﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Yang, PM
   Cheng, KC
   Yuan, SH
   Wung, BS
AF Yang, Po-Min
   Cheng, Kai-Chun
   Yuan, Shao-Ho
   Wung, Being-Sun
TI Carbon monoxide-releasing molecules protect against blue light exposure
   and inflammation in retinal pigment epithelial cells
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE carbon monoxide; blue light; nuclear factor-kappa B; glutathione;
   retinal pigment epithelial cells
ID NF-KAPPA-B; MACULAR DEGENERATION; HEME OXYGENASE-1; TRANSCRIPTION
   FACTOR; ENDOTHELIAL-CELLS; ACTIVATION; EXPRESSION; ADHESION;
   GLUTATHIONE; NRF2
AB The most common cause of vision loss among the elderly is age-related macular degeneration (AMD). The aim of the present study was to investigate the potential cytoprotective and anti-inflammatory effects of carbon monoxide-releasing molecules (CORMs), and their ability to activate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-related genes in human retinal pigment epithelium (RPE) cells, as well as the inhibition of endothelial cell migration. It was first determined that CORM2 and CORM3 suppressed blue light-induced cell damage. In addition, a decrease in the level of cleaved poly(ADP-ribose) polymerase 1 protein and dissipation of mitochondrial membrane potential were considered to reflect the anti-apoptotic activity of CORMs. Furthermore, CORM2 induced Nrf-2 activation and the expression of the Nrf2-related genes heme oxygenase-1 and glutamate-cysteine ligase. Pretreatment with CORM2 abolished the blue light-induced increase in oxidative stress, suggesting that CORM2-induced antioxidant activity was involved in the cytoprotection against blue light. It was also demonstrated that CORMs markedly suppressed tumor necrosis factor (TNF)alpha-induced intercellular adhesion molecule-1 expression. Moreover, it was further observed that CORMs exert their inhibitory effects through blocking nuclear factor-kappa B/p65 nuclear translocation and I kappa B alpha degradation in TNF alpha-treated RPE cells. It was observed that CORM2, but not CORM3, protected against oxidative stress-induced cell damage. CORMs abolished vascular endothelial growth factor-induced migration of endothelial cells. The findings of the present study demonstrated the cytoprotective, antioxidant and anti-inflammatory effects of CORMs on RPE cells and anti-angiogenic effects on endothelial cells, suggesting the potential clinical application of CORMs as anti-AMD agents.
C1 [Yang, Po-Min] Chiayi Christian Hosp, Dept Ophthalmol, Chiayi 60002, Taiwan.
   [Cheng, Kai-Chun] Kaohsiung Municipal Hsiaokang Hosp, Dept Ophthalmol, Kaohsiung 81267, Taiwan.
   [Cheng, Kai-Chun] Kaohsiung Med Univ Hosp, Dept Ophthalmol, Kaohsiung 807378, Taiwan.
   [Yuan, Shao-Ho; Wung, Being-Sun] Natl Chiayi Univ, Dept Microbiol Immunol & Biopharmaceut, 300 Shiuefu Rd, Chiayi 60002, Taiwan.
C3 Chia-Yi Christian Hospital; Kaohsiung Medical University; Kaohsiung
   Municipal Siao-Gang Hospital; Kaohsiung Medical University; Kaohsiung
   Medical University Hospital; National Chiayi University
RP Wung, BS (通讯作者)，Natl Chiayi Univ, Dept Microbiol Immunol & Biopharmaceut, 300 Shiuefu Rd, Chiayi 60002, Taiwan.
EM bswung@mail.ncyu.edu.tw
OI wung, being sun/0000-0002-9378-2798
FU National Science Council of Taiwan [105-2320-B-415-007]; Chiayi
   Christian Hospital [R107-20]
FX The present study was supported by grants from the National Science
   Council of Taiwan (no. 105-2320-B-415-007) and the Chiayi Christian
   Hospital (grant no. R107-20).
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NR 36
TC 5
Z9 5
U1 0
U2 3
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
EI 1791-244X
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD SEP
PY 2020
VL 46
IS 3
BP 1096
EP 1106
DI 10.3892/ijmm.2020.4656
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA NE7FU
UT WOS:000562767700018
PM 32582966
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Wang, LP
   Schmidt, S
   Larsen, PP
   Meyer, JH
   Roush, WR
   Latz, E
   Holz, FG
   Krohne, TU
AF Wang, Luping
   Schmidt, Sarah
   Larsen, Petra P.
   Meyer, Johanna H.
   Roush, William R.
   Latz, Eicke
   Holz, Frank G.
   Krohne, Tim U.
TI Efficacy of novel selective NLRP3 inhibitors in human and murine retinal
   pigment epithelial cells
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Age-related macular degeneration; Interleukin-1; Lysosomal membrane
   permeabilization; Oxidative damage; P2X7 receptor
ID INFLAMMASOME ACTIVATION; MACULAR DEGENERATION; P2X7 RECEPTOR; CLEARANCE;
   DISEASE; PROTEIN; RNA
AB NLRP3 inflammasome activation in the retinal pigment epithelium (RPE) is observed in atrophic age-related macular degeneration (AMD), and pharmacological NLRP3 inhibition may provide a therapeutic strategy to halt disease progression. We tested selective NLRP3 inhibitors (IFM-514, IFM-632, and CRID3) for their efficacy in human and murine RPE cells. Inflammasome activation was induced in primary human RPE cells and ARPE-19 cells following priming with IL-1 by different stimuli, including lysosomal membrane permeabilization by leucyl-leucine methyl ester (Leu-Leu-OMe), oxidative damage induced by hydrogen peroxide, lipofuscin-mediated photooxidative damage induced by incubation with 4-hydroxynonenal-modified photoreceptor outer segments and subsequent blue light irradiation, and P2X7 receptor activation by benzoylbenzoyl-ATP. Independent of the applied activation mechanism, treatment with the NLRP3 inhibitors IFM-632, IFM-514, and CRID3 resulted in a significant suppression of inflammasome activation as assessed by IL-1 and LDH release. Likewise, inflammasome activation in blue light-irradiated Abca4-/- mouse and Leu-Leu-OMe-treated wild-type mouse RPE/choroid/sclera eye cups was significantly reduced by treatment with the NLRP3 inhibitors. These results indicate that the investigated selective NLRP3 inhibitors are effective in human and murine RPE cells, thus representing promising agents for the future evaluation of inflammasome inhibition as a therapeutic strategy in atrophic AMD.Key messages center dot NLRP3 inhibitors suppress inflammasome activation in human RPE cells independent of trigger.center dot Light-induced inflammasome activation in Abca4-/- mouse eye cups is reduced by NLRP3 inhibitors.center dot Novel selective NLRP3 inhibitors are effective in human and murine RPE cells.center dot Promising compounds for pharmaceutical intervention in atrophic AMD.
C1 [Wang, Luping; Schmidt, Sarah; Larsen, Petra P.; Meyer, Johanna H.; Holz, Frank G.; Krohne, Tim U.] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
   [Roush, William R.; Latz, Eicke] IFM Therapeut, Boston, MA USA.
   [Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany.
   [Latz, Eicke] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
   [Latz, Eicke] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA USA.
   [Latz, Eicke] Norwegian Univ Sci & Technol NTNU, Ctr Mol Inflammat Res, Dept Canc Res & Mol Med, Trondheim, Norway.
C3 University of Bonn; University of Bonn; Helmholtz Association; German
   Center for Neurodegenerative Diseases (DZNE); University of
   Massachusetts System; University of Massachusetts Worcester; Norwegian
   University of Science & Technology (NTNU)
RP Krohne, TU (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM krohne@uni-bonn.de
RI Krohne, Tim/AAG-4412-2020; Krohne, Tim/D-1497-2013; Larsen,
   Petra/AAV-3114-2020; Latz, Eicke/H-3951-2014
OI Krohne, Tim/0000-0003-2280-925X; Larsen, Petra/0000-0003-2486-632X;
   Meyer, Johanna/0000-0002-2092-6842; Latz, Eicke/0000-0003-1488-5666
FU China Scholarship Council (CSC); Ernst and Berta Grimmke Foundation;
   German Research Foundation (DFG) [KR 2863/7-2]; Volker Homann
   Foundation; Dr. Eberhard und Hilde Rudiger Foundation; European Research
   Council (ERC) grant InflammAct; German Research Foundation (DFG;
   collaborative research centers) [SFB/TRR57, SFB/TRR83]
FX This work was supported by the China Scholarship Council (CSC; to L.W.),
   Ernst and Berta Grimmke Foundation (to P.P.L. and T.U.K.), German
   Research Foundation (DFG; grant KR 2863/7-2 to T.U.K., collaborative
   research centers SFB/TRR57 and SFB/TRR83), Volker Homann Foundation (to
   T.U.K.), Dr. Eberhard und Hilde Rudiger Foundation (to T.U.K.), and the
   European Research Council (ERC) grant InflammAct (to E.L.).
