona, Inst Nanociencia & Nanotecnol IN2UB, Barcelona 08028, Spain.
   [Sosa, Lilian] Natl Autonomous Univ Honduras UNAH, Pharmaceut Technol Res Grp, Fac Chem Sci & Pharm, Tegucigalpa 11101, Honduras.
   [Pesantez-Narvaez, Jessica] Univ Carlos III, Fac Ciencias Sociales, Dept Estadist, C Madrid 126, Madrid 28903, Spain.
   [Abrego, Guadalupe] Univ El Salvador, Fac Chem & Pharm, Dept Chem & Instrumental Anal, Madrid 28040, Spain.
C3 University of Barcelona; Universidad Tecnica Particular de Loja;
   University of Barcelona; University of Barcelona; Universidad Nacional
   Autonoma de Honduras; Universidad Carlos III de Madrid
RP Silva-Abreu, M (通讯作者)，Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Av Joan XXIII 27-31, Barcelona 08028, Spain.; Silva-Abreu, M (通讯作者)，Univ Barcelona, Inst Nanociencia & Nanotecnol IN2UB, Barcelona 08028, Spain.
EM silvadeabreu@ub.edu
OI Espinoza, Lupe C./0000-0003-1486-5622; CALPENA, ANA
   CRISTINA/0000-0002-4989-4821
FU Universidad Tecnica Particular de Loja-Ecuador
FX The authors want to thank Harry Paul for the English language editing.
   We also acknowledge the support received from Universidad Tecnica
   Particular de Loja-Ecuador. Moreover, thanks to Maria Luisa Garcia for
   her technical support, Elena Sanchez for helping with HPLC analysis, and
   Lyda Halbaut for her support with rheological studies.
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NR 53
TC 0
Z9 0
U1 5
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1424-8247
J9 PHARMACEUTICALS-BASE
JI Pharmaceuticals
PD OCT
PY 2022
VL 15
IS 10
AR 1185
DI 10.3390/ph15101185
PG 23
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 5S6WS
UT WOS:000875328100001
PM 36297297
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, K
   Chen, YS
   Chien, HW
   Chiou, HL
   Yang, SF
   Hsieh, YH
AF Wang, Kai
   Chen, Yong-Syuan
   Chien, Hsiang-Wen
   Chiou, Hui-Ling
   Yang, Shun-Fa
   Hsieh, Yi-Hsien
TI Melatonin inhibits NaIO3-induced ARPE-19 cell apoptosis via suppression
   of HIF-1 alpha/BNIP3-LC3B/mitophagy signaling
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Melatonin; Retinal pigment epithelial cells; BNIP3; HIF-1 alpha; LC3B;
   Mitophagy; Age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; OXIDATIVE STRESS;
   SODIUM IODATE; DNA DAMAGE; MITOCHONDRIAL; HYPOXIA; MECHANISMS;
   AUTOPHAGY; EXPRESSION
AB Background: Age-related macular degeneration (AMD) leads to gradual central vision loss and eventual irreversible blindness. Melatonin, an endogenous hormone, exhibits anti-inflammatory and antitumor effects; however, the role it plays in AMD remains unclear. Herein, we investigated the anti-AMD molecular mechanism of melatonin after sodium iodate (NaIO3) treatment of ARPE-19 cells in vitro and in animal models with the goal of improving the therapeutic effect.
   Results: The in vitro results showed that melatonin protected against NaIO3-induced cell viability decline, mitochondrial dysfunction and apoptosis in ARPE-19 cells, and melatonin also alleviated NaIO3-induced reactive oxygen species (ROS) production, mitochondrial dysfunction and mitophagy activation. Melatonin reduced NaIO3-induced mitophagy activation through HIF-1 alpha-targeted BNIP3/LC3B transcription, whereas ROS inhibition realized with N-acetylcysteine (NAC, a ROS inhibitor) combined with melatonin reduced the effect of NaIO3 on mitophagy. An animal model of AMD was established to confirm the in vitro data. Mouse tail vein injection of NaIO3 and melatonin was associated with enhanced repair of retinal layers within 7 days, as observed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. A reduction in BNIP3 and HIF-1 alpha levels, as determined by immunohistochemistry (IHC) assay, was also observed.
   Conclusions: These results indicate that melatonin attenuated NaIO3-induced mitophagy of ARPE-19 cells via reduction in ROS-mediated HIF-1 alpha targeted BNIP3/LC3B signaling in vitro and in vivo. Melatonin may be a potential therapeutic drug in the treatment of AMD.
C1 [Wang, Kai; Chien, Hsiang-Wen] Cathay Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Wang, Kai; Chien, Hsiang-Wen] Sijhih Cathay Gen Hosp, Dept Ophthalmol, New Taipei, Taiwan.
   [Wang, Kai; Chien, Hsiang-Wen] Fu Jen Catholic Univ, Coll Med, Sch Med, New Taipei, Taiwan.
   [Chen, Yong-Syuan; Yang, Shun-Fa; Hsieh, Yi-Hsien] Chung Shan Med Univ, Inst Med, Taichung, Taiwan.
   [Chien, Hsiang-Wen] Natl Tsing Hua Univ, Sch Med, Hsinchu, Taiwan.
   [Chiou, Hui-Ling] Chung Shan Med Univ, Dept Med Lab & Biotechnol, Taichung, Taiwan.
   [Yang, Shun-Fa; Hsieh, Yi-Hsien] Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan.
C3 Cathay General Hospital; Cathay General Hospital; Fu Jen Catholic
   University; Chung Shan Medical University; National Tsing Hua
   University; Chung Shan Medical University; Chung Shan Medical
   University; Chung Shan Medical University Hospital
RP Yang, SF; Hsieh, YH (通讯作者)，Chung Shan Med Univ, Inst Med, Taichung, Taiwan.; Yang, SF; Hsieh, YH (通讯作者)，Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan.
EM ysf@csmu.edu.tw; hyhsien@csmu.edu.tw
RI Yang, Shun-Fa/AAN-1519-2020
OI Yang, Shun-Fa/0000-0002-0365-7927
FU Ministry of Science and Technology [110-2320-B-040-005-MY3]
FX This work was supported by grants from Ministry of Science and
   Technology (110-2320-B-040-005-MY3).
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NR 51
TC 0
Z9 0
U1 1
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD AUG 19
PY 2022
VL 12
IS 1
AR 133
DI 10.1186/s13578-022-00879-3
PG 15
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 3W6ST
UT WOS:000842476400002
PM 35986432
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Qian, TW
   Xu, X
   Liu, XY
   Yen, MN
   Zhou, H
   Mao, MM
   Cai, HT
   Shen, HQ
   Xu, X
   Gong, YY
   Yu, SQ
AF Qian, Tianwei
   Xu, Xian
   Liu, Xinyi
   Yen, Manni
   Zhou, Hao
   Mao, Manman
   Cai, Huiting
   Shen, Hangqi
   Xu, Xun
   Gong, Yuanyuan
   Yu, Suqin
TI Efficacy of MP-3 microperimeter biofeedback fixation training for low
   vision rehabilitation in patients with maculopathy
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Maculopathy; Low vision; MP-3; Microperimeter biofeedback training;
   Visual rehabilitation
ID ECCENTRIC FIXATION; VISUAL IMPAIRMENT; READING SPEED; REORGANIZATION;
   STIMULATION; PLASTICITY; PREVALENCE; MODEL
AB Background: To evaluate the efficacy of MP-3 microperimeter biofeedback fixation training (MBFT) in vision rehabilitation of low-vision patients affected by macular disease with central vision loss.
   Methods: Seventeen eyes (7 age-related macular degeneration, 10 myopic maculopathy) of 17 patients were included in this prospective, interventional study. The preferred retinal locus was determined by comprehensive ophthalmoscopic fundus evaluation including fundus photography, autofluorescence, optical coherence tomography, and microperimetry. The rehabilitation consisted of three 10-min sessions per eye to be performed twice per week for 20 consecutive weeks using the MP-3 microperimeter. Best corrected visual acuity (BCVA), reading speed, mean central sensitivity, the percentages of fixation points within specified regions, bivariate contour ellipse area (BCEA) and the 25-item National Eye Institute visual function questionnaire (NEI-VFQ-25) were recorded pre- and post-training.
   Results: The final BCVA, reading speed and mean central sensitivity all showed significant improvements after rehabilitation (P< 0.0001, P = 0.0013, and P = 0.0002, respectively). The percentages of fixation points located within 2 degrees and 4 degrees diameter circles both significantly increased after training (P= 0.0008 and P= 0.0007, respectively). The BCEA encompassing 68.2, 95.4, 99.6% of fixation points were all significantly decreased after training (P = 0.0038, P = 0.0022, and P = 0.0021, respectively). The NEI-VFQ-25 scores were significantly increased at the end of the rehabilitation training (P< 0.0001).
   Conclusion: Rehabilitation with MP-3 MBFT is a user-friendly therapeutic option for improving visual function, fixation stability, and quality of life in advanced macular disease.
C1 [Qian, Tianwei; Xu, Xian; Zhou, Hao; Shen, Hangqi; Xu, Xun; Gong, Yuanyuan; Yu, Suqin] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
   [Qian, Tianwei; Xu, Xian; Zhou, Hao; Shen, Hangqi; Xu, Xun; Gong, Yuanyuan; Yu, Suqin] Natl Clin Res Ctr Eye Dis, Shanghai 200080, Peoples R China.
   [Qian, Tianwei; Xu, Xian; Zhou, Hao; Shen, Hangqi; Xu, Xun; Gong, Yuanyuan; Yu, Suqin] Shanghai Key Lab Ocular Fundus Dis, Shanghai 200080, Peoples R China.
   [Qian, Tianwei; Xu, Xian; Zhou, Hao; Shen, Hangqi; Xu, Xun; Gong, Yuanyuan; Yu, Suqin] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai 200080, Peoples R China.
   [Qian, Tianwei; Xu, Xian; Zhou, Hao; Shen, Hangqi; Xu, Xun; Gong, Yuanyuan; Yu, Suqin] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
   [Liu, Xinyi; Yen, Manni; Mao, Manman; Cai, Huiting] Shanghai Zhenshi Ophthalmol Clin, Shanghai 200080, Peoples R China.
C3 Shanghai Jiao Tong University
RP Gong, YY; Yu, SQ (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.; Gong, YY; Yu, SQ (通讯作者)，Natl Clin Res Ctr Eye Dis, Shanghai 200080, Peoples R China.; Gong, YY; Yu, SQ (通讯作者)，Shanghai Key Lab Ocular Fundus Dis, Shanghai 200080, Peoples R China.; Gong, YY; Yu, SQ (通讯作者)，Shanghai Engn Ctr Visual Sci & Photomed, Shanghai 200080, Peoples R China.; Gong, YY; Yu, SQ (通讯作者)，Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
EM gyydr@126.com; sg-yu@163.com
RI liu, xinyi/GWZ-8739-2022; 俞, 素勤/HDO-8369-2022
FU Shanghai Medical Guidance Project [19411961800]; National Natural
   Science Foundation of China [81800878]
FX This work was financially supported by Shanghai Medical Guidance Project
   (No.19411961800) and National Natural Science Foundation of China
   (No.81800878).
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NR 40
TC 0
Z9 0
U1 0
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD APR 28
PY 2022
VL 22
IS 1
AR 197
DI 10.1186/s12886-022-02419-6
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0V8HY
UT WOS:000788581900001
PM 35484529
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, J
   Zhang, HL
   Ren, W
   Guo, MZ
   Yu, GX
AF Wang, Jun
   Zhang, Huiling
   Ren, Wei
   Guo, Maozu
   Yu, Guoxian
TI EpiMC: Detecting Epistatic Interactions Using Multiple Clusterings
SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
LA English
DT Article
DE Genome-wide association study; epistatic interactions; stepwise search;
   multiple clusterings
ID MULTIFACTOR-DIMENSIONALITY REDUCTION; COMPLEMENT FACTOR-H; MACULAR
   DEGENERATION; BREAST-CANCER; GENOME; ASSOCIATION; POPULATION; VARIANTS;
   GENES
AB Detecting single nucleotide polymorphisms (SNPs) interactions is crucial to identify susceptibility genes associated with complex human diseases in genome-wide association studies. Clustering-based approaches are widely used in reducing search space and exploring potential relationships between SNPs in epistasis analysis. However, these approaches all only use a single measure to filter out nonsignificant SNP combinations, which may be significant ones from another perspective. In this paper, we propose a two-stage approach named EpiMC (Epistatic Interactions detection based on Multiple Clusterings) that employs multiple clusterings to obtain more precise candidate sets and more comprehensively detect high-order interactions based on these sets. In the first stage, EpiMC proposes a matrix factorization based multiple clusterings algorithm to generate multiple diverse clusterings, each of which divide all SNPs into different clusters. This stage aims to reduce the chance of filtering out potential candidates overlooked by a single clustering and groups associated SNPs together from different clustering perspectives. In the next stage, EpiMC considers both the single-locus effects and interaction effects to select high-quality disease associated SNPs, and then uses Jaccard similarity to get candidate sets. Finally, EpiMC uses exhaustive search on the obtained small candidate sets to precisely detect epsitatic interactions. Extensive simulation experiments show that EpiMC has a better performance in detecting high-order interactions than state-of-the-art solutions. On the Wellcome Trust Case Control Consortium (WTCCC) dataset, EpiMC detects several significant epistatic interactions associated with breast cancer (BC) and age-related macular degeneration (AMD), which again corroborate the effectiveness of EpiMC.
C1 [Wang, Jun] Shandong Univ, Joint SDU NTU Ctr Artificial Intelligence Res C F, Jinan 250101, Peoples R China.
   [Zhang, Huiling; Ren, Wei] Southwest Univ, Coll Comp & Informat Sci, Chongqing 400715, Peoples R China.
   [Guo, Maozu] Beijing Univ Civil Engn & Architecture, Sch Elect & Informat Engn, Beijing 100044, Peoples R China.
   [Guo, Maozu] Beijing Key Lab Intelligent Proc Bldg Big Data, Beijing 100044, Peoples R China.
   [Yu, Guoxian] Shandong Univ, Sch Software, Jinan 250101, Peoples R China.
C3 Shandong University; Southwest University - China; Beijing University of
   Civil Engineering & Architecture; Shandong University
RP Wang, J (通讯作者)，Shandong Univ, Joint SDU NTU Ctr Artificial Intelligence Res C F, Jinan 250101, Peoples R China.
EM kingjun@sdu.edu.cn; hlzhang@email.swu.edu.cn; oicq@swu.edu.cn;
   guomaozu@bucea.edu.cn; guoxian85@gmail.com
RI zhang, hui/GXH-6098-2022
OI Yu, Guoxian/0000-0002-1667-6705
FU NSFC [62072380, 62031003, 61872300]; Fundamental Research Funds of
   Shandong University [2020GN061]
FX This work was supported in part by the NSFC under Grants 62072380,
   62031003, and 61872300 and in part by the Fundamental Research Funds of
   Shandong University under Grant 2020GN061.
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NR 72
TC 0
Z9 0
U1 2
U2 5
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 JAN 1
PY 2022
VL 19
IS 1
BP 243
EP 254
DI 10.1109/TCBB.2021.3080462
PG 12
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 YU4LF
UT WOS:000752015800027
PM 33989157
DA 2022-11-30
ER

PT J
AU Yeu, E
   Cuozzo, S
AF Yeu, Elizabeth
   Cuozzo, Susan
TI Matching the Patient to the Intraocular Lens Preoperative Considerations
   to Optimize Surgical Outcomes
SO OPHTHALMOLOGY
LA English
DT Article
ID DRY EYE DISEASE; CATARACT-SURGERY; POWER PREDICTION; SPECTACLE
   INDEPENDENCE; AUTOMATED PERIMETRY; EXTENDED DEPTH; IMPLANTATION;
   MONOVISION; DEGENERATION; KERATOMETRY
AB The intraocular lens (IOL) selection process for patients requires a complex and objective assessment of patient-specific ocular characteristics, including the quality and quantity of corneal astigmatism, health of the ocular surface, and other ocular comorbidities. Potential issues that could be considered complications after surgery, including dry eye disease, anterior or epithelial basement membrane dystrophy, Salzmann nodular degeneration, and pterygium, should be addressed proactively. Aspheric IOLs are designed to eliminate the positive spherical aberration added by traditional IOLs to the pseudophakic visual axis. Spherical aberration may be a consideration with patient selection. Patient desire for increased spectacle independence after surgery is one of the main drivers for the development of multifocal IOLs and extended depth-of-focus (EDOF) IOLs. However, no one single multifocal or EDOF IOL suits all patients' needs. The wide variety of multifocal and EDOF IOLs, their optics, and their respective impact on patient quality of vision have to be understood fully to choose the appropriate IOL for each individual, and surgery has to be customized. Patients who have undergone previous LASIK or who have radial keratotomy and ocular pathologic features, including glaucoma, age-related macular degeneration, and epiretinal membrane, require specific considerations for IOL selection. Subjectively, patient-centered considerations, including visual goals, lifestyle, personality, profession, and hobbies, are key elements for the surgeon to assess and factor into an IOL recommendation. This holistic approach will help surgeons to achieve optimal surgical outcomes and to meet (and exceed) the high expectations of patients. (C) 2020 by the American Academy of Ophthalmology.
C1 [Yeu, Elizabeth] Eastern Virginia Med Sch, Dept Ophthalmol, 241 Corp Blvd, Norfolk, VA 23502 USA.
   [Yeu, Elizabeth] Virginia Eye Consultants, Norfolk, VA USA.
   [Cuozzo, Susan] Sci & Strateg Insights LLC, New York, NY USA.
C3 Eastern Virginia Medical School
RP Yeu, E (通讯作者)，Eastern Virginia Med Sch, Dept Ophthalmol, 241 Corp Blvd, Norfolk, VA 23502 USA.
EM eyeulin@gmail.com
RI Cuozzo, Susan/ADB-2916-2022
OI Yeu, Elizabeth/0000-0002-3453-3062
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NR 77
TC 6
Z9 6
U1 4
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2021
VL 128
IS 11
BP E132
EP E141
DI 10.1016/j.ophtha.2020.08.025
EA OCT 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WL5XV
UT WOS:000710479200006
PM 32882308
OA hybrid
DA 2022-11-30
ER

PT J
AU Tan, BY
   Sim, YC
   Chua, J
   Yusufi, D
   Wong, D
   Yow, AP
   Chin, C
   Tan, ACS
   Sng, CCA
   Agrawal, R
   Gopal, L
   Sim, R
   Tan, G
   Lamoureux, E
   Schmetterer, L
AF Tan, Bingyao
   Sim, Yin Ci
   Chua, Jacqueline
   Yusufi, Dheo
   Wong, Damon
   Yow, Ai Ping
   Chin, Calvin
   Tan, Anna C. S.
   Sng, Chelvin C. A.
   Agrawal, Rupesh
   Gopal, Lekha
   Sim, Ralene
   Tan, Gavin
   Lamoureux, Ecosse
   Schmetterer, Leopold
TI Developing a normative database for retinal perfusion using optical
   coherence tomography angiography
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID AGE-RELATED ALTERATIONS; FIBER BUNDLE TRAJECTORIES; INNER PLEXIFORM
   LAYER; VESSEL DENSITY; ENHANCEMENT; VARIABILITY; GLAUCOMA; BLOOD
AB Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual's data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12x12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and > 69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12x12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Tan, Bingyao; Chua, Jacqueline; Yusufi, Dheo; Wong, Damon; Yow, Ai Ping; Schmetterer, Leopold] SERI NTU Adv Ocular Engn STANCE, Singapore, Singapore.
   [Tan, Bingyao; Wong, Damon; Yow, Ai Ping; Schmetterer, Leopold] NTU Inst Hlth Technol, Singapore, Singapore.
   [Tan, Bingyao; Sim, Yin Ci; Chua, Jacqueline; Yusufi, Dheo; Wong, Damon; Yow, Ai Ping; Tan, Anna C. S.; Sng, Chelvin C. A.; Agrawal, Rupesh; Sim, Ralene; Tan, Gavin; Lamoureux, Ecosse; Schmetterer, Leopold] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Chua, Jacqueline; Chin, Calvin; Tan, Anna C. S.; Tan, Gavin; Lamoureux, Ecosse] Duke NUS Med Sch, Singapore, Singapore.
   [Chin, Calvin] Natl Heart Ctr Singapore, Singapore, Singapore.
   [Tan, Anna C. S.] Changi Gen Hosp, Singapore, Singapore.
   [Sng, Chelvin C. A.] Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.
   [Agrawal, Rupesh] Tan Tock Seng Hosp, Singapore, Singapore.
   [Agrawal, Rupesh] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
   [Gopal, Lekha] Khoo Teck Puat Hosp, Singapore, Singapore.
   [Schmetterer, Leopold] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore, Singapore.
   [Schmetterer, Leopold] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
   [Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Schmetterer, Leopold] Inst Mol & Clin Ophthalmol, Basel, Switzerland.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National Heart Centre Singapore;
   Changi General Hospital; National University of Singapore; Tan Tock Seng
   Hospital; Nanyang Technological University & National Institute of
   Education (NIE) Singapore; Nanyang Technological University; Nanyang
   Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; Medical University of
   Vienna; Medical University of Vienna
RP Schmetterer, L (通讯作者)，SERI NTU Adv Ocular Engn STANCE, Singapore, Singapore.; Schmetterer, L (通讯作者)，NTU Inst Hlth Technol, Singapore, Singapore.; Schmetterer, L (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.; Schmetterer, L (通讯作者)，Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore, Singapore.; Schmetterer, L (通讯作者)，Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.; Schmetterer, L (通讯作者)，Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.; Schmetterer, L (通讯作者)，Inst Mol & Clin Ophthalmol, Basel, Switzerland.
EM leopold.schmetterer@seri.com.sg
OI Tan, Bingyao/0000-0002-6532-9603; Sim, Yin Ci/0000-0002-9643-9266;
   Schmetterer, Leopold/0000-0002-7189-1707; Wong,
   Damon/0000-0003-4601-9121
FU National Medical Research Council [NMRC/CG/C010A/2017_SERI, MOH00024900,
   (Coll) /2018/0009A]
FX National Medical Research Council (NMRC/CG/C010A/2017_SERI,
   NMRC/OFIRG/0048/2017, NMRC/OFLCG/004c/2018, MOH00024900) ; DukeNUS
   DukeNUSKP (Coll) /2018/0009A.
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NR 46
TC 2
Z9 3
U1 1
U2 3
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 4032
EP 4045
DI 10.1364/BOE.423469
PG 14
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 TE6IL
UT WOS:000670114300005
PM 34457397
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Cervantes-Paz, B
   Yahia, EM
AF Cervantes-Paz, Braulio
   Yahia, Elhadi M.
TI Avocado oil: Production and market demand, bioactive components,
   implications in health, and tendencies and potential uses
SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY
LA English
DT Review
DE bioactive compounds; cancer; cardiovascular diseases; fatty acids;
   Persea americana; processing
ID PERSEA-AMERICANA MILL; FATTY-ACIDS; ENZYMATIC PRETREATMENT; OXIDATIVE
   STABILITY; PROSTATE-CANCER; OLIVE OILS; EDIBLE OIL; PHYSICOCHEMICAL
   PROPERTIES; CARDIOVASCULAR-DISEASE; ANTIOXIDANT ACTIVITY
AB Avocado is a subtropical/tropical fruit with creamy texture, peculiar flavor, and high nutritional value. Due to its high oil content, a significant quantity of avocado fruit is used for the production of oil using different methods. Avocado oil is rich in lipid-soluble bioactive compounds, but their content depends on different factors. Several phytochemicals in the oil have been linked to prevention of cancer, age-related macular degeneration, and cardiovascular diseases and therefore have generated an increase in consumer demand for avocado oil. The aim of this review is to critically and systematically analyze the worldwide production and commercialization of avocado oil, its extraction methods, changes in its fat-soluble phytochemical content, health benefits, and new trends and applications. There is a lack of information on the production and commercialization of the different types of avocado oil, but there are abundant data on extraction methods using solvents, centrifugation-assisted aqueous extraction, mechanical extraction by cold pressing (varying concentration and type of enzymes, temperature and time of reaction, and dilution ratio), ultrasound-assisted extraction, and supercritical fluid to enhance the yield and quality of oil. Extensive information is available on the content of fatty acids, although it is limited on carotenoids and chlorophylls. The effect of avocado oil on cancer, diabetes, and cardiovascular diseases has been demonstrated through in vitro and animal studies, but not in humans. Avocado oil continues to be of interest to the food, pharmaceutical, and cosmetic industries and is also generating increased attention in other areas including structured lipids, nanotechnology, and environmental care.
C1 [Cervantes-Paz, Braulio; Yahia, Elhadi M.] Univ Autonoma Queretaro, Fac Ciencias Nat, Juriquilla, Mexico.
   [Cervantes-Paz, Braulio] Univ Autonoma San Luis Potosi, Inst Invest Zonas Desert, San Luis Potosi, San Luis Potosi, Mexico.
C3 Universidad Autonoma de Queretaro; Universidad Autonoma de San Luis
   Potosi
RP Yahia, EM (通讯作者)，Univ Autonoma Queretaro, Fac Ciencias Nat, Ave Ciencias S-N, Queretaro 76230, Qro, Mexico.
EM yahia@uaq.mx
RI Cervantes-Paz, Braulio/G-2553-2018
OI Cervantes-Paz, Braulio/0000-0001-6976-9684
FU CONACyT [I1200/169/2019, MOD.ORD./38/2019, CB2017-2018, A1-S-28359]
FX CONACyT, Grant/Award Numbers: I1200/169/2019, MOD.ORD./38/2019,
   CB2017-2018, GENERAL, A1-S-28359
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NR 212
TC 3
Z9 3
U1 14
U2 38
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1541-4337
J9 COMPR REV FOOD SCI F
JI Compr. Rev. Food. Sci. Food Saf.
PD JUL
PY 2021
VL 20
IS 4
BP 4120
EP 4158
DI 10.1111/1541-4337.12784
EA JUN 2021
PG 39
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA TG6XQ
UT WOS:000663397200001
PM 34146454
DA 2022-11-30
ER

PT J
AU Chen, C
   Chen, JM
   Wang, Y
   Liu, ZG
   Wu, YL
AF Chen, Chao
   Chen, Jingmeng
   Wang, Yan
   Liu, Zuguo
   Wu, Yalin
TI Ferroptosis drives photoreceptor degeneration in mice with defects in
   all-trans-retinal clearance
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GLUTATHIONE-PEROXIDASE 4; CELL-DEATH; LIPID-PEROXIDATION; MECHANISM;
   DISEASE; PROTEIN; DAMAGE; METABOLISM; IDENTIFICATION; RETINOPATHY
AB The death of photoreceptor cells in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1) is closely associated with disruption in all-transretinal (atRAL) clearance in neural retina. In this study, we reveal that the overload of atRAL leads to photoreceptor degeneration through activating ferroptosis, a nonapoptotic form of cell death. Ferroptosis of photoreceptor cells induced by atRAL resulted from increased ferrous ion (Fe2+), elevated ACSL4 expression, system Xc(-) inhibition, and mitochondrial destruction. Fe2+ overload, tripeptide glutathione (GSH) depletion, and damaged mitochondria in photoreceptor cells exposed to atRAL provoked reactive oxygen species (ROS) production, which, together with ACSL4 activation, promoted lipid peroxidation and thereby evoked ferroptotic cell death. Moreover, exposure of photoreceptor cells to atRAL activated COX2, a well-accepted biomarker for ferroptosis onset. In addition to GSH supplement, inhibiting either Fe2+ by deferoxamine mesylate salt (DFO) or lipid peroxidation with ferrostatin-1 (Fer-1) protected photoreceptor cells from ferroptosis caused by atRAL. Abca4(-/-)Rdh8(-/-) mice exhibiting defects in atRAL clearance is an animal model for dry AMD and STGD1. We observed that ferroptosis was indeed present in neural retina of Abca4(-/-)Rdh8(-/-) mice after light exposure. More importantly, photoreceptor atrophy and ferroptosis in light-exposed Abca4(-/-)Rdh8(-/-) mice were effectively alleviated by intraperitoneally injected Fer-1, a selective inhibitor of ferroptosis. Our study suggests that ferroptosis is one of the important pathways of photoreceptor cell death in retinopathies arising from excess atRAL accumulation and should be pursued as a novel target for protection against dry AMD and STGD1.
C1 [Chen, Chao; Liu, Zuguo; Wu, Yalin] Xiamen Univ, Fujian Prov Key Lab Ophthalmol & Visual Sci, Dept Ophthalmol, Xiangan Hosp,Eye Inst, Xiamen, Peoples R China.
   [Chen, Jingmeng] Xiamen Univ, Sch Med, Xiamen, Fujian, Peoples R China.
   [Wang, Yan] Southern Med Univ, Shenzhen Hosp, Dept Ophthalmol, Shenzhen, Guangdong, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Xiamen Eye Ctr, Xiamen, Fujian, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Shenzhen Res Inst, Shenzhen, Guangdong, Peoples R China.
C3 Xiamen University; Xiamen University; Southern Medical University -
   China; Xiamen University; Xiamen University
RP Wu, YL (通讯作者)，Xiamen Univ, Fujian Prov Key Lab Ophthalmol & Visual Sci, Dept Ophthalmol, Xiangan Hosp,Eye Inst, Xiamen, Peoples R China.; Wu, YL (通讯作者)，Xiamen Univ, Xiamen Eye Ctr, Xiamen, Fujian, Peoples R China.; Wu, YL (通讯作者)，Xiamen Univ, Shenzhen Res Inst, Shenzhen, Guangdong, Peoples R China.
EM yalinw@xmu.edu.cn
FU National Natural Science Foundation of China [81870671, 81570857];
   Natural Science Foundation of Guangdong Province, China; Basic Research
   Program of Shenzhen [JCYJ20180306173025004]; XMU Training Program of
   Innovation and Enterpreneurship for Undergraduates
FX This work was supported in part by grants from National Natural Science
   Foundation of China (Nos. 81870671 and 81570857, to Y. Wu), the Natural
   Science Foundation of Guangdong Province, China (to Y. Wu), the Basic
   Research Program of Shenzhen (No. JCYJ20180306173025004, to Y. Wu), and
   XMU Training Program of Innovation and Enterpreneurship for
   Undergraduates.
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NR 75
TC 20
Z9 20
U1 9
U2 36
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN-JUN
PY 2021
VL 296
AR 100187
DI 10.1074/jbc.RA120.015779
PG 17
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA TI5TQ
UT WOS:000672866400165
PM 33334878
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Xiong, XJ
   Liu, DN
   Liu, SC
   Wu, MX
   Zhan, BW
   Wang, H
   Zhou, XY
AF Xiong, Xiaojing
   Liu, Danning
   Liu, Shenchun
   Wu, Mingxing
   Zhan, Bainwen
   Wang, Hao
   Zhou, Xiyuan
TI The prevalence and causes of visual impairment among ethnic Tujia adults
   in a rural community in China
SO MEDICINE
LA English
DT Article
DE causes; prevalence; rural; Tujia ethnic; visual impairment
ID LOW-VISION; CATARACT-SURGERY; BLINDNESS; POPULATION; PROVINCE
AB We aimed to investigate the prevalence and causes of visual impairment (VI) in an elderly Tujia ethnic rural population in Southwest China. From June 1 to December 31, 2018, a random cluster sampling survey was conducted among Tujia individuals aged 50 years or older in the rural areas of Qianjiang District County in Chongqing. The sampling design used village-based clusters of approximately equal size (1000 people). The sampling frame was composed of 110 clusters including 26,527 adults aged 50 years or older; 10 clusters (2556 adults) were randomly selected, and 2122 subjects were examined. Ophthalmologic examinations and questionnaires were administered to all the participants. Low vision and blindness were defined using best-corrected visual acuity (BCVA) and presenting visual acuity, according to The World Health Organization standard. The prevalence of VI was estimated, and causes of VI were identified. The participation rate was 83.0%. The prevalence of VI was 15.2% (BCVA 8.0%). In the study population, the prevalence of low vision and blindness increased with age (P < .05) and was higher among those with a low education level (P < .01). The majority of VI was attributed to cataracts (50.0%) and uncorrected refractive error (35.7%). With BCVA, cataract (79.3%) was the most common cause of VI, followed by age-related macular degeneration (10.7%). The main causes of VI in Tujia ethnic were cataracts and refractive errors. Both cataracts and refractive errors are curable eye diseases; thus, local health institutions need to adopt a more active eye care project as a strategy to prevent blindness.
C1 [Xiong, Xiaojing; Liu, Danning; Liu, Shenchun; Wu, Mingxing; Zhan, Bainwen; Wang, Hao; Zhou, Xiyuan] Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing, Peoples R China.
C3 Chongqing Medical University
RP Zhou, XY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing, Peoples R China.
EM zhouxiyuan2002@aliyun.com
FU Science and technology project of traditional Chinese Medicine
   [ZY201702079]; Chongqing Science and Technology Commission
   [cstc2015shmszx120068, cstc2016jcyjA0122]
FX The article received the funding of Science and technology project of
   traditional Chinese Medicine ZY201702079 during the experimental scheme
   was implemented.r This study was supported by Chongqing Science and
   Technology Commission cstc2015shmszx120068 and cstc2016jcyjA0122.
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NR 34
TC 1
Z9 1
U1 1
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 13
PY 2020
VL 99
IS 46
AR e22464
DI 10.1097/MD.0000000000022464
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA OS0ED
UT WOS:000589836300010
PM 33181642
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Driver, SGW
   Jackson, MR
   Richter, K
   Tomlinson, P
   Brockway, B
   Halliday, BJ
   Markie, DM
   Robertson, SP
   Wade, EM
AF Driver, Sean G. W.
   Jackson, Meremaihi R.
   Richter, Konrad
   Tomlinson, Paul
   Brockway, Ben
   Halliday, Benjamin J.
   Markie, David M.
   Robertson, Stephen P.
   Wade, Emma M.
TI Biallelic variants in EFEMP1 in a man with a pronounced connective
   tissue phenotype
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID EHLERS-DANLOS-SYNDROME; MACULAR DEGENERATION; MARFAN-SYNDROME; CUTIS
   LAXA; GENE; FIBULIN-1; MUTATION; SECRETION; FIBRILLIN; FRAMEWORK
AB Connective tissue disorders are a spectrum of diseases that affect the integrity of tissues including skin, vasculature, and joints. They are often caused by variants that disrupt genes encoding components of extracellular matrix (ECM). The fibulin glycoproteins are ECM proteins important for integrity of tissues including dermis, retina, fascia, and vasculature. The fibulin family consists of seven members (fibulins-1 to -7) and is defined by a fibulin-type domain at the C-terminus. The family is associated with human diseases, for instance a variant in FBLN1, encoding fibulin-1, is associated with synpolydactyly, while one in EFEMP1, encoding fibulin-3, causes Doyne honeycomb degeneration of the retina. Loss-of-function of fibulins-4 and -5 causes cutis laxa, while variants in fibulins-5 and -6 are associated with age-related macular degeneration. Of note, EFEMP1 is not currently associated with any connective tissue disorder. Here we show biallelic loss-of-function variants in EFEMP1 in an individual with multiple and recurrent abdominal and thoracic herniae, myopia, hypermobile joints, scoliosis, and thin translucent skin. Fibroblasts from this individual express significantly lower EFEMP1 transcript than age-matched control cells. A skin biopsy, visualised using light microscopy, showed normal structure and abundance of elastic fibres. The phenotype of this individual is remarkably similar to the Efemp1 knockout mouse model that displays multiple herniae with premature aging and scoliosis. We conclude that loss of EFEMP1 function in this individual is the cause of a connective tissue disorder with a novel combination of phenotypic features, and can perhaps explain similar, previously reported cases in the literature.
C1 [Driver, Sean G. W.; Jackson, Meremaihi R.; Halliday, Benjamin J.; Robertson, Stephen P.; Wade, Emma M.] Univ Otago, Dunedin Sch Med, Dept Womens & Childrens Hlth, Dunedin 9016, New Zealand.
   [Richter, Konrad] Univ Otago, Dunedin Sch Med, Dept Surg, Dunedin 9016, New Zealand.
   [Tomlinson, Paul] Kew Hosp, Dept Paediat, Invercargill, New Zealand.
   [Brockway, Ben] Univ Otago, Dunedin Sch Med, Dept Med, Dunedin 9016, New Zealand.
   [Markie, David M.] Univ Otago, Dunedin Sch Med, Dept Pathol, Dunedin 9016, New Zealand.
C3 University of Otago; University of Otago; University of Otago;
   University of Otago
RP Robertson, SP (通讯作者)，Univ Otago, Dunedin Sch Med, Dept Womens & Childrens Hlth, Dunedin 9016, New Zealand.
EM stephen.robertson@otago.ac.nz
RI Wade, Emma Mary/AAT-1035-2020
OI Wade, Emma M/0000-0003-2990-0232; Driver, Sean/0000-0002-2527-4716;
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NR 33
TC 7
Z9 7
U1 0
U2 2
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 2020
VL 28
IS 4
BP 445
EP 452
DI 10.1038/s41431-019-0546-7
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA KV7DA
UT WOS:000520639600006
PM 31792352
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Ruamviboonsuk, P
   Cheung, CY
   Zhang, XL
   Raman, R
   Park, SJ
   Ting, DSW
AF Ruamviboonsuk, Paisan
   Cheung, Carol Y.
   Zhang, Xiulan
   Raman, Rajiv
   Park, Sang Jun
   Ting, Daniel Shu Wei
TI Artificial Intelligence in Ophthalmology: Evolutions in Asia
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE artificial intelligence; deep learning; ophthalmology
ID OPTICAL COHERENCE TOMOGRAPHY; FIBER LAYER THICKNESS;
   DIABETIC-RETINOPATHY; AUTOMATED DETECTION; RETINAL IMAGES; DOMAIN;
   VALIDATION; AGE
AB Artificial intelligence (AI) has been studied in ophthalmology since availability of digital information in ophthalmic care. The significant turning point was availability of commercial digital color fundus photography in the late 1990s, which caused digital screening for diabetic retinopathy (DR) to take off. Automated Retinal Disease Assessment software was then developed using machine learning to detect abnormal lesions in fundus to screen DR. The use of this version of AI had not been generalized because the specificity at 45% was not high enough, although the sensitivity reached 90%. The recent breakthrough in machine learning is the invent of deep learning, which accelerates its performance to be on par with experts. The first 2 breakthrough studies on deep learning for screening DR were conducted in Asia. The first represented collaboration of datasets between Asia and the United States for algorithms development, whereas the second represented algorithms developed in Asia but validated in different populations across the world. Both found accuracy for detecting referable DR of >95%. Diversity and variety are unique strengths of Asia for AI studies. There are many more studies of AI ongoing in Asia not only as prospective deployments in DR but in glaucoma, age-related macular degeneration, cataract, and systemic disease, such as Alzheimer's disease. Some Asian countries have laid out plans for digital health care system using AI as one of the puzzle pieces for solving blindness. More studies on AI and digital health are expected to come from Asia in this new decade.
C1 [Ruamviboonsuk, Paisan] Rajavithi Hosp, Dept Ophthalmol, Bangkok 10400, Thailand.
   [Cheung, Carol Y.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
   [Zhang, Xiulan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
   [Raman, Rajiv] Sankara Nethralaya, Shri Bhagwan Mahavir Vitreoretinal Serv, Chennai, Tamil Nadu, India.
   [Ting, Daniel Shu Wei] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Bundang Hosp, Seongmam, South Korea.
   [Park, Sang Jun] Singapore Natl Eye Ctr, Duke NUS Med Sch Consultant, Vitreo Retinal Dept, Singapore, Singapore.
C3 Rajavithi Hospital; Chinese University of Hong Kong; Sun Yat Sen
   University; Seoul National University (SNU); Singapore National Eye
   Center
RP Ruamviboonsuk, P (通讯作者)，Rajavithi Hosp, Dept Ophthalmol, Bangkok 10400, Thailand.
EM paisan.trs@gmail.com
OI Bidwai, Pooja Vishal/0000-0002-3077-4395
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NR 52
TC 12
Z9 12
U1 4
U2 17
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 MAR-APR
PY 2020
VL 9
IS 2
BP 78
EP 84
DI 10.1097/01.APO.0000656980.41190.bf
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LJ4VB
UT WOS:000530163700004
PM 32349114
OA gold
DA 2022-11-30
ER

PT J
AU Qi, JH
   Bell, B
   Singh, R
   Batoki, J
   Wolk, A
   Cutler, A
   Prayson, N
   Ali, M
   Stoehr, H
   Anand-Apte, B
AF Qi, Jian Hua
   Bell, Brent
   Singh, Rupesh
   Batoki, Julia
   Wolk, Alyson
   Cutler, Alecia
   Prayson, Nicholas
   Ali, Mariya
   Stoehr, Heidi
   Anand-Apte, Bela
TI Sorsby Fundus Dystrophy Mutation in Tissue Inhibitor of
   Metalloproteinase 3 (TIMP3) promotes Choroidal Neovascularization via a
   Fibroblast Growth Factor-dependent Mechanism
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MATRIX METALLOPROTEINASES; TUMOR-GROWTH;
   FACTOR VEGF; ANGIOGENESIS; RECEPTOR; HEPARIN; BINDING; CANCER; GENE
AB Choroidal neovascularization (CNV) leads to loss of vision in patients with Sorsby Fundus Dystrophy (SFD), an inherited, macular degenerative disorder, caused by mutations in the Tissue Inhibitor of Metalloproteinase-3 (TIMP3) gene. SFD closely resembles age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly population of the Western hemisphere. Variants in TIMP3 gene have recently been identified in patients with AMD. A majority of patients with AMD also lose vision as a consequence of choroidal neovascularization (CNV). Thus, understanding the molecular mechanisms that contribute to CNV as a consequence of TIMP-3 mutations will provide insight into the pathophysiology in SFD and likely the neovascular component of the more commonly seen AMD. While the role of VEGF in CNV has been studied extensively, it is becoming increasingly clear that other factors likely play a significant role. The objective of this study was to test the hypothesis that basic Fibroblast Growth Factor (bFGF) regulates SFD-related CNV. In this study we demonstrate that mice expressing mutant TIMP3 (Timp3(S179C/S179C)) showed reduced MMP inhibitory activity with an increase in MMP2 activity and bFGF levels, as well as accentuated CNV leakage when subjected to laser injury. S179C mutant-TIMP3 in retinal pigment epithelial (RPE) cells showed increased secretion of bFGF and conditioned medium from these cells induced increased angiogenesis in endothelial cells. These studies suggest that S179C-TIMP3 may promote angiogenesis and CNV via a FGFR-1-dependent pathway by increasing bFGF release and activity.
C1 [Qi, Jian Hua; Bell, Brent; Singh, Rupesh; Batoki, Julia; Wolk, Alyson; Cutler, Alecia; Prayson, Nicholas; Ali, Mariya; Anand-Apte, Bela] Cleveland Clin Fdn, Cole Eye Inst, Cleveland Clin Lerner Coll Med, Dept Ophthalmol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
   [Stoehr, Heidi] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
   [Wolk, Alyson; Anand-Apte, Bela] Cleveland Clin Fdn, Cleveland Clin Lerner Coll Med, Dept Mol Med, 9500 Euclid Ave, Cleveland, OH 44195 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation; University
   of Regensburg; Case Western Reserve University; Cleveland Clinic
   Foundation
RP Anand-Apte, B (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, Cleveland Clin Lerner Coll Med, Dept Ophthalmol, 9500 Euclid Ave, Cleveland, OH 44195 USA.; Anand-Apte, B (通讯作者)，Cleveland Clin Fdn, Cleveland Clin Lerner Coll Med, Dept Mol Med, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM anandab@ccf.org
OI Wolk, Alyson/0000-0002-1613-0251; Anand-Apte, Bela/0000-0002-4845-9094;
   Singh, Rupesh/0000-0002-0938-9388
FU US National Institute of Health [EY027083, EY026181, EY022768,
   P30EY025585, EY024236, EY016490, EY020861, T32EY024236]; Research to
   Prevent Blindness (RPB) Challenge Grant; RPB Lew Wasserman award;
   Foundation Fighting Blindness Center Grant; Cleveland Clinic Foundation;
   NATIONAL EYE INSTITUTE [T32EY024236, R01EY026181, R01EY027083,
   P30EY025585] Funding Source: NIH RePORTER
FX Dr. Anand-Apte is the guarantor of this work, had full access to the
   data and takes full responsibility for the integrity of the data and the
   accuracy of the data analysis. This work was supported in part by US
   National Institute of Health EY027083 (BA-A), EY026181 (BA-A), EY022768
   (JHQ), P30EY025585(BA-A), EY024236 (BA-A), Research to Prevent Blindness
   (RPB) Challenge Grant and RPB Lew Wasserman award to BA-A. We wish to
   extend a sincere apology to colleagues whose work was not cited because
   of space limitations. This work was supported in part by US National
   Institute of Health EY016490 (BA-A), EY020861 (BA-A), EY022768 (JHQ),
   EY027083 (BA-A), P30EY025585 (BA-A), T32EY024236, Foundation Fighting
   Blindness Center Grant (BA-A), Cleveland Clinic Foundation institutional
   funding, Research to Prevent Blindness (RPB) Challenge Grant and RPB Lew
   Wasserman award to BA-A.
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NR 76
TC 10
Z9 11
U1 0
U2 1
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 NOV 22
PY 2019
VL 9
AR 17429
DI 10.1038/s41598-019-53433-6
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA JP1US
UT WOS:000498057700004
PM 31757977
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hagbi-Levi, S
   Abraham, M
   Tiosano, L
   Rinsky, B
   Grunin, M
   Eizenberg, O
   Peled, A
   Chowers, I
AF Hagbi-Levi, Shira
   Abraham, Michal
   Tiosano, Liran
   Rinsky, Batya
   Grunin, Michelle
   Eizenberg, Orly
   Peled, Amnon
   Chowers, Itay
TI Promiscuous Chemokine Antagonist (BKT130) Suppresses Laser-Induced
   Choroidal Neovascularization by Inhibition of Monocyte Recruitment
SO JOURNAL OF IMMUNOLOGY RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; MACROPHAGE
   POLARIZATION; MEDIATED INFLAMMATION; DIABETIC-RETINOPATHY; VEGF
   EXPRESSION; BRUCHS MEMBRANE; AQUEOUS-HUMOR; MULLER CELLS; MICROGLIA
AB Background. Age-related macular degeneration (AMD), the most common cause of blindness in the developed world, usually affects individuals older than 60 years of age. The majority of visual loss in this disease is attributable to the development of choroidal neovascularization (CNV). Mononuclear phagocytes, including monocytes and their tissue descendants, macrophages, have long been implicated in the pathogenesis of neovascular AMD (nvAMD). Current therapies for nvAMD are based on targeting vascular endothelial growth factor (VEGF). This study is aimed at assessing if perturbation of chemokine signaling and mononuclear cell recruitment may serve as novel complementary therapeutic targets for nvAMD. Methods. A promiscuous chemokine antagonist (BKT130), aflibercept treatment, or combined BKT130+aflibercept treatment was tested in an in vivo laser-induced model of choroidal neovascularization (LI-CNV) and in an ex vivo choroidal sprouting assay (CSA). Quantification of CD11b+ cell in the CNV area was performed, and mRNA levels of genes implicated in CNV growth were measured in the retina and RPE-choroid. Results. BKT130 reduced the CNV area and recruitment of CD11b+ cells by 30-35%. No effect of BKT130 on macrophages' proangiogenic phenotype was demonstrated ex vivo, but a lower VEGFA and CCR2 expression was found in the RPE-choroid and a lower expression of TNF alpha and NOS1 was found in both RPE-choroid and retinal tissues in the LI-CNV model under treatment with BKT130. Conclusions. Targeting monocyte recruitment via perturbation of chemokine signaling can reduce the size of experimental CNV and should be evaluated as a potential novel therapeutic modality for nvAMD.
C1 [Hagbi-Levi, Shira; Tiosano, Liran; Rinsky, Batya; Grunin, Michelle; Chowers, Itay] Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, POB 12000, IL-91120 Jerusalem, Israel.
   [Abraham, Michal; Eizenberg, Orly; Peled, Amnon] Biokine Therapeut Ltd, Sci Pk, Ness Ziona, Israel.
   [Peled, Amnon] Hadassah Hebrew Univ, Goldyne Savad Inst Gene Therapy, Med Ctr, POB 12000, IL-91120 Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hadassah University Medical Center;
   Hebrew University of Jerusalem; Hadassah University Medical Center
RP Chowers, I (通讯作者)，Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, POB 12000, IL-91120 Jerusalem, Israel.
EM chowers@hadassah.org.il
RI Grunin, Michelle/O-6044-2019
OI Grunin, Michelle/0000-0002-3155-2858; Hagbi-Levi,
   Shira/0000-0002-2891-0079
FU Biokine Therapeutics Ltd. [6037411]
FX This work was supported by a grant from Biokine Therapeutics Ltd.
   (#6037411) (AP).
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NR 86
TC 4
Z9 4
U1 0
U2 4
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2314-8861
EI 2314-7156
J9 J IMMUNOL RES
JI J Immunol. Res.
PD AUG 5
PY 2019
VL 2019
AR 8535273
DI 10.1155/2019/8535273
PG 12
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA IS0IE
UT WOS:000481831800001
PM 31467935
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Bohn, T
AF Bohn, Torsten
TI Determinants and Determination of Carotenoid Bioavailability from Infant
   Food Formulas and Adult Nutritionals Including Liquid Dairy Products
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Article
ID SUPERCRITICAL-FLUID EXTRACTION; RESONANCE RAMAN-SPECTROSCOPY;
   FAT-SOLUBLE VITAMINS; SINGLE-LABORATORY VALIDATION; INTESTINAL-CELL
   UPTAKE; DIODE ARRAY DETECTION; HUMAN-MILK SAMPLES; BETA-CAROTENE;
   RETINOIC ACID; ALL-TRANS
AB Carotenoids are typically tetraterpenoid phytochemicals that cannot be synthesized by humans, some of which such as beta-carotene can be metabolized into vitamin A. Sufficient carotenoid intake and tissue levels have been associated with several health benefits including the reduction of cardiovascular diseases and some types of cancer and also the amelioration of age-related macular degeneration. Carotenoids and their metabolites have also been related to reduced inflammation and oxidative stress via interacting with transcription factors, such as NF-kappa B and Nrf-2, as well as with the nuclear receptors retinoic acid receptor/retinoid X receptor, implicated in immune functions and cellular differentiation. Therefore, carotenoids are important for growth and development. They could mark beneficial constituents in infant food formulas and adult nutritionals, the latter typically constituting protein-rich liquid foods targeting meal replacements. Carotenoids may be present by nature (typically below 20 mu g/100 mL) or following fortification (up to 200 mu g/100 mL), such as for lutein and beta-carotene. However, carotenoid bioavailability may be low and variable, especially in low-fat items. Although most infant foods and adult nutritionals are rich in lipids and proteins, facilitating absorption and availability of carotenoids, unfortunately, very little data is available. In addition, carotenoid detection for such lipid-rich matrices may be challenging as a result of low concentrations and matrix effects. This review aims to highlight considerations for carotenoid bioavailability from infant food formula and adult nutritionals as well as summarize detection methods for carotenoids from these items.
C1 [Bohn, Torsten] Luxembourg Inst Hlth, Populat Hlth Dept, 1A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg.
C3 Luxembourg Institute of Health
RP Bohn, T (通讯作者)，Luxembourg Inst Hlth, Populat Hlth Dept, 1A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg.
EM torsten.bohn@gmx.ch
RI Bohn, Torsten/AAE-8393-2019
OI Bohn, Torsten/0000-0002-7825-0697
FU EU COST Action EUROCAROTEN [CA 15136]; EU COST Action POSITIVE [FA 1403]
FX The insights obtained in the EU COST Actions EUROCAROTEN (CA 15136) and
   POSITIVE (FA 1403) are much appreciated.
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NR 146
TC 8
Z9 8
U1 0
U2 21
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1060-3271
EI 1944-7922
J9 J AOAC INT
JI J. AOAC Int.
PD JUL-AUG
PY 2019
VL 102
IS 4
BP 1044
EP 1058
DI 10.5740/jaoacint.19-0015
PG 15
WC Chemistry, Analytical; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Food Science & Technology
GA IH5AN
UT WOS:000474503600012
PM 30786954
DA 2022-11-30
ER

PT J
AU Alexander, JJ
   Sankaran, JS
   Seldeen, KL
   Thiyagarajan, R
   Jacob, A
   Quigg, RJ
   Troen, BR
   Judex, S
AF Alexander, Jessy J.
   Sankaran, Jeyantt S.
   Seldeen, Kenneth L.
   Thiyagarajan, Ramkumar
   Jacob, Alexander
   Quigg, Richard J.
   Troen, Bruce R.
   Judex, Stefan
TI Absence of complement factor H alters bone architecture and dynamics
SO IMMUNOBIOLOGY
LA English
DT Article
DE Complement factor H; Bone; Osteoclast; Osteoblast; Actin
ID INTEGRIN-BINDING LIGAND; ALTERNATIVE PATHWAY; CORTICAL BONE;
   CYTOSKELETON; ACTIVATION; RESORPTION; PROTEIN; IDENTIFICATION;
   OSTEOCLASTS; RECOGNITION
AB Complement system is an important arm of the immune system that promotes inflammation. Complement Factor H (FH) is a critical regulator of the alternative complement pathway. Its absence causes pathology in different organs resulting in diseases such as age related macular degeneration and dense deposit disease. Recent studies suggest that the complement system plays a role in bone development and homeostasis. To determine the role of FH in bone architecture, we studied the FH knockout (fh-/-) mice. 3D reconstructions of femur from 16 week old fh-/- mice reveal significant changes, such as decreased BV/TV (4.5%, p < 0.02), trabecular number (22%, p < 0.01), tissue mineral density (16%, p < 0.04), and increased marrow area (16% p < 0.01), compared to their wild type (WT) counterparts. Kidney function and histology remained normal indicating that bone changes occurred prior to kidney dysfunction. Next we examined cultured osteoblasts and osteoclasts isolated from bone marrow. FH is expressed ubiquitously in the osteoblasts and in the cytoplasm of osteoclasts. The changes caused by absence of FH include: increase in number of osteoblasts (362%) and osteoclasts (342%), increase in RNA (180%) and protein expression of cathepsin K and increased osteoclast function (pit formation, 233%). Actin rearrangement in both osteoblasts and osteoclasts was altered, with a loss of integrity of the F-actin ring at the periphery of the osteoclasts. For the first time our studies demonstrate a direct role of FH in the maintenance of bone structure and function and is highlighted as a promising therapeutic target in bone diseases.
C1 [Alexander, Jessy J.; Seldeen, Kenneth L.; Thiyagarajan, Ramkumar; Jacob, Alexander; Quigg, Richard J.] Univ Buffalo, Jacobs Sch Med & Biomed Sci, Buffalo, NY 14203 USA.
   [Troen, Bruce R.] Vet Affairs Western New York Healthcare Syst, Res Serv, Buffalo, NY 14203 USA.
   [Sankaran, Jeyantt S.; Judex, Stefan] Dept Biomed Engn, Stony Brook, NY USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo
RP Alexander, JJ (通讯作者)，Univ Buffalo, Dept Med, CTRC 8030D,875 Ellicott St, Buffalo, NY 14203 USA.
EM jessyale@buffalo.edu
RI Troen, Bruce R./ABB-4959-2021; Seldeen, Kenneth/AAI-1918-2020;
   Alexander, Jessy/ABA-7664-2020; Sankaran, Jeyantt Srinivas/K-1203-2019
OI Sankaran, Jeyantt Srinivas/0000-0002-8613-9219
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NR 59
TC 4
Z9 4
U1 0
U2 2
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 DEC
PY 2018
VL 223
IS 12
BP 761
EP 771
DI 10.1016/j.imbio.2018.07.023
PG 11
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA HD6YA
UT WOS:000452695000004
PM 30107932
DA 2022-11-30
ER

PT J
AU Painter, DR
   Dwyer, MF
   Kamke, MR
   Mattingley, JB
AF Painter, David R.
   Dwyer, Michael F.
   Kamke, Marc R.
   Mattingley, Jason B.
TI Stimulus-Driven Cortical Hyperexcitability in Individuals with Charles
   Bonnet Hallucinations
SO CURRENT BIOLOGY
LA English
DT Article
ID COMPLEX VISUAL HALLUCINATIONS; MACULAR DEGENERATION; REORGANIZATION;
   LESIONS; CORTEX; BRAIN; AMPUTATION; DYNAMICS; TINNITUS; ANATOMY
AB Throughout the lifespan, the cerebral cortex adapts its structure and function in response to changing sensory input [1, 2]. Whilst such changes are typically adaptive, they can be maladaptive when they follow damage to the peripheral nervous system, including phantom limb pain and tinnitus [3, 4]. An intriguing example occurs in individuals with acquired ocular pathologies-most commonly age-related macular degeneration (MD) [5]-who lose their fovea! vision but retain intact acuity in the peripheral visual field. Up to 40% of ocular pathology patients develop long-term hallucinations involving flashes of light, shapes, or geometric patterns and/or complex hallucinations, including faces, animals, or entire scenes, a condition known as Charles Bonnet Syndrome (CBS) [6, 7, 8]. Though CBS was first described over 250 years ago [9,10], the neural basis for the hallucinations remains unclear, with no satisfactory explanation as to why some individuals develop hallucinations, while many do not. An influential but untested hypothesis for the visual hallucinations in CBS is that retinal deafferentation causes hyperexcitability in early visual cortex. To assess this, we investigated electrophysiological responses to peripheral visual field stimulation in MD patients with and without hallucinations and in matched controls without ocular pathology. Participants performed a concurrent attention task within intact portions of their peripheral visual field, while ignoring flickering checkerboards that drove periodic electrophysiological responses. CBS individuals showed strikingly elevated visual cortical responses to peripheral field stimulation compared with patients without hallucinations and controls, providing direct support for the hypothesis of visual cortical hyperexcitability in CBS.
C1 [Painter, David R.; Mattingley, Jason B.] Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia.
   [Painter, David R.; Dwyer, Michael F.; Kamke, Marc R.; Mattingley, Jason B.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
C3 University of Queensland; University of Queensland
RP Painter, DR; Mattingley, JB (通讯作者)，Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia.; Painter, DR; Dwyer, MF; Kamke, MR; Mattingley, JB (通讯作者)，Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
EM david.ross.painter@gmail.com; mdwyer@watkinsmd.com.au;
   m.kamke@uq.edu.au; j.mattingley@uq.edu.au
RI Kamke, Marc/J-4059-2014; Mattingley, Jason/J-1537-2014
OI Kamke, Marc/0000-0003-0248-9682; Mattingley, Jason/0000-0003-0929-9216;
   Painter, David/0000-0003-3328-6386
FU Australian Research Council (ARC) Special Research Initiative Science of
   Learning Research Centre [SR120300015]; ARC Australian Laureate
   Fellowship [FL110100103]; ARC Centre of Excellence for Integrative Brain
   Function (ARC Centre) [CE140100007]
FX D.R.P. was supported by the Australian Research Council (ARC) Special
   Research Initiative Science of Learning Research Centre (SR120300015).
   J.B.M. was supported by an ARC Australian Laureate Fellowship
   (FL110100103) and the ARC Centre of Excellence for Integrative Brain
   Function (ARC Centre Grant CE140100007).
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NR 41
TC 16
Z9 16
U1 1
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 NOV 5
PY 2018
VL 28
IS 21
BP 3475
EP +
DI 10.1016/j.cub.2018.08.058
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA GZ6ZB
UT WOS:000449621400031
PM 30415703
OA Bronze
DA 2022-11-30
ER

PT J
AU Li, S
   Gaur, U
   Chong, CM
   Lin, SF
   Fang, JK
   Zeng, ZW
   Wang, HT
   Zheng, WH
AF Li, Shuai
   Gaur, Uma
   Chong, Cheong-Meng
   Lin, Shaofen
   Fang, Jiankang
   Zeng, Zhiwen
   Wang, Haitao
   Zheng, Wenhua
TI Berberine Protects Human Retinal Pigment Epithelial Cells from Hydrogen
   Peroxide-Induced Oxidative Damage through Activation of AMPK
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE berberine; age-related macular degeneration; D407 cells; AMPK
ID MACULAR DEGENERATION; LIPID-PEROXIDATION; GLUCOSE-UPTAKE; STRESS;
   MECHANISMS; DYSFUNCTION; GLYCOLYSIS; RESPONSES; EPITOPES; SURVIVAL
AB Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly with less effective treatment, especially for dry AMD (90% of AMD). Although the etiology of this disease is not well elucidated, increasing evidences indicate that excessive reactive oxygen species (ROS) impairing the physiological functions of retinal pigment epithelium (RPE) cells may be one of the main causes. Therefore, it could be a great strategy to find some drugs that can effectively protect RPE cells from oxidative damage which is desired to treat and slow the process of AMD. In the present study, a well-known traditional Chinese medicine berberine (BBR) was found to suppress hydrogen peroxide (H2O2)-induced oxidative damage in D407 cells, a human RPE cell line. Pre-treatment of D407 cells with BBR significantly suppressed H2O2-induced cell apoptosis by restoring abnormal changes in nuclear morphology, preventing the decline of mitochondrial membrane potential, reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities induced by H2O2. Western blot analysis showed that BBR was able to stimulate the phosphorylation/activation of AMPK in a time- and dose-dependent manner in D407 cells, while treatment of cells with AMPK pathway inhibitor Compound C, or knockdown of the AMPK by specific siRNA blocked the effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrated that BBR was able to protect RPE cells against oxidative stress via the activation of AMPK pathway. Our findings also indicate the potential application of BBR in AMD treatment.
C1 [Li, Shuai; Gaur, Uma; Chong, Cheong-Meng; Fang, Jiankang; Zeng, Zhiwen; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Taipa 999078, Madhya Pradesh, Peoples R China.
   [Lin, Shaofen] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510000, Guangdong, Peoples R China.
   [Lin, Shaofen] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510000, Guangdong, Peoples R China.
   [Wang, Haitao] Southern Med Univ, Sch Pharmaceut Sci, Dept Neuropharmacol & Novel Drug Discovery, Guangzhou 510000, Guangdong, Peoples R China.
   [Zheng, Wenhua] UM Zhuhai Res Inst, Zhuhai 519000, Peoples R China.
C3 University of Macau; Sun Yat Sen University; Sun Yat Sen University;
   Southern Medical University - China
RP Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Taipa 999078, Madhya Pradesh, Peoples R China.; Zheng, WH (通讯作者)，UM Zhuhai Res Inst, Zhuhai 519000, Peoples R China.
EM yb67619@umac.mo; gaur.uma2906@gmail.com; legendhero91@gmail.com;
   linshaofen1970@163.com; yb57646@umac.mo; zengzw1122@gmail.com;
   wht821@smu.edu.cn; wenhuazheng@umac.mo
RI Li, Shuai/ABC-5377-2021
OI Wang, Haitao/0000-0001-6910-974X
FU National Natural Science Foundation of China [31771128, 81301099,
   31371088]; University of Macau [MYRG2016-00052-FHS, MYRG2018-00134-FHS];
   Science and Technology Development Fund (FDCT) of Macao [FDCT
   021/2015/A1, 016/2016/A1]
FX This research was supported by National Natural Science Foundation of
   China (No. 31771128, No. 81301099 and No. 31371088), MYRG2016-00052-FHS
   and MYRG2018-00134-FHS from University of Macau, and the Science and
   Technology Development Fund (FDCT) of Macao (FDCT 021/2015/A1 and
   016/2016/A1).
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TC 25
Z9 28
U1 3
U2 10
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 JUN
PY 2018
VL 19
IS 6
AR 1736
DI 10.3390/ijms19061736
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA GK8UZ
UT WOS:000436506600191
PM 29895743
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Touitou, Y
   Reinberg, A
   Touitou, D
AF Touitou, Yvan
   Reinberg, Alain
   Touitou, David
TI Association between light at night, melatonin secretion, sleep
   deprivation, and the internal clock: Health impacts and mechanisms of
   circadian disruption
SO LIFE SCIENCES
LA English
DT Review
DE Breast cancer; Cardiovascular risks; Obesity; Diabetes; Mood disorders;
   Sleep deprivation; Rhythm desynchronization; Chronodisruption; Circadian
   misalignment; Melatonin; Marker rhythms; Light at night; Shift work;
   Night work; Atypical work hours
ID BREAST-CANCER RISK; AIRLINE CABIN ATTENDANTS; DEPRESSIVE-LIKE RESPONSES;
   FEMALE FLIGHT ATTENDANTS; WHITE ADIPOSE-TISSUE; SHIFT WORK DISORDER;
   INCREASES BODY-MASS; DIM LIGHT; GLUCOSE-TOLERANCE; OXIDATIVE STRESS
AB Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50-100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption. Shift and/or night work generally decreases the time spent sleeping, and it disrupts the circadian time structure. In the long run, this desynchronization is detrimental to health, as underscored by a large number of epidemiological studies that have uncovered elevated rates of several diseases, including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. It amounts to a public health issue in the light of the very substantial number of individuals involved. The IARC has classified shift work in group 2A of "probable carcinogens to humans" since "they involve a circadian disorganization". Countermeasures to the effects of ALAN, such as melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work. We review the evidence for the ALAN impacts on health. Furthermore, we highlight the importance of an in-depth mechanistic understanding to combat the detrimental properties of exposure to ALAN and develop strategies of prevention. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Touitou, Yvan; Reinberg, Alain] Fdn Ophtalmol A de Rothschild, Unite Chronobiol, 25 Rue Manin, F-75019 Paris, France.
   [Touitou, David] UHSA Grp Hosp Paul Guiraud, 54 Ave Republ, F-94806 Villejuif, France.
RP Touitou, Y (通讯作者)，Fdn Ophtalmol A de Rothschild, Unite Chronobiol, 25 Rue Manin, F-75019 Paris, France.
EM yvan.touitou@chronobiology.fr
OI Touitou, Yvan/0000-0002-5990-0244
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   [No title captured]
NR 198
TC 254
Z9 273
U1 29
U2 305
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 2017
VL 173
BP 94
EP 106
DI 10.1016/j.lfs.2017.02.008
PG 13
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA EP9NS
UT WOS:000397700900013
PM 28214594
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Gong, Y
   Shao, Z
   Fu, ZJ
   Edin, ML
   Sun, Y
   Liegl, RG
   Wang, ZX
   Liu, CH
   Burnim, SB
   Meng, SS
   Lih, FB
   SanGiovanni, JP
   Zeldin, DC
   Hellstrom, A
   Smith, LEH
AF Gong, Yan
   Shao, Zhuo
   Fu, Zhongjie
   Edin, Matthew L.
   Sun, Ye
   Liegl, Raffael G.
   Wang, Zhongxiao
   Liu, Chi-Hsiu
   Burnim, Samuel B.
   Meng, Steven S.
   Lih, Fred B.
   SanGiovanni, John Paul
   Zeldin, Darryl C.
   Hellstrom, Ann
   Smith, Lois E. H.
TI Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress
   Pathological Ocular Angiogenesis
SO EBIOMEDICINE
LA English
DT Article
DE Fenofibrate; Choroidal neovascularization; Retinopathy; Retinal
   neovascularization; Cytochrome P450 epoxygenase 2C; Omega-3 long-chain
   polyunsaturated fatty acids
ID POLYUNSATURATED FATTY-ACIDS; OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL
   GROWTH-FACTOR; PPAR-ALPHA; CHOROIDAL NEOVASCULARIZATION;
   DIABETIC-RETINOPATHY; MOUSE; METABOLITES; MODEL; EXPRESSION
AB Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)alpha agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP) 2C with higher affinity than to PPAR alpha. CYP2C metabolizes omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). While omega-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both omega-3 and omega-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C omega-3 LCPUFA (and omega-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPAR alpha-/-mice and augmented omega-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic.-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPAR alpha. Fenofibrate augmented the overall protective effects of omega-3 LCPUFAs on neovascular eye diseases. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://reativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Gong, Yan; Shao, Zhuo; Fu, Zhongjie; Sun, Ye; Liegl, Raffael G.; Wang, Zhongxiao; Liu, Chi-Hsiu; Burnim, Samuel B.; Meng, Steven S.; Smith, Lois E. H.] Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 01248 USA.
   [Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
   [SanGiovanni, John Paul] NIAAA, Sect Nutrit Neurosci, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA.
   [Hellstrom, Ann] Univ Gothenburg, Sahlgrenska Acad, Dept Ophthalmol, S-40530 Gothenburg, Sweden.
C3 Harvard University; Boston Children's Hospital; Harvard Medical School;
   National Institutes of Health (NIH) - USA; NIH National Institute of
   Environmental Health Sciences (NIEHS); National Institutes of Health
   (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism
   (NIAAA); University of Gothenburg
RP Smith, LEH (通讯作者)，300 Longwood Ave, Boston, MA 02115 USA.
EM lois.smith@childrens.harvard.edu
RI SanGiovanni, John Paul/AAU-3895-2020; Edin, Matthew/AAI-1934-2019;
   Zeldin, Darryl C/Y-7091-2018
OI Zeldin, Darryl C/0000-0002-2087-7307; FU, ZHONGJIE/0000-0002-8182-2983;
   Gong, Yan/0000-0002-4805-0459; Sun, Ye/0000-0002-7674-9056; Edin,
   Matthew/0000-0002-7042-500X
FU NEI NIH HHS [R01 EY017017, R24 EY024864] Funding Source: Medline; NICHD
   NIH HHS [U54 HD090255] Funding Source: Medline; EUNICE KENNEDY SHRIVER
   NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD090255]
   Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE [R24EY024864,
   R01EY017017] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   ENVIRONMENTAL HEALTH SCIENCES [ZIAES025034] Funding Source: NIH RePORTER
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DI 10.1016/j.ebiom.2016.09.025
PG 11
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA EG0EU
UT WOS:000390704800035
PM 27720395
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Meunier, I
   Lenaers, G
   Bocquet, B
   Baudoin, C
   Piro-Megy, C
   Cubizolle, A
   Quiles, M
   Jean-Charles, A
   Cohen, SY
   Merle, H
   Gaudric, A
   Labesse, G
   Manes, G
   Pequignot, M
   Cazevieille, C
   Dhaenens, CM
   Fichard, A
   Ronkina, N
   Arthur, SJ
   Gaestel, M
   Hamel, CP
AF Meunier, Isabelle
   Lenaers, Guy
   Bocquet, Beatrice
   Baudoin, Corinne
   Piro-Megy, Camille
   Cubizolle, Aurelie
   Quiles, Melanie
   Jean-Charles, Albert
   Cohen, Salomon Yves
   Merle, Harold
   Gaudric, Alain
   Labesse, Gilles
   Manes, Gael
   Pequignot, Marie
   Cazevieille, Chantal
   Dhaenens, Claire-Marie
   Fichard, Agnses
   Ronkina, Natalia
   Arthur, Simon J.
   Gaestel, Matthias
   Hamel, Christian P.
TI A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway,
   causes a new retinal dystrophy involving Bruch's membrane and retinal
   pigment epithelium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; MAP KINASE; DEPENDENT PATHWAYS; RPE CELLS;
   EXPRESSION; 3PK; COMPLEX; LIGAND; ERK
AB Inherited retinal dystrophies are clinically and genetically heterogeneous with significant number of cases remaining genetically unresolved. We studied a large family from the West Indies islands with a peculiar retinal disease, the Martinique crinkled retinal pigment epitheliopathy that begins around the age of 30 with retinal pigment epithelium (RPE) and Bruch's membrane changes resembling a dry desert land and ends with a retinitis pigmentosa. Whole-exome sequencing identified a heterozygous c.518T>C (p.Leu173Pro) mutation in MAPKAPK3 that segregates with the disease in 14 affected and 28 unaffected siblings from three generations. This unknown variant is predicted to be damaging by bioinformatic predictive tools and the mutated protein to be non-functional by crystal structure analysis. MAPKAPK3 is a serine/threonine protein kinase of the p38 signaling pathway that is activated by a variety of stress stimuli and is implicated in cellular responses and gene regulation. In contrast to other tissues, MAPKAPK3 is highly expressed in the RPE, suggesting a crucial role for retinal physiology. Expression of the mutated allele in HEK cells revealed a mislocalization of the protein in the cytoplasm, leading to cytoskeleton alteration and cytodieresis inhibition. In Mapkapk3-/- mice, Bruch's membrane is irregular with both abnormal thickened and thinned portions. In conclusion, we identified the first pathogenic mutation in MAPKAPK3 associated with a retinal disease. These findings shed new lights on Bruch's membrane/RPE pathophysiology and will open studies of this signaling pathway in diseases with RPE and Bruch's membrane alterations, such as age-related macular degeneration.
C1 [Meunier, Isabelle; Lenaers, Guy; Bocquet, Beatrice; Baudoin, Corinne; Piro-Megy, Camille; Cubizolle, Aurelie; Quiles, Melanie; Pequignot, Marie; Cazevieille, Chantal; Fichard, Agnses; Hamel, Christian P.] Univ Montpellier, Montpellier Hosp, Inst Neurosci Montpellier, Natl Ctr Genet Sensory Dis,INSERM,U1051, F-34059 Montpellier, France.
   [Lenaers, Guy] Univ Angers, Mitochondrial Med Res Ctr, CNRS 6214, INSERM,U1083, Angers, France.
   [Jean-Charles, Albert; Merle, Harold] Univ Hosp Ft France, Dept Ophthalmol, Fort De France, Martinique, France.
   [Cohen, Salomon Yves] Intercity Hosp, Dept Ophthalmol, Imaging & Laser Ctr Paris, Creteil, France.
   [Cohen, Salomon Yves] Univ Paris, Creteil, France.
   [Gaudric, Alain] Lariboisiere Hosp, AP HP, Dept Ophthalmol, Paris, France.
   [Labesse, Gilles] Ctr Struct Biochem Montpellier, CNRS UMR5048, INSERM, U1054, Montpellier, France.
   [Cazevieille, Chantal] CRIC IURC, Inst Neurosci, Montpellier, France.
   [Dhaenens, Claire-Marie] Univ Lille North, CHRU Lille, Biochem & Mol Biol Dept, Lille, France.
   [Ronkina, Natalia; Gaestel, Matthias] Hannover Med Sch, Inst Biochem, Hannover, Germany.
   [Arthur, Simon J.] MRC Prot Phosphorylat Unit, Dundee, Scotland.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite de Montpellier; CHU de Montpellier; Centre National de la
   Recherche Scientifique (CNRS); Institut National de la Sante et de la
   Recherche Medicale (Inserm); Universite d'Angers; CHU Martinique;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   UDICE-French Research Universities; Universite Paris Cite; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire
   Lariboisiere-Fernand-Widal - APHP; UDICE-French Research Universities;
   Universite Paris Cite; Centre National de la Recherche Scientifique
   (CNRS); CNRS - National Institute for Biology (INSB); Institut National
   de la Sante et de la Recherche Medicale (Inserm); Universite de
   Montpellier; Universite de Montpellier; Universite de Lille - ISITE; CHU
   Lille; Universite de Lille; Hannover Medical School; University of
   Dundee
RP Meunier, I (通讯作者)，Gui de Chauliac Hosp, Dept Ophthalmol, Natl Ctr Genet Sensory Dis, 80 Ave Augustin Fliche, F-34295 Montpellier, France.
EM isabelannemeunier@yahoo.fr
RI Lenaers, guy/X-4727-2019; Pequignot, Marie O/P-1994-2017; Gaestel,
   Matthias/A-6560-2013; Bocquet, Beatrice/AAY-8447-2020; lenaers,
   guy/K-2421-2015
OI Gaestel, Matthias/0000-0002-4944-4652; Bocquet,
   Beatrice/0000-0002-6369-4818; Pequignot, Marie/0000-0002-8866-3778;
   Labesse, Gilles/0000-0002-6861-3300; Gaudric, Alain/0000-0002-2486-4722;
   Arthur, Simon/0000-0002-8135-1958; lenaers, guy/0000-0003-2736-3349
FU INSERM; CNRS;  [ANR-10-BINF-03-03]
FX This work was also supported by INSERM, CNRS and ANR-10-BINF-03-03 (to
   G.L.).
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NR 33
TC 9
Z9 9
U1 0
U2 6
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 MAR 1
PY 2016
VL 25
IS 5
BP 916
EP 926
DI 10.1093/hmg/ddv624
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DG5XA
UT WOS:000372152400007
PM 26744326
OA Bronze
DA 2022-11-30
ER

PT J
AU Cao, J
   Murat, C
   An, WJ
   Yao, X
   Lee, J
   Santulli-Marotto, S
   Harris, IR
   Inana, G
AF Cao, Jing
   Murat, Christopher
   An, Weijun
   Yao, Xiang
   Lee, John
   Santulli-Marotto, Sandra
   Harris, Ian R.
   Inana, George
TI Human Umbilical Tissue-Derived Cells Rescue Retinal Pigment Epithelium
   Dysfunction in Retinal Degeneration
SO STEM CELLS
LA English
DT Article
DE Retinal degeneration; Cell therapy; Retinal pigment epithelium;
   Phagocytosis; Receptor tyrosine kinase; Bridge molecules
ID OUTER SEGMENT PHAGOCYTOSIS; ENDOTHELIAL GROWTH-FACTOR; FOCAL ADHESION
   KINASE; EMBRYONIC STEM-CELLS; MACULAR DEGENERATION; OXIDATIVE STRESS;
   APOPTOTIC CELLS; GEOGRAPHIC ATROPHY; MERTK GENE; RCS RAT
AB Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNAtargeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases.
C1 [Cao, Jing; Lee, John; Santulli-Marotto, Sandra; Harris, Ian R.] Janssen Res & Dev LLC, Spring House, PA 19477 USA.
   [Murat, Christopher; An, Weijun; Inana, George] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Yao, Xiang] Janssen Res & Dev LLC, San Diego, CA USA.
C3 Johnson & Johnson; Johnson & Johnson USA; Janssen Biotech Inc; Bascom
   Palmer Eye Institute; University of Miami; Johnson & Johnson; Johnson &
   Johnson USA; Janssen Biotech Inc
RP Cao, J (通讯作者)，Janssen Res & Dev LLC, Cell Therapy, Spring House, PA 19477 USA.; Inana, G (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM jcao5@its.jnj.com; ginana@med.miami.edu
FU University of Miami; Janssen RD
FX We thank Carol Anne Ogden (formerly Janssen R&D, Spring House, PA),
   Jarrat Jordan, Randall Brezski, Michael Naso, and Vasilis Pikounis
   (Janssen R&D, Spring House, PA) for providing advisory suggestions, and
   Nadine Dejneka (Janssen R&D, Spring House, PA) for assistance with RNA
   extraction. This work was performed under a sponsored research agreement
   between University of Miami and Janssen R&D.
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NR 91
TC 24
Z9 25
U1 0
U2 7
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 FEB
PY 2016
VL 34
IS 2
BP 367
EP 379
DI 10.1002/stem.2239
PG 13
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 DE0ZA
UT WOS:000370353200011
PM 26523756
OA hybrid
DA 2022-11-30
ER

PT J
AU Narimatsu, T
   Negishi, K
   Miyake, S
   Hirasawa, M
   Osada, H
   Kurihara, T
   Tsubota, K
   Ozawa, Y
AF Narimatsu, Toshio
   Negishi, Kazuno
   Miyake, Seiji
   Hirasawa, Manabu
   Osada, Hideto
   Kurihara, Toshihide
   Tsubota, Kazuo
   Ozawa, Yoko
TI Blue light-induced inflammatory marker expression in the retinal pigment
   epithelium-choroid of mice and the protective effect of a yellow
   intraocular lens material in vivo
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; Reactive
   oxygen species; Blue light; Inflammatory cytokine; Macrophage
ID MACULAR DEGENERATION; GROWTH-FACTOR; NEOVASCULARIZATION; INTERLEUKIN-6;
   PATHOGENESIS; ACTIVATION; STRESS; DAMAGE
AB Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted pathogenic change in vision-threatening diseases such as age-related macular degeneration. One source of oxidative stress is excessive light exposure, which causes excessive activation of the visual cycle. Because short wavelength light (blue light) has more energy, it is reported to be more harmful to photoreceptor cells than the other wavelengths of light. However, the biological effect of blue light in the RPE of living animals and the protective effect of a yellow intraocular lens (IOW material that blocks blue light is still obscure. Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice exposed to light in a box made of a clear or a yellow IOL material. We measured the level of reactive oxygen species (ROS) using 2', 7'-dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines and a macrophage marker by real-time polymerase chain reaction, and the protein level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after light exposure was suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. In parallel, all the inflammatory cytokines that we measured and a macrophage marker were also suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL material suppressed, and thus blue light exacerbated, the increase in the ROS level and inflammatory cytokine expression as well as macrophage recruitment in the RPE-choroid in vivo after light exposure. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Narimatsu, Toshio; Miyake, Seiji; Hirasawa, Manabu; Osada, Hideto; Kurihara, Toshihide; Ozawa, Yoko] Keio Univ, Sch Med, Lab Retinal Cell Biol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Narimatsu, Toshio; Negishi, Kazuno; Hirasawa, Manabu; Kurihara, Toshihide; Tsubota, Kazuo; Ozawa, Yoko] Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan.
C3 Keio University; Keio University
RP Ozawa, Y (通讯作者)，Keio Univ, Sch Med, Dept Ophthalmol,Lab Retinal Cell Biol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ozawa@a5.keio.jp
RI Negishi, Kazuno/AAG-3260-2021; Ozawa, Yoko/AAH-9888-2020; Kurihara,
   Toshihide/ABA-7058-2020
OI Negishi, Kazuno/0000-0002-2892-9810; Kurihara,
   Toshihide/0000-0002-5457-2720; Osada, Hideto/0000-0001-9971-8992
FU JSPS KAKENHI [24592647]; Alcon Research LTD.
FX This work was supported by a Grant-in-Aid for Scientific Research, JSPS
   KAKENHI to Y.O. (24592647) and a financial support by Alcon Research
   LTD.
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NR 25
TC 50
Z9 51
U1 0
U2 13
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2015
VL 132
BP 48
EP 51
DI 10.1016/j.exer.2015.01.003
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CD6HJ
UT WOS:000351189900005
PM 25576667
OA hybrid
DA 2022-11-30
ER

PT J
AU Sur, A
   Kesaraju, S
   Prentice, H
   Ayyanathan, K
   Baronas-Lowell, D
   Zhu, DH
   Hinton, DR
   Blanks, J
   Weissbach, H
AF Sur, Arunodoy
   Kesaraju, Shailaja
   Prentice, Howard
   Ayyanathan, Kasirajan
   Baronas-Lowell, Diane
   Zhu, Danhong
   Hinton, David R.
   Blanks, Janet
   Weissbach, Herbert
TI Pharmacological protection of retinal pigmented epithelial cells by
   sulindac involves PPAR-alpha
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE preconditioning; oxidative stress; sulindac; retinal pigmented
   epithelial cells; age-related macular degeneration
ID OXIDATIVE STRESS; INDUCED APOPTOSIS; DOCOSAHEXAENOIC ACID; GAMMA
   LIGANDS; TRANSCRIPTION; PROTEINS; EPSILON; GROWTH; BRAIN; DEATH
AB The retinal pigmented epithelial (RPE) layer is one of the major ocular tissues affected by oxidative stress and is known to play an important role in the etiology of age-related macular degeneration (AMD), the major cause of blinding in the elderly. In the present study, sulindac, a nonsteroidal antiinflammatory drug (NSAID), was tested for protection against oxidative stress-induced damage in an established RPE cell line (ARPE-19). Besides its established antiinflammatory activity, sulindac has previously been shown to protect cardiac tissue against ischemia/reperfusion damage, although the exact mechanism was not elucidated. As shown here, sulindac can also protect RPE cells from chemical oxidative damage or UV light by initiating a protective mechanism similar to what is observed in ischemic preconditioning (IPC) response. The mechanism of protection appears to be triggered by reactive oxygen species (ROS) and involves known IPC signaling components such as PKG and PKC epsilon in addition to the mitochondrial ATP-sensitive K+ channel. Sulindac induced iNOS and Hsp70, late-phase IPC markers in the RPE cells. A unique feature of the sulindac protective response is that it involves activation of the peroxisome proliferator-activated receptor alpha (PPAR-alpha). We have also used low-passage human fetal RPE and polarized primary fetal RPE cells to validate the basic observation that sulindac can protect retinal cells against oxidative stress. These findings indicate a mechanism for preventing oxidative stress in RPE cells and suggest that sulindac could be used therapeutically for slowing the progression of AMD.
C1 [Sur, Arunodoy; Prentice, Howard; Blanks, Janet] Florida Atlantic Univ, Grad Program Integrat Biol, Dept Biol Sci, Charles E Schmidt Coll Sci, Boca Raton, FL 33431 USA.
   [Kesaraju, Shailaja; Prentice, Howard; Ayyanathan, Kasirajan; Baronas-Lowell, Diane; Blanks, Janet; Weissbach, Herbert] Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, Jupiter, FL 33458 USA.
   [Prentice, Howard; Blanks, Janet] Florida Atlantic Univ, Charles E Schmidt Coll Sci, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA.
   [Prentice, Howard] Florida Atlantic Univ, Coll Med, Dept Biomed Sci, Boca Raton, FL 33431 USA.
   [Zhu, Danhong; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Pathol & Ophthalmol, Los Angeles, CA 90089 USA.
C3 State University System of Florida; Florida Atlantic University; State
   University System of Florida; Florida Atlantic University; State
   University System of Florida; Florida Atlantic University; State
   University System of Florida; Florida Atlantic University; University of
   Southern California
RP Weissbach, H (通讯作者)，Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, Jupiter, FL 33458 USA.
EM hweissba@fau.edu
FU Neuroscience Research Priority Grant from Florida Atlantic University;
   National Eye Institute [EYO1545]; Florida Atlantic University
   Foundation; NATIONAL EYE INSTITUTE [R01EY001545] Funding Source: NIH
   RePORTER
FX The authors thank Dr. Miguel Lopez-Toledano for his help in studies on
   the role of cell passage on the effect of TBHP and sulindac. The study
   was supported by a Seed grant from the Neuroscience Research Priority
   Grant from Florida Atlantic University (to J.B., H.P., and H.W.) and
   National Eye Institute Grant EYO1545 (to D.R.H.). The Florida Atlantic
   University Foundation also contributed to the research.
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NR 45
TC 19
Z9 22
U1 1
U2 6
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 NOV 25
PY 2014
VL 111
IS 47
BP 16754
EP 16759
DI 10.1073/pnas.1419576111
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AU5QX
UT WOS:000345662700036
PM 25385631
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Zhang, H
   Liu, YY
   Jiang, Q
   Li, KR
   Zhao, YX
   Cao, C
   Yao, J
AF Zhang, Hui
   Liu, Yuan-yuan
   Jiang, Qin
   Li, Ke-ran
   Zhao, Yu-xia
   Cao, Cong
   Yao, Jin
TI Salvianolic acid A protects RPE cells against oxidative stress through
   activation of Nrf2/HO-1 signaling
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Salvianolic acid A; Nrf2; HO-1; Akt/mTOR; Oxidative stress; Age-related
   macular degeneration; Free radicals
ID PIGMENT EPITHELIAL-CELLS; MITOCHONDRIAL-DNA DAMAGE; HEME OXYGENASE-1
   EXPRESSION; MACULAR DEGENERATION; HYDROGEN-PEROXIDE; ANTIOXIDANT
   RESPONSE; MOLECULAR-MECHANISMS; VISUAL IMPAIRMENT; REACTIVE OXYGEN;
   KINASE
AB Reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelial (RPE) cells, which is known as one major cause of age-related macular degeneration. Salvianolic acid A (Sal A) is the main effective aqueous extract of Salvia miltiorrhiza. The aim of this study was to test the potential role of Sal A against oxidative stress in cultured RPE cells and to investigate the underlying mechanistic signaling pathways. We observed that Sal A significantly inhibited hydrogen peroxide (H2O2)-induced primary and transformed RPE cell death and apoptosis. H2O2-stimulated mitogen-activated protein kinase activation, ROS production, and subsequent proapoptotic AMP-activated protein kinase activation were largely inhibited by Sal A. Further, Sal A stimulation resulted in a fast and dramatic activation of Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling, followed by phosphorylation, accumulation, and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with increased expression of the antioxidant-response element-dependent gene heme oxygenase-1 (HO-1). Both Nrf2 and HO-1 were required for Sal A-mediated cytoprotective effect, as Nrf2/HO-1 inhibition abolished Sal A-induced beneficial effects against H2O2. Meanwhile, the PI3K/Akt/mTORC1 chemical inhibitors not only suppressed Sal A-induced Nrf2/HO-1 activation, but also eliminated its cytoprotective effect in RPE cells. These observations suggest that Sal A activates the Nrf2/H0-1 axis in RPE cells and protects against oxidative stress via activation of Akt/mTORC1 signaling. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Zhang, Hui; Jiang, Qin; Li, Ke-ran; Zhao, Yu-xia; Cao, Cong; Yao, Jin] Nanjing Med Univ, Hosp Eye, Nanjing 210029, Jiangsu, Peoples R China.
   [Liu, Yuan-yuan; Cao, Cong] Soochow Univ, Inst Neurosci, Suzhou 215123, Peoples R China.
C3 Nanjing Medical University; Soochow University - China
RP Yao, J (通讯作者)，Nanjing Med Univ, Hosp Eye, Nanjing 210029, Jiangsu, Peoples R China.
RI liu, yuanyuan/GWZ-5838-2022
FU National Natural Science Foundation of China [81070744, 81271028,
   31371139, 81302195, 81371055]; Jiangsu Province [BK20130301];
   post-doctoral fund of Jiangsu Province [1002009B]; Medical Science and
   Technology Development Project Fund of Nanjing [ZKX12047, YKK12208,
   YKK12207]
FX This work was generously supported by grants from the National Natural
   Science Foundation of China (81070744; 81271028, 31371139, 81302195 and
   81371055) and Jiangsu Province (BK20130301), the post-doctoral fund of
   Jiangsu Province (1002009B), and the Medical Science and Technology
   Development Project Fund of Nanjing (ZKX12047, YKK12208, YKK12207). 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 57
TC 199
Z9 214
U1 2
U2 70
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 219
EP 228
DI 10.1016/j.freeradbiomed.2014.01.025
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AD8BC
UT WOS:000333490500023
PM 24486344
DA 2022-11-30
ER

PT J
AU Gaffney, AJ
   Binns, AM
   Margrain, TH
AF Gaffney, Allannah J.
   Binns, Alison M.
   Margrain, Tom H.
TI Measurement of cone dark adaptation: a comparison of four psychophysical
   methods
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Cone dark adaptation; Repeatability; Psychophysics
ID AGE-RELATED MACULOPATHY; SORSBYS FUNDUS DYSTROPHY; VITAMIN-A-DEFICIENCY;
   MACULAR DEGENERATION; PIGMENT REGENERATION; RETINITIS-PIGMENTOSA; VISUAL
   FUNCTION; FELLOW EYE; ROD; ADAPTOMETER
AB Dark adaptometry is an important clinical tool for the diagnosis of a range of conditions, including age-related macular degeneration. In order to identify the most robust, clinically applicable technique for the measurement of cone dark adaptation, the repeatability and agreement of four psychophysical methods were assessed.
   Data were obtained from 31 healthy adults on two occasions, using four psychophysical methods. Participants' pupils were dilated, and 96 % of cone photopigment was bleached before threshold was monitored in the dark using one of the techniques, selected at random. This procedure was repeated for each of the remaining methods. An exponential recovery function was fitted to all threshold recovery data. The coefficient of repeatability (CoR) was calculated to assess the repeatability of the methods, and a repeated-measures analysis of variance was used to compare mean recovery parameters.
   All four methods demonstrated a similar level of intersession repeatability for measurement of cone recovery, yielding CoRs between 1.18 and 1.56 min. There were no statistically significant differences in estimates of mean time constant of cone recovery (cone tau) between the four methods (p = 0.488); however, significant differences between initial and final cone thresholds were reported (p < 0.005).
   All of the techniques were capable of monitoring the rapid changes in visual threshold that occur during cone dark adaptation, and the repeatability of the techniques was similar. This indicates that despite the respective advantages and disadvantages of these psychophysical techniques, all four methods would be suitable for measuring cone dark adaptation in clinical practice.
C1 [Gaffney, Allannah J.; Binns, Alison M.; Margrain, Tom H.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4LU, S Glam, Wales.
C3 Cardiff University
RP Gaffney, AJ (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Maindy Rd, Cardiff CF24 4LU, S Glam, Wales.
EM gaffneyaj1@cf.ac.uk; MargrainTH@cardiff.ac.uk
OI Margrain, Tom/0000-0003-1280-0809; Binns, Alison/0000-0001-8621-498X
FU College of Optometrists, UK
FX This study was funded by a research grant from the College of
   Optometrists, UK. The authors would like to thank Laura Smith for her
   help with data collection.
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NR 44
TC 5
Z9 5
U1 1
U2 14
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 FEB
PY 2014
VL 128
IS 1
BP 33
EP 41
DI 10.1007/s10633-013-9418-6
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 288XC
UT WOS:000329644400004
PM 24263533
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Cano, M
   Fijalkowski, N
   Kondo, N
   Dike, S
   Handa, J
AF Cano, Marisol
   Fijalkowski, Natalia
   Kondo, Naoshi
   Dike, Sonny
   Handa, James
TI Advanced Glycation Endproduct Changes to Bruch's Membrane Promotes
   Lipoprotein Retention by Lipoprotein Lipase
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM;
   MACULAR DEGENERATION; BASAL DEPOSITS; EXTRACELLULAR-MATRIX;
   LIPID-ACCUMULATION; HEPARAN-SULFATE; CHOLESTEROL; BINDING
AB Lipoprotein particles accumulate in Bruch's membrane before the development of basal deposits and drusen, two histopathologic lesions that define age-related macular degeneration (AMD). We therefore, sought to determine which molecules could participate in lipoprotein retention. Wild-type or lipoprotein lipase-deficient mice were injected with low-dose D-galactose or PBS subcutaneously for 8 weeks to induce advanced glycation endproduct (AGE) formation. Some mice were also injected with the AGE breaker phenacylphiazolium bromide and D-galactose. Rhodamine-labeled low-density lipoproteins were injected into mice, and the fluorescence was measured up to 72 hours later. AGEs, proteoglycans, and other lipid-retaining molecules were evaluated by IHC. Lipoprotein lipase distribution was assessed in AMD samples by IHC. D-galactose-treated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/D-galactose-treated mice at 24 and 72 hours after injection (P <= 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in D-galactose-treated mice only. Mice deficient for lipoprotein lipase treated with D-galactose did not retain lipoproteins to any measureable extent. Human AMD samples had lipoprotein lipase labeling within drusen, basal deposits, and the choroid. Mice treated with D-galactose to induce AGE formation in Bruch's membrane retain intravenously injected lipoproteins. Our results suggest that lipoprotein retention in Bruch's membrane is mediated by lipoprotein lipase. (Am J Pathol 2011, 179:850-859; DOI: 10.1016/j.ajpath.2011.04.010)
C1 [Cano, Marisol; Fijalkowski, Natalia; Kondo, Naoshi; Dike, Sonny; Handa, James] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, J (通讯作者)，Smith Bldg Rm 3015,400 N Broadway, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
OI Kondo, Naoshi/0000-0001-6025-3876; Callaway, Natalia/0000-0002-9788-9605
FU Robert Bond Welch Professorship; Research to Prevent Blindness (Wilmer
   Eye Institute);  [EY14005]; NATIONAL EYE INSTITUTE [R01EY014005,
   R01EY019904] Funding Source: NIH RePORTER
FX Supported by grant EY14005 (J.T.H.), Robert Bond Welch Professorship
   (J.T.H.), an unrestricted grant from Research to Prevent Blindness
   (Wilmer Eye Institute), and generous gifts from Ric and Sandy Forsythe
   and the Merlau family.
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NR 56
TC 20
Z9 20
U1 0
U2 16
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 2011
VL 179
IS 2
BP 850
EP 859
DI 10.1016/j.ajpath.2011.04.010
PG 10
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 865JM
UT WOS:000298307200031
PM 21801873
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Sheu, SJ
   Bee, YS
   Ma, YL
   Liu, GS
   Lin, HC
   Yeh, TL
   Liou, JC
   Tai, MH
AF Sheu, Shwu-Jiuan
   Bee, Youn-Shen
   Ma, Yi-Ling
   Liu, Guei-Sheung
   Lin, Hsiu-Chen
   Yeh, Tse-Liang
   Liou, Jau-Chen
   Tai, Ming-Hong
TI Inhibition of choroidal neovascularization by topical application of
   angiogenesis inhibitor vasostatin
SO MOLECULAR VISION
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB AVASTIN; MACULAR DEGENERATION; DRUG-DELIVERY;
   TUMOR-GROWTH; RANIBIZUMAB; SUPPRESSION; FRAGMENT; THERAPY; CALRETICULIN;
   ANTIBODY
AB Purpose: Choroidal neovascularization (CNV) is the leading cause of blindness in patients with age-related macular degeneration (AMD). This study evaluated the inhibitory effect of vasostatin (VS), an endogenous angiogenesis inhibitor, on CNV.
   Methods: Anti-angiogenic activity of VS was evaluated in vitro by migration and tube formation assays in human umbilical vein endothelial cells (HUVECs). CNV lesions were induced in Brown Norway rats by fundus argon laser photocoagulation. Beginning one day after CNV induction, rats were treated with eye drops containing 1 mu g/ml VS in PBS buffer for three times daily for 20 days. The extent of CNV was examined by flat mount analysis on day 24 or by fundus fluorescein angiography (FAG) on days 21, 28, 35, and 42, respectively. CNV lesions and choroidal vascularity were evaluated by histological analysis. The spatial distribution of topically applied VS in rat eyes was evaluated by immunoblot analysis.
   Results: VS inhibited migration and tube formation in HUVECs. Flat mount analysis revealed that, after laser-induced photocoagulation, topical VS application for 20 days significantly reduced CNV lesions. Moreover, serial FAG analysis indicated that a 20 day VS treatment significantly reduced CNV lesions on all subsequent days. Histological analysis revealed attenuated lesions, intact Bruch's membrane, and reduced choroidal vascularity in VS-treated eyes. Finally immunoblot analysis reveled VS expression in choroids.
   Conclusions: Topical VS application suppresses the progression of laser-induced CNV via angiogenesis inhibition and may constitute a therapeutic alternative for excessive neovascularization occurring with ocular diseases.
C1 [Tai, Ming-Hong] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan.
   [Sheu, Shwu-Jiuan; Bee, Youn-Shen; Lin, Hsiu-Chen] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Sheu, Shwu-Jiuan] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
   [Bee, Youn-Shen; Ma, Yi-Ling; Liou, Jau-Chen; Tai, Ming-Hong] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan.
   [Liu, Guei-Sheung; Tai, Ming-Hong] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan.
   [Yeh, Tse-Liang] Natl Cent Univ, Dept Mech Engn, Chungli 32054, Taiwan.
C3 National Sun Yat Sen University; Kaohsiung Veterans General Hospital;
   National Yang Ming Chiao Tung University; National Sun Yat Sen
   University; Kaohsiung Veterans General Hospital; National Central
   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 Liu, Guei-Sheung/Q-6472-2018
OI Liu, Guei-Sheung/0000-0003-3379-724X
FU National Science Council, Taiwan [NSC 95-2314-B-075B-005,
   94-2622B-075B-001-CC3]; VTY Joint Research [VGHUST 93-G3-03-3,
   93-P3-14]; Kaohsiung Veterans General Hospital [VGHKS 94-056, 94-099];
   National Sun Yat-Sen University-Kaohsiung Medical University Joint
   Research Center.
FX This work was supported by grants from the National Science Council,
   Taiwan (NSC 95-2314-B-075B-005 and 94-2622B-075B-001-CC3), VTY Joint
   Research Program (VGHUST 93-G3-03-3 and 93-P3-14), Kaohsiung Veterans
   General Hospital (VGHKS 94-056 and 94-099), and the National Sun Yat-Sen
   University-Kaohsiung Medical University Joint Research Center.
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NR 28
TC 10
Z9 10
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD SEP 18
PY 2009
VL 15
IS 202
BP 1897
EP 1905
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 517MI
UT WOS:000271618100001
PM 19768130
DA 2022-11-30
ER

PT J
AU Carcenac, G
   Herard, ME
   Kergoat, MJ
   Lajeunesse, Y
   Champoux, N
   Barsauskas, A
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AF Carcenac, Guillaume
   Herard, Marie-Eve
   Kergoat, Marie-Jeanne
   Lajeunesse, Yvette
   Champoux, Nathalie
   Barsauskas, Allan
   Kergoat, Helene
TI Assessment of Visual Function in Institutionalized Elderly Patients
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Dementia; frail elderly; long-term care units; visual examination
ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; ROUTINE OPTOMETRIC CARE;
   ALZHEIMERS-DISEASE; CATARACT-SURGERY; IMPAIRMENT; PREVALENCE; GLAUCOMA;
   POPULATION; COMMUNITY
AB Objective: To describe the visual function and ocular health of frail elderly patients institutionalized in a tertiary care university-affiliated geriatric hospital.
   Design: Retrospective file review.
   Setting: A university-affiliated geriatric hospital.
   Participants: 440 patient files.
   Measurements: The archived clinical files of patients from the long-term care beds of the Institut universitaire de geriatrie de Montreal, who had died between April 2000 and 2004 were reviewed. Pertinent medical and visual characteristics were extracted and entered into a database for analysis.
   Results: The age of the patients ranged from 65 to 104 years. The major ocular conditions observed were cataract, pseudophakia, conjunctivitis-blepharitis, age-related macular degeneration, and glaucoma. Of the 231 patients referred for a partial or full eye examination, visual acuity was available in 178. Visual impairment was considered absent in 87 patients; mild in 52; moderate in 17; and 22 patients were legally blind. Of the 105 patients referred for a full eye examination, an evaluation of the refraction, visual acuity, and ocular health was possible in 89, irrespective of their cognitive status.
   Conclusion: These data demonstrate that the vast majority of severely disabled elderly patients examined retained good visual acuity into advanced age. The most prevalent ocular conditions observed are treatable, thereby emphasizing the importance of regular eye care for the institutionalized frail elderly. The results clearly demonstrate that it is possible to perform a complete evaluation of visual function and ocular health in the elderly institutionalized patient, independent of age, cognitive status, or communication disorders. (J Am Med Dir Assoc 2009; 10: 45-49)
C1 [Carcenac, Guillaume; Herard, Marie-Eve; Kergoat, Helene] Univ Montreal, Ecole Optometrie, Montreal, PQ H3C 3J7, Canada.
   [Kergoat, Marie-Jeanne; Lajeunesse, Yvette; Champoux, Nathalie; Barsauskas, Allan] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada.
   [Carcenac, Guillaume; Kergoat, Marie-Jeanne; Lajeunesse, Yvette; Champoux, Nathalie; Barsauskas, Allan; Kergoat, Helene] Inst Univ Geriatrie Montreal, Montreal, PQ, Canada.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal
RP Kergoat, H (通讯作者)，Univ Montreal, Ecole Optometrie, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM helene.kergoat@umontreal.ca
FU Institut Universitaire de Geriatrie de Montreal-Comite Aviseur pour la
   Recherche Clinique; Fondation Caroline-Durand; Canadian Optometric
   Education Trust Fund; Institute of Aging of the Canadian Institutes of
   Health Research
FX This work was supported by grants from the Institut Universitaire de
   Geriatrie de Montreal-Comite Aviseur pour la Recherche Clinique, the
   Fondation Caroline-Durand, and the Canadian Optometric Education Trust
   Fund. H.K. is the recipient of a Clinician/Scientist award from the
   Institute of Aging of the Canadian Institutes of Health Research.
CR Bayer AU, 2002, EUR NEUROL, V47, P165, DOI 10.1159/000047976
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NR 29
TC 16
Z9 16
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
EI 1538-9375
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD JAN
PY 2009
VL 10
IS 1
BP 45
EP 49
DI 10.1016/j.jamda.2008.07.005
PG 5
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 399IZ
UT WOS:000262794900007
PM 19111852
DA 2022-11-30
ER

PT J
AU Bub, A
   Moeseneder, J
   Wenzel, G
   Rechkemmer, G
   Briviba, K
AF Bub, Achim
   Moeseneder, Jutta
   Wenzel, Gerhard
   Rechkemmer, Gerhard
   Briviba, Karlis
TI Zeaxanthin is bioavailable from genetically modified zeaxanthin-rich
   potatoes
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE zeaxanthin; bioavailability; age-related macular degeneration; potato
ID BETA-CAROTENE; INTESTINAL-ABSORPTION; MACULAR PIGMENT; RISK-FACTORS;
   LUTEIN; MEAL; MEN
AB The carotenoid zeaxanthin accumulates in the human macula lutea and protects retinal cells from blue light damage. However, zeaxanthin intake from food sources is low. Increasing zeaxanthin in common foods such as potatoes by traditional plant breeding or by genetic engineering could contribute to an increased intake of this carotenoid and, consequently, to a decreased risk of age-related macular degeneration. Our aim was to investigate whether zeaxanthin from genetically modified zeaxanthin-rich potatoes is bioavailable in humans. Three men participated in this randomized, controlled double-blinded, crossover pilot study. All subjects consumed 1,100 g of mashed potatoes, either genetically modified (Solanum tuberosum L. var. Baltica GM47/18; 3 mg zeaxanthin) or wild-type control potatoes (Solanum tuberosum L. var. Baltica; 0.14 mg zeaxanthin). A second treatment was followed after a 7-day wash-out period. The concentration of zeaxanthin was significantly increased in chylomicrons after consumption of genetically modified potatoes and 0.27 mg of the 3 mg zeaxanthin dose could be detected in chylomicrons. Consumption of control potatoes had no effect on concentrations of zeaxanthin in chylomicrons. After normalization of chylomicron zeaxanthin for plasma triacylglycerol, the time course of zeaxanthin concentrations peaked at 7 h after consumption of genetically modified potatoes. There were no significant differences in the concentrations of other major potato carotenoids such as lutein and beta-carotene in chylomicrons after consumption of genetically modified and wild type control potatoes. Thus, consumption of zeaxanthin-rich potatoes significantly increases chylomicron zeaxanthin concentrations suggesting that potentially such potatoes could be used as an important dietary source of zeaxanthin.
C1 [Bub, Achim; Moeseneder, Jutta; Rechkemmer, Gerhard] Fed Res Ctr Nutr & Food, Inst Nutr Physiol, D-76131 Karlsruhe, Germany.
   [Wenzel, Gerhard] Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, D-8050 Freising Weihenstephan, Germany.
C3 Technical University of Munich
RP Bub, A (通讯作者)，Fed Res Ctr Nutr & Food, Inst Nutr Physiol, Haid & Neu Str 9, D-76131 Karlsruhe, Germany.
EM achim.bub@bfel.de
OI Briviba, Karlis/0000-0003-3338-7515
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NR 26
TC 13
Z9 14
U1 0
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
EI 1436-6215
J9 EUR J NUTR
JI Eur. J. Nutr.
PD MAR
PY 2008
VL 47
IS 2
BP 99
EP 103
DI 10.1007/s00394-008-0702-2
PG 5
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 278BR
UT WOS:000254259000006
PM 18320254
DA 2022-11-30
ER

PT J
AU Takeda, M
   Takamiya, A
   Jiao, JW
   Cho, KS
   Trevino, SG
   Matsuda, T
   Chen, DF
AF Takeda, Masumi
   Takamiya, Akira
   Jiao, Jian-Wei
   Cho, Kin-Sang
   Trevino, Simon G.
   Matsuda, Takahiko
   Chen, Dong F.
TI alpha-aminoadipate induces progenitor cell properties of Muller glia in
   adult mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINALDEHYDE-BINDING PROTEIN; STEM-CELLS; NEURAL REGENERATION;
   NEUROGENESIS; PROLIFERATION; RETINA; INJURY; NEURONS; ACTIVATION;
   DEFICIENT
AB PURPOSE. Retinal Muller glia in higher vertebrates have been reported to possess progenitor cell properties and the ability to generate new neurons after injury. This study was conducted to determine the signals that can activate this dormant capacity of Muller glia in adult mice, by studying their behavior during glutamate stimulation.
   METHODS. Various concentrations of glutamate and its analogue alpha-aminoadipate, which specifically binds Muller glia, were injected subretinally in adult mice. Proliferating retinal cells were labeled by subretinal injection of 5'-bromo-2'-deoxyuridine (BrdU) followed by immunohistochemistry. Muller cell fates were analyzed in retinal sections by using double immunolabeling with primary antibodies against Muller and other retina-specific cell markers. The effects of glutamate and alpha-aminoadipate were also determined in purified Muller cell cultures.
   RESULTS. Although high levels of glutamate induce retinal damage, subtoxic levels of glutamate directly stimulate Muller glia to re-enter the cell cycle and induce neurogenesis in vivo and in purified Muller cell cultures. alpha-Aminoadipate, which selectively target glial cells, also induced expression of progenitor cell markers by Muller cells in vitro or stimulated Muller cell migration to the outer nuclear layer (ONL) and to differentiate into photoreceptors in vivo.
   CONCLUSIONS. Mature Muller glia in adult mice can be induced to dedifferentiate, migrate, and generate new retinal neurons and photoreceptor cells by alpha-aminoadipate or glutamate signaling. The results of this study suggest a novel potential strategy for treating retinal neurodegeneration, including retinitis pigmentosa and age-related macular degeneration, without transplanting exogenous cells.
C1 [Takeda, Masumi; Takamiya, Akira; Jiao, Jian-Wei; Cho, Kin-Sang; Trevino, Simon G.; Chen, Dong F.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Takeda, Masumi; Takamiya, Akira; Jiao, Jian-Wei; Cho, Kin-Sang; Chen, Dong F.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   [Takeda, Masumi; Takamiya, Akira] Asahikawa Med Coll, Dept Ophthalmol, Asahikawa, Hokkaido 078, Japan.
   [Matsuda, Takahiko] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Schepens Eye Research
   Institute; Harvard University; Harvard Medical School; Asahikawa Medical
   College; Harvard University; Harvard Medical School; Howard Hughes
   Medical Institute
RP Chen, DF (通讯作者)，Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM dongfeng.chen@schepens.harvard.edu
RI Jiao, Jianwei/AAA-7902-2020; Jiao, Jianwei/I-1452-2013
OI Jiao, Jianwei/0000-0002-7893-0721; Jiao, Jianwei/0000-0002-7893-0721;
   Cho, Kin-Sang/0000-0003-4285-615X
FU NEI NIH HHS [R01 EY017641, R01 EY017641-01A2, P30 EY003790] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [R01EY017641, P30EY003790]
   Funding Source: NIH RePORTER
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NR 37
TC 114
Z9 121
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 MAR
PY 2008
VL 49
IS 3
BP 1142
EP 1150
DI 10.1167/iovs.07-0434
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 271TZ
UT WOS:000253812900044
PM 18326742
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nicaud, V
   Francomme, C
   Ruidavets, JB
   Luc, G
   Arveiler, D
   Kee, F
   Evans, A
   Morrison, C
   Blankenberg, S
   Carnbien, F
   Tiret, L
AF Nicaud, Viviane
   Francomme, Carole
   Ruidavets, Jean-Bernard
   Luc, Grald
   Arveiler, Dominique
   Kee, Frank
   Evans, Alun
   Morrison, Caroline
   Blankenberg, Stefan
   Carnbien, Francois
   Tiret, Laurence
TI Lack of association between complement factor H polymorphisms and
   coronary artery disease or myocardial infarction
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE CFH; myocardial infarction; polymorphism; CRP; follow-up
ID HY402H GENE POLYMORPHISM; MACULAR DEGENERATION; RISK; ECTIM;
   SUSCEPTIBILITY; HAPLOTYPE
AB Complement factor H (CFH) plays a critical role in the protection of host cells and tissues from damage by complement activation and has been suggested to protect against the progression of atherosclerosis. A polymorphism in the CFH gene, Y402H, known to be strongly associated with age-related macular degeneration, has been analyzed in relation to coronary artery disease (CAD) in several studies with conflicting results. We investigated the association of polymorphisms of the CFH gene in two large-scale studies on CAD and myocardial infarction (MI). The AtheroGene Study included a cohort of cases with CAD (n=1,303) prospectively followed for a median period of 6.2 years, among whom198 experienced a cardiovascular event, and a group of 483 control subjects. The AtheroGene Study population was genotyped for the Y402H, 162V, and E936D polymorphisms. There was no significant difference in genotypic or allelic frequencies between CAD cases and controls. Among cases, no significant association was found with prospective cardiovascular outcome. Many inflammatory proteins, including the C-reactive protein, were measured, and none of the polymorphisms showed an association with these markers. The Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study compared 1,034 patients with MI and 1,039 controls from France and United Kingdom. The ECTIM Study population was genotyped for the Y402H polymorphism. Genotype and allele frequencies were similar in cases and controls. These results do not support an involvement of common nonsynonymous polymorphisms of the CFH gene in predisposition to CAD and its complications.
C1 Univ Paris 06, INSERM, UMR S525, F-75013 Paris, France.
   Univ Paris 06, UMR S 525, F-75634 Paris, France.
   Fac Med Toulouse, INSERM, U518, MONICA Toulouse, F-31073 Toulouse, France.
   Inst Pasteur, Serv Epidemiol & Sante Publ, F-59019 Lille, France.
   Fac Med Strasbourg, Lab Epidemiol & Sante Publ, EA 1801, MONICA Strasbourg, F-67085 Strasbourg, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; UDICE-French
   Research Universities; Sorbonne Universite; Institut National de la
   Sante et de la Recherche Medicale (Inserm); Le Reseau International des
   Instituts Pasteur (RIIP); Universite de Lille - ISITE; Institut Pasteur
   Lille; Universite de Lille; UDICE-French Research Universities;
   Universites de Strasbourg Etablissements Associes; Universite de
   Strasbourg
RP Tiret, L (通讯作者)，Univ Paris 06, INSERM, UMR S525, 91 Blvd Hop, F-75013 Paris, France.
EM laurence.tiret@chupsjussieu.fr
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NR 15
TC 16
Z9 22
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED-JMM
JI J. Mol. Med.
PD JUL
PY 2007
VL 85
IS 7
BP 771
EP 775
DI 10.1007/s00109-007-0185-2
PG 5
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA 190TX
UT WOS:000248084600012
PM 17396242
DA 2022-11-30
ER

PT J
AU Wang, Z
   Paik, DC
   Dillon, JP
   Gaillard, ER
AF Wang, Zhen
   Paik, David C.
   Dillon, James P.
   Gaillard, Elizabeth R.
TI Tyrosine nitration site specificity identified by LC/MS in
   nitrite-modified collagen type IV
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE 3-nitrotyrosine; Bruch membrane; collagen type IV; inflammation;
   nitrites
ID FACTOR-H POLYMORPHISM; MASS-SPECTROMETRY; MACULAR DEGENERATION;
   EXTRACELLULAR-MATRIX; PROTEIN NITRATION; HYPOCHLOROUS ACID; MAILLARD
   REACTION; REACTIVE OXYGEN; CROSS-LINKING; IN-VITRO
AB Non-enzymatic nitrite induced collagen cross-linking results in changes reminiscent of age-related damage and parallels the well-known model system, non-enzymatic glycation. We have recently observed that nitrite modification of basement membrane proteins can induce deleterious effects on overlying retinal pigment epithelial cells in studies relevant to age-related macular degeneration. The present work was undertaken in order to confirm 3-nitro-tyrosine (3-NT) as a product of the reaction and to identify the site specificity of nitration in collagen IV, a major component of basement membranes. Human collagen type IV was modified via incubation with 200 mM NaNO2 (pH = 7.38) for one week at 37 degrees C. The modified protein was prepared in 2 different ways, including acid hydrolysis and trypsin digestion for site specificity determination. The samples were analyzed by LC/MS using a C-12 RP column. Site specificity was determined from tandem MS/MS data utilizing TurboSEQUEST software and the Swiss-Prot sequence database. 3-NT was detected in protein digests and acid hydrolysates of nitrite modified collagen IV. Positive identification with standard 3-NT was confirmed by identical R-t, lambda(max) = 279 nm and 355 nm, and m/z = 227. Analyses of tryptic digests identified four sites of tyrosine nitration, alpha 1(IV)Y348, alpha 1(IV)Y534, alpha 2(IV)Y327, and alpha 2(IV)Y1081. These sites are located in the triple-helical region of the protein and provide clues regarding potential sites for nitrite modification in collagen type IV.
C1 No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA.
   Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
C3 Northern Illinois University; Columbia University; Columbia University
RP Gaillard, ER (通讯作者)，No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
EM gaillard@niu.edu
RI Gaillard, Elizabeth/M-2627-2019
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NR 53
TC 8
Z9 9
U1 0
U2 4
PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
PI SEOUL
PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1226-3613
J9 EXP MOL MED
JI Exp. Mol. Med.
PD FEB 28
PY 2007
VL 39
IS 1
BP 74
EP 83
DI 10.1038/emm.2007.9
PG 10
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 144JX
UT WOS:000244793400009
PM 17334231
OA gold
DA 2022-11-30
ER

PT J
AU Maberley, DAL
   Hollands, H
   Chuo, J
   Tam, G
   Konkal, J
   Roesch, M
   Veselinovic, A
   Witzigmann, M
   Bassett, K
AF Maberley, DAL
   Hollands, H
   Chuo, J
   Tam, G
   Konkal, J
   Roesch, M
   Veselinovic, A
   Witzigmann, M
   Bassett, K
TI The prevalence of low vision and blindness in Canada
SO EYE
LA English
DT Article
DE prevalence; blindness; visual disability; low vision; Canada; visual
   impairment
ID COPENHAGEN CITY EYE; VISUAL IMPAIRMENT; POPULATION; INFORMATION;
   INVENTORY; ACUITY
AB Purpose The purpose of this study was to ascertain the prevalence and primary causes of visual impairment in a representative Canadian population.
   Methods We reviewed a representative sample of patients who attended ophthalmologists' offices in a medium-sized Canadian city between 1996 and 2001 in order to estimate the prevalence of visual impairment. Demographic data, visual diagnoses, best-corrected visual acuities (BCVA), and visual field information were recorded. Visual status was categorized based on accepted World Health Organization ( WHO) and North American criteria. Population data were obtained from the Canadian census.
   Results The prevalence of low vision and blindness in our population was 35.6 and 3.8 per 10 000 individuals, according to the WHO classification, and 71.2 and 23.6 per 10 000 individuals, using the North American definition. Among individuals with some vision loss ( vision worse than 20/40), cataract and visual pathway disease were the most common causes, together accounting for 40% of visual impairment. Age-related macular degeneration and other retinal diseases were the next most common causes of vision loss. Diabetic retinopathy and glaucoma were less frequently encountered as causes of visual impairment.
   Conclusion The overall prevalence of low vision and blindness in Canada are in keeping with data from large population-based studies from other developed nations. Cataract, visual pathway disease, and macular degeneration are the leading causes of visual impairment. These results are important for enhancing our understanding of the scope of vision health in Canada and may direct future health planning and cost-utilization research.
C1 Univ British Columbia, Fac Med, Vancouver, BC, Canada.
   Univ British Columbia, Dept Ophthalmol, Vancouver, BC, Canada.
   Univ No British Columbia, Dept Ophthalmol, Vancouver, BC, Canada.
   Univ No British Columbia, Fac Med, Vancouver, BC, Canada.
   Univ British Columbia, Fac Family Med, Vancouver, BC V5Z 1M9, Canada.
   Univ No British Columbia, Fac Family Med, Vancouver, BC V5Z 1M9, Canada.
C3 University of British Columbia; University of British Columbia;
   University of Northern British Columbia; University of Northern British
   Columbia; University of British Columbia; University of Northern British
   Columbia
RP Maberley, DAL (通讯作者)，2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM dmaberle@vanhosp.bc.ca
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   *CAN NAT I BLIND, 2001 CLIENT DAT
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NR 10
TC 108
Z9 111
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD MAR
PY 2006
VL 20
IS 3
BP 341
EP 346
DI 10.1038/sj.eye.6701879
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 017YU
UT WOS:000235730200013
PM 15905873
OA Bronze
DA 2022-11-30
ER

PT J
AU Ritter, MR
   Aguilar, E
   Banin, E
   Scheppke, L
   Uusitalo-Jarvinen, H
   Friedlander, M
AF Ritter, MR
   Aguilar, E
   Banin, E
   Scheppke, L
   Uusitalo-Jarvinen, H
   Friedlander, M
TI Three-dimensional in vivo imaging of the mouse intraocular vasculature
   during development and disease
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL VEIN; PASSAGE; CELLS
AB PURPOSE. Aberrant growth of blood vessels in the eye is a major cause of vision loss, occurring as a complication of diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions, among others. Whereas in humans, in vivo angiography is routinely used to image such diseases, many animal models of ocular vascular disease and development rely on dissected tissues that may not accurately represent in vivo conditions and require enucleation of the eye, the death of the animal, or both.
   METHODS. A method of three-dimensional imaging of blood vessels was used in the living mouse eye that involved scanning laser confocal microscopy and computer-aided image reconstruction.
   RESULTS. This minimally invasive technique was used to collect three-dimensional images of intraocular vessels in vivo during development. The retinal and choroidal vasculature was studied during development and disease, in models of retinal degeneration, central retinal vein occlusion, and oxygen-induced retinopathy. To aid in investigations into cell-based therapies for retinal disease, two-color imaging was used to localize transplanted cells in relation to the vasculature. This technique was used to perform serial imaging of the ocular vasculature over time, when developmental regression of vessels was observed.
   CONCLUSIONS. This in vivo vascular imaging approach is valuable in monitoring normal development, disease progression, and efficacy of experimental treatments in mouse models of ocular vascular disease and may have broader applications to the field of angiogenesis by using the readily visualized ocular vascular bed as a surrogate to test pro- and antiangiogenic compounds.
C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Friedlander, M (通讯作者)，Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines Rd MB28, La Jolla, CA 92037 USA.
EM friedlan@scripps.edu
FU NEI NIH HHS [R01 EY 11254, F32 EY 13916] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY011254, F32EY013916] Funding Source: NIH
   RePORTER
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NR 21
TC 31
Z9 32
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 SEP
PY 2005
VL 46
IS 9
BP 3021
EP 3026
DI 10.1167/iovs.05-0153
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 959AH
UT WOS:000231488800002
PM 16123396
DA 2022-11-30
ER

PT J
AU Maeda, A
   Crabb, JW
   Palczewski, K
AF Maeda, A
   Crabb, JW
   Palczewski, K
TI Microsomal glutathione S-transferase 1 in the retinal pigment
   epithelium: Protection against oxidative stress and a potential role in
   aging
SO BIOCHEMISTRY
LA English
DT Article
ID GLUTATHIONE-S-TRANSFERASE; MEMBRANE-ASSOCIATED PROTEINS; 6 ANGSTROM
   RESOLUTION; MACULAR DEGENERATION; LIGHT DAMAGE; DROSOPHILA-MELANOGASTER;
   LIPID-PEROXIDATION; RNA INTERFERENCE; AQUEOUS-HUMOR; ASCORBIC-ACID
AB High oxygen tension, exposure to light, and the biochemical events of vision generate significant oxidative stress in the retina and the retinal pigment epithelium (RPE). Understanding the mechanisms and basis of susceptibility to progressive retinal diseases involving oxidative damage such as age-related macular degeneration (AMD) remains a major challenge. Here microsomal glutathione S-transferase (MGST1) is shown to be a dominant, highly expressed enzyme in bovine and mouse RPE microsomes that displays significant reduction activity toward synthetic peroxides, oxidized RPE lipids, and oxidized retinoids. This enzymatic reduction activity (GPx) can be partially neutralized with a monoclonal anti-MGST1 antibody developed in this study. MGST1-transfected HEK293 cells exhibited greater viability (70 +/- 4% survival) compared with untransfected control cells (46 +/- 4% survival) when challenged with 20 muM H2O2, and greater viability of MGST1-transfected cells following challenge with oxidized docosahexaenoic acid was also observed. Cultured ARPE19 cells transfected with silencing MGST1 siRNAs exhibited lower expression of MGST1 (12% and 26% of the controls) and significantly lower GPx activity (44 +/- 13%) and, thus, were more susceptible to oxidative damage. Immunoblotting revealed that the in vivo expression of MGST1 in mouse RPE decreases 3-4-fold with age, to trace levels in 18-month-old mice. GPx activity in the RPE was also found to be reduced in 12-month-old mice to similar to67%. These results support an important protective function for MGST1 against oxidative insult in the RPE that decreases with age and suggest that this enzyme may play a role in the development of age-related diseases such as AMD.
C1 Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
C3 University of Washington; University of Washington Seattle; University
   of Washington; University of Washington Seattle; University of
   Washington; University of Washington Seattle; Cleveland Clinic
   Foundation
RP Palczewski, K (通讯作者)，Univ Washington, Dept Ophthalmol, Box 356485, Seattle, WA 98195 USA.
EM palczews@u.washington.edu
FU NATIONAL EYE INSTITUTE [R01EY013385, R01EY009339, R01EY014239] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY14239, EY06603, R01 EY014239,
   EY09339, F32 EY006603, R01 EY009339, R01 EY013385, R01 EY006603,
   EY13385] Funding Source: Medline
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NR 59
TC 64
Z9 65
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JAN 18
PY 2005
VL 44
IS 2
BP 480
EP 489
DI 10.1021/bi048016f
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 888BA
UT WOS:000226348000005
PM 15641772
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Grisanti, S
   Tatar, O
   Canbek, S
   Lafaut, BA
   Gelisken, F
   Inhoffen, W
   Szurman, P
   Aisenbrey, S
   Oficjalska-Mlynczak, J
   Bartz-Schmidt, KU
AF Grisanti, S
   Tatar, O
   Canbek, S
   Lafaut, BA
   Gelisken, F
   Inhoffen, W
   Szurman, P
   Aisenbrey, S
   Oficjalska-Mlynczak, J
   Bartz-Schmidt, KU
TI Immunohistopathologic evaluation of choroidal neovascular membranes
   following verteporfin-photodynamic therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; ENDOTHELIAL-CELLS; SYSTEM
AB PURPOSE: To evaluate the vascularization and proliferative activity in choroidal neovascular membranes due to age-related macular degeneration after verteporfin photodynamic therapy and submacular removal.
   DESIGN: Interventional case series.
   METHODS: In a retrospective review of seven patients who underwent removal of subfoveal classic choroidal neovascular membranes after treatment with photodynamic therapy 3 to 146 days earlier, membranes were stained for CD 34, CD 105, and Ki-67 and correlated with clinical pictures and fluorescein angiography.
   RESULTS: Fluorescein angiography performed on the day of surgery disclosed nonperfusion of the treated area 3 days after photodynamic therapy, but perfusion and leakage were seen at greater post-photodynamic therapy intervals. Membranes excised 3 days after photodynamic therapy showed CD34 and CD105 positive, mostly occluded vessels. The endothelial cells appeared damaged. Ki-67 activity was low. In membranes excised 34 to 146 days after photodynamic therapy, all vessels appeared patent and were lined by healthy endothelial cells with strong expression of CD34 and CD105. Ki-67 expression was elevated after 34 days but decreased thereafter.
   CONCLUSION: Photodynamic therapy did not cause a general or complete occlusion of vessels within the choroidal neovascular membranes, as suggested by fluorescein angiography 3 days postintervention, but the endothelial cells appeared to be severely damaged. Proliferative activity within these specimens was reduced. At longer intervals after photodynamic therapy, the fibrovascular tissue seemed to recover; perfusion, hyperfluorescence, and leakage of the choroidal neovascular membranes could be detected by fluorescein angiography. The clinical appearance showed a correlation with the immunohistologic characteristics of an increased proliferative activity and patent vascularization.
C1 Univ Tubingen, Dept Ophthalmol 1, Div Vitreoretinal Surg, D-72076 Tubingen, Germany.
   Acad Hosp St Jan, Dept Ophthalmol, Brugge, Belgium.
   Univ Wroclaw, Dept Ophthalmol, PL-50138 Wroclaw, Poland.
   Tufts Univ, Dept Neurosci, Boston, MA 02111 USA.
C3 Eberhard Karls University of Tubingen; University of Wroclaw; Tufts
   University
RP Grisanti, S (通讯作者)，Univ Tubingen, Dept Ophthalmol 1, Div Vitreoretinal Surg, Schleichstr 12-15, D-72076 Tubingen, Germany.
EM salvatore.grisanti@med.uni-tuebingen.de
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NR 19
TC 20
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAY
PY 2004
VL 137
IS 5
BP 914
EP 923
DI 10.1016/j.ajo.2003.12.049
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 820KA
UT WOS:000221386400017
PM 15126158
DA 2022-11-30
ER

PT J
AU Kapoor, N
   Jasper, S
   Kalra, S
AF Kapoor, Nitin
   Jasper, Smitha
   Kalra, Sanjay
TI Ocular manifestations of Obesity: Beyond what meets the eye
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Article
DE Obesity; age-related maculopathy; body composition; premature cataract;
   glaucoma pseudotumor cerebri; retinopathy
ID BODY-MASS INDEX
AB Obesity has reached pandemic proportions across the globe. Though much literature is available on the metabolic complications of obesity, their ocular associations are underreported. Visual impairment further contributes to the poor health related quality of life in individuals living with obesity. In this manuscript, the authors have highlighted the key ocular manifestations that have been associated with obesity, the evidence that supports their association and the impact of weight loss on these co-morbidities. Obesity has often been negatively associated with visual acuity. Premature cataract, glaucoma and age-related maculopathy have also been shown to have a strong association with obesity. Furthermore, presence of associated cardiometabolic disorders linked with metabolic syndrome may also have an indirect impact on the eye. Conditions like diabetic and hypertensive retinopathy, have commonly been described in people living with obesity. Given the huge public health impact of obesity, this manuscript highlights the unmet need of comprehensive research on the association of eye disorders and obesity in the South Asian region.
C1 [Kapoor, Nitin] Christian Med Coll & Hosp, Dept Endocrinol Diabet & Metab, Vellore, Tamil Nadu, India.
   [Kapoor, Nitin] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Nossal Inst Global Hlth, Non Communicable Dis Unit, Melbourne, Vic, Australia.
   [Jasper, Smitha] Christian Med Coll & Hosp, Dept Ophthalmol, Vellore, Tamil Nadu, India.
   [Kalra, Sanjay] Bharti Hosp, Dept Endocrinol, Karnal, India.
C3 Christian Medical College & Hospital (CMCH) Vellore; University of
   Melbourne; Christian Medical College & Hospital (CMCH) Vellore
RP Kalra, S (通讯作者)，Bharti Hosp, Dept Endocrinol, Karnal, India.
EM brideknl@gmail.com
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NR 12
TC 0
Z9 0
U1 1
U2 1
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 2022
VL 72
IS 3
BP 574
EP 575
DI 10.47391/JPMA.22-020
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA ZG8PN
UT WOS:000760515000009
PM 35320250
DA 2022-11-30
ER

PT J
AU Chen, ZC
   Wang, BY
   Goldstein, AK
   Butt, E
   Mathieson, K
   Palanker, D
AF Chen, Zhijie Charles
   Wang, Bing-Yi
   Goldstein, Anna Kochnev
   Butt, Emma
   Mathieson, Keith
   Palanker, Daniel
TI Photovoltaic implant simulator reveals resolution limits in subretinal
   prosthesis
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; neural stimulation; current steering; 3D electrode;
   resolution; modeling; circuit simulation
ID RETINAL BIPOLAR CELLS; MODEL; EYE
AB Objective. PRIMA, the photovoltaic subretinal prosthesis, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100 mu m pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation strength in the inner nuclear layer (INL) or may lead to excessive crosstalk between neighboring electrodes, resulting in low contrast stimulation patterns. We study the approaches to electric field shaping in the retina for prosthetic vision with higher resolution and improved contrast. Approach. We present a new computational framework, Retinal Prosthesis Simulator (RPSim), that efficiently computes the electric field in the retina generated by a photovoltaic implant with thousands of electrodes. Leveraging the PRIMA clinical results as a benchmark, we use RPSim to predict the stimulus strength and contrast of the electric field in the retina with various pixel designs and stimulation patterns. Main results. We demonstrate that by utilizing monopolar pixels as both anodes and cathodes to suppress crosstalk, most patients may achieve resolution no worse than 48 mu m. Closer proximity between the electrodes and the INL, achieved with pillar electrodes, enhances the stimulus strength and contrast and may enable 24 mu m resolution with 20 mu m pixels, at least in some patients. Significance. A resolution of 24 mu m on the retina corresponds to a visual acuity of 20/100, which is over 4 times higher than the current best prosthetic acuity of 20/438, promising a significant improvement of central vision for many AMD patients.
C1 [Chen, Zhijie Charles; Goldstein, Anna Kochnev] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Wang, Bing-Yi] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Butt, Emma; Mathieson, Keith] Univ Strathclyde, Inst Photon, Dept Phys, Glasgow, Lanark, Scotland.
   [Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; University of Strathclyde;
   Stanford University; Stanford University
RP Chen, ZC (通讯作者)，Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
EM zcchen@stanford.edu
RI ; Mathieson, Keith/G-6308-2011
OI Kochnev Goldstein, Anna/0000-0003-4674-688X; Wang,
   Bing-Yi/0000-0001-8336-3285; Butt, Emma/0000-0003-1622-3818; Chen,
   Zhijie/0000-0003-2705-065X; Mathieson, Keith/0000-0002-9517-8076;
   Palanker, Daniel/0000-0002-0480-3025
FU National Institutes of Health [R01-EY-027786, P30-EY-026877]; Department
   of Defense [W81XWH-19-10738]; AFOSR [FA9550-19-1-0402]; Research to
   Prevent Blindness; Royal Academy of Engineering Chair in Emerging
   Technology, UK; Rhona Reid Charitable Trust; Wu Tsai Institute of
   Neurosciences at Stanford
FX The authors would like to thank Pixium Vision for providing the PRIMA
   implants used in this study. Studies were supported by the National
   Institutes of Health (Grants R01-EY-027786 and P30-EY-026877), the
   Department of Defense (Grant W81XWH-19-10738), AFOSR (Grant
   FA9550-19-1-0402), Wu Tsai Institute of Neurosciences at Stanford, and
   unrestricted grant from Research to Prevent Blindness. K M was supported
   by a Royal Academy of Engineering Chair in Emerging Technology, UK. E B
   was partially supported by the Rhona Reid Charitable Trust.
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NR 32
TC 0
Z9 0
U1 0
U2 0
PU IOP Publishing Ltd
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD OCT 1
PY 2022
VL 19
IS 5
AR 055008
DI 10.1088/1741-2552/ac8ed8
PG 14
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA 4W5YQ
UT WOS:000860238100001
PM 36055219
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Rodrigues, E
   Conci, A
   Liatsis, P
AF Rodrigues, Erick
   Conci, Aura
   Liatsis, Panos
TI ELEMENT: Multi-Modal Retinal Vessel Segmentation Based on a Coupled
   Region Growing and Machine Learning Approach
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Feature extraction; Image segmentation; Machine learning; Retinal
   vessels; Task analysis; Predictive models; Machine learning; pixel-based
   classi-fication; pixel connectivity; retinal vessel segmentation; region
   growing
ID BLOOD-VESSELS; MATCHED-FILTER; IMAGES; ALGORITHM; MODEL; DELINEATION;
   NETWORK
AB Vascular structures in the retina contain important information for the detection and analysis of ocular diseases, including age-related macular degeneration, diabetic retinopathy and glaucoma. Commonly used modalities in diagnosis of these diseases are fundus photography, scanning laser ophthalmoscope (SLO) and fluorescein angiography (FA). Typically, retinal vessel segmentation is carried out either manually or interactively, which makes it time consuming and prone to human errors. In this research, we propose a new multi-modal framework for vessel segmentation called ELEMENT (vEsseL sEgmentation using Machine lEarning and coNnecTivity). This framework consists of feature extraction and pixel-based classification using region growing and machine learning. The proposed features capture complementary evidence based on grey level and vessel connectivity properties. The latter information is seamlessly propagated through the pixels at the classification phase. ELEMENT reduces inconsistencies and speeds up the segmentation throughput. We analyze and compare the performance of the proposed approach against state-of-the-art vessel segmentation algorithms in three major groups of experiments, for each of the ocular modalities. Our method produced higher overall performance, with an overall accuracy of 97.40%, compared to 25 of the 26 state-of-the-art approaches, including six works based on deep learning, evaluated on the widely known DRIVE fundus image dataset. In the case of the STARE, CHASE-DB, VAMPIRE FA, IOSTAR SLO and RC-SLO datasets, the proposed framework outperformed all of the state-of-the-art methods with accuracies of 98.27%, 97.78%, 98.34%, 98.04% and 98.35%, respectively.
C1 [Rodrigues, Erick] Univ Tecnol Fed Parana UTFPR, Acad Dept Informat, BR-80230901 Pato Branco, Brazil.
   [Conci, Aura] Univ Fed Fluminense UFF, Dept Comp Sci, BR-24220900 Niteroi, RJ, Brazil.
   [Liatsis, Panos] Khalifa Univ, Dept Elect Engn & Comp Sci, Abu Dhabi 127788, U Arab Emirates.
C3 Universidade Tecnologica Federal do Parana; Universidade Federal
   Fluminense; Khalifa University of Science & Technology
RP Rodrigues, E (通讯作者)，Univ Tecnol Fed Parana UTFPR, Acad Dept Informat, BR-80230901 Pato Branco, Brazil.
EM erickr@id.uff.br; aconci@ic.uff.br; panos.liatsis@ku.ac.ae
RI Rodrigues, Érick Oliveira/AAE-5189-2022; Conci, Aura/ABA-8609-2021
OI Rodrigues, Érick Oliveira/0000-0001-9124-3603; 
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NR 80
TC 15
Z9 17
U1 4
U2 23
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
EI 2168-2208
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD DEC
PY 2020
VL 24
IS 12
BP 3507
EP 3519
DI 10.1109/JBHI.2020.2999257
PG 13
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Mathematical & Computational Biology;
   Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematical & Computational Biology; Medical
   Informatics
GA PC7JM
UT WOS:000597173000017
PM 32750920
DA 2022-11-30
ER

PT J
AU Reiter, GS
   Told, R
   Schranz, M
   Baumann, L
   Mylonas, G
   Sacu, S
   Pollreisz, A
   Schmidt-Erfurth, U
AF Reiter, Gregor S.
   Told, Reinhard
   Schranz, Markus
   Baumann, Lukas
   Mylonas, Georgios
   Sacu, Stefan
   Pollreisz, Andreas
   Schmidt-Erfurth, Ursula
TI Subretinal Drusenoid Deposits and Photoreceptor Loss Detecting Global
   and Local Progression of Geographic Atrophy by SD-OCT Imaging
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; photoreceptor integrity; reticular
   pseudo-drusen; retinal pigment epithelium; subretinal drusenoid deposits
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; RETICULAR PSEUDODRUSEN; END-POINTS; AGE; DISEASE;
   AREA; EYES
AB PURPOSE. To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression.
   METHODS. Eighty-three eyes of 49 patients, aged 50 years and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions.
   RESULTS. The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P < 0.001). SDD were associated with faster growth in the overall model (P = 0.039), as well as in the superior-temporal (P = 0.005) and temporal (P = 0.002) sections. Faster progression was associated with GA baseline area (P < 0.001). No difference was found between unifocal and multifocal lesions (P > 0.05). Age did not have an effect on GA progression (P > 0.05).
   CONCLUSIONS. Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium Occurs.
C1 [Reiter, Gregor S.; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, Vienna, Austria.
   [Reiter, Gregor S.; Told, Reinhard; Schranz, Markus; Mylonas, Georgios; Sacu, Stefan; Pollreisz, Andreas; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna Clin Trial Ctr VTC, Vienna, Austria.
   [Baumann, Lukas] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna
RP Pollreisz, A (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM andreas.pollreisz@meduniwien.ac.at
RI Pollreisz, Andreas/AAJ-1538-2021
OI Reiter, Gregor/0000-0001-7661-4015
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NR 43
TC 14
Z9 14
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 JUN
PY 2020
VL 61
IS 6
AR 11
DI 10.1167/iovs.61.6.11
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MD7MJ
UT WOS:000544154500009
PM 32503052
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Storm, T
   Wilson, I
   Campbell, R
   Bolinches-Amoros, A
   Russell, AJ
   Davies, SG
   Barnard, AR
   MacLaren, RE
AF Storm, Tina
   Wilson, Iain
   Campbell, Ross
   Bolinches-Amoros, Arantxa
   Russell, Angela J.
   Davies, Stephen G.
   Barnard, Alun R.
   MacLaren, Robert E.
TI A Semiautomated, Phenotypic, In Vitro Scratch Assay for Assessing
   Retinal Pigment Epithelial Cell Wound Healing
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE retinal pigment epithelium; age-related macular degeneration; geographic
   atrophy; wound healing assay
ID TO-MESENCHYMAL TRANSITION; HUMAN RPE CELLS; MACULAR DEGENERATION;
   REGENERATION; EXPRESSION; DIFFERENTIATION; INHIBITOR; ARPE-19; LINE
AB Purpose: Age-related macular degeneration leads to retinal pigment epithelium (RPE) cell death and loss of central vision. In vivo studies have shown that the RPE layer has an innate, but limited, ability to repopulate atrophic areas. We aimed to establish a semiautomated, in vitro, wound healing assay workflow for targeted screening of compounds able to influence RPE wound healing.
   Methods: The ARPE-19 phenotype was evaluated using bright-field microscopy, immunocytochemistry, and quantitative real-time polymerase chain reaction. ARPE-19 monolayers were simultaneously scratched in a 96-well format and treated with Hoechst-33342 and an array of compounds. Initial wound dimensions and wound healing were subsequently evaluated using the EVOS FL Auto 2.0 imaging platform combined with automated image analyses.
   Results: Long-term cultured ARPE-19 cells displayed a more in vivo RPE-like phenotype compared with recently seeded or short-term cultured cells. No statistical difference of initial scratch width was observed between short-term and long-term cultured cells, but more wells were excluded from analyses in total in the latter case due to scratch width, scratch smoothness, and imaging errors. Furthermore, the previous time spent in continuous culture had an effect on the observation of an altered wound healing response to different treatment conditions.
   Conclusions: We have established a semiautomated, 96-well format, in vitro wound healing assay with a reproducible workflow. This would enable screening of a significant number of compounds and greatly advances the potential of identifying novel therapeutics that may enhance the innate ability of RPE cells to repopulate atrophic areas.
C1 [Storm, Tina; Wilson, Iain; Campbell, Ross; Bolinches-Amoros, Arantxa; Barnard, Alun R.; MacLaren, Robert E.] John Radcliffe Hosp, Nuffield Lab Ophthalmol, Dept Clin Neurosci, Level 5 & 6,West Wing,Headley Way, Oxford OX3 9DU, England.
   [Barnard, Alun R.; MacLaren, Robert E.] Oxford Univ Hosp NHS Trust, Oxford Eye Hosp, John Radcliffe Hosp, Oxford, England.
   [Russell, Angela J.; Davies, Stephen G.] Univ Oxford, Chem Res Lab, Dept Chem, Oxford, England.
   [Russell, Angela J.] Univ Oxford, Dept Pharmacol, Oxford, England.
C3 University of Oxford; Oxford University Hospitals NHS Foundation Trust;
   University of Oxford; University of Oxford; University of Oxford
RP Storm, T; MacLaren, RE (通讯作者)，John Radcliffe Hosp, Nuffield Lab Ophthalmol, Dept Clin Neurosci, Level 5 & 6,West Wing,Headley Way, Oxford OX3 9DU, England.
EM tinastorm83@gmail.com; enquiries@eye.ox.ac.uk
RI Campbell, Ross/AAU-9327-2021
OI Campbell, Ross/0000-0003-2298-9887; Storm, Tina/0000-0001-6550-4072
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NR 29
TC 0
Z9 0
U1 2
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD MAY 1
PY 2020
VL 36
IS 4
BP 257
EP 266
DI 10.1089/jop.2019.0116
PG 10
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA LK6XU
UT WOS:000531007900011
PM 32027217
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Senthil, MP
   Fenwick, EK
   Lamoureux, E
   Khadka, J
   Pesudovs, K
AF Senthil, Mallika Prem
   Fenwick, Eva K.
   Lamoureux, Ecosse
   Khadka, Jyoti
   Pesudovs, Konrad
TI Identification and Evaluation of Items for Vitreoretinal Diseases
   Quality of Life Item Banks
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Retinal disease; retina; vitreoretinal diseases; hereditary;
   patient-reported outcome instruments; quality of life; item banks;
   computerised adaptive testing
ID VISUAL FUNCTION; DIABETIC-RETINOPATHY; RETINITIS; EXPERIENCE; SURGERY;
   PEOPLE; RASCH; PERFORMANCE; CANDIDATES; MOBILITY
AB Purpose: We are developing item banks assessing the impact of retinal and vitreoretinal diseases (excluding age-related macular degeneration, diabetic retinopathy, and retinal detachment, covered elsewhere) on quality of life (QoL) for adults. This study outlines the first two phases of the multi-stage process: content development and item evaluation. Methods: We grouped retinal and vitreoretinal diseases into hereditary and acquired. Development of the item banks involved two phases: item identification and item evaluation. The items were extracted from three sources: (1) 17 pre-existing PRO instruments, (2) 4 qualitative studies and (3) 79 semi-structured interviews. Item evaluation involved three stages namely, binning (grouping) and winnowing (reduction), expert panel opinion and cognitive interviews. Results: The item identification phase yielded 1,217 items. After three sessions of binning and winnowing, items were reduced to a minimally representative set (n =?411) across nine QoL domains namely, activity limitation, emotional, social, health concerns, symptoms, economic, mobility, convenience, and coping. The hereditary group had a total of 345 items and the acquired group had a total of 257 items. After 23 cognitive interviews items were amended for hereditary diseases resulting in a final set of 345 items and 3 items were amended for acquired diseases, resulting in a final set of 254 items. Overall across nine domains 189 items were common to hereditary and acquired retinal and vitreoretinal diseases. Conclusion: As most of the items were unique to hereditary versus acquired retinal and vitreoretinal disease groups separate item banks are required to capture the QoL impacts for hereditary and acquired retinal and vitreoretinal diseases.
C1 [Senthil, Mallika Prem] Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA 5001, Australia.
   [Fenwick, Eva K.; Lamoureux, Ecosse] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Fenwick, Eva K.; Lamoureux, Ecosse] Duke NUS Med Sch, Singapore, Singapore.
   [Khadka, Jyoti] South Australian Hlth & Med Res Inst, Registry Older South Australians, Adelaide, SA, Australia.
   [Khadka, Jyoti] Univ South Australia, Business Sch, Adelaide, SA, Australia.
   [Khadka, Jyoti; Pesudovs, Konrad] Univ New South Wales, Sydney, NSW, Australia.
   [Pesudovs, Konrad] Anglia Ruskin Univ, Cambridge, England.
C3 Flinders University South Australia; National University of Singapore;
   Singapore National Eye Center; National University of Singapore; South
   Australian Health & Medical Research Institute (SAHMRI); University of
   South Australia; University of New South Wales Sydney; Anglia Ruskin
   University
RP Senthil, MP (通讯作者)，Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA 5001, Australia.
EM mallika.premsenthil@flinders.edu.au
RI Prem Senthil, Mallika/N-7462-2019; Khadka, Jyoti/P-3935-2018
OI Prem Senthil, Mallika/0000-0001-6560-5594; Khadka,
   Jyoti/0000-0003-1012-2119; Pesudovs, Konrad/0000-0002-6322-9369
FU National Health and Medical Research Council [1031838]; Australian
   Government Research Training Scholarship program
FX This study is funded by National Health and Medical Research Council
   (grant no. 1031838). Mallika Prem Senthil is supported by the Australian
   Government Research Training Scholarship program.
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NR 45
TC 0
Z9 0
U1 0
U2 1
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 NOV 2
PY 2019
VL 26
IS 6
BP 448
EP 458
DI 10.1080/09286586.2019.1678655
EA OCT 2019
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 1P9AL
UT WOS:000490685300001
PM 31615298
DA 2022-11-30
ER

PT J
AU Alshamrani, M
   Sikder, S
   Coulibaly, F
   Mandal, A
   Pal, D
   Mitra, AK
AF Alshamrani, Meshal
   Sikder, Sadia
   Coulibaly, Fohona
   Mandal, Abhirup
   Pal, Dhananjay
   Mitra, Ashim K.
TI Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin
   Absorption Across Ocular Tissues
SO AAPS PHARMSCITECH
LA English
DT Article
DE curcumin; D407 cell line; ELISA; H2O2; oxidative stress
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; OXIDATIVE STRESS; VEGF;
   NANOPARTICLES; EXPRESSION; STABILITY; EYE
AB The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD. The bioavailability of curcumin is negligible due to its poor aqueous solubility. The purpose of this work is to develop an aqueous nanomicellar drop formulation of curcumin (CUR-NMF) for back of the eye delivery utilizing hydrogenated castor oil (HCO-40) and octoxynol-40 (OC-40) to treat AMD. A full factorial design was performed with JMP software analysis to optimize the formulation size, polydispersity index (PDI), entrapment efficiency, loading, and precipitation. MTT and LDH assays on human retinal pigmented epithelial (D407) cells revealed that 5-10 mu M CUR-NMF dose is safe for ophthalmic use. Furthermore, CUR-NMF exhibited significant protection of retinal (D407) cells against H2O2-induced oxidative stress. In vitro drug release kinetics suggested a sustained drug release profile indicating a long-term protection ability of CUR-NMF against oxidative stress to retinal cells. In addition, an ELISA suggested that CUR-NMF significantly reduces vascular endothelial growth factor (VEGF) release in D407 cell line, hence diminishes the risk of angiogenesis. Collectively, these results suggest that the proposed CUR-NMF can be tremendously effective in treating both types of AMD.
C1 [Alshamrani, Meshal; Sikder, Sadia; Coulibaly, Fohona; Mandal, Abhirup; Pal, Dhananjay; Mitra, Ashim K.] Univ Missouri, Sch Pharm, Div Pharmacol & Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
C3 University of Missouri System; University of Missouri Kansas City
RP Mitra, AK (通讯作者)，Univ Missouri, Sch Pharm, Div Pharmacol & Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
EM mitraa@umkc.edu
RI sikder, sadia/AAE-6712-2021; Mandal, Abhirup/I-9536-2019
OI Mandal, Abhirup/0000-0002-2543-4994; sikder, sadia/0000-0001-6798-2473
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NR 35
TC 19
Z9 20
U1 5
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-9932
J9 AAPS PHARMSCITECH
JI AAPS PharmSciTech
PD OCT
PY 2019
VL 20
IS 7
AR 254
DI 10.1208/s12249-019-1404-1
PG 16
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA IJ4UT
UT WOS:000475900100001
PM 31317354
DA 2022-11-30
ER

PT J
AU Liu, H
   Zhang, LG
   Wang, PY
AF Liu, Hong
   Zhang, Ligang
   Wang, Pengyan
TI Complement factor H-related 3 overexpression affects hepatocellular
   carcinoma proliferation and apoptosis
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE CFHR3; HCC; apoptosis; proliferation; PI3K/Akt/mTOR
ID BONE SIALOPROTEIN; CANCER; GENES; EXPRESSION; DELETION; PROTEIN; CELLS;
   RISK; CFH; OSTEOPONTIN
AB Complement factor H-related 3 (CFHR3) belongs to the human factor H protein family and is associated with various human diseases, including nephropathy, age-related macular degeneration and atypical hemolytic uremic syndrome. However, to the best of our knowledge, the role of CFHR3 in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to determine mRNA and protein expression levels of CFHR3 in HCC and normal adjacent tissue. In addition, CFHR3 was overexpressed in Huh-7 cells and cell counting kit-8 assay was used to determine cell viability. Cell proliferation and apoptosis were assessed using flow cytometry, RT-qPCR and western blotting. The results demonstrated that mRNA (2(-Delta Delta Cq)) and protein expression levels of CFHR3 were significantly lower in tumor tissue compared with in adjacent tissue. Additionally, CFHR3 overexpression decreased cell viability, inhibited cell proliferation and significantly increased apoptosis. It was also identified that CFHR3 could downregulate the expression of Ki67. The results suggested that CFHR3 induced apoptosis by downregulating the expression of survivin and B cell lymphoma 2, upregulating the expression of Bcl-2-associated X and promoting caspase-3 activity. Western blotting revealed that CFHR3 significantly inhibited the protein expression levels of phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-protein kinase B (Akt) and p-mammalian target of rapamycin (mTOR). Overexpression of CFHR3 suppressed proliferation and promoted apoptosis of HCC cells by inhibiting the PI3K/Akt/mTOR signaling pathway.
C1 [Liu, Hong; Zhang, Ligang] Yantai Infect Dis Hosp, Dept Hepatol, 62 Huanshan Rd, Yantai 264001, Shandong, Peoples R China.
   [Wang, Pengyan] Yantai Infect Dis Hosp, Dept Res & Educ, Yantai 264001, Shandong, Peoples R China.
RP Zhang, LG (通讯作者)，Yantai Infect Dis Hosp, Dept Hepatol, 62 Huanshan Rd, Yantai 264001, Shandong, Peoples R China.
EM ligangz_zhang@163.com
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NR 50
TC 12
Z9 12
U1 2
U2 6
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 SEP
PY 2019
VL 20
IS 3
BP 2694
EP 2702
DI 10.3892/mmr.2019.10514
PG 9
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA IS8YL
UT WOS:000482435500073
PM 31524260
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Jin, K
   Zhou, M
   Wang, SZ
   Lou, LX
   Xu, YF
   Ye, J
   Qian, DH
AF Jin, Kai
   Zhou, Mei
   Wang, Shaoze
   Lou, Lixia
   Xu, Yufeng
   Ye, Juan
   Qian, Dahong
TI Computer-aided diagnosis based on enhancement of degraded fundus
   photographs
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE detection; enhancement; fundus image; retina
ID RETINAL IMAGES; DIABETIC-RETINOPATHY; QUALITY; MODEL
AB PurposeRetinal imaging is an important and effective tool for detecting retinal diseases. However, degraded images caused by the aberrations of the eye can disguise lesions, so that a diseased eye can be mistakenly diagnosed as normal. In this work, we propose a new image enhancement method to improve the quality of degraded images.
   MethodsA new method is used to enhance degraded-quality fundus images. In this method, the image is converted from the input RGB colour space to LAB colour space and then each normalized component is enhanced using contrast-limited adaptive histogram equalization. Human visual system (HVS)-based fundus image quality assessment, combined with diagnosis by experts, is used to evaluate the enhancement.
   ResultsThe study included 191 degraded-quality fundus photographs of 143 subjects with optic media opacity. Objective quality assessment of image enhancement (range: 0-1) indicated that our method improved colour retinal image quality from an average of 0.0773 (variance 0.0801) to an average of 0.3973 (variance 0.0756). Following enhancement, area under curves (AUC) were 0.996 for the glaucoma classifier, 0.989 for the diabetic retinopathy (DR) classifier, 0.975 for the age-related macular degeneration (AMD) classifier and 0.979 for the other retinal diseases classifier.
   ConclusionThe relatively simple method for enhancing degraded-quality fundus images achieves superior image enhancement, as demonstrated in a qualitative HVS-based image quality assessment. This retinal image enhancement may, therefore, be employed to assist ophthalmologists in more efficient screening of retinal diseases and the development of computer-aided diagnosis.
C1 [Jin, Kai; Lou, Lixia; Xu, Yufeng; Ye, Juan] Zhejiang Univ, Affiliated Hosp 2, Coll Med, Dept Ophthalmol, Hangzhou 310009, Zhejiang, Peoples R China.
   [Zhou, Mei] East China Normal Univ, Shanghai Key Lab Multidimens Informat Proc, Shanghai, Peoples R China.
   [Wang, Shaoze] Zhejiang Univ, Inst VLSI Design, Hangzhou, Zhejiang, Peoples R China.
   [Qian, Dahong] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China.
C3 Zhejiang University; East China Normal University; Zhejiang University;
   Shanghai Jiao Tong University
RP Ye, J (通讯作者)，Zhejiang Univ, Affiliated Hosp 2, Coll Med, Dept Ophthalmol, Hangzhou 310009, Zhejiang, Peoples R China.; Qian, DH (通讯作者)，Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China.
EM yejuan@zju.edu.cn; dahong.qian@sjtu.edu.cn
RI Jin, Kai/S-9997-2019
FU Zhejiang Provincial Program for Cultivation of High-level Innovative
   Health Talents; Zhejiang Provincial Program for Medical and Health
   Science [2016137996]; Natural Science Foundation of China [81471748]
FX This work was financially supported by Zhejiang Provincial Program for
   Cultivation of High-level Innovative Health Talents, Zhejiang Provincial
   Program for Medical and Health Science Co-sponsored by Province and
   Ministry (grant number 2016137996) and the Natural Science Foundation of
   China (grant number 81471748).
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NR 30
TC 6
Z9 6
U1 0
U2 28
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 2018
VL 96
IS 3
BP E320
EP E326
DI 10.1111/aos.13573
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GE0NY
UT WOS:000430912700009
PM 29090844
OA Bronze
DA 2022-11-30
ER

PT J
AU Karlsson, M
   Kurz, T
AF Karlsson, Markus
   Kurz, Tino
TI Attenuation of iron-binding proteins in ARPE-19 cells reduces their
   resistance to oxidative stress
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; ARPE-19; ferritin; HSP70; iron;
   metallothionein; oxidative stress; retinal pigment epithelium
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; HYDROGEN-PEROXIDE;
   LYSOSOMAL IRON; HELA-CELLS; APOPTOSIS; AUTOPHAGY; AGE; FERRITIN;
   LIPOFUSCIN
AB PurposeOxidative stress-related damage to retinal pigment epithelial (RPE) cells is an important feature in the development of age-related macular degeneration. Iron-catalysed intralysosomal production of hydroxyl radicals is considered a major pathogenic factor, leading to lipofuscin formation with ensuing depressed cellular autophagic capacity, lysosomal membrane permeabilization and apoptosis. Previously, we have shown that cultured immortalized human RPE (ARPE-19) cells are extremely resistant to exposure to bolus doses of hydrogen peroxide and contain considerable amounts of the iron-binding proteins metallothionein (MT), heat-shock protein 70 (HSP70) and ferritin (FT). According to previous findings, autophagy of these proteins depresses lysosomal redox-active iron. The aim of this study was to investigate whether up- or downregulation of these proteins would affect the resistance of ARPE-19 cells to oxidative stress.
   MethodsThe sensitivity of ARPE-19 cells to H2O2 exposure was tested following upregulation of MT, HSP70 and/or FT by pretreatment with ZnSO4, heat shock or FeCl3, as well as siRNA-mediated downregulation of the same proteins.
   ResultsUpregulation of MT, HSP70 and FT did not improve survival following exposure to H2O2. This was interpreted as existence of an already maximal protection. Combined siRNA-mediated attenuation of both FT chains (H and L), or simultaneous downregulation of all three proteins, made the cells significantly more susceptible to oxidative stress confirming the importance of iron-binding proteins.
   ConclusionThe findings support our hypothesis that the oxidative stress resistance exhibited by RPE cells may be explained by a high autophagic influx of iron-binding proteins that would keep levels of redox-active lysosomal iron low.
C1 [Karlsson, Markus] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
   [Kurz, Tino] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
C3 Linkoping University; Linkoping University
RP Karlsson, M (通讯作者)，Linkoping Univ, Div Ophthalmol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden.
EM markus.karlsson@regionostergotland.se
OI Karlsson, Markus/0000-0003-1183-2526
FU Crown Princess Margareta's Foundation for the Visually Handicapped;
   Edvin Jordan Foundation for Ophthalmological Research; Linkoping
   University Hospital Research Fund (ALF)
FX The financial support by Crown Princess Margareta's Foundation for the
   Visually Handicapped, the Edvin Jordan Foundation for Ophthalmological
   Research and the Linkoping University Hospital Research Fund (ALF) is
   gratefully acknowledged.
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NR 52
TC 10
Z9 10
U1 2
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 SEP
PY 2016
VL 94
IS 6
BP 556
EP 564
DI 10.1111/aos.13076
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DW3CX
UT WOS:000383520800034
PM 27287874
DA 2022-11-30
ER

PT J
AU Dixon, P
   Dakin, H
   Wordsworth, S
AF Dixon, Padraig
   Dakin, Helen
   Wordsworth, Sarah
TI Generic and disease-specific estimates of quality of life in macular
   degeneration: mapping the MacDQoL onto the EQ-5D-3L
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE MacDQoL; Mapping algorithm; EuroQoL EQ-5D; Age-related macular
   degeneration
ID PREFERENCE-BASED MEASURES; UTILITY VALUES; OUTCOME MEASURES; HEALTH;
   SF-12
AB The macular degeneration quality of life (MacDQoL) instrument is a validated condition-specific measure of quality of life in patients with macular degeneration. This paper presents the first mapping algorithm to predict EQ-5D from responses to the MacDQoL instrument.
   Responses to the MacDQoL and EQ-5D-3L instruments from 482 patients were collected from the IVAN multicentre trial of two alternative drug treatments for neovascular age-related macular degeneration. Regression specifications were estimated using OLS, censored least absolute deviation, Tobit and two-part models. Their predictive performance was assessed using mean squared error. An internal validation sample based on a random selection of 25 % of patients was used to assess the performance of the model estimated on the remaining 75 % of patients.
   A two-part model had the best predictive performance on the full sample. The covariates of this model include responses and weighted impact scores for all 23 condition-specific domains of the MacDQoL, and responses to a general MacDQoL quality of life question. The selected models were successful at predicting means and standard deviations of target populations, but prediction is weaker at the upper and lower extremes of the EQ-5D-3L distribution.
   The mapping algorithms provide a means of predicting EQ-5D-3L index scores from MacDQoL scores, and could facilitate cost-effectiveness analyses when the latter but not the former are available to researchers. Further validation of the performance of the algorithms using external data would provide a means of establishing the robustness of the algorithms.
C1 [Dixon, Padraig] Univ Bristol, Sch Social & Community Med, Canynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England.
   [Dakin, Helen; Wordsworth, Sarah] Univ Oxford, Hlth Econ Res Ctr, Nuffield Dept Populat Hlth, Old Rd Campus, Oxford OX3 7LF, England.
C3 University of Bristol; University of Oxford
RP Dixon, P (通讯作者)，Univ Bristol, Sch Social & Community Med, Canynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England.
EM padraig.dixon@bristol.ac.uk
OI Wordsworth, Sarah/0000-0002-2361-3040; Dixon,
   Padraig/0000-0001-5285-409X; Dakin, Helen/0000-0003-3255-748X
FU National Institute for Health Research (NIHR) Health Technology
   Assessment (HTA) programme [07/36/01]; MRC [MR/K025643/1] Funding
   Source: UKRI; Medical Research Council [MR/K025643/1] Funding Source:
   researchfish; National Institute for Health Research [NF-SI-0514-10114]
   Funding Source: researchfish
FX The IVAN trial (Trial Registration: ISRCTN92166560) was funded by the
   National Institute for Health Research (NIHR) Health Technology
   Assessment (HTA) programme (Project Number 07/36/01). The views and
   opinions expressed are those of the authors and do not necessarily
   reflect those of the HTA programme, NIHR, the UK National Health Service
   or the Department of Health. The NIHR had no role in the design, conduct
   or reporting of this mapping study. We are grateful to all IVAN trial
   participants and to the IVAN research team. We are extremely grateful to
   the IVAN site staff, who collected the EQ-5D-3L data and also the
   Clinical Trials Evaluation Unit (University of Bristol) who made all the
   phone calls to collect the MacDQoL data, then managed and cleaned the
   data for the analyses for this paper. We thank two anonymous reviewers
   for helpful comments.
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NR 32
TC 6
Z9 6
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD APR
PY 2016
VL 25
IS 4
BP 935
EP 945
DI 10.1007/s11136-015-1145-x
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
   Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA DJ6DM
UT WOS:000374300200015
PM 26462812
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Mary, MCVS
   Rajsingh, EB
   Naik, GR
AF Mary, M. Caroline Viola Stella
   Rajsingh, Elijah Blessing
   Naik, Ganesh R.
TI Retinal Fundus Image Analysis for Diagnosis of Glaucoma: A Comprehensive
   Survey
SO IEEE ACCESS
LA English
DT Article
DE Glaucoma; age-related macular degeneration; Stargardt's disease;
   diabetic retinopathy; fundus image
ID OPTIC-NERVE HEAD; DISC DETECTION; FIBER LAYER; AUTOMATED SEGMENTATION;
   COHERENCE TOMOGRAPHY; FEATURE-EXTRACTION; MACULAR THICKNESS;
   NEURAL-NETWORK; FIELD; OCT
AB The rapid development of digital imaging and computer vision has increased the potential of using the image processing technologies in ophthalmology. Image processing systems are used in standard clinical practices with the development of medical diagnostic systems. The retinal images provide vital information about the health of the sensory part of the visual system. Retinal diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, Stargardt's disease, and retinopathy of prematurity, can lead to blindness manifest as artifacts in the retinal image. An automated system can be used for offering standardized large-scale screening at a lower cost, which may reduce human errors, provide services to remote areas, as well as free from observer bias and fatigue. Treatment for retinal diseases is available; the challenge lies in finding a cost-effective approach with high sensitivity and specificity that can be applied to large populations in a timely manner to identify those who are at risk at the early stages of the disease. The progress of the glaucoma disease is very often quiet in the early stages. The number of people affected has been increasing and patients are seldom aware of the disease, which can cause delay in the treatment. A review of how computer-aided approaches may be applied in the diagnosis and staging of glaucoma is discussed here. The current status of the computer technology is reviewed, covering localization and segmentation of the optic nerve head, pixel level glaucomatic changes, diagonosis using 3-D data sets, and artificial neural networks for detecting the progression of the glaucoma disease.
C1 [Mary, M. Caroline Viola Stella] Francis Xavier Engn Coll, Dept Informat Technol, Tirunelveli 627003, India.
   [Rajsingh, Elijah Blessing] Karunya Univ, Sch Comp Sci & Technol, Coimbatore 641114, Tamil Nadu, India.
   [Naik, Ganesh R.] Univ Technol Sydney, Fac Engn & Informat Technol, Sydney, NSW 2007, Australia.
C3 Karunya Institute of Technology & Sciences; University of Technology
   Sydney
RP Mary, MCVS (通讯作者)，Francis Xavier Engn Coll, Dept Informat Technol, Tirunelveli 627003, India.
EM carolsam67@googlemail.com
RI Naik, Ganesh/G-5538-2011; RAJSINGH, ELIJAH BLESSING/B-2707-2016
OI Naik, Ganesh/0000-0003-1790-9838; RAJSINGH, ELIJAH
   BLESSING/0000-0003-3424-812X
FU University of Technology Sydney through the Chancellor's Post-Doctoral
   Research Fellowship [CPDRF2013-16]
FX This work was supported by the University of Technology Sydney through
   the Chancellor's Post-Doctoral Research Fellowship under Grant
   CPDRF2013-16.
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NR 162
TC 42
Z9 44
U1 0
U2 11
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 2016
VL 4
BP 4327
EP 4354
DI 10.1109/ACCESS.2016.2596761
PG 28
WC Computer Science, Information Systems; Engineering, Electrical &
   Electronic; Telecommunications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Telecommunications
GA DV2UM
UT WOS:000382777400034
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Wakx, A
   Dutot, M
   Massicot, F
   Mascarelli, F
   Limb, GA
   Rat, P
AF Wakx, Anais
   Dutot, Melody
   Massicot, France
   Mascarelli, Frederic
   Limb, G. Astrid
   Rat, Patrice
TI Amyloid beta Peptide Induces Apoptosis Through P2X7 Cell Death Receptor
   in Retinal Cells: Modulation by Marine Omega-3 Fatty Acid DHA and EPA
SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
LA English
DT Article
DE Age-related macular degeneration; P2X7 receptor; Amyloid-beta peptide;
   Retinal cells; Apoptosis; DHA; EPA; Omega-3 fatty acid
ID MULLER CELLS; MACULAR DEGENERATION; OXIDATIVE STRESS; P2X(7) RECEPTOR;
   MODEL; ACTIVATION; EXPRESSION; DRUSEN; CYTOTOXICITY; DISRUPTION
AB Retinal Muller glial cells have already been implicated in age-related macular degeneration (AMD). AMD is characterized by accumulation of toxic amyloid-beta peptide (A beta); the question we raise is as follows: is P2X7 receptor, known to play an important role in several degenerative diseases, involved in A beta toxicity on Muller cells? Retinal Muller glial cells were incubated with A beta for 48 h. Cell viability was assessed using the alamarBlue assay and cytotoxicity using the lactate dehydrogenase (LDH) release assay. P2X7 receptor expression was highlighted by immunolabeling observed on confocal microscopy and its activation was evaluated by YO-PRO-1 assay. Hoechst 33342 was used to evaluate chromatin condensation, and caspases 8 and 3 activation was assessed using AMC assays. Lipid formulation rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) used in Age-Related Eye Disease Study 2 was incubated on cells for 15 min prior to A beta incubation. For the first time, we showed that A beta induced caspase-independent apoptosis through P2X7 receptor activation on our retinal model. DHA and EPA are polyunsaturated fatty acids recommended in food supplement to prevent AMD. We therefore modulated A beta cytotoxicity using a lipid formulation rich in DHA and EPA to have a better understanding of the results observed in clinical studies. We showed that fish oil rich in EPA and DHA, in combination with a potent P2X7 receptor antagonist, represents an efficient modulator of A beta toxicity and that P2X7 could be an interesting therapeutic target to prevent AMD.
C1 [Wakx, Anais; Dutot, Melody; Massicot, France; Rat, Patrice] Univ Paris 05, Sorbonne Paris Cite, UMR CNRS Chim Toxicol Analyt & Cellulaire 8638, Fac Pharm, 4 Ave Observ, F-75006 Paris, France.
   [Dutot, Melody] Lab Yslab, 2 Rue Felix Le Dantec, F-29000 Quimper, France.
   [Mascarelli, Frederic] Ctr Rech Cordeliers, INSERM Physiopathol Malad Oculaires Innovat Thera, 15 Rue Ecole Med, F-75006 Paris, France.
   [Limb, G. Astrid] UCL Inst Ophthalmol, Div Ocular Biol & Therapeut, 11 Bath St, London EC1V 9EL, England.
   [Limb, G. Astrid] Moorfields Eye Hosp, 11 Bath St, London EC1V 9EL, England.
   [Wakx, Anais; Dutot, Melody; Massicot, France; Mascarelli, Frederic; Rat, Patrice] Ctr Rech Biomed Cordeliers, INSERM, U598, Physiopathol Malad Oculaires,Innovat Therapeut, F-75270 Paris 06, France.
C3 UDICE-French Research Universities; Universite Paris Cite; Universite de
   Franche-Comte; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Sorbonne Universite;
   Universite Paris Cite; University of London; University College London;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; Institut National de la Sante et de la Recherche
   Medicale (Inserm)
RP Rat, P (通讯作者)，Univ Paris 05, Sorbonne Paris Cite, UMR CNRS Chim Toxicol Analyt & Cellulaire 8638, Fac Pharm, 4 Ave Observ, F-75006 Paris, France.; Rat, P (通讯作者)，Ctr Rech Biomed Cordeliers, INSERM, U598, Physiopathol Malad Oculaires,Innovat Therapeut, F-75270 Paris 06, France.
EM anais.wakx@free.fr; melody.dutot@yslab.fr;
   france.massicot@parisdescartes.fr; Frederic.mascarelli@inserm.fr;
   g.limb@ucl.ac.uk; patrice.rat@parisdescartes.fr
RI Dutot, Mélody/ABC-7648-2020; Wakx, Anaïs/A-7993-2017; DUTOT,
   Mélody/A-1796-2017; Mascarelli, Frederic/L-8916-2018
OI Dutot, Mélody/0000-0003-0964-0664; Wakx, Anaïs/0000-0003-2813-365X;
   DUTOT, Mélody/0000-0003-0964-0664; Limb, Gloria
   Astrid/0000-0001-7014-8922
FU Adebiopharm ER67; French Ministere de la Recherche; Agence Nationale de
   la Recherche (Paris, France);  [ANR-BLAN-0204]; MRC [MR/K008722/1]
   Funding Source: UKRI; Medical Research Council [MR/K008722/1] Funding
   Source: researchfish; Fight for Sight [1906] Funding Source:
   researchfish
FX The authors would like to thank Adebiopharm ER67, French Ministere de la
   Recherche and Agence Nationale de la Recherche (Paris, France) for their
   financial support. This study was a part of the ANR-BLAN-0204 project
   coordinated by INSERM U598 unit (Professor Francine Behar-Cohen, Doctor
   Frederic Mascarelli's team).
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NR 63
TC 10
Z9 11
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0273-2289
EI 1559-0291
J9 APPL BIOCHEM BIOTECH
JI Appl. Biochem. Biotechnol.
PD JAN
PY 2016
VL 178
IS 2
BP 368
EP 381
DI 10.1007/s12010-015-1878-6
PG 14
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA DB7HY
UT WOS:000368686600011
PM 26467741
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Arend, N
   Wertheimer, C
   Laubichler, P
   Wolf, A
   Kampik, A
   Kernt, M
AF Arend, Nicole
   Wertheimer, Christian
   Laubichler, Peter
   Wolf, Armin
   Kampik, Anselm
   Kernt, Marcus
TI Idebenone Prevents Oxidative Stress, Cell Death and Senescence of
   Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio
SO OPHTHALMOLOGICA
LA English
DT Article
DE Age-related macular degeneration; Oxidative stress; Apoptosis; Retinal
   pigment epithelium cells; Cell death
ID HEREDITARY OPTIC NEUROPATHY; ENDOTHELIAL GROWTH-FACTOR;
   PLACEBO-CONTROLLED TRIAL; NERVE HEAD ASTROCYTES; COENZYME-Q ANALOG;
   HUMAN RPE CELLS; SA-BETA-GAL; MACULAR DEGENERATION; INDUCED APOPTOSIS;
   FRIEDREICH ATAXIA
AB Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. Methods: ARPE-19 cells were treated with 1-100 mu M idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono-and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated beta-galactosidase (SA-beta-Gal) activity were investigated under exposure to hydrogen peroxide (H2O2). Results: Idebenone concentrations from 1 to 20 mu M showed no toxic effects on ARPE-19 cells. When cells were treated with H2O2, pretreatment with 5, 7.5, 10, and 20 mu M idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-beta-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H2O2. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H2O2-induced apoptosis, not necrosis. Conclusion: In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio. (C) 2015 S. Karger AG, Basel
C1 [Arend, Nicole; Wertheimer, Christian; Laubichler, Peter; Wolf, Armin; Kampik, Anselm; Kernt, Marcus] Univ Munich, Dept Ophthalmol, DE-80336 Munich, Germany.
C3 University of Munich
RP Arend, N (通讯作者)，Univ Munich, Dept Ophthalmol, Mathildenstr 8, DE-80336 Munich, Germany.
EM Nicole.arend@med.uni-muenchen.de
OI Wertheimer, Christian/0000-0002-7017-7560
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NR 55
TC 29
Z9 29
U1 1
U2 9
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2015
VL 234
IS 2
BP 73
EP 82
DI 10.1159/000381726
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CR9NR
UT WOS:000361684200003
PM 26044821
OA Green Accepted
DA 2022-11-30
ER