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NR 40
TC 9
Z9 10
U1 0
U2 19
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD APR
PY 2019
VL 97
IS 4
BP 523
EP 532
DI 10.1007/s00109-019-01753-5
PG 10
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA HR2MW
UT WOS:000462972100008
PM 30739141
DA 2022-11-30
ER

PT J
AU Puell, MC
   Perez-Carrasco, MJ
   Alvarez, CP
AF Cinta Puell, Maria
   Jesus Perez-Carrasco, Maria
   Palomo Alvarez, Catalina
TI Macular Thickness and Mesopic Visual Acuity in Healthy Older Subjects
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Optical coherence tomography; macular thickness; mesopic visual acuity;
   low luminance deficit; healthy eyes
ID AGE; EYES; MICROPERIMETRY; DYSFUNCTION
AB Purpose/Aim: Impaired mesopic visual acuity (VA) is a risk factor for incident early age-related macular degeneration (AMD) This study examines relationships between macular thickness measurements and photopic or mesopic VA in healthy eyes. Materials and Methods: In 38 young and 39 older healthy individuals, total, inner, and outer retinal layer (IRL and ORL) thicknesses were measured in the macula region through spectral-domain optical coherence tomography (SD-OCT). Measurements were made across three subfields centered at the fovea: central foveal, pericentral, and peripheral. Best-corrected distance high-contrast (HC) and low-contrast (LC) VA were measured using Bailey-Lovie logMAR letter charts under photopic and mesopic luminance conditions. In addition, the low luminance deficit in VA (LLD, difference between photopic and mesopic VA) was calculated. Relationships were examined through Spearman correlation in each age group and through multiple linear regressions across all eyes. Results: No significant correlations were detected between photopic VA (HC-VA and LC-VA) and macular thickness measurements in each age group. In mesopic conditions, age and pupil size were independent predictors of HC-VA (p = 0.001) and age and pericentral ORL thickness predictors of LC-VA (p = 0.001). Central foveal thickness emerged as the unique independent predictor of LLD (HC-VA, p = 0.013 and LC-VA, p = 0.005). Only in the older age group, was central foveal thicknesses correlated with LLD (HC-VA, r = + 0.45; p = 0.004 and LC-VA, r = + 0.33, p = 0.038). Conclusions: Greater macular thicknesses were related to worse mesopic VA and low luminance deficit in healthy subjects.
C1 [Cinta Puell, Maria; Jesus Perez-Carrasco, Maria; Palomo Alvarez, Catalina] Univ Complutense Madrid, Fac Opt & Optometry, Appl Vis Res Grp, Madrid, Spain.
C3 Complutense University of Madrid
RP Puell, MC (通讯作者)，Univ Complutense Madrid, Fac Opt & Optometry, Av Arcos Jalon 118, Madrid 28037, Spain.
EM puellma@ucm.es
RI Puell, MarÃa/ABE-2972-2021
OI Palomo-Alvarez, Catalina/0000-0003-2110-678X; Puell, Maria
   Cinta/0000-0002-9227-4927
FU Banco Santander-Universidad Complutense de Madrid [PR26/16-20275]
FX This work was supported by the Banco Santander-Universidad Complutense
   de Madrid [PR26/16-20275];
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NR 18
TC 4
Z9 4
U1 1
U2 3
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 JAN 2
PY 2019
VL 44
IS 1
BP 82
EP 88
DI 10.1080/02713683.2018.1522648
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HG4NL
UT WOS:000454952100012
PM 30200784
DA 2022-11-30
ER

PT J
AU Lee, SH
   Kim, YS
   Nah, SK
   Kim, HJ
   Park, HY
   Yang, JY
   Park, K
   Park, TK
AF Lee, Si Hyung
   Kim, Ye Seul
   Nah, Seung Kwan
   Kim, Hee Jong
   Park, Ha Yan
   Yang, Jin Young
   Park, Keerang
   Park, Tae Kwann
TI Transduction Patterns of Adeno-associated Viral Vectors in a
   Laser-Induced Choroidal Neovascularization Mouse Model
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID LEBERS CONGENITAL AMAUROSIS; RANDOMIZED CLINICAL-TRIAL; PIGMENT
   EPITHELIAL-CELLS; MACULAR DEGENERATION; GENE-THERAPY; RETINAL
   TRANSDUCTION; DIABETIC-RETINOPATHY; INCREASED EXPRESSION; BIPOLAR CELLS;
   RECEPTOR 1
AB Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the tropism of viral vectors, it is necessary to evaluate the transduction efficiency of different serotypes of AAV vectors in the retinas with CNVs. Here, we show the patterns and efficacy of transduction of AAV2, -5, and -8 vectors in a laser-induced CNV mouse model. C57BL/6J mice were subjected to unilateral laser photocoagulation on the right eye to induce CNV 5 days prior to intravitreal injection of AAV2, -5, and -8 capsids expressing EGFP. Transduction was increased around CNV lesions for all AAV capsid types, and AAV2 resulted in the highest transduction efficiency. In the absence of CNV, the AAV2 vector transduced ganglion and inner nuclear layer (INL) cells, and AAV5 and AAV8 transduced only a small proportion of cells in the retinal ganglion cell layer. CNV increased AAV2 vector expression throughout the retina and in and around CNVs; the transduced cells included retinal ganglion cells, Muller cells, cells from the INL and outer nuclear layer (ONL), photoreceptors, and retinal pigment epithelium (RPE) cells. Inflammatory cells and endothelial cells in CNVs were also transduced by AAV2. AAV5 and AAV8 were transduced in retinal ganglion, Muller, INL, ONL, and RPE cells in a localized pattern, and only endothelial cells at the surface of CNV lesions showed EGFP expression. Taken together, CNV formation resulted in enhanced transduction of AAV2, -5, and -8, and AAV2 exhibited the highest transduction efficiency in cells in CNV lesions.
C1 [Lee, Si Hyung; Kim, Ye Seul; Nah, Seung Kwan; Park, Tae Kwann] Soonchunhyang Univ, Dept Ophthalmol, Coll Med, Cheonan 31151, South Korea.
   [Lee, Si Hyung; Kim, Ye Seul; Nah, Seung Kwan; Park, Ha Yan; Yang, Jin Young; Park, Tae Kwann] Soonchunhyang Univ Hosp Bucheon, Dept Ophthalmol, 170 Jomaru Ro, Bucheon 14584, South Korea.
   [Kim, Hee Jong] Cdmogen Co Ltd, Cheongju 28751, South Korea.
   [Park, Keerang] Chungbuk Hlth & Sci Univ, Dept Biopharm, Cheongju 28150, Chungbuk, South Korea.
C3 Soonchunhyang University; Soonchunhyang University
RP Park, TK (通讯作者)，Soonchunhyang Univ Hosp Bucheon, Dept Ophthalmol, 170 Jomaru Ro, Bucheon 14584, South Korea.
EM tkpark@schmc.ac.kr
RI Lee, Si Hyung/ABH-1408-2020
FU Korea Health Technology R&D Project through the Korea Health Industry
   Development Institute (KHIDI) - Ministry of Health and Welfare
   [HI17C0966]; Soonchunhyang University research fund
FX This research was supported by a grant from the Korea Health Technology
   R&D Project through the Korea Health Industry Development Institute
   (KHIDI), funded by the Ministry of Health and Welfare, (grant number
   HI17C0966), and also partially supported by the Soonchunhyang University
   research fund.
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NR 55
TC 7
Z9 8
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PD JUN
PY 2018
VL 9
BP 90
EP 98
DI 10.1016/j.omtm.2018.01.008
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GJ5VX
UT WOS:000435452300009
PM 29766021
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Siedlecki, J
   Asani, B
   Wertheimer, C
   Hillenmayer, A
   Ohlmann, A
   Priglinger, C
   Priglinger, S
   Wolf, A
   Eibl-Lindner, K
AF Siedlecki, Jakob
   Asani, Ben
   Wertheimer, Christian
   Hillenmayer, Anna
   Ohlmann, Andreas
   Priglinger, Claudia
   Priglinger, Siegfried
   Wolf, Armin
   Eibl-Lindner, Kirsten
TI Combined VEGF/PDGF inhibition using axitinib induces alpha SMA
   expression and a pro-fibrotic phenotype in human pericytes
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age related macular degeneration; Choroidal neovascularization; VEGF;
   PDGF; Axitinib; Fibrosis
ID ENDOTHELIAL GROWTH-FACTOR; DEGENERATION TREATMENTS TRIALS; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; IN-VITRO; EPITHELIAL-CELLS;
   VISUAL-ACUITY; FIBROSIS; RANIBIZUMAB; ACTIN
AB Purpose Large trials on anti-VEGF/PDGF (vascular endothelial/platelet-derived growth factor) combination therapy have been established to improve management of neovascular activity in age-related macular degeneration. Targeting pericytes, PDGF is thought to induce vessel regression and reduce fibrovascular scarring. The fate of pericytes exposed to anti-VEGF/PDGF combination therapy is not clear. Therefore, this study was designed to study the influence of anti-VEGF/PDGF on pericyte phenotype and cellular behavior.
   Methods Human pericytes from placenta (hPC-PL) were treated with axitinib, a tyrosine kinase inhibitor targeting VEGFR1-3 and PDGFR. Toxic effects were excluded using live/dead staining. Phenotypic changes were evaluated using phalloidin staining for actin cytoskeleton and the expression of stress fibers. MRNA and protein expression levels of alpha-smooth muscle actin (alpha SMA) as a marker of proto-myofibroblastic transition were evaluated with real-time PCR and Western blotting. Influences of fibrotic cellular mechanisms were evaluated with a scratch wound migration and a collagen gel contraction assay.