PT J
AU McKeague, C
   Binns, AM
   Margrain, TH
AF McKeague, Claire
   Binns, Alison M.
   Margrain, Tom H.
TI An Evaluation of Two Candidate Functional Biomarkers for AMD
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE repeatability; age-related macular degeneration; biomarkers; color
   vision; flicker
ID AGE-RELATED MACULOPATHY; FOVEAL FLICKER SENSITIVITY; MEDIATED
   DARK-ADAPTATION; MACULAR DEGENERATION; COLOR-VISION; RETINAL FUNCTION;
   VISUAL FUNCTION; FELLOW EYE; ACUITY; LUMINANCE
AB Purpose. To evaluate the intersession repeatability of the Colour Assessment and Diagnosis (CAD) test and a novel 14-Hz flicker test in a population of healthy participants to provide benchmark data for their use as functional biomarkers for age-related macular degeneration (AMD).
   Methods. Visual function was assessed using both techniques in 30 healthy adults (mean [ standard deviation] age 36.3 [14.1] years) on two separate days. Intersession repeatability of RG and YB CAD thresholds and 14-Hz flicker thresholds was assessed by determining their coefficient of repeatability (CoR).
   Results. The CoR was calculated to be 0.39 CAD units (17.0%) for RG thresholds, 0.43 CAD units (31.1%) for YB thresholds, and 0.015 (53.4%) for 14-Hz flicker contrast thresholds. On average, thresholds improved by 4.72% (RG), 6.33% (YB), and 13.3% (14-Hz flicker) between visits 1 and 2, suggesting a small but consistent learning effect. The CoR for all parameters was relatively small compared to the mean thresholds obtained (RG: mean 2.27 [4.58], CoR 0.39; YB: mean 1.37 [0.55], CoR 0.43; 14-Hz flicker: mean 0.028 [0.01], CoR 0.015).
   Conclusions. This study has described the repeatability of the CAD and 14-Hz flicker tests. These data can help clinicians decide if the results from repeated measures are of clinical significance. Despite pretest training, there was some evidence of a learning effect. Therefore, clinical trials using these techniques should ensure training is sufficient to minimize these effects.
C1 [McKeague, Claire; Margrain, Tom H.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4HQ, S Glam, Wales.
   [Binns, Alison M.] City Univ London, Sch Hlth Sci, London EC1V 0HB, England.
C3 Cardiff University; City University London
RP Margrain, TH (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales.
EM margrainth@cf.ac.uk
OI Binns, Alison/0000-0001-8621-498X; Margrain, Tom/0000-0003-1280-0809
FU College of Optometrists, United Kingdom
FX This study was funded by a research grant from the College of
   Optometrists, United Kingdom.
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NR 53
TC 8
Z9 8
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD AUG
PY 2014
VL 91
IS 8
BP 916
EP 924
DI 10.1097/OPX.0000000000000318
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN4KL
UT WOS:000340556500015
PM 24978867
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Tsvetkova, D
   Obreshkova, D
   Zheleva-Dimitrova, D
   Saso, L
AF Tsvetkova, D.
   Obreshkova, D.
   Zheleva-Dimitrova, D.
   Saso, L.
TI Antioxidant Activity of Galantamine and Some of its Derivatives
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Antioxidant activity; derivatives; galantamine; oxidative stress;
   neurodegeneration
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; MODERATE ALZHEIMERS-DISEASE; PROBABLE
   VASCULAR DEMENTIA; INDUCED OXIDATIVE STRESS; NERVE GROWTH-FACTOR;
   MEDICINAL-PLANTS; AMYLOID-BETA; ALLOSTERIC POTENTIATION;
   NEURODEGENERATIVE DISEASES; MEDIATED NEUROPROTECTION
AB Oxidative stress is implicated in the pathogenesis of different human diseases: Alzheimer, Parkinson, Huntington, amyotrophic lateral sclerosis (Lou Gehrig's disease), Down's syndrome, atherosclerosis, vascular disease, cancer, diabetes mellitus type 1 and type 2, age - related macular degeneration, psoriatic arthritis. The aim of current study is to summarize the scientific evidences for the antioxidant and neuroprotective activity of Galantamine and some of its derivatives. Galantamine is a scavenger of reactive oxygen species and causes neuroprotective effect by lowering the oxidative neuronal damage, through the following pathways: 1) prevention of the activation of P2X7 receptors; 2) protection of mitochondrial membrane potential; 3) pre - vention of the membrane fluidity disturbances. Another mechanism is the decreasing of the overproduction of reactive oxygen species, a result from the increasing of acetylcholine level due to: 1) acethylcholinesterase inhibition; 2) allosteric potentiation of alpha 7 - subtype of nicotinic acetylcholine receptors. A close relationship between acethylcholinesterase inhibition and reduced oxidative injury is observed. Through allosteric potentiation of the alpha 7 -subtype of nicotinic acetylcholine receptors, the drug leads to induction of phosphorylation of serine threonine protein kinase, stimulates phosphoinositide 3 - kinase and elevates the expression of protective protein Bcl - 2. By activation of these important neuroprotective cascades, Galantamine exerts neuroprotection against a variety of cytotoxic agents (beta - amyloid peptide, glutamate, hydrogen peroxide, oxygen and glucose deprivation). The new trend in therapy of Alzheimer's disease will be the investigation and application of compounds such as Galantamine derivatives, which possess acethylcholinesterase and gamma - secretase inhibitory activity and antioxidant properties.
C1 [Tsvetkova, D.; Obreshkova, D.] Med Univ Sofia, Dept Pharmaceut Chem, Fac Pharm, Sofia 1000, Bulgaria.
   [Zheleva-Dimitrova, D.] Med Univ Sofia, Dept Pharmacognosy, Fac Pharm, Sofia 1000, Bulgaria.
   [Saso, L.] Univ Roma La Sapienza, Dept Physiol & Pharmacol Vittorio Erspamer, Rome, Italy.
C3 Medical University Sofia; Medical University Sofia; Sapienza University
   Rome
RP Tsvetkova, D (通讯作者)，Med Univ Sofia, Dept Pharmaceut Chem, Fac Pharm, Dunav Str 2, Sofia 1000, Bulgaria.
EM phddanka@yahoo.com; dobrinka30@mail.bg
RI saso, luciano/F-6306-2012; Zheleva-Dimitrova, Dimitrina/GQI-1010-2022
OI saso, luciano/0000-0003-4530-8706; Zheleva-Dimitrova,
   Dimitrina/0000-0002-1952-9903
FU Medical University of Sofia [18/2013]
FX This paper was prepared with the financial support from Grant Project No
   18/2013, Medical University of Sofia.
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NR 141
TC 39
Z9 39
U1 0
U2 29
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 DEC
PY 2013
VL 20
IS 36
BP 4595
EP 4608
DI 10.2174/09298673113209990148
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 251WU
UT WOS:000326964700009
PM 23834167
DA 2022-11-30
ER

PT J
AU Jin, J
   Yuan, F
   Shen, MQ
   Feng, YF
   He, QL
AF Jin, Jing
   Yuan, Fei
   Shen, Min-qian
   Feng, Yi-fan
   He, Qi-liu
TI Vascular endothelial growth factor regulates primate choroid-retinal
   endothelial cell proliferation and tube formation through PI3K/Akt and
   MEK/ERK dependent signaling
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Choroid-retinal endothelial cell; VEGF; ERK; Akt
ID MACULAR DEGENERATION; HIF-1-ALPHA; EXPRESSION; MIGRATION; VEGF
AB Vascular endothelial growth factor (VEGF) is a hypoxia-induced angiogenic protein that exhibits a broad range of biological and pathological effects in wet age-related macular degeneration and proliferative diabetic retinopathy. However, its specific mechanism is still not fully understood. Here, we examined the effects of VEGF on choroid-retinal endothelial cells (RF/6A) proliferation and tube formation, and the underlying signal pathways responsible in this process. RF/6A cells were pretreated with MEK inhibitor or PI3K inhibitor, and then incubated in a hypoxia chamber. Real-time PCR and Western blot analysis were carried out to explore VEGF expression on mRNA and protein levels. Hypoxia inducible factor-1 alpha (HIF-1 alpha) and VEGFR2 expression levels were also investigated in the presence and absence of hypoxic conditions. CCK-8 analysis and tube formation assay were tested under hypoxia, exogenous recombinant VEGF, and different signal pathway inhibitors, respectively. Mean while, the PI3K/Akt and MEK/ERK pathways in this process were also investigated. Our results showed that VEGF, HIF-1 alpha, VEGFR2, p-ERK, and p-Akt were up-regulated in RF/6A cells under hypoxic conditions. MEK inhibitor (PD98059) and PI3K inhibitor (LY294002) decreased ERK and Akt activity, respectively, and reduced VEGF expression. VEGF-induced RF/6A proliferation and tube formation requires MEK/ERK and PI3K/Akt signaling, and both of the two pathways were needed in regulating VEGF expression. These suggest that VEGF plays an important role in RF/6A proliferation and tube formation, and MEK/ERK and PI3K/Akt pathway may be responsible for this process.
C1 [Jin, Jing; Yuan, Fei; Shen, Min-qian; Feng, Yi-fan; He, Qi-liu] Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, Shanghai 200032, Peoples R China.
C3 Fudan University
RP Yuan, F (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.
EM yuanfei07@yahoo.cn
RI Shen, Minqian/M-2713-2016
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NR 19
TC 39
Z9 42
U1 1
U2 25
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 SEP
PY 2013
VL 381
IS 1-2
BP 267
EP 272
DI 10.1007/s11010-013-1710-y
PG 6
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 187XV
UT WOS:000322155900028
PM 23749166
DA 2022-11-30
ER

PT J
AU De Roach, JN
   McLaren, TL
   Paterson, RL
   O'Brien, EC
   Hoffmann, L
   Mackey, DA
   Hewitt, AW
   Lamey, TM
AF De Roach, John N.
   McLaren, Terri L.
   Paterson, Rachel L.
   O'Brien, Emily C.
   Hoffmann, Ling
   Mackey, David A.
   Hewitt, Alex W.
   Lamey, Tina M.
TI Establishment and evolution of the Australian Inherited Retinal Disease
   Register and DNA Bank
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE choroideraemia; Leber congenital amaurosis; retinitis pigmentosa;
   Stargardt disease; Usher syndrome
ID X-LINKED RETINOSCHISIS; RETINITIS-PIGMENTOSA; WESTERN-AUSTRALIA; GENE;
   BLINDNESS
AB Background Inherited retinal disease represents a significant cause of blindness and visual morbidity worldwide. With the development of emerging molecular technologies, accessible and well-governed repositories of data characterising inherited retinal disease patients is becoming increasingly important. This manuscript introduces such a repository. Design Participants were recruited from the Retina Australia membership, through the Royal Australian and New Zealand College of Ophthalmologists, and by recruitment of suitable patients attending the Sir Charles Gairdner Hospital visual electrophysiology clinic. Participants Four thousand one hundred ninety-three participants were recruited. All participants were members of families in which the proband was diagnosed with an inherited retinal disease (excluding age-related macular degeneration). Methods Clinical and family information was collected by interview with the participant and by examination of medical records. In 2001, we began collecting DNA from Western Australian participants. In 2009 this activity was extended Australia-wide. Genetic analysis results were stored in the register as they were obtained. Main Outcome Measures The main outcome measurement was the number of DNA samples (with associated phenotypic information) collected from Australian inherited retinal disease-affected families. Results DNA was obtained from 2873 participants. Retinitis pigmentosa, Stargardt disease and Usher syndrome participants comprised 61.0%, 9.9% and 6.4% of the register, respectively. Conclusions This resource is a valuable tool for investigating the aetiology of inherited retinal diseases. As new molecular technologies are translated into clinical applications, this well-governed repository of clinical and genetic information will become increasingly relevant for tasks such as identifying candidates for gene-specific clinical trials.
C1 [De Roach, John N.; McLaren, Terri L.; Paterson, Rachel L.; O'Brien, Emily C.; Hoffmann, Ling; Lamey, Tina M.] Sir Charles Gairdner Hosp, Dept Med Technol & Phys, Australian Inherited Retinal Dis Register & DNA B, Perth, WA, Australia.
   [Mackey, David A.; Hewitt, Alex W.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia.
   [Mackey, David A.; Hewitt, Alex W.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
C3 Lions Eye Institute; University of Western Australia; Centre for Eye
   Research Australia; Royal Victorian Eye & Ear Hospital; University of
   Melbourne
RP De Roach, JN (通讯作者)，Sir Charles Gairdner Hosp, Hosp Ave, Nedlands, WA 6009, Australia.
EM john.deroach@health.wa.gov.au
RI Hewitt, Alex W/D-1936-2013; LAMEY, TINA/AAL-6401-2021; Mackey, David
   A/H-5340-2014
OI Hewitt, Alex W/0000-0002-5123-5999; LAMEY, TINA/0000-0002-4608-4073;
   Mackey, David A/0000-0001-7914-4709
FU Retina Australia; Retina Australia (WA); Retina Australia (SA); National
   Health and Medical Research Council (NHMRC) Enabling Facility Grant;
   NHMRC
FX Retina Australia, Retina Australia (WA) and Retina Australia (SA) funded
   the development of the Australian Inherited Retinal Disease Register and
   DNA Bank. The authors gratefully acknowledge the assistance of the
   Western Australian DNA Bank, which was supported by a National Health
   and Medical Research Council (NHMRC) Enabling Facility Grant. AWH is
   supported by NHMRC Early Career Fellowship. Ongoing support is also
   provided by the Centre for Research Excellence Grant for Translation of
   Genetic Eye Research from the NHMRC.
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NR 16
TC 31
Z9 31
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD JUL
PY 2013
VL 41
IS 5
BP 476
EP 483
DI 10.1111/ceo.12020
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 171LB
UT WOS:000320928600009
PM 23078154
OA Green Published
DA 2022-11-30
ER

PT J
AU Querques, G
   Guigui, B
   Leveziel, N
   Querques, L
   Bandello, F
   Souied, EH
AF Querques, Giuseppe
   Guigui, Benjamin
   Leveziel, Nicolas
   Querques, Lea
   Bandello, Francesco
   Souied, Eric H.
TI Multimodal morphological and functional characterization of Malattia
   Leventinese
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Autofluorescence; Doyne honeycomb
   retinal dystrophy; Fluorescein angiography; Drusen; Malattia
   leventinese; Indocyanine green angiography; Optical coherence tomography
ID FUNDUS AUTOFLUORESCENCE; MACULAR DETACHMENT; DRUSEN; AGE; EFEMP1;
   ACCUMULATION; CHOLESTEROL; ANGIOGRAPHY; DEPOSITS; MUTATION
AB To analyze the morphological and functional characteristics of malattia leventinese.
   This was a chart review of patients with Malattia Leventinese. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Microperimetry and Preferential Hyperacuity Perimeter (PHP) were performed in a subset of patients.
   Twelve eyes of six patients were included. BCVA ranged from 20/25 to 20/200. The largest drusen were round, not radially distributed, localized in the perimacular area and around the optic disc. The smallest drusen were not round, radially distributed, mostly localized temporally to the macula. FAF revealed an intense autofluorescence of large drusen. On both FA and ICGA, large round drusen turned to hyperfluorescent in the late phase, while small radial drusen progressively decreased their fluorescence. OCT showed the large round drusen as focal or diffuse deposition of hyperreflective material between the RPE and Bruch membrane within the macula, determining focal dome-shaped or diffuse RPE elevation respectively, and the small radial drusen, which ranged from irregular slight thickening of the RPE/Bruch membrane complex to sawtooth RPE elevation. In three patients (six eyes) that underwent microperimetry and PHP, there was a good correspondence between macular sensitivity and PHP score. Functional impairment correlated topographically to sub-RPE deposition of drusenoid material.
   In this series, large round drusen of Malattia Leventinese appeared similar to drusen in age-related macular degeneration, while small radial drusen of Malattia Leventinese shared similarities with early-onset cuticular drusen.
C1 [Querques, Giuseppe; Guigui, Benjamin; Leveziel, Nicolas; Querques, Lea; Souied, Eric H.] Univ Paris Est Creteil, Dept Ophthalmol, Ctr Hosp Intercommunal Creteil, F-94000 Creteil, France.
   [Querques, Lea; Bandello, Francesco] Univ Vita Salute San Raffaele, Hosp San Raffaele, Dept Ophthalmol, Milan, Italy.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele
RP Querques, G (通讯作者)，Univ Paris Est Creteil, Dept Ophthalmol, Ctr Hosp Intercommunal Creteil, 40 Ave Verdun, F-94000 Creteil, France.
EM giuseppe.querques@hotmail.it
RI bandello, francesco/AAH-2405-2019
OI bandello, francesco/0000-0003-3238-9682; Querques,
   Giuseppe/0000-0002-3292-9581; Nicolas, Leveziel/0000-0001-8533-9457
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NR 32
TC 14
Z9 15
U1 0
U2 7
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 2013
VL 251
IS 3
BP 705
EP 714
DI 10.1007/s00417-012-2106-5
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 096PY
UT WOS:000315418000012
PM 22814526
DA 2022-11-30
ER

PT J
AU Manevitch, Z
   Lewis, A
   Levy, C
   Zeira, E
   Banin, E
   Manevitch, A
   Khatchatouriants, A
   Pe'er, J
   Galun, E
   Hemo, I
AF Manevitch, Zakhariya
   Lewis, Aaron
   Levy, Carol
   Zeira, Evelyne
   Banin, Eyal
   Manevitch, Alexandra
   Khatchatouriants, Artium
   Pe'er, Jacob
   Galun, Eithan
   Hemo, Itzhak
TI Subsurface Femtosecond Tissue Alteration: Selectively Photobleaching
   Macular Degeneration Pigments in Near Retinal Contact
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID LASER; RESOLUTION
AB This paper uses advances in the ultrafast manipulation of light to address a general need in medicine for a clinical approach that can provide a solution to a variety of disorders requiring subsurface tissue manipulation with ultralow collateral damage. Examples are age-related macular degeneration (AMD), fungal infections, tumors surrounded by overlying tissue, cataracts, etc. Although lasers have revolutionized the use of light in clinical settings, most lasers employed in medicine cannot address such problems of depth-selective tissue manipulation. This arises from the fact that they are mostly based on one photon based laser tissue interactions that provide a cone of excitation where the energy density is sufficiently high to excite heat or fluorescence in the entire cone. Thus, it is difficult to excite a specific depth of a tissue without affecting the overlying surface. However, the advent of femtosecond (fs) lasers has caused a revolution in multiphoton microscopy (Zipfel et al. Nat. Biotechnol. 2003, 21, 1369-1377; Denk et al. Science 1990, 248, 73-76) and fabrication (Kawata et al. Nature 2001, 412, 697-698). With such lasers, the photon energy density is only high enough for multiphoton processes in the focal volume, and this opens a new direction to address subsurface tissue manipulation. Here we show in an AMD animal model, Ccr2 KO knockout mutant mice, noninvasive, selective fs two-photon photobleaching of pigments associated with AMD that accumulate under and in ultraclose proximity to the overlying retina. Pathological evidence is presented that indicates the lack of collateral damage to the overlying retina or other surrounding tissue.
C1 [Manevitch, Zakhariya; Lewis, Aaron; Manevitch, Alexandra; Khatchatouriants, Artium] Hebrew Univ Jerusalem, Div Appl Phys, Sch Engn, IL-91904 Jerusalem, Israel.
   [Manevitch, Zakhariya; Lewis, Aaron; Banin, Eyal; Manevitch, Alexandra; Khatchatouriants, Artium; Pe'er, Jacob; Hemo, Itzhak] Hebrew Univ Jerusalem, Dept Ophthalmol, IL-91904 Jerusalem, Israel.
   [Manevitch, Zakhariya; Lewis, Aaron; Banin, Eyal; Manevitch, Alexandra; Khatchatouriants, Artium; Pe'er, Jacob; Hemo, Itzhak] Hebrew Univ Jerusalem, Hadassah Laser Ctr, IL-91904 Jerusalem, Israel.
   [Levy, Carol; Zeira, Evelyne; Galun, Eithan] Hebrew Univ Jerusalem, Goldyne Savad Inst Gene Therapy, IL-91904 Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem; Hebrew
   University of Jerusalem; Hebrew University of Jerusalem
RP Lewis, A (通讯作者)，Hebrew Univ Jerusalem, Div Appl Phys, Sch Engn, IL-91904 Jerusalem, Israel.
EM lewisu@vms.huji.ac.il
RI Galun, Eithan/AAD-9117-2022
OI Galun, Eithan/0000-0002-6243-6702
FU Horowitz Trust; Infrastructure Grant Program of the Israel Ministry of
   Science
FX This paper is dedicated to my (AL) postdoctoral mentor, Professor Harold
   Scheraga, who saw in me in a brief personal interview some 41 years ago
   an opportunity to mold a scientist. He thus gave me an opportunity to
   come to Cornell University and be introduced to first-rate science. He
   gave me the freedom to think of new ideas no matter what he had in mind
   for me and permitted me to initiate my first steps in the exploration of
   the physical processes that govern the interaction of light with
   biological materials that are critical in many biophysical
   investigations. I see the present paper as a pinnacle of some of these
   ideas where the manipulation of light, which I have focused on in my
   career and is so powerful in biophysics, is extended to a possible
   clinical application. This is the sweetest undertone of the biophysics I
   learnt from Professor Scheraga where the goal of directly helping
   mankind is highlighted. Thank you Professor Scheraga for the great
   opportunity you gave me and for the inspiration you and your wonderful
   "Woman of Valor" Miriam were for me and my family. As we say in Israel,
   we hope that you live in health and happiness until 120 and continue to
   inspire us with your science. The authors would also like to thank the
   Horowitz Trust and the Infrastructure Grant Program of the Israel
   Ministry of Science for financial support.
CR Ambati J, 2003, NAT MED, V9, P1390, DOI 10.1038/nm950
   Collins HA, 2008, NAT PHOTONICS, V2, P420, DOI 10.1038/nphoton.2008.100
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NR 11
TC 1
Z9 1
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
EI 1520-5207
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUN 14
PY 2012
VL 116
IS 23
BP 6945
EP 6951
DI 10.1021/jp300355m
PG 7
WC Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA 959ZG
UT WOS:000305356100040
PM 22482826
DA 2022-11-30
ER

PT J
AU Burzykowski, T
   Buyse, M
AF Burzykowski, Tomasz
   Buyse, M.
TI The correlation structure of longitudinal measurements of vision in
   patients with macular degeneration
SO PHARMACEUTICAL STATISTICS
LA English
DT Article
DE visual acuity; longitudinal data; variance function; correlation
   structure
AB Background: In age-related macular degeneration (ARMD) trials, the FDA-approved endpoint is the loss (or gain) of at least three lines of vision as compared to baseline. The use of such a response endpoint entails a potentially severe loss of information. A more efficient strategy could be obtained by using longitudinal measures of the change in visual acuity. In this paper we investigate, by using data from two randomized clinical trials, the mean and variance-covariance structures of the longitudinal measurements of the change in visual acuity.
   Methods: Individual patient data were collected in 234 patients in a randomized trial comparing interferon-a with placebo and in 1181 patients in a randomized trial comparing three active doses of pegaptanib with sham. A linear model for longitudinal data was used to analyze the repeated measurements of the change in visual acuity.
   Results: For both trials, the data were adequately summarized by a model that assumed a quadratic trend for the mean change in visual acuity over time, a power variance function, and an antedependence correlation structure. The power variance function was remarkably similar for the two datasets and involved the square root of the measurement time.
   Conclusions: The similarity of the estimated variance functions and correlation structures for both datasets indicates that these aspects may be a genuine feature of the measurements of changes in visual acuity in patients with ARMD. The feature can be used in the planning and analysis of trials that use visual acuity as the clinical endpoint of interest. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Burzykowski, Tomasz; Buyse, M.] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat I BioSt, B-3590 Diepenbeek, Belgium.
   [Burzykowski, Tomasz; Buyse, M.] IDDI, Louvain, Belgium.
C3 Hasselt University; International Drug Development Institute
RP Burzykowski, T (通讯作者)，Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat I BioSt, Bldg D, B-3590 Diepenbeek, Belgium.
EM tomasz.burzykowski@uhasselt.be
RI Buyse, Marc/J-4658-2013; Burzykowski, Tomasz/T-2222-2018
OI Burzykowski, Tomasz/0000-0003-3378-975X; Buyse, Marc/0000-0002-4559-0994
FU IAP research network of the Belgian government (Belgian Science Policy)
   [P6/03]
FX The authors are grateful to the pharmaceutical companies Roche,
   OSI/Eyetech, and Pfizer for providing individual patient data for the
   trials used in this analysis. Prof. Burzykowski acknowledges financial
   support from the IAP research network nr P6/03 of the Belgian government
   (Belgian Science Policy).
CR Beck RW, 2007, OPHTHALMOLOGY, V114, P1804, DOI 10.1016/j.ophtha.2007.06.047
   GRAGOUDAS AS, 2004, J MED, V351, P2805
   Guyer DR, 1997, ARCH OPHTHALMOL-CHIC, V115, P865
   Molenberghs G., 2000, LINEAR MIXED MODELS
   *SAS I, 2003, SAS STATS US GUID PR
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NR 7
TC 3
Z9 3
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1539-1604
EI 1539-1612
J9 PHARM STAT
JI Pharm. Stat.
PD MAR-APR
PY 2011
VL 10
IS 2
BP 115
EP 121
DI 10.1002/pst.419
PG 7
WC Pharmacology & Pharmacy; Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Mathematics
GA 749ZQ
UT WOS:000289512800005
PM 20146243
OA Green Published
DA 2022-11-30
ER

PT J
AU Waisbourd, M
   Goldstein, M
   Loewenstein, A
AF Waisbourd, Michael
   Goldstein, Michaella
   Loewenstein, Anat
TI National Survey of the Ophthalmic Use of Anti-Vascular Endothelial
   Growth Factor Drugs in Israel
SO ISRAEL MEDICAL ASSOCIATION JOURNAL
LA English
DT Article
DE bevacizumab; ranibizumab; anti-vascular endothelial growth factor;
   national survey; guidelines
ID MACULAR DEGENERATION; INTRAVITREAL INJECTION; RANIBIZUMAB;
   PHOTOCOAGULATION; ENDOPHTHALMITIS
AB Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin (R)) and ranibizumab (Lucent's (R)) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.
   Objectives: To describe the routine practices of retinal specialists in Israel regarding anti-VEGF drug treatment.
   Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.
   Result: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient's socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series lithe first one yielded no improvement in fluid status. The routine practice for intravitreal injection (>80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.
   Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies. IMAJ2011; 13: 141-146
C1 [Waisbourd, Michael; Goldstein, Michaella; Loewenstein, Anat] Tel Aviv Univ, Dept Ophthalmol, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, Ramat Aviv, Israel.
C3 Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky
   Medical Center
RP Waisbourd, M (通讯作者)，Tel Aviv Sourasky Med Ctr, Dept Ophthalmol, 6 Weizmann St, IL-64239 Tel Aviv, Israel.
EM mwaisbourd@hotmail.com
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NR 22
TC 6
Z9 6
U1 0
U2 0
PU ISRAEL MEDICAL ASSOC JOURNAL
PI RAMAT GAN
PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136,
   ISRAEL
SN 1565-1088
J9 ISR MED ASSOC J
JI Isr. Med. Assoc. J.
PD MAR
PY 2011
VL 13
IS 3
BP 141
EP 146
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 751FL
UT WOS:000289602800003
PM 21608333
DA 2022-11-30
ER

PT J
AU Huang, YX
   Xiang, LN
   Wang, YL
   Li, MM
   Hu, YX
AF Huang Ying-xiang
   Xiang Li-nan
   Wang Yan-ling
   Li Ming-min
   Hu Yong-xia
TI Long-term effect of prophylactic laser treatment for bilateral soft
   drusen
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE drusen; prophylactic laser treatment; macular thickness
ID MACULAR GRID PHOTOCOAGULATION; AGE-RELATED MACULOPATHY; CHOROIDAL
   NEOVASCULARIZATION; EXUDATIVE COMPLICATIONS; DEGENERATION; HEMODYNAMICS
AB Background Large drusen is a known risk factor for the development of late complications of age-related macular degeneration (AMD) and drusen reduction has been found by our previous study. To prospectively evaluate the efficacy and safety of prophylactic laser treatment in Chinese patients with bilateral soft drusen, we examined the structure and function of the macula 8 years after treatment.
   Methods Ten patients with more than 10 soft drusen (> 125 mm) and best corrected visual acuity >= 20/25 in each eye participated in the study. One eye, with relatively more drusen, was exposed to an argon laser (514 nm) to achieve a barely visible retinal lesion. The contralateral eye was used as a control. Fluorescein angiography, Amsler tests, Fourier-domain optical coherence tomography and visual evoked potential tests were carried out 8 years later.
   Results No choroidal neovascularization was seen in the laser-treated eyes or control eyes. There were no significant differences in visual acuity or P100 latency and amplitude between the laser treated eyes and contralateral eyes (t=1.685, 1.184; P > 0.05). The thickness of the retinal pigment epithelium of the treated eyes was less than that of the contralateral eyes (t=-4.540; P < 0.05). The full retinal thickness in treated eyes was slightly, but insignificantly, reduced relative to contralateral eyes (t=-1.746; P > 0.05).
   Conclusions The treatment was associated with a reduction in retinal pigment epithelium thickness elevation compared with the contralateral eyes. Macular function was not impaired. (ChiCTR-TNRC-00000221) Chin Med J 2011;124(4):541-545
C1 [Huang Ying-xiang; Xiang Li-nan; Wang Yan-ling; Li Ming-min; Hu Yong-xia] Capital Med Univ, Beijing Friendship Hosp, Dept Ophthalmol, Beijing 100050, Peoples R China.
C3 Capital Medical University
RP Huang, YX (通讯作者)，Capital Med Univ, Beijing Friendship Hosp, Dept Ophthalmol, Beijing 100050, Peoples R China.
EM bshuang@163.com
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NR 16
TC 2
Z9 2
U1 0
U2 3
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD FEB 20
PY 2011
VL 124
IS 4
BP 541
EP 545
DI 10.3760/cma.j.issn.0366-6999.2011.04.011
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 729ZF
UT WOS:000287992500011
PM 21362278
DA 2022-11-30
ER

PT J
AU Hohn, F
   Mirshahi, A
AF Hoehn, Fabian
   Mirshahi, Alireza
TI Impact of injection techniques on intraocular pressure (IOP) increase
   after intravitreal ranibizumab application
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Intraocular pressure (IOP); Ranibizumab (Lucentis (R)); Age-related
   macular degeneration (AMD); Injection techniques
ID MACULAR DEGENERATION; TRIAMCINOLONE ACETONIDE; UNITED-STATES;
   BLOOD-FLOW; BEVACIZUMAB; TRENDS; POPULATION; PEGAPTANIB; THERAPY
AB To examine the influence of different intravitreous injection techniques on the short-term intraocular pressure (IOP) in patients with exudative age-related macular degeneration (AMD) receiving 0.05 ml ranibizumab (LucentisA (R)) in the supine position.
   Forty-five eyes (45 patients, 16 male, 29 female, mean age: 78 years) received intravitreal ranibizumab injections for treatment of exudative AMD (0.05 ml = 0.5 mg). A total of 31 patients received a standard straight scleral incision, and 14 were injected using the tunneled sclera technique. IOP was measured by Schiotz tonometry immediately pre-and postoperatively, and the amount of subconjunctival reflux was documented using a semi-quantitative scale. Twenty-three eyes were phakic, and the remaining 22 were pseudophakic. No history of glaucoma was present. The Wilcoxon matched-pairs test was used for comparisons.
   The mean preoperative IOP was 22.4 +/- 5.5 mmHg in the supine position. Immediately after the injection, the IOP increased to 47.9 +/- 15.1 (range 23-82). The mean difference between preoperative IOP and immediately after the injection was 25.5 +/- 13.6 mmHg. The mean IOP increase in eyes receiving a standard straight scleral incision was 21.9 +/- 14.2 mmHg (median 22.3) versus 33.5 +/- 7.2 mmHg (median 34.7) in the tunneled scleral incision group (p = 0.001).
   IOP increased significantly in a considerable number of patients after receiving 0.05-ml intravitreal ranibizumab injections. This increase was dependent on the intravitreal injection technique and was significantly higher if a tunneled scleral injection was performed.
C1 [Hoehn, Fabian; Mirshahi, Alireza] Ludwigshafen Hosp, Dept Ophthalmol, D-67063 Ludwigshafen, Germany.
   [Mirshahi, Alireza] J Gutenberg Univ Hosp, Dept Ophthalmol, Mainz, Germany.
C3 Ludwigshafen Hospital
RP Hohn, F (通讯作者)，Ludwigshafen Hosp, Dept Ophthalmol, Bremserstr 79, D-67063 Ludwigshafen, Germany.
EM dr.hoehn@web.de
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NR 25
TC 22
Z9 22
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2010
VL 248
IS 10
BP 1371
EP 1375
DI 10.1007/s00417-010-1382-1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 641WU
UT WOS:000281162900002
PM 20407785
DA 2022-11-30
ER

PT J
AU Cohen, SY
AF Cohen, Salomon Y.
TI ANTI-VEGF DRUGS AS THE 2009 FIRST-LINE THERAPY FOR CHOROIDAL
   NEOVASCULARIZATION IN PATHOLOGIC MYOPIA
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Review
DE myopia; choroidal neovascularization; bevacizumab; ranibizumab;
   antivascular endothelial growth factor
ID INTRAVITREAL BEVACIZUMAB AVASTIN; COMBINED PHOTODYNAMIC THERAPY; OPTICAL
   COHERENCE TOMOGRAPHY; TRANSPUPILLARY THERMOTHERAPY; LASER
   PHOTOCOAGULATION; SURGICAL REMOVAL; NATURAL-HISTORY; VERTEPORFIN; AGE;
   SECONDARY
AB Background: Pathologic myopia is the second cause of choroidal neovascularization, after age-related macular degeneration (AMD), and the first cause in patients younger than 50 years. The current treatment of subfoveal myopic choroidal neovascularization (mCNV) is verteporfin photodynamic therapy, but its long-term effectiveness has been disappointing. Antivascular enclothelial growth factor (anti-VEGF) drugs are now widely used not only to treat choroidal neovascularization in AMD but also for choroidal neovascularization in other conditions. This review summarizes the data supplied by published case series studies about anti-VEGF therapy in mCNV.
   Methods: Analysis of the current literature allowed discussion of the optimal parameters for mCNV treatment by anti-VEGF, including the choice of anti-VEGF drug, its dose, the treatment protocol, and indications for retreatment.
   Results: To date, the results of intravitreal bevacizumab or ranibizumab for mCNV have been reported in at least 14 studies, but they were all pilot, monocentric, and noncomparative case series. Nevertheless, they provided useful information on >250 patients and showed similar results, with significant improvement of visual acuity and an excellent safety profile.
   Conclusion: Shifting from one treatment to another is always difficult in the absence of prospective and controlled comparative studies. However, in 2009, intravitreal ranibizumab or bevacizumab may be considered as first-line therapy for sub- and juxtafoveal mCNV for three reasons: the safety of anti-VEGF drugs and intravitreal injection procedures; the disappointing long-term results of other therapies, including verteporfin treatment; and the excellent convergent results of anti-VEGF therapy in all pilot studies. RETINA 29:1062-1066, 2009
C1 [Cohen, Salomon Y.] Ctr Ophtalmol Imagerie & Laser, F-75015 Paris, France.
   [Cohen, Salomon Y.] Univ Paris 07, Dept Ophthalmol, AP HP, Hop Lariboisiere, Paris, France.
C3 Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Lariboisiere-Fernand-Widal - APHP; UDICE-French Research Universities;
   Universite Paris Cite
RP Cohen, SY (通讯作者)，Ctr Ophtalmol Imagerie & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
EM sycohen@Club-internet.fr
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NR 67
TC 82
Z9 89
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 SEP
PY 2009
VL 29
IS 8
BP 1062
EP 1066
DI 10.1097/IAE.0b013e3181b1bb1a
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 497IG
UT WOS:000270051800002
PM 19734760
DA 2022-11-30
ER

PT J
AU Nakai, K
   Fainaru, O
   Bazinet, L
   Pakneshan, P
   Benny, O
   Pravda, E
   Folkman, J
   D'Amato, RJ
AF Nakai, Kei
   Fainaru, Ofer
   Bazinet, Lauren
   Pakneshan, Pouya
   Benny, Ofra
   Pravda, Elke
   Folkman, Judah
   D'Amato, Robert J.
TI Dendritic cells augment choroidal neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; AUTOIMMUNE UVEORETINITIS; MURINE MODEL;
   MACROPHAGES; MICE; EYE; VASCULOGENESIS; INFLAMMATION; PRECURSORS;
   EXPRESSION
AB PURPOSE. Dendritic cells (DCs) are innate immune cells that have recently been shown to support angiogenesis in tumors, endometriosis, and lymph nodes. A major cause of legal blindness is wet age-related macular degeneration (wet ARMD), wherein abnormal blood vessels grow under the retina, an abnormality also referred to as choroidal neovascularization (CNV). The purpose of the present study was to investigate the role of DCs in the development of CNV.
   METHODS. Laser photocoagulation was used to induce CNV in C57BL/6J mice. The authors analyzed CNV lesions for the presence of DCs using flow cytometry and immunostaining at designated times. They also analyzed the effects of intravenous DC transplantation on CNV development by measuring the lesion area using confocal microscopy 1 week after laser injury.
   RESULTS. The authors analyzed CNV lesions for the presence of DCs by flow cytometry and observed that CD11c(+) major histocompatibility complex (MHC) class II(+) DCs transiently infiltrated the CNV lesions, reaching a peak at 2 to 4 days after laser injury. These DCs were mostly immature (CD11c(+) MHCII(low)) and expressed vascular endothelial growth factor receptor 2. Immunostaining of laser-induced CNV lesions confirmed that DCs are located at the sites of newly formed blood vessels. Intravenously injected DCs incorporated into the CNV lesions. However, only immature DCs enhanced CNV size.
   CONCLUSIONS. These results suggest a role for DCs in promoting angiogenesis and lesion growth in laser-induced CNV. The present data suggest that DCs may represent potential cellular targets for therapeutic intervention in wet ARMD.
C1 [Nakai, Kei; Fainaru, Ofer; Bazinet, Lauren; Pakneshan, Pouya; Benny, Ofra; Pravda, Elke; Folkman, Judah; D'Amato, Robert J.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
   [D'Amato, Robert J.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
C3 Harvard University; Boston Children's Hospital; Harvard University;
   Harvard Medical School
RP D'Amato, RJ (通讯作者)，Childrens Hosp, Dept Surg, Vasc Biol Program, 300 Longwood Ave,Karp 11-210, Boston, MA 02115 USA.
EM robert.damato@childrens.harvard.edu
RI Benny, Ofra/AAB-3294-2021
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NR 29
TC 26
Z9 30
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 AUG
PY 2008
VL 49
IS 8
BP 3666
EP 3670
DI 10.1167/iovs.07-1640
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 330NW
UT WOS:000257951100054
PM 18408184
DA 2022-11-30
ER

PT J
AU Wahl, HW
   Schilling, O
   Becker, S
   Burmedi, D
AF Wahl, HW
   Schilling, O
   Becker, S
   Burmedi, D
TI A German research program on the psychosocial adaptation to age-related
   vision impairment - Recent findings based on a control theory approach
SO EUROPEAN PSYCHOLOGIST
LA English
DT Article
DE age-related visual impairment; psychosocial adaptation; psychological
   control
ID OLDER-ADULTS
AB The present paper argues that psychosocial adaptation in visually impaired older adults is substantially mediated by the use of control strategies. Our first research question against this general conceptual background is whether there are differences between visually impaired older adults and unimpaired older adults in control strategies or variables considered as major adaptational outcome variables in the behavioral and emotional domain. Our second research question addresses the kind of relations between control strategies and outcomes in visually impaired older adults. The findings are based on a sample of N = 90 visually impaired older adults (mean age: 79.5;64 women, 26 men; all suffering from, age-related macular degeneration; visual acuity less than 20/70) as well as a reference group of N = 35 unimpaired older adults. All participants underwent a standardized psychological assessment program based on internationally well-established measures. Findings support the notion that differences between the visually impaired and the unimpaired are most pronounced in behavioral indicators such as activities of daily living and leisure activity level, while control strategies were different in only one instance, pointing to a stronger tendency in visually impaired persons toward compensatory control efforts. Furthermore, selective control, which is investing time and effort to change one's environment, covaries most strongly with behavioral outcomes, while selective control aimed to strengthen the motivational commitment to important life goals covaries most strongly with emotional adaptation. The results generally illustrate the heuristic fruitfulness of psychological control theory in understanding adaptation in visually impaired older adults.
C1 Heidelberg Univ, German Ctr Res Aging, D-69115 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Wahl, HW (通讯作者)，Heidelberg Univ, German Ctr Res Aging, Bergheimer Str 20, D-69115 Heidelberg, Germany.
EM wahl@dzfa.uni-heidelberg.de
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NR 24
TC 10
Z9 10
U1 0
U2 4
PU HOGREFE & HUBER PUBLISHERS
PI KIRKLAND
PA PO BOX 2487, KIRKLAND, WA 98083-2487 USA
SN 1016-9040
EI 1878-531X
J9 EUR PSYCHOL
JI Eur. Psychol.
PD SEP
PY 2003
VL 8
IS 3
BP 168
EP 177
DI 10.1027//1016-9040.8.3.168
PG 10
WC Psychology, Multidisciplinary
WE Social Science Citation Index (SSCI)
SC Psychology
GA 730NB
UT WOS:000185835900005
DA 2022-11-30
ER

PT J
AU Elner, SG
   Elner, VM
   Kindzelskii, AL
   Horino, K
   Davis, HR
   Todd, RF
   Glagov, S
   Petty, HR
AF Elner, SG
   Elner, VM
   Kindzelskii, AL
   Horino, K
   Davis, HR
   Todd, RF
   Glagov, S
   Petty, HR
TI Human RPE cell lysis of extracellular matrix: functional urokinase
   plasminogen activator receptor (uPAR), collagenase and elastase
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelium; uPAR; collagenase; proteolysis; migration;
   resonance energy transfer
ID CANCER METASTASIS; GENE-EXPRESSION; PROTEOLYSIS; INHIBITOR;
   METALLOPROTEINASES; LOCALIZATION; INTEGRIN; INVASION; IDENTIFICATION;
   ANGIOGENESIS
AB Age-related macular degeneration (ARMD), proliferative vitreoretinopathy (PVR) and uveitis are characterized by RPE motility through the ECM of retinal lesions. The purpose of this study was to test the hypothesis that multiple proteolytic systems are functionally intact at the HRPE surface and peri-cellular region and that these activities are differentially modulated by IL-1beta. HRPE cells were evaluated: (1) as individual cells or cell extracts, (2) during migration across three-dimensional ECM-like layers and (3) in tissue sections. The urokirase plasminogen activator receptor (uPAR; CD87) was detected on HRPE cells as well as its functional activity. Although uPAR was associated with CD11b (CR3) on live resting cells, polarized migratory HRPE cells were found to dissociate uPAR from CR3; uPAR then translocated to anterior pole of the cell, where it enhanced PAI-1-inhibitable local proteolytic activity. The relative contribution of uPAR and collagenase in HRPE migration was evaluated using three-dimensional gelatin matrices. Interestingly, uPAR/uPA was found to play a key role in migration across these layers. IL-1 upregulated uPAR, collagenase, and elastase activities, suggesting that cytokines may affect the invasive program of HRPE cells in vivo. Immunohistochemistry for uPAR was performed in sections of human retina. Immunoreactive uPAR was present along the HRPE basolateral membrane in retinal sections and in sections of diseased retinal tissue at an enhanced level. Our results suggest that multiple proteolytic systems are present in association with HRPE and that the uPAR/uPA system may be particularly important. (C) 2003 Elsevier Science Ltd. All rights reserved.
C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
   Univ Michigan, Dept Pathol, Kellogg Eye Ctr, Ann Arbor, MI 48105 USA.
   Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   Univ Michigan, Kellogg Eye Ctr, Dept Med, Ann Arbor, MI 48105 USA.
   Univ Michigan, Kellogg Eye Ctr, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan; University of Chicago;
   University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan
RP Elner, VM (通讯作者)，Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM velner@umich.edu
RI Todd, Robert/GWM-4486-2022
OI Elner, Victor/0000-0001-7708-1898
FU NATIONAL EYE INSTITUTE [R01EY009441] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI027409]
   Funding Source: NIH RePORTER; NEI NIH HHS [EY007003, EY-09441] Funding
   Source: Medline; NIAID NIH HHS [AI27409] Funding Source: Medline
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NR 39
TC 22
Z9 24
U1 0
U2 0
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 2003
VL 76
IS 5
BP 585
EP 595
DI 10.1016/S0014-4835(03)00028-9
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 675RH
UT WOS:000182708700006
PM 12697422
DA 2022-11-30
ER

PT J
AU Sayanagi, K
   Fujimoto, S
   Hara, C
   Fukushima, Y
   Kawasaki, R
   Sato, S
   Sakaguchi, H
   Nishida, K
AF Sayanagi, Kaori
   Fujimoto, Satoko
   Hara, Chikako
   Fukushima, Yoko
   Kawasaki, Ryo
   Sato, Shigeru
   Sakaguchi, Hirokazu
   Nishida, Kohji
TI Characteristics of choroidal neovascularization in elderly eyes with
   high myopia not meeting the pathologic myopia definition
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; LACQUER CRACKS; RANIBIZUMAB; AFLIBERCEPT;
   PREVALENCE; BEVACIZUMAB
AB The META-Analysis of Pathologic Myopia Study group proposed a new classification system for myopic maculopathy (MM) with pathologic myopia (PM) defined as MM equal to/more serious than diffuse atrophy or the presence of plus lesions and myopic choroidal neovascularization (mCNV) defined as CNV in the eye with PM. However, CNV in elderly eyes with high myopia (HM) not meeting the PM definition (high-myopia CNV) are not classified as age-related macular degeneration (nAMD) or mCNV. This retrospective study included 39 eyes with high-myopia CNV, 20 eyes with mCNV, and 20 eyes with AMD. All patients were at least 40 years old. We compared the clinical characteristics and treatment outcomes among three groups. The high-myopia CNV group had significantly more CNV types, shorter axial length and fewer lacquer cracks (P < 0.0001, respectively); larger baseline greatest linear dimension (P = 0.0002), more fellow-eye drusen (P = 0.0106), more men (P = 0.0029), and more treatments (24 months, P = 0.0098) compared to the mCNV group. Compared with the nAMD group, the high-myopia CNV group was significantly younger (P = 0.0041), and had fewer CNV types (P = 0.0316), more lacquer cracks (P = 0.0079) and fewer drusen (affected-eye, P = 0.0006 and fellow-eye, P = 0.0222), and fewer treatments (24 months, P = 0.0030). Because the CNV in elderly eyes with HM not meeting the PM definition is classified as combined mCNV and nAMD, the clinical and angiographic findings are critical to determine the treatment strategy.
C1 [Sayanagi, Kaori; Fujimoto, Satoko; Hara, Chikako; Fukushima, Yoko; Kawasaki, Ryo; Sato, Shigeru; Sakaguchi, Hirokazu; Nishida, Kohji] Osaka Univ, Dept Ophthalmol E7, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Fujimoto, Satoko] Hawaii Macula & Retina Inst, 98-1079 Moanalua Rd,Suite 470, Honolulu, HI 96701 USA.
   [Nishida, Kohji] Osaka Univ, Inst Open & Transdisciplinary Res Initiat OTRI, Integrated Frontier Res Med Sci Div, Suita, Osaka, Japan.
C3 Osaka University; Osaka University
RP Sayanagi, K (通讯作者)，Osaka Univ, Dept Ophthalmol E7, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM sayapon@aol.com
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NR 37
TC 0
Z9 0
U1 1
U2 1
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 13
PY 2022
VL 12
IS 1
AR 13795
DI 10.1038/s41598-022-18074-2
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3T5PQ
UT WOS:000840326500017
PM 35963943
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Armento, A
   Schmidt, TL
   Sonntag, I
   Merle, DA
   Jarboui, MA
   Kilger, E
   Clark, SJ
   Ueffing, M
AF Armento, Angela
   Schmidt, Tiziana L.
   Sonntag, Inga
   Merle, David A.
   Jarboui, Mohamed Ali
   Kilger, Ellen
   Clark, Simon J.
   Ueffing, Marius
TI CFH Loss in Human RPE Cells Leads to Inflammation and Complement System
   Dysregulation via the NF-kappa B Pathway
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration (AMD); retinal pigment epithelium (RPE)
   cells; complement factor H (CFH); inflammation; cytokines; NF-kappa B
   pathway
ID RETINAL-PIGMENT EPITHELIUM; FACTOR-H Y402H; MACULAR DEGENERATION; BRUCHS
   MEMBRANE; GM-CSF; POLYMORPHISM; ACTIVATION; ABNORMALITIES; SENESCENCE;
   EXPRESSION
AB Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is a degenerative disease of the macula, where retinal pigment epithelium (RPE) cells are damaged in the early stages of the disease, and chronic inflammatory processes may be involved. Besides aging and lifestyle factors as drivers of AMD, a strong genetic association to AMD is found in genes of the complement system, with a single polymorphism in the complement factor H gene (CFH), accounting for the majority of AMD risk. However, the exact mechanism of CFH dysregulation confers such a great risk for AMD and its role in RPE cell homeostasis is unclear. To explore the role of endogenous CFH locally in RPE cells, we silenced CFH in human hTERT-RPE1 cells. We demonstrate that endogenously expressed CFH in RPE cells modulates inflammatory cytokine production and complement regulation, independent of external complement sources, or stressors. We show that loss of the factor H protein (FH) results in increased levels of inflammatory mediators (e.g., IL-6, IL-8, GM-CSF) and altered levels of complement proteins (e.g., C3, CFB upregulation, and C5 downregulation) that are known to play a role in AMD. Moreover, our results identify the NF-kappa B pathway as the major pathway involved in regulating these inflammatory and complement factors. Our findings suggest that in RPE cells, FH and the NF-kappa B pathway work in synergy to maintain inflammatory and complement balance, and in case either one of them is dysregulated, the RPE microenvironment changes towards a proinflammatory AMD-like phenotype.
C1 [Armento, Angela; Schmidt, Tiziana L.; Sonntag, Inga; Merle, David A.; Jarboui, Mohamed Ali; Kilger, Ellen; Clark, Simon J.; Ueffing, Marius] Eberhard Karls Univ Tubingen, Inst Ophthalm Res, Dept Ophthalmol, D-72076 Tubingen, Germany.
   [Merle, David A.] Med Univ Graz, Dept Ophthalmol, A-8036 Graz, Austria.
   [Clark, Simon J.; Ueffing, Marius] Eberhard Karls Univ Tubingen, Univ Eye Clin, Dept Ophthalmol, D-72076 Tubingen, Germany.
   [Clark, Simon J.] Univ Manchester, Fac Biol Med & Hlth, Lydia Becker Inst Immunol & Inflammat, Manchester M13 9PT, Lancs, England.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Medical University of Graz; Eberhard Karls University of
   Tubingen; Eberhard Karls University Hospital; University of Manchester
RP Armento, A; Ueffing, M (通讯作者)，Eberhard Karls Univ Tubingen, Inst Ophthalm Res, Dept Ophthalmol, D-72076 Tubingen, Germany.; Ueffing, M (通讯作者)，Eberhard Karls Univ Tubingen, Univ Eye Clin, Dept Ophthalmol, D-72076 Tubingen, Germany.
EM angela.armento@uni-tuebingen.de; TizianaLuisa@web.de;
   inga.sonntag@uni-tuebingen.de; david.merle@medunigraz.at;
   mohamed-ali.jarboui@uni-tuebingen.de; ellen.kilger@uni-tuebingen.de;
   simon.clark@uni-tuebingen.de; marius.ueffing@uni-tuebingen.de
RI Jarboui, Dr. Mohamed Ali/C-8496-2013
OI Jarboui, Dr. Mohamed Ali/0000-0002-5203-235X; Armento,
   Angela/0000-0002-6357-1500; Clark, Simon/0000-0001-8394-8355
FU fortune-Programm [2640-0-0]
FX Angela Armento is supported by the fortune-Programm (project number
   2640-0-0). This work was supported by donations from Jutta Emilie Paula
   Henny Granier and the Kerstan Foundation to Marius Ueffing and the
   Helmut Ecker Foundation to Simon J Clark.
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NR 69
TC 8
Z9 8
U1 2
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 AUG
PY 2021
VL 22
IS 16
AR 8727
DI 10.3390/ijms22168727
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA UG3IK
UT WOS:000689150400001
PM 34445430
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Gyorgy, BP
   Valentin, B
   Fanni, R
AF Gyorgy, Balazs Peter
   Valentin, Brodszky
   Fanni, Rencz
TI Health utility measurement by time trade-off method in Hungary
SO ORVOSI HETILAP
LA English
DT Article
DE time trade-off; health utility; quality-adjusted life year; QALY;
   cost-effectiveness
ID STATE UTILITIES; LIFE; DISEASE; VALUATION; EQ-5D; PREFERENCES;
   COUNTRIES; OUTCOMES; BURDEN; VALUES
AB Introduction: Time trade-off (TTO) is a widely used method to assess health-related quality of life and health utilities for economic evaluations of health technologies. Little is known about the use of TTO in the Hungarian context. Objective: To systematically summarize the existing literature on the method in Hungary.
   Method: In January 2020, we conducted a systematic literature search in three electronic databases (MEDLINE, Web of Science and the Hungarian Periodicals Table of Contents Database). Our inclusion criteria were: (1) original publications, which (2) measured utilities by using TTO, (3) from a Hungarian sample.
   Results: Nine publications containing seven original studies were included that reported utilities for 23 different health states in seven chronic diseases (age-related macular degeneration, chronic migraine, Crohn's disease, pemphigus, primary dysmenorrhoea, psoriasis and rheumatoid arthritis). Sample sizes ranged from 108 to 1996 respondents. Two studies used general population samples, another two used patient groups and three studies used both. Six studies used a form of conventional TTO and one used composite TTO method. The most frequent timeframe was 10 years (71%). The lowest mean utility was 0.34 (uncontrolled pemphigus vulgaris), while the highest was 0.94 (mild primary dysmenorrhoea). The overall proportion of non-traders ranged between 0 and 29% across studies.
   Conclusions: A growing number of studies are using TTO to assess utilities for chronic conditions from the general population or patients in Hungary. The majority of Hungarian TTO studies have met international quality standards. The assessment of TTO utilities is recommended also in other chronic conditions to assist health technology assessment.
C1 [Gyorgy, Balazs Peter; Valentin, Brodszky; Fanni, Rencz] Budapesti Corvinus Egyet, Egeszsegugyi Kozgazdasagtan Tanszek, Budapest, Hungary.
   [Gyorgy, Balazs Peter] Budapesti Corvinus Egyet, Gazdalkodastani Doktori Iskola, Budapest, Hungary.
   [Fanni, Rencz] Magyar Tud Acad, Premium Posztdoktori Kutatoi Program, Budapest, Hungary.
C3 Corvinus University Budapest; Corvinus University Budapest
RP Fanni, R (通讯作者)，Fovam Ter 8, H-1093 Budapest, Hungary.
EM fanni.rencz@uni-corvinus.hu
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NR 52
TC 0
Z9 0
U1 0
U2 2
PU AKADEMIAI KIADO ZRT
PI BUDAPEST
PA BUDAFOKI UT 187-189-A-3, H-1117 BUDAPEST, HUNGARY
SN 0030-6002
EI 1788-6120
J9 ORVOSI HETILAP
JI Orvosi Hetilap
PD APR
PY 2021
VL 162
IS 14
BP 542
EP 554
DI 10.1556/650.2021.32056
PG 13
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA RF7JX
UT WOS:000635017600003
PM 33784247
OA hybrid, Green Accepted
DA 2022-11-30
ER

PT J
AU Song, YM
   Ouchene, L
   Khan, AZ
AF Song, Youngmin
   Ouchene, Lydia
   Khan, Aarlenne Zein
TI Saccadic adaptation in the presence of artificial central scotomas
SO JOURNAL OF VISION
LA English
DT Article
DE saccadic adaptation; artificial scotoma; age-related macular
   degeneration; saccadic eye movements
ID EYE-MOVEMENTS; VISUAL ERROR; MACULAR DEGENERATION; SENSORY PREDICTION;
   SLEEP-DEPRIVATION; GAIN ADAPTATION; PERFORMANCE; IMPAIRMENT; MECHANISMS;
   RESPONSES
AB Saccadic adaptation can occur over a short period of time through a constant adjustment of the saccade target during the saccade, resulting in saccadic re-referencing, which directs the saccade to a location different from the target that elicited the saccade. Saccade re-referencing could be used to help patients with age-related macular degeneration to optimally use their residual visual function. However, it remains unknown whether saccade adaptation can take place in the presence of central scotomas (i.e., without central vision). We tested participants in two experiments in a conventional double-step paradigm with a central gaze-contingent artificial scotoma. Experiment 1 (N = 12) comprised a backward adaptation paradigm with no scotoma control, visible, and invisible 3 degrees diameter scotoma conditions. Experiment 2 (N = 13) comprised a forward adaptation paradigm with no scotoma control, invisible 2 degrees, and 4 degrees diameter scotoma conditions. In Experiment 1, we observed significant adaptation in both the visible and invisible scotoma conditions comparable to the control condition with no scotoma. This was the case even when the saccade landed such that the target was occluded by the scotoma. We observed that adaptation occurred based on peripheral viewing of the stepped target during the deceleration period. In Experiment 2, we found that both scotoma conditions showed adaptation again comparable to the control condition with no scotoma. We conclude that saccadic adaptation can occur with central scotomas, showing that it does not require central vision and can be driven primarily by peripheral retinal error.
C1 [Song, Youngmin] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada.
   [Song, Youngmin; Khan, Aarlenne Zein] Univ Montreal, Sch Optometry, Vis Attent & Act Lab, Montreal, PQ, Canada.
   [Ouchene, Lydia] McGill Univ, Fac Med, Montreal, PQ, Canada.
C3 McGill University; Universite de Montreal; McGill University
RP Khan, AZ (通讯作者)，Univ Montreal, Sch Optometry, Room 260-25,3744 Rue Jean Brillant, Montreal, PQ H3T 1P1, Canada.
EM aarlenne.khan@umontreal.ca
FU Canada Research Chair program; National Sciences and Engineering
   Research Council of Canada
FX AZK was funded by the Canada Research Chair program and the National
   Sciences and Engineering Research Council of Canada.
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NR 60
TC 0
Z9 0
U1 1
U2 2
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 2021
VL 21
IS 1
AR 8
DI 10.1167/jov.21.1.8
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA PV6IX
UT WOS:000610090900010
PM 33439238
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Lin, CY
   Lou, WS
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   Weng, KY
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   Hung, YW
   Chen, ZY
   Wang, MC
AF Lin, Chin-Yu
   Lou, Wan-Shiun
   Chen, Jyh-Chern
   Weng, Kuo-Yao
   Shih, Ming-Cheng
   Hung, Ya-Wen
   Chen, Zhu-Yin
   Wang, Mei-Chih
TI Bio-Compatibility and Bio-Insulation of Implantable Electrode Prosthesis
   Ameliorated by A-174 Silane Primed Parylene-C Deposited Embedment
SO MICROMACHINES
LA English
DT Article
DE interdigitated electrode; retinal prosthesis; parylene-C;
   bio-compatibility; bio-insulation
AB Microelectrodes for pain management, neural prosthesis or assistances have a huge medical demand, such as the application of pain management chip or retinal prosthesis addressed on age-related macular degeneration (AMD) and the retinitis pigmentosa (RP). Due to lifelong implanted in human body and direct adhesion of neural tissues, the electrodes and associated insulation materials should possess an ideal bio-compatibility, including non-cytotoxicity and no safety concern elicited by immune responses. Our goal intended to develop retinal prosthesis, an electrical circuit chip used for assisting neural electrons transmission on retina and ameliorating the retinal disability. Therefore, based on the ISO 10993 guidance for implantable medical devices, the electrode prosthesis with insulation material has to conduct bio-compatibility assessment including cytotoxicity, hemolysis, (skin) irritation and pathological implantation examinations. In this study, we manufactured inter-digitated electrode (IDE) chips mimic the electrode prosthesis through photolithography. The titanium and platinum composites were deposited onto a silicon wafer to prepare an electric circuit to mimic the electrode used in retinal prosthesis manufacture, which further be encapsulated to examine the bio-compatibility in compliance with ISO 10993 and ASTM guidance specifically for implantable medical devices. Parylene-C, polyimide and silicon carbide were selected as materials for electrode encapsulation in comparison. Our data revealed parylene-C coating showed a significant excellence on bio-insulation and bio-compatibility specifically addressed on implantable neuron stimulatory devices and provided an economic procedure to package the electrode prosthesis. Therefore, parylene C encapsulation should serve as a consideration for future application on retinal prosthesis manufacture and examination.
C1 [Lin, Chin-Yu; Chen, Zhu-Yin] China Med Univ, Inst New Drug Dev, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.
   [Lin, Chin-Yu] China Med Univ, Collage Biomed Engn, Master Program Biomed Engn, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.
   [Lou, Wan-Shiun; Shih, Ming-Cheng; Hung, Ya-Wen; Wang, Mei-Chih] Ind Technol Res Inst, Biomed Technol & Device Res Labs, 195,Sec 4,Chung Hsing Rd, Hsinchu 31057, Taiwan.
   [Chen, Jyh-Chern] ACE Biotek Co Ltd, 66,Shengyi 2nd Rd, Hsinchu 30261, Taiwan.
   [Weng, Kuo-Yao] Ind Technol Res Inst, Technol Transfer & Law Ctr, 195,Sec 4,Chung Hsing Rd, Hsinchu 31057, Taiwan.
C3 China Medical University Taiwan; China Medical University Taiwan;
   Industrial Technology Research Institute - Taiwan; Industrial Technology
   Research Institute - Taiwan
RP Lin, CY (通讯作者)，China Med Univ, Inst New Drug Dev, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.; Lin, CY (通讯作者)，China Med Univ, Collage Biomed Engn, Master Program Biomed Engn, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.; Wang, MC (通讯作者)，Ind Technol Res Inst, Biomed Technol & Device Res Labs, 195,Sec 4,Chung Hsing Rd, Hsinchu 31057, Taiwan.
EM geant@mail.cmu.edu.tw; WanShiunLou@itri.org.tw; jc_chen@acebiotek.com;
   allan_weng@itri.org.tw; hugoshiu@itri.org.tw; ya-wen@itri.org.tw;
   janet_emily_1@yahoo.com.tw; mcwang@itri.org.tw
RI Lin, Chin-Yu/AAH-1010-2021
OI Lin, Chin-Yu/0000-0003-2304-7381; Wang, Mei-Chih/0000-0003-0520-9316
FU Ministry of Economic Affairs, Taiwan [99-EC-17-D-02-11-1062]; China
   Medical University [CMU107-TU-08]; Ministry of Science and Technology,
   Taiwan; MOST [108-2622-E-039-002, MOST 108-2221-E-039-006-MY3]
FX This research was funded by by Ministry of Economic Affairs, Taiwan,
   under Grant No. 99-EC-17-D-02-11-1062, China Medical University
   CMU107-TU-08 and the Ministry of Science and Technology, Taiwan, under
   Grant No. MOST 108-2622-E-039-002 and MOST 108-2221-E-039-006-MY3.
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NR 31
TC 4
Z9 4
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-666X
J9 MICROMACHINES-BASEL
JI Micromachines
PD DEC
PY 2020
VL 11
IS 12
AR 1064
DI 10.3390/mi11121064
PG 16
WC Chemistry, Analytical; Nanoscience & Nanotechnology; Instruments &
   Instrumentation; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Science & Technology - Other Topics; Instruments &
   Instrumentation; Physics
GA PL4JR
UT WOS:000603090700001
PM 33266050
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ghareeb, AE
   Lako, M
   Steel, DH
AF Ghareeb, Ali E.
   Lako, Majlinda
   Steel, David H.
TI Coculture techniques for modeling retinal development and disease, and
   enabling regenerative medicine
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE biocompatible materials; cell transplantation; coculture techniques;
   microphysiological systems; organ culture techniques; organ-on-a-chip;
   organoids; retina; retinal degeneration; tissue transplantation
ID PLURIPOTENT STEM-CELLS; HONEYCOMB POROUS FILMS; FACTOR-H POLYMORPHISM;
   A-CHIP TECHNOLOGIES; PIGMENT EPITHELIUM; IN-VITRO; EXTRACELLULAR-MATRIX;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; VISUAL FUNCTION
AB Stem cell-derived retinal organoids offer the opportunity to cure retinal degeneration of wide-ranging etiology either through the study of in vitro models or the generation of tissue for transplantation. However, despite much work in animals and several human pilot studies, satisfactory therapies have not been developed. Two major challenges for retinal regenerative medicine are: (a) physical cell-cell interactions, which are critical to graft function, are not formed, and (b) the host environment does not provide suitable queues for development. Several strategies offer to improve the delivery, integration, maturation, and functionality of cell transplantation. These include minimally invasive delivery, biocompatible material vehicles, retinal cell sheets, and optogenetics. Optimizing several variables in animal models is practically difficult, limited by anatomical and disease pathology which is often different to humans, and faces regulatory and ethical challenges. High-throughput methods are needed to experimentally optimize these variables. Retinal organoids will be important to the success of these models. In their current state, they do not incorporate a representative retinal pigment epithelium (RPE)-photoreceptor interface nor vascular elements, which influence the neural retina phenotype directly and are known to be dysfunctional in common retinal diseases such as age-related macular degeneration. Advanced coculture techniques, which emulate the RPE-photoreceptor and RPE-Bruch's-choriocapillaris interactions, can incorporate disease-specific, human retinal organoids and overcome these drawbacks. Herein, we review retinal coculture models of the neural retina, RPE, and choriocapillaris. We delineate the scientific need for such systems in the study of retinal organogenesis, disease modeling, and the optimization of regenerative cell therapies for retinal degeneration.
C1 [Ghareeb, Ali E.; Steel, David H.] South Tyneside & Sunderland NHS Fdn Trust, Sunderland Eye Infirm, Sunderland, Durham, England.
   [Ghareeb, Ali E.; Lako, Majlinda; Steel, David H.] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England.
C3 Newcastle University - UK
RP Ghareeb, AE (通讯作者)，South Tyneside & Sunderland NHS Fdn Trust, Sunderland Eye Infirm, Sunderland, Durham, England.
EM ali.ghareeb@newcastle.ac.uk
OI Ghareeb, Ali/0000-0002-8552-3139
FU Fight for Sight; Medical Research Council; Biotechnology and Biological
   Sciences Research Council; European Research Council; Retina UK; Macular
   Society; BBSRC [BB/I02333X/1, BB/T004460/1] Funding Source: UKRI; MRC
   [MR/T017503/1] Funding Source: UKRI
FX Fight for Sight; Medical Research Council; Biotechnology and Biological
   Sciences Research Council; European Research Council; Retina UK; Macular
   Society
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NR 149
TC 7
Z9 7
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD DEC
PY 2020
VL 9
IS 12
BP 1531
EP 1548
DI 10.1002/sctm.20-0201
EA AUG 2020
PG 18
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA OX5SG
UT WOS:000556380000001
PM 32767661
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chen, AX
   Conti, TF
   Hom, GL
   Greenlee, TE
   Raimondi, R
   Briskin, IN
   Rich, CA
   Kampani, R
   Engel, R
   Sharma, S
   Talcott, KE
   Singh, RP
AF Chen, Andrew X.
   Conti, Thais F.
   Hom, Grant L.
   Greenlee, Tyler E.
   Raimondi, Raffaele
   Briskin, Isaac N.
   Rich, Collin A.
   Kampani, Reecha
   Engel, Robert
   Sharma, Sumit
   Talcott, Katherine E.
   Singh, Rishi P.
TI Functional imaging of mitochondria in retinal diseases using
   flavoprotein fluorescence
SO EYE
LA English
DT Review
ID PIGMENT EPITHELIUM-CELLS; OXIDATIVE STRESS; FUNDUS AUTOFLUORESCENCE;
   MACULAR DEGENERATION; PROGRESSIVE STAGES; DNA HAPLOGROUPS;
   GANGLION-CELLS; APOPTOSIS; DAMAGE; LENS
AB Mitochondria are critical for cellular energy production and homeostasis. Oxidative stress and associated mitochondrial dysfunction are integral components of the pathophysiology of retinal diseases, including diabetic retinopathy (DR), age-related macular degeneration, and glaucoma. Within mitochondria, flavoproteins are oxidized and reduced and emit a green autofluorescence when oxidized following blue light excitation. Recently, a noninvasive imaging device was developed to measure retinal flavoprotein fluorescence (FPF). Thus, oxidized FPF can act as a biomarker of mitochondrial dysfunction. This review article describes the literature surrounding mitochondrial FPF imaging in retinal disease. The authors describe the role of mitochondrial dysfunction in retinal diseases, experiments using FPF as a marker of mitochondrial dysfunction in vitro, the three generations of retinal FPF imaging devices, and the peer-reviewed publications that have examined FPF imaging in patients. Finally, the authors report their own study findings. Goals were to establish normative reference levels for FPF intensity and heterogeneity in healthy eyes, to compare between healthy eyes and eyes with diabetes and DR, and to compare across stages of DR. The authors present methods to calculate a patient's expected FPF values using baseline characteristics. FPF intensity and heterogeneity were elevated in diabetic eyes compared to age-matched control eyes, and in proliferative DR compared to diabetic eyes without retinopathy. In diabetic eyes, higher FPF heterogeneity was associated with poorer visual acuity. In conclusion, while current retinal imaging modalities frequently focus on structural features, functional mitochondrial imaging shows promise as a metabolically targeted tool to evaluate retinal disease.
C1 [Chen, Andrew X.; Sharma, Sumit; Singh, Rishi P.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA.
   [Chen, Andrew X.; Conti, Thais F.; Hom, Grant L.; Greenlee, Tyler E.; Raimondi, Raffaele; Kampani, Reecha; Engel, Robert; Sharma, Sumit; Talcott, Katherine E.; Singh, Rishi P.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
   [Chen, Andrew X.; Conti, Thais F.; Hom, Grant L.; Greenlee, Tyler E.; Raimondi, Raffaele; Sharma, Sumit; Talcott, Katherine E.; Singh, Rishi P.] Cleveland Clin, Cole Eye Inst, Ctr Ophthalm Bioinformat, Cleveland, OH 44106 USA.
   [Briskin, Isaac N.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
   [Rich, Collin A.] OcuSciences Inc, Ann Arbor, MI USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation; Cleveland Clinic Foundation
RP Singh, RP (通讯作者)，Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA.; Singh, RP (通讯作者)，Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.; Singh, RP (通讯作者)，Cleveland Clin, Cole Eye Inst, Ctr Ophthalm Bioinformat, Cleveland, OH 44106 USA.
EM SINGHR@ccf.org
OI Conti, Thais/0000-0003-4729-0706; Briskin, Isaac/0000-0002-4022-0441;
   Raimondi, Raffaele/0000-0001-8472-7984; Greenlee,
   Tyler/0000-0003-0785-9099
FU National Institutes of Health T32 Institutional Training Grant; Research
   to Prevent Blindness Medical Student Eye Research Fellowship
FX AXC was a recipient of a National Institutes of Health T32 Institutional
   Training Grant and Research to Prevent Blindness Medical Student Eye
   Research Fellowship in support of this study.
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NR 99
TC 8
Z9 8
U1 3
U2 7
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2021
VL 35
IS 1
BP 74
EP 92
DI 10.1038/s41433-020-1110-y
EA JUL 2020
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI7BU
UT WOS:000552164000003
PM 32709959
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU He, Y
   Nie, AP
   Pei, JZ
   Ji, Z
   Jia, J
   Liu, HF
   Wan, PF
   Ji, ML
   Zhang, CT
   Zhu, YN
   Wang, X
AF He, Yuan
   Nie, Aiping
   Pei, Jinzhi
   Ji, Zhi
   Jia, Jun
   Liu, Huifeng
   Wan, Pengfei
   Ji, Mingli
   Zhang, Chuntao
   Zhu, Yanni
   Wang, Xia
TI Prevalence and causes of visual impairment in population more than 50
   years old The Shaanxi Eye Study
SO MEDICINE
LA English
DT Article
DE causes; elderly rural Chinese; prevalence; visual impairment
ID LOW-VISION; CATARACT-SURGERY; GLOBAL DATA; BLINDNESS; AWARENESS; ADULTS;
   CHINA
AB To assess the prevalence and causes of visual impairment (VI) in the elderly Chinese rural population in Shaanxi Province. A population-based, cross-sectional study design was used to determine the extent of VI in Chinese people over the age of 50 years in Shaanxi Province. Visual acuity and best-corrected visual acuity were measured using the logarithm of minimum angle of resolution chart. Blindness and low vision were defined according to WHO criteria. The major cause of VI was identified for all participants who were visually impaired. A total of 1912 residents completed a standard questionnaire and underwent a detailed eye examination, and the response rate was 90%. The overall prevalence of blindness and low vision were 1.5% and 8.2%. There was no statistically significant differences between genders in the prevalence of blindness and low vision (P > .05). The prevalence of blindness and low vision was higher among older individuals (P < .05) and lower (P < .05) among those with the highest education level. Cataract, corneal opacity, and glaucoma were considered as the main causes of blindness, which accounted for 67.9%, 10.7%, and 7.1%, respectively. Cataract, refractive error, and age-related macular degeneration were always considered as the leading causes of low vision, which accounted for 66%, 14.7%, and 5.8%, respectively. Cataract, corneal opacity, and glaucoma were the main causes of blindness and low vision in the population aged 50 years or more. The prevalence of these diseases that causes blindness and low vision was higher than that reported in other studies.
C1 Xian Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Xian, Peoples R China.
   Ocular Immunol & Inflammat Inst, Xian, Peoples R China.
   Shaanxi Prov Clin Res Ctr Ophthalmol, Xian, Peoples R China.
C3 Xi'an Medical University
RP He, Y (通讯作者)，Xian Coll Med, Affiliated Hosp 2, Dept Ophthalmol, 167 Fang Dong St, Xian 710038, Peoples R China.
EM openji7127@hotmail.com
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NR 37
TC 9
Z9 10
U1 2
U2 3
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 MAY 15
PY 2020
VL 99
IS 20
AR e20109
DI 10.1097/MD.0000000000020109
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA MO4OD
UT WOS:000551506600036
PM 32443320
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, DH
   Choi, YR
   Shim, J
   Choi, YS
   Kim, YT
   Kim, MK
   Kim, MJ
AF Kim, Dong Hee
   Choi, Yae Rim
   Shim, Jaewon
   Choi, Yun-Sang
   Kim, Yun Tai
   Kim, Mina Kyungmin
   Kim, Min Jung
TI Suppressive Effect of Arctium lappa L. Leaves on Retinal Damage against
   A2E-Induced ARPE-19 Cells and Mice
SO MOLECULES
LA English
DT Article
DE Arctium lappa L; leaves; age-related macular degeneration; A2E
   accumulation; A2E-induced cell death; apoptosis
ID MACULAR DEGENERATION; BLUE-LIGHT; LIPOFUSCIN FLUOROPHORE; PROTEASOME
   INHIBITION; ANTIOXIDANT ACTIVITY; EPITHELIAL-CELLS; MOUSE MODEL; A2E;
   FRACTIONS; EXTRACT
AB Age-related macular degeneration (AMD) is a major cause of irreversible loss of vision with 80-90% of patients demonstrating dry type AMD. Dry AMD could possibly be prevented by polyphenol-rich medicinal foods by the inhibition of N-retinylidene-N-retinylethanolamine (A2E)-induced oxidative stress and cell damage. Arctium lappa L. (AL) leaves are medicinal and have antioxidant activity. The purpose of this study was to elucidate the protective effects of the extract of AL leaves (ALE) on dry AMD models, including in vitro A2E-induced damage in ARPE-19 cells, a human retinal pigment epithelial cell line, and in vivo light-induced retinal damage in BALB/c mice. According to the total phenolic contents (TPCs), total flavonoid contents (TFCs) and antioxidant activities, ALE was rich in polyphenols and had antioxidant efficacies on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2 ',7 '-dichlorofluorescin diacetate (DCFDA) assays. The effects of ALE on A2E accumulation and A2E-induced cell death were also monitored. Despite continued exposure to A2E (10 mu M), ALE attenuated A2E accumulation in APRE-19 cells with levels similar to lutein. A2E-induced cell death at high concentration (25 mu M) was also suppressed by ALE by inhibiting the apoptotic signaling pathway. Furthermore, ALE could protect the outer nuclear layer (ONL) in the retina from light-induced AMD in BALB/c mice. In conclusion, ALE could be considered a potentially valuable medicinal food for dry AMD.
C1 [Kim, Dong Hee; Choi, Yae Rim; Shim, Jaewon; Kim, Yun Tai; Kim, Min Jung] Korea Food Res Inst, Res Div Food Funct, Wonju 55365, South Korea.
   [Kim, Dong Hee; Kim, Mina Kyungmin] Jeonbuk Natl Univ, Dept Food Sci & Human Nutr, Jeonju Si 54896, South Korea.
   [Choi, Yae Rim] Ewha Womans Univ, Dept Food Sci & Engn, Seoul 03760, South Korea.
   [Choi, Yun-Sang] Korea Food Res Inst, Res Div Strateg Food Technol, Wonju 55365, South Korea.
   [Kim, Yun Tai] Korea Univ Sci & Technol, Dept Food Biotechnol, Daejeon 34113, South Korea.
C3 Korea Food Research Institute (KFRI); Ewha Womans University; Korea Food
   Research Institute (KFRI); University of Science & Technology (UST)
RP Kim, MJ (通讯作者)，Korea Food Res Inst, Res Div Food Funct, Wonju 55365, South Korea.
EM donghey543@naver.com; uiu7895@naver.com; jwshim@kfri.re.kr;
   kcys0517@kfri.re.kr; ytkim@kfri.re.kr; minakim@jbnu.ac.kr;
   mjkim14@kfri.re.kr
RI Yun-Sang, Choi/AAR-6256-2021; Kim, Mina K./AAP-6129-2020
OI Yun-Sang, Choi/0000-0001-8060-6237; Kim, Mina K./0000-0002-3546-453X;
   Shim, Jaewon/0000-0003-4818-7057
FU Ottogi Foundation; Main Research Program of the Korea Food Research
   Institute [E0164502-05]
FX This research was funded by 2017 Ottogi Foundation research program and
   Main Research Program (E0164502-05) of the Korea Food Research
   Institute.
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NR 63
TC 6
Z9 6
U1 1
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD APR
PY 2020
VL 25
IS 7
AR 1737
DI 10.3390/molecules25071737
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LL8VZ
UT WOS:000531833400262
PM 32283798
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Basilious, A
   Basilious, A
   Mao, A
   Hutnik, CML
AF Basilious, Amy
   Basilious, Alfred
   Mao, Alex
   Hutnik, Cindy M. L.
TI Trends in low vision care provided by ophthalmologists in Ontario
   between 2009 and 2015
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
AB Objective: Little is known about how low vision services by ophthalmologists are being provided. Here, we analyze the patterns of provision and utilization of vision rehabilitation services in Ontario, Canada.
   Design: Retrospective population-based study between 2009 and 2015.
   Participants: Ophthalmologists (n = 92) who billed for vision rehabilitation services through the Ontario Health Insurance Plan in Ontario and the patients (n = 8949) who received these services.
   Methods: Billing data for low vision services (2009-2015) was received from Ontario Health Insurance Plan. Data were analyzed to describe patient demographics (age, sex, geographic distribution, number, and type of visits) and service provider information (geographic location, number of years providing services, and number of services per year).
   Results: It is estimated that <= 5% of patients with low vision in Ontario accessed these vision rehabilitation services by ophthalmologists. The majority of these patients were females (61%) and > 60 years old (79%). While patient and provider geographic distributions overlapped in the areas with largest patient populations, many regions lacked services. The majority of patients (71%) made only one vision rehabilitation visit. Nine providers practiced low vision for 7 years, while 43 provided services for only 1 year. In 2015, the most common diagnostic service provided to low vision patients was Optical Coherence Tomography of the retina and the most common therapeutic service was intravitreal for wet age-related macular degeneration.
   Conclusion: Although low vision services increased between 2009 and 2015, there were differences in ability to access care based on age, sex, and geographic location.
C1 [Basilious, Amy] Univ Windsor, Dept Biol, Windsor, ON, Canada.
   [Basilious, Alfred] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
   [Mao, Alex; Hutnik, Cindy M. L.] Western Univ, Ivey Eye Inst, London, ON, Canada.
C3 University of Windsor; University of Toronto; Western University
   (University of Western Ontario)
RP Hutnik, CML (通讯作者)，Ivey Eye Inst, 268 Grosvenor St, London, ON, Canada.
EM cindy.hutnik@sjhc.london.on.ca
OI Basilious, Amy/0000-0003-4122-5321
CR [Anonymous], 2017, ONTARIO POPULATION P
   [Anonymous], 2017, CENSUS PROFILE 2016
   [Anonymous], 2017, CENSUS BRIEF MUNICIP
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NR 16
TC 4
Z9 4
U1 1
U2 1
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 2019
VL 54
IS 2
BP 229
EP 236
DI 10.1016/j.jcjo.2018.04.024
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HS4ZC
UT WOS:000463878500030
PM 30975347
DA 2022-11-30
ER

PT J
AU Gao, SQ
   Parmar, T
   Palczewska, G
   Dong, ZQ
   Golczak, M
   Palczewski, K
   Jastrzebska, B
AF Gao, Songqi
   Parmar, Tanu
   Palczewska, Grazyna
   Dong, Zhiqian
   Golczak, Marcin
   Palczewski, Krzysztof
   Jastrzebska, Beata
TI Protective Effect of a Locked Retinal Chromophore Analog against
   Light-Induced Retinal Degeneration
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; VISUAL CYCLE; MONOCLONAL-ANTIBODIES;
   STARGARDT DISEASE; MOUSE MODELS; RHODOPSIN; SENSITIVITY; RETINOIDS;
   DAMAGE; VISION
AB Continuous regeneration of the 11-cis-retinal visual chromophore from all-trans-retinal is critical for vision. Insufficiency of 11-cis-retinal arising from the dysfunction of key proteins involved in its regeneration can impair retinal health, ultimately leading to loss of human sight. Delayed recovery of visual sensitivity and night blindness caused by inadequate regeneration of the visual pigment rhodopsin are typical early signs of this condition. Excessive concentrations of unliganded, constitutively active opsin and increased levels of all-trans-retinal and its byproducts in photoreceptors also accelerate retinal degeneration after light exposure. Exogenous 9-cis-retinal isochromophore can reduce the toxicity of ligand-free opsin but fails to prevent the buildup of retinoid photoproducts when their clearance is defective in human retinopathies, such as Stargardt disease or age-related macular degeneration. Here we evaluated the effect of a locked chromophore analog, 11-cis-6-membered ring-retinal against bright light-induced retinal degeneration in Abca4(-/-)Rdh8(-/-) mice. Using in vivo imaging techniques, optical coherence tomography, scanning laser ophthalmoscopy, and two-photon microscopy, along with in vitro histologic analysis of retinal morphology, we found that treatment with 11-cis-6-membered ring-retinal before light stimulation prevented rod and cone photoreceptor degradation and preserved functional acuity in these mice. Moreover, additive accumulation of 11-cis-6-membered ring-retinal measured in the eyes of these mice by quantitative liquid chromatography-mass spectrometry indicated stable binding of this retinoid to opsin. Together, these results suggest that eliminating excess of unliganded opsin can prevent light-induced retinal degeneration in Abca4(-/-)Rdh8(-/-) mice.
C1 [Gao, Songqi; Parmar, Tanu; Golczak, Marcin; Palczewski, Krzysztof; Jastrzebska, Beata] Case Western Reserve Univ, Dept Pharmacol, Sch Med, 2109 Adelbert Rd,W343B,10900 Euclid Ave, Cleveland, OH 44106 USA.
   [Golczak, Marcin; Palczewski, Krzysztof; Jastrzebska, Beata] Case Western Reserve Univ, Cleveland Ctr Membrane & Struct Biol, Cleveland, OH 44106 USA.
   [Palczewska, Grazyna; Dong, Zhiqian] Polgenix Inc, Dept Med Devices, Cleveland, OH USA.
C3 Case Western Reserve University; Case Western Reserve University
RP Palczewski, K; Jastrzebska, B (通讯作者)，Case Western Reserve Univ, Dept Pharmacol, Sch Med, 2109 Adelbert Rd,W343B,10900 Euclid Ave, Cleveland, OH 44106 USA.
EM kxp65@case.edu; bxj27@case.edu
OI DONG, ZHIQIAN/0000-0002-8748-4532
FU National Institutes of Health (NIH) [EY025214, EY027283, EY024864,
   EY009339, EY025451, EY023948, P30EY011373]; NATIONAL EYE INSTITUTE
   [R24EY027283, R01EY009339, P30EY011373, U01EY025451, R01EY023948,
   R01EY025214, R24EY024864] Funding Source: NIH RePORTER
FX This research was supported by grants from the National Institutes of
   Health (NIH) [EY025214, EY027283, EY024864, EY009339, EY025451,
   EY023948, and P30EY011373].
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NR 55
TC 10
Z9 10
U1 0
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD OCT 1
PY 2018
VL 94
IS 4
BP 1132
EP 1144
DI 10.1124/mol.118.112581
PG 13
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GU9MG
UT WOS:000445669700005
PM 30018116
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Marie, M
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AF Marie, Melanie
   Bigot, Karine
   Angebault, Claire
   Barrau, Coralie
   Gondouin, Pauline
   Pagan, Delphine
   Fouquet, Stephane
   Villette, Thierry
   Sahel, Jose-Alain
   Lenaers, Guy
   Picaud, Serge
TI Light action spectrum on oxidative stress and mitochondrial damage in
   A2E-loaded retinal pigment epithelium cells
SO CELL DEATH & DISEASE
LA English
DT Article
ID HUMAN RPE CELLS; AGE-RELATED MACULOPATHY; BLUE-LIGHT; MACULAR
   DEGENERATION; PHOTOOXIDATIVE DAMAGE; SUNLIGHT EXPOSURE;
   INTRAOCULAR-LENS; VISIBLE-LIGHT; LIPOFUSCIN; A2E
AB Aims: Blue light is an identified risk factor for age-related macular degeneration (AMD). We investigated oxidative stress markers and mitochondrial changes in A2E-loaded retinal pigment epithelium cells under the blue-green part of the solar spectrum that reaches the retina to better understand the mechanisms underlying light-elicited toxicity.
   Results: Primary retinal pigment epithelium cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a custom-made illumination device that delivers 10 nm-wide light bands, we demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen peroxide (H2O2) and superoxide anion (O-2(center dot-)) when exposed to blue-violet light. In addition, they exhibited perinuclear clustering of mitochondria with a decrease of both their mitochondrial membrane potential and their respiratory activities. The increase of oxidative stress resulted in increased levels of the oxidized form of glutathione and decreased superoxide dismutase (SOD) and catalase activities. Furthermore, mRNA expression levels of the main antioxidant enzymes (SOD2, catalase, and GPX1) also decreased.
   Conclusions: Using an innovative illumination device, we measured the precise action spectrum of the oxidative stress mechanisms on A2E-loaded retinal pigment epithelium cells. We defined 415-455 nm blue-violet light, within the solar spectrum reaching the retina, to be the spectral band that generates the highest amount of reactive oxygen species and produces the highest level of mitochondrial dysfunction, explaining its toxic effect. This study further highlights the need to filter these wavelengths from the eyes of AMD patients.
C1 [Marie, Melanie; Bigot, Karine; Gondouin, Pauline; Pagan, Delphine; Fouquet, Stephane; Sahel, Jose-Alain; Picaud, Serge] Sorbonne Univ, INSERM, CNRS, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
   [Angebault, Claire] Inst Neurosci Montpellier, INSERM U1051, F-34091 Montpellier, France.
   [Barrau, Coralie; Villette, Thierry] Essilor Int R&D, F-94220 Charenton Le Pont, France.
   [Sahel, Jose-Alain] CHNO Quinze Vingts, DHU Sight Restore, INSERM DGOS 1423, F-75012 Paris, France.
   [Sahel, Jose-Alain] Fdn Ophtalmol Rothschild, F-75019 Paris, France.
   [Sahel, Jose-Alain] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
   [Lenaers, Guy] Univ Angers, Equipe MitoLab, Pole Rech & Enseignement Med Mitochondriale, Inst MitoVasc,UMR CNRS 6015,INSERM U1083, F-49933 Angers, France.
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; Institut
   National de la Sante et de la Recherche Medicale (Inserm); Universite de
   Montpellier; Essilor International; CHNO des Quinze-Vingts; UDICE-French
   Research Universities; Sorbonne Universite; Pennsylvania Commonwealth
   System of Higher Education (PCSHE); University of Pittsburgh; Institut
   National de la Sante et de la Recherche Medicale (Inserm); Universite
   d'Angers
RP Picaud, S (通讯作者)，Sorbonne Univ, INSERM, CNRS, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
EM serge.picaud@inserm.fr
RI Sahel, Jose-Alain/F-3172-2017; Picaud, Serge/H-4012-2014; Lenaers,
   guy/X-4727-2019
OI Sahel, Jose-Alain/0000-0002-4831-1153; Picaud,
   Serge/0000-0002-0548-5145; Villette, Thierry/0000-0003-3354-8155;
   Michaelides, Michel/0000-0002-1552-7046; MARIE,
   Melanie/0000-0003-3516-3582
FU ANR [ANR-12-TECS-0013]; Essilor International; Federation des Aveugles
   de France; city of Paris; Regional Council of Ile-de-France; LabEx
   LIFESENSES [ANR-10-LABX-65]; French state funds [ANR-11-IDEX-0004-02];
   INSERM; UPMC (Paris VI); CNRS
FX The authors thank the cell culture, imaging, HTS and sequencing
   platforms at the Institut de la Vision. This work was financially
   supported by research grants from the ANR (ANR-12-TECS-0013), by Essilor
   International, INSERM, UPMC (Paris VI), CNRS, the Federation des
   Aveugles de France, the city of Paris, the Regional Council of
   Ile-de-France, by the LabEx LIFESENSES (ANR-10-LABX-65), which was
   supported by the French state funds managed by the ANR within the
   Investissements d'Avenir programme (ANR-11-IDEX-0004-02).
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NR 56
TC 62
Z9 63
U1 1
U2 37
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 FEB 19
PY 2018
VL 9
AR 287
DI 10.1038/s41419-018-0331-5
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FZ2ME
UT WOS:000427411600003
PM 29459695
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Shang, P
   Valapala, M
   Grebe, R
   Hose, S
   Ghosh, S
   Bhutto, IA
   Handa, JT
   Lutty, GA
   Lu, LX
   Wan, J
   Qian, J
   Sergeev, Y
   Puertollano, R
   Zigler, JS
   Xu, GT
   Sinha, D
AF Shang, Peng
   Valapala, Mallika
   Grebe, Rhonda
   Hose, Stacey
   Ghosh, Sayan
   Bhutto, Imran A.
   Handa, James T.
   Lutty, Gerard A.
   Lu, Lixia
   Wan, Jun
   Qian, Jiang
   Sergeev, Yuri
   Puertollano, Rosa
   Zigler, J. Samuel
   Xu, Guo-Tong
   Sinha, Debasish
TI The amino acid transporter SLC36A4 regulates the amino acid pool in
   retinal pigmented epithelial cells and mediates the mechanistic target
   of rapamycin, complex 1 signaling
SO AGING CELL
LA English
DT Article
DE amino acid transporter (PAT4/SLC36A4); age-related macular degeneration;
   coordinated lysosomal expression and regulation (CLEAR) network;
   lysosomes; mechanistic target of rapamycin; complex 1 (mTORC1); mouse
   model; retinal pigmented epithelium (RPE); photoreceptor degeneration;
   signal transduction; transcription factors EB (TFEB) and E3 (TFE3);
   visual cycle proteins
ID LYSOSOMAL BIOGENESIS; MTORC1 ACTIVATION; RAG GTPASES; AUTOPHAGY; TFEB;
   CLEARANCE; DEGRADATION; ATPASE; SENSES; RPE65
AB The dry (nonneovascular) form of age-related macular degeneration (AMD), a leading cause of blindness in the elderly, has few, if any, treatment options at present. It is characterized by early accumulation of cellular waste products in the retinal pigmented epithelium (RPE); rejuvenating impaired lysosome function in RPE is a well-justified target for treatment. It is now clear that amino acids and vacuolar-type H+-ATPase (V-ATPase) regulate the mechanistic target of rapamycin, complex 1 (mTORC1) signaling in lysosomes. Here, we provide evidence for the first time that the amino acid transporter SLC36A4/proton-dependent amino acid transporter (PAT4) regulates the amino acid pool in the lysosomes of RPE. In Cryba1 (gene encoding A3/A1-crystallin) KO (knockout) mice, where PAT4 and amino acid levels are increased in the RPE, the transcription factors EB (TFEB) and E3 (TFE3) are retained in the cytoplasm, even after 24h of fasting. Consequently, genes in the coordinated lysosomal expression and regulation (CLEAR) network are not activated, and lysosomal function remains low. As these mice age, expression of RPE65 and lecithin retinol acyltransferase (LRAT), two vital visual cycle proteins, decreases in the RPE. A defective visual cycle would possibly slow down the regeneration of new photoreceptor outer segments (POS). Further, photoreceptor degeneration also becomes obvious during aging, reminiscent of human dry AMD disease. Electron microscopy shows basal laminar deposits in Bruch's membrane, a hallmark of development of AMD. For dry AMD patients, targeting PAT4/V-ATPase in the lysosomes of RPE cells may be an effective means of preventing or delaying disease progression.
C1 [Shang, Peng; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R China.
   [Shang, Peng; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Lab Clin Visual Sci, Tongji Eye Inst, Shanghai 200092, Peoples R China.
   [Shang, Peng; Valapala, Mallika; Grebe, Rhonda; Hose, Stacey; Ghosh, Sayan; Bhutto, Imran A.; Handa, James T.; Lutty, Gerard A.; Wan, Jun; Qian, Jiang; Zigler, J. Samuel; Sinha, Debasish] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Sergeev, Yuri] NEI, NIH, Bethesda, MD 20892 USA.
   [Puertollano, Rosa] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Xu, Guo-Tong] Tongji Univ, Sch Med, Translat Med Ctr Stem Cell Therapy, Shanghai East Hosp, Shanghai, Peoples R China.
   [Xu, Guo-Tong] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China.
C3 Tongji University; Tongji University; Johns Hopkins University; Johns
   Hopkins Medicine; National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI); National Institutes of Health (NIH) - USA;
   NIH National Heart Lung & Blood Institute (NHLBI); Tongji University;
   Tongji University
RP Xu, GT (通讯作者)，Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R China.; Xu, GT (通讯作者)，Tongji Univ, Sch Med, Lab Clin Visual Sci, Tongji Eye Inst, Shanghai 200092, Peoples R China.; Sinha, D (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM gtxu@tongji.edu; Debasish@jhmi.edu
RI Ghosh, Sayan/ABB-8587-2021; Wan, Jun/AAN-1337-2020
OI Wan, Jun/0000-0001-9286-6562; /0000-0002-3780-5641
FU Wilmer Eye Institute from the Research to Prevent Blindness; National
   Eye Institute [EY019037-S, EY019044, EY14005, EY01765]; National High
   Technology Research and Development Program of China [2013CB967501,
   2015CB964601, 2013CB967101]; Shanghai East Hospital [ZJ2014-2D-002];
   Tongji Eye Institute [TEI-201403001]; NATIONAL EYE INSTITUTE
   [ZIAEY000476, R01EY019904] Funding Source: NIH RePORTER; NATIONAL HEART,
   LUNG, AND BLOOD INSTITUTE [ZIAHL006151, ZIAHL006075] Funding Source: NIH
   RePORTER
FX This study was funded by an unrestricted grant to the Wilmer Eye
   Institute from the Research to Prevent Blindness, National Eye
   Institute: EY019037-S (DS), EY019044 (JTH), EY14005 (JTH), EY01765
   (Wilmer Imaging Core), and the National High Technology Research and
   Development Program of China (2013CB967501, 2015CB964601, 2013CB967101),
   Shanghai East Hospital (ZJ2014-2D-002), and Tongji Eye Institute
   (TEI-201403001).
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NR 44
TC 22
Z9 24
U1 1
U2 14
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9726
J9 AGING CELL
JI Aging Cell
PD APR
PY 2017
VL 16
IS 2
BP 349
EP 359
DI 10.1111/acel.12561
PG 11
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA EM5UP
UT WOS:000395379500017
PM 28083894
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Foss, AJE
   Scott, LJ
   Rogers, CA
   Reeves, BC
   Ghanchi, F
   Gibson, J
   Chakravarthy, U
AF Foss, Alexander J. E.
   Scott, Lauren J.
   Rogers, Chris A.
   Reeves, Barney C.
   Ghanchi, Faruque
   Gibson, Jonathan
   Chakravarthy, Usha
CA IVAN Study Grp
TI Changes in intraocular pressure in study and fellow eyes in the IVAN
   trial
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FIBER LAYER THICKNESS; INTRAVITREAL
   INJECTIONS; MACULAR DEGENERATION; REPACKAGED BEVACIZUMAB; SUSTAINED
   ELEVATION; FACTOR THERAPY; RANIBIZUMAB; PEGAPTANIB
AB Purpose To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560).
   Design Randomised controlled clinical trial with factorial design.
   Participants Patients (n=610) with treatment naive neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment.
   Methods At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye.
   Outcome measures The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined.
   Results For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively).
   Conclusions Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance.
C1 [Foss, Alexander J. E.] Queens Med Ctr, Dept Ophthalmol, Nottingham, England.
   [Scott, Lauren J.; Rogers, Chris A.; Reeves, Barney C.] Univ Bristol, Sch Clin Sci, Clin Trials Evaluat Unit, Bristol, Avon, England.
   [Ghanchi, Faruque] Bradford Royal Infirm, Dept Ophthalmol, Bradford, W Yorkshire, England.
   [Gibson, Jonathan] Aston Univ, Sch Life & Hlth Sci, Birmingham, W Midlands, England.
   [Chakravarthy, Usha] Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.
C3 University of Nottingham; University of Bristol; Bradford Royal
   Infirmary; Aston University; Queens University Belfast
RP Rogers, CA (通讯作者)，Univ Bristol, Clin Trials Evaluat Unit, Bristol, Avon, England.
EM chris.rogers@bristol.ac.uk
OI Chakravarthy, Usha/0000-0002-2606-3734; Reeves,
   Barnaby/0000-0002-5101-9487; Gibson, Jonathan M/0000-0002-9281-5244
FU National Institute for Health Research (NIHR) Health Technology
   Assessment (HTA) programme [07/36/01]; National Institute for Health
   Research [07/36/01] Funding Source: researchfish
FX The IVAN trial was funded by the National Institute for Health Research
   (NIHR) Health Technology Assessment (HTA) programme (project number
   07/36/01). The views and opinions expressed are those of the authors and
   do not necessarily reflect those of the Health Technology Assessment
   programme, National Institute for Health Research, the UK National
   Health Service, or the Department of Health.
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NR 25
TC 9
Z9 9
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 DEC
PY 2016
VL 100
IS 12
BP 1662
EP 1667
DI 10.1136/bjophthalmol-2015-307595
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EC7XD
UT WOS:000388353500014
PM 27073205
OA Green Published, Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Schafer, N
   Grosche, A
   Reinders, J
   Hauck, SM
   Pouw, RB
   Kuijpers, TW
   Wouters, D
   Ehrenstein, B
   Enzmann, V
   Zipfel, PF
   Skerka, C
   Pauly, D
AF Schaefer, Nicole
   Grosche, Antje
   Reinders, Joerg
   Hauck, Stefanie M.
   Pouw, Richard B.
   Kuijpers, Taco W.
   Wouters, Diana
   Ehrenstein, Boris
   Enzmann, Volker
   Zipfel, Peter F.
   Skerka, Christine
   Pauly, Diana
TI Complement Regular FHR-3 Is Elevated either Locally or Systemically in a
   Selection of Autoimmune Diseases
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE FHR-3/CFHR3; specific antibody; rheumatic disease; microglia/macrophage;
   FH competition; immune therapy; retinal degeneration
ID H-RELATED PROTEINS; HEMOLYTIC-UREMIC SYNDROME; MACULAR DEGENERATION;
   POLYMYALGIA-RHEUMATICA; IMMUNE-COMPLEXES; BINDING; CELLS; CFH; MEMBRANE;
   PROTEOME
AB The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-family. These antibodies detected FHR-3 from human serum with a mean concentration of 1 mu g/mL. FHR-3 levels in patients were significantly increased in sera from systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica but remained almost unchanged in samples from AMD or aHUS patients. Moreover, by immunostaining of an aged human donor retina, we discovered a local FHR-3 production by microglia/macrophages. The mAb RETC-2 modulated FHR-3 binding to C3b but not the binding of FHR-3 to heparin. Interestingly, FHR-3 competed with FH for binding C3b and the mAb RETC-2 reduced the interaction of FHR-3 and C3b, resulting in increased FH binding. Our results unveil a previously unknown systemic involvement of FHR-3 in rheumatoid diseases and a putative local role of FHR-3 mediated by microglia/macrophages in the damaged retina. We conclude that the local FHR-3/FH equilibrium in AMD is a potential therapeutic target, which can be modulated by our specific mAb RETC-2.
C1 [Schaefer, Nicole; Pauly, Diana] Univ Hosp Regensburg, Dept Ophthalmol, Regensburg, Germany.
   [Grosche, Antje] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
   [Reinders, Joerg] Univ Regensburg, Inst Funct Genom, Regensburg, Germany.
   [Hauck, Stefanie M.] German Res Ctr Environm Hlth GmbH, Res Unit Prot Sci, Helmholtz Zentrum Munchen, Neuherberg, Germany.
   [Pouw, Richard B.; Wouters, Diana] Univ Amsterdam, Acad Med Ctr, Dept Immunopathol, Sanquin Res & Landsteiner Lab, Amsterdam, Netherlands.
   [Kuijpers, Taco W.] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat Hematol Immunol & Infect Dis, Amsterdam, Netherlands.
   [Kuijpers, Taco W.] Univ Amsterdam, Acad Med Ctr, Dept Blood Cell Res, Sanquin Res & Landsteiner Lab, Amsterdam, Netherlands.
   [Ehrenstein, Boris] Asklepios Klinikum Bad Abbach, Klin & Poliklin Rheumatol & Klin Immunol, Bad Abbach, Germany.
   [Enzmann, Volker] Univ Bern, Dept Ophthalmol, Inselspital, Bern, Switzerland.
   [Zipfel, Peter F.; Skerka, Christine] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
   [Zipfel, Peter F.] Friedrich Schiller Univ, Jena, Germany.
C3 University of Regensburg; University of Regensburg; University of
   Regensburg; Helmholtz Association; Helmholtz-Center Munich - German
   Research Center for Environmental Health; University of Amsterdam;
   Academic Medical Center Amsterdam; Emma Children's Hospital; University
   of Amsterdam; Academic Medical Center Amsterdam; University of
   Amsterdam; Academic Medical Center Amsterdam; University of Bern; Hans
   Knoll Institute (HKI); Friedrich Schiller University of Jena
RP Pauly, D (通讯作者)，Univ Hosp Regensburg, Dept Ophthalmol, Regensburg, Germany.
EM diana.pauly@ukr.de
RI Grosche, Antje/N-1978-2014; Pouw, Richard/AAE-1042-2020; Hauck,
   Stefanie/B-3300-2013
OI Grosche, Antje/0000-0003-0338-7530; Pouw, Richard/0000-0003-3469-8454;
   Hauck, Stefanie/0000-0002-1630-6827; Reinders, Joerg/0000-0003-1025-7849
FU ProRetina Foundation; Deutsche Forschungsgemeinschaft (DFG) [INST
   89/386-1 FUGG]; BrightFocus Fondation [M2015186]; Jackstadt Foundation
FX The authors thank the following foundations for their generous support
   for this project: NS was founded by the Maloch Foundation; AG received
   support from the ProRetina Foundation and from Deutsche
   Forschungsgemeinschaft (DFG) for the VisiScope CSU-X1 Confocal System
   (INST 89/386-1 FUGG); and DP was supported by the BrightFocus Fondation
   (M2015186) and the Jackstadt Foundation.
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NR 76
TC 23
Z9 23
U1 0
U2 12
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 NOV 28
PY 2016
VL 7
AR 542
DI 10.3389/fimmu.2016.00542
PG 16
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA ED0ZM
UT WOS:000388573200001
PM 27965669
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, GH
   Kim, HI
   Paik, SS
   Jung, SW
   Kang, S
   Kim, IB
AF Kim, Gyu Hyun
   Kim, Hyung Il
   Paik, Sun-Sook
   Jung, Sung Won
   Kang, Seungbum
   Kim, In-Beom
TI Functional and morphological evaluation of blue light-emitting
   diode-induced retinal degeneration in mice
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Retinal degeneration; Blue light-emitting diode; Photoreceptor;
   Apoptotic cell death; Animal model
ID METHYL-N-NITROSOUREA; MACULAR DEGENERATION; OXIDATIVE STRESS; IN-VITRO;
   AGE; DAMAGE; CELLS; MICROGLIA; APOPTOSIS; EYE
AB The purpose of this study was to evaluate a retinal degeneration (RD) model induced by exposing mice to a blue light-emitting diode (LED), which led to photoreceptor cell death.
   RD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 hours. Retinal function was examined using scotopic electroretinography (ERG). Histopathological changes were assessed by hematoxylin and eosin (H&E) staining and electron microscopy. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In addition, retinal inflammation and oxidative stress were evaluated by immunohistochemistry with anti-glial fibrillary acidic protein (GFAP) and anti-8-hydroxy-2'-deoxyguanosine (8-OHdG), respectively.
   Scotopic ERG showed that blue LED exposure resulted in a decrease in both a-waves and b-waves in mice retinas in an illuminance-dependent manner. H&E, TUNEL assay, and electron microscopy revealed massive photoreceptor cell death by apoptosis in the central region of the retina. Retinal stress and inflammation were detected by increased expression of GFAP and by electron microscopy findings demonstrating microglia infiltration in the outer nuclear layer and subretinal space. In addition, increased labeling of 8-OHdG was observed in the retinas from blue LED exposure.
   These results suggest that blue LED-induced RD may be a useful animal model in which to study the pathogenesis of RD, including age-related macular degeneration, and to evaluate the effects of new therapeutic agents prior to clinical trials, where oxidative stress and inflammation are the underlying RD mechanisms.
C1 [Kim, Gyu Hyun; Paik, Sun-Sook; Jung, Sung Won; Kim, In-Beom] Catholic Univ Korea, Coll Med, Dept Anat, Catholic Neurosci Inst, 505 Banpo Dong, Seoul 137701, South Korea.
   [Kim, Hyung Il] Gyeongju St Marys Eye Clin, 293 Wonhwa Ro, Gyeongju Si 780946, Gyeongsangbuk D, England.
   [Kang, Seungbum] Catholic Univ Korea, Coll Med, Dept Ophthalmol, 505 Banpo Dong, Seoul 137701, South Korea.
   [Kim, In-Beom] Catholic Univ Korea, Coll Med, Catholic Inst Appl Anat, 505 Banpo Dong, Seoul 137701, South Korea.
C3 Catholic University of Korea; Catholic University of Korea; Catholic
   University of Korea
RP Kim, IB (通讯作者)，Catholic Univ Korea, Coll Med, Dept Anat, Catholic Neurosci Inst, 505 Banpo Dong, Seoul 137701, South Korea.; Kim, IB (通讯作者)，Catholic Univ Korea, Coll Med, Catholic Inst Appl Anat, 505 Banpo Dong, Seoul 137701, South Korea.
EM ibkimmd@catholic.ac.kr
RI Kim, In-Beom/A-6728-2011
FU Catholic Medical Center Research Foundation; National Research
   Foundation (NRF) of Korea [2013R1A2A2A01014070]
FX Financial support was provided by the Catholic Medical Center Research
   Foundation in program year 2013 and by the National Research Foundation
   (NRF) of Korea in the form of Basic Science Research Program no.
   2013R1A2A2A01014070.
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   Zhao LL, 2014, INVEST OPHTH VIS SCI, V55, P5979, DOI 10.1167/iovs.14-15025
NR 45
TC 41
Z9 46
U1 1
U2 20
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 APR
PY 2016
VL 254
IS 4
BP 705
EP 716
DI 10.1007/s00417-015-3258-x
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DH2IJ
UT WOS:000372608100013
PM 26743754
DA 2022-11-30
ER

PT J
AU Olchawa, MM
   Pilat, AK
   Szewczyk, GM
   Sarna, TJ
AF Olchawa, Magdalena M.
   Pilat, Anna K.
   Szewczyk, Grzegorz M.
   Sarna, Tadeusz Jan
TI Inhibition of phagocytic activity of ARPE-19 cells by free radical
   mediated oxidative stress
SO FREE RADICAL RESEARCH
LA English
DT Article
DE Cholesterol hydroperoxides; flow cytometry; hydrogen peroxide; rose
   Bengal; photoreceptor outer segments
ID ROD OUTER SEGMENTS; PERFORMANCE LIQUID-CHROMATOGRAPHY; ROSE-BENGAL;
   SINGLET-OXYGEN; HYDROGEN-PEROXIDE; PHOTOCHEMICAL DAMAGE; PIGMENT;
   ALPHA-V-BETA-5; ELIMINATION; MELANOSOMES
AB Oxidative stress is a main factor responsible for key changes leading to the onset of age-related macular degeneration (ARMD) that occur in the retinal pigment epithelium (RPE), which is involved in phagocytosis of photoreceptor outer segments (POS). In this study, hydrogen peroxide (H2O2), H2O2 and iron ions (Fe) or rose Bengal (RB) in the presence of NADH and Fe were used to model free radical mediated oxidative stress to test if free radicals and singlet oxygen have different efficiency to inhibit phagocytosis of ARPE-19 cells. Free radical mediated oxidative stress was confirmed by HPLC-EC(Hg) measurements of cholesterol hydroperoxides in treated cells. Electron paramagnetic resonance (EPR) spin trapping was employed to detect superoxide anion. Cell survival was analyzed by the MTT assay. Specific phagocytosis of fluorescein-5-isothiocyanate-labeled POS and non-specific phagocytosis of fluorescent beads were measured by flow cytometry. HPLC analysis of cells photosensitized with RB in the presence of NADH and Fe indicated substantial increase in formation of free radical-dependent 7/7-hydroperoxides. EPR spin trapping confirmed the photogeneration of superoxide anion in samples enriched with RB, NADH and Fe. For all three protocols sub-lethal oxidative stress induced significant inhibition of the specific phagocytosis of POS. In contrast, non-specific phagocytosis was inhibited only by H2O2 or H2O2 and Fe treatment. Inhibition of phagocytosis was transient and recoverable by 24h. These results suggest that free radicals may exert similar to singlet oxygen efficiency in inhibiting phagocytosis of RPE cells, and that the effect depends on the location where initial reactive species are formed.
C1 [Olchawa, Magdalena M.; Pilat, Anna K.; Szewczyk, Grzegorz M.; Sarna, Tadeusz Jan] Jagiellonian Univ, Dept Biophys, Fac Biochem Biophys & Biotechnol, Gronostajowa 7, PL-30387 Krakow, Poland.
C3 Jagiellonian University
RP Sarna, TJ (通讯作者)，Jagiellonian Univ, Dept Biophys, Fac Biochem Biophys & Biotechnol, Gronostajowa 7, PL-30387 Krakow, Poland.
EM tadeusz.sarna@uj.edu.pl
RI Olchawa, Magdalena/AAG-2654-2021; Szewczyk, Grzegorz/AAL-7326-2020;
   Olchawa, Magdalena/AAC-4992-2021
OI Szewczyk, Grzegorz/0000-0003-0834-1080; Olchawa,
   Magdalena/0000-0003-3276-7671
FU Poland National Science Centre [2661/B/P01/2010/39, MAESTRO 4
   2013/08/A/NZ1/00194]
FX This work was supported by research Grants 2661/B/P01/2010/39 and
   MAESTRO 4 2013/08/A/NZ1/00194 from the Poland National Science Centre
   (T.S.).
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NR 59
TC 14
Z9 14
U1 0
U2 12
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1071-5762
EI 1029-2470
J9 FREE RADICAL RES
JI Free Radic. Res.
PY 2016
VL 50
IS 8
BP 887
EP 897
DI 10.1080/10715762.2016.1194519
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DS8MC
UT WOS:000381036500009
PM 27225587
DA 2022-11-30
ER

PT J
AU Gong, Y
   Li, J
   Sun, Y
   Fu, ZJ
   Liu, CH
   Evans, L
   Tian, K
   Saba, N
   Fredrick, T
   Morss, P
   Chen, J
   Smith, LEH
AF Gong, Yan
   Li, Jie
   Sun, Ye
   Fu, Zhongjie
   Liu, Chi-Hsiu
   Evans, Lucy
   Tian, Katherine
   Saba, Nicholas
   Fredrick, Thomas
   Morss, Peyton
   Chen, Jing
   Smith, Lois E. H.
TI Optimization of an Image-Guided Laser-Induced Choroidal
   Neovascularization Model in Mice
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; MURINE MODEL; AGE;
   ANGIOGENESIS; SEVERITY; DYSFUNCTION; MECHANISMS; MOUSE
AB The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.
C1 [Gong, Yan; Li, Jie; Sun, Ye; Fu, Zhongjie; Liu, Chi-Hsiu; Evans, Lucy; Tian, Katherine; Saba, Nicholas; Fredrick, Thomas; Morss, Peyton; Chen, Jing; Smith, Lois E. H.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA 02138 USA.
   [Li, Jie] Sichuan Prov Hosp, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China.
   [Li, Jie] Sichuan Acad Med Sci, Chengdu, Sichuan, Peoples R China.
C3 Harvard University; Boston Children's Hospital; Harvard Medical School;
   Sichuan Provincial People's Hospital
RP Smith, LEH (通讯作者)，Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA 02138 USA.
EM lois.smith@childrens.harvard.edu
OI Morss-Walton, Peyton/0000-0002-9200-9939; Gong, Yan/0000-0002-4805-0459;
   Sun, Ye/0000-0002-7674-9056; FU, ZHONGJIE/0000-0002-8182-2983
FU National Institutes of Health/National Eye Institute [R01 EY022275, R01
   EY017017, P01 HD18655, R01 EY024963]; Lowy Medical Research Institute;
   European Commission FP7 [305485]; Ministry of Science and Technology,
   Taiwan, R.O.C. [104-2917-I-564-026]; China Scholarship Council
   [201306240082]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD
   HEALTH & HUMAN DEVELOPMENT [P30HD018655] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY017017, R01EY024963, R01EY022275] Funding
   Source: NIH RePORTER
FX This work was supported by National Institutes of Health/National Eye
   Institute (https://www.nei.nih.gov/, R01 EY022275, R01 EY017017, P01
   HD18655), Lowy Medical Research Institute (http://www.lmri.net/),
   European Commission FP7 (http://cordis.europa.eu/fp7/home_en.html)
   project 305485 PREVENT-ROP (LEHS), National Institutes of
   Health/National Eye Institute (https://www.nei.nih.gov/, R01 EY024963,
   JC), Ministry of Science and Technology, Taiwan, R.O.C.
   (http://www.most.gov.tw/mp.aspx?mp=7) Postdoctoral Research Abroad
   Program (104-2917-I-564-026, CHL), and China Scholarship Council
   (http://en.csc.edu.cn/) State Scholarship Fund (201306240082, JL). 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 49
Z9 53
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 10
PY 2015
VL 10
IS 7
AR e0132643
DI 10.1371/journal.pone.0132643
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CN1FD
UT WOS:000358162300164
PM 26161975
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Liu, T
   Liu, XJ
   Wen, R
   Lam, BL
   Jiao, SL
AF Liu, Tan
   Liu, Xiaojing
   Wen, Rong
   Lam, Byron L.
   Jiao, Shuliang
TI In vivo imaging rhodopsin distribution in the photoreceptors with
   nano-second pulsed scanning laser ophthalmoscopy
SO QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
LA English
DT Article
DE Densitometry; optical reflectometry; photoreceptors; rhodopsin; scanning
   laser ophthalmoscopy (SLO)
AB Background: Rhodopsin is a biomarker for the function of rod photoreceptors, the dysfunction of which is related to many blinding diseases like retinitis pigmentosa and age-related macular degeneration. Imaging rhodopsin quantitatively may provide a powerful clinical tool for diagnosis of these diseases. To map rhodopsin distribution accurately in the retina, absorption by rhodopsin intermediates need to be minimized.
   Methods and materials: We developed nano-second pulsed scanning laser ophthalmoscopy (SLO) to image rhodopsin distribution in the retina. The system takes advantage of the light-induced shift of rhodopsin absorption spectra, which in turn affects the fundus spectral reflection before and after photo-bleaching. By imaging the retina twice, one in the dark-adapted state and the other one in the light-adapted state, the rhodopsin absorption change can be calculated from the differential image, which is a function of the rhodopsin concentration in the rod photoreceptors.
   Results: The system was successfully applied to in vivo imaging of rat retina in different bleaching conditions to verify its feasibility. Our studies showed that the differential image between the dark-and light-adapted states represents rhodopsin distribution in the retina. We also conducted a dynamic bleaching experiment to prove the importance of reducing light absorption of rhodopsin intermediates.
   Conclusions: The preliminary results showed that our nano-second pulsed-light SLO is promising in imaging the functional biomarker of the rod photoreceptors. By using nanosecond pulsed laser, in which one laser pulse generates one pixel of the image, the absorption of rhodopsin intermediates can be reduced.
C1 [Liu, Tan; Liu, Xiaojing; Jiao, Shuliang] Florida Int Univ, Dept Biomed Engn, 10555 W Flagler St,EC 2610, Miami, FL 33174 USA.
   [Wen, Rong; Lam, Byron L.] Univ Miami, Bascom Palmer Eye Inst, Miller Sch Med, Miami, FL 33136 USA.
C3 State University System of Florida; Florida International University;
   Bascom Palmer Eye Institute; University of Miami
RP Jiao, SL (通讯作者)，Florida Int Univ, Dept Biomed Engn, 10555 W Flagler St,EC 2610, Miami, FL 33174 USA.
EM shjiao@fiu.edu
RI Liu, Tan/G-7209-2012
OI Liu, Tan/0000-0001-5656-9552
FU NIH [5R01EY019951-04]
FX The work is supported in part by the NIH grant 5R01EY019951-04.
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NR 17
TC 4
Z9 4
U1 0
U2 3
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 IMAGING MED SU
JI Quant. Imaging Med. Surg.
PD FEB
PY 2015
VL 5
IS 1
BP 63
EP 68
DI 10.3978/j.issn.2223-4292.2014.11.06
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA V21HZ
UT WOS:000214946600009
PM 25694955
DA 2022-11-30
ER

PT J
AU Sohn, EH
   Flamme-Wiese, MJ
   Whitmore, SS
   Wang, K
   Tucker, BA
   Mullins, RF
AF Sohn, Elliott H.
   Flamme-Wiese, Miles J.
   Whitmore, S. Scott
   Wang, Kai
   Tucker, Budd A.
   Mullins, Robert F.
TI Loss of CD34 Expression in Aging Human Choriocapillaris Endothelial
   Cells
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; HUMAN EYES; MACROPHAGES; RETINA; HETEROGENEITY;
   CCR3
AB Structural and gene expression changes in the microvasculature of the human choroid occur during normal aging and age-related macular degeneration (AMD). In this study, we sought to determine the impact of aging and AMD on expression of the endothelial cell glycoprotein CD34. Sections from 58 human donor eyes were categorized as either young (under age 40), age-matched controls (>age 60 without AMD), or AMD affected (>age 60 with early AMD, geographic atrophy, or choroidal neovascularization). Dual labeling of sections with Ulex europaeus agglutinin-I lectin (UEA-I) and CD34 antibodies was performed, and the percentage of capillaries labeled with UEA-I but negative for anti-CD34 was determined. In addition, published databases of mouse and human retinal pigment epithelium-choroid were evaluated and CD34 expression compared between young and old eyes. Immunohistochemical studies revealed that while CD34 and UEA-I were colocalized in young eyes, there was variable loss of CD34 immunoreactivity in older donor eyes. While differences between normal aging and AMD were not significant, the percentage of CD34 negative capillaries in old eyes, compared to young eyes, was highly significant (p = 3.8 x 10(-6)). Endothelial cells in neovascular membranes were invariably CD34 positive. Published databases show either a significant decrease in Cd34 (mouse) or a trend toward decreased CD34 (human) in aging. These findings suggest that UEA-I and endogenous alkaline phosphatase activity are more consistent markers of aging endothelial cells in the choroid, and suggest a possible mechanism for the increased inflammatory milieu in the aging choroid.
C1 [Sohn, Elliott H.; Flamme-Wiese, Miles J.; Whitmore, S. Scott; Tucker, Budd A.; Mullins, Robert F.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52240 USA.
   [Sohn, Elliott H.; Flamme-Wiese, Miles J.; Whitmore, S. Scott; Wang, Kai; Tucker, Budd A.; Mullins, Robert F.] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
   [Wang, Kai] Univ Iowa, Dept Biostat, Iowa City, IA USA.
C3 University of Iowa; University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52240 USA.
EM Robert-Mullins@Uiowa.Edu
RI Mullins, Robert F/I-6717-2013
OI Tucker, Budd/0000-0003-2178-1742; Mullins, Robert/0000-0002-5006-0891;
   Sohn, Elliott/0000-0002-3778-9362; Whitmore, S.
   Scott/0000-0003-0161-9625
FU Elmer and Sylvia Sramek Charitable Foundation, National Institutes of
   Health [EY017451, 1-DP2-OD007483-01]; Stephen A. Wynn Foundation;
   Hansjoerg EJW Kolder MD, PhD Professorship for Best Disease; NATIONAL
   EYE INSTITUTE [R01EY017451] 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 Elmer and Sylvia Sramek Charitable Foundation,
   National Institutes of Health grants EY017451 and 1-DP2-OD007483-01, the
   Stephen A. Wynn Foundation, and the Hansjoerg EJW Kolder MD, PhD
   Professorship for Best Disease. 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 31
TC 15
Z9 16
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 JAN 21
PY 2014
VL 9
IS 1
AR e86538
DI 10.1371/journal.pone.0086538
PG 5
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500254
PM 24466138
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Kubista, KE
   Brunner, S
   Glittenberg, CG
   Hochwarter, A
   Binder, S
AF Kubista, Katharina E.
   Brunner, Simon
   Glittenberg, Carl G.
   Hochwarter, Anelia
   Binder, Susanne
TI Influence of blue-light-filtering intraocular lenses on daytime levels
   of melatonin (BluMel-Study)
SO SPEKTRUM DER AUGENHEILKUNDE
LA English
DT Article
DE Melatonin; Cataract; Blue light; Circadian rhythm; Aging
ID AGE
AB Blue-light-filtering intraocular lenses have been developed to avoid the "blue-light-hazard," which is thought to induce age-related macular degeneration. However, the intrinsically photosensitive retinal ganglion cells have their peak sensitivity at 480 nm, and their sent information influences melatonin production in the pineal gland.
   To analyze the effect of these blue-light-filtering intraocular lenses we compared the change in melatonin daytime levels after implantation of blue-light-filtering or white intraocular lenses. Eight subjects with cataract were randomized to receive either blue-light-filtering or white intraocular lenses. Melatonin analysis, visual acuity, complete slit lamp analysis, and questionnaire about sleeping habits and quality were performed before and 1 month after cataract surgery.
   Five subjects received a blue-light-filtering and three a white intraocular lens. The average amounts of wakes during the night increased postoperatively in three out of the five subjects who received the blue-light-filtering lens. Subjects with the white lens only had < 1.0 pg/ml increase, while subjects with blue-light-filtering intraocular lenses had > 1.0 pg/ml increase of melatonin after surgery.
   We found that subjects who received blue-light-filtering intraocular lenses had an increase in uneasy sleep and more wakes during the night. Since melatonin secretion is not blocked by the blue-light-filtering lenses, which leads to elevated levels of melatonin during day time, and can increase retinal damage in light, the effectiveness of the blue-light-filtering intraocular lenses has to be questioned and needs to be further investigated.
C1 [Kubista, Katharina E.; Brunner, Simon; Glittenberg, Carl G.; Hochwarter, Anelia; Binder, Susanne] Rudolf Fdn Clin, Dept Ophthalmol, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, A-1030 Vienna, Austria.
C3 Ludwig Boltzmann Institute
RP Kubista, KE (通讯作者)，Rudolf Fdn Clin, Dept Ophthalmol, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Juchgasse 25, A-1030 Vienna, Austria.
EM kubista@proeyes.at; simon.brunner@wienkav.at;
   carl.glittenberg@wienkav.at; anelia.hochwarter@wienkav.at;
   susanne.binder@wienkav.at
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NR 14
TC 2
Z9 3
U1 3
U2 23
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0930-4282
EI 1613-7523
J9 SPEKTRUM AUGENHEILKD
JI Spektrum Augenheilkd.
PD AUG
PY 2013
VL 27
IS 4
BP 176
EP 180
DI 10.1007/s00717-013-0174-5
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 215NC
UT WOS:000324215900002
DA 2022-11-30
ER

PT J
AU Brunner, S
   Mora, A
   Fonseca, J
   Weber, T
   Falkner-Radler, CI
   Oeser, R
   Binder, S
AF Brunner, Simon
   Mora, Andre
   Fonseca, Jose
   Weber, Tina
   Falkner-Radler, Christiane I.
   Oeser, Reinhard
   Binder, Susanne
TI Monitoring of Drusen and Geographic Atrophy Area Size after Cataract
   Surgery Using the MD3RI Tool for Computer-Aided Contour Drawing
SO OPHTHALMOLOGICA
LA English
DT Article
DE Nonexudative age-related macular degeneration; Drusen; Geographic
   atrophy; Cataract surgery
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; BLUE MOUNTAINS EYE;
   QUALITY-OF-LIFE; MACULAR DEGENERATION; VISUAL-ACUITY; LENS IMPLANTATION;
   INTRAOCULAR-LENS; 5-YEAR INCIDENCE; RISK-FACTORS
AB Background/Aims: To monitor possible changes in the cumulated drusen or geographic atrophy area size (CDGAS) of nonexudative age-related macular degeneration (AMD) in patients before and after cataract surgery, using a new tool for computer-aided image quantification. Methods: Randomized, prospective, clinical trial. 54 patients with cataract and nonexudative AMD were randomly assigned into an early surgery group (ES = 28) and a control group (CO = 26) with a 6-month delay of surgery. CDGAS was determined with the MD3RI tool for contour drawing in a central region of digitized fundus photographs, measuring 3,000 mu m in diameter. To evaluate CDGAS progression, differences in pixels and square millimeters were calculated by equivalent tests. Results: Forty-nine patients completed the visits over the 12-month period (ES = 27 and CO = 22). Mean pixel values increased from 201.5 (11.33 x 10(-3) mm(2)) to 202.7 (11.39 x 10(-3) mm(2)) in the ES group and from 191.6 (10.77 x 10(-3) mm(2)) to 194.6 (10.94 x 10(-3) mm(2)) in the CO group. Finally, equivalence of CDGAS differences between ES and CO could be demonstrated. No exudative AMD was recorded during the study period. Conclusion: In our cohorts, no significant changes were found in CDGAS 12 months after cataract surgery. The MD3RI software could serve as an efficient, precise and objective tool for AMD quantification and monitoring in future trials. Copyright (C) 2012 S. Karger AG, Basel
C1 [Brunner, Simon; Weber, Tina; Falkner-Radler, Christiane I.; Binder, Susanne] Rudolfstiftung Hosp, Dept Ophthalmol, Vienna, Austria.
   [Brunner, Simon; Weber, Tina; Falkner-Radler, Christiane I.; Binder, Susanne] Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Vienna, Austria.
   [Oeser, Reinhard] Oeser GmbH, Stat & Documentat, Vienna, Austria.
   [Mora, Andre; Fonseca, Jose] Uninova Univ, Lisbon, Portugal.
C3 Rudolfstiftung Hospital; Ludwig Boltzmann Institute
RP Brunner, S (通讯作者)，Rudolfstiftung Hosp Vienna, Dept Ophthalmol, Juchgasse 25, AT-1030 Vienna, Austria.
EM simon.brunner@wienkav.at
RI Mora, André/A-7912-2012; Fonseca, Jose MMR/C-9497-2013
OI Mora, André/0000-0003-1354-4739; Fonseca, Jose MMR/0000-0001-7173-7374
FU Scientific Fund of the Major of Vienna, Austria
FX The authors wish to thank the Department of Ophthalmology and the
   Rudolph Foundation Hospital for expendable items, especially
   photographic articles. Special thanks to our second randomizing center
   at the University Eye Clinic in Innsbruck, Austria and to our grading
   center at Uninova University, Lisbon, Portugal. The statistical study
   design was supported by the Institute for Medical Statistics and
   Documentation, University of Vienna. All statistical analyses were
   performed by Oeser GmbH, Vienna. The study was supported by a grant from
   the Scientific Fund of the Major of Vienna, Austria. The sponsor had no
   role in the conduct of this research.
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NR 53
TC 7
Z9 8
U1 0
U2 3
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 86
EP 93
DI 10.1159/000345492
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 085NO
UT WOS:000314621700004
PM 23235439
DA 2022-11-30
ER

PT J
AU Kinnunen, PKJ
   Kaarniranta, K
   Mahalka, AK
AF Kinnunen, Paavo K. J.
   Kaarniranta, Kai
   Mahalka, Ajay K.
TI Protein-oxidized phospholipid interactions in cellular signaling for
   cell death: From biophysics to clinical correlations
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Review
DE Oxidized phospholipid; Biomembrane; Protein aggregation; Misfolding;
   Amyloid
ID SYNUCLEIN MEMBRANE INTERACTIONS; CYTOCHROME-C; ALPHA-SYNUCLEIN;
   OXIDATION-PRODUCTS; TRANSBILAYER MOVEMENT; LIPID-PEROXIDATION;
   ALZHEIMER-DISEASE; CRYSTAL-STRUCTURE; BINDING; CARDIOLIPIN
AB Oxidative stress is associated with several major ailments. However, it is only recently that the developments in our molecular level understanding of the consequences of oxidative stress in modifying the chemical structures of biomolecules, lipids in particular, are beginning to open new emerging insights into the significance of oxidative stress in providing mechanistic insights into the etiologies of these diseases. In this brief review we will first discuss the role of lipid oxidation in controlling the membrane binding of cytochrome c, a key protein in the control of apoptosis. We then present an overview of the impact of oxidized phospholipids on the biophysical properties of lipid bilayers and continue to discuss, how these altered properties can account for the observed enhancement of formation of intermediate state oligomers by cytotoxic amyloid forming peptides associated with pathological conditions as well as host defense peptides of innate immunity. In the third part, we will discuss how the targeting of oxidized phospholipids by i) pathology associated peptides and ii) host defense peptides can readily explain the observed clinical correlations associating Alzheimer's and Parkinson's diseases with increased risk for type 2 diabetes and age-related macular degeneration, and the apparent protective effect of Alzheimer's and Parkinson's diseases from some cancers, as well as the inverse, apparent protection by cancer from Alzheimer's and Parkinson's diseases. This article is part of a Special Issue entitled: Oxidized phospholipids-Their properties and interactions with proteins. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Kinnunen, Paavo K. J.; Mahalka, Ajay K.] Aalto Univ, Helsinki Biophys & Biomembrane Grp, Dept Biomed Engn & Computat Sci, Espoo, Finland.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
C3 Aalto University; University of Eastern Finland; Kuopio University
   Hospital; University of Eastern Finland
RP Kinnunen, PKJ (通讯作者)，Dept Biomed Engn & Computat Sci, Helsinki Biophys & Biomembrane Grp, POB 12200,Rakentajanaukio 3, FIN-00076 Aalto, Finland.
EM paavo.kinnunen@aalto.fi
RI Mahalka, Ajay Kumar/G-6875-2012; Mahalka, Ajay/K-3993-2015
OI Mahalka, Ajay Kumar/0000-0002-0716-9947; Kaarniranta,
   Kai/0000-0003-2600-8679
FU Academy of Finland; ESF EuroMEMBRANE CRP OXPL; EU; Sigrid Juselius
   Foundation
FX The authors thank Vladimir Zamotin PhD for the careful reading of the
   manuscript and Prof. Stephen White (UC Irvine), and Prof. Ken Dill
   (SUNY) for their kind permission to reproduce Figs. (4) and (6),
   respectively. HBBG is supported by grants from the Academy of Finland,
   ESF EuroMEMBRANE CRP OXPL, EU FP6 (Nanoear) and FP7 (Sonodrugs), and the
   Sigrid Juselius Foundation.
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NR 104
TC 45
Z9 46
U1 0
U2 25
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 1879-2642
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD OCT
PY 2012
VL 1818
IS 10
SI SI
BP 2446
EP 2455
DI 10.1016/j.bbamem.2012.04.008
PG 10
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 983RD
UT WOS:000307135500008
PM 22542574
OA Bronze
DA 2022-11-30
ER

PT J
AU Tosh, J
   Brazier, J
   Evans, P
   Longworth, L
AF Tosh, Jonathan
   Brazier, John
   Evans, Philippa
   Longworth, Louise
TI A Review of Generic Preference-Based Measures of Health-Related Quality
   of Life in Visual Disorders
SO VALUE IN HEALTH
LA English
DT Review
DE Health-related quality of life; quality of life; QALYs; utilities;
   vision
ID SEASONAL ALLERGIC CONJUNCTIVITIS; MACULAR DEGENERATION; UTILITY VALUES;
   RESOURCE UTILIZATION; CATARACT-SURGERY; IMPAIRMENT; IMPACT; EQ-5D;
   GLAUCOMA; BURDEN
AB Objective: This review examines generic preference-based measures and their ability to reflect health-related quality of life in patients with visual disorders. Methods: A systematic search was undertaken to identify clinical studies of patients with visual disorders where health state utility values were measured and reported. Data were extracted to assess the validity and responsiveness of the measures. A narrative synthesis of the data was undertaken due to the heterogeneity between different studies. Results: There was considerable heterogeneity in the 31 studies identified in terms of patient characteristics, visual disorders, and outcomes reported. Vision loss was associated with a reduction in scores across the preference-based measure, but the evidence on validity and responsiveness was mixed. The EQ-5D healthrelated assessment instrument's performance differed according to condition, with poor performance in age-related macular degeneration (AMD) and diabetic retinopathy. The more limited evidence on the HUI-3 instrument found it performed best in differentiating between severity groups of patients with glaucoma, AMD, cataracts, and diabetic retinopathy. One study reported data on the SF-6D instrument and showed it was able to differentiate between patients with AMD. Conclusions: The performance of the EQ-5D in visual disorders was mixed. The HUI-3 seemed to perform better in some conditions, but the evidence on this and SF-6D is limited. More head to head comparisons of these three measures are required. The new five-level version of EQ-5D may do better at the milder end of visual function.
C1 [Tosh, Jonathan; Brazier, John; Evans, Philippa] Univ Sheffield, Sch Hlth & Related Res, Sheffield S1 4DA, S Yorkshire, England.
   [Longworth, Louise] Brunel Univ, Hlth Econ Res Grp, Uxbridge UB8 3PH, Middx, England.
C3 University of Sheffield; Brunel University
RP Tosh, J (通讯作者)，Univ Sheffield, Sch Hlth & Related Res, 30 Regent St, Sheffield S1 4DA, S Yorkshire, England.
EM j.tosh@sheffield.ac.uk
RI brazier, john e/B-1936-2008
OI Longworth, Louise/0000-0003-2512-4862; Tosh,
   Jonathan/0000-0002-8288-4270; Brazier, John/0000-0001-8645-4780
FU Medical Research Council as part of the Medical Research
   Council-National Institute for Health [G0901486]; MRC [G0901486] Funding
   Source: UKRI; Medical Research Council [G0901486] Funding Source:
   researchfish
FX This project was funded by the Medical Research Council as part of the
   Medical Research Council-National Institute for Health Research
   Methodology Research programme (G0901486).
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NR 45
TC 98
Z9 100
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD JAN-FEB
PY 2012
VL 15
IS 1
BP 118
EP 127
DI 10.1016/j.jval.2011.08.002
PG 10
WC Economics; Health Care Sciences & Services; Health Policy & Services
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Business & Economics; Health Care Sciences & Services
GA 879GU
UT WOS:000299318500014
PM 22264979
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Biron, KE
   Dickstein, DL
   Gopaul, R
   Jefferies, WA
AF Biron, Kaan E.
   Dickstein, Dara L.
   Gopaul, Rayshad
   Jefferies, Wilfred A.
TI Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain
   Barrier Permeability and Hypervascularity in Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR RISK-FACTORS; A-BETA PEPTIDE;
   TRANSGENIC MOUSE MODEL; PRECURSOR PROTEIN; ENDOGLIN CD105; PROGNOSTIC
   MARKERS; MULTIPLE-SCLEROSIS; WHITE-MATTER; IN-VIVO
AB Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the "Vascular hypothesis", holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration.
C1 [Biron, Kaan E.; Gopaul, Rayshad; Jefferies, Wilfred A.] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada.
   [Biron, Kaan E.; Gopaul, Rayshad; Jefferies, Wilfred A.] Univ British Columbia, Biomed Res Ctr, Vancouver, BC, Canada.
   [Biron, Kaan E.; Gopaul, Rayshad; Jefferies, Wilfred A.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada.
   [Dickstein, Dara L.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA.
   [Dickstein, Dara L.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA.
   [Gopaul, Rayshad; Jefferies, Wilfred A.] Univ British Columbia, Dept Zool, Vancouver, BC, Canada.
   [Gopaul, Rayshad; Jefferies, Wilfred A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
C3 University of British Columbia; University of British Columbia;
   University of British Columbia; Icahn School of Medicine at Mount Sinai;
   Icahn School of Medicine at Mount Sinai; University of British Columbia;
   University of British Columbia
RP Biron, KE (通讯作者)，Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada.
EM wilf@brc.ubc.ca
RI Dickstein, Dara/AAH-6603-2020; Dickstein, Dara/F-3036-2013
FU Canadian Institutes of Health Research (CIHR)
FX This work was supported by grants to Dr. Jefferies from the Canadian
   Institutes of Health Research (CIHR). 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 71
TC 196
Z9 207
U1 0
U2 27
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 31
PY 2011
VL 6
IS 8
AR e23789
DI 10.1371/journal.pone.0023789
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 817NM
UT WOS:000294680800022
PM 21909359
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Good, TJ
   Kimura, AE
   Mandava, N
   Kahook, MY
AF Good, Travis J.
   Kimura, Alan E.
   Mandava, Naresh
   Kahook, Malik Y.
TI Sustained elevation of intraocular pressure after intravitreal
   injections of anti-VEGF agents
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; ANGIOGENESIS; EFFICACY;
   SAFETY
AB Aims To report the rate of intraocular pressure (IOP) elevation associated with repeated intravitreal injections of antivascular endothelial growth factor (VEGF) agents and to determine if a pre-existing diagnosis of glaucoma is a risk factor for this phenomenon.
   Methods The charts of 215 eyes undergoing intravitreal injection with anti-VEGF agents for wet age-related macular degeneration (AMD) were retrospectively examined with respect to frequency of injections, number of injections and changes in IOP. Data were analysed independently for two groups (1) pre-existing glaucoma and (2) no history of glaucoma.
   Results Of the 215 eyes receiving injections with bevacizumab and/or ranibizumab, 6% (n=13) had sustained IOP elevation requiring medical or laser interventions. Of the eyes receiving only bevacizumab, 9.9% (10/101) had sustained elevated IOP, while 3.1% (3/96) of eyes receiving only ranibizumab experienced increases (p=0.049). Patients with pre-existing glaucoma experienced higher rates of elevated IOP when compared with patients without pre-existing glaucoma (33% vs 3.1% respectively; p<0.001). The glaucoma subgroup had a lower median number of injections (6; interquartile range 5-10) compared with the non-glaucoma group (9.5; interquartile range 6-13.7; p=0.031).
   Conclusions The incidence of sustained elevated IOP in patients receiving intravitreal anti-VEGF injections is significant. Additionally, these data suggest the possibility of a heightened risk for further elevation of IOP in patients with pre-existing glaucoma who receive either bevacizumab or ranibizumab. Prospective studies are needed to verify these results and better understand the implications of these findings.
C1 [Good, Travis J.; Mandava, Naresh; Kahook, Malik Y.] Univ Colorado, Sch Med, Denver, CO USA.
   [Kimura, Alan E.] Colorado Retina Associates, Denver, CO USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; University of Colorado Denver
RP Kahook, MY (通讯作者)，Univ Colorado Denver, Sch Med, Dept Ophthalmol, Rocky Mt Lions Eye Inst, 1675 Aurora Court,POB 6510,Mail Stop F-731, Aurora, CO 80045 USA.
EM malik.kahook@gmail.com
FU Genentech
FX MYK, AEK and NM have received research support from Genentech in the
   past. Genentech had no involvement in this study nor with the
   preparation of this manuscript.
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NR 21
TC 150
Z9 155
U1 0
U2 12
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 2011
VL 95
IS 8
BP 1111
EP 1114
DI 10.1136/bjo.2010.180729
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 793ST
UT WOS:000292844100016
PM 20702430
DA 2022-11-30
ER

PT J
AU Awdeh, RM
   Elsing, SH
   Deramo, VA
   Stinnett, S
   Lee, PP
   Fekrat, S
AF Awdeh, Richard M.
   Elsing, Sarah H.
   Deramo, Vincent A.
   Stinnett, Sandra
   Lee, Paul P.
   Fekrat, Sharon
TI Vision-related quality of life in persons with unilateral branch retinal
   vein occlusion using the 25-item National Eye Institute Visual Function
   Questionnaire
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PEOPLE
AB Aim To evaluate vision-related quality of life in persons with branch retinal vein occlusion (BRVO) using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).
   Design Observational, cross-sectional, interviewer-administered study.
   Methods 46 patients with unilateral BRVO were included in this study. Scores on the VFQ-25 were analysed and converted to scaled scores per NEI VFQ-25 algorithms. Clinical data including age, gender, employment status, living arrangements, visual acuity, number of systemic diseases and duration of BRVO were also recorded. Subscale results were compared with previously published data, and subgroup analyses were performed.
   Results Mean adjusted subscale responses among BRVO patients were higher (except for ocular pain) than known averages in patients with diabetic retinopathy, central retinal vein occlusion, age-related macular degeneration and low vision, but lower than known averages in a reference group of people without ocular disease. Subscale responses correlated significantly with visual acuity in the involved eye. This observation held true in eight of 12 subscales, even in patients who maintained vision of 20/25 or better in the uninvolved eye. The General Health subscale and number of systemic diseases correlated significantly with both the General Vision and Peripheral Vision subscale scores. There was no correlation between subscale responses and age.
   Conclusions BRVO is a retinal vascular disease that is associated with a decrease in vision-related quality of life as determined by the VFQ-25. A decrease in VFQ-25 score is correlated with involved eye visual acuity, even when good visual acuity is maintained in the uninvolved eye.
C1 [Awdeh, Richard M.; Stinnett, Sandra; Lee, Paul P.; Fekrat, Sharon] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
   [Elsing, Sarah H.] Duluth Clin, Duluth, MN USA.
   [Deramo, Vincent A.] Albert Einstein Coll Med, N Shore Long Isl Jewish Hlth Syst, Dept Ophthalmol, New Hyde Pk, NY USA.
   [Deramo, Vincent A.] Long Isl Vitreoretinal Consultants, Great Neck, NY USA.
C3 Duke University; Northwell Health; Yeshiva University
RP Fekrat, S (通讯作者)，Duke Univ, Ctr Eye, Box 3802, Durham, NC 27710 USA.
EM fekra001@mc.duke.edu
RI Lee, Paul/D-1018-2013
OI Stinnett, Sandra/0000-0001-7192-0195; Lee, Paul/0000-0002-3338-136X
FU Research to Prevent Blindness; Heed Ophthalmic Foundation; Ronald G
   Michels Fellowship Foundation; AOS-Knapp Fellowship
FX Supported by Research to Prevent Blindness (SHE, PPL, SF), Heed
   Ophthalmic Foundation Fellowship (VAD); Ronald G Michels Fellowship
   Foundation (VAD); AOS-Knapp Fellowship (VAD).
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NR 12
TC 69
Z9 69
U1 0
U2 4
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 2010
VL 94
IS 3
BP 319
EP 323
DI 10.1136/bjo.2007.135913
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 566BZ
UT WOS:000275346200014
PM 19737736
DA 2022-11-30
ER

PT J
AU Carr, AJ
   Vugler, AA
   Hikita, ST
   Lawrence, JM
   Gias, C
   Chen, LL
   Buchholz, DE
   Ahmado, A
   Semo, M
   Smart, MJK
   Hasan, S
   da Cruz, L
   Johnson, LV
   Clegg, DO
   Coffey, PJ
AF Carr, Amanda-Jayne
   Vugler, Anthony A.
   Hikita, Sherry T.
   Lawrence, Jean M.
   Gias, Carlos
   Chen, Li Li
   Buchholz, David E.
   Ahmado, Ahmad
   Semo, Ma'ayan
   Smart, Matthew J. K.
   Hasan, Shazeen
   da Cruz, Lyndon
   Johnson, Lincoln V.
   Clegg, Dennis O.
   Coffey, Pete J.
TI Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell
   Transplantation in the Retinal Dystrophic Rat
SO PLOS ONE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; RCS RAT; SUBRETINAL TRANSPLANTATION; AUTOLOGOUS
   TRANSPLANTATION; PHOTORECEPTOR DEGENERATION; MACULAR TRANSLOCATION;
   HUMAN FIBROBLASTS; PROGENITOR CELLS; VISUAL FUNCTION; RPE
AB Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Longterm visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients.
C1 [Carr, Amanda-Jayne; Vugler, Anthony A.; Lawrence, Jean M.; Gias, Carlos; Chen, Li Li; Ahmado, Ahmad; Semo, Ma'ayan; Smart, Matthew J. K.; Hasan, Shazeen; Coffey, Pete J.] UCL, Inst Ophthalmol, Dept Ocular Biol & Therapeut, London, England.
   [Hikita, Sherry T.; Buchholz, David E.; Johnson, Lincoln V.; Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Ctr Stem Cell Biol & Engn, Santa Barbara, CA 93106 USA.
   [Johnson, Lincoln V.; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
   [da Cruz, Lyndon] Moorfields Eye Hosp, Dept Vitreoretinal Surg, London, England.
C3 University of London; University College London; University of
   California System; University of California Santa Barbara; University of
   California System; University of California Santa Barbara; University of
   London; University College London; Moorfields Eye Hospital NHS
   Foundation Trust
RP Carr, AJ (通讯作者)，UCL, Inst Ophthalmol, Dept Ocular Biol & Therapeut, London, England.
EM a.carr@ucl.ac.uk
RI Carr, Amanda/ABG-6282-2020; Ahmado, Ahmad/R-5537-2019
OI Carr, Amanda/0000-0002-5469-0030; Semo, Ma'ayan/0000-0002-3890-721X;
   Coffey, Peter/0000-0002-5427-2939
FU London Project to Cure Blindness; The California Institute for
   Regenerative Medicine
FX This work was supported by funding from the London Project to Cure
   Blindness and The California Institute for Regenerative Medicine. 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 78
TC 331
Z9 353
U1 1
U2 78
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 3
PY 2009
VL 4
IS 12
AR e8152
DI 10.1371/journal.pone.0008152
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 533MW
UT WOS:000272829000010
PM 19997644
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Thurman, JM
   Renner, B
   Kunchithapautham, K
   Ferreira, VP
   Pangburn, MK
   Ablonczy, Z
   Tomlinson, S
   Holers, VM
   Rohrer, B
AF Thurman, Joshua M.
   Renner, Brandon
   Kunchithapautham, Kannan
   Ferreira, Viviana P.
   Pangburn, Michael K.
   Ablonczy, Zsolt
   Tomlinson, Stephen
   Holers, V. Michael
   Rohrer, Baerbel
TI Oxidative Stress Renders Retinal Pigment Epithelial Cells Susceptible to
   Complement-mediated Injury
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; FUNDUS CHANGES; ACTIVATION; SECRETION;
   DRUSEN; RPE; RECEPTORS
AB Uncontrolled activation of the alternative pathway of complement is thought to be associated with age-related macular degeneration (AMD). The alternative pathway is continuously activated in the fluid phase, and tissue surfaces require continuous complement inhibition to prevent spontaneous autologous tissue injury. Here, we examined the effects of oxidative stress on the ability of immortalized human retinal pigment epithelial cells (ARPE-19) to regulate complement activation on their cell surface. Combined treatment with H2O2 (to induce oxidative stress) and complement-sufficient serum was found to disrupt the barrier function of stable ARPE-19 monolayers as determined by transepithelial resistance (TER) measurements. Neither treatment alone had any effect. TER reduction was correlated with increased cell surface deposition of C3, and could be prevented by using C7-depleted serum, an essential component of the terminal complement pathway. Treatment with H2O2 reduced surface expression of the complement inhibitors DAF, CD55, and CD59, and impaired regulation at the cell surface by factor H present within the serum. Combined treatment of the monolayers with H2O2 and serum elicited polarized secretion of vascular epidermal growth factor (VEGF). Both, secretion of VEGF and TER reduction could be attenuated using either an alternative pathway inhibitor or by blocking VEGF receptor-1/2 signaling. Regarded together, these studies demonstrate that oxidative stress reduces regulation of complement on the surface of ARPE-19 cells, increasing complement activation. This sublytic activation results in VEGF release, which mediates disruption of the cell monolayer. These findings link oxidative stress, complement activation, and apical VEGF release, which have all been associated with the pathogenesis of AMD.
C1 [Holers, V. Michael] Univ Colorado Denver, Sch Med, Dept Med, Aurora, CO 80045 USA.
   [Kunchithapautham, Kannan; Ablonczy, Zsolt; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Div Res, Charleston, SC 29425 USA.
   [Kunchithapautham, Kannan; Ablonczy, Zsolt; Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA.
   [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
   [Ferreira, Viviana P.; Pangburn, Michael K.] Univ Texas Hlth Ctr Tyler, Dept Biochem, Tyler, TX 75708 USA.
C3 Children's Hospital Colorado; University of Colorado System; University
   of Colorado Anschutz Medical Campus; Medical University of South
   Carolina; Medical University of South Carolina; Medical University of
   South Carolina; University of Texas System; University of Texas-Health
   Sciences Center at Tyler (UTHSCT)
RP Rohrer, B (通讯作者)，167 Ashley Ave,SEI 511, Charleston, SC 29425 USA.
EM rohrer@musc.edu
OI Ferreira, Viviana/0000-0001-8923-5671
FU National Institutes of Health [DK077661, DK076690, DK035081, EY13520,
   EY017465, HL082485]; Vision Core [EY014793]; Foundation Fighting
   Blindness; American Heart Association [0735101N]; Medical University of
   South Carolina; NATIONAL EYE INSTITUTE [R01EY013520, R43EY017465,
   R24EY014793] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R01HL082485] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK076690,
   R37DK035081, R03DK077661, R01DK035081] Funding Source: NIH RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants DK077661 and DK076690 (to J.M.T.), DK035081 (to M. K. P.),
   EY13520 and EY017465 (to B. R.), and HL082485 (to S. T.). This work was
   also supported by Vision Core Grant EY014793, the Foundation Fighting
   Blindness, American Heart Association Grant 0735101N (to V. P. F.), and
   an unrestricted grant to the Medical University of South Carolina from
   Research to Prevent Blindness, Inc., New York.
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NR 32
TC 136
Z9 142
U1 1
U2 9
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 JUN 19
PY 2009
VL 284
IS 25
BP 16939
EP 16947
DI 10.1074/jbc.M808166200
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 457VM
UT WOS:000266962400031
PM 19386604
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Santos, AF
   Zaltsman, AB
   Martin, RC
   Kuzmin, A
   Alexandrov, Y
   Roquemore, EP
   Jessop, RA
   van Erck, MGM
   Verheijen, JH
AF Santos, Albert Francis
   Zaltsman, Alla Borisovna
   Martin, Rhian Clare
   Kuzmin, Alexandru
   Alexandrov, Yuriy
   Roquemore, Elizabeth Price
   Jessop, Robert Arnold
   van Erck, Monique Gertruida Maria
   Verheijen, Johan Hendrikus
TI Angiogenesis: An Improved In Vitro Biological System and Automated
   Image-Based Workflow to Aid Identification and Characterization of
   Angiogenesis and Angiogenic Modulators
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CELL-MIGRATION; RHO-KINASE; ASSAYS; CANCER;
   METASTASIS; INVASION; VIVO
AB Angiogenesis is a general term describing formation of new tube-like microvessel sprouts that are the size of capillary blood vessels. Angiogenesis is fundamental in key stages of embryonic development, organ formation, and wound repair and is also involved in the development and progression of a variety of pathological conditions, including cancer (tumor growth and metastasis), cardiovascular disease, diabetic retinopathy, age-related macular degeneration, atherosclerosis, and rheumatoid arthritis. Because of its diverse roles in key physiological and pathological processes, angiogenesis is an important area of medical research, with a considerable number of angiogenic and anti-angiogenic drugs currently undergoing clinical trials. Cost-effective and efficient screening for potential lead compounds is therefore of prime importance. However, screening methodologies vary in their physiological relevance depending on how faithfully critical aspects of angiogenesis are represented. Cell-based in vitro angiogenesis assays are important tools for screening, which in many cases rely on imaging microscopy to ascertain drug effects. Unfortunately, such screens can be hampered by poorly defined biology, slow image acquisition by manual or semiautomated hardware, and slow data analysis by non-dedicated software. This article describes use of a 96-well microplate in vitro angiogenesis screening system as part of an integrated workflow, comprising (1) setting up the biology in a three-dimensional physiologically relevant system, (2) acquiring a series of image slices ("stacks") using an automated z-stage instrument, (3) collapsing the image stack series into sets of two-dimensional images, (4) segmenting objects of interest, and (5) analyzing the segmentation patterns in order to obtain statistically relevant data.
C1 [Santos, Albert Francis] GE Healthcare, Maynard Ctr, Cardiff CF14 7YT, S Glam, Wales.
   [Kuzmin, Alexandru] GE Healthcare, Piscataway, NJ USA.
   [van Erck, Monique Gertruida Maria; Verheijen, Johan Hendrikus] TNO Qual Life, Business Unit Biosci, Leiden, Netherlands.
C3 General Electric; General Electric; Netherlands Organization Applied
   Science Research
RP Santos, AF (通讯作者)，GE Healthcare, Maynard Ctr, Forest Farm, Cardiff CF14 7YT, S Glam, Wales.
EM albie.santos@ge.com
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NR 55
TC 15
Z9 15
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
EI 1557-8127
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD OCT
PY 2008
VL 6
IS 5
BP 693
EP 710
DI 10.1089/adt.2008.146
PG 18
WC Biochemical Research Methods; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 385QR
UT WOS:000261829200006
PM 19035850
DA 2022-11-30
ER

PT J
AU Economou, MA
   Wu, JM
   Vasilcanu, D
   Rosengren, L
   All-Ericsson, C
   van der Ploeg, I
   Menu, E
   Girnita, L
   Axelson, M
   Larsson, O
   Seregard, S
   Kvanta, A
AF Economou, Mario A.
   Wu, Jiangmei
   Vasilcanu, Daiana
   Rosengren, Linda
   All-Ericsson, Charlotta
   van der Ploeg, Ingeborg
   Menu, Eline
   Girnita, Leonard
   Axelson, Magnus
   Larsson, Olle
   Seregard, Stefan
   Kvanta, Anders
TI Inhibition of VEGF secretion and experimental choroidal
   neovascularization by picropodophyllin (PPP), an inhibitor of the
   insulin-like growth factor-1 receptor
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; TYROSINE KINASE;
   CYCLOLIGNAN PPP; ENDOTHELIAL-CELLS; MULTIPLE-MYELOMA; UVEAL MELANOMA;
   MOUSE MODEL; IGF-I; EXPRESSION
AB INTRODUCTION. Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration (AMD) and a leading cause of vision loss. Along with other angiogenic factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV.
   PURPOSE. A prior study has shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in vivo model. In this study we investigated the effect of PPP on VEGF expression, both in vitro and in vivo, and whether this effect has antiangiogenic consequences in a murine CNV model.
   METHODS. C57BL/6J mice with laser-induced CNVs were treated with PPP. Effects on CNV area were assayed by image analysis. VEGF levels in the choroid and retinal pigment epithelial cells (ARPE-19) were measured by Western blot or ELISA. Transcriptional activation of the VEGF promoter was determined by luciferase reporter gene assay.
   RESULTS. Mice treated with PPP, administered intraperitoneally or orally, showed a 22% to 32% (P = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroid were significantly reduced. In cultured ARPE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. PPP reduced the level of transcriptional activity of the VEGF promoter.
   CONCLUSIONS. PPP reduces IGF-1-dependent VEGF expression and CNV in vivo. Accordingly, IGF-1R inhibitors may be useful tools in the treatment of conditions associated with CNV, including neovascular AMD.
C1 [Economou, Mario A.; Wu, Jiangmei; All-Ericsson, Charlotta; van der Ploeg, Ingeborg; Seregard, Stefan; Kvanta, Anders] St Eriks Eye Hosp, SE-11282 Stockholm, Sweden.
   [Economou, Mario A.; Vasilcanu, Daiana; Rosengren, Linda; Girnita, Leonard; Larsson, Olle] Karolinska Inst, Canc Ctr Karolinska R8 04, Dept Pathol & Oncol, Stockholm, Sweden.
   [Menu, Eline] Vrije Univ Brussels, Dept Hematol & Immunol, Brussels, Belgium.
   [Axelson, Magnus] Karolinska Hosp, Dept Clin Chem, S-10401 Stockholm, Sweden.
C3 Karolinska Institutet; Vrije Universiteit Brussel; Karolinska
   Institutet; Karolinska University Hospital
RP Economou, MA (通讯作者)，St Eriks Eye Hosp, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
EM mario-alexander.economou@sankterik.se
RI All-Ericsson, Charlotta/C-3642-2016; Menu, Eline/K-2856-2015; Girnita,
   Leonard/A-4168-2008
OI All-Ericsson, Charlotta/0000-0002-8428-6418; Menu,
   Eline/0000-0002-0805-6581; Girnita, Leonard/0000-0003-0280-9500
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NR 45
TC 36
Z9 38
U1 1
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 JUN
PY 2008
VL 49
IS 6
BP 2620
EP 2626
DI 10.1167/iovs.07-0742
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 307GG
UT WOS:000256306800044
PM 18515591
DA 2022-11-30
ER

PT J
AU Lipski, A
   Bornfeld, N
   Jurklies, B
AF Lipski, Andreas
   Bornfeld, Norbert
   Jurklies, Bernhard
TI Multifocal electroretinography in patients with exudative AMD and
   intravitreal treatment with pegaptanib sodium
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE mfERG; CNV; AMD; pegaptanib; Macugen
ID MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; CHOROIDAL NEOVASCULARIZATION;
   PROFESSIONAL-ASSOCIATION; PHOTODYNAMIC THERAPY; RETINAL FUNCTION; AGE;
   OPHTHALMOLOGISTS; ANGIOGENESIS; PATHOGENESIS
AB Background: To objectively investigate central retinal function in patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) before and after treatment with pegaptanib sodium (PS).
   Methods: Patients with CNV due to exudative AMD received intravitreal injections of 0.3 mg PS every sixth week if angiographic activity was evident. Longitudinal observation included recordings with multifocal electroretinography (mfERG) before the first treatment and before each injection at follow-up intervals.
   Results: During the observation period of 30.5 +/- 8 weeks (mean +/- SID) a mean number of 5.3 +/- 1.3 injections were applied. Final mean log(MAR) visual acuity decreased, statistically nonsignificant, from 0.67 +/- 0.3 at baseline to 0.74 +/- 0.16. mfERG recordings in 12 patients after 25 +/- 9 weeks evinced a decrease in response density which was statistically significant in the central 5 degrees. Mean P1-amplitudes of ring 1, 2, and 3 were reduced by 66%, 39% and 30%, respectively. During follow-up, implicit times of the P1 components remained stable within 4% of baseline. In three of four patients with vision loss of 2 lines or more, P1 -response amplitudes decreased substantially at least 6 weeks prior vision loss.
   Conclusion: Treatment with PS resulted in a decrease of central retinal function more obvious in mfERG than in VA longitudinal testing. Good correlations were seen between changes in mean vision and changes in mfERG response density components. As a decline in P1 -response amplitudes anteceded vision loss in this study, our results indicate a possible role of mfERG to predict vision loss during intravitreal pharmacotherapy.
C1 Univ Klinikum Essen, Dept Ophthalmol, D-45122 Essen, Germany.
C3 University of Duisburg Essen
RP Lipski, A (通讯作者)，Univ Klinikum Essen, Dept Ophthalmol, Hufelandstr 55, D-45122 Essen, Germany.
EM andreas.lipski@uni-duisburg-essen.de
CR Adamis AP, 2005, RETINA-J RET VIT DIS, V25, P111, DOI 10.1097/00006982-200502000-00001
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NR 25
TC 12
Z9 12
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2007
VL 27
IS 7
BP 864
EP 872
DI 10.1097/IAE.0b013e318154b9b9
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 212QT
UT WOS:000249612600010
PM 17891010
DA 2022-11-30
ER

PT J
AU Olafsdottir, E
   Andersson, DK
   Stefansson, E
AF Olafsdottir, Eydis
   Andersson, Dan K.
   Stefansson, Einar
TI Visual acuity in a population with regular screening for type 2 diabetes
   mellitus and eye disease
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
DE type 2 diabetes mellitus; blindness; visual impairment; screening
ID EARLY-DIAGNOSIS; IMPAIRMENT; BLINDNESS; RETINOPATHY; PREVALENCE;
   AUSTRALIA; VISION
AB Purpose: Regular screening for both diabetes mellitus and diabetic eye disease should be the gold standard in preventing diabetic blindness. In the community of Laxa, County of Orebro, Sweden, such screening has been carried out since 1983. We evaluate visual impairment and blindness in this population.
   Methods: All persons in the community of Laxa with a diagnosis of type 2 diabetes mellitus (n = 276) participated in the study. An age- and gender-matched control group (n = 259) was assembled. Best corrected visual acuity (BCVA) was tested in all participants, and a detailed eye examination performed by an ophthalmologist.
   Results: No significant statistical differences were seen between the diabetes and control groups regarding visual acuity ( VA). In all, 2.9% of the diabetes patients and 1.2% of the controls had BCVA <= 0.1. Only one person in the diabetes group was blind as a result of diabetic retinopathy. In both groups the leading cause of blindness was age- related macular degeneration. In a logistic regression analysis we found that in both the diabetes and the control populations, increasing age was related to worsening BCVA ( odds ratio [OR] 1.13, 95% confidence interval [CI] 1.10-1.16 versus OR 1.16, 95% CI 1.13-1.19), as was female gender in the diabetes group only (OR 2.73, 95% CI 1.69-4.40).
   Conclusions: In a population that is carefully screened for diabetes mellitus and provided with regular screening for diabetic retinopathy, the loss of vision from diabetic retinopathy is uncommon.
C1 Natl Univ Hosp Reykjavik, Dept Ophthalmol, Reykjavik, Iceland.
   Univ Iceland, Dept Ophthalmol, Reykjavik, Iceland.
   Uppsala Univ, Dept Publ Hlth & Caring Sci, Family Med & Clin Epidemiol Sect, Uppsala, Sweden.
   Natl Board Hlth & Welf, Reg Supervising Unit, Orebro, Sweden.
C3 Landspitali National University Hospital; University of Iceland; Uppsala
   University; National Board of Health & Welfare
RP Olafsdottir, E (通讯作者)，Landspitali Haskolasjukrahus, IS-101 Reykjavik, Iceland.
EM eydiso@landspitali.is
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NR 27
TC 33
Z9 37
U1 0
U2 3
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 FEB
PY 2007
VL 85
IS 1
BP 40
EP 45
DI 10.1111/j.1600-0420.2006.00753.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 128CJ
UT WOS:000243634100007
PM 17244208
OA Bronze
DA 2022-11-30
ER

PT J
AU Boscia, F
   Furino, C
   Prascina, F
   Delle Noci, N
   Sborgia, L
   Sborgia, C
AF Boscia, F
   Furino, C
   Prascina, F
   Delle Noci, N
   Sborgia, L
   Sborgia, C
TI Combined surgical ablation and intravitreal triamcinolone acetonide for
   retinal angiomatous proliferation
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE choroidal neovascularization; retinal angiomatous proliferations;
   triamcinolone acetonide
ID OCCULT CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; ANASTOMOSES;
   VERTEPORFIN; THERAPY
AB PURPOSE. Neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) has a poor natural history and the efficacy of any treatment has not yet been established. The authors describe a combined surgical treatment.
   METHODS. A 76-year-old woman presented with a best-corrected visual acuity (BCVA) of 201600 in the right eye and macula with stage 3 RAP as identified by fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). After a standard three-port pars plana core vitrectomy (PPV), endodiathermy of the arteriolar and venous feeder vessels of each lesion was performed, intraretinal RAP feeder vessels were cut with manual vertical intraocular scissors, and 0.1 mL of triamcinolone acetonide (TAAC) was injected intravitreally. At 1 and 4 weeks and at the sixth month, the patient underwent a complete eye examination, FA, ICGA, and OCT to assess outcomes and complications.
   RESULTS. Six months later, BCVA was stable at 20/300, intraocular pressure was 15 mmHg, anterior segment and vitreous cavity were clear without evidence of TAAC granules, and retina was attached. FA and ICGA showed a complete occlusion of the RAP and absence of leakage or ischemia and OCT demonstrated decreased macular thickness with resolution of both intraretinal edema and pigment epithelium detachment, and the restoration of the normal macular profile. At the end of follow-up, the authors did not observe any ocular or systemic complication.
   CONCLUSIONS. Surgical approach to RAP stage 3 with intravitreal injection of 4 mg of TAAC was safe and anatomically effective.
C1 Univ Bari, Dipartimento Oftalmol & Otorinolaringoiatria, I-70124 Bari, Italy.
   Univ Foggia, Dept Ophthalmol & Otorhinolaryngol, Foggia, Italy.
C3 Universita degli Studi di Bari Aldo Moro; University of Foggia
RP Boscia, F (通讯作者)，Univ Bari, Dipartimento Oftalmol & Otorinolaringoiatria, Piazza Giulio Cesare 11, I-70124 Bari, Italy.
EM francescoboscia@hotmail.com
RI Boscia, Francesco/AAC-7729-2022
OI Boscia, Francesco/0000-0002-5478-060X; Sborgia,
   Luigi/0000-0003-4433-9527
CR Axer-Siegel R, 2002, OPHTHALMOLOGY, V109, P1726, DOI 10.1016/S0161-6420(02)01149-1
   Blinder KJ, 2003, AM J OPHTHALMOL, V136, P407, DOI 10.1016/S0002-9394(03)00223-X
   Borrillo JL, 2003, ARCH OPHTHALMOL-CHIC, V121, P558, DOI 10.1001/archopht.121.4.558
   Danis RP, 2000, RETINA-J RET VIT DIS, V20, P244, DOI 10.1097/00006982-200003000-00004
   Hartnett ME, 1996, OPHTHALMOLOGY, V103, P2042, DOI 10.1016/S0161-6420(96)30389-8
   KUHN D, 1995, ARCH OPHTHALMOL-CHIC, V113, P1392, DOI 10.1001/archopht.1995.01100110052025
   Kuroiwa S, 2003, RETINA-J RET VIT DIS, V23, P417, DOI 10.1097/00006982-200306000-00027
   Slakter JS, 2000, OPHTHALMOLOGY, V107, P742, DOI 10.1016/S0161-6420(00)00009-9
   Spaide RF, 2003, OPHTHALMOLOGY, V110, P1517, DOI 10.1016/S0161-6420(03)00544-X
   Yannuzzi LA, 2001, RETINA-J RET VIT DIS, V21, P416, DOI 10.1097/00006982-200110000-00003
NR 10
TC 19
Z9 19
U1 0
U2 1
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JUL-AUG
PY 2005
VL 15
IS 4
BP 513
EP 516
DI 10.1177/112067210501500418
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 945OD
UT WOS:000230510900018
PM 16001389
DA 2022-11-30
ER

PT J
AU Yeh, DC
   Bula, DV
   Miller, JW
   Gragoudas, ES
   Arroyo, JG
AF Yeh, DC
   Bula, DV
   Miller, JW
   Gragoudas, ES
   Arroyo, JG
TI Expression of leukocyte adhesion molecules in human subfoveal choroidal
   neovascular membranes treated with and without photodynamic therapy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; GRANULOMATOUS INFLAMMATION; BREAST-CANCER; HUMAN RETINA;
   ANGIOGENESIS; VERTEPORFIN; RAT; MODULATION
AB PURPOSE. The purposes of this study were to investigate the immunostaining of the leukocyte adhesion molecules intercellular adhesion molecule (ICAM)-1 and E-selectin in subfoveal choroidal neovascular membranes (CNVMs) surgically excised from patients with age-related macular degeneration (AMD) and to determine whether prior photodynamic therapy (PDT) alters their immunostaining.
   METHODS. The localization of ICAM-1 and E-selectin in 10 subfoveal CNVMs was determined by immunohistochemistry. Membranes were also immunostained for CD31 to assess vascularity.
   RESULTS. Significantly higher numbers of CD31-staining vessels per unit membrane area were found in the peripheral regions of the membranes compared with the central regions (P = 0.05). ICAM-1 immunoreactivity in the CNVMs was found predominantly on RPE cells, but also on small vessels in the periphery. ICAM-1 staining was significantly more intense in the peripheral, more cellular areas of the membranes than in the central, more fibrotic regions (P = 0.04). ICAM-1 staining in the periphery of the CNVMs was greater than that in choroidal vessels and the RPE of the normal control eye. ICAM-1 immunostaining grade in peripheral regions of the CNVMs decreased with the increasing number of PDT treatments (P = 0.05). Some of the CNVMs also stained for E-selectin in RPE cells and small vessels in the periphery.
   CONCLUSIONS. In subfoveal CNVMs from patients with AMD, there is increased immunostaining for leukocyte adhesion molecules, particularly in the peripheral, more cellular regions where angiogenesis may be ongoing. Increasing numbers of PDT treatments may be associated with decreased ICAM-1 immunostaining in the proliferating edges of the CNVMs.
C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02215 USA.
C3 Harvard University; Beth Israel Deaconess Medical Center; Harvard
   Medical School; Massachusetts Eye & Ear Infirmary
RP Arroyo, JG (通讯作者)，Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Ophthalmol,Retina Serv, 330 Brookline Ave,Shapiro 5th Floor, Boston, MA 02215 USA.
EM jarroyo@bidmc.harvard.edu
OI Miller, Joan/0000-0003-2046-3996; Arroyo, Jorge/0000-0001-9812-296X
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NR 40
TC 36
Z9 40
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 JUL
PY 2004
VL 45
IS 7
BP 2368
EP 2373
DI 10.1167/iovs.03-0981
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 833VH
UT WOS:000222367900044
PM 15223819
DA 2022-11-30
ER

PT J
AU Saint-Geniez, M
   D'Amore, PA
AF Saint-Geniez, M
   D'Amore, PA
TI Development and pathology of the hyaloid, choroidal and retinal
   vasculature
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE angiogenesis; vascularization; retinopathy of prematurity; diabetic
   retinopathy
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; PROLIFERATIVE
   DIABETIC-RETINOPATHY; PROGRAMMED CAPILLARY REGRESSION;
   TUNICA-VASCULOSA-LENTIS; CELL-CELL INTERACTIONS; FACTOR MESSENGER-RNA;
   SMOOTH-MUSCLE-CELLS; PIGMENT EPITHELIUM; MACULAR DEGENERATION
AB During embryogenesis, the development and differentiation of the eye requires the concomitant formation of the neural/glial elements along with a dense vascular network. The adult neural retina is supported by two distinct vascular systems, the proper retinal vessels and the choroidal vessels. The two beds differ not only in their pattern of embryonic differentiation, but also in their function in the adult organism. The retinal vasculature has barrier properties similar to those observed in the brain, whereas the choroidal vessels display a highly fenestrated phenotype. The hyaloid vasculature is a transient embryonic vascular bed which is complete at birth in mammals and regresses contemporaneously with the formation of the retinal vasculature. The dependence of the retina on its blood supply makes it highly vulnerable to any vascular changes and indeed ocular diseases, such as proliferative retinopathy, age-related macular degeneration and the hyperplastic primary vitreous, which are associated with abnormalities of the different vascular beds of the eye. A number of factors have been implicated in developmental and pathological changes in vessel formation and regression, including fibroblast growth factors, platelet-derived endothelial growth factor and vascular endothelial growth factor, among others. The purpose of this review is to describe and discuss new insights into the mechanisms and molecular cues involved in the development of the normal and pathological vascular systems of the eye. The characterization of the molecules and cell-cell interactions involved in the formation, stabilization and regression of new vessels has led to the identification of potential control points for therapeutic intervention.
C1 Schepens Eye Res Inst, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA.
C3 Harvard University; Schepens Eye Research Institute; Harvard University;
   Harvard Medical School; Harvard University; Harvard Medical School
RP D'Amore, PA (通讯作者)，Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM pdamore@vision.eri.harvard.edu
RI SAINT-GENIEZ, MAGALI/P-3509-2019; D'Amore, Patricia A/G-5660-2017
OI SAINT-GENIEZ, MAGALI/0000-0001-9897-138X; D'Amore, Patricia
   A/0000-0001-9652-8974
FU NATIONAL CANCER INSTITUTE [P01CA045548] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY015435] Funding Source: NIH RePORTER; NCI
   NIH HHS [CA45548] Funding Source: Medline; NEI NIH HHS [EY05318,
   EY015435] Funding Source: Medline
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NR 133
TC 296
Z9 303
U1 3
U2 20
PU UNIV BASQUE COUNTRY UPV-EHU PRESS
PI BILBAO
PA PO BOX 1397, BILBAO, BIZKAIA E-48080, SPAIN
SN 0214-6282
EI 1696-3547
J9 INT J DEV BIOL
JI Int. J. Dev. Biol.
PY 2004
VL 48
IS 8-9
SI SI
BP 1045
EP 1058
DI 10.1387/ijdb.041895ms
PG 14
WC Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Developmental Biology
GA 882SH
UT WOS:000225958100036
PM 15558494
OA Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Nagineni, CN
   Samuel, W
   Nagineni, S
   Pardhasaradhi, K
   Wiggert, B
   Detrick, B
   Hooks, JJ
AF Nagineni, CN
   Samuel, W
   Nagineni, S
   Pardhasaradhi, K
   Wiggert, B
   Detrick, B
   Hooks, JJ
TI Transforming growth factor-beta induces expression of vascular
   endothelial growth factor in human retinal pigment epithelial cells:
   Involvement of mitogen-activated protein kinases
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; FACTOR VEGF; CROSS-TALK; DIABETIC-RETINOPATHY;
   MEDIATED EXPRESSION; MESSENGER-RNA; MAP KINASE; SMAD; SECRETION;
   PERMEABILITY
AB Vascular endothelial growth factor (VEGF) is a major agent in choroidal and retinal neovascularization, events associated with age-related macular degeneration (AMD) and diabetic retinopathy. Retinal pigment epithelium (RPE), strategically located between retina and choroid, plays a critical role in retinal disorders. We have examined the effects of various growth factors on the expression and secretion of VEGF by human retinal pigment epithelial cell cultures (HRPE). RT-PCR analyses revealed the presence of three isoforms of mRNA corresponding to VEGF 121, 165, and 189 that were up regulated by TGF-beta1. TGF-beta1, beta2, and beta3 were the potent inducers of VEGF secretion by HRPE cells whereas bFGF, PDGF, TGF-alpha, and GMCSF had no effects. TGF-beta receptor type 11 antibody significantly reversed induction of VEGF secretion by TGF-beta. In contrast activin, inhibin and BMP, members of TGF-beta super family, had no effects on VEGF expression in HRPE. VEGF mRNA levels and protein secretion induced by TGF-beta were significantly inhibited by SB203580 and U0126, inhibitors of MAP kinases, but not by staurosporine and PDTC, protein kinase C and NF-kappaB pathway inhibitors, respectively. TGF-beta also induced VEGF expression by fibroblasts derived from human choroid of eye. TGF-beta induction of VEGF secretion by RPE and choroid cells may play a significant role in choroidal neovascularization (CNV) in AMD. Since the secretion of VEGF by HRPE is regulated by MAP kinase pathways, MAP kinase inhibitors may have potential use as therapeutic agents for CNV in AMD. 2003. Published 2003 Wiley-Liss, lnc.(dagger).
C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   Walter Reed Army Inst Res, Dept Biochem, Washington, DC USA.
   Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); United States Department of Defense; United States
   Army; Walter Reed Army Institute of Research (WRAIR); Johns Hopkins
   University; Johns Hopkins Medicine
RP Hooks, JJ (通讯作者)，NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 6N 228, Bethesda, MD 20892 USA.
EM jjhooks@helix.nih.gov
FU NATIONAL EYE INSTITUTE [Z01EY000070, Z01EY000277, ZIAEY000233,
   Z01EY000233, ZIAEY000277] Funding Source: NIH RePORTER
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NR 66
TC 143
Z9 155
U1 0
U2 10
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 DEC
PY 2003
VL 197
IS 3
BP 453
EP 462
DI 10.1002/jcp.10378
PG 10
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA 737NU
UT WOS:000186239300016
PM 14566975
DA 2022-11-30
ER