   Results Treatment with 0.5, 1, and 2.5 mu g/ml axitinib strongly induced a proto-myofibroblast-like actin cytoskeleton with a marked increase in stress fibers. Quantitative real-time PCR and Western blotting revealed these changes to be linked to dose-dependent increases in aSMA mRNA and protein expression. However, fibrotic cellular mechanisms were significantly reduced in the presence of axitinib (scratch wound closure: up to -78.4%, collagen gel contraction: up to -37.4%).
   Conclusions Combined anti-VEGF/PDGF inhibition seems to induce a proto-myofibroblast-like phenotype in human pericytes in vitro, but reduce profibrotic cellular mechanisms due to prolonged anti-PDGF inhibition.
C1 [Siedlecki, Jakob; Asani, Ben; Wertheimer, Christian; Hillenmayer, Anna; Ohlmann, Andreas; Priglinger, Claudia; Priglinger, Siegfried; Wolf, Armin; Eibl-Lindner, Kirsten] Ludwig Maximilians Univ Munchen, Dept Ophthalmol, Mathildenstr 8, D-80336 Munich, Germany.
C3 University of Munich
RP Siedlecki, J (通讯作者)，Ludwig Maximilians Univ Munchen, Dept Ophthalmol, Mathildenstr 8, D-80336 Munich, Germany.
EM jakob.siedlecki@med.uni-muenchen.de
OI Asani, Ben/0000-0003-4809-2859; Ohlmann, Andreas/0000-0002-7101-9361
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NR 56
TC 7
Z9 8
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2018
VL 256
IS 6
BP 1141
EP 1149
DI 10.1007/s00417-018-3987-8
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GG1AY
UT WOS:000432412900012
PM 29721663
DA 2022-11-30
ER

PT J
AU Galloway, CA
   Dalvi, S
   Hung, SSC
   MacDonald, LA
   Latchney, LR
   Wong, RCB
   Guymer, RH
   Mackey, DA
   Williams, DS
   Chung, MM
   Gamm, DM
   Pebay, A
   Hewitt, AW
   Singh, R
AF Galloway, Chad A.
   Dalvi, Sonal
   Hung, Sandy S. C.
   MacDonald, Leslie A.
   Latchney, Lisa R.
   Wong, Raymond C. B.
   Guymer, Robyn H.
   Mackey, David A.
   Williams, David S.
   Chung, Mina M.
   Gamm, David M.
   Pebay, Alice
   Hewitt, Alex W.
   Singh, Ruchira
TI Drusen in patient-derived hiPSC-RPE models of macular dystrophies
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE human induced pluripotent stem cells; retinal pigment epithelium;
   macular dystrophies; drusen; sub-RPE deposits
ID PLURIPOTENT STEM-CELLS; RETINAL-PIGMENT EPITHELIUM; SORSBY FUNDUS
   DYSTROPHY; GROWTH-FACTOR SECRETION; VESICLE-LIKE STRUCTURES; TISSUE
   INHIBITOR; COMPLEMENT ACTIVATION; EXTRACELLULAR-MATRIX;
   RETINITIS-PIGMENTOSA; MALATTIA LEVENTINESE
AB Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid-and protein-rich "drusen-like" composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE-ECM interface.
C1 [Galloway, Chad A.; Dalvi, Sonal; MacDonald, Leslie A.; Latchney, Lisa R.; Chung, Mina M.; Singh, Ruchira] Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA.
   [Galloway, Chad A.; Dalvi, Sonal; MacDonald, Leslie A.; Singh, Ruchira] Univ Rochester, Dept Biomed Genet, Rochester, NY 14642 USA.
   [Hung, Sandy S. C.; Wong, Raymond C. B.; Guymer, Robyn H.; Pebay, Alice; Hewitt, Alex W.] Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.
   [Hung, Sandy S. C.; Wong, Raymond C. B.; Guymer, Robyn H.; Pebay, Alice; Hewitt, Alex W.] Royal Victorian Eye & Ear Hosp, East Melbourne, Vic 3002, Australia.
   [Hung, Sandy S. C.; Wong, Raymond C. B.; Guymer, Robyn H.; Pebay, Alice; Hewitt, Alex W.] Univ Melbourne, Dept Surg, Ophthalmol, Parkville, Vic 3010, Australia.
   [Mackey, David A.] Lions Eye Inst, Nedlands, WA 6009, Australia.
   [Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
   [Mackey, David A.; Hewitt, Alex W.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7005, Australia.
   [Mackey, David A.; Hewitt, Alex W.] Univ Tasmania, Sch Med, Hobart, Tas 7005, Australia.
   [Williams, David S.; Singh, Ruchira] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Williams, David S.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Mackey, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
   [Williams, David S.] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA.
   [Williams, David S.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
   [Chung, Mina M.; Singh, Ruchira] Univ Rochester, Ctr Visual Sci, Rochester, NY 14642 USA.
   [Gamm, David M.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
   [Gamm, David M.] Univ Wisconsin, McPherson Eye Res Inst, Madison, WI 53706 USA.
   [Gamm, David M.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
C3 University of Rochester; University of Rochester; Centre for Eye
   Research Australia; Royal Victorian Eye & Ear Hospital; University of
   Melbourne; Lions Eye Institute; University of Western Australia;
   University of Western Australia; University of Tasmania; Menzies
   Institute for Medical Research; University of Tasmania; 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 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 System;
   University of California Los Angeles; University of Rochester;
   University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison
RP Singh, R (通讯作者)，Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA.; Singh, R (通讯作者)，Univ Rochester, Dept Biomed Genet, Rochester, NY 14642 USA.; Singh, R (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.; Singh, R (通讯作者)，Univ Rochester, Ctr Visual Sci, Rochester, NY 14642 USA.
EM ruchira_singh@urmc.rochester.edu
RI Dalvi, Sonal/GSD-5839-2022; Mackey, David A/H-5340-2014; Dalvi,
   Sonal/AAC-6768-2019
OI Mackey, David A/0000-0001-7914-4709; Hewitt, Alex/0000-0002-5123-5999;
   Guymer, Robyn/0000-0002-9441-4356; Pebay, Alice/0000-0002-7408-9453;
   Wong, Raymond Ching-Bong/0000-0002-8092-9455; Hung,
   Sandy/0000-0002-7496-7092; Galloway, Chad/0000-0002-1978-7339
FU BrightFocus Foundation; David Bryant Trust; Foundation Fighting
   Blindness; Knights Templar Eye Foundation; Research to Prevent
   Blindness; Retina Research Foundation; University of Rochester
   University Research Award; Retina Research Foundation E.A. Humble
   Directorship of the McPherson Eye Research Institute; Sandra Lemke Trout
   Chair in Eye Research; NIH [EY013048]; Australian Research Council
   [FT140100047]; National Health and Medical Research Council (NHMRC)
   [1059369]; NHMRC Practitioner Fellowship [1103329]; NHMRC Elizabeth
   Blackburn Fellowship [1103013]; Ophthalmic Research Institute of
   Australia; Retina Australia; Clinical and Translational Science
   Institute Grant [UL1TR000042]; NATIONAL CENTER FOR ADVANCING
   TRANSLATIONAL SCIENCES [UL1TR000042] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [P30EY000331, R01EY027442] Funding Source: NIH
   RePORTER
FX We thank Dr. Helena Hai Liang [Centre for Eye Research Australia (CERA)]
   for fibroblast culturing; Dr. Robert Buttery, Melinda Cain (CERA), and
   Lisa S. Kearns (CERA) for assistance with clinical phenotyping; Stacey
   Jackson (CERA) for help with CRISPR screening; Stefanie Volland
   (University of California, Los Angeles) for her assistance and advice
   with electron microscopy; Gavin Jenkins (University of Rochester) for
   helping with qPCR analyses; and Dr. Bela-Anand Apte (Cleveland Clinic)
   for help with writing and editing the manuscript. This work was
   supported by funding from BrightFocus Foundation (R.S.), David Bryant
   Trust (R.S.), Foundation Fighting Blindness (R.S.), Knights Templar Eye
   Foundation (R.S.), Research to Prevent Blindness (R.S. and Department of
   Ophthalmology, University of Rochester), Retina Research Foundation
   (R.S.), University of Rochester University Research Award (R.S.), Retina
   Research Foundation E.A. Humble Directorship of the McPherson Eye
   Research Institute (D.M.G.), Sandra Lemke Trout Chair in Eye Research
   (D.M.G.), NIH Grant EY013048 (to D.S.W.), an Australian Research Council
   Future Fellowship FT140100047 (to A.P.), National Health and Medical
   Research Council (NHMRC) Project Grant 1059369 (to R.H.G. and A.P.),
   NHMRC Practitioner Fellowship 1103329 (to A.W.H.), NHMRC Elizabeth
   Blackburn Fellowship 1103013 (to R.H.G.), the Ophthalmic Research
   Institute of Australia (A.P. and A.W.H.), Retina Australia (S.S.H.,
   A.P., and A.W.H.), and Clinical and Translational Science Institute
   Grant UL1TR000042 (University of Rochester).