PT J
AU Shamsi, F
   Liu, R
   Owsley, C
   Kwon, M
AF Shamsi, Foroogh
   Liu, Rong
   Owsley, Cynthia
   Kwon, MiYoung
TI Identifying the Retinal Layers Linked to Human Contrast Sensitivity Via
   Deep Learning
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE OCT; contrast sensitivity; deep learning; retinal ganglion cells;
   glaucoma
ID VISUAL-FIELD SENSITIVITY; NERVE-FIBER LAYER; CONVOLUTIONAL
   NEURAL-NETWORKS; GANGLION-CELL; MACULAR DEGENERATION; READING SPEED;
   GLAUCOMA; THICKNESS; OCT; VISION
AB PURPOSE. Luminance contrast is the fundamental building block of human spatial vision. Therefore contrast sensitivity, the reciprocal of contrast threshold required for target detection, has been a barometer of human visual function. Although retinal ganglion cells (RGCs) are known to be involved in contrast coding, it still remains unknown whether the retinal layers containing RGCs are linked to a person's contrast sensitivity (e.g., Pelli-Robson contrast sensitivity) and, if so, to what extent the retinal layers are related to behavioral contrast sensitivity. Thus the current study aims to identify the retinal layers and features critical for predicting a person's contrast sensitivity via deep learning.
   METHODS. Data were collected from 225 subjects including individuals with either glaucoma, age-related macular degeneration, or normal vision. A deep convolutional neural network trained to predict a person's Pelli-Robson contrast sensitivity from structural retinal images measured with optical coherence tomography was used. Then, activation maps that represent the critical features learned by the network for the output prediction were computed.
   RESULTS. The thickness of both ganglion cell and inner plexiform layers, reflecting RGC counts, were found to be significantly correlated with contrast sensitivity (r = 0.26 similar to 0.58, Ps < 0.001 for different eccentricities). Importantly, the results showed that retinal layers containing RGCs were the critical features the network uses to predict a person's contrast sensitivity (an average R-2 = 0.36 +/- 0.10).
   CONCLUSIONS. The findings confirmed the structure and function relationship for contrast sensitivity while highlighting the role of RGC density for human contrast sensitivity.
C1 [Shamsi, Foroogh; Liu, Rong; Kwon, MiYoung] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
   [Liu, Rong; Owsley, Cynthia; Kwon, MiYoung] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Heersink Sch Med, Birmingham, AL USA.
   [Liu, Rong] Univ Sci & Technol China, Dept Life Sci & Med, Hefei, Peoples R China.
C3 Northeastern University; University of Alabama System; University of
   Alabama Birmingham; Chinese Academy of Sciences; University of Science &
   Technology of China, CAS
RP Kwon, M (通讯作者)，125 Nightingale Hall,360 Huntington Ave, Boston, MA 02115 USA.
EM m.kwon@northeastern.edu
FU Research to Prevent Blindness (RPB)/Lions' Clubs International
   Foundation (LCIF) Low Vision Research Award; NIH/NEI [R01 EY027857];
   NIH/NIA [P30AG22838]; Eyesight Foundation of Alabama
FX Supported by Research to Prevent Blindness (RPB)/Lions' Clubs
   International Foundation (LCIF) Low Vision Research Award, NIH/NEI Grant
   R01 EY027857, NIH/NIA grant P30AG22838, and Eyesight Foundation of
   Alabama.
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NR 102
TC 3
Z9 3
U1 5
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 2022
VL 63
IS 2
AR 27
DI 10.1167/iovs.63.2.27
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZI0MB
UT WOS:000761320100001
PM 35179554
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hsu, ML
   Huang, WC
   Zhou, YR
   Hu, S
   Huang, CH
   Wu, SJ
AF Hsu, Ming-Lung
   Huang, Wen-Chung
   Zhou, Yi-Rong
   Hu, Sindy
   Huang, Chun-Hsun
   Wu, Shu-Ju
TI Oleuropein Protects Human Retinal Pigment Epithelium Cells from IL-1
   beta-Induced Inflammation by Blocking MAPK/NF-kappa B Signaling Pathways
SO INFLAMMATION
LA English
DT Article
DE oleuropein; ARPE-19; IL-1 beta; MAPK; NF-kappa B
ID MACULAR DEGENERATION; IN-VITRO; DIFFERENTIATION; PATHOGENESIS;
   DYSFUNCTION; MECHANISMS; DAMAGE
AB Proinflammatory mediators such as interleukin (IL)-1 beta cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1 beta-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1 beta induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-kappa B. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-kappa B suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.
C1 [Hsu, Ming-Lung; Zhou, Yi-Rong; Huang, Chun-Hsun; Wu, Shu-Ju] Chang Gung Univ Sci & Technol, Dept Nutr & Hlth Sci, Res Ctr Food & Cosmet Safety, Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.
   [Hsu, Ming-Lung; Zhou, Yi-Rong; Huang, Chun-Hsun; Wu, Shu-Ju] Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.
   [Huang, Wen-Chung] Chang Gung Univ Sci & Technol, Grad Inst Hlth Ind Technol, Res Ctr Ind Human Ecol, Res Ctr Chinese Herbal Med,Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.
   [Huang, Wen-Chung] Chang Gung Mem Hosp, Div Allergy Asthma & Rheumatol, Dept Pediat, Linkou 33303, Taiwan.
   [Hu, Sindy; Huang, Chun-Hsun; Wu, Shu-Ju] Chang Gung Mem Hosp, Aesthet Med Ctr, Dept Dermatol, Taoyuan 33303, Taiwan.
   [Huang, Chun-Hsun] Chang Gung Univ Sci & Technol, Dept Cosmet Sci, Res Ctr Food & Cosmet Safety, Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.
C3 Chang Gung University of Science & Technology; Chang Gung University of
   Science & Technology; Chang Gung University of Science & Technology;
   Chang Gung Memorial Hospital; Chang Gung Memorial Hospital; Chang Gung
   University of Science & Technology
RP Huang, CH; Wu, SJ (通讯作者)，Chang Gung Univ Sci & Technol, Dept Nutr & Hlth Sci, Res Ctr Food & Cosmet Safety, Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.; Huang, CH; Wu, SJ (通讯作者)，Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Coll Human Ecol, 261 Wenhua 1st Rd, Taoyuan 33303, Taiwan.
EM chuang@mail.cgust.edu.tw; sjwu@mail.cgust.edu.tw
FU Chang Gung Memorial Hospital [CMRPF1L0011, CMRPF1K0081, CMRPF1H0111];
   Ministry of Science and Technology in Taiwan [109-2320-B-255-006-MY3]
FX The present study was supported by grants from the Chang Gung Memorial
   Hospital (grants CMRPF1L0011, CMRPF1K0081, and CMRPF1H0111) and the
   Ministry of Science and Technology in Taiwan (grant
   109-2320-B-255-006-MY3).
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NR 37
TC 5
Z9 5
U1 2
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0360-3997
EI 1573-2576
J9 INFLAMMATION
JI Inflammation
PD FEB
PY 2022
VL 45
IS 1
BP 297
EP 307
DI 10.1007/s10753-021-01546-4
EA OCT 2021
PG 11
WC Cell Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Immunology
GA YP9WY
UT WOS:000704218500001
PM 34613549
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Abootorabi, S
   Tripathi, A
   Yu, HW
   Davila, LP
AF Abootorabi, Seyedalireza
   Tripathi, Abhimanyu
   Yu, Huidan Whitney
   Davila, Lilian P.
TI Computational modeling of intraocular drug delivery supplied by porous
   implants
SO DRUG DELIVERY AND TRANSLATIONAL RESEARCH
LA English
DT Article
DE Drug delivery; Posterior eye; Computational modeling; Age-related
   macular degeneration; Transcleral delivery
ID POSTERIOR SEGMENT; EYE; TRANSPORT; CHAMBER; PROTEIN; BLOOD; FLOW
AB New and efficient drug delivery to the posterior part of the eye is a growing health necessity worldwide. Current treatment of eye diseases, such as age-related macular degeneration (AMD), relies on repeated intravitreal injections of drug-containing solutions. Such a drug delivery has major drawbacks including short drug life, significant medical service, and high medical cost. In this study, we explored a new approach to controlled drug delivery by introducing unique porous implants. Our computational modeling contained key physiological and anatomical traits. Incompressible flow in a porous media field, including the sclera, choroid, and retina layers, is governed by Darcy law and the time evolution of the drug concentration was solved via three convection-diffusion equations in the three layers, respectively. The computational model was validated by established results from independent studies and experimental data. Simulations of the IgG1 Fab drug delivery to the posterior eye were performed to evaluate the effectiveness of the porous implants for controlled delivery. Overall, our results indicate that drug therapeutic levels in the posterior eye sustain for eight weeks similarly to those using intravitreal injection. We first evaluated the effects of the porous implants on the drug delivery in the posterior layers. Subsequent simulations were carried out with varying porosity values in a porous episcleral implant. We found that the time evolution of drug concentration is distinctively correlated to drug source location and pore size. A correlation between porosity and fluid properties for selected porous implants was revealed for the first time in this study.
C1 [Abootorabi, Seyedalireza; Yu, Huidan Whitney] Indiana Univ Purdue Univ, Purdue Sch Engn & Technol, Dept Mech & Energy Engn, 723 West Michigan St, Indianapolis, IN 46202 USA.
   [Tripathi, Abhimanyu; Davila, Lilian P.] Univ Calif Merced, Sch Engn, Dept Mat Sci & Engn, 5200 N Lake Rd, Merced, CA 95343 USA.
C3 Indiana University System; Indiana University-Purdue University
   Indianapolis; Purdue University System; Purdue University; University of
   California System; University of California Merced
RP Davila, LP (通讯作者)，Univ Calif Merced, Sch Engn, Dept Mat Sci & Engn, 5200 N Lake Rd, Merced, CA 95343 USA.
EM ldavila@ucmerced.edu
OI Davila, Lilian/0000-0002-8558-9074
FU Indiana University through a MSI Seed Funding - STEM Initiative
   [18-0512]
FX This work received funds from Indiana University through a MSI Seed
   Funding - STEM Initiative, award number 18-0512.
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NR 24
TC 1
Z9 1
U1 5
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 2190-393X
EI 2190-3948
J9 DRUG DELIV TRANSL RE
JI Drug Deliv. Transl. Res.
PD OCT
PY 2021
VL 11
IS 5
BP 2134
EP 2143
DI 10.1007/s13346-020-00878-2
EA JAN 2021
PG 10
WC Instruments & Instrumentation; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Instruments & Instrumentation; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA UO0VO
UT WOS:000607046200005
PM 33432523
DA 2022-11-30
ER

PT J
AU Lin, YY
   Yang, YP
   Lai, WY
   Chien, CS
   Chen, SJ
   Hwang, D
   Lai, YH
   Lin, TC
   Chiou, SH
   Lo, YL
   Huo, TI
   Chien, Y
AF Lin, Yi-Ying
   Yang, Yi-Ping
   Lai, Wei-Yi
   Chien, Chian-Shiu
   Chen, Shih-Jen
   Hwang, De-Kuang
   Lai, Ying-Hsiu
   Lin, Tai-Chi
   Chiou, Shih-Hwa
   Lo, Yu-Li
   Huo, Teh-Ia
   Chien, Yueh
TI Development of polydimethylsiloxane-based biomimetic scaffolds with
   cylinder micropillars for retinal pigment epithelial cell cultivation
SO JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
LA English
DT Article
DE Macular degeneration; Pluripotent stem cells; Retinal pigment epithelium
ID STEM-CELLS
AB Background:
   Age-related macular degeneration (AMD) is one of the leading causes of vision loss. Once the retinal pigment epithelium (RPE) layers are destroyed, the poor visual acuity and recognition are generally irreversible. Cell therapy that possesses enormous potential in regenerative medicine may provide an alternative treatment for several incurable diseases such as AMD. In this study, we developed an innovative polydimethylsiloxane (PDMS)-based biomimetic scaffolds with cylinder micropillars for the cultivation of induced pluripotent stem cell-derived RPEs (iPSC-RPEs). RPEs were cultured on the PDMS-based biomimetic scaffolds and validated the cells gene expression.
   Methods:
   The biomimetic PDMS scaffold was fabricated through spin coating and lithography method. It was further modified on surface with biomolecules to improve cell affinity and stability. The iPSC-RPEs were seeded on the scaffold and analyzed with characteristic gene expression.
   Results:
   PDMS biomimetic scaffold was analyzed with Fourier transform infrared spectroscopy and proved its chemical composition. iPSC-RPEs demonstrated confluent cell monolayer on the scaffold and maintained RPE-specific gene expression, which proved the PDMS-based biomimetic scaffold to be supportive for iPSC-RPEs growth.
   Conclusion:
   The PDMS interface allowed regular growth of iPSC-RPEs and the design of cylinder micropillars further provided the bioscaffold high motion resistance may improve the engraftment stability of iPSC-RPEs after transplantation. Taken together, this innovative PDMS-based biomimetic scaffold may serve as an ideal interface for in vitro iPSC-RPE cultivation and subsequent transplantation in vivo. This novel device exhibits better bioavailability than conventional injection of donor cells and may be an alternative option for the treatment of AMD.
C1 [Lin, Yi-Ying; Chiou, Shih-Hwa; Lo, Yu-Li; Huo, Teh-Ia; Chien, Yueh] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei, Taiwan.
   [Lin, Yi-Ying; Yang, Yi-Ping; Lai, Wei-Yi; Chien, Chian-Shiu; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Huo, Teh-Ia; Chien, Yueh] Taipei Vet Gen Hosp, Dept Med Res, 201,Sect 2,Shi Pai Rd, Taipei 112, Taiwan.
   [Chen, Shih-Jen; Hwang, De-Kuang; Lin, Tai-Chi; Chiou, Shih-Hwa] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Yang, Yi-Ping; Chien, Chian-Shiu; Chen, Shih-Jen; Hwang, De-Kuang; Lin, Tai-Chi; Chiou, Shih-Hwa; Huo, Teh-Ia; Chien, Yueh] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
   [Lo, Yu-Li] Natl Yang Ming Univ, Ctr Adv Pharmaceut & Drug Delivery Res, Taipei, Taiwan.
   [Huo, Teh-Ia] Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol, Taipei, Taiwan.
   [Chien, Yueh] Natl Yang Ming Univ, Canc Progress Res Ctr, 155,Sect 2,Linong St, Taipei 112, Taiwan.
C3 National Yang Ming Chiao Tung University; Taipei Veterans General
   Hospital; Taipei Veterans General Hospital; National Yang Ming Chiao
   Tung University; National Yang Ming Chiao Tung University; Taipei
   Veterans General Hospital; National Yang Ming Chiao Tung University
RP Huo, TI (通讯作者)，Taipei Vet Gen Hosp, Dept Med Res, 201,Sect 2,Shi Pai Rd, Taipei 112, Taiwan.; Chien, Y (通讯作者)，Natl Yang Ming Univ, Canc Progress Res Ctr, 155,Sect 2,Linong St, Taipei 112, Taiwan.
EM tihuo@vghtpe.gov.tw; g39005005@gmail.com
RI Hwang, DK De-Kuang/J-3931-2016
OI Hwang, DK De-Kuang/0000-0001-6346-8485; Lo, Yu-Li/0000-0002-6548-3280
FU VGH; TSGH; NDMC; AS Joint Research Program [VTA109-V1-6-1]
FX This work was financially supported by the VGH, TSGH, NDMC, AS Joint
   Research Program (VTA109-V1-6-1).
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NR 12
TC 1
Z9 1
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1726-4901
EI 1728-7731
J9 J CHIN MED ASSOC
JI J. Chin. Med. Assoc.
PD NOV
PY 2020
VL 83
IS 11
BP 1029
EP 1033
DI 10.1097/JCMA.0000000000000428
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA OP0SL
UT WOS:000587785600011
PM 32898088
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Mokhles, P
   van Gorcom, L
   Schouten, JSAG
   Berendschot, TTJM
   Beckers, HJM
   Webers, CAB
AF Mokhles, Palwasha
   van Gorcom, Luuk
   Schouten, Jan S. A. G.
   Berendschot, Tos T. J. M.
   Beckers, Henny J. M.
   Webers, Carroll A. B.
TI Contributing ocular comorbidity to end-of-life visual acuity in
   medically treated glaucoma patients, ocular hypertension and glaucoma
   suspect patients
SO EYE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; VISION LOSS; IMPAIRMENT; BLINDNESS; RISK;
   PREVALENCE; PROGNOSIS
AB Aim To assess the visual acuity at the end of life in glaucoma suspect patients, ocular hypertension, and patients treated for glaucoma and to find factors contributing to a reduced visual acuity in this cohort of deceased patients. Methods In a cohort of 3883 medically treated glaucoma patients, glaucoma suspect, or patients with ocular hypertension assembled in 2001-2004, 1639 were deceased. Patient data were collected from electronic and paper patient files. The files of 1378 patients were studied and the last measured visual acuity and ocular comorbidities influencing the visual acuity were extracted. Results Our results show that only 37.2% of patients had no visual impairment in either eye, 30.5% was visually impaired or blind in both eyes and 4.1% was blind in both eyes, all based on VA. The most common contributing factors for severe visual impairment or blindness (prevalence >= 1%) were: glaucoma, retinal vein occlusion, dry and exudative age-related macular degeneration, past retinal detachment, amblyopia, diabetic retinopathy, anterior ischemic optic neuropathy, trauma, decompensated cornea, past keratitis, enucleation, corneal transplantation, and macular hole. Conclusions Despite the current advanced treatment modalities for glaucoma, 30.5% of patients had a VA < 0.5 in both eyes and 4.1% was blind in both eyes. However, this disability cannot be confidently attributed only to glaucoma. Besides glaucoma, most common contributing factors were among others retinal and macular diseases. Patient management in glaucoma should be based on more than lowering the intraocular pressure to prevent blindness at the end of life.
C1 [Mokhles, Palwasha; van Gorcom, Luuk; Schouten, Jan S. A. G.; Berendschot, Tos T. J. M.; Beckers, Henny J. M.; Webers, Carroll A. B.] Univ Eye Clin Maastricht, Maastricht, Netherlands.
   [Schouten, Jan S. A. G.] Canisius Wilhelmina Ziekenhuis, Nijmegen, Netherlands.
C3 Maastricht University; Maastricht University Medical Centre (MUMC);
   Canisius-Wilhelmina Hospital
RP Mokhles, P (通讯作者)，Univ Eye Clin Maastricht, Maastricht, Netherlands.
EM palwasha.mokhles@mumc.nl
RI Berendschot, Tos TJM/M-8509-2016; Schouten, Johannes S.A.G./M-9376-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X; Schouten, Johannes
   S.A.G./0000-0001-6495-7758
FU algemene Nederlandse vereniging ter voorkoming van blindheid; glaucoom
   fonds; landelijke stichting voor blinden en slechtzienden through
   UitZicht
FX The author was supported by the following foundations: algemene
   Nederlandse vereniging ter voorkoming van blindheid, glaucoom fonds and
   landelijke stichting voor blinden en slechtzienden that contributed
   through UitZicht. The funding organizations had no role in the design or
   conduct of this research.
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NR 30
TC 2
Z9 2
U1 2
U2 5
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAR
PY 2021
VL 35
IS 3
BP 883
EP 891
DI 10.1038/s41433-020-0991-0
EA JUN 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QM1CD
UT WOS:000537654100003
PM 32494040
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Garland, DL
   Fernandez-Godino, R
   Kaur, I
   Speicher, KD
   Harnly, JM
   Lambris, JD
   Speicher, DW
   Pierce, EA
AF Garland, Donita L.
   Fernandez-Godino, Rosario
   Kaur, Inderjeet
   Speicher, Kaye D.
   Harnly, James M.
   Lambris, John D.
   Speicher, David W.
   Pierce, Eric A.
TI Mouse genetics and proteomic analyses demonstrate a critical role for
   complement in a model of DHRD/ML, an inherited macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID AGE-RELATED MACULOPATHY; BASAL LAMINAR DEPOSIT; FACTOR-H POLYMORPHISM;
   EXTRACELLULAR-MATRIX; DRUSEN FORMATION; BRUCHS MEMBRANE; ABERRANT
   ACCUMULATION; MALATTIA LEVENTINESE; PIGMENT-EPITHELIUM; TISSUE INHIBITOR
AB Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1(R345W/R345W) mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1(R345W/R345W) mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1(R345W/R345W):C3(-/-) double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations.
C1 [Garland, Donita L.; Fernandez-Godino, Rosario; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA 02114 USA.
   [Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA 02114 USA.
   [Kaur, Inderjeet] LV Prasad Eye Inst, Kallam Anji Reddy Mol Genet Lab, Hyderabad, Andhra Pradesh, India.
   [Speicher, Kaye D.; Speicher, David W.] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA.
   [Speicher, Kaye D.; Speicher, David W.] Wistar Inst Anat & Biol, Mol Oncogenesis Program, Philadelphia, PA 19104 USA.
   [Harnly, James M.] USDA, Food Composit & Methods Dev Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
   [Lambris, John D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Harvard University; Harvard Medical School; Massachusetts Eye
   & Ear Infirmary; L. V. Prasad Eye Institute; The Wistar Institute; The
   Wistar Institute; United States Department of Agriculture (USDA);
   University of Pennsylvania; Pennsylvania Medicine
RP Garland, DL (通讯作者)，Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM donita_garland@meei.harvard.edu; eric_pierce@meei.harvard.edu
RI Lambris, John/Q-5633-2018; Kaur, Inderjeet/ABD-1833-2021
OI Lambris, John/0000-0002-9370-5776; Pierce, Eric/0000-0002-2354-4102
FU Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical
   School, Boston, MA; Rosanne Silbermann Foundation; National Cancer
   Institute (NCI Cancer Core Grant) [CA010815]; National Eye Institute
   (MEEI Core Grant) [P30 EY014104]; National Institutes of Health
   [AI068730, EY020633]; NATIONAL CANCER INSTITUTE [P30CA010815] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [P30EY014104, R01EY020633]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND
   INFECTIOUS DISEASES [P01AI068730] Funding Source: NIH RePORTER
FX This work was supported by the Ocular Genomics Institute, Department of
   Ophthalmology, Harvard Medical School, Boston, MA 02114; the Rosanne
   Silbermann Foundation; the National Cancer Institute (NCI Cancer Core
   Grant CA010815 to The Wistar Institute); the National Eye Institute
   (MEEI Core Grant P30 EY014104) and the National Institutes of Health
   (AI068730 and EY020633 to J.D.L.).
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NR 128
TC 34
Z9 34
U1 0
U2 10
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 JAN 1
PY 2014
VL 23
IS 1
BP 52
EP 68
DI 10.1093/hmg/ddt395
PG 17
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 272SZ
UT WOS:000328482300005
PM 23943789
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Dev, MK
   Shrestha, GS
   Paudel, N
   Joshi, ND
   Thapa, M
   Shah, DN
AF Dev, Mahesh Kumar
   Shrestha, Gauri Shankar
   Paudel, Nabin
   Joshi, Niraj Dev
   Thapa, Madhu
   Shah, Dev Narayan
TI Visual status and ocular morbidity in older adults living in residential
   care
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Residential care/old age home; Visual acuity; Visual impairment;
   Blindness; Low vision; Prevalence; Kathmandu
ID NURSING-HOME RESIDENTS; SALISBURY-EYE-EVALUATION; QUALITY-OF-LIFE;
   CATARACT-SURGERY; VISION IMPAIRMENT; REFRACTIVE ERROR; PREVALENCE;
   BLINDNESS; POPULATION; DISEASE
AB The frequency of visual impairment and blindness increases with age and is more prevalent among older adults living in residential care centers. The main aim of this study was to assess the visual status and determine the prevalence and major causes of visual impairment and blindness among the older adults living in residential care centers of Kathmandu Valley, Nepal.
   A cross-sectional study was conducted on 385 residents of 60 years or older residing in seven residential care centers of Kathmandu Valley. Presenting distance visual acuity was assessed in each eye with a Snellen chart at 6-m distance in non-standardized outdoor illumination. Objective and subjective refractions were performed and the best-corrected distance visual acuity was considered in the better eye. Near acuity was assessed binocularly with The Lighthouse Near Acuity Card. Complete anterior and posterior segment examination was carried out.
   The mean age of residents was 74.34 +/- 8.19 years. The majority was female residents (78.2 %). The prevalence of visual impairment and blindness was 43.70 %. Adequate refractive correction could alone reduce the prevalence of visual impairment and blindness by 15.40 %. Cataract was the leading cause of visual impairment and blindness, which was followed by age-related macular degeneration, corneal opacity, glaucoma, and macular scar.
   The prevalence of visual impairment and blindness is significant among the older adults living in residential care centers. The frequency of visual impairment and blindness can be prevented by adequate refractive correction, frequent eye examination, and appropriate high use of cataract surgery.
C1 [Dev, Mahesh Kumar; Shrestha, Gauri Shankar; Paudel, Nabin; Joshi, Niraj Dev; Thapa, Madhu; Shah, Dev Narayan] Tribhuvan Univ, Dept Ophthalmol, Inst Med, BP Koirala Lions Ctr Ophthalm Studies, Kathmandu, Nepal.
C3 Tribhuvan University; Institute of Medicine (IoM) - Nepal
RP Dev, MK (通讯作者)，Tribhuvan Univ, Dept Ophthalmol, Inst Med, BP Koirala Lions Ctr Ophthalm Studies, Kathmandu, Nepal.
EM maheshdev2002@yahoo.com
RI Paudel, Nabin/W-3265-2019; Shrestha, Gauri S/B-8195-2014; Dev, Mahesh
   Kumar/T-9113-2019
OI Paudel, Nabin/0000-0003-1583-9856; Dev, Mahesh
   Kumar/0000-0003-1339-8727; Shrestha, Gauri Shankar/0000-0001-6792-3027
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NR 26
TC 11
Z9 12
U1 0
U2 5
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 SEP
PY 2012
VL 250
IS 9
BP 1387
EP 1393
DI 10.1007/s00417-012-2056-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 995FS
UT WOS:000307993900019
PM 22614911
DA 2022-11-30
ER

PT J
AU Schrier, SA
   Falk, MJ
AF Schrier, Samantha A.
   Falk, Marni J.
TI Mitochondrial disorders and the eye
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Article
DE antioxidant; apoptosis; diabetic retinopathy; mitochondria; ocular
   neoplasm; oxidative stress
ID HEREDITARY OPTIC NEUROPATHY; OPA1 MUTATIONS; MOUSE MODEL; CELL-DEATH;
   DISEASE; GLAUCOMA; ATROPHY; DNA; GENE; RETINOBLASTOMA
AB Purpose of review
   Mitochondrial disease is a heterogeneous group of energy metabolism disorders that present across all ages with a wide range of ocular or multisystemic manifestations. This review focuses on recent progress made toward understanding the various ophthalmologic manifestations of primary mitochondrial diseases and discusses the implications of mitochondrial dysfunction, placing particular emphasis on recent investigations into the pathogenesis and emerging therapies for mitochondrial-based ophthalmologic disorders.
   Recent findings
   Novel pathogenic mitochondrial DNA mutations continue to be detected in diverse ethnic populations for primary mitochondrial ophthalmologic disorders that commonly affect the optic nerve, retina, and extraocular muscles. Promising antioxidant and gene therapy approaches are being actively investigated to treat these ophthalmologic manifestations, as in Leber's hereditary optic neuropathy. Mitochondrial dysfunction is also increasingly implicated in common ophthalmologic disorders of aging, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Several proteins recently recognized to play a role in the mitochondrial oxidative stress response within retinal cells, such as prohibitin and MMP2, may serve as novel biomarkers and therapeutic targets for common ophthalmologic disorders. Therapies that inhibit mitochondrial function and induce apoptosis within tumor cells, such as EDL-155 and curcumin, may offer novel therapeutic agents for ocular neoplasms such as retinoblastoma and uveal melanoma.
   Summary
   Primary mitochondrial genetic disease manifestations can involve almost all aspects of the eye. Mitochondrial dysfunction is increasingly recognized as playing a causative role in the common ophthalmologic disorders in aging. This understanding has unleashed a range of emerging therapeutic approaches for mitochondrial-based ophthalmologic disorders directed at optimizing mitochondrial function.
C1 Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet & Child Dev, Philadelphia, PA 19104 USA.
   Childrens Hosp Philadelphia, Dept Pediat, Div Rehabil, Philadelphia, PA 19104 USA.
   Childrens Hosp Philadelphia, Dept Pediat, Div Metab Dis, Philadelphia, PA 19104 USA.
   Univ Pennsylvania Perelman Sch Med, Philadelphia, PA USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of
   Philadelphia; University of Pennsylvania; Pennsylvania Medicine;
   Childrens Hospital of Philadelphia; University of Pennsylvania;
   Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of
   Pennsylvania; Pennsylvania Medicine
RP Falk, MJ (通讯作者)，ARC 1002C,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM falkm@email.chop.edu
RI Falk, Marni/K-1997-2014
OI Falk, Marni/0000-0002-1723-6728
FU NIH [T32GM008638]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD
   HEALTH & HUMAN DEVELOPMENT [R01HD065858] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008638] Funding
   Source: NIH RePORTER
FX This work was supported, in part, by NIH training grant T32GM008638
   (S.A.S.).
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NR 46
TC 64
Z9 68
U1 0
U2 28
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 SEP
PY 2011
VL 22
IS 5
BP 325
EP 331
DI 10.1097/ICU.0b013e328349419d
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 806BM
UT WOS:000293776700003
PM 21730846
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Roberts, JE
AF Roberts, Joan E.
TI Ultraviolet Radiation as a Risk Factor for Cataract and Macular
   Degeneration
SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE
LA English
DT Review
DE Ultraviolet radiation; Cataract; Blue light hazard; Macular
   degeneration; Singlet oxygen; Superoxide; Xantherenic acid; Lipofuscin;
   A2E; Contact lens
ID OXIDATION-PRODUCTS; XANTHURENIC ACID; BLUE-LIGHT; PIGMENT; EYE; DAMAGE;
   CAROTENOIDS; LIPOFUSCIN; IDENTIFICATION; ANTIOXIDANTS
AB The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm, and therefore, light absorbed by the eye must be benign. However, exposure to the intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. This radiation exposure can lead to impaired vision and transient or permanent blindness.
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C1 Fordham Univ, Dept Nat Sci, New York, NY 10023 USA.
C3 Fordham University
RP Roberts, JE (通讯作者)，Fordham Univ, Dept Nat Sci, 113 W 60th St, New York, NY 10023 USA.
EM jroberts@fordham.edu
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NR 53
TC 102
Z9 104
U1 1
U2 78
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1542-2321
EI 1542-233X
J9 EYE CONTACT LENS
JI Eye Contact Lens-Sci. Clin. Pra.
PD JUL
PY 2011
VL 37
IS 4
BP 246
EP 249
DI 10.1097/ICL.0b013e31821cbcc9
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 784BJ
UT WOS:000292128300011
PM 21617534
DA 2022-11-30
ER

PT J
AU Hawkins, BS
   Bressler, NM
   Reynolds, SM
AF Hawkins, Barbara S.
   Bressler, Neil M.
   Reynolds, Sandra M.
TI Patient-Reported Outcomes Among Sham vs No-Treatment Controls From
   Randomized Trials
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; QUALITY-OF-LIFE; MACULAR
   DEGENERATION; SURGERY; RANIBIZUMAB
AB Objective: To compare 2-year changes from baseline scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ) between similar participants assigned to sham and no-treatment control arms in randomized clinical trials of treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.
   Methods: We retrospectively matched sham controls from a randomized trial to no-treatment controls (no sham or placebo) from another trial on 7 baseline prognostic criteria. Two-year changes in overall and subscale scores were compared using data from those who had 2-year interviews and also using the last follow-up observation carried forward to impute missing 2-year interview scores.
   Results: A match to a no-treatment control on all 7 criteria was identified for 62 of 238 sham controls. Among the 42 matched pairs of controls interviewed at 2 years, no important difference in 2-year change in NEI-VFQ scores overall or by subscale was observed. Findings were similar for the 56 matched pairs of controls who could be analyzed for 2-year changes in scores using the method of last follow-up observation carried forward.
   Conclusions: Findings from this retrospective matched-pairs analysis suggest that sham treatment to mask patient participants in clinical trials may be unnecessary when patient-reported outcomes are of interest and standard instruments are administered by interviewers masked to treatment assignment. This analysis, together with our earlier analysis of visual acuity outcomes, questions the necessity for sham (placebo) controls in randomized clinical trials in ophthalmology when other methods to minimize outcome assessment bias are incorporated into the design.
C1 [Hawkins, Barbara S.; Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Hawkins, Barbara S.; Reynolds, Sandra M.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins Bloomberg School of Public Health
RP Hawkins, BS (通讯作者)，Wilmer Clin Trials & Biometry, 550 N Broadway,Room 930, Baltimore, MD 21205 USA.
EM bhawkins@jhmi.edu
FU Genentech Inc.; Johns Hopkins University School of Medicine through the
   Office of Research Administration; School of Medicine policy; Karl P.
   Hagen Professorship in Ophthalmology; James P. Gill Professorship in
   Ophthalmology; Genentech Inc; Wilmer Eye Institute; Research to Prevent
   Blindness, New York, New York; National Eye Institute, National
   Institutes of Health; US Department of Health and Human Services
FX Dr Bressler is principal investigator of grants to the Johns Hopkins
   University School of Medicine that are sponsored by Genentech Inc. Such
   grants are negotiated and administered by the Johns Hopkins University
   School of Medicine through the Office of Research Administration. Under
   School of Medicine policy, support for the costs of research
   administered by the institution does not constitute a financial conflict
   of interest.; This investigation was supported in part by the Karl P.
   Hagen Professorship in Ophthalmology (Dr Hawkins), the James P. Gill
   Professorship in Ophthalmology (Dr Bressler), a grant from Genentech Inc
   to the Johns Hopkins University School of Medicine, the Retina Division
   Research Fund of the Wilmer Eye Institute, and an unrestricted grant to
   the Wilmer Eye Institute from Research to Prevent Blindness, New York,
   New York.; MARINA was sponsored by Genentech Inc and is registered at
   http://www.clinicaltrials.gov (NCT00056836). The SSTs were sponsored by
   the National Eye Institute, National Institutes of Health, and the US
   Department of Health and Human Services and are registered at
   http://www.clinicaltrials.gov NCT00000150).
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NR 14
TC 2
Z9 2
U1 0
U2 0
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 FEB
PY 2011
VL 129
IS 2
BP 200
EP 205
DI 10.1001/archophthalmol.2010.359
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 721CQ
UT WOS:000287329500014
PM 21320967
OA Bronze
DA 2022-11-30
ER

PT J
AU Butler, MC
   Itotia, PN
   Sullivan, JM
AF Butler, Mark C.
   Itotia, Patrick N.
   Sullivan, Jack M.
TI A High-Throughput Biophotonics Instrument to Screen for Novel Ocular
   Photosensitizing Therapeutic Agents
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VERTEPORFIN PHOTODYNAMIC THERAPY; EXPERIMENTAL CHOROIDAL
   NEOVASCULARIZATION; VASCULAR ENDOTHELIAL-CELLS; RED UPTAKE ASSAY;
   MACULAR DEGENERATION; IN-VITRO; GENE-TRANSFER; RANIBIZUMAB; DELIVERY;
   TROPISM
AB PURPOSE. High-throughput techniques are needed to identify and optimize novel photodynamic therapy (PDT) agents with greater efficacy and to lower toxicity. Novel agents with the capacity to completely ablate pathologic angiogenesis could be of substantial utility in diseases such as wet age-related macular degeneration (AMD).
   METHODS. An instrument and approach was developed based on light-emitting diode (LED) technology for high-throughput screening (HTS) of libraries of potential chemical and biological photosensitizing agents. Ninety-six-well LED arrays were generated at multiple wavelengths and under rigorous intensity control. Cell toxicity was measured in 96-well culture arrays with the nuclear dye SYTOX Green (Invitrogen-Molecular Probes, Eugene, OR).
   RESULTS. Rapid screening of photoactivatable chemicals or biological molecules has been realized in 96-well arrays of cultured human cells. This instrument can be used to identify new PDT agents that exert cell toxicity on presentation of light of the appropriate energy. The system is further demonstrated through determination of the dose dependence of model compounds having or lacking cellular phototoxicity. Killer Red (KR), a genetically encoded red fluorescent protein expressed from transfected plasmids, is examined as a potential cellular photosensitizing agent and offers unique opportunities as a cell-type-specific phototoxic protein.
   CONCLUSIONS. This instrument has the capacity to screen large chemical or biological libraries for rapid identification and optimization of potential novel phototoxic lead candidates. KR and its derivatives have unique potential in ocular gene therapy for pathologic angiogenesis or tumors. (Invest Ophthalmol Vis Sci. 2010; 51: 2705-2720) DOI: 10.1167/iovs.08-2862
C1 [Sullivan, Jack M.] SUNY Buffalo, Ira G Ross Eye Inst, Vet Adm Western New York Healthcare Syst, Dept Ophthalmol, Buffalo, NY 14215 USA.
   [Sullivan, Jack M.] SUNY Buffalo, Ira G Ross Eye Inst, Dept Pharmacol & Toxicol, Buffalo, NY 14215 USA.
   [Sullivan, Jack M.] SUNY Buffalo, Ira G Ross Eye Inst, Dept Physiol & Biophys, Buffalo, NY 14215 USA.
   [Itotia, Patrick N.; Sullivan, Jack M.] SUNY Buffalo, Ira G Ross Eye Inst, Neurosci Program, Buffalo, NY 14215 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo; State University of New York (SUNY) System; State
   University of New York (SUNY) Buffalo; State University of New York
   (SUNY) System; State University of New York (SUNY) Buffalo; State
   University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo
RP Sullivan, JM (通讯作者)，SUNY Buffalo, Ira G Ross Eye Inst, Vet Adm Western New York Healthcare Syst, Dept Ophthalmol, Bldg 20,Room 245,3495 Bailey Ave, Buffalo, NY 14215 USA.
EM jackmsullivanmdphd@yahoo.com
FU University at Buffalo; National Eye Institute [R24 EY016662,
   5R24EY016662-039001]; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [R24EY016662] Funding Source: NIH RePORTER
FX Supported by a University at Buffalo Interdisciplinary Research Creative
   Activities Fund (IRCAF) award; National Eye Institute Core Grant R24
   EY016662 to the Vision Science group at University at Buffalo
   (University at Buffalo Vision Infrastructure Center [CORE]),
   Biophotonics Module 5R24EY016662-039001 (JMS); University at Buffalo
   Ophthalmology Departmental faculty startup funds (originating from the
   Oishei Foundation, Buffalo, NY); and challenge and unrestricted grants
   from Research to Prevent Blindness to the Department of Ophthalmology at
   the University at Buffalo. The study was conducted in its entirety at
   the Veterans Administration Western New York Healthcare System.
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NR 43
TC 12
Z9 13
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2010
VL 51
IS 5
BP 2705
EP 2720
DI 10.1167/iovs.08-2862
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 589UU
UT WOS:000277180500055
PM 19834043
OA Green Published
DA 2022-11-30
ER

PT J
AU Kim, JY
   Ali, R
   Cremers, SL
   Yun, SC
   Henderson, BA
AF Kim, Jae Yong
   Ali, Rasha
   Cremers, Sandra Lora
   Yun, Sung-Cheol
   Henderson, Bonnie An
TI Incidence of intraoperative complications in cataract surgery performed
   by left-handed residents
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID PSEUDOEXFOLIATION SYNDROME; VITREOUS LOSS; RISK-FACTORS;
   PHACOEMULSIFICATION; EXTRACTION; OUTCOMES; DISPLACEMENT; DOMINANCE;
   GENDER; EYES
AB PURPOSE: To compare the incidence of intraoperative complications during cataract surgery performed by left-handed and right-handed residents and to find predictor variables for complications in resident-performed surgery.
   SETTING: Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
   METHODS: This retrospective chart review comprised cataract extractions performed by postgraduate fourth-year residents from July 1, 2001, to June 30, 2006. The incidence of posterior capsule tear and vitreous loss were the main outcomes. Univariate and multivariate logistic analyses incorporated the variables of patient age and sex; laterality of surgical eye; presence of diabetes mellitus, glaucoma, or age-related macular degeneration; history of vitrectomy; axial length; pseudoexfoliation; small pupils; white cataract; posterior polar cataract; handedness of resident; and academic quarter during which surgery occurred.
   RESULTS: Left-handed residents performed 170 (9.8%) of the 1730 surgeries. The incidence of posterior capsule tear and vitreous loss was significantly lower in surgeries performed by left-handed residents than in those performed by right-handed residents (P = .03 and P<.001, respectively). Multivariate logistic analysis showed that resident right-handedness and older patient age were predictive of an increased incidence of posterior capsule tear and vitreous loss. A small pupil was predictive of an increased incidence of vitreous loss.
   CONCLUSIONS: The incidence of posterior capsule tear and vitreous loss was significantly lower in cataract surgeries performed by left-handed residents. Handedness and patient age were significant predictor variables for these complications. J Cataract Refract Surg 2009; 35:1019-1025 (C) 2009 ASCRS and ESCRS
C1 [Kim, Jae Yong] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Ophthalmol, Seoul 138736, South Korea.
   [Yun, Sung-Cheol] Univ Ulsan, Coll Med, Dept Prevent Med, Seoul 138736, South Korea.
   [Ali, Rasha] Univ Maryland, Dept Internal Med, Baltimore, MD 21201 USA.
   [Kim, Jae Yong; Ali, Rasha; Cremers, Sandra Lora] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA.
C3 University of Ulsan; Asan Medical Center; University of Ulsan;
   University System of Maryland; University of Maryland Baltimore; Harvard
   University; Massachusetts Eye & Ear Infirmary
RP Kim, JY (通讯作者)，Univ Ulsan, Coll Med, Asan Med Ctr, Dept Ophthalmol, 388-1 Pungnab,2 Dong, Seoul 138736, South Korea.
EM jykim2311@amc.seoul.kr
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NR 34
TC 27
Z9 28
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD JUN
PY 2009
VL 35
IS 6
BP 1019
EP 1025
DI 10.1016/j.jcrs.2009.01.025
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 455WF
UT WOS:000266797900023
PM 19465287
DA 2022-11-30
ER

PT J
AU Caballero, S
   Swaney, J
   Moreno, K
   Afzal, A
   Kielczewski, J
   Stoller, G
   Cavalli, A
   Garland, W
   Hansen, G
   Sabbadini, R
   Grant, MB
AF Caballero, Sergio
   Swaney, James
   Moreno, Kelli
   Afzal, Aqeela
   Kielczewski, Jennifer
   Stoller, Glenn
   Cavalli, Amy
   Garland, William
   Hansen, Genevieve
   Sabbadini, Roger
   Grant, Maria B.
TI Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis
   and sub-retinal fibrosis in a murine model of laser-induced choroidal
   neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE sphingosine; anti-angiogenesis; age-related macular degeneration;
   choroidal neovascularization; fibrosis; animal model
ID RETINAL ENDOTHELIAL-CELLS; GROWTH-FACTOR RECEPTORS; NITRIC-OXIDE
   SYNTHASE; SPHINGOSINE 1-PHOSPHATE; MACULAR DEGENERATION;
   SPHINGOSINE-1-PHOSPHATE RECEPTOR-2; PROGENITOR CELLS; EXPRESSION;
   KINASE; MIGRATION
AB The efficacy of novel monoclonal antibodies that neutralize the pro-angiogenic mediator, sphingosine-1-phosphate (S1P), were tested using in vitro and in vivo angiogenesis models, including choroidal neovascularization (CNV) induced by laser disruption of Bruch's membrane. S1P receptor levels in human brain choroid plexus endothelial cells (CPEC), human lung microvascular endothelial cells, human retinal vascular endothelial cells, and circulating endothelial progenitor cells were examined by semi-quantitative PCR. The ability of murine or humanized anti-SIP monoclonal antibodies (mAbs) to inhibit S1P-mediated microvessel tube formation by CPEC on Matrigel was evaluated and capillary density in subcutaneous growth factor-loaded Matrigel plugs was determined following anti-SIP treatment. SIP promoted in vitro capillary tube formation in CPEC consistent with the presence of cognate S1P(1-5) receptor expression by these cells and the SIP antibody induced a dose-dependent reduction in microvessel tube formation. In a murine model of laser-induced rupture of Bruch's membrane, SIP was detected in posterior cups of mice receiving laser injury, but not in uninjured controls. Intravitreous injection of anti-S1P mAbs dramatically inhibited CNV formation and sub-retinal collagen deposition in all treatment groups (p<0.05 compared to controls), thereby identifying SIP as a previously unrecognized mediator of angiogenesis and subretinal fibrosis in this model. These findings suggest that neutralizing SIP with anti-S1P mAbs may be a novel method of treating patients with exudative age-related macular degeneration by reducing angiogenesis and sub-retinal fibrosis, which are responsible for visual acuity loss in this disease. Published by Elsevier Ltd.
C1 [Caballero, Sergio; Afzal, Aqeela; Kielczewski, Jennifer; Grant, Maria B.] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
   [Swaney, James; Moreno, Kelli; Stoller, Glenn; Cavalli, Amy; Garland, William; Hansen, Genevieve; Sabbadini, Roger] Lpath Inc, San Diego, CA 92121 USA.
   [Stoller, Glenn] Ophthalm Consultants Long Isl, Lynbrook, NY 11563 USA.
   [Sabbadini, Roger] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
C3 State University System of Florida; University of Florida; California
   State University System; San Diego State University
RP Grant, MB (通讯作者)，Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
EM grantma@ufl.edu
OI Afzal, Aqeela/0000-0001-6406-2233
FU NEI NIH HHS [R01 EY012601, R21 EY014818, R01 EY007739] Funding Source:
   Medline; NIDDK NIH HHS [R01 DK090730] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R01EY012601, R21EY014818, R01EY007739] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [R01DK090730] Funding Source: NIH RePORTER
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NR 48
TC 69
Z9 78
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2009
VL 88
IS 3
BP 367
EP 377
DI 10.1016/j.exer.2008.07.012
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 427MR
UT WOS:000264783900007
PM 18723015
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chucair, AJ
   Rotstein, NP
   SanGiovanni, JP
   During, A
   Chew, EY
   Politi, LE
AF Chucair, Ana J.
   Rotstein, Nora P.
   SanGiovanni, John Paul
   During, Alexandrine
   Chew, Emily Y.
   Politi, Luis E.
TI Lutein and zeaxanthin protect photoreceptors from apoptosis induced by
   oxidative stress: Relation with docosahexaenoic acid
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RETINAL PHOTORECEPTORS;
   MONOCLONAL-ANTIBODIES; NEURITE GROWTH; DIETARY-FAT; CAROTENOIDS;
   PIGMENT; PREVALENCE; RADICALS
AB PURPOSE. Oxidative stress has been proposed as a major pathogenic factor in age- related macular degeneration ( AMD), the leading cause of vision loss among elderly people of western European ancestry. Lutein ( LUT) and zeaxanthin ( ZEA), major components in macular pigment, are among the retinal antioxidants. Though xanthophyll intake may reduce the likelihood of having advanced AMD, direct evidence of neuroprotection is lacking. Prior work has shown that docosahexaenoic acid ( DHA), the major polyunsaturated fatty acid in the retina, delays apoptosis and promotes differentiation of photoreceptors. This study was conducted to investigate whether LUT, ZEA, and beta- carotene ( BC), major dietary carotenoids protect photoreceptors from oxidative stress and whether this protection is synergistic with that of DHA.
   METHODS. Pure rat retinal neurons in culture, supplemented with LUT, ZEA, or BC, with or without DHA, were subjected to oxidative stress induced with paraquat and hydrogen peroxide. Apoptosis, preservation of mitochondrial membrane potential, cytochrome c translocation, and opsin expression were evaluated.
   RESULTS. Pretreatment with DHA, LUT, ZEA, and BC reduced oxidative stress- induced apoptosis in photoreceptors, preserved mitochondrial potential, and prevented cytochrome c release from mitochondria. ZEA and LUT also enhanced photoreceptor differentiation. In control cultures, photoreceptors failed to grow their characteristic outer segments; addition of DHA, ZEA, or LUT increased opsin expression and promoted the development of outer- segment - like processes.
   CONCLUSIONS. These results show for the first time the direct neuroprotection of photoreceptors by xanthophylls and suggest that ZEA and LUT, along with DHA, are important environmental influences that together promote photoreceptor survival and differentiation.
C1 Univ Nacl Sur, Buenos Aires, DF, Argentina.
   NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA.
   Catholic Univ Louvain, Biochim Cellulaire Lab, B-1348 Louvain La Neuve, Belgium.
C3 National University of the South; National Institutes of Health (NIH) -
   USA; NIH National Eye Institute (NEI); Universite Catholique Louvain
RP Politi, LE (通讯作者)，CC 857,B8000FWB Bahia Blanca, Buenos Aires, DF, Argentina.
EM inpoliti@criba.edu.ar
RI SanGiovanni, John Paul/A-7605-2008; SanGiovanni, John
   Paul/AAU-3895-2020; During, Alexandrine/AAA-2931-2021; During,
   Alexandrine/I-5405-2015
OI During, Alexandrine/0000-0002-6878-0870; Chucair-Elliott,
   Ana/0000-0002-0172-1876
FU Intramural NIH HHS [ZIA EY000485-01, Z99 EY999999] Funding Source:
   Medline
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NR 51
TC 131
Z9 146
U1 0
U2 22
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 2007
VL 48
IS 11
BP 5168
EP 5177
DI 10.1167/iovs.07-0037
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 228MU
UT WOS:000250734800041
PM 17962470
DA 2022-11-30
ER

PT J
AU Thiankhaw, K
   Chattipakorn, K
   Chattipakorn, SC
   Chattipakorn, N
AF Thiankhaw, Kitti
   Chattipakorn, Kenneth
   Chattipakorn, Siriporn C.
   Chattipakorn, Nipon
TI Roles of humanin and derivatives on the pathology of neurodegenerative
   diseases and cognition
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Humanin; Brain; Dementia; Mitochondria; Autophagy
ID ISCHEMIA-REPERFUSION INJURY; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE;
   MYOCARDIAL-ISCHEMIA; SYNAPTIC PLASTICITY; PARKINSONS-DISEASE;
   CELL-DEATH; S14G-HUMANIN; RISK; NEUROPROTECTION
AB Background: Alzheimer's disease (AD), Parkinson's disease (PD), and age-related macular degeneration (AMD) are common among neurodegenerative diseases, but investigations into novel therapeutic approaches are currently limited. Humanin (HN) is a mitochondrial-derived peptide found in brain tissues of patients with familial AD and has been increasingly investigated in AD and other neurodegenerative diseases.Scope of review: In this review, we summarize and discuss the effects of HN on the pathology of neurodegenerative diseases and cognition based on several studies from preclinical to clinical models. The association between cardiac ischemia-reperfusion (I/R) injury and brain are also included. Findings from in vitro studies and those involving mice provide the most fundamental information on the impact of HN and its potential association with clinical studies.Major conclusions: HN plays a considerable role in countering the progression and neuropathology of AD. Inhibition and reduction of oxidative stress and neuroinflammation of the original amyloid hypothesis is the mainstay mechanism. Multiple intracellular mechanisms will be elucidated, including those involved in the antiapoptotic signaling cascades, the insulin signaling pathway, and mitochondrial function, and especially autophagic activity. These beneficial roles are also found following cardiac I/R injury. Cognitive improvement was found to be related to maintenance of synaptic integrity and neurotransmitter modulation. Small humanin-like peptide 2 demonstrates the neuroprotective effects in PD and AMD via prevention of mitochondrial loss.General significance: Comprehensive knowledge of HN effects on cognition and neurodegenerative diseases emphasizes its potential to treat a viable disease, as it ameliorates the pathogenesis of the disease.
C1 [Thiankhaw, Kitti] Chiang Mai Univ, Fac Med, Dept Internal Med, Chiang Mai 50200, Thailand.
   [Chattipakorn, Kenneth; Chattipakorn, Siriporn C.; Chattipakorn, Nipon] Chiang Mai Univ, Fac Med, Cardiac Electrophysiol Res & Training Ctr, Neurophysiol Unit, Chiang Mai 50200, Thailand.
   [Chattipakorn, Kenneth; Chattipakorn, Siriporn C.; Chattipakorn, Nipon] Chiang Mai Univ, Ctr Excellence Cardiac Electrophysiol Res, Chiang Mai 50200, Thailand.
   [Chattipakorn, Kenneth] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand.
   [Chattipakorn, Siriporn C.] Chiang Mai Univ, Fac Dent, Dept Oral Biol & Diagnost Sci, Chiang Mai 50200, Thailand.
   [Chattipakorn, Nipon] Chiang Mai Univ, Fac Med, Cardiac Electrophysiol Res & Training Ctr, Neurophysiol Unit, Chiang Mai, Thailand.
C3 Chiang Mai University; Chiang Mai University; Chiang Mai University;
   Mahidol University; Chiang Mai University; Chiang Mai University
RP Chattipakorn, N (通讯作者)，Chiang Mai Univ, Fac Med, Cardiac Electrophysiol Res & Training Ctr, Neurophysiol Unit, Chiang Mai, Thailand.
EM nchattip@gmail.com
RI Thiankhaw, Kitti/GLT-3486-2022
FU Senior Research Scholar grant from the National Research Council of
   Thailand (SCC); NSTDA Research Chair Grant from the National Science and
   Technology Development Agency Thailand (NC); Chiang Mai University
   Excellence Center Award
FX This work was supported by a Senior Research Scholar grant from the
   National Research Council of Thailand (SCC) ; an NSTDA Research Chair
   Grant from the National Science and Technology Development Agency
   Thailand (NC) and a Chiang Mai University Excellence Center Award (NC) .
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NR 66
TC 0
Z9 0
U1 3
U2 6
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29a, 1043 NX AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD APR
PY 2022
VL 1866
IS 4
AR 130097
DI 10.1016/j.bbagen.2022.130097
PG 9
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 1J3DR
UT WOS:000797800900001
PM 35104624
OA Bronze
DA 2022-11-30
ER

PT J
AU Belmouhand, M
   Rothenbuehler, SP
   Hjelmborg, JB
   Dabbah, S
   Bjerager, J
   Sander, BA
   Dalgard, C
   Larsen, M
AF Belmouhand, Mohamed
   Rothenbuehler, Simon Paul
   Hjelmborg, Jacob B.
   Dabbah, Sami
   Bjerager, Jakob
   Sander, Birgit Agnes
   Dalgard, Christine
   Larsen, Michael
TI Heritability of retinal drusen in the Copenhagen Twin Cohort Eye Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE Copenhagen Twin Cohort Eye Study; drusen; heritability; small hard
   drusen; twins
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   RISK; ASSOCIATIONS; POLYMORPHISM; PROGRESSION; PREVALENCE; HEREDITY
AB Purpose To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort. Methods This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location. Results The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes >= 20 small hard macular drusen (largest diameter < 63 mu m), >= 20 small hard extramacular drusen, intermediate drusen (63-125 mu m) anywhere, and large drusen (>125 mu m) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of >= 20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier. Conclusion Numerous (>= 20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.
C1 [Belmouhand, Mohamed; Rothenbuehler, Simon Paul; Dabbah, Sami; Bjerager, Jakob; Sander, Birgit Agnes; Larsen, Michael] Copenhagen Univ Hosp, Rigshosp, Dept Ophthalmol, Glostrup, Denmark.
   [Belmouhand, Mohamed; Larsen, Michael] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
   [Rothenbuehler, Simon Paul] Univ Hosp Basel, Dept Ophthalmol, Basel, Switzerland.
   [Hjelmborg, Jacob B.] Univ Southern Denmark, Dept Publ Hlth, Epidemiol Biostat & Biodemog, Odense, Denmark.
   [Hjelmborg, Jacob B.; Dalgard, Christine] Univ Southern Denmark, Danish Twin Res Ctr, Odense, Denmark.
   [Dabbah, Sami] Odense Univ Hosp, Dept Ophthalmol, Odense, Denmark.
   [Dalgard, Christine] Univ Southern Denmark, Dept Publ Hlth Clin Pharmacol Pharm & Environm Me, Odense, Denmark.
C3 Rigshospitalet; University of Copenhagen; University of Copenhagen;
   University of Basel; University of Southern Denmark; University of
   Southern Denmark; University of Southern Denmark; Odense University
   Hospital; University of Southern Denmark
RP Belmouhand, M (通讯作者)，Rigshosp, Dept Ophthalmol, Valdemar Hansens Vej 13, DK-2600 Glostrup, Denmark.
EM mohamed.belmouhand@regionh.dk
RI Bjerager, Jakob/AAQ-6010-2021; Larsen, Michael/E-9620-2010
OI Bjerager, Jakob/0000-0002-6620-6242; Larsen,
   Michael/0000-0002-5172-5891; Dalgard, Christine/0000-0001-8184-3429;
   Belmouhand, Mohamed/0000-0001-5855-4733; Hjelmborg,
   Jacob/0000-0001-9630-9149; Rothenbuehler, Simon/0000-0002-5223-6483;
   Dabbah, Sami/0000-0003-4061-9361
FU Rigshospitalet [E-23334-02]; P. Carl Petersens Fond [19102]; Helsefonden
   [19-B-0063]; Aase og Ejnar Danielsens Fond [18-10-0698]; Beckett Fonden
   [19-2-3490]; Einar Willumsen Fonden [500028]; Horizon 2020, the European
   Union's Framework Programme for Research and Innovation [780989]; VELUX
   Foundation [00028975]; OPUS Foundation; Alfred-Vogt Foundation
FX The study was supported by the Rigshospitalet (grant E-23334-02), P.
   Carl Petersens Fond (grant 19102), Helsefonden (grant 19-B-0063), Aase
   og Ejnar Danielsens Fond (grant 18-10-0698), Beckett Fonden (grant
   19-2-3490), Einar Willumsen Fonden (grant 500028) and Horizon 2020, the
   European Union's Framework Programme for Research and Innovation, under
   grant agreement no. 780989 (MERLIN). JB was supported by the VELUX
   Foundation (grant 00028975). SPR was supported by the OPUS Foundation
   and the Alfred-Vogt Foundation. The funding organizations had no role in
   the design or conduct of this research.
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NR 31
TC 0
Z9 0
U1 1
U2 1
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 2022
VL 100
IS 8
BP E1561
EP E1568
DI 10.1111/aos.15136
EA MAR 2022
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 6D4SX
UT WOS:000772390300001
PM 35322936
DA 2022-11-30
ER

PT J
AU Ramachandran, N
   Schmiedel, O
   Vaghefi, E
   Hill, S
   Wilson, G
   Squirrell, D
AF Ramachandran, Nishanthan
   Schmiedel, Ole
   Vaghefi, Ehsan
   Hill, Sophie
   Wilson, Graham
   Squirrell, David
TI Evaluation of the prevalence of non-diabetic eye disease detected at
   first screen from a single region diabetic retinopathy screening
   program: a cross-sectional cohort study in Auckland, New Zealand
SO BMJ OPEN
LA English
DT Article
DE ophthalmology; medical ophthalmology; diabetic retinopathy; medical
   retina
ID AGE-RELATED MACULOPATHY; CARDIOVASCULAR-DISEASE; MACULAR DEGENERATION;
   GLAUCOMA; POPULATION; CLASSIFICATION; ASSOCIATIONS; HYPERTENSION;
   AUSTRALIA
AB Objectives To evaluate the prevalence of incidental non-diabetic ocular comorbidities detected at first screen in a large diabetic retinopathy (DR) screening programme. Design Cross-sectional cohort study. Setting Single large metropolitan diabetic eye screening programme in Auckland, New Zealand. Participants Twenty-two thousand seven hundred and seventy-one participants who attended screening from September 2008 to August 2018. Results Hypertensive retinopathy (HTR) was observed in 14.2% (3236/22 771) participants. Drusen were present in 14.0% participants under the age of 55 years, increasing to 20.5% in those 55 years and older. The prevalence of neovascular age-related macular degeneration (AMD) was 0.5% in participants aged<55 years, 2.4% in participants aged 55-75 years and 16% in participants aged>75 years. Retinal vein occlusion and retinal arterial embolus were prevalent in 0.7% and 0.02%, respectively, in participants aged<55 years, increasing to 2.2% and 0.4%, respectively, in those >75 years. Cataracts were common being present in 37.1% of participants over the age of 75 years. Only 386 individuals (1.7%) were labelled as glaucoma suspects. Geographic atrophy, epiretinal membrane, choroidal nevi and posterior capsular opacification had an increased prevalence in older individuals. Conclusions Our data suggest that AMD, HTR and cataracts are routinely detected during DR screening. The incorporation of the detection of these ocular comorbidities during DR screening provide opportunities for patients to modify risk factors (smoking cessation and diet for AMD, blood pressure for HTR) and allow access to cataract surgery.
C1 [Ramachandran, Nishanthan; Schmiedel, Ole; Hill, Sophie; Squirrell, David] Auckland Dist Hlth Board Ophthalmol, Dept Ophthalmol, Auckland, New Zealand.
   [Vaghefi, Ehsan] Univ Auckland, Optometry & Vis Sci, Auckland, New Zealand.
   [Vaghefi, Ehsan] Univ Auckland, Auckland Bioengn Inst, Auckland, New Zealand.
   [Wilson, Graham] Gisborne Hosp, Ophthalmol, Gisborne, New Zealand.
C3 University of Auckland; University of Auckland
RP Ramachandran, N (通讯作者)，Auckland Dist Hlth Board Ophthalmol, Dept Ophthalmol, Auckland, New Zealand.
EM nishan.rama@gmail.com
OI Ramachandran, Nishanthan/0000-0002-6919-4136; Vaghefi,
   Ehsan/0000-0002-9482-3168
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NR 37
TC 3
Z9 3
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD DEC
PY 2021
VL 11
IS 12
AR e054225
DI 10.1136/bmjopen-2021-054225
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA XP3OG
UT WOS:000730777400009
PM 34907067
OA Green Published
DA 2022-11-30
ER

PT J
AU Josan, AS
   Buckley, TMW
   Wood, LJ
   Jolly, JK
   Cehajic-Kapetanovic, J
   MacLaren, RE
AF Josan, Amandeep Singh
   Buckley, Thomas M. W.
   Wood, Laura J.
   Jolly, Jasleen K.
   Cehajic-Kapetanovic, Jasmina
   MacLaren, Robert E.
TI Microperimetry Hill of Vision and Volumetric Measures of Retinal
   Sensitivity
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE microperimetry; hill of vision; volume; retinal function; functional
   imaging
ID INTERPOLATION
AB Purpose: Mean retinal sensitivity is the main output measure used in microperimetry. It is, however, of limited use in patients with poor vision because averaging is weighted toward zero in those with significant scotomas creating an artificial floor effect. In contrast, volumetric measures avoid these issues and are displayed graphically as a hill of vision.
   Methods: An open-source program was created to manipulate raw sensitivity threshold data files obtained from MAIA microperimetry. Thin plate spline interpolated heat maps and three-dimensional hill of vision plots with an associated volume were generated. Retrospective analyses of microperimetry volumes were undertaken in patients with a range of retinal diseases to assess the qualitative benefits of three-dimensional visualization and volumetric measures. Simulated pathology was applied to radial grid patterns to investigate the performance of volumetric sensitivity in nonuniform grids.
   Results: Volumetric analyses from microperimetry in RPGR-related retinitis pigmentosa, choroideremia, Stargardt disease, and age-related macular degeneration were analyzed. In simulated nonuniform testing grids, volumetric sensitivity was able to detect differences in retinal sensitivity where mean sensitivity could not.
   Conclusions: Volumetric measures do not suffer from averaging issues and demonstrate superior performance in nonuniform testing grids. Additionally, volume measures enable detection of localized retinal sensitivity changes that might otherwise be undetectable in a mean change.
   Translational Relevance: As microperimetry has become an outcome measure in several gene-therapy clinical trials, three-dimensional visualization and volumetric sensitivity enables a complementary analysis of baseline disease characteristics and subsequent response to treatment, both as a signal of safety and efficacy.
C1 [Josan, Amandeep Singh; Wood, Laura J.; Jolly, Jasleen K.; Cehajic-Kapetanovic, Jasmina; MacLaren, Robert E.] Univ Oxford, Oxford Biomed Res Ctr, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England.
   [Josan, Amandeep Singh; Buckley, Thomas M. W.; Wood, Laura J.; Jolly, Jasleen K.; Cehajic-Kapetanovic, Jasmina; MacLaren, Robert E.] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England.
C3 University of Oxford; Oxford University Hospitals NHS Foundation Trust
RP Josan, AS (通讯作者)，Univ Oxford Nuffield Coll Ophthalmol Lab, Level 6 John Radcliffe Hosp West Wing,Headley Way, Oxford OX3 9DU, England.
EM enquiries@eye.ox.ac.uk
RI Jolly, Jasleen Kaur/AAC-1873-2019
OI Jolly, Jasleen Kaur/0000-0001-9878-4621; (Wood) Taylor,
   Laura/0000-0001-7072-0853; Cehajic-Kapetanovic,
   Jasmina/0000-0002-9956-6412
FU National Institute for Health Research (NIHR) [CA-CDRF-2016-02002];
   Winstanley Fund; Bayer; National Institute for Health Research (NIHR);
   NIHR Oxford Biomedical Research Centre
FX The authors thank the kind donation made by Jean Williams (known as the
   Winstanley donation) to the University of Oxford for research into
   inherited macular diseases.; Supported by the NIHR Oxford Biomedical
   Research Centre. Jasleen K Jolly is funded by the National Institute for
   Health Research (NIHR) [Clinical DoctoralResearch
   FellowshipCA-CDRF-2016-02002], and the Winstanley Fund. Jasmina
   Kapetanovic is funded by the National Institute for Health Research
   (NIHR) and Global Ophthalmology Awards Fellowship, Bayer.
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NR 23
TC 5
Z9 5
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2021
VL 10
IS 7
AR 12
DI 10.1167/tvst.10.7.12
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TD3KI
UT WOS:000669229400012
PM 34110386
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Annamalai, B
   Parsons, N
   Brandon, C
   Rohrer, B
AF Annamalai, Balasubramaniam
   Parsons, Nathaniel
   Brandon, Carlene
   Rohrer, Barbel
TI The use of Matrigel combined with encapsulated cell technology to
   deliver a complement inhibitor in a mouse model of choroidal
   neovascularization
SO MOLECULAR VISION
LA English
DT Article
ID CILIARY NEUROTROPHIC FACTOR; ALTERNATIVE PATHWAY; INTRAOCULAR IMPLANTS;
   TARGETED INHIBITOR; RISK; C3; PROTEIN; SYSTEM; RARE; TT30
AB Purpose: Risk for age-related macular degeneration (AMD), a slowly progressing, complex disease, is tied to an overactive complement system. Efforts are under way to develop an anticomplement-based treatment to be delivered locally or systemically. We developed an alternative pathway (AP) inhibitor fusion protein consisting of a complement receptor-2 fragment linked to the inhibitory domain of factor H (CR2-fH), which reduces the size of mouse choroidal neovascularization (CNV) when delivered locally or systemically. Specifically, we confirmed that ARPE-19 cells genetically engineered to produce CR2-fH reduce CNV lesion size when encapsulated and placed intravitreally. We extend this observation by delivering the encapsulated cells systemically in Matrigel.
   Methods: ARPE-19 cells were generated to stably express CR2 or CR2-fH, microencapsulated using sodium alginate, and injected subcutaneously in Matrigel into 2-month-old C57BL/6J mice. Four weeks after implantation, CNV was induced using argon laser photocoagulation. Progression of CNV was analyzed using optical coherence tomography. Bioavailability of CR2-fH was evaluated in Matrigel plugs with immunohistochemistry, as well as in ocular tissue with dot blots. Efficacy as an AP inhibitor was confirmed with protein chemistry.
   Results: An efficacious number of implanted capsules to reduce CNV was identified. Expression of the fusion protein systemically did not elicit an immune response. Bioavailability studies showed that CR2-fH was present in the RPE/choroid fractions of the treated mice, and reduced CNV-associated ocular complement activation.
   Conclusions: These findings indicate that systemic production of the AP inhibitor CR2-fH can reduce CNV in the mouse model.
C1 [Annamalai, Balasubramaniam; Parsons, Nathaniel; Brandon, Carlene; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 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 Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU National Institutes of Health [R01EY024581]; Department of Veterans
   Affairs [I01RX000444, I01BX003050, IK6BX004858]; South Carolina
   SmartState Endowment
FX The study was supported in part by the National Institutes of Health
   (R01EY024581), the Department of Veterans Affairs (I01RX000444,
   I01BX003050 and IK6BX004858) and the South Carolina SmartState
   Endowment. The authors thank Marwa Belhaj and Jay Potts for helping with
   the cell encapsulation protocol and Stephen Tomlinson for providing
   reagents (plasmids for CR2 and CR2-fH). Conflict of interest: BR holds
   patents that describe the CR2-fH technology. The remaining authors
   declare that they have no conflict of interest.
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NR 38
TC 2
Z9 2
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAY 15
PY 2020
VL 26
BP 370
EP 377
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA LR6HM
UT WOS:000535793800001
PM 32476817
DA 2022-11-30
ER

PT J
AU Koh, AEH
   Alsaeedi, HA
   Abd Rashid, MB
   Lam, CS
   Harun, MHN
   Saleh, MFB
   Luu, CD
   Kumar, SS
   Ng, MH
   Isa, HM
   Leow, SN
   Then, KY
   Bastion, MLC
   Khan, MSA
   Mok, PL
AF Koh, Avin Ee-Hwan
   Alsaeedi, Hiba Amer
   Abd Rashid, Munirah Binti
   Lam, Chenshen
   Harun, Mohd Hairul Nizam
   Saleh, Muhamad Fakhri bin Mohd
   Luu, Chi D.
   Kumar, S. Suresh
   Ng, Min Hwei
   Isa, Hazlita Mohd
   Leow, Sue Ngein
   Then, Kong Yong
   Bastion, Mae-Lynn Catherine
   Khan, Mohammed Safwan Ali
   Mok, Pooi Ling
TI Retinal degeneration rat model: A study on the structural and functional
   changes in the retina following injection of sodium iodate
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE Electroretinography; Retinal degeneration; Retinal pigment epithelium;
   Photoreceptors; Sodium iodate
ID NEURITE OUTGROWTH; INSIGHTS; THERAPY; RPE
AB Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.
C1 [Koh, Avin Ee-Hwan; Alsaeedi, Hiba Amer; Khan, Mohammed Safwan Ali; Mok, Pooi Ling] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Upm Serdang 43400, Selangor, Malaysia.
   [Abd Rashid, Munirah Binti; Lam, Chenshen; Harun, Mohd Hairul Nizam; Isa, Hazlita Mohd; Then, Kong Yong; Bastion, Mae-Lynn Catherine] Univ Kebangsaan Malaysia, Med Ctr, Fac Med, Dept Ophthalmol, Kuala Lumpur 56000, Malaysia.
   [Saleh, Muhamad Fakhri bin Mohd] Univ Kebangsaan Malaysia, Med Ctr, Fac Med, Dept Pathol, Kuala Lumpur 56000, Malaysia.
   [Luu, Chi D.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Luu, Chi D.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
   [Kumar, S. Suresh] Univ Putra Malaysia, Dept Med Microbiol & Parasitol, Upm Serdang 43400, Selangor, Malaysia.
   [Kumar, S. Suresh; Mok, Pooi Ling] Univ Putra Malaysia, Genet & Regenerat Med Res Ctr, Upm Serdang 43400, Selangor, Malaysia.
   [Kumar, S. Suresh] Univ Putra Malaysia, Inst Biosci, Upm Serdang 43400, Selangor, Malaysia.
   [Ng, Min Hwei] Univ Kebangsaan Malaysia, Med Ctr, Tissue Engn Ctr, Kuala Lumpur 56000, Malaysia.
   [Leow, Sue Ngein] Hosp Sultanah Aminah, Dept Ophthalmol, Johor Baharu 80100, Johor, Malaysia.
   [Khan, Mohammed Safwan Ali] Texas A&M Univ, Texas A&M Hlth Sci Ctr, Irma Lerma Rangel Coll Pharm, Dept Pharmaceut Sci, College Stn, TX 77843 USA.
   [Mok, Pooi Ling] Jouf Univ, Coll Appl Med Sci, Dept Clin Lab Sci, POB 2014, Sakaka, Aljouf Province, Saudi Arabia.
C3 Universiti Putra Malaysia; Universiti Kebangsaan Malaysia; Universiti
   Kebangsaan Malaysia; Centre for Eye Research Australia; Royal Victorian
   Eye & Ear Hospital; University of Melbourne; Universiti Putra Malaysia;
   Universiti Putra Malaysia; Universiti Putra Malaysia; Universiti
   Kebangsaan Malaysia; Texas A&M University System; Texas A&M University
   College Station; Texas A&M Health Science Center; Al Jouf University
RP Mok, PL (通讯作者)，Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Upm Serdang 43400, Selangor, Malaysia.; Kumar, SS (通讯作者)，Univ Putra Malaysia, Dept Med Microbiol & Parasitol, Upm Serdang 43400, Selangor, Malaysia.
EM sureshkudsc@gmail.com; rachelmok2005@gmail.com
RI Khan, Mohammed Safwan Ali/U-9132-2017; Mok, Pooi Ling/AAJ-7480-2021;
   Koh, Avin/ABD-6921-2020; Bastion, Mae-Lynn/ABE-1237-2020; KUMAR, P.
   SURESH/AAT-8951-2020; Kumar, suresh S/J-2423-2017; Ng, Angela Min
   Hwei/ABC-6726-2020; Ali Khan, Mohammed Safwan/HDN-7110-2022; Ali Khan,
   Mohammed safwan/HCH-3996-2022; HARUN, MOHD HAIRUL NIZAM/D-5351-2017
OI Khan, Mohammed Safwan Ali/0000-0002-6186-5740; Koh,
   Avin/0000-0002-6519-0939; Bastion, Mae-Lynn/0000-0002-6856-8052; KUMAR,
   P. SURESH/0000-0003-3222-2604; Kumar, suresh S/0000-0002-0505-7554; Ng,
   Angela Min Hwei/0000-0002-5791-639X; Ali Khan, Mohammed
   Safwan/0000-0002-6186-5740; HARUN, MOHD HAIRUL
   NIZAM/0000-0002-2387-9834; Isa, Hazlita/0000-0002-2731-8233; LAM,
   CHENSHEN/0000-0001-9259-5846
FU Ministry of Science, Technology, Environment & Climate Change (MESTECC),
   Malaysia through the Science Fund [5450817]
FX This research was supported by the Ministry of Science, Technology,
   Environment & Climate Change (MESTECC), Malaysia through the Science
   Fund (Grant No.: 5450817).
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NR 47
TC 15
Z9 16
U1 1
U2 11
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
PY 2019
VL 196
AR 111514
DI 10.1016/j.jphotobiol.2019.111514
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA IL0CW
UT WOS:000476964700012
PM 31154277
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chae, SY
   Park, SY
   Park, G
AF Chae, Seon Yeong
   Park, Sun Young
   Park, Geuntae
TI Lutein protects human retinal pigment epithelial cells from oxidative
   stress-induced cellular senescence
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE lutein; cellular senescence; H2O2; ARPE-19 cells; age-related macular
   degeneration
ID INDUCED PREMATURE SENESCENCE; HEME OXYGENASE-1; EXPRESSION
AB Oxidative stress-induced cellular senescence is an important contributor to the pathogenesis of age-related macular degeneration (AMD). Characteristics of premature cellular senescence include a loss of proliferation, change in cell shape, irreversible cell cycle arrest, and elevated senescence-associated -galactosidase (SA--gal) activity. It was hypothesized that lutein may have anti-senescence potential and may be useful as a treatment for AMD. In the present study, premature cellular senescence was induced in ARPE-19 cells via treatment with H2O2 and the effects of lutein application were confirmed by observing cell morphology, lysosome contents, reactive oxygen species (ROS) generation and SA--gal activity, and cell cycle progression. The protein expression was also analyzed via western blotting in order to identify the affected signaling pathways. The results revealed that H2O2 treatment induced premature cellular senescence in ARPE-19 cells, as evidenced by an increased production of ROS and SA--gal, altered lysosome contents, changed cellular morphology and arrested cell cycle progression. However, when treated with lutein, ARPE-19 cells were effectively protected from these H2O2-induced effects. Western blot analysis revealed that lutein induced the expression of heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, sirtuin (SIRT)-1, and SIRT3. Together, the results indicated that lutein protects cells from cellular senescence induced by oxidative stress; therefore, it may be able to suppress the progression of AMD. In addition, our increased understanding of the pathways through which lutein acts is useful for the development of novel therapies for the treatment of oxidative stress-associated retinal disease.
C1 [Chae, Seon Yeong; Park, Geuntae] Pusan Natl Univ, Dept Nanomat Engn, 2 Busandaehak Ro 63 Beon Gil, Busan 46241, South Korea.
   [Chae, Seon Yeong; Park, Sun Young] Pusan Natl Univ, BioIT Fus Technol Res Inst, 2 Busandaehak Ro 63 Beon Gil, Busan 46241, South Korea.
C3 Pusan National University; Pusan National University
RP Park, G (通讯作者)，Pusan Natl Univ, Dept Nanomat Engn, 2 Busandaehak Ro 63 Beon Gil, Busan 46241, South Korea.; Park, SY (通讯作者)，Pusan Natl Univ, BioIT Fus Technol Res Inst, 2 Busandaehak Ro 63 Beon Gil, Busan 46241, South Korea.
EM sundeng99@pusan.ac.kr; gtpark@pusan.ac.kr
RI Park, Sun/GSD-9620-2022; Park, Sun/ABB-2937-2021
OI Park, Sun/0000-0002-9283-2642
FU Basic Science Research Program through the National Research Foundation
   of Korea (NRF) - Ministry of Education [NRF-2018R1D1A1B07047497,
   NRF-2018R1D1A3B07047983]
FX The present study was supported by the Basic Science Research Program
   through the National Research Foundation of Korea (NRF), funded by the
   Ministry of Education (grant nos. NRF-2018R1D1A1B07047497 and
   NRF-2018R1D1A3B07047983).
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NR 19
TC 14
Z9 14
U1 1
U2 16
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 2018
VL 18
IS 6
BP 5182
EP 5190
DI 10.3892/mmr.2018.9538
PG 9
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA HA7DE
UT WOS:000450440600048
PM 30320359
OA Bronze
DA 2022-11-30
ER

PT J
AU Cheng, J
   Li, ZG
   Gu, ZW
   Fu, HZ
   Wong, DWK
   Liu, J
AF Cheng, Jun
   Li, Zhengguo
   Gu, Zaiwang
   Fu, Huazhu
   Wong, Damon Wing Kee
   Liu, Jiang
TI Structure-Preserving Guided Retinal Image Filtering and Its Application
   for Optic Disk Analysis
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Retinal image processing; segmentation; computer aided diagnosis
ID MACULAR DEGENERATION; DIABETIC-RETINOPATHY; AUTOMATIC DETECTION; VISUAL
   IMPAIRMENT; SEGMENTATION; ENHANCEMENT; BOUNDARY
AB Retinal fundus photographs have been used in the diagnosis of many ocular diseases such as glaucoma, pathological myopia, age-related macular degeneration, and diabetic retinopathy. With the development of computer science, computer aided diagnosis has been developed to process and analyze the retinal images automatically. One of the challenges in the analysis is that the quality of the retinal image is often degraded. For example, a cataract in human lens will attenuate the retinal image, just as a cloudy camera lens which reduces the quality of a photograph. It often obscures the details in the retinal images and posts challenges in retinal image processing and analyzing tasks. In this paper, we approximate the degradation of the retinal images as a combination of human-lens attenuation and scattering. A novel structure-preserving guided retinal image filtering (SGRIF) is then proposed to restore images based on the attenuation and scattering model. The proposed SGRIF consists of a step of global structure transferring and a step of global edge-preserving smoothing. Our results show that the proposed SGRIF method is able to improve the contrast of retinal images, measured by histogram flatness measure, histogram spread, and variability of local luminosity. In addition, we further explored the benefits of SGRIF for subsequent retinal image processing and analyzing tasks. In the two applications of deep learning-based optic cup segmentation and sparse learning-based cup-to-disk ratio (CDR) computation, our results show that we are able to achieve more accurate optic cup segmentation and CDR measurements from images processed by SGRIF.
C1 [Cheng, Jun; Gu, Zaiwang; Liu, Jiang] Chinese Acad Sci, Cixi Inst Biomed Engn, Ningbo 315201, Zhejiang, Peoples R China.
   [Li, Zhengguo] Agcy Sci Technol & Res, Inst Infocomm Res, Singapore 138632, Singapore.
   [Gu, Zaiwang] Shanghai Univ, Sch Mechatron Engn & Automat, Shanghai 200444, Peoples R China.
   [Fu, Huazhu; Wong, Damon Wing Kee] Agcy Sci Technol & Res, Inst Infocomm Res, Ocular Imaging iMED Dept, Singapore 138632, Singapore.
C3 Chinese Academy of Sciences; Agency for Science Technology & Research
   (A*STAR); A*STAR - Institute for Infocomm Research (I2R); Shanghai
   University; Agency for Science Technology & Research (A*STAR); A*STAR -
   Institute for Infocomm Research (I2R)
RP Cheng, J (通讯作者)，Chinese Acad Sci, Cixi Inst Biomed Engn, Ningbo 315201, Zhejiang, Peoples R China.
EM chengjun@nimte.ac.cn; ezgli@i2r.a-star.edu.sg; guzaiwang@nitme.ac.cn;
   huazhufu@gmail.com; wkwong@i2r.a-star.edu.sg; jimmyliu@nimtec.ac.cn
RI LIU, JIANG Jimmy/AHB-8921-2022; Fu, Huazhu/A-1411-2014; Cheng,
   Jun/E-7778-2016
OI LIU, JIANG Jimmy/0000-0001-6281-6505; Fu, Huazhu/0000-0002-9702-5524;
   Cheng, Jun/0000-0003-1786-6188; Wong, Damon/0000-0003-4601-9121; Li,
   Zhengguo/0000-0002-4525-1204; Gu, Zaiwang/0000-0001-8764-0622
FU Cixi Institute of Biomedical Engineering, Chinese Academy of Sciences,
   China [Y80002RA01]; Ningbo 3315 Innovation Team [Y61102DL03]
FX This work was supported in part by the Cixi Institute of Biomedical
   Engineering, Chinese Academy of Sciences, China, under Grant Y80002RA01,
   and in part by the Ningbo 3315 Innovation Team under Grant Y61102DL03.
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NR 46
TC 35
Z9 35
U1 4
U2 27
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD NOV
PY 2018
VL 37
IS 11
BP 2536
EP 2546
DI 10.1109/TMI.2018.2838550
PG 11
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA GZ1FZ
UT WOS:000449113800015
PM 29994522
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Li, J
   Sun, JH
   Li, B
   Li, ZL
AF Li, Jia
   Sun, Jianhua
   Li, Bing
   Li, Zheli
TI Astaxanthin protects ARPE-19 cells against oxidative stress injury
   induced by hydrogen peroxide
SO BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT
LA English
DT Article
DE Adult retinal pigment epithelium-19; astaxanthin; age-related macular
   degeneration; oxidative stress
ID PIGMENT EPITHELIAL-CELLS; UP-REGULATION; ANTIOXIDANTS; MECHANISM;
   APOPTOSIS; PI3K/AKT; PATHWAY; ENZYMES; DAMAGE
AB The present study aimed to investigate the protective effect and mechanism of action of astaxanthin (AST) on the oxidative stress injury of adult retinal pigment epithelium-19 (ARPE-19) cells induced by hydrogen peroxide (H2O2). ARPE-19 cells were divided into five groups, including control group, H2O2 model group, AST1 group, AST2 group and AST3 group. MTT was used to determine cell viability. Cell morphology was visualized under an inverted fluorescence microscope. TUNEL assay and flow cytometry was performed to detect cell apoptosis. To examine the levels of ROS, SOD and MDA, we used DCFH-DA, WST-1 and TBA assays. The optimal concentration of AST for increasing cell viability was 40 mu g/L. Pretreatment with AST alleviated damages in cell morphology induced by H2O2. Pretreatment with AST had the best protective effect on ARPE-19 cells from oxidative stress injury induced by H2O2. AST treatment had protective effect on ARPE-19 cells against apoptosis. Treatment with AST reduced the apoptotic rate of ARPE-19 cells induced by H2O2. Treatment with AST altered the levels of ROS, SOD and MDA in ARPE-19 cells induced by H2O2. The present study demonstrates that AST protects ARPE-19 cells against oxidative stress injury, probably by inhibiting the production of ROS, elevating the activity of SOD and reducing the content of MDA. Of note, preventive delivery of AST (40 mu g/L) has the best effect. The present study also provides a theoretical basis for the prevention and treatment of age-related macular degeneration.
C1 [Li, Jia; Li, Bing] Jinzhou Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Jinzhou 121000, Peoples R China.
   [Sun, Jianhua] Jinzhou Cent Hosp, Dept Otolaryngol, Jinzhou, Peoples R China.
   [Li, Zheli] China Med Univ, Dept Ophthalmol, Hosp 1, Shenyang, Liaoning, Peoples R China.
C3 Jinzhou Medical University; China Medical University
RP Li, B (通讯作者)，Jinzhou Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Jinzhou 121000, Peoples R China.; Li, ZL (通讯作者)，China Med Univ, Dept Ophthalmol, Hosp 1, Shenyang, Liaoning, Peoples R China.
EM jzslibingv@163.com; Jia820323@163.com
FU Science and Technology Project of Liaoning Province [2015020351]
FX This work was supported by the Science and Technology Project of
   Liaoning Province under grant number 2015020351.
CR Awh CC, 2015, OPHTHALMOLOGY, V122, P162, DOI 10.1016/j.ophtha.2014.07.049
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NR 28
TC 2
Z9 4
U1 1
U2 7
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1310-2818
EI 1314-3530
J9 BIOTECHNOL BIOTEC EQ
JI Biotechnol. Biotechnol. Equip.
PD SEP 3
PY 2018
VL 32
IS 5
BP 1277
EP 1284
DI 10.1080/13102818.2018.1512378
PG 8
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA HO6ND
UT WOS:000461045700024
OA gold
DA 2022-11-30
ER

PT J
AU Ozkaya, A
   Garip, R
   Tarakcioglu, HN
   Atkin, Z
   Taskapili, M
AF Ozkaya, A.
   Garip, R.
   Tarakcioglu, H. Nur
   Atkin, Z.
   Taskapili, M.
TI Clinical and imaging findings of pattern dystrophy subtypes; Diagnostic
   errors and unnecessary treatment in clinical practice
SO JOURNAL FRANCAIS D OPHTALMOLOGIE
LA English
DT Article
DE Autofluorescence; Imaging; Optical coherence tomography; Pattern
   dystrophy
ID OPTICAL COHERENCE TOMOGRAPHY; FOVEOMACULAR VITELLIFORM DYSTROPHY
AB Purpose. - To evaluate the clinical and multimodal imaging findings of various pattern dystrophy (PD) subtypes and report the initial misdiagnosis rate of PD patients resulting in unnecessary treatment in actual clinical practice.
   Methods. - Retrospective, observational study. Forty eyes of 24 patients with PD were included. The distribution of PD subtypes, optical coherence tomography (OCT) and fundus autofluorescence (FAF) findings, initial misdiagnoses, revised diagnoses, duration between misdiagnosis and revised diagnosis, and unnecessary treatments administered were evaluated over this time-period.
   Results. - Twenty-eight eyes (70%) showed adult-onset foveomacular vitelliform dystrophy, 6 eyes (15%) showed butterfly PD (BPD), 4 eyes (10%) showed reticular PD, and 2 eyes (5%) showed PD simulating fundus flavimaculatus and BPD mixed type PD. Most of the patients showed various types of hyperreflective material in the subretinal space on OCT, and hyperautofluorescence on FAF imaging. Eighteen eyes (45%) had a true PD diagnosis initially, whereas 22 (55%) of them were misdiagnosed as age-related macular degeneration, central serous chorioretinopathy, or non-specific RPE change. The mean duration between the initial and revised diagnosis was 18.7 +/- 16.8 months. In addition, 5 eyes in the misdiagnosed group underwent intravitreal anti vascular endothelial growth factor treatment during this period.
   Conclusion. Pattern dystrophies are a heterogeneous group of macular disorders which may mimic several macular diseases. By knowing the multimodal imaging findings, especially the distinctive FAF findings of the PDs, we may easily diagnose the disease and save our patients from unnecessary treatments. (C) 2017 Elsevier Masson SAS. All rights reserved.
C1 [Ozkaya, A.; Garip, R.; Tarakcioglu, H. Nur; Atkin, Z.; Taskapili, M.] Beyoglu Eye Training & Res Hosp, TR-34421 Istanbul, Turkey.
C3 Istanbul Prof Dr N Resat Belger Beyoglu Eye Training & Research Hospital
RP Ozkaya, A (通讯作者)，Beyoglu Eye Training & Res Hosp, TR-34421 Istanbul, Turkey.
EM abdozkaya@gmail.com
RI Alkin, Zeynep/V-7252-2017; tarakçıoğlu, hatice nur/ABB-5178-2020
OI Alkin, Zeynep/0000-0002-5363-1944; tarakçıoğlu, hatice
   nur/0000-0002-8611-4353
CR Adhi M, 2013, CURR OPIN OPHTHALMOL, V24, P213, DOI 10.1097/ICU.0b013e32835f8bf8
   Alkin Z, 2014, J OCUL PHARMACOL TH, V30, P359, DOI 10.1089/jop.2013.0162
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NR 20
TC 9
Z9 9
U1 0
U2 2
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 0181-5512
EI 1773-0597
J9 J FR OPHTALMOL
JI J. Fr. Ophthamol.
PD JAN
PY 2018
VL 41
IS 1
BP 21
EP 29
DI 10.1016/j.jfo.2017.06.009
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FW7ZL
UT WOS:000425546600013
PM 29195727
DA 2022-11-30
ER

PT J
AU Wu, S
   Lu, QJ
   Wang, NL
   Zhang, JX
   Liu, Q
   Gao, M
   Chen, JQ
   Liu, W
   Xu, L
AF Wu, Shen
   Lu, Qingjun
   Wang, Ningli
   Zhang, Jingxue
   Liu, Qian
   Gao, Meng
   Chen, Jinqiu
   Liu, Wu
   Xu, Liang
TI Cyclic stretch induced-retinal pigment epithelial cell apoptosis and
   cytokine changes
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Retinal pigment epithelium; Apoptosis; Cytoskeleton; Age-related macular
   degeneration; Mechanical stretch
ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; MACULAR DEGENERATION;
   VITREOMACULAR ADHESION; MECHANICAL-STRESS; DNA-DAMAGE; PATHWAY;
   INFLAMMATION; PERSPECTIVE; EXPRESSION
AB Background: The pathogenesis of age-related macular degeneration (AMD) is complex. It has been shown that vitreomacular traction (VMT) plays a role in the pathogenesis of AMD. We speculate that the continuous stretch induced by VMT might impair the function of retinal pigment epithelium (RPE) cells and it might also be involved in the progression of AMD.
   Methods: Cultured ARPE-19 cells were subjected to cyclic stretch on the Flexcell Strain system at a level of 25% increment on the surface area for 8 h, 14 h, 20 h, 24 h. In another group, the stretch was withdrawn at 14 h and the cell cultured for another 6 h. Then, we observed the changes in morphology, apoptosis and expression of interleukin 6 (IL6) and vascular endothelial growth factor (VEGF) in RPE cells under stretch.
   Results: We found that stretch induced the RPE cells to change from a spreading shape into a rounded shape, and that the morphological changes were positively correlated with the duration of the stretch. The expression of pFAK397 and pRac1/cdc42 were elevated in a time-dependent fashion. The stretch resulted in an increase in the apoptosis ratio, with Bcl2, Bax and p53 also showing time-dependent changes. In addition, up-regulation of IL6 and VEGF expression levels was also observed. After withdrawal of the stretch, all of these changes were significantly diminished.
   Conclusion: Stretch may induce morphological, cell apoptosis, and up-regulation of cytokines changes in RPE cells, indicating that cyclic stretching may participate in the progression of AMD by impeding the functions of the RPE.
C1 [Wu, Shen; Wang, Ningli; Zhang, Jingxue; Liu, Qian; Xu, Liang] Capital Med Univ, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.
   [Wu, Shen; Wang, Ningli; Zhang, Jingxue; Liu, Qian; Gao, Meng; Chen, Jinqiu; Liu, Wu; Xu, Liang] Capital Med Univ, Beijing Tongren Eye Ctr, Beijing 100005, Peoples R China.
   [Wu, Shen; Wang, Ningli; Zhang, Jingxue; Liu, Qian; Gao, Meng; Chen, Jinqiu; Liu, Wu; Xu, Liang] Capital Med Univ, Beijing Tongren Hosp, Beijing 100005, Peoples R China.
   [Wu, Shen; Wang, Ningli; Zhang, Jingxue; Liu, Qian; Gao, Meng; Chen, Jinqiu; Liu, Wu; Xu, Liang] Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100005, Peoples R China.
   [Lu, Qingjun] China Japan Friendship Hosp, Beijing 100029, Peoples R China.
C3 Capital Medical University; Capital Medical University; Capital Medical
   University; China-Japan Friendship Hospital
RP Xu, L (通讯作者)，Capital Med Univ, Beijing Inst Ophthalmol, Beijing 100005, Peoples R China.; Liu, W; Xu, L (通讯作者)，Capital Med Univ, Beijing Tongren Eye Ctr, Beijing 100005, Peoples R China.; Liu, W; Xu, L (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing 100005, Peoples R China.; Liu, W; Xu, L (通讯作者)，Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100005, Peoples R China.
EM wuliubj@sina.com; xlbio1@163.com
RI liu, qian/HDM-2936-2022
FU National Natural Science Foundation of China [81541106]; Beijing Natural
   Science Foundation [7164243]; Basic-Clinical Research Cooperation
   Funding of Capital Medical University [16JL52]
FX This work was supported by the National Natural Science Foundation of
   China (81541106), Beijing Natural Science Foundation (7164243),
   Basic-Clinical Research Cooperation Funding of Capital Medical
   University (16JL52).
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NR 35
TC 9
Z9 10
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD NOV 22
PY 2017
VL 17
AR 208
DI 10.1186/s12886-017-0606-0
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FN3RI
UT WOS:000415916100002
PM 29166888
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ueda, K
   Zhao, J
   Kim, HJ
   Sparrow, JR
AF Ueda, Keiko
   Zhao, Jin
   Kim, Hye Jin
   Sparrow, Janet R.
TI Photodegradation of retinal bisretinoids in mouse models and
   implications for macular degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE bisretinoid; visual cycle; retina; retinal pigment epithelium; macular
   degeneration
ID AGE-RELATED MACULOPATHY; PIGMENT EPITHELIAL-CELLS; FUNDUS
   AUTOFLUORESCENCE; LIPOFUSCIN BISRETINOIDS; SUNLIGHT EXPOSURE; RPE
   LIPOFUSCIN; LIGHT DAMAGE; VITAMIN-E; A2E; MICE
AB Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age-related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2-GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans-retinal dimerphosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with darkness. In albino Abca4(-/-) mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure.
C1 [Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R.] Columbia Univ, Med Ctr, Dept Ophthalmol, New York, NY 10032 USA.
   [Sparrow, Janet R.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University
RP Sparrow, JR (通讯作者)，Columbia Univ, Med Ctr, Dept Ophthalmol, New York, NY 10032 USA.; Sparrow, JR (通讯作者)，Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA.
EM jrs88@cumc.columbia.edu
FU National Eye Institute [EY12951, P30EY019007]; Foundation Fighting
   Blindness; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [R01EY012951, P30EY019007] Funding Source: NIH RePORTER
FX Dr. Zhao Liu contributed to some experiments. This work was supported by
   grants from the National Eye Institute (EY12951 and P30EY019007),
   Foundation Fighting Blindness, and Research to Prevent Blindness to the
   Department of Ophthalmology, Columbia University.
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NR 62
TC 63
Z9 63
U1 0
U2 11
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 JUN 21
PY 2016
VL 113
IS 25
BP 6904
EP 6909
DI 10.1073/pnas.1524774113
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DP1TN
UT WOS:000378272400041
PM 27274068
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Cammalleri, M
   Dal Monte, M
   Locri, F
   Lista, L
   Aronsson, M
   Kvanta, A
   Rusciano, D
   De Rosa, M
   Pavone, V
   Andre, H
   Bagnoli, P
AF Cammalleri, Maurizio
   Dal Monte, Massimo
   Locri, Filippo
   Lista, Liliana
   Aronsson, Monica
   Kvanta, Anders
   Rusciano, Dario
   De Rosa, Mario
   Pavone, Vincenzo
   Andre, Helder
   Bagnoli, Paola
TI The Urokinase Receptor-Derived Peptide UPARANT Mitigates Angiogenesis in
   a Mouse Model of Laser-Induced Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; angiogenic factors; inflammatory factors; transcription factors
ID MACULAR DEGENERATION; RETINAL NEOVASCULARIZATION; PLASMINOGEN-ACTIVATOR;
   VEGF; INHIBITION; UPA; PATHOGENESIS; INFLAMMATION; THERAPIES; SYSTEM
AB PURPOSE. A mouse model of age-related macular degeneration (AMD) was used to investigate the anti-angiogenic and anti-inflammatory role of UPARANT in laser-induced choroidal neovascularization (CNV).
   METHODS. Choroidal neovascularization was induced by laser photocoagulation, and UPARANT was intravitreally injected. Some experiments were also performed after either intravitreal injection of anti-VEGF drugs or systemic administration of UPARANT. Immunohistochemistry using CD31 antibodies was used to evaluate the area of CNV. Evans blue dye extravasation was quantitatively assessed. Transcripts of markers of outer blood retinal barrier were measured by quantitative RT-PCR, also used to evaluate angiogenesis and inflammation markers. Western blot was used to determine levels of transcription factors encoding genes involved in angiogenesis and inflammation. Levels of urokinase-type plasminogen activator (uPA), its receptor (uPAR), and formyl peptide receptors (FPRs) were determined at the transcript and the protein level.
   RESULTS. Intravitreal UPARANT reduced the CNV area and the leakage from the choroid. The uPA/uPAR/FPR system was upregulated in CNV, but was not influenced by UPARANT. UPARANT recovered laser-induced upregulation of transcription factors encoding angiogenic and inflammatory markers. Accordingly, angiogenic and inflammatory factors were also reduced. UPARANT as compared to anti-VEGF drugs displayed similar effects on CNV area.
   CONCLUSIONS. UPARANT mitigates laser-induced CNV by inhibiting angiogenesis and inflammation through an action on transcription factors encoding angiogenesis and inflammatory genes. The finding that UPARANT is effective against CNV may help to establish uPAR and its membrane partners as putative targets in the treatment of AMD.
C1 [Cammalleri, Maurizio; Dal Monte, Massimo; Locri, Filippo; Bagnoli, Paola] Univ Pisa, Dept Biol, Via San Zeno 31, I-56127 Pisa, Italy.
   [Lista, Liliana; Pavone, Vincenzo] Univ Naples Federico II, Dept Chem Sci, Naples, Italy.
   [Aronsson, Monica; Kvanta, Anders; Andre, Helder] Karolinska Inst, St Erik Hosp, Dept Clin Neurosci, Sect Ophthalmol & Vis, Stockholm, Sweden.
   [Rusciano, Dario] Sooft Italia Spa, Montegiorgio, Italy.
   [De Rosa, Mario] Univ Naples 2, Dept Expt Med, Naples, Italy.
C3 University of Pisa; University of Naples Federico II; Karolinska
   Institutet; Universita della Campania Vanvitelli
RP Bagnoli, P (通讯作者)，Univ Pisa, Dept Biol, Via San Zeno 31, I-56127 Pisa, Italy.
EM paola.bagnoli@unipi.it
RI Dal Monte, Massimo/AAA-9275-2022; Rusciano, Dario/AAP-7450-2020; Andre,
   Helder/AAC-5220-2019; Pavone, Vincenzo/D-1688-2011
OI Rusciano, Dario/0000-0002-9577-2585; Andre, Helder/0000-0002-2926-2376;
   Pavone, Vincenzo/0000-0001-6432-0802; LISTA,
   Liliana/0000-0002-9767-1972; De Rosa, Mario/0000-0002-2976-0818
FU Italian Ministero della Salute (Roma, Italy) [RF-2011-02351158]; BIOOS
   Italia (Montegiorgio, Italy); Crown Princess Margareta Association for
   the Visually Impaired (Valdemarsvik, Sweden); Edwin Jordan Foundation
   (Stockholm, Sweden); Tore Nilsson Foundation (Stockholm, Sweden);
   Swedish Research Council (Stockholm, Sweden); Swedish Eye Foundation
   (Umea, Sweden); European Union-Fondi Europei per lo Sviluppo Regionale;
   Italian Ministero dell'Istruzione e dell'Universita; Italian Ministero
   dello Sviluppo Economico (Roma, Italy) [PON01 02464]
FX Supported by grants from Italian Ministero della Salute
   (RF-2011-02351158; PB; Roma, Italy), BIOOS Italia (PB; Montegiorgio,
   Italy); The Crown Princess Margareta Association for the Visually
   Impaired (HA; Valdemarsvik, Sweden), Edwin Jordan Foundation (HA;
   Stockholm, Sweden), Tore Nilsson Foundation (HA; Stockholm, Sweden), The
   Swedish Research Council (HA; Stockholm, Sweden), The Swedish Eye
   Foundation (HA; Umea, Sweden); European Union-Fondi Europei per lo
   Sviluppo Regionale, Italian Ministero dell'Istruzione e dell'Universita,
   and Italian Ministero dello Sviluppo Economico (PON01 02464; MDR and VP;
   Roma, Italy).
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NR 64
TC 19
Z9 19
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2016
VL 57
IS 6
BP 2600
EP 2611
DI 10.1167/iovs.15-18758
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DO8OA
UT WOS:000378041700029
PM 27168367
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Quartilho, A
   Simkiss, P
   Zekite, A
   Xing, W
   Wormald, R
   Bunce, C
AF Quartilho, A.
   Simkiss, P.
   Zekite, A.
   Xing, W.
   Wormald, R.
   Bunce, C.
TI Leading causes of certifiable visual loss in England and Wales during
   the year ending 31 March 2013
SO EYE
LA English
DT Article
ID PARTIAL SIGHT; CERTIFICATIONS; BLIND
AB Purpose The last article on causes of sight impairment (SI) in England and Wales was for April 2007-March 2008. This report updates these figures for April 2012-March 2013.
   Methods In England and Wales, registration for SI is initiated by completion of a certificate of vision impairment (CVI). The main cause of visual impairment was ascertained for certificates completed April 2012-March 2013. A proportional comparison against April 2007-March 2008 was made.
   Results We received 24 009 CVIs of which 10 410 were for severe sight impairment (SSI) and 13 129 were for SI. These numbers were slightly higher than those observed in April 2007-March 2008 (9823 SSI; 12 607 SI). The ratio SI: SSI has remained static with 55% of all certifications being SI. The proportion of certificates without a single main cause has fallen slightly (16.6 to 14%). The proportion of certificates with a main cause of degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) decreased from 58.6 to 50% SSI and from 57.2 to 52.5% SI. Glaucoma remains the second most common cause (11% SSI; 7.6% SI) but hereditary retinal disorders overtook diabetes as third leading cause of SSI.
   Conclusion AMD is still by far the leading cause of certifications for sight impairment in England and Wales (both SI and SSI). Proportionate changes have been observed since 2008, but it is important to note that a proportionate increase in one condition will impact on others.
C1 [Quartilho, A.; Zekite, A.; Xing, W.; Wormald, R.; Bunce, C.] NIHR BRC Ophthalmol, Dept R&D, London, England.
   [Quartilho, A.; Zekite, A.; Xing, W.; Wormald, R.; Bunce, C.] UCL Inst Ophthalmol, London, England.
   [Simkiss, P.] Royal Natl Inst Blind People RNIB, London, England.
   [Wormald, R.; Bunce, C.] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Keppel St, London WC1E 7HT, England.
C3 University of London; University College London; University of London;
   London School of Hygiene & Tropical Medicine
RP Bunce, C (通讯作者)，Moorfields Eye Hosp, Res & Dev, 162 City Rd, London EC1V 2PD, England.
EM c.bunce@ucl.ac.uk
OI Quartilho, Ana/0000-0002-0800-9259; Bunce, Catey/0000-0002-0935-3713
FU RNIB; National Institute for Health Research (NIHR) Biomedical Research
   Centre (BRC) at Moorfields Eye Hospital NHS Foundation Trust; UCL
   Institute of Ophthalmology
FX This study was supported by a grant from the RNIB. The posts of AQ, AZ,
   WX, RW and CB are partly funded by the National Institute for Health
   Research (NIHR) Biomedical Research Centre (BRC) based at Moorfields Eye
   Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The
   data captured by the CVI are DH copyright and this work was made
   possible by collaboration with the Royal College of Ophthalmologists We
   thank Emilia Gnat and Zabed Ahmed for their support to the CVI Office.
   The views expressed in this paper are those of the author and not
   necessarily any funding body or the Department of Health.
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NR 15
TC 72
Z9 73
U1 1
U2 18
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 2016
VL 30
IS 4
BP 602
EP 607
DI 10.1038/eye.2015.288
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DJ3RY
UT WOS:000374124600015
PM 26821759
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Celik, N
   Scheuerle, A
   Auffarth, GU
   Kopitz, J
   Dithmar, S
AF Celik, Nil
   Scheuerle, Alexander
   Auffarth, Gerd U.
   Kopitz, Juergen
   Dithmar, Stefan
TI Intraocular Pharmacokinetics of Aflibercept and Vascular Endothelial
   Growth Factor-A
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aflibercpt; VEGF; pharmacokinetics; macular edema
ID AQUEOUS-HUMOR LEVELS; VEGF TRAP-EYE; MACULAR DEGENERATION; INTRAVITREAL
   RANIBIZUMAB; BEVACIZUMAB AVASTIN; VITRECTOMIZED EYES; VITREOUS LEVELS;
   CYTOKINES; RABBIT; EDEMA
AB PURPOSE. To determine intraocular pharmacokinetics of aflibercept and VEGF-A in patients with neovascular age-related macular degeneration (nAMD) during a treatment period of 6 months.
   METHODS. Seven nonvitrectomized patients diagnosed with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of aflibercept. Patients were treatment naive at least for the last 2 months and received intravitreal injection of 2 mg aflibercept for the first time. Aqueous humor samples were obtained prior to each injection procedure during a 6-month period: three times monthly, then bimonthly. Over all 35 samples were analyzed with ELISA for unbound VEGF-A and a self-developed assay for unbound aflibercept.
   RESULTS. In all cases, wet AMD was inactive after IVI. Unbound aflibercept could be detected in all samples. Initial mean concentration of aflibercept was 305.4 +/- 43.8 mu g/mL and remained stable after the first injection with 0.8 +/- 0.5 mu g/mL. Initial mean level of unbound VEGF-A was 190.7 +/- 26.9 pg/mL. A significant decrease of the concentration to 92.6 +/- 10.2 pg/mL (P < 0.05, Wilcoxon rank sum test) after the first injection was observed. This level remained stable during further treatment.
   CONCLUSIONS. Levels of unbound aflibercept and unbound VEGF-A remained stable after every month and every second month of IVI. The findings of these small case series support suggestions that treatment intervals with bimonthly IVI of aflibercept are sufficient due to a detectable remaining biologic active concentration of aflibercept.
C1 [Celik, Nil; Scheuerle, Alexander; Auffarth, Gerd U.; Dithmar, Stefan] Univ Heidelberg Hosp, Dept Ophthalmol, Heidelberg, Germany.
   [Kopitz, Juergen] Heidelberg Univ, Dept Pathol, Heidelberg, Germany.
   [Dithmar, Stefan] Klinikum Wiesbaden HSK, Dept Ophthalmol, Wiesbaden, Germany.
C3 Ruprecht Karls University Heidelberg; Ruprecht Karls University
   Heidelberg
RP Dithmar, S (通讯作者)，Dr Horst Schmidt Kliniken, Dept Ophthalmol, Ludwig Erhard Str 100, D-65199 Wiesbaden, Germany.
EM stefan.dithmar@gmx.de
RI Auffarth, Gerd/AAE-6805-2021
OI Auffarth, Gerd/0000-0002-6927-5251
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NR 21
TC 14
Z9 14
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2015
VL 56
IS 9
BP 5574
EP 5578
DI 10.1167/iovs.15-16418
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT5WW
UT WOS:000362882800068
PM 26305529
DA 2022-11-30
ER

PT J
AU Spaide, RF
AF Spaide, Richard F.
TI Optical Coherence Tomography Angiography Signs of Vascular
   Abnormalization With Antiangiogenic Therapy for Choroidal
   Neovascularization
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID FLUID SHEAR-STRESS; PHYSIOLOGICAL PRINCIPLE; TUMOR ANGIOGENESIS;
   GROWTH-FACTOR; ARTERIOGENESIS; SYSTEM; NORMALIZATION; MECHANISMS;
   PATHWAYS; COST
AB PURPOSE: To investigate the vascular appearance of choroidal neovascularization (CNV) treated with recurrent intravitreous anti vascular endothelial growth factor (VEGF) injections, which have been proposed to cause transient vascular normalization along with decreased vascularity and leakage.
   DESIGN: Retrospective case series with perspective on the topic.
   METHODS: Patients with treated CNV secondary to age-related macular degeneration from a community-based retinal referral practice were evaluated with optical coherence tomography angiography employing split-spectrum amplitude decorrelation. The choroidal neovascular morphology of the 17 eyes of 14 consecutive patients was described.
   RESULTS: The mean age of the patients, 8 men and 6 women, was 78.4 (standard deviation +/- 9.3) years. The mean greatest linear dimension of the lesion was 3600 mu m. The mean number of anti-VEGF injections Was 47 (+/- 21). The vascular diameter of the vessels in the CNV appeared large even in small lesions, with feeder vessels approaching the size of the major arcade vessels of the retina. The vessels had few branch points and many vascular anastomotic connections among larger vessels. There was a paucity of capillaries visualized within the lesions.
   CONCLUSIONS: The findings of this study do not support the hypothesis of vascular normalization in eyes receiving recurrent periodic antiangiogenic treatment. The observed "abnormalization" of the vessels may be explained by periodic pruning of angiogenic vascular sprouts by VEGF withdrawal in the face of unimpeded arteriogenesis. As the eye is a readily accessible VEGF laboratory, features expressed therein may also apply to neovascularization elsewhere in the body, such as in tumors. (C) 2015 by Elsevier Inc. All rights reserved.
C1 Macula Consultants New York, Vitreous Retina, New York, NY 10022 USA.
C3 Vitreous Retina Macula Consultants of New York
RP Spaide, RF (通讯作者)，Macula Consultants New York, Vitreous Retina, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
EM rickspaide@gmail.com
RI Spaide, Richard/ABD-7368-2020
FU Macula Foundation, New York, New York
FX Supported in part by the Macula Foundation, New York, New York. The
   support involved no input to the content or wording of the article. The
   author attests that he meets the current ICMJE requirements to qualify
   as author.
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NR 40
TC 200
Z9 211
U1 1
U2 21
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 JUL
PY 2015
VL 160
IS 1
BP 6
EP 16
DI 10.1016/j.ajo.2015.04.012
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CL4FS
UT WOS:000356908600003
PM 25887628
DA 2022-11-30
ER

PT J
AU Liu, XX
AF Liu, Xunxian
TI Overstimulation can create health problems due to increases in
   PI3K/Akt/GSK3 insensitivity and GSK3 activity
SO SPRINGERPLUS
LA English
DT Article
DE Aging; AMD; Complement; Death hormones; Insensitivity; IL17/IL17RC;
   PI3K/Akt/GSK3/GSK3 substrates; Signaling; VEGF
ID GLYCOGEN-SYNTHASE KINASE-3; MACULAR DEGENERATION; BETA-CATENIN; WNT
   PATHWAY; AGE; PHOSPHORYLATION; CELLS; EXPRESSION; DISEASE; INFLAMMATION
AB Aging is linked to decrease of the body cell use of growth hormone (GH) and thyroxine, whereas the decrease is via "death hormones" inhibition? This study proposes different viewpoints. Since interleukin 17 receptor C (IL17RC) is highly expressed in tissues from age-related macular degeneration (AMD) patients, IL17RC signaling pathways are explored to evaluate Wnts/vascular endothelial growth factor (VEGF) expression and complement activity, which are pathological factors in AMD. IL17RC overexpression or VEGF treatment was performed in two cell lines for up to two-day. Real-time Quantitative PCR, confocal microscopy, immune-blot, MTT assay, etc. measured downstream effects. IL17RC overexpression increases Wnts and VEGF that forms complexes with Wnt-signaling components. VEGF or the Wnt-signaling components interacting with C3 suggests alternative complement pathway activation. Moreover, IL17RC-overexpressed cells or VEGF-treated cells for two-day, which is overstimulation, increase PI3K/Akt/GSK3 insensitivity and GSK3 activity, and decrease growth/survival. High GSK3 activity associates with many chronic diseases including type II Diabetes. This study shows high GSK3 activity can result from PI3K/Akt overstimulation. Type II Diabetes shows insulin resistance that the body cells decrease insulin use. Possessing little sensitive PI3K/Akt for receptor activation, cells after overstimulation, although live, hardly respond to PI3K/Akt activators including GH, thyroxine and insulin. These results suggest an alternative explanation of the body cells declining hormone use since various kinds of cell signaling-induced overstimulation events almost always linked to PI3K/Akt, increase with age. Playing pathological roles in senescence and diseases, overstimulation eventually generates health problems.
C1 NIH, Intramural Res Program, Natl Ctr Complementary & Alternat Med, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Center for
   Complementary & Alternative Medicine
RP Liu, XX (通讯作者)，NIH, Intramural Res Program, Natl Ctr Complementary & Alternat Med, US Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA.
EM xunxianl@mail.nih.gov
FU NCCAM, National Institutes of Health, US Department of Health and Human
   Services
FX This research was supported by intramural research program in NCCAM,
   National Institutes of Health, US Department of Health and Human
   Services. The author thanks Drs. Julia T Arnold, Hui Chen and Min Chen
   for their constructive critiques of the manuscript.
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NR 43
TC 16
Z9 18
U1 0
U2 4
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-1801
J9 SPRINGERPLUS
JI SpringerPlus
PD JUL 14
PY 2014
VL 3
AR 356
DI 10.1186/2193-1801-3-356
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CO3KC
UT WOS:000359055100002
PM 25089247
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Holz, FG
   Strauss, EC
   Schmitz-Valckenberg, S
   Campagne, MV
AF Holz, Frank G.
   Strauss, Erich C.
   Schmitz-Valckenberg, Steffen
   Campagne, Menno van Lookeren
TI Geographic Atrophy Clinical Features and Potential Therapeutic
   Approaches
SO OPHTHALMOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; COMPLEMENT ACTIVATION;
   NLRP3 INFLAMMASOME; HIGH-RISK; PROGRESSION; VARIANTS; AMD; FLUORESCENCE;
   PATHOGENESIS
AB In contrast to wet age-related macular degeneration (AMD), where loss of vision is typically acute and treatment leads to a relatively rapid reduction in retinal fluid and subsequent improvements in visual acuity (VA), disease progression and vision loss in geographic atrophy (GA) owing to AMD are gradual processes. Although GA can result in significant visual function deficits in reading, night vision, and dark adaptation, and produce dense, irreversible scotomas in the visual field, the initial decline in VA may be relatively minor if the fovea is spared. Because best-corrected VA does not correlate well with GA lesions or progression, alternative clinical endpoints are being sought. These include reduction in drusen burden, slowing the enlargement rate of GA lesion area, and slowing or eliminating the progression of intermediate to advanced AMD. Among these considerations, slowing the expansion of the GA lesion area seems to be a clinically suitable primary efficacy endpoint. Because GA lesion growth is characterized by loss of photoreceptors, it is considered a surrogate endpoint for vision loss. Detection of GA can be achieved with a number of different imaging techniques, including color fundus photography, fluorescein angiography, fundus autofluorescence (FAF), near-infrared reflectance, and spectral-domain optical coherence tomography. Previous studies have identified predictive characteristics for progression rates including abnormal patterns of FAF in the perilesional retina. Although there is currently no approved or effective treatment to prevent the onset and progression of GA, potential therapies are being evaluated in clinical studies. (C) 2014 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.
C1 [Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Strauss, Erich C.; Campagne, Menno van Lookeren] Genentech Inc, San Francisco, CA 94080 USA.
C3 University of Bonn; Roche Holding; Genentech
RP Holz, FG (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM Frank.Holz@ukb.uni-bonn.de
FU Genentech, Inc., South San Francisco, California
FX Support for third-party writing and formatting assistance for this
   manuscript was provided by Linda Merkel, PhD, CMPP, and was funded by
   Genentech, Inc., South San Francisco, California.
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NR 57
TC 245
Z9 251
U1 1
U2 39
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2014
VL 121
IS 5
BP 1079
EP 1091
DI 10.1016/j.ophtha.2013.11.023
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AG6BT
UT WOS:000335504200022
PM 24433969
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Rutar, M
   Valter, K
   Natoli, R
   Provis, JM
AF Rutar, Matt
   Valter, Krisztina
   Natoli, Riccardo
   Provis, Jan M.
TI Synthesis and Propagation of Complement C3 by Microglia/Monocytes in the
   Aging Retina
SO PLOS ONE
LA English
DT Article
ID SENILE MACULAR DEGENERATION; FACTOR-H POLYMORPHISM; PARA-INFLAMMATION;
   GENE-EXPRESSION; IMMUNE; CELLS; DEFICIENCY; RISK; MICROGLIA; RECRUITMENT
AB Introduction: Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging.
   Methods: SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes.
   Results: C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines.
   Conclusions: Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.
C1 [Rutar, Matt; Valter, Krisztina; Natoli, Riccardo; Provis, Jan M.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
   [Valter, Krisztina; Natoli, Riccardo; Provis, Jan M.] Australian Natl Univ, Sch Med, Canberra, ACT 2601, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
EM matt.rutar@anu.edu.au
RI Valter, Krisztina/L-3015-2016; Provis, Jan/C-9529-2009
OI Rutar, Matthew/0000-0002-8893-5120; Natoli,
   Riccardo/0000-0002-9350-0439; Valter, Krisztina/0000-0002-2033-0408;
   Provis, Jan/0000-0002-6405-2868
FU Australian Research Council Centres of Excellence Program Grant
   [CE0561903]
FX Funding provided by Australian Research Council Centres of Excellence
   Program Grant (CE0561903). 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 76
TC 37
Z9 38
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 4
PY 2014
VL 9
IS 4
AR e93343
DI 10.1371/journal.pone.0093343
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AE6MJ
UT WOS:000334107500032
PM 24705166
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Burke, TR
   Fishman, GA
   Zernant, J
   Schubert, C
   Tsang, SH
   Smith, RT
   Ayyagari, R
   Koenekoop, RK
   Umfress, A
   Ciccarelli, ML
   Baldi, A
   Iannaccone, A
   Cremers, FPM
   Klaver, CCW
   Allikmets, R
AF Burke, Tomas R.
   Fishman, Gerald A.
   Zernant, Jana
   Schubert, Carl
   Tsang, Stephen H.
   Smith, R. Theodore
   Ayyagari, Radha
   Koenekoop, Robert K.
   Umfress, Allison
   Ciccarelli, Maria Laura
   Baldi, Alfonso
   Iannaccone, Alessandro
   Cremers, Frans P. M.
   Klaver, Caroline C. W.
   Allikmets, Rando
TI Retinal Phenotypes in Patients Homozygous for the G1961E Mutation in the
   ABCA4 Gene
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CONE-ROD DYSTROPHY; STARGARDT-DISEASE GENE; MACULAR DEGENERATION;
   RETINITIS-PIGMENTOSA; FUNDUS FLAVIMACULATUS; SEQUENCE VARIATIONS;
   TRANSPORTER GENE; ITALIAN PATIENTS; ALLELES; AUTOFLUORESCENCE
AB PURPOSE. We evaluated the pathogenicity of the G1961E mutation in the ABCA4 gene, and present the range of retinal phenotypes associated with this mutation in homozygosity in a patient cohort with ABCA4-associated phenotypes.
   METHODS. Patients were enrolled from the ABCA4 disease database at Columbia University or by inquiry from collaborating physicians. Only patients homozygous for the G1961E mutation were enrolled. The entire ABCA4 gene open reading frame, including all exons and flanking intronic sequences, was sequenced in all patients. Phenotype data were obtained from clinical history and examination, fundus photography, infrared imaging, fundus autofluorescence, fluorescein angiography, and spectral domain-optical coherence tomography. Additional functional data were obtained using the full-field electroretinogram, and static or kinetic perimetry.
   RESULTS. We evaluated 12 patients homozygous for the G1961E mutation. All patients had evidence of retinal pathology consistent with the range of phenotypes observed in ABCA4 disease. The latest age of onset was recorded at 64 years, in a patient diagnosed initially with age-related macular degeneration (AMD). Of 6 patients in whom severe structural (with/without functional) fundus changes were detected, 5 had additional, heterozygous or homozygous, variants detected in the ABCA4 gene.
   CONCLUSIONS. Homozygous G1961E mutation in ABCA4 results in a range of retinal pathology. The phenotype usually is at the milder end of the disease spectrum, with severe phenotypes linked to the presence of additional ABCA4 variants. Our report also highlights that milder, late-onset Stargardt disease may be confused with AMD. (Invest Ophthalmol Vis Sci. 2012;53:4458-4467) DOI:10.1167/iovs.11-9166
C1 [Allikmets, Rando] Columbia Univ, Eye Res Inst, Dept Ophthalmol, New York, NY 10032 USA.
   [Fishman, Gerald A.] Chicago Lighthouse People Who Are Blind Visually, Pangere Ctr Hereditary Retinal Dis, Chicago, IL USA.
   [Tsang, Stephen H.; Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA.
   [Smith, R. Theodore] Columbia Univ, Dept Biomed Engn, New York, NY USA.
   [Ayyagari, Radha] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA.
   [Koenekoop, Robert K.] McGill Univ, Ctr Hlth, Dept Paediat Surg, Montreal, PQ, Canada.
   [Koenekoop, Robert K.] McGill Univ, Ctr Hlth, Dept Ophthalmol, Montreal, PQ, Canada.
   [Koenekoop, Robert K.] McGill Univ, Ctr Hlth, Dept Human Genet, Montreal, PQ, Canada.
   [Umfress, Allison; Iannaccone, Alessandro] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Hamilton Eye Inst, Memphis, TN USA.
   [Ciccarelli, Maria Laura] Israelit Hosp, Div Ophthalmol, Rome, Italy.
   [Baldi, Alfonso] Univ Naples 2, Biochem & Biophys Dept F Cedragnolo, Pathol Sect, Naples, Italy.
   [Cremers, Frans P. M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
   [Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
C3 Columbia University; Columbia University; Columbia University;
   University of California System; University of California San Diego;
   McGill University; McGill University; McGill University; University of
   Tennessee System; University of Tennessee Health Science Center;
   Universita della Campania Vanvitelli; Radboud University Nijmegen;
   Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC
RP Allikmets, R (通讯作者)，Columbia Univ, Eye Res Inst, Dept Ophthalmol, Rm 202,630 W 168th St, New York, NY 10032 USA.
EM rla22@columbia.edu
RI Cremers, Frans/A-5625-2014; Allikmets, Rando/ABD-4533-2021; Baldi,
   Alfonso/ABG-2397-2021; Koenekoop, Robert/AAT-6676-2021; Klaver, Caroline
   C.W./A-2013-2016
OI Cremers, Frans/0000-0002-4954-5592; Iannaccone,
   Alessandro/0000-0001-5737-8424; smith, theodore/0000-0002-1693-943X;
   Baldi, Alfonso/0000-0002-8693-3842; Klaver, Caroline/0000-0002-2355-5258
FU National Eye Institute/NIH [EY021163, EY013435, EY019861, EY019007];
   Foundation Fighting Blindness (Owings Mills, MD); Foundation Fighting
   Blindness Canada (Toronto, Ontario, Canada); Canadian Institutes for
   Health Research (Ottawa, Ontario, Canada); Reseau Vision (Montreal,
   Quebec, Canada); Research to Prevent Blindness (New York, NY); NATIONAL
   EYE INSTITUTE [R01EY021237, R01EY013435, R01EY021163, R24EY019861,
   R01EY018213, P30EY019007] Funding Source: NIH RePORTER
FX Supported in part by grants from the National Eye Institute/NIH
   EY021163, EY013435, EY019861, and EY019007 (Core Support for Vision
   Research); Foundation Fighting Blindness (Owings Mills, MD), Foundation
   Fighting Blindness Canada (Toronto, Ontario, Canada), Canadian
   Institutes for Health Research (Ottawa, Ontario, Canada), Reseau Vision
   (Montreal, Quebec, Canada) and unrestricted funds from Research to
   Prevent Blindness (New York, NY) to the Department of Ophthalmology,
   Columbia University, The Eye Surgery Fund and the Wynn-Gund Foundation.
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NR 48
TC 59
Z9 64
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 JUL
PY 2012
VL 53
IS 8
BP 4458
EP 4467
DI 10.1167/iovs.11-9166
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400017
PM 22661473
OA Green Published
DA 2022-11-30
ER

PT J
AU Jitsanong, T
   Khanobdee, K
   Piyachaturawat, P
   Wongprasert, K
AF Jitsanong, Thunchnok
   Khanobdee, Kornnika
   Piyachaturawat, Pawinee
   Wongprasert, Kanokpan
TI Diarylheptanoid 7-(3,4
   dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene from Curcuma comosa
   Roxb. protects retinal pigment epithelial cells against oxidative
   stress-induced cell death
SO TOXICOLOGY IN VITRO
LA English
DT Article
DE Curcuma comosa Roxb.; Diarylheptanoids; Anti-oxidant activities; Retinal
   pigment epithelial cell; Oxidative stress
ID SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION; EXPRESSION; CATALASE;
   INACTIVATION; APOPTOSIS; ISCHEMIA; INHIBIT; EXTRACT; ARPE-19
AB Chronic exposure to oxidative stress causes damage to retinal pigment epithelial cells which may lead to the development of age-related macular degeneration, the major cause of vision loss in humans. Anti-oxidants provide a natural defense against retinal cell damage. The present study was designed to evaluate the potential anti-oxidant activity and protective effect of two diarylheptanoids isolated from a medicinal herb Curcuma comosa; 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound A), and 1,7-diphenyl-4(E),6(E)-heptadien-3-ol (compound B) against oxidative stress (H2O2)-induced human retinal pigment epithelial (APRE-19) cell death. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay indicated that the anti-oxidant activity (IC50) of compound A was similar to that of vitamin C. Pre-treatment of ARPE-19 cells with 20 mu M compound A for 4 h afforded greater protection against the insult from 500 mu M H2O2, compared to a similar protection period for compound B. Compound A lowered H2O2-induced lipid peroxidation, malondialdehyde formation and intracellular reactive oxygen species. Furthermore, compound A ameliorated the H2O2-induced decrease in anti-oxidant enzyme activities and subsequent apoptotic cell death in ARPE-19 cells in a dose and time-dependent manner. These results suggest that compound A protects ARPE-19 cells against oxidative stress, in part, by enhancing several anti-oxidant defense mechanisms. Therefore, compound A may have therapeutic potential for diseases associated with oxidative stress, particularly degenerative retinal diseases. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Wongprasert, Kanokpan] Mahidol Univ, Fac Sci, Dept Anat, Bangkok 10400, Thailand.
   [Jitsanong, Thunchnok] Mahidol Univ, Fac Sci, Toxicol Grad Program, Bangkok 10400, Thailand.
   [Khanobdee, Kornnika] Suranaree Univ Technol, Sch Biol, Inst Sci, Nakhon Ratchasima, Thailand.
   [Piyachaturawat, Pawinee] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand.
C3 Mahidol University; Mahidol University; Suranaree University of
   Technology; Mahidol University
RP Wongprasert, K (通讯作者)，Mahidol Univ, Fac Sci, Dept Anat, Bangkok 10400, Thailand.
EM sckbp@mahidol.ac.th
RI Piyachaturawat, Pawinee/R-5817-2019
FU Mahidol University
FX This study was supported by Mahidol University Grant. The authors would
   like to thank Professor Apichart Suksamrarn for diarylheptanoids,
   Professor Suthat Fucharoen for contributing valuable suggestion and
   support, Dr. John Swinscoe and Gregory Kemp for critical comment on the
   manuscript.
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NR 39
TC 23
Z9 24
U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-2333
J9 TOXICOL IN VITRO
JI Toxicol. Vitro
PD FEB
PY 2011
VL 25
IS 1
BP 167
EP 176
DI 10.1016/j.tiv.2010.10.014
PG 10
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA 716YY
UT WOS:000287010600022
PM 21044678
DA 2022-11-30
ER

PT J
AU Shastry, B
AF Shastry, Barkur S.
TI Genetic diversity and medicinal drug response in eye care
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Genetics; Medicine; Ophthalmology; Polymorphism
ID COMPLEMENT FACTOR-H; INTRAOCULAR-PRESSURE RESPONSE; MACULAR
   DEGENERATION; PERSONALIZED MEDICINE; PHOTODYNAMIC THERAPY;
   GLUCOCORTICOID-RECEPTOR; PREDICTIVE ROLE; POLYMORPHISM;
   PHARMACOGENETICS; RANIBIZUMAB
AB Individual variation in drug response and adverse drug reactions are a serious problem in medicine. This inter-individual variation in drug response could be due to multiple factors such as disease determinants, environmental and genetic factors. Much has been published in the literature in recent years about the potential of pharmacogenetic testing and individualized medicine. The development of personalized medicine is truly an exciting area of research.
   This pharmacogenetic concept in ophthalmology has existed for more than a century. Although substantial studies that link genetic variants to inter-individual difference in drug response have been reported in several diseases such as cancer and heart diseases, such studies are progressing slowly in the eye field. In this short article, an attempt has been made to summarize these results.
   Recently, there have been some small-scale studies that seem to associate the drug response to the genotype of patients in two major eye disorders, namely age-related macular degeneration (ARMD) and glaucoma.
   These studies are still in their infancy, and do not suggest that a pharmacogenetic basis of drug development is a credible concept and can become reality in the future. This is because most drug responses involve a large number of genes that have several polymorphisms and it is unlikely that any one single gene dictates the drug response. Therefore, a polygenic approach, whole genome single nucleotide polymorphism (SNP) analysis and a molecular understanding of disease itself may provide a better insight in the future about genetic predisposing factors for adverse drug reactions.
C1 Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA.
C3 Oakland University
RP Shastry, B (通讯作者)，Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA.
EM shastry@oakland.edu
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NR 54
TC 14
Z9 16
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2010
VL 248
IS 8
BP 1057
EP 1061
DI 10.1007/s00417-010-1333-x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 622RO
UT WOS:000279683300001
PM 20204657
DA 2022-11-30
ER

PT J
AU Ueki, Y
   Le, YZ
   Chollangi, S
   Muller, W
   Ash, JD
AF Ueki, Yumi
   Le, Yun-Zheng
   Chollangi, Srinivas
   Muller, Werner
   Ash, John D.
TI Preconditioning-induced protection of photoreceptors requires activation
   of the signal-transducing receptor gp130 in photoreceptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE IL6 signal transducing receptor; neuroprotection; conditional gp130
   knockout; inherited retinal degeneration; light damage
ID CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; LIGHT-INDUCED
   DEGENERATION; FIBROBLAST-GROWTH-FACTOR; BRIGHT CYCLIC LIGHT;
   RETINAL-DEGENERATION; MOUSE RETINA; RAT RETINA; ROD PHOTORECEPTORS; CRE
   RECOMBINASE
AB Retinal degenerations are a class of neurodegenerative disorders that ultimately lead to blindness due to the death of retinal photoreceptors. In most cases, death is the result of long-term exposure to environmental, inflammatory, and genetic insults. In age-related macular degeneration, significant vision loss may take up to 70-80 years to develop. The protracted time to develop blindness suggests that retinal neurons have an endogenous mechanism for protection from chronic injury. Previous studies have shown that endogenous protective mechanisms can be induced by preconditioning animals with sublethal bright cyclic light. Such preconditioning can protect photoreceptors from a subsequent damaging insult and is thought to be accomplished through induced expression of protective factors. Some of the factors shown to be associated with protection bind and activate the signal transducing receptor gp130. To determine whether stress-induced endogenous protection of photoreceptors requires gp130, we generated conditional gp130 knockout (KO) mice with the Cre/lox system and used light-preconditioning to induce neuroprotection in these mice. Functional and morphological analyses demonstrated that the retina-specific gp130 KO impaired preconditioning-induced endogenous protection. Photoreceptor-specific gp130 KO mice had reduced protection, although the Muller cell KO mice did not, thus gp130-induced protection was restricted to photoreceptors. Using an animal model of retinitis pigmentosa, we found that the photoreceptor-specific gp130 KO increased sensitivity to genetically induced photoreceptor cell death, demonstrating that gp130 activation in photoreceptors had a general protective role independent of whether stress was caused by light or genetic mutations.
C1 [Ueki, Yumi; Ash, John D.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng; Ash, John D.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK 73104 USA.
   [Chollangi, Srinivas] Univ Oklahoma, Dept Bioengn, Norman, OK 73109 USA.
   [Ash, John D.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
   [Muller, Werner] Univ Manchester, Manchester M13 9PT, Lancs, England.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Oklahoma System; University of Oklahoma
   Health Sciences Center; University of Oklahoma System; University of
   Oklahoma Health Sciences Center; University of Oklahoma System;
   University of Oklahoma - Norman; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; University of Manchester
RP Ash, JD (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK 73104 USA.
EM john-ash@ouhsc.edu
RI Muller, Werner/B-9044-2008
OI Muller, Werner/0000-0002-1297-9725; Ash, John/0000-0002-8330-7301
FU National Eye Institute; National Institutes of Health [R01 EY016459, P20
   RR017703, P30 EY012190]; Research to Prevent Blindness; NATIONAL CENTER
   FOR RESEARCH RESOURCES [P20RR017703] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [P30EY012190, R01EY016459] Funding Source: NIH
   RePORTER
FX The authors thank the outstanding technical assistance from Louisa
   Williams and Linda Boone. This work is supported by National Eye
   Institute, National Institutes of Health Grant R01 EY016459, and core
   facilities provided by Grants P20 RR017703 and P30 EY012190. Additional
   funding was from an unrestricted departmental grant from Research to
   Prevent Blindness.
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NR 46
TC 36
Z9 36
U1 0
U2 4
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 DEC 15
PY 2009
VL 106
IS 50
BP 21389
EP 21394
DI 10.1073/pnas.0906156106
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 533AW
UT WOS:000272795300068
PM 19948961
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Bekkering, GE
   Rutjes, AWS
   Vlassov, VV
   Aebersold, DM
   von Bremen, K
   Juni, P
   Kleijnen, J
AF Bekkering, Geertruida E.
   Rutjes, Anne W. S.
   Vlassov, Vasiliy V.
   Aebersold, Daniel M.
   von Bremen, Konrade
   Jueni, Peter
   Kleijnen, Jos
TI The Effectiveness and Safety of Proton Radiation Therapy for Indications
   of the Eye
SO STRAHLENTHERAPIE UND ONKOLOGIE
LA English
DT Review
DE Proton therapy; Effectiveness; Safety; Eye melanoma
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; LARGE UVEAL MELANOMAS; BEAM
   IRRADIATION; CONSERVATIVE TREATMENT; MACULAR DEGENERATION;
   PROGNOSTIC-FACTORS; LOCAL RECURRENCE; RADIOTHERAPY; SURVIVAL;
   ENUCLEATION
AB Proton radiation has been used for the treatment of uveal melanoma since 1975, but few studies have been conducted to assess its efficacy and safety. This paper aims to systematically review the effects and side effects of proton therapy for any indication of the eye.
   A range of databases were searched from inception to 2007. All studies that included at least ten patients and that assessed the efficacy or safety of proton therapy for any indication of the eye were included.
   The search generated 2,385 references, of which 37 met the inclusion criteria. Five controlled trials, two comparative studies and 30 case series were found, most often reporting on uveal melanoma, choroidal melanoma and age-related macular degeneration (AMD). Methodological quality of these studies was poor. Studies were characterized by large differences in radiation techniques applied within the studies, and by variation in patient characteristics within and between studies. Results for uveal melanoma and choroidal melanoma suggest favorable survival, with, however, significant rates of side effects. Results for choroidal hemangioma and AMD did not reveal beneficial effects from proton radiation.
   There is limited evidence on the effectiveness and safety of proton radiation due to the lack of well-designed and well-reported studies. There is a need to lift evidence on proton therapy to a higher level by performing dose-finding randomized controlled trials (RCTs), comparative studies of proton radiation versus standard given alternatives and prospective case studies enrolling only patients treated with up-to-date techniques, allowing extrapolation of results to similar patient groups.
C1 [Bekkering, Geertruida E.] Katholieke Univ Leuven, Acad Ctr Gen Practice, B-3000 Louvain, Belgium.
   [Bekkering, Geertruida E.] BeSyRe Bekkering Systemat Reviews, Geel, Belgium.
   [Rutjes, Anne W. S.] Univ Bern, ISPM, Div Clin Epidemiol & Biostat, CH-3012 Bern, Switzerland.
   [Rutjes, Anne W. S.] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Chieti, Italy.
   [Vlassov, Vasiliy V.] Moscow Med Acad, Dept Res Methodol, Moscow, Russia.
   [Aebersold, Daniel M.; von Bremen, Konrade] Univ Hosp Bern, Inselspital, Dept Radiat Oncol, Bern, Switzerland.
   [Jueni, Peter] Univ Hosp Bern, CTU Bern, Bern, Switzerland.
   [Kleijnen, Jos] Kleijen Systemat Reviews Ltd, York, N Yorkshire, England.
C3 KU Leuven; University of Bern; Consorzio Mario Negri Sud; Sechenov First
   Moscow State Medical University; University of Bern; University Hospital
   of Bern; University of Bern; University Hospital of Bern; Kleijnen
   Systematic Reviews
RP Bekkering, GE (通讯作者)，Katholieke Univ Leuven, Acad Ctr Gen Practice, Kapucijnenvoer 33 Blok J Bus 7001, B-3000 Louvain, Belgium.
EM Trudy.Bekkering@med.kuleuven.be
RI Aebersold, Daniel Matthias/C-2946-2013; Rutjes, Anne/L-8750-2017; Juni,
   Peter/Q-8700-2016; Vlassov, Valentin/F-4720-2013; Vlassov,
   Vasiliy/B-4036-2014
OI Aebersold, Daniel Matthias/0000-0002-9493-3834; Rutjes,
   Anne/0000-0001-9782-779X; Juni, Peter/0000-0002-5985-0670; Vlassov,
   Valentin/0000-0003-2845-2992; Bekkering, Geertruida
   E/0000-0002-3845-1507; Vlassov, Vasiliy/0000-0001-5203-549X
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NR 80
TC 17
Z9 21
U1 0
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0179-7158
EI 1439-099X
J9 STRAHLENTHER ONKOL
JI Strahlenther. Onkol.
PD APR
PY 2009
VL 185
IS 4
BP 211
EP 221
DI 10.1007/s00066-009-1900-4
PG 11
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 434AO
UT WOS:000265247800001
PM 19370423
OA Green Published
DA 2022-11-30
ER

PT J
AU Schmidt, S
   Qin, XJ
   Schmidt, MA
   Martin, ER
   Hauser, ER
AF Schmidt, Silke
   Qin, Xuejun
   Schmidt, Michael A.
   Martin, Eden R.
   Hauser, Elizabeth R.
TI Interpreting analyses of continuous covariates in affected sibling pair
   linkage studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE simulation; ordered subset analysis; quantitative trait locus;
   gene-environment interaction; heterogeneity
ID GENE-ENVIRONMENT INTERACTION; ORDERED SUBSET ANALYSIS;
   QUANTITATIVE-TRAIT; GENOME SCAN; MODELS; PEDIGREES; LOCUS
AB Datasets collected for linkage analyses of complex human diseases often include a number of clinical or environmental covariates. In this study, we evaluated the performance of three linkage analysis methods when the relationship between continuous covariates and disease risk or linkage heterogeneity was modeled in three different ways: (1) The covariate distribution is determined by a quantitative trait locus (QTL), which contributes indirectly to the disease risk; (2) the covariate is not genetically determined, but influences the disease risk through statistical interaction with a disease susceptibility locus; (3) the covariate distribution differs in families linked or unlinked to a particular disease susceptibility locus. We analyzed simulated datasets with a regression-based QTL analysis, a nonparametric analysis of the binary affection status, and the ordered subset analysis (OSA). We found that a significant OSA result may be due to a gene that influences variability in the population distribution of a continuous disease risk factor. Conversely, a regression-based QTL analysis may detect the presence of gene-environment (G x E) interaction in a sample of primarily affected individuals. The contribution of unaffected siblings and the size of baseline lod scores may help distinguish between QTL and G x E models. As illustrated by a linkage study of multiplex families with age-related macular degeneration, our findings assist in the interpretation of analysis results in real datasets. They suggest that the side-by-side evaluation of OSA and QTL results may provide important information about the relationship of measured covariates with either disease risk or linkage heterogeneity.
C1 Duke Univ, Ctr Med, Ctr Human Genet, Durham, NC 27710 USA.
C3 Duke University
RP Schmidt, S (通讯作者)，Duke Univ, Ctr Med, Ctr Human Genet, Box 3445, Durham, NC 27710 USA.
EM silke.schmidt@duke.edu
OI Hauser, Elizabeth/0000-0003-0367-9189
FU NATIONAL EYE INSTITUTE [R03EY015216, R01EY012118] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON AGING [R01AG020135] Funding Source: NIH
   RePORTER; NEI NIH HHS [R03-EY015216, R01-EY12118] Funding Source:
   Medline; NIA NIH HHS [R01-AG20135] Funding Source: Medline; NIMH NIH HHS
   [R01-MH595228] Funding Source: Medline
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NR 25
TC 4
Z9 4
U1 0
U2 1
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 SEP
PY 2007
VL 31
IS 6
BP 541
EP 552
DI 10.1002/gepi.20227
PG 12
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 210SP
UT WOS:000249476200003
PM 17410529
DA 2022-11-30
ER

PT J
AU Chapman, JA
   Beckey, C
AF Chapman, Julie A.
   Beckey, Cherylyn
TI Pegaptanib: A novel approach to ocular neovascularization
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE age-related macular degeneration; ocular neovascularization; pegaptanib;
   vascular enclothelial growth factor
AB OBJECTIVE: To review pegaptanib, a novel aptamer for the treatment of age-related macular degeneration (AMD).
   DATA SOURCES: A literature search using MEDLINE (1980-January 2006) and the Cochrane Database of Systematic Reviews (1978-January 2006) for peer-reviewed, English-language publications was conducted. Abstracts from recent meetings, including the Association for Research in Vision and Ophthalmology and American Society of Retinal Specialists, were reviewed for relevant abstracts and poster presentations.
   STUDY SELECTION AND DATA EXTRACTION: Pharmacokinetic and pharmacology data were extracted from animal and human studies, and double-blind, randomized, controlled trials were included to describe the efficacy and adverse effects of pegaptanib.
   DATA SYNTHESIS: The efficacy of pegaptanib has been evaluated in 2 concurrent, prospective, randomized, double-blind trials. Patients with AMD were randomly assigned to receive placebo or pegaptanib intravitreous injection into 1 eye every 6 weeks for 48 weeks. The effectiveness of pegaptanib was realized as early as week 6 and continued through week 54. At week 54, 38% of patients receiving pegaptanib 0.3 mg were classified as legally blind versus 56% of those receiving the sham injection.
   CONCLUSIONS: Pegaptanib, a new inhibitor of ocular neovascularization, provides patients with an alternative to photodynamic therapy with verteporfin and offers a novel approach to future drug developments for AMD. Pegaptanib offers the advantage of not requiring photodynamic therapy in conjunction with drug delivery and may be a viable option for institutions where this service is not easily accessible. Results of clinical trials have shown that pegaptanib is effective in delaying progression of AMD.
C1 VA Med Ctr, Pharm Serv 119, W Palm Beach, FL 33410 USA.
   Nova SE Univ, Coll Pharm, W Palm Beach, FL USA.
C3 Nova Southeastern University
RP Chapman, JA (通讯作者)，VA Med Ctr, Pharm Serv 119, 7305 N Mil Trail, W Palm Beach, FL 33410 USA.
EM Julie.chapman3@med.va.gov
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NR 16
TC 34
Z9 37
U1 1
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1060-0280
EI 1542-6270
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUL-AUG
PY 2006
VL 40
IS 7-8
BP 1322
EP 1326
DI 10.1345/aph.1G604
PG 5
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 073BE
UT WOS:000239716500012
PM 16849623
DA 2022-11-30
ER

PT J
AU Trivino, A
   de Hoz, R
   Rojas, B
   Salazar, JJ
   Ramirez, AI
   Ramirez, JM
AF Trivino, A
   de Hoz, R
   Rojas, B
   Salazar, JJ
   Ramirez, AI
   Ramirez, JM
TI NPY and TH innervation in human choroidal whole-mounts
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Article
DE choroid; ganglion cells; innervation; tyroxine hydroxilase; NPY
ID NEUROPEPTIDE Y-LIKE; BLOOD-FLOW; GANGLION; NEURONS; NERVE; IRIS;
   IMMUNOREACTIVITY; AUTOREGULATION; PRESSURE; VESSELS
AB To determine the distribution of NPY and TH human choroidal innervation, choroidal whole-mounts were processed for indirect immunofluorescence. An antibody to a component of the neuronal cytoskeleton, neurofilament 200 kDa (NF-200) was used to identify neurons and axons. A double immunostaining was performed, antibodies against NF-200 being combined with antibodies against neuropeptide Y (NPY) and tyroxine hydroxylase (TH). Fibers containing both NPY and TH were distributed in three plexuses, one in the suprachoroid large-sized vessel layer, and two in the medium-sized vessel layer. Intrinsic choroidal neurons (ICNs) containing NPY and TH were observed in the suprachoroid. The TH(+) ICNs were located in the medium-sized vessel layer. Overall, NPY(+) and TH(+) ICNs were more frequent in the central temporal area, both in isolation and forming microganglia. We also detected small spindle elements intensely immunoreactive to TH(+) and distributed mainly in the suprachoroid from the equator to the periphery. In conclusion, the human choroid contains abundant NPY and TH nerve fibers related to chroroidal vascular structures; it further possesses NPY(+) and TH(+) ICNs which contribute to the choroidal self-regulation persisting after sympathetic denervation. Additionally, these ICNs may at least partially explain why the choroidal blood flow does not respond to the factors that influence systemic vascular control. The preferential location of these cells in the submacular area suggests that dysfunction or degeneration of these cells may be a factor in vascular pathologies found in ocular disease, such as diabetic macular edema or age-related macular degeneration.
C1 Univ Complutense Madrid, Fac Med, Inst Invest Offalmol Ramon Castrovejo, E-28040 Madrid, Spain.
C3 Complutense University of Madrid
RP Ramirez, JM (通讯作者)，Univ Complutense Madrid, Fac Med, Inst Invest Offalmol Ramon Castrovejo, E-28040 Madrid, Spain.
EM ramirezs@med.ucm.es
RI Alberto, Trivino/ABG-2416-2020; De Hoz, Rosa/ABF-9295-2020; ROJAS,
   BLANCA/V-8292-2017; Salazar, Juan J/L-6887-2014; Ramírez, José
   Manuel/L-6325-2014
OI De Hoz, Rosa/0000-0002-1581-087X; Salazar, Juan J/0000-0001-5480-5902;
   Ramírez, José Manuel/0000-0002-5145-5094
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NR 49
TC 11
Z9 13
U1 0
U2 2
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
EI 1699-5848
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD APR
PY 2005
VL 20
IS 2
BP 393
EP 402
PG 10
WC Cell Biology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Pathology
GA 912FX
UT WOS:000228064100007
PM 15736042
DA 2022-11-30
ER

PT J
AU Clemons, TE
   Kurinij, N
   Sperduto, RD
   Bressler, SB
   Kassoff, A
   Kassoff, J
   Buehler, J
   Eglow, M
   Silverman, S
   Mehu, M
   Kieval, S
   Kaufman, F
   Mairs, M
   Graig, B
   Quattrocchi, A
   Jones, D
   Locatelli, J
   Ruby, A
   Capone, A
   Garretson, B
   Hassan, T
   Trese, MT
   Williams, GA
   Regan, V
   Manatrey, P
   Streasick, P
   Szydlowski, L
   McIver, F
   Bridges, C
   Stanley, C
   Cumming, K
   Mitchell, B
   Holloway, J
   Lewis, B
   Zajechowski, M
   Margherio, RR
   Cox, MS
   Werner, JC
   Falk, R
   Siedlak, P
   Neubert, C
   Klein, ML
   Stout, JT
   Lauer, AK
   Beardsley, C
   Anderson, H
   Wallace, P
   Smith, G
   Howard, S
   Dreyer, RF
   Ma, C
   Chenoweth, RG
   Zilis, JD
   O'Malley, A
   Robertson, JE
   Wilson, DJ
   Johnson, M
   Rice, P
   Daniel, H
   Crider, H
   Parker, S
   Sherman, K
   Martin, DF
   Aaberg, TM
   Hubbard, GB
   Garcia, E
   Curtis, LT
   DeLeon, A
   Myles, B
   Capone, A
   Lambert, M
   Meredith, T
   Aaberg, TM
   Sternberg, P
   Saperstein, D
   Lim, JI
   Stribling, B
   Ju, B
   Armiger, D
   Gilman, J
   Jordan, D
   Strittman, S
   Swords, R
   Orth, DH
   Flood, TP
   Civantos, J
   deBustros, S
   Packo, KH
   Merrill, PT
   Cohen, JA
   Chow, D
   Figliulo, C
   Morrison, C
   Bryant, DA
   Doherty, D
   McVicker, M
   Drefcinski, T
   Seddon, JM
   Pinnolis, MK
   Sachdeva, M
   Taytsel, T
   Burton, I
   Walsh, D
   Callahan, C
   Evans, C
   Snow, KK
   Jones-Devonish, DA
   Crouse, VD
   Rosenberg, J
   Davis, N
   Dubois-Moran, J
   Chew, EY
   Csaky, K
   Ferris, FL
   Shimel, KH
   Woods, MA
   Cunningham, D
   Kuehl, EM
   Palmer, M
   Babilonia-Ayukawa, G
   Foster, GE
   Kim, YJ
   Kivitz, IJ
   Koutsandreas, D
   LaReau, A
   Mercer, RF
   Nashwinter, R
   Rowan, J
   Short, G
   McCarthy, SA
   Ciatto, PF
   Ayres, LM
   Goodman, L
   Lopez, P
   Perry, C
   Randalls, A
   Friberg, TR
   Eller, AW
   Gorin, MB
   Mack, B
   Curtin, DY
   Ostroska, PP
   Fijewski, E
   Alexander, J
   Nixon, S
   Paine, MK
   Corbin, PS
   Warnicki, J
   Bressler, SB
   Bressler, NM
   Cassel, G
   Finkelstein, D
   Goldberg, M
   Haller, JA
   Ratner, L
   Schachat, AP
   Sherman, SH
   Sunness, JS
   Schenning, S
   Sackett, C
   Cain, D
   Emmert, D
   Herring, M
   McDonald, J
   Falk, R
   Wheeler, S
   Mcmillan, M
   George, T
   Elman, MJ
   Ballinger, R
   Betancourt, A
   Herr, M
   Lammlein, J
   Raden, RZ
   Seff, R
   Shuman, M
   Starr, J
   Firestone, D
   Sloan, M
   Sotirakos, P
   Cain, T
   Mathews, T
   Glasser, D
   Hirsch, D
   Killingsworth, D
   Kohlhepp, P
   Ringrose, C
   Carrigan, A
   Chandra, SR
   Gottlieb, JL
   Ip, MS
   Klein, R
   Nork, M
   Stevens, TS
   Blodi, BA
   Altaweel, M
   Klein, BEK
   Davis, MD
   Olson, M
   Skoldberg, A
   Christianson, E
   Solerling, B
   Perry-Raymond, JR
   Burke, K
   Knutson, G
   Peterson, J
   Krolnik, D
   Harrison, R
   Somers, G
   Myers, FL
   Wallow, I
   Olsen, TW
   Bresnik, G
   De Venecia, G
   Perkins, T
   Walker, W
   Miller, JL
   Blatz, M
   Neider, M
   Wabers, HD
   Weber, G
   Amspaugh, B
   Buechner, J
   Myers, HEL
   Davis, MD
   Klein, BEK
   Klein, R
   Blodi, B
   Danis, R
   Hubbard, L
   Neider, M
   Vargo, P
   Wabers, HD
   Armstrong, J
   Benz, W
   Dohm, KL
   Fink, C
   Harding, T
   Hurtenbach, C
   Lang, K
   Reed, S
   Fisher, MR
   Gangnon, R
   Lee, LY
   Carr, A
   Baliker, J
   Kastorff, L
   Robinson, N
   Glander, KE
   Surfus, J
   Ansay, S
   Magli, YL
   Badal, D
   Craanen, S
   Elledge, J
   Esser, B
   Geithman, PL
   Miner, KD
   Reimers, J
   Webster, M
   Gai, CY
   King, W
   Osterby, K
   Onofrey, J
   Brickbauer, J
   Schleicher, RL
   Miller, DT
   Sowell, AL
   Gunter, EW
   Bowman, BA
   Lindblad, AS
   Milton, RC
   Clemons, TE
   Gensler, G
   Rankin, M
   Henning, A
   Entler, G
   McBee, W
   Watson, V
   Davis, C
   Stine, E
   Berlin, SH
   Thotapally, K
   Jackson, M
   Tomlin, K
   Pallas, S
   Scholl, PR
   Mengers, SA
   Ederer, F
   Anand, R
   Roberts, K
   Ferris, FL
   Sperduto, RD
   Kurinij, N
   Chew, EY
   SanGiovanni, JP
AF Clemons, TE
   Kurinij, N
   Sperduto, RD
   Bressler, SB
   Kassoff, A
   Kassoff, J
   Buehler, J
   Eglow, M
   Silverman, S
   Mehu, M
   Kieval, S
   Kaufman, F
   Mairs, M
   Graig, B
   Quattrocchi, A
   Jones, D
   Locatelli, J
   Ruby, A
   Capone, A
   Garretson, B
   Hassan, T
   Trese, MT
   Williams, GA
   Regan, V
   Manatrey, P
   Streasick, P
   Szydlowski, L
   McIver, F
   Bridges, C
   Stanley, C
   Cumming, K
   Mitchell, B
   Holloway, J
   Lewis, B
   Zajechowski, M
   Margherio, RR
   Cox, MS
   Werner, JC
   Falk, R
   Siedlak, P
   Neubert, C
   Klein, ML
   Stout, JT
   Lauer, AK
   Beardsley, C
   Anderson, H
   Wallace, P
   Smith, G
   Howard, S
   Dreyer, RF
   Ma, C
   Chenoweth, RG
   Zilis, JD
   O'Malley, A
   Robertson, JE
   Wilson, DJ
   Johnson, M
   Rice, P
   Daniel, H
   Crider, H
   Parker, S
   Sherman, K
   Martin, DF
   Aaberg, TM
   Hubbard, GB
   Garcia, E
   Curtis, LT
   DeLeon, A
   Myles, B
   Capone, A
   Lambert, M
   Meredith, T
   Aaberg, TM
   Sternberg, P
   Saperstein, D
   Lim, JI
   Stribling, B
   Ju, B
   Armiger, D
   Gilman, J
   Jordan, D
   Strittman, S
   Swords, R
   Orth, DH
   Flood, TP
   Civantos, J
   deBustros, S
   Packo, KH
   Merrill, PT
   Cohen, JA
   Chow, D
   Figliulo, C
   Morrison, C
   Bryant, DA
   Doherty, D
   McVicker, M
   Drefcinski, T
   Seddon, JM
   Pinnolis, MK
   Sachdeva, M
   Taytsel, T
   Burton, I
   Walsh, D
   Callahan, C
   Evans, C
   Snow, KK
   Jones-Devonish, DA
   Crouse, VD
   Rosenberg, J
   Davis, N
   Dubois-Moran, J
   Chew, EY
   Csaky, K
   Ferris, FL
   Shimel, KH
   Woods, MA
   Cunningham, D
   Kuehl, EM
   Palmer, M
   Babilonia-Ayukawa, G
   Foster, GE
   Kim, YJ
   Kivitz, IJ
   Koutsandreas, D
   LaReau, A
   Mercer, RF
   Nashwinter, R
   Rowan, J
   Short, G
   McCarthy, SA
   Ciatto, PF
   Ayres, LM
   Goodman, L
   Lopez, P
   Perry, C
   Randalls, A
   Friberg, TR
   Eller, AW
   Gorin, MB
   Mack, B
   Curtin, DY
   Ostroska, PP
   Fijewski, E
   Alexander, J
   Nixon, S
   Paine, MK
   Corbin, PS
   Warnicki, J
   Bressler, SB
   Bressler, NM
   Cassel, G
   Finkelstein, D
   Goldberg, M
   Haller, JA
   Ratner, L
   Schachat, AP
   Sherman, SH
   Sunness, JS
   Schenning, S
   Sackett, C
   Cain, D
   Emmert, D
   Herring, M
   McDonald, J
   Falk, R
   Wheeler, S
   Mcmillan, M
   George, T
   Elman, MJ
   Ballinger, R
   Betancourt, A
   Herr, M
   Lammlein, J
   Raden, RZ
   Seff, R
   Shuman, M
   Starr, J
   Firestone, D
   Sloan, M
   Sotirakos, P
   Cain, T
   Mathews, T
   Glasser, D
   Hirsch, D
   Killingsworth, D
   Kohlhepp, P
   Ringrose, C
   Carrigan, A
   Chandra, SR
   Gottlieb, JL
   Ip, MS
   Klein, R
   Nork, M
   Stevens, TS
   Blodi, BA
   Altaweel, M
   Klein, BEK
   Davis, MD
   Olson, M
   Skoldberg, A
   Christianson, E
   Solerling, B
   Perry-Raymond, JR
   Burke, K
   Knutson, G
   Peterson, J
   Krolnik, D
   Harrison, R
   Somers, G
   Myers, FL
   Wallow, I
   Olsen, TW
   Bresnik, G
   De Venecia, G
   Perkins, T
   Walker, W
   Miller, JL
   Blatz, M
   Neider, M
   Wabers, HD
   Weber, G
   Amspaugh, B
   Buechner, J
   Myers, HEL
   Davis, MD
   Klein, BEK
   Klein, R
   Blodi, B
   Danis, R
   Hubbard, L
   Neider, M
   Vargo, P
   Wabers, HD
   Armstrong, J
   Benz, W
   Dohm, KL
   Fink, C
   Harding, T
   Hurtenbach, C
   Lang, K
   Reed, S
   Fisher, MR
   Gangnon, R
   Lee, LY
   Carr, A
   Baliker, J
   Kastorff, L
   Robinson, N
   Glander, KE
   Surfus, J
   Ansay, S
   Magli, YL
   Badal, D
   Craanen, S
   Elledge, J
   Esser, B
   Geithman, PL
   Miner, KD
   Reimers, J
   Webster, M
   Gai, CY
   King, W
   Osterby, K
   Onofrey, J
   Brickbauer, J
   Schleicher, RL
   Miller, DT
   Sowell, AL
   Gunter, EW
   Bowman, BA
   Lindblad, AS
   Milton, RC
   Clemons, TE
   Gensler, G
   Rankin, M
   Henning, A
   Entler, G
   McBee, W
   Watson, V
   Davis, C
   Stine, E
   Berlin, SH
   Thotapally, K
   Jackson, M
   Tomlin, K
   Pallas, S
   Scholl, PR
   Mengers, SA
   Ederer, F
   Anand, R
   Roberts, K
   Ferris, FL
   Sperduto, RD
   Kurinij, N
   Chew, EY
   SanGiovanni, JP
CA AREDS Res Grp
TI Associations of mortality with ocular disorders and an intervention of
   high-dose antioxidants and zinc in the age-related eye disease study -
   AREDS report no. 13
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID CORONARY-HEART-DISEASE; DEPRESSIVE SYMPTOMS; ELDERLY-PATIENTS; LENS
   OPACITIES; CATARACT; SURVIVAL; HYPERTENSION; IMPAIRMENT; INPATIENT
AB Objective: To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS).
   Methods: Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models.
   Results: During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89).
   Conclusions: The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.
C1 EMMES Corp, Rockville, MD 20850 USA.
   Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   NEI, Bethesda, MD 20892 USA.
C3 Emmes Corporation; Johns Hopkins University; Johns Hopkins Medicine;
   National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Clemons, TE (通讯作者)，EMMES Corp, 401 N Washington St,Suite 700, Rockville, MD 20850 USA.
RI SanGiovanni, John Paul/A-7605-2008; SanGiovanni, John
   Paul/AAU-3895-2020; Foster, Glen/AAF-3696-2021
OI Glander, Kenneth/0000-0001-9563-4660
FU NATIONAL EYE INSTITUTE [Z01EY000394] Funding Source: NIH RePORTER; NEI
   NIH HHS [Z01 EY000394-03] Funding Source: Medline
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NR 31
TC 160
Z9 162
U1 0
U2 28
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 MAY
PY 2004
VL 122
IS 5
BP 716
EP 726
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 819TU
UT WOS:000221339400006
PM 15136320
DA 2022-11-30
ER

PT J
AU Pang, CP
   Lam, DSC
AF Pang, CP
   Lam, DSC
TI Differential occurrence of mutations causative of eye diseases in the
   Chinese population
SO HUMAN MUTATION
LA English
DT Review
DE eye diseases; mutation analysis; MYOC; RHO; RP1; RB1; APC; BIGH3; TGFBI;
   PAX6; Chinese
ID RETINAL-PIGMENT EPITHELIUM; HEREDITARY OPTIC NEUROPATHY; FAMILIAL
   ADENOMATOUS POLYPOSIS; AGE-RELATED MACULOPATHY; OPEN-ANGLE GLAUCOMA;
   MITOCHONDRIAL-DNA MUTATION; TRANSPORTER GENE ABCR; APOLIPOPROTEIN-E;
   CONGENITAL HYPERTROPHY; RETINITIS-PIGMENTOSA
AB Ethnic differences and geographic variations affect the frequencies and nature of human mutations. In the literature, descriptions of causative mutations of eye diseases in the Chinese population are few. In this paper we attempt to reveal molecular information on genetic eye diseases involving Chinese patients from published and unpublished works by us and other groups. Our studies on candidate genes of eye diseases in the Chinese population in Hong Kong include MYOC and TISR for primary open angle glaucoma, RHO and RP1 for retinitis pigmentosa, ABCA4 and APOE for age-related macular degeneration, RB1 for retinoblastoma, APC for familial adenomatous polyposis with congenital hypertrophy of retinal pigment epithelium, BIGH3/TGFBI for corneal dystrophies, PAX6 for aniridia and Reiger syndrome, CRYAA and CRYBB2 for cataracts, and mtDNA for Leber hereditary optic neuropathy. We have revealed novel mutations in most of these genes, and in RHO, RP1, RB1, BIGH3, and PAX6 we have reported mutations that contribute to better understanding of the functions and properties of the respective gene products. We showed absence of MYOC does not necessarily cause glaucoma. No disease causative mutations have been identified in MYOC or ABCA4. There are similarities in the patterns of sequence alterations and phenotype-genotype associations in comparison with other ethnic groups, while the MYOC, RB1, APC, and PAX6 genes have more Chinese specific sequence alterations. Establishment of a mutation database specific for the Chinese is essential for identification of genetic markers with diagnostic, prognostic, or pharmacological values. Hum Mutat 19:189-208, 2002. (C) 2002 Wiley-Liss, Inc.
C1 Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Chinese University of Hong Kong
RP Pang, CP (通讯作者)，Chinese Univ Hong Kong, Hong Kong Eye Hosp, 147K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
RI Pang, Chi P/I-5388-2014; Lam, Dennis/AAL-1211-2020
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NR 183
TC 29
Z9 34
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PY 2002
VL 19
IS 3
BP 189
EP 208
DI 10.1002/humu.10053
PG 20
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 527YL
UT WOS:000174215500001
PM 11857735
DA 2022-11-30
ER

PT J
AU Tang, DN
   Macniven, R
   Bender, N
   Jones, C
   Gopinath, B
AF Tang, Diana
   Macniven, Rona
   Bender, Nicholas
   Jones, Charlotte
   Gopinath, Bamini
TI Development, implementation and evaluation of the online Movement,
   Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE)
   program: The protocol for a pilot trial
SO PLOS ONE
LA English
DT Article
ID LONELINESS; RELIABILITY; DEPRESSION; VALIDITY; HEALTH; SCALE
AB Introduction
   People with age-related macular degeneration (AMD) are more likely to experience loneliness, have poorer diets and be less physically active than people without AMD. The online Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) program is a holistic evidence-based intervention aiming to support people with AMD by incorporating physical activity, social interaction and nutrition education components all delivered via a COVID-19-safe Zoom platform. This study will involve two phases: 1) a formative qualitative study with AMD patients to identify the barriers and facilitators to participating in the proposed MINGLE program; and 2) a 10-week pilot study to evaluate the feasibility, acceptability and preliminary efficacy of MINGLE.
   Methods and analysis
   Phase 1 involves AMD patients who will be recruited from an eye clinic in Western Sydney, Australia to participate in audio-recorded semi-structured interviews. Verbatim interview transcripts will be coded using the Capability, Opportunity, Motivation and Behaviour (COM-B) model and themes established. These themes will be used as a guide to specifically tailor the proposed MINGLE program to people with AMD. Phase 2 involves 52 AMD patients who will then be recruited from the same clinic to participate in the MINGLE program. Pre-post questionnaires will be administered to intervention participants to collect information on the following variables: demographics, socioeconomic status, vision function, loneliness, quality of life (including depression), falls risk, physical activity (level), and dietary intake. The acceptability and feasibility of the MINGLE program will also be evaluated using descriptive statistics.
C1 [Tang, Diana; Macniven, Rona; Gopinath, Bamini] Macquarie Univ, Macquarie Univ Hearing, N Ryde, NSW, Australia.
   [Macniven, Rona] UNSW Sydney, Sch Populat Hlth, Fac Med & Hlth, Kensington, NSW, Australia.
   [Bender, Nicholas] Middlesex Univ, London, England.
   [Jones, Charlotte] Univ British Columbia, Southern Med Program, Okanagan Campus, Kelowna, BC, Canada.
C3 Macquarie University; University of New South Wales Sydney; Middlesex
   University; University of British Columbia
RP Tang, DN (通讯作者)，Macquarie Univ, Macquarie Univ Hearing, N Ryde, NSW, Australia.
EM d.tang@mq.edu.au
OI Macniven, Rona/0000-0002-2967-7977; Tang, Diana/0000-0003-2007-9054
FU Macular Disease Foundation Australia Research Grant by the Macular
   Disease Foundation Australia
FX D.T, R.M, C.J, and B.G were awarded the Macular Disease Foundation
   Australia Research Grant by the Macular Disease Foundation Australia to
   conduct this research project. https://www.mdfoundation.com.au/The
   funders had and will have a role in the study design, data collection
   and analysis, decision to publish or preparation of the manuscript.
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NR 37
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 MAY 12
PY 2022
VL 17
IS 5
AR e0267581
DI 10.1371/journal.pone.0267581
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 5I1ZV
UT WOS:000868164600027
PM 35551541
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Maneu, V
   Lax, P
   De Diego, AMG
   Cuenca, N
   Garcia, AG
AF Maneu, Victoria
   Lax, Pedro
   De Diego, Antonio Miguel G.
   Cuenca, Nicolas
   Garcia, Antonio G.
TI Combined drug triads for synergic neuroprotection in retinal
   degeneration
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Review
DE Retina degeneration; Calcium dyshomeostasis; Oxidative stress;
   Neuroinflammation; Drug repositioning; Drug combinations;
   Neuroprotection
ID AMYOTROPHIC-LATERAL-SCLEROSIS; RANDOMIZED CLINICAL-TRIAL; GANGLION-CELL
   APOPTOSIS; D-ASPARTATE RECEPTOR; OXIDATIVE STRESS; DOUBLE-BLIND;
   RETINITIS-PIGMENTOSA; DIABETIC-RETINOPATHY; ALZHEIMERS-DISEASE;
   PHOTORECEPTOR APOPTOSIS
AB This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myriad pathogenic mechanisms have been implicated in these disorders, common signaling pathways leading to apoptotic cell death to all of them, and to all neurodegenerative diseases are (i) calcium dyshomeostasis/excitotoxicity; (ii) oxidative stress/mitochondrial dysfunction, and (iii) neuroinflammation/ P2X7 receptor activation. From a therapeutic point of view, it is relevant to consider the multitarget approach based on the use of combined medicines acting on complementary pathogenic mechanisms that has been highly successful in the treatment of chronic diseases such as cancer, AIDS, pain, hypertension, Parkinson's disease, cardiac failure, depression, or the epilepsies as the basic mechanisms of cell death do not differ between the different CNS degenerative diseases. We suggest the multi-target therapy approach could be more effective compared with single-drug treatments. Used at doses lower than standard, these triads may also be safer and more efficient. After the establishment of a proof-of-concept in animal models of retinal degeneration, potential successful preclinical trials of such combinations may eventually drive to test this concept in clinical trials in patients, first to evaluate the safety and efficacy of the drug combinations in humans and then their therapeutic advantages, if any, seeking the prevention and/or the delay of retina degeneration and blindness.
C1 [Maneu, Victoria] Univ Alicante, Dept Opt Farmacol & Anat, Ctra San Vicente del Raspeig S-N, San Vicente Del Raspeig 03690, Spain.
   [Lax, Pedro; Cuenca, Nicolas] Univ Alicante, Dept Fisiol Genet & Microbiol, Ctra San Vicente del Raspeig S-N, San Vicente Del Raspeig 03690, Spain.
   [De Diego, Antonio Miguel G.; Garcia, Antonio G.] Univ Autonoma Madrid, Fac Med, Inst Teofilo Hernando, Dept Farmacol, Madrid, Spain.
   [De Diego, Antonio Miguel G.; Garcia, Antonio G.] Univ Autonoma Madrid, Hosp Univ La Princesa, Inst Invest Sanitarias, Madrid, Spain.
   [Garcia, Antonio G.] Fdn Teofilo Hernando, Parque Cient Madrid, Madrid, Spain.
C3 Universitat d'Alacant; Universitat d'Alacant; Autonomous University of
   Madrid; Autonomous University of Madrid; Hospital de La Princesa
RP Maneu, V (通讯作者)，Univ Alicante, Dept Opt Farmacol & Anat, Ctra San Vicente del Raspeig S-N, San Vicente Del Raspeig 03690, Spain.; Garcia, AG (通讯作者)，Fdn Teofilo Hernando, Parque Cient Madrid, Madrid, Spain.
EM vmaneu@ua.es; agg@uam.es
RI Lax, Pedro/M-9074-2014; Maneu, Victoria/N-4147-2014
OI Lax, Pedro/0000-0001-6931-1008; Maneu, Victoria/0000-0002-5265-1361
FU EU [766124]; Fundacion Teofilo Hernando; Spanish Ministry of Science and
   Innovation [FEDER-PID2019106230RB-I00]; Generalitat Valenciana
   [IDIFEDER/2017/064, PROMETEO/2021/024]
FX We thank the support received from the EU Horizon 2020 Research and
   Innovation Program under Maria Slodowska-Curie, Grant/Award Number:
   Grant Agreement N. 766124; Fundacion Teofilo Hernando; Spanish Ministry
   of Science and Innovation (FEDER-PID2019106230RB-I00) and Generalitat
   Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024).
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NR 430
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI ISSY-LES-MOULINEAUX
PA 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE
SN 0753-3322
EI 1950-6007
J9 BIOMED PHARMACOTHER
JI Biomed. Pharmacother.
PD MAY
PY 2022
VL 149
AR 112911
DI 10.1016/j.biopha.2022.112911
PG 25
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 1D0YC
UT WOS:000793534600004
PM 36068774
OA gold
DA 2022-11-30
ER

PT J
AU Abud, MB
   Baranov, P
   Patel, S
   Hicks, CA
   Isaac, DLC
   Louzada, RN
   Dromel, P
   Singh, D
   Sinden, J
   Avila, MP
   Young, M
AF Abud, Murilo Batista
   Baranov, Petr
   Patel, Sara
   Hicks, Caroline A.
   Cruvinel Isaac, David Leonardo
   Louzada, Ricardo Noguera
   Dromel, Pierre
   Singh, Deepti
   Sinden, John
   Avila, Marcos P.
   Young, Michael
TI In vivo study to assess dosage of allogeneic pig retinal progenitor
   cells: Long-term survival, engraftment, differentiation and safety
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE retina regeneration; retinal progenitor cells; retinitis pigmentosa;
   stem cell
ID STEM-CELLS; TRANSGENIC PIGS; TRANSPLANTATION; REGENERATION; GENERATION;
   PROTEIN; SYSTEM; MODEL
AB Despite notable efforts and significant therapeutical advances, age-related macular degeneration remains the single most common reason for vision loss. Retinal progenitor cells (RPCs) are considered promising candidates for cellular treatments that repair and restore vision. In this allogenic study, the phenotypic profile of pig and human RPCs derived using similar manufacturing processes is compared. The long-term (12-week) survival of green fluorescent protein-pig retinal progenitor cells GFP-pRPC after subretinal transplantation into normal miniature pig (mini-pig) retina is investigated. Human eyes are both anatomically and physiologically mimicked by pig eyes, so the pig is an ideal model to show an equivalent way of delivering cells, immunological response and dosage. The phenotypic equivalency of porcine and clinically intended human RPCs was established. Thirty-nine mini-pigs are used in this study, and vehicle-injected eyes and non-injected eyes serve as controls. Six groups are given different dosages of pRPCs, and the cells are found to survive well in all groups. At 12 weeks, strong evidence of integration is indicated by the location of the grafted cells within the neuro-retina, extension of processes to the plexiform layers and expression of key retinal markers such as recoverin, rhodopsin and synaptophysin. No immunosuppression is used, and no immune response is found in any of the groups. No pRPC-related histopathology findings are reported in the major organs investigated. An initial dose of 250 k cells in 100 mu l of buffer is established as an appropriate initial dose for future human clinical trials.
C1 [Abud, Murilo Batista; Cruvinel Isaac, David Leonardo; Louzada, Ricardo Noguera; Avila, Marcos P.] Univ Fed Goias, Goiania, Go, Brazil.
   [Abud, Murilo Batista; Baranov, Petr; Singh, Deepti; Young, Michael] Harvard Med Sch, Schepens Eye Res Inst, Massachusetts Eye & Ear, Boston, MA 02115 USA.
   [Patel, Sara; Hicks, Caroline A.; Sinden, John] ReNeuron, Pencoed, Wales.
   [Louzada, Ricardo Noguera] Univ Fed Rio de Janeiro, Sch Med, Postgrad Program Surg Sci, Rio De Janeiro, Brazil.
   [Dromel, Pierre] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
C3 Universidade Federal de Goias; Harvard University; Harvard Medical
   School; Massachusetts Eye & Ear Infirmary; Schepens Eye Research
   Institute; Universidade Federal do Rio de Janeiro; Massachusetts
   Institute of Technology (MIT)
RP Abud, MB (通讯作者)，Rua Caracu 101,Damha 2, BR-38042230 Uberaba, MG, Brazil.
EM abudmurilo@gmail.com
RI Isaac, David Leonardo Cruvinel/ABI-5513-2020; Colombe Dromel,
   Pierre/AAL-6770-2020
OI Isaac, David Leonardo Cruvinel/0000-0002-0821-2660; Colombe Dromel,
   Pierre/0000-0002-8426-4489
FU Foundation Fighting Blindness (FFB)
FX This work was supported by Foundation Fighting Blindness (FFB)
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NR 35
TC 0
Z9 0
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD JUN
PY 2022
VL 26
IS 11
BP 3254
EP 3268
DI 10.1111/jcmm.17332
EA APR 2022
PG 15
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA 1X6SL
UT WOS:000788185500001
PM 35481949
OA Green Published
DA 2022-11-30
ER

PT J
AU Liu, YR
   Bell, BA
   Song, Y
   Kim, HJ
   Sterling, JK
   Kim, BJ
   Poli, M
   Guo, M
   Zhang, K
   Rao, A
   Sparrow, JR
   Su, GF
   Dunaief, JL
AF Liu, Yingrui
   Bell, Brent A.
   Song, Ying
   Kim, Hye J.
   Sterling, Jacob K.
   Kim, Benjamin J.
   Poli, Maura
   Guo, Michelle
   Zhang, Kevin
   Rao, Aditya
   Sparrow, Janet R.
   Su, Guanfang
   Dunaief, Joshua L.
TI Intraocular iron injection induces oxidative stress followed by elements
   of geographic atrophy and sympathetic ophthalmia
SO AGING CELL
LA English
DT Article
DE iron; lipid peroxidation; lipofuscin; oxidative stress; photoreceptor
   cells
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; POTENTIAL FACTOR; LIPOFUSCIN; ACCUMULATION; OVERLOAD;
   DISEASE; MICE; FEATURES
AB Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.
C1 [Liu, Yingrui; Su, Guanfang] Second Hosp Jilin Univ, Dept Ophthalmol, Changchun, Peoples R China.
   [Liu, Yingrui; Bell, Brent A.; Song, Ying; Sterling, Jacob K.; Guo, Michelle; Zhang, Kevin; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.
   [Kim, Hye J.; Sparrow, Janet R.] Columbia Univ, Harkness Eye Inst, Med Ctr, Dept Ophthalmol, New York, NY 10027 USA.
   [Kim, Benjamin J.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Poli, Maura] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy.
   [Rao, Aditya] Univ Penn, Dept Mol Life Sci, Philadelphia, PA 19104 USA.
C3 Jilin University; University of Pennsylvania; Pennsylvania Medicine;
   Columbia University; University of Pennsylvania; Pennsylvania Medicine;
   University of Brescia; University of Pennsylvania
RP Dunaief, JL (通讯作者)，Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@pennmedicine.upenn.edu
OI Su, Guanfang/0000-0003-4820-6537; Guo, Michelle/0000-0003-4633-3997
FU FM Kirby Foundation; Paul and Evanina Bell Mackall Foundation Trust;
   Research to Prevent Blindness; National Institutes of Health [EY015240,
   EY028916, EY028131, S10OD026860]
FX FM Kirby Foundation; Paul and Evanina Bell Mackall Foundation Trust;
   Research to Prevent Blindness; National Institutes of Health,
   Grant/Award Number: EY015240, EY028916, EY028131 and S10OD026860
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NR 43
TC 7
Z9 7
U1 2
U2 14
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 NOV
PY 2021
VL 20
IS 11
AR e13490
DI 10.1111/acel.13490
EA OCT 2021
PG 16
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA WW5IH
UT WOS:000705035100001
PM 34626070
OA Green Published
DA 2022-11-30
ER

PT J
AU Balaskas, K
   Amoaku, WM
   Cudrnak, T
   Downey, LM
   Groppe, M
   Mahmood, S
   Mehta, H
   Mohamed, Q
   Mushtaq, B
   Severn, P
   Vardarinos, A
   Yang, YC
AF Balaskas, Konstantinos
   Amoaku, Winfried M.
   Cudrnak, Tomas
   Downey, Louise M.
   Groppe, Markus
   Mahmood, Sajjad
   Mehta, Hemal
   Mohamed, Quresh
   Mushtaq, Bushra
   Severn, Philip
   Vardarinos, Athanasios
   Yang, Yit C.
TI Importance of Anatomical Efficacy for Disease Control in Neovascular
   AMD: An Expert Opinion
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Review
DE Anatomical efficacy; Disease control fluid; OCT; Stability
AB Background Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control. Methods An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management of nAMD. Results The ROG has developed recommendations for achieving disease control through a zero-tolerance approach to the presence of fluid in nAMD as patients who avoid fluctuations in fluid at the macula have better visual outcomes. Recommendations cover five key areas: service protocol, training, regimen, multidisciplinary teams and engagement. This approach facilitates more standardised protocol-based treatment strategies. Conclusions Targeting a fluid-free macula and aiming for disease control are essential to improve outcomes. As new therapies and technologies become available, drying the macula and maintaining disease control will become even more achievable. The outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes.
C1 [Balaskas, Konstantinos] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Balaskas, Konstantinos] UCL, Inst Ophthalmol, London, England.
   [Amoaku, Winfried M.] Univ Nottingham, Acad Ophthalmol, Div Clin Neurosci, Nottingham, England.
   [Cudrnak, Tomas] Univ Hosp Plymouth NHS Trust, Royal Eye Infirm, Plymouth, Devon, England.
   [Downey, Louise M.] Hull Univ Teaching Hosp, Kingston Upon Hull, N Humberside, England.
   [Groppe, Markus] Buckinghamshire Healthcare NHS Trust, Ophthalmol Stoke Mandeville, Aylesbury, Bucks, England.
   [Mahmood, Sajjad] Univ Manchester, Manchester Univ NHS Fdn Trust, Manchester Royal Eye Hosp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
   [Mehta, Hemal] Royal Free London NHS Fdn Trust, London, England.
   [Mohamed, Quresh] Gloucestershire Hosp NHS Fdn Trust, Cheltenham Gen Hosp, Gloucestershire Eye Unit, Gloucester, England.
   [Mushtaq, Bushra] Sandwell & West Birmingham NHS Trust, Birmingham & Midland Eye Ctr, Birmingham, W Midlands, England.
   [Severn, Philip] South Tees Hosp NHS Fdn Trust, Middlesbrough, Cleveland, England.
   [Vardarinos, Athanasios] West Suffolk NHS Fdn Trust, West Suffolk Hosp, Eye Treatment Ctr, Bury St Edmunds, Suffolk, England.
   [Yang, Yit C.] Royal Wolverhampton NHS Trust, Wolverhampton Eye Infirm, Wolverhampton, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   University of Nottingham; Manchester Royal Eye Hospital; University of
   Manchester; University of London; University College London; Royal Free
   London NHS Foundation Trust; Gloucestershire Hospitals NHS Foundation
   Trust; Cheltenham General Hospital
RP Balaskas, K (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.; Balaskas, K (通讯作者)，UCL, Inst Ophthalmol, London, England.
EM k.balaskas@nhs.net
RI Balaskas, Konstantinos/ABD-5979-2020
OI Balaskas, Konstantinos/0000-0002-7690-6277; Amoaku,
   Winfried/0000-0001-5028-7984; Groppe, Markus/0000-0003-1963-3484
FU Novartis Pharmaceuticals UK Ltd.
FX This article and the journal's Rapid Service Fee were sponsored by
   Novartis Pharmaceuticals UK Ltd. group which developed it were sponsored
   by Novartis Pharmaceuticals UK Ltd. All authors received honoraria,
   contributed to the development of the manuscript, and retained final
   control of the content and editorial decisions.
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NR 48
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-8245
EI 2193-6528
J9 OPHTHALMOL THER
JI OPHTHALMOL. THER.
PD JUN
PY 2021
VL 10
IS 2
BP 231
EP 243
DI 10.1007/s40123-021-00342-5
EA APR 2021
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RU0LP
UT WOS:000638829600001
PM 33840064
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, YJ
   Fang, QY
   Zhang, CM
   Chen, YJ
   Gou, T
   Cai, QL
   Yin, HY
   Gao, YX
   Feng, YL
   Qiu, S
   Zhang, M
   Cen, XB
   Zhang, H
   Chen, DN
AF Wang, Yujiao
   Fang, Qiyao
   Zhang, Chaomao
   Chen, Yongjiang
   Gou, Tao
   Cai, Qinglin
   Yin, Hongyu
   Gao, Yunxia
   Feng, Yuliang
   Qiu, Shuang
   Zhang, Ming
   Cen, Xiaobo
   Zhang, Hui
   Chen, Danian
TI Multimodal imaging and electroretinography highlights the role of VEGF
   in the laser-induced subretinal fibrosis of monkey
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Rhesus macaques; Age-related macular degeneration; Subretinal fibrosis;
   Laser photocoagulation; VEGF; SHRM
AB Age-related macular degeneration (AMD) is a leading cause of blindness. Laser-induced nonhuman primate choroidal neovascularization (CNV) is a widely used animal model of neovascular AMD. Subretinal fibrosis (SFb) is the major limiting factor of effective anti-VEGF therapy for neovascular AMD, yet SFb has never been systematically analyzed in the primate CNV model and if VEGF directly affect SFb is unknown. We recruited a large cohort of rhesus macaques to study the occurrence, multimodal imaging and electroretinography (ERG) features, and related cytokines of SFb. Here we show that among 33 rhesus macaques, 88% CNV eyes developed SFb. Spectral domain optical coherence tomography (SD-OCT) identified four types of subretinal hyper-reflective material (SHRM) of SFb in primate. Multimodal imaging is reliable for monitoring SFb and matches the histological results well. Reduced amplitude of oscillatory potentials correlates with the thinning of inner retina layers and is a possible SFb indicator. Iba1(+) microglia/macrophage cells infiltrated in the fibrotic lesions, and aqueous cytokine analysis identified four fibrosis-related factors (GM-CSF, IL-10, TGF beta 2 and VEGF). Unexpectedly, we found sustained expression of VEGF may be an important inducer of SFb, and anti-VEGF therapy actually partially suppresses SFb. Taken together, our data suggest the laser-induced primate SFb model, coupled with multimodal imaging and ERG recording, is a useful system to dissect the pathogenesis and explore the rationale of treatment for SFb; and combined therapy with anti-VEGF and anti-fibrosis agents is necessary for AMD treatment.
C1 [Wang, Yujiao; Gao, Yunxia; Feng, Yuliang; Zhang, Ming; Chen, Danian] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Res Lab Ophthalmol & Vis Sci,Dept Ophthalmol, Chengdu 610041, Peoples R China.
   [Wang, Yujiao; Fang, Qiyao; Zhang, Chaomao; Gou, Tao; Cai, Qinglin; Yin, Hongyu; Qiu, Shuang; Cen, Xiaobo; Zhang, Hui] Sichuan Univ, West China Hosp, Natl Chengdu Ctr Safety Evaluat Drugs, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.
   [Wang, Yujiao; Fang, Qiyao; Zhang, Chaomao; Gou, Tao; Cai, Qinglin; Yin, Hongyu; Qiu, Shuang; Cen, Xiaobo; Zhang, Hui] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China.
   [Chen, Yongjiang] Univ Waterloo, Sch Optometry & Vis Sci, 200 Univ Ave W, Waterloo, ON N2L 3G1, Canada.
C3 Sichuan University; Sichuan University; Sichuan University; University
   of Waterloo
RP Cen, XB; Zhang, H (通讯作者)，Sichuan Univ, West China Hosp, Natl Chengdu Ctr Safety Evaluat Drugs, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.; Cen, XB (通讯作者)，Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China.; Chen, DN (通讯作者)，Sichuan Univ, West China Hosp, Res Lab Ophthalmol & Vis Sci, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.
EM xbcen@scu.edu.cn; hz.lund@gmail.com; danianchen2006@qq.com
RI Chen, Danian/GXV-7996-2022
OI Chen, Danian/0000-0002-6916-2978
FU National Program of High Technology Research and Development of China
   [2012AA020702]; National Natural Science Foundation of China [81870665];
   Science and Technology Program of Sichuan Province [21ZDYF1739]; West
   China Hospital of Sichuan University [2019HXBH051]
FX This work was supported by the National Program of High Technology
   Research and Development of China (2012AA020702), the National Natural
   Science Foundation of China (81870665), the Science and Technology
   Program of Sichuan Province (Mechanism and application research of VEGF
   in rhesus monkey model of subretinal fibrosis, 21ZDYF1739) and West
   China Hospital of Sichuan University (2019HXBH051). The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 55
TC 1
Z9 1
U1 1
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 FEB
PY 2021
VL 203
AR 108417
DI 10.1016/j.exer.2020.108417
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QG8GX
UT WOS:000617820900002
PM 33358768
DA 2022-11-30
ER

PT J
AU Liu, YM
   Feng, ML
   Cai, JJ
   Li, SF
   Dai, XF
   Shan, G
   Wu, SZ
AF Liu, Yimei
   Feng, Meiling
   Cai, Jingjing
   Li, Shifeng
   Dai, Xufeng
   Shan, Ge
   Wu, Shengzhou
TI Repurposing bortezomib for choroidal neovascularization treatment via
   antagonizing VEGF-A and PDGF-D mediated signaling
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Choroidal neovascularization; Age-related macular degeneration; Vascular
   endothelial growth factor; Platelet-derived growth factor; Proteasome
   inhibitor; Fluorescein fundus angiography
AB Neovascular age-related macular degeneration (neoAMD) is the leading cause of blindness in AMD and manifests as choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) therapies are the mainstay treatments but with limited efficacy and cause detrimental effects on the retina after long-term application. These disadvantages warrant alternative strategy. Herein, we examined the effect on CNV by intravitreal injection of bortezomib, a reversible pmteasome inhibitor, and further dissected the mechanism. Krypton red Laser was used to create CNV model in mice. The angiogenesis volume was assessed in choroidal flat-mount with isolectin GS-IB4 labeling and the leakage was examined with fluorescein fundus angiography. Injection of Bor(sub) inhibited angiogenesis in the CNV model which was dose-dependent; the injection significantly inhibited leakage as well. Furthermore, Bor(sub) injection reduced the contents of VEGF-A, macrophage chemotactic factor 1 (MCP-1), and platelet-derived growth factor (PDGF)-D but not PDGF-B, examined by enzyme-linked immunosorbent assay, in choroid/retinal pigment epithelium (RPE) tissue. These injections also reduced phospho-VEGFR-2 and phospho-PDGFRB in choroid/RPE tissue examined by immunoblotting. Moreover, Bor(sub) inhibited the recruitment of mural cells or macrophages to laser-injured spots. Injection of Bor(sub) indicated negative effect on scotopic and photopic responses recorded by electroretinogram. Altogether, intravitreal injection of Bor(sub) significantly reduced CNV by antagonizing VEGF-A/Flk-1 and PDGF-D/PDGER beta pathways without impacting electroretinography parameters. Thus, Bor(sub) may offer an invaluable therapy for the prevention and treatment of neoAMD.
C1 [Liu, Yimei; Feng, Meiling; Cai, Jingjing; Dai, Xufeng; Wu, Shengzhou] Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou, Peoples R China.
   [Liu, Yimei; Feng, Meiling; Cai, Jingjing; Dai, Xufeng; Wu, Shengzhou] Wenzhou Med Univ, Eye Hosp, Wenzhou, Peoples R China.
   [Liu, Yimei; Feng, Meiling; Cai, Jingjing; Dai, Xufeng; Wu, Shengzhou] State Key Lab Optometry Ophthalmol & Visual Sci, 270 Xueyuan Rd, Wenzhou 325003, Zhejiang, Peoples R China.
   [Li, Shifeng] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Lab Mol Cell Biol, Shanghai 200031, Peoples R China.
   [Shan, Ge] Univ Sci & Technol China, CAS Ctr Excellence Mol Cell Sci, Sch Life Sci, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University; Chinese Academy
   of Sciences; Shanghai Institutes for Biological Sciences, CAS; Chinese
   Academy of Sciences; University of Science & Technology of China, CAS
RP Wu, SZ (通讯作者)，Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou, Peoples R China.
EM wszlab@mail.eye.ac.cn
RI wu, shengzhou/ABG-8579-2021
OI wu, shengzhou/0000-0003-1154-2369
FU Chinese Academy of Science; Natural Science Foundation of Zhejiang
   Province, China [LY18H120003]
FX The authors sincerely appreciate the help from Pro. Yiping Li and Ms.
   Zhili Wu from Shanghai Institute of Biochemistry and Cell Biology
   (SIBCB) , Chinese Academy of Science. The project was sponsored by
   Natural Science Foundation of Zhejiang Province, China (grant ID:
   LY18H120003) .
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NR 61
TC 1
Z9 1
U1 1
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 MAR
PY 2021
VL 204
AR 108446
DI 10.1016/j.exer.2021.108446
EA JAN 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RC8HC
UT WOS:000633034000002
PM 33476605
DA 2022-11-30
ER

PT J
AU Jang, KH
   Hwang, Y
   Kim, E
AF Jang, Ki-Hong
   Hwang, Yeseong
   Kim, Eunhee
TI PARP1 Impedes SIRT1-Mediated Autophagy during Degeneration of the
   Retinal Pigment Epithelium under Oxidative Stress
SO MOLECULES AND CELLS
LA English
DT Article
DE autophagy; dry AMD; oxidative stress; PARP1; SIRT1
ID CELL-DEATH; NUCLEAR LC3; SIRT1; POLY(ADP-RIBOSE); MECHANISMS; PROTEIN;
   DEACETYLATION; ACTIVATION; PARTHANATOS; METABOLISM
AB The molecular mechanism underlying autophagy impairment in the retinal pigment epithelium (RPE) in dry age-related macular degeneration (AMD) is not yet clear. Based on the causative role of poly(ADP-ribose) polymerase 1 (PARP1) in RPE necrosis, this study examined whether PARP1 is involved in the autophagy impairment observed during dry AMD pathogenesis. We found that autophagy was downregulated following H2O2-induced PARP1 activation in ARPE-19 cells and olaparib, PARP1 inhibitor, preserved the autophagy process upon H2O2 exposure in ARPE-19 cells. These findings imply that PARP1 participates in the autophagy impairment upon oxidative stress in ARPE-19 cells. Furthermore, PARP1 inhibited autolysosome formation but did not affect autophagosome formation in H2O2-exposed ARPE-19 cells, demonstrating that PARP1 is responsible for impairment of late-stage autophagy in particular. Because PARP1 consumes NAD+ while exerting its catalytic activity, we investigated whether PARP1 impedes autophagy mediated by sirtuin1 (SIRT1), which uses NAD+ as its cofactor. A NAD(+) precursor restored autophagy and protected mitochondria in ARPE-19 cells by preserving SIRT1 activity upon H2O2. Moreover, olaparib failed to restore autophagy in SIRT1-depleted ARPE-19 cells, indicating that PARP1 inhibits autophagy through SIRT1 inhibition. Next, we further examined whether PARP1-induced autophagy impairment occurs in the retinas of dry AMD model mice. Histological analyses revealed that olaparib treatment protected mouse retinas against sodium iodate (SI) insult, but not in retinas cotreated with SI and wortmannin, an autophagy inhibitor. Collectively, our data demonstrate that PARP1-dependent inhibition of SIRT1 activity impedes autophagic survival of RPE cells, leading to retinal degeneration during dry AMD pathogenesis.
C1 [Jang, Ki-Hong; Hwang, Yeseong; Kim, Eunhee] Chungnam Natl Univ, Dept Biol Sci, Daejeon, South Korea.
C3 Chungnam National University
RP Kim, E (通讯作者)，Chungnam Natl Univ, Dept Biol Sci, Daejeon, South Korea.
EM eunhee@cnu.ac.kr
RI Jang, Ki-Hong/AAR-2399-2021
FU Korea Health Technology R&D Project through the Korea Health Industry
   Development Institute (KHIDI) - Ministry of Health & Welfare, Republic
   of Korea [HI16C0947]
FX This research was supported by a grant of the Korea Health Technology
   R&D Project through the Korea Health Industry Development Institute
   (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea
   (grant No. HI16C0947).
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PU KOREAN SOC MOLECULAR & CELLULAR  BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
EI 0219-1032
J9 MOL CELLS
JI Mol. Cells
PD JUL
PY 2020
VL 43
IS 7
BP 632
EP 644
DI 10.14348/molcells.2020.0078
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA MV1QM
UT WOS:000556137800006
PM 32732457
DA 2022-11-30
ER

PT J
AU Zhang, LW
   Zeng, HL
   Wang, JH
   Zhao, H
   Zhang, BX
   Zou, JL
   Yoshida, S
   Zhou, YD
AF Zhang, Liwei
   Zeng, Huilan
   Wang, Jiang-Hui
   Zhao, Han
   Zhang, Boxiang
   Zou, Jingling
   Yoshida, Shigeo
   Zhou, Yedi
TI Altered Long Non-coding RNAs Involved in Immunological Regulation and
   Associated with Choroidal Neovascularization in Mice
SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
LA English
DT Article
DE long non-coding RNA; choroidal neovascularization; angiogenesis;
   age-related macular degeneration; immunological regulation
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; TACHYPHYLAXIS;
   ANGIOGENESIS; MACROPHAGES; INHIBITION; RECEPTOR; MODEL
AB Choroidal neovascularization (CNV) is a severe complication of the wet form of age-related macular degeneration (AMD). Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of different ocular neovascular diseases. To identify the function and therapeutic potential of lncRNAs in CNV, we assessed lncRNAs and mRNA expression profile in a mouse model of laser-induced CNV by microarray analysis. The results of altered lncRNAs were validated by qRT-PCR. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed to clarify the potential biological functions and signaling pathways with which altered genes are most closely related. Moreover, to identify the interaction of lncRNAs and mRNAs, we constructed a coding-non-coding gene co-expression (CNC) network. By microarray analysis, we identified 716 altered lncRNAs and 821 altered mRNAs in CNV mice compared to controls. A CNC network profile based on 7 validated altered lncRNAs (uc009ewo.1, AK148935, uc029sdr.1, ENSMUST00000132340, AK030988, uc007mds.1, ENSMUST00000180519) as well as 282 interacted and altered mRNAs, and were connected by 713 edges. GO and KEGG analyses suggested that altered mRNAs, as well as those lncRNA-interacted mRNAs were enriched in immune system process and chemokine signaling pathway. Thus, lncRNAs are significantly altered in this mouse model of CNV and are involved in immunological regulation, suggesting that lncRNAs may play a critical role in the pathogenesis of CNV. Thus, dysregulated lncRNAs and their target genes might be promising therapeutic targets to suppress CNV in AMD.
C1 [Zhang, Liwei; Zeng, Huilan; Zhao, Han; Zhang, Boxiang; Zou, Jingling; Zhou, Yedi] Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha 410011, Hunan, Peoples R China.
   [Zhang, Liwei; Zeng, Huilan; Zhao, Han; Zhang, Boxiang; Zou, Jingling; Zhou, Yedi] Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China.
   [Wang, Jiang-Hui] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
   [Wang, Jiang-Hui] Univ Melbourne, Dept Surg, Ophthalmol, East Melbourne, Vic, Australia.
   [Yoshida, Shigeo] Kurume Univ, Sch Med, Dept Ophthalmol, Kurume, Fukuoka, Japan.
C3 Central South University; Centre for Eye Research Australia; Royal
   Victorian Eye & Ear Hospital; University of Melbourne; Kurume University
RP Zhou, YD (通讯作者)，Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha 410011, Hunan, Peoples R China.
EM zhouyedi@csu.edu.cn
OI Zhou, Yedi/0000-0002-8948-1108
FU National Natural Science Foundation of China [81500746, 81800855];
   Natural Science Foundation of Hunan Province [2018JJ3765]; Department of
   Science and Technology, Hunan [2015TP2007]
FX This work was supported by National Natural Science Foundation of China
   (No. 81500746 and 81800855), Natural Science Foundation of Hunan
   Province (No. 2018JJ3765), and Department of Science and Technology,
   Hunan (No.2015TP2007). The authors declare that they have no competing
   interests.
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U2 5
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1449-1907
J9 INT J MED SCI
JI Int. J. Med. Sci.
PY 2020
VL 17
IS 3
BP 292
EP 301
DI 10.7150/ijms.37804
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA KN5BC
UT WOS:000514851300002
PM 32132863
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lim, RR
   Hainsworth, DP
   Mohan, RR
   Chaurasia, SS
AF Lim, Rayne R.
   Hainsworth, Dean P.
   Mohan, Rajiv R.
   Chaurasia, Shyam S.
TI Characterization of a functionally active primary microglial cell
   culture from the pig retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retina; Inflammation; Microglia; Primary cell culture; Pig; Innate
   immune system; Diabetic retinopathy
ID DIABETIC-RETINOPATHY; ACTIVATION; TOPOGRAPHY; EXPRESSION; PHENOTYPE;
   MARKERS; CSF-1
AB Retinal inflammation is an integral component of many retinal diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). Inflammation is commonly initiated and perpetuated by myeloid-derived immune cells. In the retina, microglial cells are resident macrophages with myeloid origins, which acts as the first responders involved in the innate immune system. To understand the disease pathogenesis, the use of isolated retinal cell culture model is vital for the examination of multiple cellular responses to injury or trauma. The pig retina resembles human retina in terms of tissue architecture, vasculature, and topography. Additionally, it is a better model than the rodent retina because of the presence of the pseudomacula. In the present study, we sought to establish and characterize pig retinal primary microglial cell (pMicroglia) culture. We used pig eyes from the local abattoir and optimized pMicroglia cultures using multiple cell culture conditions and methods. The best results were obtained by seeding cells in DMEM-high glucose media for 18 days followed by shaking of the culture plate. The resulting pMicroglia were characterized by cellular morphology, phenotype, and immunostaining with Iba-1, CD68, P2Y12, CD163, CD14, and Isolectin GS-034. Generated pMicroglia were found functionally active in phagocytosis assay and responsive to lipopolysaccharides (LPS) in dose-dependent production of IL-1 beta. Furthermore, they showed increased secretion of pro inflammatory cytokines with LPS treatment. Thus, we report a novel and reproducible method for the isolation of primary microglial cells from pig eyes, which may be useful for studying retinal diseases.
C1 [Lim, Rayne R.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Univ Missouri, Dept Vet Med & Surg, Ocular Immunol & Angiogenesis Lab, Columbia, MO 65211 USA.
   [Lim, Rayne R.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA.
   [Lim, Rayne R.; Mohan, Rajiv R.; Chaurasia, Shyam S.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA.
   [Hainsworth, Dean P.; Mohan, Rajiv R.] Univ Missouri, Mason Eye Inst, Columbia, MO 65211 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
RP Chaurasia, SS (通讯作者)，Univ Missouri, Dept Vet Med & Surg, One Hlth One Med Ophthalmol & Vis Sci Program, Ophthalmol & Vis Sci,Ocular Immunol & Angiogenesi, Columbia, MO 65211 USA.
EM chaurasias@missouri.edu
RI Chaurasia, Shyam/AAB-4709-2019
OI Chaurasia, Shyam/0000-0001-8725-676X
FU Department of Veterinary Medicine and Surgery, University of Missouri;
   Ruth M. Kraeuchi Missouri Endowed Chair Ophthalmology Fund from the
   University of Missouri; NATIONAL EYE INSTITUTE [R01EY029795] Funding
   Source: NIH RePORTER
FX Supported by a start-up grant from Department of Veterinary Medicine and
   Surgery, University of Missouri to SSC, and the Ruth M. Kraeuchi
   Missouri Endowed Chair Ophthalmology Fund from the University of
   Missouri to RRM. 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 8
Z9 8
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 AUG
PY 2019
VL 185
AR 107670
DI 10.1016/j.exer.2019.05.010
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IT8NU
UT WOS:000483140000030
PM 31103710
DA 2022-11-30
ER

PT J
AU Karmakar, S
   Biswas, S
   Das, KP
   Tripathy, U
AF Karmakar, Srabani
   Biswas, Shrutidhara
   Das, Kali P.
   Tripathy, Umakanta
TI Surface plasmon resonance study of the interaction of 4,4
   '-dianilino-1,1 '-binaphthyl-5,5 '-disulfonic acid dipotassium salt
   (bis-ANS) and adenosine triphosphate (ATP) with oligomeric recombinant
   human lens alpha A-crystallin
SO CANADIAN JOURNAL OF CHEMISTRY
LA English
DT Article
DE alpha A-crystallin; ATP; bis-ANS; surface plasmon resonance (SPR)
ID CHAPERONE-LIKE ACTIVITY; HEAT-SHOCK-PROTEIN; B-CRYSTALLIN;
   1,1'-BI(4-ANILINO)NAPHTHALENE-5,5'-DISULFONIC ACID; STRUCTURAL
   PERTURBATION; NONLENTICULAR TISSUES; IDENTIFICATION; STABILITY;
   HYDROPHOBICITY; EXPRESSION
AB alpha-Crystallin, an abundant mammalian lens protein made up of two subunits (alpha A- and alpha B-crystallin), is involved in the maintenance of the optimal refractive index in the lens. The protein is implicated in the pathophysiology of a large number of retinal diseases including cataract, age-related macular degeneration, diabetic retinopathy, and uveitis. alpha-Crystallin belongs to the small heat shock protein (sHSP) family, forms large oligomeric structures, and functions as a molecular chaperone appearing very early during embryonic development. To gain mechanistic insight into the structural and functional role of alpha-crystallin and its alterations in various retinal diseases, it is important to study the interaction chemistry with its known partners. The hydrophobic sites in alpha-crystallin have been studied extensively using environmentally sensitive fluorescent probes such as 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt (bis-ANS) that interacts with both subunits of alpha-cystallin in 1:1 stoichiometry at 37 degrees C and diminishes the chaperone-like activity of the protein. Furthermore, it has been shown that ATP plays a crucial role in the association of alpha-crystallin with substrate proteins. We use surface plasmon resonance (SPR) to monitor the interactions of immobilized oligomeric recombinant alpha A subunit of human alpha-crystallin protein with bis-ANS and ATP. We assess the thermodynamic parameters and kinetics of such interactions at various temperatures. Our results indicate that bis-ANS binds to alpha A-crystallin with higher affinity when compared with ATP, although both alpha A-crystallin and alpha B-crystallin display fast interaction kinetics.
C1 [Karmakar, Srabani] Techno India Univ, Dept Biotechnol, EM 4-1,Sect 5, Kolkata 700091, India.
   [Biswas, Shrutidhara] Indian Inst Technol, Dept Biosci & Bioengn, Gauhati 781029, India.
   [Das, Kali P.] Bose Inst, Dept Chem, Prot Chem Lab, 93-1 APC Rd, Kolkata 700009, India.
   [Tripathy, Umakanta] Indian Sch Mines, Indian Inst Technol, Dept Appl Phys, Dhanbad 826004, Bihar, India.
C3 Indian Institute of Technology System (IIT System); Indian Institute of
   Technology (IIT) - Guwahati; Department of Science & Technology (India);
   Bose Institute; Indian Institute of Technology System (IIT System);
   Indian Institute of Technology (Indian School of Mines) Dhanbad
RP Karmakar, S (通讯作者)，Techno India Univ, Dept Biotechnol, EM 4-1,Sect 5, Kolkata 700091, India.; Tripathy, U (通讯作者)，Indian Sch Mines, Indian Inst Technol, Dept Appl Phys, Dhanbad 826004, Bihar, India.
EM snat14@gmail.com; utripathy@iitism.ac.in
RI Tripathy, Umakanta/AAJ-1358-2020
OI Tripathy, Umakanta/0000-0001-7417-8731; Das, Kali/0000-0001-7686-9077;
   Biswas, Shrutidhara/0000-0003-2568-2282
FU Bose Institute
FX We acknowledge the Bose Institute for financial support. We also
   acknowledge Mr. Dipak Chandra Konar and the late Mr. Tapas Ghosh,
   technical officer from the Department of Chemistry, Bose Institute,
   Kolkata, and GE application specialist, Lalith Kishore, for their help
   and support.
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NR 54
TC 0
Z9 0
U1 0
U2 3
PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
PI OTTAWA
PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA
SN 0008-4042
EI 1480-3291
J9 CAN J CHEM
JI Can. J. Chem.
PD JUN
PY 2019
VL 97
IS 6
SI SI
BP 504
EP 511
DI 10.1139/cjc-2018-0412
PG 8
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA IA0HP
UT WOS:000469237900016
DA 2022-11-30
ER

PT J
AU Harrison, RES
   Morkis, D
AF Harrison, Reed E. S.
   Morkis, Dimitrios
TI Molecular Mechanisms of Macular Degeneration Associated with the
   Complement Factor H Y402H Mutation
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID C-REACTIVE PROTEIN; SOFTWARE PACKAGE; ELECTROSTATICS; HEPARIN; PROGRAM;
   LIBRARY; PDB2PQR; HIS-384; VARIANT; SITE
AB A single nucleotide polymorphism, tyrosine at position 402 to histidine (Y402H), within the gene encoding complement factor H (FH) predisposes individuals to acquiring age-related macular degeneration (AMD) after aging. This polymorphism occurs in short consensus repeat (SCR) 7 of FH and results in decreased binding affinity of SCR6-8 for heparin. As FH is responsible for regulating the complement system, decreased affinity for heparin results in decreased regulation on surfaces of self. To understand the involvement of the Y402H polymorphism in AMD, we leverage methods from bioinformatics and computational biophysics to quantify structural and dynamical differences between SCR7 isoforms that contribute to decreased pattern recognition in SCR7(H402). Our data from molecular and Brownian dynamics simulations suggest a revised mechanism for decreased heparin binding. In this model, transient contacts not observed in structures for SCR7 are predicted to occur in molecular dynamics simulations between coevolved residues Y402 and 1412, stabilizing SCR7(Y402) in a conformation that promotes association with heparin. H402 in the risk isoform is less likely to form a contact with 1412 and samples a larger conformational space than Y402. We observe energy minima for sidechains of Y402 and R404 from SCR7(Y402) that are predicted to associate with heparin at a rate constant faster than energy minima for sidechains of H402 and R404 from SCR7(H402). As both carbohydrate density and degree of sulfation decrease with age in Bruch's membrane of the macula, the decreased heparin recognition of SCR7(H402) may contribute to the pathogenesis of AMD.
C1 [Harrison, Reed E. S.; Morkis, Dimitrios] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside
RP Morkis, D (通讯作者)，Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
EM dmorikis@ucr.edu
OI Harrison, Reed/0000-0003-2512-4344
FU University of California; National Science Foundation; Whitaker
   Foundation; NIH [R01EY027440]; NATIONAL EYE INSTITUTE [R01EY027440]
   Funding Source: NIH RePORTER
FX R.E.S.H. has received funding from the University of California
   President's Dissertation-Year Fellowship, the National Science
   Foundation Integrative Graduate Education and Research Traineeship, and
   a Whitaker Foundation Summer grant in support of this study. This work
   was partially supported by NIH grant R01EY027440.
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NR 48
TC 7
Z9 7
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 22
PY 2019
VL 116
IS 2
BP 215
EP 226
DI 10.1016/j.bpj.2018.12.007
PG 12
WC Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics
GA HI3DO
UT WOS:000456327100005
PM 30616835
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Baranov, P
   Lin, H
   McCabe, K
   Gale, D
   Cai, SS
   Lieppman, B
   Morrow, D
   Lei, P
   Liao, J
   Young, M
AF Baranov, Petr
   Lin, Hong
   McCabe, Kathryn
   Gale, David
   Cai, Shenshen
   Lieppman, Burke
   Morrow, Dwight
   Lei, Phoebe
   Liao, Justin
   Young, Michael
TI A Novel Neuroprotective Small Molecule for Glial Cell Derived
   Neurotrophic Factor Induction and Photoreceptor Rescue
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE GDNF; neuroprotection; photoreceptors
ID RETINAL DEGENERATION; RETINITIS-PIGMENTOSA; VALPROIC ACID; RAT MODEL;
   GDNF; MOUSE; SURVIVAL; CNTF; MICE; EXPRESSION
AB Purpose: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors. Methods: GDNF induction in vitro was assessed in human ARPE-19, human retinal progenitor cells (RPCs) and mouse pluripotent cell-derived eyecups. For time course pharmacokinetic and GDNF induction studies in C57Bl/6 mice, GSK812 sustained release formulation was injected intravitreally. The same delivery approach was used in the rhodopsin knockout mice and Royal College of Surgeon (RCS) rats to assess long-term GDNF induction and photoreceptor rescue. Results: The suspension provided sustained GSK812 delivery with 28g of drug remaining in the eye 2 weeks after a single injection. GSK812 suspension injection in C57Bl/6 mice resulted in significant upregulation of GDNF mRNA (>1.8-fold) and protein levels (>2.8-fold). Importantly, GSK812 treatment resulted in outer nuclear layer preservation in rho(-/-) mice with a 2-fold difference in photoreceptor number. In the RCS rat, the GSK812 injection provided long-term rescue of photoreceptors and outer segments, accompanied by function preservation as well. Conclusions: GSK812 is a potent neuroprotectant that can induce GDNF in normal and diseased retina. This induction results in photoreceptor rescue in 2 models of retinal degeneration.
C1 [Baranov, Petr; Lieppman, Burke; Young, Michael] Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
   [Lin, Hong; McCabe, Kathryn; Gale, David; Cai, Shenshen; Morrow, Dwight; Lei, Phoebe; Liao, Justin] GlaxoSmithKline LLC, Philadelphia, PA USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute; GlaxoSmithKline
RP Baranov, P (通讯作者)，Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM petr_baranov@meei.harvard.edu
FU HSCI-GSK grant; Minda de Gunzburg Ocular Regeneration Center; National
   Eye Institute [P30EY003790]; NATIONAL EYE INSTITUTE [P30EY003790]
   Funding Source: NIH RePORTER
FX The authors thank Yan Sun for providing free base drug substance;
   Caroline Sychterz, Clara Andonian, Pratik Saha, James Thomas, and Todd
   Koretke for analytical support; Rennan Pan, Yanli Deng, and Tom Wilde
   for the discussion around pharmacokinetic studies. This work was
   supported by the HSCI-GSK grant, Minda de Gunzburg Ocular Regeneration
   Center, and the National Eye Institute core grant P30EY003790.
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NR 36
TC 9
Z9 9
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN
PY 2017
VL 33
IS 5
BP 412
EP 422
DI 10.1089/jop.2016.0121
PG 11
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA EX2KB
UT WOS:000403054100012
PM 28441076
OA Green Published
DA 2022-11-30
ER

PT J
AU Spaide, RF
AF Spaide, Richard F.
TI Choriocapillaris Flow Features Follow a Power Law Distribution:
   Implications for Characterization and Mechanisms of Disease Progression
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MODEL; DEGENERATION; WASHOUT
AB PURPOSE: To investigate flow characteristics of the choriocapillaris using optical coherence tomography angiography.
   DESIGN: Retrospective observational case series.
   METHODS: Visualization of flow in individual choriocapillary vessels is below the current resolution limit of optical coherence tomography angiography instruments, but areas of absent flow signal, called flow voids, are resolvable. The central macula was imaged with the Optovue RTVue XR Avanti using a 10-mu m slab thickness in 104 eyes of 80 patients who ranged in age from 24 to 99 years of age. Automatic local thresholding of the resultant raw data with the Phansalkar method was analyzed with generalized estimating equations.
   RESULTS: The distribution of flow voids vs size of the voids was highly skewed. The data showed a linear log log plot and goodness-of-fit methods showed the data followed a power law distribution over the relevant range. A slope intercept relationship was also evaluated for the log transform and significant predictors for variables included age, hypertension, pseudodrusen, and the presence of late age-related macular degeneration (AMD) in the fellow eye.
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C1 [Spaide, Richard F.] Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
C3 Vitreous Retina Macula Consultants of New York
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@gmail.com
RI Spaide, Richard/ABD-7368-2020
FU MACULA FOUNDATION, INC, NEW YORK, NY
FX SUPPORTED IN PART BY THE MACULA FOUNDATION, INC, NEW YORK, NY, WHICH HAD
   NO INFLUENCE ON the content.
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NR 35
TC 219
Z9 224
U1 1
U2 7
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 OCT
PY 2016
VL 170
BP 58
EP 67
DI 10.1016/j.ajo.2016.07.023
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DZ5KF
UT WOS:000385900300009
PM 27496785
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Wylegala, A
   Teper, S
   Dobrowolski, D
   Wylegala, E
AF Wylegala, Adam
   Teper, Slawomir
   Dobrowolski, Dariusz
   Wylegala, Edward
TI Optical coherence angiography: A review
SO MEDICINE
LA English
DT Review
DE AMD; anti-VEGF; CNV; diabetic retinopathy; optical coherence tomography;
   Optical Coherence Tomography Angiography (OCT-A)
ID AMPLITUDE-DECORRELATION ANGIOGRAPHY; SOURCE OCT ANGIOGRAPHY; FOVEAL
   AVASCULAR ZONE; TOMOGRAPHY ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION;
   MACULAR DEGENERATION; FLUORESCEIN-ANGIOGRAPHY; ULTRAHIGH-SPEED;
   DIABETIC-RETINOPATHY; VASCULATURE
AB Background:Retinal vascular diseases are one of the most common causes of blindness in the developed world. Optical Coherence Tomography Angiography (OCT-A) is a new noninvasive method that uses several algorithms to detect blood movement. This enables the creation of high-resolution vascular images with contrast depicting motionless tissue.Methods:This review presents the results of articles relevant to age-related macular degeneration (AMD), diabetic retinopathy (DR), and OCT-A. The OCT-A technique can successfully be used in the diagnosis of neovascularization, retinal vein occlusion (RVO) and retinal artery occlusion (RAO), vessel abnormalities and even anterior segment neovascularization. OCT-A can also be applied to compute data such as vessel density, and flow index in both superficial and deep plexuses.Results:Many studies have compared fluorescein angiography with OCT-A. Other studies have reported differences in vascular density in AMD patients and have compared them with people having healthy eyes. Although OCT-A offers rapid picture acquisition, high repeatability and resolution, it also has many drawbacks. The most common are: motion artifacts, projections from overlying vessels and limited field of view.An interesting new application is the possibility to assess changes during antivascular endothelial growth factor (anti-VEGF) therapy. Another function of OCT-A is the possible application in the study of choriocapillaries in many fields of ocular pathology.Conclusion:OCT-A is a new promising method that allows the visualization of the retinal vascular network and the counting of blood flow parameters. This technique provides reliable images useful in clinical routines.
C1 [Wylegala, Adam; Dobrowolski, Dariusz] Santa Barbara Hosp, Dept Ophthalmol, Pl Med 1, PL-41200 Sosnowiec, Poland.
   [Teper, Slawomir; Dobrowolski, Dariusz; Wylegala, Edward] Silesian Med Univ, Railway Hosp Katowice, Ophthalmol Clin, Sch Med 2,Div Dent Zabrze, Katowice, Poland.
C3 Medical University Silesia
RP Wylegala, A (通讯作者)，Santa Barbara Hosp, Dept Ophthalmol, Pl Med 1, PL-41200 Sosnowiec, Poland.
EM adam.wylegala@gmail.com
RI Wylegala, Edward/AAD-3961-2019; Wylęgała, Edward
   Aleksander/AGL-6056-2022; Wylęgała, Adam/AAK-5951-2020; Teper,
   Slawomir/AAQ-1938-2021
OI Wylęgała, Edward Aleksander/0000-0002-6707-5790; Teper,
   Slawomir/0000-0002-0935-8880; Wylegala, Adam/0000-0001-7295-4936;
   Dobrowolski, Dariusz/0000-0002-8768-1691
FU National Centre for Research and Development
   [STRATEGMED1/234261/2/NCBR/2014]
FX This work was supported by the National Centre for Research and
   Development grant STRATEGMED1/234261/2/NCBR/2014.
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NR 94
TC 57
Z9 59
U1 3
U2 25
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 OCT
PY 2016
VL 95
IS 41
AR e4907
DI 10.1097/MD.0000000000004907
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA EA1LV
UT WOS:000386354700008
PM 27741104
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Silvan, JM
   Reguero, M
   de Pascual-Teresa, S
AF Silvan, Jose Manuel
   Reguero, Marina
   de Pascual-Teresa, Sonia
TI A protective effect of anthocyanins and xanthophylls on UVB-induced
   damage in retinal pigment epithelial cells
SO FOOD & FUNCTION
LA English
DT Article
ID OXIDATIVE-STRESS; INDUCED APOPTOSIS; BINDING PROTEIN; LUTEIN;
   ZEAXANTHIN; CAROTENOIDS; HEALTH; INFLAMMATION; PATHWAYS; EXTRACT
AB Increased exposure to solar ultraviolet B (UVB) radiation causes oxidative damage that may promote age related macular degeneration (AMD) and other ocular pathologies. This study is aimed to demonstrate the protective effects of some anthocyanins and xanthophylls against the UVB-induced oxidative damage to retinal pigment epithelial (RPE) cells. ARPE-19 cells were treated with 5 mu M cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, lutein, zeaxanthin or a mixture of cyanidin-3-O-glucoside : zeaxanthin prior to UVB exposure (500 J m(-2)). Cell viability and mitogen-activated protein kinase (MAPK) phosphorylation were determined by MTT assay and western blot analysis, respectively. Oxidative damage was evaluated by measuring the intracellular reactive oxygen species (ROS). The data showed that UVB irradiation reduces the cell viability to 46% with increasing of intracellular ROS levels and phosphorylation of MAPKs. However, pre-treatment (60 min) with 5 mu M cyanidin-3-O-glucoside, lutein or zeaxanthin significantly reduced cellular ROS levels and phosphorylation of MAPKs (JNK1/2 and p38) mediated by UVB irradiation and subsequently increased cell viability. Thus, results show that UVB irradiation is able to induce apoptosis in ARPE-19 cells through oxidative stress; however anthocyanins and xanthophylls pre-treatment can attenuate this damage. This suggests that cyanidin-3-O-glucoside, lutein and zeaxanthin are effective in preventing UVB-induced damage in RPE cells and may be suitable as chemoprotective factors for the prevention of ocular damage. The use of natural dietary antioxidants might reduce ocular oxidative damage caused by UVB radiation.
C1 [Silvan, Jose Manuel; Reguero, Marina; de Pascual-Teresa, Sonia] CSIC, Spanish Natl Res Council, Inst Food Sci Food Technol & Nutr ICTAN, Dept Metab & Nutr, Jose Antonio Novais 10, Madrid 28040, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto
   de Ciencia y Tecnologia de Alimentos y Nutricion (ICTAN)
RP de Pascual-Teresa, S (通讯作者)，CSIC, Spanish Natl Res Council, Inst Food Sci Food Technol & Nutr ICTAN, Dept Metab & Nutr, Jose Antonio Novais 10, Madrid 28040, Spain.
EM s.depascualteresa@csic.es
RI Jimenez, Jose Manuel Silvan/F-3032-2013; de Pascual-Teresa,
   Sonia/F-5321-2011
OI Jimenez, Jose Manuel Silvan/0000-0001-8266-3761; de Pascual-Teresa,
   Sonia/0000-0001-8546-8507
FU Spanish Ministry of Economy and Competitiveness [AGL2012-30803]; CSIC
   [JAEDoc_2010_087]
FX This work was supported by the Spanish Ministry of Economy and
   Competitiveness through project AGL2012-30803. J. M. Silvan wishes to
   thank the Ministry of Science and Innovation and CSIC for a JAE
   post-doctoral contract (JAEDoc_2010_087).
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NR 56
TC 49
Z9 56
U1 6
U2 64
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 2042-6496
EI 2042-650X
J9 FOOD FUNCT
JI Food Funct.
PY 2016
VL 7
IS 2
BP 1067
EP 1076
DI 10.1039/c5fo01368b
PG 10
WC Biochemistry & Molecular Biology; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Food Science & Technology
GA DE5SP
UT WOS:000370692900044
PM 26781209
DA 2022-11-30
ER

PT J
AU Murugappan, SK
   Zhou, YF
AF Murugappan, Suresh Kanna
   Zhou, Yufeng
TI Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound
   (HIFU): An Ex Vivo Study
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Fluorescence; high-intensity focused ultrasound; penetration; pulse
   duration; transsclera drug delivery
ID GENE DELIVERY; IONTOPHORESIS; PHARMACOKINETICS; MICROBUBBLES; RETINA
AB Purpose/aim of study: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use.
   Materials and methods: In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10-50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex vivo porcine sclera specimen.
   Results: In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 +/- 126.4 mu m versus 252.4 +/- 29.2 mu m) using bicinchoninic acid assay and Rhodamine 6G fluorescence intensity by 3.1 folds (22.4 +/- 12.3 versus 7.1 +/- 4.1) and coverage area by 2.6 folds (40.4 +/- 9.1% versus 15.8 +/- 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope.
   Conclusions: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.
C1 [Murugappan, Suresh Kanna; Zhou, Yufeng] Nanyang Technol Univ, Div Engn Mech, Sch Mech & Aerosp Engn, Singapore 639798, Singapore.
C3 Nanyang Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University
RP Zhou, YF (通讯作者)，Nanyang Technol Univ, Sch Mech & Aerosp Engn, 50 Nanyang Ave, Singapore 639798, Singapore.
EM yfzhou@ntu.edu.sg
RI Zhou, Yufeng/A-1127-2011
OI Zhou, Yufeng/0000-0003-4086-2150; Murugappan, Suresh
   Kanna/0000-0003-0734-4634
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NR 31
TC 6
Z9 7
U1 1
U2 10
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 2015
VL 40
IS 11
BP 1172
EP 1180
DI 10.3109/02713683.2014.980006
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DD4KM
UT WOS:000369891500012
PM 25380302
DA 2022-11-30
ER

PT J
AU Ratnapriya, R
   Zhan, XW
   Fariss, RN
   Branham, KE
   Zipprer, D
   Chakarova, CF
   Sergeev, YV
   Campos, MM
   Othman, M
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   Maminishkis, A
   Waseem, NH
   Brooks, M
   Rajasimha, HK
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   Lotery, A
   Klein, BE
   Truitt, BJ
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   Morgan, DJ
   Morrison, MA
   Souied, E
   Tsironi, EE
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   Fishman, GA
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   Merriam, JC
   Park, KH
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   Farrer, LA
   Johnson, MP
   Peachey, NS
   Lathrop, M
   Baron, RV
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   Kamatani, Y
   Martin, TM
   Jiang, YD
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   Zack, DJ
   Chan, CC
   Pericak-Vance, MA
   Jacobson, SG
   Gorin, MB
   Klein, ML
   Allikmets, R
   Iyengar, SK
   Weber, BH
   Haines, JL
   Leveillard, T
   Deangelis, MM
   Stambolian, D
   Weeks, DE
   Bhattacharya, SS
   Chew, EY
   Heckenlively, JR
   Abecasis, GR
   Swaroop, A
AF Ratnapriya, Rinki
   Zhan, Xiaowei
   Fariss, Robert N.
   Branham, Kari E.
   Zipprer, David
   Chakarova, Christina F.
   Sergeev, Yuri V.
   Campos, Maria M.
   Othman, Mohammad
   Friedman, James S.
   Maminishkis, Arvydas
   Waseem, Naushin H.
   Brooks, Matthew
   Rajasimha, Harsha K.
   Edwards, Albert O.
   Lotery, Andrew
   Klein, Barbara E.
   Truitt, Barbara J.
   Li, Bingshan
   Schaumberg, Debra A.
   Morgan, Denise J.
   Morrison, Margaux A.
   Souied, Eric
   Tsironi, Evangelia E.
   Grassmann, Felix
   Fishman, Gerald A.
   Silvestri, Giuliana
   Scholl, Hendrik P. N.
   Kim, Ivana K.
   Ramke, Jacqueline
   Tuo, Jingsheng
   Merriam, Joanna E.
   Merriam, John C.
   Park, Kyu Hyung
   Olson, Lana M.
   Farrer, Lindsay A.
   Johnson, Matthew P.
   Peachey, Neal S.
   Lathrop, Mark
   Baron, Robert V.
   Igo, Robert P., Jr.
   Klein, Ronald
   Hagstrom, Stephanie A.
   Kamatani, Yoichiro
   Martin, Tammy M.
   Jiang, Yingda
   Conley, Yvette
   Sahel, Jose-Alan
   Zack, Donald J.
   Chan, Chi-Chao
   Pericak-Vance, Margaret A.
   Jacobson, Samuel G.
   Gorin, Michael B.
   Klein, Michael L.
   Allikmets, Rando
   Iyengar, Sudha K.
   Weber, Bernhard H.
   Haines, Jonathan L.
   Leveillard, Thierry
   Deangelis, Margaret M.
   Stambolian, Dwight
   Weeks, Daniel E.
   Bhattacharya, Shomi S.
   Chew, Emily Y.
   Heckenlively, John R.
   Abecasis, Goncalo R.
   Swaroop, Anand
TI Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2)
   are associated with macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRUCHS MEMBRANE; TISSUE INHIBITOR; HIGH-RISK;
   METALLOPROTEINASES-3 TIMP3; RETINAL DEGENERATION; MALATTIA LEVENTINESE;
   DRUSEN FORMATION; GROWTH-FACTOR; MUTATIONS
AB Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 x 10(-5)). Thus, it appears that rare and common variants in a single gene-FBN2-can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.
C1 [Ratnapriya, Rinki; Zipprer, David; Friedman, James S.; Brooks, Matthew; Rajasimha, Harsha K.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Fariss, Robert N.; Campos, Maria M.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
   [Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
   [Maminishkis, Arvydas] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA.
   [Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, NIH, Bethesda, MD 20892 USA.
   [Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [Zhan, Xiaowei; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Zhan, Xiaowei; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Branham, Kari E.; Othman, Mohammad; Heckenlively, John R.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [Chakarova, Christina F.; Waseem, Naushin H.; Bhattacharya, Shomi S.] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Edwards, Albert O.] Univ Oregon, Inst Mol Biol, Eugene, OR 97401 USA.
   [Edwards, Albert O.] Oregon Retina, Eugene, OR 97401 USA.
   [Lotery, Andrew] Univ Southampton, Fac Med Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
   [Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
   [Truitt, Barbara J.; Igo, Robert P., Jr.; Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Li, Bingshan; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Schaumberg, Debra A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
   [Schaumberg, Debra A.; Morgan, Denise J.; Morrison, Margaux A.; Deangelis, Margaret M.] Univ Utah, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Souied, Eric] Univ Paris Est Creteil, Hop Intercommunal Creteil, Hop Henri Mondor, F-94000 Creteil, France.
   [Tsironi, Evangelia E.] Univ Thessaly, Sch Med, Dept Ophthalmol, Larisa, Greece.
   [Grassmann, Felix; Weber, Bernhard H.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Fishman, Gerald A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA.
   [Silvestri, Giuliana] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
   [Scholl, Hendrik P. N.; Zack, Donald J.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
   [Ramke, Jacqueline] Fred Hollows Fdn, Auckland, New Zealand.
   [Ramke, Jacqueline] Univ New S Wales, Sch Social Sci, Sydney, NSW, Australia.
   [Merriam, Joanna E.; Merriam, John C.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seoul 463707, South Korea.
   [Farrer, Lindsay A.] Boston Univ, Dept Med, Sect Biomed Genet, Sch Med, Boston, MA 02215 USA.
   [Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Sect Biomed Genet, Sch Med, Boston, MA 02215 USA.
   [Farrer, Lindsay A.] Boston Univ, Dept Biostat, Sch Med, Sect Biomed Genet, Boston, MA 02215 USA.
   [Farrer, Lindsay A.] Boston Univ, Dept Med, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
   [Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
   [Farrer, Lindsay A.] Boston Univ, Dept Biostat, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
   [Johnson, Matthew P.] Texas Biomed Res Inst, San Antonio, TX 78245 USA.
   [Peachey, Neal S.; Hagstrom, Stephanie A.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Peachey, Neal S.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44195 USA.
   [Lathrop, Mark; Kamatani, Yoichiro; Sahel, Jose-Alan; Leveillard, Thierry] Univ Paris 06, INSERM, Dept Genet, Inst Vis,UMR S 968, Paris, France.
   [Baron, Robert V.; Weeks, Daniel E.] Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
   [Jiang, Yingda; Weeks, Daniel E.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
   [Martin, Tammy M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Conley, Yvette] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
   [Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33125 USA.
   [Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Miami, FL 33125 USA.
   [Jacobson, Samuel G.] Univ Penn, Dept Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Klein, Michael L.] Univ Portland, Macular Degenerat Ctr, Casey Eye Inst, Portland, OR 97201 USA.
   [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA USA.
   [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); National Institutes of Health (NIH) - USA; NIH National
   Eye Institute (NEI); National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI); National Institutes of Health (NIH) - USA;
   NIH National Eye Institute (NEI); National Institutes of Health (NIH) -
   USA; NIH National Eye Institute (NEI); University of Michigan System;
   University of Michigan; University of Michigan System; University of
   Michigan; University of Michigan System; University of Michigan;
   University of London; University College London; University of Oregon;
   University of Southampton; University of Wisconsin System; University of
   Wisconsin Madison; Case Western Reserve University; Vanderbilt
   University; Harvard University; Brigham & Women's Hospital; Utah System
   of Higher Education; University of Utah; Assistance Publique Hopitaux
   Paris (APHP); Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Hopital
   Universitaire Henri-Mondor - APHP; CHI Creteil; University of Thessaly;
   University of Regensburg; University of Illinois System; University of
   Illinois Chicago; University of Illinois Chicago Hospital; Queens
   University Belfast; Johns Hopkins University; Johns Hopkins Medicine;
   Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; University of New South Wales Sydney; Columbia University;
   Columbia University; Seoul National University (SNU); Seoul National
   University Hospital; Boston University; Boston University; Boston
   University; Boston University; Boston University; Boston University;
   Texas Biomedical Research Institute; Cleveland Clinic Foundation; US
   Department of Veterans Affairs; Veterans Health Administration (VHA);
   Case Western Reserve University; Louis Stokes Cleveland Veterans Affairs
   Medical Center; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh; Oregon Health &
   Science University; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Bascom Palmer Eye Institute;
   University of Miami; University of Miami; University of Pennsylvania;
   Pennsylvania Medicine; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; University of Portland;
   University of Pennsylvania; University of Pennsylvania
RP Swaroop, A (通讯作者)，NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Farrer, Lindsay/AAS-1035-2020; Ramke, Jacqueline/I-8844-2019;
   Bhattacharya, Shom/N-2926-2016; Weeks, Daniel E/B-2995-2012; Fariss,
   Robert/ABI-1771-2020; DeAngelis, e/J-7863-2015; Sahel,
   Jose-Alain/F-3172-2017; Haines, Jonathan/C-3374-2012; Igo,
   Rob/P-3438-2019; Kamatani, Yoichiro/N-5513-2015; Allikmets,
   Rando/ABD-4533-2021; Peachey, Neal/G-5533-2010; Léveillard,
   Thierry/AAR-1804-2020; Branham, Kari/AAA-8336-2022; /S-1190-2019
OI Ramke, Jacqueline/0000-0002-5764-1306; Bhattacharya,
   Shom/0000-0002-1601-6344; Weeks, Daniel E/0000-0001-9410-7228; Sahel,
   Jose-Alain/0000-0002-4831-1153; Haines, Jonathan/0000-0002-4351-4728;
   Igo, Rob/0000-0002-0024-1993; Peachey, Neal/0000-0002-4419-7226;
   Léveillard, Thierry/0000-0001-5692-8770; /0000-0001-7488-250X; Branham,
   Kari/0000-0002-2492-254X; Lotery, Andrew/0000-0001-5541-4305;
   Maminishkis, Arvydas/0000-0003-3345-3375; Kim,
   Ivana/0000-0003-0310-6129; Ratnapriya, Rinki/0000-0002-0469-4631;
   Farrer, Lindsay/0000-0001-5533-4225; Conley, Yvette/0000-0002-1784-6067;
   Fariss, Robert/0000-0003-3227-7170; Jacobson,
   Samuel/0000-0003-2122-169X; Grassmann, Felix/0000-0003-1390-7528; Weber,
   Bernhard H.F./0000-0002-8808-7723; Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute and National Institutes of Health [EY016862,
   EY013435, EY09859, EY017362, EY014458, EY019007]; Macula Vision Research
   Foundation; Foundation Fighting Blindness; Kaplen Foundation; Widgeon
   Point Charitable Foundation; Harold and Pauline Price Foundation; Elmer
   and Sylvia Sramek Foundation; Veterans Administration; German Research
   Foundation [WE 1259/19-2]; NIHR; Welcome Trust [076169/A]; American
   Health Assistance Foundation [M2007110]; Frost Charitable Trust; Brian
   Mercer Charitable Trust; Macular Society; Gift of Sight; Research to
   Prevent Blindness; NATIONAL EYE INSTITUTE [R01EY017362, ZIAEY000546,
   ZIAEY000485, ZICEY000459, ZIAEY000475, R01EY009859, ZIAEY000476,
   ZIAEY000419, R01EY021532, P30EY019007, R01EY016862, R01EY013435,
   R01EY014458] Funding Source: NIH RePORTER
FX This study was supported by Intramural Research Program of the National
   Eye Institute and National Institutes of Health grants (EY016862,
   EY013435, EY09859, EY017362, EY014458, EY019007), Macula Vision Research
   Foundation, Foundation Fighting Blindness, Kaplen Foundation, Widgeon
   Point Charitable Foundation, Harold and Pauline Price Foundation, Elmer
   and Sylvia Sramek Foundation, Veterans Administration, Harold and
   Pauline Price Foundation, German Research Foundation (WE 1259/19-2),
   NIHR supported BRC at Moorfields Eye Hospital (London), Welcome Trust
   (076169/A), American Health Assistance Foundation (M2007110), Frost
   Charitable Trust, Brian Mercer Charitable Trust, Macular Society and the
   Gift of Sight, and Research to Prevent Blindness.
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NR 63
TC 38
Z9 40
U1 0
U2 30
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 NOV 1
PY 2014
VL 23
IS 21
BP 5827
EP 5837
DI 10.1093/hmg/ddu276
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UX
UT WOS:000343203600020
PM 24899048
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Boochoon, KS
   Manarang, JC
   Davis, JT
   McDermott, AM
   Foster, WJ
AF Boochoon, Kieran S.
   Manarang, Joseph C.
   Davis, Joshua T.
   McDermott, Alison M.
   Foster, William J.
TI The influence of substrate elastic modulus on retinal pigment epithelial
   cell phagocytosis
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Mechanotransduction; Retinal pigment epithelium; Phagocytosis; Flow
   cytometry
ID MATRIX; EXPRESSION; STIFFNESS; ROD
AB To better understand if a complex process such as phagocytosis is influenced by substrate stiffness, we investigated the influence of substrate elastic modulus on phagocytosis in the retinal pigment epithelial (RPE) cell line ARPE-19. RPE cells lie on Bruch's membrane, directly under the retina, and phagocytose the shed photoreceptor outer segments. Bruch's membrane is known to increase in stiffness by an order of magnitude with age and thus, this study has potential relevance in explaining retinal changes in age-related macular degeneration.
   ARPE-19 cells were plated on laminin-coated polyacrylamide substrates of varying elastic modulus. After 14 days in culture, a solution of latex fluorescent beads suspended in PBS was placed in each well. After an incubation time of 4 h, flow cytometry was performed to determine the number of cells that phagocytosed a bead. The number of ARPE-19 cells that phagocytosed a bead decreased continuously as a function of increasing substrate elastic modulus (p=0.0135), and this was found to be a linear relationship (slope=-0.03305 +/- 0.01104, R2=0.4726 per 10,000 cells).
   Our results suggest that RPE cells display decreased phagocytosis when grown on firmer substrates, and thus, APE cells in older eyes, in which Bruch's membrane is stiffer, may demonstrate decreased phagocytosis. Impaired phagocytosis by RPE cells may contribute to impaired metabolism of photoreceptor outer segments and to development of macular degeneration. Material stiffness may be a critical parameter in the development of neural therapies, including retinal prosthetics and stem cell therapies. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Boochoon, Kieran S.; McDermott, Alison M.] Univ Houston, Dept Biol & Biochem, Houston, TX USA.
   [Davis, Joshua T.; Foster, William J.] Univ Houston, Dept Phys, Houston, TX USA.
   [Manarang, Joseph C.; McDermott, Alison M.] Univ Houston, Coll Optometry, Houston, TX USA.
   [Foster, William J.] Methodist Hosp, Weill Cornell Med Coll, Houston, TX 77030 USA.
   [Foster, William J.] Temple Univ, Dept Ophthalmol, Philadelphia, PA 19140 USA.
   [Foster, William J.] Temple Univ, Dept Bioengn, Philadelphia, PA 19140 USA.
C3 University of Houston System; University of Houston; University of
   Houston System; University of Houston; University of Houston System;
   University of Houston; Cornell University; The Methodist Hospital
   System; The Methodist Hospital - Houston; Pennsylvania Commonwealth
   System of Higher Education (PCSHE); Temple University; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Temple University;
   University of Pennsylvania
RP Foster, WJ (通讯作者)，Temple Univ, Dept Ophthalmol, Philadelphia, PA 19140 USA.
EM William.Foster@Temple.edu
OI Foster, William/0000-0002-6668-3831
FU National Eye Institute/National Institutes of Health [K08EY017112,
   P30EY007551, R01EY013175]; National Academies Keck Futures Initiative
   Grant in Advanced Prosthetics; NATIONAL EYE INSTITUTE [P30EY007551,
   R01EY013175, K08EY017112] Funding Source: NIH RePORTER
FX WJF acknowledges the support from the National Eye Institute/National
   Institutes of Health (K08EY017112 and P30EY007551) and a National
   Academies Keck Futures Initiative Grant in Advanced Prosthetics. AMM
   acknowledges support from the National Eye Institute/National Institutes
   of Health (R01EY013175 and P30EY007551). The study sponsors had no role
   in the study design, the collection, analysis, or interpretation of
   data, the writing of the manuscript, or the decision to submit the
   manuscript.
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NR 17
TC 18
Z9 18
U1 2
U2 22
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 SEP 22
PY 2014
VL 47
IS 12
BP 3237
EP 3240
DI 10.1016/j.jbiomech.2014.06.021
PG 4
WC Biophysics; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Engineering
GA AR2CU
UT WOS:000343392000058
PM 25016484
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Timberlake, GT
   Omoscharka, E
   Grose, SA
   Bothwell, R
AF Timberlake, George T.
   Omoscharka, Evanthia
   Grose, Susan A.
   Bothwell, Rebecca
TI Preferred Retinal Locus-Hand Coordination in a Maze-Tracing Task
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID EYE-MOVEMENTS; BEHAVIOR; LOCATION
AB PURPOSE. Fine manual tasks require coordination of vision, eye movements, and motor control. Macular scotomas from age-related macular degeneration (AMD) may adversely affect this coordination. The purpose of this research was to find whether the preferred retina locus for fixation (fPRL) also guided the hand in performing fine manual tasks and how the fingers, fPRL, and scotomas interacted in task performance.
   METHODS. Subjects with bilateral macular scotomas from AMD and normally sighted controls traced an irregular "maze" line pattern with the index finger while viewing their hand and the maze in a scanning laser ophthalmoscope (SLO). Video images from the SLO showing the fingers and maze on the retina during the task were analyzed to produce retinal maps showing the scotoma and bivariate ellipses of fPRL and fingertip retinal positions.
   RESULTS. Fingertip retinal ellipses surrounded and were approximately centered on the fPRL ellipses. Fingertip retinal bivariate area was positively correlated with fPRL bivariate area and the percent time the fPRL was on the maze was correlated with visual acuity. Maze-tracing accuracy was positively correlated with saccade rate for scotoma subjects.
   CONCLUSIONS. Concentric overlap of fPRL and fingertip retinal ellipses indicates that it is the fPRL that guides the hand in the maze-tracing visuomotor task, just as the fovea guides the fingertip for visually normal subjects. It is likely that factors other than fPRL and scotoma characteristics contribute to poorer maze-tracing performance by scotoma subjects in comparison with controls. (Invest Ophthalmol Vis Sci. 2012;53:1810-1820) DOI:10.1167/iovs.11-9282
C1 [Timberlake, George T.; Omoscharka, Evanthia; Grose, Susan A.; Bothwell, Rebecca] Kansas City VA Med Ctr, Kansas City, MO 64128 USA.
   [Timberlake, George T.; Bothwell, Rebecca] Univ Kansas, Med Ctr, Dept Ophthalmol, Kansas City, KS 66103 USA.
C3 University of Kansas; University of Kansas Medical Center
RP Timberlake, GT (通讯作者)，Kansas City VA Med Ctr, 4801 Linwood Blvd, Kansas City, MO 64128 USA.
EM gtimberl@kumc.edu
FU Department of Veterans Affairs, Rehabilitation, Research, and
   Development Service [C6218R]
FX Supported by Department of Veterans Affairs, Rehabilitation, Research,
   and Development Service Grant C6218R.
CR BALLARD DH, 1992, PHILOS T R SOC B, V337, P331, DOI 10.1098/rstb.1992.0111
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   Timberlake GT, 2005, OPTOMETRY VISION SCI, V82, P177
NR 18
TC 3
Z9 3
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 APR
PY 2012
VL 53
IS 4
BP 1810
EP 1820
DI 10.1167/iovs.11-9282
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937PC
UT WOS:000303669400015
PM 22395879
DA 2022-11-30
ER

PT J
AU Wills, NK
   Ramanujam, VMS
   Chang, J
   Kalariya, N
   Lewis, JR
   Weng, TX
   van Kuijk, FJGM
AF Wills, N. K.
   Ramanujam, V. M. Sadagopa
   Chang, J.
   Kalariya, N.
   Lewis, J. R.
   Weng, T. -X.
   van Kuijk, F. J. G. M.
TI Cadmium accumulation in the human retina: Effects of age, gender, and
   cellular toxicity
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE cadmium; neural retina; retinal pigment epithelium; choroid; aging;
   human; women; graphite furnace atomic absorption spectrophotometry;
   inductively coupled plasma mass spectrometry; ARPE-19; membrane
ID CELLS; MODULATION; TRANSPORT; SMOKING
AB Tobacco smoking and aging are among the few factors linked to age-related macular degeneration (AMD), a major cause of blindness in the elderly. Recent studies indicate that cadmium (Cd), an environmental toxic trace metal, is approximately four-fold higher in the retinas of smokers compared to non-smokers. In this study, we determined the effects of age and gender on Cd accumulation in human retinal tissues, specifically the neural retina, retinal pigment epithelium (RPE), and choroid. Cadmium levels in cultured RPE cells or retinal tissues isolated from frozen donor eyes were measured using inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectrophotometry (GF-AAS). Cadmium uptake in cultured human RPE cells (ARPE-19) was also assessed using GF-AAS. Toxic effects of cadmium were determined from cell loss (measured as a decrease in cell density) and lactate dehydrogenase release (an indicator of membrane disruption). In "young" eyes (<55 years) Cd was highest in the retinal pigment epithelium and lowest in the neural retina. Cd was higher in all tissues in aged eyes (>= 55 years) and was significantly higher in the neural retina and RPE in older females. Cultured RPE cells exposed to Cd showed altered cell morphology, decreased cell survival, elevated ROS levels and concentration-dependent disruption of membrane integrity. We conclude that cadmium is accumulated differently in the neural retinal and RPE of older men and women. The deleterious effects of Cd on RPE cells indicate that this environmental toxin is a potentially important factor in age-related retinal disease. (C) 2007 Elsevier Ltd. All rights reserved.
C1 [Wills, N. K.; Lewis, J. R.; Weng, T. -X.] Univ Texas Galveston, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.
   [Wills, N. K.; Chang, J.; Kalariya, N.; van Kuijk, F. J. G. M.] Univ Texas Galveston, Med Branch, Dept Ophthalmol & Visual Sci, AMD Ctr, Galveston, TX 77555 USA.
   [Ramanujam, V. M. Sadagopa] Univ Texas Galveston, Med Branch, Div Nutr, Dept Prevent Med & Community Hlth, 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 Wills, NK (通讯作者)，Univ Texas Galveston, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.
EM nkwills@utmb.edu
CR ALCOCK NW, 1987, BIOL TRACE ELEM RES, V13, P363, DOI 10.1007/BF02796647
   ATSDR, 1999, TOX PROF CADM
   Bertin G, 2006, BIOCHIMIE, V88, P1549, DOI 10.1016/j.biochi.2006.10.001
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NR 29
TC 50
Z9 52
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 JAN
PY 2008
VL 86
IS 1
BP 41
EP 51
DI 10.1016/j.exer.2007.09.005
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 249ED
UT WOS:000252209100006
PM 17967453
DA 2022-11-30
ER

PT J
AU Konopatskaya, O
   Churchill, A
   Harper, S
   Bates, DO
   Gardiner, T
AF Konopatskaya, O.
   Churchill, A. J.
   Harper, S. J.
   Bates, David O.
   Gardiner, T. A.
TI VEGF(165)b, an endogenous C-terminal splice variant of VEGF, inhibits
   retinal neovascularization in mice
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; ISCHEMIC RETINOPATHY;
   MESSENGER-RNA; IN-VIVO; CELLS; ANGIOGENESIS; EXPRESSION; PROTEIN
AB Purpose: Hypoxia driven ocular angiogenesis occurs in a range of ischemic retinopathies including proliferative diabetic retinopathy and retinopathy of prematurity. These conditions are initiated and sustained by hypoxia dependent vascular endothelial growth factor (VEGF) expression in the eye. There are two families of VEGF isoforms formed by differential splicing, the pro-angiogenic VEGF family, known to contribute to ocular neovascularization, and the anti-angiogenic VEGF family, which are downregulated in diabetic retinopathy in humans. The first member of the VEGF family to be isolated was VEGF(165)b. To determine whether VEGF(165)b could inhibit hypoxia driven angiogenesis in the eye, the oxygen induced retinopathy mouse model of ocular neovascularization was used.
   Methods: 1 ng of recombinant human VEGF(165)b peptide was injected intraocularly upon return to normoxia after 5 days exposure to 95% oxygen, and neovascularization assessed.
   Results: VEGF(165)b significantly inhibited the percentage area of retinal neovascularization from 23 +/- 3% to 12 +/- 3.3%, and significantly increased normal vascular areas from 62 +/- 4% to 74 +/- 4%. The percentage area of residual ischemic retina was not affected.
   Conclusions: These results show that a single injection of VEGF(165)b can significantly reduce preretinal neovascularization without inhibition of physiological intraretinal angiogenesis. Controlling the balance of VEGF(xxx) to VEGF(xxx) isoforms may therefore be therapeutically valuable in the treatment of proliferative eye diseases such as diabetic retinopathy and age related macular degeneration. The regulation of splicing between these two families of isoforms may provide a novel therapeutic strategy for proliferative eye disease.
C1 Univ Bristol, Dept Physiol, Preclin Vet Sch, Microvasc Res Labs, Bristol BS2 8EJ, Avon, England.
   Bristol Eye Hosp, Dept Ophthalmol, Bristol BS1 2LX, Avon, England.
   Queens Univ Belfast, Royal Victoria Hosp, Belfast, Antrim, North Ireland.
C3 University of Bristol; Bristol Eye Hospital; Queens University Belfast
RP Bates, DO (通讯作者)，Univ Bristol, Dept Physiol, Preclin Vet Sch, Microvasc Res Labs, Southwell St, Bristol BS2 8EJ, Avon, England.
EM Dave.Bates@bristol.ac.uk
OI Bates, David/0000-0003-4850-2360; Gardiner, Tom/0000-0003-4907-2630
FU Wellcome Trust [69029] Funding Source: Medline
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NR 23
TC 107
Z9 132
U1 0
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAY 26
PY 2006
VL 12
IS 67-69
BP 626
EP 632
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 050PA
UT WOS:000238099200003
PM 16735996
DA 2022-11-30
ER

PT J
AU Weale, RA
AF Weale, Robert A.
TI A note on age-related comorbidity
SO ARCHIVES OF GERONTOLOGY AND GERIATRICS
LA English
DT Article
DE Age-related prevalence; Partial correlation; Elimination of the variable
   of age
ID BLUE MOUNTAINS EYE; BONE-MINERAL DENSITY; OPEN-ANGLE GLAUCOMA; BEAVER
   DAM EYE; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; TASTE
   DISORDERS; ACUTE-STROKE; PREVALENCE
AB A few years ago a link was found between age-related maculopathy and senile dementia. A pointer to this might have been provided prospectively by a comparison of the partial correlation of the respective age-related prevalences. Here the question is asked whether this was an isolated example or whether it can be confirmed in a statistically significant number of comparisons. Published data on age-related prevalences of 15 conditions have been partially correlated in order to determine whether their correlations, if any, persist when the variable of age has been eliminated. This was the case in a significant fraction of the data, and, for a smaller, but still significant, fraction it was possible to find retrospective confirmatory evidence. The approach is held to provide a short-cut method for exploring possible, hitherto unestablished, links between existing studies, which, in turn, may lead to a better understanding of the nosology underlying them. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Weale, Robert A.] Kings Coll London, Inst Gerontol, London WC2B 4LL, England.
   [Weale, Robert A.] Univ Coll London Hosp, Eye Dept, London WC1, England.
C3 University of London; King's College London; University College London
   Hospitals NHS Foundation Trust
RP Weale, RA (通讯作者)，Kings Coll London, Inst Gerontol, 46 Aldwych, London WC2B 4LL, England.
EM robert.weale@kcl.ac.uk
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NR 62
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-4943
EI 1872-6976
J9 ARCH GERONTOL GERIAT
JI Arch. Gerontol. Geriatr.
PD JUL-AUG
PY 2009
VL 49
IS 1
BP 93
EP 97
DI 10.1016/j.archger.2008.05.010
PG 5
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 455CF
UT WOS:000266733300019
PM 18614243
DA 2022-11-30
ER

PT J
AU Gao, FR
   Wang, L
   Wu, BX
   Ou, QJ
   Tian, HB
   Xu, JY
   Jin, CX
   Zhang, JP
   Wang, J
   Lu, LX
   Xu, GT
AF Gao, Furong
   Wang, Lei
   Wu, Binxin
   Ou, Qingjian
   Tian, Haibin
   Xu, Jingying
   Jin, Caixia
   Zhang, Jieping
   Wang, Juan
   Lu, Lixia
   Xu, Guo-Tong
TI Elimination of senescent cells inhibits epithelial-mesenchymal
   transition of retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age -related macular degeneration; Retinal pigment epithelium;
   Epithelial-mesenchymal transition; Senescence
ID FIBROSIS
AB Age-related macular degeneration (AMD) is one of the most common leading causes of irreversible blindness, and there is no effective treatment for it. It has been reported that aging is the greatest risk factor for AMD, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of AMD. To clarify the relationship between senescence and EMT in RPE cells, we used the replicative senescence model, H2O2- and/or Nutlin3a-induced senescence model, and low-density and/or TGF-beta-induced EMT model to detect the expression of senescence-, RPE-and EMT-related genes, and assessed the motility of cells by using a scratch wound migration assay. The results showed that replicative senescence of RPE cells was accompanied by increased expression of EMT markers. However, senescent RPE cells themselves did not undergo EMT, as the H(2)O(2)and Nutlin3a treated cells showed no increase in EMT characteristics, including unchanged or decreased expression of EMT markers and decreased motility. Furthermore, conditioned medium (CM) from senescent cells induced EMT in presenescent RPE cells, and EMT accelerated the process of senes-cence. Importantly, dasatinib plus quercetin, which selectively eliminates senescent cells, inhibited low-density -induced EMT in RPE cells. These findings provide a better understanding of the interconnection between senescence and EMT in RPE cells. Removal of senescent cells by certain methods such as senolytics, might be a promising potential approach to prevent or delay the progression of RPE-EMT-related retinal diseases such as AMD.
C1 [Gao, Furong; Wu, Binxin; Ou, Qingjian; Tian, Haibin; Xu, Jingying; Jin, Caixia; Zhang, Jieping; Wang, Juan; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Dept Ophthalmol, Sch Med, Tongji Hosp, 389 Xincun Rd, Shanghai 200065, Peoples R China.
   [Gao, Furong; Wu, Binxin; Ou, Qingjian; Tian, Haibin; Xu, Jingying; Jin, Caixia; Zhang, Jieping; Wang, Juan; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Tongji Eye Inst, Lab Clin & Visual Sci, Sch Med, 389 Xincun Rd, Shanghai 200065, Peoples R China.
   [Gao, Furong; Wang, Lei; Wu, Binxin; Tian, Haibin; Jin, Caixia; Lu, Lixia] Tongji Univ, Dept Biochem & Mol Biol, Sch Med, Shanghai 200092, Peoples R China.
   [Zhang, Jieping; Xu, Guo-Tong] Tongji Univ, Dept Pharmacol, Sch Med, Shanghai 200092, Peoples R China.
C3 Tongji University; Tongji University; Tongji University; Tongji
   University
RP Gao, FR; Lu, LX; Xu, GT (通讯作者)，Tongji Univ, Dept Ophthalmol, Sch Med, Tongji Hosp, 389 Xincun Rd, Shanghai 200065, Peoples R China.; Gao, FR; Lu, LX; Xu, GT (通讯作者)，Tongji Univ, Tongji Eye Inst, Lab Clin & Visual Sci, Sch Med, 389 Xincun Rd, Shanghai 200065, Peoples R China.
EM frgao@tongji.edu.cn; lulixia@tongji.edu.cn; gtxu@tongji.edu.cn
OI Ou, Qingjian/0000-0002-6881-8680
FU Ministry of Science and Technology of China [2020YFA0113101]; China
   National Innovation and Entrepreneurship Training Program for College
   Students [G202014001]
FX Funding This work was supported by grants from the Ministry of Science
   and Technology of China (2020YFA0113101) and the China National
   Innovation and Entrepreneurship Training Program for College Students
   (G202014001) .
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NR 40
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2022
VL 223
AR 109207
DI 10.1016/j.exer.2022.109207
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5S0DM
UT WOS:000874871800001
PM 35926646
DA 2022-11-30
ER

PT J
AU Li, KV
   Flores-Bellver, M
   Aparicio-Domingo, S
   Petrash, C
   Cobb, H
   Chen, CA
   Canto-Soler, MV
   Mathias, MT
AF Li, Kang V.
   Flores-Bellver, Miguel
   Aparicio-Domingo, Silvia
   Petrash, Carson
   Cobb, Hannah
   Chen, Conan
   Canto-Soler, M. Valeria
   Mathias, Marc T.
TI A Surgical Kit for Stem Cell-Derived Retinal Pigment Epithelium
   Transplants: Collection, Transportation, and Subretinal Delivery
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE retinal regeneration; transplantation; surgical instrument; retinal
   pigment epithelium; human induced pluripotent stem cells
ID SPECIFICATION; LOCALIZATION; THICKNESS
AB Transplantation of stem cell-derived retinal pigment epithelium (RPE) cells is a promising potential therapy for currently incurable retinal degenerative diseases like advanced dry age-related macular degeneration. In this study, we designed a set of clinically applicable devices for subretinal implantation of RPE grafts, towards the overarching goal of establishing enabling technologies for cell-based therapeutic approaches to regenerate RPE cells. This RPE transplant kit includes a custom-designed trephine for the production of RPE transplants, a carrier for storage and transportation, and a surgical device for subretinal delivery of RPE transplants. Cell viability assay confirmed biocompatibility of the transplant carrier and high preservation of RPE transplants upon storage and transportation. The transplant surgical device combines foldable technology that minimizes incision size, controlled delivery speed, no fluid reflux, curved translucent tip, usability of loading and in vivo reloading, and ergonomic handle. Furthermore, the complementary design of the transplant carrier and the delivery device resulted in proper grasping, loading, and orientation of the RPE transplants into the delivery device. Proof-of-concept transplantation studies in a porcine model demonstrated no damage or structural change in RPE transplants during surgical manipulation and subretinal deployment. Post-operative assessment confirmed that RPE transplants were delivered precisely, with no damage to the host retina or choroid, and no significant structural change to the RPE transplants. Our novel surgical kit provides a comprehensive set of tools encompassing RPE graft manufacturing to surgical implantation rendering key enabling technologies for pre-clinical and clinical phases of stem cell-derived RPE regenerative therapies.
C1 [Li, Kang V.; Flores-Bellver, Miguel; Aparicio-Domingo, Silvia; Petrash, Carson; Cobb, Hannah; Chen, Conan; Canto-Soler, M. Valeria; Mathias, Marc T.] Univ Colorado, Sch Med, CellSight Ocular Stem Cell & Regenerat Res Progra, Sue Anschutz Rodgers Eye Ctr,Dept Ophthalmol, Aurora, CO 80045 USA.
   [Petrash, Carson; Mathias, Marc T.] Univ Colorado, Sch Med, Sue Anschutz Rodgers Eye Ctr, Dept Ophthalmol, Aurora, CO 80045 USA.
   [Canto-Soler, M. Valeria] Univ Colorado, Sch Med, Charles C Gates Ctr Regenerat Med, Aurora, CO 80045 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; University of Colorado System; University of Colorado Anschutz
   Medical Campus; University of Colorado System; University of Colorado
   Anschutz Medical Campus
RP Li, KV; Canto-Soler, MV; Mathias, MT (通讯作者)，Univ Colorado, Sch Med, CellSight Ocular Stem Cell & Regenerat Res Progra, Sue Anschutz Rodgers Eye Ctr,Dept Ophthalmol, Aurora, CO 80045 USA.; Mathias, MT (通讯作者)，Univ Colorado, Sch Med, Sue Anschutz Rodgers Eye Ctr, Dept Ophthalmol, Aurora, CO 80045 USA.; Canto-Soler, MV (通讯作者)，Univ Colorado, Sch Med, Charles C Gates Ctr Regenerat Med, Aurora, CO 80045 USA.
EM marc.mathias@cuanschutz.edu; valeria.canto-soler@cuanschutz.edu;
   kang.li@cuanschutz.edu
OI Flores-Bellver, Miguel/0000-0003-3421-3699
FU Gates Grubstake Award [GGF012-18-01]; Gates Frontiers Fund; Solich
   Found; CellSight Fund; Research to Prevent Blindness
FX This work was supported by funding to MVC-S from The Gates Grubstake
   Award (GGF012-18-01), The Gates Frontiers Fund, The Solich Found,
   CellSight Fund, and an unrestricted Research Award to the Department of
   Ophthalmology from Research to Prevent Blindness.
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NR 42
TC 0
Z9 0
U1 1
U2 2
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 FEB 18
PY 2022
VL 10
AR 813538
DI 10.3389/fcell.2022.813538
PG 10
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA ZW2RC
UT WOS:000771064100001
PM 35252183
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Najeeb, BH
   Deak, GG
   Schmidt-Erfurth, UM
   Gerendas, BS
AF Haj Najeeb, Bilal
   Deak, Gabor G.
   Schmidt-Erfurth, Ursula Margarethe
   Gerendas, Bianca S.
TI RAP study, report 1: novel subtype of macular neovascularisation type
   III, cilioretinal MNV3
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE retina; angiogenesis; imaging; macula; neovascularisation
ID RETINAL ANGIOMATOUS PROLIFERATION; DEGENERATION; ARTERY; EYES
AB Purpose To report on patients with macular neovascularisation type III (MNV3) arising from cilioretinal arteries (CRAs) (cilioretinal macular neovascularisation type III (cMNV3)).
   Methods We reviewed baseline examinations of patients with neovascular age-related macular degeneration using multimodal imaging. We determined the type and distribution of MNV lesions in each cMNV3 case, the range of distances from the fovea, existence of exudative maculopathy, intraretinal haemorrhage and other morphological characteristics. 50 consecutive eyes with usual MNV3 without CRA were included as a control group.
   Results 102 eyes of 102 patients were identified with MNV3 lesions. Among these, we found 12 eyes (12%) with cMNV3, 84 eyes (82%) with usual MNV3 without CRA and 6 eyes (6%) with usual MNV3 with CRA. Ten cases of cMNV3 had one lesion, and two cases had two lesions. The lesions were distributed equally between the superior and inferior halves of the macula, whereas in the nasal and temporal halves, there were 8 (57%) and 6 (43%) lesions, respectively. All cMNV3 lesions were located between 500 and 1500 mu m from the central fovea except one, which was located between 1500 and 3000 mu m. None of the lesions had macular neovascularisation type I (MNV1) or macular neovascularisation type II (MNV2) elsewhere in both groups. Exudative maculopathy and intraretinal haemorrhage were found in seven (88%) and five (63%) of the eight pure cMNV3 cases, respectively.
   Conclusion cMNV3 can be solitary or multiple, isolated or accompanied with usual MNV3 lesions, but not with concurrent MNV1 or MNV2. It is frequently associated with extensive exudative maculopathy, intraretinal haemorrhage and subretinal fluid.
C1 [Haj Najeeb, Bilal; Deak, Gabor G.; Schmidt-Erfurth, Ursula Margarethe; Gerendas, Bianca S.] Med Univ Vienna, Vienna Reading Ctr, Dept Ophthalmol & Optometry, Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, UM (通讯作者)，Med Univ Vienna, Dept Opththalmol, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Haj Najeeb, Bilal/0000-0002-8147-1415; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Gerendas, Bianca S./0000-0001-8940-8130
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NR 25
TC 6
Z9 6
U1 1
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 2021
VL 105
IS 1
BP 113
EP 117
DI 10.1136/bjophthalmol-2019-315311
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PR6JI
UT WOS:000607340000021
PM 32161004
DA 2022-11-30
ER

PT J
AU Thomas, SA
   Titus, G
AF Thomas, Siji A.
   Titus, Geevarghese
TI Design of a portable retinal imaging module with automatic abnormality
   detection
SO BIOMEDICAL SIGNAL PROCESSING AND CONTROL
LA English
DT Article
DE Diabetic retinopathy (DR); Age related macular degeneration (AMD);
   Fundus camera; Convolutional neural networks (CNN); Optical coherence
   tomography (OCT)
ID DIABETIC-RETINOPATHY
AB Regular eye examinations are required for the early identification of retinal diseases, but the non-availability of medical resources and time are the main concerns in semi-urban areas with the scenario becoming more critical in rural areas. This paper discusses on the design of a cost-effective universal retinal fundus camera and the development of a novel algorithm for the identification of two prominent vision threatening diseases such as Diabetic Retinopathy (DR) and Age-related Macular Degeneration (AMD) employing the state-of-the-art, Convolutional Neural Networks (CNN) for higher classification accuracy. Furthermore, the proposed system is capable of predicting the disease severity level as well as providing suggestions as to whether an ophthalmic consultation is required for the subject under consideration. Experiments were conducted on images from publicly available databases and hospital repository. The condition Normal-DR-AMD and their severity levels were predicted. The performance scores employed were accuracy (95.83 %), sensitivity (0.93) and specificity (0.97), where the values corresponds to the average scores across different datasets. Furthermore, the developed system predicts the retinopathy stages with an average computational time of about 3.98 s. Both the scores clearly indicate the effectiveness of the proposed algorithm both in terms of correctness of the finding and speed of the generating the medical inference. This model can be extremely useful for rural campaign, where availability of trained medical practitioners is less as well as space for setting up and maintaining an eye care facility are not feasible. (C) 2020 Elsevier Ltd. All rights reserved.
C1 [Thomas, Siji A.; Titus, Geevarghese] Amal Jyothi Coll Engn, Dept ECE, Kottayam, Kerala, India.
RP Titus, G (通讯作者)，Amal Jyothi Coll Engn, Dept ECE, Kottayam, Kerala, India.
EM sijiathomas@ec.ajce.in; geevarghesetitus@amaljyothi.ac.in
RI TITUS, GEEVARGHESE/L-2125-2016
OI TITUS, GEEVARGHESE/0000-0002-2666-8047
FU Amal Jyothi Research Scholars Community [ACSIIEC0112018]
FX This work is fully supported by Innovation Ideas Unleashed, a
   institutional research funding agency organized by Amal Jyothi Research
   Scholars Community which is the subsidiary agency of Innovation and
   Entrepreneurship Development Centre (IEDC) of DST, Government of India
   with Grant ID ACSIIEC0112018.
CR Bhuvaneshwari K, 2017, J APPL SCI TECHNOL, V1, P27
   E-Ophtha, 2006, E OPHTHA COLOR FUNDU
   Govindaiah A, 2018, I S BIOMED IMAGING, P1525, DOI 10.1109/ISBI.2018.8363863
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   World Health Organization (WHO), 2013, UN EYE HLTH GLOB ACT
   Zhang Xiang, 2019, RECENT ADV NEW FRONT
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NR 17
TC 1
Z9 1
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1746-8094
EI 1746-8108
J9 BIOMED SIGNAL PROCES
JI Biomed. Signal Process. Control
PD JUL
PY 2020
VL 60
AR 101962
DI 10.1016/j.bspc.2020.101962
PG 7
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA LY1SP
UT WOS:000540302000021
DA 2022-11-30
ER

PT J
AU Liao, CY
   Cai, BX
   Feng, YF
   Chen, JM
   Wu, YP
   Zhuang, JB
   Liu, ZG
   Wu, YL
AF Liao, Chunyan
   Cai, Binxiang
   Feng, Yufeng
   Chen, Jingmeng
   Wu, Yiping
   Zhuang, Jingbin
   Liu, Zuguo
   Wu, Yalin
TI Activation of JNK signaling promotes all-trans-retinal?induced
   photoreceptor apoptosis in mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE retina; retinal metabolism; photoreceptor; apoptosis; DNA damage
ID CYTOCHROME-C; VISUAL CYCLE; DNA-DAMAGE; CASPASE-9 ACTIVATION; INDUCED
   RETINOPATHY; NUCLEOTIDE-BINDING; STARGARDT DISEASE; PROTEIN-KINASE;
   OUTER SEGMENTS; CELL-DEATH
AB Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of ?H2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4(?/?) Rdh8(?/?) mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4(?/?)Rdh8(?/?) mice. Of note, intraperitoneal administration of JNK?IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4(?/?)Rdh8(?/?) mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.
C1 [Liao, Chunyan; Cai, Binxiang; Wu, Yiping; Zhuang, Jingbin; Liu, Zuguo; Wu, Yalin] Xiamen Univ, Sch Med, Fujian Prov Key Lab Ophthalmol & Visual Sci, Dept Ophthalmol Xiangan Hosp,Eye Inst, Xiamen 361102, FJ, Peoples R China.
   [Feng, Yufeng] Xiamen Univ, Affiliated Hosp 1, Dept Anesthesiol, Xiamen 361003, FJ, Peoples R China.
   [Chen, Jingmeng] Xiamen Univ, Sch Med, Xiamen 361102, FJ, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Xiamen Eye Ctr, Wutong West Rd, Xiamen 361001, FJ, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Shenzhen Res Inst, Shenzhen 518063, GD, Peoples R China.
C3 Xiamen University; Xiamen University; Xiamen University; Xiamen
   University; Xiamen University
RP Wu, YL (通讯作者)，Xiamen Univ, Xiamen Eye Ctr, Wutong West Rd, Xiamen 361001, FJ, Peoples R China.; Wu, YL (通讯作者)，Xiamen Univ, Sch Med, Xiangan Hosp, Inst Eye, Xiangan South Rd, Xiamen, FJ, Peoples R China.
EM yalinw@xmu.edu.cn
FU China National Natural Science Foundation [81870671, 81570857]; Basic
   Research Program of Shenzhen Grant [JCYJ20180306173025004]; Natural
   Science Foundation of Fujian Province [2017J01148]; Sanming Project of
   Medicine in Shenzhen Grant [SZSM201612022]
FX This work was supported in part by China National Natural Science
   Foundation Grants 81870671 and 81570857 (to Yalin Wu), Basic Research
   Program of Shenzhen Grant JCYJ20180306173025004 (to Yalin Wu), Natural
   Science Foundation of Fujian Province Grant 2017J01148 (to Yalin Wu),
   and Sanming Project of Medicine in Shenzhen Grant SZSM201612022 (to Z.
   L. and Yalin Wu). The authors declare that they have no conflicts of
   interest with the contents of this article.
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NR 56
TC 3
Z9 4
U1 0
U2 12
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 15
PY 2020
VL 295
IS 20
BP 6958
EP 6971
DI 10.1074/jbc.RA120.013189
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA LS2IH
UT WOS:000536212600014
PM 32265302
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Borras, C
   Delaunay, K
   Slaoui, Y
   Abache, T
   Jorieux, S
   Naud, MC
   El Sanharawi, M
   Gelize, E
   Lassiaz, P
   An, N
   Kowalczuk, L
   Ayassami, C
   Moulin, A
   Behar-Cohen, F
   Mascarelli, F
   Dinet, V
AF Borras, Celine
   Delaunay, Kimberley
   Slaoui, Yousri
   Abache, Toufik
   Jorieux, Sylvie
   Naud, Marie-Christine
   El Sanharawi, Mohamed
   Gelize, Emmanuelle
   Lassiaz, Patricia
   An, Na
   Kowalczuk, Laura
   Ayassami, Cedric
   Moulin, Alexandre
   Behar-Cohen, Francine
   Mascarelli, Frederic
   Dinet, Virginia
TI Mechanisms of FH Protection Against Neovascular AMD
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE AMD; complement factor H; FH Y402H polymorphism; TSP-1; therapeutic
   target
ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; MEMBRANE ATTACK COMPLEX;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; GEOGRAPHIC ATROPHY;
   HEPARAN-SULFATE; MOUSE MODEL; IDENTIFICATION; LOCALIZATION
AB A common allele (402H) of the complement factor H (FH) gene is the major risk factor for age-related macular degeneration (AMD), the leading cause of blindness in the elderly population. Development and progression of AMD involves vascular and inflammatory components partly by deregulation of the alternative pathway of the complement system (AP). The loss of central vision results from atrophy and/or from abnormal neovascularization arising from the choroid. The functional link between FH, the main inhibitor of AP, and choroidal neovascularization (CNV) in AMD remains unclear. In a murine model of CNV used as a model for neovascular AMD (nAMD), intraocular human recombinant FH (recFH) reduced CNV as efficiently as currently used anti-VEGF (vascular endothelial growth factor) antibody, decreasing deposition of C3 cleavage fragments, membrane attack complex (MAC), and microglia/macrophage recruitment markers in the CNV lesion site. In sharp contrast, recFH carrying the H402 risk variant had no effect on CNV indicating a causal link to disease etiology. Only the recFH NTal region (recFH1-7), containing the CCPs1-4 C3-convertase inhibition domains and the CCP7 binding domain, exerted all differential biological effects. The CTal region (recFH7-20) containing the CCP7 and CCPs19-20 binding domains was antiangiogenic but did not reduce the microglia/macrophage recruitment. The antiangiogenic effect of both recFH1-20 and recFH-CCP7-20 resulted from thrombospondin-1 (TSP-1) upregulation independently of the C3 cleavage fragments generation. This study provides insight on the mechanistic role of FH in nAMD and invites to reconsider its therapeutic potential.
C1 [Borras, Celine; Delaunay, Kimberley; Naud, Marie-Christine; El Sanharawi, Mohamed; Gelize, Emmanuelle; Lassiaz, Patricia; An, Na; Ayassami, Cedric; Mascarelli, Frederic; Dinet, Virginia] Univ Paris, Sorbonne Univ, Inserm UMR1138, Ctr Rech Cordeliers, Paris, France.
   [Borras, Celine] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
   [Delaunay, Kimberley; Naud, Marie-Christine; El Sanharawi, Mohamed; Gelize, Emmanuelle; Lassiaz, Patricia; An, Na; Kowalczuk, Laura; Ayassami, Cedric; Moulin, Alexandre; Mascarelli, Frederic; Dinet, Virginia] INSERM, U1138, Paris, France.
   [Delaunay, Kimberley; Naud, Marie-Christine; El Sanharawi, Mohamed; Gelize, Emmanuelle; Lassiaz, Patricia; An, Na; Mascarelli, Frederic; Dinet, Virginia] Univ Pierre & Marie Curie Paris6, UMRS1138, Paris, France.
   [Slaoui, Yousri] CNRS, Lab Math & Applicat UMR 7348, Poitiers, France.
   [Abache, Toufik; Jorieux, Sylvie] Lab Francais Fractionnement & Biotechnol LFB, Lille, France.
   [Kowalczuk, Laura; Moulin, Alexandre] Lausanne Univ, Jules Gonin Eye Hosp, Dept Ophthalmol, Lausanne, Switzerland.
   [Behar-Cohen, Francine] Hop Cochin, AP HP, Ophtalmopole, Paris, France.
C3 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;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Universite Paris Cite; UDICE-French
   Research Universities; Sorbonne Universite; Universite Paris Cite;
   Centre National de la Recherche Scientifique (CNRS); Universite de
   Poitiers; University of Lausanne; Assistance Publique Hopitaux Paris
   (APHP); Hopital Universitaire Cochin - APHP; UDICE-French Research
   Universities; Universite Paris Cite
RP Behar-Cohen, F (通讯作者)，Hop Cochin, AP HP, Ophtalmopole, Paris, France.
EM francine.behar@gmail.com
OI behar cohen, francine/0000-0001-8571-9513; Dinet,
   virginie/0000-0002-5458-0253
FU Agence Nationale de la Recherche Scientifique RPIB Innovision; Ministere
   de la Recherche
FX This work was supported by the Agence Nationale de la Recherche
   Scientifique RPIB Innovision and the Ministere de la Recherche (Celine
   Borras, PhD).
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NR 39
TC 1
Z9 1
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 APR 3
PY 2020
VL 11
AR 443
DI 10.3389/fimmu.2020.00443
PG 16
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA LH1EB
UT WOS:000528531400001
PM 32318056
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kern, C
   Fu, DJ
   Kortuem, K
   Huemer, J
   Barker, D
   Davis, A
   Balaskas, K
   Keane, PA
   McKinnon, T
   Sim, DA
AF Kern, Christoph
   Fu, Dun Jack
   Kortuem, Karsten
   Huemer, Josef
   Barker, David
   Davis, Alison
   Balaskas, Konstantinos
   Keane, Pearse A.
   McKinnon, Tom
   Sim, Dawn A.
TI Implementation of a cloud-based referral platform in ophthalmology:
   making telemedicine services a reality in eye care
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PREVALENCE
AB Background Hospital Eye Services (HES) in the UK face an increasing number of optometric referrals driven by progress in retinal imaging. The National Health Service (NHS) published a 10-year strategy (NHS Long-Term Plan) to transform services to meet this challenge. In this study, we implemented a cloud-based referral platform to improve communication between optometrists and ophthalmologists.
   Methods Retrospective cohort study conducted at Moorfields Eye Hospital, Croydon (NHS Foundation Trust, London, UK). Patients classified into the HES referral pathway by contributing optometrists have been included into this study. Main outcome measures was the reduction of unnecessary referrals.
   Results After reviewing the patient's data in a web-based interface 54 (52%) out of 103 attending patients initially classified into the referral pathway did not need a specialist referral. Fourteen (14%) patients needing urgent treatment were identified. Usability was measured in duration for data input and reviewing which was an average of 9.2 min (median: 5.4; IQR: 3.4-8.7) for optometrists and 3.0 min (median: 3.0; IQR: 1.7-3.9) min for ophthalmologists. A variety of diagnosis was covered by this tool with dry age-related macular degeneration (n=34) being most common.
   Conclusion After implementation more than half of the HES referrals have been avoided. This platform offers a digital-first solution that enables rapid-access eye care for patients in community optometrists, facilitates communication between healthcare providers and may serve as a foundation for implementation of artificial intelligence.
C1 [Kern, Christoph; Fu, Dun Jack; Kortuem, Karsten; Huemer, Josef; Davis, Alison; Balaskas, Konstantinos; Keane, Pearse A.; Sim, Dawn A.] Moorfields Eye Hosp, London, England.
   [Kern, Christoph; Kortuem, Karsten] LMU, Univ Eye Hosp, Dept Ophthalmol, Munich, Germany.
   [Huemer, Josef] Tauernklinikum, Eye Dept, Zell, Austria.
   [Barker, David] Rawlings Opt, Purley, England.
   [Keane, Pearse A.; Sim, Dawn A.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, Biomed Ctr, London, England.
   [Keane, Pearse A.; Sim, Dawn A.] UCL Inst Ophthalmol, London, England.
   [Keane, Pearse A.; Sim, Dawn A.] UCL, Inst Ophthalmol, London, England.
   [McKinnon, Tom] Big Picture Med, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Munich; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London; University of London;
   University College London
RP Sim, DA (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, Med Retina Dept, London EC1V 2PD, England.
EM dawnsim@nhs.net
RI Balaskas, Konstantinos/ABD-5979-2020
OI Balaskas, Konstantinos/0000-0002-7690-6277; Kortuem,
   Karsten/0000-0001-9442-0708; Keane, Pearse/0000-0002-9239-745X
FU Department of Health [CS-2014-14-023] Funding Source: Medline
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NR 29
TC 40
Z9 40
U1 0
U2 6
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 2020
VL 104
IS 3
BP 312
EP 317
DI 10.1136/bjophthalmol-2019-314161
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KU8NM
UT WOS:000519969000004
PM 31320383
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Cheng, ZQ
   Yao, WJ
   Zheng, J
   Ding, WM
   Wan, Y
   Zhang, T
   Zhu, L
   Zhou, FF
AF Cheng, Zhengqi
   Yao, Wenjuan
   Zheng, Jian
   Ding, Weimin
   Wan, Yang
   Zhang, Ting
   Zhu, Ling
   Zhou, Fanfan
TI A derivative of betulinic acid protects human Retinal Pigment Epithelial
   (RPE) cells from cobalt chloride-induced acute hypoxic stress
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal Pigment Epithelium; Betulinic acid; Cobalt chloride; Hypoxic
   stress; Signaling pathways
ID OXIDATIVE STRESS; INDUCED APOPTOSIS; ARPE-19 CELLS; MACULAR
   DEGENERATION; PROGRAMMED NECROSIS; GLOBAL PREVALENCE; ERK1/2 ACTIVATION;
   ANTITUMOR AGENTS; CYCLE ARREST; Y-79 CELLS
AB The Retinal Pigment Epithelium (RPE) is a monolayer of cells located above the choroid. It mediates human visual cycle and nourishes photoreceptors. Hypoxia-induced oxidative stress to RPE is a vital cause of retinal degeneration such as the Age-related Macular Degeneration. Most of these retinal diseases are irreversible with no efficient treatment, therefore protecting RPE cells from hypoxia stress is an important way to prevent or slow down the progression of retinal degeneration. Betulinic acid (BA) and betulin (BE) are pentacyclic triterpenoids with anti-oxidative property, but little is known about their effect on RPE cells. We investigated the protective effect of BA, BE and their derivatives against cobalt chloride-induced hypoxia stress in RPE cells. Human ARPE-19 cells were exposed to BA, BE and their eighteen derivatives (named as H3-H20) that we customized through replacing moieties at C3 and C28 positions. We found that cobalt chloride reduced cell viability, increased Reactive Oxygen Species (ROS) production as well as induced apoptosis and necrosis in ARPE-19 cells. Interestingly, the pretreatment of 3-O-acetyl-glycyl- 28-O-glycyl-betulinic acid effectively protected cells from acute hypoxia stress induced by cobalt chloride. Our immunoblotting results suggested that this derivative attenuated the cobalt chloride-induced activation of Akt, Erk and JNK pathways. All findings were further validated in human primary RPE cells. In summary, this BA derivate has protective effect against the acute hypoxic stress in human RPE cells and may be developed into a candidate agent effective in the prevention of prevalent retinal diseases.
C1 [Cheng, Zhengqi; Zhou, Fanfan] Univ Sydney, Sch Pharm, Sydney, NSW 2006, Australia.
   [Yao, Wenjuan] Nantong Univ, Sch Pharm, Nantong, Jiangsu, Peoples R China.
   [Zheng, Jian; Wan, Yang] Northeast Forestry Univ, Ctr Bioact Prod, Minist Educ, Key Lab Salinealkali Vegetat Ecol Restorat, Harbin 150040, Heilongjiang, Peoples R China.
   [Ding, Weimin] Harbin Univ Sci & Technol, Sch Chem & Environm Engn, Harbin 150080, Heilongjiang, Peoples R China.
   [Zhang, Ting; Zhu, Ling] Univ Sydney, Save Sight Inst, Sydney, NSW 2000, Australia.
   [Zhang, Ting] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China.
   [Zhang, Ting] Sichuan Univ, West China Hosp, Canc Ctr, Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China.
C3 University of Sydney; Nantong University; Northeast Forestry University
   - China; Harbin University of Science & Technology; University of
   Sydney; Sichuan University; Sichuan University
RP Zhou, FF (通讯作者)，Univ Sydney, Sch Pharm, Sydney, NSW 2006, Australia.
EM Fanfan.zhou@sydney.edu.au
RI Zhu, Ling/M-3887-2013; Zhou, Fanfan/J-2327-2019; Zhou,
   Fanfan/M-4404-2013; Zhang, Ting/P-8913-2017
OI Zhu, Ling/0000-0003-0776-1630; Zhou, Fanfan/0000-0002-1982-1541; Zhou,
   Fanfan/0000-0002-1982-1541; Zhang, Ting/0000-0001-8074-8999
FU School of Pharmacy, the University of Sydney; University of Sydney
FX We want to thank Professor Paul Groundwater for his help in chemical
   description. This work was supported by internal grants of the School of
   Pharmacy, the University of Sydney. Dr. Fanfan Zhou is the Equity
   Fellowship holder of the University of Sydney.
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NR 91
TC 17
Z9 18
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2019
VL 180
BP 92
EP 101
DI 10.1016/j.exer.2018.12.011
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN7KO
UT WOS:000460368500013
PM 30578788
DA 2022-11-30
ER

PT J
AU Yang, C
   Tahiri, H
   Cai, CRR
   Gu, MQ
   Gagnon, C
   Hardy, P
AF Yang, Chun
   Tahiri, Houda
   Cai, Chenrongrong
   Gu, Muqing
   Gagnon, Carmen
   Hardy, Pierre
TI microRNA-181a inhibits ocular neovascularization by interfering with
   vascular endothelial growth factor expression
SO CARDIOVASCULAR THERAPEUTICS
LA English
DT Article
DE angiogenic factor; anti-angiogenesis; endothelial cell; extracellular
   miRNAs; miR-181a; neovascularization
ID OXYGEN-INDUCED RETINOPATHY; IN-VIVO; ANGIOGENIC PROPERTIES; CELL
   SURVIVAL; MODULATE; MICROPARTICLES; ERK5; IDENTIFICATION; MACROPHAGES;
   ATTENUATION
AB Aim: Excess angiogenesis or neovascularization plays a key role in the pathophysiology of several ocular diseases such as retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. microRNA-181a (miR-181a) was found highly expressed in retina and choroidal tissues. This study intends to investigate the role of miR-181a in the regulation of ocular neovascularization in different pathophysiological conditions.
   Method: We performed the RNA sequence to identify the microRNAs components of anti-angiogenic lymphocyte-derived microparticles (LMPs). The effect of miR-181a on human retinal endothelial cells proliferation was assessed in vitro. The impact of miR-181a on angiogenesis was confirmed using in vitro angiogenesis assay, ex vivo choroidal explant, and in vivo retinal neovascularization. The expression of major angiogenic factors was assessed by real-time qPCR.
   Results: RNA sequence revealed that miR-181a is selectively enriched in LMPs. Importantly, the inhibition of miR-181a significantly abrogated the effect of LMPs on endothelial viability, but overexpression of miR-181a reduced endothelial cell viability in a dose-dependent manner. miR-181a strongly inhibited in vitro angiogenesis and ex vivo choroidal neovascularization. The strong anti-angiogenic effect of miR-181a was also displayed on the retinal neovascularization of the in vivo mouse model of oxygen-induced retinopathy. In keeping with its effect, several angiogenesis-related genes were dysregulated in the miR-181a overexpressed endothelial cells.
   Conclusion: These data may open unexpected avenues for the development of miR-181a as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of neovascular diseases.
C1 [Yang, Chun; Tahiri, Houda; Cai, Chenrongrong; Gagnon, Carmen; Hardy, Pierre] Univ Montreal, Dept Pediat, Montreal, PQ, Canada.
   [Yang, Chun; Tahiri, Houda; Cai, Chenrongrong; Gagnon, Carmen; Hardy, Pierre] Univ Montreal, Dept Physiol, Montreal, PQ, Canada.
   [Yang, Chun; Tahiri, Houda; Cai, Chenrongrong; Gagnon, Carmen; Hardy, Pierre] Univ Montreal, Dept Pharmacol, Montreal, PQ, Canada.
   [Gu, Muqing] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Dept Gynecol Endocrinol, Beijing, Peoples R China.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal;
   Capital Medical University
RP Hardy, P (通讯作者)，CHU St Justine, Dept Pediat, Res Ctr, Montreal, PQ, Canada.
EM pierre.hardy@recherche-ste-justine.qc.ca
OI Yang, Chun/0000-0002-2648-9444
FU Canadian Institutes of Health Research [362383]
FX This work was supported by an operating grant to Pierre Hardy from the
   Canadian Institutes of Health Research (362383).
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NR 64
TC 14
Z9 16
U1 0
U2 5
PU WILEY-HINDAWI
PI LONDON
PA ADAM HOUSE, 3RD FL, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND
SN 1755-5914
EI 1755-5922
J9 CARDIOVASC THER
JI Cardiovasc. Ther.
PD JUN
PY 2018
VL 36
IS 3
AR e12329
DI 10.1111/1755-5922.12329
PG 9
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA GF4ZL
UT WOS:000431973600009
PM 29608244
OA Bronze
DA 2022-11-30
ER

PT J
AU Yang, JJ
   Chen, S
   Abecasis, G
AF Yang, Jingjing
   Chen, Sai
   Abecasis, Goncalo
CA IAMDGC
TI Improved score statistics for meta-analysis in single-variant and
   gene-level association studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE meta-analysis; multi-ethnic studies; population stratification; score
   statistics; unbalanced studies
ID GENOME-WIDE ASSOCIATION; RARE VARIANTS; LOCI; RISK
AB Meta-analysis is now an essential tool for genetic association studies, allowing them to combine large studies and greatly accelerating the pace of genetic discovery. Although the standard meta-analysis methods perform equivalently as the more cumbersome joint analysis under ideal settings, they result in substantial power loss under unbalanced settings with various case-control ratios. Here, we investigate the power loss problem by the standard meta-analysis methods for unbalanced studies, and further propose novel meta-analysis methods performing equivalently to the joint analysis under both balanced and unbalanced settings. We derive improved meta-score-statistics that can accurately approximate the joint-score-statistics with combined individual-level data, for both linear and logistic regression models, with and without covariates. In addition, we propose a novel approach to adjust for population stratification by correcting for known population structures through minor allele frequencies. In the simulated gene-level association studies under unbalanced settings, our method recovered up to 85% power loss caused by the standard methods. We further showed the power gain of our methods in gene-level tests with 26 unbalanced studies of age-related macular degeneration. In addition, we took the meta-analysis of three unbalanced studies of type 2 diabetes as an example to discuss the challenges of meta-analyzing multi-ethnic samples. In summary, our improved meta-score-statistics with corrections for population stratification can be used to construct both single-variant and gene-level association studies, providing a useful framework for ensuring well-powered, convenient, cross-study analyses.
C1 [Yang, Jingjing; Chen, Sai; Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Yang, Jingjing] Emory Univ, Sch Med, Ctr Computat & Quantitat Genet, Dept Human Genet, Atlanta, GA USA.
C3 University of Michigan System; University of Michigan; Emory University
RP Abecasis, G (通讯作者)，Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.; Yang, JJ (通讯作者)，Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
EM jyang51@emory.edu; goncalo@umich.edu
RI Yang, Jingjing/X-5013-2019
OI Yang, Jingjing/0000-0002-4191-4138
FU National Institutes of Health (NIH) [R01HG007022]; Department of Human
   Genetics at the Emory University School of Medicine; NATIONAL HUMAN
   GENOME RESEARCH INSTITUTE [R01HG007022] Funding Source: NIH RePORTER
FX This work was supported by the National Institutes of Health (NIH) grant
   R01HG007022 and the start-up fund provided by Department of Human
   Genetics at the Emory University School of Medicine. The authors would
   like to thank Dr. Dajiang Liu (Pennsylvania StateUniversity), Dr. Shuang
   Feng (graduated Ph.D. student from University of Michigan), and Dr.
   Shawn Lee (University of Michigan) for their inspiration and valuable
   comments on this work. Especially, the authors want to thank all
   investigators of the IAMDGC, FUSION, METSIM, and MGI studies for
   providing the real data of the AMD and T2D studies in this work.
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NR 29
TC 5
Z9 5
U1 0
U2 4
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 JUN
PY 2018
VL 42
IS 4
BP 333
EP 343
DI 10.1002/gepi.22123
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA GK1MV
UT WOS:000435882500002
PM 29696691
OA Green Published, Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Maa, AY
   Patel, S
   Chasan, JE
   Delaune, W
   Lynch, MG
AF Maa, April Y.
   Patel, Shivangi
   Chasan, Joel E.
   Delaune, William
   Lynch, Mary G.
TI Retrospective Evaluation of a Teleretinal Screening Program in Detecting
   Multiple Nondiabetic Eye Diseases
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE telemedicine; teleophthalmology; teleretinal; ocular screening
ID DIABETIC-RETINOPATHY; MACULAR DEGENERATION; RETINAL PHOTOGRAPHY;
   TELEMEDICINE; TELEOPHTHALMOLOGY; OPHTHALMOSCOPY; GLAUCOMA; ALBERTA;
   TELEGLAUCOMA; SPECIFICITY
AB Background: Diabetic teleretinal screening programs have been utilized successfully across the world to detect diabetic retinopathy (DR) and are well validated. Less information, however, exists on the ability of teleretinal imaging to detect nondiabetic ocular pathology. Introduction: This study performed a retrospective evaluation to assess the ability of a community-based diabetic teleretinal screening program to detect common ocular disease other than DR. Materials and Methods: A retrospective chart review of 1,774 patients who underwent diabetic teleretinal screening was performed. Eye clinic notes from the Veterans Health Administration's electronic medical record, Computerized Patient Record System, were searched for each of the patients screened through teleretinal imaging. When a face-to-face examination note was present, the physical findings were compared to those obtained through teleretinal imaging. Sensitivity, specificity, and positive and negative predictive values were calculated for suspicious nerve, cataract, and age-related macular degeneration. Results: A total of 903 patients underwent a clinical examination. The positive predictive value was highest for cataract (100%), suspicious nerve (93%), and macular degeneration (90%). The negative predictive value and the percent agreement between teleretinal imaging and a clinical examination were over 90% for each disease category. Discussion: A teleretinal imaging protocol may be used to screen for other common ocular diseases. Conclusion: It may be feasible to use diabetic teleretinal photographs to screen patients for other potential eye diseases. Additional elements of the eye workup may be added to enhance accuracy of disease detection. Further study is necessary to confirm this initial retrospective review.
C1 [Maa, April Y.; Patel, Shivangi; Lynch, Mary G.] Atlanta VA Med Ctr, Div Ophthalmol, MC 112E,1670 Clairmont Rd, Decatur, GA 30033 USA.
   [Maa, April Y.; Chasan, Joel E.; Lynch, Mary G.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
   [Delaune, William] Atlanta VA Med Ctr, Ctr Visual & Neurocognit Rehabil, Decatur, GA USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Atlanta VA Health Care System; Atlanta VA Medical Center; Emory
   University; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Atlanta VA Health Care System; Atlanta VA Medical
   Center
RP Maa, AY (通讯作者)，Atlanta VA Med Ctr, Div Ophthalmol, MC 112E,1670 Clairmont Rd, Decatur, GA 30033 USA.
EM april.maa2@va.gov
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NR 45
TC 18
Z9 18
U1 0
U2 2
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 JAN
PY 2017
VL 23
IS 1
BP 42
EP 49
DI 10.1089/tmj.2016.0039
PG 8
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA EH5XM
UT WOS:000391846400007
PM 27310867
DA 2022-11-30
ER

PT J
AU Mollick, T
   Mohlin, C
   Johansson, K
AF Mollick, Tanzina
   Mohlin, Camilla
   Johansson, Kjell
TI Human neural progenitor cells decrease photoreceptor degeneration,
   normalize opsin distribution and support synapse structure in cultured
   porcine retina
SO BRAIN RESEARCH
LA English
DT Article
DE Photoreceptor degeneration; Synapse; Opsin; Gliosis; Neuroprotection
ID PIGMENT EPITHELIUM; STEM-CELLS; IN-VITRO; ORGANOTYPIC CULTURE;
   NEUROTROPHIC FACTOR; EXPERIMENTAL-MODEL; PROTEIN PSD-95; GANGLION-CELLS;
   MOUSE RETINA; TIME-COURSE
AB Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Muller cell gliosis only seemed to be alleviated in terms of reduced Muller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Muller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Mollick, Tanzina; Johansson, Kjell] Univ Orebro, Sch Hlth & Med, S-31705 Orebro, Sweden.
   [Mohlin, Camilla] Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden.
C3 Orebro University; Linnaeus University
RP Johansson, K (通讯作者)，Univ Orebro, Sch Hlth & Med, S-31705 Orebro, Sweden.
EM kjell.johansson@oru.se
RI mohlin, camilla/AAP-2726-2020
OI mohlin, camilla/0000-0002-9301-1977
FU faculty of Natural Sciences at Linnaeus University; faculty of Medical
   Sciences at Orebro University; Olle Engkvist Foundation; Ogonfonden;
   Crown Princess Margaretas Committee for the Blind; Edwin Jordan
   Foundation
FX Funding to support this study was provided by the faculty of Natural
   Sciences at Linnaeus University, the faculty of Medical Sciences at
   Orebro University, Olle Engkvist Foundation, Ogonfonden, the Crown
   Princess Margaretas Committee for the Blind and Edwin Jordan Foundation.
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NR 75
TC 19
Z9 19
U1 0
U2 12
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD SEP 1
PY 2016
VL 1646
BP 522
EP 534
DI 10.1016/j.brainres.2016.06.039
PG 13
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA DT9TH
UT WOS:000381844700059
PM 27369448
DA 2022-11-30
ER

PT J
AU Gille, H
   Hulsmeyer, M
   Trentmann, S
   Matschiner, G
   Christian, HJ
   Meyer, T
   Amirkhosravi, A
   Audoly, LP
   Hohlbaum, AM
   Skerra, A
AF Gille, Hendrik
   Huelsmeyer, Martin
   Trentmann, Stefan
   Matschiner, Gabriele
   Christian, Hans Juergen
   Meyer, Todd
   Amirkhosravi, Ali
   Audoly, Laurent P.
   Hohlbaum, Andreas M.
   Skerra, Arne
TI Functional characterization of a VEGF-A-targeting Anticalin, prototype
   of a novel therapeutic human protein class
SO ANGIOGENESIS
LA English
DT Article
DE Angiogenesis; Cancer; Lipocalin; Protein; engineering; Protein scaffold
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN MONOCLONAL-ANTIBODY; TEAR LIPOCALIN
   REVEALS; VASCULAR-PERMEABILITY; CRYSTAL-STRUCTURE; HIGHLY POTENT; TUMOR;
   BEVACIZUMAB; PHARMACOKINETICS; COMPLEXES
AB Human tear lipocalin (Tlc) was utilized as a protein scaffold to engineer an Anticalin that specifically binds and functionally blocks vascular endothelial growth factor A (VEGF-A), a pivotal inducer of physiological angiogenesis that also plays a crucial role in several neovascular diseases. Starting from a naive combinatorial library where residues that form the natural ligand-binding site of Tlc were randomized, followed by affinity maturation, the final Anticalin PRS-050 was selected to bind all major splice forms of VEGF-A with picomolar affinity. Moreover, this Anticalin cross-reacts with the murine ortholog. PRS-050 efficiently antagonizes the interaction between VEGF-A and its cellular receptors, and it inhibits VEGF-induced mitogenic signaling as well as proliferation of primary human endothelial cells with subnanomolar IC50 values. Intravitreal administration of the Anticalin suppressed VEGF-induced blood-retinal barrier breakdown in a rabbit model. To allow lasting systemic neutralization of VEGF-A in vivo, the plasma half-life of the Anticalin was extended by site-directed PEGylation. The modified Anticalin efficiently blocked VEGF-mediated vascular permeability as well as growth of tumor xenografts in nude mice, concomitantly with reduction in microvessel density. In contrast to bevacizumab, the Anticalin did not trigger platelet aggregation and thrombosis in human Fc gamma RIIa transgenic mice, thus suggesting an improved safety profile. Since neutralization of VEGF-A activity is well known to exert beneficial effects in cancer and other neovascular diseases, including wet age-related macular degeneration, this Anticalin offers a novel potent small protein antagonist for differentiated therapeutic intervention in oncology and ophthalmology.
C1 [Gille, Hendrik; Huelsmeyer, Martin; Trentmann, Stefan; Matschiner, Gabriele; Christian, Hans Juergen; Audoly, Laurent P.; Hohlbaum, Andreas M.] Pieris Pharmaceut GmbH, D-85354 Freising Weihenstephan, Germany.
   [Skerra, Arne] Tech Univ Munich, Lehrstuhl Biol Chem, D-85350 Freising Weihenstephan, Germany.
   [Meyer, Todd; Amirkhosravi, Ali] Florida Hosp, Thrombosis Res Ctr, Orlando, FL USA.
C3 Technical University of Munich; Adventist Health Services; AdventHealth
RP Matschiner, G (通讯作者)，Pieris Pharmaceut GmbH, Lise Meitner Str 30, D-85354 Freising Weihenstephan, Germany.
EM Matschiner@pieris.com; skerra@tum.de
RI Skerra, Arne/A-2269-2013
OI Skerra, Arne/0000-0002-5717-498X
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NR 60
TC 24
Z9 26
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2016
VL 19
IS 1
BP 79
EP 94
DI 10.1007/s10456-015-9490-5
PG 16
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA DA2KY
UT WOS:000367624900007
PM 26650228
DA 2022-11-30
ER

PT J
AU Dhakal, K
   Batabyal, S
   Wright, W
   Kim, YT
   Mohanty, S
AF Dhakal, Kamal
   Batabyal, Subrata
   Wright, Weldon
   Kim, Young-tae
   Mohanty, Samarendra
TI Optical delivery of multiple opsin-encoding genes leads to targeted
   expression and white-light activation
SO LIGHT-SCIENCE & APPLICATIONS
LA English
DT Article
DE gene delivery; optogenetics; optoporation; vision restoration
ID FEMTOSECOND LASER-PULSES; RESTORES VISUAL RESPONSES; PHOTORECEPTOR
   DEGENERATION; MAMMALIAN-CELLS; INFRARED-LASER; ECTOPIC EXPRESSION;
   MACROMOLECULES; TRANSFECTION; OPTOPORATION; EXCITATION
AB In photodegenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), progressive loss of vision occurs as a result of degeneration of the periphery of the retina and the macula, respectively. Current optogenetic stimulation-based approaches to vision restoration offer the advantages of cellular specificity, high resolution, and minimal invasiveness over electrode arrays; however, the clinical translation of optogenetic activation suffers from the lack of a method for the delivery of opsins into spatially targeted regions of a retina that has degenerated. Non-targeted opsin delivery through viral or non-viral methods to non-photodegenerated retinal areas will perturb these already functioning retinal regions. Furthermore, viral methods are subject to limitations on the delivery of large plasmids, such as fusion constructs of multiple spectrally separated opsins (e.g., channelrhodopsin-2 (ChR2), chimeric opsin variants (C1V1), ReaChR), which can provide higher photo-excitability than can a single narrow-band opsin under ambient light conditions. Here, we report the ultrafast near-infrared laser-based spatially targeted transfection of single and multiple opsins and present a comparison with the opsin expression distribution achieved using another non-viral, but non-targeted, transfection method, lipofection. Functional evaluation of cells transfected with multiple opsins using the laser method revealed a significantly higher white-light-induced photocurrent than in cells expressing a single opsin (ChR2). The laser-assisted targeted delivery of multiple opsin-encoding genes to the peripheral retina/macula is ideal for sensitizing retinal areas that have degenerated, thus paving the way toward the restoration of lost vision in RP/AMD patients.
C1 [Dhakal, Kamal; Batabyal, Subrata; Mohanty, Samarendra] Univ Texas Arlington, Biophys & Physiol Lab, Arlington, TX 76019 USA.
   [Wright, Weldon; Mohanty, Samarendra] NanoScope Technol LLC, Arlington, TX USA.
   [Kim, Young-tae] Univ Texas Arlington, Dept Bioengn, Arlington, TX 76019 USA.
C3 University of Texas System; University of Texas Arlington; University of
   Texas System; University of Texas Arlington
RP Mohanty, S (通讯作者)，Univ Texas Arlington, Biophys & Physiol Lab, Arlington, TX 76019 USA.
EM smohanty@uta.edu
FU National Institute of Health [NS084311]; Office of the President and
   Provost of The University of Texas at Arlington
FX The authors would like to thank Christopher Cote, Gregory Cervenka,
   Prof. Qing Lin, Saurabh Kokane, and Sarmishtha Satpathy (UTA) for their
   assistance with the experiments. Samarendra Mohanty would like to thank
   K. Deisseroth (Stanford) for the ChR2 and C1V1 plasmids and J. Lin
   (UCSD) for the ReaChR construct. Samarendra Mohanty would also like to
   acknowledge the support from the National Institute of Health (NS084311)
   and the Office of the President and Provost of The University of Texas
   at Arlington.
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NR 29
TC 12
Z9 13
U1 0
U2 14
PU CHINESE ACAD SCIENCES, CHANGCHUN INST OPTICS FINE MECHANICS AND PHYSICS
PI CHANGCHUN
PA 3888, DONGNANHU ROAD, CHANGCHUN, 130033, PEOPLES R CHINA
SN 2047-7538
J9 LIGHT-SCI APPL
JI Light-Sci. Appl.
PD NOV
PY 2015
VL 4
AR e352
DI 10.1038/lsa.2015.125
PG 8
WC Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Optics
GA CY9KO
UT WOS:000366726000003
OA gold
DA 2022-11-30
ER

PT J
AU Kambhampati, SP
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AF Kambhampati, Siva P.
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TI Systemic and Intravitreal Delivery of Dendrimers to Activated
   Microglia/Macrophage in Ischemia/Reperfusion Mouse Retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroid; dendrimers; ischemia; microglia; retina
ID ISCHEMIA-REPERFUSION INJURY; POLYAMIDOAMINE DENDRIMERS; IN-VITRO;
   MICROGLIA; NEUROINFLAMMATION; BIODISTRIBUTION; DEGENERATION;
   BEVACIZUMAB; MINOCYCLINE; INHIBITION
AB PURPOSE. Microglial activation and associated neuroinflammation play a key role in the pathogenesis of many diseases of the retina, including viral infection, diabetes, and retinal degeneration. Strategies to target activated microglia and macrophages and attenuate inflammation may be valuable in treating these diseases. We seek to develop dendrimer-based formulations that target retinal microglia and macrophages in a pathology-dependent manner, and deliver drugs, either intravenously or intravitreally.
   METHODS. Retinal uptake of cyanine dye (Cy5)-conjugated dendrimer (D-Cy5) was assessed in normal and ischemia/reperfusion (I/R) mouse eyes. Microglia/macrophage uptake of the dendrimer was assessed with immunofluorescence using rabbit Iba-1 antibody with Cy3-tagged secondary antibody (microglia/macrophage). Uptake in retina and other organs was quantified using fluorescence spectroscopy.
   RESULTS. Clearance of D-Cy5 from normal eyes was almost complete by 72 hours after intravitreal injection and 24 hours after intravenous delivery. In eyes with activated microglia after I/R injury, D-Cy5 was retained by activated microglia/macrophage (Iba1(+) cells) up to 21 days after intravitreal and intravenous administration. In I/R eyes, the relative retention of intravitreal and intravenous D-Cy5 was comparable, if a 30-fold higher intravenous dose was used.
   CONCLUSIONS. Intravitreal and systemic dendrimers target activated microglia and show qualitatively similar retinal biodistribution when administered by either route. Results provide proof-of-concept insights for developing dendrimer drug formulations as treatment options for retinal diseases associated with microglia or macrophage activation such as age-related macular degeneration, diabetic retinopathy, and retinal degenerations.
C1 [Kambhampati, Siva P.; Clunies-Ross, Alexander J. M.; Bhutto, Imran; Mishra, Manoj K.; Edwards, Malia; McLeod, D. Scott; Kannan, Rangaramanujam M.; Lutty, Gerard] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Ctr Nanomed, Dept Ophthalmol, Baltimore, MD 21287 USA.
   [Kambhampati, Siva P.] Wayne State Univ, Dept Biomed Engn, Detroit, MI USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Wayne State University
RP Lutty, G (通讯作者)，Johns Hopkins Univ Hosp, Wilmer Eye Inst, M041 Smith Bldg,400 North Broadway, Baltimore, MD 21287 USA.
EM krangar1@jhmi.edu; glutty@jhmi.edu
RI Kambhampati, Siva Pramodh/AAK-6269-2020
FU NATIONAL EYE INSTITUTE [R01EY025304, P30EY001765, R01EY023962,
   R01EY009357, R01EY016151] Funding Source: NIH RePORTER; NEI NIH HHS
   [EY016151, P30 EY001765, EY01765, R01 EY009357, R01 EY016151, R01
   EY025304, EY09357, EY025304, R01 EY023962] Funding Source: Medline
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NR 37
TC 54
Z9 54
U1 1
U2 17
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 2015
VL 56
IS 8
BP 4413
EP 4424
DI 10.1167/iovs.14-16250
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT5WV
UT WOS:000362882700026
PM 26193917
OA Green Published
DA 2022-11-30
ER

PT J
AU Adler, L
   Boyer, NP
   Anderson, DM
   Spraggins, JM
   Schey, KL
   Hanneken, A
   Ablonczy, Z
   Crouch, RK
   Koutalos, Y
AF Adler, Leopold
   Boyer, Nicholas P.
   Anderson, David M.
   Spraggins, Jeffrey M.
   Schey, Kevin L.
   Hanneken, Anne
   Ablonczy, Zsolt
   Crouch, Rosalie K.
   Koutalos, Yiannis
TI Determination of N-retinylidene-N-retinylethanolamine (A2E) levels in
   central and peripheral areas of human retinal pigment epithelium
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID LIPOFUSCIN FLUOROPHORE; AGE PIGMENT; FUNDUS AUTOFLUORESCENCE; COMPLEMENT
   ACTIVATION; SPATIAL-DISTRIBUTION; FLUORESCENCE; RPE; ACCUMULATION;
   BIOSYNTHESIS; BISRETINOIDS
AB The bis-retinoid N-retinylidene-N-retinylethanolamine (A2E) is one of the major components of lipofuscin, a fluorescent material that accumulates with age in the lysosomes of the retinal pigment epithelium (RPE) of the human eye. Lipofuscin, as well as A2E, exhibit a range of cytotoxic properties, which are thought to contribute to the pathogenesis of degenerative diseases of the retina such as Age-related Macular Degeneration. Consistent with such a pathogenic role, high levels of lipofuscin fluorescence are found in the central area of the human RPE, and decline toward the periphery. Recent reports have however suggested a surprising incongruence between the distributions of lipofuscin and A2E in the human RPE, with A2E levels being lowest in the central area and increasing toward the periphery. To appraise such a possibility, we have quantified the levels of A2E in the central and peripheral RPE areas of 10 eyes from 6 human donors (ages 75-91 years) with HPLC and UV/VIS spectroscopy. The levels of A2E in the central area were on average 3-6 times lower than in peripheral areas of the same eye. Furthermore, continuous accumulation of selected ions (CASI) imaging mass spectrometry showed the presence of A2E in the central RPE, and at lower intensities than in the periphery. We have therefore corroborated that in human RPE the levels of A2E are lower in the central area compared to the periphery. We conclude that the levels of A2E cannot by themselves provide an explanation for the higher lipofuscin fluorescence found in the central area of the human RPE.
C1 [Adler, Leopold; Boyer, Nicholas P.; Ablonczy, Zsolt; Crouch, Rosalie K.; Koutalos, Yiannis] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Anderson, David M.; Spraggins, Jeffrey M.; Schey, Kevin L.] Vanderbilt Univ Sch Med, Mass Spectrometry Res Ctr, Nashville, TN USA.
   [Hanneken, Anne] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
C3 Medical University of South Carolina; Vanderbilt University; Scripps
   Research Institute
RP Koutalos, Y (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA.
EM koutalo@musc.edu
OI Spraggins, Jeffrey/0000-0001-9198-5498; Hanneken,
   Anne/0000-0002-7390-2596
FU NIH [EY014850, EY019065, GM103391]; Research to Prevent Blindness, Inc.,
   New York, NY; NATIONAL EYE INSTITUTE [R01EY019065, R01EY014850] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [P41GM103391] Funding Source: NIH RePORTER
FX The research was supported by NIH grants EY014850, EY019065, GM103391,
   and an unrestricted grant to MUSC Storm Eye Institute from Research to
   Prevent Blindness, Inc., New York, NY.
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NR 41
TC 20
Z9 20
U1 0
U2 8
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1474-905X
EI 1474-9092
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PY 2015
VL 14
IS 11
BP 1983
EP 1990
DI 10.1039/c5pp00156k
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA CV2KH
UT WOS:000364085000007
PM 26323192
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Duisdieker, V
   Fleckenstein, M
   Zilkens, KM
   Steinberg, JS
   Holz, FG
   Schmitz-Valckenberg, S
AF Duisdieker, Viola
   Fleckenstein, Monika
   Zilkens, Katharina M.
   Steinberg, Julia S.
   Holz, Frank G.
   Schmitz-Valckenberg, Steffen
TI Long-Term Follow-Up of Fundus Autofluorescence Imaging Using Wide-Field
   Scanning Laser Ophthalmoscopy
SO OPHTHALMOLOGICA
LA English
DT Article
DE Wide-field fundus autofluorescence; Peripheral retinal pathologies;
   Scanning laser ophthalmoscopy
ID PERIPHERAL AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; ABNORMALITIES
AB Aim: To evaluate the variation of peripheral alterations in different retinal diseases over a period of >3 years by using wide-field fundus autofluorescence (FAF) scanning laser ophthalmoscopy (SLO). Methods: A total of 26 eyes from 13 patients (median age 66 years, range 19-80) with age-related macular degeneration and other retinal degenerations were examined. In 2009, the Optos P200CAF prototype and from 2012 onwards, the Optos 200Tx (Optos plc, Scotland) were used for wide-field FAF SLO (excitation 532 nm). Results: The area involvement in outer retinal pathological alterations, such as atrophy and mottling of the retinal pigment epithelium far beyond the vascular arcades, was readily and better visualized within one image frame using wide-field FAF as compared to pseudocolor SLO of the same device. Over time, progression of existing and the development of de novo peripheral lesions were recorded with a concomitant enlargement of central lesions. In two cases (unilateral paravenous pigmented choroidal atrophy and suspected phenocopy of retinal dystrophy), no longitudinal changes of the topographic distribution of peripheral FAF intensities were noted. Conclusions: Wide-field FAF SLO allows the mapping of dynamic changes at the outer retina far beyond the vascular arcades. While its ability to detect and monitor these changes appears to be better than that of pseudocolor imaging, wide-field FAF SLO may not only be helpful to assess more widespread retinal dysfunction, but may also be useful for longitudinal assessments in natural history studies and interventional clinical trials. (C) 2015 S. Karger AG, Basel
C1 [Duisdieker, Viola; Fleckenstein, Monika; Zilkens, Katharina M.; Steinberg, Julia S.; Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, Dept Ophthalmol, DE-53127 Bonn, Germany.
C3 University of Bonn
RP Schmitz-Valckenberg, S (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, DE-53127 Bonn, Germany.
EM steffen.schmitz-valckenberg@ukb.uni-bonn.de
OI Fleckenstein, Monika/0000-0001-8321-8037
FU Optos Ltd.; Heidelberg Engineering GmbH; Zeiss MediTec
FX Optos Ltd. has provided research funding and material (P200 CAF
   prototype and 200Tx device). All authors have received research funding
   and material by Heidelberg Engineering GmbH and Zeiss MediTec.
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NR 17
TC 6
Z9 6
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2015
VL 234
IS 4
BP 218
EP 226
DI 10.1159/000439358
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CU3NW
UT WOS:000363433100005
PM 26394020
DA 2022-11-30
ER

PT J
AU Chen, Y
   Zhong, MR
   Liang, L
   Gu, FJ
   Peng, H
AF Chen, Ying
   Zhong, Murui
   Liang, Liang
   Gu, Fengjuan
   Peng, Hui
TI Interleukin-17 Induces Angiogenesis in Human Choroidal Endothelial Cells
   In Vitro
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroidal endothelial cell; neovascularization; PI3K; Rac1; RhoA;
   F-actin
ID MACULAR DEGENERATION; MIGRATION; IL-17; NEOVASCULARIZATION; ACTIVATION;
   GROWTH; RAC; RANIBIZUMAB; RECEPTOR; HORIZON
AB PURPOSE. The proinflammatory cytokine interleukin-17 (IL-17) has recently been shown to promote angiogenesis. In addition, a receptor for IL-17, IL-17 receptor C (IL-17RC), is enriched in patients with wet, age-related macular degeneration (AMD), a disease characterized by the formation of choroidal neovascularization. However, the role of IL-17 in choroidal endothelial cells (CECs) angiogenesis has not been defined. This study was conducted to determine the effect of IL-17 on proliferation, migration, and tube formation of human CECs.
   METHODS. Expression patterns of IL-17 receptor A (IL-17RA) and IL-17RC on isolated human CECs were analyzed by flow cytometry and immunofluorescent staining. Proangiogenic effects of IL-17 on CECs was determined by proliferation assays with a water-soluble tetrazolium cell proliferation reagent kit, wound healing migration assays, and tube formation assays using basement membrane matrix. Cytoskeletal changes were observed by F-actin immunofluorescent staining. Activated Rac1 and RhoA levels were analyzed by pull-down assays.
   RESULTS. Interleukin-17RA and IL-17RC were present on human CECs. Interleukin-17 enhanced migration and tube formation but did not affect proliferation. Moreover, IL-17 induced rearrangement of the actin cytoskeleton and upregulated activated Rac1 and RhoA in CECs. The PI3K inhibitor wortmannin suppressed CEC migration, cytoskeleton rearrangement, and upregulation of activated Rac1 and RhoA induced by IL-17.
   CONCLUSIONS. Interleukin-17 elicits a proangiogenesis effect on human CECs in vitro by promoting migration and tube formation. The promoted migration effect was dependent on PI3K-Rac1 and RhoA-mediated actin cytoskeleton remodeling.
C1 [Peng, Hui] Chongqing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Chongqing 400016, Peoples R China.
   [Chen, Ying; Zhong, Murui; Liang, Liang; Gu, Fengjuan; Peng, Hui] Chongqing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Chongqing Key Lab Ophthalmol,Chongqing Eye Inst, Chongqing 400016, Peoples R China.
C3 Chongqing Medical University; Chongqing Medical University
RP Peng, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, 1 You Yi Rd, Chongqing 400016, Peoples R China.
EM penghui20140614@126.com
FU National Natural Science Foundation of China [81200704]; National Basic
   Research Program of China (program 973) [2011CB510200]
FX Supported by National Natural Science Foundation of China Grant 81200704
   and National Basic Research Program of China (program 973) Grant
   2011CB510200.
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NR 31
TC 25
Z9 27
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 2014
VL 55
IS 10
DI 10.1167/iovs.14-15029
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AT1ZS
UT WOS:000344730500046
PM 25228547
DA 2022-11-30
ER

PT J
AU Chang, YC
   Chang, WC
   Hung, KH
   Yang, DM
   Cheng, YH
   Liao, YW
   Woung, LC
   Tsai, CY
   Hsu, CC
   Lin, TC
   Liu, JH
   Chiou, SH
   Peng, CH
   Chen, SJ
AF Chang, Yun-Ching
   Chang, Wei-Chao
   Hung, Kuo-Hsuan
   Yang, Der-Ming
   Cheng, Yung-Hsin
   Liao, Yi-Wen
   Woung, Lin-Chung
   Tsai, Ching-Yao
   Hsu, Chih-Chien
   Lin, Tai-Chi
   Liu, Jorn-Hon
   Chiou, Shih-Hwa
   Peng, Chi-Hsien
   Chen, Shih-Jen
TI The generation of induced pluripotent stem cells for macular
   degeneration as a drug screening platform: identification of curcumin as
   a protective agent for retinal pigment epithelial cells against
   oxidative stress
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE oxidative stress; age-related macular degeneration; patient-specific
   induced pluripotent stem cells; retinal pigment epithelial; antioxidant;
   curcumin
ID IN-VITRO; T-CELLS; PATHOGENESIS; INDUCTION; DISEASE; PATHOPHYSIOLOGY;
   ANTIOXIDANTS; EXPRESSION; MODEL; RISK
AB Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress.
C1 [Chang, Yun-Ching; Yang, Der-Ming; Cheng, Yung-Hsin; Liao, Yi-Wen; Hsu, Chih-Chien; Lin, Tai-Chi; Chiou, Shih-Hwa; Peng, Chi-Hsien; Chen, Shih-Jen] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei 11217, Taiwan.
   [Chang, Yun-Ching; Cheng, Yung-Hsin; Chiou, Shih-Hwa] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 112, Taiwan.
   [Chang, Yun-Ching; Hsu, Chih-Chien; Lin, Tai-Chi; Chiou, Shih-Hwa; Chen, Shih-Jen] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 11217, Taiwan.
   [Chang, Wei-Chao] China Med Univ, Grad Inst Canc Biol, Taichung, Taiwan.
   [Chang, Wei-Chao] China Med Univ Hosp, Ctr Mol Med, Taichung, Taiwan.
   [Hung, Kuo-Hsuan] Natl Yang Ming Univ Hosp, Div Ophthalmol, Ilan, Taiwan.
   [Hung, Kuo-Hsuan; Chiou, Shih-Hwa] Natl Yang Ming Univ, Sch Med, Inst Clin Med, Taipei 112, Taiwan.
   [Woung, Lin-Chung; Tsai, Ching-Yao] Taipei City Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Liu, Jorn-Hon] Cheng Hsin Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Peng, Chi-Hsien] Shin Kong Wu Ho Su Mem Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Peng, Chi-Hsien] Fu Jen Catholic Univ, Taipei, Taiwan.
C3 Taipei Veterans General Hospital; National Yang Ming Chiao Tung
   University; Taipei Veterans General Hospital; China Medical University
   Taiwan; China Medical University Taiwan; China Medical University
   Hospital - Taiwan; National Yang Ming Chiao Tung University; Taipei City
   Hospital; Cheng Hsin General Hospital; Shin Kong Wu Ho Su Memorial
   Hospital; Fu Jen Catholic University
RP Peng, CH (通讯作者)，Taipei Vet Gen Hosp, Dept Med Res & Educ, 201 Sec 2,Shih Pai Rd, Taipei 11217, Taiwan.
EM chpeng1008@gmail.com; sjchen@vghtpe.gov.tw
RI Yang, De-Ming/AAW-9886-2020
OI Yang, De-Ming/0000-0002-6923-4855; WOUNG, LIN-CHUNG/0000-0002-0700-7606
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NR 50
TC 67
Z9 71
U1 2
U2 25
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 AUG 1
PY 2014
VL 6
AR 191
DI 10.3389/fnagi.2014.00191
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AN9MA
UT WOS:000340929800001
PM 25136316
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Danis, RP
   Domalpally, A
   Chew, EY
   Clemons, TE
   Armstrong, J
   SanGiovanni, JP
   Ferris, FL
AF Danis, Ronald P.
   Domalpally, Amitha
   Chew, Emily Y.
   Clemons, Traci E.
   Armstrong, Jane
   SanGiovanni, John Paul
   Ferris, Frederick L., III
CA AREDS2 Study Grp
TI Methods and Reproducibility of Grading Optimized Digital Color Fundus
   Photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number
   2)
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE color photographic imaging; AMD; reproducibility
ID OPTICAL COHERENCE TOMOGRAPHY; AUTOFLUORESCENCE PATTERNS; GEOGRAPHIC
   ATROPHY; MACULAR DEGENERATION; SEVERITY SCALE; DRUSEN; FILM;
   CLASSIFICATION; COMPLICATIONS; OCT
AB PURPOSE. To establish continuity with the grading procedures and outcomes from the historical data of the Age-Related Eye Disease Study (AREDS), color photographic imaging and evaluation procedures for the assessment of age-related macular degeneration (AMD) were modified for digital imaging in the AREDS2. The reproducibility of the grading of index AMD lesion components and for the AREDS severity scale was tested at the AREDS2 reading center.
   METHODS. Digital color stereoscopic fundus photographs from 4203 AREDS2 subjects collected at baseline and annual follow-up visits were optimized for tonal balance and graded according to a standard protocol slightly modified from AREDS. The reproducibility of digital grading of AREDS2 images was assessed by reproducibility exercises, temporal drift (regrading a subset of baseline annually, n = 88), and contemporaneous masked regrading (ongoing, monthly regrade on 5% of submissions, n = 1335 eyes).
   RESULTS. In AREDS2, 91% and 96% of images received replicate grades within two steps of the baseline value on the AREDS severity scale for temporal drift and contemporaneous assessment, respectively (weighted Kappa of 0.73 and 0.76). Historical data for temporal drift in replicate gradings on the AREDS film-based images were 88% within two steps (weighted Kappa 0.88). There was no difference in AREDS2-AREDS concordance for temporal drift (exact P = 0.57).
   CONCLUSIONS. Digital color grading has nearly the same reproducibility as historical film grading. There is substantial agreement for testing the predictive utility of the AREDS severity scale in AREDS2 as a clinical trial outcome. (ClinicalTrials.gov number, NCT00345176.)
C1 [Danis, Ronald P.; Domalpally, Amitha; Armstrong, Jane] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53717 USA.
   [Chew, Emily Y.; SanGiovanni, John Paul; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
   [Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Emmes Corporation
RP Danis, RP (通讯作者)，Univ Wisconsin, Dept Ophthalmol & Visual Sci, 8010 Excelsior Dr, Madison, WI 53717 USA.
EM rpdanis@wisc.edu
RI Domalpally, Amitha/B-2367-2015; SanGiovanni, John Paul/AAU-3895-2020;
   Hunter, Allan/AAJ-5848-2020
OI Domalpally, Amitha/0000-0002-8145-9619; Folk, James/0000-0002-6271-2906;
   DiLoreto, David/0000-0002-1787-8069; Ferris,
   Frederick/0000-0002-4933-0639; Klein, Ronald/0000-0002-4428-6237
FU National Eye Institute [HHS-N-260-2005-00007-C]; NATIONAL EYE INSTITUTE
   [ZIAEY000485, ZIEEY000487] Funding Source: NIH RePORTER
FX Supported by National Eye Institute Grant HHS-N-260-2005-00007-C (TEC).
CR Age-Related Eye Dis Study Res Grp, 2001, AM J OPHTHALMOL, V132, P668
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   Davis MD, 2008, INVEST OPHTH VIS SCI, V49, P1745, DOI 10.1167/iovs.07-1257
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NR 30
TC 80
Z9 81
U1 0
U2 53
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 2013
VL 54
IS 7
BP 4548
EP 4554
DI 10.1167/iovs.13-11804
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 194MI
UT WOS:000322637000018
PM 23620429
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhang, QX
   Lu, RW
   Curcio, CA
   Yao, XC
AF Zhang, Qiu-Xiang
   Lu, Rong-Wen
   Curcio, Christine A.
   Yao, Xin-Cheng
TI In Vivo Confocal Intrinsic Optical Signal Identification of Localized
   Retinal Dysfunction
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; HUMAN CONE PHOTORECEPTORS; MACULAR
   DEGENERATION; COHERENCE TOMOGRAPHY; MULTIFOCAL ELECTRORETINOGRAPHY;
   RETINITIS-PIGMENTOSA; SCATTERING CHANGES; LIGHT-SCATTERING; MACAQUE
   MONKEYS; DARK-ADAPTATION
AB PURPOSE. The purposes of this study were to investigate the physiological mechanism of stimulus-evoked fast intrinsic optical signals (IOSs) recorded in dynamic confocal imaging of the retina, and to demonstrate the feasibility of in vivo confocal IOS mapping of localized retinal dysfunctions.
   METHODS. A rapid line-scan confocal ophthalmoscope was constructed to achieve in vivo confocal IOS imaging of frog (Rana pipiens) retinas at cellular resolution. In order to investigate the physiological mechanism of confocal IOS, comparative IOS and electroretinography (ERG) measurements were made using normal frog eyes activated by variable-intensity stimuli. A dynamic spatiotemporal filtering algorithm was developed to reject the contamination of hemodynamic changes on fast IOS recording. Laser-injured frog eyes were employed to test the potential of confocal IOS mapping of localized retinal dysfunctions.
   RESULTS. Comparative IOS and ERG experiments revealed a close correlation between the confocal IOS and retinal ERG, particularly the ERG a-wave, which has been widely used to evaluate photoreceptor function. IOS imaging of laser-injured frog eyes indicated that the confocal IOS could unambiguously detect localized (30 mu m) functional lesions in the retina before a morphological abnormality is detectable.
   CONCLUSIONS. The confocal IOS predominantly results from retinal photoreceptors, and can be used to map localized photoreceptor lesion in laser-injured frog eyes. We anticipate that confocal IOS imaging can provide applications in early detection of age-related macular degeneration, retinitis pigmentosa, and other retinal diseases that can cause pathological changes in the photoreceptors. (Invest Ophthalmol Vis Sci. 2012; 53: 8139-8145) DOI:10.1167/iovs.12-10732
C1 [Zhang, Qiu-Xiang; Lu, Rong-Wen; Yao, Xin-Cheng] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
   [Yao, Xin-Cheng] Univ Alabama Birmingham, Dept Vis Sci, Birmingham, AL USA.
C3 University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham;
   University of Alabama System; University of Alabama Birmingham
RP Yao, XC (通讯作者)，390B Volker Hall,1670 Univ Blvd, Birmingham, AL 35294 USA.
EM xcy@uab.edu
RI Lu, Rongwen/B-4261-2015; Lu, Rongwen/J-6169-2015; Yao,
   Xincheng/ABA-1526-2020
OI Lu, Rongwen/0000-0002-1167-6001; 
FU Dana Foundation (Brain and Immuno-Imaging Grant program); Eyesight
   Foundation of Alabama; NSF [CBET-1055889]; NIH [R21 RR025788, R21
   EB012264, R01 EY06109]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [R21RR025788] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY006109] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB012264] Funding Source: NIH
   RePORTER; Div Of Chem, Bioeng, Env, & Transp Sys [1055889] Funding
   Source: National Science Foundation
FX Supported in part by the Dana Foundation (Brain and Immuno-Imaging Grant
   program), the Eyesight Foundation of Alabama, NSF CBET-1055889, NIH R21
   RR025788, NIH R21 EB012264, and NIH R01 EY06109.
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NR 53
TC 25
Z9 26
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2012
VL 53
IS 13
BP 8139
EP 8145
DI 10.1167/iovs.12-10732
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EX
UT WOS:000313056000031
PM 23150616
OA Green Published
DA 2022-11-30
ER

PT J
AU Rasmussen, HM
   Muzhingi, T
   Eggert, EMR
   Johnson, EJ
AF Rasmussen, Helen M.
   Muzhingi, Tawanda
   Eggert, Emily M. R.
   Johnson, Elizabeth J.
TI Lutein, zeaxanthin, meso-zeaxanthin content in egg yolk and their
   absence in fish and seafood
SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS
LA English
DT Article
DE Lutein; Zeaxanthin; Meso-zeaxanthin; Macular pigments; Pigments in food;
   Fish; Seafood; Eggs; Dietary intake; Food analysis; Food composition
ID MACULAR PIGMENT; ADIPOSE-TISSUE; CAROTENOIDS; SUPPLEMENTATION;
   BIOAVAILABILITY; VEGETABLES; DIETARY; SPINACH; MONKEYS; RETINA
AB Lutein (L) and zeaxanthin (Z) are carotenoids that are selectively taken up into the macula of the eye where they may protect against age-related macular degeneration. Meso-zeaxanthin (MZ) is also found in the macula, but is derived from L It has been reported that MZ was found in certain fish and seafood. However, concentrations were not quantitated. MZ is used as an ingredient in poultry feed in Mexico but not in the United States (US). The purpose of this work was to quantify MZ in fish, seafood, and egg in efforts to determine dietary contributions to its presence in the macula. Fish, seafood and eggs from California, Illinois, Massachusetts and Mexico were analyzed for L, Z. and MZ using reverse- and chiral normal-phase HPLC. For all fish and seafoods,L, Z, and MZ were not detected. In eggs from the US, L + Z levels ranged from 1.0 to 1.6 mg/100 g yolk with L levels being 1.3-1.6 times higher than that of Z. One egg (California) contained a small amount of MZ (0.01 mg/100 g yolk). Carotenoid concentrations were significantly higher in Mexican eggs (p < 0.025, 3.44 mg/100 g yolk) with the ratio of L:Z:MZ being 1:1:1.3. In the US the presence of MZ in the macula is not likely due to dietary sources, although this a possibility when consuming eggs of chickens fed MZ. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Rasmussen, Helen M.; Muzhingi, Tawanda; Eggert, Emily M. R.; Johnson, Elizabeth J.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
C3 Tufts University; United States Department of Agriculture (USDA)
RP Johnson, EJ (通讯作者)，Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM helen.rasmussen@tufts.edu; tawanda.muzhingi@tufts.edu;
   eggerte@verizon.net; elizabeth.johnson@tufts.edu
FU USDA [58-1950-7-707]; Zeaxanthin Trade Association
FX Supported by USDA 58-1950-7-707 and Zeaxanthin Trade Association. Any
   opinions, findings, conclusions, or recommendations expressed in this
   publication are those of the author(s) and do not necessarily reflect
   the view of the US Department of Agriculture.
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   [No title captured]
NR 25
TC 27
Z9 27
U1 2
U2 40
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1575
J9 J FOOD COMPOS ANAL
JI J. Food Compos. Anal.
PD SEP
PY 2012
VL 27
IS 2
BP 139
EP 144
DI 10.1016/j.jfca.2012.04.009
PG 6
WC Chemistry, Applied; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Food Science & Technology
GA 024KI
UT WOS:000310107700004
DA 2022-11-30
ER

PT J
AU Yin, LL
   Shi, YH
   Liu, XJ
   Zhang, HM
   Gong, YY
   Gu, Q
   Wu, XW
   Xu, X
AF Yin, Lili
   Shi, Yuhua
   Liu, Xiaojuan
   Zhang, Hongmei
   Gong, Yuanyuan
   Gu, Qing
   Wu, Xingwei
   Xu, Xun
TI A Rat Model for Studying the Biological Effects of Circulating LDL in
   the Choriocapillaris-BrM-RPE Complex
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; MEDIATED MULTIFOCAL
   ELECTRORETINOGRAM; LOW-DENSITY LIPOPROTEINS; MACULAR DEGENERATION;
   BRUCHS MEMBRANE; BASAL DEPOSITS; MATRIX METALLOPROTEINASE-2;
   EXTRACELLULAR-MATRIX; TISSUE INHIBITOR
AB Retention of apolipoprotein B-containing lipoproteins In Bruch's membrane (BrM) is believed to be important in early age-related macular degeneration (AMD). The origin of the lipoproteins in BrM is a hot topic in (AMD) research. Some studies hypothesize an intraocular origin. BrM is in direct contact to the choriocapillaris; a plasma origin has also been suggested for the low-density lipoprotein (LDL) particles. We developed an animal model to study the biological effects of circulating LDL on the retina. After injection of LDL for 7 days, our results showed evidence of circulating apolipoprotein B100 retention in BrM and showed induction of early AMD-like alterations in the rat retina, such as thickening of BrM, photoreceptor TUNEL-positive cells, and inflammatory cell infiltration. In vitro assays showed that oxidized LDL (ox-LDL) treatment decreased ARPE-19 cell viability in a dose-dependent manner and that 10 mg/L ox-LDL induced marked apoptosis. The ratio of matrix metalloproteinase-2 to tissue inhibitors of metalloproteinase-3 was dysregulated after LDL and ox-LDL treatment in ARPE-19 cells, which can produce profound changes in the extracellular matrix, including thickening of and deposit formation in BrM. The observation that circulating LDL may be a significant, but not complete, origin of the lipoprotein in BrM suggests that these findings can be readily exploited for the development of new model systems and the future benefit of patients with AMD. (Ant J Pathol 2012, 180:541-549; DOI: 10.1016/j.ajpath.2011.10.015)
C1 [Yin, Lili; Liu, Xiaojuan; Zhang, Hongmei; Gong, Yuanyuan; Gu, Qing; Wu, Xingwei; Xu, Xun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
   [Shi, Yuhua] Nanjing Jinling Hosp, Dept Ophthalmol, Nanjing, Peoples R China.
C3 Shanghai Jiao Tong University
RP Wu, XW (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
EM wuxingwei2010@tom.com
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NR 43
TC 13
Z9 14
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD FEB
PY 2012
VL 180
IS 2
BP 541
EP 549
DI 10.1016/j.ajpath.2011.10.015
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 887HZ
UT WOS:000299918800011
PM 22107828
DA 2022-11-30
ER

PT J
AU Xie, WK
   Yu, WZ
   Zhao, M
   Zhou, WY
   Chen, H
   Du, W
   Huang, LZ
   Xu, YS
   Li, XX
AF Xie Wankun
   Yu Wenzhen
   Zhao Min
   Zhou Weiyan
   Chen Huan
   Du Wei
   Huang Lvzhen
   Xu, Yongsheng
   Li Xiaoxin
TI Protective effect of paeoniflorin against oxidative stress in human
   retinal pigment epithelium in vitro
SO MOLECULAR VISION
LA English
DT Article
ID PROTEIN-INDUCING COMPOUND; KINASE-DEPENDENT PATHWAYS; HUMAN RPE CELLS;
   MACULAR DEGENERATION; INDUCED APOPTOSIS; GENE-EXPRESSION; ARPE-19 CELLS;
   VISUAL IMPAIRMENT; ACTIVATING MAPK; H2O2
AB Purpose: This study was conducted to determine whether paeoniflorin (PF) could prevent H2O2-induced oxidative stress in ARPE-19 cells and to elucidate the molecular pathways involved in this protection.
   Methods: Cultured ARPE-19 cells were subjected to oxidative stress with H2O2 in the presence and absence of PF. The preventive effective of PF on reactive oxygen species (ROS) production and retinal pigment epithelium (RPE) cell death induced by H2O2 was determined by 2', 7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) fluorescence and 3-(4, 5dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) assay. The ability of PF to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and 4', 6-diamidino-2-phenylindole (DAPI) staining. Furthermore, the protective effect of PF via the mitogen-activated protein kinase (MAPK) pathway was determined by western blot analysis.
   Results: PF protected ARPE-19 cells from H2O2-induced cell death with low toxicity. H2O2-induced oxidative stress increased ROS production and caspase-3 activity, which was significantly inhibited by PF in a dose-dependent manner. Pretreatment with PF attenuated H2O2-induced p38MAPK and extracellular signal regulated kinase (ERK) phosphorylation in human RPE cells, which contributed to cell viability in ARPE-19 cells.
   Conclusions: This is the first report to show that PF can protect ARPE-19 cells from the cellular apoptosis induced by oxidative stress. The results of this study open new avenues for the use of PF in treatment of ocular diseases, such as age-related macular degeneration (AMD), where oxidative stress plays a major role in disease pathogenesis.
C1 [Xie Wankun; Yu Wenzhen; Zhao Min; Zhou Weiyan; Chen Huan; Du Wei; Huang Lvzhen; Xu, Yongsheng; Li Xiaoxin] Peking Univ, Peoples Hosp, Peoples Eye Inst,Minist Educ, Dept Ophthalmol,Key Lab Vis Loss & Restorat, Beijing 100044, Peoples R China.
C3 Peking University
RP Li, XX (通讯作者)，Peking Univ, Peoples Hosp, Peoples Eye Inst,Minist Educ, Dept Ophthalmol,Key Lab Vis Loss & Restorat, Xizhimen S St 11, Beijing 100044, Peoples R China.
EM drlixiaoxin@163.com
RI Xie, Wankun/K-8623-2017
OI Xie, Wankun/0000-0003-0178-3361
FU Peking University People's Hospital Research and Development Funds
   [RDB2010-25]; National Basic Research Program of China (973 Program)
   [2011CB510200]
FX This work was supported by Peking University People's Hospital Research
   and Development Funds Project (RDB2010-25) and the National Basic
   Research Program of China (973 Program, Grant No. 2011CB510200).
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NR 42
TC 61
Z9 66
U1 0
U2 9
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 29
PY 2011
VL 17
IS 373-78
BP 3512
EP 3522
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 871LM
UT WOS:000298739600005
PM 22219646
DA 2022-11-30
ER

PT J
AU Koss, MJ
   Pfister, M
   Koch, FH
AF Koss, M. J.
   Pfister, M.
   Koch, F. H.
TI Inflammatory and Angiogenic Protein Detection in the Human Vitreous:
   Cytometric Bead Assay
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CYTOKINES; QUANTIFICATION; INTERLEUKIN-6;
   EXPRESSION; ARRAY
AB Introduction. To evaluate clinical feasibility and reproducibility of cytometric bead assay (CBA) in nondiluted vitreous samples of patients with age-related macular degeneration (ARMD), diabetic macular edema (DME), and central retinal vein occlusion (CRVO). Methods. Twelve patients from a single clinics day qualified for intravitreal injections (ARMD n = 6, DME n = 3, CRVO n = 3) and underwent a combination treatment including a single-site 23 gauge core vitrectomy which yielded a volume of 0.6mL undiluted vitreous per patient. Interleukin-6 (IL-6), vascular endothelial growth factor isoform A (VEGF-A), and monocyte chemo-attractant protein-1 (MCP-1) were assessed directly from 0.3mL at the same day (fresh samples). To assess the reproducibility 0.3 ml were frozen for 60 days at -80 degrees, on which the CBA was repeated (frozen samples). Results. In the fresh samples IL-6 was highest in CRVO (median IL-6 55.8 pg/mL) > DME (50.6) > ARMD (3.1). Highest VEGF was measured in CRVO (447.4) > DME (3.9) > ARMD (2.0). MCP-1 was highest in CRVO (595.7) > AMD (530.8) > DME (178). The CBA reproducibility after frozen storage was examined to be most accurate for MCP1 (P = 0.91) > VEGF (P = 0.68) > IL-6 (P = 0.49). Conclusions. CBA is an innovative, fast determining, and reliable technology to analyze proteins in fluids, like the undiluted vitreous, which is important to better understand ocular pathophysiology and pharmacology. There is no influence of intermittent storage at -80 degrees for the reproducibility of the CBA.
C1 [Koss, M. J.; Pfister, M.; Koch, F. H.] Goethe Univ Frankfurt, Hosp Goethe Univ, Dept Ophthalmol, Sect Vitreoretinal Surg, D-60590 Frankfurt, Germany.
C3 Goethe University Frankfurt; Goethe University Frankfurt Hospital
RP Koss, MJ (通讯作者)，Goethe Univ Frankfurt, Hosp Goethe Univ, Dept Ophthalmol, Sect Vitreoretinal Surg, D-60590 Frankfurt, Germany.
EM michael.koss@kgu.de
FU Adolf Messer Foundation, Konigstein, Germany
FX The Adolf Messer Foundation, Konigstein, Germany, supports the research
   group.
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NR 20
TC 12
Z9 13
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PY 2011
VL 2011
AR 459251
DI 10.1155/2011/459251
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 979BO
UT WOS:000306790100016
PM 22254128
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Khurana, M
   Collins, HA
   Karotki, A
   Anderson, HL
   Cramb, DT
   Wilson, BC
AF Khurana, Mamta
   Collins, Hazel A.
   Karotki, Aliaksandr
   Anderson, Harry L.
   Cramb, David T.
   Wilson, Brian C.
TI Quantitative in vitro demonstration of two-photon photodynamic therapy
   using Photofrin (R) and Visudyne (R)
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID EXCITATION; CELLS; ABSORPTION; LASER; ACTIVATION; MECHANISM
AB Photodynamic therapy (PDT), the combined action of a photosensitizer and light to produce a cytotoxic effect, is an approved therapy for a number of diseases. At present, clinical PDT treatments involve one-photon excitation of the photosensitizer. A major limitation is that damage may be caused to healthy tissues that have absorbed the drug and lie in the beam path. Two-photon excitation may minimize this collateral damage, as the probability of absorption increases with the square of the light intensity, enabling spatial confinement of the photosensitizer activation. A potential application is the treatment of the wet-form of age-related macular degeneration, the foremost cause of central vision loss in the elderly. Herein, the commercial photosensitizers Visudyne (R) and Photofrin (R) are used to demonstrate quantitative in vitro two-photon PDT. A uniform layer of endothelial cells (YPEN-1) was irradiated with a Ti:sapphire laser (300 fs, 865 nm, 90 MHz) using a confocal scanning microscope. Quantification of the two-photon PDT effect was achieved using the permeability stain Hoechst 33258 and a SYTOX (R) Orange viability stain. Visudyne was found to be around seven times more effective as a two-photon photosensitizer than Photofrin under the conditions used, consistent with its higher two-photon absorption cross-section. We also demonstrate for the first time the quadratic intensity dependence of cellular two-photon PDT. This simple in vitro method for quantifying the efficacy of photosensitizers for two-photon excited PDT will be valuable to test specifically designed two-photon photosensitizers before proceeding to in vivo studies in preclinical animal models.
C1 Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON, Canada.
   Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 2JD, England.
   Univ Calgary, Dept Chem, Calgary, AB T2N 1N4, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto; University of Oxford; University of Calgary
RP Wilson, BC (通讯作者)，Univ Toronto, Ontario Canc Inst, Dept Med Biophys, 100 Coll St, Toronto, ON, Canada.
EM wilson@uhnres.utoronto.ca
RI Anderson, Harry Laurence/E-7843-2011
OI Anderson, Harry Laurence/0000-0002-1801-8132; Wilson, Brian
   C./0000-0001-5543-666X
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NR 41
TC 109
Z9 113
U1 1
U2 37
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD NOV-DEC
PY 2007
VL 83
IS 6
BP 1441
EP 1448
DI 10.1111/j.1751-1097.2007.00185.x
PG 8
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 236HQ
UT WOS:000251294100020
PM 18028219
DA 2022-11-30
ER

PT J
AU Ahlers, C
   Michels, S
   Elsner, H
   Birngruber, R
   Pruente, C
   Schmidt-Erfurth, U
AF Ahlers, C
   Michels, S
   Elsner, H
   Birngruber, R
   Pruente, C
   Schmidt-Erfurth, U
TI Topographic angiography and optical coherence tomography: A correlation
   of imaging characteristics
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   geographic atrophy; imaging; optical coherence tomography; pigment
   epithelial detachment; topographic angiography
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; DISEASE
AB PURPOSE. Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality.
   METHODS. TAG using fluorescein angiography (FA) provides a three-dimensional pro file of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD).
   RESULTS. In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution.
   CONCLUSIONS. TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.
C1 Univ Vienna, Hosp Eye, Vienna, Austria.
   Univ Lubeck, Hosp Eye, Lubeck, Germany.
   Med Laser Ctr Lubeck, Lubeck, Germany.
   Univ Basel, Hosp Eye, Basel, Switzerland.
C3 University of Vienna; University of Lubeck; University of Basel
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Klin Augenheilkunde & Optometrie, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
RI Birngruber, Reginald/Q-2342-2016
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NR 8
TC 8
Z9 8
U1 0
U2 1
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 2005
VL 15
IS 6
BP 774
EP 781
DI 10.1177/112067210501500619
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 990KX
UT WOS:000233742900019
PM 16329065
DA 2022-11-30
ER

PT J
AU Shimizu, K
   Oku, N
AF Shimizu, K
   Oku, N
TI Cancer anti-angiogenic therapy
SO BIOLOGICAL & PHARMACEUTICAL BULLETIN
LA English
DT Review
DE angiogenesis; anti-neovascular thrapy; metronomic-dosing; chemotherapy;
   photodynamic therapy (PDT); drug delivery system (DDS)
ID ENDOTHELIAL GROWTH-FACTOR; VEGF-INDUCED ANGIOGENESIS; FOCAL ADHESION
   KINASE; TUMOR-GROWTH; CELL-PROLIFERATION; TISSUE INHIBITOR;
   MONOCLONAL-ANTIBODY; IN-VITRO; MATRIX METALLOPROTEINASES; ANTIANGIOGENIC
   THERAPY
AB Tumor angiogenesis affords new targets for cancer therapy, since inhibition of angiogenesis suppresses tumor growth by cutting out the supply of oxygen and nutrients. Anti-angiogenic therapy is thought to be free of the severe side effects that are usually seen with cytotoxic anticancer drugs. Furthermore, anti-angiogenic therapy is thought not only to eradicate primary tumor tissues, but also to suppress tumor metastases. However, it is uncertain whether this therapy causes tumor regression because it inhibits only angiogenic events. Recently, a novel anti-angiogenic therapy called anti-neovascular therapy (ANET) has become notable. This therapy inflicts indirect lethal damage on tumor cells by damaging newly formed blood vessels using anti-cancer drugs targeting the angiogenic vasculature, since cytotoxic anti-cancer drugs cause damage to proliferating neovascular endothelial cells as well as tumor cells. Moreover, neovascular endothelial cells would not be expected to acquire drug-resistance. Traditional chemotherapy, which directly targets tumor cells, has potential problems such as low specificity and severe side effects. On the contrary, in ANET, severe side effects may be suppressed, since traditional anti-cancer agents are delivered to the neovessels by DDS technology. Besides the usage of DDS technology, anti-neovascular scheduling of chemotherapy, or metronomic-dosing chemotherapy, has also been attempted in which anti-cancer drugs are administered on a schedule to damage neovessels. In this review, we describe traditional anti-angiogenic therapy and ANET. We also discuss anti-angiogenic cancer photodynamic therapy (PDT), since PDT is clinically applied to treat age-related macular degeneration (AMD), in which uncontrolled angiogenesis occurs.
C1 Univ Shizuoka, Sch Pharmaceut Sci, Dept Biochem Med, Shizuoka 4228526, Japan.
C3 University of Shizuoka
RP Oku, N (通讯作者)，Univ Shizuoka, Sch Pharmaceut Sci, Dept Biochem Med, Shizuoka 4228526, Japan.
EM oku@u-shizuoka-ken.ac.jp
OI Shimizu, Kosuke/0000-0003-3789-2447
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NR 112
TC 63
Z9 80
U1 2
U2 16
PU PHARMACEUTICAL SOC JAPAN
PI TOKYO
PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN
SN 0918-6158
J9 BIOL PHARM BULL
JI Biol. Pharm. Bull.
PD MAY
PY 2004
VL 27
IS 5
BP 599
EP 605
DI 10.1248/bpb.27.599
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 817EQ
UT WOS:000221161200001
PM 15133229
DA 2022-11-30
ER