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NR 66
TC 60
Z9 60
U1 2
U2 12
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 26
PY 2017
VL 114
IS 39
BP E8214
EP E8223
DI 10.1073/pnas.1710430114
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FI1OR
UT WOS:000411704000013
PM 28878022
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Wecker, T
   Ehlken, C
   Buhler, A
   Lange, C
   Agostini, H
   Bohringer, D
   Stahl, A
AF Wecker, Thomas
   Ehlken, Christoph
   Buehler, Anima
   Lange, Clemens
   Agostini, Hansjuergen
   Boehringer, Daniel
   Stahl, Andreas
TI Five-year visual acuity outcomes and injection patterns in patients with
   pro-re-nata treatments for AMD, DME, RVO and myopic CNV
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Angiogenesis; Macula; Neovascularisation; Retina
ID MACULAR DEGENERATION; RANIBIZUMAB; BEVACIZUMAB; AFLIBERCEPT; CARE; EYE
AB Background Anti vascular endothelial growth factor (VEGF) therapy is an established treatment for various retinal diseases. Long-term data on injection frequencies and visual acuity (VA), however, are still rare.
   Methods Five-year analysis of real-life VA developments and injection patterns from 2072 patients (2577 eyes; 33187 injections) with chronically active disease undergoing pro-re-nata treatment for age-related macular degeneration (AMD), diabetic macular oedema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularisation (CNV).
   Results Maximum mean VA gain in year 1 was+5.2 letters in AMD, +6.2 in DME, +10 in RVO and+7.2 in myopic CNV. Over 5years, however, VA in patients with AMD declined. By year 5, 34% of patients with AMD had experienced VA loss of >15 letters, 56% had remained stable and 10% had gained >15 letters. Long-term VA developments in DME and RVO were more favourable with 81% of DME and 79% of patients with RVO gaining or maintaining vision at 5years. In AMD, median injection frequency was six in year 1 and between four and five in consecutive years. In DME and RVO, median injection frequency was six in year 1 but lower compared with AMD in consecutive years. Injection frequency in DME was weakly associated with patient age (r(s)=0.1; p=0.03).
   Conclusions In AMD, the initial VA gain was not maintained long term despite higher injection numbers compared with DME, RVO and myopic CNV. The presented real-world data provide a peer-group-based estimate of VA developments and injection frequencies for counselling patients undergoing long-term anti-VEGF therapy.
C1 [Wecker, Thomas; Ehlken, Christoph; Buehler, Anima; Lange, Clemens; Agostini, Hansjuergen; Boehringer, Daniel; Stahl, Andreas] Univ Freiburg, Ctr Eye, Med Ctr, Fac Med, Killianstr 5, D-79106 Freiburg, Germany.
C3 University of Freiburg
RP Stahl, A (通讯作者)，Univ Freiburg, Ctr Eye, Med Ctr, Fac Med, Killianstr 5, D-79106 Freiburg, Germany.
EM andreas.stahl@uniklinik-freiburg.de
OI Wecker, Thomas/0000-0003-1452-9127
FU DFG [STA 1102/5-1]; German Ophthalmic Society (DOG); Novartis Germany
FX AS is supported by the DFG (STA 1102/5-1) and the German Ophthalmic
   Society (DOG). This work was supported by a research grant from Novartis
   Germany.
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NR 21
TC 98
Z9 99
U1 1
U2 8
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 2017
VL 101
IS 3
BP 353
EP 359
DI 10.1136/bjophthalmol-2016-308668
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EM8BQ
UT WOS:000395536600021
PM 27215744
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Liu, XB
   Ward, K
   Xavier, C
   Jann, J
   Clark, AF
   Pang, IH
   Wu, HL
AF Liu, Xiaobin
   Ward, Keith
   Xavier, Christy
   Jann, Jamieson
   Clark, Abbot F.
   Pang, Iok-Hou
   Wu, Hongli
TI The novel triterpenoid RTA 408 protects human retinal pigment epithelial
   cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2)
   activation
SO REDOX BIOLOGY
LA English
DT Article
DE Retinal pigment epithelial cells; Oxidative stress; RTA 408; Nrf2
ID TOPICAL APPLICATION; OXIDATIVE STRESS; GLUTAREDOXIN; GLUTATHIOLATION;
   THIOREDOXIN; CATALASE; DAMAGE; GENES; ACID
AB Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD). Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200 mu M H2O2 for 6 h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining and Hoechst 33342 fluorescent staining. Reduced (GSH) and oxidized glutathione (GSSG) were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100 nM) of RTA 408 markedly attenuated H2O2 induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQ01, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQ01, Grxl, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
C1 [Liu, Xiaobin; Xavier, Christy; Jann, Jamieson; Pang, Iok-Hou; Wu, Hongli] Univ N Texas, Hlth Sci Ctr, Pharmaceut Sci, Univ North Texas Syst,Coll Pharm, Ft Worth, TX USA.
   [Ward, Keith] REATA Pharmaceut Inc, Irving, TX USA.
   [Clark, Abbot F.] UNTHSC, Dept Cell Biol & Immunol, Ft Worth, TX USA.
   [Clark, Abbot F.; Pang, Iok-Hou; Wu, Hongli] Univ N Texas, Hlth Sci Ctr, North Texas Eye Res Inst, Ft Worth, TX USA.
   [Wu, Hongli] Univ N Texas, Hlth Sci Ctr, Inst Canc Res, Ft Worth, TX USA.
C3 University of North Texas System; University of North Texas Health
   Science Center; University of North Texas System; University of North
   Texas Health Science Center; University of North Texas System;
   University of North Texas Health Science Center; University of North
   Texas System; University of North Texas Health Science Center
RP Wu, HL (通讯作者)，Univ N Texas, Hlth Sci Ctr, North Texas Eye Res Inst, Ft Worth, TX USA.
FU REATA Pharmaceuticals, Inc. (Irving, TX); REATA Pharmaceuticals, Inc.
   [RP0162]; REATA Pharmaceuticals, Inc.
FX This study was supported by REATA Pharmaceuticals, Inc. (Irving, TX).
   Keith Ward is employed by and has a financial interest in REATA
   Pharmaceuticals, Inc. Abbot F. Clark and Hongli Wu received a
   commercrest were disclosed by the other authors.ial research Grant from
   REATA Pharmaceuticals, Inc. (RP0162). No potential conflicts of inte
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NR 43
TC 44
Z9 49
U1 1
U2 28
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD AUG
PY 2016
VL 8
BP 98
EP 109
DI 10.1016/j.redox.2015.12.005
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DN9UU
UT WOS:000377427000012
PM 26773873
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cunea, A
   Powner, MB
   Jeffery, G
AF Cunea, Alexander
   Powner, Michael B.
   Jeffery, Glen
TI Death by color: differential cone loss in the aging mouse retina
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Photoreceptor; Aging; Cone
ID AGE-RELATED MACULOPATHY; WAVELENGTH-SENSITIVE PATHWAYS; COMPLEMENT
   FACTOR-H; MACULAR DEGENERATION; CONTRAST SENSITIVITY; VISUAL PIGMENTS;
   SELECTIVE LOSS; S-CONES; PHOTORECEPTOR; DENSITY
AB Differential cell death is a common feature of aging and age-related disease. In the retina, 30% of rod photoreceptors are lost over life in humans and rodents. However, studies have failed to show age-related cell death in mouse cone photoreceptors, which is surprising because cone physiological function declines with age. Moreover in human, differential loss of short wavelength cone function is an aspect of age-related retinal disease. Here, cones are examined in young (3-month-old) and aged (12-month-old) C57 mice and also in complement factor H knock out mice (CFH-/- that have been proposed as a murine model of age-related macular degeneration. In vivo imaging showed significant age-related reductions in outer retinal thickness in both groups over this period. Immunostaining for opsins revealed a specific significant decline of >20% for the medium/long (M/L)-wavelength cones but only in the periphery. S cones numbers were not significantly affected by age. This differential cell loss was backed up with quantitative real-time polymerase chain reaction for the 2 opsins, again showing S opsin was unaffected, but that M/L opsin was reduced particularly in CFH-/- mice. These results demonstrate aged cone loss, but surprisingly, in both genotypes, it is only significant in the peripheral ventral retina and focused on the M/L population and not S cones. We speculate that there may be fundamental differences in differential cone loss between human and mouse that may question the validity of mouse models of human outer retinal aging and pathology. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Cunea, Alexander; Powner, Michael B.; Jeffery, Glen] UCL, Inst Ophthalmol, London EC1V 9EL, England.
C3 University of London; University College London
RP Jeffery, G (通讯作者)，UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM g.jeffery@ucl.ac.uk
RI Powner, Michael/CAG-7455-2022
OI Powner, Michael/0000-0003-4913-1004; Cunea,
   Alexander/0000-0003-2480-062X
FU Rosetrees Trust
FX The authors are extremely grateful to the following persons for their
   help and valuable critical suggestions: Anne Wesselmann, Rana Begum,
   Livia Carvalho, Katharina Lueck, Ulrich F. Luhmann, Jaimie Ho Kam,
   Kristis Vevis, and Kirsty Watson. They also thank Anthony Vugler and
   Ma'ayan Semo for their assistance with early stages of this project.
   This research was supported by The Rosetrees Trust.