PT J
AU Tan, LX
   Li, JL
   Germer, CJ
   Lakkaraju, A
AF Tan, Li Xuan
   Li, Jianlong
   Germer, Colin J. J.
   Lakkaraju, Aparna
TI Analysis of mitochondrial dynamics and function in the retinal pigment
   epithelium by high-speed high-resolution live imaging
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE mitochondria; live imaging; retina; RPE; pigmented and albino mice
ID LIGHT DAMAGE; OXIDATIVE STRESS; MOUSE MODEL; RPE; ACCUMULATION;
   DEGRADATION; RESPONSES; FISSION; NETWORK; CALCIUM
AB Mitochondrial dysfunction is strongly implicated in neurodegenerative diseases including age-related macular degeneration (AMD), which causes irreversible blindness in over 50 million older adults worldwide. A key site of insult in AMD is the retinal pigment epithelium (RPE), a monolayer of postmitotic polarized cells that performs essential functions for photoreceptor health and vision. Recent studies from our group and others have identified several features of mitochondrial dysfunction in AMD including mitochondrial fragmentation and bioenergetic defects. While these studies provide valuable insight at fixed points in time, high-resolution, high-speed live imaging is essential for following mitochondrial injury in real time and identifying disease mechanisms. Here, we demonstrate the advantages of live imaging to investigate RPE mitochondrial dynamics in cell-based and mouse models. We show that mitochondria in the RPE form extensive networks that are destroyed by fixation and discuss important live imaging considerations that can interfere with accurate evaluation of mitochondrial integrity such as RPE differentiation status and acquisition parameters. Our data demonstrate that RPE mitochondria show localized heterogeneities in membrane potential and ATP production that could reflect focal changes in metabolism and oxidative stress. Contacts between the mitochondria and organelles such as the ER and lysosomes mediate calcium flux and mitochondrial fission. Live imaging of mouse RPE flatmounts revealed a striking loss of mitochondrial integrity in albino mouse RPE compared to pigmented mice that could have significant functional consequences for cellular metabolism. Our studies lay a framework to guide experimental design and selection of model systems for evaluating mitochondrial health and function in the RPE.
C1 [Tan, Li Xuan; Germer, Colin J. J.; Lakkaraju, Aparna] Univ Calif San Francisco, Sch Med, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Li, Jianlong] Univ Calif San Francisco, Sch Dent, Dept Cell & Tissue Biol, San Francisco, CA USA.
   [Germer, Colin J. J.; Lakkaraju, Aparna] Univ Calif San Francisco, Pharmaceut Sci & Pharmacogen Grad Program, San Francisco, CA 94143 USA.
   [Lakkaraju, Aparna] Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco;
   University of California System; University of California San Francisco;
   University of California System; University of California San Francisco;
   University of California System; University of California San Francisco
RP Lakkaraju, A (通讯作者)，Univ Calif San Francisco, Sch Med, Dept Ophthalmol, San Francisco, CA 94143 USA.; Lakkaraju, A (通讯作者)，Univ Calif San Francisco, Pharmaceut Sci & Pharmacogen Grad Program, San Francisco, CA 94143 USA.; Lakkaraju, A (通讯作者)，Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA 94143 USA.
EM Aparna.Lakkaraju@ucsf.edu
FU NIH [R01EY023299, R01EY030668]; UCSF Department of Ophthalmology
   [EY002162]; Research to Prevent Blindness/AMDF Catalyst Award for novel
   approaches; BrightFocus Foundation Lorraine Maresca award for Innovative
   research [M2021020I]; Reeves Foundation; All May See Foundation
   Postdoctoral Grant Award
FX Supported by the NIH grants R01EY023299 (AL) and R01EY030668 (AL), P30
   core grant EY002162 (UCSF Department of Ophthalmology), the Research to
   Prevent Blindness/AMDF Catalyst Award for novel approaches to AMD (AL),
   the BrightFocus Foundation Lorraine Maresca award for Innovative
   research in AMD M2021020I (AL), Reeves Foundation award for AMD (AL),
   and the All May See Foundation Postdoctoral Grant Award (LXT). We thank
   the Knox lab for the albino BALB/c mice.
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NR 77
TC 0
Z9 0
U1 0
U2 0
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 OCT 28
PY 2022
VL 10
AR 1044672
DI 10.3389/fcell.2022.1044672
PG 16
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA 6F9YV
UT WOS:000884418300001
PM 36393836
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU DeMaio, A
   Mehrotra, S
   Sambamurti, K
   Husain, S
AF DeMaio, Alexa
   Mehrotra, Shikhar
   Sambamurti, Kumar
   Husain, Shahid
TI The role of the adaptive immune system and T cell dysfunction in
   neurodegenerative diseases
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Review
DE T cells; Neurodegeneration; Inflammation; Immune system; Lymphocytes
ID RETINAL GANGLION-CELLS; HEAT-SHOCK PROTEINS; OPTIC-NERVE HEAD; IGG
   ANTIBODY PATTERNS; TUMOR-NECROSIS-FACTOR; COMPLEMENT FACTOR-H;
   OPEN-ANGLE GLAUCOMA; EXPERIMENTAL AUTOIMMUNE UVEITIS; TYPE-2
   DIABETES-MELLITUS; MYELIN BASIC-PROTEIN
AB The adaptive immune system and associated inflammation are vital in surveillance and host protection against internal and external threats, but can secondarily damage host tissues. The central nervous system is immune-privileged and largely protected from the circulating inflammatory pathways. However, T cell involvement and the disruption of the blood-brain barriers have been linked to several neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Under normal physiological conditions, regulatory T cells (Treg cells) dampen the inflammatory response of effector T cells. In the pathological states of many neurodegenerative disorders, the ability of Treg cells to mitigate inflammation is reduced, and a pro-inflammatory environment persists. This perspective review provides current knowledge on the roles of T cell subsets (e.g., effector T cells, Treg cells) in neurodegenerative and ocular diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, and glaucoma. Many neurodegenerative and ocular diseases have been linked to immune dysregulation, but the cellular events and molecular mechanisms involved in such processes remain largely unknown. Moreover, the role of T cells in ocular pathologies remains poorly defined and limited literature is available in this area of research. Adoptive transfer of Treg cells appears to be a vital immunological approach to control ocular pathologies. Similarities in T cell dysfunction seen among non-ocular neurodegenerative diseases suggest that this area of research has a great potential to develop better therapeutic agents for ocular diseases and warrants further studies. Overall, this perspective review article provides significant information on the roles of T cells in numerous ocular and non-ocular neurodegenerative diseases.
C1 [DeMaio, Alexa; Husain, Shahid] Med Univ South Carolina, Storm Eye Inst, Dept Ophthalmol, 167 Ashley Ave, Room 713, Charleston, SC 29425 USA.
   [Mehrotra, Shikhar] Med Univ South Carolina, Hollings Canc Ctr, Dept Surg, Charleston, SC 29425 USA.
   [Sambamurti, Kumar] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; Medical University of South Carolina
RP Husain, S (通讯作者)，Med Univ South Carolina, Storm Eye Inst, Dept Ophthalmol, 167 Ashley Ave, Room 713, Charleston, SC 29425 USA.
EM husain@musc.edu
FU NIH/NEI [EY-027355]
FX This study was supported by NIH/NEI Grant EY-027355 (SH). This funding
   body helped in writing of this review article.
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NR 365
TC 0
Z9 0
U1 3
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD OCT 8
PY 2022
VL 19
IS 1
AR 251
DI 10.1186/s12974-022-02605-9
PG 19
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 5D8FH
UT WOS:000865171200001
PM 36209107
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ayhan, MS
   Kummerle, LB
   Kuhlewein, L
   Inhoffen, W
   Aliyeva, G
   Ziemssen, F
   Berens, P
AF Ayhan, Murat Seckin
   Kuemmerle, Louis Benedikt
   Kuehlewein, Laura
   Inhoffen, Werner
   Aliyeva, Gulnar
   Ziemssen, Focke
   Berens, Philipp
TI Clinical validation of saliency maps for understanding deep neural
   networks in ophthalmology
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Deep neural networks; Saliency maps; Diabetic retinopathy; Neovascular
   age-related macular; degeneration
ID DIABETIC-RETINOPATHY; MACULAR DEGENERATION; CLASSIFICATION; CONVERGENCE;
   UNCERTAINTY; DECISIONS; MEDICINE
AB Deep neural networks (DNNs) have achieved physician-level accuracy on many imaging-based medical diagnostic tasks, for example classification of retinal images in ophthalmology. However, their decision mechanisms are often considered impenetrable leading to a lack of trust by clinicians and patients. To alleviate this issue, a range of explanation methods have been proposed to expose the inner workings of DNNs leading to their decisions. For imaging-based tasks, this is often achieved via saliency maps. The quality of these maps are typically evaluated via perturbation analysis without experts involved. To facilitate the adoption and success of such automated systems, however, it is crucial to validate saliency maps against clinicians. In this study, we used three different network architectures and developed ensembles of DNNs to detect diabetic retinopathy and neovascular age-related macular degeneration from retinal fundus images and optical coherence tomography scans, respectively. We used a variety of explanation methods and obtained a comprehensive set of saliency maps for explaining the ensemble-based diagnostic decisions. Then, we systematically validated saliency maps against clinicians through two main analyses - a direct comparison of saliency maps with the expert annotations of disease-specific pathologies and perturbation analyses using also expert annotations as saliency maps. We found the choice of DNN architecture and explanation method to significantly influence the quality of saliency maps. Guided Backprop showed consistently good performance across disease scenarios and DNN architectures, suggesting that it provides a suitable starting point for explaining the decisions of DNNs on retinal images. (c) 2022 Elsevier B.V. All rights reserved.
C1 [Ayhan, Murat Seckin; Kuemmerle, Louis Benedikt; Kuehlewein, Laura; Berens, Philipp] Univ Tubingen, Inst Ophthalm Res, Tubingen, Germany.
   [Kuemmerle, Louis Benedikt] Helmholtz Ctr Munich, Inst Computat Biol, Munich, Germany.
   [Kuemmerle, Louis Benedikt] Helmholtz Ctr Munich, Inst Tissue Engn & Regenerat Med iTERM, Munich, Germany.
   [Kuehlewein, Laura; Inhoffen, Werner; Aliyeva, Gulnar; Ziemssen, Focke] Univ Tubingen, Univ Eye Clin, Tubingen, Germany.
   [Berens, Philipp] Univ Tubingen, Dept Comp Sci, Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Helmholtz Association; Helmholtz-Center Munich - German
   Research Center for Environmental Health; Helmholtz Association;
   Helmholtz-Center Munich - German Research Center for Environmental
   Health; Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen
RP Ayhan, MS (通讯作者)，Univ Tubingen, Inst Ophthalm Res, Tubingen, Germany.
FU German Ministry of Science and Education (BMBF) [01GQ1601, 01IS18039A];
   German Science Foundation [BE5601/4-1, EXC 2064, 390727645]; Novartis AG
FX This research was supported by the German Ministry of Science and
   Education (BMBF, 01GQ1601 and 01IS18039A) and the German Science
   Foundation (BE5601/4-1 and EXC 2064, project number 390727645).
   Additional funding was provided by Novartis AG through a research grant.
   The funders did not have any influence in the study planning and design.
   The Messidor 2 collection (Decenciere et al., 2014) was kindly provided
   by the Messidor program partners. More information can be found at
   http://www.adcis.net/en/third-party/messidor/.
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NR 98
TC 6
Z9 6
U1 5
U2 5
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD APR
PY 2022
VL 77
AR 102364
DI 10.1016/j.media.2022.102364
PG 29
WC Computer Science, Artificial Intelligence; Computer Science,
   Interdisciplinary Applications; Engineering, Biomedical; Radiology,
   Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
   Imaging
GA 1D2SH
UT WOS:000793655000008
PM 35101727
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Yan, MF
   Li, JJ
   Yan, L
   Li, X
   Chen, JG
AF Yan, Meifang
   Li, Junjian
   Yan, Li
   Li, Xue
   Chen, Jie-Guang
TI Transcription factor Foxp1 is essential for the induction of choroidal
   neovascularization
SO EYE AND VISION
LA English
DT Article
DE Foxp1; Choroidal neovascularization; Angiogenesis; Laser
   photocoagulation; Age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; INTELLECTUAL
   DISABILITY; MACULAR DEGENERATION; EXPRESSION; VEGF; CELLS; MUTATIONS;
   MODEL
AB Background The exudative form of age-related macular degeneration (AMD) is characterized by abnormal blood vessel growth, which is stimulated by vascular endothelial growth factor (VEGF) released from retinal pigment epithelium (RPE). The angiogenic behaviors of vascular endothelial cells in vitro depend on forkhead box protein P1 (Foxp1), a transcription repressor widely expressed in human and murine tissues during development. In this study, we aimed to determine whether loss of Foxp1 affects laser-induced choroidal neovascularization (CNV) in mouse. Methods Eye-selective deletion of Foxp1 was obtained by crossing Foxp1(flox/flox) with Six3-Cre mice. Laser photocoagulation was delivered to six- to eight-week-old mice to induce CNV. The expression of Foxp1 and Cre was determined by immunofluorescence in cryostat sections of the eyes. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and B4 isolectin staining were applied to analyze the leakage, bulge height, and area of CNV lesions, respectively. RPE-choroid tissues were isolated for the determination of VEGF and pigment epithelium derived factor (PEDF) by Western blotting. Results Foxp1 was expressed in retinal ganglion cells, RPE, and the choroidal endothelial cells. Laser photocoagulation increased the number of Foxp1(+)-endothelial cells and induced CNV. Six3-Cre reduced Foxp1 expression in RPE but not the endothelium, leading to a lower level of VEGF in the RPE-choroid. Foxp1 knockout inhibited pathological angiogenesis and vascular leakage of the laser-induced CNV lesions. Conclusions Foxp1 regulates the expression of VEGF in the RPE, and inhibition of Foxp1 could potentially be a novel strategy for the prevention and therapy of neovascularization related to AMD.
C1 [Yan, Meifang; Li, Junjian; Li, Xue; Chen, Jie-Guang] Sch Ophthalmol & Optometry, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.
   [Yan, Meifang; Li, Junjian; Li, Xue; Chen, Jie-Guang] Wenzhou Med Univ, Eye Hosp, State Key Lab Optometry Ophthalmol & Vis Sci, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.
   [Yan, Meifang; Li, Junjian; Li, Xue; Chen, Jie-Guang] Zhejiang Prov Key Lab Optometry & Ophthalmol, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.
   [Yan, Li] Shantou Univ, Joint Shantou Int Eye Ctr JSIEC, Shantou 515000, Guangdong, Peoples R China.
   [Yan, Li] Chinese Univ Hong Kong, Shantou 515000, Guangdong, Peoples R China.
C3 Wenzhou Medical University; Shantou University
RP Li, X; Chen, JG (通讯作者)，Sch Ophthalmol & Optometry, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.; Li, X; Chen, JG (通讯作者)，Wenzhou Med Univ, Eye Hosp, State Key Lab Optometry Ophthalmol & Vis Sci, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.; Li, X; Chen, JG (通讯作者)，Zhejiang Prov Key Lab Optometry & Ophthalmol, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.
EM lixue007@hotmail.com; jgchen@mail.eye.ac.cn
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NR 45
TC 0
Z9 0
U1 2
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2326-0254
J9 EYE VISION
JI Eye Vis.
PD MAR 6
PY 2022
VL 9
IS 1
AR 10
DI 10.1186/s40662-022-00281-7
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZN4NA
UT WOS:000765011800001
PM 35248156
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Zibetti, C
AF Zibetti, Cristina
TI Deciphering the Retinal Epigenome during Development, Disease and
   Reprogramming: Advancements, Challenges and Perspectives
SO CELLS
LA English
DT Review
DE retinal epigenome; next-generation sequencing; transcription factors;
   retinal progenitor cells; neurogenesis; cell fate; gene regulatory
   networks; neurodegeneration; reprogramming; stem cells; retina; genome;
   chromatin; non-coding RNA; enhancer; epigenetics; iPS cells; animal
   models; single-cell analysis; transcriptomic
ID TRANSCRIPTION-FACTOR-BINDING; OPEN-ACCESS DATABASE; PIGMENT EPITHELIUM
   DEVELOPMENT; OPTICAL COHERENCE TOMOGRAPHY; CELL-FATE SPECIFICATION;
   PLURIPOTENT STEM-CELLS; GENOME-WIDE EXPRESSION; FIBER LAYER THICKNESS;
   MULLER GLIAL-CELLS; PROGENITOR CELLS
AB Retinal neurogenesis is driven by concerted actions of transcription factors, some of which are expressed in a continuum and across several cell subtypes throughout development. While seemingly redundant, many factors diversify their regulatory outcome on gene expression, by coordinating variations in chromatin landscapes to drive divergent retinal specification programs. Recent studies have furthered the understanding of the epigenetic contribution to the progression of age-related macular degeneration, a leading cause of blindness in the elderly. The knowledge of the epigenomic mechanisms that control the acquisition and stabilization of retinal cell fates and are evoked upon damage, holds the potential for the treatment of retinal degeneration. Herein, this review presents the state-of-the-art approaches to investigate the retinal epigenome during development, disease, and reprogramming. A pipeline is then reviewed to functionally interrogate the epigenetic and transcriptional networks underlying cell fate specification, relying on a truly unbiased screening of open chromatin states. The related work proposes an inferential model to identify gene regulatory networks, features the first footprinting analysis and the first tentative, systematic query of candidate pioneer factors in the retina ever conducted in any model organism, leading to the identification of previously uncharacterized master regulators of retinal cell identity, such as the nuclear factor I, NFI. This pipeline is virtually applicable to the study of genetic programs and candidate pioneer factors in any developmental context. Finally, challenges and limitations intrinsic to the current next-generation sequencing techniques are discussed, as well as recent advances in super-resolution imaging, enabling spatio-temporal resolution of the genome.
C1 [Zibetti, Cristina] Univ Oslo, Inst Clin Med, Dept Ophthalmol, Kirkeveien 166, Bldg 36, N-0455 Oslo, Norway.
C3 University of Oslo
RP Zibetti, C (通讯作者)，Univ Oslo, Inst Clin Med, Dept Ophthalmol, Kirkeveien 166, Bldg 36, N-0455 Oslo, Norway.
EM zibettic@gmail.com
RI Zibetti, Cristina/V-7566-2019
OI Zibetti, Cristina/0000-0003-4922-1245
FU Marie Sklodowska Curie research fellowship, under the Scientia Fellows
   Marie Sklodowska Curie COFUND [801133]; European Union
FX This review is self-financed. C.Z. is a current recipient of a Marie
   Sklodowska Curie research fellowship, under the Scientia Fellows Marie
   Sklodowska Curie COFUND, grant agreement 801133, a European Union
   Horizon 2020 Research and Innovation program. C.Z. is currently hosted
   by the Department of Ophthalmology, Institute of Clinical Medicine, at
   the University of Oslo. As project proposer, C.Z. is currently working
   on iPSC derived RPE, investigating the epigenomic contribution to the
   induction and maintenance of the RPE cell fate and has received funding
   support from the Norges Blindeforbund and Unifor associations. AMD: the
   most common cause of blindness in the elderly, affects the
   photoreceptors and RPE in the macula of the eye, responsible for central
   vision. By leveraging a recently described workflow on stem cells
   derived, clinical-grade autologous RPE, C.Z. intends to identify sources
   of variability among transplantable RPE lines, to decipher, assess and
   tentatively correct, the relative contribution of the genome, in its
   predetermined and acquired configurations. Induced RPEs may potentially
   serve as platform for disease modelling, drugs screening and
   genome-editing studies to instruct patient-tailored strategies of
   precision medicine for treatment of AMD.
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NR 439
TC 0
Z9 0
U1 4
U2 6
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 5
AR 806
DI 10.3390/cells11050806
PG 50
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA ZX3KA
UT WOS:000771795700001
PM 35269428
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Toptas, B
   Toptas, M
   Hanbay, D
AF Toptas, Buket
   Toptas, Murat
   Hanbay, Davut
TI Detection of Optic Disc Localization from Retinal Fundus Image Using
   Optimized Color Space
SO JOURNAL OF DIGITAL IMAGING
LA English
DT Article
DE Artificial bee colony; Fundus image; Optic disc localization; Eigenvalue
ID NERVE HEAD; AUTOMATED DETECTION; SEGMENTATION; IDENTIFICATION;
   HEMORRHAGE; LOCATION; CUP
AB Optic disc localization offers an important clue in detecting other retinal components such as the macula, fovea, and retinal vessels. With the correct detection of this area, sudden vision loss caused by diseases such as age-related macular degeneration and diabetic retinopathy can be prevented. Therefore, there is an increase in computer-aided diagnosis systems in this field. In this paper, an automated method for detecting optic disc localization is proposed. In the proposed method, the fundus images are moved from RGB color space to a new color space by using an artificial bee colony algorithm. In the new color space, the localization of the optical disc is clearer than in the RGB color space. In this method, a matrix called the feature matrix is created. This matrix is obtained from the color pixel values of the image patches containing the optical disc and the image patches not containing the optical disc. Then, the conversion matrix is created. The initial values of this matrix are randomly determined. These two matrices are processed in the artificial bee colony algorithm. Ultimately, the conversion matrix becomes optimal and is applied over the original fundus images. Thus, the images are moved to the new color space. Thresholding is applied to these images, and the optic disc localization is obtained. The success rate of the proposed method has been tested on three general datasets. The accuracy success rate for the DRIVE, DRIONS, and MESSIDOR datasets, respectively, is 100%, 96.37%, and 94.42% for the proposed method.
C1 [Toptas, Buket] Bandirma Onyedi Eylul Univ, Engn & Nat Sci Fac, Comp Engn Dept, Balikesir, Turkey.
   [Toptas, Murat] Bandirma Onyedi Eylul Univ, Engn & Nat Sci Fac, Software Engn Dept, Balikesir, Turkey.
   [Hanbay, Davut] Inonu Univ, Engn Fac, Comp Engn Dept, TR-44280 Malatya, Turkey.
C3 Bandirma Onyedi Eylul University; Bandirma Onyedi Eylul University;
   Inonu University
RP Toptas, B (通讯作者)，Bandirma Onyedi Eylul Univ, Engn & Nat Sci Fac, Comp Engn Dept, Balikesir, Turkey.
EM btoptas@bandirma.edu.tr; mtoptas@bandirma.edu.tr;
   davut.hanbay@inonu.edu.tr
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NR 48
TC 1
Z9 1
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0897-1889
EI 1618-727X
J9 J DIGIT IMAGING
JI J. Digit. Imaging
PD APR
PY 2022
VL 35
IS 2
BP 302
EP 319
DI 10.1007/s10278-021-00566-8
EA JAN 2022
PG 18
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA ZT0ZZ
UT WOS:000741249100002
PM 35018540
DA 2022-11-30
ER

PT J
AU Chen, WP
   Ye, YX
   Wu, ZR
   Lin, JL
   Wang, YT
   Ding, Q
   Yang, XR
   Yang, W
   Lin, BQ
   Lin, BQ
AF Chen, Wenpei
   Ye, Yuxin
   Wu, Zhongrui
   Lin, Junli
   Wang, Yiting
   Ding, Qi
   Yang, Xinrong
   Yang, Wei
   Lin, Bingqing
   Lin, Baoqin
TI Temporary Upregulation of Nrf2 by Naringenin Alleviates Oxidative Damage
   in the Retina and ARPE-19 Cells
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID MACULAR DEGENERATION; STRESS; DYSFUNCTION; ACTIVATION; PATHWAY; DEATH
AB Dry age-related macular degeneration (dAMD) is a chronic degenerative ophthalmopathy that leads to serious burden of visual impairment. Antioxidation in retinal pigment epithelium (RPE) cells is considered as a potential treatment for dAMD. Our previous studies have showed that naringenin (NAR) protects RPE cells from oxidative damage partly through SIRT1-mediated antioxidation. In this study, we tested the hypothesis that the Nrf2 signaling is another protective mechanism of NAR on dAMD. NaIO3-induced mouse retinopathy and ARPE-19 cell injury models were established. Immunochemical staining, immunofluorescence, and western blotting were performed to detect the protein expressions of Nrf2 and HO-1. In addition, ML385 (activity inhibitor of Nrf2) and zinc protoporphyrin (ZnPP, activity inhibitor of HO-1) were applied to explore the effect of NaIO3 or NAR. The results showed that NAR increased the protein expressions of Nrf2 and HO-1 in the retinas in mice exposed to NaIO3 at the early stage. NAR treatment also resulted in a stronger activation of Nrf2 at the early stage in NaIO3-treated ARPE-19 cells. Moreover, inhibition of HO-1 by ZnPP weakened the cytoprotective effect of NAR. The constitutive accumulation and activation of Nrf2 induced by NaIO3 led to the death of RPE cells. However, NAR decreased the protein expressions of Nrf2 and HO-1 towards normal level in the mouse retinas and ARPE-19 cells exposed to NaIO3 at the late stage. Our findings indicate that NAR protects RPE cells from oxidative damage via activating the Nrf2 signaling pathway.
C1 [Chen, Wenpei; Ye, Yuxin; Wu, Zhongrui; Wang, Yiting; Ding, Qi; Yang, Xinrong; Lin, Baoqin] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
   [Chen, Wenpei; Lin, Junli; Yang, Wei] Guangdong Lewwin Pharmaceut Res Inst Co Ltd, Guangdong Prov Ctr Ophthalm Drug Creat & Evaluat, Guangdong Prov Key Lab Drug Nonclin Evaluat & Res, TCM Nonclin Evaluat Branch,Natl Engn Res Ctr Mode, Guangzhou 510990, Guangdong, Peoples R China.
   [Lin, Bingqing] Shenzhen Univ, Coll Math & Stat, Shenzhen 518060, Guangdong, Peoples R China.
C3 Guangzhou University of Chinese Medicine; Shenzhen University
RP Lin, BQ (通讯作者)，Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
EM chenwp317@126.com; mistyalk@163.com; 971035562@qq.com; 815395427@qq.com;
   www.1054331373@qq.com; dqing9715@163.com; 2297697584@qq.com;
   ywdocnn@163.com; bqlin@szu.edu.cn; linbaoqin@gzucm.edu.cn
RI WU, ZR/GSJ-2243-2022
OI , Zhongrui/0000-0001-5758-8800; Lin, Baoqin/0000-0003-2497-7118
FU National Natural Science Foundation of China [11701386]; Guangdong
   Provincial Key Laboratory of Drug Non-clinical Evaluation and Research
   Fund; Guangzhou Science and Technology Basic [2018B030323024]; Guangzhou
   Science and Technology Basic and Applied Basic Research Project
   [202002030108]
FX This work was supported by the National Natural Science Foundation of
   China (No. 11701386), the Guangdong Provincial Key Laboratory of Drug
   Non-clinical Evaluation and Research Fund, the Guangzhou Science and
   Technology Basic (No. 2018B030323024), and the Guangzhou Science and
   Technology Basic and Applied Basic Research Project (No. 202002030108).
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NR 30
TC 4
Z9 4
U1 2
U2 6
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 NOV 17
PY 2021
VL 2021
AR 4053276
DI 10.1155/2021/4053276
PG 9
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA XL2KQ
UT WOS:000727978500003
PM 34840667
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shi, YY
   Zhang, QQ
   Zhou, H
   Wang, L
   Chu, ZD
   Jiang, XS
   Shen, MX
   Thulliez, M
   Lyu, C
   Feuer, W
   de Sisternes, L
   Durbin, MK
   Gregori, G
   Wang, RK
   Rosenfeld, PJ
AF Shi, Yingying
   Zhang, Qinqin
   Zhou, Hao
   Wang, Liang
   Chu, Zhongdi
   Jiang, Xiaoshuang
   Shen, Mengxi
   Thulliez, Marie
   Lyu, Cancan
   Feuer, William
   de Sisternes, Luis
   Durbin, Mary K.
   Gregori, Giovanni
   Wang, Ruikang K.
   Rosenfeld, Philip J.
TI Correlations Between Choriocapillaris and Choroidal Measurements and the
   Growth of Geographic Atrophy Using Swept Source OCT Imaging
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SUBRETINAL DRUSENOID DEPOSITS; MACULAR
   DEGENERATION; RETICULAR PSEUDODRUSEN; FLOW DEFICITS; PROGRESSION;
   PREVALENCE; THICKNESS; VASCULATURE; ASSOCIATION
AB PURPOSE: Correlations among enlargement rates (ERs) of geographic atrophy (GA) and choriocapillaris (CC) flow deficits (FDs), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were investigated using swept source-optical coherence tomography (SSOCT) in age-related macular degeneration (AMD).
   DESIGN: A retrospective review of prospective, observational case series.
   METHODS: Eyes with GA from AMD were imaged with SS-OCT using 6 x 6-mm scan pattern. GA lesions were identified and measured using customized en face structural images, and annual square root ERs of GA were calculated. At baseline, choriocapillaris FDs from different regions outside the GA were measured, and MCT and CVI from the entire scan area were measured. All measurements were performed using previously published and validated algorithms.
   RESULTS: A total of 38 eyes from 27 patients were included. The CC FDs within each region around GA lesions were highly correlated with ERs of GA (all P < .005). CVI inside the GA region was correlated with the ERs (P [ .03), whereas other choroidal measurements had no significant correlation with the ERs of GA (P > .06).
   CONCLUSIONS: Statistically significant correlations were found between the ERs of GA and CC percentage of FD (FD%) from the entire scan region outside the GA and not just the region immediately adjacent to the GA. These results suggest that abnormal CC perfusion throughout the macula contributes to disease progression in eyes with GA. CVI inside the GA region could also be a potential indicator for the growth of GA. (Am J Ophthalmol 2021;224:321-331. (c) 2020 Elsevier Inc. All rights reserved.)
C1 [Shi, Yingying; Wang, Liang; Jiang, Xiaoshuang; Shen, Mengxi; Thulliez, Marie; Lyu, Cancan; Feuer, William; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Zhang, Qinqin; Zhou, Hao; Chu, Zhongdi; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
   [de Sisternes, Luis; Durbin, Mary K.] Carl Zeiss Meditec Inc, Res & Dev, Dublin, CA USA.
C3 Bascom Palmer Eye Institute; University of Miami; University of
   Washington; University of Washington Seattle; Carl Zeiss AG
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@miami.edu
RI Lyu, Cancan/ABC-4635-2021; Shen, Mengxi/ABC-6941-2021; Wang,
   Ruikang/L-3889-2019; Zhou, Hao/U-7850-2017
OI Wang, Ruikang/0000-0001-5169-8822; Zhou, Hao/0000-0003-0068-5102; Shen,
   Mengxi/0000-0002-1336-1695; Lyu, Cancan/0000-0003-2078-3471
FU Carl Zeiss Meditec, Inc.; Stealth BioTherapeutics; Moptim Inc.; Colgate
   Palmolive Company; Facebook Technologies LLC
FX Giovanni Gregori, Liang Wang, and Philip J. Rosenfeld received research
   support from Carl Zeiss Meditec, Inc. Giovanni Gregori and the
   University of Miami co-own a patent licensed to Carl Zeiss Meditec, Inc.
   Philip J. Rosenfeld also receives additional research funding from
   Stealth BioTherapeutics; and is a consultant for Apellis, Biogen,
   Boehringer Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech,
   EyePoint, Ocunexus Therapeutics, Ocudyne, and Unity Biotechnology; and
   holds equity interest in Apellis, Valitor, Verana Health, and Ocudyne.
   Liang Wang holds intellectual property owned by the Oregon Health and
   Science University and University of Washington; and receives research
   support from Moptim Inc., Colgate Palmolive Company, and Facebook
   Technologies LLC; and is a consultant for Insight Photonic Solutions,
   Kowa, and Carl Zeiss Meditec. All other authors have reported that they
   have no relationships relevant to the contents of this paper to
   disclose.
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NR 48
TC 18
Z9 18
U1 0
U2 2
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 APR
PY 2021
VL 224
BP 321
EP 331
DI 10.1016/j.ajo.2020.12.015
EA FEB 2021
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RN7UW
UT WOS:000640559300032
PM 33359715
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, WP
   Lin, BQ
   Xie, SC
   Yang, W
   Lin, JL
   Li, ZJ
   Zhan, YX
   Gui, SH
   Lin, BQ
AF Chen, Wenpei
   Lin, Bingqing
   Xie, Shichuan
   Yang, Wei
   Lin, Junli
   Li, Zhaojia
   Zhan, Yaxian
   Gui, Shuhua
   Lin, Baoqin
TI Naringenin protects RPE cells from NaIO3-induced oxidative damage in
   vivo and in vitro through up-regulation of SIRT1
SO PHYTOMEDICINE
LA English
DT Article
DE Naringenin; Retinal pigment epithelium cells; Oxidative stress; SIRT1;
   Sodium iodate
ID MACULAR DEGENERATION; SODIUM IODATE; EYE DROPS; STRESS; INJURY; MICE
AB Background: Dry age-related macular degeneration (dAMD) leads to serious burden of visual impairment and there is no definitive treatment. Previous studies have showed that naringenin (NAR) significantly increased electroretinography (ERG) c-wave in sodium iodate (NaIO3)-treated rats and viability of NaIO3-treated ARPE-19 cells. But the underlying mechanism is still unknown.
   Purpose: We tested the hypothesis that anti-oxidation mediated by Sirtuin 1 (SIRT1) was important to the protective effect of NAR on dAMD.
   Study design/Methods: NaIO3-induced mice retinopathy and ARPE-19 cells injury models were established. In vivo, the protective effect of NAR eye drops on retina was evaluated by flash ERG (FERG) recording and histopathological examination. In vitro, viability of ARPE-19 cells, and the levels of lactic dehydrogenase (LDH), reactive oxygen species (ROS) and carbonyl protein were detected. Protein expression of SIRT1 was analyzed by immunochemical staining, immunofluorescence and western blotting.
   Results: NAR eye drops improved retinal function and morphology and normalized the protein expression of SIRT1 in mice exposed to NaIO3. NAR promoted the survival of ARPE-19 cells in a concentration-dependent manner. NAR up-regulated SIRT1 protein expression, and decreased levels of ROS and carbonyl protein. Moreover, EX527, a selective inhibitor of SIRT1, abolished the effects of NAR on the cell viability and ROS. In addition, SRT1720, a selective agonist of SIRT1, improved the viability of cells and suppressed the production of ROS.
   Conclusion: Our findings indicate that SIRT1-mediated anti-oxidation contributes to the protective effect of NAR eye drops on dAMD.
C1 [Chen, Wenpei; Xie, Shichuan; Li, Zhaojia; Zhan, Yaxian; Gui, Shuhua; Lin, Baoqin] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
   [Lin, Bingqing] Shenzhen Univ, Coll Math & Stat, Shenzhen 518060, Guangdong, Peoples R China.
   [Chen, Wenpei; Yang, Wei; Lin, Junli] Guangdong Lewwin Pharmaceut Res Inst Co Ltd, Guangdong Prov Key Lab Drug Nonclin Evaluat & Res, Guangzhou 510990, Guangdong, Peoples R China.
C3 Guangzhou University of Chinese Medicine; Shenzhen University
RP Lin, BQ (通讯作者)，Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
EM linbaoqin@gzucm.edu.cn
FU Guangdong Provincial Key Laboratory of Drug Non-clinical Evaluation and
   Research Fund, Guangzhou Science and Technology Basic [2018B030323024];
   Guangzhou Science and Technology Basic and Applied Basic Research
   Project [202002030108]
FX This work was supported by Guangdong Provincial Key Laboratory of Drug
   Non-clinical Evaluation and Research Fund, Guangzhou Science and
   Technology Basic (No. 2018B030323024), and Guangzhou Science and
   Technology Basic and Applied Basic Research Project (No. 202002030108).
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NR 32
TC 12
Z9 12
U1 4
U2 18
PU ELSEVIER GMBH
PI MUNICH
PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY
SN 0944-7113
EI 1618-095X
J9 PHYTOMEDICINE
JI Phytomedicine
PD JAN
PY 2021
VL 80
AR 153375
DI 10.1016/j.phymed.2020.153375
PG 10
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
   Medicine; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
   Medicine
GA OW5IU
UT WOS:000592920900018
PM 33096452
DA 2022-11-30
ER

PT J
AU Li, YT
   Lee, SG
AF Li, Yatong
   Lee, Seunggeun
TI Novel score test to increase power in association test by integrating
   external controls
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE case&#8211; control study; external controls; GWAS; saddlepoint
   approximation
ID POPULATION STRATIFICATION; RARE VARIANTS; HIGH-RISK; GENES; C3
AB Recent advances in genotyping and sequencing technologies have enabled genetic association studies to leverage high-quality genotyped data to identify variants accounting for a substantial portion of disease risk. The usage of external controls, whose genomes have already been genotyped and are publicly available, could be a cost-effective approach to increase the power of association testing. There has been recent effort to integrate external controls while adjusting for possible batch effects, such as the integrating External Controls into Association Test (iECAT). The original iECAT test, however, cannot adjust for covariates such as age, gender, and so forth. Hence, based on the insight of iECAT, we propose a novel score-based test that allows for covariate adjustment and constructs a shrinkage score statistic that is a weighted sum of the score statistics using exclusively internal samples and uses both internal and external control samples. We assess the existence of batch effect at a variant by comparing control samples of internal and external sources. We show by simulation studies that our method has increased power over the original iECAT while controlling for type I error rates. We present the application of our method to the association studies of age-related macular degeneration (AMD) utilizing data from the International AMD Genomics Consortium and Michigan Genomics Initiative. Through the incorporation of the score test approach, we extend the use of iECAT to adjust for covariates and improve power, further honing the statistical methods needed to identify disease-causing variants within the human genome.
C1 [Li, Yatong; Lee, Seunggeun] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Lee, Seunggeun] Seoul Natl Univ, Grad Sch Data Sci, Dept Data Sci, Seoul, South Korea.
C3 University of Michigan System; University of Michigan; Seoul National
   University (SNU)
RP Lee, SG (通讯作者)，Seoul Natl Univ, Grad Sch Data Sci, Seoul, South Korea.
EM lee7801@snu.ac.kr
FU National Institutes of Health [R01-HG008773]; Ministry of Science and
   ICT, National Research Foundation of Korea (NRF) [2020H1D3A2A03100666]
FX National Institutes of Health, Grant/Award Number: R01-HG008773;
   Ministry of Science and ICT, National Research Foundation of Korea
   (NRF), Grant/Award Number: 2020H1D3A2A03100666
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NR 27
TC 6
Z9 6
U1 0
U2 1
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 APR
PY 2021
VL 45
IS 3
BP 293
EP 304
DI 10.1002/gepi.22370
EA NOV 2020
PG 12
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA RC7VF
UT WOS:000587146600001
PM 33161601
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Keegan, G
   Pardhan, S
   Chichger, H
AF Keegan, Gianne
   Pardhan, Shahina
   Chichger, Havovi
TI Lutein and zeaxanthin attenuates VEGF-induced neovascularisation in
   human retinal microvascular endothelial cells through a Nox4-dependent
   pathway
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Basic science research; Cell biology; Neovascularisation; Retinopathy;
   Endothelium; Carotenoids
ID MACULAR DEGENERATION; NADPH OXIDASE; DIABETIC-RETINOPATHY;
   GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB; METABOLIC ABNORMALITIES;
   CAROTENOIDS; SUPPLEMENTATION; INHIBITION; PREVALENCE
AB Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are two of the most common and severe causes of vision loss in the population. Both conditions are associated with excessive levels of vascular endothelial growth factor (VEGF) in the eye which results in an increase in the formation of new blood vessels through a process called neovascularisation. As such, anti-VEGF therapies are currently utilised as a treatment for patients with AMD however they are associated with painful administration of injections and potential degeneration of healthy endothelium. There is therefore growing interest in alternate treatment options to reduce neovascularisation in the eye. The use of carotenoids, lutein (L) and zeaxanthin (Z), has been shown to improve vision loss parameters in patients with AMD, however the underlying mechanisms are not well-understood. We studied the impact of these compounds on neovascularisation processes using an in vitro cell model of the retinal microvascular endothelium. Our findings show that L and Z reduced VEGF-induced tube formation whilst, in combination (5:1 ratio), the compounds significantly blocked VEGF-induced neovascularisation. The carotenoids, individually and in combination, reduced VEGF-induced oxidative stress concomitant with increased activity of the NADPH oxidase, Nox4. We further demonstrated that the Nox4 inhibitor, GLX7013114, attenuated the protective effect of L and Z. Taken together, these findings indicate the protective effect of the carotenoids, L and Z, in reducing VEGF-mediated neovascularisation via a Nox4-dependent pathway. These studies implicate the potential for these compounds to be used as a therapeutic approach for patients suffering from AMD and proliferative DR.
C1 [Keegan, Gianne; Chichger, Havovi] Anglia Ruskin Univ, Fac Sci & Engn, Sch Life Sci, Cambridge, England.
   [Pardhan, Shahina; Chichger, Havovi] Anglia Ruskin Univ, Fac Hlth Educ Med & Social Care, Vis & Eye Res Inst, Cambridge, England.
C3 Anglia Ruskin University; Anglia Ruskin University
RP Chichger, H (通讯作者)，Sch Life Sci, Biomed Res Grp, East Rd, Cambridge CB1 1PT, England.
EM Havovi.Chichger@anglia.ac.uk
RI Pardhan, Shahina/AAZ-7509-2020; Chichger, Havovi/M-5129-2015
OI Chichger, Havovi/0000-0002-8549-7583; Keegan, Gianne/0000-0001-6474-6563
FU Diabetes UK [15/0005284]
FX This material is based on work supported by Diabetes UK Grant 15/0005284
   (H.Chichger).
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NR 64
TC 10
Z9 10
U1 2
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2020
VL 197
AR 108104
DI 10.1016/j.exer.2020.108104
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NI9OB
UT WOS:000565674000006
PM 32522479
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Jiang, PF
   Jacobs, KM
   Ohr, MP
   Swindle-Reilly, KE
AF Jiang, Pengfei
   Jacobs, Kane M.
   Ohr, Matthew P.
   Swindle-Reilly, Katelyn E.
TI Chitosan-Polycaprolactone Core-Shell Microparticles for Sustained
   Delivery of Bevacizumab
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE wet age-related macular degeneration; AMD; microparticles; core-shell;
   bevacizumab; anti-VEGF; drug delivery; intravitreal injection;
   angiogenesis; ocular
ID ENDOTHELIAL GROWTH-FACTOR; SINGLE INTRAVITREAL INJECTION; IN-VITRO
   FEASIBILITY; CLOSE RETINAL BREAKS; PLGA MICROPARTICLES;
   CONTROLLED-RELEASE; DRUG-DELIVERY; FACTOR VEGF; INTRAOCULAR
   PHARMACOKINETICS; MEMBRANE EMULSIFICATION
AB The current therapy for treating neovascular age-related macular degeneration requires monthly intravitreal injection of angiogenesis inhibitors such as bevacizumab or ranibizumab via a 31-gauge needle to inhibit choroidal neovascularization. However, repeated intravitreal injections are associated with poor patient compliance and potential side effects. Microparticle-based injectable devices have shown great promise to address this issue by sustained delivery of protein therapeutics, but critical barriers remain, including limited loading capacity and steady long-term release without compromising the anti-angiogenic activity of drugs. Addressing these challenges, we developed a unique method for synthesizing biodegradable polymer-based core-shell microparticles with sizes around 10 mu m, high physical integrity, and uniform size. Subsequent electrostatic and physical interactions to control protein diffusion were designed for the core-shell microparticles to effectively increase the capacity of drug loading to 25%, reduce burst release by almost 30%, and extend the period of drug release from 3 to 6 months. Remarkably, the microparticles enabled a longer-term drug administration and maintained high drug potency up to 6 months in vitro, representing significant advancement compared to conventional microparticle-based delivery platforms or currently commercialized devices. Additionally, the microparticles presented minimal toxicity to human retinal cells in vitro with over 90% cell viability, and they also exhibited good injection feasibility through 31-gauge needles in an ex vivo porcine eye model. These results warrant further studies to evaluate the clinical potential for treating posterior ophthalmic diseases as well as other conditions or injuries requiring long-term local drug administration.
C1 [Swindle-Reilly, Katelyn E.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Dept Ophthalmol & Visual Sci, Columbus, OH 43210 USA.
   [Swindle-Reilly, Katelyn E.] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA.
   [Jiang, Pengfei; Jacobs, Kane M.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
   [Ohr, Matthew P.] Ohio State Univ, Dept Ophthalmol & Visual Sci, Columbus, OH 43212 USA.
C3 University System of Ohio; Ohio State University; University System of
   Ohio; Ohio State University; University System of Ohio; Ohio State
   University; University System of Ohio; Ohio State University
RP Swindle-Reilly, KE (通讯作者)，Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Dept Ophthalmol & Visual Sci, Columbus, OH 43210 USA.; Swindle-Reilly, KE (通讯作者)，Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA.
EM reilly.198@osu.edu
OI Swindle-Reilly, Katelyn/0000-0003-1739-0263
FU Lois Hagelberger Huebner Young Investigator Grant from the Ohio Lions
   Eye Research Foundation; Ohio State University Institute for Materials
   Research Facility Grant
FX This work was funded by the Lois Hagelberger Huebner Young Investigator
   Grant from the Ohio Lions Eye Research Foundation and partially
   supported by The Ohio State University Institute for Materials Research
   Facility Grant. Dr. Yi Zhao provided a fluorescent microscope. Dr.
   Matthew Reilly and Wade Rich provided porcine eyes for ex vivo injection
   study.
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NR 78
TC 15
Z9 15
U1 2
U2 28
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 JUL 6
PY 2020
VL 17
IS 7
BP 2570
EP 2584
DI 10.1021/acs.molpharmaceut.0c00260
PG 15
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA MK0CS
UT WOS:000548455300029
PM 32484677
DA 2022-11-30
ER

PT J
AU Yakovleva, MA
   Radchenko, AS
   Feldman, TB
   Kostyukov, AA
   Arbukhanova, PM
   Borzenok, SA
   Kuzmin, VA
   Ostrovsky, MA
AF Yakovleva, Marina A.
   Radchenko, Aleksandra Sh
   Feldman, Tatiana B.
   Kostyukov, Alexey A.
   Arbukhanova, Patimat M.
   Borzenok, Sergey A.
   Kuzmin, Vladimir A.
   Ostrovsky, Mikhail A.
TI Fluorescence characteristics of lipofuscin fluorophores from human
   retinal pigment epithelium
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID VIVO FUNDUS AUTOFLUORESCENCE; A2E; AGE; OXIDATION; A2-E; PRECURSOR;
   COMPONENT; PRODUCTS; PATTERNS; CELLS
AB Lipofuscin granules accumulate in the retinal pigment epithelium (RPE) with age, especially in patients with visual diseases, including progressive age-related macular degeneration (AMD). Bisretinoids and their photooxidation and photodegradation products are major sources of lipofuscin granule fluorescence. The present study focused on examining the fluorescence decay characteristics of bisretinoid photooxidation and photodegradation products to evaluate the connection between fluorescence lifetime and spectral characteristics of target fluorophore groups. The primary objective of the study was to apply experimental spectral analysis results of lipofuscin granule fluorescence properties to interpretation of fluorescence lifetime imaging ophthalmoscopy data. Fluorescence analysis of the lipofuscin granule fluorophores in RPE collected from cadaver eyes was performed. The fluorescence lifetimes were measured by picosecond-resolved time correlated single photon counting technique. A global analytical method was applied to analyze data sets. The photooxidation and photodegradation products of bisretinoids exhibited a longer fluorescence lifetime (average value approximately 6 ns) and a shorter wavelength maximum (530-580 nm). Further, these products significantly contributed (more than 30%), to total fluorescence compared to the other fluorophores in lipofuscin granules. Thus, the contribution of oxidized lipofuscin bisretinoids to autofluorescence decay kinetics is an important characteristic for fluorescence lifetime imaging microscopy data analysis. The higher average fluorescence lifetime in AMD eyes was likely due to the higher abundance of oxidized bisretinoids compared with non-oxidized bisretinoids. Because higher level of oxidized bisretinoids is indicative of pathological processes in the retina and RPE, the present findings have the potential to improve fluorescence lifetime imaging approaches for early diagnosis of degenerative processes in the retina and RPE.
C1 [Yakovleva, Marina A.; Radchenko, Aleksandra Sh; Feldman, Tatiana B.; Kostyukov, Alexey A.; Kuzmin, Vladimir A.; Ostrovsky, Mikhail A.] Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygin St 4, Moscow 119334, Russia.
   [Feldman, Tatiana B.; Ostrovsky, Mikhail A.] Lomonosov Moscow State Univ, Biol Fac, Dept Mol Physiol, Leninskie Gory 1, Moscow 119991, Russia.
   [Arbukhanova, Patimat M.; Borzenok, Sergey A.] Sv Fyodorov Eye Microsurg Complex, Beskudnikovsky Bld 59a, Moscow 127486, Russia.
C3 Russian Academy of Sciences; Emanuel Institute of Biochemical Physics;
   Lomonosov Moscow State University
RP Feldman, TB (通讯作者)，Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygin St 4, Moscow 119334, Russia.; Feldman, TB (通讯作者)，Lomonosov Moscow State Univ, Biol Fac, Dept Mol Physiol, Leninskie Gory 1, Moscow 119991, Russia.
RI Kostyukov, Alexey/V-1238-2017; Borzenok, Sergey/ABF-9757-2021;
   Radchenko, Alexandra/B-5733-2014; Feldman, Tatiana/F-2286-2014
OI Kostyukov, Alexey/0000-0002-4574-8624; Borzenok,
   Sergey/0000-0001-9160-6240; Radchenko, Alexandra/0000-0002-6140-7053;
   Kuzmin, Vladimir/0000-0001-6586-3251; Feldman,
   Tatiana/0000-0003-2613-056X
FU Program of Fundamental Research of Presidium of the Russian Academy of
   Sciences "Fundamental research for biomedical technologies"
FX This work was supported by the Program of Fundamental Research of
   Presidium of the Russian Academy of Sciences "Fundamental research for
   biomedical technologies".
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NR 50
TC 11
Z9 11
U1 0
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1474-905X
EI 1474-9092
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PD JUL 1
PY 2020
VL 19
IS 7
BP 920
EP 930
DI 10.1039/c9pp00406h
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA MK2PL
UT WOS:000548627600005
PM 32441276
DA 2022-11-30
ER

PT J
AU Queguiner, F
   Bezirganyan, K
   Courjaret, JC
   Curel, L
   Penaranda, G
   Chossegros, MR
AF Queguiner, Frederic
   Bezirganyan, Kristina
   Courjaret, Jean Christophe
   Curel, Laurence
   Penaranda, Guillaume
   Chossegros, Maud Righini
TI Impact of switching from ranibizumab to aflibercept on the number of
   intravitreous injection and follow up visit in wet AMD: results of real
   life ELU study
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE wet age-related macular degeneration; anti-VEGF; aflibercept;
   ranibizumab; follow up visit; intravitreal injection; visual acuity
ID MACULAR DEGENERATION; RECURRENT; OUTCOMES
AB AIM: To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection (IVI) with the same efficacy.
   METHODS: ELU (or "elected" in French) study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI (phase 1) and secondary switched to aflibercept (phase 2). The number of follow up visits and IVI were compared in both phases. Visual acuity (VA) evolution and "switching" reasons were secondary analyzed.
   RESULTS: We retrospectively included data of 33 patients (38 eyes) with age-related macular degeneration (AMD; mean age: 77 +/- 7.7y). The number of monthly follow up visits [median (Q1; Q3)1: was significantly lower with aflibercept (phase 2), respectively 1.0 (0.81; 1.49) visits in phase 1, versus 0.79 (0.67; 0.86) visits in phase 2. The median number of monthly IVI also significantly decreased in phase 2, respectively 0.67 (0.55; 0.90) IVI in phase 1, versus 0.55 (0.45; 0.67) IVI in phase 2. The mean VA evolution (VA final-VA initial) was similar in both phases, (P>0.05). Whatever the reason for "switching" (loss of efficacy, tachyphylaxis, tolerance problems), there was no incidence on VA evolution over the time.
   CONCLUSION: Our results show that switching from ranibizumab to aflibercept in "suboptimal" patients significantly reduce the number of follow up visits and IVI, with a comparable efficacy. This decrease in visit number could improve patients' quality of life and reduce surgical risk by reducing the number of injections.
C1 [Queguiner, Frederic; Bezirganyan, Kristina; Courjaret, Jean Christophe; Curel, Laurence; Chossegros, Maud Righini] Hop St Joseph, Ophthalmol Dept, 26 BD Louvain, F-13008 Marseille, France.
   [Queguiner, Frederic; Bezirganyan, Kristina; Courjaret, Jean Christophe; Curel, Laurence; Chossegros, Maud Righini] Hop St Joseph, Clin Res Dept, F-13008 Marseille, France.
   [Penaranda, Guillaume] Biostat Dept, Alphabio Lab, F-13003 Marseille, France.
RP Queguiner, F (通讯作者)，Hop St Joseph, Ophthalmol Dept, 26 BD Louvain, F-13008 Marseille, France.
EM visionauriol@orange.fr
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NR 36
TC 2
Z9 3
U1 0
U2 1
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 FEB 18
PY 2020
VL 13
IS 2
BP 252
EP 256
DI 10.18240/ijo.2020.02.08
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KM4QX
UT WOS:000514116900008
PM 32090034
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Karacorlu, M
   Muslubas, IS
   Arf, S
   Hocaoglu, M
   Ersoz, MG
AF Karacorlu, Murat
   Muslubas, Isil Sayman
   Arf, Serra
   Hocaoglu, Mumin
   Ersoz, M. Giray
TI Membrane patterns in eyes with choroidal neovascularization on optical
   coherence tomography angiography
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; TYPE-1 NEOVASCULARIZATION; FEATURES
AB Background To evaluate morphologic patterns of choroidal neovascular membranes using optical coherence tomography angiography (OCTA) in patients with treatment-naive, continuously treated, and previously treated exudative age-related macular degeneration (AMD).
   Subjects We assessed retrospectively 184 eyes of 153 patients diagnosed with type 1, type 2, and mixed-type neovascularization associated with AMD. The type of neovascularization and clinical activity were assessed by clinical examination and spectral domain optical coherence tomography (SD-OCT). Morphological patterns of neovascular membranes were categorized using en face images on the AngioVue (Optovue) OCTA system.
   Results The mean age of patients was 77.9 +/- 8.6 years (range, 52-96 years). The most frequently identified type of membrane morphology was well-defined in the treatment-naive group (69% of the eyes) and in eyes receiving ongoing antiVEGF treatments (77% of the eyes). Long-filamentous morphology was the most frequent type in the previously treated group (53%), in which only 33% had a well-defined membrane. All clinically active cases had a well-defined pattern, such as a medusa or sea-fan shaped pattern, or an ill-defined pattern, and none had a long-filamentous neovascular network. Almost half of the clinically inactive cases (47%) had well- or ill-defined, identifiable membrane morphology on OCTA. A long-filamentous membrane pattern, which was consistent with chronicity of lesion, was seen only in eyes with inactive neovascularization.
   Conclusions The membrane morphology on OCTA was not associated with clinical activity, except that the presence of long dilated filamentous linear vessels was associated with chronicity and lesion inactivity.
C1 [Karacorlu, Murat; Muslubas, Isil Sayman; Arf, Serra; Hocaoglu, Mumin; Ersoz, M. Giray] Istanbul Retina Inst, Istanbul, Turkey.
C3 Istanbul Retina Enstitusu
RP Karacorlu, M (通讯作者)，Istanbul Retina Inst, Istanbul, Turkey.
EM mkaracorlu@gmail.com
RI Karaçorlu, Murat/AFK-0782-2022; Hocaoglu, Mumin/B-5999-2017; Karaçorlu,
   Murat/AAF-7763-2022; muslubas, isil sayman/B-3948-2019
OI muslubas, isil sayman/0000-0002-5464-8713
CR Al-Sheikh M, 2018, RETINA-J RET VIT DIS, V38, P220, DOI 10.1097/IAE.0000000000001628
   Ambati J, 2003, SURV OPHTHALMOL, V48, P257, DOI 10.1016/S0039-6257(03)00030-4
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   Querques G, 2016, DEV OPHTHALMOL, V56, P57, DOI 10.1159/000442779
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   Sulzbacher F, 2011, AM J OPHTHALMOL, V152, P799, DOI 10.1016/j.ajo.2011.04.011
   Xu D, 2018, AM J OPHTHALMOL, V187, P10, DOI 10.1016/j.ajo.2017.12.005
NR 22
TC 14
Z9 14
U1 0
U2 1
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 2019
VL 33
IS 8
BP 1280
EP 1289
DI 10.1038/s41433-019-0415-1
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IP8ZQ
UT WOS:000480336800014
PM 30932032
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU McKone, E
   Robbins, RA
   He, XM
   Barnes, N
AF McKone, Elinor
   Robbins, Rachel A.
   He, Xuming
   Barnes, Nick
TI Caricaturing faces to improve identity recognition in low vision
   simulations: How effective is current-generation automatic assignment of
   landmark points?
SO PLOS ONE
LA English
DT Article
AB Purpose
   Previous behavioural studies demonstrate that face caricaturing can provide an effective image enhancement method for improving poor face identity perception in low vision simulations (e.g., age-related macular degeneration, bionic eye). To translate caricaturing usefully to patients, assignment of the multiple face landmark points needed to produce the caricatures needs to be fully automatised. Recent development in computer science allows automatic face landmark detection of 68 points in real time and in multiple viewpoints. However, previous demonstrations of the behavioural effectiveness of caricaturing have used higher-precision caricatures with 147 landmark points per face, assigned by hand. Here, we test the effectiveness of the auto-assigned 68-point caricatures. We also compare this to the hand-assigned 147-point caricatures.
   Method
   We assessed human perception of how different in identity pairs of faces appear, when veridical (uncaricatured), caricatured with 68-points, and caricatured with 147-points. Across two experiments, we tested two types of low-vision images: a simulation of blur, as experienced in macular degeneration (testing two blur levels); and a simulation of the phos-phenised images seen in prosthetic vision (at three resolutions).
   Results
   The 68-point caricatures produced significant improvements in identity discrimination relative to veridical. They were approximately 50% as effective as the 147-point caricatures.
   Conclusion
   Realistic translation to patients (e.g., via real time caricaturing with the enhanced signal sent to smart glasses or visual prosthetic) is approaching feasibility. For maximum effectiveness software needs to be able to assign landmark points tracing out all details of feature and face shape, to produce high-precision caricatures.
C1 [McKone, Elinor; Robbins, Rachel A.] Australian Natl Univ, Res Sch Psychol, Canberra, ACT, Australia.
   [McKone, Elinor] Australian Natl Univ, ARC Ctr Excellence Cognit & Its Disorders, Canberra, ACT, Australia.
   [He, Xuming] ShanghaiTech Univ, Sch Informat Sci & Technol, Shanghai, Peoples R China.
   [Barnes, Nick] Australian Natl Univ, Res Sch Engn, Canberra, ACT, Australia.
   [Barnes, Nick] CSIRO, Data61, Canberra, ACT, Australia.
   [Barnes, Nick] Bion Vis Australia, Carlton, Vic, Australia.
C3 Australian National University; Australian National University;
   ShanghaiTech University; Australian National University; Commonwealth
   Scientific & Industrial Research Organisation (CSIRO)
RP McKone, E (通讯作者)，Australian Natl Univ, Res Sch Psychol, Canberra, ACT, Australia.; McKone, E (通讯作者)，Australian Natl Univ, ARC Ctr Excellence Cognit & Its Disorders, Canberra, ACT, Australia.
EM Elinor.McKone@anu.edu.au
RI Robbins, Rachel A/A-5542-2008; Barnes, Nick/Y-2744-2018
OI Barnes, Nick/0000-0002-9343-9535; McKone, Elinor/0000-0003-1655-4297;
   Robbins, Rachel/0000-0001-9363-4528
FU Australian Research Council [DP150100684]; National Health and Medical
   Research Council [1082358]
FX This work was funded by the Australian Research Council
   (http://www.arc.gov.au/) grant DP150100684 to EM and National Health and
   Medical Research Council (https://www.nhmrc.gov.au/) 1082358 to NB. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 55
TC 8
Z9 8
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 4
PY 2018
VL 13
IS 10
AR e0204361
DI 10.1371/journal.pone.0204361
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Science & Technology - Other Topics
GA GV8IQ
UT WOS:000446383500018
PM 30286112
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Moriguchi, M
   Nakamura, S
   Inoue, Y
   Nishinaka, A
   Nakamura, M
   Shimazawa, M
   Hara, H
AF Moriguchi, Mayu
   Nakamura, Shinsuke
   Inoue, Yuki
   Nishinaka, Anri
   Nakamura, Maho
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Irreversible Photoreceptors and RPE Cells Damage by Intravenous Sodium
   Iodate in Mice Is Related to Macrophage Accumulation
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE sodium iodate; retinal pigment epithelium; AMD
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; INDUCED MODEL;
   COMPLEMENT; VARIANT; INJURY; AMD
AB PURPOSE. To determine the mechanism causing degeneration of the retinal pigment epithelium (RPE) and photoreceptors in mice after an intravenous injection of sodium iodate (NaIO3).
   METHODS. The time-dependent changes in NaIO3-induced retinal degeneration were determined by analyzing the retinal morphology by optical coherence tomographic (OCT) images, histological sections of the retina, physiology of the retina by electroretinography (ERG), and retinal blood flow by laser speckle flowgraphy. In addition, the expression of the genes associated with age-related macular degeneration in humans was assessed in the NaIO3-treated mice by RT-PCR. We also investigated whether macrophages were involved in the NaIO3-induced retinal degeneration.
   RESULTS. The intravenous injection of 20 mg/kg NaIO3 altered the morphology of the RPE cells and the ERGs transiently. With 40 mg/kg of NaIO3, the degeneration of the RPE cells was still present at 28 days. Aggregated melanin granules were surrounded by zonula occludens protein 1 (ZO-1)-positive cells. In addition, 40 mg/kg of NaIO3 led to a reduction in the amplitudes of the a-and b-waves of the dark-adapted ERGs. Histological studies showed that macrophages had infiltrated the retina and were present around the altered RPE cells. Depletion of the macrophages by a prior injection of clodronate liposomes prevented the damage of the outer retina after the NaIO3 injection but not the RPE.
   CONCLUSIONS. The NaIO3-induced retinal damage was reversible at low concentrations but permanent at high concentrations of NaIO3. The accumulation of macrophages around the RPE cells caused the photoreceptor cell death.
C1 [Moriguchi, Mayu; Nakamura, Shinsuke; Inoue, Yuki; Nishinaka, Anri; Nakamura, Maho; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
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NR 49
TC 33
Z9 35
U1 1
U2 6
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 3476
EP 3487
DI 10.1167/iovs.17-23532
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GM7KT
UT WOS:000438365900016
PM 30025075
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU McCarter, RV
   McKay, GJ
   Quinn, NB
   Chakravarthy, U
   MacGillivray, TJ
   Robertson, G
   Pellegrini, E
   Trucco, E
   Williams, MC
   Peto, T
   Dhillon, B
   van Beek, EJR
   Newby, DE
   Kee, F
   Young, IS
   Hogg, RE
AF McCarter, Rachel V.
   McKay, Gareth J.
   Quinn, Nicola B.
   Chakravarthy, Usha
   MacGillivray, Tom J.
   Robertson, Gavin
   Pellegrini, Enrico
   Trucco, Emanuele
   Williams, Michelle C.
   Peto, Tunde
   Dhillon, Baljean
   van Beek, Edwin J. R.
   Newby, David E.
   Kee, Frank
   Young, Ian S.
   Hogg, Ruth E.
TI Evaluation of coronary artery disease as a risk factor for reticular
   pseudodrusen
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE retina; epidemiology; imaging
ID SUBRETINAL DRUSENOID DEPOSITS; MACULAR DEGENERATION; CHOROIDAL
   THICKNESS; PREVALENCE; ASSOCIATION; ATROPHY; EPIDEMIOLOGY; POPULATION;
   ROTTERDAM; EYES
AB Purpose Reticular pseudodrusen (RPD) are a risk factor for late age-related macular degeneration (AMD). Associations between RPD and coronary artery disease (CAD) have been reported from small case-control studies. This study investigated the association of RPD within a predominantly CAD cohort.
   Methods A subgroup of subjects from a multicentre randomised controlled trial of CT coronary angiography (CTCA) underwent ultrawide field (UWF) retinal imaging CAD determined by CTCA and was categorised as normal, non-obstructive or obstructive. Specific AMD features in UWF images were graded. Standardised grids were used to record the spatial location of AMD features, including RPD. Multivariate confounder adjusted regression models assessed the association between RPD and CAD.
   Results The 534 participants were aged 27-75 years (mean 589 years; 425 (80%) 50 years) with a male preponderance (56%). Within the study sample, 178 (33%) had no CAD, 351 (66%) had CAD. RPD was detected in 30 participants (5.6%) and bilaterally in 23. Most participants with bilateral RPD had intermediate AMD 17 (74%). After adjustment for potential confounders (age, sex, drusen >125 mu m, smoking status), multivariate analysis found no significant association between CAD and RPD (OR 1.31; 95% CI (0.57 to 3.01); p=0.52). A significant association was identified between RPD and intermediate AMD (OR 3.18; 95%CI (1.61 to 6.27); p=0.001).
   Conclusion We found no evidence to support an association between CAD and RPD. RPD was strongly associated with intermediate AMD features.
   Trial registration number NCT01149590, Post results.
C1 [McCarter, Rachel V.; McKay, Gareth J.; Quinn, Nicola B.; Chakravarthy, Usha; Peto, Tunde; Kee, Frank; Young, Ian S.; Hogg, Ruth E.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
   [MacGillivray, Tom J.; Robertson, Gavin; Pellegrini, Enrico; Dhillon, Baljean] Univ Edinburgh, Ctr Clin Brain Sci, VAMPIRE Project, Edinburgh, Midlothian, Scotland.
   [Trucco, Emanuele] Univ Dundee, Sch Sci & Engn, VAMPIRE Project, Comp, Dundee, Scotland.
   [Williams, Michelle C.; Newby, David E.] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
   [van Beek, Edwin J. R.] Univ Edinburgh, Clin Res Imaging Ctr, Edinburgh, Midlothian, Scotland.
C3 Queens University Belfast; University of Edinburgh; University of
   Dundee; University of Edinburgh; University of Edinburgh
RP Hogg, RE (通讯作者)，Queens Univ Belfast, Inst Clin Sci, Royal Hosp, Ctr Publ Hlth, 1 Block A,Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM r.e.hogg@qub.ac.uk
RI Peto, Tunde/G-8812-2018; McKay, Gareth/AAZ-2601-2020; Newby, David
   Ernest/AAB-1364-2019; Hogg, Ruth E./ABC-9602-2020; Williams, Michelle
   C/K-7555-2012
OI Peto, Tunde/0000-0001-6265-0381; McKay, Gareth/0000-0001-8197-6280;
   Hogg, Ruth E./0000-0001-9413-2669; Williams, Michelle
   C/0000-0003-3556-2428; MacGillivray, Tom/0000-0001-5120-0086; Young,
   Ian/0000-0003-3890-3152; Trucco, Emanuele/0000-0002-5055-0794; Quinn,
   Nicola/0000-0002-3224-5091; Pellegrini, Enrico/0000-0001-6913-1760;
   McCarter, Rachel/0000-0002-6270-026X; Chakravarthy,
   Usha/0000-0002-2606-3734
FU Chief Scientist Office of the Scottish Government Health and Social Care
   Directorates; Edinburgh and Lothian's Health Foundation Trust; Heart
   Diseases Research Fund; EPSRC [EP/M005976/1] Funding Source: UKRI; ESRC
   [ES/L008459/1] Funding Source: UKRI; MRC [MC_PC_15027] Funding Source:
   UKRI; Economic and Social Research Council [ES/L008459/1] Funding
   Source: researchfish; Engineering and Physical Sciences Research Council
   [EP/M005976/1] Funding Source: researchfish; Medical Research Council
   [MC_PC_15027, MC_CF023241] Funding Source: researchfish; Public Health
   Agency [STL/4936/13] Funding Source: researchfish
FX The Chief Scientist Office of the Scottish Government Health and Social
   Care Directorates funded the SCOT-HEART trial with supplementary awards
   from Edinburgh and Lothian's Health Foundation Trust and the Heart
   Diseases Research Fund.
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NR 36
TC 6
Z9 7
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 APR
PY 2018
VL 102
IS 4
BP 483
EP 489
DI 10.1136/bjophthalmol-2017-310526
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GC4DD
UT WOS:000429732500012
PM 28822985
OA Green Published, Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Ho, JH
   Liu, JH
   Chang, Y
   Chan, CT
AF Ho, Jung-Hua
   Liu, Jorn-Hon
   Chang, Yin
   Chan, Chia-Tai
TI A Technique for Real-Time Overlap of a Reflection Image and an
   Autofluorescence Image Using cSLO
SO JOURNAL OF MEDICAL AND BIOLOGICAL ENGINEERING
LA English
DT Article
DE Age-related macular degeneration; Autofluorescence; Confocal scanning
   laser ophthalmoscopy; Lipofuscin; Color imaging technique; Real-time
   overlapping display
ID PIGMENT EPITHELIAL-CELLS; SCANNING LASER OPHTHALMOSCOPE; BIOMEDICAL
   DATA; OCULAR FUNDUS; LIPOFUSCIN; FLUORESCENCE; A2E
AB For age-related macular degeneration examination, imaging techniques of confocal scanning laser ophthalmoscopy (cSLO), indocyanine green angiography, and fluorescein angiography have been used for studying the fundus, but in a monochromatic manner. When an autofluorescence image is required to be added on a gray-scale reflection image, the software plays a key role to form the colored image. In this study, we develop a hardware plug-in device for traditional cSLO to upgrade it so that it will show an overlapped color image containing both the reflection and autofluorescence images. We only use the laser (488/514 nm) within cSLO to incorporate with the hardware image overlapping system (HIOS) developed herein to real-time detect and convert both the monochromatic reflection and autofluorescence signals into a colored image. A model-retina and fluorescein isothiocyanate (FITC) dye with different concentrations is painted on the "retina" to simulate the drusen in real retina. System validation and sensitivity are evaluated by examining the "retina" image, while the observance of fluorescence results from various concentrations of FITC. The reflection and autofluorescence images are successfully separated by the optic system, further overlapped through the HIOS, and real-time displayed on a color monitor. The system sensitivity to detect fluorescence of FITC is as low as 5 x 10(-10) mol. The results of this study suggest that this type of hardware add-on technology can help upgradation of traditional cSLO to the level of autofluorescence fundus imaging economically and with a broadening of the diagnostic capability of cSLO.
C1 [Ho, Jung-Hua; Chang, Yin; Chan, Chia-Tai] Natl Yang Ming Univ, Dept Biomed Engn, 155 Sect 2,Li Nong St, Taipei 11211, Taiwan.
   [Liu, Jorn-Hon] Cheng Hsin Gen Hosp, Dept Ophthalmol, 45 Cheng Hsin St, Taipei 11220, Taiwan.
C3 National Yang Ming Chiao Tung University; Cheng Hsin General Hospital
RP Chan, CT (通讯作者)，Natl Yang Ming Univ, Dept Biomed Engn, 155 Sect 2,Li Nong St, Taipei 11211, Taiwan.
EM ch9043@chgh.org.tw; ctchan@ym.edu.tw
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PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1609-0985
EI 2199-4757
J9 J MED BIOL ENG
JI J. Med. Biol. Eng.
PD FEB
PY 2018
VL 38
IS 1
BP 55
EP 62
DI 10.1007/s40846-017-0314-5
PG 8
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA FY8LL
UT WOS:000427116100006
DA 2022-11-30
ER

PT J
AU Musolf, AM
   Simpson, CL
   Long, KA
   Moiz, BA
   Lewis, DD
   Middlebrooks, CD
   Portas, L
   Murgia, F
   Ciner, EB
   Bailey-Wilson, JE
   Stambolian, D
AF Musolf, Anthony M.
   Simpson, Claire L.
   Long, Kyle A.
   Moiz, Bilal A.
   Lewis, Deyana D.
   Middlebrooks, Candace D.
   Portas, Laura
   Murgia, Federico
   Ciner, Elise B.
   Bailey-Wilson, Joan E.
   Stambolian, Dwight
TI Myopia in Chinese families shows linkage to 10q26.13
SO MOLECULAR VISION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; BREAST-CANCER; GENETIC
   POLYMORPHISMS; HTRA1 POLYMORPHISMS; OCULAR REFRACTION; AGE; SCAN; RISK;
   SUSCEPTIBILITY
AB Purpose: To determine genetic linkage between myopia and Han Chinese patients with a family history of the disease. Methods: One hundred seventy-six Han Chinese patients from 34 extended families were given eye examinations, and mean spherical equivalent (MSE) in diopters (D) was calculated by adding the spherical component of the refraction to one-half the cylindrical component and taking the average of both eyes. The MSE was converted to a binary phenotype, where all patients with an MSE of -1.00 D or less were coded as affected. Unaffected individuals had an MSE greater than 0.00 D (ages 21 years and up), +1.50 (ages 11-20), or +2.00 D (ages 6-10 years). Individuals between the given upper threshold and -1.00 were coded as unknown. Patients were genotyped on an exome chip. Three types of linkage analyses were performed: single-variant two-point, multipoint, and collapsed haplotype pattern (CHP) variant two-point. Results: The CHP variant two-point results identified a significant peak (heterogeneity logarithm of the odds [HLOD] = 3.73) at 10q26.13 in TACC2. The single-variant two-point and multipoint analyses showed highly suggestive linkage to the same region. The single-variant two-point results identified 25 suggestive variants at HTRA1, also at 10q26.13. Conclusions: We report a significant genetic linkage between myopia and Han Chinese patients at 10q26.13. 10q26.13 contains several good candidate genes, such as TACC2 and the known age-related macular degeneration gene HTRA1. Targeted sequencing of the region is planned to identify the causal variant(s).
C1 [Musolf, Anthony M.; Simpson, Claire L.; Long, Kyle A.; Moiz, Bilal A.; Lewis, Deyana D.; Middlebrooks, Candace D.; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
   [Simpson, Claire L.] Univ Tennessee, Ctr Hlth Sci, Dept Genet Genom & Informat, Memphis, TN 38163 USA.
   [Portas, Laura; Murgia, Federico] CNR, Inst Populat Genet, Sassari, Italy.
   [Ciner, Elise B.] Salus Univ, Penn Coll Optometry, Elkins Pk, PA USA.
   [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome
   Research Institute (NHGRI); NIH National Institute on Aging (NIA);
   University of Tennessee System; University of Tennessee Health Science
   Center; Consiglio Nazionale delle Ricerche (CNR); University of
   Pennsylvania
RP Bailey-Wilson, JE (通讯作者)，333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA.
EM jebw@mail.nih.gov
OI Murgia, Federico/0000-0002-3608-845X; Bailey-Wilson,
   Joan/0000-0002-9153-2920; Simpson, Claire/0000-0003-2244-7690; Portas,
   Laura/0000-0003-1789-1893
FU National Eye Institute [R01EY020483]; National Human Genome Research
   Institute, National Institutes of Health; NATIONAL EYE INSTITUTE
   [R01EY020483] Funding Source: NIH RePORTER; NATIONAL HUMAN GENOME
   RESEARCH INSTITUTE [ZIAHG200327] Funding Source: NIH RePORTER
FX The authors would like to thank all study participants and their
   families. This work was funded in part by the National Eye Institute
   Grant R01EY020483 and the Intramural Research Program of the National
   Human Genome Research Institute, National Institutes of Health. The
   authors have no competing, commercial, or conflicts of interest to
   disclose.
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NR 83
TC 3
Z9 3
U1 0
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JAN 14
PY 2018
VL 24
BP 29
EP 42
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA FT1BR
UT WOS:000422868200001
PM 29383007
DA 2022-11-30
ER

PT J
AU Yang, JJ
   Fritsche, LG
   Zhou, X
   Abecasis, G
AF Yang, Jingjing
   Fritsche, Lars G.
   Zhou, Xiang
   Abecasis, Goncalo
CA Int Age-Related Macular Degene
TI A Scalable Bayesian Method for Integrating Functional Information in
   Genome-wide Association Studies
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID PARTITIONING HERITABILITY; LINKAGE DISEQUILIBRIUM; VARIABLE SELECTION;
   HAPLOTYPE BLOCKS; HIGH-RISK; VARIANTS; DISEASES; LOCI; IDENTIFICATION;
   ANNOTATION
AB Genome-wide association studies (GWASs) have identified many complex loci. However, most loci reside in noncoding regions and have unknown biological functions. Integrative analysis that incorporates known functional information into GWASs can help elucidate the underlying biological mechanisms and prioritize important functional variants. Hence, we develop a flexible Bayesian variable selection model with efficient computational techniques for such integrative analysis. Different from previous approaches, our method models the effect-size distribution and probability of causality for variants with different annotations and jointly models genome-wide variants to account for linkage disequilibrium (LD), thus prioritizing associations based on the quantification of the annotations and allowing for multiple associated variants per locus. Our method dramatically improves both computational speed and posterior sampling convergence by taking advantage of the block-wise LD structures in human genomes. In simulations, our method accurately quantifies the functional enrichment and performs more powerfully for prioritizing the true associations than alternative methods, where the power gain is especially apparent when multiple associated variants in LD reside in the same locus. We applied our method to an in-depth GWAS of age-related macular degeneration with 33,976 individuals and 9,857,286 variants. We find the strongest enrichment for causality among non-synonymous variants (543 more likely to be causal, 1.43 larger effect sizes) and variants in transcription, repressed Polycomb, and enhancer regions, as well as identify five additional candidate loci beyond the 32 known AMD risk loci. In conclusion, our method is shown to efficiently integrate functional information in GWASs, helping identify functional associated-variants and underlying biology.
C1 [Yang, Jingjing; Fritsche, Lars G.; Zhou, Xiang; Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
   [Fritsche, Lars G.] Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth & Nursing, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.
C3 University of Michigan System; University of Michigan; Norwegian
   University of Science & Technology (NTNU)
RP Zhou, X; Abecasis, G (通讯作者)，Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM xzhousph@umich.edu; goncalo@umich.edu
RI Fritsche, Lars G/AAF-9387-2019; Yang, Jingjing/X-5013-2019
OI Fritsche, Lars G/0000-0002-2110-1690; Yang, Jingjing/0000-0002-4191-4138
FU NIH [R01HG009124, R01GM126553, R01HG007022, R01EY022005]; National
   Science Foundation (NSF) [DMS1712933]; NATIONAL HUMAN GENOME RESEARCH
   INSTITUTE [R01HG009124] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF GENERAL MEDICAL SCIENCES [R01GM126553] Funding Source: NIH RePORTER
FX X.Z. is supported by NIH grants R01HG009124 and R01GM126553 and the
   National Science Foundation (NSF) grant DMS1712933. J.Y. and G.A. are
   supported by NIH grants R01HG007022 and R01EY022005. The authors would
   like to thank the Michigan Genomics Initiative (MGI) for allowing us to
   use the GWAS data about the skin cancer phenotype.
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PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD SEP 7
PY 2017
VL 101
IS 3
BP 404
EP 416
DI 10.1016/j.ajhg.2017.08.002
PG 13
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA FG1CS
UT WOS:000409530900007
PM 28844487
OA Bronze, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Tuzcu, M
   Orhan, C
   Muz, OE
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AF Tuzcu, Mehmet
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   Sahin, Kazim
TI Lutein and zeaxanthin isomers modulates lipid metabolism and the
   inflammatory state of retina in obesity-induced high-fat diet rodent
   model
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE High fat diet; Lutein; Zeaxanthin; NF-kappa B; Nrf2; Retina
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; KAPPA-B; MACULAR
   DEGENERATION; VEGF EXPRESSION; INDUCED UVEITIS; RISK-FACTORS;
   ANTIOXIDANT; SUPPLEMENTATION; RANIBIZUMAB
AB Background: Several studies associated high-fat intakes with a high incidence of age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may counteract reactive oxygen species produced by oxidative stress. The present study was conducted to determine the possible effects of L/Zi administration on lipid profile, protein genes associated with oxidative stress and inflammation pathways in the obesity induced by a high-fat diet (HFD) in rodents.
   Methods: Twenty-eight male Wistar rats were allocated into four groups as follows: (i) Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z. L/Zi was administrated for 8 weeks at a daily dose of 100 mg/kg BW.
   Results: L/Zi administration significantly reduced insulin and free fatty acid (FFA) levels (P < 0.001) and ameliorated the oxidative damage by reducing malondialdehyde (MDA) concentration and increasing antioxidant enzymes activities of retina induced by HFD. In addition, supplementation decreased the levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kappa B) and intercellular adhesion molecule-1 (ICAM) (P < 0.001, respectively) and improved nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) gene proteins in retinal tissues (P < 0.001).
   Conclusion: Rats fed with HFD exhibited increased oxidative stress and upregulation of inflammatory indicators. However, L/Zi supplementation modulates genes involved oxidative stress and inflammation including NF-kappa B and Nrf2 signaling pathways in the retina which may contribute to ameliorating retinal damage induced by HFD.
C1 [Tuzcu, Mehmet] Firat Univ, Div Biol, Fac Sci, Elazig, Turkey.
   [Orhan, Cemal; Sahin, Nurhan; Sahin, Kazim] Firat Univ, Dept Anim Nutr, Fac Vet, Elazig, Turkey.
   [Muz, Omer Ersin] Elazig Educ & Res Hosp, Dept Ophthalmol, Elazig, Turkey.
   [Juturu, Vijaya] OmniAct Hlth Technol Inc, Res & Dev, Morristown, NJ USA.
C3 Firat University; Firat University; Elazig Training & Research Hospital
RP Sahin, K (通讯作者)，Firat Univ, Dept Anim Nutr, Fac Vet, Elazig, Turkey.
EM nsahinkm@yahoo.com
RI Orhan, Cemal/Q-2086-2015; sahin, nurhan/ABF-8007-2020; Sahin,
   Kazim/D-5625-2009; Sahin, Nurhan/D-5626-2009; Muz, Ömer
   Ersin/ABG-6956-2020; Tuzcu, Mehmet/H-2953-2018
OI Orhan, Cemal/0000-0003-4138-7689; sahin, nurhan/0000-0001-9487-1154;
   Sahin, Kazim/0000-0001-9542-5244; Muz, Ömer Ersin/0000-0003-2264-9591;
   Tuzcu, Mehmet/0000-0002-1329-3143
FU OmniActive Health Technologies Inc. (NJ, USA) [2015-0005]; Turkish
   Academy of Sciences
FX This study was financially supported by a grant (No: 2015-0005) for
   animals and chemicals from the OmniActive Health Technologies Inc. (NJ,
   USA). This work was also financially supported in part by the Turkish
   Academy of Sciences (KS).
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NR 51
TC 45
Z9 46
U1 0
U2 15
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUL 24
PY 2017
VL 17
AR 129
DI 10.1186/s12886-017-0524-1
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FC1CZ
UT WOS:000406576300001
PM 28738845
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Song, DL
   Kanu, LN
   Li, YF
   Kelly, KL
   Bhuyan, RK
   Aleman, T
   Morgan, JIW
   Dunaief, JL
AF Song, Delu
   Kanu, Levi N.
   Li, Yafeng
   Kelly, Kristen L.
   Bhuyan, Rupak K.
   Aleman, Tomas
   Morgan, Jessica I. W.
   Dunaief, Joshua L.
TI AMD-like retinopathy associated with intravenous iron
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE AMD; Macular degeneration; Iron; Oxidative stress; RPE
ID RETINAL-PIGMENT EPITHELIUM; CHELATOR DEFERIPRONE PROTECTS; HEPCIDIN
   KNOCKOUT MICE; COMPLEMENT COMPONENT 2; MACULAR DEGENERATION; BRUCHS
   MEMBRANE; MOUSE RETINA; DRUSEN; OVERLOAD; ACCUMULATION
AB Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (-Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls' iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch's membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas of high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch's membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Song, Delu; Kanu, Levi N.; Li, Yafeng; Kelly, Kristen L.; Bhuyan, Rupak K.; Morgan, Jessica I. W.; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Aleman, Tomas] Univ Penn, Scheie Eye Inst, 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.
EM jdunaief@mail.med.upenn.edu
OI Kanu, Levi/0000-0001-6428-4696; Song, Delu/0000-0002-9030-7211
FU National Eye Institute [EY015240, U01EY025477]; National Heart, Lung and
   Blood Institute, National Institutes of Health [R25-HL084665]; National
   Center for Advancing Translational Sciences of the NIH [KL2TR001879];
   University of Pennsylvania, through Vision Science Training Grant;
   Research to Prevent Blindness; Foundation Fighting Blindness; Paula and
   Evanina Bell Mackall Foundation Trust; F. M. Kirby Foundation; NATIONAL
   CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR001879] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [P30EY001583, K12EY015398,
   U01EY025477, R01EY015240] Funding Source: NIH RePORTER; NATIONAL HEART,
   LUNG, AND BLOOD INSTITUTE [R25HL084665] Funding Source: NIH RePORTER
FX We acknowledge the support of the National Eye Institute, through grants
   EY015240 and U01EY025477; the National Heart, Lung and Blood Institute,
   National Institutes of Health, through grant R25-HL084665; the National
   Center for Advancing Translational Sciences of the NIH, through grant
   KL2TR001879; the University of Pennsylvania, through the Vision Science
   Training Grant; Research to Prevent Blindness, Foundation Fighting
   Blindness; the Paula and Evanina Bell Mackall Foundation Trust; the F.
   M. Kirby Foundation; and a gift in memory of Dr. Lee F. Mauger. The
   content is solely the responsibility of the authors and does not
   necessarily represent the official views of the NIH.
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NR 47
TC 21
Z9 21
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 OCT
PY 2016
VL 151
BP 122
EP 133
DI 10.1016/j.exer.2016.08.008
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DZ1OI
UT WOS:000385607300017
PM 27565570
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Tokarz, P
   Piastowska-Ciesielska, AW
   Kaarniranta, K
   Blasiak, J
AF Tokarz, Paulina
   Piastowska-Ciesielska, Agnieszka Wanda
   Kaarniranta, Kai
   Blasiak, Janusz
TI All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression
   of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative
   Stress
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE AMD; ARPE-19 cells; ATRA; cell death; DDR; DNA damage response;
   oxidative stress; retinoic acid; ROS
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; IN-VITRO; PROMOTER
   HYPOMETHYLATION; TRANSCRIPTION FACTOR; VISUAL CYCLE; DIFFERENTIATION;
   APOPTOSIS; INDUCTION; PROLIFERATION
AB Age-related macular degeneration (AMD) is characterized by the progressive degradation of photoreceptors and retinal pigment epithelium (RPE) cells. ARPE-19 is an RPE cell line established as an in vitro model for the study of AMD pathogenesis. Oxidative stress is an AMD pathogenesis factor that induces DNA damage. Thus, the oxidative stress-mediated DNA damage response (DDR) of ARPE-19 cells can be important in AMD pathogenesis. The metabolism of retinoids-which regulates cell proliferation, differentiation, and the visual cycle in the retina-was reported to be disturbed in AMD patients. In the present work, we studied the effect of all-trans retinoic acid (ATRA, a retinoid) on DDR in ARPE-19 cells subjected to oxidative stress. We observed that ATRA increased the level of reactive oxygen species (ROS), alkali-labile sites in DNA, DNA single-strand breaks, and cell death evoked by oxidative stress. ATRA did not modulate DNA repair or the distribution of cells in cell cycle in the response of ARPE-19 cells to oxidative stress. ATRA induced autophagy in the absence of oxidative stress, but had no effect on this process in the stress. ATRA induced over-expression of proliferation marker MKI67 and neovascularization marker VEGF-A. In conclusion, ATRA increased oxidative stress in ARPE-19 cells, resulting in more lesions to their DNA and cell death. Moreover, ATRA can modulate some properties of these cells, including neovascularization, which is associated with the exudative form of AMD. Therefore, ATRA can be important in the prevention, diagnosis, and therapy of AMD.
C1 [Tokarz, Paulina; Blasiak, Janusz] Univ Lodz, Dept Mol Genet, PL-90236 Lodz, Poland.
   [Piastowska-Ciesielska, Agnieszka Wanda] Med Univ Lodz, Dept Comparat Endocrinol, PL-90752 Lodz, Poland.
   [Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Kuopio 70210, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, SF-70210 Kuopio, Finland.
C3 University of Lodz; Medical University Lodz; University of Eastern
   Finland; Kuopio University Hospital; University of Eastern Finland
RP Blasiak, J (通讯作者)，Univ Lodz, Dept Mol Genet, PL-90236 Lodz, Poland.
EM ptokarz@biol.uni.lodz.pl; agnieszka.piastowska@umed.lodz.pl;
   kai.kaarniranta@kuh.fi; jblasiak@biol.uni.lodz.pl
RI Tokarz, Paulina/L-9983-2013; Piastowska-Ciesielska,
   Agnieszka/C-7724-2014
OI Piastowska-Ciesielska, Agnieszka/0000-0001-7462-8528; Kaarniranta,
   Kai/0000-0003-2600-8679; Tokarz, Paulina/0000-0001-9016-3089; Blasiak,
   Janusz/0000-0001-9539-9584
FU National Science Centre [DEC-2012/07/N/NZ3/01755]; VTR Grants of Kuopio
   University Hospital [5503743]; Finnish Eye Foundation
FX The authors would like to express their deepest gratitude to Mieczyslaw
   Puchala and Aleksandra Rodacka for their time and assistance in
   experiments with irradiation. This work was supported by the National
   Science Centre, decision No. DEC-2012/07/N/NZ3/01755, and the VTR Grants
   of Kuopio University Hospital (5503743), and the Finnish Eye Foundation.
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NR 46
TC 25
Z9 27
U1 1
U2 21
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUN
PY 2016
VL 17
IS 6
AR 898
DI 10.3390/ijms17060898
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA DP9EK
UT WOS:000378799300112
PM 27314326
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Gibault, F
   Corvaisier, M
   Bailly, F
   Huet, G
   Melnyk, P
   Cotelle, P
AF Gibault, Floriane
   Corvaisier, Matthieu
   Bailly, Fabrice
   Huet, Guillemette
   Melnyk, Patricia
   Cotelle, Philippe
TI Non-Photoinduced Biological Properties of Verteporfin
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Hippo pathway; YAP/TEAD complex; non-photoinduced therapy; oncogene;
   autophagy; proteotoxicity
ID PROTEIN-PROTEIN INTERACTION; HIPPO SIGNALING PATHWAY; YAP-TEAD;
   PHOTOSENSITIZER VERTEPORFIN; THERAPEUTIC TARGET; CELL-PROLIFERATION;
   ANTITUMOR-ACTIVITY; CANCER-CELLS; ACTIVATION; IDENTIFICATION
AB Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy. Results: Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models. Conclusion: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.
C1 [Gibault, Floriane; Bailly, Fabrice; Melnyk, Patricia; Cotelle, Philippe] Univ Lille, INSERM, Jean Pierre Aubert Res Ctr, Onco & NeuroChem Team,UMR S 1172, F-59000 Lille, France.
   [Corvaisier, Matthieu; Huet, Guillemette] Univ Lille, INSERM, Mucins Epithelial Differenciat & Carcinogenesis, Jean Pierre Aubert Res Ctr,UMR S 1172, F-59000 Lille, France.
C3 Universite de Lille - ISITE; Universite de Lille; Institut National de
   la Sante et de la Recherche Medicale (Inserm); Universite de Lille -
   ISITE; Universite de Lille; Institut National de la Sante et de la
   Recherche Medicale (Inserm)
RP Cotelle, P (通讯作者)，Fac Sci Pharmaceut & Biol, 3 Rue Prof Laguesse,BP 83, F-59006 Lille, France.
EM phi-lippe.cotelle@inserm.fr
RI Cotelle, P/AAX-3905-2020; cotelle, philippe/C-3297-2017
OI bailly, fabrice/0000-0001-9681-9309
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NR 67
TC 65
Z9 70
U1 3
U2 20
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 11
BP 1171
EP 1184
DI 10.2174/0929867323666160316125048
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA DJ8YZ
UT WOS:000374501900006
PM 26980565
DA 2022-11-30
ER

PT J
AU Kim, J
   Kim, TE
   Kim, JA
   Yun, JH
   Sohn, S
   Shim, SR
   Lee, SH
   Kim, SJ
AF Kim, Jaeryung
   Kim, Tae Eun
   Kim, Ju-A
   Yun, Ji-Hyun
   Sohn, Seongsoo
   Shim, Sang Ryeol
   Lee, Sang Hoon
   Kim, Sang Jin
TI Intravitreal Tanibirumab, a Fully Human Monoclonal Antibody Against
   Vascular Endothelial Growth Factor Receptor 2, Partially Suppresses and
   Regresses Laser-Induced Choroidal Neovascularization in a Rat Model
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID MACULAR DEGENERATION; TYROSINE KINASE; IN-VITRO; VEGF-A; INHIBITOR;
   CANCER; BEVACIZUMAB; THERAPY; DISEASE; RETINA
AB Purpose: The study investigated the effect of intravitreally administered tanibirumab, a fully human monoclonal antibody against vascular endothelial growth factor receptor 2, in a rat model of laser-induced choroidal neovascularization (CNV).
   Methods: CNV was induced by laser photocoagulation on day 0 in the eyes of Brown Norway rats. Intravitreal injection of tanibirumab or phosphate-buffered saline (PBS) was done on day 0 (prevention arm) or day 7 (treatment arm). Seven days after injection, the eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in the flat mounts using tetramethylrhodamine isothiocyanate Bandeiraea simplicifolia (BS) isolectin labeling and intravenously administered fluorescein isothiocyanate-dextran and quantified using an image analysis program.
   Results: In the prevention arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.2% and 53.9% in tanibirumab-treated eyes (20 and 60 mu g, respectively) compared with PBS-treated control eyes on day 7 (P=0.038 and P<0.001, respectively). In the treatment arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.7% and 46.0% in tanibirumab-treated eyes (20 and 60 mu g, respectively) compared with PBS-treated control eyes on day 14 (P=0.048 and P<0.001, respectively).
   Conclusions: Intravitreally administered tanibirumab partially suppressed the formation of new CNV and partially regressed preformed laser-induced CNV in the rat model. Tanibirumab may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.
C1 [Kim, Jaeryung] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Vasc Biol & Stem Cells, Taejon 305701, South Korea.
   [Kim, Tae Eun; Kim, Ju-A; Yun, Ji-Hyun; Kim, Sang Jin] Samsung Biomed Res Inst, Seoul, South Korea.
   [Sohn, Seongsoo; Kim, Sang Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul 135710, South Korea.
   [Shim, Sang Ryeol] PharmAbcine Inc, Taejon, South Korea.
   [Lee, Sang Hoon] Hanwha Chem, Ctr Res & Dev, Biol Business, Taejon, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST); Sungkyunkwan
   University (SKKU); Samsung Medical Center; Sungkyunkwan University
   (SKKU); Samsung Medical Center; Hanwha Corporation; Hanwha Chemical
RP Kim, SJ (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, 50 Irwon Dong, Seoul 135710, South Korea.
EM sangjinkim@skku.edu
RI Kim, Jaeryung/AAB-6693-2022
OI Kim, Jaeryung/0000-0002-8003-5849; Shim, Sang Ryeol/0000-0002-5188-688X
FU Samsung Medical Center grant [SMR112051]; PharmAbcine, Inc. [PHX1127081,
   PHX1127161]
FX This study was supported by the Samsung Medical Center grant (SMR112051)
   and grant from the PharmAbcine, Inc. (PHX1127081 and PHX1127161). The
   authors thank Dr. Jin-San Yoo, Dr. Weon Sup Lee, and Dr. Sung-Woo Kim at
   PharmAbcine for helpful scientific discussions and comments.
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NR 32
TC 3
Z9 5
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
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD DEC 1
PY 2014
VL 30
IS 10
BP 847
EP 853
DI 10.1089/jop.2014.0021
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA AU6AL
UT WOS:000345684400010
PM 25188901
OA Green Published
DA 2022-11-30
ER

PT J
AU Hasegawa, E
   Sweigard, H
   Husain, D
   Olivares, AM
   Chang, B
   Smith, KE
   Birsner, AE
   D'Amato, RJ
   Michaud, NA
   Han, YN
   Vavvas, DG
   Miller, JW
   Haider, NB
   Connor, KM
AF Hasegawa, Eiichi
   Sweigard, Harry
   Husain, Deeba
   Olivares, Ana M.
   Chang, Bo
   Smith, Kaylee E.
   Birsner, Amy E.
   D'Amato, Robert J.
   Michaud, Norman A.
   Han, Yinan
   Vavvas, Demetrios G.
   Miller, Joan W.
   Haider, Neena B.
   Connor, Kip M.
TI Characterization of a Spontaneous Retinal Neovascular Mouse Model
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; ANGIOMATOUS
   PROLIFERATION; SUBRETINAL NEOVASCULARIZATION; CHOROIDAL
   NEOVASCULARIZATION; CHORIORETINAL ANASTOMOSIS; PIGMENT EPITHELIUM;
   TRANSGENIC MICE; MULLER CELLS; EXPRESSION
AB Background: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model.
   Methods: The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software.
   Results: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p) 15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space.
   Conclusions: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.
C1 [Hasegawa, Eiichi; Sweigard, Harry; Husain, Deeba; Smith, Kaylee E.; Michaud, Norman A.; Vavvas, Demetrios G.; Miller, Joan W.; Connor, Kip M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA.
   [Hasegawa, Eiichi; Sweigard, Harry; Husain, Deeba; D'Amato, Robert J.; Vavvas, Demetrios G.; Miller, Joan W.; Haider, Neena B.; Connor, Kip M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   [Olivares, Ana M.; Han, Yinan; Haider, Neena B.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Chang, Bo] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Birsner, Amy E.; D'Amato, Robert J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program,Dept Surg, Boston, MA USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Harvard
   University; Harvard Medical School; Harvard University; Massachusetts
   Eye & Ear Infirmary; Schepens Eye Research Institute; Jackson
   Laboratory; Harvard University; Boston Children's Hospital; Harvard
   Medical School
RP Connor, KM (通讯作者)，Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA.
EM kip_connor@meei.harvard.edu
OI Chang, Bo/0000-0001-8259-7290; Vavvas, Demetrios/0000-0002-8622-6478;
   Miller, Joan/0000-0003-2046-3996; Connor, Kip/0000-0002-2048-9080;
   Husain, Deeba/0000-0002-8494-0950
FU Research to Prevent Blindness; Bright Focus Foundation; National Eye
   Institute of the National Institutes of Health [R01EY022084/S1,
   P30EY014104]; NATIONAL EYE INSTITUTE [R01EY019943, P30EY014104,
   R01EY022084] Funding Source: NIH RePORTER
FX Research reported in this publication was supported by a Special Scholar
   Award (to KMC) and unrestricted grant (to JM) from Research to Prevent
   Blindness, as well as a Bright Focus Foundation grant (to KMC and NH).
   Additionally, research reported in this publication was supported by
   National Eye Institute of the National Institutes of Health under award
   numbers R01EY022084/S1 (to KMC) and P30EY014104. The content is solely
   the responsibility of the authors and does not necessarily represent the
   official views of the National Institutes of Health. 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 25
Z9 25
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 SEP 4
PY 2014
VL 9
IS 9
AR e106507
DI 10.1371/journal.pone.0106507
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AO3XV
UT WOS:000341271500047
PM 25188381
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Suzuki, M
   Ozawa, Y
   Kubota, S
   Hirasawa, M
   Miyake, S
   Noda, K
   Tsubota, K
   Kadonosono, K
   Ishida, S
AF Suzuki, Misa
   Ozawa, Yoko
   Kubota, Shunsuke
   Hirasawa, Manabu
   Miyake, Seiji
   Noda, Kousuke
   Tsubota, Kazuo
   Kadonosono, Kazuaki
   Ishida, Susumu
TI Neuroprotective response after photodynamic therapy: Role of vascular
   endothelial growth factor
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE VEGF; PDT; retina; neuroprotection; Akt; BAX
ID VEGF; VERTEPORFIN; INFLAMMATION; RANIBIZUMAB; ANGIOGENESIS; EXPRESSION;
   APOPTOSIS; ISCHEMIA; SURVIVAL; HYPOXIA
AB Background: Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood.
   Methods: We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively.
   Results: At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis.
   Conclusion: Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective.
C1 [Suzuki, Misa; Ozawa, Yoko; Kubota, Shunsuke; Hirasawa, Manabu; Miyake, Seiji; Ishida, Susumu] Keio Univ, Sch Med, Lab Retinal Cell Biol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Suzuki, Misa; Ozawa, Yoko; Kubota, Shunsuke; Hirasawa, Manabu; Tsubota, Kazuo] Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Suzuki, Misa; Kadonosono, Kazuaki] Yokohama City Univ, Med Ctr, Dept Ophthalmol, Minami Ku, Yokohama, Kanagawa 2320024, Japan.
   [Noda, Kousuke; Ishida, Susumu] Hokkaido Univ, Grad Sch Med, Dept Ophthalmol, Kita Ku, Sapporo, Hokkaido 0608638, Japan.
C3 Keio University; Keio University; Yokohama City University; Hokkaido
   University
RP Ozawa, Y (通讯作者)，Keio Univ, Sch Med, Lab Retinal Cell Biol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ozawa@a5.keio.jp
RI ISHIDA, SUSUMU/D-7067-2012; Ozawa, Yoko/AAH-9888-2020
FU NOVARTIS Pharmacetutical Co., Ltd.; Grants-in-Aid for Scientific
   Research [23592588] Funding Source: KAKEN
FX The authors receive financial support from NOVARTIS Pharmacetutical Co.,
   Ltd.
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NR 43
TC 18
Z9 20
U1 1
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD DEC 16
PY 2011
VL 8
AR 176
DI 10.1186/1742-2094-8-176
PG 11
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 893FL
UT WOS:000300341500001
PM 22171708
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Fingert, JH
   Robin, AL
   Stone, JL
   Roos, BR
   Davis, LK
   Scheetz, TE
   Bennett, SR
   Wassink, TH
   Kwon, YH
   Alward, WLM
   Mullins, RF
   Sheffield, VC
   Stone, EM
AF Fingert, John H.
   Robin, Alan L.
   Stone, Jennifer L.
   Roos, Ben R.
   Davis, Lea K.
   Scheetz, Todd E.
   Bennett, Steve R.
   Wassink, Thomas H.
   Kwon, Young H.
   Alward, Wallace L. M.
   Mullins, Robert F.
   Sheffield, Val C.
   Stone, Edwin M.
TI Copy number variations on chromosome 12q14 in patients with normal
   tension glaucoma
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; TOOTH DISEASE TYPE-1A; TRANSCRIPTION FACTOR GENE;
   OPTIC DISK ANOMALIES; CLINICAL-FEATURES; VISUAL IMPAIRMENT; COMMON
   VARIANTS; UNITED-STATES; WDR36 GENE; MUTATIONS
AB We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reaction (PCR) experiments identified a 780 kbp duplication within the GLC1P locus that is co-inherited with NTG in the pedigree. Real-time PCR studies showed that the genes within this duplication [TBK1 (TANK-binding kinase 1), XPOT, RASSF3 and GNS] are all expressed in the human retina. Cohorts of 478 glaucoma patients (including 152 NTG patients), 100 normal control subjects and 400 age-related macular degeneration patients were subsequently tested for copy number variation in GLC1P. Overlapping duplications were detected in 2 (1.3%) of the 152 NTG subjects, one of which had a strong family history of glaucoma. These duplications defined a 300 kbp critical region of GLC1P that spans two genes (TBK1 and XPOT). Microarray expression experiments and northern blot analysis using RNA obtained from human skin fibroblast cells showed that duplication of chromosome 12q14 results in increased TBK1 and GNS transcription. Finally, immunohistochemistry studies showed that TBK1 is expressed in the ganglion cells, nerve fiber layer and microvasculature of the human retina. Together, these data link the duplication of genes on chromosome 12q14 with familial NTG and suggest that an extra copy of the encompassed TBK1 gene is likely responsible for these cases of glaucoma. However, animal studies will be necessary to rule out a role for the other duplicated or neighboring genes.
C1 [Fingert, John H.; Roos, Ben R.; Scheetz, Todd E.; Kwon, Young H.; Alward, Wallace L. M.; Mullins, Robert F.; Stone, Edwin M.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
   [Davis, Lea K.; Wassink, Thomas H.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA.
   [Sheffield, Val C.] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA.
   [Robin, Alan L.; Stone, Jennifer L.] Glaucoma Specialists, Baltimore, MD USA.
   [Robin, Alan L.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol & Int Hlth, Baltimore, MD USA.
   [Robin, Alan L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Bennett, Steve R.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
   [Sheffield, Val C.; Stone, Edwin M.] Howard Hughes Med Inst, Iowa City, IA USA.
C3 University of Iowa; University of Iowa; University of Iowa; Johns
   Hopkins University; Johns Hopkins University; Johns Hopkins Bloomberg
   School of Public Health; University of Minnesota System; University of
   Minnesota Twin Cities; Howard Hughes Medical Institute
RP Fingert, JH (通讯作者)，Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, 1269B CBRB,285 Newton Rd, Iowa City, IA 52242 USA.
EM john-fingert@uiowa.edu
RI Fingert, John/AAX-4750-2021; Alward, Wallace/AAY-4149-2020; Mullins,
   Robert F/I-6717-2013; Fingert, John/F-8787-2012
OI Fingert, John/0000-0002-0377-0479; Fingert, John/0000-0002-0377-0479;
   Sheffield, Val/0000-0002-6282-0835; Alward, Wallace/0000-0001-6368-9018;
   Kwon, Young/0000-0002-1116-8250; Robin, Alan/0000-0003-1959-8770;
   Wassink, Thomas/0000-0002-0952-8333; Scheetz, Todd/0000-0002-1965-5811;
   Mullins, Robert/0000-0002-5006-0891; Stone, Edwin M./0000-0003-3343-4414
FU Research to Prevent Blindness; Gustavus and Louise Pfeiffer Research
   Foundation; Marlene S. and Leonard A. Hadley Glaucoma Research Fund;
   National Institutes of Health [RO1EY018825, K08 EY017698, R01EY010564];
   NATIONAL EYE INSTITUTE [K08EY017698, R01EY010564, R01EY018825] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [T32GM008629] Funding Source: NIH RePORTER
FX This work was supported by Research to Prevent Blindness, the Gustavus
   and Louise Pfeiffer Research Foundation, the Marlene S. and Leonard A.
   Hadley Glaucoma Research Fund and the National Institutes of Health
   (RO1EY018825 and K08 EY017698 to J.H.F. and R01EY010564 to V.C.S.).
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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 JUN 15
PY 2011
VL 20
IS 12
BP 2482
EP 2494
DI 10.1093/hmg/ddr123
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 767IK
UT WOS:000290849200018
PM 21447600
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Wang, Y
   Bian, ZM
   Yu, WZ
   Yan, Z
   Chen, WC
   Li, XX
AF Wang, Yu
   Bian, Zong-Mei
   Yu, Wen-Zhen
   Yan, Zheng
   Chen, Wei-Chih
   Li, Xiao-Xin
TI Induction of interleukin-8 gene expression and protein secretion by
   C-reactive protein in ARPE-19 cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; C-reactive protein; ARPE-19;
   interlukin-8
ID AORTIC ENDOTHELIAL-CELLS; FC-GAMMA-RIIA; NF-KAPPA-B; MACULAR
   DEGENERATION; SYNTHETIC PEPTIDE; TISSUE FACTOR; AGE; ACTIVATION; MCP-1;
   CRP
AB C-reactive protein (CRP) is an acute phase reactant and its level rises rapidly during inflammation. Recent studies have suggested the potential involvement of CRP in the pathogenesis of age-related macular degeneration (AMD). To delineate the functional roles of CRP in inflammatory response by the ocular posterior segments, the effects of CRP on ARPE-19, an immortalized human retinal pigment epithelia (hRPE) cell line, were investigated in the present study. Treatment of ARPE-19 cells with CRP resulted in enhanced NF-kB nuclear translocation and dose-dependent transient induction of IL-8 mRNA synthesis and protein secretion. Stimulated expression of VEGF, but not MCP-1 by CRP was also observed. The induced IL-8 expression was transient and peaked at 12 h post stimulation. In the presence of inhibitors for NF-kB, p38, MEK and JNK, the CRP-induced IL-8 production was abolished by 99.5 +/- 2.3, 97.8 +/- 2.1, 55.3 +/- 2.5 and 37.3 +/- 1.3%, respectively. Neutralization of Fc gamma receptors by anti-CD32 and CD64 antibodies produced 39.9 +/- 1.6 and 59.5 +/- 2.6% reduction, respectively, of CRP-stimulated IL-8 secretion, whereas that by anti-CD16 antibody had no effect. This study suggests that the pro-inflammatory effects of CRP in ARPE-19 cells may contribute to the inflammatory retinal diseases by induction of pro-inflammatory cytokines such as IL-8. This induction is mediated by NF-kB and multiple MAPK pathways through Fc gamma receptors. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Wang, Yu; Yu, Wen-Zhen; Yan, Zheng; Chen, Wei-Chih; Li, Xiao-Xin] Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China.
   [Bian, Zong-Mei] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA.
C3 Peking University; University of Michigan System; University of Michigan
RP Li, XX (通讯作者)，Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China.
EM drlixiaoxin@163.com
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NR 58
TC 23
Z9 24
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 AUG
PY 2010
VL 91
IS 2
BP 135
EP 142
DI 10.1016/j.exer.2010.02.008
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 633NG
UT WOS:000280509100004
PM 20188089
DA 2022-11-30
ER

PT J
AU Lara-Castillo, N
   Zandi, S
   Nakao, S
   Ito, Y
   Noda, K
   She, HC
   Ahmed, M
   Frimmel, S
   Ablonczy, Z
   Hafezi-Moghadam, A
AF Lara-Castillo, Nuria
   Zandi, Souska
   Nakao, Shintaro
   Ito, Yasuhiro
   Noda, Kousuke
   She, Haicheng
   Ahmed, Muna
   Frimmel, Sonja
   Ablonczy, Zsolt
   Hafezi-Moghadam, Ali
TI Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal
   Neovascularization
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID RETINAL BARRIER BREAKDOWN; MACULAR DEGENERATION; PERMEABILITY FACTOR;
   GROWTH-FACTOR; VEGF; ANGIOGENESIS; RECEPTOR; CELLS
AB Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to I mu mol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP's effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP's TEER response was concentration but not time dependent. lit vivo, ANP significantly reduced VFGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. (Am J Pathol 2009, 175:2343-2350; DOI: 10.2353/ajpath.2009.090439)
C1 [Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA USA.
   [Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   [Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Harvard University; Harvard Medical School; Medical
   University of South Carolina
RP Hafezi-Moghadam, A (通讯作者)，325 Cambridge St,3rd Floor, Boston, MA 02114 USA.
EM AHM@meei.harvard.edu
OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Zandi,
   Souska/0000-0001-9351-4278
FU NEI NIH HHS [R24 EY014793, P30 EY014104, EY14793, EY14104] Funding
   Source: Medline; NIAID NIH HHS [AI050775, K08 AI050775] Funding Source:
   Medline; NATIONAL EYE INSTITUTE [P30EY014104, R24EY014793] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS
   DISEASES [K08AI050775] Funding Source: NIH RePORTER
CR Ablonczy Z, 2007, EXP EYE RES, V85, P762, DOI 10.1016/j.exer.2007.08.010
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NR 25
TC 36
Z9 38
U1 1
U2 5
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 DEC
PY 2009
VL 175
IS 6
BP 2343
EP 2350
DI 10.2353/ajpath.2009.090439
PG 8
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 530NW
UT WOS:000272600600011
PM 19910509
OA Green Published
DA 2022-11-30
ER

PT J
AU Sacu, S
   Michels, S
   Prager, F
   Weigert, G
   Dunavoelgyi, R
   Geitzenauer, W
   Pruente, C
   Schmidt-Erfurth, U
AF Sacu, S.
   Michels, S.
   Prager, F.
   Weigert, G.
   Dunavoelgyi, R.
   Geitzenauer, W.
   Pruente, C.
   Schmidt-Erfurth, U.
TI Randomised clinical trial of intravitreal Avastin vs photodynamic
   therapy and intravitreal triamcinolone: long-term results
SO EYE
LA English
DT Article
DE intravitreal bevacizumab; age-related macular degeneration; photodynamic
   therapy; triamcinolone acetonide
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; BEVACIZUMAB AVASTIN;
   RANIBIZUMAB; VERTEPORFIN; MEMBRANES; ACETONIDE
AB Purpose To compare 1-year functional and anatomic outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone (PDT + IVTA) combination in patients with neovascular age-related macular degeneration (AMD).
   Methods In this prospective, randomised, controlled clinical trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1 mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT + IVTA). Follow-up examinations were performed in monthly intervals in IVB group and every 3 months in PDT + IVTA group. Main outcomes were change in mean visual acuity (VA), mean central retinal thickness (CRT) and the mean number of treatments.
   Results At month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three letters in PDT + IVTA group (P = 0.02). Mean CRT was reduced from 357 mu m at baseline to 244 mu m at month 12 in IVB group and from 326 mu m to 254 mu m, respectively, in PDT + IVTA group (P = 0.8). The mean number of treatments was 6.8 in the IVB group vs 1.9 in the PDT + IVTA group. No significant local or systemic safety concerns were detected during follow-up time.
   Conclusions Patients treated with IVB showed a significant better VA outcome compared with the PDT + IVTA group despite the fact that both modalities showed equal potency in reducing CRT during a 12-month period. Eye (2009) 23, 2223-2227; doi:10.1038/eye.2008.423; published online 23 January 2009
C1 [Sacu, S.; Prager, F.; Weigert, G.; Dunavoelgyi, R.; Geitzenauer, W.; Pruente, C.; Schmidt-Erfurth, U.] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
   [Michels, S.] Univ Zurich, Dept Ophthalmol, Zurich, Switzerland.
   [Weigert, G.] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria.
C3 Medical University of Vienna; University of Zurich; Medical University
   of Vienna
RP Sacu, S (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM stefan.sacu@meduniwien.ac.at
OI Dunavoelgyi, Roman/0000-0002-1842-240X; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311
CR Ahmadieh H, 2008, EUR J OPHTHALMOL, V18, P297, DOI 10.1177/112067210801800222
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   Schmidt-Erfurth UM, 2003, OPHTHALMOLOGY, V110, P1306, DOI 10.1016/S0161-6420(03)00452-4
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NR 16
TC 36
Z9 37
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD DEC
PY 2009
VL 23
IS 12
BP 2223
EP 2227
DI 10.1038/eye.2008.423
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 530JK
UT WOS:000272585500012
PM 19169239
OA Bronze
DA 2022-11-30
ER

PT J
AU Hadziahmetovic, M
   Dentchev, T
   Song, Y
   Haddad, N
   He, XN
   Hahn, P
   Pratico, D
   Wen, R
   Harris, ZL
   Lambris, JD
   Beard, J
   Dunaief, JL
AF Hadziahmetovic, Majda
   Dentchev, Tzvete
   Song, Ying
   Haddad, Nadine
   He, Xining
   Hahn, Paul
   Pratico, Domenico
   Wen, Rong
   Harris, Z. Leah
   Lambris, John D.
   Beard, John
   Dunaief, Joshua L.
TI Ceruloplasmin/hephaestin knockout mice model morphologic and molecular
   features of AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   LIPID-PEROXIDATION; LIPOFUSCIN ACCUMULATION; ALZHEIMERS-DISEASE;
   IRON-DEFICIENCY; AGE; DRUSEN; TRANSFERRIN
AB PURPOSE. Iron is an essential element in human metabolism but also is a potent generator of oxidative damage with levels that increase with age. Several studies suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). In prior studies, both iron overload and features of AMD were identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its homologue hephaestin (Heph) (double knockout, DKO). In this study, the location and timing of iron accumulation, the rate and reproducibility of retinal degeneration, and the roles of oxidative stress and complement activation were determined.
   METHODS. Morphologic analysis and histochemical iron detection by Perls' staining was performed on retina sections from DKO and control mice. Immunofluorescence and immunohistochemistry were performed with antibodies detecting activated complement factor C3, transferrin receptor, L-ferritin, and macrophages. Tissue iron levels were measured by atomic absorption spectrophotometry. Isoprostane F2 alpha-VI, a specific marker of oxidative stress, was quantified in the tissue by gas chromatography/mass spectrometry.
   RESULTS. DKOs exhibited highly reproducible age-dependent iron overload, which plateaued at 6 months of age, with subsequent progressive retinal degeneration continuing to at least 12 months. The degeneration shared some features of AMD, including RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement activation.
   CONCLUSIONS. DKOs have age-dependent iron accumulation followed by retinal degeneration modeling some of the morphologic and molecular features of AMD. Therefore, these mice are a good platform on which to test therapeutic agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents.
C1 [Hadziahmetovic, Majda; Dentchev, Tzvete; Song, Ying; Haddad, Nadine; He, Xining; Hahn, Paul; Dunaief, Joshua L.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   [Lambris, John D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Pratico, Domenico] Temple Univ, Dept Pharmacol, Philadelphia, PA 19122 USA.
   [Wen, Rong] Univ Miami, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA.
   [Harris, Z. Leah] Johns Hopkins Sch Med, Dept Pediat Anesthesia & Crit Care, Baltimore, MD USA.
   [Beard, John] Penn State Univ, Coll Hlth & Human Dev, Dept Nutr, University Pk, PA 16802 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); Temple University; Bascom Palmer Eye Institute; University of
   Miami; Johns Hopkins University; Johns Hopkins Medicine; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Pennsylvania State
   University; Pennsylvania State University - University Park
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
RI Mohammed, Imran/J-8271-2012; Pratico, Domenico/ABA-9590-2020; Lambris,
   John/Q-5633-2018
OI Mohammed, Imran/0000-0002-8412-0768; Lambris, John/0000-0002-9370-5776;
   Harris, Zena Leah/0000-0003-0110-8438; Hahn, Paul/0000-0002-6574-388X
FU NEI NIH HHS [R01 EY015240, EY015240, R01 EY015240-04] Funding Source:
   Medline; NATIONAL EYE INSTITUTE [R01EY015240] Funding Source: NIH
   RePORTER
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NR 47
TC 104
Z9 106
U1 1
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2008
VL 49
IS 6
BP 2728
EP 2736
DI 10.1167/iovs.07-1472
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 307GG
UT WOS:000256306800058
PM 18326691
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Muller, A
   Keeffe, JE
   Taylor, HR
AF Muller, Andreas
   Keeffe, Jill E.
   Taylor, Hugh R.
TI Changes in eye care utilization following an eye health promotion
   campaign
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE diabetic retinopathy; public health; service utilization
ID MELBOURNE
AB Background: The Vision Initiative is a public health campaign that promotes the early detection of the main causes of vision loss through regular eye examinations. Target groups are people over 50 years, with diabetes, a family history of glaucoma or age-related macular degeneration and those who have noted a change in vision.
   Methods: In 2005, a range of initiatives promoted the main campaign messages using metropolitan and regional television, radio and newspapers. Campaign outcomes such as last visits to an eye specialist were evaluated comparing pre- and post-campaign data. Participation was volunteer based from randomly selected Melbourne suburbs. Recruitment was by mail. Participants were between 70 and 79 years of age. A questionnaire collected information about demographics, utilization of eye care services, general health and lifestyle. Key features of the five main eye diseases that cause vision loss in Australia were assessed.
   Results: The percentage of people that reported to have visited an eye specialist within the last year increased significantly from 61% to 70% (P < 0.001). Also the percentage of people with diabetes that reported to have a dilated fundus examination within the last 2 years increased significantly from 52% to 70% (P < 0.001) and the percentage of people reporting to always wear sunglasses when going out in the sun increased significantly from 33% to 39% (P < 0.001).
   Conclusions: Following the campaign, there was an improvement in the utilization of eye care services, especially by people with diabetes. However, other Australian public campaigns may contribute to the increased awareness of the effect of diabetes on eye health.
C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   Univ New S Wales, Vis Cooperat Res Ctr, Sydney, NSW, Australia.
C3 Centre for Eye Research Australia; University of Melbourne; University
   of New South Wales Sydney; Visa Inc
RP Muller, A (通讯作者)，Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM amuller@hollows.org
OI Taylor, Hugh/0000-0002-9437-784X
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NR 10
TC 28
Z9 29
U1 0
U2 10
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 MAY-JUN
PY 2007
VL 35
IS 4
BP 305
EP 309
DI 10.1111/j.1442-9071.2007.01450.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 172GC
UT WOS:000246791100003
PM 17539780
DA 2022-11-30
ER

PT J
AU Liew, SHM
   Gilbert, CE
   Spector, TD
   Mellerio, J
   Marshall, J
   van Kuijk, FJ
   Beatty, S
   Fitzke, F
   Hammond, CJ
AF Liew, SHM
   Gilbert, CE
   Spector, TD
   Mellerio, J
   Marshall, J
   van Kuijk, FJ
   Beatty, S
   Fitzke, F
   Hammond, CJ
TI Heritability of macular pigment: A twin study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM; OPTICAL-DENSITY;
   SPATIAL-DISTRIBUTION; FLICKER PHOTOMETRY; PRIMATE RETINAS; HUMAN EYES;
   DEGENERATION; ZEAXANTHIN; CAROTENOIDS
AB PURPOSE. Several studies have reported higher levels of macular pigment (MP) in association with reduced risk for age-related macular degeneration (ARMD), a disease to which there is a genetic predisposition. A classic twin study was performed to determine the heritability of MP in the healthy eye.
   METHODS. One hundred fifty twin pairs (76 monozygotic [MZ] and 74 dizygotic [DZ]), aged 18 to 50 years, participated. MP optical density was measured psychophysically with heterochromatic flicker photometry (HFP) and also with an imaging method involving fundus autofluorescence (AF). The covariance of MP within MZ and DZ twin pairs was compared, and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in MP.
   RESULTS. The mean MP optical density, measured using HFP, was 0.43 +/- 0.21. Using AF, the mean MP optical density, measured at 1 eccentricity, was 0.28 +/- 0.11. MP optical densities correlated more highly in MZ twins than in DZ twins, according to both HFP (MZ: 0.65; DZ: 0.24) and AF (MZ: 0.83; DZ: 0.50). A model combining additive genetic and unique environmental effects provided the best fit and resulted in MP heritability estimates of 0.67 (95% CI, 0.52-0.77) and 0.85 (95% CI, 0.78-0.90) for HFP and AF readings, respectively.
   CONCLUSIONS. This classic twin study demonstrates that genetic background is an important determinant of MP optical density, reflected in heritability estimates of 0.67 and 0.85 for HFP and AF measures, respectively.
C1 St Thomas Hosp, Twin Res & Genet Epidemiol Unit, London SE1 7EH, England.
   St Thomas Hosp, Rayne Inst, Dept Ophthalmol, London SE1 7EH, England.
   Univ London, London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London, England.
   Univ Westminster, Sch Biosci, London W1R 8AL, England.
   Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77550 USA.
   Waterford Inst Technol, Dept Chem & Life Sci, Waterford, Ireland.
   Inst Ophthalmol, London, England.
   Princess Royal Univ Hosp, Bromley Hosp NHS Trust, Orpington, England.
C3 Guy's & St Thomas' NHS Foundation Trust; Guy's & St Thomas' NHS
   Foundation Trust; University of London; King's College London;
   University of London; London School of Hygiene & Tropical Medicine;
   University of Westminster; University of Texas System; University of
   Texas Medical Branch Galveston; South East Technological University
   (SETU); University of London; University College London
RP Hammond, CJ (通讯作者)，St Thomas Hosp, Twin Res & Genet Epidemiol Unit, Lambeth Palace Rd, London SE1 7EH, England.
EM chammond@btopenworld.com
RI Fitzke, Fred/C-3535-2008
FU Wellcome Trust Funding Source: Medline
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NR 60
TC 66
Z9 67
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 DEC
PY 2005
VL 46
IS 12
BP 4430
EP 4436
DI 10.1167/iovs.05-0519
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 988FV
UT WOS:000233578600012
PM 16303930
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wagner, N
   Safaei, A
   Hurst, J
   Vogt, PA
   Dick, HB
   Joachim, SC
   Schnichels, S
AF Wagner, Natalie
   Safaei, Armin
   Hurst, Jose
   Vogt, Pia A.
   Dick, H. Burkhard
   Joachim, Stephanie C.
   Schnichels, Sven
TI Impact of Primary RPE Cells in a Porcine Organotypic Co-Cultivation
   Model
SO BIOMOLECULES
LA English
DT Article
DE co-cultivation; complement system; cytokines; porcine; retina; retinal
   pigment epithelium (RPE) cells
ID RETINAL-PIGMENT EPITHELIUM; PHOTORECEPTOR DEGENERATION; CONDITIONED
   MEDIA; GENE-EXPRESSION; PROTEIN PSD-95; CULTURED ADULT; ANIMAL-MODELS;
   CONE ARRESTIN; FACTOR-H; MICROGLIA
AB The pathological events of age-related macular degeneration are characterized by degenerative processes involving the photoreceptor cells, retinal pigment epithelium (RPE), and the Bruch's membrane as well as choroidal alterations. To mimic in vivo interactions between photoreceptor cells and RPE cells ex vivo, complex models are required. Hence, the aim of this study was to establish a porcine organotypic co-cultivation model and enlighten the interactions of photoreceptor and RPE cells, with a special emphasis on potential neuroprotective effects. Porcine neuroretina explants were cultured with primary porcine RPE cells (ppRPE) or medium derived from these cells (=conditioned medium). Neuroretina explants cultured alone served as controls. After eight days, RT-qPCR and immunohistology were performed to analyze photoreceptors, synapses, macroglia, microglia, complement factors, and pro-inflammatory cytokines (e.g., IL1B, IL6, TNF) in the neuroretina samples. The presence of ppRPE cells preserved photoreceptors, whereas synaptical density was unaltered. Interestingly, on an immunohistological as well as on an mRNA level, microglia and complement factors were comparable in all groups. Increased IL6 levels were noted in ppRPE and conditioned medium samples, while TNF was only upregulated in the ppRPE group. IL1B was elevated in conditioned medium samples. In conclusion, a co-cultivation of ppRPE cells and neuroretina seem to have beneficial effects on the neuroretina, preserving photoreceptors and maintaining synaptic vesicles in vitro. This organotypic co-cultivation model can be used to investigate the complex interactions between the retina and RPE cells, gain further insight into neurodegenerative pathomechanisms occurring in retinal diseases, and evaluate potential therapeutics.
C1 [Wagner, Natalie; Safaei, Armin; Vogt, Pia A.; Dick, H. Burkhard; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, D-44892 Bochum, Germany.
   [Hurst, Jose; Schnichels, Sven] Univ Eye Hosp Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
C3 Ruhr University Bochum; Eberhard Karls University of Tubingen; Eberhard
   Karls University Hospital
RP Joachim, SC (通讯作者)，Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, D-44892 Bochum, Germany.; Schnichels, S (通讯作者)，Univ Eye Hosp Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
EM natalie.wagner@rub.de; armin.safaei@rub.de;
   jose.hurst@med.uni-tuebingen.de; pia.vogt@rub.de;
   burkhard.dick@kk-bochum.de; stephanie.joachim@rub.de;
   sven.schnichels@med.uni-tuebingen.de
OI Joachim, Stephanie/0000-0001-7056-0829
FU PRO RETINA-Foundation for Prevention of Blindness; Novartis Pharma GmbH,
   Germany
FX This study was in part supported by the PRO RETINA-Foundation for
   Prevention of Blindness and Novartis Pharma GmbH, Germany.
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NR 85
TC 0
Z9 0
U1 1
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD JUL
PY 2022
VL 12
IS 7
AR 990
DI 10.3390/biom12070990
PG 22
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 3J2DI
UT WOS:000833210700001
PM 35883547
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Awh, CC
   Davis, EC
   Thomas, MK
   Thomas, AS
AF Awh, Caroline C.
   Davis, Emily C.
   Thomas, Mridul K.
   Thomas, Akshay S.
TI SHORT-TERM OUTCOMES AFTER INTERIM TREATMENT WITH BROLUCIZUMAB A
   Retrospective Case Series of a Single Center Experience
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; anti-VEGF; brolucizumab; inflammation;
   retina
ID MACULAR DEGENERATION; SWITCHING TREATMENT; AFLIBERCEPT; RANIBIZUMAB
AB Purpose: To examine outcomes of eyes with neovascular age-related macular degeneration that were switched to brolucizumab because of an unsatisfactory response to bevacizumab, ranibizumab, and/or aflibercept and then switched back because of the presence or risk of intraocular inflammation. Methods: Retrospective case series of 51 eyes. Visual acuity and retinal anatomy on optical coherence tomography were recorded at the first brolucizumab injection (T1), the final brolucizumab injection (T2), and 6 months following the final brolucizumab injection (T3). Results: At T2, 41 eyes (41/51%, 80%) had decreased subretinal fluid (31 eyes), intraretinal fluid (12 eyes), or pigment epithelial detachment height (12 eyes). At T3, decreased subretinal fluid was sustained in 17 eyes (17/31%, 55%), decreased intraretinal fluid was sustained in eight eyes (8/12%, 67%), and decreased pigment epithelial detachment height was sustained in eight eyes (8/12%, 67%). Mean logarithm of the minimum angle of resolution visual acuity at T1, T2, and T3 was 0.396 (similar to 20/50), 0.441 (similar to 20/55), and 0.468 (similar to 20/59), respectively. During the brolucizumab treatment period, 11 eyes (11/51%, 22%) developed intraocular inflammation, including one case of retinal vasculitis. Conclusion: Interim treatment with brolucizumab resulted in anatomical improvements in 41 eyes (41/51%, 80%) that were maintained in 22 of these eyes (22/41%, 54%) for at least 6 months after switching back to the original anti-vascular endothelial growth factor therapeutic. There were no corresponding significant changes in visual acuity.
C1 [Awh, Caroline C.; Davis, Emily C.; Thomas, Akshay S.] Tennessee Retina, 345 23rd Ave N,Ste 350, Nashville, TN 37203 USA.
   [Thomas, Mridul K.] Univ Geneva, Dept FA Forel Environm & Aquat Sci DEFSE, CH-1211 Geneva, Switzerland.
   [Thomas, Mridul K.] Univ Geneva, Inst Environm Sci, CH-1211 Geneva, Switzerland.
C3 University of Geneva; University of Geneva
RP Thomas, AS (通讯作者)，345 23rd Ave N,Ste 350, Nashville, TN 37203 USA.
EM caroline.awh@gmail.com; emilychristinadavis@gmail.com;
   Mridul.thomas@unige.ch; akshaysthomas@gmail.com
CR [Anonymous], 2020, BEOV US PRESCR INF E
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NR 25
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2022
VL 42
IS 5
BP 899
EP 905
DI 10.1097/IAE.0000000000003418
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0U0LT
UT WOS:000787351800012
PM 35067611
DA 2022-11-30
ER

PT J
AU Udsen, M
   Tagmose, C
   Garred, P
   Nissen, MH
   Faber, C
AF Udsen, Maja
   Tagmose, Christian
   Garred, Peter
   Nissen, Mogens Holst
   Faber, Carsten
TI Complement activation by RPE cells preexposed to TNF alpha and IFN gamma
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; Complement; Membrane attack complex;
   Interferons; Tumor necrosis factor
ID PIGMENT EPITHELIAL-CELLS; MEMBRANE-ATTACK-COMPLEX; C-REACTIVE PROTEIN;
   MACULAR DEGENERATION; CHEMOKINE EXPRESSION; PLASMA-LEVELS; HIGH-RISK;
   T-CELLS; PATHWAY; RATHER
AB Age-related macular degeneration (AMD) has been associated with both complement activation and increased levels of circulating cytokines. Here, we sougth to investigate if cytokine-preexposure of retinal pigment epithelial (RPE) leads to increased complement activation and deposition of membrane attack complex (MAC). Primary human RPE and the ARPE19 cell line cultured in serum-free conditions were preexposed to 100 ng/ml interferon-gamma (IFN gamma) and 20 ng/ml tumor necrosis factor-alpha (TNF alpha) for 48 h followed by exposure to diluted serum from healthy donors or complement factor B deficient (CFBd) serum for 70 min. Deposition of membrane attack complexes (MAC) was examined by use of a MAC-ELISA kit and by immunofluorescence. Eculizumab (anti-C5) was examined for its ability to prevent deposition of MAC on RPE cells exposed to serum. Lactatdehydrogenase (LDH) and thiazolyl blue tetrazolium bromide (MTT) assays were used to assess cellular metabolism and survival. MAC was deposited only on RPE preexposed to both IFN gamma and TNF alpha. Lack of complement factor B or inhibition of C5 abrogated the MAC-deposition on RPE cells, while reconstitution of CFBd serum with CFB resulted in MAC-deposition. MAC-deposition resulted in RPE-release of LDH, but unaltered mitochondrial activity estimated by MTT. We conclude that preexposure of primary RPE and ARPE19 with inflammatory cytokines promoted alternative pathway activation of complement and deposition of MAC. This implies that circulating inflammatory mediators may increase susceptibility to local complement activation and MAC-deposition, which may represent an early event in the pathogenesis leading to AMD development.
C1 [Udsen, Maja; Tagmose, Christian; Nissen, Mogens Holst; Faber, Carsten] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark.
   [Garred, Peter] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Lab Mol Med, Sect 7631, Copenhagen, Denmark.
   [Faber, Carsten] Copenhagen Univ Hosp, Rigshosp, Dept Ophthalmol, Copenhagen, Denmark.
C3 University of Copenhagen; Rigshospitalet; University of Copenhagen;
   Rigshospitalet; University of Copenhagen
RP Faber, C (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark.
EM carstenfaber@gmail.com
RI Faber, Carsten/I-4150-2013
OI Faber, Carsten/0000-0002-2517-7270
FU Fight for Sight Denmark; Synoptik-Fonden
FX & nbsp;Fight for Sight Denmark and Synoptik-Fonden.
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NR 49
TC 2
Z9 2
U1 2
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 MAY
PY 2022
VL 218
AR 108982
DI 10.1016/j.exer.2022.108982
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0Y1YV
UT WOS:000790192300006
PM 35183540
OA hybrid
DA 2022-11-30
ER

PT J
AU Kelley, RF
   Tesar, DB
   Wang, Y
   Agard, NJ
   Holder, PG
   Chan, J
   Comps-Agrar, L
   Horvath, J
   Horvath, JD
   Crowell, SR
AF Kelley, Robert F.
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   Chan, Joyce
   Comps-Agrar, Laetitia
   Horvath, Judit
   Horvath, Joshua D.
   Crowell, Susan R.
TI Generation of a Porcine Antibody Fab Fragment Using Protein Engineering
   to Facilitate the Evaluation of Ocular Sustained Delivery Technology
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE pharmacokinetics; long-acting delivery; ocular clearance
ID LONG-ACTING DELIVERY; RABBIT; RANIBIZUMAB; SEQUENCE; MONKEY; EYE
AB Treatment of age-related macular degeneration (AMD) with anti-vascular endothelial growth factor (VEGF) biologicagents has been shown to restore and maintain visual acuity for many patients afflicted with wet AMD. These agents are usuallyadministered via intravitreal injection at a dosing interval of 4-8 weeks. Employment of long-acting delivery (LAD) technologiescould improve the therapeutic outcome, ensure timely treatment, and reduce burden on patients, caregivers, and the health caresystem. Development of LAD approaches requires thorough testing in pre-clinical species; however, therapeutic proteins of humanorigin may not be well tolerated during testing in non-human species due to immunogenicity. Here, we have engineered a surrogateporcine antibody Fab fragment (pigG6.31) from a human antibody for testing ocular LAD technologies in a porcine model. Theengineered Fab retains the VEGF-A-binding and inhibition properties of the parental human Fab and has stability properties suitablefor LAD evaluation. Upon intravitreal injection in minipigs, pigG6.31 showedfirst-order clearance from the ocular compartmentswith vitreal elimination rates consistent with other molecules of this size. Application of the surrogate molecule in an in vivoevaluation in minipigs of a prototype of the port delivery (PD) platform indicated continuous ocular delivery from the implant, withrelease kinetics consistent with both the results from in vitro release studies and the efficacy observed in human clinical studies of thePD system with ranibizumab (PDS). Anti-drug antibodies in the serum against pigG6.31 were not detected over exposure durationsup to 16 weeks, suggesting that this molecule has low porcine immunogenicity
C1 [Kelley, Robert F.; Tesar, Devin B.; Wang, Yue; Horvath, Judit] Genentech Inc, Pharmaceut Dev, San Francisco, CA 94080 USA.
   [Agard, Nicholas J.] Genentech Inc, Antibody Engn, San Francisco, CA 94080 USA.
   [Holder, Patrick G.] Genentech Inc, Prot Chem, San Francisco, CA 94080 USA.
   [Chan, Joyce; Comps-Agrar, Laetitia] Genentech Inc, Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
   [Horvath, Joshua D.] Genentech Inc, Device Dev, San Francisco, CA 94080 USA.
   [Crowell, Susan R.] Genentech Inc, Preclin & Translat Pharmacokinet & Pharmacodynam, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Roche Holding;
   Genentech; Roche Holding; Genentech; Roche Holding; Genentech; Roche
   Holding; Genentech
RP Kelley, RF (通讯作者)，Genentech Inc, Pharmaceut Dev, San Francisco, CA 94080 USA.
EM rk@gene.com
OI Comps-Agrar, Laetitia/0000-0002-5260-6536; Crowell,
   Susan/0000-0002-8086-5981
CR Bantseev V, 2021, TOXICOL PATHOL, V49, P663, DOI 10.1177/0192623320968079
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NR 26
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
EI 1543-8392
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD MAR 16
PY 2022
VL 19
IS 5
BP 1540
EP 1547
DI 10.1021/acs.molpharmaceut.2c00048
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 1K3JZ
UT WOS:000798502800025
PM 35393854
DA 2022-11-30
ER

PT J
AU Felfeli, T
   Alon, R
   Merritt, R
   Brent, MH
AF Felfeli, Tina
   Alon, Roy
   Merritt, Rebecca
   Brent, Michael H.
TI Toronto tele-retinal screening program for detection of diabetic
   retinopathy and macular edema
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; COST-EFFECTIVENESS; FUNDUS PHOTOGRAPHY;
   EYE EXAMINATIONS; TELEMEDICINE; IMAGES; TELEOPHTHALMOLOGY; PREVALENCE;
   MANAGEMENT; VISION
AB Background: There are currently low rates of screening for diabetic retinopathy (DR) and sight-threatening diabetic macular edema (DME) in Ontario.
   Objective: To present results of the Toronto Tele-Retinal screening program for patients with diabetes mellitus and to evaluate the benefit of optical coherence tomography (OCT) in combination with monoscopic colour fundus photographs for detection of DME.
   Methods: All electronic medical records for adults with type I and II diabetes mellitus screened through the Toronto Tele-Retinal screening program between September 2013 to August 2017 across 7 sc similar to reening sites in urban and rural settings were reviewed. Monoscopic colour fundus photographs were graded for presence or absence of DR and DME alone and in combination with OCT scans.
   Results: A total of 775 patient screens, consisting of 566 first-time screens and 209 re-screens were completed over the 48-month study period. Approximately 37% of all patients with a mean disease duration of 7 years had never had an eye examination. Across the sample, 27% of patients had DR, with majority graded to have mild DR, whereas DME was detected in 5% of patients in at least 1 eye. Of all DME detected in the Toronto Tele-Retinal screening program, 38% required the use of adjunct OCT. Other pathologies, including age-related macular degeneration (19%) and glaucomatous or optic nerve findings (8%), were also identified.
   Conclusion: Tele-retinal screening programs may circumvent low rates of DR screening for patients with diabetes mellitus and increase the rate of detection of DME with monoscopic colour fundus photographs and adjunct OCT.
C1 [Felfeli, Tina; Brent, Michael H.] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
   [Alon, Roy] Meir Med Ctr, Dept Ophthalmol, Kefar Sava, Israel.
   [Merritt, Rebecca] South Riverdale Community Hlth Ctr, Toronto, ON, Canada.
   [Brent, Michael H.] Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Toronto, ON, Canada.
C3 University of Toronto; Tel Aviv University; Sackler Faculty of Medicine;
   University of Toronto; University Toronto Affiliates; University Health
   Network Toronto
RP Brent, MH (通讯作者)，Univ Toronto, Dept Ophthalmol & Vis Sci, Retina Serv, 6E-423,399 Bathurst St, Toronto, ON M5T 2S8, Canada.
EM michael.brent@uhn.ca
OI Felfeli, Tina/0000-0002-0927-3086
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NR 74
TC 7
Z9 7
U1 0
U2 3
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 2019
VL 54
IS 2
BP 203
EP 211
DI 10.1016/j.jcjo.2018.07.004
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HS4ZC
UT WOS:000463878500027
PM 30975344
DA 2022-11-30
ER

PT J
AU Maloca, P
   Hasler, PW
   Barthelmes, D
   Arnold, P
   Matthias, M
   Scholl, HPN
   Gerding, H
   Garweg, J
   Heeren, T
   Balaskas, K
   de Carvalho, JER
   Egan, C
   Tufail, A
   Zweifel, SA
AF Maloca, Peter
   Hasler, Pascal W.
   Barthelmes, Daniel
   Arnold, Patrik
   Matthias, Mooser
   Scholl, Hendrik P. N.
   Gerding, Heinrich
   Garweg, Justus
   Heeren, Tjebo
   Balaskas, Konstantinos
   de Carvalho, J. Emanuel Ramos
   Egan, Catherine
   Tufail, Adnan
   Zweifel, Sandrine A.
TI Safety and Feasibility of a Novel Sparse Optical Coherence Tomography
   Device for Patient-Delivered Retina Home Monitoring
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; monitoring; optical coherence
   tomography; retina
ID INTRAVITREAL AFLIBERCEPT INJECTION; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; THICKNESS MEASUREMENTS;
   RESOURCE UTILIZATION; RANIBIZUMAB; EYES; REPRODUCIBILITY; DISEASES
AB Purpose: To study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device.
   Methods: In this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements.
   Results: Sixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69-92 years). The mean difference in the CRT measurements between the devices was 4.52 mu m (SD +/- 20.0 mu m; range, -65.6 to 41.5 mu m). The inter-and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was <0.54 mW for spOCT and <1.4 mW for SDOCT. No adverse events were reported, and the visual acuity before and after the measurements was stable.
   Conclusion: This study demonstrated the safety and feasibility of this home-based OCT monitoring under real-life conditions, and it provided evidence for the potential clinical benefit of the device.
   Translational Relevance: The newly developed spOCT is a valid and readily available retina scanner. It could be applied as a portable self-measuring OCT system. Its use may facilitate the sustainable monitoring of chronic retinal diseases by providing easily accessible and continuous retinal monitoring.
C1 [Maloca, Peter; Hasler, Pascal W.] Univ Hosp Basel, Dept Ophthalmol, OCTlab, Basel, Switzerland.
   [Barthelmes, Daniel; Zweifel, Sandrine A.] Univ Zurich, Dept Ophthalmol, Univ Hosp, Zurich, Switzerland.
   [Barthelmes, Daniel] Univ Sydney, Save Sight Inst, Sydney, NSW, Australia.
   [Arnold, Patrik; Matthias, Mooser] Univ Appl Sci Engn & Informat Technol, Inst Human Ctr Engn OptoLab, Biel, Switzerland.
   [Gerding, Heinrich] Inst Mol & Clin Ophthalmol Basel IOB, Basel, Switzerland.
   [Maloca, Peter; Hasler, Pascal W.; Scholl, Hendrik P. N.] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Scholl, Hendrik P. N.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
   [Gerding, Heinrich] Pallas Kliniken AG, Olten, Switzerland.
   [Gerding, Heinrich] Univ Munster, Augenklin, Munster, Germany.
   [Garweg, Justus] Lindenhofspital, Berner Augenklin, Bern, Switzerland.
   [Garweg, Justus] Univ Bern, Bern, Switzerland.
   [Heeren, Tjebo] UCL, Inst Ophthalmol, London, England.
   [Balaskas, Konstantinos] Moorfields Ophthalm Reading Ctr, London, England.
   [Maloca, Peter; Balaskas, Konstantinos; de Carvalho, J. Emanuel Ramos; Egan, Catherine; Tufail, Adnan] Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England.
C3 University of Basel; University of Zurich; University Zurich Hospital;
   University of Sydney; University of Basel; Johns Hopkins University;
   Johns Hopkins Medicine; University of Hamburg; University Medical Center
   Hamburg-Eppendorf; University of Munster; University of Bern; University
   of London; University College London; University of London; University
   College London; Moorfields Eye Hospital NHS Foundation Trust
RP Maloca, P (通讯作者)，Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England.
EM peter.maloca@moorfields.nhs.uk
RI Balaskas, Konstantinos/ABD-5979-2020; Gerding, Heinrich/M-2363-2019;
   Maloca, Peter/N-4908-2018; Heeren, Tjebo/R-5055-2019; Zweifel,
   Sandrine/AAX-5045-2020; Maloca, Peter/AAG-6214-2020
OI Balaskas, Konstantinos/0000-0002-7690-6277; Gerding,
   Heinrich/0000-0003-3968-5601; Maloca, Peter/0000-0002-4794-5859; Heeren,
   Tjebo/0000-0001-5297-2301; Tufail, Adnan/0000-0001-6131-7640; Egan,
   Catherine/0000-0001-5593-1169
FU Swiss Commission for Technology and Innovation (CTI) [14761.1PFLS-LS];
   MIMO AG, Bern, Switzerland
FX This work was supported in part by the Swiss Commission for Technology
   and Innovation (CTI, no. 14761.1PFLS-LS) and MIMO AG, Bern, Switzerland.
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NR 53
TC 26
Z9 27
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 JUL
PY 2018
VL 7
IS 4
AR 8
DI 10.1167/tvst.7.4.8
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GO5HD
UT WOS:000440049100003
PM 30050725
OA gold, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Nesper, PL
   Lutty, GA
   Fawzi, AA
AF Nesper, Peter L.
   Lutty, Gerard A.
   Fawzi, Amani A.
TI RESIDUAL CHOROIDAL VESSELS IN ATROPHY CAN MASQUERADE AS CHOROIDAL
   NEOVASCULARIZATION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
   Introducing a Clinical and Software Approach
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; choriocapillaris; choroidal
   neovascularization; geographic atrophy; OCT; optical coherence
   tomography angiography
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; SPECTRAL-DOMAIN; RANIBIZUMAB;
   BEVACIZUMAB; GROWTH; RISK; EYES; RPE
AB Purpose: To present a postprocessing approach in optical coherence tomography angiography (OCTA) to facilitate the visualization and interpretation of lesions in age-related macular degeneration with coexisting atrophy and choroidal neovascularization (CNV).
   Methods: This retrospective study included 32 eyes of 26 patients with atrophy and treated CNV and 8 eyes with treatment-naive geographic atrophy. En face optical coherence tomography slabs highlighting atrophy were pseudocolored and merged with the corresponding OCTA. Cross-sectional optical coherence tomography and postprocessed OCTA were analyzed to identify CNV and normal choroidal vessels in relationship to the atrophy. We correlate the OCTA findings with those in a donor eye with treatment-naive geographic atrophy studied with transmission electronic microscopy.
   Results: Medium-sized choroidal vessels were displaced anteriorly in areas of atrophy in all 40 eyes (100%), visualized in the choriocapillaris slab in all eyes, and in the outer retinal slab in 30 of 40 eyes (75.0%). Cross-sectional OCTA was used to confirm the presence of CNV. Postprocessing successfully highlighted the CNV and distinguished it from choroidal vessels in atrophy. Donor eye transmission electronic microscopy confirmed the anterior displacement of medium-sized choroidal vessels in geographic atrophy.
   Conclusion: The anterior displacement of larger choroidal vessels in atrophy requires clinician vigilance to avoid misinterpreting these vessels as CNV on en face OCTA. Our proposed postprocessing approach offers a potential solution to facilitate the interpretation of en face OCTA in these cases. In the absence of other tools, clinicians are encouraged to rely on the location of flow relative to Bruch membrane on cross-sectional OCTA flow images.
C1 [Nesper, Peter L.; Fawzi, Amani A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
   [Lutty, Gerard A.] Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, Baltimore, MD 21287 USA.
C3 Northwestern University; Feinberg School of Medicine; Johns Hopkins
   University; Johns Hopkins Medicine
RP Fawzi, AA (通讯作者)，Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
EM afawzimd@gmail.com
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558
FU NIH [EY021470, EY016151, EY01765]; OptoVue, Inc.; NATIONAL EYE INSTITUTE
   [P30EY001765, R01EY016151, R01EY021470] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
   [DP3DK108248] Funding Source: NIH RePORTER
FX Supported in part by NIH grants EY021470 (A.A.F.), EY016151 (G.A.L.),
   and EY01765 (Wilmer) and research instrument support by OptoVue, Inc.
   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 36
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUL
PY 2018
VL 38
IS 7
BP 1289
EP 1300
DI 10.1097/IAE.0000000000001863
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GP2CX
UT WOS:000440630000010
PM 29059100
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ebrahimi, KB
   Cano, M
   Rhee, J
   Datta, S
   Wang, L
   Handa, JT
AF Ebrahimi, Katayoon B.
   Cano, Marisol
   Rhee, John
   Datta, Sayantan
   Wang, Lei
   Handa, James T.
TI Oxidative Stress Induces an Interactive Decline in Wnt and Nrf2
   Signaling in Degenerating Retinal Pigment Epithelium
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
DE aging; age-related macular degeneration; oxidative stress; Nrf2;
   smoking; high-fat diet; Wnt
ID COMPLEMENT FACTOR-H; SYNTHASE KINASE 3-BETA; FORKHEAD-BOX-O;
   T-CELL-FACTOR; MACULAR DEGENERATION; BETA-CATENIN; IN-VIVO; AGE;
   PROTEIN; APOPTOSIS
AB Aims: Cells have evolved a highly sophisticated web of cytoprotective systems to neutralize unwanted oxidative stress, but are challenged by unique modern day stresses such as cigarette smoking and ingestion of a high-fat diet (HFD). Age-related disease, such as age-related macular degeneration (AMD), the most common cause of blindness among the elderly in Western societies, develops in part, when oxidative stress overwhelms cytoprotective systems to injure tissue. Since most studies focus on the protection by a single protective system, the aim of this study was to investigate the impact of more than one cytoprotective system against oxidative stress.
   Results: Wingless (Wnt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), two fundamental signaling systems that are vital to cell survival, decline after mice are exposed to chronic cigarette smoke and HFD, two established AMD risk factors, in a bidirectional feedback loop through phosphorylated glycogen synthase kinase 3 beta. Decreased Wnt and Nrf2 signaling leads to retinal pigment epithelial dysfunction and apoptosis, and a phenotype that is strikingly similar to geographic atrophy (GA), an advanced form of AMD with no effective treatment.
   Innovation: This study is the first to show that chronic oxidative stress from common modern day environmental exposures reduces two fundamental and vital cytoprotective networks in a bidirectional feedback loop, and their decline leads to advanced disease phenotype.
   Conclusion: Our data offer new insights into how combined modern oxidative stresses of cigarette smoking and HFD contribute to GA through an interactive decline in Wnt and Nrf2 signaling.
C1 [Ebrahimi, Katayoon B.; Cano, Marisol; Rhee, John; Datta, Sayantan; Wang, Lei; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, 400N Broadway,Smith Bldg,Room 3015, Baltimore, MD 21287 USA.
   [Ebrahimi, Katayoon B.] Univ Penn, Sch Med, Scheie Eye Inst, Philadelphia, PA 19104 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; University of
   Pennsylvania
RP Handa, JT (通讯作者)，Johns Hopkins Sch Med, Wilmer Eye Inst, 400N 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 NIH [EY019904, EY14005, EY027691, EY 01765, K12 EY108198]; RPB Senior
   Scientist Award; RBP; NATIONAL EYE INSTITUTE [P30EY001765] Funding
   Source: NIH RePORTER
FX We thank Stephen Chan, Sonny Dike, Natalia Vergara, Christian Gutierrez,
   and Gillian Shaw for their technical expertise and guidance, and Akrit
   Sodhi, MD, PhD, and Debasish Sinha, PhD, for carefully critiquing the
   article. We thank Victor Perez, MD, for providing CEP-BSA. Supported by
   the NIH EY019904 (J.T.H.), EY14005 (J.T.H.), EY027691 (J.T.H.), EY 01765
   (Wilmer Imaging Core grant), K12 EY108198 (K.B.E.), RPB Senior Scientist
   Award (J.T.H.), unrestricted grant from RBP, and gifts from the Merlau
   family and Aleda Wright.
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NR 75
TC 20
Z9 21
U1 2
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD AUG
PY 2018
VL 29
IS 4
BP 389
EP 407
DI 10.1089/ars.2017.7084
EA JAN 2018
PG 19
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA GL0WF
UT WOS:000419562300001
PM 29186981
OA Green Published
DA 2022-11-30
ER

PT J
AU Prieto-Dominguez, N
   Garcia-Mediavilla, MV
   Sanchez-Campos, S
   Mauriz, JL
   Gonzalez-Gallego, J
AF Prieto-Dominguez, Nestor
   Garcia-Mediavilla, Maria V.
   Sanchez-Campos, Sonia
   Mauriz, Jose L.
   Gonzalez-Gallego, Javier
TI Autophagy as a Molecular Target of Flavonoids Underlying their
   Protective Effects in Human Disease
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Flavonoids; autophagy; cancer; neurodegenerative disorders;
   cardiovascular diseases; hepatic diseases; infectious diseases; diabetes
ID CELL-DEATH INDUCTION; FATTY LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA
   CELLS; ROTENONE-INDUCED NEUROTOXICITY; HELICOBACTER-PYLORI INFECTION;
   APIGENIN-INDUCED APOPTOSIS; BREAST-CANCER CELLS; A VIRUS-INFECTION;
   OXIDATIVE STRESS; REACTIVE OXYGEN
AB Background: Autophagy is a cellular pathway with the ability to maintain cell homeostasis through the elimination of damaged or useless cellular components, and its deregulation may initiate or aggravate different human diseases. Flavonoids, a group of plant metabolites, are able to modulate different molecular and cellular processes including autophagy.
   Objective: To review the effects of flavonoids on autophagy pathway in both invasive and non-invasive human diseases, focusing on the global outcomes in their progression. Moreover, the efficacy of the combination of flavonoids with drugs or other natural nontoxic compounds was also reviewed.
   Methods: A literature search was performed to identify and analyze peer-reviewed publications containing in vitro and in vivo studies focused on autophagy deregulation in different proliferative and non-proliferative pathologies and the potential protective effects of flavonoids.
   Results: Analyzed publications indicated that imbalance between cell death and survival induced by changes in autophagy play an important role in the pathophysiology of a number of human diseases. The use of different flavonoids as autophagy modulators, alone or in combination with other molecules, might be a worthy strategy in the treatment of cancer, neurodegenerative disorders, cardiovascular diseases, hepatic diseases, leishmaniasis, influenza, gastric ulcers produced by Helicobacter pylori infection, diabetes, asthma, age-related macular degeneration or osteoporosis.
   Conclusion: Flavonoids could potentially constitute important adjuvant agents of conventional therapies in the treatment of autophagy deregulation-related diseases. Moreover, combined therapy may help to diminish the doses of those conventional treatments, leading to reduced drug-derivative side effects and to improved patients' survival.
C1 [Prieto-Dominguez, Nestor; Garcia-Mediavilla, Maria V.; Sanchez-Campos, Sonia; Mauriz, Jose L.; Gonzalez-Gallego, Javier] Univ Leon, Inst Biomed IBIOMED, Leon, Spain.
   [Garcia-Mediavilla, Maria V.; Sanchez-Campos, Sonia; Mauriz, Jose L.; Gonzalez-Gallego, Javier] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain.
C3 Universidad de Leon; CIBER - Centro de Investigacion Biomedica en Red;
   CIBEREHD; Instituto de Salud Carlos III
RP Gonzalez-Gallego, J (通讯作者)，Inst Biomed IBIOMED, Campus Univ, Leon 24071, Spain.
EM jgonga@unileon.es
RI Gonzalez-Gallego, Javier/D-8219-2012; Mauriz, Jose L/G-9970-2014;
   Garcia-Mediavilla, María Victoria/F-9641-2015; Prieto-Domínguez,
   Néstor/F-3424-2016; Sanchez-Campos, Sonia/F-9654-2015
OI Gonzalez-Gallego, Javier/0000-0002-4386-9342; Mauriz, Jose
   L/0000-0003-3160-8599; Garcia-Mediavilla, María
   Victoria/0000-0002-5722-7500; Prieto-Domínguez,
   Néstor/0000-0002-7844-3093; Sanchez-Campos, Sonia/0000-0003-2672-734X
FU JCyL [LE063U16]; Fondo Europeo de Desarrollo Regional (FEDER)
   [LE063U16]; Spanish Ministry of Education, Culture and Sports
   [FPU13/04173]; Instituto de la Salud Carlos III (Spain); CIBERehd
   contracts
FX Supported by LE063U16 (JCyL and Fondo Europeo de Desarrollo Regional
   (FEDER). Prieto-Dominguez N is granted by the program "Formacion del
   Profesorado Universitario" (reference FPU13/04173) from Spanish Ministry
   of Education, Culture and Sports. CIBERehd is funded by Instituto de la
   Salud Carlos III (Spain). Garcia-Mediavilla is supported by CIBERehd
   contracts.
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NR 226
TC 19
Z9 20
U1 2
U2 31
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 2018
VL 25
IS 7
BP 814
EP 838
DI 10.2174/0929867324666170918125155
PG 25
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA FZ6OS
UT WOS:000427719500004
PM 28925866
DA 2022-11-30
ER

PT J
AU Chen, X
   Jiang, C
   Qin, B
   Liu, GH
   Ji, JD
   Sun, XT
   Xu, M
   Ding, SJ
   Zhu, MD
   Huang, GF
   Yan, B
   Zhao, C
AF Chen, Xue
   Jiang, Chao
   Qin, Bing
   Liu, Guohua
   Ji, Jiangdong
   Sun, Xiantao
   Xu, Min
   Ding, Sijia
   Zhu, Meidong
   Huang, Guofu
   Yan, Biao
   Zhao, Chen
TI LncRNA ZNF503-AS1 promotes RPE differentiation by downregulating ZNF503
   expression
SO CELL DEATH & DISEASE
LA English
DT Article
ID LONG NONCODING RNAS; RETINAL-PIGMENT EPITHELIUM; DOMINANT
   RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; CELLS; IDENTIFICATION;
   DEDIFFERENTIATION; PROLIFERATION; RETINOPATHY; MECHANISMS
AB Long noncoding RNAs (lncRNAs) have important roles in various biological processes. Our previous work has revealed that dedifferentiation of retinal pigment epithelium (RPE) cells contributes to the pathology of age-related macular degeneration (AMD). Herein, we show roles of lncRNAs in RPE differentiation. We used microarray to identify lncRNA expression profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived RPE cells. A total of 217 differentially expressed lncRNAs along with the differentiation were initially identified, among which 13 lncRNAs showed a consistent fold change of over 2. LncRNA ZNF503-AS1, located in the cytoplasm of RPE cells, was found consistently upregulated along with RPE differentiation, and downregulated in the RPE-choroid of AMD patients. In vitro study further suggested that ZNF503-AS1 insufficiency could inhibit RPE differentiation, and promote its proliferation and migration. As ZNF503-AS1 is transcribed from the antisense strand of the ZNF503 gene locus, we further revealed its regulatory role in ZNF503 expression. ZNF503-AS1 was reversely correlated with ZNF503 expression. Our results also suggested that ZNF503 could inhibit RPE differentiation, and promote its proliferation and migration. Thus, ZNF503-AS1 potentially promotes RPE differentiation through downregulation of ZNF503 expression. In addition, nuclear factor-kappa B was recognized as a potential upstream transcript factor for ZNF503-AS1, which might participate in promoting RPE differentiation by regulating the expression of ZNF503-AS1. Taken together, our study identifies a group of RPE differentiation relevant lncRNAs, and the potential role of ZNF503-AS1 in the pathology of atrophic AMD, which might help with the intervention of AMD patients.
C1 [Chen, Xue; Jiang, Chao; Qin, Bing; Ji, Jiangdong; Ding, Sijia; Zhao, Chen] Nanjing Med Univ, State Key Lab Reprod Med, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Xue; Zhao, Chen] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200023, Peoples R China.
   [Chen, Xue; Zhao, Chen] Fudan Univ, Key Lab Myopia, State Hlth Minist, Shanghai 200023, Peoples R China.
   [Chen, Xue; Zhao, Chen] Shanghai Key Lab Visual Impairment & Restorat, Shanghai 200023, Peoples R China.
   [Qin, Bing] First Peoples Hosp Suqian, Dept Ophthalmol, Suqian 223800, Peoples R China.
   [Liu, Guohua] Shandong Univ, Qilu Childrens Hosp, Dept Ophthalmol, Jinan 250000, Shandong, Peoples R China.
   [Sun, Xiantao; Zhao, Chen] Childrens Hosp Zhengzhou, Dept Ophthalmol, Zhengzhou 450053, Henan, Peoples R China.
   [Xu, Min] Northern Jiangsu Peoples Hosp, Dept Ophthalmol, Yangzhou 225000, Jiangsu, Peoples R China.
   [Zhu, Meidong] Univ Sydney, Save Sight Inst, Discipline Clin Ophthalmol & Eye Hlth, Sydney, NSW 2000, Australia.
   [Huang, Guofu] Nanchang Univ, Affiliated Hosp 3, Dept Ophthalmol, Nanchang 330000, Jiangxi, Peoples R China.
   [Yan, Biao] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Res Ctr, Shanghai 200023, Peoples R China.
C3 Nanjing Medical University; Fudan University; Fudan University; Shandong
   University; University of Sydney; Nanchang University; Fudan University
RP Huang, GF; Yan, B; Zhao, C (通讯作者)，Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, 83 Fenyang Rd, Shanghai 200023, Peoples R China.
EM hgf2222@sina.com; yanbiao1982@hotmail.com; dr_zhaochen@163.com
RI Ji, Jiang-Dong/ABE-6033-2021
FU National Natural Science Foundation of China [81525006, 81670864,
   81730025, 81700877]; Jiangsu Province's Innovation Team; Fundamental
   Research Funds of the State Key Laboratory of Ophthalmology; Natural
   Science Foundation of Jiangsu Province [BK20171087]; Open Foundation of
   State Key Laboratory of Reproductive Medicine (Nanjing Medical
   University) [SKLRM-KA201607]; Priority Academic Program Development of
   Jiangsu Higher Education Institutions (PAPD) [JX10231801]
FX We thank all donors for their donations. We thank Prof Joshua L. Dunaief
   and Dr Delu Song from University of Pennsylvania for their technical
   support. This study was supported by National Natural Science Foundation
   of China (81525006, 81670864, 81730025, and 81700877); Jiangsu
   Province's Innovation Team (to CZ); the Fundamental Research Funds of
   the State Key Laboratory of Ophthalmology (to CZ); Natural Science
   Foundation of Jiangsu Province (BK20171087 to XC); Open Foundation of
   State Key Laboratory of Reproductive Medicine (Nanjing Medical
   University, SKLRM-KA201607); and A Project Funded by the Priority
   Academic Program Development of Jiangsu Higher Education Institutions
   (PAPD, JX10231801). The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 45
TC 27
Z9 28
U1 2
U2 13
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 SEP
PY 2017
VL 8
AR e3046
DI 10.1038/cddis.2017.382
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FG7IP
UT WOS:000410590100001
PM 28880276
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, M
   Liu, BQ
   Ma, J
   Ge, J
   Wang, KJ
AF Chen, Min
   Liu, Bingqian
   Ma, Jian
   Ge, Jian
   Wang, Kaijun
TI Protective effect of mitochondria-targeted peptide MTP-131 against
   oxidative stress-induced apoptosis in RGC-5 cells
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE retinal ganglion cell; mitochondria; oxidative stress; apoptosis; eye;
   antioxidants
ID DYSFUNCTION; ANTIOXIDANTS; CARDIOLIPIN; TRANSPORT; COMPOUND; DAMAGE
AB The retina of the human eye is extremely vulnerable to oxidative damage. Previous studies have demonstrated that oxidative stress is the predominant mechanism associated with the pathogenesis of age-related macular degeneration, diabetic retinopathy, glaucoma and retinitis pigmentosa. MTP-131, a novel mitochondria-targeted peptide, has been demonstrated to specifically concentrate in the inner mitochondria membrane and to exhibit remarkable antioxidant effects both invitro and in animal models. In the present study, the protective effect of MTP-131 was evaluated in response to hydrogen peroxide (H2O2)-induced oxidative damage in a retinal ganglion cell line, RGC-5. Cell viability was measured by lactate dehydrogenase (LDH) assay. Changes of mitochondrial membrane potential and generation of intracellular reactive oxygen species (ROS) were measured by flow cytometry and confocal microscopy, respectively. Annexin V-fluorescein isothiocyanate/propidium iodide staining was used for assessment of apoptosis. Release of cytochrome c was analyzed by confocal microscopy. Pretreatment of cells with MTP-131 inhibited H2O2-induced cytotoxicity and reduced LDH release in a dose-dependent manner, compared with cells treated with H2O2 alone. Mitochondrial depolarization and ROS generation were also prevented by MTP-131 pretreatment. In addition, MTP-131 pretreatment inhibited cytochrome c release from mitochondria to cytoplasm, and significantly reduced apoptosis in RGC-5 cells, compared with cells treated with H2O2 alone. In conclusion, mitochondria-targeted peptide MTP-131 exhibited a protective effect against oxidative stress-induced apoptosis in RGC-5 cells, which may provide a novel approach for the treatment of age-associated retinal diseases.
C1 [Chen, Min; Ma, Jian; Wang, Kaijun] Zhejiang Univ, Zhejiang Prov Key Lab Ophthalmol, Coll Med, Eye Ctr,Affiliated Hosp 2, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.
   [Liu, Bingqian; Ge, Jian] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
C3 Zhejiang University; Sun Yat Sen University
RP Wang, KJ (通讯作者)，Zhejiang Univ, Zhejiang Prov Key Lab Ophthalmol, Coll Med, Eye Ctr,Affiliated Hosp 2, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.; Ge, J (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM gejian@mail.sysu.edu.cn; kaijwang@126.com
FU Stealth Peptides International Inc. [MTP-131]; Zhejiang Provincial
   Natural Science Foundation of China [LQ15H120001, LY12H12008]; National
   Natural Science Foundation of China [81372930]
FX The authors would like to thank Stealth Peptides International Inc. for
   providing us with MTP-131 and a research grant. The present study was
   supported by the Zhejiang Provincial Natural Science Foundation of China
   (grant nos. LQ15H120001 and LY12H12008) and the National Natural Science
   Foundation of China (grant no. 81372930).
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NR 27
TC 15
Z9 16
U1 1
U2 10
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1791-2997
EI 1791-3004
J9 MOL MED REP
JI Mol. Med. Rep.
PD APR
PY 2017
VL 15
IS 4
BP 2179
EP 2185
DI 10.3892/mmr.2017.6271
PG 7
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA EP2HE
UT WOS:000397203200092
PM 28260075
OA Green Submitted, Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Seong, H
   Ryu, J
   Yoo, WS
   Kim, SJ
   Han, YS
   Park, JM
   Kang, SS
   Seo, SW
AF Seong, Hyemin
   Ryu, Jinhyun
   Yoo, Woong-Sun
   Kim, Seong Jae
   Han, Yong-Seop
   Park, Jong Moon
   Kang, Sang Soo
   Seo, Seong Wook
TI Resveratrol Ameliorates Retinal Ischemia/Reperfusion Injury in C57BL/6J
   Mice via Downregulation of Caspase-3
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Caspase-3; caspase-8; ischemia/reperfusion injury; resveratrol; retina
ID ENDOTHELIAL GROWTH-FACTOR; GANGLION-CELL DEATH; FACTOR-KAPPA-B;
   ISCHEMIA-REPERFUSION; OXIDATIVE STRESS; APOPTOSIS; INFLAMMATION;
   MECHANISMS; ANGIOGENESIS; BEVACIZUMAB
AB Purpose: Ischemia/reperfusion (I/R) injury induces apoptosis in retinal ganglion cells (RGCs). Resveratrol (Res) is a potent natural antioxidant with beneficial effects in many ocular diseases, such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Because caspase-3 expression is highly correlated with activation of the apoptotic pathway, the present study aimed to determine whether Res regulates the expression of caspase-3 using an I/R retinal injury mouse model.
   Methods: Male C57BL/6J mice were injected with Res for 2 consecutive days before I/R retinal injury. I/R retinal injury was induced by increasing the intraocular pressure for 1 h. Res was then injected for 3 consecutive days. Changes in retinal morphology were monitored for 3 days after injury by histochemistry using hematoxylin and eosin staining. mRNAs and proteins were extracted 2 days after injury. The expression levels of caspase-8 and caspase-3 mRNA and protein were determined using reversetranscriptase polymerase chain reaction (RT-PCR) and western blot analyses.
   Results: I/R injury induced declines in retinal thickness and number of RGCs during 5 days after injury. Caspase-8 and caspase-3 mRNA and protein activation increased. Res treatment reduced the significant loss of retinal morphology and downregulated the expression of mRNA and activation of caspase-8 and caspase-3 protein.
   Conclusions: The observed changes in retinal morphology suggest that I/R injury promotes retinal degeneration. Increased expression of caspase-8 and caspase-3 mRNA indicates apoptosis activation. Res, however, suppresses apoptosis via downregulation of caspase-8 and caspase-3 expression.
C1 [Seong, Hyemin; Ryu, Jinhyun; Kang, Sang Soo] Gyeongsang Natl Univ, Coll Med, Dept Anat & Convergence Med Sci, Jinju, Gyeongnam, South Korea.
   [Yoo, Woong-Sun; Kim, Seong Jae; Han, Yong-Seop; Park, Jong Moon; Seo, Seong Wook] Gyeongsang Natl Univ, Inst Hlth Sci, Sch Med, Dept Ophthalmol, 15 Jinju Daero 816 Beon Gil, Jinju 52727, Gyeongnam, South Korea.
C3 Gyeongsang National University; Gyeongsang National University
RP Seo, SW (通讯作者)，Gyeongsang Natl Univ, Inst Hlth Sci, Sch Med, Dept Ophthalmol, 15 Jinju Daero 816 Beon Gil, Jinju 52727, Gyeongnam, South Korea.; Kang, SS (通讯作者)，Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Anat & Convergence Med Sci, 15 Jinju Daero 816 Beon Gil, Jinju 52727, Gyeongnam, South Korea.
EM kangss@gnu.ac.kr; stramast@naver.com
RI Yoo, Woong-Sun/O-2777-2019
FU Hanmi Pharmaceuticals Co., Ltd (Seoul, Korea)
FX This study was supported by special research funds from Hanmi
   Pharmaceuticals Co., Ltd (Seoul, Korea) in 2016.
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NR 54
TC 34
Z9 41
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 2017
VL 42
IS 12
BP 1650
EP 1658
DI 10.1080/02713683.2017.1344713
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FT0XR
UT WOS:000422853400014
PM 28985092
DA 2022-11-30
ER

PT J
AU Joyal, JS
   Sun, Y
   Gantner, ML
   Shao, Z
   Evans, LP
   Saba, N
   Fredrick, T
   Burnim, S
   Kim, JS
   Patel, G
   Juan, AM
   Hurst, CG
   Hatton, CJ
   Cui, ZH
   Pierce, KA
   Bherer, P
   Aguilar, E
   Powner, MB
   Vevis, K
   Boisvert, M
   Fu, ZJ
   Levy, E
   Fruttiger, M
   Packard, A
   Rezende, FA
   Maranda, B
   Sapieha, P
   Chen, J
   Friedlander, M
   Clish, CB
   Smith, LEH
AF Joyal, Jean-Sebastien
   Sun, Ye
   Gantner, Marin L.
   Shao, Zhuo
   Evans, Lucy P.
   Saba, Nicholas
   Fredrick, Thomas
   Burnim, Samuel
   Kim, Jin Sung
   Patel, Gauri
   Juan, Aimee M.
   Hurst, Christian G.
   Hatton, Colman J.
   Cui, Zhenghao
   Pierce, Kerry A.
   Bherer, Patrick
   Aguilar, Edith
   Powner, Michael B.
   Vevis, Kristis
   Boisvert, Michel
   Fu, Zhongjie
   Levy, Emile
   Fruttiger, Marcus
   Packard, Alan
   Rezende, Flavio A.
   Maranda, Bruno
   Sapieha, Przemyslaw
   Chen, Jing
   Friedlander, Martin
   Clish, Clary B.
   Smith, Lois E. H.
TI Retinal lipid and glucose metabolism dictates angiogenesis through the
   lipid sensor Ffar1
SO NATURE MEDICINE
LA English
DT Article
ID ENERGY-METABOLISM; RECEPTOR GPR40; INSULIN-SECRETION; FATTY-ACIDS;
   EXPRESSION; RETINOPATHY; DEGENERATION; NEOVASCULARIZATION; INFLAMMATION;
   TUMORS
AB Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine(1). Current dogma suggests that high-energy-consuming photoreceptors depend on glucose(2,3). Here we show that the retina also uses fatty acid beta-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors(4) and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid(5,6). In the retinas of Vldlr(-/-) mice with low fatty acid uptake(6) but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate alpha-ketoglutarate (alpha-KG). Low alpha-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr(-/-) photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr(-/) retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD)(7), which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases.
C1 [Joyal, Jean-Sebastien] Univ Montreal, Dept Pediat, Ctr Hosp Univ CHU St Justine Res Ctr, Montreal, PQ H3C 3J7, Canada.
   [Joyal, Jean-Sebastien; Patel, Gauri] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada.
   [Joyal, Jean-Sebastien; Kim, Jin Sung] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
   [Sun, Ye; Shao, Zhuo; Evans, Lucy P.; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Cui, Zhenghao; Fu, Zhongjie; Chen, Jing; Smith, Lois E. H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
   [Gantner, Marin L.] Lowy Med Res Inst, La Jolla, CA USA.
   [Pierce, Kerry A.; Clish, Clary B.] Broad Inst Massachusetts Inst Technol MIT & Harva, Metabolite Profiling Platform, Cambridge, MA 02139 USA.
   [Bherer, Patrick; Maranda, Bruno] Univ Sherbrooke, Dept Genet, Sherbrooke, PQ J1K 2R1, Canada.
   [Aguilar, Edith; Friedlander, Martin] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
   [Powner, Michael B.; Vevis, Kristis; Fruttiger, Marcus] UCL, Inst Ophthalmol, London, England.
   [Boisvert, Michel; Levy, Emile] Univ Montreal, Ctr Hosp Univ CHU St Justine Res Ctr, Dept Nutr, Montreal, PQ, Canada.
   [Packard, Alan] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA.
   [Rezende, Flavio A.; Sapieha, Przemyslaw] Univ Montreal, Maisonneuve Rosemont Hosp Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.
C3 Universite de Montreal; Centre Hospitalier Universitaire Sainte-Justine;
   Universite de Montreal; McGill University; Harvard University; Boston
   Children's Hospital; Harvard Medical School; Harvard University;
   Massachusetts Institute of Technology (MIT); Broad Institute; University
   of Sherbrooke; Scripps Research Institute; University of London;
   University College London; Universite de Montreal; Centre Hospitalier
   Universitaire Sainte-Justine; Harvard University; Boston Children's
   Hospital; Harvard Medical School; Universite de Montreal
RP Joyal, JS (通讯作者)，Univ Montreal, Dept Pediat, Ctr Hosp Univ CHU St Justine Res Ctr, Montreal, PQ H3C 3J7, Canada.; Joyal, JS (通讯作者)，Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada.; Joyal, JS (通讯作者)，McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.; Smith, LEH (通讯作者)，Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
EM js.joyal@umontreal.ca; lois.smith@childrens.harvard.edu
RI Powner, Michael/CAG-7455-2022; Clish, Clary B/ABB-9374-2021; Clish,
   Clary/AAB-7124-2019
OI Clish, Clary B/0000-0001-8259-9245; Powner, Michael/0000-0003-4913-1004;
   Fruttiger, Marcus/0000-0002-6962-5485; FU, ZHONGJIE/0000-0002-8182-2983;
   Juan, Aimee/0000-0002-0221-2280; Sun, Ye/0000-0002-7674-9056
FU US National Institutes of Health (NIH) [EY024864, EY017017, EY022275,
   P01 HD18655, EY024963, EY11254]; Lowy Medical Research Institute;
   European Commission FP7 project PREVENT-ROP [305485]; Burroughs Wellcome
   Fund Career Award for Medical Scientists; Foundation Fighting Blindness;
   Canadian Institute of Health Research (CIHR) grant [143077]; Fonds de
   Recherche du Quebec-Sante (FRQS); Canadian Child Health Clinician
   Scientist Program; CIHR New Investigator Award; Knights Templar Eye
   Foundation; Bernadotte Foundation; Canada Research chair and CIHR grant
   [221478]; Boston Children's Hospital Ophthalmology Foundation; Boston
   Children's Hospital Faculty Career Development Award; Bright Focus
   Foundation; Massachussetts Lions Eye Research Fund; EUNICE KENNEDY
   SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
   [P30HD018655, U54HD090255] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY024963, R24EY024864, R01EY022275, R01EY011254,
   R01EY017017, R01EY008670] Funding Source: NIH RePORTER
FX This work was supported by the US National Institutes of Health (NIH)
   grants EY024864 (L.E.H.S.), EY017017 (L.E.H.S.), EY022275 (L.E.H.S.),
   P01 HD18655 (L.E.H.S.) and EY024963 (J.C.) and EY11254 (M. Friedlander),
   the Lowy Medical Research Institute (M. Friedlander, L.E.H.S. and M.
   Fruttiger), the European Commission FP7 project 305485 PREVENT-ROP
   (L.E.H.S.), a Burroughs Wellcome Fund Career Award for Medical
   Scientists (J.-S.J.), the Foundation Fighting Blindness (J.-S.J.), the
   Canadian Institute of Health Research (CIHR) grant 143077 (J.-S.J.), the
   Fonds de Recherche du Quebec-Sante (FRQS) (J.-S.J.), the Canadian Child
   Health Clinician Scientist Program (J.-S.J.), a CIHR New Investigator
   Award (J.-S.J.), the Knights Templar Eye Foundation (Z.F.), the
   Bernadotte Foundation (Z.F.), the Canada Research chair and CIHR grant
   221478 (P.S.), the Boston Children's Hospital Ophthalmology Foundation
   (J.C.), a Boston Children's Hospital Faculty Career Development Award
   (J.C.), the Bright Focus Foundation (J.C.) and the Massachussetts Lions
   Eye Research Fund, Inc. (J.C.). We thank M. Puder and P. Nandivada
   (Harvard Medical School, Boston Children's Hospital) for sharing the
   Ffar1<SUP>-/-</SUP> mice; M. Al-Ubaidi (University of Oklahoma) for
   sharing the 661W photoreceptor cells; Z. Lin and W.T. Pu (Harvard
   Medical School, Boston Children's Hospital) for sharing a modified
   CAG-GFP-miR30 construct; and C. Cepko (Harvard Medical School) and T. Li
   (National Eye Institute) for providing the pAAV-RK-GFP vector.
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NR 54
TC 139
Z9 143
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD APR
PY 2016
VL 22
IS 4
BP 439
EP +
DI 10.1038/nm.4059
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA DI4GF
UT WOS:000373457700021
PM 26974308
OA Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Danner, M
   Vennedey, V
   Hiligsmann, M
   Fauser, S
   Stock, S
AF Danner, Marion
   Vennedey, Vera
   Hiligsmann, Mickael
   Fauser, Sascha
   Stock, Stephanie
TI Focus Groups in Elderly Ophthalmologic Patients: Setting the Stage for
   Quantitative Preference Elicitation
SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH
LA English
DT Article
ID DISCRETE-CHOICE EXPERIMENTS; ANALYTIC HIERARCHY PROCESS; MACULAR
   DEGENERATION; HEALTH ECONOMICS; CHECKLIST
AB Patients suffering from age-related macular degeneration (AMD) are rarely actively involved in decision-making, despite facing preference-sensitive treatment decisions. This paper presents a qualitative study to prepare quantitative preference elicitation in AMD patients. The aims of this study were (1) to gain familiarity with and learn about the special requirements of the AMD patient population for quantitative data collection; and (2) to select/refine patient-relevant treatment attributes and levels, and gain insights into preference structures.
   Semi-structured focus group interviews were performed. An interview guide including preselected categories in the form of seven potentially patient-relevant treatment attributes was followed. To identify the most patient-relevant treatment attributes, a ranking exercise was performed. Deductive content analyses were done by two independent reviewers for each attribute to derive subcategories (potential levels of attributes) and depict preference trends.
   The focus group interviews included 21 patients. The interviews revealed that quantitative preference surveys in this population will have to be interviewer assisted to make the survey feasible for patients. The five most patient-relevant attributes were the effect on visual function [ranking score (RS): 139], injection frequency (RS: 101), approval status (RS: 83), side effects (RS: 79), and monitoring frequency (RS: 76). Attribute and level refinement was based on patients' statements. Preference trends and dependencies between attributes informed the quantitative instrument design.
   This study suggests that qualitative research is a very helpful step to prepare the design and administration of quantitative preference elicitation instruments. It especially facilitated familiarization with the target population and its preferences, and it supported attribute/level refinement.
C1 [Danner, Marion; Vennedey, Vera; Stock, Stephanie] Cologne Univ Hosp, Inst Hlth Econ & Clin Epidemiol, Gleueler Str 176-178, D-50935 Cologne, Germany.
   [Hiligsmann, Mickael] Maastricht Univ, Dept Hlth Serv Res, CAPHRI Sch Primary Care & Publ Hlth, NL-6200 MD Maastricht, Netherlands.
   [Fauser, Sascha] Cologne Univ Hosp, Ctr Ophthalmol, D-50935 Cologne, Germany.
C3 University of Cologne; Maastricht University; University of Cologne
RP Danner, M (通讯作者)，Cologne Univ Hosp, Inst Hlth Econ & Clin Epidemiol, Gleueler Str 176-178, D-50935 Cologne, Germany.
EM marion.danner@uk-koeln.de
FU Bayer Vital GmbH, Germany
FX This investigator-initiated study was financially supported by Bayer
   Vital GmbH, Germany (which markets the product aflibercept). The sponsor
   had no role in the study design, data collection, data analysis or
   writing and publishing of the report. The authors report no conflicts of
   interest.
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NR 38
TC 13
Z9 13
U1 0
U2 11
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1178-1653
EI 1178-1661
J9 PATIENT
JI Patient
PD FEB
PY 2016
VL 9
IS 1
BP 47
EP 57
DI 10.1007/s40271-015-0122-3
PG 11
WC Health Care Sciences & Services; Health Policy & Services
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services
GA DB7YT
UT WOS:000368734300006
PM 25726011
DA 2022-11-30
ER

PT J
AU Widomska, J
   Zareba, M
   Subczynski, WK
AF Widomska, Justyna
   Zareba, Mariusz
   Subczynski, Witold Karol
TI Can Xanthophyll-Membrane Interactions Explain Their Selective Presence
   in the Retina and Brain?
SO FOODS
LA English
DT Review
DE lutein; carotenoids; age-related neurodegenerative diseases; neural
   tissue; zeaxanthin; macular xanthophylls; age-related macular
   degeneration (AMD); lipid antioxidants
ID POLYUNSATURATED FATTY-ACIDS; PIGMENT OPTICAL-DENSITY; BLUE-LIGHT DAMAGE;
   MACULAR PIGMENT; BETA-CAROTENE; SINGLET OXYGEN; LIPID-BILAYERS;
   LONG-CHAIN; ANTIOXIDANT ACTIVITY; RADICALS RELATIONSHIP
AB Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as beta-carotene, alpha-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and beta-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases.
C1 [Widomska, Justyna] Med Univ Lublin, Dept Biophys, PL-20090 Lublin, Poland.
   [Zareba, Mariusz] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
   [Subczynski, Witold Karol] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA.
C3 Medical University of Lublin; Medical College of Wisconsin; Medical
   College of Wisconsin
RP Widomska, J (通讯作者)，Med Univ Lublin, Dept Biophys, PL-20090 Lublin, Poland.
EM jwidomska@gmail.com; mariusz@mcw.edu; subczyn@mcw.edu
FU National Institutes of Health [EY015526, EB002052, EB001980, EY001931];
   NATIONAL EYE INSTITUTE [P30EY001931, R01EY015526] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
   [P41EB001980, R01EB002052] Funding Source: NIH RePORTER
FX This work was supported by Grants EY015526, EB002052, EB001980 and
   EY001931 from the National Institutes of Health.
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NR 138
TC 34
Z9 35
U1 0
U2 8
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2304-8158
J9 FOODS
JI Foods
PY 2016
VL 5
IS 1
AR 7
DI 10.3390/foods5010007
PG 19
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA DI5JB
UT WOS:000373533600007
PM 27030822
OA Green Published, Green Submitted, Green Accepted, gold
DA 2022-11-30
ER

PT J
AU Nagai, H
   Hirano, Y
   Yasukawa, T
   Morita, H
   Nozaki, M
   Wolf-Schnurrbusch, U
   Wolf, S
   Ogura, Y
AF Nagai, Hiroyuki
   Hirano, Yoshio
   Yasukawa, Tsutomu
   Morita, Hiroshi
   Nozaki, Miho
   Wolf-Schnurrbusch, Ute
   Wolf, Sebastian
   Ogura, Yuichiro
TI Prevention of increased abnormal fundus autofluorescence with blue
   light-filtering intraocular lenses
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; CATARACT-SURGERY; MACULAR DEGENERATION;
   ASSOCIATION; PATTERNS; RISK
AB PURPOSE: To observe changes in fundus autofluorescence 2 years after implantation of blue light-filtering (yellow-tinted) and ultraviolet light-filtering (colorless) intraocular lenses (IOLs).
   SETTING: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, and the Department of Ophthalmology, University of Bern, Bern, Switzerland.
   DESIGN: Prospective comparative observational study.
   METHODS: Patients were enrolled who had cataract surgery with implantation of a yellow-tinted or colorless IOL and for whom images were obtained on which the fundus autofluorescence was measurable using the Heidelberg Retina Angiogram 2 postoperatively. The fundus autofluorescence in the images was classified into 8 abnormal patterns based on the classification of the International Fundus Autofluorescence Classification Group, The presence of normal fundus autofluorescence, geographic atrophy, and wet age-related macular degeneration (AMD) also was recorded. The fundus findings at baseline and 2 years postoperatively were compared.
   RESULTS: Fifty-two eyes with a yellow-tinted IOL and 79 eyes with a colorless IOL were included. Abnormal fundus autofluorescence did not develop or increase in the yellow-tinted IOL group; however, progressive abnormal fundus autofluorescence developed or increased in 12 eyes (15.2%) in the colorless IOL group (P = .0016). New drusen, geographic atrophy, and choroidal neovascularization were observed mainly in the colorless IOL group. The incidence of AMD was statistically significantly higher in the colorless IOL group (P =.042).
   CONCLUSIONS: Two years after cataract surgery, significant differences were seen in the progression of abnormal fundus autofluorescence between the 2 groups. The incidence of AMD was lower in eyes with a yellow-tinted IOL.
C1 [Nagai, Hiroyuki; Hirano, Yoshio; Yasukawa, Tsutomu; Morita, Hiroshi; Nozaki, Miho; Ogura, Yuichiro] Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Nagoya, Aichi 4678601, Japan.
   [Wolf-Schnurrbusch, Ute; Wolf, Sebastian] Univ Bern, Dept Ophthalmol, Bern, Switzerland.
C3 Nagoya City University; University of Bern
RP Hirano, Y (通讯作者)，Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
EM yoshio.hirano@gmail.com; yasukawa@med.nagoya-cu.ac.jp
RI Wolf, Sebastian/B-8782-2008
OI Wolf, Sebastian/0000-0002-7467-7028; Hirano, Yoshio/0000-0002-9173-0839
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NR 15
TC 9
Z9 10
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0886-3350
EI 1873-4502
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD SEP
PY 2015
VL 41
IS 9
BP 1855
EP 1859
DI 10.1016/j.jcrs.2015.01.017
PG 5
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA CY2KN
UT WOS:000366237600010
PM 26471051
DA 2022-11-30
ER

PT J
AU Shin, JY
   Yu, HG
AF Shin, Joo Young
   Yu, Hyeong Gon
TI OPTICAL COHERENCE TOMOGRAPHY-BASED RANIBIZUMAB MONOTHERAPY FOR RETINAL
   ANGIOMATOUS PROLIFERATION IN KOREAN PATIENTS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; anti-vascular endothelial growth
   factor antibody; choroidal neovascularization; optical coherence
   tomography; retinal angiomatous proliferation
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY;
   INTRAVITREAL RANIBIZUMAB; TRIAMCINOLONE; BEVACIZUMAB;
   NEOVASCULARIZATION; PROGNOSIS; REGIMEN; EYES
AB Purpose: To evaluate the visual outcome of optical coherence tomography-based ranibizumab monotherapy in Korean patients with retinal angiomatous proliferation and identify prognostic factors of visual outcome.
   Methods: A prospective single-arm clinical study of 31 retinal angiomatous proliferation patients who underwent 3 consecutive monthly intravitreal ranibizumab injections was conducted. Additional treatment was given based on optical coherence tomography at monthly follow-ups over 24 months.
   Results: Best-corrected visual acuity improved from 48.7 +/- 19.3 to 56.3 +/- 19.1 letters at 24 months (P = 0.010). Total cumulative numbers of injection were 5.5 +/- 2.2 and 7.7 +/- 3.4 times at 12 and 24 months, respectively. Older age, larger choroidal neovascularization size, and poor initial best-corrected visual acuity were associated with poor visual outcome. Final best-corrected visual acuity was significantly worse with Stage 3 disease (70.4 +/- 5.1, 62.3 +/- 11.6, 46.2 +/- 22.3 letters improved in each stage; P = 0.015). Among factors associated with poor visual outcome, only the stage of retinal angiomatous proliferation remained statistically significant on multiple linear regression analysis (P = 0.006). Although baseline best-corrected visual acuity was similar, Stage 3 patients exhibited limited visual improvement despite anatomical improvement, and more recurrences requiring more injections.
   Conclusion: Retinal angiomatous proliferation may be successfully managed with ranibizumab monotherapy in Korean patients, with the number of treatments required comparable to other forms of neovascular age-related macular degeneration. However, visual improvement was limited in late-stage RAP.
C1 [Shin, Joo Young; Yu, Hyeong Gon] Seoul Natl Univ Hosp, Dept Ophthalmol, Seoul 110744, South Korea.
   [Yu, Hyeong Gon] Seoul Natl Univ, Sensory Organs Inst, Med Res Ctr, Seoul 110744, South Korea.
C3 Seoul National University (SNU); Seoul National University Hospital;
   Seoul National University (SNU)
RP Yu, HG (通讯作者)，Seoul Natl Univ, Coll Med, Dept Ophthalmol, 101 Daehak Roe, Seoul 110744, South Korea.
EM hgonyu@snu.ac.kr
OI Yu, Hyeong Gon/0000-0002-1795-202X; Shin, Joo Young/0000-0001-5062-6392
FU Novartis Pharmaceuticals
FX Supported by Novartis Pharmaceuticals.
CR Atmani K, 2010, EYE, V24, P1193, DOI 10.1038/eye.2010.9
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NR 35
TC 26
Z9 26
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD DEC
PY 2014
VL 34
IS 12
BP 2359
EP 2366
DI 10.1097/IAE.0000000000000225
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AU9KK
UT WOS:000345911300011
PM 25011025
DA 2022-11-30
ER

PT J
AU Yan, TQ
   Bi, HS
   Wang, Y
AF Yan, Tingqin
   Bi, Hongsheng
   Wang, Yun
TI Wogonin modulates hydroperoxide-induced apoptosis via PI3K/Akt pathway
   in retinal pigment epithelium cells
SO DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE Age-related macular degeneration; Hydrogen peroxide; Oxidative stress;
   Retinal pigment epithelial cell; ARPE-19
AB Background: Oxidative stress causes the defects of retinal pigment epithelial (RPE) cells that contribute to age-related macular degeneration (AMD). This study was conducted to determine whether wogonin could prevent H2O2-induced oxidative stress in RPE cells.
   Methods: A RPE cell line, ARPE-19, was obtained for the cell model. ARPE-19 cells were pre-treated with various concentrations of wogonin for 24 h before being exposed to H2O2 for 2 h to induce oxidative stress. Cell metabolic activity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was quantified by the flow cytometry. Protein level was assed by western blot.
   Results: The RPE cells exposed to to 200 mM H2O2 demonstrated a significant depression in the cell viability; whereas pre-treatment with 50 and 100 mmol/l wogonin could significantly improve the cell viability in a dose-dependent manner. The proportion of PI-positive cells was increased significantly in RPE cells treated with H2O2 alone; whereas pretreatment with 100 mM wogonin significantly reduced H2O2-induced RPE cell death rate. In protein level, the wogonin use could reduce the level of p-Akt significantly and this is the possible mechanism of the antioxidant effect of wogonin.
   Conclusions: Our study showed that wogonin pre-treatment can protect RPE cells from H2O2-induced apoptosis. This suggests potential effect of wogonin in the prevention of retinal diseases associated with H2O2-induced oxidative stress such as AMD.
   Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_154
C1 [Yan, Tingqin] Shandong Univ Tradit Chinese Med, Clin Coll, Jinan 250355, Peoples R China.
   [Yan, Tingqin] Cent Hosp, Tai An 271000, Shandong, Peoples R China.
   [Bi, Hongsheng; Wang, Yun] Shandong Univ Tradit Chinese Med, Hosp Eye, Jinan 250002, Peoples R China.
C3 Shandong University of Traditional Chinese Medicine; Shandong University
   of Traditional Chinese Medicine
RP Bi, HS (通讯作者)，Shandong Univ Tradit Chinese Med, Hosp Eye, Jinan 250002, Peoples R China.
EM yanyanqin2@163.com
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NR 22
TC 12
Z9 13
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-1596
J9 DIAGN PATHOL
JI Diagn. Pathol.
PD NOV 29
PY 2014
VL 9
AR 154
DI 10.1186/s13000-014-0154-3
PG 6
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA V44TP
UT WOS:000209771600001
PM 25432585
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nagai, N
   Kubota, S
   Tsubota, K
   Ozawa, Y
AF Nagai, Norihiro
   Kubota, Shunsuke
   Tsubota, Kazuo
   Ozawa, Yoko
TI Resveratrol prevents the development of choroidal neovascularization by
   modulating AMP-activated protein kinase in macrophages and other cell
   types
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Retina; AMPK; Inflammation; Macrophage; Neovascularization; Resveratrol
ID ENDOTHELIAL GROWTH-FACTOR; EMERGING DRUG TARGET; MACULAR DEGENERATION;
   CLINICAL-TRIAL; EYE DISEASE; INHIBITION; ANGIOGENESIS; MICE;
   INFLAMMATION; RANIBIZUMAB
AB The development of choroidal neovascularization (CNV) is a critical step in the pathogenesis of age-related macular degeneration (AMD), a vision-threatening disease. In this study, we used a mouse model of AMD to study the protective effects of resveratrol (RSV) supplementation against CNV as well as the underlying molecular mechanisms. Mice were orally pretreated with RSV daily for 5 days. On the fifth day, the mice underwent laser photocoagulation to induce CNV. One week after laser treatment, CNV volume was significantly lower in the RSV-treated mice compared with vehicle-treated animals. In addition, RSV treatment significantly inhibited macrophage infiltration into the retinal pigment epithelium (RPE)-choroid and suppressed the expression of inflammatory and angiogenic molecules, including vascular endothelial growth factor, monocyte chemotactic protein-1 and intercellular adhesion molecule-1. Importantly, RSV prevented the CNV-induced decrease in activated AMP-activated protein kinase and increase in activated nuclear factor-kappa B in the RPE-choroid complex. The regulatory effects of RSV on these molecules were confirmed in RPE, microvascular endothelial and macrophage cell lines. Inhibition of macrophage infiltration by RSV was confirmed by in vitro scratch and migration assays. RSV suppressed CNV development, reducing the levels of multiple cytokines secreted from several cell types and inhibiting macrophage migration. The direct effects of RSV on each cell type were confirmed in vitro. Although further studies are needed, RSV could potentially be applied in the clinic to prevent CNV development in AMD. (C) 2014 The Authors. Published by Elsevier Inc.
C1 [Nagai, Norihiro; Kubota, Shunsuke; Ozawa, Yoko] Keio Univ, Sch Med, Lab Retinal Cell Biol, Tokyo 1608582, Japan.
   [Nagai, Norihiro; Kubota, Shunsuke; Tsubota, Kazuo; Ozawa, Yoko] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo 1608582, Japan.
C3 Keio University; Keio University
RP Ozawa, Y (通讯作者)，Keio Univ, Sch Med, Dept Ophthalmol, Lab Retinal Cell Biol,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ozawa@a5.keio.jp
RI Ozawa, Yoko/AAH-9888-2020
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NR 59
TC 39
Z9 42
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD NOV
PY 2014
VL 25
IS 11
BP 1218
EP 1225
DI 10.1016/j.jnutbio.2014.05.015
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA AS3WI
UT WOS:000344205600013
PM 25091551
OA hybrid
DA 2022-11-30
ER

PT J
AU Zou, X
   Gao, J
   Zheng, Y
   Wang, X
   Chen, C
   Cao, K
   Xu, J
   Li, Y
   Lu, W
   Liu, J
   Feng, Z
AF Zou, X.
   Gao, J.
   Zheng, Y.
   Wang, X.
   Chen, C.
   Cao, K.
   Xu, J.
   Li, Y.
   Lu, W.
   Liu, J.
   Feng, Z.
TI Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell
   death
SO CELL DEATH & DISEASE
LA English
DT Article
DE zeaxanthin; glutathione; reactive oxygen species; Nrf2; mitochondria
ID PIGMENT EPITHELIAL-CELLS; OXIDATIVE STRESS; MACULAR DEGENERATION;
   MITOCHONDRIAL DYSFUNCTION; GLUTATHIONE DEPLETION; PHOTOOXIDATIVE DAMAGE;
   ANTIOXIDANT RESPONSE; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR;
   NEUROBLASTOMA-CELLS
AB Zeaxanthin (Zea) is a major carotenoid pigment contained in human retina, and its daily supplementation associated with lower risk of age-related macular degeneration. Despite known property of Zea as an antioxidant, its underlying molecular mechanisms of action remain poorly understood. In this study, we aim to study the regulation mechanism of Zea on phase II detoxification enzymes. In normal human retinal pigment epithelium cells, Zea promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and induced mRNA and protein expression of phase II enzymes, the induction was suppressed by specific knockdown of Nrf2. Zea also effectively protected against tert-butyl hydroperoxide-induced mitochondrial dysfunction and apoptosis. Glutathione (GSH) as the most important antioxidant was also induced by Zea through Nrf2 activation in a time-and dose-dependent manner, whereas the protective effects of Zea were decimated by inhibition of GSH synthesis. Finally, Zea activated the PI3K/Akt and MAPK/ERK pathway, whereas only PI3K/Akt activation correlated with phase II enzymes induction and Zea protection. In further in vivo analyses, Zea showed effects of inducing phase II enzymes and increased GSH content, which contributed to the reduced lipid and protein peroxidation in the retina as well as the liver, heart, and serum of the Sprague-Dawley rats. For the first time, Zea is presented as a phase II enzymes inducer instead of being an antioxidant. By activating Nrf2-mediated phase II enzymes, Zea could enhance anti-oxidative capacity and prevent cell death both in vivo and in vitro.
C1 [Zou, X.; Gao, J.; Wang, X.; Chen, C.; Cao, K.; Xu, J.; Li, Y.; Lu, W.; Liu, J.; Feng, Z.] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China.
   [Zou, X.; Lu, W.] Xi An Jiao Tong Univ, FIST, Ctr Translat Med, Xian 710049, Peoples R China.
   [Gao, J.; Wang, X.; Chen, C.; Cao, K.; Xu, J.; Li, Y.; Liu, J.; Feng, Z.] Xi An Jiao Tong Univ, FIST, Ctr Mitochondrial Biol & Med, Xian 710049, Peoples R China.
   [Zheng, Y.] Shandong Univ, Jinan Cent Hosp, Jinan 250100, Peoples R China.
C3 Xi'an Jiaotong University; Xi'an Jiaotong University; Xi'an Jiaotong
   University; Shandong First Medical University & Shandong Academy of
   Medical Sciences; Shandong University
RP Feng, Z (通讯作者)，Xi An Jiao Tong Univ, FIST, Ctr Mitochondrial Biol & Med, 28 W Xian Ning Rd, Xian 710049, Peoples R China.
EM zhfeng@mail.xjtu.edu.cn
RI Feng, Zhihui/E-7408-2011; Lu, Wuyuan/B-2268-2010; Zou, Xuan/A-6452-2015
OI Feng, Zhihui/0000-0002-2448-6565; Wang, Xun/0000-0001-5172-0305
FU National Natural Science Foundation of China [81201023, 31370844]; 973
   program [2014CB548200]; National 'Twelfth Five-Year' Plan for Science
   and Technology Support [2012BAH30F03]; Fundamental Research Funds for
   the Central Universities; 985 project of Xi'an Jiaotong University; 211
   project of Xi'an Jiaotong University
FX This study is supported by the National Natural Science Foundation of
   China (81201023, 31370844), the 973 program (No. 2014CB548200), National
   'Twelfth Five-Year' Plan for Science and Technology Support
   (2012BAH30F03), the Fundamental Research Funds for the Central
   Universities, 985 and 211 projects of Xi'an Jiaotong University.
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NR 47
TC 69
Z9 70
U1 0
U2 23
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 MAY
PY 2014
VL 5
SI SI
AR e1218
DI 10.1038/cddis.2014.190
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA AI9DN
UT WOS:000337229300018
PM 24810054
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Campbell, M
   Doyle, SL
AF Campbell, Matthew
   Doyle, Sarah L.
TI An eye on the future of inflammasomes and drug development in AMD
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Age related macular degeneration (AMD); Inflammasome; NLRP3; IL-1beta;
   IL-18
ID STERILE INFLAMMATORY RESPONSE; RETINAL-PIGMENT EPITHELIUM; TOLL-LIKE
   RECEPTORS; MACULAR DEGENERATION; NLRP3 INFLAMMASOME; OXIDATIVE STRESS;
   NALP3 INFLAMMASOME; MITOCHONDRIAL DYSFUNCTION; INSULIN-RESISTANCE; CELLS
AB Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. While activation of the immune system has been implicated in disease progression, the pathways involved remain relatively unclear. Typically, inflammatory responses are caused as a result of pathogenic infection. However, in chronic conditions, like AMD, a form of 'sterile' inflammation can exist in localised areas of the body in response to modified host-derived elements and particulate matter accumulation, due to the activation of a complex termed the 'inflammasome'. Inflammasomes control the activity of two major pro-inflammatory cytokines, namely, interleukin (IL)-1 beta and IL-18, by allowing for their cleavage from inactive pro-forms into mature cytokines. The major pathological hallmark common to both 'dry' and 'wet' AMD is the presence of extracellular deposits, known as drusen, below the retinal pigment epithelium in the macula of the eye. Past studies have shown that host-derived particulate matter such as amyloid deposits and atherosclerotic plaques can be 'sensed' by the NLRP3-inflammasome causing cleavage of pro-IL-1 beta and pro-IL-18. We have recently reported that the NLRP3-inflammasome can also 'sense' drusen isolated from human AMD donor eyes and that IL-18 protects against the development of choroidal neovascularisation in a model that mimics 'wet' AMD. In fact, since then, a number of studies have reported roles for the NLRP3-inflammasome in AMD. This review will focus on describing, comparing and contrasting these reports and analyzing the potential for manipulating the NLRP3-inflammasome as a therapy for AMD.
C1 [Campbell, Matthew] Trinity Coll Dublin, Ocular Genet Unit, Dublin 2, Ireland.
   [Doyle, Sarah L.] Trinity Coll Dublin, Sch Med, Dept Clin Med, Dublin 2, Ireland.
   [Doyle, Sarah L.] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin 12, Ireland.
C3 Trinity College Dublin; Trinity College Dublin; National Children's
   Research Centre (NCRC); Our Ladys Children Hospital Crumlin; Trinity
   College Dublin
RP Campbell, M (通讯作者)，Trinity Coll Dublin, Ocular Genet Unit, Lincoln Pl Gate, Dublin 2, Ireland.
EM matthew.campbell@tcd.ie; Sarah.Doyle@tcd.ie
RI Doyle, Sarah/C-1453-2014
OI Doyle, Sarah/0000-0002-6294-9380
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NR 75
TC 18
Z9 24
U1 1
U2 28
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD SEP
PY 2013
VL 91
IS 9
BP 1059
EP 1070
DI 10.1007/s00109-013-1050-0
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA 213OU
UT WOS:000324068100005
PM 23661041
DA 2022-11-30
ER

PT J
AU Krohne, TU
   Liu, ZP
   Holz, FG
   Meyer, CH
AF Krohne, Tim U.
   Liu, Zengping
   Holz, Frank G.
   Meyer, Carsten H.
TI Intraocular Pharmacokinetics of Ranibizumab Following a Single
   Intravitreal Injection in Humans
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; NEONATAL FC-RECEPTOR; MACULAR DEGENERATION;
   TRIAMCINOLONE ACETONIDE; BEVACIZUMAB; AGE; FRAGMENT; RABBITS; EYES
AB PURPOSE: To investigate intraocular concentrations and pharmacokinetics of ranibizumab after a single intravitreal injection in humans.
   DESIGN: Prospective, noncomparative, interventional case series.
   METHODS: We included 18 nonvitrectomized eyes of 18 patients (age range, 61-85 years) that were diagnosed with both clinically significant cataract and macular edema secondary to either exudative age-related macular degeneration, diabetic maculopathy, or retinal vein occlusion. Each eye received a single intravitreal injection of 0.5 mg ranibizumab. An aqueous humor sample was obtained during cataract surgery between 1 and 37 days after injection. Concentrations of unbound ranibizumab in these samples were quantified by enzyme-linked immunosorbent assay.
   RESULTS: Ranibizumab concentration in aqueous humor peaked the first day after injection (range, 36.9-66.1 mu g/mL) and subsequently declined in a mono-exponential fashion. Nonlinear regression analysis determined an initial peak concentration (c(max)) of 56.1 mu g/mL and an elimination half-life (t(1/2)) of 7.19 days with a coefficient of determination (R-2) of 0.90. Correction of ranibizumab concentrations for ocular volume as calculated from axial length measurements did not alter regression analysis results significantly (t(1/2), 7.15 days; R-2, 0.89).
   CONCLUSIONS: In human nonvitrectomized eyes, the aqueous half-life of 0.5 mg intravitreally injected ranibizumab is 7.19 days, slightly shorter than the half-life of 9.82 days previously determined for bevacizumab by comparable methods. (Am J Ophthalmol 2012;154: 682-686. (C) 2012 by Elsevier Inc. All rights reserved.)
C1 [Krohne, Tim U.; Liu, Zengping; Holz, Frank G.; Meyer, Carsten H.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
C3 University of Bonn
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; Meyer, Carsten/A-3981-2017; Liu,
   Zengping/GQO-9030-2022; Krohne, Tim/AAG-4412-2020
OI Krohne, Tim/0000-0003-2280-925X; Meyer, Carsten/0000-0002-0530-5298;
   Liu, Zengping/0000-0002-2578-293X
FU China Scholarship Council, Beijing, China [2008627116]; Novartis; Bayer
   Healthcare; Heidelberg Engineering; GSK; Alcon; Carl Zeiss Meditec;
   Optos; Pfizer; Allergan; Hilde Rudiger Foundation, Bonn, Germany
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF Interest. T.U.K. received consultancy
   honoraria from Novartis, research grants from Novartis and Alcon, and
   lecture fees from Novartis. F.G.H. received consultancy honoraria from
   Novartis, Genentech, Bayer Healthcare, Heidelberg Engineering, Pfizer,
   Acucela, Allergan, and Alcon; research grants from Novartis, Bayer
   Healthcare, Heidelberg Engineering, GSK, Alcon, Carl Zeiss Meditec, and
   Optos; and lecture fees from Novartis, Bayer Healthcare, Heidelberg
   Engineering, Pfizer, and Alcon. C.H.M. received board membership and
   consultancy honoraria from GSK, research grants from Novartis, and
   lecture fees from Novartis and Allergan. The study was funded by a grant
   from the Dr Eberhard and Hilde Rudiger Foundation, Bonn, Germany (to
   T.U.K.). Z.L. is supported by the China Scholarship Council, Beijing,
   China (grant 2008627116). Involved in design and conduct of the study
   (T.U.K., Z.L., F.G.H., C.H.M.); patient recruitment and sample taking
   (C.H.M.); sample analysis and statistical evaluation of the data
   (T.U.K., Z.L.); interpretation of the data (T.U.K., F.G.H., C.H.M.);
   preparation of the manuscript (T.U.K.); and review and approval of the
   manuscript (T.U.K., Z.L., F.G.H., C.H.M.). This was a prospective
   protocol-driven institutional review board (IRB)-approved study (IRB of
   the Medical Faculty of University of Bonn, Germany) with patient written
   informed consent for participation in research.
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NR 26
TC 161
Z9 168
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2012
VL 154
IS 4
BP 682
EP 686
DI 10.1016/j.ajo.2012.03.047
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 018UK
UT WOS:000309691800009
PM 22818800
DA 2022-11-30
ER

PT J
AU Nowak-Sliwinska, P
   Weiss, A
   van Beijnum, JR
   Wong, TJ
   Ballini, JP
   Lovisa, B
   van den Bergh, H
   Griffioen, AW
AF Nowak-Sliwinska, Patrycja
   Weiss, Andrea
   van Beijnum, Judy R.
   Wong, Tse J.
   Ballini, Jean-Pierre
   Lovisa, Blaise
   van den Bergh, Hubert
   Griffioen, Arjan W.
TI Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE anti-angiogenic; bevacizumab; CAM model; ImageJ; kinase inhibitor;
   photodynamic therapy
ID COMBINATION THERAPY; TUMOR ANGIOGENESIS; TARGETED THERAPIES;
   GENE-EXPRESSION; VERTEPORFIN; SUNITINIB; EFFICACY; CANCER; SORAFENIB;
   DISEASES
AB Targeted angiostatic therapy receives major attention for the treatment of cancer and exudative age-related macular degeneration (AMD). Photodynamic therapy (PDT) has been used as an effective clinical approach for these diseases. As PDT can cause an angiogenic response in the treated tissue, combination of PDT with anti-angiogenic compounds should lead to improved therapy. This study was undertaken to test the clinically used small molecule kinase inhibitors Nexavar (R) (sorafenib), Tarceva (R) (erlotinib) and Sutent (R) (sunitinib) for this purpose, and to compare the results to the combination of Visudyne (R)-PDT with Avastin (R) (bevacizumab) treatment. When topically applied to the chicken chorioallantoic membrane at embryo development day (EDD) 7, a clear inhibition of blood vessel development was observed, with sorafenib being most efficient. To investigate the combination with phototherapy, Visudyne (R)-PDT was first applied on EDD11 to close all <100 mu m vessels. Application of angiostatics after PDT resulted in a significant decrease in vessel regrowth in terms of reduced vessel density and number of branching points/mm2. As the 50% effective dose (ED50) for all compounds was approximately 10-fold lower, Sorafenib outperformed the other compounds. In vitro, all kinase inhibitors decreased the viability of human umbilical vein endothelial cells. Sunitinib convincingly inhibited the in vitro migration of endothelial cells. These results suggest the therapeutic potential of these compounds for application in combination with PDT in anti-cancer approaches, and possibly also in the treatment of other diseases where angiogenesis plays an important role.
C1 [Nowak-Sliwinska, Patrycja; van Beijnum, Judy R.; Wong, Tse J.; Griffioen, Arjan W.] Vrije Univ Amsterdam, Angiogenesis Lab, Dept Med Oncol, Med Ctr, Amsterdam, Netherlands.
   [Weiss, Andrea; Ballini, Jean-Pierre; Lovisa, Blaise; van den Bergh, Hubert] Ecole Polytech Fed Lausanne, Med Photon Grp, Inst Bioengn, Swiss Fed Inst Technol, CH-1015 Lausanne, Switzerland.
C3 Vrije Universiteit Amsterdam; Swiss Federal Institutes of Technology
   Domain; Ecole Polytechnique Federale de Lausanne
RP Nowak-Sliwinska, P (通讯作者)，Univ Lausanne Hosp, Dept Urol, CHUV, CH-1011 Lausanne, Switzerland.
EM Patrycja.Nowak-Sliwinska@epfl.ch
RI Nowak-Sliwinska, Patrycja/T-7663-2018; Gasser-Weiss, Andrea/M-4469-2017
OI Nowak-Sliwinska, Patrycja/0000-0002-8299-0444; Gasser-Weiss,
   Andrea/0000-0002-1566-7428
FU Dutch Science Foundation [NWO 40.11.195]; Swiss Federal Institute of
   Technology (EPFL)
FX The authors are grateful for financial support from Dr. Julia Jacobi.
   This work was also supported by a grant from the Dutch Science
   Foundation (NWO 40.11.195) and the Swiss Federal Institute of Technology
   (EPFL).
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NR 41
TC 40
Z9 42
U1 3
U2 15
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD JUL
PY 2012
VL 16
IS 7
BP 1553
EP 1562
DI 10.1111/j.1582-4934.2011.01440.x
PG 10
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA 965UA
UT WOS:000305791600019
PM 21880113
OA Green Published
DA 2022-11-30
ER

PT J
AU Afzal, A
   Caballero, S
   Palii, SS
   Jurczyk, S
   Pardue, M
   Geroski, D
   Edelhauser, H
   Hochhaus, G
   Kim, M
   Franklin, A
   Shapiro, G
   Grant, MB
AF Afzal, Aqeela
   Caballero, Sergio
   Palii, Stela S.
   Jurczyk, Simona
   Pardue, Machelle
   Geroski, Dale
   Edelhauser, Henry
   Hochhaus, Guenther
   Kim, Moon
   Franklin, Alan
   Shapiro, Gideon
   Grant, Maria B.
TI Targeting retinal and choroid neovascularization using the small
   molecule inhibitor carboxyamidotriazole
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE Angiogenesis; Therapy; Choroidal Neovascularization; Endothelial cell;
   Animal model; Carboxyamidotriazole
ID MEDIATED SIGNAL-TRANSDUCTION; MACULAR DEGENERATION; GROWTH; CELLS;
   CALCIUM; EFFICACY; RECEPTOR; CAI; PROLIFERATION; ANGIOGENESIS
AB Neovascular ocular diseases as exemplified by proliferative diabetic retinopathy (PDR), exudative age-related macular degeneration (AMD), and retinopathy of prematurity (ROP) are severe diseases affecting all age groups in the US. We asked whether a small molecule, carboxyamidotriazole (CAI) known for its anti-angiogenic and anti-tumor effects and its ability to be administered orally in humans, could have anti-angiogenic effects in ocular in vitro and in vivo angiogenesis models. The anti-proliferative effects of CAI were examined by BrdU incorporation using human retinal and dermal endothelial cells and human pigment epithelial cells. The effect of CAI was determined using the Matrigel tube formation assay. The mouse model of choroidal neovascularization (CNV) initiated by laser rupture of Bruch's membrane was used to quantify in vivo effects of aqueous beta-hydroxypropyl cyclodextrin (bHPCD) formulations of CAI on neovascularization. The pharmacokinetics (PK) of CAI after intravitreal administration of bHPCD-CAI was studied in rabbit. The intravitreal toxicology of bHPCD-CAI was also examined in rat ocular tissue. We observed that CAI treatment of human endothelial cells decreased cell proliferation in a dose-dependent manner. In the in vivo tests bHPCD-CAI treatment reduced choroidal neovascular lesion volume, also in a dose-dependent manner. The intravitreal PK of bHPCD-CAI demonstrated that highly efficacious concentrations of CAI are reached in the vitreous compartment. No ocular toxicology was observed with intravitreous injection of CAI. These studies support the potential of developing intravitreal CAI in an bHPCD ocular formulation for treatment of proliferative retinopathies in humans. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Afzal, Aqeela; Caballero, Sergio; Grant, Maria B.] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
   [Palii, Stela S.] NIEHS, Mol Toxicol Lab, Environm Stress & Canc Grp, NIH, Bethesda, MD USA.
   [Jurczyk, Simona] Pharmor Inc, Alachua, FL USA.
   [Pardue, Machelle; Geroski, Dale; Edelhauser, Henry] Emory Univ, Dept Ophthalmol, Atlanta VA Med Ctr, Rehab R&D CoE, Atlanta, GA 30322 USA.
   [Hochhaus, Guenther] Univ Florida, Dept Pharmaceut, Gainesville, FL 32610 USA.
   [Franklin, Alan] Retina Specialty Inst, Pensacola, FL USA.
   [Shapiro, Gideon] Pharmore Inc, Gainesville, FL USA.
C3 State University System of Florida; University of Florida; National
   Institutes of Health (NIH) - USA; NIH National Institute of
   Environmental Health Sciences (NIEHS); Emory University; US Department
   of Veterans Affairs; Veterans Health Administration (VHA); Atlanta VA
   Health Care System; Atlanta VA Medical Center; State University System
   of Florida; University of Florida
RP Grant, MB (通讯作者)，Univ Florida, Dept Pharmacol & Therapeut, POB 100267, Gainesville, FL 32610 USA.
EM grantma@ufl.edu
RI Pardue, Machelle T/N-9795-2013
OI Afzal, Aqeela/0000-0001-6406-2233; Hochhaus,
   Guenther/0000-0002-7406-5558
FU NIH [EY01 8294, EY01 2601, EY007739]; NATIONAL EYE INSTITUTE
   [R41EY018294, R29EY007739, R01EY012601, R01EY007739] Funding Source: NIH
   RePORTER
FX This work was supported by research grants NIH Grants EY01 8294 (GS),
   EY01 2601 (MBG) and EY007739 (MBG).
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NR 26
TC 8
Z9 10
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
EI 1873-2747
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD FEB 15
PY 2010
VL 81
IS 2-3
SI SI
BP 320
EP 326
DI 10.1016/j.brainresbull.2009.08.001
PG 7
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 556SA
UT WOS:000274610500016
PM 19679174
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Aung, KZ
   Robman, L
   Chong, EWT
   English, DR
   Giles, GG
   Guymer, RH
AF Aung, Khin Zaw
   Robman, Luba
   Chong, Elaine W. T.
   English, Dallas R.
   Giles, Graham G.
   Guymer, Robyn H.
TI Non-mydriatic Digital Macular Photography: How Good is the Second Eye
   Photograph?
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Age-Related macular degeneration; aged; grading; quality of photographs
ID AGE-RELATED MACULOPATHY; DIABETIC-RETINOPATHY; FUNDUS CAMERA; GRADING
   SYSTEM; DEGENERATION; PROGRESSION; PREVALENCE; QUALITY; FILM
AB Purpose: In an elderly Australian population, to evaluate the quality of fundus photographs taken non-mydriatically in both eyes, and to compare the quality of those taken second with those taken first. Methods: From 2258 participants (4516 images) aged 70 years and older who participated in the Melbourne Collaborative Cohort Study (MCCS), digital non-stereoscopic 45 degrees retinal photographs were taken with a Canon CR6-45NM Non-mydriatic Retinal Camera and evaluated. The quality of macular images was assessed as good, fair, and poor and McNemar's test was used to analyze variation in quality. Results: Gradable quality images were obtained from 95.8% eyes of participants, with 93.9% of participants having gradable photos of both eyes. The gradable rate for the eye photographed first (right), was significantly higher than that for the eye photographed second (left): 89.7% vs. 85.6%, respectively (difference of 4.12%, confidence interval [CI] of 2.68-5.54%, p < 0.001). The rate of ungradable photographs from the second eye was slightly greater than the first eye (4.5% and 3.8%, respectively), but the difference in proportion was not statistically significant (difference of 3.6%, Cl of 0.17-1.5%, p = 0.384). Conclusions: In the setting of a large elderly cohort study, non-dilated 45 degrees digital retinal imaging is an excellent method for fundus examination. It is fast, easy to use, non-invasive, and a reliable AMD (age-related macular degeneration)-detecting technique with only a minor loss of information from the second eye.
C1 [Aung, Khin Zaw; Robman, Luba; Chong, Elaine W. T.; Guymer, Robyn H.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia.
   [English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Melbourne, Vic, Australia.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Cancer Council Victoria
RP Aung, KZ (通讯作者)，Ctr Eye Res Australia, Locked Bag 8, Melbourne, Vic 8002, Australia.
EM kzaung@unimelb.edu.au
RI English, Dallas/AAH-5005-2019; Robman, Liubov/N-9075-2013
OI English, Dallas/0000-0001-7828-8188; Guymer, Robyn/0000-0002-9441-4356;
   Giles, Graham/0000-0003-4946-9099
FU National Health and Medical Research Council Program [209057]; The
   Cancer Council Victoria; The Ophthalmic Research Institute of Australia;
   John T. Reid Charitable Trust; Perpetual Trustees; Royal Victorian Eye
   Ear Hospital
FX VicHealth and the Cancer Council Victoria funded cohort recruitment.
   This study was supported by the National Health and Medical Research
   Council Program Grant (209057) and was further supported by
   infrastructure funding provided by The Cancer Council Victoria. The
   Ophthalmic Research Institute of Australia, John T. Reid Charitable
   Trust, Perpetual Trustees and the Research Committee of the Royal
   Victorian Eye & Ear Hospital funded the ophthalmic component. These
   organizations did not participate in the analysis and writing of the
   article.
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NR 18
TC 25
Z9 25
U1 0
U2 0
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 JUL-AUG
PY 2009
VL 16
IS 4
BP 254
EP 261
DI 10.1080/09286580902864419
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 487GF
UT WOS:000269258600010
PM 19874148
DA 2022-11-30
ER

PT J
AU Qin, SF
   De Vries, GW
AF Qin, Suofu
   De Vries, Gerald W.
TI alpha 2 but not alpha 1 AMP-activated protein kinase mediates oxidative
   stress-induced inhibition of retinal pigment epithelium cell
   phagocytosis of photoreceptor outer segments
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOTHELIAL-CELLS; RAT-LIVER; STIMULATION; GLUCOSE; ENERGY; EXPRESSION;
   APOPTOSIS; RPE
AB Oxidative stress causes retinal pigment epithelium (RPE) cell dysfunction and is a major risk factor leading to the development of dry-type age- related macular degeneration. Taking pharmacological and genetic approaches, we address the mechanisms by which sublethal oxidative stress inhibits RPE cell phagocytosis. Sublethal oxidative stress dose-dependently inhibited RPE cell phagocytosis of photoreceptor outer segments (POS) and activated AMP-activated protein kinase ( AMPK) as determined by increased Thr(172) and Ser(79) phosphorylation of AMPK alpha and its substrate acetyl-CoA carboxylase, respectively. Similar to oxidative stress, 5-aminoimidazole-4-carboxamide riboside ( AICAR), a pharmacological activator of AMPK, inhibited RPE cell phagocytosis of POS in a dose-dependent manner. Inhibition of RPE cell phagocytosis by AICAR was fully reversed by blockade of AICAR translocation into cells by dipyridamole or inhibition of AICAR conversion to ZMP by adenosine kinase inhibitor 5-iodotubercidin. In agreement, AICAR-induced activation of AMPK was abolished by preincubation with dipyridamole or 5-iodotubercidin. Knock-out experiments further revealed that alpha 2 but not alpha 1 AMPK was involved in RPE cell phagocytosis and that activation of alpha 2 AMPK contributed to the inhibition of RPE cell phagocytosis by oxidative stress. Inhibition of RPE cell phagocytosis by activation of alpha 2 AMPK was associated with a dramatic increase in acetyl-CoA carboxylase phosphorylation. In comparison, AMPK had no role in oxidative stress-induced breakdown of RPE barrier function. Taken together, reduction in POS load under oxidative stress might direct RPE cells to a self-protected status. Thus, activating AMPK could have therapeutic potential in treating dry macular degeneration.
C1 [Qin, Suofu; De Vries, Gerald W.] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA 92612 USA.
C3 AbbVie; Allergan
RP Qin, SF (通讯作者)，Allergan Pharmaceut Inc, Dept Biol Sci, RD3-2D,2525 Dupont Dr, Irvine, CA 92612 USA.
EM qin_suofu@allergan.com
OI Qin, Suofu/0000-0002-3323-8846
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NR 38
TC 31
Z9 32
U1 0
U2 2
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 MAR 14
PY 2008
VL 283
IS 11
BP 6744
EP 6751
DI 10.1074/jbc.M708848200
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 271HN
UT WOS:000253779600016
PM 18195011
OA hybrid
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Kreissig, I
   Degenring, RF
AF Jonas, JB
   Kreissig, I
   Degenring, RF
TI Cataract surgery after intravitreal injection of triamcinolone acetonide
SO EYE
LA English
DT Article
DE age-related macular degeneration; cataract; diabetic macular oedema;
   intraocular pressure; triamcinolone acetonide
ID CYSTOID MACULAR EDEMA; RETINAL VEIN OCCLUSION; CRYSTALLINE CORTISONE;
   ADJUNCTIVE TREATMENT; CHOROIDAL NEOVASCULARIZATION;
   INTRAOCULAR-PRESSURE; DEGENERATION; PHARMACOKINETICS; DEXAMETHASONE;
   RECURRENCE
AB Purpose To report the clinical outcome of patients undergoing cataract surgery after one or repeated intravitreal injections of triamcinolone acetonide as treatment of intraocular neovascular or oedematous diseases.
   Methods The interventional clinical case series study included all patients ( n = 22) who presented with cataract which had progressed after a single or repeated intravitreal injection of 25 mg of triamcinolone acetonide as treatment of exudative age-related macular degeneration ( n = 18) or diffuse diabetic macular oedema ( n = 4). Duration of the follow-up period was 3.76 +/- 4.99 months. With topical anaesthesia, the patients underwent standard cataract surgery including clear cornea incision, phakoemulsification and aspiration of the lens nucleus and cortex, and implantation of a foldable posterior chamber lens. The main outcome measures were frequencies of capsular rupture, vitreous loss, postoperative infectious endophthalmitis, secondary cataract, and decentration of the intraocular lens, visual acuity and intraocular pressure.
   Results Intraoperative dialysis of the lens zonules occurred in one (4.5%) eye and resulted in a loss of vitreous. Secondary cataract leading to Nd: YAG laser capsulotomy was observed in one ( 4.5%) eye. An optically significant decentration of the IOL or infectious endophthalmitis was not encountered in any patient. Visual acuity increased from 0.11 +/- 0.10 to 0.13 +/- 0.94 during the follow-up. Within 1 week after surgery, intraocular pressure was in the normal range in all the eyes.
   Conclusions Cataract surgery after single or repeated intravitreal injection of 25 mg of triamcinolone acetonide does not harbour a markedly elevated frequency or a markedly changed profile of surgical complications.
C1 Univ Heidelberg, Fac Clin Med Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Jonas, JB (通讯作者)，Univ Augenklin, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM Jost.Jonas@ma.augen.uni-heidelberg.de
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NR 32
TC 30
Z9 33
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD APR
PY 2004
VL 18
IS 4
BP 361
EP 364
DI 10.1038/sj.eye.6700654
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 810GK
UT WOS:000220692600004
PM 15069430
OA Bronze
DA 2022-11-30
ER

PT J
AU Kim, SG
   Lee, SC
   Scong, YS
   Kim, SW
   Kwon, OW
AF Kim, SG
   Lee, SC
   Scong, YS
   Kim, SW
   Kwon, OW
TI Choroidal neovascularization characteristics and its size in optical
   coherence tomography
SO YONSEI MEDICAL JOURNAL
LA English
DT Article
DE choroidal neovascularization; fluorescein angiography; indocyanine green
   angiography; optical coherence tomography
ID MACULAR DEGENERATION; IN-VIVO; PHOTOCOAGULATION
AB The classification, size and activity of choroidal neovascularization (CNV) by optical coherence tomography (OCT) were compared with those obtained by fluorescein angiography (FA) and Inclocyanine green angiography (ICG). This study included 32 patients (32 eyes) diagnosed as having CNV. The etiology of CNV was found to be age-related macular degeneration (AMD) or non-AMD. Patients were studied retrospectively by FA, ICG, and OCT. Of the 13 eyes with AMD, the boundary of the lesion could not be defined using FA in 7 patients. Among the 7 poorly defined CNV cases by FA, the identification of the boundary was possible in one case by OCT. The mean diameter of the classic well-defined lesions was 3500 +/- 421 mum by FA, 2624 +/- 1044 mum by 1CG, and 1927 +/- 1272 mum by OCT. The size of the CNV by OCT was always smaller than by FA or ICG. Of the 19 eyes with Non-AMD, the boundary of the lesion could not be defined by FA in 5 patients. Among the 5 poorly defined cases by FA, the identification of the boundary was possible in 3 cases by OCT. The mean diameter of the well-defined CNV lesions was 2153 +/- 759 pin by FA, 1929 +/- 673 mum by ICG, and 1322 +/- 566 mum by OCT. Retinal thickness, which represents retinal edema, was found to be proportional to lesion size, although the relationship was not statistically significant. Regardless of CNV type, FA, ICG and OCT used in combination increase the specificity of diagnosis if their findings are compared.
C1 Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul 120752, South Korea.
   Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Ophthalmol, Seoul, South Korea.
C3 Yonsei University; Yonsei University Health System; Sungkyunkwan
   University (SKKU); Samsung Medical Center
RP Lee, SC (通讯作者)，Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, 134 Shinchon Dong, Seoul 120752, South Korea.
OI , Sung Chul/0000-0001-9438-2385
CR Bressler NM, 1999, ARCH OPHTHALMOL-CHIC, V117, P1329
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NR 14
TC 11
Z9 14
U1 0
U2 3
PU YONSEI UNIV COLLEGE MEDICINE
PI SEOUL
PA C/O KYUN0-IL IM, M.D., PH.D, SHINCHON DONG 134, SEODAEMOON KU, SEOUL
   120-752, SOUTH KOREA
SN 0513-5796
J9 YONSEI MED J
JI Yonsei Med. J.
PD OCT 30
PY 2003
VL 44
IS 5
BP 821
EP 827
DI 10.3349/ymj.2003.44.5.821
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 739XX
UT WOS:000186373000010
PM 14584098
OA gold
DA 2022-11-30
ER

PT J
AU Asareh, SM
   Savei, T
   Arjmand, S
   Siadat, SOR
   Fatemi, F
   Pourmadadi, M
   Shayeh, JS
AF Asareh, Shirin Movaghar
   Savei, Tahereh
   Arjmand, Sareh
   Siadat, Seyed Omid Ranaei
   Fatemi, Fateneh
   Pourmadadi, Mehrab
   Shayeh, Javad Shabani
TI Expression of functional eGFP-fused antigen-binding fragment of
   ranibizumab in Pichia pastoris
SO BIOIMPACTS
LA English
DT Article
DE Ranibizumab; Fab fragment; VEGF-A; Pichia pastoris; Split reporter; eGFP
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; RECOMBINANT;
   PURIFICATION; ANTIBODIES; PROTEINS
AB Introduction: Ranibizumab is a mouse monoclonal antibody fragment antigen-binding (Fab) against human vascular endothelial growth factor-A (VEGF-A), inhibiting angiogenesis. This antibody is commercially produced in Escherichia coli host and used to treat wet age-related macular degeneration (AMD).
   Methods: In this study, the heavy and light chains of ranibizumab were expressed in Pichia pastoris. The expressed chains were incubated overnight at 4 degrees C for interaction. The formation of an active structure was evaluated based on the interaction with substrate VEGF-A using an indirect ELISA, and an electrochemical setup. Furthermore, reconstruction of split enhanced green fluorescent protein (eGFP) reporter, chimerized at the C-terminus of the heavy and light chains, was used to characterize chains' interaction.
   Results: P. pastoris efficiently expressed designed constructs and secreted them into the culture medium. The anti-Fab antibody detected the constructed Fab structure in western blot analysis. Reconstruction of the split reporter confirmed the interaction between heavy and light chains. The designed ELISA and electrochemical setup results verified the binding activity of the recombinant Fab structure against VEGF-A.
   Conclusion: In this work, we indicated that the heavy and light chains of ranibizumab Fab fragments (with or without linkage to split parts of eGFP protein) were produced in P. pastoris. The fluorescence of reconstructed eGFP was detected after incubating the equal ratio of chimeric-heavy and light chains. Immunoassay and electrochemical tests verified the bioactivity of constructed Fab. The data suggested that P. pastoris could be considered a potential efficient eukaryotic host for ranibizumab production.
C1 [Asareh, Shirin Movaghar; Savei, Tahereh; Arjmand, Sareh; Siadat, Seyed Omid Ranaei; Fatemi, Fateneh; Pourmadadi, Mehrab; Shayeh, Javad Shabani] Shahid Beheshti Univ, Prot Res Ctr, Tehran, Iran.
C3 Shahid Beheshti University
RP Arjmand, S; Siadat, SOR (通讯作者)，Shahid Beheshti Univ, Prot Res Ctr, Tehran, Iran.
EM s_arjmand@sbu.ac.ir; o_ranaei@sbu.ac.ir
OI Arjmand, Sareh/0000-0002-4225-5891
CR Al-Zamil WM, 2017, CLIN INTERV AGING, V12, P1313, DOI 10.2147/CIA.S143508
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NR 33
TC 1
Z9 1
U1 0
U2 5
PU TABRIZ UNIV MEDICAL SCIENCES & HEALTH SERVICES
PI TABRIZ
PA DANESHGHAH ST, TABRIZ, REPUBLIC ISLAMIC 51664-14766, IRAN
SN 2228-5652
EI 2228-5660
J9 BIOIMPACTS
JI BioImpacts
PY 2022
VL 12
IS 3
BP 203
EP 210
DI 10.34172/bi.2021.23219
EA OCT 2021
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 1F3AD
UT WOS:000719813300001
PM 35677669
OA Green Published
DA 2022-11-30
ER

PT J
AU Luo, X
   Li, JY
   Chen, MJ
   Yang, X
   Li, XJ
AF Luo, Xiong
   Li, Jianyuan
   Chen, Maojian
   Yang, Xi
   Li, Xiangjun
TI Ophthalmic Disease Detection via Deep Learning With a Novel Mixture Loss
   Function
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Deep learning; Diseases; Retina; Optical imaging; Biomedical optical
   imaging; Bioinformatics; Cataracts; Deep learning; Ophthalmic disease
   detection; Convolutional neural network (CNN); Loss function
ID COVID-19 CLASSIFICATION; FUSION
AB With the popularization of computer-aided diagnosis (CAD) technologies, more and more deep learning methods are developed to facilitate the detection of ophthalmic diseases. In this article, the deep learning-based detections for some common eye diseases, including cataract, glaucoma, and age-related macular degeneration (AMD), are analyzed. Generally speaking, morphological change in retina reveals the presence of eye disease. Then, while using some existing deep learning methods to achieve this analysis task, the satisfactory performance may not be given, since fundus images usually suffer from the impact of data imbalance and outliers. It is, therefore, expected that with the exploration of effective and robust deep learning algorithms, the detection performance could be further improved. Here, we propose a deep learning model combined with a novel mixture loss function to automatically detect eye diseases, through the analysis of retinal fundus color images. Specifically, given the good generalization and robustness of focal loss and correntropy-induced loss functions in addressing complex dataset with class imbalance and outliers, we present a mixture of those two losses in deep neural network model to improve the recognition performance of classifier for biomedical data. The proposed model is evaluated on a real-life ophthalmic dataset. Meanwhile, the performance of deep learning model with our proposed loss function is compared with the baseline models, while adopting accuracy, sensitivity, specificity, Kappa, and area under the receiver operating characteristic curve (AUC) as the evaluation metrics. The experimental results verify the effectiveness and robustness of the proposed algorithm.
C1 [Luo, Xiong; Li, Jianyuan; Chen, Maojian] Univ Sci & Technol Beijing, Sch Comp & Commun Engn, Beijing 100083, Peoples R China.
   [Luo, Xiong; Li, Jianyuan; Chen, Maojian] Beijing Key Lab Knowledge Engn Mat Sci, Beijing 100083, Peoples R China.
   [Luo, Xiong; Li, Jianyuan; Chen, Maojian] Univ Sci & Technol Beijing, Shunde Grad Sch, Foshan 528399, Peoples R China.
   [Yang, Xi] Beijing Intelligent Logist Syst Collaborat Innova, Beijing 101149, Peoples R China.
   [Li, Xiangjun] China Mobile Informat Secur Ctr, Beijing 100053, Peoples R China.
C3 University of Science & Technology Beijing; University of Science &
   Technology Beijing; China Mobile
RP Luo, X (通讯作者)，Univ Sci & Technol Beijing, Sch Comp & Commun Engn, Beijing 100083, Peoples R China.; Luo, X (通讯作者)，Beijing Key Lab Knowledge Engn Mat Sci, Beijing 100083, Peoples R China.
EM xluo@ustb.edu.cn; B20200341@xs.ustb.edu.cn; B20190321@xs.ustb.edu.cn;
   yangxi@bwu.edu.cn; lixiangjun@chinamobile.com
OI Yang, Xi/0000-0003-3568-8071; Luo, Xiong/0000-0002-1929-8447
FU National Natural Science Foundation of China [U1836106, 81961138010];
   Beijing Natural Science Foundation [19L2029, M21032]; Beijing
   Intelligent Logistics System Collaborative Innovation Center
   [BILSCIC-2019KF-08]; Scientific and Technological Innovation Foundation
   of Shunde Graduate School, USTB [BK20BF010]; Fundamental Research Funds
   for the University of Science, and Technology Beijing [FRF-BD-19-012 A]
FX This work was supported in part by the National Natural Science
   Foundation of China under Grants U1836106 and 81961138010, in part by
   the Beijing Natural Science Foundation under Grants 19L2029 and
   M21032,Beijing Intelligent Logistics System Collaborative Innovation
   Center under Grant BILSCIC-2019KF-08, in part by the Scientific and
   Technological Innovation Foundation of Shunde Graduate School, USTB,
   under Grant BK20BF010, and in part by the Fundamental Research Funds for
   the University of Science, and Technology Beijing under Grant
   FRF-BD-19-012 A.
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NR 36
TC 13
Z9 13
U1 8
U2 22
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
EI 2168-2208
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD SEP
PY 2021
VL 25
IS 9
BP 3332
EP 3339
DI 10.1109/JBHI.2021.3083605
PG 8
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Mathematical & Computational Biology;
   Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematical & Computational Biology; Medical
   Informatics
GA UL4AS
UT WOS:000692596400014
PM 34033552
DA 2022-11-30
ER

PT J
AU Moshfeghi, DM
   Thompson, D
   Saroj, N
AF Moshfeghi, Darius M.
   Thompson, Desmond
   Saroj, Namrata
TI Changes in neovascular activity following fixed dosing with an
   anti-vascular endothelial growth factor agent over 52 weeks in the phase
   III VIEW 1 and VIEW 2 studies
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; INTRAVITREAL
   RANIBIZUMAB; INJECTION
AB Background/aims To understand changes in disease activity as assessed by leakage and retinal fluid status in patients with neovascular age-related macular degeneration (nAMD) receiving fixed dosing with an antivascular endothelial growth factor (anti-VEGF) agent.
   Methods In the phase III VIEW 1 (NCT00509795) and VIEW 2 (NCT00637377) studies, eyes with nAMD were treated with intravitreal aflibercept or ranibizumab. Independent, masked reading centres determined the presence/absence of leakage (fluorescein angiography) and retinal fluid (optical coherence tomography) at baseline, week 24 and week 52. In this integrated, post hoc analysis of the VIEW studies, the relationship between leakage/fluid status and best-corrected visual acuity (BCVA) was assessed. The impact of baseline lesion type (predominantly classic (PC), minimally classic (MC), occult) was also evaluated. Data from all treatment groups were pooled.
   Results 2373 eyes were included in this analysis. At baseline, 95.4% of eyes presented with both leakage and fluid. By week 52, leakage and fluid were present in 16.0% of eyes. Mean BCVA gains at week 52 were numerically greater in eyes without leakage and fluid versus eyes with both leakage and fluid (10.3 vs 9.2 letters). At week 52, 11.6%, 15.3% and 20.1% of eyes with PC, MC and occult lesions, respectively, had both leakage and fluid present.
   Conclusion In this post hoc analysis, fixed dosing with an anti-VEGF agent over 52 weeks eliminated disease activity (absence of both leakage and fluid) in most eyes. The effect of anti-VEGF treatment on leakage/fluid status favoured PC versus occult lesions.
C1 [Moshfeghi, Darius M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
   [Thompson, Desmond; Saroj, Namrata] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
C3 Stanford University; Regeneron
RP Moshfeghi, DM (通讯作者)，Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
EM dariusm@stanford.edu
OI Moshfeghi, Darius Mohammad/0000-0003-2254-292X
FU Regeneron Pharmaceuticals, Inc., Tarrytown, New York; Bayer HealthCare,
   Berlin, Germany
FX VIEW 1 and VIEW 2 were funded by Regeneron Pharmaceuticals, Inc.,
   Tarrytown, New York, and Bayer HealthCare, Berlin, Germany. The sponsors
   participated in the design and conduct of these studies, analysis of the
   data and preparation of this manuscript.
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NR 14
TC 4
Z9 4
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 SEP
PY 2020
VL 104
IS 9
BP 1223
EP 1227
DI 10.1136/bjophthalmol-2019-315021
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI3IA
UT WOS:000600986900008
PM 31826853
DA 2022-11-30
ER

PT J
AU Totsuka, K
   Ueta, T
   Uchida, T
   Roggia, MF
   Nakagawa, S
   Vavvas, DG
   Honjo, M
   Aihara, M
AF Totsuka, Kiyohito
   Ueta, Takashi
   Uchida, Takatoshi
   Roggia, Murilo F.
   Nakagawa, Suguru
   Vavvas, Demetrios G.
   Honjo, Megumi
   Aihara, Makoto
TI Oxidative stress induces ferroptotic cell death in retinal pigment
   epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelial cells; Cell death; Oxidative stress;
   Ferroptosis
ID MACULAR DEGENERATION; INDUCED APOPTOSIS; LIPID-PEROXIDATION;
   HYDROGEN-PEROXIDE; IRON UPTAKE; AGE; RPE; INCREASE; DISEASE; FORM
AB The dysfunction and cell death of retinal pigment epithelial (RPE) cells are hallmarks of late-stage dry (atrophic) age-related macular degeneration (AMD), for which no effective therapy has yet been developed. Previous studies have indicated that iron accumulation is a source of excess free radical production in RPE, and age-dependent iron accumulation in RPE is accelerated in patients with dry AMD. Although the pathogenic role of oxidative stress in RPE in the development of dry AMD is widely accepted, the mechanisms of oxidative stressinduced RPE cell death remain elusive. Here, we show that ferroptotic cell death, a mode of regulated necrosis mediated by iron and lipid peroxidation, is implicated in oxidative stress-induced RPE cell death in vitro. In ARPE-19 cells we observed that the ferroptosis inhibitors ferrostatin-1 and deferoxamine (DFO) rescued tertbutyl hydroperoxide (tBH)-induced RPE cell death more effectively than inhibitors of apoptosis or necroptosis. tBH-induced RPE cell death was accompanied by the three characteristics of ferroptotic cell death: lipid peroxidation, glutathione depletion, and ferrous iron accumulation, which were all significantly attenuated by ferrostatin-1 and DFO. Exogenous iron overload enhanced tBH-induced RPE cell death, but this effect was also attenuated by ferrostatin-1 and DFO. Furthermore, mRNA levels of numerous genes known to regulate iron metabolism were observed to be influenced by oxidative stress. Taken together, our observations suggest that multiple modes of cell death are involved in oxidative stress-induced RPE cell death, with ferroptosis playing a particularly important role.
C1 [Totsuka, Kiyohito; Ueta, Takashi; Uchida, Takatoshi; Roggia, Murilo F.; Nakagawa, Suguru; Honjo, Megumi; Aihara, Makoto] Univ Tokyo, Dept Ophthalmol, Grad Sch Med, Tokyo 1138655, Japan.
   [Totsuka, Kiyohito; Ueta, Takashi; Uchida, Takatoshi; Roggia, Murilo F.; Nakagawa, Suguru; Honjo, Megumi; Aihara, Makoto] Univ Tokyo, Fac Med, Tokyo 1138655, Japan.
   [Ueta, Takashi] Natl Ctr Global Hlth & Med, Ctr Hosp, Dept Ophthalmol, Shinjyuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan.
   [Uchida, Takatoshi] Senju Pharmaceut Co Ltd, Senju Lab, Kobe, Hyogo, Japan.
   [Vavvas, Demetrios G.] Harvard Med Sch, Angiogenesis Lab, Dept Ophthalmol, Massachusetts Eye & Ear, Boston, MA 02114 USA.
C3 University of Tokyo; University of Tokyo; National Center for Global
   Health & Medicine - Japan; Senju Pharmaceutical Co. Ltd.; Harvard
   University; Harvard Medical School; Massachusetts Eye & Ear Infirmary
RP Aihara, M (通讯作者)，Univ Tokyo, Dept Ophthalmol, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.; Aihara, M (通讯作者)，Univ Tokyo, Fac Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM kiyototsuka916@gmail.com; ueta-tky@umin.ac.jp; t-uchida@senju.co.jp;
   mfroggia@gmail.com; Demetrios_Vavvas@meei.harvard.edu;
   DemetriosVavvas@meei.harvard.edu; m_honjo@kuhp.kyoto-u.ac.jp;
   aihara-tky@umin.net
OI Kiyohito, Totsuka/0000-0003-1677-6746; Vavvas,
   Demetrios/0000-0002-8622-6478
FU Japan Society of Promotion of Science [26861437]; Nakayama Foundation
   for Human Science [H26]; Mitsui Sumitomo Insurance Welfare Foundation
   [H26]
FX This work was supported by Japan Society of Promotion of Science
   (26861437), Nakayama Foundation for Human Science (H26), and Mitsui
   Sumitomo Insurance Welfare Foundation (H26).
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NR 59
TC 66
Z9 66
U1 5
U2 40
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 2019
VL 181
BP 316
EP 324
DI 10.1016/j.exer.2018.08.019
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HT5TJ
UT WOS:000464625900039
PM 30171859
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lains, I
   Gantner, M
   Murinello, S
   Lasky-Su, JA
   Miller, JW
   Friedlander, M
   Husain, D
AF Lains, Ines
   Gantner, Mari
   Murinello, Salome
   Lasky-Su, Jessica A.
   Miller, Joan W.
   Friedlander, Martin
   Husain, Deeba
TI Metabolomics in the study of retinal health and disease
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Metabolomics; Retina; Vitreous; Biomarkers; Mass spectrometry; Nuclear
   magnetic resonance spectroscopy
ID CHROMATOGRAPHY-MASS SPECTROMETRY; MACULAR DEGENERATION;
   LIQUID-CHROMATOGRAPHY; PROLIFERATIVE VITREORETINOPATHY;
   DIABETIC-RETINOPATHY; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; BIOMARKER
   DISCOVERY; GAS-CHROMATOGRAPHY; LIPID MEDIATORS
AB Metabolomics is the qualitative and quantitative assessment of the metabolites (small molecules < 1.5 kDa) in body fluids. The metabolites are the downstream of the genetic transcription and translation processes and also downstream of the interactions with environmental exposures; thus, they are thought to closely relate to the phenotype, especially for multifactorial diseases. In the last decade, metabolomics has been increasingly used to identify biomarkers in disease, and it is currently recognized as a very powerful tool with great potential for clinical translation. The metabolome and the associated pathways also help improve our understanding of the pathophysiology and mechanisms of disease.
   While there has been increasing interest and research in metabolomics of the eye, the application of metabolomics to retinal diseases has been limited, even though these are leading causes of blindness. In this manuscript, we perform a comprehensive summary of the tools and knowledge required to perform a metabolomics study, and we highlight essential statistical methods for rigorous study design and data analysis. We review available protocols, summarize the best approaches, and address the current unmet need for information on collection and processing of tissues and biofluids that can be used for metabolomics of retinal diseases. Additionally, we critically analyze recent work in this field, both in animal models and in human clinical disease, including diabetic retinopathy and age-related macular degeneration. Finally, we identify opportunities for future research applying metabolomics to improve our current assessment and understanding of mechanisms of vitreoretinal diseases, and to hence improve patient assessment and care.
C1 [Lains, Ines; Miller, Joan W.; Husain, Deeba] Harvard Med Sch, Massachusetts Eye & Ear, Retina Serv, 243 Charles St, Boston, MA 02114 USA.
   [Lains, Ines] Univ Coimbra, Fac Med, P-3000 Coimbra, Portugal.
   [Gantner, Mari; Murinello, Salome; Friedlander, Martin] Lowy Med Res Inst, La Jolla, CA 92037 USA.
   [Gantner, Mari; Murinello, Salome; Friedlander, Martin] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Lasky-Su, Jessica A.] Brigham & Womens Hosp, Syst Genet & Genom Unit, Charming Div Network Med, 75 Francis St, Boston, MA 02115 USA.
   [Lasky-Su, Jessica A.] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Universidade de Coimbra; Scripps Research Institute; Harvard
   University; Brigham & Women's Hospital; Harvard University; Harvard
   Medical School
RP Husain, D (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear, Retina Serv, 243 Charles St, Boston, MA 02114 USA.
EM ines_lains@meei.harvard.edu; mgantner@gmail.com; mgantner@gmail.com;
   jessica.a.su@gmail.com; joan_miller@meei.harvard.edu;
   friedlan@scripps.edu; Deeba_Husain@meei.harvard.edu
OI Husain, Deeba/0000-0002-8494-0950; Murinello, Salome/0000-0002-9694-2160
FU Miller Retina Research Fund (Mass. Eye and Ear); Champalimaud Vision
   Award; Research to Prevent Blindness, Inc. New York; Commonwealth
   Unrestricted Grant for Eye Research Grant; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R01HL123915] Funding Source: NIH RePORTER
FX This work was possible due to the financial support of the Miller Retina
   Research Fund (Mass. Eye and Ear), the Champalimaud Vision Award (JWM),
   the unrestricted departmental Grant from Research to Prevent Blindness,
   Inc. New York, and the Commonwealth Unrestricted Grant for Eye Research
   Grant (DH). None of the aforementioned funding organizations had any
   role in the design or conduct of this work.
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NR 202
TC 56
Z9 60
U1 4
U2 34
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 57
EP 79
DI 10.1016/j.preteyeres.2018.11.002
PG 23
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HW1OL
UT WOS:000466452100003
PM 30423446
DA 2022-11-30
ER

PT J
AU Zhang, Y
   Bazzazi, H
   Silva, RLE
   Pandey, NB
   Green, JJ
   Campochiaro, PA
   Popel, AS
AF Zhang, Yu
   Bazzazi, Hojjat
   e Silva, Raquel Lima
   Pandey, Niranjan B.
   Green, Jordan J.
   Campochiaro, Peter A.
   Popel, Aleksander S.
TI Three-Dimensional Transport Model for Intravitreal and Suprachoroidal
   Drug Injection
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE ocular drug delivery; antiangiogenic; pharmacokinetics; computational
   model; systems pharmacology model
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; TRIAMCINOLONE
   ACETONIDE; MICRONEEDLE INJECTION; POSTERIOR SEGMENT; MOLECULAR-WEIGHT;
   EYE; DELIVERY; SPACE; AGE
AB PURPOSE. Quantitative understanding of the transport of therapeutic macromolecules following intraocular injections is critical for the design of efficient strategies in treating eye diseases, such as neovascular (wet) age-related macular degeneration (AMD) and macular edema (ME). Antiangiogenic treatments, such as neutralizing antibodies against VEGF or recently characterized antiangiogenic peptides, have shown promise in slowing disease progression.
   METHODS. We developed a comprehensive three-dimensional (3D) transport model for intraocular injections using published data on drug distribution in rabbit eyes following intravitreal and suprachoroidal (SC) injection of sodium fluorescein (SF), bevacizumab, and ranibizumab. The model then was applied to evaluate the distribution of small molecules and antiangiogenic proteins following intravitreal and SC injections in human eyes.
   RESULTS. The model predicts that intravitreally administered molecules are substantially mixed within the vitreous following injection, and that the long-term behavior of the injected drug does not depend on the initial mixing. Ocular pharmacokinetics of different drugs is sensitive to different clearance mechanisms. Effective retinal drug delivery is impacted by RPE permeability. For VEGF antibody, intravitreal injection provides sustained delivery to the retina, whereas SC injection provides more efficient, but short-lived, retinal delivery for smaller-sized molecules. Long-term suppression of neovascularization through SC administration of antiangiogenic drugs necessitates frequent injection or sustained delivery, such as microparticle-based delivery of antiangiogenic peptides.
   CONCLUSIONS. A comprehensive 3D model for intravitreal and SC drug injection is developed to provide a framework and platform for testing drug delivery routes and sustained delivery devices for new and existing drugs.
C1 [Zhang, Yu; Bazzazi, Hojjat; Pandey, Niranjan B.; Green, Jordan J.; Popel, Aleksander S.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [e Silva, Raquel Lima; Green, Jordan J.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   Medicine
RP Zhang, Y (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
EM zhangyu@jhmi.edu
RI Zhang, Yu/U-2687-2019; Green, Jordan/B-9001-2009; Popel, Aleksander
   S/A-6724-2009; Zhang, Yu/AFV-5724-2022
OI Zhang, Yu/0000-0003-3643-6589; Green, Jordan/0000-0003-4176-3808; Zhang,
   Yu/0000-0003-3643-6589
FU National Institutes of Health (NIH; Bethesda, MD, USA) [1R21EY026148,
   1R21EY022986]; Edward N. and Della L. Thome Memorial Foundation;
   NATIONAL EYE INSTITUTE [R21EY026148] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health (NIH; Bethesda, MD, USA)
   Grants 1R21EY026148 and 1R21EY022986, and the Edward N. and Della L.
   Thome Memorial Foundation.
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NR 39
TC 17
Z9 17
U1 2
U2 12
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 2018
VL 59
IS 12
BP 5266
EP 5276
DI 10.1167/iovs.17-23632
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GZ4YH
UT WOS:000449417000026
PM 30383198
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Chichagova, V
   Hallam, D
   Collin, J
   Zerti, D
   Dorgau, B
   Felemban, M
   Lako, M
   Steel, DH
AF Chichagova, Valeria
   Hallam, Dean
   Collin, Joseph
   Zerti, Darin
   Dorgau, Birthe
   Felemban, Majed
   Lako, Majlinda
   Steel, David H.
TI Cellular regeneration strategies for macular degeneration: past, present
   and future
SO EYE
LA English
DT Review
ID RETINAL-PIGMENT EPITHELIUM; PLURIPOTENT STEM-CELLS; HUMAN BRUCHS
   MEMBRANE; TRANSPLANTED PHOTORECEPTOR PRECURSORS; VESICLE-LIKE
   STRUCTURES; VISUAL FUNCTION; RETINITIS-PIGMENTOSA; PROGENITOR CELLS;
   NEURAL RETINA; MULLER GLIA
AB Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.
C1 [Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H.] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England.
   [Steel, David H.] Sunderland Eye Infirm, Queen Alexandra Rd, Sunderland, England.
C3 Newcastle University - UK
RP Steel, DH (通讯作者)，Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England.; Steel, DH (通讯作者)，Sunderland Eye Infirm, Queen Alexandra Rd, Sunderland, England.
EM David.steel@ncl.ac.uk
RI Zerti, Darin/AAF-7078-2021; Steel, David/I-8053-2015
OI Zerti, Darin/0000-0003-0865-8088; Chichagova,
   Valeria/0000-0002-7289-3640; lako, majlinda/0000-0003-1327-8573; Steel,
   David/0000-0001-8734-3089; Hallam, Dean/0000-0001-9165-3020; Felemban,
   Majed/0000-0001-8397-3630; Dorgau, Birthe/0000-0003-4031-4402
FU European Research Council [CoG_614620]; Dr. William Edmund Harker
   Foundation; Newcastle University; Macular Society; Fight for Sight
   [1456/1457]; RP Fighting Blindness [GR584]; Newcastle University
   Confidence in Concept scheme [MC_PC_15030]; NC3R [NC/CO16206/1];
   Sunderland Eye Infirmary; MRC [MC_PC_16054] Funding Source: UKRI
FX This work was supported by the European Research Council (CoG_614620),
   the Dr. William Edmund Harker Foundation, Newcastle University, Macular
   Society, Fight for Sight (1456/1457), RP Fighting Blindness (GR584),
   Newcastle University Confidence in Concept scheme (MC_PC_15030), NC3R
   (NC/CO16206/1) and Sunderland Eye Infirmary.
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NR 214
TC 55
Z9 57
U1 0
U2 16
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 946
EP 971
DI 10.1038/s41433-018-0061-z
PG 26
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GF3FR
UT WOS:000431831500013
PM 29503449
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Llonch, S
   Carido, M
   Ader, M
AF Llonch, Silvia
   Carido, Madalena
   Ader, Marius
TI Organoid technology for retinal repair
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Pluripotent stem cells; Retinal organoid; Retinal degeneration;
   Photoreceptor; Transplantation
ID PLURIPOTENT STEM-CELLS; VESICLE-LIKE STRUCTURES; OPTIC-CUP
   MORPHOGENESIS; HUMAN IPS CELLS; XENO-FREE; RETINITIS-PIGMENTOSA;
   GANGLION-CELLS; PHOTORECEPTOR PRECURSORS; NEURAL RETINA; CONE
   PHOTORECEPTORS
AB A major cause for vision impairment and blindness in industrialized countries is the loss of the light-sensing retinal tissue in the eye. Photoreceptor damage is one of the main characteristics found in retinal degeneration diseases, such as Retinitis Pigmentosa or age-related macular degeneration. The lack of effective therapies to stop photoreceptor loss together with the absence of significant intrinsic regeneration in the human retina converts such degenerative diseases into permanent conditions that are currently irreversible. Cell replacement by means of photoreceptor transplantation has been proposed as a potential approach to tackle cell loss in the retina. Since the first attempt of photoreceptor transplantation in humans, about twenty years ago, several research groups have focused in the development and improvement of technologies necessary to bring cell transplantation for retinal degeneration diseases to reality. Progress in recent years in the generation of human tissue derived from pluripotent stem cells (PSCs) has significantly improved our tools to study human development and disease in the dish. Particularly the availability of 3D culture systems for the generation of PSC-derived organoids, including the human retina, has dramatically increased access to human material for basic and medical research. In this review, we focus on important milestones towards the generation of transplantable photoreceptor precursors from PSC-derived retinal organoids and discuss recent pre-clinical transplantation studies using organoid-derived photoreceptors in context to related in vivo work using primary photoreceptors as donor material. Additionally, we summarize remaining challenges for developing photoreceptor transplantation towards clinical application.
C1 [Llonch, Silvia; Carido, Madalena; Ader, Marius] Tech Univ Dresden, CMCB, CRTD, Fetscherstr 105, D-01307 Dresden, Germany.
   [Carido, Madalena] German Ctr Neurodegenerat Dis Dresden DZNE, Arnoldstr 18, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden
RP Ader, M (通讯作者)，Tech Univ Dresden, CMCB, CRTD, 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; Carido, Madalena/0000-0001-8969-0877
FU Deutsche Forschungsgemeinschaft (DFG) [FZT 111]; Center for Regenerative
   Therapies Dresden [FZT 111]; Bundesministerium fur Bildung and Forschung
   (BMBF) [01EK1613A]; CRTD White Paper Initiative [FZT 111]; 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, FZT 111 Cluster of
   Excellence (M.A.), Bundesministerium fur Bildung and Forschung (BMBF)
   Research Grant 01EK1613A (M.A.), CRTD White Paper Initiative FZT 111
   (MA.), and the ProRetina Stiftung, Pro-Re/Prom-stip/Ader-Llonch.1-2016
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NR 125
TC 88
Z9 93
U1 8
U2 43
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD JAN 15
PY 2018
VL 433
IS 2
SI SI
BP 132
EP 143
DI 10.1016/j.ydbio.2017.09.028
PG 12
WC Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Developmental Biology
GA FT2XQ
UT WOS:000423009700005
PM 29291970
OA hybrid
DA 2022-11-30
ER

PT J
AU Wong, SS
   Vuong, VS
   Cunefare, D
   Farsiu, S
   Moshiri, A
   Yiu, G
AF Wong, Sophia S.
   Vuong, Vivian S.
   Cunefare, David
   Farsiu, Sina
   Moshiri, Ala
   Yiu, Glenn
TI Macular Fluid Reduces Reproducibility of Choroidal Thickness
   Measurements on Enhanced Depth Optical Coherence Tomography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL VEIN OCCLUSION; CENTRAL SEROUS CHORIORETINOPATHY; GROWTH-FACTOR
   THERAPY; DIABETIC-RETINOPATHY; PANRETINAL PHOTOCOAGULATION; NORMAL EYES;
   REPEATABILITY; DEGENERATION; EDEMA
AB PURPOSE: To determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT).
   DESIGN: Retrospective reliability analysis.
   METHODS: EDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR).
   RESULTS: Of 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1 mu m) and 0.96 (63.9 mu m) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend.
   CONCLUSIONS: The presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1 mu m in subfoveal CT or 63.9 pm in average CT may be necessary to detect true clinical change in eyes with macular fluid. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Wong, Sophia S.; Vuong, Vivian S.; Moshiri, Ala; Yiu, Glenn] Univ Calif Davis, Dept Ophthalmol, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
   [Cunefare, David; Farsiu, Sina] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
   [Farsiu, Sina] Duke Univ, Dept Ophthalmol, Durham, NC USA.
C3 University of California System; University of California Davis; Duke
   University; Duke University
RP Yiu, G (通讯作者)，Univ Calif Davis, Dept Ophthalmol, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
EM gyiu@ucdavis.edu
RI Yiu, Glenn/AAF-2858-2020
OI Farsiu, Sina/0000-0003-4872-2902; Yiu, Glenn/0000-0003-3061-3310
FU NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; NIH (Bethesda,
   Maryland) [UL1TR000002, TL1TR000133, P30 EY005722, K08 EY027463, K08
   EY026101]; Research to Prevent Blindness (New York, New York);
   International Retina Research Foundation (Birmingham, Alabama); E.
   Matilda Ziegler Foundation for the Blind (Darien, Connecticut); Barr
   Foundation for Retinal Research (Boston, Massachusetts); Alcon Research
   Institute (Fort Worth, Texas); ARVO Foundation (Rockville, Maryland)
FX VIVIAN S. VUONG IS SUPPORTED BY THE NATIONAL CENTER FOR ADVANCING
   TRANSLATIONAL SCIENCES, and NIH (grant UL1TR000002 and linked award
   TL1TR000133; Bethesda, Maryland). Sina Farsiu is supported by NIH (grant
   P30 EY005722; Bethesda, Maryland). Ala Moshiri is supported by Research
   to Prevent Blindness (New York, New York), the International Retina
   Research Foundation (Birmingham, Alabama), and NIH (grant K08 EY027463;
   Bethesda, Maryland). Glenn Yiu is supported by the E. Matilda Ziegler
   Foundation for the Blind (Darien, Connecticut), Barr Foundation for
   Retinal Research (Boston, Massachusetts), Alcon Research Institute (Fort
   Worth, Texas), ARVO Foundation (Rockville, Maryland), and NIH (grant K08
   EY026101; Bethesda, Maryland). No funding organizations had any role in
   the design or conduct of this research. The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the funding agencies. criteria for authorship.
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NR 41
TC 13
Z9 13
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 DEC
PY 2017
VL 184
BP 108
EP 114
DI 10.1016/j.ajo.2017.10.005
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FP6ZP
UT WOS:000417776400012
PM 29038011
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nowacka, B
   Lubinski, W
   Honczarenko, K
   Potemkowski, A
   Safranow, K
AF Nowacka, Barbara
   Lubinski, Wojciech
   Honczarenko, Krystyna
   Potemkowski, Andrzej
   Safranow, Krzysztof
TI Ophthalmological Features of Parkinson Disease
SO MEDICAL SCIENCE MONITOR
LA English
DT Article
DE Cataract; Dry Eye Syndromes; Glaucoma; Macular Degeneration; Parkinson
   Disease; Vision Disorders
ID VISUAL HALLUCINATIONS; CONTRAST SENSITIVITY; SYMPTOMS; DISCRIMINATION;
   DOPAMINE; DEATH; RISK
AB Background: The aim of this study was to determine the type and frequency of ophthalmologic changes occurring in patients with Parkinson disease (PD).
   Material/Methods: One hundred consecutive patients (196 eyes) with idiopathic PD and a control group consisting of 100 healthy patients (196 eyes) matched for age and sex underwent a complete ophthalmological examination of both eyes, including assessment of patient medical history, dry eye questionare, and visual hallucinations questionnaire, distance and near best corrected visual acuity (DBCVA, NBCVA), color vision, distance photopic contrast sensitivity, near point of convergence, slit lamp examination of the eye anterior segment, tear film osmolarity and breakup time, aqueous tear production, and intraocular pressure, as well as fundus examination and evaluation of the perimacular retinal thickness (RT) and peripapillary retinal nerve fiber layer (RNFL) thickness.
   Results: In the eyes of PD patients DBCVA, NBCVA, contrast sensitivity, and color discrimination were significantly reduced. We also detected increased frequency of convergence insufficiency, seborrhoic blepharitis, meibomian gland disease (MGD), dry eye syndrome, nuclear and posterior subcapsular cataract, and glaucoma (p<0.05). However, intraocular pressure (IOP) was significantly lower in the PD group compared to controls. The frequency of visual hallucinations, age-related macular degeneration (ARMD), and other ophthalmological diseases, as well as RT and RNFL thickness, did not significantly differ between investigated groups.
   Conclusions: Clinicians need to be aware of the association between PD and ophthalmological changes. Restoration of good-quality vision has a great impact on PD patients' quality of life, reduction of costs of treatment and care, and rehabilitation.
C1 [Nowacka, Barbara; Lubinski, Wojciech] Pomeranian Med Univ, Dept Ophthalmol, Szczecin, Poland.
   [Honczarenko, Krystyna] Pomeranian Med Univ, Dept Neurol, Szczecin, Poland.
   [Potemkowski, Andrzej] Univ Szczecin, Dept Clin Psychol, PL-70453 Szczecin, Poland.
   [Safranow, Krzysztof] Pomeranian Med Univ, Dept Biochem & Med Chem, Szczecin, Poland.
C3 Pomeranian Medical University; Pomeranian Medical University; University
   of Szczecin; Pomeranian Medical University
RP Nowacka, B (通讯作者)，Pomeranian Med Univ, Dept Ophthalmol, Szczecin, Poland.
EM barbara_nowacka@vp.pl
RI Safranow, Krzysztof/B-5127-2015; Lubiński, Wojciech/S-8520-2016
OI Safranow, Krzysztof/0000-0001-9415-2758; Lubinski,
   Wojciech/0000-0002-3729-9750
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NR 42
TC 65
Z9 76
U1 0
U2 12
PU INT SCIENTIFIC INFORMATION, INC
PI MELVILLE
PA 150 BROADHOLLOW RD, STE 114, MELVILLE, NY 11747 USA
SN 1643-3750
J9 MED SCI MONITOR
JI Med. Sci. Monitor
PD NOV 11
PY 2014
VL 20
BP 2243
EP 2249
DI 10.12659/MSM.890861
PG 7
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA CC0RK
UT WOS:000350043300002
PM 25387009
OA Green Published
DA 2022-11-30
ER

PT J
AU Sekiyama, E
   Saint-Geniez, M
   Yoneda, K
   Hisatomi, T
   Nakao, S
   Walshe, TE
   Maruyama, K
   Hafezi-Moghadam, A
   Miller, JW
   Kinoshita, S
   D'Amore, PA
AF Sekiyama, Eiichi
   Saint-Geniez, Magali
   Yoneda, Kazuhito
   Hisatomi, Toshio
   Nakao, Shintaro
   Walshe, Tony E.
   Maruyama, Kazuichi
   Hafezi-Moghadam, Ali
   Miller, Joan W.
   Kinoshita, Shigeru
   D'Amore, Patricia A.
TI Heat treatment of retinal pigment epithelium induces production of
   elastic lamina components and antiangiogenic activity
SO FASEB JOURNAL
LA English
DT Article
DE choroidal neovascularization; transpupillary thermotherapy; endostatin;
   thrombospondin-1; elastin
ID CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   IN-VIVO; EXPRESSION; ANGIOGENESIS; ENDOSTATIN; CELLS; EYES;
   CHORIOCAPILLARIS
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth.-Sekiyama, E., Saint-Geniez, M., Yoneda, K., Hisatomi, T., Nakao, S., Walshe, T. E., Maruyama, K., Hafezi-Moghadam, A., Miller, J. W., Kinoshita, S., D'Amore, P. A. Heat treatment of retinal pigment epithelium induces production of elastic lamina components and anti-angiogenic activity. FASEB J. 26, 567-575 (2012). www.fasebj.org
C1 [Sekiyama, Eiichi; Saint-Geniez, Magali; Walshe, Tony E.; Maruyama, Kazuichi; D'Amore, Patricia A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Sekiyama, Eiichi; Saint-Geniez, Magali; Walshe, Tony E.; D'Amore, Patricia A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   [D'Amore, Patricia A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Pathol, Boston, MA 02114 USA.
   [Hisatomi, Toshio; Nakao, Shintaro; Hafezi-Moghadam, Ali; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA 02114 USA.
   [Yoneda, Kazuhito; Maruyama, Kazuichi; Kinoshita, Shigeru] Kyoto Prefectural Univ Med, Dept Ophthalmol, Grad Sch Med, Kyoto, Japan.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Schepens Eye Research Institute; Harvard University; Harvard
   Medical School; Massachusetts Eye & Ear Infirmary; Harvard University;
   Harvard Medical School; Massachusetts Eye & Ear Infirmary; Harvard
   University; Harvard Medical School; Massachusetts Eye & Ear Infirmary;
   Kyoto Prefectural University of Medicine
RP D'Amore, PA (通讯作者)，Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM patricia.damore@schepens.harvard.edu
RI Walshe, Tony/AAJ-8833-2020; D'Amore, Patricia A/G-5660-2017; Maruyama,
   Kazuichi/GRX-8129-2022; SAINT-GENIEZ, MAGALI/P-3509-2019
OI D'Amore, Patricia A/0000-0001-9652-8974; Maruyama,
   Kazuichi/0000-0001-6283-5466; SAINT-GENIEZ, MAGALI/0000-0001-9897-138X;
   Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi,
   Toshio/0000-0003-2552-9595; Miller, Joan/0000-0003-2046-3996
FU NATIONAL EYE INSTITUTE [R01EY015435] Funding Source: NIH RePORTER;
   Grants-in-Aid for Scientific Research [22791679] Funding Source: KAKEN;
   NEI NIH HHS [R01 EY015435] Funding Source: Medline
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NR 26
TC 10
Z9 10
U1 0
U2 1
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 2012
VL 26
IS 2
BP 567
EP 575
DI 10.1096/fj.11-184127
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 895HA
UT WOS:000300485700010
PM 22067481
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Giani, A
   Esmaili, DD
   Luiselli, C
   Cigada, M
   Salvetti, P
   Miller, JW
   Staurenghi, G
AF Giani, Andrea
   Esmaili, Daniel D.
   Luiselli, Cristiano
   Cigada, Mario
   Salvetti, Paola
   Miller, Joan W.
   Staurenghi, Giovanni
TI DISPLAYED REFLECTIVITY OF CHOROIDAL NEOVASCULAR MEMBRANES BY OPTICAL
   COHERENCE TOMOGRAPHY CORRELATES WITH PRESENCE OF LEAKAGE BY FLUORESCEIN
   ANGIOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   fluorescein angiography; optical coherence tomography; optical
   reflectivity
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY;
   BRUCHS MEMBRANE; VERTEPORFIN; RISK; TAP; EYE
AB Purpose: To evaluate and correlate the displayed optical reflectivity of choroidal neovascularization (CNV) subretinal material on spectral-domain optical coherence tomography with the presence of dye leakage on fluorescein angiography (FA).
   Methods: Thirty-nine eyes of 39 patients with a diagnosis of predominantly classic CNV from age-related macular degeneration underwent simultaneous spectral-domain optical coherence tomography and FA imaging. Eight patients had a newly diagnosed untreated CNV. Thirty-one patients had already been treated with anti-vascular endothelial growth factor agents. In 18 of these eyes, CNV lesions showed persistent leakage on FA. In 13 eyes, CNV lesions did not show leakage by FA. Subretinal CNV material boundaries visualized on spectral-domain optical coherence tomography B-scans were manually traced, and optical reflectivity was calculated using the mean grayscale value. To account for variable image brightness, the retinal pigment epithelial reflectivity was measured. The absolute difference between CNV material and retinal pigment epithelial reflectivity (Delta REF) from the three groups (newly diagnosed CNV, previously treated CNV showing FA leakage, and previously treated CNV not showing FA leakage) was compared.
   Results: In untreated lesions, Delta REF was significantly higher compared with previously treated, but still leaky CNV (P < 0.0001). Lesions showing FA leakage had significantly higher Delta REF compared with those that did not display leakage (P < 0.0001).
   Conclusion: The displayed reflectivity of subretinal CNV material in spectral-domain optical coherence tomography appears to be an important parameter that can provide information regarding the FA leakage status. RETINA 31:942-948, 2011
C1 [Giani, Andrea; Esmaili, Daniel D.; Miller, Joan W.] Harvard Univ, Retina Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
   [Giani, Andrea; Luiselli, Cristiano; Cigada, Mario; Salvetti, Paola; Staurenghi, Giovanni] Univ Milan, Eye Clin, Dept Clin Sci Luigi Sacco, Sacco Hosp, Milan, Italy.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; University of Milan; Luigi Sacco Hospital
RP Giani, A (通讯作者)，Harvard Univ, Retina Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM andrea_giani@meei.harvard.edu
RI ; Staurenghi, Giovanni/K-4388-2017; Giani, Andrea/L-5926-2017
OI Salvetti, Anna Paola/0000-0002-5513-2241; Miller,
   Joan/0000-0003-2046-3996; Staurenghi, Giovanni/0000-0002-2299-5251;
   Giani, Andrea/0000-0003-0682-1945
FU Heidelberg Engineering, Heidelberg, Germany; Zeiss Meditec, Dublin, CA
FX A. Giani received travel fees for attending a meeting from Heidelberg
   Engineering, Heidelberg, Germany. C. Luiselli received travel fees for
   attending a meeting from Heidelberg Engineering, Heidelberg, Germany,
   and Zeiss Meditec, Dublin, CA. G. Staurenghi received fees for advisory
   board from Heidelberg Engineering, Heidelberg, Germany, and received
   fees for attending a meeting from Zeiss Meditec, Dublin, CA.
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NR 23
TC 20
Z9 24
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2011
VL 31
IS 5
BP 942
EP 948
DI 10.1097/IAE.0b013e31820a68cc
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 755LV
UT WOS:000289933600018
PM 21358457
DA 2022-11-30
ER

PT J
AU Marra, MT
   Khamphavong, P
   Wisniecki, P
   Gukasyan, HJ
   Sueda, K
AF Marra, Michelle T.
   Khamphavong, Penney
   Wisniecki, Peter
   Gukasyan, Hovhannes J.
   Sueda, Katsuhiko
TI Solution Formulation Development of a VEGF Inhibitor for Intravitreal
   Injection
SO AAPS PHARMSCITECH
LA English
DT Article
DE AMD; depot; ophthalmic; parenteral; sustained delivery
ID PHARMACOKINETICS; CHALLENGES; ANTIBODY; THERAPY
AB PF-00337210 is a potent, selective small molecule inhibitor of VEGFRs and has been under consideration for the treatment of age-related macular degeneration. An ophthalmic solution formulation intended for intravitreal injection was developed. This formulation was designed to maximize drug properties such that the formulation would precipitate upon injection into the vitreous for sustained delivery. As a parenteral formulation with additional constraints dictated by this specialized delivery route, multiple features were balanced in order to develop a successful formulation. Some of these considerations included low dosing volumes (a parts per thousand currency sign0.1 mL), a limited repertoire of safe excipients for intravitreal injection, and the unique physical chemical properties of the drug. The aqueous solubility as a function of pH was characterized, buffer stressing studies to select the minimal amount of buffer were conducted, and both chemical and physical stability studies were executed. The selected formulation consisted of an isotonic solution comprised of PF-00337210 free base in a citrate-buffered vehicle containing NaCl for tonicity. The highest strength for regulatory toxicology studies was 60 mg/mL. The selected formulation exhibited sufficient chemical stability upon storage with no precipitation, and acceptable potency and recovery through an intravitreal dosing syringe. Formulation performance was simulated by precipitation experiments using extracted vitreous humor. In simulated injection experiments, PF-00337210 solutions reproducibly precipitated upon introduction to the vitreous so that a depot was formed. To our knowledge, this is the first time that a nonpolymeric in situ-forming depot formulation has been developed for intravitreal delivery, with the active ingredient as the precipitating agent.
C1 [Marra, Michelle T.; Khamphavong, Penney; Gukasyan, Hovhannes J.] Pfizer Inc, Res Enabling Grp, San Diego, CA 92121 USA.
   [Wisniecki, Peter] Pfizer Inc, Parenteral Ctr Emphasis, Groton, CT 06340 USA.
   [Sueda, Katsuhiko] GlaxoSmithKline, Pharmaceut Dev, Res Triangle Pk, NC USA.
C3 Pfizer; Pfizer; GlaxoSmithKline
RP Marra, MT (通讯作者)，Pfizer Inc, Res Enabling Grp, 10777 Sci Ctr Dr, San Diego, CA 92121 USA.
EM michelle.marra@pfizer.com
RI Gukasyan, Hovhannes/AAX-8570-2020
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NR 37
TC 4
Z9 9
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-9932
J9 AAPS PHARMSCITECH
JI AAPS PharmSciTech
PD MAR
PY 2011
VL 12
IS 1
BP 362
EP 371
DI 10.1208/s12249-011-9591-4
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 742ON
UT WOS:000288954100040
PM 21312012
OA Green Published
DA 2022-11-30
ER

PT J
AU Asher, A
   Segal, WA
   Baccus, SA
   Yaroslavsky, LP
   Palanker, DV
AF Asher, Alon
   Segal, William A.
   Baccus, Stephen A.
   Yaroslavsky, Leonid P.
   Palanker, Daniel V.
TI Image processing for a high-resolution optoelectronic retinal prosthesis
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE biomedical image processing; macular degeneration; retinal prosthesis;
   retinitis pigmentosa
ID CAT VISUAL-CORTEX; BIPOLAR CELLS; ELECTRICAL-STIMULATION;
   GANGLION-CELLS; PRIMATE RETINA; MORPHOMETRIC ANALYSIS; MACULAR
   DEGENERATION; CONTRAST ADAPTATION; NEURONS; RECORDINGS
AB In an effort to restore visual perception in retinal diseases such as age-related macular degeneration or retinitis pigmentosa, a design was recently presented for a high-resolution optoelectronic retinal prosthesis having thousands of electrodes. This system requires real-time image processing fast enough to convert a video stream of images into electrical stimulus patterns that can be properly interpreted by the brain. Here, we present image-processing and tracking algorithms for a subretinal implant designed to stimulate the second neuron in the visual pathway, bypassing the degenerated first synaptic layer. For this task, we have developed and implemented: 1) A tracking algorithm that determines the implant's position in each frame. 2) Image cropping outside of the implant boundaries. 3) A geometrical transformation that distorts the image appropriate to the geometry of the fovea. 4) Spatio-temporal image filtering to reproduce the visual processing normally occurring in photoceptors and at the photoreceptor-bipolar cell synapse. 5) Conversion of the filtered visual information into a pattern of electrical current. Methods to accelerate real-time transformations include the exploitation of data redundancy in the time domain, and the use of precomputed lookup tables that are adjustable to retinal physiology and allow flexible control of stimulation parameters. A software implementation of these algorithms processes natural visual scenes with sufficient speed for real-time operation. This computationally efficient algorithm resembles, in some aspects, biological strategies of efficient coding in the retina and could provide a refresh rate higher than fifty frames per second on our system.
C1 Tel Aviv Univ, Fac Engn, Dept Interdisciplinary Studies, IL-69978 Ramat Aviv, Israel.
   Stanford Univ, Program Neurosci, Stanford, CA 94305 USA.
   Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
C3 Tel Aviv University; Stanford University; Stanford University; Stanford
   University; Stanford University
RP Asher, A (通讯作者)，Tel Aviv Univ, Fac Engn, Dept Interdisciplinary Studies, IL-69978 Ramat Aviv, Israel.
EM alon.asher@gmail.com; wsegal@stanford.edu; baccus@stanford.edu;
   yaro@eng.tau.ac.il; palanker@stanford.edu
RI Palanker, Daniel V/G-5447-2013
OI Palanker, Daniel/0000-0002-0480-3025
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NR 38
TC 37
Z9 44
U1 0
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD JUN
PY 2007
VL 54
IS 6
BP 993
EP 1004
DI 10.1109/TBME.2007.894828
PN 1
PG 12
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 172RK
UT WOS:000246821500005
PM 17554819
OA Green Published
DA 2022-11-30
ER

PT J
AU Chen, JY
   Hood, DC
   Odel, JG
   Behrens, MM
AF Chen, John Y.
   Hood, Donald C.
   Odel, Jeffrey G.
   Behrens, Myles M.
TI The effects of retinal abnormalities on the multifocal visual evoked
   potential
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINITIS-PIGMENTOSA; GLAUCOMATOUS DAMAGE; VEP; ERG; TOPOGRAPHY;
   LATENCIES
AB PURPOSE. To examine the effects on the amplitude and latency of the multifocal visual evoked potential (mfVEP) in retinal diseases associated with depressed multifocal electroretinograms (mfERG).
   METHODS. Static automated perimetry (SAP), mfERGs, and mfVEPs were obtained from 15 individuals seen by neuro-ophthalmologists and diagnosed with retinal disease based on funduscopic examination, visual field, and mfERG. Optic neuropathy was ruled out in all cases. Diagnoses included autoimmune retinopathy (n = 3), branch retinal arterial occlusion (n = 3), branch retinal vein occlusion (n = 1), vitamin A deficiency (n = 1), digoxin/age-related macular degeneration (n = 1), multiple evanescent white dot syndrome (n = 1), and nonspecific retinal disease (n = 5). Patients were selected from a larger group based on abnormal mfERG amplitudes covering a diameter of 20 or greater.
   RESULTS. Fourteen (93%) of 15 patients showed significant mfVEP delays, as determined by either mean latency or the probability of a cluster of delayed local responses. Thirteen of 15 patients had normal mfVEP amplitudes in regions corresponding to markedly reduced or nonrecordable mfERG responses. These findings can be mimicked in normal individuals by viewing the display through a neutral-density filter.
   CONCLUSIONS. Retinal diseases can result in mfVEPs of relatively normal amplitudes, often with delays, in regions showing decreased mfERG responses and visual field sensitivity loss. Consequently, a retinal problem can be missed, or dismissed as functional, if a diagnosis is based on an mfVEP of normal or near-normal amplitude. Further, in patients with marked mfVEP delays, a retinal problem could be confused with optic neuritis, especially in a patient with a normal appearing fundus.
C1 Columbia Univ, Dept Psychol, New York, NY 10027 USA.
   Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA.
C3 Columbia University; Columbia University
RP Hood, DC (通讯作者)，Columbia Univ, Dept Psychol, 406 Schermerhorn Hall, New York, NY 10027 USA.
EM dch3@columbia.edu
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NR 25
TC 11
Z9 14
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2006
VL 47
IS 10
BP 4378
EP 4385
DI 10.1167/iovs.06-0242
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 088AU
UT WOS:000240784700027
PM 17003429
DA 2022-11-30
ER

PT J
AU Maksimiuk, M
   Sobiborowicz, A
   Tuzimek, A
   Deptala, A
   Czerw, A
   Badowska-Kozakiewicz, A
AF Maksimiuk, Marta
   Sobiborowicz, Aleksandra
   Tuzimek, Agnieszka
   Deptala, Andrzej
   Czerw, Aleksandra
   Badowska-Kozakiewicz, Anna
TI alpha B-crystallin as a promising target in pathological conditions - A
   review
SO ANNALS OF AGRICULTURAL AND ENVIRONMENTAL MEDICINE
LA English
DT Review
DE alpha B-crystallin; small heat-shock proteins; breast cancer; renal cell
   carcinoma
ID SHOCK-PROTEIN GENE; SQUAMOUS-CELL CARCINOMA; CRYAB MUTATION; CHAPERONE
   ACTIVITY; EPIRETINAL MEMBRANE; MULTIPLE-SCLEROSIS; UP-REGULATION;
   EXPRESSION; LENS; CATARACT
AB Introduction and objective. alpha B-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, alpha B-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of alpha B-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies.
   State of knowledge. alpha-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight alpha B-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. alpha B-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of alpha B-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas.
   Conclusions. Further studies concerning alpha B-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.
C1 [Maksimiuk, Marta; Sobiborowicz, Aleksandra; Tuzimek, Agnieszka] Med Univ, Canc Cell Biol Students Res Grp, Warsaw, Poland.
   [Deptala, Andrzej; Badowska-Kozakiewicz, Anna] Med Univ, Fac Hlth Sci, Dept Canc Prevent, Warsaw, Poland.
   [Czerw, Aleksandra] Med Univ, Dept Hlth Econ & Med Law, Warsaw, Poland.
   [Czerw, Aleksandra] Natl Inst Publ Hlth, Dept Econ & Syst Anal, Warsaw, Poland.
C3 National Institute of Public Health (NIPH)
RP Maksimiuk, M (通讯作者)，Med Univ, Canc Cell Biol Students Res Grp, Warsaw, Poland.
EM marcioszka.m@gmail.com
RI ; Badowska-Kozakiewicz, Anna Maria/T-7432-2018
OI Sobiborowicz-Sadowska, Aleksandra Maria/0000-0002-8245-9311; czerw,
   aleksandra/0000-0002-6189-6678; Badowska-Kozakiewicz, Anna
   Maria/0000-0002-4990-8760; Tuzimek, Agnieszka/0000-0002-7476-7023;
   Fudalej, Marta/0000-0001-8665-2875
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NR 111
TC 4
Z9 4
U1 1
U2 5
PU INST AGRICULTURAL MEDICINE
PI LUBLIN
PA JACZEWSKIEGO 2, PO BOX 185, 20-950 LUBLIN, POLAND
SN 1232-1966
EI 1898-2263
J9 ANN AGR ENV MED
JI Ann. Agr. Env. Med.
PY 2020
VL 27
IS 3
BP 326
EP 334
DI 10.26444/aaem/111759
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA NO4MB
UT WOS:000569458100002
PM 32955210
OA gold
DA 2022-11-30
ER

PT J
AU Esquerdo-Barragan, M
   Brooks, MJ
   Toulis, V
   Swaroop, A
   Marfany, G
AF Esquerdo-Barragan, Mariona
   Brooks, Matthew J.
   Toulis, Vasileios
   Swaroop, Anand
   Marfany, Gemma
TI Expression of deubiquitinating enzyme genes in the developing mammal
   retina
SO MOLECULAR VISION
LA English
DT Article
ID NUCLEAR RECEPTOR NR2E3; UBIQUITIN-BINDING; PHOTORECEPTOR; MUTATIONS;
   DIFFERENTIATION; PIGMENTOSA; PROTEIN; NRL; SPECIFICATION; FAMILIES
AB Purpose: Genes involved in the development and differentiation of the mammalian retina are also associated with inherited retinal dystrophies (IRDs) and age-related macular degeneration. Transcriptional regulation of retinal cell differentiation has been addressed by genetic and transcriptomic studies. Much less is known about the posttranslational regulation of key regulatory proteins, although mutations in some genes involved in ubiquitination and proteostasis-E3 ligases and deubiquitinating enzymes (DUBs)-cause IRDs. This study intends to provide new data on DUB gene expression during different developmental stages of mouse and human fetal retinas.
   Methods: We performed a comprehensive transcriptomic analysis of all the annotated human and mouse DUBs (87) in the developing mouse retina at several embryonic and postnatal time points compared with the transcriptome of the fetal human retina. An integrated comparison of data from transcriptomics, reported chromatin immunoprecipitation sequencing (ChIP-seq) of CRX and NRL transcription factors, and the phenotypic retinal alterations in different animal models is presented.
   Results: Several DUB genes are differentially expressed during the development of the mouse and human retinas in relation to proliferation or differentiation stages. Some DUB genes appear to be distinctly expressed during the differentiation stages of rod and cone photoreceptor cells, and their expression is altered in mouse knockout models of relevant photoreceptor transcription factors. We complemented this RNA-sequencing (RNA-seq) analysis with other reported expression and phenotypic data to underscore the involvement of DUBs in cell fate decision and photoreceptor differentiation.
   Conclusions: The present results highlight a short list of potential DUB candidates for retinal disorders, which require further study.
C1 [Esquerdo-Barragan, Mariona; Toulis, Vasileios; Marfany, Gemma] Univ Barcelona, Dept Genet Microbiol & Estadist, Avda Diagonal 643, E-08028 Barcelona, Spain.
   [Esquerdo-Barragan, Mariona; Toulis, Vasileios; Marfany, Gemma] Univ Barcelona, Inst Biomed IBUB IRSJD, Barcelona, Spain.
   [Brooks, Matthew J.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Toulis, Vasileios; Marfany, Gemma] Univ Barcelona, ISCIII, CIBERER, Barcelona, Spain.
C3 University of Barcelona; University of Barcelona; National Institutes of
   Health (NIH) - USA; NIH National Eye Institute (NEI); CIBER - Centro de
   Investigacion Biomedica en Red; CIBERER; Instituto de Salud Carlos III;
   University of Barcelona
RP Marfany, G (通讯作者)，Univ Barcelona, Dept Genet Microbiol & Estadist, Fac Biol, Avda Diagonal 643, E-08028 Barcelona, Spain.
EM gmarfany@ub.edu
RI Toulis, Vasileios/AAV-6473-2021
OI TOULIS, VASILEIOS/0000-0002-5516-7663
FU Ministerio de Economia y Competitividad/FEDER [SAF2013-49069-C2-1-R,
   SAF2016-80937-R]; Generalitat de Catalunya [2017 SGR 738]; La Marato TV3
   [Marato 201,417-30-31-32]; Intramural Research Program of the National
   Eye Institute [ZIAEY000450, ZIAEY000546]
FX This research was supported by grants SAF2013-49069-C2-1-R and
   SAF2016-80937-R (Ministerio de Economia y Competitividad/FEDER), 2017
   SGR 738 (Generalitat de Catalunya), and La Marato TV3 (Project Marato
   201,417-30-31-32) to GM, and by the Intramural Research Program of the
   National Eye Institute (ZIAEY000450 and ZIAEY000546) to AS. VT is fellow
   of the MINECO (BES-2014-068639, Ministerio de Economia, Industria y
   Competitividad, Spain). Authors acknowledge past and present members of
   the group for helpful comments and discussion.
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NR 46
TC 7
Z9 7
U1 1
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 2
PY 2019
VL 25
BP 800
EP 813
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA KA1YY
UT WOS:000505596200002
PM 31819342
DA 2022-11-30
ER

PT J
AU Notomi, S
   Ishihara, K
   Efstathiou, NE
   Lee, JJ
   Hisatomi, T
   Tachibana, T
   Konstantinou, EK
   Ueta, T
   Murakami, Y
   Maidana, DE
   Ikeda, Y
   Kume, S
   Terasaki, H
   Sonoda, S
   Blanz, J
   Young, L
   Sakamoto, T
   Sonoda, KH
   Saftig, P
   Ishibashi, T
   Miller, JW
   Kroemer, G
   Vavvas, DG
AF Notomi, Shoji
   Ishihara, Kenji
   Efstathiou, Nikolaos E.
   Lee, Jong-Jer
   Hisatomi, Toshio
   Tachibana, Takashi
   Konstantinou, Eleni K.
   Ueta, Takashi
   Murakami, Yusuke
   Maidana, Daniel E.
   Ikeda, Yasuhiro
   Kume, Shinji
   Terasaki, Hiroto
   Sonoda, Shozo
   Blanz, Judith
   Young, Lucy
   Sakamoto, Taiji
   Sonoda, Koh-Hei
   Saftig, Paul
   Ishibashi, Tatsuro
   Miller, Joan W.
   Kroemer, Guido
   Vavvas, Demetrios G.
TI Genetic LAMP2 deficiency accelerates the age-associated formation of
   basal laminar deposits in the retina
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE lysosome; LAMP2; retinal degeneration; aging
ID CHAPERONE-MEDIATED AUTOPHAGY; SUB-RPE DEPOSITS; PIGMENT-EPITHELIUM;
   DRUSEN FORMATION; BRUCHS MEMBRANE; AUTOFLUORESCENCE; ACCUMULATION;
   LIPOFUSCIN; EYES; CHOLESTEROL
AB The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch's membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD-namely, the accumulation of APOE, APOA1, clusterin, and vitronectin-adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch's membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.
C1 [Notomi, Shoji; Ishihara, Kenji; Efstathiou, Nikolaos E.; Lee, Jong-Jer; Konstantinou, Eleni K.; Ueta, Takashi; Maidana, Daniel E.; Young, Lucy; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Dept Ophthalmol, Boston, MA 02114 USA.
   [Notomi, Shoji; Hisatomi, Toshio; Tachibana, Takashi; Murakami, Yusuke; Ikeda, Yasuhiro; Sonoda, Koh-Hei; Ishibashi, Tatsuro] Kyushu Univ, Dept Ophthalmol, Fukuoka, Fukuoka 8128582, Japan.
   [Lee, Jong-Jer] Kaohsiung Chang Gung Mem Hosp, Dept Ophthalmol, Kaohsiung 833, Taiwan.
   [Kume, Shinji] Shiga Univ Med Sci, Dept Med, Shiga 5202192, Japan.
   [Terasaki, Hiroto; Sonoda, Shozo; Sakamoto, Taiji] Kagoshima Univ, Dept Ophthalmol, Kagoshima 8908520, Japan.
   [Blanz, Judith] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
   [Saftig, Paul] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany.
   [Kroemer, Guido] Univ Paris, Sorbonne Univ, Ctr Rech Cordeliers, Metab Canc & Immun Lab,INSERM,U1138, F-75006 Paris, France.
   [Kroemer, Guido] Inst Gustave Roussy, Metabol & Cell Biol Platforms, F-94800 Villejuif, France.
   [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France.
   [Kroemer, Guido] Chinese Acad Med Sci, Suzhou Inst Syst Med, Suzhou 100050, Peoples R China.
   [Kroemer, Guido] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Kyushu University; Chang Gung Memorial Hospital; Shiga
   University of Medical Science; Kagoshima University; Northwestern
   University; Feinberg School of Medicine; University of Kiel; Institut
   National de la Sante et de la Recherche Medicale (Inserm); UDICE-French
   Research Universities; Sorbonne Universite; Universite Paris Cite;
   UNICANCER; Gustave Roussy; Assistance Publique Hopitaux Paris (APHP);
   Hopital Universitaire Europeen Georges-Pompidou - APHP; UDICE-French
   Research Universities; Universite Paris Cite; Chinese Academy of Medical
   Sciences - Peking Union Medical College; Karolinska Institutet;
   Karolinska University Hospital
RP Vavvas, DG (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Dept Ophthalmol, Boston, MA 02114 USA.; Kroemer, G (通讯作者)，Univ Paris, Sorbonne Univ, Ctr Rech Cordeliers, Metab Canc & Immun Lab,INSERM,U1138, F-75006 Paris, France.; Kroemer, G (通讯作者)，Inst Gustave Roussy, Metabol & Cell Biol Platforms, F-94800 Villejuif, France.; Kroemer, G (通讯作者)，Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France.; Kroemer, G (通讯作者)，Chinese Acad Med Sci, Suzhou Inst Syst Med, Suzhou 100050, Peoples R China.; Kroemer, G (通讯作者)，Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden.
EM kroemer@orange.fr; vavvas@meei.harvard.edu
RI KROEMER, Guido/B-4263-2013; Konstantinou, Eleni/ABD-1753-2020; Saftig,
   Paul/A-7966-2010; Kroemer, Guido/AAY-9859-2020
OI KROEMER, Guido/0000-0002-9334-4405; Efstathiou,
   Nikolaos/0000-0002-6635-0391; Notomi, Shoji/0000-0002-7935-4244; Young,
   Lucy/0000-0001-8634-7512; Hisatomi, Toshio/0000-0003-2552-9595
FU Robert Machemer Foundation Vitreoretinal Research Scholarship;
   Foundation Lions Eye Research Fund; Yeatts Family Foundation; 2013
   Macula Society Research Grant award; Research to Prevent Blindness
   Physician Scientist Award; Research to Prevent Blindness Foundation;
   National Eye Institute (NEI) [R21EY023079-01/A1, EY014104]; Loeffler
   Family fund; Alcon Research Institute (ARI) Young Investigator Award;
   National Institutes of Health (NIH) NEI Core grant [P30EY003790]; Agence
   National de la Recherche (ANR), the ERA-Net for Research on Rare
   Diseases, the Institut Universitaire de France; Japan Society for the
   Promotion of Science [19K18880];  [R01EY025362-01]; NATIONAL EYE
   INSTITUTE [P30EY003790, R01EY025362] Funding Source: NIH RePORTER
FX We thank Philip Seifert (Schepens Eye Research Institute) and Fumiyo
   Morikawa (Kyushu University) for their technical assistance and Wendy
   Chao (Massachusetts Eye and Ear Infirmary) for her support in critical
   review. This work was supported by the Robert Machemer Foundation
   Vitreoretinal Research Scholarship (S.N.); the Foundation Lions Eye
   Research Fund; the Yeatts Family Foundation; a 2013 Macula Society
   Research Grant award; a Research to Prevent Blindness Physician
   Scientist Award; an unrestricted grant from the Research to Prevent
   Blindness Foundation; the National Eye Institute (NEI) (grant nos.
   R21EY023079-01/A1 and EY014104 [a MEEI Core Grant]); the Loeffler Family
   fund; R01EY025362-01; an Alcon Research Institute (ARI) Young
   Investigator Award; a National Institutes of Health (NIH) NEI Core grant
   (grant no. P30EY003790); the Agence National de la Recherche (ANR), the
   ERA-Net for Research on Rare Diseases, the Institut Universitaire de
   France; and a Grant-in-Aid for Young Scientists (Grant no. 19K18880),
   Japan Society for the Promotion of Science.
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NR 76
TC 26
Z9 26
U1 0
U2 9
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 NOV 19
PY 2019
VL 116
IS 47
BP 23724
EP 23734
DI 10.1073/pnas.1906643116
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA JQ0ZJ
UT WOS:000498683000053
PM 31699817
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Xiao, Y
   Wang, YQ
   Li, FT
   Lin, TZ
   Huffman, K
   Landeros, S
   Bosse, B
   Jing, Y
   Bartsch, DU
   Thorogood, S
   Freeman, WR
   Cheng, LY
AF Xiao, Ying
   Wang, Yuqin
   Li, Fangting
   Lin, Tiezhu
   Huffman, Kristyn
   Landeros, Stephanie
   Bosse, Brandon
   Jing, Yi
   Bartsch, Dirk-Uwe
   Thorogood, Scott
   Freeman, William R.
   Cheng, Lingyun
TI Acute Rabbit Eye Model for Testing Subretinal Prostheses
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE retinal prosthesis; rabbit eye model; subretinal implantation; acute
   visual electrophysiology eye model; longitudinal OCT
ID RETINAL PROSTHESIS; ELECTRICAL-STIMULATION; RETINITIS-PIGMENTOSA;
   IMPLANTATION; ARRAYS
AB Purpose: Subretinal prostheses are a novel technology for restoring useful vision in patients with retinitis pigmentosa or age-related macular degeneration. We characterize the surgical implantation technique and functional time window of an acute rabbit eye model for testing of human subretinal prostheses.
   Methods: Retinal prostheses were implanted subretinally in 26 rabbits using a twostep technique. Fundus imaging, fluorescein fundus angiography, and optical coherence topography (OCT) were conducted postoperatively from days 1 to 21 to monitor prosthesis positioning and retinal anatomic changes.
   Results: Successful implantation and excellent retina apposition were achieved in 84.6% of the rabbits. OCTs showed the overlying retina at full thickness for the first 2 days after implantation. Histology confirmed intact inner layers of the overlying retina until day 3. Progressive atrophy of the overlying retina was revealed by repeated OCTs; approximately 40% of the retina thickness remained on postoperative days 5 and 6.
   Conclusions: The two-step implantation technique works well for the rabbit eye model with human prostheses. Rabbit retina may be used for acute electrophysiologic testing of a retinal prosthesis, but is unsuitable for chronic studies due to the merangiotic retina and its limited time window of validity. Translational Relevance: The improved efficacy in prosthesis surgery using this technique will circumvent the challenges in animal models that provide human-like features critical for the transition into human clinical trials.
   Translational Relevance: The improved efficacy in prosthesis surgery using this technique will circumvent the challenges in animal models that provide human-like features critical for the transition into human clinical trials.
C1 [Xiao, Ying; Wang, Yuqin; Li, Fangting; Lin, Tiezhu; Huffman, Kristyn; Landeros, Stephanie; Bartsch, Dirk-Uwe; Freeman, William R.; Cheng, Lingyun] Univ Calif San Diego, Dept Ophthalmol, Jacobs Retina Ctr, Shiley Eye Inst, La Jolla, CA 92093 USA.
   [Bosse, Brandon; Jing, Yi; Thorogood, Scott] Nanovis Biosci Inc, La Jolla, CA USA.
C3 University of California System; University of California San Diego
RP Cheng, LY (通讯作者)，Univ Calif San Diego, Jacobs Retina Ctr, Shiley Eye Inst, La Jolla, CA 92037 USA.; Xiao, Y (通讯作者)，Shandong Univ, Prov Hosp, 324 Jingwu Weiqi Rd, Jinan 250021, Shandong, Peoples R China.; Wang, YQ (通讯作者)，Wenzhou Med Univ, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China.; Wang, YQ (通讯作者)，Wenzhou Med Univ, Sch Ophthalmol & Optometry, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China.
EM l1cheng@ucsd.edu
RI Huffman, Kristyn/AAT-9231-2020; Huffman, Kristyn/AAP-2194-2020; lin,
   Tiezhu/AAY-1971-2020
OI Huffman, Kristyn/0000-0002-3271-2518; 
FU NIH [P30EY022589]; Nanovision Biosciences, Inc.; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [P30EY022589] Funding Source: NIH
   RePORTER
FX Supported by the NIH under core grant P30EY022589, funding from
   Nanovision Biosciences, Inc., and unrestricted funds to Jacobs Retina
   Center from Research to Prevent Blindness.
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NR 34
TC 2
Z9 2
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD SEP
PY 2019
VL 8
IS 5
AR 20
DI 10.1167/tvst.8.5.20
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JB8ZU
UT WOS:000488870900010
PM 31602345
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yin, Y
   Liu, DJ
   Tian, DH
AF Yin, Yan
   Liu, Dejie
   Tian, Donghua
TI Salidroside prevents hydroperoxide-induced oxidative stress and
   apoptosis in retinal pigment epithelium cells
SO EXPERIMENTAL AND THERAPEUTIC MEDICINE
LA English
DT Article
DE salidroside; age-related macular degeneration; oxidative stress;
   apoptosis
ID PEROXIDE-INDUCED INJURY; HUMAN RPE CELLS; MACULAR DEGENERATION;
   AKT/GSK-3-BETA PATHWAY; H9C2 CELLS; PROTECTS; ACTIVATION; PROMOTES; MICE
AB Salidroside (SAL) is the major pharmacologically active constituent of Rhodiola rosea, which possesses a wide range of pharmacological functions, including anti-aging, anti-inflammatory, antioxidant, anticancer and neuroprotective activities. However, the effects and mechanisms of SAL on oxidative stress in retinal pigment epithelial (RPE) cells exposed to hydrogen peroxide (H2O2) remain unclear. The present study investigated the protective effects of SAL and the underlying mechanisms against H2O2-induced oxidative stress in human RPE cells. ARPE-19 cells were treated with various doses of SAL for 24 h and then exposed to 200 mu M H2O2 for 24 h. Cell viability was analyzed by a MTT assay, and the intracellular levels of reactive oxygen species were measured using CellROX orange reagent. Cell apoptosis was analyzed by annexin V/propidium iodide double staining, followed by flow cytometry. The levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, phospho (p)-protein kinase B (Akt), Akt, p-glycogen synthase kinase (GSK)-3 and GSK-3 were evaluated using western blotting. The results demonstrated that SAL markedly attenuated H2O2-induced loss of cell viability. SAL also ameliorated H2O2-induced oxidative stress and cell apoptosis in RPE cells. In addition, pretreatment with SAL significantly increased the phosphorylation levels of Akt and GSK-3 in H2O2-treated ARPE-19 cells. In conclusion, the present study demonstrated that SAL protected RPE cells against H2O2-induced cell injury through the activation of the Akt/GSK-3 signaling pathway. This suggests that SAL may be a potential therapeutic strategy for the treatment of age-related macular degeneration.
C1 [Yin, Yan; Tian, Donghua] Jining 1 Peoples Hosp, Dept Ophthalmol, 6 Hlth Rd, Jining 272011, Shandong, Peoples R China.
   [Liu, Dejie] Yantai Yeda Hosp, Dept Ophthalmol, Yantai 264006, Shandong, Peoples R China.
RP Tian, DH (通讯作者)，Jining 1 Peoples Hosp, Dept Ophthalmol, 6 Hlth Rd, Jining 272011, Shandong, Peoples R China.
EM tiandong_hua@126.com
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NR 29
TC 10
Z9 11
U1 1
U2 13
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-0981
EI 1792-1015
J9 EXP THER MED
JI Exp. Ther. Med.
PD SEP
PY 2018
VL 16
IS 3
BP 2363
EP 2368
DI 10.3892/etm.2018.6494
PG 6
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GS5UZ
UT WOS:000443738300111
PM 30210588
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Bohn, T
AF Bohn, Torsten
TI Carotenoids, Chronic Disease Prevention and Dietary Recommendations
SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH
LA English
DT Article
DE Xanthophylls; carotenes; cardiovascular disease; brain; eye; vitamin A;
   cellular signalling
ID CAUSE-SPECIFIC MORTALITY; BETA-CAROTENE; OXIDATIVE STRESS; PLASMA
   CAROTENOIDS; PROSTATE-CANCER; INTERINDIVIDUAL VARIABILITY;
   CONTROLLED-TRIAL; POOLED ANALYSIS; LUNG-CANCER; VITAMIN-E
AB Carotenoids are C-30, C-40 or C-50 terpenoids produced by a number of bacteria, fungi, and plants. In addition to acting as vitamin A precursors such as beta-carotene, their dietary intake and blood plasma/serum and tissue levels have been associated in several epidemiological studies to the reduced incidence of chronic diseases, including the reduction of type 2 diabetes and other cardiometabolic diseases, as well as some types of cancer. Lutein and zeaxanthin also appear to play a role in the amelioration of age-related macular degeneration (AMD), the main cause of blindness in the elderly, and may be regarded as conditionally essential nutrients for the elderly. Furthermore, some studies have proposed that carotenoids may improve cognitive functions. Though the underlying mechanisms remain to be fully elucidated, it is perceived that direct antioxidant effects and protection from UV-light, as well as rather indirect effects, acting on transcription factors such as NF-kappa B, Nrf-2, and nuclear receptors such as RAR/RXR (retinoic acid receptor/retinoid X receptor), altering gene expression, all can play a role. Despite individual intervention trials suggesting negative effects of high doses of beta-carotene on smokers, perhaps due to effects related to cytochrome enzyme activation, there is accumulating evidence that these colourful pigments indeed contribute to a healthy life and well-being. However, further research is warranted to better understand factors influencing variable inter-individual responses following carotenoid consumption and to establish more detailed recommendations regarding their dietary intake and toward establishing health claims.
C1 [Bohn, Torsten] LIH, Dept Populat Hlth, Rue 1 A-B Thomas Edison, L-1445 Strassen, Luxembourg.
C3 Luxembourg Institute of Health
RP Bohn, T (通讯作者)，LIH, Dept Populat Hlth, Rue 1 A-B Thomas Edison, L-1445 Strassen, Luxembourg.
EM torsten.bohn@gmx.ch
RI Bohn, Torsten/AAE-8393-2019
OI Bohn, Torsten/0000-0002-7825-0697
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NR 94
TC 15
Z9 15
U1 0
U2 13
PU VERLAG HANS HUBER
PI BERN 9
PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND
SN 0300-9831
EI 1664-2821
J9 INT J VITAM NUTR RES
JI Int. J. Vitam. Nutr. Res.
PD MAY
PY 2017
VL 87
IS 3-4
BP 121
EP 130
DI 10.1024/0300-9831/a000525
PG 10
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA VI3AA
UT WOS:000468731600001
PM 30545279
DA 2022-11-30
ER

PT J
AU Soleimannejad, M
   Ebrahimi-Barough, S
   Nadri, S
   Riazi-Esfahani, M
   Soleimani, M
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   Ai, J
AF Soleimannejad, Mostafa
   Ebrahimi-Barough, Somayeh
   Nadri, Samad
   Riazi-Esfahani, Mohammad
   Soleimani, Masoud
   Tavangar, Seyed Mohammad
   Ai, Jafar
TI Retina tissue engineering by conjunctiva mesenchymal stem cells
   encapsulated in fibrin gel: Hypotheses on novel approach to retinal
   diseases treatment
SO MEDICAL HYPOTHESES
LA English
DT Article
DE Retina; Conjunctiva mesenchymal stem cells; Hydrogel; Photoreceptors;
   Tissue engineering
ID MACULAR DEGENERATION; DIFFERENTIATION; GROWTH
AB Background: Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision.
   Presentation of the hypothesis: Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders.
   Testing the hypothesis: In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells.
   Implications of the hypothesis: Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Ai, Jafar] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Tissue Engn & Appl Cell Sci, Tehran, Iran.
   [Nadri, Samad] Zanjan Univ Med Sci, Sch Med, Dept Med Biotechnol & Nanotechnol, Zanjan, Iran.
   [Riazi-Esfahani, Mohammad] Univ Tehran Med Sci, Farabi Eye Hosp, Eye Res Ctr, Tehran, Iran.
   [Soleimani, Masoud] Tarbiat Modares Univ, Dept Hematol & Blood Banking, Fac Med, Tehran, Iran.
   [Tavangar, Seyed Mohammad] Univ Tehran Med Sci, Shariati Hosp, Dept Pathol, Tehran, Iran.
C3 Tehran University of Medical Sciences; Tehran University of Medical
   Sciences; Tarbiat Modares University; Tehran University of Medical
   Sciences
RP Ai, J (通讯作者)，Univ Tehran Med Sci, Sch Adv Technol Med, Dept Tissue Engn & Appl Cell Sci, Tehran, Iran.
EM jafar_ai@tums.ac.ir
RI Soleimannejad, Mostafa/D-9965-2018; Nadri, Samad/M-9349-2016
OI Soleimannejad, Mostafa/0000-0002-9097-4356; Tavangar, Seyed
   Mohammad/0000-0002-4253-2385; ai, jafar/0000-0001-8417-5913;
   ebrahimibarough, somayeh/0000-0002-5234-4791
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NR 21
TC 15
Z9 15
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 APR
PY 2017
VL 101
BP 75
EP 77
DI 10.1016/j.mehy.2017.02.019
PG 3
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA ES1DQ
UT WOS:000399268500020
PM 28351499
DA 2022-11-30
ER

PT J
AU Amini, Z
   Rabbani, H
AF Amini, Zahra
   Rabbani, Hossein
TI Statistical Modeling of Retinal Optical Coherence Tomography
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Contrast enhancement; Gaussianization transform; normal-Laplace mixture
   model; optical coherence tomography (OCT) images; statistical model
ID MEDICAL ULTRASOUND IMAGES; COMPLEX WAVELET DOMAIN; CONTRAST ENHANCEMENT;
   GAUSSIANIZATION; MIXTURE; DISTRIBUTIONS; GEOMETRY; REMOVAL
AB In this paper, a new model for retinal Optical Coherence Tomography (OCT) images is proposed. This statistical model is based on introducing a nonlinear Gaussianization transform to convert the probability distribution function (pdf) of each OCT intra-retinal layer to a Gaussian distribution. The retina is a layered structure and in OCT each of these layers has a specific pdf which is corrupted by speckle noise, therefore a mixture model for statistical modeling of OCT images is proposed. A Normal-Laplace distribution, which is a convolution of a Laplace pdf and Gaussian noise, is proposed as the distribution of each component of this model. The reason for choosing Laplace pdf is the monotonically decaying behavior of OCT intensities in each layer for healthy cases. After fitting a mixture model to the data, each component is gaussianized and all of them are combined by Averaged Maximum A Posterior (AMAP) method. To demonstrate the ability of this method, a new contrast enhancement method based on this statistical model is proposed and tested on thirteen healthy 3D OCTs taken by the Topcon 3D OCT and five 3D OCTs from Age-related Macular Degeneration (AMD) patients, taken by Zeiss Cirrus HD-OCT. Comparing the results with two contending techniques, the prominence of the proposed method is demonstrated both visually and numerically. Furthermore, to prove the efficacy of the proposed method for a more direct and specific purpose, an improvement in the segmentation of intra-retinal layers using the proposed contrast enhancement method as a preprocessing step, is demonstrated.
C1 [Amini, Zahra] Isfahan Univ Med Sci, Student Res Ctr, Sch Adv Technol, Esfahan 81745319, Iran.
   [Rabbani, Hossein] Isfahan Univ Med Sci, Image & Signal Proc Res Ctr, Esfahan 81745319, Iran.
C3 Isfahan University Medical Science; Isfahan University Medical Science
RP Rabbani, H (通讯作者)，Isfahan Univ Med Sci, Image & Signal Proc Res Ctr, Esfahan 81745319, Iran.
EM rabbani.h@ieee.org
RI Amini, Zahra/U-8374-2017; Rabbani, Hossein/O-4987-2019; Rabbani,
   Hossein/H-7515-2014
OI Amini, Zahra/0000-0001-6495-1313; Rabbani, Hossein/0000-0002-0551-3636;
   Rabbani, Hossein/0000-0002-0551-3636
CR Achim A, 2001, IEEE T MED IMAGING, V20, P772, DOI 10.1109/42.938245
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NR 33
TC 27
Z9 27
U1 1
U2 18
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD JUN
PY 2016
VL 35
IS 6
BP 1544
EP 1554
DI 10.1109/TMI.2016.2519439
PG 11
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DR5GA
UT WOS:000379930300016
PM 26800532
DA 2022-11-30
ER

PT J
AU Butt, T
   Crossland, MD
   West, P
   Orr, SW
   Rubin, GS
AF Butt, Thomas
   Crossland, Michael D.
   West, Peter
   Orr, Shepley W.
   Rubin, Gary S.
TI Simulation contact lenses for AMD health state utility values in NICE
   appraisals: a different reality
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; MACULAR DEGENERATION; FIXATION STABILITY;
   VISUAL-ACUITY; DISEASE; VISION
AB Background/aims The National Institute for Health and Care Excellence (NICE) has recommended the use of ranibizumab for neovascular age-related macular degeneration (AMD) and for diabetic macular oedema (DMO) as part of its health technology appraisal process. In the economic evaluations of both interventions, utility values were derived from members of the general public wearing contact lenses with a central opacity that was meant to simulate the blind spot experienced by many patients with advanced retinal disease. This paper tests the validity of the contact lens simulation, and finding it to be invalid, explores the impact on prior economic evaluations.
   Methods Visual acuity, contrast sensitivity and visual fields were assessed with and without simulation lenses in five healthy subjects with normal vision.
   Results We identified important differences between the contact lens simulation and vision loss experienced by patients with AMD. The contact lens simulator did not cause the central scotoma which is characteristic of late-stage AMD and which leads to severe difficulty with everyday activities such as reading or recognising faces and objects. The contact lens instead caused a reduction in retinal illumination experienced by the subjects as a general dimming across the retina.
   Conclusions A contact lens with a central opacity does not simulate a central scotoma. The clinical differences between simulated and actual AMD suggest there has been an underestimation of the severity of AMD health states. This brings into question the validity of the economic evaluations of treatments for AMD and DMO used by NICE.
C1 [Butt, Thomas; Crossland, Michael D.; West, Peter; Rubin, Gary S.] UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Crossland, Michael D.] Moorfields Eye Hosp, London, England.
   [Orr, Shepley W.] UCL Dept Civil Environm & Geomat Engn, London, England.
   [Rubin, Gary S.] NIHR Moorfields Biomed Res Ctr Ophthalmol, London, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London
RP Butt, T (通讯作者)，UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM thomas.butt.10@ucl.ac.uk
RI Crossland, Michael D/B-5600-2008; Butt, Thomas/AAH-7882-2019
OI Crossland, Michael D/0000-0001-6833-6043; Butt,
   Thomas/0000-0002-0387-4550
FU Fight for Sight Programme Grant [1777]; National Institute for Health
   Research (NIHR) Biomedical Research Centre based at Moorfields Eye
   Hospital NHS Foundation Trust; UCL Institute of Ophthalmology; Fight for
   Sight [1777/78] Funding Source: researchfish
FX Fight for Sight Programme Grant 1777, Moorfields Special Trustees,
   National Institute for Health Research (NIHR) Biomedical Research Centre
   based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
   of Ophthalmology.
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NR 20
TC 13
Z9 15
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2015
VL 99
IS 4
BP 540
EP 544
DI 10.1136/bjophthalmol-2014-305802
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE2YI
UT WOS:000351687800018
PM 25351679
OA Green Published, hybrid, Green Submitted
DA 2022-11-30
ER

PT J
AU Chan, EC
   Liu, GS
   Dusting, GJ
AF Chan, Elsa C.
   Liu, Guei-Sheung
   Dusting, Gregory J.
TI Redox Mechanisms in Pathological Angiogenesis in the Retina: Roles for
   NADPH Oxidase
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Article
DE Retinal neovascularisation; NADPH oxidase; VEGF; HIF; hypoxia;
   nanomedicine
ID OXYGEN-INDUCED RETINOPATHY; OXIDATIVE STRESS; DIABETIC-RETINOPATHY;
   UP-REGULATION; MACULAR DEGENERATION; PHOTORECEPTOR CELLS; ANTIOXIDANT
   ENZYMES; NOX4 EXPRESSION; ERYTHROPOIETIN; GROWTH
AB Pathological angiogenesis in the retina is a leading cause of serious vision loss in potentially blinding eye diseases, including proliferative diabetic retinopathy, retinopathy of prematurity and the wet form of age-related macular degeneration. Hypoxia is thought to be the driver of pathological angiogenesis, and transcription factors such as hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) are key mediators in these processes. Current treatments employ either laser photocoagulation or intravitreal injection of therapeutic antibodies for VEGF, in order to arrest the growth of leaky blood vessels in the avascular vitreous cavity and to restore visual acuity. However, all such therapeutic approaches are limited by low or variable efficacy, and the inconvenience, risk and financial burden of such treatments, which need to be given frequently. The lack of non-invasive and efficacious therapy has therefore driven the search for alternative strategies. We have been interested in the roles of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which when produced intracellularly at low concentration can act as second messengers to regulate physiological and pathological angiogenesis. Accumulating evidence suggests NADPH oxidase-dependent ROS are involved in regulation of the angiogenic signalling pathways of HIF and VEGF. Suppressing pathological neovascularisation in the retina by manipulating such redox mechanisms appears to be an attractive and clinically translatable therapeutic strategy to treat proliferative neovascular eye diseases. Here we provide a brief overview of the roles of NADPH oxidase in the sensing and regulation processes involving HIF and VEGF that contribute to the development of pathological angiogenesis in the retina.
C1 [Chan, Elsa C.; Liu, Guei-Sheung; Dusting, Gregory J.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
   [Chan, Elsa C.; Liu, Guei-Sheung; Dusting, Gregory J.] Univ Melbourne, Dept Surg, Ophthalmol, East Melbourne, Vic 3002, Australia.
   [Dusting, Gregory J.] St Vincents Inst Med Res, OBrien Inst Dept, Fitzroy, Vic, Australia.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; St. Vincent's Institute of Medical Research
RP Dusting, GJ (通讯作者)，Ctr Eye Res Australia, Level 1,32 Gisborne St, East Melbourne, Vic 3002, Australia.
EM dusting@unimelb.edu.au
RI Liu, Guei-Sheung/Q-6472-2018
OI Liu, Guei-Sheung/0000-0003-3379-724X
FU NHMRC project grant (NHMRC) [1061912]; Ansell Foundation
FX We are most grateful for the helpful comments of the editor in preparing
   this review. GJD holds an NHMRC Principal Research Fellowship The Centre
   for Eye Research Australia acknowledges the Victorian State Government's
   Department of Innovation, Industry and Regional Development's
   Operational Infrastructure Support Program, ECH and GSL are supported by
   NHMRC project grant (NHMRC #1061912) and the Ansell Foundation.
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NR 118
TC 16
Z9 16
U1 0
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
EI 1873-4286
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PY 2015
VL 21
IS 41
BP 5988
EP 5998
DI 10.2174/1381612821666151029111127
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA CY1VN
UT WOS:000366196200007
PM 26510439
DA 2022-11-30
ER

PT J
AU Biswas, S
   Xia, S
   Lin, SL
AF Biswas, Swati
   Xia, Shuang
   Lin, Shili
TI Detecting Rare Haplotype-Environment Interaction With Logistic Bayesian
   LASSO
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE age-related macular degeneration; Complement Factor H gene; GXE; GWAS;
   LBL; MCMC; missing heritability; rare variants; regularization;
   retrospective likelihood
ID GENE-ENVIRONMENT; MACULAR DEGENERATION; MISSING HERITABILITY; COMPLEX
   DISEASES; ASSOCIATION; VARIANTS; INFERENCE; Y402H; INDEPENDENCE;
   IMPUTATION
AB Two important contributors to missing heritability are believed to be rare variants and gene-environment interaction (GXE). Thus, detecting GXE where G is a rare haplotype variant (rHTV) is a pressing problem. Haplotype analysis is usually the natural second step to follow up on a genomic region that is implicated to be associated through single nucleotide variants (SNV) analysis. Further, rHTV can tag associated rare SNV and provide greater power to detect them than popular collapsing methods. Recently we proposed Logistic Bayesian LASSO (LBL) for detecting rHTV association with case-control data. LBL shrinks the unassociated (especially common) haplotypes toward zero so that an associated rHTV can be identified with greater power. Here, we incorporate environmental factors and their interactions with haplotypes in LBL. As LBL is based on retrospective likelihood, this extension is not trivial. We model the joint distribution of haplotypes and covariates given the case-control status. We apply the approach (LBL-GXE) to the Michigan, Mayo, AREDS, Pennsylvania Cohort Study on Age-related Macular Degeneration (AMD). LBL-GXE detects interaction of a specific rHTV in CFH gene with smoking. To the best of our knowledge, this is the first time in the AMD literature that an interaction of smoking with a specific (rather than pooled) rHTV has been implicated. We also carry out simulations and find that LBL-GXE has reasonably good powers for detecting interactions with rHTV while keeping the type I error rates well controlled. Thus, we conclude that LBL-GXE is a useful tool for uncovering missing heritability.
C1 [Biswas, Swati] Univ Texas Dallas, Dept Math Sci, Richardson, TX 75080 USA.
   [Xia, Shuang; Lin, Shili] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA.
C3 University of Texas System; University of Texas Dallas; University
   System of Ohio; Ohio State University
RP Biswas, S (通讯作者)，Univ Texas Dallas, Dept Math Sci, 800 West Campbell Rd,FO35, Richardson, TX 75080 USA.
EM swati.biswas@utdallas.edu; shili@stat.osu.edu
FU NCI [R03CA171011-01]; NSF [DMS-1208968]; National Eye Institute; Direct
   For Mathematical & Physical Scien [1208968] Funding Source: National
   Science Foundation; NATIONAL CANCER INSTITUTE [R03CA171011] Funding
   Source: NIH RePORTER
FX This work was partially supported by the grant R03CA171011-01 from NCI,
   the grant DMS-1208968 from NSF, and by allocations of computing times
   from the Ohio Supercomputer Center and the Texas Advanced Computing
   Center at the University of Texas at Austin. The MMAP dataset used for
   the analyses described in this manuscript was obtained from the NEI
   Study of Age-Related Macular Degeneration (NEI-AMD) Database found at
   http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0
   00182.v2.p1 through dbGaP accession number phs000182.v2.p1. Funding
   support for NEI-AMD was provided by the National Eye Institute. The
   authors would like to thank NEI-AMD participants and the NEI-AMD
   Research Group for their valuable contribution to this research. The
   authors are also thankful to the two anonymous reviewers for their
   helpful comments and suggestions, which led to improvement of the
   manuscript. The authors have no conflict of interest to declare.
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NR 39
TC 15
Z9 17
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2014
VL 38
IS 1
BP 31
EP 41
DI 10.1002/gepi.21773
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 272LW
UT WOS:000328463200004
PM 24272913
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chu, LH
   Rivera, CG
   Popel, AS
   Bader, JS
AF Chu, Liang-Hui
   Rivera, Corban G.
   Popel, Aleksander S.
   Bader, Joel S.
TI Constructing the angiome: a global angiogenesis protein interaction
   network
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE bioinformatics; systems biology; interactome; endothelial cell;
   tubulogenesis
ID GENE-FUNCTION PREDICTION; BIOLOGICAL NETWORKS; ENRICHMENT ANALYSIS;
   MORPHOGENESIS; INFLAMMATION; CYTOSCAPE; FRAMEWORK; KERNEL; PLUGIN
AB Chu LH, Rivera CG, Popel AS, Bader JS. Constructing the angiome: a global angiogenesis protein interaction network. Physiol Genomics 44: 915-924, 2012. First published August 21, 2012; doi:10.1152/physiolgenomics.00181.2011.-Angiogenesis is the formation of new blood vessels from pre-existing microvessels. Excessive and insufficient angiogenesis have been associated with many diseases including cancer, age-related macular degeneration, ischemic heart, brain, and skeletal muscle diseases. A comprehensive understanding of angiogenesis regulatory processes is needed to improve treatment of these diseases. To identify proteins related to angiogenesis, we developed a novel integrative framework for diverse sources of high-throughput data. The system, called GeneHits, was used to expand on known angiogenesis pathways to construct the angiome, a protein-protein interaction network for angiogenesis. The network consists of 478 proteins and 1,488 interactions. The network was validated through cross validation and analysis of five gene expression datasets from in vitro angiogenesis assays. We calculated the topological properties of the angiome. We analyzed the functional enrichment of angiogenesis-annotated and associated proteins. We also constructed an extended angiome with 1,233 proteins and 5,726 interactions to derive a more complete map of protein-protein interactions in angiogenesis. Finally, the extended angiome was used to identify growth factor signaling networks that drive angiogenesis and antiangiogenic signaling networks. The results of this analysis can be used to identify genes and proteins in different disease conditions and putative targets for therapeutic interventions as high-ranked candidates for experimental validation.
C1 [Chu, Liang-Hui] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Rivera, Corban G.; Bader, Joel S.] Johns Hopkins Univ, High Throughput Biol Ctr, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Chu, LH (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 720 Rutland Ave,617 Traylor Bldg, Baltimore, MD 21205 USA.
EM lchu5@jhu.edu
RI Popel, Aleksander S/A-6724-2009; Bader, Joel/A-1818-2009
OI Bader, Joel/0000-0002-6020-4625; Popel, Aleksander/0000-0002-6706-9235
FU National Institutes of Health [R01 CA-138264, R01 HL-101200, U54
   RR-020839]; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation;
   NATIONAL CANCER INSTITUTE [R01CA138264] Funding Source: NIH RePORTER;
   NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020839] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL101200,
   R21HL122721] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [U54GM103520] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health Grants R01
   CA-138264 and R01 HL-101200 (A. S. Popel), and U54 RR-020839 and the
   Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation (J. S. Bader).
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NR 38
TC 21
Z9 21
U1 0
U2 9
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 OCT
PY 2012
VL 44
IS 19
BP 915
EP 924
DI 10.1152/physiolgenomics.00181.2011
PG 10
WC Cell Biology; Genetics & Heredity; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Genetics & Heredity; Physiology
GA 016WR
UT WOS:000309551000002
PM 22911453
OA Green Published
DA 2022-11-30
ER

PT J
AU Haque, R
   Chun, E
   Howell, JC
   Sengupta, T
   Chen, D
   Kim, H
AF Haque, Rashidul
   Chun, Eugene
   Howell, Jennifer C.
   Sengupta, Trisha
   Chen, Dan
   Kim, Hana
TI MicroRNA-30b-Mediated Regulation of Catalase Expression in Human ARPE-19
   Cells
SO PLOS ONE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; ARYLALKYLAMINE N-ACETYLTRANSFERASE;
   MITOCHONDRIAL-DNA DAMAGE; OXIDATIVE STRESS; GENE-EXPRESSION; MICROARRAY
   ANALYSIS; OCULAR NEOVASCULARIZATION; MACULAR DEGENERATION;
   MESSENGER-RNA; HUMAN RPE
AB Background: Oxidative injury to retinal pigment epithelium (RPE) and retinal photoreceptors has been linked to a number of retinal diseases, including age-related macular degeneration (AMD). Reactive oxygen species (ROS)-mediated gene expression has been extensively studied at transcriptional levels. Also, the post-transcriptional control of gene expression at the level of translational regulation has been recently reported. However, the microRNA (miRNA/miR)-mediated post-transcriptional regulation in human RPE cells has not been thoroughly looked at. Increasing evidence points to a potential role of miRNAs in diverse physiological processes.
   Methodology/Principal Findings: We demonstrated for the first time in a human retinal pigment epithelial cell line (ARPE-19) that the post-transcriptional control of gene expression via miRNA modulation regulates human catalase, an important and potent component of cell's antioxidant defensive network, which detoxifies hydrogen peroxide (H2O2) radicals. Exposure to several stress-inducing agents including H2O2 has been reported to alter miRNA expression profile. Here, we demonstrated that a sublethal dose of H2O2 (200 mu M) up-regulated the expression of miR-30b, a member of the miR-30 family, which inhibited the expression of endogenous catalase both at the transcript and protein levels. However, antisense (antagomirs) of miR-30b was not only found to suppress the miR-30b mimics-mediated inhibitions, but also to dramatically increase the expression of catalase even under an oxidant environment.
   Conclusions/Significance: We propose that a microRNA antisense approach could enhance cytoprotective mechanisms against oxidative stress by increasing the antioxidant defense system.
C1 [Haque, Rashidul; Chun, Eugene; Howell, Jennifer C.; Sengupta, Trisha; Chen, Dan; Kim, Hana] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
C3 Emory University
RP Haque, R (通讯作者)，Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
EM rhaque@emory.edu
FU Research to Prevent Blindnes (RPB) [R01EY004864, P30EY006360]; NATIONAL
   EYE INSTITUTE [R01EY004864, P30EY006360] Funding Source: NIH RePORTER
FX Research to Prevent Blindnes (RPB), R01EY004864, P30EY006360. 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 62
TC 75
Z9 79
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 AUG 6
PY 2012
VL 7
IS 8
AR e42542
DI 10.1371/journal.pone.0042542
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 992WD
UT WOS:000307810000044
PM 22880027
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Ebrahem, Q
   Qi, JH
   Sugimoto, M
   Ali, M
   Sears, JE
   Cutler, A
   Khokha, R
   Vasanji, A
   Anand-Apte, B
AF Ebrahem, Quteba
   Qi, Jian Hua
   Sugimoto, Masahiko
   Ali, Mariya
   Sears, Jonathan E.
   Cutler, Alecia
   Khokha, Rama
   Vasanji, Amit
   Anand-Apte, Bela
TI Increased Neovascularization in Mice Lacking Tissue Inhibitor of
   Metalloproteinases-3
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-H POLYMORPHISM; MAST-CELLS; MATRIX
   METALLOPROTEINASES; ANGIOGENESIS; VEGF; TIMP3; GENE; EXPRESSION; TUMOR
AB PURPOSE. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a matrix-bound inhibitor of matrix metalloproteinases (MMPs). The authors have previously determined a novel function of TIMP-3 to inhibit vascular endothelial growth factor (VEGF)-mediated angiogenesis. Here, the authors examined the in vivo angiogenic phenotype of ocular vessels in mice deficient in TIMP-3.
   METHODS. VEGF-mediated corneal neovascularization and laser-induced choroidal neovascularization (CNV) were examined in TIMP-3-null mice. The effects of the absence of TIMP-3 on the phosphorylation status of the VEGF-receptor-2 (VEGFR-2) and the downstream signaling pathways were evaluated biochemically. In addition, the activation state of MMPs in the retina of TIMP-3-deficient mice was examined by in situ zymography.
   RESULTS. The results of these studies determine an accentuation of pathologic VEGF-mediated angiogenesis in the cornea and laser-induced CNV in mice lacking TIMP-3. In the absence of the MMP inhibitor, pathophysiological changes were observed in the choroidal vasculature concomitantly with an increase in gelatinolytic activity. These results suggest that an imbalance of extracellular matrix homeostasis, together with a loss of an angiogenesis inhibitor, can prime vascular beds to be more responsive to an angiogenic stimulus.
   CONCLUSIONS. In light of the recent studies suggesting that genetic variants near TIMP-3 influence susceptibility to age-related macular degeneration, these results imply that TIMP-3 may regulate the development of the choroidal vasculature and is a likely contributor to increased susceptibility to choroidal neovascularization. (Invest Ophthalmol Vis Sci. 2011; 52: 6117-6123) DOI:10.1167/iovs.10-5899
C1 [Ebrahem, Quteba; Qi, Jian Hua; Sugimoto, Masahiko; Ali, Mariya; Sears, Jonathan E.; Cutler, Alecia; Anand-Apte, Bela] Cleveland Clin, Dept Ophthalmol, Lerner Coll Med, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Khokha, Rama] Univ Toronto, Ontario Canc Inst, Toronto, ON, Canada.
   [Vasanji, Amit] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA.
   [Anand-Apte, Bela] Cleveland Clin, Lerner Res Inst, Dept Mol Med, Cleveland, OH 44195 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation; University
   of Toronto; University Toronto Affiliates; University Health Network
   Toronto; Cleveland Clinic Foundation; Cleveland Clinic Foundation
RP Anand-Apte, B (通讯作者)，Cleveland Clin, Dept Ophthalmol, Lerner Coll Med, Cole Eye Inst, 13-161,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM anandab@ccf.org
FU National Institutes of Health [EY016490, CA106415, EY015638]; Foundation
   Fighting Blindness Center; Research to Prevent Blindness Challenge
   Grant; Ohio BRTT [05-29]; Research to Prevent Blindness Lew Wasserman
   Award; NATIONAL CANCER INSTITUTE [R01CA106415] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R24EY015638, R01EY016490] Funding
   Source: NIH RePORTER
FX Supported in part by National Institutes of Health Grants EY016490,
   CA106415, and EY015638; Foundation Fighting Blindness Center Grant;
   Research to Prevent Blindness Challenge Grant; Ohio BRTT Grant 05-29
   (BA-A); and a Research to Prevent Blindness Lew Wasserman Award (BA-A).
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NR 54
TC 31
Z9 35
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2011
VL 52
IS 9
BP 6117
EP 6123
DI 10.1167/iovs.10-5899
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 806XC
UT WOS:000293849400009
PM 21282576
OA Green Published
DA 2022-11-30
ER

PT J
AU da Silva, GR
   Junior, ADC
   Saliba, JB
   Berdugo, M
   Goldenberg, BT
   Naud, MC
   Ayres, E
   Orefice, RL
   Cohen, FB
AF da Silva, Gisele R.
   Junior, Armando da S. C.
   Saliba, Juliana B.
   Berdugo, Marianne
   Goldenberg, Brigitte T.
   Naud, Marie C.
   Ayres, Eliane
   Orefice, Rodrigo L.
   Cohen, Francine B.
TI Polyurethanes as supports for human retinal pigment epithelium cell
   growth
SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
LA English
DT Article
DE Retinal pigment epithelium (RPE); Biodegradable polyurethane;
   Polyurethane aqueous dispersion; In vivo short-term biocompatibility;
   Age-related macular degeneration; RPE graft
ID SYNTHETIC BIODEGRADABLE POLYMERS; HUMAN BRUCHS MEMBRANE; MACULAR
   DEGENERATION; AMNIOTIC MEMBRANE; TRANSPLANTATION; RPE; CULTURE;
   PATHOGENESIS; JUNCTIONS; DELIVERY
AB Purpose: The transplant of retinal pigment epithelium (RPE) cells on supports may well be an effective therapeutic approach to improve the visual results of patients with age-related macular degeneration. In this study, two biodegradable polyurethanes were investigated as supports for human RPE cells (ARPE-19).
   Methods: Polyurethane aqueous dispersions based on poly(caprolactone) and/or poly(ethylene glycol) as soft segments, and isophorone diisocyanate and hydrazine as hard segments were prepared. Polyurethane films were produced by casting the dispersions and allowing them to dry at room temperature for one week. The ARPE-19 cells were seeded onto the polyurethane films and they were investigated as supports for in vitro adhesion, proliferation, and uniform distribution of differentiated ARPE-19 cells. Additionally, the in vivo ocular biocompatibility of the polyurethane films was evaluated.
   Results: The RPE adhered to and proliferated onto the polyurethane supports, thus establishing cell-PUD surface interactions. Upon confluence, the cells formed an organized monolayer, exhibited a polygonal appearance, and displayed actin filaments which ran along the upper cytoplasm. At 15 days of seeding, the occluding expression was confirmed between adjacent cells, representing the barrier functionality of epithelial cells on polymeric surfaces and the establishment of cell-cell interactions. Results from the in vivo study indicated that polyurethanes exhibited a high degree of short-term intraocular biocompatibility.
   Conclusions: Biodegradable polyurethane films display the proper mechanical properties for an easy transscleral-driven subretinal implantation and can be considered as biocompatible supports for a functional ARPE-19 monolayer.
C1 [Berdugo, Marianne; Goldenberg, Brigitte T.; Naud, Marie C.; Cohen, Francine B.] INSERM, Inst Cordeliers, UMR872, F-75006 Paris, France.
   [da Silva, Gisele R.] Univ Fed Sao Joao del Rei, Sch Pharm, Chanadour, Divinopolis, Brazil.
   [Junior, Armando da S. C.; Saliba, Juliana B.] Univ Fed Minas Gerais, Sch Pharm, Belo Horizonte, MG, Brazil.
   [Ayres, Eliane; Orefice, Rodrigo L.] Univ Fed Minas Gerais, Dept Met & Mat Engn, Belo Horizonte, MG, Brazil.
   [Cohen, Francine B.] Fdn Ophtalmol Adolphe de Rothschild, Paris, France.
   [Cohen, Francine B.] Univ Paris 05, Hotel Dieu, Univ Hosp, Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; Universidade Federal de Sao Joao del-Rei; Universidade
   Federal de Minas Gerais; Universidade Federal de Minas Gerais;
   Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Hotel-Dieu - APHP; UDICE-French Research Universities; Universite Paris
   Cite
RP Cohen, FB (通讯作者)，INSERM, Inst Cordeliers, UMR872, 15 Rue Ecole Med, F-75006 Paris, France.
EM francine.behar@gmail.com
RI Cunha, Armando/G-1157-2012; Ayres, Eliane/AAG-2738-2020; Orefice,
   Rodrigo L/N-8055-2018
OI Cunha, Armando/0000-0002-1161-8936; Orefice, Rodrigo
   L/0000-0002-6046-4056; Ayres, Eliane/0000-0001-8734-0056
FU CAPES/MEC (Brazil); CNPq/MCT (Brazil); FAPEMIG (Minas Gerais - Brazil)
FX The authors would like to acknowledge financial support from the
   following institutions: CAPES/MEC (Brazil), CNPq/MCT (Brazil) and
   FAPEMIG (Minas Gerais - Brazil).
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NR 47
TC 12
Z9 12
U1 0
U2 6
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 0391-3988
J9 INT J ARTIF ORGANS
JI Int. J. Artif. Organs
PD FEB
PY 2011
VL 34
IS 2
BP 198
EP 209
DI 10.5301/IJAO.2011.6398
PG 12
WC Engineering, Biomedical; Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Transplantation
GA 748FI
UT WOS:000289375000018
PM 21374562
DA 2022-11-30
ER

PT J
AU Vojnikovic, B
   Synek, S
   Micovic, V
   Telezar, M
   Linsak, Z
AF Vojnikovic, Bozo
   Synek, Svatopluk
   Micovic, Vladimir
   Telezar, Mirna
   Linsak, Zeljko
TI Epidemiological Study of Sun Exposure and Visual Field Damage in
   Children in Primorsko-Goranska County - the Risk Factors of Earlier
   Development of Macular Degeneration
SO COLLEGIUM ANTROPOLOGICUM
LA English
DT Article
DE sunlight exposure; children; visual field damage
ID ISLAND RAB
AB The aim of this study was to examine the possible harmful effects of solar exposure on visual field damage in children living in Primorko-Goranska Country. Our previous work has shown noxious influence on visual field in children with anamnesis long term exposure to sunlight. This is an extended study, including children in Novi Vinodolski and Gorski kotar. We measured possible defect in isopteric visual field and macular-meridian thresholds. In the area of island of Rab these changes were the biggest, subsequently is Novi Vinodolski and at least Gorski kotar with the smallest range of eye complicates according to exposure to sunlight. These damages correlate with the areas of great solar emission. Damages in periphery isopters of visual field have shown the characteristics of periphery defect invagination, while increased macular thresholds in complete visual field was from 5 to 15 Asb. We can conclude that there is direct connection between increased sunlight and long-term exposure to sunlight on one side, and on the other side, damages of retinal perception. Increased sun exposure may represent very important factors in early occurrence and develop of Age-Related Macular Degeneration (AMD). It is recommended the children protection in summer months, as well as taking derivates of vitamin A and antioxidants. Nowadays, AMD is one of the most important causes of damaged visual field, pretend to be national problem if we don't use the adequate prevention. World Health Organization has to begin with prevention of AMD, including these risk factors.
C1 [Vojnikovic, Bozo] Daily Eye Clin Dr Bozo Vojnikovic, Rijeka 51000, Croatia.
   [Synek, Svatopluk] Masaryk Univ, Dept Ophthalmol & Optometry, St Anne Hosp, Fac Med, Brno, Czech Republic.
   [Micovic, Vladimir; Telezar, Mirna; Linsak, Zeljko] Teaching Inst Publ Hlth Primorsko Goranska Cty, Rijeka, Croatia.
C3 Masaryk University Brno; St Anne's University Hospital Brno
   (FNUSA-ICRC); University of Rijeka
RP Vojnikovic, B (通讯作者)，Daily Eye Clin Dr Bozo Vojnikovic, A Barca 3B, Rijeka 51000, Croatia.
EM decv@decv.com
RI Linšak, Željko ŽL/R-4873-2018; Mićović, Vladimir/R-4240-2018; Synek,
   Svatopluk/B-9815-2011; Linšak, Željko/AAX-1764-2020
OI Linšak, Željko ŽL/0000-0003-2389-1128; Mićović,
   Vladimir/0000-0002-0973-4823; 
CR Kovacevic D, 2008, COLLEGIUM ANTROPOL, V32, P9
   VOJNIKOVIC B, 2005, EINSTEINOV ZAKON ELE
   Vojnikovic B, 2007, COLLEGIUM ANTROPOL, V31, P43
   Vojnikovic B, 2009, COLLEGIUM ANTROPOL, V33, P747
NR 4
TC 6
Z9 7
U1 0
U2 3
PU COLLEGIUM ANTROPOLOGICUM
PI ZAGREB
PA INST ANTHROPOLOGICAL RES, P O BOX 290, ULICA GRADA VUKOVARA 72/IV, 10000
   ZAGREB, CROATIA
SN 0350-6134
J9 COLLEGIUM ANTROPOL
JI Coll. Anthropol.
PD APR
PY 2010
VL 34
SU 2
BP 57
EP 59
PG 3
WC Anthropology
WE Social Science Citation Index (SSCI)
SC Anthropology
GA 677AI
UT WOS:000283961100012
PM 21302703
DA 2022-11-30
ER

PT J
AU Cai, CS
   Li, LM
   Li, XL
   Chai, XY
   Sun, JJ
   Lu, YL
   Sui, XH
   Chen, PP
   Ren, QS
AF Cai, Changsi
   Li, Liming
   Li, Xiaoliang
   Chai, Xinyu
   Sun, Jingjing
   Lu, Yiliang
   Sui, Xiaohong
   Chen, Panpan
   Ren, Qiushi
TI Response properties of electrically evoked potential elicited by
   multi-channel penetrative optic nerve stimulation in rabbits
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Electrically evoked potential (EEP); Multi-electrode array; Rabbit;
   Optic nerve stimulation; Response properties; Visual prosthesis
ID SUBRETINAL MICROPHOTODIODES; VISUAL PROSTHESIS; HUMAN RETINA;
   FEASIBILITY; ELECTRODES; IMPLANTS; CORTEX; THRESHOLDS; VISION; ARRAYS
AB Visual prosthesis is a potential way to restore partial vision for the patients with degenerative retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Optic nerve stimulation with penetrating microelectrode array has been suggested as a possible method for visual prosthesis. The purpose of this study was to investigate the feasibility and basic response properties of cortical responses elicited by optic nerve stimulation with penetrating electrodes in rabbits. In this study, three triangularly or linearly configured platinum-iridium wire electrodes were inserted into the optic nerves of rabbits for electrical stimulation. The charge-balanced current pulses with amplitudes ranging from 10 to 100 mu A at 0.5 ms pulse duration were used as the electrical stimuli. The electrically evoked potentials (EEPs) were recorded with a 16-channel silver-ball electrode array in the rabbit visual cortex. Our experimental results showed that the activities of visual cortex could be effectively evoked by the optic nerve stimulation with penetrating electrodes. The threshold of current and charge density to elicit EEPs under optic nerve stimulation at 0.5 ms pulse duration was 20.3 +/- A 7.5 mu A and 37.8 +/- A 13.9 mu C/cm(2), respectively. Current stimuli with cathode-first pulses elicited larger cortical responses than that with anode-first pulses. The amplitude of P1 and extent of EEPs increased as the stimulating current amplitude increased, while the latency of P1 decreased. The spatial distributions of multi-channel EEPs in visual cortex demonstrated distinctively different properties under stimulation with different orientations of the stimulating electrodes.
C1 [Cai, Changsi; Li, Liming; Li, Xiaoliang; Chai, Xinyu; Sun, Jingjing; Lu, Yiliang; Sui, Xiaohong; Chen, Panpan; Ren, Qiushi] Shanghai Jiao Tong Univ, Dept Biomed Engn, Lab Visual Sci, Inst Laser Med & Biophoton, Shanghai 200240, Peoples R China.
C3 Shanghai Jiao Tong University
RP Ren, QS (通讯作者)，Shanghai Jiao Tong Univ, Dept Biomed Engn, Lab Visual Sci, Inst Laser Med & Biophoton, Room 406 Life Sci Bldg 2,800 Dong Chuan Rd, Shanghai 200240, Peoples R China.
EM renqsh@sjtu.edu.cn
RI Cai, Changsi/U-4729-2019; Ren, Qiushi/D-1451-2012
FU National Basic Research Program of China [2005CB724302]; National
   Natural Science Foundation of China [60588101, 60871091]; Shanghai
   Pujiang Program [07PJ14050]; National High Technology Research and
   Development Program of China [2006AA04Z356]; Shanghai Commission of
   Science and Technology [064119540]
FX The authors thank Yuxiu Liu and Ting Liang for their contributions to
   the performance of animal surgery. This research is supported by the
   National Basic Research Program of China ( 973 Program, 2005CB724302),
   National Science Fund for Distinguished Young Scholars from the National
   Natural Science Foundation of China ( 60588101), Shanghai Pujiang
   Program ( 07PJ14050), The National Natural Science Foundation of China (
   60871091), National High Technology Research and Development Program of
   China ( 863 Program, 2006AA04Z356), Shanghai Commission of Science and
   Technology ( 064119540).
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NR 43
TC 15
Z9 17
U1 0
U2 9
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 JUN
PY 2009
VL 118
IS 3
BP 191
EP 204
DI 10.1007/s10633-008-9157-2
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 448KH
UT WOS:000266261000003
PM 19050950
DA 2022-11-30
ER