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NR 49
TC 24
Z9 24
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2014
VL 35
IS 11
BP 2584
EP 2591
DI 10.1016/j.neurobiolaging.2014.05.012
PG 8
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AR2LX
UT WOS:000343419800019
PM 24929970
OA Green Published, Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Li, Y
   Zou, X
   Cao, K
   Xu, J
   Yue, TT
   Dai, F
   Zhou, B
   Lu, WY
   Feng, ZH
   Liu, JK
AF Li, Yuan
   Zou, Xuan
   Cao, Ke
   Xu, Jie
   Yue, Tingting
   Dai, Fang
   Zhou, Bo
   Lu, Wuyuan
   Feng, Zhihui
   Liu, Jiankang
TI Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one
   exhibits enhanced ability on Nrf2 activation and protection against
   acrolein-induced ARPE-19 cell toxicity
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Age-related macular degeneration; Mitochondrial membrane potential;
   Oxidative stress; Reactive oxygen species; Glutathione
ID PIGMENT EPITHELIAL-CELLS; INDUCED OXIDATIVE STRESS; NF-KAPPA-B;
   MITOCHONDRIAL DYSFUNCTION; MACULAR DEGENERATION; MOLECULAR-MECHANISMS;
   RESPIRATORY-FUNCTION; CIGARETTE-SMOKING; HEME OXYGENASE-1; FACTOR-2 NRF2
AB Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 mu M, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondria! function. Surprisingly, C3 displayed a complete protective effect at 0.5 mu M, which was much more efficient than curcumin. Both 0.5 mu M C3 and 5 mu M curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Li, Yuan; Cao, Ke; Xu, Jie; Yue, Tingting; Feng, Zhihui; Liu, Jiankang] Xi An Jiao Tong Univ, Ctr Mitochondrial Biol & Med, Key Lab Biomed Informat Engn, Minist Educ,Sch Life Sci & Technol,FIST, Xian 710049, Peoples R China.
   [Li, Yuan; Cao, Ke; Xu, Jie; Yue, Tingting; Feng, Zhihui; Liu, Jiankang] Xi An Jiao Tong Univ, Frontier Inst Life Sci, FIST, Xian 710049, Peoples R China.
   [Zou, Xuan; Lu, Wuyuan] Xi An Jiao Tong Univ, Ctr Translat Med, FIST, Xian 710049, Peoples R China.
   [Dai, Fang; Zhou, Bo] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China.
C3 Xi'an Jiaotong University; Xi'an Jiaotong University; Xi'an Jiaotong
   University; Lanzhou University
RP Feng, ZH (通讯作者)，Xi An Jiao Tong Univ, Ctr Mitochondrial Biol & Med, FIST, 28 W,Xian Ning Rd, Xian 710049, Peoples R China.
EM zhfeng@mail.xjtu.edu.cn; j.liu@mail.xjtu.edu.cn
RI Feng, Zhihui/E-7408-2011; Liu, Jiankang/A-1610-2011; Lu,
   Wuyuan/B-2268-2010; Zou, Xuan/A-6452-2015; Lu, Wuyuan/J-8452-2017
OI Feng, Zhihui/0000-0002-2448-6565; Lu, Wuyuan/0000-0003-1318-9968
FU National Natural Science Foundation of China [81201023, 31100607,
   30930105]; Xi'an Jiaotong University
FX We thank Dr. Edward Sharman at the University of California, Irvine for
   reading and editing this manuscript. This work was supported by the
   National Natural Science Foundation of China (81201023, 31100607,
   30930105) and the 985 and 211 Projects of the Xi'an Jiaotong University.
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NR 49
TC 27
Z9 27
U1 1
U2 32
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD NOV 1
PY 2013
VL 272
IS 3
BP 726
EP 735
DI 10.1016/j.taap.2013.07.029
PG 10
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA 241BM
UT WOS:000326141400018
PM 23954767
DA 2022-11-30
ER

PT J
AU Rajala, A
   Dighe, R
   Agbaga, MP
   Anderson, RE
   Rajala, RVS
AF Rajala, Ammaji
   Dighe, Radhika
   Agbaga, Martin-Paul
   Anderson, Robert E.
   Rajala, Raju V. S.
TI Insulin Receptor Signaling in Cones
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID KINASE B-GAMMA; MOLECULAR-CLONING; PROTEIN-KINASE; PHOSPHOINOSITIDE
   3-KINASE; RETINAL DEGENERATION; BRAIN INSULIN; PHOTORECEPTOR CELLS;
   MESSENGER-RNA; MOUSE RETINA; MICE LACKING
AB In humans, age-related macular degeneration and diabetic retinopathy are the most common disorders affecting cones. In retinitis pigmentosa (RP), cone cell death precedes rod cell death. Systemic administration of insulin delays the death of cones in RP mouse models lacking rods. To date there are no studies on the insulin receptor signaling in cones; however, mRNA levels of IR signaling proteins are significantly higher in cone-dominant neural retina leucine zipper (Nrl) knock-out mouse retinas compared with wild type rod-dominant retinas. We previously reported that conditional deletion of the p85 alpha subunit of phosphoinositide 3-kinase (PI3K) in cones resulted in age-related cone degeneration, and the phenotype was not rescued by healthy rods, raising the question of why cones are not protected by the rod-derived cone survival factors. Interestingly, systemic administration of insulin has been shown to delay the death of cones in mouse models of RP lacking rods. These observations led to the hypothesis that cones may have their own endogenous neuroprotective pathway, or rod-derived cone survival factors may be signaled through cone PI3K. To test this hypothesis we generated p85 alpha(-/-) /Nrl(-/-) double knock-out mice and also rhodopsin mutant mice lacking p85 alpha and examined the effect of the p85 alpha. subunit of PI3K on cone survival. We found that the rate of cone degeneration is significantly faster in both of these models compared with respective mice with competent p85 alpha. These studies suggest that cones may have their own endogenous PI3K-mediated neuroprotective pathway in addition to the cone viability survival signals derived from rods.
C1 Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
   [Anderson, Robert E.; Rajala, Raju V. S.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Rajala, Raju V. S.] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA.
   [Rajala, Ammaji; Dighe, Radhika; Agbaga, Martin-Paul; Anderson, Robert E.; Rajala, Raju V. S.] Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Oklahoma System; University of Oklahoma
   Health Sciences Center
RP Rajala, RVS (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
EM raju-rajala@ouhsc.edu
FU National Institutes of Health [EY016507, EY00871, RR17703, EY12190,
   EY021725]; Research to Prevent Blindness, Inc.; NATIONAL CENTER FOR
   RESEARCH RESOURCES [P20RR017703] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [P30EY012190, P30EY021725, R01EY000871, R01EY016507]
   Funding Source: NIH RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY016507, EY00871, RR17703, EY12190, and EY021725. This
   work was also supported by an unrestricted departmental grant from
   Research to Prevent Blindness, Inc.
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NR 76
TC 40
Z9 40
U1 0
U2 8
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 JUL 5
PY 2013
VL 288
IS 27
BP 19503
EP 19515
DI 10.1074/jbc.M113.469064
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 179JG
UT WOS:000321515800017
PM 23673657
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Pilch, M
   Stieger, K
   Wenner, Y
   Preising, MN
   Friedburg, C
   Bexten, EMZ
   Lorenz, B
AF Pilch, Matthaeus
   Stieger, Knut
   Wenner, Yaroslava
   Preising, Markus N.
   Friedburg, Christoph
   Bexten, Erdmuthe Meyer Zu
   Lorenz, Birgit
TI Automated Segmentation of Pathological Cavities in Optical Coherence
   Tomography Scans
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; retinoschisis; retina; analysis software; bullous cavities
ID MACULAR DEGENERATION; FUNDUS AUTOFLUORESCENCE; RETINOSCHISIS; IMAGES;
   RANIBIZUMAB; DIAGNOSIS; SPECKLE; OCT
AB PURPOSE. To develop and evaluate a method for automated segmentation and quantitative analysis of pathological cavities in the retina visualized by spectral-domain optical coherence tomography (SD-OCT) scans.
   METHODS. The algorithm is based on the segmentation of the gray-level intensities within a B-scan by a k-means cluster analysis and subsequent classification by a k-nearest neighbor algorithm. Accuracy was evaluated against three clinical experts using 130 bullous cavities identified on eight SD-OCT B-scans of three patients with wet age-related macular degeneration (AMD) and five patients with X-linked retinoschisis, as well as on one volume scan of a patient with X-linked retinoschisis. The algorithm calculated the surface area of the cavities for the B-scans and the volume of all cavities for the volume scan. In order to validate the applicability of the algorithm in clinical use, we analyzed 31 volume scans taken over the course of 4 years for one AMD patient with a serous retinal detachment.
   RESULTS. Discrepancies in area measurements between the segmentation results of the algorithm and the experts were within the range of the area deviations among the experts. Volumes interpolated from the B-scan series of the volume scan were comparable among experts and algorithm (0.249 mm(3) for the algorithm, 0.271 mm(3) for expert 1, 0.239 mm(3) for expert 2, and 0.262 mm(3) for expert 3). Volume changes of the serous retinal detachment were quantifiable.
   CONCLUSIONS. The segmentation algorithm represents a method for the automated analysis of large numbers of volume scans during routine diagnostics and in clinical trials.
C1 [Pilch, Matthaeus; Stieger, Knut; Wenner, Yaroslava; Preising, Markus N.; Friedburg, Christoph; Lorenz, Birgit] Univ Giessen, Dept Ophthalmol, D-35392 Giessen, Germany.
   [Pilch, Matthaeus; Bexten, Erdmuthe Meyer Zu] Univ Appl Sci Giessen, Dept Informat, Giessen, Germany.
C3 Justus Liebig University Giessen
RP Stieger, K (通讯作者)，Univ Giessen, Dept Ophthalmol, Friedrichstr 18, D-35392 Giessen, Germany.