PT J
AU Yu, AL
   Lorenz, RL
   Haritoglou, C
   Kampik, A
   Welge-Lussen, U
AF Yu, Alice L.
   Lorenz, Reinhard L.
   Haritoglou, Christos
   Kampik, Anselm
   Welge-Lussen, Ulrich
TI Biological effects of native and oxidized low-density lipoproteins in
   cultured human retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE lipoprotein; retinal pigment epithelium; age-related macular
   degeneration
ID AGE-RELATED MACULOPATHY; EXTRACELLULAR-MATRIX SYNTHESIS;
   SMOOTH-MUSCLE-CELLS; BLUE MOUNTAINS EYE; BEAVER DAM EYE; MACULAR
   DEGENERATION; IN-VIVO; OXIDATIVE MODIFICATION; INCREASED EXPRESSION;
   SCAVENGER RECEPTORS
AB Age-related macular degeneration (AMD) and artherosclerosis share common characteristics in their pathogenesis. In this study, we investigated the effects of lipoproteins like native (n)-LDL, oxidized (ox)-LDL and high-density lipoprotein (HDL) on advanced senescence, extracellular matrix accumulation, cell loss, and transforming growth factor-beta2 (TGF-beta 2) expression in cultured human retinal pigment epithelial (RPE) cells. Primary human RPE cells were incubated with 10-100 mu g/ml n-LDL, ox-LDL, and HDL for 24 h. For determination of advanced senescence, beta-galactosidase staining was used. The induction of fibronectin (Fn), laminin alpha 1 (Laa1), and collagen type IV alpha 2 (Col4a2) mRNA was quantified by real-time PCR. Cell loss was investigated by live dead assay. Expression of TGF-beta 2 was analyzed by real-time PCR and ELISA assays. Ox-LDL accelerated dose-dependently the onset of RPE senescence, whereas LDL and HDL had no effect. LDL and ox-LDL led to induced expression of Fn, Laa1 and Col4a2, whereas HDL had no influence. Incubation of RPE cells with 100 mu g/ml ox-LDL induced marked cell death compared to untreated control cells. Expression of TGF-beta 2 was dose-dependently increased by LDL and ox-LDL.
   LDL and ox-LDL induced cellular changes in RPE cells in vitro, which may resemble pathogenic events of AMD. These results may provide further information about the effects of LDL and ox-LDL in the human RPE and their potential role in the pathogenesis of AMD. (C) 2008 Published by Elsevier Ltd.
C1 [Welge-Lussen, Ulrich] Univ Erlangen Nurnberg, Augenklin, Dept Ophthalmol, D-91054 Erlangen, Germany.
   [Yu, Alice L.; Haritoglou, Christos; Kampik, Anselm; Welge-Lussen, Ulrich] Univ Munich, Dept Ophthalmol, D-80336 Munich, Germany.
   [Lorenz, Reinhard L.] Univ Munich, Inst Prophylaxis Cardiovasc Dis, D-80336 Munich, Germany.
C3 University of Erlangen Nuremberg; University of Hamburg; University
   Medical Center Hamburg-Eppendorf; University of Munich; University of
   Munich
RP Welge-Lussen, U (通讯作者)，Univ Erlangen Nurnberg, Augenklin, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany.
EM Ulrich.Welge@uk-erlangen.de
FU DFG WE [2577/2-1]; DOG Research
FX This work was supported by DFG WE 2577/2-1 and DOG Research Support to
   UW-L.
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NR 73
TC 26
Z9 26
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 MAR
PY 2009
VL 88
IS 3
BP 495
EP 503
DI 10.1016/j.exer.2008.10.028
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 427MR
UT WOS:000264783900020
PM 19071111
DA 2022-11-30
ER

PT J
AU Shin, TM
   Isas, JM
   Hsieh, CL
   Kayed, R
   Glabe, CG
   Langen, R
   Chen, J
AF Shin, Thuzar M.
   Isas, J. Mario
   Hsieh, Chia-Ling
   Kayed, Rakez
   Glabe, Charles G.
   Langen, Ralf
   Chen, Jeannie
TI Formation of soluble amyloid oligomers and amyloid fibrils by the
   multifunctional protein vitronectin
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID HUMAN PLASMA VITRONECTIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1;
   DESMIN-RELATED CARDIOMYOPATHY; MACULAR DEGENERATION; ALZHEIMERS-DISEASE;
   IMMUNOHISTOCHEMICAL LOCALIZATION; IN-VIVO; COMPLEMENT ACTIVATION;
   MISFOLDING DISEASES; COMMON MECHANISM
AB Background: The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins.
   Results: We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation.
   Conclusion: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.
C1 [Shin, Thuzar M.; Isas, J. Mario; Hsieh, Chia-Ling; Langen, Ralf; Chen, Jeannie] Estelle Doheny Eye Fdn, Zilhka Neurogenet Inst, Los Angeles, CA 90033 USA.
   [Kayed, Rakez] Univ Texas Med Branch, Sch Med, Dept Neurol, Galveston, TX 77555 USA.
   [Glabe, Charles G.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
C3 Doheny Eye Institute; University of Texas System; University of Texas
   Medical Branch Galveston; University of California System; University of
   California Irvine
RP Langen, R (通讯作者)，Estelle Doheny Eye Fdn, Zilhka Neurogenet Inst, Los Angeles, CA 90033 USA.
EM thuzar@usc.edu; isas@usc.edu; chialing@usc.edu; rakayed@utmb.edu;
   cglabe@uci.edu; langen@usc.edu; jeannie@usc.edu
OI Shin, Thuzar/0000-0002-1880-7422
FU National Aging Institute in the form of an Alzheimer disease research
   center [NIA AG05142]; National Eye Institute [EY03040]; Larry L.
   Hillblom Foundation; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [P30EY003040, R01EY012155] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [P50AG005142] Funding Source: NIH RePORTER
FX This work was supported by National Aging Institute in the form of an
   Alzheimer disease research center (NIA AG05142), the National Eye
   Institute in the form of a Vision Core Grant to Doheny Eye Institute
   (EY03040), a network grant from the Larry L. Hillblom Foundation (C. G.,
   J. C. and R. L.), and a Medical Student Research Fellowship from
   Research to Prevent Blindness (to T. M. S. and J. C.).
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NR 78
TC 44
Z9 46
U1 0
U2 9
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD OCT 21
PY 2008
VL 3
AR 16
DI 10.1186/1750-1326-3-16
PG 12
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 439RS
UT WOS:000265645300002
PM 18939994
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Boucart, M
   Dinon, JF
   Despretz, P
   Desmettre, T
   Hladiuk, K
   Oliva, A
AF Boucart, Muriel
   Dinon, Jean-Francois
   Despretz, Pascal
   Desmettre, Thomas
   Hladiuk, Katrine
   Oliva, Aude
TI Recognition of facial emotion in low vision: A flexible usage of facial
   features
SO VISUAL NEUROSCIENCE
LA English
DT Article
DE low vision; macular degeneration; face perception; emotion; spatial
   frequency
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; FACE RECOGNITION;
   CONTRAST SENSITIVITY; PERIPHERAL-VISION; SEX-DIFFERENCES; READING SPEED;
   PERCEPTION; EXPRESSIONS; INFORMATION
AB Age-related macular degeneration (AMD) is I major Cause of visual impairment in people older than 50 years in Western countries, affecting essential tasks Such as reading and face recognition. Here we investigated the mechanisms underlying the deficit in recognition of facial expressions in an AMD population with low vision. Pictures of faces displaying different emotions with the mouth open or closed were centrally displayed for 300 ms. Participants with AMD with low acuity (mean 20/200) and normally sighted age-matched controls performed one of two emotion tasks: detecting whether a face had an expression or not (expressive/non expressive (EXNEX) task) or categorizing the facial emotion as happy, angry, or neutral (categorization of expression (CATEX) task). Previous research has shown that healthy observers are mainly using high spatial frequencies in an EXNEX task while performance at a CATEX task was preferentially based on low spatial frequencies. Due to impaired processing of high spatial frequencies in central vision, we expected and observed that AMD participants failed Lit deciding whether a face was expressive or not but categorized normally the emotion of the face (e.g., happy, angry, neutral). Moreover, we observed that AMD participants mostly identified emotions using the lower part of the face (mouth). Accuracy did not differ between the two tasks for normally sighted observers. The results indicate that AMD participants are able to identify facial emotion but must base their decision mainly on the low spatial frequencies, as they lack the perception of finer details.
C1 [Boucart, Muriel; Dinon, Jean-Francois; Despretz, Pascal] Univ Lille 2, CNRS, Lab Neurosci Fonct & Pathol, Lille, France.
   [Desmettre, Thomas; Hladiuk, Katrine] Ctr Imagerie Laser & Readaptat Basse Vis, Lambersart, France.
   [Oliva, Aude] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 Centre National de la Recherche Scientifique (CNRS); Universite de Lille
   - ISITE; Universite de Lille; Massachusetts Institute of Technology
   (MIT)
RP Boucart, M (通讯作者)，CHRU, Hop Roger Salengro, Serv EFV, Lab Neurosci Fonct & Pathol CNRS UMR 8160, F-59037 Lille, France.
EM m-boucart@chru-lille.fr
FU CNRS; University Lille 2; Nord-Pas de Calais, France
FX The authors would like to thank Michelle Greene, Danny Dilks, and two
   anonymous reviewers for helpful comments on the manuscript. This work
   was funded by a CNRS interdisciplinary grant for life sciences to M.B.
   and engineering to J.C. Kastelik. J.-F.D. was supported by a Ph.D.
   graduate fellowship from University Lille 2 and from Nord-Pas de Calais,
   France.
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NR 57
TC 33
Z9 33
U1 1
U2 27
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PD JUL-AUG
PY 2008
VL 25
IS 4
BP 603
EP 609
DI 10.1017/S0952523808080656
PG 7
WC Neurosciences; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology
GA 347YB
UT WOS:000259176500007
PM 18631411
DA 2022-11-30
ER

PT J
AU Hammer, M
   Richter, S
   Kobuch, K
   Mata, N
   Schweitzer, D
AF Hammer, Martin
   Richter, Sandra
   Kobuch, Karin
   Mata, Nathan
   Schweitzer, Dietrich
TI Intrinsic tissue fluorescence in an organotypic perfusion culture of the
   porcine ocular fundus exposed to blue light and free radicals
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE ocular fundus; organ culture; autofluorescence; fluorescence
   spectroscopy; lipofuscin
ID PIGMENT EPITHELIAL-CELLS; RETINAL LIPOFUSCIN GRANULES;
   LIPID-PEROXIDATION; BRUCHS MEMBRANE; AUTOFLUORESCENCE; PRODUCTS;
   PROTEIN; A2E; ACCUMULATION; DAMAGE
AB Background A wide variety of pathological pathways may result in age-related macular degeneration. Because of its complexity, there is no comprehensive model of the disease yet. One key feature is the accumulation of the autofluorescent pigment lipofuscin in the retinal pigment epithelium (RPE). Thus, we developed an organotypic perfusion culture model of the porcine ocular fundus, generating lipofuscin under exposure to blue light and hydrogen peroxide.
   Methods Porcine fundi (choroid, Bruch's membrane, RPE, and retina) were explanted in toto, transferred into a perfusion culture chamber, perfused with cell culture medium and kept at 37 degrees C. Free radical stress was induced by supplementation of H2O2, and/or the specimens were exposed to blue light, or kept untreated as controls. After a culture period of 7 days, the specimens were subject to microscopic inspection, histology, fluorescence microscopy, and measurement of fluorescence spectra as well as fluorescence decay times.
   Results Histology showed atrophic ganglion cells and rod outer segments. All other tissue structures were morphologically intact. Compared to the controls, RPE and retina exposed to light showed increased fluorescence, which was shifted towards shorter wavelengths. The fluorescence spectra and decays resembled that of lipofuscin granules isolated from human donor eyes. HPLC analysis revealed the abundance of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E), its precursor products, as well as two new, green-emitting fluorophores.
   Conclusions Porcine ocular fundi were successfully preserved in an organotypic perfusion culture for 7 days, and exhibited remarkable autofluorescence after light and free radical exposure, making the model suitable for investigations of lipofuscinogenesis.
C1 [Hammer, Martin; Richter, Sandra; Schweitzer, Dietrich] Univ Jena, Dept Ophthalmol, D-07740 Jena, Germany.
   [Kobuch, Karin] Univ Regensburg, Dept Ophthalmol, D-93053 Regensburg, Germany.
   [Mata, Nathan] SIRiON Therapeut, San Diego, CA 92121 USA.
C3 Friedrich Schiller University of Jena; University of Regensburg
RP Hammer, M (通讯作者)，Univ Jena, Dept Ophthalmol, Bachstr 18, D-07740 Jena, Germany.
EM martin.hammer@med.uni-jena.de
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NR 45
TC 16
Z9 16
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2008
VL 246
IS 7
BP 979
EP 988
DI 10.1007/s00417-008-0789-4
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 307JO
UT WOS:000256315400007
PM 18351374
DA 2022-11-30
ER

PT J
AU Ghazi, NG
   Knape, RM
   Kirk, TQ
   Tiedeman, JS
   Conway, BP
AF Ghazi, Nicola G.
   Knape, Robert M.
   Kirk, Tyler Q.
   Tiedeman, James S.
   Conway, Brian P.
TI Intravitreal bevacizumab (Avastin) treatment of retinal angiomatous
   proliferation
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE bevacizumab (Avastin); age-related macular degeneration; retinal
   angiomatous proliferation
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; MACULAR DEGENERATION;
   PHOTODYNAMIC THERAPY; SURGICAL ABLATION; TRIAMCINOLONE ACETONIDE;
   VERTEPORFIN; RANIBIZUMAB; ANASTOMOSES; DETACHMENTS; TOXICITY
AB Purpose: To report our short-term experience with intravitreal bevacizumab treatment of retinal angiomatous proliferation (RAP) in neovascular age-related macular degeneration (AM D).
   Methods: A retrospective, interventional case series was performed that included 13 patients who received intravitreal injection of bevacizumab (1.25 mg) for treatment of RAP and completed 12 weeks of follow-up. Ophthalmic assessment included determination of best-corrected Snellen visual acuity (BCVA), complete ocular examination, fluorescein angiography, and optical coherence tomography (OCT). Injections were repeated if no further improvement or worsening was observed after an initial favorable functional and/or anatomical response. Main outcome measures were BCVA and central macular thickness (CMT) measured by OCT.
   Results: Twelve eyes (92.3%) had stable or improved BCVA, and 8 eyes (61.5%) had at least 2 lines of vision improvement. The average BCVA improved from 20/203 at baseline to 20/113 at 12 weeks (P = 0.001). Average CMT improved from 369 mu m at baseline to 216 mu m (P = 0.016) and 315 mu m (P = 0.020) at 8 weeks and 12 weeks, respectively. Six eyes underwent fluorescein angiography at the 12-week follow-up visit; 3 (50%) of these eyes had decreased leakage compared with baseline. Both stabilization of vision and improved CMT were maintained for at least 8 weeks after a single injection in almost all eyes. No significant side effects were observed.
   Conclusion: These short-term data suggest that bevacizumab is a viable treatment option for RAP in AMD. The initial treatment effect appears to be maintained for at least 8 weeks.
C1 [Ghazi, Nicola G.; Knape, Robert M.; Kirk, Tyler Q.; Tiedeman, James S.; Conway, Brian P.] Univ Virginia, Dept Ophthalmol, Charlottesville, VA 22908 USA.
C3 University of Virginia
RP Ghazi, NG (通讯作者)，Univ Virginia, Dept Ophthalmol, POB 800715, Charlottesville, VA 22908 USA.
EM ngg6f@virginia.edu
RI Ghazi, Nicola/AAH-4169-2020
OI Ghazi, Nicola/0000-0001-9255-8025
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NR 45
TC 36
Z9 39
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2008
VL 28
IS 5
BP 689
EP 695
DI 10.1097/IAE.0b013e318162d982
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 302KQ
UT WOS:000255967600003
PM 18463511
DA 2022-11-30
ER

PT J
AU Stopa, M
   Bower, BA
   Davies, E
   Izatt, JA
   Toth, CA
AF Stopa, Marcin
   Bower, Bradley A.
   Davies, Emily
   Izatt, Joseph A.
   Toth, Cynthia A.
TI Correlation of pathologic features in spectral domain optical coherence
   tomography with conventional retinal studies
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE spectral domain optical coherence tomography; three-dimensional imaging
   of the retina; Fourier domain optical coherence tomography; image
   processing; imaging of the retina; age-related macular degeneration;
   choroidal neovascularization; cystoid macular edema; macular
   degeneration
ID DIABETIC MACULAR EDEMA; ULTRAHIGH-RESOLUTION; HIGH-SPEED; CHOROIDAL
   NEOVASCULARIZATION; DEGENERATION; IMAGES; DISEASES; FLUID
AB Purpose: To delineate pathologic changes in retinal cross sections obtained with spectral (Fourier) domain optical coherence tomography (SDOCT), so that the findings are maintained when collapsed into a two-dimensional fundus image for comparison with conventional retinal studies.
   Methods: SDOCT of the posterior pole of 12 eyes (5 with neovascular age-related macular degeneration [AMD]; 7 with nonneovascular AMD) produced three-dimensional stacks of scans. Location of pathologic features was delineated with color markings in each scan before the stack was collapsed along the depth axis. This en face image contained retinal vessel shadowing and preserved color markings of delineated pathologic features relative to the vessel pattern and was superimposed onto conventional studies.
   Results: For patients with neovascular AMD, location and extent of choroidal neovascularization, macular edema, and subretinal fluid were visible on the two-dimensional summed images and, in some cases, involved sites not suspected with conventional imaging. For patients with nonneovascular AMD, the location of drusen and geographic atrophy were correlated with autofluorescence images. For one eye with drusen and three eyes with neovascular AMD, presence or extent of subretinal fluid identified by SDOCT was not visible using other imaging methods.
   Conclusions: In this pilot AMD study, pathologic features within SDOCT scans were transferred into two-dimensional en face projections, enabling researchers to correlate lateral extent of pathologic features from SDOCT with conventional studies. This integration of SDOCT with other retinal studies is promising and will be useful to study the relationship between local OCT morphology and other parameters of retinal disease or function.
C1 [Stopa, Marcin; Davies, Emily; Izatt, Joseph A.; Toth, Cynthia A.] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
   [Stopa, Marcin; Bower, Bradley A.] Poznan Univ Med Sci, Dept Ophthalmol, Poznan, Poland.
   [Bower, Bradley A.; Izatt, Joseph A.; Toth, Cynthia A.] Duke Univ, Sch Engn, Dept Biomed Engn, Durham, NC 27706 USA.
C3 Duke University; Poznan University of Medical Sciences; Duke University
RP Toth, CA (通讯作者)，Duke Univ, Ctr Eye, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM cynthia.toth@duke.edu
RI toth, cynthia a/F-5614-2011; Toth, Cynthia/L-5534-2019; Izatt,
   Joseph/C-9067-2014; Stopa, Marcin/R-2772-2018
OI Toth, Cynthia/0000-0002-2324-0854; Izatt, Joseph/0000-0003-1993-2249;
   Stopa, Marcin/0000-0001-9540-9500
FU NATIONAL CENTER FOR RESEARCH RESOURCES [R21RR019769] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
   [R24EB000243] Funding Source: NIH RePORTER; NCRR NIH HHS [RR 019769]
   Funding Source: Medline; NIBIB NIH HHS [EB 000243] Funding Source:
   Medline
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NR 41
TC 55
Z9 57
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 FEB
PY 2008
VL 28
IS 2
BP 298
EP 308
DI 10.1097/IAE.0b013e3181567798
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 266TV
UT WOS:000253460800014
PM 18301035
DA 2022-11-30
ER

PT J
AU Rosenthal, JM
   Kim, J
   de Monastario, F
   Thompson, DJS
   Bone, RA
   Landrum, JT
   de Moura, FF
   Khachik, F
   Chen, H
   Schleicher, RL
   Ferris, FL
   Chew, EY
AF Rosenthal, Julie M.
   Kim, Jonghyeon
   de Monastario, Francisco
   Thompson, Darby J. S.
   Bone, Richard A.
   Landrum, John T.
   de Moura, Fabiana F.
   Khachik, Frederick
   Chen, Huiping
   Schleicher, Rosemary L.
   Ferris, Frederick L., III
   Chew, Emily Y.
TI Dose-ranging study of lutein supplementation in persons aged 60 years or
   older
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SUBFOVEAL CHOROIDAL
   NEOVASCULARIZATION; RESONANCE RAMAN MEASUREMENT; RANDOMIZED
   CLINICAL-TRIALS; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; BIOLOGICAL
   VARIATION; BEVACIZUMAB AVASTIN; BETA-CAROTENE
AB PURPOSE. To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age- related macular degeneration (AMD).
   METHODS. Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation.
   RESULTS. The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5- ,5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 mu g/dL (2-fold increase), from 17.8 to 59.2 mu g/dL (2.9-fold increase), and from 15.1 to 66.8 mu g/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests.
   CONCLUSIONS. Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD.
C1 NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
   EMMES Corp, Rockville, MD USA.
   NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA.
   Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Emmes Corporation; National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI); State University System of Florida;
   Florida International University; University System of Maryland;
   University of Maryland College Park; US Food & Drug Administration
   (FDA); Centers for Disease Control & Prevention - USA
RP Chew, EY (通讯作者)，CRC, Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
RI Khachik, Frederick/C-5055-2009
OI De Moura, Fabiana F./0000-0001-8176-5352; Ferris,
   Frederick/0000-0002-4933-0639
FU Intramural NIH HHS [ZIA EY000485-01, Z99 EY999999] Funding Source:
   Medline; NIGMS NIH HHS [S06GM0825] Funding Source: Medline
CR Arnold J, 2001, AM J OPHTHALMOL, V131, P541
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NR 35
TC 48
Z9 56
U1 1
U2 6
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 2006
VL 47
IS 12
BP 5227
EP 5233
DI 10.1167/iovs.05-1513
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 110TW
UT WOS:000242404900016
PM 17122107
DA 2022-11-30
ER

PT J
AU Costa, RA
   Farah, ME
   Cardillo, JA
   Calucci, D
   Williams, GA
AF Costa, RA
   Farah, ME
   Cardillo, JA
   Calucci, D
   Williams, GA
TI Immediate indocyanine green angiography and optical coherence tomography
   evaluation after photodynamic therapy for subfoveal choroidal
   neovascularization
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-realted macular degeneration; neovascular; complex; subretinal
   membrane; verteporfin
ID MACULAR DEGENERATION; VERTEPORFIN
AB Purpose: To better understand the mechanisms of action of photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV), the authors evaluated the retinal and choroidal response immediately after treatment with serial optical coherence tomography (OCT) and indocyanine green angiography (ICGA).
   Methods: This study was a prospective, noncomparative case series. PDT was performed on nine eyes of nine consecutive patients who presented with subfoveal CNV due to age-related macular degeneration, and serial evaluation with OCT as well as ICGA was performed at 20-minute intervals for the first 2 hours and then at 1 week, 1 month, and 3 months.
   Results: In the first 2 hours after PDT, OCT showed an increase in the thickness of the retina in the treatment area due to fluid leakage from the neovascular complex as confirmed by ICGA. At 1 week, marked reduction of intraretinal/subretinal fluid was observed in all patients. Neovascular complex nonperfusion by ICGA was associated with some degree of choroidal hypoperfusion in the treatment area. Return of the foveal contour by OCT was optimal after 1 month of treatment. At 3 months, choroidal reperfusion by ICGA and recurrent intraretinal/subretinal fluid by OCT were observed.
   Conclusions: Serial OCT and ICGA evaluation after PDT suggests that the initial successful CNV nonperfusion as shown by fluorescein angiography at 1 week occurs by means of selective PDT damage to the lesion and/or reduced choroidal blood flow in the treatment area, thereby decreasing intraretinal/subretinal fluid and facilitating restoration of the retinal architecture.
C1 Univ Fed Sao Paulo, Dept Ophthalmol, Inst Visao, IPEPO, Sao Paulo, Brazil.
   Beaumont Eye Inst, Associated Retinal Consultants, Royal Oak, MI USA.
C3 Universidade Federal de Sao Paulo (UNIFESP)
RP Costa, RA (通讯作者)，Rua Italia 1905 Apto 74, BR-14801350 Sao Paulo, Brazil.
EM roger.retina@globo.com
RI Farah, Michel Eid E/F-3285-2012; Costa, Rogerio A/E-6930-2013
OI Farah, Michel Eid E/0000-0001-5951-0193; Costa, Rogerio
   A/0000-0002-0800-2233; Cardillo, Jose Augusto/0000-0002-5791-3201
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NR 20
TC 62
Z9 70
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD APR
PY 2003
VL 23
IS 2
BP 159
EP 165
DI 10.1097/00006982-200304000-00004
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 679AK
UT WOS:000182898700004
PM 12707593
DA 2022-11-30
ER

PT J
AU Abdouh, M
   Lu, MLS
   Chen, YX
   Goyeneche, AN
   Burnier, JV
   Burnier, MN
AF Abdouh, Mohamed
   Lu, Melissa
   Chen, Yunxi
   Goyeneche, Alicia N.
   Burnier, Julia Valdemarin
   Burnier, Miguel N.
TI Filtering blue light mitigates the deleterious effects induced by the
   oxidative stress in human retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Blue light; Retinal pigment epithelial cells; Intraocular lens;
   Oxidative stress
ID MACULAR DEGENERATION; UVEAL MELANOMA; HUMAN RPE; LIPOFUSCIN; A2E;
   PROTECTION; EXPOSURE; LENS; SUNLIGHT; DISEASE
AB Age-related macular degeneration (AMD) is a major cause of blindness in elderly. It is characterized by the loss of central vision due to damaged retinal pigment epithelial (RPE) cells and photoreceptors. Blue Light (BL) exposure was proposed as a risk factor for AMD progression. We undertook this study to determine the effects of BL on the behaviour of RPE cells and their potential mitigation by BL-filtering intraocular lenses (IOL). Human RPE cells were exposed or not to BL, with the absence or presence of either a clear ultraviolet (UV)-filtering IOL (CIOL), or a yellow UV-and BL-filtering IOL (YIOL). Cells were analyzed for their oxidative stress by measuring the levels of reactive oxygen species (ROS), and their viability. BL exposure significantly increased the levels of both total cellular and mitochondrial ROS. While this increase was not affected by placing the CIOL in the BL beam, YIOL decreased the levels of both ROS reservoirs. Increased ROS production was accompanied by increased cell death which was similarly decreased when cells were protected with the YIOL. Pre-treatment of cells with N-acetylcycteine (NAC) abolished the increased cell death, suggesting that the effects of BL on cell viability were mainly due to increased levels of ROS. BL is deleterious to RPE cells due to increased oxidative stress and cell death. These effects were mitigated by filtering these radiations. The use of BL-filtering devices may represent a strategy to reduce these effects on RPE cells and delay the onset of AMD.
C1 [Abdouh, Mohamed; Lu, Melissa; Chen, Yunxi; Goyeneche, Alicia N.; Burnier, Julia Valdemarin; Burnier, Miguel N.] McGill Univ, Hlth Ctr, Res Inst, Canc Res Program, Montreal, PQ, Canada.
   [Abdouh, Mohamed; Lu, Melissa; Goyeneche, Alicia N.; Burnier, Miguel N.] McGill Univ, Henry C Witelson Ocular Pathol Lab, Montreal, PQ, Canada.
   [Burnier, Julia Valdemarin] McGill Univ, Dept Pathol, Expt Pathol Unit, Montreal, PQ, Canada.
   [Burnier, Julia Valdemarin] McGill Univ, Gerald Bronfman Dept Oncol, Montreal, PQ, Canada.
C3 McGill University; McGill University; McGill University; McGill
   University
RP Abdouh, M (通讯作者)，1001 Decarie Blvd E02-2389, Montreal, PQ H4A 3J1, Canada.
EM mohamed.abdouh@muhc.mcgill.ca
OI Chen, Yunxi/0000-0001-7575-2686; burnier, julia/0000-0002-2184-2157;
   Abdouh, Mohamed/0000-0003-0702-9335
FU Alcon Research LLC
FX This work was supported by Alcon Research LLC. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. We would like to acknowledge the
   technical expertise and scientific support of the Drug Discovery
   Platform of RI-MUHC for A2E synthesis, especially Anne-Laure Larroque
   and Sanjoy Kumar-Das. We also like to acknowledge the Alcon Laboratories
   for providing the intraocular lenses.
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NR 56
TC 1
Z9 1
U1 3
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2022
VL 217
AR 108978
DI 10.1016/j.exer.2022.108978
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZR0VU
UT WOS:000767512600004
PM 35134392
DA 2022-11-30
ER

PT J
AU Trott, M
   Smith, L
   Veronese, N
   Pizzol, D
   Barnett, Y
   Gorely, T
   Pardhan, S
AF Trott, Mike
   Smith, Lee
   Veronese, Nicola
   Pizzol, Damiano
   Barnett, Yvonne
   Gorely, Trish
   Pardhan, Shahina
TI Eye disease and mortality, cognition, disease, and modifiable risk
   factors: an umbrella review of meta-analyses of observational studies
SO EYE
LA English
DT Review
ID OPEN-ANGLE GLAUCOMA; SYSTEMATIC REVIEWS; MACULAR DEGENERATION; VISUAL
   IMPAIRMENT; VISION IMPAIRMENT; ASSOCIATION; HEALTH; EXCESS
AB Globally, 2.2 billion people live with some form of vision impairment and/or eye disease. To date, most systematic reviews examining associations have focused on a single eye disease and there is no systematic evaluation of the relationships between eye diseases and diverse physical and mental health outcomes. Moreover, the strength and reliability of the literature is unclear. We performed an umbrella review of observational studies with meta analyses for any physical and/or mental comorbidities associated with eye disease. For each association, random-effects summary effect size, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence from convincing to weak. 34 studies were included covering 58 outcomes. No outcomes yielded convincing evidence, six outcomes yielded highly suggestive results (cataract positively associated with type 2 diabetes, open-angled glaucoma positively associated with myopia and diabetes, diabetic retinopathy positively associated with cardiovascular disease and cardiovascular mortality, and retinopathy of prematurity positively associated with chorioamnionitis), eight outcomes yielded suggestive results (diabetic retinopathy positively associated with all-cause mortality and depression, diabetic macular oedema positively associated with dyslipidaemia, cataract positively associated with gout, nuclear sclerosis positively associated with all-cause mortality, open angled glaucoma positively associated with migraine and hypertension, and age-related macular degeneration positively associated with diabetes), and 18 outcomes yielded weak evidence. Results show highly suggestive or suggestive evidence for associations between several types of eye diseases with several comorbid outcomes. Practitioners and public health policies should note these findings when developing healthcare policies.
C1 [Trott, Mike; Pardhan, Shahina] Anglia Ruskin Univ, Sch Med, Vis & Eye Res Inst VERI, Cambridge, England.
   [Trott, Mike; Smith, Lee] Anglia Ruskin Univ, Cambridge Ctr Sport & Exercise Sci, Cambridge, England.
   [Veronese, Nicola] CNR, Neurosci Inst, Aging Branch, Padua, Italy.
   [Veronese, Nicola] Univ Palermo, Dept Geriatr, Palermo, Italy.
   [Pizzol, Damiano] Italian Agcy Dev Cooperat Khartoum, Khartoum, Sudan.
   [Barnett, Yvonne] Anglia Ruskin Univ, Sch Life Sci, Cambridge, England.
   [Gorely, Trish] Univ Highlands & Isl, Ctr Hlth Sci, Dept Nursing & Midwifery, Inverness, Scotland.
C3 Anglia Ruskin University; University of Cambridge; Anglia Ruskin
   University; Consiglio Nazionale delle Ricerche (CNR); University of
   Palermo; Anglia Ruskin University; UHI Millennium Institute
RP Trott, M (通讯作者)，Anglia Ruskin Univ, Sch Med, Vis & Eye Res Inst VERI, Cambridge, England.; Trott, M (通讯作者)，Anglia Ruskin Univ, Cambridge Ctr Sport & Exercise Sci, Cambridge, England.
EM mike.trott@aru.ac.uk
RI Trott, Mike/AAU-2633-2021; Veronese, Nicola/K-4343-2018
OI Trott, Mike/0000-0001-5978-3407; Veronese, Nicola/0000-0002-9328-289X
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NR 70
TC 3
Z9 3
U1 2
U2 5
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2022
VL 36
IS 2
BP 369
EP 378
DI 10.1038/s41433-021-01684-x
EA JUL 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YQ7VR
UT WOS:000673191800002
PM 34272511
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Dan, TT
   Hu, Y
   Han, C
   Fan, ZH
   Huang, ZB
   Zhang, B
   Tao, GH
   Liu, BY
   Yu, HH
   Cai, HM
AF Dan, Tingting
   Hu, Yu
   Han, Chu
   Fan, Zhihao
   Huang, Zhuobin
   Zhang, Bin
   Tao, Guihua
   Liu, Baoyi
   Yu, Honghua
   Cai, Hongmin
TI Fusion of multi-source retinal fundus images via automatic registration
   for clinical diagnosis
SO NEUROCOMPUTING
LA English
DT Article
DE Retinal fundus image registration; Multiple sources; Adjustable
   threshold selection; Multiple features; Geometric structure constraint
AB Diabetic retinopathy, age-related macular degeneration and glaucoma, are the leading causes of visual impairment or blindness of the population across different ages. Retinal fundus imaging is a clinically regular tool for the diagnosis of retinal diseases. In the interest of having a comprehensive understanding of the fundus condition, it is valuable to leverage multiple fundus images from different modalities. However, a direct fusion of the multi-source fundus images eases to mis-align the physiological structure or spatial position due to possible eyeball rotations or head movements. The problem turns out to be more severe if the images were corrupted by ill conditions on eyes, such as micro-bleeding and plaques. To tackle this problem, we propose a multi-source registration model for retinal fundus images. Our proposed method considers multiple correspondences and dual structural constraints during the registration process. The method firstly selects adequate feature points by an adjustable threshold selection strategy. Then a feature-guided correspondence estimation model is established to build complementary features. Finally, their spatial transformation is built by using mean shift evolution. The evolution is guided by Tikhonov regularization on dual geometric structures. It overcomes the mess of mean shift vector field and mitigating the ill-posed displacement in field recovery. We have conducted our method on the collected 220 multi-source retinal fundus image pairs, which involve minor and larger displacement or severe retinopathy lesions, as well as additive different intensities of Gaussian noises. Extensive experiments demonstrate that the proposed method consistently outperforms seven feature-based methods. (c) 2021 Published by Elsevier B.V.
C1 [Dan, Tingting; Hu, Yu; Fan, Zhihao; Huang, Zhuobin; Zhang, Bin; Tao, Guihua; Cai, Hongmin] South China Univ Technol, Sch Comp Sci & Engn, Guangzhou 510006, Guangdong, Peoples R China.
   [Han, Chu] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Radiol, Guangzhou 510080, Guangdong, Peoples R China.
   [Liu, Baoyi; Yu, Honghua] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China.
C3 South China University of Technology; Guangdong Academy of Medical
   Sciences & Guangdong General Hospital; Guangdong Academy of Medical
   Sciences & Guangdong General Hospital
RP Cai, HM (通讯作者)，South China Univ Technol, Sch Comp Sci & Engn, Guangzhou 510006, Guangdong, Peoples R China.; Yu, HH (通讯作者)，Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China.
EM yuhonghua@gdph.org.cn; hmcai@scut.edu.cn
RI Han, Chu/GWM-9255-2022
OI Han, Chu/0000-0001-7557-9131
FU National Natural Science Foundation of China [61771007, 61472145,
   81870663]; Key-Area Research and Development of Guangdong Province
   [2020B010166002, 2020B1111190001]; Guangdong Natural Science Foundation
   [2017A030312008]; Health & Medical Collaborative Innovation Project of
   Guangzhou City [201803010021, 202002020049]; Science and Technology
   Program of Guangzhou [202002030074]
FX The authors would like to thank D. G. Lowe, J. Y. Ma, Y. Yang, A.
   Myronenko, S. Belongie and G. Wang for providing their implementation
   source codes. This greatly facilitated the comparison experiments. This
   work was partially supported by the National Natural Science Foundation
   of China (Grant No. 61771007, 61472145, 81870663), the Key-Area Research
   and Development of Guangdong Province (Grant No. 2020B010166002,
   2020B1111190001), Guangdong Natural Science Foundation (Grant No.
   2017A030312008), the Health & Medical Collaborative Innovation Project
   of Guangzhou City (Grant No. 201803010021, 202002020049), the Science
   and Technology Program of Guangzhou (Grant No. 202002030074).
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NR 33
TC 1
Z9 1
U1 0
U2 11
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0925-2312
EI 1872-8286
J9 NEUROCOMPUTING
JI Neurocomputing
PD OCT 12
PY 2021
VL 459
BP 370
EP 382
DI 10.1016/j.neucom.2021.05.091
EA JUL 2021
PG 13
WC Computer Science, Artificial Intelligence
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science
GA WM4QE
UT WOS:000711070700013
DA 2022-11-30
ER

PT J
AU Ito, A
   Ye, K
   Onda, M
   Morimoto, N
   Osakada, F
AF Ito, Arisa
   Ye, Ke
   Onda, Masanari
   Morimoto, Nao
   Osakada, Fumitaka
TI Efficient and robust induction of retinal pigment epithelium cells by
   tankyrase inhibition regardless of the differentiation propensity of
   human induced pluripotent stem cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Cell therapy; Induced pluripotent stem cells; Retinal pigment
   epithelium; RPE replacement therapy; Tankyrase; Wnt/beta-catenin
ID DIRECTED DIFFERENTIATION; GENERATION; MOUSE
AB Transplantation of retinal pigment epithelium (RPE) cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) hold great promise as a new therapeutic modality for age-related macular degeneration and Stargardt disease. The development of hESC/hiPSC-derived RPE cells as cell-based therapeutic products requires a robust, scalable production for every hiPSC line congruent for patients. However, individual hESC/hiPSC lines show bias in differentiation. Here we report an efficient, robust method that induces RPE cells regardless of the differentiation propensity of the hiPSC lines. Application of the tankyrase inhibitor IWR-1-endo, which potentially inhibits Wnt signaling, promoted retinal differentiation in dissociated hiPSCs under feeder-free, two-dimensional culture conditions. The other tankyrase inhibitor, XAV939, also promoted retinal differentiation. However, Wnt signaling inhibitors, IWP-2 and iCRT3, that target porcupine and beta-catenin/TCF, respectively, did not. Further treatment with the GSK3 beta inhibitor CHIR99021 and FGF receptor inhibitor SU5402 induced hexagonal pigmented cells with phagocytotic ability. Notably, the IWR-1-endo-based differentiation method induced RPE cells even in an hiPSC line that expresses a lower level of the differentiation propensity marker SALL3, which is indicative of resistance to ectoderm differentiation. The present study demonstrated that tankyrase inhibitors cause efficient and robust RPE differentiation, irrespective of the SALL3 expression levels in hiPSC lines. This differentiation method will resolve line-to-line variations of hiPSCs in RPE production and facilitate clinical application and industrialization of RPE cell products for regenerative medicine. (C) 2021 Elsevier Inc. All rights reserved.
C1 [Ito, Arisa; Ye, Ke; Onda, Masanari; Morimoto, Nao; Osakada, Fumitaka] Nagoya Univ, Grad Sch Pharmaceut Sci, Lab Cellular Pharmacol, Nagoya, Aichi, Japan.
   [Morimoto, Nao; Osakada, Fumitaka] Nagoya Univ, Inst Adv Res, Lab Neural Informat Proc, Nagoya, Aichi, Japan.
C3 Nagoya University; Nagoya University
RP Osakada, F (通讯作者)，Nagoya Univ, Grad Sch Pharmaceut Sci, Lab Cellular Pharmacol, Nagoya, Aichi, Japan.
EM fosakada@ps.nagoya-u.ac.jp
OI Osakada, Fumitaka/0000-0002-9078-1458; KE, YE/0000-0002-9593-9007
FU Japan Society for the Promotion of Science; Mochida Memorial Foundation
   for Medical and Pharmaceutical Research; Suzuken Memorial Foundation;
   Naito Foundation; Astellas Foundation for Research on Metabolic
   Disorders; Takeda Science Foundation; Novartis Pharma Grants for Basic
   Research; Japanese Retinitis Pigmentosa Society
FX We thank members of the Osakada laboratory for discussions. This work
   was supported by GrantsinAid from the Japan Society for the Promotion of
   Science (F.O.) , the Mochida Memorial Foundation for Medical and
   Pharmaceutical Research (F.O.) , the Suzuken Memorial Foundation (F.O) ,
   the Naito Foundation (F.O.) , the Astellas Foundation for Research on
   Metabolic Disorders (F.O.) , the Takeda Science Foundation (F.O.) , the
   Novartis Pharma Grants for Basic Research (F.O.) , and the Japanese
   Retinitis Pigmentosa Society (F.O.) .
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NR 27
TC 0
Z9 0
U1 4
U2 7
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 MAY 7
PY 2021
VL 552
BP 66
EP 72
DI 10.1016/j.bbrc.2021.03.012
EA MAR 2021
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA RB3QX
UT WOS:000632030500001
PM 33743349
DA 2022-11-30
ER

PT J
AU Gong, CJ
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   Zhang, YP
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   Li, SY
AF Gong, Chaoju
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   Feng, Ruifang
   Xu, Qing
   Zhang, Yipeng
   Fang, Zejun
   Shen, Jie
   Li, Suyan
TI IL-6-induced acetylation of E2F1 aggravates oxidative damage of retinal
   pigment epithelial cell line
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE E2F1; Glucose-6-phosphate dehydrogenase (G6PD); Interleukin-6 (IL-6);
   Oxidative damage; Retinal pigment epithelial (RPE)
ID DNA-DAMAGE; MACULAR DEGENERATION; COLORECTAL-CANCER; INFLAMMATION;
   EXPRESSION; PROLIFERATION; RESISTANCE; PROMOTE; TARGET; HMGA
AB Oxidative damage in retinal pigment epithelial cells (RPE) is considered to be a crucial pathogenesis of age-related macular degeneration (AMD). Although dysregulation of the DNA repair system has been found in RPE cells of AMD patients, the detailed molecular mechanisms of this dysregulation and their relationship with the intraocular microenvironment of AMD patients remain unclear. Here, we established an RPE model of H2O2-induced oxidative stress and found that Sirtuin 1 (Sirt1)-mediated deacetylation of E2F transcription factor 1 (E2F1) was required for oxidation resistance in RPE cells. Moreover, E2F1 induced the expression of the chromatin-binding protein, high mobility group AT-Hook 1 (HMGA1), which promoted the transcription of glucose 6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, to increase NADPH level for antioxidant defense. Interrupting the E2F1/HMGA1/G6PD regulatory axis increased reactive oxygen species (ROS) levels, DNA damage, and apoptosis in RPE cells under oxidative stress. Notably, interleukin 6 (IL-6), an inflammatory cytokine that is known to be upregulated in the intraocular fluid of AMD patients, induced phosphorylation (S47) of Sirtl by activating PI3K/AKT/mTOR signaling, thereby inhibiting Sirtl activity and increasing the acetylation of E2F1. Specific inhibitors of PI3K/AKT/mTOR signaling decreased DNA damage and ROS while increasing NADPH in RPE cells. Collectively, our findings demonstrate that IL-6-induced acetylation of E2F1 impairs the antioxidant capacity of RPE cells by disturbing the pentose phosphate pathway, which elucidates a relationship between the intraocular microenvironment and RPE oxidative damage in AMD and provides a possible therapeutic target for AMD.
C1 [Gong, Chaoju; Qiao, Lei; Feng, Ruifang; Xu, Qing; Zhang, Yipeng; Li, Suyan] Xuzhou Med Univ, Xuzhou Peoples Hosp 1, Eye Inst Xuzhou, Xuzhou Key Lab Ophthalmol,Affiliated Xuzhou Munic, Xuzhou 221100, Jiangsu, Peoples R China.
   [Fang, Zejun] Zhejiang Univ, Sanmen Peoples Hosp Zhejiang, Affiliated Hosp 1, Coll Med,Sanmenwan Branch,Cent Lab, Sanmen 317100, Peoples R China.
   [Shen, Jie] Xuzhou Med Univ, Xuzhou Peoples Hosp 1, Eye Inst Xuzhou, Dept Nursing,Affiliated Xuzhou Municipal Hosp, Xuzhou 221100, Jiangsu, Peoples R China.
   [Li, Suyan] Xuzhou Med Univ, Xuzhou Peoples Hosp 1, Eye Inst Xuzhou, Dept Ophthalmol,Affiliated Xuzhou Municipal Hosp, Xuzhou 221100, Jiangsu, Peoples R China.
C3 Xuzhou Medical University; Zhejiang University; Xuzhou Medical
   University; Xuzhou Medical University
RP Li, SY (通讯作者)，Xuzhou Med Univ, Xuzhou Peoples Hosp 1, Eye Inst Xuzhou, Xuzhou Key Lab Ophthalmol,Affiliated Xuzhou Munic, Xuzhou 221100, Jiangsu, Peoples R China.; Shen, J (通讯作者)，Xuzhou Med Univ, Xuzhou Peoples Hosp 1, Eye Inst Xuzhou, Dept Nursing,Affiliated Xuzhou Municipal Hosp, Xuzhou 221100, Jiangsu, Peoples R China.
EM 1258250807@qq.com; lisuyan_med@163.com
OI Li, Suyan/0000-0003-3860-1381
FU Applied Basic Research Plan of Xuzhou [KC18031]; Jiangsu high-level
   innovation and entrepreneurship talents introduction program-"E&I"
   doctoral project
FX This work was mainly supported by the Applied Basic Research Plan of
   Xuzhou (KC18031); Jiangsu high-level innovation and entrepreneurship
   talents introduction program-"E&I" doctoral project.
CR Ayene IS, 2002, J BIOL CHEM, V277, P9929, DOI 10.1074/jbc.M111366200
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NR 35
TC 7
Z9 8
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2020
VL 200
AR 108219
DI 10.1016/j.exer.2020.108219
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OP5UI
UT WOS:000588151200019
PM 32910941
DA 2022-11-30
ER

PT J
AU Tsai, YC
   Wu, JJS
   Lin, PK
   Lin, BJ
   Wang, PS
   Liu, CH
   Wu, CY
   Chiao, CC
AF Tsai, Yueh-Chun
   Wu, Jose Jiun-Shian
   Lin, Po-Kang
   Lin, Bo-Jyun
   Wang, Pin-Shiou
   Liu, Ching-Hsiang
   Wu, Chung-Yu
   Chiao, Chuan-Chin
TI Spatiotemporal integration of visual stimuli and its relevance to the
   use of a divisional power supply scheme for retinal prosthesis
SO PLOS ONE
LA English
DT Article
ID GANGLION-CELLS; ELECTRICAL-STIMULATION; TEMPORAL CHARACTERISTICS;
   RESPONSES; THRESHOLDS; PERCEPTION; ACTIVATION; RESOLUTION
AB A wireless photovoltaic retinal prosthesis is currently being studied with the aim of providing prosthetic vision to patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). The major challenge of a photovoltaic device is its limited power efficiency. Our retinal prosthetic design implements a unique divisional power supply scheme (DPSS) system that provides the electrical power generated by all of the solar cells to only a subset of electrodes at any moment in time. The aim of the present study was to systematically characterize the spatiotemporal integration performance of the system under various DPSS conditions using human subjects and a psychophysical approach. A 16x16 pixels LED array controlled by Arduino was used to simulate the output signal of the DPSS design, and human performance under different visual stimulations at various update frequencies was then used to assess the spatiotemporal capability of retinal prostheses. The results showed that the contrast polarity of the image, image brightness, and division number influenced the lower limit of the update frequency of the DPSS system, while, on the other hand, visual angle, ambient light level, and stimulation order did not affect performance significantly. Pattern recognition by visual persistence with spatiotemporal integration of multiple frames of sparse dots is a feasible approach in retinal prosthesis design. These findings provide an insight into how to optimize a photovoltaic retinal prosthesis using a DPSS design with an appropriate update frequency for reliable pattern recognition. This will help the development of a wireless device able to restore vision to RP and AMD patients in the future.
C1 [Tsai, Yueh-Chun; Wu, Jose Jiun-Shian; Chiao, Chuan-Chin] Natl Tsing Hua Univ, Inst Syst Neurosci, Hsinchu, Taiwan.
   [Tsai, Yueh-Chun; Chiao, Chuan-Chin] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan.
   [Lin, Po-Kang] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
   [Lin, Po-Kang] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Lin, Bo-Jyun; Wang, Pin-Shiou; Liu, Ching-Hsiang] Hsinchu Sci Pk, Natl Expt High Sch, Hsinchu, Taiwan.
   [Wu, Chung-Yu] Natl Chiao Tung Univ, Dept Elect Engn, Hsinchu, Taiwan.
   [Wu, Chung-Yu] Natl Chiao Tung Univ, Biomed Elect Translat Res Ctr, Hsinchu, Taiwan.
C3 National Tsing Hua University; National Tsing Hua University; National
   Yang Ming Chiao Tung University; Taipei Veterans General Hospital;
   National Yang Ming Chiao Tung University; National Yang Ming Chiao Tung
   University
RP Chiao, CC (通讯作者)，Natl Tsing Hua Univ, Inst Syst Neurosci, Hsinchu, Taiwan.; Chiao, CC (通讯作者)，Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan.
EM ccchiao@life.nthu.edu.tw
FU [MOST-107-2311-B-007002-MY3];  [NSC-103-2923-E-009-003-MY3]; 
   [MOST-107-2633-B-009-003]
FX Funded by CCC, MOST-107-2311-B-007002-MY3. CYW,
   NSC-103-2923-E-009-003-MY3. CYW&CCC, MOST-107-2633-B-009-003.
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NR 41
TC 1
Z9 1
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 FEB 21
PY 2020
VL 15
IS 2
AR e0228861
DI 10.1371/journal.pone.0228861
PG 22
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA LQ8DJ
UT WOS:000535227900032
PM 32084146
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Thakur, A
   Mishra, AP
   Panda, B
   Sweta, K
   Majhi, B
AF Thakur, Abhimanyu
   Mishra, Ambika Prasad
   Panda, Bishnupriya
   Sweta, Kumari
   Majhi, Babita
TI Detection of Disease-Specific Parent Cells Via Distinct Population of
   Nano-Vesicles by Machine Learning
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Article
DE Nano-vesicles; exosome; diagnosis; initiating parent cells; machine
   learning; artificial intelligence
ID BREAST-CANCER; EXOSOMES; ANGIOGENESIS; AGE
AB Background: The diagnosis and prognosis of pathological conditions, such as age-related macular degeneration (AMD) and cancer still need improvement. AMD is primarily caused due to the dysfunction of retinal pigment epithelium (RPE), whereas endothelial cells (ECs) play one of the major roles in angiogenesis; an important process which occurs in malignant progression of cancer. Several reports suggested the augmented release of nano-vesicles under pathological conditions, including from RPE as well as cancer-associated ECs, which take part in various biological processes, including intercellular communication in disease progression. importantly, these nano-vesicles are around 30-1000 nm and carry the fingerprint of their initiating parent cells (IPCs). Therefore, these nano-vesicles could be utilized as the diagnostic tool for AMD and cancer, respectively. However, the analysis of nano-vesicles for biomarker study is confounded by their extensive heterogeneous nature.
   Methods: To confront this challenge, we utilized artificial intelligence (AI) based machine learning (ML) algorithms such as support vector machine (SVM) and decision tree model on the dataset of nano-vesicles from RPE and ECs cell lines with low dimensionality.
   Results: Overall, Gaussian SVM demonstrated the highest prediction accuracy of the IPCs of nano-vesicles, among all the chosen SVM classifiers. Additionally, the bagged tree showed the highest prediction among the chosen decision tree-based classifiers.
   Conclusion: Therefore, the overall bagged tree showed the best performance for the prediction of IPCs of nanovesicles, suggesting the applicability of AI-based prediction approach in diagnosis and prognosis of pathological conditions, including non-invasive liquid biopsy via various biofluids-derived nano-vesicles.
C1 [Thakur, Abhimanyu] City Univ Hong Kong, Dept Biomed Sci, Kowloon Tong, Hong Kong, Peoples R China.
   [Mishra, Ambika Prasad; Panda, Bishnupriya] Siksha O Anusandhan Univ, Inst Tech Educ & Res, Dept Comp Sci & Engn, Bhubaneswar, Orissa, India.
   [Sweta, Kumari] Birla Inst Technol Mesra, Dept Pharmaceut Sci & Technol, Ranchi, Bihar, India.
   [Majhi, Babita] Guru Ghashidas Vishwavidyalaya, Dept Comp Sci & Informat Technol, Bilaspur, Chhattisgarh, India.
C3 City University of Hong Kong; Siksha 'O' Anusandhan University; Birla
   Institute of Technology Mesra; Guru Ghasidas Vishwavidyalaya
RP Thakur, A (通讯作者)，City Univ Hong Kong, Dept Biomed Sci, Kowloon Tong, Hong Kong, Peoples R China.
EM abhithakurmanyu@gmail.com
OI MISHRA, Ambika Prasad/0000-0002-0942-0787
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NR 35
TC 9
Z9 9
U1 1
U2 9
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
EI 1873-4286
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PY 2020
VL 26
IS 32
BP 3985
EP 3996
DI 10.2174/1381612826666200422091753
PG 12
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA NV9RQ
UT WOS:000574649400009
PM 32321392
DA 2022-11-30
ER

PT J
AU Bergen, AA
   Arya, S
   Koster, C
   Pilgrim, MG
   Wiatrek-Moumoulidis, D
   van der Spek, PJ
   Hauck, SM
   Boon, CJF
   Emri, E
   Stewart, AJ
   Lengyel, I
AF Bergen, Arthur A.
   Arya, Swati
   Koster, Celine
   Pilgrim, Matthew G.
   Wiatrek-Moumoulidis, Dagmara
   van der Spek, Peter J.
   Hauck, Stefanie M.
   Boon, Camiel J. F.
   Emri, Eszter
   Stewart, Alan J.
   Lengyel, Imre
TI On the origin of proteins in human drusen: The meet, greet and stick
   hypothesis
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Drusen proteins; Retinal pigment epithelium (RPE); Bruch's membrane;
   Blood; Age-related macular degeneration (AMD); Alzheimer's disease
ID RETINAL-PIGMENT EPITHELIUM; COMPLEMENT FACTOR-H; AGE-RELATED
   MACULOPATHY; HUMAN BRUCHS MEMBRANE; C-REACTIVE PROTEIN; SENILE MACULAR
   DEGENERATION; APOLIPOPROTEIN-E GENE; BASAL LINEAR DEPOSIT; ADULT HUMAN
   RETINA; EXTRACELLULAR HISTONES
AB Retinal drusen formation is not only a clinical hallmark for the development of age-related macular degeneration (AMD) but also for other disorders, such as Alzheimer's disease and renal diseases. The initiation and growth of drusen is poorly understood. Attention has focused on lipids and minerals, but relatively little is known about the origin of drusen-associated proteins and how they are retained in the space between the basal lamina of the retinal pigment epithelium and the inner collagenous layer space (sub-RPE-BL space). While some authors suggested that drusen proteins are mainly derived from cellular debris from processed photoreceptor outer segments and the RPE, others suggest a choroidal cell or blood origin.
   Here, we reviewed and supplemented the existing literature on the molecular composition of the retina/choroid complex, to gain a more complete understanding of the sources of proteins in drusen. These "drusenomics" studies showed that a considerable proportion of currently identified drusen proteins is uniquely originating from the blood. A smaller, but still large fraction of drusen proteins comes from both blood and/or RPE. Only a small proportion of drusen proteins is uniquely derived from the photoreceptors or choroid. We next evaluated how drusen components may "meet, greet and stick" to each other and/or to structures like hydroxyapatite spherules to form macroscopic deposits in the sub-RPE-BL space. Finally, we discuss implications of our findings with respect to the previously proposed homology between drusenogenesis in AMD and plaque formation in atherosclerosis.
C1 [Bergen, Arthur A.; Koster, Celine] Univ Amsterdam, Dept Clin Genet, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
   [Bergen, Arthur A.; Boon, Camiel J. F.] Univ Amsterdam, Dept Ophthalmol, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
   [Bergen, Arthur A.] NIN, KNAW, Amsterdam, Netherlands.
   [Arya, Swati; Wiatrek-Moumoulidis, Dagmara; Stewart, Alan J.] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland.
   [Pilgrim, Matthew G.; Lengyel, Imre] UCL, Inst Ophthalmol, London, England.
   [Wiatrek-Moumoulidis, Dagmara] UCL, Eastman Dent Inst, Div Biomat & Tissue Engn, London, England.
   [van der Spek, Peter J.] Erasmus MC, Div Clin Bioinformat, Dept Pathol, Rotterdam, Netherlands.
   [Hauck, Stefanie M.] German Res Ctr Environm Hlth GmbH, Res Unit Prot Sci, Helmholtz Zentrum Munchen, Neuherberg, Germany.
   [Boon, Camiel J. F.] Leiden Univ, Dept Ophthalmol, Med Ctr, Leiden, Netherlands.
   [Emri, Eszter; Lengyel, Imre] Queens Univ, Sch Med Dent & Biomed Sci, Ctr Expt Med, Belfast, Antrim, North Ireland.
C3 University of Amsterdam; University of Amsterdam; Vrije Universiteit
   Amsterdam; Royal Netherlands Academy of Arts & Sciences; Netherlands
   Institute for Neuroscience (NIN-KNAW); University of St Andrews;
   University of London; University College London; University of London;
   University College London; Erasmus University Rotterdam; Erasmus MC;
   Helmholtz Association; Helmholtz-Center Munich - German Research Center
   for Environmental Health; Leiden University; Leiden University Medical
   Center (LUMC); Leiden University - Excl LUMC; Queens University Belfast
RP Bergen, AA (通讯作者)，Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM aabergen@amc.uva.nl
RI Emri, Eszter/ABE-9363-2020; Lengyel, Imre/B-5217-2009; Stewart, Alan
   J./B-6569-2008; Hauck, Stefanie/B-3300-2013; Boon, CJF/P-7534-2014
OI Lengyel, Imre/0000-0001-7467-2174; Koster, Celine/0000-0002-0936-3970;
   Pilgrim, Matthew/0000-0001-8144-5631; Stewart, Alan
   J./0000-0003-4580-1840; Hauck, Stefanie/0000-0002-1630-6827; Boon,
   CJF/0000-0002-6737-7932; Bergen, Arthur/0000-0002-6333-9576; van der
   Spek, Peter/0000-0002-2203-0652
FU de Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB);
   Stichting Oogfonds Nederland; Stichting Retina Nederland Fonds [2011-6,
   2014-7]; de Haagse Stichting Blindenhulp; ZonMW [446001002]; Bill Brown
   Charitable Trust; Eye-Risk project - European Union's Horizon 2020
   research and innovation programme [634479]; Fight for Sight; Bright
   Focus Foundation [M2015370]; de Stichting Blinden-Penning; de Gelderse
   Blinden Stichting; de Landelijke Stichting voor Blinden en Slechtzienden
   (LSBS); Stichting MD Fonds; Stichting Lijf en Leven; Stichting voor
   Ooglijders; de Rotterdamse Stichting Blindenbelangen (RSB)
FX This research was part-supported by de Algemene Nederlandse Vereniging
   ter Voorkoming van Blindheid (ANVVB), de Stichting Blinden-Penning, de
   Gelderse Blinden Stichting, de Landelijke Stichting voor Blinden en
   Slechtzienden (LSBS), Stichting Oogfonds Nederland, Stichting MD Fonds
   and Stichting Retina Nederland Fonds (represented by Uitzicht, grants
   2011-6 and 2014-7 to A.A.B.), de Rotterdamse Stichting Blindenbelangen
   (RSB), de Haagse Stichting Blindenhulp, Stichting Lijf en Leven,
   Stichting voor Ooglijders (to A.A.B.); ZonMW grant nr 446001002 (to
   A.A.B. and C.K.); the Bill Brown Charitable Trust, Moorfields Eye
   Hospital Special Trustees, Mercer Fund from Fight for Sight, the
   Eye-Risk project funded by the European Union's Horizon 2020 research
   and innovation programme under grant agreement No 634479 (L.L. and
   E.E.), Fight for Sight project grant (L.L. and A.S.), the Bright Focus
   Foundation grant nr M2015370 (to S.M.H.). The authros thank Dr J. Booij
   for partly unpublished data and the reviewers for their invaluable
   comments to improve the manuscript.
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NR 292
TC 44
Z9 46
U1 4
U2 20
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 2019
VL 70
BP 55
EP 84
DI 10.1016/j.preteyeres.2018.12.003
PG 30
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IE9IO
UT WOS:000472688300003
PM 30572124
OA Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Dick, AD
AF Dick, A. D.
TI Doyne lecture 2016: intraocular health and the many faces of
   inflammation
SO EYE
LA English
DT Review
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; UVEITIS STEROID TREATMENT;
   KOYANAGI-HARADA-DISEASE; MYELOID CELL-FUNCTION; FACTOR-H POLYMORPHISM;
   MACULAR DEGENERATION; NLRP3 INFLAMMASOME; BRUCHS MEMBRANE; CHOROIDAL
   NEOVASCULARIZATION; CD200 RECEPTOR
AB Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew inter-action between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses.
C1 [Dick, A. D.] UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
   [Dick, A. D.] Univ Bristol, Acad Unit Ophthalmol, Sch Clin Sci, Bristol, Avon, England.
   [Dick, A. D.] Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, England.
   [Dick, A. D.] UCL Inst Ophthalmol, London, England.
C3 University of London; University College London; University of Bristol;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London
RP Dick, AD (通讯作者)，UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM a.dick@ucl.ac.uk
OI Dick, Andrew/0000-0002-0742-3159
FU National Institute for Health Research (NIHR) Biomedical Research Centre
   based at Moorfields Eye Hospital NHS Foundation Trust; UCL Institute of
   Ophthalmology
FX This work was partly supported by the National Institute for Health
   Research (NIHR) Biomedical Research Centre based at Moorfields Eye
   Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. I have
   been most fortunate to work with excellent colleagues and friends who
   remain long-standing collaborators. The post-docs and students have been
   inspirational and driven this work forward. I am therefore indebted to a
   large number of folk over the years. The lecture has developed from many
   conversations and the collaborative generation of data. I wish to
   particularly acknowledge with respect to the work presented here
   (although worried I will miss so many out deserving of acknowledgement):
   John Forrester, Lindsey Nicholson, Richard Lee, Robert Nussenblatt, Paul
   McMenamin, Jon Sedgwick, Dave Copland, Heping Xu, Janet Liversidge, Jian
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NR 116
TC 27
Z9 28
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2017
VL 31
IS 1
BP 87
EP 96
DI 10.1038/eye.2016.177
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EL1AU
UT WOS:000394353700008
PM 27636226
OA Green Submitted, Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Fauser, S
   Muether, PS
AF Fauser, Sascha
   Muether, Philipp S.
TI Clinical correlation to differences in ranibizumab and aflibercept
   vascular endothelial growth factor suppression times
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Treatment Medical; Retina; Pharmacology; Neovascularisation; Macula
ID MACULAR DEGENERATION; TRAP-EYE; PHARMACOKINETICS; BEVACIZUMAB; EDEMA
AB Aim To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea).
   Methods Seven of 89 treatment-naive nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 284months. The treatment was switched to PRN aflibercept injections and patients were followed for another 152months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT.
   Results The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34 +/- 5 (26-69) days for ranibizumab and 67 +/- 14 (49-89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re-activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept.
   Conclusions The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST.
   Trial registration number NCT01213667, post-results
C1 [Fauser, Sascha; Muether, Philipp S.] Univ Hosp Cologne, Dept Ophthalmol, Kerpener Str 62, D-50924 Cologne, Germany.
C3 University of Cologne
RP Muether, PS (通讯作者)，Univ Hosp Cologne, Dept Ophthalmol, Kerpener Str 62, D-50924 Cologne, Germany.
EM philmuether@mac.com
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NR 12
TC 32
Z9 34
U1 2
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD NOV
PY 2016
VL 100
IS 11
BP 1494
EP 1498
DI 10.1136/bjophthalmol-2015-308264
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EC3DJ
UT WOS:000388004900010
PM 26888975
DA 2022-11-30
ER

PT J
AU Lee, YM
   Lee, YR
   Kim, CS
   Jo, K
   Sohn, E
   Kim, JS
   Kim, J
AF Lee, Yun Mi
   Lee, Yu-Ri
   Kim, Chan-Sik
   Jo, Kyuhyung
   Sohn, Eunjin
   Kim, Jin Sook
   Kim, Junghyun
TI Cnidium officinale extract and butylidenephthalide inhibits retinal
   neovascularization in vitro and in vivo
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
DE Retinal neovascularization; Butylidenephthalide; Cnidium officinale;
   Oxygen-induced retinopathy; Vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; MOUSE MODEL; OXYGEN; MAKINO; ANGIOGENESIS;
   RETINOPATHY; EXPRESSION; APOPTOSIS; PROCTOR; ROLES
AB Background: Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model.
   Method: The HUVECs were incubated with COE and BP (0.1-10 mu g/ml). The mice were exposed to 75 % oxygen for 5 days starting on the 7th postnatal day (P7-P12). Then, the mice were returned to room air and intraperitoneally injected with COE (100 mg/kg) and BP (5 mg/kg) once per day for 5 days (P12-P16). On P17, we measured retinal neovascularization and analyzed the angiogenesis-related proteins expression using protein arrays.
   Results: COE and BP inhibit the HUVECs migration and the tube formation in a dose-dependent manner. In addition, COE significantly decreased retinal neovascularization in the OIR mice. COE reduced the expression levels of AREG, ANG, DLL4, Endostatin, IGFBP-2 and VEGF. Additionally, BP also inhibited the retinal neovascularization and down-regulated the expression of AREG, ANG, DLL4 and VEGF.
   Conclusion: These results suggest that COE and BP exerts antiangiogenic effects on retinal neovascularization by inhibiting the expression of AREG, ANG, DLL4 and VEGF, indicating that antiangiogenic activities of COE may be in part due to its bioactive compound, BP.
C1 [Lee, Yun Mi; Kim, Chan-Sik; Jo, Kyuhyung; Sohn, Eunjin; Kim, Jin Sook; Kim, Junghyun] Korea Inst Oriental Med, Korean Med Convergence Res Div, 1672 Yuseongdaero, Daejeon 34054, South Korea.
   [Lee, Yu-Ri] Chungnam Natl Univ, Dept Biol, Daejeon 34134, South Korea.
C3 Korea Institute of Oriental Medicine (KIOM); Chungnam National
   University
RP Kim, J (通讯作者)，Korea Inst Oriental Med, Korean Med Convergence Res Div, 1672 Yuseongdaero, Daejeon 34054, South Korea.
EM dvmhyun@kiom.re.kr
FU Korea Institute of Oriental Medicine [K16817]
FX This research was supported by a grant of the Korea Institute of
   Oriental Medicine (K16817).
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NR 43
TC 21
Z9 22
U1 1
U2 4
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD JUL 19
PY 2016
VL 16
AR 231
DI 10.1186/s12906-016-1216-8
PG 10
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA DR3RV
UT WOS:000379821200004
PM 27435599
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Liu, XJ
   Zhu, MH
   Yang, XW
   Wang, Y
   Qin, B
   Cui, C
   Chen, H
   Sang, AM
AF Liu, Xiaojuan
   Zhu, Manhui
   Yang, Xiaowei
   Wang, Ying
   Qin, Bai
   Cui, Chen
   Chen, Hui
   Sang, Aimin
TI Inhibition of RACK1 ameliorates choroidal neovascularization formation
   in vitro and in vivo
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Choroidal neovascularization (CNV); Age-related macular degeneration
   (AMD); Receptor for activated C-kinase 1 (RACK1); Vascular endothelial
   growth factor (VEGF)
ID PROTEIN-KINASE-C; RETINAL-PIGMENT EPITHELIUM; TISSUE FACTOR;
   ANGIOGENESIS; INFILTRATION; RECEPTOR; GROWTH; MODEL
AB Choroidal neovascularization (CNV) occurs as a result of age-related macular degeneration (AMD) and causes severe vision loss among elderly patients. The receptor for activated C-kinase 1 (RACK1) serves as a scaffold protein which is recently found to promote angiogenesis. However, the impact of RACK1 on the vascular endothelial growth factor (VEGF) expression in endothelial cells and subsequent choroidal angiogenesis formation remains to be elucidated. In this study, we found that RACK1 and VEGF expression increased, and reached the peak at 7 d in mouse CNV model by laser application. Furthermore, on RPE/choroid cryosections, RACK1 co-localized with CD31, suggesting that RACK1 was expressed in endothelial cells. In vitro, RF/6A cell hypoxia model showed that RACK1 expression was up-regulated in parallel with hypoxia-induced factor 1 (HIF-1 alpha) and VEGF expression, reaching the peak at 6 h. Silencing of RACK1 suppressed the invasion and tube formation activity of RF/6A cells in ARPE-19 and RF/6A co-culture system, possibly through VEGF signal pathway. Overexpression of RACK1 showed the opposite effect Intravitreal injection of anti-RACK1 monoclonal antibody predominantly decreased RACK1 and VEGF expression in mouse laser-induced CNV model. Meanwhile, anti-RACK1 monoclonal antibody intravitreal injection also decreased incidence of CNV and leakage area. These data indicated that RACK1 promoted CNV formation via VEGF pathway. Additionally, anti-RACK1 monoclonal antibody significantly decreased CNV in mouse model and may have therapeutic potential in human CNV. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Liu, Xiaojuan] Nantong Univ, Coll Med, Dept Pathogen Biol, Nantong 226001, Jiangsu, Peoples R China.
   [Zhu, Manhui; Yang, Xiaowei; Wang, Ying; Qin, Bai; Cui, Chen; Chen, Hui; Sang, Aimin] Nantong Univ, Affiliated Hosp, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
   [Liu, Xiaojuan; Zhu, Manhui; Yang, Xiaowei; Wang, Ying; Qin, Bai; Cui, Chen; Chen, Hui; Sang, Aimin] Nantong Univ, Coll Med, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Jiangsu, Peoples R China.
C3 Nantong University; Nantong University; Nantong University
RP Chen, H; Sang, AM (通讯作者)，Nantong Univ, Affiliated Hosp, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
EM chenhuieye@126.com; sangam@ntu.edu.cn
FU National Natural Science Foundation of China [81401365]; Nantong science
   and technology project [MS12015056]; Priority Academic Program
   Development of Jiangsu Higher Education Institutions (PAPD)
FX The study was supported by National Natural Science Foundation of China
   (No. 81401365); Nantong science and technology project (MS12015056); a
   project funded by the Priority Academic Program Development of Jiangsu
   Higher Education Institutions (PAPD).
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NR 32
TC 11
Z9 11
U1 2
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD JUN
PY 2016
VL 100
IS 3
BP 451
EP 459
DI 10.1016/j.yexmp.2016.04.004
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA DO6XO
UT WOS:000377927000013
PM 27112838
DA 2022-11-30
ER

PT J
AU Jones, BW
   Pfeiffer, RL
   Ferrell, WD
   Watt, CB
   Tucker, J
   Marc, RE
AF Jones, Bryan W.
   Pfeiffer, Rebecca L.
   Ferrell, William D.
   Watt, Carl B.
   Tucker, James
   Marc, Robert E.
TI Retinal Remodeling and Metabolic Alterations in Human AMD
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE age-related macular degeneration(AMD); retinal pigment epithelium(RPE);
   computational molecular phenotyping (CMP); retina; photoreceptor; Muller
   cell; retinalre modeling; neural modeling
ID PIGMENT EPITHELIAL-CELLS; AMINO-ACID SIGNATURES; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; RAT RETINA; GEOGRAPHIC ATROPHY;
   OXIDATIVE STRESS; GOLDFISH RETINA; GANGLION-CELLS; PHOTORECEPTOR
   DEGENERATIONS
AB Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.
C1 [Jones, Bryan W.; Pfeiffer, Rebecca L.; Ferrell, William D.; Watt, Carl B.; Marc, Robert E.] Univ Utah, Dept Ophthalmol, Moran Eye Ctr, Salt Lake City, UT USA.
   [Pfeiffer, Rebecca L.] Univ Utah, Interdept Program Neurosci, Salt Lake City, UT USA.
   [Tucker, James] Univ Calif Davis, Dept Ophthalmol, Davis, CA 95616 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; University of California System;
   University of California Davis
RP Jones, BW (通讯作者)，Univ Utah, Dept Ophthalmol, Moran Eye Ctr, Salt Lake City, UT USA.
EM bryan.jones@m.cc.utah.edu
OI Jones, Bryan/0000-0001-5527-6643; Pfeiffer, Rebecca/0000-0002-4123-516X
FU Research to Prevent Blindness [NIH EY015128, EY02576, EY014800]; Edward
   N. and Della L. Thome Memorial Foundation; NATIONAL EYE INSTITUTE
   [R01EY015128, P30EY014800, R01EY002576] Funding Source: NIH RePORTER
FX NIH EY015128, EY02576, EY014800 Vision Core, an unrestricted grant from
   Research to Prevent Blindness to the Moran Eye Center; Edward N. and
   Della L. Thome Memorial Foundation grant for Age-Related Macular
   Degeneration Research.
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NR 112
TC 49
Z9 49
U1 0
U2 11
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 APR 28
PY 2016
VL 10
AR 103
DI 10.3389/fncel.2016.00103
PG 15
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA DK4YK
UT WOS:000374926000001
PM 27199657
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Karthikeyan, B
   Arun, A
   Harini, L
   Sundar, K
   Kathiresan, T
AF Karthikeyan, Bose
   Arun, Arumugaperumal
   Harini, Lakshminarasimhan
   Sundar, Krishnan
   Kathiresan, Thandavarayan
TI Role of ZnS Nanoparticles on Endoplasmic Reticulum Stress-mediated
   Apoptosis in Retinal Pigment Epithelial Cells
SO BIOLOGICAL TRACE ELEMENT RESEARCH
LA English
DT Article
DE Mice retinal pigment epithelial cells; ZnS-NPs; Reactive oxygen species;
   GRP78; CHOP; Caspase
ID YTTRIUM-OXIDE NANOPARTICLES; OXIDATIVE STRESS; MACULAR DEGENERATION;
   OPTICAL-PROPERTIES; ZINC; AGE; DEFICIENCY; COPPER; DISRUPTION;
   EXPRESSION
AB Age-related macular degeneration (AMD) is the leading cause for irreversible visual impairment affecting 30-50 million individuals every year. Oxidative stress and endoplasmic reticulum stress have been identified as crucial factors for the pathogenesis of AMD. Current treatments do not focus on underlying stimuli responsible for the disease like AMD. Zinc is an important trace metal in retina and its deficiency leads to AMD. Recent studies on zinc sulphide nanoparticles (ZnS-NPs) are gaining attention in the field of physical and biological research. In this present study, in investigating the role of ZnS-NPs on hydrogen peroxide and thapsigargin-treated primary mice retinal pigment epithelial (MRPE) cells, we synthesized ZnS-NPs and characterized using atomic force microscope (AFM) and SEM-EDX. The ZnS-NPs abrogate the primary MRPE cell death through inhibition of oxidative stress-induced reactive oxygen species production and cell permeability. Oxidant molecules hydrogen peroxide and thapsigargin alter unfolded protein response such as glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP) expressions, whereas ZnS-NPs-pre-treated primary MRPE cells downregulated the overexpression of such proteins. The expressions of apoptotic proteins caspase 12 and cleaved caspase 9 and caspase 3 were also significantly controlled in ZnS-NPs-treated primary MRPE cells when comparing with thapsigargin- and hydrogen peroxide-treated cells. From these results, ZnS-NPs stabilize reactive oxygen species elevation, when subjected to hydrogen peroxide- and thapsigargin-mediated oxidant injury and helps in maintaining normal homeostasis through regulating endoplasmic reticulum (ER) stress response proteins which is the lead cause for apoptosis-mediated pathogenesis of AMD.
C1 [Karthikeyan, Bose; Arun, Arumugaperumal; Harini, Lakshminarasimhan; Sundar, Krishnan; Kathiresan, Thandavarayan] Kalasalingam Univ, Dept Biotechnol, Krishnankoil 626126, Tamil Nadu, India.
   [Sundar, Krishnan; Kathiresan, Thandavarayan] Kalasalingam Univ, Int Res Ctr, Krishnankoil 626126, Tamil Nadu, India.
C3 Kalasalingam Academy of Research & Education; Kalasalingam Academy of
   Research & Education
RP Kathiresan, T (通讯作者)，Kalasalingam Univ, Dept Biotechnol, Krishnankoil 626126, Tamil Nadu, India.; Kathiresan, T (通讯作者)，Kalasalingam Univ, Int Res Ctr, Krishnankoil 626126, Tamil Nadu, India.
EM t.kathiresan@klu.ac.in
RI Arumugaperumal, Arun/H-2044-2013; Sundar, Krishnan/E-2748-2015; Bose,
   Karthikeyan/GRN-8684-2022
OI Arumugaperumal, Arun/0000-0001-5686-640X; Sundar,
   Krishnan/0000-0001-7156-1057
FU Department of Science and Technology (SERB) of India
   [SB/FT/LS-204/2012]; Council of Scientific and Industrial Research
   (CSIR), India [09/ 1012 (0005) 2 K11 - EMR - I]
FX This study was supported in part by a Grant-in-Aid from Department of
   Science and Technology (SERB) of India (SB/FT/LS-204/2012 to T. K). B.
   K. is the recipient of senior research fellowship (09/ 1012 (0005) 2 K11
   - EMR - I) from the Council of Scientific and Industrial Research
   (CSIR), India.
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NR 48
TC 11
Z9 11
U1 0
U2 15
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0163-4984
EI 1559-0720
J9 BIOL TRACE ELEM RES
JI Biol. Trace Elem. Res.
PD APR
PY 2016
VL 170
IS 2
BP 390
EP 400
DI 10.1007/s12011-015-0493-2
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DH0JT
UT WOS:000372471200018
PM 26329999
DA 2022-11-30
ER

PT J
AU Lu, HY
   Lu, QX
   Gaddipati, S
   Kasetti, RB
   Wang, W
   Pasparakis, M
   Kaplan, HJ
   Li, QT
AF Lu, Huayi
   Lu, Qingxian
   Gaddipati, Subhash
   Kasetti, Ramesh Babu
   Wang, Wei
   Pasparakis, Manolis
   Kaplan, Henry J.
   Li, Qiutang
TI IKK2 Inhibition Attenuates Laser-Induced Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS;
   ALPHA-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; MACULAR DEGENERATION;
   CANCER-CELLS; TRANSCRIPTIONAL REGULATION; INCREASED EXPRESSION; MOUSE
   MODEL
AB Choroidal neovascularization (CNV) is aberrant angiogenesis associated with exudative age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Inflammation has been suggested as a risk factor for AMD. The IKK2/NF-kappa B pathway plays a key role in the inflammatory response through regulation of the transcription of cytokines, chemokines, growth factors and angiogenic factors. We investigated the functional role of IKK2 in development of the laser-induced CNV using either Ikk2 conditional knockout mice or an IKK2 inhibitor. The retinal neuronal tissue and RPE deletion of IKK2 was generated by breeding Ikk2(-/flox) mice with Nestin-Cre mice. Deletion of Ikk2 in the retina caused no obvious defect in retinal development or function, but resulted in a significant reduction in laser-induced CNV. In addition, intravitreal or retrobulbar injection of an IKK2 specific chemical inhibitor, TPCA-1, also showed similar inhibition of CNV. Furthermore, in vitro inhibition of IKK2 in ARPE-19 cells significantly reduced heat shock-induced expression of NFKBIA, IL1B, CCL2, VEGFA, PDGFA, HIF1A, and MMP-2, suggesting that IKK2 may regulate multiple molecular pathways involved in laser-induced CNV. The in vivo laser-induced expression of VEGFA, and HIF1A in RPE and choroidal tissue was also blocked by TPCA-1 treatment. Thus, IKK2/NF-kappa B signaling appears responsible for production of pro-inflammatory and pro-angiogenic factors in laser-induced CNV, suggesting that this intracellular pathway may serve as an important therapeutic target for aberrant angiogenesis in exudative AMD.
C1 [Lu, Huayi; Lu, Qingxian; Gaddipati, Subhash; Kasetti, Ramesh Babu; Wang, Wei; Kaplan, Henry J.; Li, Qiutang] Univ Louisville, Sch Med, Dept Ophthalmol, Louisville, KY 40292 USA.
   [Lu, Huayi; Lu, Qingxian; Gaddipati, Subhash; Kasetti, Ramesh Babu; Wang, Wei; Kaplan, Henry J.; Li, Qiutang] Univ Louisville, Sch Med, Dept Visual Sci, Louisville, KY 40292 USA.
   [Lu, Qingxian; Gaddipati, Subhash; Li, Qiutang] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
   [Lu, Huayi] Jilin Univ, Hosp 2, Changchun, Jilin Province, Peoples R China.
   [Pasparakis, Manolis] Univ Cologne, Inst Genet, Cologne, Germany.
C3 University of Louisville; University of Louisville; University of
   Louisville; Jilin University; University of Cologne
RP Li, QT (通讯作者)，Univ Louisville, Sch Med, Dept Ophthalmol, Louisville, KY 40292 USA.
EM q.li@louisville.edu
RI Kasetti, Ramesh Babu/H-5157-2019; Pasparakis, Manolis/N-4350-2019;
   Pasparakis, Manolis/H-9292-2017
OI Pasparakis, Manolis/0000-0002-9870-0966; Pasparakis,
   Manolis/0000-0002-9870-0966; KASETTI, RAMESH/0000-0001-7874-3988;
   Gaddipati, Subhash/0000-0002-5323-5466
FU National Institutes of Health [EY019891, EY021584]; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [R01EY019891, R21EY021584] Funding
   Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants EY019891
   and EY021584 and Ernest & Elizabeth Althose Special Scholar Award to
   Qiutang Li from Research to Prevent Blindness. 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 67
TC 20
Z9 21
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 JAN 28
PY 2014
VL 9
IS 1
AR e87530
DI 10.1371/journal.pone.0087530
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 301CJ
UT WOS:000330510000141
PM 24489934
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Bhavsar, KV
   Branchini, L
   Shah, H
   Regatieri, CV
   Duker, JS
AF Bhavsar, Kavita V.
   Branchini, Lauren
   Shah, Heeral
   Regatieri, Caio V.
   Duker, Jay S.
TI CHOROIDAL THICKNESS IN RETINAL PIGMENT EPITHELIAL TEAR AS MEASURED BY
   SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal thickness; retinal pigment epithelial tear; spectral domain
   optical coherence tomography
ID TOTAL BLOOD-FLOW; INTRAVITREAL INJECTION; PHOTODYNAMIC THERAPY; MACULAR
   DEGENERATION; NEOVASCULARIZATION; PATHOGENESIS; PREDICTORS; VEGF
AB Purpose: To evaluate the choroidal thickness with spectral domain optical coherence tomography in subjects with retinal pigment epithelial (RPE) tear compared with the choroidal thickness of their fellow eye.
   Methods: For this cross-sectional investigation, seven eyes of seven patients with neovascular age-related macular degeneration and RPE tear in one eye imaged with spectral domain optical coherence tomography were identified. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500 mu m intervals up to 2,500 mu m temporal and nasal to the fovea in both the eye with the RPE tear and the eye with intact RPE. All measurements were performed by two independent observers and averaged for the purpose of the analysis. Measurements were compared using paired t-test.
   Results: The average age of patients was 79 years (range, 66-88 years). All subjects had dome-shaped pigment epithelial detachments before RPE tear and no dome-shaped pigment epithelial detachments in the unaffected eye. Average subfoveal choroidal thickness in the eye with the RPE tear was 154.9 +/- 10.1 mu m. Average subfoveal choroidal thickness in the eye with intact RPE was 212.9 +/- 10.6 mu m (P = 0.035).
   Conclusion: There is a significant decrease in subfoveal choroidal thickness in the subjects with RPE tear compared with their fellow eye with intact RPE. It is unclear if this thinning is a consequence of or precedes the RPE tear. Further studies are necessary to prospectively follow choroidal thickness in subjects with dome-shaped pigment epithelial detachments.
C1 [Bhavsar, Kavita V.; Branchini, Lauren; Shah, Heeral; Regatieri, Caio V.; Duker, Jay S.] Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA.
   [Regatieri, Caio V.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
C3 Tufts Medical Center; Universidade Federal de Sao Paulo (UNIFESP)
RP Duker, JS (通讯作者)，Tufts Med Ctr, New England Eye Ctr, 800 Washington St, Boston, MA 02111 USA.
EM jduker@tuftsmedicalcenter.org
RI Regatieri, Caio/G-8152-2014
OI Regatieri, Caio/0000-0003-1511-8696
FU Research to Prevent Blindness; Tufts University School of Medicine,
   National Institutes of Health [RO1-EY11289-23, R01-EY13178-07,
   R01-EY013516-07]; Massachusetts Lions Eye Research Fund; Carl Zeiss
   Meditech, Inc; Optovue, Inc.; NATIONAL EYE INSTITUTE [R01EY013516,
   R01EY013178, R01EY011289] Funding Source: NIH RePORTER
FX Supported in part by a Research to Prevent Blindness Unrestricted Grant
   to the New England Eye Center/Department of Ophthalmology, Tufts
   University School of Medicine, National Institutes of Health contracts
   RO1-EY11289-23, R01-EY13178-07, R01-EY013516-07, and the Massachusetts
   Lions Eye Research Fund.; J. S. Duker receives research support from
   Carl Zeiss Meditech, Inc, and Optovue, Inc. The remaining authors have
   no conflicting interests to disclose.
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NR 59
TC 3
Z9 3
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 JAN
PY 2014
VL 34
IS 1
BP 63
EP 68
DI 10.1097/IAE.0b013e318297a061
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AI6CZ
UT WOS:000336958700011
PM 23764968
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sin, M
   Chrapek, O
   Karhanova, M
   Pracharova, Z
   Langova, K
   Rehak, J
AF Sin, Martin
   Chrapek, Oldrich
   Karhanova, Marta
   Pracharova, Zuzana
   Langova, Katerina
   Rehak, Jiri
TI Progression of macular atrophy after PDT combined with the COX-2
   inhibitor Nabumetone in the treatment of neovascular ARMD
SO BIOMEDICAL PAPERS-OLOMOUC
LA English
DT Article
DE age-related macular degeneration; cyclooxygenase-2; CD36 metabolic
   pathway; combination therapy; nabumetone; macula atrophy progression;
   choroidal atrophy
ID VERTEPORFIN PHOTODYNAMIC THERAPY; CHOROIDAL NEOVASCULARIZATION;
   GROWTH-FACTOR; RHEUMATOID-ARTHRITIS; PIGMENT EPITHELIUM; DEGENERATION;
   EXPRESSION; MEMBRANES; MODEL; VEGF
AB Aim. To evaluate photodynamic therapy (PDT) combined with the preferential the cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the neovascular age-related macular degeneration (ARMD).
   Methods. A prospective, double-blind, randomized study on 60 patients with subfoveal CNV secondary to ARMD without any previous treatment. Patients were divided into a nabumetone or placebo group. The main endpoints were the change of best-corrected visual acuity (BCVA), central macular thickness (CRT) and number of required PDT treatments.
   Results. In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo group completed the follow-up of 12 months. In the nabumetone group, the mean CRT decreased from 332 m (SD 68 m) to 220 m (SD 46 m). In the placebo group, CRT decreased from 331 m (SD 72 m) to 254 m (SD 61 m). The mean BCVA was 0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23 log MAR) in the placebo group at baseline. This stabilised in the placebo group to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 logMAR (SD 0.41 log MAR). There was a significant reduction in the number of required PDTs in the nabumetone group, but significant progression of the RPE atrophy area.
   Conclusion. Combined PDT with oral intake of the COX-2 inhibitor, nabumetone reduced the number of required PDT retreatments, but worsening BCVA caused by macular atrophy progression. Therefore the combination of the PDT with the nabumetone is not recommended.
C1 [Sin, Martin; Chrapek, Oldrich; Karhanova, Marta; Pracharova, Zuzana; Rehak, Jiri] Univ Hosp Olomouc, Dept Ophthalmol, Olomouc, Czech Republic.
   [Sin, Martin; Chrapek, Oldrich; Karhanova, Marta; Pracharova, Zuzana; Rehak, Jiri] Palacky Univ Olomouc, Fac Med & Dent, Olomouc, Czech Republic.
   [Langova, Katerina] Palacky Univ Olomouc, Inst Mol & Translat Med, Fac Med & Dent, Dept Med Biophys, Olomouc, Czech Republic.
C3 University Hospital Olomouc; Palacky University Olomouc; Palacky
   University Olomouc
RP Sin, M (通讯作者)，Univ Hosp Olomouc, Dept Ophthalmol, Olomouc, Czech Republic.
EM sin.martin@seznam.cz
RI Chrapek, Oldrich/ABD-9894-2020; Sin, Martin/AAJ-6818-2021
OI Chrapek, Oldrich/0000-0002-1403-4936; Sin, Martin/0000-0002-5073-9482
FU  [CZ.1.05/2.1.00/01.0030]
FX This work was supported by Grant Project CZ.1.05/2.1.00/01.0030
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NR 26
TC 3
Z9 3
U1 0
U2 4
PU PALACKY UNIV, MEDICAL FAC
PI OLOMOUC
PA CENTRAL LIBRARY, HNEVOTINSKA 3, OLOMOUC, 00000, CZECH REPUBLIC
SN 1213-8118
EI 1804-7521
J9 BIOMED PAP
JI Biomed. Pap-Olomouc
PY 2014
VL 158
IS 1
BP 138
EP 143
DI 10.5507/bp.2012.066
PG 6
WC Engineering, Biomedical; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Research & Experimental Medicine
GA AK7SG
UT WOS:000338627400023
PM 23132511
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Kang, S
   Roh, YJ
   Kim, IB
AF Kang, Seungbum
   Roh, Young-Jung
   Kim, In-Beom
TI Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine
   kinase inhibitor, on experimental choroidal neovascularization in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE angiogenesis; choroidal neovascularization; receptor tyrosine kinase
   inhibitor; tivozanib; vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; TUMOR ANGIOGENESIS;
   ANTITUMOR-ACTIVITY; POTENT INHIBITOR; EXPRESSION; PHOSPHORYLATION;
   BEVACIZUMAB; ACTIVATION; PROMOTES
AB We investigated the effects of tivozanib, an oral vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization (CNV) in mice. C57BL/6 mice were treated with tivozanib (1 mg/kg/day) or vehicle at the onset (day 0) of the study and experimental CNV was induced by laser photocoagulation the following day. In the other groups, tivozanib or vehicle was started 7 days after the laser photocoagulation to determine the effects of the drug on established CNV. To evaluate changes in the CNV lesions, choroidal flat mounts, fluorescein angiography, immunofluorescence staining with isolectin B4, and histological examinations were performed 14 days after CNV induction. Expression of phosphorylated ERK1/2 in choroidal tissues was measured by western blot analysis to demonstrate the inhibitory effect of tivozanib on intracellular signaling pathways involved in CNV development. Compared to vehicle-treatment, tivozanib suppressed the development of CNV lesions and led to a significant regression of established CNV, reducing the affected areas by 80.7% and 67.7%, respectively. On fluorescein angiography, tivozanib-treated mice had significantly less fluorescence leakage than vehicle-treated mice (P < 0.001). On immunofluorescence staining, the isolectin B4-labeled area was smaller in tivozanib-treated mice (P < 0.001). Phosphorylated ERK 1/2 levels increased after CNV induction by laser application and were suppressed by tivozanib treatment. Tivozanib effectively inhibited the progression of CNV in an experimental CNV model. These results suggest that tivozanib may be a therapeutic alternative for the treatment of neovascular age-related macular degeneration. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Kang, Seungbum; Kim, In-Beom] Catholic Univ Korea, Dept Anat, Coll Med, Seoul 137701, South Korea.
   [Kang, Seungbum; Roh, Young-Jung] Catholic Univ Korea, Dept Ophthalmol & Visual Sci, Coll Med, Seoul 137701, South Korea.
   [Kang, Seungbum] Catholic Univ Korea, Clin Res Inst, Daejeon St Marys Hosp, Taejon 301012, South Korea.
C3 Catholic University of Korea; Catholic University of Korea; Catholic
   University of Korea
RP Kim, IB (通讯作者)，Catholic Univ Korea, Dept Anat, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea.
EM ibkimmd@catholic.ac.kr
RI Kim, In-Beom/A-6728-2011
FU Clinical Research Institute Grant; Daejeon St. Mary's Hospital, The
   Catholic University of Korea [CMCDJ-201102]
FX This work was supported by Clinical Research Institute Grant funded by
   Daejeon St. Mary's Hospital, The Catholic University of Korea
   (CMCDJ-201102).
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NR 44
TC 10
Z9 11
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2013
VL 112
BP 125
EP 133
DI 10.1016/j.exer.2013.05.006
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 180OS
UT WOS:000321605100015
PM 23701975
DA 2022-11-30
ER

PT J
AU Garita-Hernandez, M
   Diaz-Corrales, F
   Lukovic, D
   Gonzalez-Guede, I
   Diez-Lloret, A
   Valdes-Sanchez, ML
   Massalini, S
   Erceg, S
   Bhattacharya, SS
AF Garita-Hernandez, Marcela
   Diaz-Corrales, Francisco
   Lukovic, Dunja
   Gonzalez-Guede, Irene
   Diez-Lloret, Andrea
   Lourdes Valdes-Sanchez, M.
   Massalini, Simone
   Erceg, Slaven
   Bhattacharya, Shomi S.
TI Hypoxia Increases the Yield of Photoreceptors Differentiating from Mouse
   Embryonic Stem Cells and Improves the Modeling of Retinogenesis In Vitro
SO STEM CELLS
LA English
DT Article
DE Cellular therapy; Differentiation; Embryoid bodies; Embryonic stem
   cells; Stem cell transplantation; Retina
ID GENE-EXPRESSION PROFILE; NEURAL PRECURSORS; VERTEBRATE EYE; RETINAL
   CELLS; EFFICIENT DIFFERENTIATION; BODY FORMATION; HOMEOBOX GENE;
   GENERATION; ROD; OXYGEN
AB Retinitis pigmentosa (RP), a genetically heterogeneous group of diseases together with age-related macular degeneration (AMD), are the leading causes of permanent blindness and are characterized by the progressive dysfunction and death of the light sensing photoreceptors of the retina. Due to the limited regeneration capacity of the mammalian retina, the scientific community has invested significantly in trying to obtain retinal progenitor cells from embryonic stem cells (ESC). These represent an unlimited source of retinal cells, but it has not yet been possible to achieve specific populations, such as photoreceptors, efficiently enough to allow them to be used safely in the future as cell therapy of RP or AMD. In this study, we generated a high yield of photoreceptors from directed differentiation of mouse ESC (mESC) by recapitulating crucial phases of retinal development. We present a new protocol of differentiation, involving hypoxia and taking into account extrinsic and intrinsic cues. These include niche-specific conditions as well as the manipulation of the signaling pathways involved in retinal development. Our results show that hypoxia promotes and improves the differentiation of mESC toward photoreceptors. Different populations of retinal cells are increased in number under the hypoxic conditions applied, such as Crx-positive cells, S-Opsin-positive cells, and double positive cells for Rhodopsin and Recoverin, as shown by immunofluorescence analysis. For the first time, this manuscript reports the high efficiency of differentiation in vivo and the expression of mature rod photoreceptor markers in a large number of differentiated cells, transplanted in the subretinal space of wild-type mice. STEM CELLS 2013;31:966-978
C1 [Garita-Hernandez, Marcela; Diaz-Corrales, Francisco; Lukovic, Dunja; Gonzalez-Guede, Irene; Diez-Lloret, Andrea; Lourdes Valdes-Sanchez, M.; Massalini, Simone; Erceg, Slaven; Bhattacharya, Shomi S.] CABIMER Ctr Andaluz Biol Mol & Med Regenerat, Seville, Spain.
   [Bhattacharya, Shomi S.] UCL Inst Ophthalmol, Dept Genet, London, England.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); Universidad
   Pablo de Olavide; University of Sevilla; CSIC - Centro Andaluz de
   Biologia Molecular y Medicina Regenerativa (CABIMER); University of
   London; University College London
RP Erceg, S (通讯作者)，CABIMER Ctr Andaluz Biol Mol & Med Regenerat, Avda Americo Vespucio S-N,Parque Cient & Tecnol C, Seville, Spain.
EM slaven.erceg@cabimer.es; shomi.bhattacharya@cabimer.es
RI Bhattacharya, Shom/N-2926-2016; Valdes-Sanchez, Lourdes/C-2058-2017;
   Erceg, Slaven/ABC-4946-2021; Diaz-Corrales, Francisco/L-7559-2014
OI Bhattacharya, Shom/0000-0002-1601-6344; Valdes-Sanchez,
   Lourdes/0000-0001-9385-3915; Diaz-Corrales,
   Francisco/0000-0002-5752-0205; Gonzalez-Guede,
   Irene/0000-0002-9977-6110; Erceg, Slaven/0000-0003-3208-7705;
   Garita-Hernandez, Marcela/0000-0002-4311-138X
FU Junta de Andalucia [PI-0113-2010]; "Miguel Servet" contract of Instituto
   de Salud Carlos III of Spanish Ministry of Science and Innovation
FX This work was supported by funds for research from Junta de Andalucia
   PI-0113-2010 (S. E.) and "Miguel Servet" contract of Instituto de Salud
   Carlos III of Spanish Ministry of Science and Innovation (S. E.). Thanks
   to Dr. Anand Swaroop for the Nrl antibody.
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NR 71
TC 27
Z9 27
U1 0
U2 24
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 2013
VL 31
IS 5
BP 966
EP 978
DI 10.1002/stem.1339
PG 13
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 131RV
UT WOS:000318014100013
PM 23362204
DA 2022-11-30
ER

PT J
AU Mandal, MNA
   Moiseyev, GP
   Elliott, MH
   Kasus-Jacobi, A
   Li, XM
   Chen, H
   Zheng, LX
   Nikolaeva, O
   Floyd, RA
   Ma, JX
   Anderson, RE
AF Mandal, Md Nawajes A.
   Moiseyev, Gennadiy P.
   Elliott, Michael H.
   Kasus-Jacobi, Anne
   Li, Xiaoman
   Chen, Hui
   Zheng, Lixin
   Nikolaeva, Olga
   Floyd, Robert A.
   Ma, Jian-Xing
   Anderson, Robert E.
TI alpha-Phenyl-N-tert-butylnitrone (PBN) Prevents Light-induced
   Degeneration of the Retina by Inhibiting RPE65 Protein Isomerohydrolase
   Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID APOPTOTIC CELL-DEATH; SPIN-TRAPPING AGENT; VISUAL CYCLE; MACULAR
   DEGENERATION; RAT RETINA; IN-VIVO; CONGENITAL AMAUROSIS;
   LIPID-PEROXIDATION; BUTYL NITRONE; VITAMIN-A
AB alpha-Phenyl-N-tert-butylnitrone (PBN), a free radical spin trap, has been shown previously to protect retinas against light-induced neurodegeneration, but the mechanism of protection is not known. Here we report that PBN-mediated retinal protection probably occurs by slowing down the rate of rhodopsin regeneration by inhibiting RPE65 activity. PBN (50 mg/kg) protected albino Sprague-Dawley rat retinas when injected 0.5-12 h before exposure to damaging light at 2,700 lux intensity for 6 h but had no effect when administered after the exposure. PBN injection significantly inhibited in vivo recovery of rod photoresponses and the rate of recovery of functional rhodopsin photopigment. Assays for visual cycle enzyme activities indicated that PBN inhibited one of the key enzymes of the visual cycle, RPE65, with an IC50 = 0.1 mM. The inhibition type for RPE65 was found to be uncompetitive with K-i = 53 mu M. PBN had no effect on the activity of other visual cycle enzymes, lecithin retinol acyltransferase and retinol dehydrogenases. Interestingly, a more soluble form of PBN, N-tert-butyl-alpha-(2-sulfophenyl) nitrone, which has similar free radical trapping activity, did not protect the retina or inhibit RPE65 activity, providing some insight into the mechanism of PBN specificity and action. Slowing down the visual cycle is considered a treatment strategy for retinal diseases, such as Stargardt disease and dry age-related macular degeneration, in which toxic byproducts of the visual cycle accumulate in retinal cells. Thus, PBN inhibition of RPE65 catalytic action may provide therapeutic benefit for such retinal diseases.
C1 [Mandal, Md Nawajes A.] Univ Oklahoma Hlth Sci Ctr, Dept Ophthalmol, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA.
   [Mandal, Md Nawajes A.; Moiseyev, Gennadiy P.; Elliott, Michael H.; Kasus-Jacobi, Anne; Nikolaeva, Olga; Ma, Jian-Xing] Univ Oklahoma Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA.
   [Floyd, Robert A.] Univ Oklahoma Hlth Sci Ctr, Dept Biochem, Oklahoma City, OK 73104 USA.
   [Anderson, Robert E.] Univ Oklahoma Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Moiseyev, Gennadiy P.; Nikolaeva, Olga; Ma, Jian-Xing] Univ Oklahoma Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK 73104 USA.
   [Floyd, Robert A.] Oklahoma Med Res Fdn, Expt Therapeut Res Lab, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Oklahoma System; University of Oklahoma
   Health Sciences Center; University of Oklahoma System; University of
   Oklahoma Health Sciences Center; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; Oklahoma Medical Research
   Foundation
RP Mandal, MNA (通讯作者)，Univ Oklahoma Hlth Sci Ctr, Dept Ophthalmol, Dean A McGee Eye Inst, 608 SL Young Blvd, Oklahoma City, OK 73104 USA.
EM mmandal@ouhsc.edu
RI KASUS-JACOBI, Anne/V-7799-2019; du, zhao jiang/F-6229-2011
OI KASUS-JACOBI, Anne/0000-0003-3844-0450; hui, chen/0000-0001-5276-2515
FU National Institutes of Health (NIH), NEI [EY 012190, EY 04149, EY
   019494, EY 012231, EY 00871]; NIH, NCRR [RR 17703]; Foundation Fighting
   Blindness, USA; Research to Prevent Blindness, Inc., USA; University of
   Oklahoma College of Medicine Alumni Association
FX This work was supported, in whole or in part, by National Institutes of
   Health (NIH), NEI Grants EY 012190, EY 04149, EY 019494, EY 012231, and
   EY 00871 and NIH, NCRR, Grant RR 17703. This work was also supported by
   the Foundation Fighting Blindness, USA, Research to Prevent Blindness,
   Inc., USA, and the University of Oklahoma College of Medicine Alumni
   Association.
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NR 65
TC 44
Z9 44
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 16
PY 2011
VL 286
IS 37
BP 32491
EP 32501
DI 10.1074/jbc.M111.255877
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 818CK
UT WOS:000294726800059
PM 21785167
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Igarashi, T
   Miyake, K
   Masuda, I
   Takahashi, H
   Shimada, T
AF Igarashi, Tsutomu
   Miyake, Koichi
   Masuda, Ikuya
   Takahashi, Hiroshi
   Shimada, Takashi
TI Adeno-Associated Vector (Type 8)-Mediated Expression of Soluble Flt-1
   Efficiently Inhibits Neovascularization in a Murine Choroidal
   Neovascularization Model
SO HUMAN GENE THERAPY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; MACULAR
   DEGENERATION; GENE-TRANSFER; OCULAR NEOVASCULARIZATION; MEDIATED
   EXPRESSION; THERAPY; DISEASE; VIRUS; VEGF
AB To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated a recombinant adeno-associated viral (AAV) vector (type 8) encoding soluble Flt-1 (AAV-sflt-1), and determined its ability to inhibit angiogenesis. When we treated human umbilical vein endothelial cells (HUVECs) with the supernatant of cells transduced with AAV-sflt-1 or AAV-EGFP (control), we found that tube formation was significantly inhibited by the former but not the latter (area: 25,121 +/- 557 vs. 68,628 +/- 1357 pixels [p < 0.01]; length: 4811 +/- 246 vs. 10,894 +/- 297 pixels [p < 0.01]). CNV was induced in C57BL/6 mice by making four separate choroidal burns around the optic nerve in each eye, using a diode laser. Thereafter, 2 ml (5 x 10(11) vector genomes/ml) of AAV-sflt-1 (n = 11) or control AAV-LacZ (n = 12) was injected into the subretinal space, and 2 weeks later the eyes were removed for flatmount analysis of CNV surface area. Notably, subretinal delivery of AAV-sflt-1 significantly diminished CNV at the laser lesions, as compared with AAV-LacZ (555 +/- 304 vs. 1470 +/- 1000 mu m(2); p = 0.007). These results suggest that there was diffusion of the secreted sFlt-1 across the retina and that long-term suppression of CNV is possible through the use of stable rAAV-mediated sflt-1 expression. In vivo gene therapy thus appears to be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration.
C1 [Miyake, Koichi] Nippon Med Sch, Dept Biochem & Mol Biol, Bunkyo Ku, Div Gene Therapy,Res Ctr Adv Med Technol, Tokyo 1138602, Japan.
   [Igarashi, Tsutomu; Takahashi, Hiroshi] Nippon Med Sch, Res Ctr Adv Med Technol, Dept Ophthalmol, Tokyo 1138603, Japan.
   [Masuda, Ikuya] Okayama Univ, Dept Ophthalmol, Okayama 7008558, Japan.
C3 Nippon Medical School; Nippon Medical School; Okayama University
RP Miyake, K (通讯作者)，Nippon Med Sch, Dept Biochem & Mol Biol, Bunkyo Ku, Div Gene Therapy,Res Ctr Adv Med Technol, 1-1-5 Sendagi, Tokyo 1138602, Japan.
EM kmiyake@nms.ac.jp
OI Igarashi, Tsutomu/0000-0002-7467-6746
FU Ministry of Health and Welfare of Japan; Ministry of Education, Science,
   and Culture of Japan
FX This work was supported in part by grants from the Ministry of Health
   and Welfare of Japan and the Ministry of Education, Science, and Culture
   of Japan. The authors thank Dr. James Wilson at the University of
   Pennsylvania for providing AAV packaging plasmids (pacH, and
   p5E18-VD2/8). The authors also thank Yukihiko Hirai and Yuko Odagaki for
   making AAV viral vectors, and Nagisa Asakawa for technical assistance.
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NR 39
TC 30
Z9 32
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD MAY
PY 2010
VL 21
IS 5
BP 631
EP 637
DI 10.1089/hum.2009.153
PG 7
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 591EL
UT WOS:000277282000010
PM 20053138
DA 2022-11-30
ER

PT J
AU Yamada, M
   Hiratsuka, Y
   Roberts, CB
   Pezzullo, ML
   Yates, K
   Takano, S
   Miyake, K
   Taylor, HR
AF Yamada, Masakazu
   Hiratsuka, Yoshimune
   Roberts, Chris B.
   Pezzullo, M. Lynne
   Yates, Katie
   Takano, Shigeru
   Miyake, Kensaku
   Taylor, Hugh R.
TI Prevalence of Visual Impairment in the Adult Japanese Population by
   Cause and Severity and Future Projections
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Burden of disease; Epidemiology; Eye disease; Prevalence; Visual
   impairment
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; POLYPOIDAL CHOROIDAL
   VASCULOPATHY; BLUE MOUNTAINS EYE; QUALITY-OF-LIFE; MACULAR DEGENERATION;
   OLDER POPULATION; BLINDNESS; HISAYAMA; ACUITY
AB Purpose: To present a comprehensive estimate of the total number of people with visual impairment in the adult Japanese population by age, gender, severity and cause, and to estimate future prevalence based on population projections and expected demographic changes.
   Methods: Definitions of visual impairment used in this study were based on the United States criteria. Total visual impairment was calculated as the sum of low vision and blindness. The prevalence estimates were based on input from a number of Japanese epidemiological surveys, census material and official population projections.
   Results: There were an estimated 1.64 million people with visual impairment in 2007 in Japan. Of these, 187,800 were estimated to be blind. The prevalence of visual impairment in Japan increased with age and half of the people with visual impairment were aged 70 years or older. The leading causes of visual impairment in Japan were glaucoma (24.3%), diabetic retinopathy (20.6%), degenerative myopia (12.2%), age-related macular degeneration (10.9%), and cataract (7.2%). These five major causes comprised three-quarters of all visual impairment. The prevalence of visual impairment was projected to increase from 1.3% of the population in 2007 to 2.0% by 2050.
   Conclusions: This comprehensive study presents the prevalence of total visual impairment in the adult Japanese population. The projected increases in the prevalence of visual impairment over time reflect the demographic changes of a declining and aging Japanese population. These projections highlight that the burden of disease due to visual impairment and imposed on society is likely to increase.
C1 [Yamada, Masakazu] Natl Tokyo Med Ctr, Natl Inst Sensory Organs, Div Vis Res, Meguro Ku, Tokyo 1528902, Japan.
   [Hiratsuka, Yoshimune] Juntendo Univ, Sch Med, Dept Ophthalmol, Tokyo 113, Japan.
   [Roberts, Chris B.; Pezzullo, M. Lynne; Yates, Katie] Access Econ Pty Ltd, Barton, ACT, Australia.
   [Takano, Shigeru] Takano Eye Clin, Kawasaki, Kanagawa, Japan.
   [Miyake, Kensaku] Shozan Kai Miyake Eye Hosp, Nagoya, Aichi, Japan.
   [Taylor, Hugh R.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia.
C3 Juntendo University; University of Melbourne
RP Yamada, M (通讯作者)，Natl Tokyo Med Ctr, Natl Inst Sensory Organs, Div Vis Res, Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
EM yamadamasakazu@kankakuki.go.jp
OI Taylor, Hugh/0000-0002-9437-784X
FU National Hospital Organization in Japan
FX This study was supported by the grant from National Hospital
   Organization in Japan and the grant from the Japan Ophthalmologists
   Association. Assistance was provided by Professor Akira Murakami from
   the Department of Ophthalmology, Juntendo University School of Medicine,
   and Professor Shunichi Fukuhara from the Department of Epidemiology and
   Health Care Research, Kyoto University.
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   Yuzawa M, 1997, INT OPHTHALMOL, V21, P1, DOI 10.1023/A:1005845521424
NR 31
TC 118
Z9 129
U1 0
U2 10
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 FEB
PY 2010
VL 17
IS 1
BP 50
EP 57
DI 10.3109/09286580903450346
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 569IX
UT WOS:000275590900007
PM 20100100
DA 2022-11-30
ER

PT J
AU Lakkaraju, A
   Finnemann, SC
   Rodriguez-Boulan, E
AF Lakkaraju, Aparna
   Finnemann, Silvia C.
   Rodriguez-Boulan, Enrique
TI The lipofuscin fluorophore A2E perturbs cholesterol metabolism in
   refinal treatment epithelial cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE drusen; lysosome; macular degeneration; phagocytosis; retina
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; LIPOPROTEIN-LIKE
   PARTICLES; LYSOSOMAL ACID LIPASE; MACULAR DEGENERATION; MEMBRANE
   CHOLESTEROL; BASAL DEPOSITS; DRUSEN; PHOSPHOLIPIDS; MODULATION
AB Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the presence of cholesterol and cholesteryl ester deposits beneath the retinal pigment epithelium (RPE), implicating abnormal cholesterol trafficking in disease progression. Here, we show that A2E, a quaternary amine and retinoid by-product of the visual cycle, causes the accumulation of free and esterified cholesterol in RPE cells. The mechanism involves neither generalized alterations in late endosomal/lysosomal pH nor a direct inhibition of acid lipase activity. Rather, A2E prevents cholesterol efflux from these organelles, which in turn indirectly inhibits acid lipase, leading to a subsequent accumulation of cholesteryl esters. Transcriptional activation of the ABCA1 cholesterol transporter by agonists of the liver X receptor/peroxisome proliferator-activated receptor pathway relieves the A2E-induced block on cholesterol efflux and restores cholesterol homeostasis in RPE cells. Our data also demonstrate that A2E, which is a cone-shaped lipid, increases the chemical activity and displacement of cholesterol from model membranes, providing a biophysical mechanism for cholesterol sequestration in A2E-loaded cells. Although endogenously produced A2E in the RPE has been associated with macular degeneration, the precise mechanisms are unclear. Our results provide direct evidence that A2E causes aberrant cholesterol metabolism in RPE cells which could likely contribute to AMD progression.
C1 Cornell Univ, Weill Med Coll, Margaret M Dyson Vis Res Inst, Dept Ophthalmol, New York, NY 10021 USA.
   Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10021 USA.
   Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
C3 Cornell University; Cornell University; Cornell University
RP Lakkaraju, A (通讯作者)，Cornell Univ, Weill Med Coll, Margaret M Dyson Vis Res Inst, Dept Ophthalmol, New York, NY 10021 USA.
EM apl200l@med.cornell.edu; boulan@mail.med.cornell.edu
FU NATIONAL EYE INSTITUTE [R01EY008538, F32EY015363, R01EY013295] Funding
   Source: NIH RePORTER; NEI NIH HHS [R01 EY008538, R01 EY013295, EY13295,
   EY08538, F32 EY015363] Funding Source: Medline
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NR 39
TC 123
Z9 126
U1 0
U2 4
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 JUN 26
PY 2007
VL 104
IS 26
BP 11026
EP 11031
DI 10.1073/pnas.0702504104
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 184LC
UT WOS:000247641900051
PM 17578916
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Trivino, A
   Ramirez, AI
   Salazar, JJ
   de Hoz, R
   Rojas, B
   Padilla, E
   Tejerina, T
   Ramirez, JM
AF Trivino, Alberto
   Ramirez, Ana I.
   Salazar, Juan J.
   de Hoz, Rosa
   Rojas, Blanca
   Padilla, Eugenia
   Tejerina, Teresa
   Ramirez, Jose M.
TI A cholesterol-enriched diet induces ultrastructural changes in retinal
   and macroglial rabbit cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE cholesterol-fed rabbit; retina; electron microscopy; Bruch's membrane;
   astrocytes; Muller cells; AMD
ID FIBRILLARY ACIDIC PROTEIN; APOLIPOPROTEIN-E; BRAIN; RAT; ASTROCYTES;
   EXPRESSION; MODEL; DEGENERATION; METABOLISM; TURNOVER
AB The purpose of this study was to ascertain whether the excess of cholesterol in rabbits induces ultrastructural retinal changes similar to those observed in human age-related macular degeneration (AMD). New Zealand rabbits were divided into two groups: Control (GO; n = 10), fed standard diet for 8 months; hypercholesterolemic (G1; n = 10), fed with 0.5% cholesterol-enriched diet for 8 months. Eyes were processed for transmission electron microscopy (TEM) and immunohistochemistry (anti-glial fibrillary acidic protein, GPAP). In comparison with GO, G1 exhibited alterations in all the retinal layers that were more intense in areas overlying altered retinal pigment epithelium (RPE). RPE changes showed no preferential location. In G1, Bruch's membrane was thicker as a result particle build-up in the collagen layers; the cytoplasm of RPE showed dense bodies, debris from cell membranes, vacuoles and numerous clumps of lipids; necrosis and apoptosis were detected in different retinal layers; Muller cells and astrocytes were reactive with instances of apoptosis and necrosis; some Muller cells filled up the empty spaces left by degenerated neurons in all retinal layers; some Muller cell nuclei were displaced to the nerve-fiber layer (NFL); epiretinal perivascular astrocytes contained drops of lipids; the NFL had very few astrocytes and the basal membranes of capillaries in the NFL was thicker. Excess cholesterol induces ultrastructural changes in the rabbit retina similar to those in human AMD. Given that lipid intake is most dependent on food composition, dietary regimen could help induce or prevent retinal disease. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Univ Complutense Madrid, Fac Med, Inst Invest Oftalmol Ramon Castroviejo, E-28040 Madrid, Spain.
   Univ Complutense Madrid, Sch Med, Dept Pharmacol, E-28040 Madrid, Spain.
C3 Complutense University of Madrid; Complutense University of Madrid
RP Ramirez, AI (通讯作者)，Univ Complutense Madrid, Fac Med, Inst Invest Oftalmol Ramon Castroviejo, E-28040 Madrid, Spain.
EM ramirezs@med.ucm.es
RI De Hoz, Rosa/ABF-9295-2020; Salazar, Juan J/L-6887-2014; Alberto,
   Trivino/ABG-2416-2020; Ramírez, Ana I/ABF-4789-2021; ROJAS,
   BLANCA/V-8292-2017; Ramírez, José Manuel/L-6325-2014
OI De Hoz, Rosa/0000-0002-1581-087X; Salazar, Juan J/0000-0001-5480-5902;
   Ramírez, Ana I/0000-0002-2656-4723; Ramírez, José
   Manuel/0000-0002-5145-5094; ROJAS LOPEZ, MARIA
   BLANCA/0000-0002-8980-4659
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NR 52
TC 34
Z9 34
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2006
VL 83
IS 2
BP 357
EP 366
DI 10.1016/j.exer.2005.12.020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 061ND
UT WOS:000238878400015
PM 16580665
DA 2022-11-30
ER

PT J
AU Nozaki, M
   Raisler, BJ
   Sakurai, E
   Sarma, JV
   Barnum, SR
   Lambris, JD
   Chen, Y
   Zhang, K
   Ambati, BK
   Baffi, JZ
   Ambati, J
AF Nozaki, M
   Raisler, BJ
   Sakurai, E
   Sarma, JV
   Barnum, SR
   Lambris, JD
   Chen, Y
   Zhang, K
   Ambati, BK
   Baffi, JZ
   Ambati, J
TI Drusen complement components C3a and C5a promote choroidal
   neovascularization
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE angiogenesis; inflammation; injury
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MONOCYTE
   CHEMOTACTIC PROTEIN-1; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   RECEPTOR; EXPRESSION; ACTIVATION; CELLS; ANAPHYLATOXIN
AB Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30-50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD.
C1 Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40536 USA.
   Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
   Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   Univ Utah, Dept Ohpthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   Univ Utah, Program Human Mol Biol & Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA.
   Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 University of Kentucky; University of Michigan System; University of
   Michigan; University of Alabama System; University of Alabama
   Birmingham; University of Pennsylvania; Utah System of Higher Education;
   University of Utah; Utah System of Higher Education; University of Utah;
   University System of Georgia; Augusta University
RP Ambati, J (通讯作者)，Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40536 USA.
EM jamba2@uky.edu
RI Lambris, John/Q-5633-2018; Zhang, Kang/Y-2740-2019; Mohammed,
   Imran/J-8271-2012
OI Lambris, John/0000-0002-9370-5776; Zhang, Kang/0000-0002-4549-1697;
   Mohammed, Imran/0000-0002-8412-0768
FU NCRR NIH HHS [M01 RR000064, M01-RR00064] Funding Source: Medline; NEI
   NIH HHS [EY15422, R01 EY014428, P30EY014800, EY14428, R01 EY015422, R01
   EY014448, EY14448, P30 EY014800] Funding Source: Medline; NIDCD NIH HHS
   [5T32DC00065, T32 DC000065] Funding Source: Medline; NIGMS NIH HHS
   [GM62134, GM69736, R24 GM069736, R01 GM062134] Funding Source: Medline;
   NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000064] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY015422, R01EY014428, P30EY014800,
   R01EY014448] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R24GM069736, R01GM062134] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION
   DISORDERS [T32DC000065] Funding Source: NIH RePORTER
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NR 48
TC 466
Z9 543
U1 0
U2 25
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 FEB 14
PY 2006
VL 103
IS 7
BP 2328
EP 2333
DI 10.1073/pnas.0408835103
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 013LU
UT WOS:000235411600059
PM 16452172
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Papetti, M
   Shujath, J
   Riley, KN
   Herman, IM
AF Papetti, M
   Shujath, J
   Riley, KN
   Herman, IM
TI FGF-2 antagonizes the TGF-beta 1-mediated induction of pericyte
   alpha-smooth muscle actin expression: A role for Myf-5 and Smad-mediated
   signaling pathways
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GROWTH-FACTOR-BETA; ACTIVATOR INHIBITOR-1 GENE; HYPERTENSIVE-RAT BRAINS;
   TGF-BETA; FIBROBLAST-GROWTH; TRANSFORMING GROWTH-FACTOR-BETA-1;
   MICROVASCULAR PERICYTES; RETINOBLASTOMA PROTEIN; INDUCED TRANSCRIPTION;
   SKELETAL-MUSCLE
AB PURPOSE. Although the FGF and TGF-beta families are known to play an important role in regulating vascular endothelial and smooth muscle cell behavior, the influence of these matrix-binding growth factors on microvascular pericyte morphogenesis is not well understood. The current study was undertaken to examine the molecular mechanisms that mediate the effects of the endothelium-produced growth regulators FGF-2 and TGF-beta1 on retinal pericyte proliferation and contractile phenotype.
   METHODS. Using purified retinal pericytes, a series of assays were implemented, including RT-PCR, DNA binding, immuno-precipitation, electrophoretic mobility shift, and indirect immunofluorescence, in an attempt to elucidate the FGF/TGF-beta1 signaling cascades that mediate retinal microvascular cell growth and contractile phenotype.
   RESULTS. Treatment of retinal pericytes with FGF-2 and heparin stimulated nearly a log order increase in proliferation, whereas removal of FGF-2 or addition of TGF-beta1 caused withdrawal from the growth cycle, inducing a smooth-muscle-like contractile phenotype, as indicated by upregulation of alpha-smooth muscle actin (alpha-SMA). This switch from a growth-potentiated to a growth-arrested state followed induction of the transcriptional regulator myf-5, as well as the nuclear translocation of myf-5 and Smad2.
   CONCLUSIONS. Several critical features of the endothelial cell-extracellular matrix-pericyte molecular signaling axis were elucidated in the study that are likely to be responsible for regulating retinal microvascular morphogenesis during normal development, as well as the pathologic angiogenesis accompanying several ocular disorders, including diabetic retinopathy and age-related macular degeneration.
C1 Tufts Univ, Sch Med, Dept Physiol, Program Cellular & Mol Physiol, Boston, MA 02111 USA.
C3 Tufts University
RP Herman, IM (通讯作者)，Tufts Univ, Sch Med, Dept Physiol, Program Cellular & Mol Physiol, 136 Harrison Ave, Boston, MA 02111 USA.
EM ira.herman@tufts.edu
FU NATIONAL EYE INSTITUTE [R01EY009033] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY09033] Funding Source: Medline
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NR 77
TC 75
Z9 80
U1 1
U2 6
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 2003
VL 44
IS 11
BP 4994
EP 5005
DI 10.1167/iovs.03-0291
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 737LL
UT WOS:000186231800054
PM 14578427
DA 2022-11-30
ER

PT J
AU Baxter, SL
   Quackenbush, Q
   Cerda, J
   Gregg, C
   Millen, M
   Thorne, C
AF Baxter, Sally L.
   Quackenbush, Quinn
   Cerda, John
   Gregg, Chhavi
   Millen, Marlene
   Thorne, Christine
TI Implementing Clinical Informatics Tools for Primary Care-Based Diabetic
   Retinopathy Screening
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID ARTIFICIAL-INTELLIGENCE; TELEMEDICINE; WORKLOAD
AB OBJECTIVES: To improve diabetic retinopathy (DR) screening rates through a primary care-based "teleretina" screening program incorporating clinical informatics tools.STUDY DESIGN: Quality improvement study at an academic institution.METHODS: Existing DR screening workflows using in-person eye examinations were analyzed via a needs assessment. We identified gaps, which clarified the need for expanding DR screening to primary care settings. We developed informatics tools and described associated challenges and solutions. We also longitudinally monitored imaging volume and quality.RESULTS: The needs assessment identified several gaps in baseline DR screening workflows. Health information technology (IT) considerations for the new primary care- based teleretina screening program included integrating the new program with existing information systems, facilitating care coordination, and decreasing barriers to adoption by incorporating automation and other features aimed at decreasing end-user burden. We successfully developed several tools fulfilling these goals, including integration with the ophthalmology picture and archiving communication system, a customized aggregated report in the electronic health record to monitor screenings, automation of billing and health maintenance documentation, and automated results notification to primary care physicians. Of 316 primary care patients screened between October 2020 and July 2021, 73 (23%) were found to have ocular pathology, including DR, glaucoma, age-related macular degeneration, and a range of other eye conditions that were previously undiagnosed.CONCLUSIONS: New models of health care delivery, including telemedicine workflows, have become increasingly important for complex diabetic care coordination and require substantial health IT engagement. This program illustrates how clinical informatics tools can make substantial contributions to improving diabetes care.
C1 [Baxter, Sally L.] Univ Calif San Diego, Viterbi Family Dept Ophthalmol, La Jolla, CA USA.
   [Baxter, Sally L.] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA USA.
   [Baxter, Sally L.; Cerda, John; Gregg, Chhavi; Millen, Marlene] Univ Calif San Diego, Dept Biomed Informat, La Jolla, CA USA.
   [Quackenbush, Quinn; Millen, Marlene; Thorne, Christine] Univ Calif San Diego, Dept Internal Med, La Jolla, CA USA.
   [Baxter, Sally L.] Univ Calif San Diego, 9415 Campus Point Dr,MC0946, La Jolla, CA 92093 USA.
C3 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;
   University of California System; University of California San Diego;
   University of California System; University of California San Diego
RP Baxter, SL (通讯作者)，Univ Calif San Diego, 9415 Campus Point Dr,MC0946, La Jolla, CA 92093 USA.
EM S1baxter@health.ucsd.edu
FU National Institutes of Health; Research to Prevent Blindness; 
   [1DP5OD029610]
FX Source of Funding: Dr Baxter has funding support from National
   Institutes of Health grant 1DP5OD029610 and an unrestricted departmental
   grant from Research to Prevent Blindness. The funders had no role in the
   design or conduct of the study.
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NR 48
TC 0
Z9 0
U1 1
U2 1
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD OCT
PY 2022
VL 28
IS 10
DI 10.37765/ajmc.2022.89253
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
   General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services; General & Internal Medicine
GA 5R5AU
UT WOS:000874524100001
PM 36252175
DA 2022-11-30
ER

PT J
AU Abdolalizadeh, P
   Falavarjani, KG
AF Abdolalizadeh, Parya
   Falavarjani, Khalil Ghasemi
TI Correlation between global prevalence of vision impairment and
   depressive disorders
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE blindness; depression; global burden of disease; prevalence; vision
   impairment
ID QUALITY-OF-LIFE; VISUAL IMPAIRMENT; OLDER-ADULTS; DRY EYE; BLINDNESS;
   PEOPLE; SCHOOL; SYMPTOMS; CHILDREN; POVERTY
AB Purpose To assess the correlation of the worldwide prevalence of visual impairment and depressive disorders. Methods This is an ecologic study on Global Burden of Disease 2019 data. Global and national prevalence numbers and rates of vision impairment (VI) and depressive disorders were obtained from database. The human development index (HDI) and socio-demographic index (SDI) were derived from international open databases. Main outcome measures were the correlation of the VI and depressive disorders in total and different age, sex, and socioeconomic subgroups. Results In 2019, the worldwide prevalence of total VI and total depressive disorders were 9.6% (95% Uncertainty Interval (UI): 8.0-11.3) and 3.8% (95% UI: 3.4-4.2), respectively. The prevalence rates of total VI (r = 0.38, P < 0.001) as well as cataract (r = 0.43, P < 0.001), age-related macular degeneration (AMD) (r = 0.32, P < 0.001), refractive disorders (r = 0.19, P < 0.001) and near vision loss (r = 0.33, P < 0.001) correlated, positively, with dysthymia. In addition, the prevalence rates of glaucoma (r for total depressive disorders = 0.37, P < 0.001 and r for major depressive disorders (MDD) = 0.38, P < 0.001) and AMD (r for total depressive disorders = 0.37, P < 0.001 and r for MDD = 0.28, P < 0.001) had a positive correlation with MDD and total depressive disorders. The correlations remained significant in sociodemographic subgroups. Conclusion There was a significant correlation between national prevalence rates of VI and ocular disabilities with depressive disorders, worldwide.
C1 [Abdolalizadeh, Parya; Falavarjani, Khalil Ghasemi] Iran Univ Med Sci, Rassoul Akram Hosp, Eye Res Ctr, Five Senses Hlth Inst,Eye Dept, Tehran, Iran.
   [Falavarjani, Khalil Ghasemi] Iran Univ Med Sci, Stem Cell & Regenerat Med Res Ctr, Tehran, Iran.
C3 Iran University of Medical Sciences; Iran University of Medical Sciences
RP Falavarjani, KG (通讯作者)，Rassoul Akram Hosp, Sattarkhan Niayesh St, Tehran 1455364, Iran.
EM drghasemi@yahoo.com
OI Ghasemi Falavarjani, Khalil/0000-0001-5221-1844; Abdolalizadeh,
   Parya/0000-0002-7420-7448
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NR 37
TC 1
Z9 1
U1 3
U2 4
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
PY 2022
VL 32
IS 6
BP 3227
EP 3236
AR 11206721221086152
DI 10.1177/11206721221086152
EA MAR 2022
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4Z0VS
UT WOS:000769413400001
PM 35275499
DA 2022-11-30
ER

PT J
AU De Rossi, G
   Lobo, MED
   Greenwood, J
   Moss, SE
AF De Rossi, Giulia
   Da Vitoria Lobo, Marlene E.
   Greenwood, John
   Moss, Stephen E.
TI LRG1 as a novel therapeutic target in eye disease
SO EYE
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION;
   LEUCINE-RICH ALPHA-2-GLYCOPROTEIN; RETINAL-PIGMENT EPITHELIUM;
   DIABETIC-RETINOPATHY; AQUEOUS-HUMOR; CYTOCHROME-C; MACULAR DEGENERATION;
   ALPHA-2 GLYCOPROTEIN; SIGNALING PATHWAYS
AB Retinal and choroidal diseases are major causes of blindness and visual impairment in the developed world and on the rise due to an ageing population and diabetes epidemic. Standard of care is centred around blockade of vascular endothelial growth factor (VEGF), but despite having halved the number of patients losing sight, a high rate of patient non-response and loss of efficacy over time are key challenges. Dysregulation of vascular homoeostasis, coupled with fibrosis and inflammation, are major culprits driving sight-threatening eye diseases. Improving our knowledge of these pathological processes should inform the development of new drugs to address the current clinical challenges for patients. Leucine-rich alpha-2 glycoprotein 1 (LRG1) is an emerging key player in vascular dysfunction, inflammation and fibrosis. Under physiological conditions, LRG1 is constitutively expressed by the liver and granulocytes, but little is known about its normal biological function. In pathological scenarios, such as diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD), its expression is ectopically upregulated and it acquires a much better understood pathogenic role. Context-dependent modulation of the transforming growth-factor beta (TGF beta) pathway is one of the main activities of LRG1, but additional roles have recently been emerging. This review aims to highlight the clinical and pre-clinical evidence for the pathogenic contribution of LRG1 to vascular retinopathies, as well as extrapolate from other diseases, functions which may be relevant to eye disease. Finally, we will provide a current update on the development of anti-LRG1 therapies for the treatment of nvAMD.
C1 [De Rossi, Giulia; Da Vitoria Lobo, Marlene E.; Greenwood, John; Moss, Stephen E.] UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
C3 University of London; University College London
RP De Rossi, G; Lobo, MED; Greenwood, J; Moss, SE (通讯作者)，UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM giulia.derossi@ucl.ac.uk; marlene.lobo@ucl.ac.uk; j.greenwood@ucl.ac.uk;
   s.moss@ucl.ac.uk
OI De Rossi, Giulia/0000-0001-6163-4590; Greenwood,
   John/0000-0003-4496-2984; Moss, Stephen/0000-0002-7304-8879; Da Vitoria
   Lobo, Marlene Elisa/0000-0001-5620-1010
FU Wellcome Trust (Wellcome); RCUK Medical Research Council (MRC); Diabetes
   UK; British Heart Foundation (BHF); Rosetrees Trust; Wellcome; MRC; RCUK
   Biotechnology and Biological Sciences Research Council (BBSRC)
FX GDR is funded by Diabetes UK, MDVL is funded by RCUK Biotechnology and
   Biological Sciences Research Council (BBSRC). JG is funded by Wellcome
   Trust (Wellcome), RCUK Medical Research Council (MRC), Diabetes UK,
   British Heart Foundation (BHF) and Rosetrees Trust. SM is funded by
   Wellcome, MRC and Diabetes UK.
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NR 151
TC 3
Z9 3
U1 2
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2022
VL 36
IS 2
BP 328
EP 340
DI 10.1038/s41433-021-01807-4
EA JAN 2022
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YQ7VR
UT WOS:000739256700004
PM 34987199
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ahmed, I
   Maghsoudlou, P
   Hasan, H
   Abumattar, A
   Shah, N
AF Ahmed, Ibrar
   Maghsoudlou, Panayiotis
   Hasan, Hani
   Abumattar, Allaaeldin
   Shah, Nimish
TI Safety and efficacy of nurse led intravitreal injection service with
   Precivia (R) injection assist device
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF; intravitreal injections; nurses; service delivery; safety;
   retina; age-related macular degeneration
ID RANIBIZUMAB
AB Introduction Intravitreal anti-VEGF injections are the most frequently performed outpatient procedure in the UK. Ophthalmic allied healthcare professionals are replacing medical professionals in delivering injections nationwide. The use of injection assist devices such as Precivia (R) has been well established and increasingly adopted to aid in their safe delivery. We present outcomes of nurse-led intravitreal injections using the Precivia (R) injection assist device over a five-year period in the UK. Methods A retrospective review was completed of all anti-VEGF intravitreal injections delivered at the Great Western Hospital between May 2015 and May 2020. Results Over the five-year study period, 2318 patients underwent a total of 26,923 intravitreal injections; 20,421 (75.8%) of which were delivered by appropriately trained ophthalmic nurses. The annual number of injections increased year-on-year from 2112 injections in 2015-2016 to 5410 injections in 2019-2020. The mean age of patients was 75.7 +/- 12.2 years with a female-to-male ratio was 1.17:1. Wet age-related macular degeneration represented the major indication for injections followed by retinal vein occlusion and diabetic maculopathy respectively. Three cases of post-injection endophthalmitis out of 20,421 (0.015%) injections in nurse injection group were identified during the study period. There were no cases of lens touch, retinal detachment or systemic thromboembolic events. Conclusion Use of the Precivia (R) intravitreal injection assist device by trained ophthalmic allied health professionals is a safe and cost-effective way to deliver intravitreal injections service.
C1 [Ahmed, Ibrar; Maghsoudlou, Panayiotis; Abumattar, Allaaeldin; Shah, Nimish] Great Western Hosp NHS Fdn Trust, Dept Ophthalmol, Swindon, Wilts, England.
   [Maghsoudlou, Panayiotis] UCL, Gower St, London WC1E 6BT, England.
   [Hasan, Hani] North West Anglia NHS Fdn Trust, Peterborough, England.
C3 University of London; University College London
RP Maghsoudlou, P (通讯作者)，UCL, Gower St, London WC1E 6BT, England.
EM p.maghsoudlou@ucl.ac.uk
CR Boddie T, 2014, CLIN OPHTHALMOLOGY A
   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
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NR 14
TC 0
Z9 0
U1 0
U2 1
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 SEP
PY 2022
VL 32
IS 5
BP 2771
EP 2776
AR 11206721211060947
DI 10.1177/11206721211060947
EA NOV 2021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3S5GW
UT WOS:000721375700001
PM 34791908
DA 2022-11-30
ER

PT J
AU Ye, SH
   Chen, Q
   Jiang, N
   Liang, X
   Li, JM
   Zong, RR
   Huang, CH
   Qiu, Y
   Ma, JX
   Liu, ZG
AF Ye, Sihao
   Chen, Qian
   Jiang, Nan
   Liang, Xu
   Li, Jingming
   Zong, Rongrong
   Huang, Caihong
   Qiu, Yan
   Ma, Jian-Xing
   Liu, Zuguo
TI PPAR alpha-Dependent Effects of Palmitoylethanolamide Against Retinal
   Neovascularization and Fibrosis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE palmitoylethanolamide; neovascularization; retinal fibrosis;
   proliferative retinopathy; neovascular age-related macular degeneration
ID OXYGEN-INDUCED RETINOPATHY; DIABETIC-RETINOPATHY; MULLER CELLS;
   EXPRESSION; PROLIFERATION; ANGIOGENESIS; RECEPTOR; MOUSE; ACTIVATION;
   MODEL
AB PURPOSE. Pathological neovascularization and fibrosis are common pathological changes of many retinal diseases, such as proliferative retinopathy (PR) and age-related macular degeneration (AMD). Treatment modalities for these pathological changes are limited. The purpose of the present study was to test the effects of palmitoylethanolamide (PEA), an endocannabinoid mimetic amide, on retinal neovascularization and fibrosis and to determine its molecular mechanism of action.
   METHODS. A rat Muller cell line (rMC-1), a mouse model of oxygen-induced retinopathy (OIR), and the very-low-density lipoprotein receptor (VLDLR) knockout mouse model were used. PEA was intraperitoneally injected or orally administrated in animal models. Inflammation and profibrotic changes were evaluated by western blot analysis. Glial fibrillary acidic protein (GFAP) and peroxisome proliferator-activated receptor alpha (PPAR alpha) were measured by RT-PCR and western blot analysis.
   RESULTS. Profibrotic changes were present in OIR and Vldlr(-/-) retinas. PEA significantly alleviated inflammation and inhibited neovascularization in OIR and Vldlr(-/-) retinas and suppressed profibrotic changes in OIR and Vldlr(-/-) retinas. Moreover, PEA potently suppressed Muller gliosis in these retinas. In rMC-1 cells, PEA suppressed Muller gliosis, reduced inflammatory cytokines, and attenuated profibrotic changes. Further, both mRNA and protein levels of PPAR alpha were elevated in the retina under PEA treatment, and the effects of PEA were abolished in Ppara(-/-) OIR mice.
   CONCLUSIONS. PEA reduced retinal neovascularization and fibrotic changes and suppressed Muller gliosis in experimental PR and neovascular AMD by activating PPAR alpha. PEA may be a potential treatment for retinopathies with pathological neovascularization and fibrosis.
C1 [Ye, Sihao; Chen, Qian; Jiang, Nan; Liang, Xu; Zong, Rongrong; Huang, Caihong; Qiu, Yan; Liu, Zuguo] Xiamen Univ, Xiangan Hosp, Dept Ophthalmol, Xiamen, Fujian, Peoples R China.
   [Ye, Sihao; Chen, Qian; Jiang, Nan; Liang, Xu; Zong, Rongrong; Huang, Caihong; Qiu, Yan; Liu, Zuguo] Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China.
   [Ye, Sihao; Chen, Qian; Jiang, Nan; Liang, Xu; Zong, Rongrong; Huang, Caihong; Qiu, Yan; Liu, Zuguo] Xiamen Univ, Eye Inst, 4221 South Xiangan Rd, Xiamen, Fujian, Peoples R China.
   [Ye, Sihao; Chen, Qian; Jiang, Nan; Liang, Xu; Zong, Rongrong; Huang, Caihong; Qiu, Yan; Liu, Zuguo] Xiamen Univ, Sch Med, Xiamen, Fujian, Peoples R China.
   [Chen, Qian; Huang, Caihong; Qiu, Yan; Liu, Zuguo] Xiamen Univ, Affiliated Xiamen Eye Ctr, Xiamen, Fujian, Peoples R China.
   [Li, Jingming] Nanchang Univ, Affiliated Eye Hosp, Nanchang, Jiangxi, Peoples R China.
   [Ma, Jian-Xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA.
C3 Xiamen University; Xiamen University; Xiamen University; Xiamen
   University; Nanchang University; University of Oklahoma System;
   University of Oklahoma Health Sciences Center
RP Chen, Q; Liu, ZG (通讯作者)，Xiamen Univ, Eye Inst, 4221 South Xiangan Rd, Xiamen, Fujian, Peoples R China.
EM qchen2@xmu.edu.cn; zuguoliu@xmu.edu.cn
FU National Science Foundation for Young Scientists of China [31807795];
   National Key R&D program of China [2018YFA0107302]
FX Supported by grants from the National Science Foundation for Young
   Scientists of China (31807795) and the National Key R&D program of China
   (2018YFA0107302).
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NR 48
TC 6
Z9 6
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2020
VL 61
IS 4
AR 15
DI 10.1167/iovs.61.4.15
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LR3XI
UT WOS:000535625700019
PM 32298438
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sun, Q
   Gong, LL
   Qi, RL
   Qing, WJ
   Zou, M
   Ke, Q
   Zhang, LC
   Tang, X
   Nie, Q
   Yang, Y
   Hu, A
   Ding, XY
   Lu, L
   Liu, YZ
   Li, DWC
AF Sun, Qian
   Gong, Lili
   Qi, Ruili
   Qing, Wenjie
   Zou, Ming
   Ke, Qin
   Zhang, Lan
   Tang, Xiangcheng
   Nie, Qian
   Yang, Yuan
   Hu, Andina
   Ding, Xiaoyan
   Lu, Lin
   Liu, Yizhi
   Li, David Wan-Cheng
TI Oxidative stress-induced KLF4 activates inflammatory response through
   IL17RA and its downstream targets in retinal pigment epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Oxidative stress; Age-related macular degeneration (AMD); KLF4; IL17RA;
   Inflammatory response; Gene regulation
ID MACULAR DEGENERATION; GENE-EXPRESSION; SODIUM IODATE; CUTTING EDGE; RPE
   CELLS; IL-17; GROWTH; DAMAGE
AB Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide. Oxidative stress (OS), inflammation and genetics are considered the key pathogenic factors contributing to AMD development. Recent evidence shows the pro-inflammatory interleukin 17 (IL17) signaling is activated in AMD patients and promotes disease pathogenesis. However, the interplay between OS and IL17 signaling, and the regulatory mechanism of IL17 pathway are largely unknown. OS-induced retinal pigment epithelial cell (RPE) damage causes both the initial pathogenesis of AMD and secondary degeneration of rods and cones. Healthy RPE is essential for ocular immune privilege, however, damaged RPE cells can activate inflammatory response. In the present study, we identified IL17RA, the principle receptor of IL17 signaling, is one of the most upregulated inflammatory genes in human RPE cells upon OS exposure. The prominent increase of IL17RA was also observed in RPE and retina of an AMD-like mouse model. Knockdown of IL17RA in RPE cells prevented OS-induced RPE cell apoptosis and reduced the inflammatory response in both RPE and macrophages. Furthermore, we found that transcription factor KLF4 directly activates IL17RA expression, therefore, promotes the production of IL1 beta and IL8 in an IL17RA-dependent manner. In addition, the mRNA level of KLF4 isoform 2 was positively correlated with that of IL17RA in AMD patients. Together, our study demonstrates an unrevealed relationship between IL17RA and OS, and a new regulatory mechanism of IL17RA by KLF4 in RPE cells. These findings suggest that inhibition of IL17RA as a new potential therapeutic target for AMD through RPE protection and inflammatory suppression upon OS exposure.
C1 [Sun, Qian; Gong, Lili; Qi, Ruili; Qing, Wenjie; Zou, Ming; Ke, Qin; Zhang, Lan; Tang, Xiangcheng; Nie, Qian; Yang, Yuan; Hu, Andina; Ding, Xiaoyan; Lu, Lin; Liu, Yizhi; Li, David Wan-Cheng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Li, DWC (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 7 Jinsui Rd,Res Bldg,Room 602-5, Guangzhou 510230, Guangdong, Peoples R China.; Gong, LL (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 7 Jinsui Rd,Res Bldg,Room 602-7, Guangzhou 510230, Guangdong, Peoples R China.
EM gonglili@gzzoc.com; liwancheng@gzzoc.com
RI liu, yi/GXE-9662-2022; Li, David/AAN-9205-2021
OI Gong, Lili/0000-0002-3129-3868
FU National Natural Science Foundation of China [81570824, 81770910,
   81500738, 81500707]; Fundamental Research Fund of the State Key
   Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
   University in China
FX We thank Dr. Huangxuan Shen from the State Key Laboratory of
   Ophthalmology, Zhongshan Ophthalmic Center for providing us with the
   KLF4 plasmid. We thank Zhiquan Li and Huan Yu from the State Key
   Laboratory of Ophthalmology, Zhongshan Ophthalmic Center for assisting
   of fundus photography. This work was supported by the National Natural
   Science Foundation of China (Grants 81570824, 81770910, 81500738, and
   81500707), and the Fundamental Research Fund of the State Key Laboratory
   of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in
   China.
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NR 43
TC 14
Z9 16
U1 0
U2 18
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 FEB 1
PY 2020
VL 147
BP 271
EP 281
DI 10.1016/j.freeradbiomed.2019.12.029
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA KC0MT
UT WOS:000506882400026
PM 31881336
DA 2022-11-30
ER

PT J
AU Taibouni, K
   Chenoune, Y
   Miere, A
   Colantuono, D
   Souied, E
   Petit, E
AF Taibouni, Kawther
   Chenoune, Yasmina
   Miere, Alexandra
   Colantuono, Donato
   Souied, Eric
   Petit, Eric
TI Automated quantification of choroidal neovascularization on Optical
   Coherence Tomography Angiography images
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Age-related macular degeneration; Choroidal neovascularization; Optical
   Coherence Tomography Angiography; Vascular segmentation; Vessel
   enhancement filtering
AB Objectives: To report the design of an automated quantification algorithm for choroidal neovascularization (CNV) in the context of neovascular age-related macular degeneration (AMD), based on Optical Coherence Tomography Angiography (OCTA) images.
   Material and methods: In this study, 54 patients (mean age 75.80 +/- 14.29 years) with neovascular AMD (type 1 and type 2 CNV) were included retrospectively and separated into two groups (Group 1-24 images; Group 2-30 images), according to the lesion topology. All patients underwent a 3 x 3 mm OCTA examination (AngioVue, Optovue, Freemont, California). The proposed algorithm is based on segmentation and enhancement methods including Frangi filter, Gabor wavelets and Fuzzy-C-Means Classification. Our results were compared to the manual quantifications given by the embedded quantification software "AngioAnalytics".
   Results: Automated CNV segmentation and quantification of three neovascular AMD biomarkers: the total vascular area (TVA), the total area (TA) and the vascular density (VD) were possible in all cases. Automated versus manual quantification comparison revealed a statistically significant difference for TVA and VD measurements for both groups (p = 0.00036 for Group 1 TVA, p < 0.0001 for Group 1 VD and Group 2 TVA and VD). The difference in TA measurements was not significant in Group 2 (p = 0.143). Bland-Altman analysis revealed low inter-method bias for TA measurements and higher bias for TVA and VD.
   Conclusion: This paper presents a method for segmenting and quantifying CNV that constitutes a valid option for clinicians. Complementary validations have to be carried out to compare our method's accuracy to "AngioAnalytics".
C1 [Taibouni, Kawther; Chenoune, Yasmina; Miere, Alexandra; Petit, Eric] Univ Paris Est, UPEC, LISSI EA 3956, F-94010 Vitry Sur Seine, France.
   [Chenoune, Yasmina] ESME Sudria Res Lab, 40 Rue Docteur Roux, F-75015 Paris, France.
   [Miere, Alexandra; Colantuono, Donato; Souied, Eric] Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Taibouni, K (通讯作者)，Univ Paris Est, UPEC, LISSI EA 3956, F-94010 Vitry Sur Seine, France.
EM kawther.taibouni@univ-paris-est.fr; yasmina.chenoune@esme.fr;
   alexandramiere@gmail.com; colantuono.donato88@gmail.com;
   esouied@hotmail.com; petit@u-pec.fr
RI Chenoune Leroul, Yasmina/GSE-3131-2022; Miere, Alexandra/AIC-4074-2022
OI Chenoune Leroul, Yasmina/0000-0002-8143-4796; Miere,
   Alexandra/0000-0003-4123-8210
FU Age-related Macular Degeneration Association
FX Authors are thankful to "Age-related Macular Degeneration
   Association"(http://www.association-dmla.com)for providing the primary
   funding for this study.
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NR 30
TC 5
Z9 5
U1 0
U2 6
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
PY 2019
VL 114
AR 103450
DI 10.1016/j.compbiomed.2019.103450
PG 9
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
   Engineering; Mathematical & Computational Biology
GA JL4SL
UT WOS:000495520100015
PM 31550556
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Mirando, AC
   Shen, JK
   Silva, RLE
   Chu, Z
   Sass, NC
   Lorenc, VE
   Green, JJ
   Campochiaro, PA
   Popel, AS
   Pandey, NB
AF Mirando, Adam C.
   Shen, Jikui
   Lima e Silva, Raquel
   Chu, Zenny
   Sass, Nicholas C.
   Lorenc, Valeria E.
   Green, Jordan J.
   Campochiaro, Peter A.
   Popel, Aleksander S.
   Pandey, Niranjan B.
TI A collagen IV-derived peptide disrupts alpha(5)beta(1) integrin and
   potentiates Ang2/Tie2 signaling
SO JCI INSIGHT
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ALPHA-5-BETA-1 INTEGRIN; N-GLYCOSYLATION;
   CELL-MIGRATION; IN-VIVO; TIE2; ANGIOPOIETIN-2; ANGIOGENESIS;
   STIMULATION; ACTIVATION
AB The angiopoietin (Ang)/Tie2 signaling pathway is essential for maintaining vascular homeostasis, and its dysregulation is associated with several diseases. Interactions between Tie2 and alpha(5)beta(1) integrin have emerged as part of this control; however, the mechanism is incompletely understood. AXT107, a collagen IV-derived peptide, has strong antipermeability activity and has enabled the elucidation of this previously undetermined mechanism. Previously, AXT107 was shown to inhibit VEGFR2 and other growth factor signaling via receptor tyrosine kinase association with specific integrins. AXT107 disrupts alpha(5)beta(1) and stimulates the relocation of Tie2 and alpha(5) to cell junctions. In the presence of Ang2 and AXT107, junctional Tie2 is activated, downstream survival signals are upregulated, F-actin is rearranged to strengthen junctions, and, as a result, endothelial junctional permeability is reduced. These data suggest that alpha(5)beta(1) sequesters Tie2 in nonjunctional locations in endothelial cell membranes and that AXT107-induced disruption of alpha(5)beta(1) promotes clustering of Tie2 at junctions and converts Ang2 into a strong agonist, similar to responses observed when Ang1 levels greatly exceed those of Ang2. The potentiation of Tie2 activation by Ang2 even extended to mouse models in which AXT107 induced Tie2 phosphorylation in a model of hypoxia and inhibited vascular leakage in an Ang2-overexpression transgenic model and an LPS-induced inflammation model. Because Ang2 levels are very high in ischemic diseases, such as diabetic macular edema, neovascular age-related macular degeneration, uveitis, and cancer, targeting alpha(5)beta(1) with AXT107 provides a potentially more effective approach to treat these diseases.
C1 [Mirando, Adam C.; Chu, Zenny; Sass, Nicholas C.; Green, Jordan J.; Popel, Aleksander S.; Pandey, Niranjan B.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 611 Traylor Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA.
   [Shen, Jikui; Lima e Silva, Raquel; Lorenc, Valeria E.; Green, Jordan J.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Green, Jordan J.; Popel, Aleksander S.; Pandey, Niranjan B.] AsclepiX Therapeut Inc, 301 West 29th St,Suite 2004, Baltimore, MD 21211 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Popel, AS (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 611 Traylor Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA.; Pandey, NB (通讯作者)，AsclepiX Therapeut Inc, 301 West 29th St,Suite 2004, Baltimore, MD 21211 USA.
EM apopel@jhu.edu; npandey4@jhmi.edu
RI Green, Jordan/B-9001-2009; Popel, Aleksander S/A-6724-2009
OI Green, Jordan/0000-0003-4176-3808; 
FU Office of the Director of the NIH [S10OD016374]; NIH [F32CA210482,
   R21EY026148, R01CA138264, R43EY025903, R01EY028996, R01HL101200,
   R44EY025470]; Research to Prevent Blindness/Dr. H. James and Carole Free
   Catalyst Award; Life Science Investment Fund (LSIF, Maryland Technology
   Development Corporation); NATIONAL CANCER INSTITUTE [R01CA138264,
   F32CA210482] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R21EY026148, R01EY028996, R44EY025447] Funding Source: NIH RePORTER;
   NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL101200] Funding Source:
   NIH RePORTER
FX We thank the Johns Hopkins University ChemCore facility for the use of
   their BD Pathway 855 automated confocal microscope and School of
   Medicine Microscopy Facility (MicFac) for the use of the Zeiss LSM700
   confocal microscope, supported by the Office of the Director of the NIH
   under the award S10OD016374. This research was supported by NIH grants
   F32CA210482 (to ACM), R21EY026148, R01CA138264, R43EY025903,
   R01EY028996, R01HL101200, and R44EY025470, the Research to Prevent
   Blindness/Dr. H. James and Carole Free Catalyst Award, and Life Science
   Investment Fund (LSIF, Maryland Technology Development Corporation). We
   thank Christopher D. Kontos for helpful comments.
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NR 52
TC 24
Z9 24
U1 0
U2 13
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 FEB 21
PY 2019
VL 4
IS 4
AR e122043
DI 10.1172/jci.insight.122043
PG 19
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA HM3EA
UT WOS:000459354800004
PM 30668550
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, SB
   Wang, XR
   Cheng, YQ
   Ouyang, WJ
   Sang, X
   Liu, JH
   Su, YR
   Liu, Y
   Li, CY
   Yang, L
   Jin, L
   Wang, ZC
AF Wang, Shoubi
   Wang, Xiaoran
   Cheng, Yaqi
   Ouyang, Weijie
   Sang, Xuan
   Liu, Jiahui
   Su, Yaru
   Liu, Ying
   Li, Chaoyang
   Yang, Liu
   Jin, Lin
   Wang, Zhichong
TI Autophagy Dysfunction, Cellular Senescence, and Abnormal
   Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic
   Potential
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Review
ID OXIDATIVE STRESS; RPE
AB Age-related macular degeneration (AMD) is a blinding disease caused by multiple factors and is the primary cause of vision loss in the elderly. The morbidity of AMD increases every year. Currently, there is no effective treatment option for AMD. Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) is currently the most widely used therapy, but it only aims at neovascularization, which is an intermediate pathological phenomenon of wet AMD, not at the etiological treatment. Anti-VEGF therapy can only temporarily delay the degeneration process of wet AMD, and AMD is easy to relapse after drug withdrawal. Therefore, it is urgent to deepen our understanding of the pathophysiological processes underlying AMD and to identify integrated or new strategies for AMD prevention and treatment. Recent studies have found that autophagy dysfunction in retinal pigment epithelial (RPE) cells, cellular senescence, and abnormal immune-inflammatory responses play key roles in the pathogenesis of AMD. For many age-related diseases, the main focus is currently the clearing of senescent cells (SNCs) as an antiaging treatment, thereby delaying diseases. However, in AMD, there is no relevant antiaging application. This review will discuss the pathogenesis of AMD and how interactions among RPE autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory responses are involved in AMD, and it will summarize the three antiaging strategies that have been developed, with the aim of providing important information for the integrated prevention and treatment of AMD and laying the ground work for the application of antiaging strategies in AMD treatment.
C1 [Wang, Shoubi; Wang, Xiaoran; Cheng, Yaqi; Sang, Xuan; Su, Yaru; Liu, Ying; Li, Chaoyang; Yang, Liu; Jin, Lin; Wang, Zhichong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [Ouyang, Weijie] Xiamen Univ, Sch Med, Fujian Prov Key Lab Ophthalmol & Visual Sci, Eye Inst, Xiamen 361102, Fujian, Peoples R China.
   [Liu, Jiahui] Dongguan Peoples Hosp, Dept Ophthalmol, Dongguan 523059, Peoples R China.
C3 Sun Yat Sen University; Xiamen University
RP Wang, SB; Wang, ZC (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
EM wangzhichong@gzzoc.com
RI Li, Chao/GSM-8117-2022
OI Li, Chao/0000-0001-6110-6210; Wang, Shoubi/0000-0003-4970-2276; Cheng,
   Yaqi/0000-0001-7716-3500
FU Provincial Frontier and Key Technology Innovation Special Fund of
   Guangdong Province [2015B020227001]; Science and Technology Program of
   Guangzhou [2016201604030016]
FX This work was supported by grants from the Provincial Frontier and Key
   Technology Innovation Special Fund of Guangdong Province (No.
   2015B020227001) and the Science and Technology Program of Guangzhou (No.
   2016201604030016).
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NR 92
TC 43
Z9 47
U1 5
U2 17
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 2019
VL 2019
AR 3632169
DI 10.1155/2019/3632169
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA IB3RB
UT WOS:000470183500001
PM 31249643
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Mones, J
   Biarnes, M
AF Mones, Jordi
   Biarnes, Marc
TI Geographic atrophy phenotype identification by cluster analysis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; soft drusen;
   reticular pseudodrusen; cluster analysis
ID OPTICAL COHERENCE TOMOGRAPHY; POLYPOIDAL CHOROIDAL VASCULOPATHY; FUNDUS
   AUTOFLUORESCENCE PATTERNS; SUBRETINAL DRUSENOID DEPOSITS; MACULAR
   DEGENERATION; RETICULAR PSEUDODRUSEN; PROGRESSION; CLASSIFICATION;
   ASSOCIATION; PREVALENCE
AB Background/aims To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis.
   Methods This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for 6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared.
   Results Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm(2)/year, respectively, p=0.0005).
   Conclusion Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern.
C1 [Mones, Jordi; Biarnes, Marc] Inst Macula, Barcelona, Spain.
   [Mones, Jordi; Biarnes, Marc] Barcelona Macula Fdn, Barcelona, Spain.
RP Mones, J (通讯作者)，Barcelona Macula Fdn, Inst Macula, Barcelona 08022, Spain.
EM jmones@institutmacula.com
RI mones, jordi/CAJ-2963-2022
OI mones, jordi/0000-0003-3685-2160; Biarnes, Marc/0000-0003-2584-4894
FU EYE-RISK Consortium, European Union's Horizon research and innovation
   programme [634479]
FX This work was supported by the EYE-RISK Consortium, European Union's
   Horizon 2020 research and innovation programme, grant no 634479.
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NR 32
TC 11
Z9 11
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 MAR
PY 2018
VL 102
IS 3
BP 388
EP 392
DI 10.1136/bjophthalmol-2017-310268
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GC5HJ
UT WOS:000429817700018
PM 28729371
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Kim, KL
   Suh, W
AF Kim, Koung Li
   Suh, Wonhee
TI Apatinib, an Inhibitor of Vascular Endothelial Growth Factor Receptor 2,
   Suppresses Pathologic Ocular Neovascularization in Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE apatinib; choroidal neovascularization; oxygen-induced retinopathy;
   receptor tyrosine kinase inhibitor; vascular endothelial growth factor
ID OXYGEN-INDUCED RETINOPATHY; MACULAR DEGENERATION; IN-VIVO; CHOROIDAL
   NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION; DIABETIC-RETINOPATHY;
   TYROSINE KINASE; GASTRIC-CANCER; VEGF-D; ANGIOGENESIS
AB PURPOSE. Vascular endothelial growth factor (VEGF) signaling via VEGF receptor 2 (VEGFR2) plays a crucial role in pathologic ocular neovascularization. In this study, we investigated the antiangiogenic effect of apatinib, a pharmacologic inhibitor of VEGFR2 tyrosine kinase, against oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) in mice.
   METHODS. Western blotting and in vitro angiogenesis assays were performed using human retinal microvascular endothelial cells (HRMECs). OIR was induced in neonatal mice by exposure to 75% oxygen from postnatal day (P) 7 to P12 and to room air from P12 to P17. Experimental CNV was induced in mice using laser photocoagulation. Apatinib was intravitreally and orally administered to mice. Neovascularization and phosphorylation of VEGFR2 were evaluated by immunofluorescence staining.
   RESULTS. Apatinib inhibited VEGF-mediated activation of VEGFR2 signaling and substantially reduced VEGF-induced proliferation, migration, and cord formation in HRMECs. A single intravitreal injection of apatinib significantly attenuated retinal or choroidal neovascularization in mice with OIR or laser injury-induced CNV, respectively. Retinal or choroidal tissues of the eyes treated with apatinib exhibited substantially lower phosphorylation of VEGFR2 than those of controls injected with vehicle. Intravitreal injection of apatinib did not cause noticeable ocular toxicity. Moreover, oral administration of apatinib significantly reduced laser-induced CNV in mice.
   CONCLUSIONS. Our study demonstrates that apatinib inhibits pathologic ocular neovascularization in mice with OIR or laser-induced CNV. Apatinib may, therefore, be a promising drug for the prevention and treatment of ischemia-induced proliferative retinopathy and neovascular age-related macular degeneration.
C1 [Kim, Koung Li; Suh, Wonhee] Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea.
C3 Chung Ang University
RP Suh, W (通讯作者)，Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea.
EM wsuh@cau.ac.kr
FU National Research Foundation of Korea (NRF) grant - Korean government
   (MSIP) [2015R1A2A1A15052509, 2016M3A9A8918381]
FX Supported by a National Research Foundation of Korea (NRF) grant funded
   by the Korean government (MSIP) (No. 2015R1A2A1A15052509,
   2016M3A9A8918381).
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NR 31
TC 24
Z9 28
U1 0
U2 6
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 2017
VL 58
IS 9
BP 3592
EP 3599
DI 10.1167/iovs.17-21416
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FH1WU
UT WOS:000410931200037
PM 28715845
OA gold
DA 2022-11-30
ER

PT J
AU Lauwen, S
   de Jong, EK
   Lefeber, DJ
   den Hollander, AI
AF Lauwen, Susette
   de Jong, Eiko K.
   Lefeber, Dirk J.
   den Hollander, Anneke I.
TI Omics Biomarkers in Ophthalmology
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE omics; genomics; proteomics; transcriptomics; metabolomics
ID GENOME-WIDE ASSOCIATION; OPEN-ANGLE GLAUCOMA; GENE-EXPRESSION PATTERNS;
   CENTRAL CORNEAL THICKNESS; LONG NONCODING RNAS; MACULAR DEGENERATION;
   DIABETIC-RETINOPATHY; PROTEOMIC ANALYSIS; REFRACTIVE ERROR; DNA
   METHYLATION
AB "Omics'' refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omicsbased studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.
C1 [Lauwen, Susette; de Jong, Eiko K.; den Hollander, Anneke I.] Radboud Univ Nijmegen, Dept Ophthalmol, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Lefeber, Dirk J.] Radboud Univ Nijmegen, Dept Neurol, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Lefeber, Dirk J.] Radboud Univ Nijmegen, Translat Metab Lab, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [den Hollander, Anneke I.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen; Radboud University Nijmegen
RP den Hollander, AI (通讯作者)，409 Radboud Univ, Dept Ophthalmol, Med Ctr, Philips van Leydenlaan 15, NL-6525 EX Nijmegen, Netherlands.
EM anneke.denhollander@radboudumc.nl
RI Lauwen, Susette/C-2309-2018; de Jong, Eiko/P-3407-2015; Lefeber, Dirk
   DJ/A-2146-2014; Hollander, Anneke den/N-4911-2014
OI de Jong, Eiko/0000-0001-6520-0407; 
FU Radboud University Medical Center - Donders Institute for Brain,
   Cognition and Behaviour
FX Supported by the Radboud University Medical Center through a junior
   researcher grant awarded by the Donders Institute for Brain, Cognition
   and Behaviour.
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NR 149
TC 36
Z9 37
U1 2
U2 31
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2017
VL 58
IS 6
SI SI
BP BIO88
EP BIO98
DI 10.1167/iovs.17-21809
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EZ3EI
UT WOS:000404593000012
PM 28525563
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Balaratnasingam, C
   Hoang, QV
   Inoue, M
   Curcio, CA
   Dolz-Marco, R
   Yannuzzi, NA
   Dhrami-Gavazi, E
   Yannuzzi, LA
   Freund, KB
AF Balaratnasingam, Chandrakumar
   Hoang, Quan V.
   Inoue, Maiko
   Curcio, Christine A.
   Dolz-Marco, Rosa
   Yannuzzi, Nicolas A.
   Dhrami-Gavazi, Elona
   Yannuzzi, Lawrence A.
   Freund, K. Bailey
TI Clinical Characteristics, Choroidal Neovascularization, and Predictors
   of Visual Outcomes in Acquired Vitelliform Lesions
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; SPECTRAL-DOMAIN; DYSTROPHY; DRUSEN; 7-KETOCHOLESTEROL;
   CLASSIFICATION; MACULOPATHY; MORPHOLOGY
AB PURPOSE: To quantify the temporal properties of the acquired vitelliform lesion (AVL) life cycle, define the clinical characteristics of choroidal neovascularization (NV) in this setting, and determine the predictors of long-term visual outcomes.
   DESIGN: Retrospective cohort study.
   METHODS: Clinical and imaging data from 199 eyes of 124 consecutive patients with AVLs associated with age related macular degeneration (AMD) and adult-onset foveomacular vitelliform dystrophy (AOFVD) were analyzed. Volumetric calculations of vitelliform material were determined using spectral-domain optical coherence tomography and the temporal properties of the AVL life cycle were quantified. The clinical characteristics of NV were assessed, as were the predictors of final best corrected visual acuity (BCVA) and change in BCVA.
   RESULTS: Mean age was 79.2 +/- 12.1 years. AVLs grew and collapsed at approximately the same rate (P = .275). Fifteen eyes (7.5%) developed NV, of which all were type 1. In 13 of these eyes, NV occurred during the collapse phase of the AVL life cycle, after the peak AVL volume was reached. The risk of NV (P = .006) and the decline in BCVA (P = .001) were both significantly greater among eyes with AMD. Foveal atrophy was the characteristic most significantly associated with. final BCVA and change in BCVA from baseline (both P < .0005). The development of NV was not predictive of long-term visual outcomes (all P = .216).
   CONCLUSIONS: Complications associated with AVLs typically occur during the collapse phase of the AVL life cycle. Visual outcomes and risk of NV are related to the underlying disease associated with AVLs. ((C) 2016 Elsevier Inc. All rights reserved.)
C1 [Balaratnasingam, Chandrakumar; Inoue, Maiko; Dolz-Marco, Rosa; Yannuzzi, Nicolas A.; Dhrami-Gavazi, Elona; Yannuzzi, Lawrence A.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Balaratnasingam, Chandrakumar; Inoue, Maiko; Dolz-Marco, Rosa; Yannuzzi, Nicolas A.; Dhrami-Gavazi, Elona; Yannuzzi, Lawrence A.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
   [Balaratnasingam, Chandrakumar; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
   [Balaratnasingam, Chandrakumar] Univ Western Australia, Lions Eye Inst, Dept Physiol & Pharmacol, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia.
   [Hoang, Quan V.; Dhrami-Gavazi, Elona] Columbia Univ, Dept Ophthalmol, Coll Phys & Surg, Edward S Harkness Eye Inst, New York, NY 10027 USA.
   [Hoang, Quan V.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Hoang, Quan V.] Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
C3 Manhattan Eye Ear & Throat Hospital; Vitreous Retina Macula Consultants
   of New York; New York University; Lions Eye Institute; University of
   Western Australia; Columbia University; National University of
   Singapore; Singapore National Eye Center; National University of
   Singapore; University of Alabama System; University of Alabama
   Birmingham
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
EM kbfnyf@aol.com
RI Freund, K. Bailey/V-7488-2018
OI Freund, K. Bailey/0000-0002-7888-9773; Dolz-Marco,
   Rosa/0000-0002-2963-2541
FU LUESTHER T. MERTZ RETINAL RESEARCH CENTER, MANHATTAN EYE, EAR AND THROAT
   HOSPITAL, NEW York, New York, USA; Macula Foundation, Inc, New York, New
   York, USA [NEI EY06109]; Research to Prevent Blindness, Inc, New York,
   USA; EyeSight Foundation of America, Alabama, USA; Macula Foundation,
   New York, USA
FX LUESTHER T. MERTZ RETINAL RESEARCH CENTER, MANHATTAN EYE, EAR AND THROAT
   HOSPITAL, NEW York, New York, USA, and The Macula Foundation, Inc, New
   York, New York, USA. NEI EY06109; Research to Prevent Blindness, Inc,
   New York, USA; EyeSight Foundation of America, Alabama, USA; Macula
   Foundation, New York, USA.
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NR 56
TC 24
Z9 24
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2016
VL 172
BP 28
EP 38
DI 10.1016/j.ajo.2016.09.008
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EE5AF
UT WOS:000389616400005
PM 27640006
DA 2022-11-30
ER

PT J
AU Chan, CM
   Huang, DY
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AF Chan, Chi-Ming
   Huang, Duen-Yi
   Huang, Yi-Pin
   Hsu, Shu-Hao
   Kang, Lan-Ya
   Shen, Chung-Min
   Lin, Wan-Wan
TI Methylglyoxal induces cell death through endoplasmic reticulum
   stress-associated ROS production and mitochondrial dysfunction
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE methylglyoxal; ER stress; retinal pigment epithelium; mitochondria;
   reactive oxygen species; intracellular calcium
ID OXIDATIVE STRESS; ER STRESS; DIABETIC-RETINOPATHY; INDUCED APOPTOSIS;
   CALCIUM-ENTRY; CA2+; MECHANISMS; RECEPTOR; INHIBITION; GLYCOLYSIS
AB Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO-induced RPE cell death. Using ARPE-19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase-independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO-induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store-operated calcium channel inhibitors MRS1845 and YM-58483, but not the inositol 1,4,5-trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO-induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE-19 cells. Lastly, inhibition of ER stress by salubrinal and 4-PBA can reduce the MGO-induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress-dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.
C1 [Chan, Chi-Ming; Huang, Duen-Yi; Kang, Lan-Ya; Lin, Wan-Wan] Natl Taiwan Univ, Dept Pharmacol, Coll Med, Taipei, Taiwan.
   [Chan, Chi-Ming] Cardinal Tien Hosp, Dept Ophthalmol, New Taipei, Taiwan.
   [Chan, Chi-Ming] Fu Jen Catholic Univ, Sch Med, New Taipei, Taiwan.
   [Huang, Yi-Pin; Hsu, Shu-Hao] Cardinal Tien Hosp, Med Res Ctr, New Taipei, Taiwan.
   [Shen, Chung-Min] Cathay Gen Hosp, Dept Pediat, Taipei, Taiwan.
   [Lin, Wan-Wan] Taipei Med Univ, Grad Inst Med Sci, Taipei, Taiwan.
C3 National Taiwan University; Fu Jen Catholic University; Cathay General
   Hospital; Taipei Medical University
RP Lin, WW (通讯作者)，Natl Taiwan Univ, Dept Pharmacol, Coll Med, Taipei, Taiwan.; Shen, CM (通讯作者)，Cathay Gen Hosp, Dept Pediat, Taipei, Taiwan.; Lin, WW (通讯作者)，Taipei Med Univ, Grad Inst Med Sci, Taipei, Taiwan.
EM shen8471@yahoo.com.tw; wwllaura1119@ntu.edu.tw
RI Chan, Chi-Ming/GWZ-3612-2022
OI Lin, Wan Wan/0000-0002-3207-734X
FU MOST [103-2320-B-038-025 -MY3, 102CGH-TMU-01-1, 103CGH-TMU-01-1,
   CTH-102-1-2A30, CTH-103-27]
FX This research work was supported by MOST 103-2320-B-038-025 -MY3,
   102CGH-TMU-01-1, 103CGH-TMU-01-1, CTH-102-1-2A30 and CTH-103-27.
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NR 57
TC 70
Z9 74
U1 0
U2 20
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD SEP
PY 2016
VL 20
IS 9
BP 1749
EP 1760
DI 10.1111/jcmm.12893
PG 12
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA DW4BL
UT WOS:000383586900014
PM 27307396
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rowland, TJ
   Blaschke, AJ
   Buchholz, DE
   Hikita, ST
   Johnson, LV
   Clegg, DO
AF Rowland, Teisha J.
   Blaschke, Alison J.
   Buchholz, David E.
   Hikita, Sherry T.
   Johnson, Lincoln V.
   Clegg, Dennis O.
TI Differentiation of human pluripotent stem cells to retinal pigmented
   epithelium in defined conditions using purified extracellular matrix
   proteins
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE retinal pigmented epithelium; induced pluripotent stem cells; human
   embryonic stem cells; age-related macular degeneration; pluripotent stem
   cells; extracellular matrix; integrins; laminin
ID MACULAR DEGENERATION; RPE; VITRONECTIN; EXPRESSION; EXPANSION;
   APOPTOSIS; MEMBRANE; SUPPORTS; GROWTH
AB A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC-RPEs) and iPSCs (iPSC-RPEs) express essential RPE markers and can rescue visual function in animal models. However, standard differentiation protocols yield RPE cells at low frequency, especially from iPSC lines, and the common use of Matrigel and xenogeneic feeder cells is not compatible with clinical applications. The extracellular matrix (ECM) can affect differentiation, and therefore changes in ECM composition may improve the frequency of stem cell-RPE differentiation. We selected several purified ECM proteins and substrates, based on the in vivo RPE ECM environment, and tested their ability to support iPSC-RPE differentiation and maintenance. iPSCs differentiated on nearly all tested substrates developed pigmented regions, with Matrigel and mouse laminin-111 supporting the highest pigmentation frequencies. Although iPSC-RPEs cultured on the majority of the tested substrates expressed key RPE genes, only six substrates supported development of confluent monolayers with normal RPE morphology, including Matrigel and mouse laminin-111. iPSCs differentiated on mouse laminin-111 produced iPSC-RPEs expressing RPE proteins, and hESCs differentiated on mouse laminin-111 resulted in high yields of functional hESC-RPEs. This identification of key ECM proteins may assist with future scaffold designs and provide peptide sequences for use in synthetic, xeno-free, GMP-compliant generation of RPE from human pluripotent stem cells relevant to clinical translation. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Rowland, Teisha J.; Blaschke, Alison J.; Buchholz, David E.; Hikita, Sherry T.; Johnson, Lincoln V.; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Santa Barbara, CA 93106 USA.
   [Rowland, Teisha J.; Blaschke, Alison J.; Buchholz, David E.; Hikita, Sherry T.; Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Rowland, Teisha J.; Buchholz, David E.; Hikita, Sherry T.; Johnson, Lincoln V.; Clegg, Dennis O.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Johnson, Lincoln V.; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Study Macular Degenerat, 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, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
EM clegg@lifesci.ucsb.edu
OI Rowland, Teisha/0000-0001-5038-6763
FU California Institute for Regenerative Medicine (CIRM) [TG2-01151,
   T3-00009]; Institute for Collaborative Biotechnologies from U.S. Army
   Research Office [W911NF-09-0001]
FX We thank Jamie Thomson for iPSCs and zbFGF, and Andrew James Bonham for
   a critical reading of the manuscript. T.J.R. and D. E. B. were supported
   by the California Institute for Regenerative Medicine (CIRM) (Training
   Award Nos TG2-01151 and T3-00009, respectively) and supported by the
   Institute for Collaborative Biotechnologies through grant W911NF-09-0001
   from the U.S. Army Research Office. The content of the information does
   not necessarily reflect the position or the policy of the Government,
   and no official endorsement should be inferred.
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NR 47
TC 64
Z9 70
U1 1
U2 56
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 AUG
PY 2013
VL 7
IS 8
BP 642
EP 653
DI 10.1002/term.1458
PG 12
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 186BG
UT WOS:000322015800005
PM 22514096
DA 2022-11-30
ER

PT J
AU Habib, AG
   Cameron, MA
   Suaning, GJ
   Lovell, NH
   Morley, JW
AF Habib, Amgad G.
   Cameron, Morven A.
   Suaning, Gregg J.
   Lovell, Nigel H.
   Morley, John W.
TI Spatially restricted electrical activation of retinal ganglion cells in
   the rabbit retina by hexapolar electrode return configuration
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
ID EPIRETINAL STIMULATION; SUBRETINAL STIMULATION; MORPHOMETRIC-ANALYSIS;
   BIDOMAIN MODEL; THRESHOLDS; PIGMENTOSA; ARRAY; NEUROPROSTHESIS;
   MICROELECTRODE; PRESERVATION
AB Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed 'phosphenes'. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.
C1 [Habib, Amgad G.; Suaning, Gregg J.; Lovell, Nigel H.] Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia.
   [Cameron, Morven A.; Morley, John W.] Univ Western Sydney, Sch Med, Campbelltown, NSW, Australia.
C3 University of New South Wales Sydney; Western Sydney University
RP Habib, AG (通讯作者)，Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia.
EM amgad.habib@student.unsw.edu.au; m.cameron@uws.edu.au;
   g.suaning@unsw.edu.au; n.lovell@unsw.edu.au; j.morley@uws.edu.au
RI Lovell, Nigel H/AGF-6679-2022
OI Lovell, Nigel H/0000-0003-1637-1079; Suaning, Gregg/0000-0003-1918-3313;
   Cameron, Morven/0000-0002-2277-7035; Morley, John/0000-0001-9246-853X
FU Australian Research Council (ARC) through its Special Research
   Initiative (SRI) in Bionic Vision Science and Technology; Bionic Vision
   Australia (BVA)
FX This research was supported by the Australian Research Council (ARC)
   through its Special Research Initiative (SRI) in Bionic Vision Science
   and Technology grant to Bionic Vision Australia (BVA). The authorswould
   like to thank David Tsai and Phillip Byrnes-Preston for their continuous
   technical assistance and S Sugiharto for his help with general
   laboratory tasks.
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NR 31
TC 25
Z9 25
U1 1
U2 12
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2013
VL 10
IS 3
AR 036013
DI 10.1088/1741-2560/10/3/036013
PG 8
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA 152DM
UT WOS:000319510800016
PM 23612906
DA 2022-11-30
ER