EM knut.stieger@uniklinikum-giessen.de
RI Stieger, Knut/A-1600-2012; Preising, Markus/GQA-9591-2022; Lorenz,
   Birgit/AAJ-1351-2020
OI Stieger, Knut/0000-0002-8298-5629; Lorenz, Birgit/0000-0002-9737-8127
FU von Behring Rontgen Foundation [57-0016]
FX Supported by the von Behring Rontgen Foundation (57-0016).
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NR 33
TC 25
Z9 25
U1 1
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2013
VL 54
IS 6
BP 4385
EP 4393
DI 10.1167/iovs.12-11396
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 173YW
UT WOS:000321120700073
PM 23737469
DA 2022-11-30
ER

PT J
AU Lauridsen, LH
   Shamaileh, HA
   Edwards, SL
   Taran, E
   Veedu, RN
AF Lauridsen, Lasse H.
   Shamaileh, Hadi A.
   Edwards, Stacey L.
   Taran, Elena
   Veedu, Rakesh N.
TI Rapid One-Step Selection Method for Generating Nucleic Acid Aptamers:
   Development of a DNA Aptamer against alpha-Bungarotoxin
SO PLOS ONE
LA English
DT Article
ID IN-VITRO; EMERGING CLASS; EVOLUTION; SELEX; RECOGNITION; MICRORNAS;
   MOLECULES
AB Background: Nucleic acids based therapeutic approaches have gained significant interest in recent years towards the development of therapeutics against many diseases. Recently, research on aptamers led to the marketing of Macugen (R), an inhibitor of vascular endothelial growth factor (VEGF) for the treatment of age related macular degeneration (AMD). Aptamer technology may prove useful as a therapeutic alternative against an array of human maladies. Considering the increased interest in aptamer technology globally that rival antibody mediated therapeutic approaches, a simplified selection, possibly in one-step, technique is required for developing aptamers in limited time period.
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C1 [Lauridsen, Lasse H.; Shamaileh, Hadi A.; Edwards, Stacey L.; Veedu, Rakesh N.] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia.
   [Lauridsen, Lasse H.] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, Horsholm, Denmark.
   [Taran, Elena] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Australian Natl Fabricat Facil, Brisbane, Qld, Australia.
C3 University of Queensland; Technical University of Denmark; University of
   Queensland
RP Lauridsen, LH (通讯作者)，Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia.
EM rakesh@uq.edu.au
RI Taran, Elena/C-5833-2009; Edwards, Stacey/A-4980-2011
OI Taran, Elena/0000-0001-7575-5545; Edwards, Stacey/0000-0001-7428-4139
FU University of Queensland ECR grant [2010002143]; Novo Nordisk Fonden
   [NNF10CC1016517] Funding Source: researchfish
FX The work was supported by The University of Queensland ECR grant
   (Project ID 2010002143) awarded to RNV. LHL acknowledges the Novo
   Nordisk Foundation for supporting his stay at The University of
   Queensland, Australia. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 28
TC 44
Z9 45
U1 1
U2 53
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 30
PY 2012
VL 7
IS 7
AR e41702
DI 10.1371/journal.pone.0041702
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 981EY
UT WOS:000306950900034
PM 22860007
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Brantley, MA
   Osborn, MP
   Sanders, BJ
   Rezaei, KA
   Lu, PC
   Li, C
   Milne, GL
   Cai, JY
   Sternberg, P
AF Brantley, Milam A., Jr.
   Osborn, Melissa P.
   Sanders, Barton J.
   Rezaei, Kasra A.
   Lu, Pengcheng
   Li, Chun
   Milne, Ginger L.
   Cai, Jiyang
   Sternberg, Paul, Jr.
TI The Short-term Effects of Antioxidant and Zinc Supplements on Oxidative
   Stress Biomarker Levels in Plasma: A Pilot Investigation
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; LIPID-PEROXIDATION; VITAMIN-E; ALZHEIMERS-DISEASE;
   OXIDANT STRESS; AGE; F-2-ISOPROSTANES; GLUTATHIONE; REDOX;
   QUANTIFICATION
AB center dot PURPOSE: To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy.
   center dot DESIGN: Prospective interventional case series.
   center dot METHODS: Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMID) (AREDS categories 3 or 4) and 7 non-AMID controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined.
   center dot RESULTS: Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls.
   center dot CONCLUSIONS: This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status. (Am J Ophthalmol 2012;153: 1104-1109. (C) 2012 by Elsevier Inc. All rights reserved.)
C1 [Brantley, Milam A., Jr.; Osborn, Melissa P.; Sanders, Barton J.; Rezaei, Kasra A.; Cai, Jiyang; Sternberg, Paul, Jr.] Vanderbilt Univ, Vanderbilt Eye Inst, Med Ctr, Nashville, TN 37232 USA.
   [Lu, Pengcheng; Li, Chun] Vanderbilt Univ, Dept Biostat, Med Ctr, Nashville, TN 37232 USA.
   [Li, Chun] Vanderbilt Univ, Ctr Human Genet Res, Med Ctr, Nashville, TN 37232 USA.
   [Milne, Ginger L.] Vanderbilt Univ, Div Clin Pharmacol, Med Ctr, Nashville, TN 37232 USA.
C3 Vanderbilt University; Vanderbilt University; Vanderbilt University;
   Vanderbilt University
RP Sternberg, P (通讯作者)，Vanderbilt Univ, Vanderbilt Eye Inst, Med Ctr, 2311 Pierce Ave, Nashville, TN 37232 USA.
EM paul.sternberg@vanderbilt.edu
RI Milne, Ginger/D-7648-2014; Li, Chun/B-8388-2012; Li, Chun/R-1095-2019
OI Milne, Ginger/0000-0003-3890-151X; Li, Chun/0000-0002-8819-2443
FU CTSA from the National Institutes of Health, Bethesda, Maryland [1 UL1
   RR024975]; American Geriatrics Society, New York, New York; Carl M. &.
   Mildred A. Reeves Foundation, Columbus, Indiana; Research to Prevent
   Blindness Inc, New York, New York;  [EY007892];  [P30 EY08126];  [P30
   ES000267]; NATIONAL CENTER FOR RESEARCH RESOURCES [KL2RR024977,
   TL1RR024978, UL1RR024975] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [P30EY008126, R29EY007892, R01EY007892] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
   [P30ES000267] Funding Source: NIH RePORTER
FX Publication of this article was supported by Grants EY007892 (P.S.), P30
   EY08126, P30 ES000267 (G.L.M.), and CTSA grant 1 UL1 RR024975 from the
   National Institutes of Health, Bethesda, Maryland; the Jahnigen Career
   Development Award from the American Geriatrics Society, New York, New
   York (M.A.B.); the Carl M. &. Mildred A. Reeves Foundation, Columbus,
   Indiana (M.A.B.); and an unrestricted departmental grant from Research
   to Prevent Blindness Inc, New York, New York. Involved in study design
   and conduct (M.A.B., J.C., P.S.); data collection (B.J.S., K.A.R.,
   G.L.M., J.C.); data management, analysis, and interpretation (M.A.B.,
   M.P.O., P.L., C.L., G.L.M., J.C., P.S.); manuscript preparation (M.A.B.,
   M.P.O., P.S.); and manuscript review and approval (M.A.B., M.P.O.,
   B.J.S., K.A.R., P.L., C.L., G.L.M., J.C., P.S.). All procedures were
   approved prospectively by the local Institutional Review Board, the
   Vanderbilt University Human Research Protection Program. Research
   adhered to the tenets of the Declaration of Helsinki and was conducted
   in accordance with Health Insurance Portability and Accountability Act
   regulations. Informed consent was obtained from all participants upon
   study enrollment. The NCT Registry Number for this clinical trial is
   NCT00668213. The authors would like to thank the staff of the Eicosanoid
   Core Laboratory for the measurements of isoprostanes and isofurans,
   Cindy Dossett for designing controlled meal plans, and the staff of the
   Vanderbilt General Clinical Research Center.
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   2001, ARCH OPHTHALMOL, V119, P1417
NR 31
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUN
PY 2012
VL 153
IS 6
BP 1104
EP 1109
DI 10.1016/j.ajo.2011.12.010
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 953US
UT WOS:000304899300014
PM 22381365
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Schmitt, F
   Juillerat-Jeanneret, L
AF Schmitt, Frederic
   Juillerat-Jeanneret, Lucienne
TI Drug Targeting Strategies for Photodynamic Therapy
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE Photodynamic Therapy; Drug Targeting; Peptides; Proteins; Nanoparticles;
   Organometallics
ID LOW-DENSITY-LIPOPROTEIN; PROTOPORPHYRIN-IX PRODUCTION; INTERNALIZING
   MONOCLONAL-ANTIBODIES; FIBROBLAST ACTIVATION PROTEIN; CHLORIN-TYPE
   PHOTOSENSITIZER; ENDOTHELIAL GROWTH-FACTOR; 5-AMINOLEVULINIC ACID;
   IN-VIVO; RUTHENIUM-PORPHYRIN; EFFICIENT SYNTHESIS
AB In human pathologies, therapeutic treatments are often limited by the lack of selectivity of drugs and their elevated effective concentrations. Targeting these agents to a defined tissue could enhance their selectivity and then diminish their side effects when compared to drugs that accumulate in the entire body. Targeting could also improve treatment efficiency by allowing a localized high concentration of the agents. Based on the different behaviors and patterns of expression between diseased and normal cells, strategies for targeting can be explored. For example, receptors, proteases or trans-membrane carriers could be different or differently expressed. Many therapeutic procedures rely on this fact, including photodynamic therapy (PDT). PDT is already used in the treatment of some cancers, of inflammatory diseases and others diseases such as age-related macular degeneration or acne. PDT relies on the activation of a photosensitizer (PS) by visible light which results in the production of cytotoxic reactive oxygen species. In PDT, the general distribution of PS to the whole body leads to generalized photosensitization and poor acceptance of treatments by patients. One way to avoid these effects is to improve the targeting of PSs to diseased tissues using modification of PS with peptides or proteins that will target specific receptors or enzymes. PSs could also be functionalized with non-proteic ligands such as organometalics to achieve targeted and/or combined therapies. Alternatively, PSs could be encapsulated in nanoparticles bearing targeting agents which will decrease concentration of free circulating PS and improve photodynamic efficiency. These different approaches will be discussed in the present review with an emphasis on the use of peptides and proteins.
C1 [Schmitt, Frederic; Juillerat-Jeanneret, Lucienne] Univ Lausanne Hosp, Inst Pathol, CHUV UNIL Bugnon 25, CH-1011 Lausanne, Switzerland.
C3 University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV)
RP Juillerat-Jeanneret, L (通讯作者)，Univ Lausanne Hosp, Inst Pathol, CHUV UNIL Bugnon 25, CH-1011 Lausanne, Switzerland.
EM lucienne.juillerat@chuv.ch
FU Swiss Commission for Technology and Innovation (CTI) [10550.1 PFLS-LS]
FX FS was financially supported by the Swiss Commission for Technology and
   Innovation (CTI grant No 10550.1 PFLS-LS).
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   Zheng G, 2001, J ORG CHEM, V66, P8709, DOI 10.1021/jo0105080
   Zheng G, 2005, P NATL ACAD SCI USA, V102, P17757, DOI 10.1073/pnas.0508677102
   Zheng G, 2007, P NATL ACAD SCI USA, V104, P8989, DOI 10.1073/pnas.0611142104
   ZHOU C, 1988, PHOTOCHEM PHOTOBIOL, V48, P487, DOI 10.1111/j.1751-1097.1988.tb02850.x
NR 195
TC 46
Z9 48
U1 1
U2 73
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1871-5206
EI 1875-5992
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PD JUN
PY 2012
VL 12
IS 5
BP 500
EP 525
DI 10.2174/187152012800617830
PG 26
WC Oncology; Chemistry, Medicinal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pharmacology & Pharmacy
GA 947PT
UT WOS:000304442700006
PM 22292760
DA 2022-11-30
ER

PT J
AU Pujari, S
   Siddique, SS
   Dohlman, CH
   Chodosh, J
AF Pujari, Siddharth
   Siddique, Sana S.
   Dohlman, Claes H.
   Chodosh, James
TI The Boston Keratoprosthesis Type II: The Massachusetts Eye and Ear
   Infirmary Experience
SO CORNEA
LA English
DT Article
DE Boston keratoprosthesis; mucous membrane pemphigoid; Stevens-Johnson
   syndrome; long-term outcomes
ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; INTRAVENOUS
   IMMUNOGLOBULIN; COMPLICATIONS; PREVENTION
AB Purpose: To report the long-term outcomes of Boston keratoprosthesis type II implantation in the management of severe ocular surface disease and corneal blindness through a retrospective interventional case series.
   Methods: This retrospective review included medical records of patients who underwent Boston keratoprosthesis type II implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000 through December 31, 2009. The main outcome measures analyzed were visual acuity, keratoprosthesis retention, and postoperative complications.
   Results: A total of 29 eyes of 26 patients received a Boston keratoprosthesis type II during the study period. Patients undergoing operation had corneal blindness because of mucous membrane pemphigoid (51.7%), Stevens-Johnson syndrome/toxic epidermal necrolysis (41.4%), or other ocular surface disease (6.9%). Visual acuity after surgery improved to 20/200 or better in 23 eyes (79.3%) and to 20/30 or better in 10 eyes (34.5%). In patients with at least 1 year of follow-up (n = 21), visual acuity of 20/200 or better was maintained in 12 eyes (57.1%). Of 13 eyes followed-up for more than 5 years, 6 eyes (46.2%) had visual acuity of 20/200 or better at the last follow-up examination. Eyes that did not improve to 20/200 or lost vision during the follow-up had end-stage glaucoma, previous retinal detachment, or age-related macular degeneration. Of the total of 29 eyes, 17 devices (58.6%) were retained without extrusion or replacement during a total follow-up time of 107.9 person-years.
   Conclusions: The Boston keratoprosthesis type II is a viable option for corneal blindness from severe autoimmune ocular surface diseases.
C1 [Pujari, Siddharth; Siddique, Sana S.; Dohlman, Claes H.; Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary
RP Chodosh, J (通讯作者)，Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM james_chodosh@meei.harvard.edu
FU Research to Prevent Blindness, New York, NY
FX Supported in part by an unrestricted grant to the Department of
   Ophthalmology, Harvard Medical School from the Research to Prevent
   Blindness, New York, NY.
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NR 19
TC 55
Z9 57
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3740
J9 CORNEA
JI Cornea
PD DEC
PY 2011
VL 30
IS 12
BP 1298
EP 1303
DI 10.1097/ICO.0b013e318215207c
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 849GC
UT WOS:000297112600003
PM 21963861
DA 2022-11-30
ER

PT J
AU Acton, JH
   Cubbidge, RP
   King, H
   Galsworthy, P
   Gibson, JM
AF Acton, Jennifer H.
   Cubbidge, Robert P.
   King, Helen
   Galsworthy, Paul
   Gibson, Jonathan M.
TI Drusen detection in retro-mode imaging by a scanning laser
   ophthalmoscope
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; drusen; grading; scanning laser
   ophthalmoscope
ID AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; FOLLOW-UP
AB Purpose: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called `retro-mode' imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging.
   Methods: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging.
   Results: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 mu m smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted kappa = 0.69) and moderate for size of deposits (weighted kappa = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients.
   Conclusion: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.
C1 [Acton, Jennifer H.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Acton, Jennifer H.; Cubbidge, Robert P.; Gibson, Jonathan M.] Aston Univ, Ophthalm Res Grp, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
   [King, Helen; Galsworthy, Paul; Gibson, Jonathan M.] Birmingham Heartlands Hosp, Heart England Diabet Retinopathy Grading Ctr, Birmingham B9 5ST, W Midlands, England.
C3 Columbia University; Aston University; Heart of England NHS Foundation
   Trust; University of Birmingham
RP Acton, JH (通讯作者)，Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
EM ja2660@columbia.edu
RI Acton, Jennifer/AAU-3307-2021
OI Acton, Jennifer/0000-0002-0347-7651; Gibson, Jonathan
   M/0000-0002-9281-5244; Cubbidge, Robert P/0000-0002-7851-1375
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NR 22
TC 28
Z9 29
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD AUG
PY 2011
VL 89
IS 5
BP E404
EP E411
DI 10.1111/j.1755-3768.2011.02123.x
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 792KH
UT WOS:000292742800003
PM 21332676
OA Bronze
DA 2022-11-30
ER

PT J
AU Ablonczy, Z
   Prakasam, A
   Fant, J
   Fauq, A
   Crosson, C
   Sambamurti, K
AF Ablonczy, Zsolt
   Prakasam, Annamalai
   Fant, James
   Fauq, Abdul
   Crosson, Craig
   Sambamurti, Kumar
TI Pigment Epithelium-derived Factor Maintains Retinal Pigment Epithelium
   Function by Inhibiting Vascular Endothelial Growth Factor-R2 Signaling
   through gamma-Secretase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FAMILIAL ALZHEIMERS-DISEASE; FACTOR VEGF EXPRESSION; MACULAR
   DEGENERATION; AMYLOID-BETA; CHOROIDAL NEOVASCULARIZATION;
   DIABETIC-RETINOPATHY; OXIDATIVE STRESS; FACTOR PEDF; A-BETA; CELLS
AB Wet age-related macular degeneration (AMD) attacks the integrity of the retinal pigment epithelium (RPE) barrier system. The pathogenic process was hypothesized to be mediated by vascular endothelial growth factor (VEGF) and antagonized by pigment epithelium-derived factor (PEDF). To dissect these functional interactions, monolayer cultures of RPE cells were established, and changes in transepithelial resistance were evaluated after administration of PEDF, placenta growth factor (VEGF-R1 agonist), and VEGF-E (VEGF-R2 agonist). A recently described mechanism of VEGF inhibition in endothelia required the release of VEGF-R1 intracellular domain by gamma-secretase. To evaluate this pathway in the RPE, cells were pretreated with inhibitors DAPT or LY411575. Processing of VEGF receptors was assessed by Western blot analysis. Administration of VEGF-E rapidly increased RPE permeability, and PEDF inhibited the VEGF-E response dose-dependently. Both gamma-secretase antagonists prevented the inhibitory effects of PEDF. The co-administration of PEDF and VEGF-E depleted the amount of VEGF-R2 in the membrane and increased the amount of VEGF-R2 ectodomain in the media. Therefore, the inhibitory effect of PEDF appears to be mediated via the processing of VEGF-R2 by gamma-secretase. gamma-Secretase generates the amyloid-beta(A beta) peptide of Alzheimer disease from its precursor (amyloid precursor protein). This peptide is also a component of drusen in dry AMD. The results support the hypothesis that misregulation of gamma-secretase may not only lead to A beta deposits in dry AMD but can also be damaging to RPE function by blocking the protective effects of PEDF to prevent VEGF from driving the dry to wet AMD transition.