PT J
AU Jin, KT
   Lan, HR
   Cao, FL
   Xu, ZZ
   Han, N
   Li, GL
   He, KF
   Teng, LS
AF Jin, Ketao
   Lan, Huanrong
   Cao, Feilin
   Xu, Zhenzhen
   Han, Na
   Li, Guangliang
   He, Kuifeng
   Teng, Lisong
TI Antitumor effect of FP3 in a patient-derived tumor tissue xenograft
   model of gastric carcinoma through an antiangiogenic mechanism
SO ONCOLOGY LETTERS
LA English
DT Article
DE antiangiogenic effect; antitumor effect; FP3; gastric carcinoma;
   vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; BASEMENT-MEMBRANE; LIVER METASTASES;
   BLOOD-VESSELS; IN-VITRO; VEGF; VASCULATURE; REGRESSION; ABNORMALITIES;
   ANGIOGENESIS
AB FP3 (KH902/KH903) is a novel vascular endothelial growth factor (VEGF) blocker with antiangiogenic properties. Previous studies revealed that FP3, a humanized fusion protein that combines ligand binding elements from the extracellular domains of VEGF receptors 1 and 2 and the Fc portion of IgG1, has an inhibitory effect on the VEGF-ediated proliferation and migration of human umbilical vein endothelial cells, and VEGF-mediated vessel sprouting of rat aortic rings in vitro. Thus, FP3 was considered as a new promising agent in treating human choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). FP3 also has an antitumor effect in a non-small cell lung cancer cell line (A549) xenograft model in nude mice. However, little is known of the direct effect of FP3 on tumor vessels. In this study, we investigated the effects of FP3 on blood vessels in a patient-derived tumor tissue (PDTT) xenograft model of gastric carcinoma, using large tumors with established vasculature. Treatment with FP3 caused robust and early changes in endothelial cells and pericytes of vessels in the PDTT xenograft model. Vascular density decreased and vascular sprouting was suppressed by treatment with FP3. Pericytes did not degenerate to the same extent as endothelial cells, and those on surviving tumor vessels achieved a more normal phenotype. Our results revealed that FP3 has a direct and rapid antiangiogenic effect on tumor vessels, which was achieved mainly via regression of tumor vasculature, inhibition of new and recurrent vessel growth, and normalization of existing tumor vasculature.
C1 [Jin, Ketao; Xu, Zhenzhen; Li, Guangliang; He, Kuifeng; Teng, Lisong] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Surg Oncol, Hangzhou 310003, Zhejiang, Peoples R China.
   [Jin, Ketao; Cao, Feilin] Wenzhou Med Coll, Taizhou Hosp, Dept Surg Oncol, Linhai 317000, Zhejiang, Peoples R China.
   [Jin, Ketao] Wenzhou Med Coll, Affiliated Zhuji Hosp, Dept Surg, Zhuji, Zhejiang, Peoples R China.
   [Lan, Huanrong] Wenzhou Med Coll, Taizhou Hosp, Dept Gynecol & Obstet, Linhai, Zhejiang, Peoples R China.
   [Han, Na] Zhejiang Univ Chinese Med, Zhejiang Canc Hosp, Canc Chemotherapy Ctr, Hangzhou 310003, Zhejiang, Peoples R China.
C3 Zhejiang University; Wenzhou Medical University; Wenzhou Medical
   University; Wenzhou Medical University; Zhejiang Cancer Hospital;
   Zhejiang Chinese Medical University
RP Teng, LS (通讯作者)，Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Surg Oncol, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.
EM jinketao2001@zju.edu.cn
RI Li, Guangliang/B-6715-2011
FU State Key Basic Research and Development Program of China (973 Program)
   [2009CB521704]; National High-Tech Research and Development Program of
   China (863 Program) [2006AA02A245]; National Natural Science Foundation
   of China [81000894]; Zhejiang Provincial Science and Technology Project
   [2009C13021, 2011C23087]; Science Research Fund of Shaoxing
   [2011D10013]; Science Research Fund of Zhuji [2011CC7874]
FX This study was supported by the State Key Basic Research and Development
   Program of China (973 Program, Grant No. 2009CB521704), the National
   High-Tech Research and Development Program of China (863 Program, Grant
   No. 2006AA02A245), the National Natural Science Foundation of China
   (Grant No. 81000894), the Zhejiang Provincial Science and Technology
   Project (Grants No. 2009C13021, 2011C23087), the Science Research Fund
   of Shaoxing (Grants No. 2011D10013) and the Science Research Fund of
   Zhuji (Grants No. 2011CC7874). The funding groups had no role in the
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 34
TC 10
Z9 10
U1 0
U2 12
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-1074
EI 1792-1082
J9 ONCOL LETT
JI Oncol. Lett.
PD MAY
PY 2012
VL 3
IS 5
BP 1052
EP 1058
DI 10.3892/ol.2012.603
PG 7
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 932HN
UT WOS:000303281400019
PM 22783390
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kolomeyer, AM
   Sugino, IK
   Zarbin, MA
AF Kolomeyer, Anton M.
   Sugino, Ilene K.
   Zarbin, Marco A.
TI Characterization of Conditioned Media Collected from Aged versus Young
   Human Eye Cups
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; CILIARY NEUROTROPHIC FACTOR; ENDOTHELIAL
   GROWTH-FACTOR; RESCUE PHOTORECEPTOR CELLS; EMBRYONIC STEM-CELLS; MACULAR
   DEGENERATION; IN-VITRO; FACTOR EXPRESSION; BASIC FIBROBLAST;
   GENE-EXPRESSION
AB PURPOSE. To characterize secretion of in situ retinal pigment epithelium (RPE) from healthy, aged adult, age-related macular degeneration (AMD) adult, and fetal donor eyes and to assess the impact on retinal survival in vitro.
   METHODS. Conditioned medium (CM) was collected from adult and fetal donor eyes and analyzed for trophic factor composition by multiplex ELISA. Trophic factor receptor occupancy was calculated to evaluate differences in trophic factor concentrations. RPE trophic factor mRNA expression was quantified by real-time PCR. Retina-preserving activity of the collected CM was evaluated using degenerating porcine retina in vitro.
   RESULTS. Compared with CM from adult donors, AMD donor CM contained a significantly higher concentration of brain-derived neurotrophic factor (BDNF), whereas fetal donor CM contained significantly higher concentrations of hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF). No consistent correlation was found between trophic factor mRNA expression and protein secretion. Non-RPE components of the RPE-Bruch's membrane-choroid-sclera complex were major contributors of vascular endothelial growth factor-A (VEGF-A). CM of fetal donors was significantly better than CM of adult or AMD donors at improving the survival of degenerating porcine retina.
   CONCLUSIONS. RPE cells of adult and fetal eyes have significantly different trophic factor production capabilities, which correlated with changes in preservation of porcine retina. Combined with trophic factor receptor occupancy calculations, these data may implicate HGF and PEDF as key factors promoting the preservation of retinal structure and function. (Invest Ophthalmol Vis Sci. 2011;52:5963-5972) DOI: 10.1167/iovs.10-6440
C1 [Kolomeyer, Anton M.; Sugino, Ilene K.; Zarbin, Marco A.] Univ Med & Dent New Jersey, Inst Ophthalmol & Visual Sci, New Jersey Med Sch, Newark, NJ 07101 USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center
RP Zarbin, MA (通讯作者)，Univ Med & Dent New Jersey, Inst Ophthalmol & Visual Sci, New Jersey Med Sch, 90 Bergen St,DOC6155, Newark, NJ 07101 USA.
EM zarbin@umdnj.edu
OI Zarbin, Marco/0000-0002-7811-7132
FU Janice Mitchell Vassar and Ashby John Mitchell Fellowship; Joseph J. and
   Marguerite DiSepio Retina Research Fund; Research to Prevent Blindness;
   Medical Student Fellowship; Midwest Eye Banks Student Stipend; American
   Foundation for Aging
FX Supported by The Janice Mitchell Vassar and Ashby John Mitchell
   Fellowship (MAZ), the Joseph J. and Marguerite DiSepio Retina Research
   Fund (MAZ), Research to Prevent Blindness Unrestricted Department Grant
   (MAZ) and Medical Student Fellowship (AMK), Midwest Eye Banks Student
   Stipend (AMK), and American Foundation for Aging Research Graduate
   Student Fellowship (AMK).
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NR 63
TC 16
Z9 16
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 JUL
PY 2011
VL 52
IS 8
BP 5963
EP 5972
DI 10.1167/iovs.10-6440
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800QC
UT WOS:000293377400123
PM 21398279
DA 2022-11-30
ER

PT J
AU Liao, JL
   Yu, JH
   Huang, K
   Hu, J
   Diemer, T
   Ma, ZC
   Dvash, T
   Yang, XJ
   Travis, GH
   Williams, DS
   Bok, D
   Fan, GP
AF Liao, Jo-Ling
   Yu, Juehua
   Huang, Kevin
   Hu, Jane
   Diemer, Tanja
   Ma, Zhicheng
   Dvash, Tamar
   Yang, Xian-Jie
   Travis, Gabriel H.
   Williams, David S.
   Bok, Dean
   Fan, Guoping
TI Molecular signature of primary retinal pigment epithelium and
   stem-cell-derived RPE cells
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MACULAR DEGENERATION; VISUAL FUNCTION; DIFFERENTIATION; EXPRESSION;
   GENES
AB Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies. Despite a significant amount of research on deriving functional RPE cells from various stem cell sources, it is still unclear whether stem-cell-derived RPE cells fully mimic primary RPE cells. In this report, we demonstrate that functional RPE cells can be derived from multiple lines of hESCs and hiPSCs with varying efficiencies. Stem-cell-derived RPE cells exhibit cobblestone-like morphology, transcripts, proteins and phagocytic function similar to human fetal RPE (fRPE) cells. In addition, we performed global gene expression profiling of stem-cell-derived RPE cells, native and cultured fRPE cells, undifferentiated hESCs and fibroblasts to determine the differentiation state of stem-cell-derived RPE cells. Our data indicate that hESC-derived RPE cells closely resemble human fRPE cells, whereas hiPSC-derived RPE cells are in a unique differentiation state. Furthermore, we identified a set of 87 signature genes that are unique to human fRPE and a majority of these signature genes are shared by stem-cell-derived RPE cells. These results establish a panel of molecular markers for evaluating the fidelity of human pluripotent stem cell to RPE conversion. This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy.
C1 [Liao, Jo-Ling; Yu, Juehua; Huang, Kevin; Ma, Zhicheng; Dvash, Tamar; Fan, Guoping] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Hu, Jane; Diemer, Tanja; Yang, Xian-Jie; Travis, Gabriel H.; Williams, David S.; Bok, Dean] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Fan, GP (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, 695 Charles Young Dr S, Los Angeles, CA 90095 USA.
EM gfan@mednet.ucla.edu
RI Travis, Gabriel Harvey/AIF-1062-2022; Yu, Juehua/G-4596-2013; feng,
   jian/G-9313-2011
OI Travis, Gabriel Harvey/0000-0003-4020-9493; Fan,
   Guoping/0000-0001-5235-6410
FU California Institute for Regenerative Medicine [TR1-272]; NATIONAL EYE
   INSTITUTE [P30EY000331, R01EY011713, R01EY007042] Funding Source: NIH
   RePORTER
FX This work is supported by Translational I Grant TR1-272 from California
   Institute for Regenerative Medicine to X.-J.Y., G. H. T., D. S. W., D.
   B. and G. F. G. F. is a Carol Moss Spivak Scholar in Neuroscience.
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NR 31
TC 146
Z9 156
U1 0
U2 29
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 NOV 1
PY 2010
VL 19
IS 21
BP 4229
EP 4238
DI 10.1093/hmg/ddq341
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 661TR
UT WOS:000282751500010
PM 20709808
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Edwards, AO
   Fridley, BL
   James, KM
   Sharma, AS
   Cunningham, JM
   Tosakulwong, N
AF Edwards, Albert O.
   Fridley, Brooke L.
   James, Katherine M.
   Sharma, Anil S.
   Cunningham, Julie M.
   Tosakulwong, Nirubol
TI Evaluation of Clustering and Genotype Distribution for Replication in
   Genome Wide Association Studies: The Age-Related Eye Disease Study
SO PLOS ONE
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; SUSCEPTIBILITY GENES; RISK;
   VARIANT; POLYMORPHISMS; HAPLOTYPES; LOC387715; ALLOTYPES; TESTS
AB Genome-wide association studies (GWASs) assess correlation between traits and DNA sequence variation using large numbers of genetic variants such as single nucleotide polymorphisms (SNPs) distributed across the genome. A GWAS produces many trait-SNP associations with low p-values, but few are replicated in subsequent studies. We sought to determine if characteristics of the genomic loci associated with a trait could be used to identify initial associations with a higher chance of replication in a second cohort. Data from the age-related eye disease study (AREDS) of 100,000 SNPs on 395 subjects with and 198 without age-related macular degeneration (AMD) were employed. Loci highly associated with AMD were characterized based on the distribution of genotypes, level of significance, and clustering of adjacent SNPs also associated with AMD suggesting linkage disequilibrium or multiple effects. Forty nine loci were highly associated with AMD, including 3 loci (CFH, C2/BF, LOC387715/HTRA1) already known to contain important genetic risks for AMD. One additional locus (C3) reported during the course of this study was identified and replicated in an additional study group. Tag-SNPs and haplotypes for each locus were evaluated for association with AMD in additional cohorts to account for population differences between discovery and replication subjects, but no additional clearly significant associations were identified. Relying on a significant genotype tests using a log-additive model would have excluded 57% of the non-replicated and none of the replicated loci, while use of other SNP features and clustering might have missed true associations.
C1 [Edwards, Albert O.; James, Katherine M.; Sharma, Anil S.; Tosakulwong, Nirubol] Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
   [Fridley, Brooke L.] Mayo Clin, Div Biostat, Rochester, MN USA.
   [Cunningham, Julie M.] Mayo Clin, Lab Med & Pathol, Rochester, MN USA.
C3 Mayo Clinic; Mayo Clinic; Mayo Clinic
RP Edwards, AO (通讯作者)，Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
EM edwardslab@mayo.edu
RI Fridley, Brooke L/D-8315-2015
OI Fridley, Brooke L/0000-0001-7739-7956; Sharma, Anil/0000-0002-4471-7172
FU Foundation Fighting Blindness, Owing Mills, MD; American Health
   Assistance Foundation, Clarksburg, MD; Research to Prevent Blindness,
   New York, NY; Mayo Clinic Foundation;  [EY014467]; NATIONAL EYE
   INSTITUTE [R01EY014467] Funding Source: NIH RePORTER
FX The research was supported by EY014467, the Foundation Fighting
   Blindness, Owing Mills, MD, the American Health Assistance Foundation,
   Clarksburg, MD, unrestricted departmental grants from Research to
   Prevent Blindness, New York, NY, and the Mayo Clinic Foundation. The
   sponsors had no role in the design or conduct of the study.
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NR 36
TC 33
Z9 33
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 NOV 26
PY 2008
VL 3
IS 11
AR e3813
DI 10.1371/journal.pone.0003813
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 436YG
UT WOS:000265451400005
PM 19043567
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU O'Connor, PM
   Mu, LC
   Keeffe, JE
AF O'Connor, Patricia M.
   Mu, Lisa C.
   Keeffe, Jill E.
TI Access and utilization of a new low-vision rehabilitation service
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE barrier; facilitator; low vision; referral pathway; rehabilitation
ID IMPAIRMENT; BARRIERS
AB Background: A new low-vision service linking a public hospital and a non-governmental organization was trialled in Melbourne, Australia. The factors associated with service use were investigated.
   Methods: A survey was conducted with patients who used the service, those who accepted referrals but failed to attend and those who refused a referral. Hospital and non-governmental organization representatives were also interviewed.
   Results: Ninety-eight eligible vision impaired people who were referred to the new service were recruited. Less than half (49%) followed through with their referral and attended the service. Proximity and convenience were listed as the main facilitators to service use while issues relating to transport, needing an accompanying person, lack of information about the service and poor health were the main barriers. More than a third of the non-compliant and referral refusers spoke a language other than English. Sixty-three per cent of all participants had not previously used low-vision services. Of the two main eye conditions, 81% of referred age-related macular degeneration participants (n = 26) attended the service, but only 32% of those with diabetic retinopathy (n = 31) did so.
   Conclusion: As more than 60% of participants in each of the three groups had no prior use of low-vision services, clearly current models of care are not reaching many who could benefit from such services. This suggests that higher rates of referral are warranted. However, given that substantially more were referred than attended, referral alone is obviously not the answer. Access and attitudinal barriers also need to be addressed.
C1 [Keeffe, Jill E.] Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Melbourne, Vic 8002, Australia.
   [O'Connor, Patricia M.; Keeffe, Jill E.] Vis CRC, Sydney, NSW, Australia.
C3 Centre for Eye Research Australia; University of Melbourne
RP Keeffe, JE (通讯作者)，Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Locked Bag 8, Melbourne, Vic 8002, Australia.
EM jillek@unimelb.edu.au
FU Australian Government Cooperative Research Program; Royal Victorian Eye
   and Ear Hospital Wagstaff Fellowship; Guide Dogs Victoria; Royal
   Victorian Eye and Ear Hospital
FX This work was supported by the Australian Government Cooperative
   Research Program, Royal Victorian Eye and Ear Hospital Wagstaff
   Fellowship (Prof Keeffe), Guide Dogs Victoria and the Royal Victorian
   Eye and Ear Hospital.
CR [Anonymous], 2004, Community Eye Health, V17, P1
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NR 13
TC 35
Z9 36
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD AUG
PY 2008
VL 36
IS 6
BP 547
EP 552
DI 10.1111/j.1442-9071.2008.01830.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 359SS
UT WOS:000260009000011
PM 18954318
DA 2022-11-30
ER

PT J
AU Broekmans, WMR
   Berendschot, TTJM
   Klopping-Ketelaars, IAA
   de Vries, AJ
   Goldbohm, RA
   Tijburg, LBM
   Kardinaal, AFM
   van Poppel, G
AF Broekmans, WMR
   Berendschot, TTJM
   Klopping-Ketelaars, IAA
   de Vries, AJ
   Goldbohm, RA
   Tijburg, LBM
   Kardinaal, AFM
   van Poppel, G
TI Macular pigment density in relation to serum and adipose tissue
   concentrations of lutein and serum concentrations of zeaxanthin
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE macular pigment; lutein; zeaxanthin; carotenoids; macular degeneration;
   Netherlands
ID AGE-RELATED MACULOPATHY; PLASMA CAROTENOID CONCENTRATIONS; NUTRITION
   EXAMINATION SURVEY; OPTICAL-DENSITY; MENSTRUAL-CYCLE; NATIONAL-HEALTH;
   IRIS COLOR; VITAMIN-A; DEGENERATION; DIETARY
AB Background: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxanthin and adipose lutein concentrations in a general population.
   Objective: The objective was to investigate the associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein, taking into account potential confounders in a population.
   Design: Volunteers (n = 376) aged 18-75 y were recruited. In a cross-sectional design, serum (n = 376) and adipose tissue (n = 187) were analyzed for carotenoids, and MP density was measured by spectral fundus reflectance.
   Results: Mean MP density in the total study group was 0.33 +/- 0.15. MP density was 13% higher in men than in women (P < 0.05). Serum and blood concentrations of a-tocopherol, vitamin C, and all carotenoids except lycopene were significantly higher in women. Adipose lutein concentrations were also significantly higher in women than in men. Regression models showed a positive significant association between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations in men after adjustment for age, but no relation in women. In men, serum lutein remained significantly associated with MP density after adjustment for age, total cholesterol, body mass index, and smoking.
   Conclusion: The associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations are stronger in men than in women.
C1 TNO Nutr & Food Res, Dept Nutr Physiol, NL-3700 AJ Zeist, Netherlands.
   Wageningen UR, Div Human Nutr & Epidemiol, Wageningen, Netherlands.
   TNO WU, Ctr Micronutr Res, Wageningen, Netherlands.
   UMC, Dept Ophthalmol, Utrecht, Netherlands.
   Unilever Hlth Inst, Unilever Res & Dev, Vlaardingen, Netherlands.
C3 Netherlands Organization Applied Science Research; Wageningen University
   & Research; Netherlands Organization Applied Science Research; Unilever
RP Kardinaal, AFM (通讯作者)，TNO Nutr & Food Res, Dept Nutr Physiol, POB 360, NL-3700 AJ Zeist, Netherlands.
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X
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NR 32
TC 135
Z9 143
U1 0
U2 11
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
   USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD SEP
PY 2002
VL 76
IS 3
BP 595
EP 603
DI 10.1093/ajcn/76.3.595
PG 9
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 586LZ
UT WOS:000177586600018
PM 12198005
OA Bronze
DA 2022-11-30
ER

PT J
AU Cubbidge, RP
   Hosking, SL
   Embleton, S
AF Cubbidge, RP
   Hosking, SL
   Embleton, S
TI Statistical modelling of the central 10-degree visual field in
   short-wavelength automated perimetry
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID BLUE-ON-YELLOW; AGE-RELATED MACULOPATHY; DIABETIC MACULAR EDEMA;
   GLAUCOMA SUSPECTS; CRYSTALLINE LENS; SENSITIVITY; VARIABILITY; STANDARD;
   STRATEGY; ANALYZER
AB Background: Reports of short-wavelength pathway dysfunction in retinal eye disease suggest that short-wavelength automated perimetry may be a useful technique for the investigation of central visual function. The aim of this study was to adapt existing statistical procedures used for the investigation of 30-2 short-wavelength automated perimetry to the 10-2 program of the Humphrey Field Analyser. Methods: A four- or six-point linear interpolation procedure was used to calculate normal visual field sensitivity for each of the 68 stimulus locations of the 10-2 program using empirical normal data from 51 normal subjects examined using the 30-2 program. Prediction limits for normality were derived at each stimulus location, enabling the calculation of age-corrected global perimetric indices and construction of probability maps for diffuse and focal visual field loss. The normal database was validated by empirical data from five normal subjects, stratified for age. Results: The pointwise distribution of normal sensitivity exhibited a Gaussian distribution at the majority of stimulus locations. The pointwise coefficient of variation did not vary significantly across the visual field. Examples of diabetic pseudophakic patients and a patient with age-related macular degeneration are presented to illustrate the effectiveness of SWAP at detecting visual field abnormality in the central visual field. Conclusion: Ten-degree SWAP is able to effectively detect focal visual field loss in central retinal eye disease which may precede those found using conventional perimetry. SWAP may prove to be an invaluable technique for the investigation of central retinal eye disease.
C1 Aston Univ, Neurosci Res Inst, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
C3 Aston University
RP Cubbidge, RP (通讯作者)，Aston Univ, Neurosci Res Inst, Sch Life & Hlth Sci, Aston Triangle, Birmingham B4 7ET, W Midlands, England.
EM R.P.Cubbidge@aston.ac.uk
OI Cubbidge, Robert P/0000-0002-7851-1375
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NR 43
TC 2
Z9 2
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2002
VL 240
IS 8
BP 650
EP 657
DI 10.1007/s00417-002-0509-4
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 594UG
UT WOS:000178068900008
PM 12192459
DA 2022-11-30
ER

PT J
AU Qin, YJ
   Zhang, YL
   Zhang, YQ
   He, BT
   Wang, S
   Yu, HH
   Chan, SO
   Zhang, HY
AF Qin, Yong Jie
   Zhang, Yu Lin
   Zhang, Yu Qiao
   He, Bei Ting
   Wang, Sheng
   Yu, Hong Hua
   Chan, Sun On
   Zhang, Hong Yang
TI ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK
   FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE diabetes mellitus; diabetic macular edema; uric acid; glucose; central
   retinal thickness
ID SERUM; RETINOPATHY
AB Purpose: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. Methods: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. Results: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (>= 2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (>= 6.43 mg/dL) alone was not associated with DME. Conclusion: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.
C1 [Qin, Yong Jie; Zhang, Yu Lin; Zhang, Yu Qiao; He, Bei Ting; Wang, Sheng; Yu, Hong Hua; Zhang, Hong Yang] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Eye Inst, Dept Ophthalmol, 106 Zhongshan Er Rd, Guangzhou 510080, Peoples R China.
   [Zhang, Yu Lin; Zhang, Yu Qiao; Zhang, Hong Yang] Shantou Univ Med Coll, Shantou, Peoples R China.
   [He, Bei Ting; Wang, Sheng; Zhang, Hong Yang] South China Univ Technol, Sch Med, Guangzhou, Peoples R China.
   [Chan, Sun On] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China.
   [Zhang, Hong Yang] Southern Med Univ, Sch Clin Med 2, Guangzhou, Peoples R China.
C3 Guangdong Academy of Medical Sciences & Guangdong General Hospital;
   South China University of Technology; Chinese University of Hong Kong;
   Southern Medical University - China
RP Zhang, HY (通讯作者)，Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Eye Inst, Dept Ophthalmol, 106 Zhongshan Er Rd, Guangzhou 510080, Peoples R China.
EM hy3005716@163.com
FU National Natural Science Foundation Incubation Program of Guangdong
   Provincial People's Hospital [KY01201146, KY01201147]; National Natural
   Science Foundation of Guangdong Province, China [2020A1515010103,
   2018A030313833]
FX Supported by a grant from National Natural Science Foundation Incubation
   Program of Guangdong Provincial People's Hospital (grant number,
   KY01201146 to Y. J. Qin and KY01201147 to H. Y. Zhang) and National
   Natural Science Foundation of Guangdong Province, China (grant number,
   2020A1515010103 to Y. J. Qin and 2018A030313833 to H. Y. Zhang).
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NR 30
TC 0
Z9 0
U1 4
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 2022
VL 42
IS 6
BP 1121
EP 1129
DI 10.1097/IAE.0000000000003424
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1K9HA
UT WOS:000798904200017
PM 35174802
DA 2022-11-30
ER

PT J
AU Chiang, YW
   Su, CH
   Sun, HY
   Chen, SP
   Chen, CJ
   Chen, WY
   Chang, CC
   Chen, CM
   Kuan, YH
AF Chiang, Yun-Wei
   Su, Chun-Hung
   Sun, Han-Yin
   Chen, Shih-Pin
   Chen, Chun-Jung
   Chen, Wen-Ying
   Chang, Chia-Che
   Chen, Chuan-Mu
   Kuan, Yu-Hsiang
TI Bisphenol A induced apoptosis via oxidative stress generation involved
   Nrf2/HO-1 pathway and mitochondrial dependent pathways in human retinal
   pigment epithelium (ARPE-19) cells
SO ENVIRONMENTAL TOXICOLOGY
LA English
DT Article
DE apoptosis; ARPE-19 cells; bisphenol A; mitochondrial dysfunction; Nrf2;
   HO-1 pathway
ID ACETYL-L-CYSTEINE; DNA-DAMAGE; OXYGEN; NRF2; DYSFUNCTION; EXPOSURE; RPE;
   ROS; CYTOTOXICITY; ACCUMULATION
AB Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.
C1 [Chiang, Yun-Wei; Chen, Chuan-Mu] Natl Chung Hsing Univ, Dept Life Sci, Taichung, Taiwan.
   [Chiang, Yun-Wei] Cent Taiwan Univ Sci & Technol, Dept Optometry, Taichung, Taiwan.
   [Su, Chun-Hung; Chen, Shih-Pin] Chung Shan Med Univ Hosp, Dept Internal Med, Taichung, Taiwan.
   [Su, Chun-Hung; Chen, Shih-Pin] Chung Shan Med Univ, Sch Med, Dept Internal Med, Taichung, Taiwan.
   [Sun, Han-Yin] Chung Shan Med Univ, Dept Optometry, Taichung, Taiwan.
   [Sun, Han-Yin] Chung Shan Med Univ Hosp, Dept Ophthalmol, Taichung, Taiwan.
   [Chen, Chun-Jung] Taichung Vet Gen Hosp, Dept Educ & Res, Taichung, Taiwan.
   [Chen, Wen-Ying] Natl Chung Hsing Univ, Dept Vet Med, Taichung, Taiwan.
   [Chang, Chia-Che] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung, Taiwan.
   [Chang, Chia-Che] Asia Univ, Dept Biotechnol, Taichung, Taiwan.
   [Chang, Chia-Che] China Med Univ Hosp, Dept Med Res, Taichung, Taiwan.
   [Chang, Chia-Che] Taipei Med Univ Hosp, Tradit Herbal Med Res Ctr, Taipei, Taiwan.
   [Kuan, Yu-Hsiang] Chung Shan Med Univ, Sch Med, Dept Pharmacol, 110,Sec 1,Jianguo N Rd, Taichung 402, Taiwan.
   [Kuan, Yu-Hsiang] Chung Shan Med Univ Hosp, Dept Pharm, Taichung, Taiwan.
C3 National Chung Hsing University; Central Taiwan University Science &
   Technology; Chung Shan Medical University; Chung Shan Medical University
   Hospital; Chung Shan Medical University; Chung Shan Medical University;
   Chung Shan Medical University; Chung Shan Medical University Hospital;
   Taichung Veterans General Hospital; National Chung Hsing University;
   National Chung Hsing University; Asia University Taiwan; China Medical
   University Taiwan; China Medical University Hospital - Taiwan; Taipei
   Medical University; Taipei Medical University Hospital; Chung Shan
   Medical University; Chung Shan Medical University; Chung Shan Medical
   University Hospital
RP Kuan, YH (通讯作者)，Chung Shan Med Univ, Sch Med, Dept Pharmacol, 110,Sec 1,Jianguo N Rd, Taichung 402, Taiwan.
EM kuanyh@csmu.edu.tw
RI Chiang, Yun/GRJ-5251-2022; Chen, Chuan-Mu/K-7049-2013
OI Chen, Chuan-Mu/0000-0003-2461-9150; Kuan, Yu-Hsiang/0000-0002-8991-6394
FU Ministry of Science and Technology of Taiwan [MOST
   106-2320-B040-022-MY3, 109-2320-B-040-MY3]; National Chung Hsing
   University; Chung Shan Medical University [NCHU-CSMU-10810,
   NCHU-CSMU-11005]
FX Ministry of Science and Technology of Taiwan, Grant/Award Numbers: MOST
   106-2320-B040-022-MY3, 109-2320-B-040-MY3; National Chung Hsing
   University; Chung Shan Medical University, Grant/Award Numbers:
   NCHU-CSMU-10810, NCHU-CSMU-11005
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NR 47
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Z9 9
U1 1
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1520-4081
EI 1522-7278
J9 ENVIRON TOXICOL
JI Environ. Toxicol.
PD JAN
PY 2022
VL 37
IS 1
BP 131
EP 141
DI 10.1002/tox.23384
EA OCT 2021
PG 11
WC Environmental Sciences; Toxicology; Water Resources
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Environmental Sciences & Ecology; Toxicology; Water Resources
GA XI4QC
UT WOS:000708488800001
PM 34664771
DA 2022-11-30
ER

PT J
AU Schlecht, A
   Vallon, M
   Wagner, N
   Ergun, S
   Braunger, BM
AF Schlecht, Anja
   Vallon, Mario
   Wagner, Nicole
   Erguen, Suleyman
   Braunger, Barbara M.
TI TGF beta-Neurotrophin Interactions in Heart, Retina, and Brain
SO BIOMOLECULES
LA English
DT Review
DE heart-brain axis; brain-retina axis; neurotrophins; TGF beta signaling;
   myocardial infarction; diabetic retinopathy; age-related macular
   degeneration; ischemic stroke
ID GROWTH-FACTOR-BETA; CENTRAL-NERVOUS-SYSTEM; CHOROIDAL NEOVASCULAR
   MEMBRANES; CEREBRAL-ARTERY OCCLUSION; SMOOTH-MUSCLE-CELLS; MICE LACKING;
   TRANSFORMING GROWTH-FACTOR-BETA-1; GANGLION-CELLS;
   MYOCARDIAL-INFARCTION; INFLAMMATORY RESPONSE
AB Ischemic insults to the heart and brain, i.e., myocardial and cerebral infarction, respectively, are amongst the leading causes of death worldwide. While there are therapeutic options to allow reperfusion of ischemic myocardial and brain tissue by reopening obstructed vessels, mitigating primary tissue damage, post-infarction inflammation and tissue remodeling can lead to secondary tissue damage. Similarly, ischemia in retinal tissue is the driving force in the progression of neovascular eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), which eventually lead to functional blindness, if left untreated. Intriguingly, the easily observable retinal blood vessels can be used as a window to the heart and brain to allow judgement of microvascular damages in diseases such as diabetes or hypertension. The complex neuronal and endocrine interactions between heart, retina and brain have also been appreciated in myocardial infarction, ischemic stroke, and retinal diseases. To describe the intimate relationship between the individual tissues, we use the terms heart-brain and brain-retina axis in this review and focus on the role of transforming growth factor beta (TGF beta) and neurotrophins in regulation of these axes under physiologic and pathologic conditions. Moreover, we particularly discuss their roles in inflammation and repair following ischemic/neovascular insults. As there is evidence that TGF beta signaling has the potential to regulate expression of neurotrophins, it is tempting to speculate, and is discussed here, that cross-talk between TGF beta and neurotrophin signaling protects cells from harmful and/or damaging events in the heart, retina, and brain.
C1 [Schlecht, Anja; Vallon, Mario; Wagner, Nicole; Erguen, Suleyman; Braunger, Barbara M.] Julius Maximilians Univ Wuerzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany.
C3 University of Wurzburg
RP Braunger, BM (通讯作者)，Julius Maximilians Univ Wuerzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany.
EM anja.schlecht@uni-wuerzburg.de; mario.vallon@uni-wuerzburg.de;
   nicole.wagner@uni-wuerzburg.de; sueleyman.erguen@uni-wuerzburg.de;
   barbara.braunger@uni-wuerzburg.de
RI Braunger, Barbara Maria/K-4272-2015
OI Braunger, Barbara Maria/0000-0002-3926-6725
FU DFG [BR 4957/3-1]
FX This work was supported by DFG grant BR 4957/3-1. The funder had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 303
TC 5
Z9 5
U1 1
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD SEP
PY 2021
VL 11
IS 9
AR 1360
DI 10.3390/biom11091360
PG 34
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA UV1CM
UT WOS:000699225900001
PM 34572573
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Pundlik, S
   Nigalye, A
   Lains, I
   Mendez, KM
   Katz, R
   Kim, J
   Kim, IK
   Miller, JB
   Vavvas, D
   Miller, JW
   Luo, G
   Husain, D
AF Pundlik, Shrinivas
   Nigalye, Archana
   Lains, Ines
   Mendez, Kevin M.
   Katz, Raviv
   Kim, Janice
   Kim, Ivana K.
   Miller, John B.
   Vavvas, Demetrios
   Miller, Joan W.
   Luo, Gang
   Husain, Deeba
TI Area under the dark adaptation curve as a reliable alternate measure of
   dark adaptation response
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE macula; vision; visual perception; diagnostic tests; investigation
ID ROD
AB Purpose Quantification of dark adaptation (DA) response using the conventional rod intercept time (RIT) requires very long testing time and may not be measurable in the presence of impairments due to diseases such as age-related macular degeneration (AMD). The goal of this study was to investigate the advantages of using area under the DA curve (AUDAC) as an alternative to the conventional parameters to quantify DA response. Methods Data on 136 eyes (AMD: 98, normal controls: 38) from an ongoing longitudinal study on AMD were used. DA was measured using the AdaptDx 20 min protocol. AUDAC was computed from the raw DA characteristic curve at different time points, including 6.5 min and 20 min (default). The presence of AMD in the given eye was predicted using a logistic regression model within the leave-one-out cross-validation framework, with DA response as the predictor while adjusting for age and gender. The DA response variable was either the AUDAC values computed at 6.5 min (AUDAC6.5) or at 20 min (AUDAC20) cut-off, or the conventional RIT. Results AUDAC6.5 was strongly correlated with AUDAC20 (beta=86, p<0.001, R-2=0.87). The accuracy of predicting the presence of AMD using AUDAC20 was 76%, compared with 79% when using RIT, the current gold standard. In addition, when limiting AUDAC calculation to 6.5 min cut-off, the predictive accuracy of AUDAC6.5 was 80%. Conclusions AUDAC can be a valuable measure to quantify the overall DA response and can potentially facilitate shorter testing duration while maintaining diagnostic accuracy.
C1 [Pundlik, Shrinivas; Luo, Gang] Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Pundlik, Shrinivas; Nigalye, Archana; Lains, Ines; Mendez, Kevin M.; Katz, Raviv; Kim, Janice; Kim, Ivana K.; Miller, John B.; Vavvas, Demetrios; Miller, Joan W.; Luo, Gang; Husain, Deeba] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
   [Nigalye, Archana; Lains, Ines; Mendez, Kevin M.; Katz, Raviv; Kim, Janice; Kim, Ivana K.; Miller, John B.; Vavvas, Demetrios; Miller, Joan W.; Husain, Deeba] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA.
   [Mendez, Kevin M.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute; Harvard University; Harvard Medical School; Harvard
   University; Massachusetts Eye & Ear Infirmary; Harvard University;
   Brigham & Women's Hospital
RP Pundlik, S (通讯作者)，Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA 02114 USA.
EM shrinivas_pundlik@meei.harvard.edu
RI Miller, John J/GZG-5663-2022
OI Miller, Joan/0000-0003-2046-3996
FU NIH [EY029847]; Miller Retina Research Fund (Mass. Eye and Ear);
   Champalimaud Vision Award; Research to Prevent Blindness, New York;
   Commonwealth Unrestricted Grant for Eye Research
FX This work was funded in part by NIH grant EY029847, the Miller Retina
   Research Fund (Mass. Eye and Ear) (Award No.: NA), the Champalimaud
   Vision Award (Award No.: NA), the unrestricted departmental Grant from
   Research to Prevent Blindness, New York (Award No.: NA) and the
   Commonwealth Unrestricted Grant for Eye Research (Award No.: NA).
CR AdaptDx, 2014, USER MANUAL
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NR 23
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Z9 2
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 OCT
PY 2022
VL 106
IS 10
BP 1450
EP 1456
DI 10.1136/bjophthalmol-2021-318806
EA APR 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4W0KS
UT WOS:000726803800001
PM 33888461
DA 2022-11-30
ER

PT J
AU Schnichels, S
   Paquet-Durand, F
   Loscher, M
   Tsai, T
   Hurst, J
   Joachim, SC
   Klettner, A
AF Schnichels, Sven
   Paquet-Durand, Francois
   Loescher, Marina
   Tsai, Teresa
   Hurst, Jose
   Joachim, Stephanie C.
   Klettner, Alexa
TI Retina in a dish: Cell cultures, retinal explants and animal models for
   common diseases of the retina
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Age-related macular degeneration (AMD); Cell culture; Diabetic
   retinopathy (DR); Glaucoma; Organ culture; Porcine; Retinal ganglion
   cell; Retinal pigment epithelium (RPE); Retina
ID PIGMENT EPITHELIAL-CELLS; PLURIPOTENT STEM-CELLS; ENDOTHELIAL
   GROWTH-FACTOR; COMPLEMENT FACTOR-H; NEONATAL MOUSE RETINA;
   BLUE-SENSITIVE CONES; TOLL-LIKE RECEPTOR-3; OPTIC-NERVE CRUSH; LONG-TERM
   CULTURE; GANGLION-CELLS
AB For many retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the exact pathogenesis is still unclear. Moreover, the currently available therapeutic options are often unsatisfactory. Research designed to remedy this situation heavily relies on experimental animals. However, animal models often do not faithfully reproduce human disease and, currently, there is strong pressure from society to reduce animal research. Overall, this creates a need for improved disease models to understand pathologies and develop treatment options that, at the same time, require fewer or no experimental animals. Here, we review recent advances in the field of in vitro and ex vivo models for AMD, glaucoma, and DR. We highlight the difficulties associated with studies on complex diseases, in which both the initial trigger and the ensuing pathomechanisms are unclear, and then delineate which model systems are optimal for disease modelling. To this end, we present a variety of model systems, ranging from primary cell cultures, over organotypic cultures and whole eye cultures, to animal models. Specific advantages and disadvantages of such models are discussed, with a special focus on their relevance to putative in vivo disease mechanisms. In many cases, a replacement of in vivo research will mean that several different in vitro models are used in conjunction, for instance to analyze and validate causative molecular pathways. Finally, we argue that the analytical decomposition into appropriate cell and tissue model systems will allow making significant progress in our understanding of complex retinal diseases and may furthermore advance the treatment testing.
C1 [Schnichels, Sven; Loescher, Marina; Hurst, Jose] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany.
   [Paquet-Durand, Francois] Univ Tubingen, Ctr Ophthalmol, Inst Ophthalm Res, Tubingen, Germany.
   [Tsai, Teresa; Joachim, Stephanie C.] Ruhr Univ Bochum, Univ Eye Hosp, Expt Eye Res Inst, Bochum, Germany.
   [Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Kiel, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen; Eberhard Karls
   University Hospital; Ruhr University Bochum; University of Kiel;
   Schleswig Holstein University Hospital
RP Schnichels, S (通讯作者)，Univ Eye Hosp Tubingen, Ctr Ophthalmol, Elfriede Aulhorn Str 7, D-72076 Tubingen, Germany.
EM sven.schnichels@med.uni-tuebingen.de
RI Joachim, Stephanie/AAV-5980-2021; Paquet-Durand, Francois/G-6709-2015
OI Paquet-Durand, Francois/0000-0001-7355-5742; Schnichels,
   Sven/0000-0002-2385-5517; Loscher, Marina/0000-0001-9264-5145; Klettner,
   Alexa/0000-0002-2709-1059
FU Deutsche Forschungsgemeinschaft (DFG) [KL2425/11-1, PA1751/8-1,
   PA1751/10-1]; Tistou and Charlotte Kerstan foundation; set Stiftung;
   FoRUM (RuhrUniversity Bochum); ProRetina Stiftung; Bundesinstitut fur
   Risikobewertung
FX This work was supported in part by research grants from Deutsche
   Forschungsgemeinschaft (DFG, KL2425/11-1; PA1751/8-1, 10-1), Tistou and
   Charlotte Kerstan foundation, set Stiftung, FoRUM (RuhrUniversity
   Bochum), ProRetina Stiftung, and Bundesinstitut fur Risikobewertung.
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NR 569
TC 35
Z9 35
U1 15
U2 59
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 2021
VL 81
AR 100880
DI 10.1016/j.preteyeres.2020.100880
EA MAR 2021
PG 32
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RC0YC
UT WOS:000632528400001
PM 32721458
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Chen, KL
   Xu, W
   Zheng, J
   Shen, YP
   Ma, J
   Chen, ZQ
AF Chen, Kailin
   Xu, Wen
   Zheng, Jiao
   Shen, Yupeng
   Ma, Jian
   Chen, Zhiqing
TI Angiogenin, FGF-alpha, and IL-36 beta have higher expression levels in
   aqueous humor of nAMD patients in comparison to cataract patients
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Neovascular age-related macular degeneration; Aqueous humor; Cytokines;
   Inflammation; Anti-vascular endothelial growth factor; Ranibizumab
ID ENDOTHELIAL GROWTH-FACTOR; POLYPOIDAL CHOROIDAL VASCULOPATHY; MACULAR
   DEGENERATION; INTRAVITREAL AFLIBERCEPT; CYTOKINES; PATHOGENESIS;
   PROFILE; AMD
AB Background Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients. Methods This prospective study included 20 treatment-naive nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples were collected before the first (baseline), second (1 month later), and third (2 months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3 mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA). Results Three cytokines in aqueous humor, including angiogenin, interleukin-36 beta (IL-36 beta), and fibroblast growth factor-acidic (FGF-alpha) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients' basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3 mm, and GLD. Conclusions Angiogenin, IL-36 beta, and FGF-alpha have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2 months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.
C1 [Chen, Kailin; Xu, Wen; Zheng, Jiao; Shen, Yupeng; Ma, Jian; Chen, Zhiqing] Zhejiang Univ, Affiliated Hosp 2, Eye Ctr, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.
   [Chen, Kailin] Zhejiang Univ, Affiliated Sir Run Run Shaw Hosp, Sch Med, Dept Head & Neck Surg, Hangzhou, Zhejiang, Peoples R China.
   [Zheng, Jiao] Ningbo Women & Childrens Hosp, Dept Ophthalmol, Ningbo, Zhejiang, Peoples R China.
C3 Zhejiang University; Zhejiang University
RP Chen, ZQ (通讯作者)，Zhejiang Univ, Affiliated Hosp 2, Eye Ctr, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.
EM chenzhiqing@zju.edu.cn
OI Chen, Kailin/0000-0002-3224-2472
FU Program of National Natural Science Foundation of China [81571819];
   Major Science and Technology Projects of Zhejiang Province [2017C03046]
FX Supported by the Program of National Natural Science Foundation of China
   (No. 81571819) and the Major Science and Technology Projects of Zhejiang
   Province (No. 2017C03046). Corresponding funds were used to purchase
   experimental materials, use instruments, and seek technical supports.
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NR 35
TC 0
Z9 0
U1 1
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD OCT 28
PY 2020
VL 20
IS 1
AR 431
DI 10.1186/s12886-020-01684-7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OP3AJ
UT WOS:000587954700001
PM 33115414
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Waldner, DM
   Ito, K
   Chen, LL
   Nguyen, L
   Chow, RL
   Lee, A
   Rancourt, DE
   Tremblay, F
   Stell, WK
   Bech-Hansen, NT
AF Waldner, Derek M.
   Ito, Kenichi
   Chen, Li-Li
   Lisa Nguyen
   Chow, Robert L.
   Lee, Amy
   Rancourt, Derrick E.
   Tremblay, Francois
   Stell, William K.
   Bech-Hansen, N. Torben
TI Transgenic Expression of Cacna1f Rescues Vision and Retinal Morphology
   in a Mouse Model of Congenital Stationary Night Blindness 2A (CSNB2A)
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE CSNB2A; Cav1.4; Cacna1f; channelopathies; calcium channels
ID GATED CALCIUM-CHANNELS; SYNAPTIC-TRANSMISSION; INCOMPLETE TYPES; DOUBLE
   REPORTER; GENE; CELLS; MUTATION; EYE; ELECTRORETINOGRAM; PHOTORECEPTORS
AB Purpose: Congenital stationary night blindness 2A (CSNB2A) is a genetic retinal disorder characterized by poor visual acuity, nystagmus, strabismus, and other signs of retinal dysfunction resulting from mutations in Cacna1f-the gene coding for the pore-forming subunit of the calcium channel Ca(V)1.4. Mouse models of CSNB2A have shown that mutations causing the disease deleteriously affect photoreceptors and their synapses with second-order neurons. This study was undertaken to evaluate whether transgenic expression of Cacna1f could rescue morphology and visual function in a Cacna1f-KO model of CSNB2A.
   Methods: Strategic creation, breeding and use of transgenic mouse lines allowed for Cre-driven retina-specific expression of Cacna1f in a CSNB2A model. Transgene expression and retinal morphology were investigated with immunohistochemistry in retinal wholemounts or cross-sections. Visual function was assessed by optokinetic response (OKR) analysis and electroretinography (ERG).
   Results: Mosaic, prenatal expression of Cacna1f in the otherwise Cacna1f-KO retina was sufficient to rescue some visual function. Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f.
   Conclusions: This report describes a novel system for Cre-inducible expression of Cacna1fin a Cacna1f-KO mouse model of CSNB2A and provides preclinical evidence for the potential use of gene therapy in the treatment of CSNB2A.
   Translational Relevance: These data have relevance in the treatment of CSNB2A and in understanding how photoreceptor integration might be achieved in retinas in which photoreceptors have been lost, such as retinitis pigmentosa, age-related macular degeneration, and other degenerative conditions.
C1 [Waldner, Derek M.] Univ Calgary, Cumming Sch Med, Grad Dept Neurosci, Calgary, AB T2N 4N1, Canada.
   [Ito, Kenichi; Rancourt, Derrick E.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada.
   [Chen, Li-Li; Chow, Robert L.] Univ Victoria, Dept Biol, Victoria, BC, Canada.
   [Lisa Nguyen] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada.
   [Lee, Amy] Univ Iowa, Dept Otolaryngol Head Neck Surg, Dept Mol Physiol & Biophys, Iowa City, IA USA.
   [Lee, Amy] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
   [Tremblay, Francois] Dalhousie Univ, Fac Med, Dept Ophthalmol & Visual Sci, Halifax, NS, Canada.
   [Tremblay, Francois] Dalhousie Univ, Fac Hlth, Clin Vis Sci Program, Halifax, NS, Canada.
   [Stell, William K.] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada.
   [Stell, William K.] Univ Calgary, Dept Surg, Hotchkiss Brain Inst, Calgary, AB, Canada.
   [Stell, William K.] Univ Calgary, Alberta Childrens Hosp, Res Inst, Cumming Sch Med, Calgary, AB, Canada.
   [Bech-Hansen, N. Torben] Univ Calgary, Dept Med Genet, Calgary, AB, Canada.
   [Bech-Hansen, N. Torben] Univ Calgary, Dept Surg, Alberta Childrens Hosp, Res Inst, Calgary, AB, Canada.
   [Bech-Hansen, N. Torben] Univ Calgary, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada.
C3 University of Calgary; University of Calgary; University of Victoria;
   University of Calgary; University of Iowa; University of Iowa; Dalhousie
   University; Dalhousie University; University of Calgary; University of
   Calgary; Alberta Childrens Hospital; University of Calgary; University
   of Calgary; Alberta Childrens Hospital; University of Calgary;
   University of Calgary
RP Waldner, DM (通讯作者)，Univ Calgary, Cumming Sch Med, Grad Dept Neurosci, Calgary, AB T2N 4N1, Canada.
EM derek.waldner@ucalgary.ca
FU Alberta Ride for Sight; Fighting Blindness Canada; University of Calgary
   Centre for Genome Engineering; CIHR; FBC-EyeGeye Research Training Fund;
   Live Cell Imaging Facility at the University of Calgary
FX Supported in part by Alberta Ride for Sight, Fighting Blindness Canada,
   University of Calgary Centre for Genome Engineering, CIHR (NTBH, WKS),
   FBC-EyeGeye Research Training Fund (DMW, WKS), and the Live Cell Imaging
   Facility at the University of Calgary.
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NR 60
TC 3
Z9 3
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD OCT
PY 2020
VL 9
IS 11
AR 19
DI 10.1167/tvst.9.11.19
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OO8KU
UT WOS:000587624500011
PM 33117610
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Benati, D
   Patrizi, C
   Recchia, A
AF Benati, Daniela
   Patrizi, Clarissa
   Recchia, Alessandra
TI Gene editing prospects for treating inherited retinal diseases
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Review
DE inherited retinal disease; CRISPR; Cas genome editing
ID PLURIPOTENT STEM-CELLS; RETINITIS-PIGMENTOSA; CRISPR-CAS9 NUCLEASES;
   ADENOASSOCIATED VIRUS; GENOME; CAS9; CRISPR/CAS9; THERAPY; MOUSE; DNA
AB Retinal diseases (RD) include inherited retinal dystrophy (IRD), for example, retinitis pigmentosa and Leber's congenital amaurosis, or multifactorial forms, for example, age-related macular degeneration (AMD). IRDs are clinically and genetically heterogeneous in nature. To date, more than 200 genes are known to cause IRDs, which perturb the development, function and survival of rod and cone photoreceptors or retinal pigment epithelial cells. Conversely, AMD, the most common cause of blindness in the developed world, is an acquired disease of the macula characterised by progressive visual impairment. To date, available therapeutic approaches for RD include nutritional supplements, neurotrophic factors, antiangiogenic drugs for wet AMD and gene augmentation/interference strategy for IRDs. However, these therapies do not aim at correcting the genetic defect and result in inefficient and expensive treatments. The genome editing technology based on clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) and an RNA that guides the Cas protein to a predetermined region of the genome, represents an attractive strategy to tackle IRDs without available cure. Indeed, CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease, representing a molecular tool to cure a genetic disorder. In this review, we will introduce the mechanism of CRISPR/Cas system, presenting an updated panel of Cas variants and delivery systems, then we will focus on applications of CRISPR/Cas genome editing in the retina, and, as emerging treatment options, in patient-derived induced pluripotent stem cells followed by transplantation of retinal progenitor cells into the eye.
C1 [Benati, Daniela; Patrizi, Clarissa; Recchia, Alessandra] Univ Modena & Reggio Emilia, Life Sci, I-41125 Modena, Italy.
C3 Universita di Modena e Reggio Emilia
RP Recchia, A (通讯作者)，Univ Modena & Reggio Emilia, Life Sci, I-41125 Modena, Italy.
EM alessandra.recchia@unimore.it
RI ; Recchia, Alessandra/B-7954-2015
OI Benati, Daniela/0000-0002-6599-7193; Recchia,
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NR 100
TC 13
Z9 15
U1 3
U2 29
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 JUL
PY 2020
VL 57
IS 7
BP 437
EP 444
DI 10.1136/jmedgenet-2019-106473
PG 8
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA MG0MM
UT WOS:000545729400001
PM 31857428
DA 2022-11-30
ER

PT J
AU Neal, SE
   Buehne, KL
   Besley, NA
   Yang, P
   Silinski, P
   Hong, JY
   Ryde, IT
   Meyer, JN
   Jaffe, GJ
AF Neal, Samantha E.
   Buehne, Kristen L.
   Besley, Nicholas A.
   Yang, Ping
   Silinski, Peter
   Hong, Jiyong
   Ryde, Ian T.
   Meyer, Joel N.
   Jaffe, Glenn J.
TI Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in
   Retinal Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; RPE; resveratrol; hydroquinone
ID CANCER CHEMOPREVENTIVE ACTIVITY; ENDOPLASMIC-RETICULUM STRESS; HEME
   OXYGENASE-1; RPE; APOPTOSIS; ANTIOXIDANT; CYTOTOXICITY; GLUTATHIONE;
   ACTIVATION; EXPRESSION
AB PURPOSE. Oxidative stress in retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD). Resveratrol exerts a range of protective biologic effects, but its mechanism(s) are not well understood. The aim of this study was to investigate how resveratrol could affect biologic pathways in oxidatively stressed RPE cells.
   METHODS. Cultured human RPE cells were treated with hydroquinone (HQ) in the presence or absence of resveratrol. Cell viability was determined with WST-1 reagent and trypan blue exclusion. Mitochondrial function was measured with the XFe24 Extracellular Flux Analyzer. Expression of heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit was evaluated by qPCR. Endoplasmic reticulum stress protein expression was measured by Western blot. Potential reactions between HQ and resveratrol were investigated using high-performance liquid chromatography mass spectrometry with resveratrol and additional oxidants for comparison.
   RESULTS. RPE cells treated with the combination of resveratrol and HQ had significantly increased cell viability and improved mitochondrial function when compared with HQ-treated cells alone. Resveratrol in combination with HQ significantly upregulated HO-1 mRNA expression above that of HQ-treated cells alone. Resveratrol in combination with HQ upregulated C/EBP homologous protein and spliced X-box binding protein 1. Additionally, new compounds were formed from resveratrol and HQ coincubation.
   CONCLUSIONS. Resveratrol can ameliorate HQ-induced toxicity in RPE cells through improved mitochondrial bioenergetics, upregulated antioxidant genes, stimulated unfolded protein response, and direct oxidant interaction. This study provides insight into pathways through which resveratrol can protect RPE cells from oxidative damage, a factor thought to contribute to AMD pathogenesis.
C1 [Neal, Samantha E.; Buehne, Kristen L.; Besley, Nicholas A.; Yang, Ping; Hong, Jiyong; Jaffe, Glenn J.] Duke Univ, Med Ctr, Dept Ophthalmol, 2351 Erwin Rd, Durham, NC 27710 USA.
   [Silinski, Peter] Duke Univ, Dept Chem, Durham, NC 27706 USA.
   [Ryde, Ian T.; Meyer, Joel N.] Duke Univ, Dept Nicholas Sch Environm, Durham, NC 27710 USA.
C3 Duke University; Duke University; Duke University
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
RI ; Meyer, Joel/G-9836-2017
OI Neal, Samantha/0000-0002-0173-6752; Meyer, Joel/0000-0003-1219-0983;
   Buehne, Kristen/0000-0002-4816-6216
FU Unrestricted Research to Prevent Blindness; National Institutes of
   Health Core Grant [P30EY005722]; National Science Foundation
   [CHE-0923097]
FX Supported in part by the Unrestricted Research to Prevent Blindness
   grant; the National Institutes of Health Core Grant P30EY005722; and the
   National Science Foundation Award no. CHE-0923097.
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NR 45
TC 12
Z9 13
U1 2
U2 12
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 2020
VL 61
IS 4
AR 32
DI 10.1167/iovs.61.4.32
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LR3XI
UT WOS:000535625700038
PM 32334435
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Mastropasqua, L
   Perilli, R
   D'Aloisio, R
   Toto, L
   Mastropasqua, A
   Donato, S
   Taraborrelli, M
   Ginestra, F
   Porta, M
   Consoli, A
AF Mastropasqua, Leonardo
   Perilli, Roberto
   D'Aloisio, Rossella
   Toto, Lisa
   Mastropasqua, Alessandra
   Donato, Simone
   Taraborrelli, Merilda
   Ginestra, Federica
   Porta, Massimo
   Consoli, Agostino
TI Why Miss the Chance? Incidental Findings while Telescreening for
   Diabetic Retinopathy
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Telemedicine; teleretinography; fundus imaging; diabetic retinopathy;
   age-related macular degeneration; glaucoma; vitreoretinal interface
   disease
ID FUNDUS PHOTOGRAPHY; AGE; HYPERTENSION; TELEMEDICINE; ASSOCIATION;
   GLAUCOMA; DISEASE; EYE
AB Purpose: To report on incidental pathological findings met while screening for Diabetic Retinopathy (DR) in Diabetes Clinics (DC) by ophthalmologist-graded digital fundus imaging.
   Methods: At the DC of Pescara (central Italy), for 3,859 eyes of 1,930 consecutive patients having not undergone fundus examination in the last year, two mydriatic fundus digital images, taken with a CenterVue DRS Digital Retinal Camera, were sent along with Best Corrected Visual Acuity, on a "store-and-forward" basis, to an ophthalmologist trained in DR screening, and graded according to the UK Diabetic Eye Screening Programme. Incidental fundus abnormalities other than DR were reported.
   Results: No adverse event to mydriasis was reported. One hundred and eighty eyes (4.66%) were ungradable. Among the 3,679 gradable ones, 1,105 (30.04%) showed different degrees of DR (R1 to R3), and 126 (3.42%) maculopathy (M1). Any Age-Related Macular Degeneration was present in 387 eyes (10.52%), any optic disc and parapapillary area features suspect for glaucoma in 562 eyes (15.27%), any hypertensive retinopathy in 1,263 eyes (34.33%), vitreoretinal interface disease in 252 eyes (6.84%), myopic choroidopathy in 92 eyes (2.50%), disc pallor in 31 eyes (0.84%). Mean time was 5 min for screening, 2 min for grading.
   Conclusion: Teleretinography is a well-established, cost-effective procedure in DR screening. Along with increased attendance, locating a digital camera in a DC with a retina-specialist grader results in finding fundus pathologies also beyond DR, very similarly to fundus examination in an outpatient ophthalmic setting.
C1 [Mastropasqua, Leonardo; D'Aloisio, Rossella; Toto, Lisa; Mastropasqua, Alessandra] Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalmol Clin, Chieti, Italy.
   [Perilli, Roberto] Local Hlth Author, Terr Ophthalmol Unit, Pescara, Italy.
   [Donato, Simone; Taraborrelli, Merilda; Ginestra, Federica; Consoli, Agostino] Univ G dAnnunzio, Chair Endocrinol & Metab Dis, Chieti, Italy.
   [Porta, Massimo] Univ Turin, Dept Med Sci, Chair Internal Med, Turin, Italy.
C3 G d'Annunzio University of Chieti-Pescara; G d'Annunzio University of
   Chieti-Pescara; University of Turin
RP Perilli, R (通讯作者)，Local Hlth Author, Terr Ophthalmol Unit, Pescara, Italy.; Perilli, R (通讯作者)，Distretto Sanitario Base Pescara Nord, Via Nazl Adriatica Nord 140, I-65123 Pescara, Italy.
EM roberto.perilli@ausl.pe.it
RI DAloisio, Rossella/L-2251-2019; Toto, Lisa/K-3473-2018; Perilli,
   Roberto/AAP-6568-2021; Consoli, Agostino/J-8027-2018
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   [No title captured]
   [No title captured]
   [No title captured]
   [No title captured]
   [No title captured]
NR 70
TC 8
Z9 8
U1 0
U2 3
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.
PY 2020
VL 27
IS 4
BP 237
EP 245
DI 10.1080/09286586.2020.1715450
EA JAN 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PP1TH
UT WOS:000508293800001
PM 31958252
DA 2022-11-30
ER

PT J
AU Hou, KK
   Au, A
   Kashani, AH
   Freund, KB
   Sadda, SR
   Sarraf, D
AF Hou, Kirk K.
   Au, Adrian
   Kashani, Amir H.
   Freund, K. Bailey
   Sadda, Srinivas R.
   Sarraf, David
TI Pseudoflow with OCT Angiography in Eyes with Hard Exudates and Macular
   Drusen
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE RVO; macular edema; age-related macular degeneration; OCTA; artifact
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; TYPE-3 NEOVASCULARIZATION; IMAGE
   ARTIFACTS; DEGENERATION
AB Purpose: To analyze "pseudoflow,'' a false positive flow-artifact observed with optical coherence tomography angiography (OCTA) of stationary hyperreflective structures corresponding to hard exudates and macular drusen.
   Methods: Retrospective case series of patients with hard exudates (due to diabetic macular edema [DME] or retinal vein occlusion [RVO]) or macular drusen (due to nonneovascular, or dry, age-related macular degeneration [AMD]) studied with OCTA by using volume-based projection artifact removal (3D PAR).
   Results: OCTA of 20 eyes (10 DME/10 RVO) with hard exudates were analyzed. All eyes exhibited pseudoflow corresponding to hard exudates. Seven eyes concurrently demonstrated hard exudates without pseudoflow that were noted in areas lacking vascular flow in the overlying retina. Eight eyes exhibited suspended scattering particles in motion. In 26 of 30 eyes with nonneovascular AMD, pseudoflow associated with macular drusen of any type was noted. Two of 11 eyes with small drusen, 16 of 17 eyes with medium or large drusen, 5 of 5 eyes with drusenoid pigment epithelial detachment, 12 of 16 eyes with ribbon-like subretinal drusenoid deposits, and 13 of 17 eyes with dot-like SDD exhibited pseudoflow.
   Conclusions: Pseudoflow due to projection artifact is common in eyes with hard exudates or macular drusen. 3D PAR reduces but does not eliminate pseudoflow, and pseudoflow may be detected within the foveal avascular zone, indicating that other factors, such as Z-axis micromotion, may also contribute to pseudoflow.
   Translational Relevance: This study provides insight into the etiology of pseudoflow noted on OCTA and will guide more accurate clinical interpretation and investigation of OCTA images.
C1 [Hou, Kirk K.; Au, Adrian; Sadda, Srinivas R.; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Kashani, Amir H.] Univ Calif Los Angeles, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA USA.
   [Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY USA.
   [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
   [Sadda, Srinivas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
   [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; University of California System; University of
   California Los Angeles; Vitreous Retina Macula Consultants of New York;
   New York University; 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)，UCLA, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
RI Au, Adrian/AAE-9654-2019; Freund, K. Bailey/V-7488-2018
OI Au, Adrian/0000-0001-8110-9988; Freund, K. Bailey/0000-0002-7888-9773
FU Research to Prevent Blindness Inc, New York, NY; Macula Foundation Inc,
   New York, NY
FX Research was supported by Research to Prevent Blindness Inc, New York,
   NY (DS) and Macula Foundation Inc, New York, NY (KBF, DS).
CR Bhavsar Kavita V, 2017, Am J Ophthalmol Case Rep, V8, P53, DOI 10.1016/j.ajoc.2017.10.001
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NR 25
TC 12
Z9 12
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2019
VL 8
IS 3
AR 50
DI 10.1167/tvst.8.3.50
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IH5ET
UT WOS:000474517900002
PM 31293805
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lin, JB
   Sene, A
   Wiley, LA
   Santeford, A
   Nudleman, E
   Nakamura, R
   Lin, JB
   Moolani, HV
   Apte, RS
AF Lin, Joseph B.
   Sene, Abdoulaye
   Wiley, Luke A.
   Santeford, Andrea
   Nudleman, Eric
   Nakamura, Rei
   Lin, Jonathan B.
   Moolani, Harsh V.
   Apte, Rajendra S.
TI WNT7A/B promote choroidal neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE WNT7A; WNT7B; beta-catenin; Age-related macular degeneration; Choroidal
   neovascularization; Angiogenesis
ID FAMILIAL EXUDATIVE VITREORETINOPATHY; WNT SIGNALING PATHWAY;
   WNT/BETA-CATENIN PATHWAY; VASCULAR DEVELOPMENT; PATHOGENIC ROLE; NORRIE
   DISEASE; BETA-CATENIN; MUTATIONS; FRIZZLED-4; CELLS
AB Perturbations in WNT signaling are associated with congenital eye disorders, including familial exudative vitreoretinopathy and Norrie disease. More recently, activation of the WNT pathway has also been shown to be associated with age-related macular degeneration (AMD). In this study, we identified that in choroidal neovascular membranes from AMD patients, beta-catenin is activated specifically in the vascular endothelium, suggesting that WNT promotes pathologic angiogenesis by directly affecting vascular endothelial cells. WNT7B has been shown to be important during eye development for regression of the fetal hyaloid vasculature. However, it has not yet been established whether WNT7A and/or WNT7B are involved in neovascular AMD pathogenesis. Here, we show that WNT7A and WNT7B increase the proliferation of human dermal microvascular endothelial cells in a dose-dependent manner. Both WNT7A and WNT7B also stimulated vascular sprouting from mouse choroidal explants in vitro. To evaluate in vivo relevance, we generated mice systemically deficient in Wnt7a and/or Wnt7b. Genetic deletion of both Wnt7a and Wnt7b decreased the severity of laser injury-induced choroidal neovascularization (CNV), while individual deletion of either Wnt7a or Wnt7b did not have a significant effect on CNV, suggesting that WNT7A and WNT7B have redundant pro-angiogenic roles in vivo. Cumulatively, these findings identify specific WNT isoforms that may play a pathologic role in CNV as observed in patients with neovascular AMD. Although the source of increased WNT7A and/or WNT7B in CNV requires further investigation, WNT signaling may be a potential target for therapeutic intervention if these results are demonstrated to be relevant in human disease.
C1 [Lin, Joseph B.; Sene, Abdoulaye; Wiley, Luke A.; Santeford, Andrea; Nudleman, Eric; Nakamura, Rei; Lin, Jonathan B.; Moolani, Harsh V.; Apte, Rajendra S.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA.
   [Wiley, Luke A.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Inst Vis Res, Iowa City, IA USA.
   [Apte, Rajendra 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 USA.
C3 Washington University (WUSTL); University of Iowa; Washington University
   (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Apte, RS (通讯作者)，Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA.
EM apte@wustl.edu
OI Wiley, Luke/0000-0003-0136-2364; Moolani, Harsh/0000-0001-7061-0312;
   Lin, Joseph/0000-0001-6667-9018
FU NIH [R01 EY019287, P30 EY02687, T32 GM07200, UL1 TR002345, TL1
   TR002344]; Starr Foundation; Carl Marshall Reeves and Mildred Almen
   Reeves Foundation; Physician-Scientist Award from Research to Prevent
   Blindness; Nelson Trust Award from Research to Prevent Blindness;
   Jeffrey Fort Innovation Fund; Glenn Foundation; Macula Society Cox
   Research Award; Thome Foundation; Research to Prevent Blindness;
   Washington University in St. Louis Medical Scientist Training Program
   (NIH) [T32 GM07200]; VitreoRetinal Surgery Foundation; NATIONAL CENTER
   FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR002345, TL1TR002344] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [P30EY002687, R01EY019287]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [T32GM007200] Funding Source: NIH RePORTER
FX This work was supported by NIH grants R01 EY019287 (RSA), P30 EY02687
   (Vision Core Grant); the Starr Foundation; 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); the Glenn Foundation (RSA); the Macula
   Society Cox Research Award (RSA); and the Thome Foundation (RSA).
   Additional funding comes from an unrestricted grant to the Department of
   Ophthalmology & Visual Sciences of Washington University School of
   Medicine from Research to Prevent Blindness. Joseph B. Lin was supported
   by the Washington University in St. Louis Medical Scientist Training
   Program (NIH grant T32 GM07200) and the VitreoRetinal Surgery
   Foundation. Jonathan B. Lin was supported by NIH grants T32 GM07200, UL1
   TR002345, and TL1 TR002344. None of these funding sources were involved
   in study design; in data collection, analysis, or interpretation; or in
   the preparation of the manuscript.
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TC 8
Z9 8
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2018
VL 174
BP 107
EP 112
DI 10.1016/j.exer.2018.05.033
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GU0HT
UT WOS:000444931100011
PM 29864439
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Orban, T
   Leinonen, H
   Getter, T
   Dong, ZQ
   Sun, WY
   Gao, SQ
   Veenstra, A
   Heidari-Torkabadi, H
   Kern, TS
   Kiser, PD
   Palczewski, K
AF Orban, Tivadar
   Leinonen, Henri
   Getter, Tamar
   Dong, Zhiqian
   Sun, Wenyu
   Gao, Songqi
   Veenstra, Alexander
   Heidari-Torkabadi, Hossein
   Kern, Timothy S.
   Kiser, Philip D.
   Palczewski, Krzysztof
TI A Combination of G Protein-Coupled Receptor Modulators Protects
   Photoreceptors from Degenerations
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; RETINAL DEGENERATION; MACULAR DEGENERATION;
   STARGARDT DISEASE; S-CONE; MICE; RETINOPATHY; BROMOCRIPTINE;
   PHAGOCYTOSIS; DISPOSITION
AB Degeneration of retinal photoreceptor cells can arise from environmental and/or genetic causes. Since photoreceptor cells, the retinal pigment epithelium(RPE), neurons, and glial cells of the retina are intimately associated, all cell types eventually are affected by retinal degenerative diseases. Such diseases often originate either in rod and/or cone photoreceptor cells or the RPE. Of these, cone cells located in the central retina are especially important for daily human activity. Here we describe the protection of cone cells by a combination therapy consisting of the G protein-coupled receptormodulators metoprolol, tamsulosin, and bromocriptine. These drugs were tested in Abca(-/-)Rdh8(-/-) mice, a preclinical model for retinal degeneration. The specificity of these drugs was determined with an essentially complete panel of human G protein-coupled receptors. Significantly, the combination of metoprolol, tamsulosin, and bromocriptine had no deleterious effects on electroretinographic responses of wildtype mice. Moreover, putative G protein-coupled receptor targets of these drugs were shown to be expressed in human and mouse eyes by RNA sequencing and quantitative polymerase chain reaction. Liquid chromatography together with mass spectrometry using validated internal standards confirmed that metoprolol, tamsulosin, and bromocriptine individually or together penetrate the eye after either intraperitoneal delivery or oral gavage. Collectively, these findings support human trials with combined therapy composed of lower doses of metoprolol, tamsulosin, and bromocriptine designed to safely impede retinal degeneration associated with certain genetic diseases (e.g., Stargardt disease). The same low-dose combination also could protect the retina against diseases with complex or unknown etiologies such as age-related macular degeneration.
C1 [Orban, Tivadar; Leinonen, Henri; Getter, Tamar; Gao, Songqi; Heidari-Torkabadi, Hossein; Kern, Timothy S.; Kiser, Philip D.; Palczewski, Krzysztof] Case Western Reserve Univ, Cleveland Ctr Membrane & Struct Biol, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Kern, Timothy S.; Kiser, Philip D.] Louis Stokes Cleveland Vet Affairs Med Ctr, Res Serv, Cleveland, OH USA.
   [Dong, Zhiqian; Sun, Wenyu] Polgenix Inc, Cleveland, OH USA.
C3 Case Western Reserve University; US Department of Veterans Affairs;
   Veterans Health Administration (VHA); Case Western Reserve University;
   Louis Stokes Cleveland Veterans Affairs Medical Center
RP Palczewski, K (通讯作者)，Case Western Reserve Univ, Sch Med, Dept Pharmacol, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM kxp65@case.edu
RI Leinonen, Henri/V-2684-2019
OI Leinonen, Henri/0000-0002-0388-832X; DONG, ZHIQIAN/0000-0002-8748-4532
FU National Institutes of Health National Institute of Mental Health (NIMH)
   Psychoactive Drug Screening Program (PDSP) [HHSN-271-2013-00017-C];
   NATIONAL EYE INSTITUTE [R01EY009339, R24EY027283, P30EY011373,
   R24EY024864, P30EY025585] Funding Source: NIH RePORTER; Veterans Affairs
   [IK2BX002683] Funding Source: NIH RePORTER
FX We thank Dr. Leslie T. Webster Jr. and members of the K.P. and P.D.K.
   laboratories for their helpful comments regarding this manuscript. We
   also thank members of the National Institutes of Health National
   Institute of Mental Health (NIMH) Psychoactive Drug Screening Program
   (PDSP; contract HHSN-271-2013-00017-C) for conducting the GPCR-ome
   screen. The NIMH Psychoactive Drug Screening Program is directed by
   Bryan L. Roth (University of North Carolina, Chapel Hill, NC) and
   Project Officer Jamie Driscoll (NIMH, Bethesda, MD). We thank Dr. Yu
   Chen (Shanghai University, Shanghai, China) and Dr. Debarshi Mustafi
   (University of Southern California, Los Angeles, CA) for generating the
   RNA-seq data, Anthony Gardella (CWRU, Visual Sciences Research Core) for
   technical assistance in the analysis of retinal images, and Xiuli Ma for
   help with the perfusion experiments.
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NR 37
TC 15
Z9 15
U1 0
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD FEB 1
PY 2018
VL 364
IS 2
BP 207
EP 220
DI 10.1124/jpet.117.245167
PG 14
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA FS9BL
UT WOS:000422709100006
PM 29162627
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Yan, FX
   Wang, HT
   Gao, Y
   Xu, JP
   Zheng, WH
AF Yan, Fengxia
   Wang, Haitao
   Gao, Yang
   Xu, Jiangping
   Zheng, Wenhua
TI Artemisinin DamageProtects Retinal Neuronal Cells against Oxidative
   Stress and Restores Rat Retinal Physiological Function from Light
   Exposed
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE AMD; artemisin; H2O2; ROS; p38; ERK1/2
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; OSTEOPOROTIC FRACTURES;
   APOPTOSIS; ANTIOXIDANTS; MACROPHAGES; ACTIVATION; MECHANISMS; THERAPY;
   PATHWAY
AB Oxidative stress plays a key role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of severe visual loss and blindness in the aging population which lacks any effective treatments currently. In this study, artemisinin, a well-known antimalarial drug was found to suppress hydrogen peroxide (H2O2)-induced cell death in retinal neuronal RGC-5 cells. Artemisinin, in the therapeutically relevant dosage, concentration-dependently attenuated the accumulation of intracellular reactive oxygen species (ROS), increased mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells induced by H2O2. Western blot analysis showed that artemisinin upregulated the phosphorylation of p38 and extracellular signal-regulated kinasesl/2 (ERK1/2) and reversed the inhibitory effect of H2O2 on the phosphorylation of these two kinases. Moreover, protective effect of artemisinin was blocked by the p38 kinase inhibitor PD169316 or ERK1/2 kinase pathway inhibitor PD98059, respectively. In contrast, c-Jun N-terminal kinase inhibitor and rapamycin had no effect in the protective effect of artemisinin. Taken together, these results demonstrated that artemisinin promoted the survival of RGC-5 cells from H2O2 toxicity via the activation of the p38 and ERK1/2 pathways. Interestingly, intravitreous injection of artimisinin, concentration-dependently reversed light exposed-damage (a dry AMD animal model) of rat retinal physiological function detected by flash electroretinogram. These results indicate that artemisinin can protect retinal neuronal functions from H2O2-induced damage in vitro and in vivo and suggest the potential application of artemisinin as a new drug in the treatment of retinal disorders like AMD.
C1 [Yan, Fengxia; Wang, Haitao; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Taipa 999078, Macau, Peoples R China.
   [Yan, Fengxia; Zheng, Wenhua] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510006, Guangdong, Peoples R China.
   [Yan, Fengxia; Zheng, Wenhua] Sun Yat Sen Univ, Neuroparmacol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
   [Wang, Haitao; Xu, Jiangping] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China.
   [Gao, Yang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510006, Guangdong, Peoples R China.
C3 University of Macau; Sun Yat Sen University; Sun Yat Sen University;
   Southern Medical University - China; Sun Yat Sen University
RP Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Taipa 999078, Macau, Peoples R China.; Zheng, WH (通讯作者)，Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510006, Guangdong, Peoples R China.; Zheng, WH (通讯作者)，Sun Yat Sen Univ, Neuroparmacol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
EM wenhuazheng@umac.mo
OI Wang, Haitao/0000-0001-6910-974X; Wang, Haitao/0000-0001-9900-8528
FU Guangdong Provincial Project of Science and Technology [2011B050200005];
   National Natural Science Foundation of China [31371088]; University of
   Macau [SRG2015-00004-FHS]; Science and Technology Development Fund
   (FDCT) of Macao [FDCT 021/2015/A1, FDCT016/2016/A1]
FX This research was financially supported by the Guangdong Provincial
   Project of Science and Technology (2011B050200005), the National Natural
   Science Foundation of China (31371088), SRG2015-00004-FHS from
   University of Macau and the Science and Technology Development Fund
   (FDCT) of Macao (FDCT 021/2015/A1 and FDCT016/2016/A1).
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NR 36
TC 25
Z9 26
U1 3
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD AUG
PY 2017
VL 8
IS 8
BP 1713
EP 1723
DI 10.1021/acschemneuro.7b00021
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
   & Neurology
GA FE2WK
UT WOS:000408077700016
PM 28447781
DA 2022-11-30
ER

PT J
AU Li, L
   Heiduschka, P
   Alex, AF
   Niekamper, D
   Eter, N
AF Li, Lu
   Heiduschka, Peter
   Alex, Anne F.
   Niekaemper, Daniel
   Eter, Nicole
TI Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced
   Choroidal Neovascularisation
SO OPHTHALMOLOGICA
LA English
DT Article
DE Microglia; Macrophages; Age-related macular degeneration;
   Neovascularisation; Migration; Inflammatory behaviour
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; TNF-ALPHA; OCULAR NEOVASCULARIZATION;
   INCREASED EXPRESSION; AQUEOUS-HUMOR; AMYLOID-BETA; FACTOR-B
AB Background/Aim: Immune cells, e.g. microglial cells of the retina, appear to be involved in pathological processes in neovascular age-related macular degeneration. Therefore, the purpose of this study was to immunohistochemically check the expression of various factors and cytokines by CD11b-positive (CD11b+) immune cells in an animal model of choroidal neovascularisation (CNV). Methods: We used the animal model of laser-induced CNV in mice. Eyes were isolated at 1, 4, 7, and 14 days after laser treatment. Cryosections were prepared and checked immunohistochemically for the presence of different growth factors and cytokines on microglial cells and other immune cells identified by CD11b immunoreactivity. Results: We found that the number of CD11b+ cells at the laser spots increased dramatically 4 days after laser treatment, the majority of them entering the laser spot most probably by migration. CD11b+ cells in the laser spot were positive for a variety of pro-angiogenic factors, such as PDGF-beta, FGF-1, FGF-2, and TGF-beta(1). They were also positive for some inflammatory cytokines, in particular TNF-alpha, IL-6, and CXCL1. In non-treated retinas, CD11b+ cells showed almost no immunoreactivity for these proteins. Conclusion: Microglial cells, macrophages, and other CD11b+ cells may promote the neovascularisation in the laser spot and show a moderate inflammatory behaviour. Immunoreactivity for most of these molecules was found to decrease during the time of observation. Modulation of immune cell activity may thus be a tool to reduce the extent of CNV. (C) 2017 S. Karger AG, Basel
C1 [Li, Lu; Heiduschka, Peter; Alex, Anne F.; Niekaemper, Daniel; Eter, Nicole] Univ Munster, Sch Med, Dept Ophthalmol, Domagkstr 15, DE-48149 Munster, Germany.
   [Li, Lu] Wuhan Univ, Renmin Hosp, Dept Ophthalmol, Wuhan, Peoples R China.
   [Eter, Nicole] Cells in Mot Cluster Excellence Munster EXC 1003, Munster, Germany.
C3 University of Munster; Wuhan University
RP Heiduschka, P (通讯作者)，Univ Munster, Sch Med, Dept Ophthalmol, Domagkstr 15, DE-48149 Munster, Germany.
EM peter.heiduschka@ukmuenster.de
RI Heiduschka, Peter/AAX-3882-2021
FU Cells-in-Motion Cluster of Excellence at the University of Munster [EXC
   1003-CiM]; Interdisciplinary Centre for Clinical Research (IZKF) of the
   University of Munster Medical Faculty [Et3/019/12]; China Scholarship
   Council [201206270088]
FX We thank the Cells-in-Motion Cluster of Excellence (EXC 1003-CiM) at the
   University of Munster for the support.; This work was supported in part
   by a grant (No. Et3/019/12) from the Interdisciplinary Centre for
   Clinical Research (IZKF) of the University of Munster Medical Faculty to
   N.E. and a grant (No. 201206270088) from China Scholarship Council to
   L.L.
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NR 71
TC 21
Z9 23
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 2017
VL 237
IS 1
BP 29
EP 41
DI 10.1159/000453550
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EM5MW
UT WOS:000395356700004
PM 28092911
DA 2022-11-30
ER

PT J
AU Reisenhofer, MH
   Balmer, JM
   Enzmann, V
AF Reisenhofer, M. H.
   Balmer, J. M.
   Enzmann, V.
TI What Can Pharmacological Models of Retinal Degeneration Tell Us?
SO CURRENT MOLECULAR MEDICINE
LA English
DT Review
DE Retina; degeneration; photoreceptors; retinal pigment epithelium;
   N-methyl-N-nitrosourea; sodium iodate; iodoacetic acid
ID METHYL-N-NITROSOUREA; PHOTORECEPTOR CELL-DEATH; PIGMENT EPITHELIUM
   DEGENERATION; FIBROBLAST-GROWTH-FACTOR; SODIUM IODATE INJECTION;
   IODOACETIC ACID; INTRAVITREAL INJECTION; MOUSE MODEL; B-WAVE; C-WAVE
AB Animal models with pharmacologically induced retinal degeneration including sodium iodate (NaIO3) and N-methyl-N-nitrosourea (MNU) have been extensively used in ophthalmic research to investigate retinal degeneration. NaIO3 induces degeneration of the retinal pigment epithelium (RPE) followed by photoreceptor (PRC) cell death, mimicking features of age-related macular degeneration. In contrast, MNU leads to rapid destruction of the PRCs only, enabling the use of the MNU model to investigate degeneration induced in retinitis pigmentosa. It has been shown that multiple cell death pathways are involved in the cell-specific effects of the toxins. Necrosis has been identified as the cause of the NaIO3-induced RPE loss. PRC degeneration in the described models is mainly induced by programmed cell death, indicated by the upregulation of conventional apoptosis initiator and effector caspases. However, recent research points to the additional involvement of caspase-independent processes as endoplasmic reticulum stress and calpain activation. Since there is still a substantial amount of contradictory hypotheses concerning triggers of cell death, the use of pharmacological models is controversial. Thereby, the advantages of such models like the application reaching across species and strains as well as modulation of onset and severity of damage are not exploited to a full extent. Thus, the present review aims to give more insight into the involved cell death pathways and discusses recent findings in the most widely used retinal degeneration models. It might facilitate further studies aiming to develop putative therapeutic approaches for retinal degenerative diseases including combinatory treatment with cell death inhibitors and cell transplantation therapy.
C1 [Reisenhofer, M. H.; Enzmann, V.] Univ Bern, Bern Univ Hosp, Inselspital, Dept Ophthalmol, Bern, Switzerland.
   [Reisenhofer, M. H.; Enzmann, V.] Univ Bern, Dept Clin Res, Bern, Switzerland.
   [Reisenhofer, M. H.] Univ Zurich, Dept Chem, Zurich, Switzerland.
   [Balmer, J. M.] Univ Bern, Vetsuisse Fac, Div Vet Anat, Bern, Switzerland.
C3 University of Bern; University Hospital of Bern; University of Bern;
   University of Zurich; University of Bern
RP Enzmann, V (通讯作者)，Univ Bern, Bern Univ Hosp, Inselspital, Dept Ophthalmol, Bern, Switzerland.
EM volker.enzmann@insel.ch
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NR 98
TC 15
Z9 15
U1 0
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.
PY 2017
VL 17
IS 2
BP 100
EP 107
DI 10.2174/1566524017666170331162048
PG 8
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EW6MC
UT WOS:000402623600002
PM 28429669
DA 2022-11-30
ER

PT J
AU Puddu, A
   Sanguineti, R
   Traverso, CE
   Viviani, GL
   Nicolo, M
AF Puddu, Alessandra
   Sanguineti, Roberta
   Traverso, Carlo Enrico
   Viviani, Giorgio L.
   Nicolo, Massimo
TI Response to anti-VEGF-A treatment of retinal pigment epithelial cells in
   vitro
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Ranibizumab; Retinal pigment epithelial cells; Vascular
   endothelial growth factors
ID ENDOTHELIAL-GROWTH-FACTOR; PATHOLOGICAL CONDITIONS; MACULAR
   DEGENERATION; OCULAR CELLS; ANGIOGENESIS; RANIBIZUMAB; BEVACIZUMAB;
   AFLIBERCEPT; SURVIVAL; EXPRESSION
AB Purpose: The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro.
   Methods: ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
   Results: Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs.
   Conclusions: Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.
C1 [Puddu, Alessandra; Sanguineti, Roberta; Viviani, Giorgio L.] Dept Internal Med & Med Specialties, Viale Benedetto 15 6, I-16132 Genoa, Italy.
   [Traverso, Carlo Enrico; Nicolo, Massimo] Dept Neurosci Ophthalmol & Genet, Genoa, Italy.
   [Nicolo, Massimo] Fdn Macula Onlus, Genoa, Italy.
C3 University of Genoa
RP Puddu, A (通讯作者)，Dept Internal Med & Med Specialties, Viale Benedetto 15 6, I-16132 Genoa, Italy.
EM alep100@hotmail.com
RI Puddu, Alessandra/AAU-2485-2021
FU Novartis Farma SpA
FX This research was supported by an unconditional research grant from
   Novartis Farma SpA, which did not influence the planning, conduct, or
   analysis of the research, writing of the manuscript, or its submission
   for publication.
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NR 26
TC 8
Z9 9
U1 0
U2 2
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 425
EP 430
DI 10.5301/ejo.5000786
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EK1MB
UT WOS:000393688500019
PM 27079208
DA 2022-11-30
ER

PT J
AU Chen, Q
   Niu, SJ
   Yuan, ST
   Fan, W
   Liu, QH
AF Chen, Qiang
   Niu, Sijie
   Yuan, Songtao
   Fan, Wen
   Liu, Qinghuai
TI Choroidal vasculature characteristics based choroid segmentation for
   enhanced depth imaging optical coherence tomography images
SO MEDICAL PHYSICS
LA English
DT Article
DE choroidal vasculature characteristics; choroid segmentation; EDI-OCT
   image; maximum intensity image
ID SPECTRAL-DOMAIN; AUTOMATIC SEGMENTATION; THICKNESS MEASUREMENTS; OCT
   IMAGES; REPRODUCIBILITY; EYES
AB Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging.
   Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller's layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary.
   Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors' proposed method and manual segmentation drawn by experts were -11.43 mu m and 86.29%, respectively.
   Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors' method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging. (C) 2016 American Association of Physicists in Medicine.
C1 [Chen, Qiang; Niu, Sijie] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [Yuan, Songtao; Fan, Wen; Liu, Qinghuai] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing University of Science & Technology; Nanjing Medical University
RP Fan, W (通讯作者)，Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China.
EM fanwen1029@163.com
RI chen, qiang/GWZ-7308-2022
OI Liu, Qinghuai/0000-0003-1605-1964
FU Fundamental Research Funds for the Central Universities
   [30920140111004]; six talent peaks project in Jiangsu Province
   [2014-SWYY-024]; Qing Lan Project
FX The authors sincerely thank the reviewers whose valuable comments have
   improved this paper and thank Ph.D. students Loza Bekalo Sappa and Idowu
   Paul Okuwobi for the English writing and editing. This work was
   supported by a grant from the Fundamental Research Funds for the Central
   Universities (No. 30920140111004), a six talent peaks project in Jiangsu
   Province (No. 2014-SWYY-024), and the Qing Lan Project.
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NR 35
TC 12
Z9 12
U1 0
U2 12
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD APR
PY 2016
VL 43
IS 4
BP 1649
EP 1661
DI 10.1118/1.4943382
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA DI7VV
UT WOS:000373711000008
PM 27036564
DA 2022-11-30
ER

PT J
AU Johansson, I
   Monsen, VT
   Pettersen, K
   Mildenberger, J
   Misund, K
   Kaarniranta, K
   Schonberg, S
   Bjorkoy, G
AF Johansson, Ida
   Monsen, Vivi Talstad
   Pettersen, Kristine
   Mildenberger, Jennifer
   Misund, Kristine
   Kaarniranta, Kai
   Schonberg, Svanhild
   Bjorkoy, Geir
TI The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress
   and protein misfolding by inducing autophagy and NFE2L2 in human retinal
   pigment epithelial cells
SO AUTOPHAGY
LA English
DT Article
DE AA; antioxidants; autophagy; DHA; HMOX1; LC3B; MAP1LC3B; NFE2L2; NRF2;
   OA; omega-3; p62; PUFA; ROS; SQSTM1
ID TRANSCRIPTION FACTOR NRF2; MACULAR DEGENERATION; FATTY-ACIDS;
   CANCER-CELLS; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; FISH
   CONSUMPTION; KEAP1; P62; DEGRADATION
AB Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.
C1 [Johansson, Ida; Monsen, Vivi Talstad; Pettersen, Kristine; Schonberg, Svanhild] Norwegian Univ Sci & Technol, Fac Med, Childrens & Womens Hlth, Dept Lab Med, N-7034 Trondheim, Norway.
   [Johansson, Ida; Pettersen, Kristine; Mildenberger, Jennifer; Bjorkoy, Geir] Univ Coll Sor Trondelag, Dept Technol, Trondheim, Norway.
   [Johansson, Ida; Pettersen, Kristine; Mildenberger, Jennifer; Bjorkoy, Geir] Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, N-7034 Trondheim, Norway.
   [Johansson, Ida; Pettersen, Kristine; Mildenberger, Jennifer; Bjorkoy, Geir] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7034 Trondheim, Norway.
   [Mildenberger, Jennifer; Misund, Kristine] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7034 Trondheim, Norway.
   [Misund, Kristine] Norwegian Univ Sci & Technol, KG Jebsen Ctr Myeloma Res, N-7034 Trondheim, Norway.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, SF-70210 Kuopio, Finland.
C3 Norwegian University of Science & Technology (NTNU); Norwegian
   University of Science & Technology (NTNU); Norwegian University of
   Science & Technology (NTNU); Norwegian University of Science &
   Technology (NTNU); Norwegian University of Science & Technology (NTNU);
   Norwegian University of Science & Technology (NTNU); University of
   Eastern Finland; Kuopio University Hospital; University of Eastern
   Finland
RP Bjorkoy, G (通讯作者)，Univ Coll Sor Trondelag, Dept Technol, Trondheim, Norway.
EM geir.bjorkoy@hist.no
OI Kaarniranta, Kai/0000-0003-2600-8679; Pettersen,
   Kristine/0000-0002-6446-0984; Mildenberger,
   Jennifer/0000-0001-8371-3652; Monsen, Vivi Talstad/0000-0003-2821-5145
FU Norwegian Cancer Society; Research Council of Norway [223255/F50]
FX This work was supported by grants from the Norwegian Cancer Society and
   from the Research Council of Norway through its Centres of Excellence
   funding program, project number 223255/F50.
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NR 100
TC 69
Z9 76
U1 0
U2 14
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD SEP
PY 2015
VL 11
IS 9
BP 1636
EP 1651
DI 10.1080/15548627.2015.1061170
PG 16
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA CR8UK
UT WOS:000361629400014
PM 26237736
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Sowmya, PR
   Arathi, BP
   Vijay, K
   Baskaran, V
   Lakshminarayana, R
AF Sowmya, Poorigali Raghavendra
   Arathi, Bangalore Prabhashankar
   Vijay, Kariyappa
   Baskaran, Vallikannan
   Lakshminarayana, Rangaswamy
TI Optimization of LC/MS (APCI)(+) Methods for the Determination of
   Possible Lutein Oxidation Products in Plasma and Tissues of Adult Rats
SO CHROMATOGRAPHIA
LA English
DT Article
DE Liquid chromatography-mass spectrometry; Lutein; Zeaxanthin; Rat
   tissues; Lutein oxidation products
ID ZEAXANTHIN STEREOISOMERS; APCI-MS; CAROTENOIDS; HPLC; IDENTIFICATION;
   PHASE; VEGETABLES; SEPARATION; SPINACH; NMR
AB In spite of lutein and its isomer zeaxanthin being richly available in natural sources, the role of these components on reduction of age-related macular degeneration, cancer, and cardiovascular disorders suggested that an update of the analytical procedure is required to determine the oxidative products and to understand their nutritional significance. In the present study, we have standardized and developed an improved method to obtain characteristic ions of lutein, zeaxanthin, and its major oxidative products in vivo (rats) using LC-MS (APCI)(+). In addition, lutein and zeaxanthin isomer were separated on a C30 column with shorter run time with high resolution and calibrated on the basis of picomolar concentration on HPLC (DAD), with the lower detection limit of 0.125 for lutein and 0.128 pmol for zeaxanthin. Characteristic mass spectral ion for lutein is m/z 568.7 [M](+) and 551.5 [M + H-H2O](+) and for zeaxanthin isomer is m/z 568.8 [M](+), 569.8 [M + H](+). Further, optimized conditions produced structurally characteristic fragmented ions under standardized MS (APCI)(+) conditions. Total ionic chromatogram together with fine UV-Visible and mass spectra were used to differentiate lutein isomers and its oxidative products, such as 523 [M+ + H+-3CH(3)], 479 [M+ + H+-6CH(3)], 551 [M+ + H+-H2O], 276.43 [M+-C22H19O], di-epoxides and 3'-oxolutein. The APCI mass spectral characteristics of major oxidative products of lutein in adult rat tissues are reported here for the first time, to our knowledge. These findings could provide new insights into lutein bioavailability and bioconversions with respect to health benefits.
C1 [Sowmya, Poorigali Raghavendra; Arathi, Bangalore Prabhashankar; Vijay, Kariyappa; Lakshminarayana, Rangaswamy] Bangalore Univ, Dept Biotechnol, Bangalore 560056, Karnataka, India.
   [Baskaran, Vallikannan] Cent Food Technol Res Inst CSIR, Dept Mol Nutr, Mysore 570020, Karnataka, India.
C3 Bangalore University; Council of Scientific & Industrial Research (CSIR)
   - India; CSIR - Central Food Technological Research Institute (CFTRI)
RP Lakshminarayana, R (通讯作者)，Bangalore Univ, Dept Biotechnol, Jnana Bharathi Campus, Bangalore 560056, Karnataka, India.
EM rlnarn2@yahoo.com
RI Lakshminarayana, Rangaswamy/AAC-5824-2019
FU Department of Biotechnology, Bangalore University; University Grant
   Commission, New Delhi, India [37-84/2009-SR]; UGC-SAP; DST-FIST;
   Department of Science and Technology (New Delhi, India)
FX Authors acknowledge the Department of Biotechnology, Bangalore
   University, for their encouragement and support. R. Lakshminarayana
   acknowledges the University Grant Commission, New Delhi, India, for the
   grant of Major Research Project (F. No. 37-84/2009-SR), UGC-SAP and
   DST-FIST facilities and support. P. R. Sowmya acknowledges the grant of
   Women Scientist Fellowship by Department of Science and Technology (New
   Delhi, India).
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NR 22
TC 4
Z9 4
U1 2
U2 42
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0009-5893
EI 1612-1112
J9 CHROMATOGRAPHIA
JI Chromatographia
PD DEC
PY 2014
VL 77
IS 23-24
BP 1633
EP 1642
DI 10.1007/s10337-014-2765-y
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA AU1LQ
UT WOS:000345382600008
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ueda-Arakawa, N
   Ooto, S
   Ellabban, AA
   Takahashi, A
   Oishi, A
   Tamura, H
   Yamashiro, K
   Tsujikawa, A
   Yoshimura, N
AF Ueda-Arakawa, Naoko
   Ooto, Sotaro
   Ellabban, Abdallah A.
   Takahashi, Ayako
   Oishi, Akio
   Tamura, Hiroshi
   Yamashiro, Kenji
   Tsujikawa, Akitaka
   Yoshimura, Nagahisa
TI Macular Choroidal Thickness and Volume of Eyes With Reticular
   Pseudodrusen Using Swept-Source Optical Coherence Tomography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; CENTRAL SEROUS CHORIORETINOPATHY;
   DEGENERATION; PREVALENCE; SENSITIVITY; FEATURES; DISEASE; ATROPHY
AB PURPOSE: To investigate the choroidal thickness/volume of eyes with reticular pseudodrusen using high-penetration swept-source optical coherence tomography (SS-OCT) and to evaluate the choroidal vasculature changes using en face images.
   DESIGN: Prospective cross-sectional study.
   METHODS: Thirty-eight eyes with reticular pseudodrusen and 14 normal eyes were studied with prototype SS-OCT. Eyes with reticular pseudodrusen were classified into 3 subgroups: eyes without late age-related macular degeneration (AMD) (Group 1), eyes with neovascular AMD (Group2), and eyes with geographic atrophy (Group3). Mean regional choroidal thickness/volume measurements were obtained by 3-dimensional (3D) raster scanning. The choroidal vascular area was measured using en face images reconstructed from a 3D SS-OCT data set.
   RESULTS: Mean age and axial length did not differ between eyes with reticular pseudodrusen and normal eyes. The mean choroidal thickness and volume of each sector was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P < .020 for all). Mean choroidal thickness and volume of each area showed no significant difference between the 3 groups; however, most of them showed decreased thickness compared with normal eyes. En face images through the choroid revealed narrow and sparse choroidal vessels in eyes with reticular pseudodrusen. The area of choroidal vasculature was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P = .037).
   CONCLUSIONS: In eyes with reticular pseudodrusen, macular choroidal thickness/volume was reduced regardless of choroidal neovascularization/geographic atrophy. Thinned vessels in the choroid suggest choroidal involvement in the pathogenesis of reticular pseudodrusen. (C) 2014 by Elsevier Inc. All rights reserved.
C1 [Ueda-Arakawa, Naoko; Ooto, Sotaro; Ellabban, Abdallah A.; Takahashi, Ayako; Oishi, Akio; Tamura, Hiroshi; Yamashiro, Kenji; Tsujikawa, Akitaka; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan.
C3 Kyoto University
RP Ooto, S (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan.
EM ohoto@kuhp.kyoto-u.ac.jp
RI Oishi, Akio/AAE-9996-2020; TAMURA, Hiroshi/H-1855-2011
OI Oishi, Akio/0000-0002-0977-9458; TAMURA, Hiroshi/0000-0002-7740-2732;
   Yamashiro, Kenji/0000-0001-9354-8558; Ellabban,
   Abdallah/0000-0002-6033-2969; Tsujikawa, Akitaka/0000-0003-0779-7799
FU Japan Society for the Promotion of Science (JSPS) [21791679]; Topcon
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST. Financial disclosures: Nagahisa
   Yoshimura: advisory board of Topcon. This research was supported in part
   by the Grant-in-Aid for Scientific Research (21791679) from the Japan
   Society for the Promotion of Science (JSPS) and Topcon. Author
   contributions: conception and design (N.U.A., S.O.); analysis and
   interpretation (N.U.A., S.O.); writing the article (N.U.A., S.O.);
   critical revision of the article (S.O., N.Y.); final approval of the
   article (N.U.A., S.O., A.A.E., A.Takahashi, A.O., H.T., K.Y.,
   A.Tsujikawa, N.Y.); data collection (N.U.A., A.A.E., A.Takahashi);
   provision of materials (S.O., A.O., H.T., KY., A.Tsujikawa., N.Y.);
   statistical expertise (N.U.A., S.O.); obtaining funding (S.O.);
   literature search (N.U.A., S.O.).
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NR 41
TC 66
Z9 67
U1 0
U2 8
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 MAY
PY 2014
VL 157
IS 5
BP 994
EP 1004
DI 10.1016/j.ajo.2014.01.018
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AG1TU
UT WOS:000335199900010
PM 24491418
DA 2022-11-30
ER

PT J
AU Kumar, A
   Zhao, L
   Fariss, RN
   McMenamin, PG
   Wong, WT
AF Kumar, Anil
   Zhao, Lian
   Fariss, Robert N.
   McMenamin, Paul G.
   Wong, Wai T.
TI Vascular Associations and Dynamic Process Motility in Perivascular
   Myeloid Cells of the Mouse Choroid: Implications for Function and
   Senescent Change
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE eye; choroid; mouse; myeloid cell; macrophage; dendritic cell;
   vasculature; live imaging; motility
ID MACROPHAGE-LIKE MELANOCYTES; II-POSITIVE CELLS; MACULAR DEGENERATION;
   UVEAL TRACT; DENDRITIC CELLS; BRUCHS MEMBRANE; AUTOIMMUNE UVEORETINITIS;
   MORPHOMETRIC-ANALYSIS; RETINAL MICROGLIA; BLOOD-VESSELS
AB PURPOSE. Immune and vascular alterations in the choroid are implicated in age-related macular degeneration (AMD). As choroidal immune cells are incompletely understood with regard to their physiology and interactions with choroidal vessels, we examined the associations between myeloid and vascular components of the choroid in young and aged mice.
   METHODS. Albino CX3CR1(GFP/+) transgenic mice, whose choroidal myeloid cells possess green fluorescence, were perfused intraluminally with the vital dye DiI to label choroidal vessels. The distribution, morphology, behavior, and vascular associations of resident myeloid cells were examined using time-lapse live confocal imaging and immunohistochemical analysis.
   RESULTS. Dendritiform myeloid cells, comprising most of the resident immune cell population in the choroid, were widely distributed across the choroid and demonstrated close associations with choroidal vessels that varied with their position in the vascular tree. Notably, myeloid cells associated with choroidal arteries and arterioles appeared as elongated cells flanking the long axes of vessels, whereas those associated with the choriocapillaris were distributed as a layer of stellate cells on the scleral but not vitreal choriocapillaris surface. While stationary in position, dendritiform myeloid cells demonstrated the rapid process dynamism well suited to comprehensive immunosurveillance of the perivascular space. Myeloid cells also increased in density as a function of aging, correlating locally with greater choroidal vascular attenuation.
   CONCLUSIONS. Resident myeloid cells demonstrated close but dynamic physical interactions with choroidal vessels, indicative of constitutive immune-vascular interactions in the normal choroid. These interactions may alter progressively with aging, providing a basis for understanding age-related choroidal dysfunction underlying AMD.
C1 [Kumar, Anil; Zhao, Lian; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA.
   [Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
   [McMenamin, Paul G.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); Monash University
RP Wong, WT (通讯作者)，NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017; Fariss, Robert/ABI-1771-2020
OI Wong, Wai/0000-0003-0681-4016; Fariss, Robert/0000-0003-3227-7170;
   McMenamin, Paul/0000-0002-7141-1283
FU Intramural Research Program of the National Eye Institute, National
   Institutes of Health; NATIONAL EYE INSTITUTE [ZIAEY000463, ZICEY000459,
   ZIAEY000541] Funding Source: NIH RePORTER
FX Supported by the Intramural Research Program of the National Eye
   Institute, National Institutes of Health.
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NR 53
TC 30
Z9 30
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 MAR
PY 2014
VL 55
IS 3
BP 1787
EP 1796
DI 10.1167/iovs.13-13522
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AE0HZ
UT WOS:000333645900011
PM 24458147
OA Green Published
DA 2022-11-30
ER

PT J
AU Zarkali, A
   Karageorgopoulos, DE
   Rafailidis, PI
   Falagas, ME
AF Zarkali, Angeliki
   Karageorgopoulos, Drosos E.
   Rafailidis, Petros I.
   Falagas, Matthew E.
TI Frequency of the off-label use of monoclonal antibodies in clinical
   practice: a systematic review of the literature
SO CURRENT MEDICAL RESEARCH AND OPINION
LA English
DT Review
DE Off-label use; Monoclonal antibodies; Drug prescriptions; Unlicensed
   use; Unapproved use
ID METASTATIC BREAST-CANCER; RITUXIMAB; BEVACIZUMAB; RANIBIZUMAB;
   EXPERIENCE; CHILDREN; THERAPY; SAFETY; PERIOD; COSTS
AB Background:
   The monoclonal antibodies represent novel therapeutic options for many clinical entities. This study aimed to study the frequency of the off-label use to total use of different monoclonal antibodies in clinical practice.
   Methods:
   This study systematically searched the PubMed and Scopus databases for relevant studies.
   Results:
   Fifteen studies were considered eligible for inclusion in this review. Eight of the included studies referred to the off-label use of anti-neoplastic monoclonal antibodies, three referred to immunosuppressive ones, and four to other types of monoclonal antibodies. The most studied anti-neoplastic monoclonal antibody was rituximab; which was prescribed off-label at a frequency varying between 16-75%, mostly for an unapproved diagnosis. Bevacizumab was prescribed off-label for age-related macular degeneration more often than ranibizumab, the approved monoclonal antibody for this condition. Of the immunosuppressive monoclonal antibodies, infliximab was used off-label in an average of 15.4% (range = 2.8-25%) and adalimumab in 10.5% (range = 0-15.4% in different years).
   Conclusion:
   The frequency of off-label use of different types of monoclonal antibodies varies, but appears to be considerably high for specific monoclonal antibodies or indications. In certain examples, this might reflect implementation into clinical practice of relevant scientific data, albeit not of the strength or quality that suffices for receipt of regulatory approval. In others, it might relate to the sub-optimal effectiveness and considerable toxicity of the conventional therapies. Still, the clinician should bear in mind the potential costs and toxicity that can be associated with off-label use of monoclonal antibodies.
C1 [Zarkali, Angeliki; Karageorgopoulos, Drosos E.; Rafailidis, Petros I.; Falagas, Matthew E.] Alfa Inst Biomed Sci, Athens 15123, Greece.
   [Karageorgopoulos, Drosos E.] Hygeia Hosp, Dept Med, Athens, Greece.
   [Karageorgopoulos, Drosos E.] Hellen Ctr Dis Control & Prevent, Athens, Greece.
   [Rafailidis, Petros I.; Falagas, Matthew E.] Henry Dunant Hosp, Dept Med, Athens, Greece.
   [Falagas, Matthew E.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
C3 Alfa Institute Of Biomedical Sciences; Hygeia Hospital; Henry Dunant
   Hospital; Tufts University
RP Falagas, ME (通讯作者)，Alfa Inst Biomed Sci, 9 Neapoleos St, Athens 15123, Greece.
EM m.falagas@aibs.gr
RI Rafailidis, PI/AAO-8679-2021; Karageorgopoulos, Drosos/K-9241-2018;
   Rafailidis, Petros/AAI-1376-2021
OI Karageorgopoulos, Drosos/0000-0002-9959-9978; Zarkali,
   Angeliki/0000-0003-2808-072X
CR Alasfoor K, 2009, ANN HEMATOL, V88, P239, DOI 10.1007/s00277-008-0574-9
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NR 33
TC 8
Z9 9
U1 0
U2 13
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0300-7995
EI 1473-4877
J9 CURR MED RES OPIN
JI Curr. Med. Res. Opin.
PD MAR
PY 2014
VL 30
IS 3
BP 471
EP 480
DI 10.1185/03007995.2013.855186
PG 10
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA AB8IT
UT WOS:000332034300016
PM 24127749
DA 2022-11-30
ER

PT J
AU Li, J
   Yao, K
   Yu, XN
   Dong, XR
   Gan, LS
   Luo, CQ
   Wu, YL
AF Li, Jie
   Yao, Ke
   Yu, Xiaoning
   Dong, Xinran
   Gan, Lishe
   Luo, Chenqi
   Wu, Yalin
TI Identification of a Novel Lipofuscin Pigment (iisoA2E) in Retina and Its
   Effects in the Retinal Pigment Epithelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Aging; Phosphatidylethanolamine; Phospholipase D; Retina; Retinal
   Degeneration; Retinoid; Lipofuscin; Pigment
ID LIGHT-INDUCED DAMAGE; MACULAR DEGENERATION; STARGARDT-DISEASE; A2E;
   FLUOROPHORE; ABCR; RPE; OXIDATION; RHODOPSIN; PRODUCTS
AB Background: Macular degeneration implicates lipofuscin deposition in the retina. Results: Bisretinoid iisoA2E in the retina was characterized; excessive accumulation of iisoA2E was cytotoxic to retinal pigment epithelial cells. Conclusion: Pyridinium iisoA2E is a unique diretinal adduct and serves as a fluorescent biomarker of aberrant all-trans-retinal metabolism. Significance: Characterization of iisoA2E gives a more complete understanding of the biosynthesis of retinal bisretinoid lipofuscin.
   Lipofuscin accumulation in retinal pigment epithelial (RPE) cells of the eye implicates the etiologies of Stargardt disease and age-related macular degeneration, a leading cause of blindness in the elderly. Here, we have identified a previously unknown RPE lipofuscin component. By one- and two-dimensional NMR techniques and mass spectrometry, we confirmed that this compound is a new type of pyridinium bisretinoid presenting an unusual structure, in which two polyenic side chains are attached to adjacent carbons of a pyridinium ring. This pigment is a light-induced isomer of isoA2E, rather than A2E, referred to as iisoA2E. This pigment is a fluorescent lipofuscin compound with absorbance maxima at approximate to 430 and 352 nm detected in human, pig, mouse, and bovine eyes. Formation of iisoA2E was found in reaction mixtures of all-trans-retinal and ethanolamine. Excess intracellular accumulation of this adduct in RPE cells in vitro leads to a significant loss of cell viability and caused membrane damage. Phospholipase D-mediated phosphodiester cleavage of the A2PE series generated isoA2E and iisoA2E, in addition to A2E, thus corroborating the presence of isoA2PE and iisoA2PE that may serve as biosynthetic precursors of isoA2E and iisoA2E.
C1 [Li, Jie; Gan, Lishe; Wu, Yalin] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.
   [Yao, Ke; Yu, Xiaoning; Dong, Xinran; Luo, Chenqi; Wu, Yalin] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Ctr Eye, Hangzhou 310009, Zhejiang, Peoples R China.
C3 Zhejiang University; Zhejiang University
RP Wu, YL (通讯作者)，Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.
EM yalinw@zju.edu.cn
RI Yao, Ke/AAM-6866-2021
OI Li, Jie/0000-0001-5463-3995; Yao, Ke/0000-0002-6764-7365
FU National Science Foundation of the People's Republic of China [21202146,
   81271018]; Fundamental Research Funds for the Central Universities;
   Zhejiang Key Innovation Team Project of China Grant [2009R50039];
   Zhejiang Key Laboratory Fund of China Grant [2011E10006]
FX This work was supported in part by National Science Foundation of the
   People's Republic of China Grants 21202146 and 81271018 and by the
   Fundamental Research Funds for the Central Universities.; Supported by
   Zhejiang Key Innovation Team Project of China Grant 2009R50039 and
   Zhejiang Key Laboratory Fund of China Grant 2011E10006.
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NR 47
TC 11
Z9 11
U1 1
U2 25
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 DEC 13
PY 2013
VL 288
IS 50
BP 35671
EP 35682
DI 10.1074/jbc.M113.511386
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 291FZ
UT WOS:000329814700006
PM 24169698
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Yandrapu, SK
   Upadhyay, AK
   Petrash, JM
   Kompella, UB
AF Yandrapu, Sarath K.
   Upadhyay, Arun K.
   Petrash, J. Mark
   Kompella, Uday B.
TI Nanoparticles in Porous Microparticles Prepared by Supercritical
   Infusion and Pressure Quench Technology for Sustained Delivery of
   Bevacizumab
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE supercritical fluid; bevacizumab; PLGA; intravitreal; sustained release;
   noninvasive fluorophotometry
ID MACULAR DEGENERATION; INTRAVITREAL BEVACIZUMAB; PROTEIN DELIVERY;
   DRUG-DELIVERY; RELEASE; SYSTEMS; PLGA; MICROSPHERES; NEOVASCULARIZATION;
   RANIBIZUMAB
AB Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9-fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Fluor 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases.
C1 [Yandrapu, Sarath K.; Upadhyay, Arun K.; Kompella, Uday B.] Univ Colorado, Dept Pharmaceut Sci, Nanomed & Drug Delivery Lab, Aurora, CO 80045 USA.
   [Petrash, J. Mark; Kompella, Uday B.] Univ Colorado, Dept Ophthlamol, Aurora, CO 80045 USA.
   [Kompella, Uday B.] Univ Colorado, Dept Bioengn, Aurora, CO 80045 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; University of Colorado System; University of Colorado Anschutz
   Medical Campus; University of Colorado System; University of Colorado
   Anschutz Medical Campus
RP Kompella, UB (通讯作者)，Univ Colorado Denver, Dept Pharmaceut Sci & Ophthalmol, 12850 E Montview Blvd, Aurora, CO 80045 USA.
EM uday.kompella@ucdenver.edu
RI Upadhyay, Arun/D-4510-2014
FU NIH [R01 EY018940, RC1 EY020361, R01 EY022097]; NATIONAL EYE INSTITUTE
   [RC1EY020361, R01EY022097, R01EY018940] Funding Source: NIH RePORTER
FX This work was supported in part by NIH Grants R01 EY018940, RC1
   EY020361, and R01 EY022097. The authors are thankful to Ms. Rinku Baid
   for her assistance with the intravitreal injections in this study.
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NR 29
TC 66
Z9 68
U1 3
U2 47
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 2013
VL 10
IS 12
BP 4676
EP 4686
DI 10.1021/mp400487f
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 263TS
UT WOS:000327831500027
PM 24131101
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Hu, YN
   Li, L
   Ehm, MG
   Bing, N
   Song, K
   Nelson, MR
   Talmud, PJ
   Hingorani, AD
   Kumari, M
   Kivimaki, M
   Xu, CF
   Waterworth, DM
   Whittaker, JC
   Abecasis, GR
   Spino, C
   Kang, HM
AF Hu, Youna
   Li, Li
   Ehm, Margaret G.
   Bing, Nan
   Song, Kijoung
   Nelson, Matthew R.
   Talmud, Philippa J.
   Hingorani, Aroon D.
   Kumari, Meena
   Kivimaeki, Mika
   Xu, Chun-Fang
   Waterworth, Dawn M.
   Whittaker, John C.
   Abecasis, Goncalo R.
   Spino, Cathie
   Kang, Hyun Min
TI The Benefits of Using Genetic Information to Design Prevention Trials
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; PREDICTION; AGE; RISK;
   SUSCEPTIBILITY; POLYMORPHISMS; PREVALENCE; MODEL; POWER
AB Clinical trials for preventative therapies are complex and costly endeavors focused on individuals likely to develop disease in a short time frame, randomizing them to treatment groups, and following them over time. In such trials, statistical power is governed by the rate of disease events in each group and cost is determined by randomization, treatment, and follow-up. Strategies that increase the rate of disease events by enrolling individuals with high risk of disease can significantly reduce study size, duration, and cost. Comprehensive study of common, complex diseases has resulted in a growing list of robustly associated genetic markers. Here, we evaluate the utility-in terms of trial size, duration, and cost-of enriching prevention trial samples by combining clinical information with genetic risk scores to identify individuals at greater risk of disease. We also describe a framework for utilizing genetic risk scores in these trials and evaluating the associated cost and time savings. With type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), and advanced age-related macular degeneration (AMD) as examples, we illustrate the potential and limitations of using genetic data for prevention trial design. We illustrate settings where incorporating genetic information could reduce trial cost or duration considerably, as well as settings where potential savings are negligible. Results are strongly dependent on the genetic architecture of the disease, but we also show that these benefits should increase as the list of robustly associated markers for each disease grows and as large samples of genotyped individuals become available.
C1 [Hu, Youna; Abecasis, Goncalo R.; Spino, Cathie; Kang, Hyun Min] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Hu, Youna] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Li, Li; Ehm, Margaret G.; Bing, Nan; Nelson, Matthew R.] GlaxoSmithKline GSK, Dept Quantitat Sci, Res Triangle Pk, NC 27709 USA.
   [Song, Kijoung; Waterworth, Dawn M.] GlaxoSmithKline GSK, Dept Quantitat Sci, Collegeville, PA 19426 USA.
   [Talmud, Philippa J.] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London WC1E 6JF, England.
   [Hingorani, Aroon D.; Kumari, Meena; Kivimaeki, Mika] UCL, Inst Cardiovasc Sci, Genet Epidemiol Grp, London WC1E 6BT, England.
   [Xu, Chun-Fang; Whittaker, John C.] GlaxoSmithKline GSK, Dept Quantitat Sci, Stevenage SG1 2NY, Herts, England.
C3 University of Michigan System; University of Michigan; University of
   California System; University of California Berkeley; GlaxoSmithKline;
   GlaxoSmithKline; University of London; University College London;
   University of London; University College London; GlaxoSmithKline
RP Kang, HM (通讯作者)，Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
EM hmkang@umich.edu
RI Kivimaki, Mika/B-3607-2012; Abecasis, Goncalo R/B-7840-2010; Whittaker,
   John C/B-8609-2012
OI Kivimaki, Mika/0000-0002-4699-5627; Whittaker, John
   C/0000-0002-3529-2379; Xu, Chun-Fang/0000-0002-8747-0683; Abecasis,
   Goncalo/0000-0003-1509-1825; Talmud, Philippa/0000-0002-5560-1933;
   Hingorani, Aroon/0000-0001-8365-0081; Kumari, Meena/0000-0001-9716-1035
FU NHGRI NIH HHS [R01 HG007022] Funding Source: Medline; ESRC
   [ES/J023299/1] Funding Source: UKRI; MRC [MR/K013351/1] Funding Source:
   UKRI; Economic and Social Research Council [ES/J023299/1] Funding
   Source: researchfish; Medical Research Council [MR/K013351/1] Funding
   Source: researchfish; NATIONAL HUMAN GENOME RESEARCH INSTITUTE
   [R01HG007022] Funding Source: NIH RePORTER
CR Barrett JC, 2009, NAT GENET, V41, P703, DOI 10.1038/ng.381
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NR 35
TC 15
Z9 15
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 4
PY 2013
VL 92
IS 4
BP 547
EP 557
DI 10.1016/j.ajhg.2013.03.003
PG 11
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 124FR
UT WOS:000317449700006
PM 23541341
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Byeon, SH
   Lee, SC
   Choi, SH
   Lee, HK
   Lee, JH
   Chu, YK
   Kwon, OW
AF Byeon, Suk Ho
   Lee, Sung Chul
   Choi, Soo Hyun
   Lee, Hyung-Keun
   Lee, Joon H.
   Chu, Young Kwang
   Kwon, Oh Woong
TI Vascular Endothelial Growth Factor as an Autocrine Survival Factor for
   Retinal Pigment Epithelial Cells under Oxidative Stress via the
   VEGF-R2/PI3K/Akt
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID INTRAVITREAL INJECTION; FACTOR VEGF; EXPRESSION; BEVACIZUMAB; RPE;
   RECEPTOR; NEOVASCULARIZATION; PARACRINE; TOXICITY; ANTIBODY
AB PURPOSE. Vascular endothelial cell growth factor (VEGF) is strongly induced by oxidative stress in retinal pigment epithelial (RPE) cells, and VEGF-A is a survival factor for various cell types. This study was conducted to determine whether the autocrine VEGF signaling pathway in RPE cells is involved in the mechanism of adaptive response to oxidative stress.
   METHODS. ARPE-19 cells were treated with hydrogen peroxide, and cell death was measured by flow cytometry with annexin V-fluorescein isothiocyanate. Survival analysis was performed with pretreatment of VEGF-A-neutralizing antibodies, VEGF receptor tyrosine kinase inhibitor (SU5416), or VEGF-A receptor-neutralizing antibodies (anti-VEGF-R1 and anti-VEGF-R2). The expression of VEGF-A, -R1, -R2, and soluble VEGF-R1 was determined by semiquantitative RT-PCR or Western blot analysis. Phosphorylation of VEGF-R2 was detected with immunoprecipitation and immunoblot analysis.
   RESULTS. Hydrogen peroxide-induced cell death was promoted by pretreatment with VEGF-A and anti-VEGF-R2-neutralizing antibodies, but not with anti-VEGF-R1-neutralizing antibody. Phosphorylation of VEGF-R2 in RPE cells was induced by hydrogen peroxide, and pretreatment with anti-VEGF-A-neutralizing antibody inhibited phosphorylation. Phosphorylation of Akt under oxidative stress was abrogated by pretreatment with neutralizing antibodies against either VEGF-A or SU5416.
   CONCLUSIONS. Autocrine VEGF-A enhanced RPE cell survival under oxidative stress; the autocrine VEGF-A/VEGF-R2/PI3K/Akt pathway is involved. Neutralization of VEGF-A signaling, as in eyes with age-related macular degeneration, may influence RPE cell survival. (Invest Ophthalmol Vis Sci. 2010; 51: 1190-1197) DOI: 10.1167/iovs.09-4144
C1 [Byeon, Suk Ho; Lee, Sung Chul; Choi, Soo Hyun; Lee, Hyung-Keun; Kwon, Oh Woong] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul 120752, South Korea.
   [Lee, Joon H.] Konyang Univ, Coll Med, Myung Gok Eye Res Inst, Seoul, South Korea.
   [Chu, Young Kwang] Siloam Eye Hosp, Seoul, South Korea.
C3 Yonsei University; Yonsei University Health System; Konyang University;
   Konyang University Hospital
RP Byeon, SH (通讯作者)，Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, 134 Shinchon Dong, Seoul 120752, South Korea.
EM shbyeon@yuhs.ac
OI Byeon, suk ho/0000-0001-8101-0830; , Sung Chul/0000-0001-9438-2385
FU Korean Research Foundation [KRF-2008-331-E00208]; Korean Government;
   MOEHRD [Ministry Of Education and Human Resources Development]; National
   Research Foundation (NRF) of Korea [M1AQ19, 2009-0082186]; Korean
   Government (MEST [Ministry of Science, Education, and Technology]
FX Supported by Korean Research Foundation Grant KRF-2008-331-E00208
   provided by the Korean Government ( Basic Research Promotion Fund,
   MOEHRD [Ministry Of Education and Human Resources Development]) and
   National Research Foundation (NRF) of Korea Grant M1AQ19, 2009-0082186
   provided by the Korean Government (MEST [Ministry of Science, Education,
   and Technology]).
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NR 45
TC 102
Z9 106
U1 0
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2010
VL 51
IS 2
BP 1190
EP 1197
DI 10.1167/iovs.09-4144
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 545AS
UT WOS:000273704700077
PM 19834034
DA 2022-11-30
ER

PT J
AU Hocking, HG
   Herbert, AP
   Kavanagh, D
   Soares, DC
   Ferreira, VP
   Pangburn, MK
   Uhrin, D
   Barlow, PN
AF Hocking, Henry G.
   Herbert, Andrew P.
   Kavanagh, David
   Soares, Dinesh C.
   Ferreira, Viviana P.
   Pangburn, Michael K.
   Uhrin, Dusan
   Barlow, Paul N.
TI Structure of the N-terminal region of complement factor H and
   conformational implications of disease-linked sequence variations
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MEMBRANE COFACTOR PROTEIN; ALTERNATIVE PATHWAY; REGULATORY DOMAINS;
   BINDING-SITES; NEUTRON-SCATTERING; CRYSTAL-STRUCTURE; COMPONENT C3; NMR;
   DECAY; ACTIVATION
AB Factor H is a regulatory glycoprotein of the complement system. We expressed the three N-terminal complement control protein modules of human factor H (FH1-3) and confirmed FH1-3 to be the minimal unit with cofactor activity for C3b proteolysis by factor I. We reconstructed FH1-3 from NMR-derived structures of FH1-2 and FH2-3 revealing an similar to 105-angstrom-long rod-like arrangement of the modules. In structural comparisons with other C3b-engaging proteins, factor H module 3 most closely resembles factor B module 3, consistent with factor H competing with factor B for binding C3b. Factor H modules 1, 2, and 3 each has a similar backbone structure to first, second, and third modules, respectively, of functional sites in decay accelerating factor and complement receptor type 1; the equivalent intermodular tilt and twist angles are also broadly similar. Resemblance between molecular surfaces is closest for first modules but absent in the case of second modules. Substitution of buried Val-62 with Ile (a factor H single nucleotide polymorphism potentially protective for age-related macular degeneration and dense deposit disease) causes rearrangements within the module 1 core and increases thermal stability but does not disturb the interface with module 2. Replacement of partially exposed (in module 1) Arg-53 by His (an atypical hemolytic uremic syndrome-linked mutation) did not impair structural integrity at 37 C, but this FH1-2 mutant was less stable at higher temperatures; furthermore, chemical shift differences indicated potential for small structural changes at the module 1-2 interface.
C1 [Hocking, Henry G.; Herbert, Andrew P.; Kavanagh, David; Soares, Dinesh C.; Uhrin, Dusan; Barlow, Paul N.] Univ Edinburgh, Sch Chem, Edinburgh Biomol NMR Unit, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Hocking, Henry G.; Herbert, Andrew P.; Kavanagh, David; Soares, Dinesh C.; Uhrin, Dusan; Barlow, Paul N.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Soares, Dinesh C.] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Ferreira, Viviana P.; Pangburn, Michael K.] Univ Texas Hlth Sci Ctr Tyler, Dept Biochem, Tyler, TX 75708 USA.
C3 University of Edinburgh; University of Edinburgh; University of
   Edinburgh; University of Texas System; University of Texas-Health
   Sciences Center at Tyler (UTHSCT)
RP Barlow, PN (通讯作者)，Univ Edinburgh, Sch Chem, Edinburgh Biomol NMR Unit, Joseph Black Chem Bldg,W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM Paul.Barlow@ed.ac.uk
RI Mohammed, Imran/J-8271-2012; Kavanagh, David/E-8498-2011; Herbert, Andy
   P/F-6693-2010; Barlow, Paul N/G-2853-2011; Soares, Dinesh C/A-4425-2012;
   Herbert, Andrew P/C-4755-2008
OI Mohammed, Imran/0000-0002-8412-0768; Kavanagh,
   David/0000-0003-4718-0072; Herbert, Andy P/0000-0002-4549-6965; Soares,
   Dinesh C/0000-0001-7557-0495; Herbert, Andrew P/0000-0002-4549-6965;
   Ferreira, Viviana/0000-0001-8923-5671; Hocking,
   Henry/0000-0003-0933-9265
FU Medical Research Council Funding Source: Medline; Wellcome Trust Funding
   Source: Medline
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NR 81
TC 52
Z9 54
U1 0
U2 9
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 APR 4
PY 2008
VL 283
IS 14
BP 9475
EP 9487
DI 10.1074/jbc.M709587200
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 280ZO
UT WOS:000254465800077
PM 18252712
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Kiuchi, K
   Matsuoka, M
   Wu, JC
   Silva, RLE
   Kengatharan, M
   Verghese, M
   Ueno, S
   Yokoi, K
   Khu, NH
   Cooke, JP
   Campochiaro, PA
AF Kiuchi, Katsuji
   Matsuoka, Masato
   Wu, Jenny C.
   Lima e Silva, Raquel
   Kengatharan, Muralitharan
   Verghese, Mary
   Ueno, Shinji
   Yokoi, Katsutoshi
   Khu, Naw Htee
   Cooke, John P.
   Campochiaro, Peter A.
TI Mecamylamine suppresses basal and nicotine-stimulated choroidal
   neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; RISK; ACETYLCHOLINE;
   POLYMORPHISM; RANIBIZUMAB; INCREASES; GROWTH; MODEL; GENE
AB PURPOSE. Nicotinic acetylcholine receptors ( nAChR) are best known for their role in neurotransmission, but they have recently been demonstrated on vascular endothelial cells. Acetylcholine is their endogenous ligand, but they are also stimulated by nicotine. By stimulating nAChR, nicotine promotes tumor angiogenesis as well as atherosclerotic plaque neovascularization. In this study, the authors investigated the role of nAChR in the pathogenesis of choroidal neovascularization (CNV).
   METHODS. The effect of the nonselective nAChR antagonist mecamylamine was tested on human retinal and choroidal endothelial cells in vitro and in a murine model of CNV.
   RESULTS. Several nAChR isoforms were identified in retinal and choroidal microvascular endothelial cells, and the ability of these cells to form tubules when grown in growth factor reduced basement membrane matrix and supplemented with VEGF was suppressed by the nAChR antagonist mecamylamine. Supplementation of the drinking water of mice with nicotine increased the size of CNV lesions at Bruch membrane rupture sites, an effect that was blocked by subcutaneous administration of mecamylamine ( 50 mg/kg/d) by an osmotic pump. In the absence of nicotine, CNV formation was suppressed by the infusion of 50 mg/kg/d mecamylamine or by topical application 0.1 or 1% mecamylamine to the cornea.
   CONCLUSIONS. These data suggest that endogenous activation of nAChR promotes CNV and that activation of nAChR by nicotine may contribute to the increased incidence of CNV seen in smokers with age-related macular degeneration (AMD). Topically administered mecamylamine could provide an appealing new treatment approach for CNV.
C1 [Kiuchi, Katsuji; Matsuoka, Masato; Lima e Silva, Raquel; Ueno, Shinji; Yokoi, Katsutoshi; Khu, Naw Htee; Campochiaro, Peter A.] Johns Hopkins Univ Hosp, Dept Ophthalmol, Sch Med, Baltimore, MD 21287 USA.
   [Kiuchi, Katsuji; Matsuoka, Masato; Lima e Silva, Raquel; Ueno, Shinji; Yokoi, Katsutoshi; Khu, Naw Htee; Campochiaro, Peter A.] Johns Hopkins Univ Hosp, Dept Neurosci, Sch Med, Baltimore, MD 21287 USA.
   [Wu, Jenny C.; Cooke, John P.] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA.
   [Kengatharan, Muralitharan; Verghese, Mary] CoMentis Inc, San Francisco, CA USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins Medicine; Stanford University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ Hosp, Dept Ophthalmol, Sch Med, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
RI Ueno, Shinji/M-5063-2014
OI Cooke, John/0000-0003-0033-9138
FU NATIONAL EYE INSTITUTE [R01EY012609] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY012609, R01 EY012609-09] Funding Source: Medline
CR Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   Edwards AO, 2005, SCIENCE, V308, P421, DOI 10.1126/science.1110189
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NR 20
TC 45
Z9 47
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 2008
VL 49
IS 4
BP 1705
EP 1711
DI 10.1167/iovs.07-0089
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 282ON
UT WOS:000254577200056
PM 18385094
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mei, M
   Leat, SJ
AF Mei, Ming
   Leat, Susan J.
TI Suprathreshold contrast matching in maculopathy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PERCEIVED CONTRAST; VISUAL-ACUITY; SENSITIVITY; VISION; PSYCHOPHYSICS;
   PERFORMANCE; PERCEPTION; CONSTANCY; SYSTEM; LIFE
AB Purpose. To compare suprathreshold contrast perception among three groups of participants with maculopathy (atrophic age-related macular degeneration [ARMD], exudative ARMD, and juvenile macular dystrophy [JMD]) and to compare suprathreshold contrast matching between controls and subjects with maculopathy.
   Methods. Three groups of subjects with macular disorders (13 atrophic ARMD, 14 exudative ARMD, and 8 JMD) and one group of control subjects (15 subjects 50 years and older) participated. Contrast sensitivity (CS) up to 8.53 cycles per degree (cpd) was measured with a temporal two- alternative forced- choice staircase procedure. Suprathreshold contrast matching was measured using a method of limits. A 0.58 cpd sine- wave grating was the standard; the subject was asked to match the contrast of gratings of different spatial frequencies.
   Results. Subjects with maculopathy showed marked deficits of contrast threshold. Suprathreshold contrast constancy was shown, though deficits were observed in absolute matches compared with control subjects. The slopes of matched contrast against standard contrast for the subjects with maculopathy were significantly different from those for the controls, and these differences were in the direction that implies compensation for differences in thresholds. There were no significant differences among the three groups of subjects with maculopathy.
   Conclusions. In this study, the authors observed a degree of contrast constancy in subjects with maculopathy, though there were still deficits compared with control subjects. This is discussed in terms of gain of the visual system adjusting to compensate for CS losses (though incompletely) or contrast overconstancy, present in normal peripheral vision, which helps to compensate for CS loss.
C1 Univ Waterloo, Sch Optometry, Waterloo, ON, Canada.
C3 University of Waterloo
RP Mei, M (通讯作者)，Univ Waterloo, Sch Optometry, Waterloo, ON, Canada.
EM m2mei@uwaterloo.ca
OI Leat, Susan/0000-0002-7082-035X
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NR 33
TC 16
Z9 16
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2007
VL 48
IS 7
BP 3419
EP 3424
DI 10.1167/iovs.06-0731
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 187NT
UT WOS:000247855600060
PM 17591917
DA 2022-11-30
ER

PT J
AU Wang, FE
   Shi, G
   Niesman, MR
   Rewolinski, DA
   Miller, SS
AF Wang, F. E.
   Shi, G.
   Niesman, M. R.
   Rewolinski, D. A.
   Miller, S. S.
TI Receptor tyrosine kinase inhibitors AG013764 and AG013711 reduce
   choroidal neovascularization in rat eye
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization; gene
   transfer; adeno-associated viral vector; anti-angiogenesis; receptor
   tyrosine kinase; VEGF; PDGF; combination therapy
ID ENDOTHELIAL GROWTH-FACTOR; AAV-MEDIATED EXPRESSION; RETINAL
   DEGENERATION; MACULAR DEGENERATION; NONHUMAN PRIMATE; FACTOR VEGF;
   MODELS; OVEREXPRESSION; ANGIOGENESIS; SUPPRESSION
AB Age-related macular degeneration (AMD) is the major cause of blindness for people over 60. In the "wet" form of AMD compounds targeting growth factor signaling pathways such as VEGF have been a major focus for therapeutic interventions. In a previously developed rat model of CNV, we utilized two receptor tyrosine kinase inhibitors (RTKi) to block VEGFR-1, VEGFR-2 and PDGFR signaling following the establishment of CNV. AAV-VEGF(165) was injected into the subretinal space of rats at postnatal days 15-17. Six weeks later, a suspension of RTK inhibitors, AGO 13764 or AGO 13711, was injected intraperitoneally (IP, twice daily) or intravitreally (every five days) over a two week period. FITC-dextran whole-mounts of RPE-choroid-sclera were prepared after the animals were sacrificed. CNV area was quantified using Neurolucida to measure the hyperfluorescence on FITC-dextran whole-mounts. Histology and inummohistochemistry were performed as described previously. VEGF expression in control and treated eyes was confirmed by inummohistochemistry and histological sections indicated recovery of retinal morphology and CNV reduction in treated eyes. In the animals IP injected with AG013764 or AG013711 the mean CNV level was reduced by 25 to 33% compared to control, but this effect did not achieve statistical significance. Intravitreal injections of AG013764 or AG013711 reduced the level of CNV by approximately 60% compared to control (p < 0.005 or p < 0.05, respectively). These data show that two RTK inhibitors, AG013764 or AG013711, delivered intravitreally, significantly reduce blood vessel proliferation in this AAV-VEGF(165) model of CNV. (C) 2007 Elsevier Ltd. All rights reserved.
C1 NEI, NIH, Bethesda, MD 20892 USA.
   Pfizer Global Res & Dev, Ophthamol Drug Discovery, San Diego, CA USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Pfizer
RP Miller, SS (通讯作者)，NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A22, Bethesda, MD 20892 USA.
EM millers@nei.nih.gov
OI Niesman, Michael/0000-0002-6700-8985
FU NATIONAL EYE INSTITUTE [Z01EY000420] Funding Source: NIH RePORTER;
   Intramural NIH HHS Funding Source: Medline; NEI NIH HHS [Z01
   EY000420-02] Funding Source: Medline
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NR 59
TC 8
Z9 9
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAY
PY 2007
VL 84
IS 5
BP 922
EP 933
DI 10.1016/j.exer.2007.01.022
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 168ON
UT WOS:000246534000015
PM 17399700
OA Green Accepted
DA 2022-11-30
ER

PT J
AU King, RE
   Kent, KD
   Bomser, JA
AF King, RE
   Kent, KD
   Bomser, JA
TI Resveratrol reduces oxidation and proliferation of human retinal pigment
   epithelial cells via extracellular signal-regulated kinase inhibition
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE resveratrol; retinal pigment epithelial cells; extracellular
   signal-regulated kinase; antioxidant; antiproliferative
ID ACTIVATED PROTEIN-KINASES; APOPTOSIS; ANTIOXIDANTS; GROWTH;
   IDENTIFICATION; POLYPHENOLS; ABSORPTION; MECHANISMS; MODULATE; TISSUES
AB Epidemiological evidence suggests that moderate wine consumption and antioxidant-rich diets may protect against age-related macular degeneration (AMD), the leading cause of vision loss among the elderly. Development of AMD and other retinal diseases, such as proliferative vitreoretinopathy (PVR), is associated with oxidative stress in the retinal pigment epithelium (RPE), a cell layer responsible for maintaining the health of the retina by providing structural and nutritional support. We hypothesize that resveratrol, a red wine polyphenol, may be responsible, in part, for the health benefits of moderate red wine consumption on retinal disease. To test this hypothesis, the antioxidant and antiproliferative effects of resveratrol were examined in a human RPE cell line (designated AR-PE- 19). Cell proliferation was determined using the bromodeoxyuridine (BrdU) assay, intracellular oxidation was assessed by dichlorofluorescein fluorescence, and activation of the mitogen-activated protein kinase (MAPK) cascade was measured by inummoblotting. Treatment with 50 and 100 mumol/L resveratrol significantly reduced proliferation of RPE cells by 10% and 25 %, respectively (P < 0.05). This reduction in proliferation was not associated with resveratrol-induced cytotoxicity. ResveFatrol (100 mumol/L) inhibited basal and H2O2-induced intracellular oxidation and protected RPE cells from H2O2-induced cell death. The observed reduction in cell proliferation was associated with inhibition of mitogen activated protein kinase/ERK (MEK) and extracellular signal-regulated kinase (ERK 1/2) activities at concentrations of resveratrol as low'as 5 mumol/L. These results suggest that resveratrol can reduce oxidative stress and hyperproliferation of the RPE. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
C1 Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA.
   Ohio State Univ, Dept Food Sci & Technol, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; University System of
   Ohio; Ohio State University
RP Bomser, JA (通讯作者)，Ohio State Univ, Dept Human Nutr, 1787 Neil Ave, Columbus, OH 43210 USA.
EM bomser.1@osu.edu
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NR 42
TC 136
Z9 145
U1 1
U2 22
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD JAN 15
PY 2005
VL 151
IS 2
BP 143
EP 149
DI 10.1016/j.cbi.2004.11.003
PG 7
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 901VP
UT WOS:000227310600009
PM 15698585
DA 2022-11-30
ER

PT J
AU Schutt, F
   Bergmann, M
   Holz, FG
   Kopitz, J
AF Schutt, F
   Bergmann, M
   Holz, FG
   Kopitz, J
TI Proteins modified by malondialdehyde, 4-hydroxynonenal, or advanced
   glycation end products in lipofuscin of human retinal pigment epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE PIGMENT; LIPID-PEROXIDATION; PROTEOME ANALYSIS; BRUCHS MEMBRANE; RPE
   CELLS; DRUSEN; AUTOFLUORESCENCE; GLYCOSYLATION; FLUOROPHORE; INHIBITION
AB PURPOSE. Lipofuscin (LF) accumulation in the retinal pigment epithelium (RPE) is associated with age and various retinal diseases. Toxic LF compounds may interfere with normal RPE function. Oxidative modification of proteins was determined in LF granules from human eyes.
   METHODS. LF was isolated from the RPE-choroid complex of 10 pairs of donor eyes by gradient ultracentrifugation. Protein compounds were separated by two-dimensional (2-D) gel electrophoresis and screened by Western blot analysis for lipid peroxidation- or glucoxidation-induced damage-in particular, by malondialdehyde (MDA), 4-hydroxynonenal (HNE), and advanced glycation end products (AGES). Identity of the immunostained proteins was revealed using 2-D software for comparison of the spot position with Coomassie-stained 2-D gels of the same samples.
   RESULTS. By comparing the results taken from the authors' previous proteome analysis of RPE LF with an immunoblot analysis of the same samples, this study shows that a variety of LF-associated proteins were damaged by aberrant covalent modifications of MDA, 4-HNE, and AGES. Several proteins were altered by two or three different modification types. Modified mitochondrial proteins indicated that autophagy of altered proteins also contributed to lipofuscin formation.
   CONCLUSIONS. The identification of lipid peroxidation and glucoxidation products in proteinaceous LF components in human RPE supports the hypothesis that these compounds are involved in lipofuscinogenesis and may contribute to the cytotoxic effects of LF in retinal diseases such as age-related macular degeneration and Stargardt disease. Their identification may help to identify potential future treatment targets.
C1 Heidelberg Univ, Dept Ophthalmol, D-69120 Heidelberg, Germany.
   Heidelberg Univ, Dept Mol Pathol, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg; Ruprecht Karls University
   Heidelberg
RP Schutt, F (通讯作者)，Heidelberg Univ, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
EM florian_schuett@med.uni-heidelberg.de
RI Cerviño, Alejandro/L-5853-2014
OI Cerviño, Alejandro/0000-0001-8014-3279
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NR 43
TC 195
Z9 200
U1 0
U2 15
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 2003
VL 44
IS 8
BP 3663
EP 3668
DI 10.1167/iovs.03-0172
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 705EV
UT WOS:000184383500055
PM 12882821
DA 2022-11-30
ER

PT J
AU Li, HT
   Wen, F
   Wu, DZ
AF Li, HT
   Wen, F
   Wu, DZ
TI Polypoidal choroidal vasculopathy in a patient with circumscribed
   choroidal hemangioma
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE internal limiting membrane; macular hole surgery; triamcinolone
   acetonide
C1 Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Peoples R China.
C3 Sun Yat Sen University
RP Wen, F (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, 54 Xianlie Rd, Guangzhou 510060, Peoples R China.
EM wfwzt@163.net
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NR 7
TC 9
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD AUG
PY 2004
VL 24
IS 4
BP 629
EP 631
DI 10.1097/00006982-200408000-00026
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 847QY
UT WOS:000223411200026
PM 15300094
DA 2022-11-30
ER

PT J
AU Li, Y
   You, QS
   Wen, WB
   Xu, J
   Chen, CX
   Wang, YX
   Xu, L
   Jonas, JB
AF Li, Yang
   You, Qi Sheng
   Wei, Wen Bin
   Xu, Jie
   Chen, Chang Xi
   Wang, Ya Xing
   Xu, Liang
   Jonas, Jost B.
TI Polypoidal Choroidal Vasculopathy in Adult Chinese: The Beijing Eye
   Study
SO OPHTHALMOLOGY
LA English
DT Article
C1 [Li, Yang; Wei, Wen Bin; Xu, Jie] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China.
   [You, Qi Sheng; Chen, Chang Xi; Wang, Ya Xing; Xu, Liang; Jonas, Jost B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Heidelberg, Germany.
C3 Capital Medical University; Capital Medical University; Ruprecht Karls
   University Heidelberg
RP Wen, WB (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Key Lab Ophthalmol & Visual Sci, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.
EM weiwenbintr@163.com
RI You, Qisheng/AAG-7153-2020; xu, jie/GQR-1913-2022; 温, 家琦/GYV-3177-2022;
   wang, YA XING/K-9671-2016; Xu, Jie/AIE-0524-2022
OI You, Qisheng/0000-0003-0743-7320; xu, jie/0000-0002-2039-7055; wang, YA
   XING/0000-0003-2749-7793; Jonas, Jost/0000-0003-2972-5227
FU State National Sciences Fund [81170890]; National Key Technology R&D
   Program of the Ministry of Science and Technology [2012BAH05F05,
   2013BAH19F04]
FX Supported by the State National Sciences Fund (no. 81170890) and by the
   National Key Technology R&D Program of the Ministry of Science and
   Technology (No. 2012BAH05F05 and 2013BAH19F04).
CR Chung SE, 2011, OPHTHALMOLOGY, V118, P840, DOI 10.1016/j.ophtha.2010.09.012
   Imamura Y, 2010, SURV OPHTHALMOL, V55, P501, DOI 10.1016/j.survophthal.2010.03.004
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NR 5
TC 28
Z9 28
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2014
VL 121
IS 11
BP 2290
EP 2291
DI 10.1016/j.ophtha.2014.06.016
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AS8DM
UT WOS:000344480400038
PM 25109927
DA 2022-11-30
ER

PT J
AU Lee, K
   Chin, HS
AF Lee, Kanghoon
   Chin, Hee Seung
TI LONGITUDINAL ASSESSMENT OF CHOROIDAL STRUCTURE IN PATIENTS WITH MACULAR
   NEOVASCULARIZATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE enhanced depth imaging optical coherence tomography; Haller's layer;
   neovascular age-related macular degeneration; pachychoroid; pachychoroid
   neovasculopathy; polypoidal choroidal vasculopathy
ID ENDOTHELIAL GROWTH-FACTOR; AFLIBERCEPT THERAPY; THICKNESS; SUBFOVEAL;
   VASCULOPATHY; DEGENERATION; EYES
AB Purpose: To investigate morphologic changes of choroidal structure through chronologic aspect in progression of macular neovascularization (MNV) with pachychoroid features. Methods: One hundred seventy-one MNV participants above 50 years old with or without pachychoroid features were included in the analysis. Age-matched 132 normal patients were analyzed as control group. The total choroidal area and ratio of Sattler's layer area to total choroidal area, derived by summing 25 horizontal raster scans of the 30 degrees x 20 degrees scan area on enhanced depth imaging optical coherence tomography, were calculated to compare the difference among the normal eyes and the MNV eyes with/without pachychoroid features. Results: The mean ratio of Sattler's layer area to total choroidal area is maintained at around 40% in normal eyes and MNV eyes without pachychoroid features. In MNV with pachychoroid features, the ratio of Sattler's layer area to total choroidal area changes according to the disease activity. Ratio of Sattler's layer area to total choroidal area is 34.1 +/- 4.4% at the time of onset, 37.2 +/- 4.8% at the time of remission, and decreases during recurrence from 36.8 +/- 3.8% to 33.4 +/- 3.8% (all P < 0.001). Conclusion: MNV with pachychoroid features is a disease whose development and progression are related to a change in the choroidal interlayer area ratio following the relatively larger dilation of Haller's layer vessels.
C1 [Lee, Kanghoon; Chin, Hee Seung] Inha Univ, Sch Med, Dept Ophthalmol, 27 Inhang Ro, Incheon 22332, South Korea.
C3 Inha University
RP Chin, HS (通讯作者)，Inha Univ, Sch Med, Dept Ophthalmol, 27 Inhang Ro, Incheon 22332, South Korea.
EM hschin@inha.ac.kr
FU Inha University Hospital Research Grant
FX This work was supported by the Inha University Hospital Research Grant.
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NR 30
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD NOV
PY 2022
VL 42
IS 11
BP 2083
EP 2090
DI 10.1097/IAE.0000000000003580
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5M0WB
UT WOS:000870825900011
PM 35982515
DA 2022-11-30
ER

PT J
AU Esteban, JJN
   Martinez, MS
   Navalon, PG
   Serrano, OP
   Patino, JRC
   Puron, MEC
   Martinez-Vizcaino, V
AF Esteban, J. J. Navarro
   Martinez, M. Solera
   Navalon, P. Garcia
   Serrano, O. Pinar
   Patino, J. R. Cerrillo
   Puron, M. E. Calle
   Martinez-Vizcaino, V.
TI Visual impairment and quality of life: gender differences in the elderly
   in Cuenca, Spain
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE elderly; quality of life; vision disorders; visual acuity
ID FUNCTION INDEX VF-14; FULL THRESHOLD; URBAN-POPULATION;
   CATARACT-SURGERY; HEALTH-STATUS; EYE; PREVALENCE; IMPACT; SITA;
   BLINDNESS
AB Purpose To estimate the prevalence of visual impairment (VI) in a population sample of older adults of the province of Cuenca, Spain and to evaluate the impact of VI on health-related quality of life (HRQOL) in this population group.
   Methods Cross-sectional observational study of the cohort of all persons over the age of 64 years from an urban area and rural nucleus of the province of Cuenca, Spain. Sociodemographic data were obtained and the VF-14 and SF-12 questionnaires were administered in an interview. One ophthalmologist evaluated the visual acuity (VA) and the presence of lens opacities, glaucoma, diabetic retinopathy, and age-related maculopathy. Prevalence of VI and blindness was defined according to the WHO criteria (0.5 log MAR <= VA < 1.2 log MAR and VA >= 1.2 log MAR) and the European criteria (0.3 log MAR > VA < 1 log MAR and VA >= 1 log MAR) in the better eye.
   Results The study enrolled 1155 people out of a total of 1435 who were invited to participate (response rate 80.5%). The prevalence of VI and blindness according to the WHO criteria was 6.3 and 2%, respectively. Using the European criteria, the prevalence of VI was 21.1 and 2.4% the prevalence of blindness. The prevalence of VI was greater in older subjects (p < 0.0001); no significant gender-related differences were observed. The mean VF-14 score and means of the Physical Composite Score (PCS) and Mental Composite Score (MCS) of the SF-12 were lower in women than in men for all categories of visual acuity. The mean VF-14 score diminished as the degree of VI increased in all the pathologies studied, except glaucoma. The mean PCS score differed significantly by categories of VI, cataract, and diabetic retinopathy. The mean MCS score only differed with the degree of impairment of diabetic retinopathy.
   Conclusions The prevalence of VI was among the highest reported until now in adults over 64 years old and increased with age. The deterioration in quality of life related to visual function increased with increased degree of VI for all the pathologies studied (cataract, diabetic retinopathy, age-related maculopathy) except glaucoma. The HRQOL was consistently worse in women than in men for all categories of deterioration of visual acuity.
C1 [Martinez, M. Solera; Navalon, P. Garcia; Serrano, O. Pinar; Patino, J. R. Cerrillo; Martinez-Vizcaino, V.] Univ Castilla La Mancha, Social & Hlth Res Ctr, Cuenca 16071, Spain.
   [Esteban, J. J. Navarro] Hosp Virgen de la Luz, Dept Ophthalmol, Cuenca, Spain.
   [Puron, M. E. Calle] Univ Complutense Madrid, Sch Med, Dept Publ Hlth, Madrid, Spain.
C3 Universidad de Castilla-La Mancha; Complutense University of Madrid
RP Martinez-Vizcaino, V (通讯作者)，Univ Castilla La Mancha, Social & Hlth Res Ctr, Santa Teresa Jornet S-N, Cuenca 16071, Spain.
EM Vicente.Martinez@uclm.es
RI VIZCAINO, VICENTE MARTINEZ/R-4336-2017; VIZCAINO, VICENTE
   MARTINEZ/AAZ-9034-2021
OI VIZCAINO, VICENTE MARTINEZ/0000-0001-6121-7893; VIZCAINO, VICENTE
   MARTINEZ/0000-0001-6121-7893
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NR 50
TC 37
Z9 39
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD FEB
PY 2008
VL 17
IS 1
BP 37
EP 45
DI 10.1007/s11136-007-9280-7
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
   Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA 246GQ
UT WOS:000251995900005
PM 18026851
DA 2022-11-30
ER

PT J
AU Kim, JY
   Kim, M
   Kim, RY
   Park, WK
   Park, YH
AF Kim, Joo Young
   Kim, Mirinae
   Kim, Rae Young
   Park, Woo Kyung
   Park, Young-Hoon
TI A 12-week, randomized, double-blind, placebo-controlled study assessing
   the efficacy of EGHB010, a standardized extract of Paeoniae radix and
   Glycyrrhizae radix, in patients with early age-related macular
   degeneration
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Age-related macular degeneration (AMD); EGHB010; Glycyrrhizae radix;
   macular pigment optical density (MPOD); Paeoniae radix
ID PIGMENT OPTICAL-DENSITY; SERUM CONCENTRATIONS; PAEONIFLORIN; LUTEIN;
   CAROTENOIDS; ZEAXANTHIN; PATHOGENESIS; ASSOCIATION; LIPOPROTEIN;
   PREVALENCE
AB Background: EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, inhibits choroidal neovascularization. The aim of this study is to evaluate the efficacy and safety of EGHB010 on early agerelated macular degeneration (AMD) progression inhibition. Methods: The study was designed as a randomized, double-blind, single-center, placebo-controlled study. Subjects were 50 years of age or older, and early AMD satisfied the criteria of more than 15 small (<63 ?m) drusen, less than 20 intermediate (?63, <125 ?m) drusen, or pigment abnormalities. For 12 weeks, the treatment group received EGHB010 and the control received the placebo. The main outcomes were changes in macular pigment optical density (MPOD), central macular thickness (CMT), and central choroidal thickness (CCT). Subgroup analysis was performed on subjects with MPOD <0.75 at baseline. Results: Forty-eight subjects out of 94 were assigned to the treatment group, and 46 to the control group. At 12 weeks, mean MPOD of the treatment group increased by 0.04?0.27 (P=0.2730), and that of the control group decreased by 0.03?0.21 (P=0.7240), but there was no significant difference between the two groups (P=0.1234). There were no significant differences between the two groups in mean CMT and CCT (P=0.6718 and 0.6608, respectively). In subgroup analysis, there were 39 subjects with MPOD <0.75 in the treatment group and 36 in the control. Mean MPOD of the treatment group significantly increased by 0.09?0.25 (P=0.0218), and there was a significant difference in mean MPOD at 12 weeks between the two groups (P=0.0248). Adverse reactions were similar in both groups, and no subjects had serious adverse events. Conclusions: EGHB010 is expected to increase MPOD when administered to subjects with MPOD
   Background: EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, inhibits choroidal neovascularization. The aim of this study is to evaluate the efficacy and safety of EGHB010 on early agerelated macular degeneration (AMD) progression inhibition. Methods: The study was designed as a randomized, double-blind, single-center, placebo-controlled study. Subjects were 50 years of age or older, and early AMD satisfied the criteria of more than 15 small (<63 ?m) drusen, less than 20 intermediate (?63, <125 ?m) drusen, or pigment abnormalities. For 12 weeks, the treatment group received EGHB010 and the control received the placebo. The main outcomes were changes in macular pigment optical density (MPOD), central macular thickness (CMT), and central choroidal thickness (CCT). Subgroup analysis was performed on subjects with MPOD <0.75 at baseline. Results: Forty-eight subjects out of 94 were assigned to the treatment group, and 46 to the control group. At 12 weeks, mean MPOD of the treatment group increased by 0.04?0.27 (P=0.2730), and that of the control group decreased by 0.03?0.21 (P=0.7240), but there was no significant difference between the two groups (P=0.1234). There were no significant differences between the two groups in mean CMT and CCT (P=0.6718 and 0.6608, respectively). In subgroup analysis, there were 39 subjects with MPOD <0.75 in the treatment group and 36 in the control. Mean MPOD of the treatment group significantly increased by 0.09?0.25 (P=0.0218), and there was a significant difference in mean MPOD at 12 weeks between the two groups (P=0.0248). Adverse reactions were similar in both groups, and no subjects had serious adverse events. Conclusions: EGHB010 is expected to increase MPOD when administered to subjects with MPOD
C1 [Kim, Joo Young; Kim, Mirinae; Kim, Rae Young; Park, Woo Kyung; Park, Young-Hoon] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, 222 Banpo Daero, Seoul 06591, South Korea.
   [Kim, Joo Young; Kim, Mirinae; Kim, Rae Young; Park, Woo Kyung; Park, Young-Hoon] Catholic Univ Korea, Coll Med, Catholic Inst Visual Sci, Seoul, South Korea.
C3 Catholic University of Korea; Seoul St. Mary's Hospital; Catholic
   University of Korea
RP Park, YH (通讯作者)，Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, 222 Banpo Daero, Seoul 06591, South Korea.
EM parkyh@catholic.ac.kr
FU EYEGENE Inc.
FX EYEGENE Inc. for the overall study and editorial assistance for this
   article.
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NR 44
TC 0
Z9 0
U1 0
U2 1
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 APR
PY 2021
VL 9
IS 7
AR 20-4701
DI 10.21037/atm-20-4701
PG 14
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA RP0GW
UT WOS:000641416400012
PM 33987239
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shukla, D
   Vidhya, N
   Prasad, NM
   Mahalakshmi, R
   Kolluru, C
   Krishnadas, R
AF Shukla, Dhananjay
   Vidhya, Nagasubramaniam
   Prasad, Noela M.
   Mahalakshmi, Rajendran
   Kolluru, Chandarmohan
   Krishnadas, Ramaswami
TI Evaluation of patient age as a risk factor for Intraocular pressure
   elevation after intravitreal triamcinolone
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ACETONIDE; INJECTION
AB PURPOSE: To evaluate the effect of patient age on intraocular pressure (IOP) response after intravitreal injection of triamcinolone acetonide (IVTA).
   DESIGN: Interventional case series.
   METHODS: A total of 164 outpatients (164 eyes) aged 21 to 80 years (mean, 56.8 years), presenting with exudative age-related maculopathy (5 1) or macular edema of various etiologies (113), received IVTA (4 mg/0.1 ml). The pri,mary outcome measure was IOP elevation > 21 mm. Hg. Patients were re-evaluated at one week, and one, three, and six months.
   RESULTS: The mean baseline IOP was 15.07 mm Hg; the mean rise was 6.6 mm Hg. IOP > 21 mm Hg was observed in 42 (25.6%) patients. In the age group <= 45 years, IOP rise occurred in 45% (14/31) patients, compared with 21% (28/133) of older patients (P=.006). The groups were similar in baseline IOP, lop rise, mean time-lag to maximum IOP, and response to treatment.
   CONCLUSIONS: IVTA caused more frequent IOP elevation in younger patients; other aspects of IOP response and its treatment were similar to older patients.
C1 Aravind Eye Hosp, Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India.
   Lions Aravind Inst Commun Ophthalmol, Madurai, Tamil Nadu, India.
RP Shukla, D (通讯作者)，Aravind Eye Hosp, Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India.
EM daksh66@gmail.com
CR Jonas JB, 2003, BRIT J OPHTHALMOL, V87, P24, DOI 10.1136/bjo.87.1.24
   Jonas JB, 2005, OPHTHALMOLOGY, V112, P593, DOI 10.1016/j.ophtha.2004.10.042
   Kersey JP, 2006, EYE, V20, P407, DOI 10.1038/sj.eye.6701895
   *NAT EYE I, CLIN STUD DAT STAND
   Rhee DJ, 2006, BRIT J OPHTHALMOL, V90, P999, DOI 10.1136/bjo.2006.090340
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   Thompson JT, 2006, AM J OPHTHALMOL, V141, P629, DOI 10.1016/j.ajo.2005.11.050
NR 7
TC 25
Z9 25
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2007
VL 144
IS 3
BP 453
EP 454
DI 10.1016/j.ajo.2007.04.021
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 209TW
UT WOS:000249411900022
PM 17765428
DA 2022-11-30
ER

PT J
AU Kotnala, A
   Senthilkumari, S
   Wu, G
   Stewart, TG
   Curcio, CA
   Halder, N
   Singh, SB
   Kumar, A
   Velpandian, T
AF Kotnala, Ankita
   Senthilkumari, Srinivasan
   Wu, Gong
   Stewart, Thomas G.
   Curcio, Christine A.
   Halder, Nabanita
   Singh, Sundararajan Baskar
   Kumar, Atul
   Velpandian, Thirumurthy
TI Retinal Pigment Epithelium in Human Donor Eyes Contains Higher Levels of
   Bisretinoids Including A2E in Periphery than Macula
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE A2E; bisretinoids; age-related macular degeneration (AMD); macula;
   liquid chromatography - electrospray ionization - mass spectrometry
   (LC-ESI-MS); retinal pigment epithelium (RPE)
ID QUANTITATIVE FUNDUS AUTOFLUORESCENCE;
   RETINYLIDENE-N-RETINYLETHANOLAMINE; PHOTOOXIDATION PRODUCTS; LIPOFUSCIN;
   AGE; RPE; FLUOROPHORES; FLUORESCENCE; MOUSE; MODEL
AB PURPOSE. With age, human retinal pigment epithelium (RPE) accumulates bisretinoid fluorophores that may impact cellular function and contribute to age-related macular degeneration (AMD). Bisretinoids are comprised of a central pyridinium, dihydropyridinium, or cyclohexadiene ring. The pyridinium bisretinoid A2E has been extensively studied, and its quantity in the macula has been questioned. Age-changes and distributions of other bisretinoids are not well characterized. We measured levels of three bisretinoids and oxidized A2E in macula and periphery in human donor eyes of different ages.
   METHODS. Eyes (N = 139 donors, 61 women and 78 men, aged 40-80 years) were dissected into 8 mm diameter macular and temporal periphery punches. Using liquid chromatography - electrospray ionization - mass spectrometry (LC-ESI-MS) and an authentic synthesized standard, we quantified A2E (ng). Using LC-ESI-MS and a 50-eye-extract of A2E, we semiquantified A2E and 3 other compounds (eye extract equivalent units [EEEUs): A2-glycerophosphoethanolamine (A2GPE), dihydropyridine phosphatidyl ethanolamine (A2DHPE), and monofuranA2E (MFA2E).
   RESULTS. A2E quantities in ng and EEEUs were highly correlated (r = 0.97, P < 0.001). From 262 eyes, 5 to 9-fold higher levels were observed in the peripheral retina than in the macula for all assayed compounds. A2E, A2DHPE, and MFA2E increased with age, whereas A2GPE remained unaffected. No significant right-left or male-female differences were detected.
   CONCLUSIONS. Significantly higher levels were observed in the periphery than in the macula for all assayed compounds signifying biologic differences between these regions. Levels of oxidized A2E parallel native A2E and not the distribution of retinal illuminance. Data will assist with the interpretion of clinical trial outcomes of agents targeting bisretinoid-related pathways.
C1 [Kotnala, Ankita; Halder, Nabanita; Velpandian, Thirumurthy] All India Inst Med Sci, Ocular Pharmacol & Pharm Div, New Delhi, India.
   [Senthilkumari, Srinivasan] Aravind Med Res Fdn AMRF, Dr G Venkataswamy Eye Res Inst, Dept Ocular Pharmacol, Madurai 20, Tamil Nadu, India.
   [Wu, Gong; Stewart, Thomas G.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL USA.
   [Singh, Sundararajan Baskar] All India Inst Med Sci, Dept Biophys, New Delhi, India.
   [Kumar, Atul] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ophthalmol, New Delhi, India.
   [Kotnala, Ankita] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Kotnala, Ankita] Univ Alabama Birmingham, Birmingham, AL USA.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Vanderbilt
   University; University of Alabama System; University of Alabama
   Birmingham; All India Institute of Medical Sciences (AIIMS) New Delhi;
   All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences; Vanderbilt University; University
   of Alabama System; University of Alabama Birmingham
RP Velpandian, T (通讯作者)，All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Ocular Pharmacol & Pharm Div, New Delhi 110029, India.
EM tvelpandian@hotmail.com
FU Department of Science & Technology-Fund for Improvement of S&T
   Infrastructure in Universities and Higher Educational Institutions
   (DST-FIST); Council Of Scientific And Industrial Research (CSIR);
   SERB-Young Scientist -Life Sciences (SERB-YSS-LS) [SR/FT/LS-117/2010];
   Vanderbilt Institute for Clinical Research [NCATS UL1 TR002243]; NIH
   [R01EY027948]
FX Financial support: Department of Science & Technology-Fund for
   Improvement of S&T Infrastructure in Universities and Higher Educational
   Institutions (DST-FIST) sponsored High Precision Bio-analytical Facility
   (HPBAF) and Senior Research Fellowship from Council Of Scientific And
   Industrial Research (CSIR) (A. Kotnala) . This study was supported by
   SERB-Young Scientist -Life Sciences (SERB-YSS-LS) : SR/FT/LS-117/2010
   (Dr. S. Senthilkumari) . Vanderbilt Institute for Clinical Research
   (NCATS UL1 TR002243; W. Gong and T.G. Stewart) ; NIH grant R01EY027948
   (A. Kotnala, C.A. Curcio) , Heidelberg Engineer-ing (C.A. Curcio) ;
   institutional support to University of Alabama at Birmingham from
   EyeSight Foundation of Alabama and Research to Prevent Blindness Inc
   (C.A. Curcio) .
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NR 63
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 JUN
PY 2022
VL 63
IS 6
AR 6
DI 10.1167/iovs.63.6.6
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2A8JJ
UT WOS:000809741600001
PM 35671050
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Shin, CY
   Lee, MH
   Kim, HM
   Chung, HC
   Kim, DU
   Lee, JH
   Jeong, KW
AF Shin, Chae Young
   Lee, Mun-Hoe
   Kim, Hyeong-Min
   Chung, Hee-Chul
   Kim, Do-Un
   Lee, Jin-Hee
   Jeong, Kwang Won
TI Protective Effect of Ribes nigrum Extract against Blue Light-Induced
   Retinal Degeneration In Vitro and In Vivo
SO ANTIOXIDANTS
LA English
DT Article
DE N-retinylidene-N-retinylethanolamine (A2E); antioxidant; black currant;
   blue light; drusen; dry age-related macular degeneration (AMD)
ID VACCINIUM-ULIGINOSUM L.; MACULAR DEGENERATION; ANTIOXIDANT ACTIVITY;
   OXIDATIVE STRESS; CELL-DEATH; KAPPA-B; ANTHOCYANINS; MICE; MECHANISMS;
   EXPRESSION
AB Although blackcurrant has several health benefits, such as antioxidant and anti-inflammatory properties, its effects on the retina remain unclear. In this study, we investigated the efficacy of black currant extract (BCE) in an in vitro and in vivo model of dry age-related macular degeneration (AMD) induced by blue light. Dry macular degeneration is characterized by the abnormal accumulation of lipofuscin (e.g., N-retinylidene-N-retinylethanolamine, A2E) in the retina. Blue light (BL) significantly decreased the viability of A2E-laden human retinal pigment epithelial cells (ARPE-19). However, BCE treatment protected ARPE-19 cells from A2E and BL. A2E, which is oxidized by blue light, generates reactive oxygen species in RPE cells. Treatment with BCE significantly decreased (80.8%) reactive oxygen species levels induced by A2E and BL in a concentration-dependent manner. BCE inhibited A2E accumulation in ARPE-19 cells and significantly downregulated the expression of genes increased by A2E and BL in ARPE-19 cells. In vivo, oral administration of BCE (25-100 mg/kg) ameliorated ocular lesions of BL-induced retinal damage in a mouse model and rescued the thickness of the whole retina, photoreceptor segment layer, outer nuclear layer, and inner nuclear layer. The decrease in the number of nuclei in the outer nuclear layer induced by BL was also rescued by BCE. Additionally, BCE administration rescued (40.0%) the BL-induced reduction in the expression level of superoxide dismutase 1. Taken together, our results suggest that BCE may have preventive and therapeutic effects on dry AMD through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.
C1 [Shin, Chae Young; Jeong, Kwang Won] Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
   [Lee, Mun-Hoe; Kim, Hyeong-Min; Chung, Hee-Chul; Kim, Do-Un; Lee, Jin-Hee] NEWTREE Co Ltd, Hlth Food Res & Dev, Seoul 05604, South Korea.
C3 Gachon University
RP Jeong, KW (通讯作者)，Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
EM codud132@gachon.ac.kr; mhlee@inewtree.com; hmkim@inewtree.com;
   hchung@inewtree.com; dkim@inewtree.com; jhlee@inewtree.com;
   kwjeong@gachon.ac.kr
OI Lee, JinHee/0000-0003-2222-7663
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NR 50
TC 2
Z9 2
U1 17
U2 18
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD MAY
PY 2022
VL 11
IS 5
AR 832
DI 10.3390/antiox11050832
PG 12
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 1Q2MB
UT WOS:000802527300001
PM 35624696
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wong, JKW
   Zhu, MM
   Lam, JCH
   Leung, KMK
   Lian, JX
   Lam, CLK
   Shih, KC
   Lai, JSM
AF Wong, Jasper Ka-Wai
   Zhu, Ming Ming
   Lam, Jason Chi-Hang
   Leung, Keith Man-Kei
   Lian, Jin Xiao
   Lam, Cindy Lo-Kuen
   Shih, Kendrick Co
   Lai, Jimmy Shiu-Ming
TI Prospective Comparative Study Investigating Agreement between
   Tele-Ophthalmology and Face-to-face Consultations in Patients Presenting
   with Chronic Visual Loss
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Article
DE Tele-ophthalmology; Prospective comparative trial; Cataracts; Glaucoma;
   Age-related macular degeneration; Chronic visual loss
ID DIABETIC-RETINOPATHY; GLAUCOMA; AGE
AB Introduction: This study aims to investigate the diagnostic accuracy of store-and-forward tele-ophthalmology consultations for non-diabetic patients, aged 40 and above, presenting with vision impairment of 3 months or more, in terms of cataracts, glaucoma, and age-related macular degeneration.
   Methods: This is a prospective comparative study. Enrolled subjects were independently assessed by both tele-ophthalmology and face-to-face assessment. Agreement level between the two modalities for diagnosis and severity were compared using kappa statistic. Diagnostic accuracy of tele-ophthalmology was determined using the face-to-face consultation serving as the gold standard. Costs were compared by calculating the downstream costs generated by each modality in terms of investigations and treatment.
   Results: A total of 860 eyes of 430 patients were assessed during the study period. Tele-ophthalmology consultations had significantly high agreement with face-to-face consultations in the diagnosis and grading of all three ocular conditions; cataracts, glaucoma, and AMD. Diagnosis and grading of cataracts and AMD reached kappa values of > 0.8, while diagnosis and grading of glaucoma reached kappa values between 0.61 and 0.8. In terms of diagnostic accuracy, tele-ophthalmology consultations were highly sensitive and specific for AMD with greater than 99% sensitivity and specificity achieved by teleophthalmology. There was high specificity when diagnosing cataracts, but lower sensitivity at 87.8%. Conversely, there was high sensitivity for diagnosing glaucoma, but lower specificity at 76.5%. Downstream costs were similar between groups.
   Conclusions: Store-and-forward tele-ophthalmology consultations are accurate and comparable to face-to-face consultations for diagnosis and grading of cataracts, glaucoma, and AMD.
C1 [Wong, Jasper Ka-Wai; Zhu, Ming Ming; Lam, Jason Chi-Hang; Leung, Keith Man-Kei; Shih, Kendrick Co; Lai, Jimmy Shiu-Ming] Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Pokfulam, 301B Cyberport 4,100 Cyberport Rd, Hong Kong, Peoples R China.
   [Lian, Jin Xiao] Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Peoples R China.
   [Lam, Cindy Lo-Kuen] Univ Hong Kong SAR, Li Ka Shing Fac Med, Dept Family Med & Primary Care, Hong Kong, Peoples R China.
C3 University of Hong Kong; Hong Kong Polytechnic University; University of
   Hong Kong
RP Shih, KC; Lai, JSM (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Pokfulam, 301B Cyberport 4,100 Cyberport Rd, Hong Kong, Peoples R China.
EM kcshih@hku.hk; smjlai@netvigator.com
RI Shih, Kendrick Co/E-9883-2010
OI Shih, Kendrick Co/0000-0001-6255-2941; LIAN, Jinxiao/0000-0002-6830-4196
FU Health and Medical Research Fund, Food and Health Bureau, Hong Kong SAR
   Government [16172111]
FX This study was supported by the Health and Medical Research Fund, Food
   and Health Bureau, Hong Kong SAR Government (#16172111). The journal's
   Rapid Service Fee was funded by the authors.
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NR 25
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBL AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-8245
EI 2193-6528
J9 OPHTHALMOL THER
JI OPHTHALMOL. THER.
PD JUN
PY 2022
VL 11
IS 3
BP 1199
EP 1213
DI 10.1007/s40123-022-00506-x
EA APR 2022
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1I2EU
UT WOS:000783459200001
PM 35416584
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Polat, OA
   Sener, H
   Erkilic, K
AF Polat, Osman Ahmet
   Sener, Hidayet
   Erkilic, Kuddusi
TI Corneal Nerve Fiber and Sensitivity Loss After Repeated Intravitreal
   Anti-VEGF Injections: An In Vivo Confocal Microscopy Study
SO CORNEA
LA English
DT Article
DE intravitreal injection; confocal microscopy; cornea; subbasal nerve
   plexus
ID POVIDONE-IODINE; OCULAR SURFACE; DAMAGE; NEUROPATHY; MORPHOLOGY;
   SURROGATE
AB Purpose: The purpose of this study was to investigate corneal sensation, subbasal nerve plexus (SBNP), and ocular surface symptoms in patients who underwent multiple intravitreal antivascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD) and diabetic macular edema (DME). Methods: Forty patients with previous anti-VEGF intravitreal injections (20 AMD and 20 DME) and 30 healthy controls were included in this study. In vivo corneal confocal microscopy (IVCM) of the SBNP, corneal sensitivity measurement with a Cochet-Bonnet esthesiometer, noninvasive tear break-up times, and ocular surface disease score index (OSDI) calculation were performed for each participant. Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, corneal total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fiber fractal dimension parameters were obtained by automatic digital analysis. Results: Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, and corneal nerve fiber fractal dimension in IVCM imaging and corneal sensitivity were significantly decreased in both AMD and DME groups compared with the control group. Corneal nerve fiber width and OSDI scores were significantly increased in AMD and DME groups compared with the control group. None of the IVCM parameters were significantly different between AMD and DME groups. Corneal sensitivity was decreased in patients with DME compared with patients with AMD. Tear break-up time was not different among the groups. Conclusions: Corneal SBNP parameters were affected, corneal sensitivity was decreased, and OSDI scores were increased in patients with multiple intravitreal anti-VEGF injections. IVCM parameters were not significantly different between AMD and DME groups.
C1 [Polat, Osman Ahmet; Erkilic, Kuddusi] Erciyes Univ, Fac Med, Dept Ophthalmol, TR-38039 Kayseri, Turkey.
   [Sener, Hidayet] Cukurca State Hosp, Dept Ophthalmol, Hakkari, Turkey.
C3 Erciyes University; Hakkari State Hospital
RP Polat, OA (通讯作者)，Erciyes Univ, Fac Med, Dept Ophthalmol, TR-38039 Kayseri, Turkey.
EM osmanahmet@gmail.com
RI Sener, Hidayet/AEO-7790-2022; POLAT, OSMAN AHMET/AAT-6194-2021
OI POLAT, OSMAN AHMET/0000-0002-3905-4941; Sener,
   Hidayet/0000-0001-5836-0170
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NR 25
TC 2
Z9 2
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD MAR
PY 2022
VL 41
IS 3
BP 317
EP 321
DI 10.1097/ICO.0000000000002836
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YU3PV
UT WOS:000751960200008
PM 34469335
DA 2022-11-30
ER

EF