C1 [Ablonczy, Zsolt; Fant, James; Crosson, Craig] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Prakasam, Annamalai; Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
   [Fauq, Abdul] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; Mayo Clinic
RP Ablonczy, Z (通讯作者)，167 Ashley Ave,SEI 518E, Charleston, SC 29425 USA.
EM ablonczy@musc.edu
RI Sambamurti, Kumar/A-1620-2012
OI Sambamurti, Kumar/0000-0001-9507-9214
FU National Institutes of Health [EY14793, AG023055, EY009741]; NEI; NIA;
   Medical University of South Carolina (MUSC) [P28918]; Research to
   Prevent Blindness, New York, NY; NIH/NEI [EY13520]; NATIONAL EYE
   INSTITUTE [R01EY009741, R24EY014793, R01EY013520] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON AGING [R01AG023055] Funding Source: NIH
   RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY14793, AG023055, and EY009741 from NEI, NIA, and NEI,
   respectively. This work was also supported by Medical University of
   South Carolina (MUSC) Grant URC P28918 and an unrestricted grant to MUSC
   from Research to Prevent Blindness, New York, NY. The Leica DM LFSA
   confocal microscope was obtained through a supplement to NIH/NEI
   EY13520.
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NR 47
TC 55
Z9 61
U1 0
U2 8
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 OCT 30
PY 2009
VL 284
IS 44
BP 30177
EP 30186
DI 10.1074/jbc.M109.032391
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 510LM
UT WOS:000271090000021
PM 19723623
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Patil, AJ
   Gramajo, AL
   Sharma, A
   Seigel, GM
   Kuppermann, BD
   Kenney, MC
AF Patil, A. Jayaprakash
   Gramajo, Ana L.
   Sharma, Ashish
   Seigel, Gail M.
   Kuppermann, Baruch D.
   Kenney, M. Cristina
TI Differential effects of nicotine on retinal and vascular cells in vitro
SO TOXICOLOGY
LA English
DT Article
DE Nicotine; Cell viability; Caspase-3/7; DNA ladder; Apoptosis; Necrosis
AB The purpose of the current Study is to understand the effects of nicotine in human retinal pigment epithelial (ARPE-19), human microvascular endothelial cells (HMVEC) and rat neurosensory retinal (R28) cells. ARPE-19, HMVEC and R28 cell cultures were treated with 10(-2) and 10(-4) M nicotine for 24 h. R28 cells were also pre-treated for 4 h with ALLN and ALLM (calpain inhibitors) or epicatechin, an antioxidant flavonoid compound. Trypan blue dye exclusion assay, caspase-3/7, LDH activity and DNA laddering assays were performed. With 10(-2) M nicotine treatment, R28 cell cultures showed decreased cell viability that was partially reversed by pre-treatment with the antioxidant epicatechin but not with calpain inhibitors. The DNA ladder assay showed a 200 bp banding pattern consistent with apoptosis, however, caspase-3/7 activity was not increased. After treatment with 10(-2) M nicotine, HMVEC cultures showed decreased cell viability and increased LDH activity but no DNA banding patterns or caspase-3/7 activity. ARPE-19 cells showed no change in cell viability or caspase-3/7 activity at any of the nicotine concentrations. We conclude of dissimilar responses to nicotine treatment in three different cell lines. Nicotine was toxic to HMVEC and R28 cell cultures but the ARPE-19 cells were unaffected. In R28 cells. the nicotine effects were through an oxidant pathway that is non-caspase, non-calpain mediated while the HMVEC toxicity was via necrosis. Understanding the mechanisms of cell death may have potential therapeutic implications in the treatment of cigarette smoking related retinal diseases such as age-related macular degeneration (AMD). (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Patil, A. Jayaprakash; Gramajo, Ana L.; Sharma, Ashish; Kuppermann, Baruch D.; Kenney, M. Cristina] Univ Calif Irvine, Med Ctr, Gavin S Herbert Eye Inst, Dept Ophthalmol, Orange, CA 92868 USA.
   [Gramajo, Ana L.] Ctr Privado Ojos Romagosa Fdn VER, Dept Oftalmol, Cordoba, Argentina.
   [Sharma, Ashish] Univ Miami, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA.
   [Seigel, Gail M.] SUNY Buffalo, Ross Eye Inst, Dept Ophthalmol Physiol & Biophys, Buffalo, NY 14260 USA.
C3 University of California System; University of California Irvine; Bascom
   Palmer Eye Institute; University of Miami; State University of New York
   (SUNY) System; State University of New York (SUNY) Buffalo
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Med Ctr, Gavin S Herbert Eye Inst, Dept Ophthalmol, 101 City Dr, Orange, CA 92868 USA.
EM jppatilaries@hotmail.com; mkenney@uci.edu
OI Sharma, Ashish/0000-0002-8550-9791
FU Pan-American Association of Ophthalmology Foundation; Discovery Eye
   Foundation; Iris and B. Gerald Cantor Foundation; Research to Prevent
   Blindness Foundation; The Ko Family Foundation; Gilbert Foundation
FX Supported by Pan-American Association of Ophthalmology Foundation (David
   & Julianna Pyott Pan-American Retinal Research Fellowship), Discovery
   Eye Foundation, Iris and B. Gerald Cantor Foundation, Research to
   Prevent Blindness Foundation,The Ko Family Foundation, Gilbert
   Foundation.
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NR 87
TC 24
Z9 24
U1 0
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD MAY 2
PY 2009
VL 259
IS 1-2
BP 69
EP 76
DI 10.1016/j.tox.2009.02.004
PG 8
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA 440WX
UT WOS:000265731500009
PM 19428945
DA 2022-11-30
ER

PT J
AU Bacolod, MD
   Schemmann, GS
   Wang, S
   Shattock, R
   Giardina, SF
   Zeng, ZS
   Shia, JR
   Stengel, RF
   Gerry, N
   Hoh, J
   Kirchhoff, T
   Gold, B
   Christman, MF
   Offit, K
   Gerald, WL
   Notterman, DA
   Ott, J
   Paty, PB
   Barany, F
AF Bacolod, Manny D.
   Schemmann, Gunter S.
   Wang, Shuang
   Shattock, Richard
   Giardina, Sarah F.
   Zeng, Zhaoshi
   Shia, Jinru
   Stengel, Robert F.
   Gerry, Norman
   Hoh, Josephine
   Kirchhoff, Tomas
   Gold, Bert
   Christman, Michael F.
   Offit, Kenneth
   Gerald, William L.
   Notterman, Daniel A.
   Ott, Jurg
   Paty, Philip B.
   Barany, Francis
TI The signatures of autozygosity among patients with colorectal cancer
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; UNIPARENTAL DISOMY; GENE-EXPRESSION; HAPLOTYPE
   MAP; COLON-CANCER; RISK; MUTATIONS; DISEASE; SUSCEPTIBILITY; FAMILIES
AB Previous studies have shown that among populations with a high rate of consanguinity, there is a significant increase in the prevalence of cancer. Single nucleotide polymorphism (SNP) array data (Affymetrix, 50K XbaI) analysis revealed long regions of homozygosity in genomic DNAs taken from tumor and matched normal tissues of colorectal cancer (CRC) patients. The presence of these regions in the genome may indicate levels of consanguinity in the individual's family lineage. We refer to these autozygous regions as identity-by-descent (IBD) segments. In this study, we compared IBD segments in 74 mostly Caucasian CRC patients (mean age of 66 years) to two control data sets: (a) 146 Caucasian individuals (mean age of 80 years) who participated in an age-related macular degeneration (AMD) study and (b) 118 cancer-free Caucasian individuals from the Framingham Heart Study (mean age of 67 years). Our results show that the percentage of CRC patients with IBD segments (>= 4 Mb length and 50 SNPs probed) in the genome is at least twice as high as the AMD or Framingham control groups. Also, the average length of these IBD regions in the CRC patients is more than twice the length of the two control data sets. Compared with control groups, IBD segments are found to be more common among individuals of Jewish background. We believe that these HID segments within CRC patients are likely to harbor important CRC-related genes with low-penetrance SNPs and/or mutations, and, indeed, two recently identified CRC predisposition SNPs in the 8q24 region were confirmed to be homozygous in one particular patient carrying an IBD segment covering the region.
C1 [Bacolod, Manny D.; Shattock, Richard; Giardina, Sarah F.; Barany, Francis] Cornell Univ, Weill Med Coll, Dept Microbiol, New York, NY 10021 USA.
   [Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA.
   [Zeng, Zhaoshi; Paty, Philip B.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA.
   [Shia, Jinru; Gerald, William L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Kirchhoff, Tomas; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA.
   [Schemmann, Gunter S.; Stengel, Robert F.] Princeton Univ, Sch Engn & Appl Sci, Princeton, NJ 08544 USA.
   [Notterman, Daniel A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Gold, Bert] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
   [Gerry, Norman; Christman, Michael F.] Boston Univ, Dept Genet & Genom, Boston, MA 02215 USA.
   [Hoh, Josephine] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
C3 Cornell University; Columbia University; Memorial Sloan Kettering Cancer
   Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering
   Cancer Center; Rockefeller University; Princeton University; Princeton
   University; National Institutes of Health (NIH) - USA; NIH National
   Cancer Institute (NCI); Boston University; Yale University
RP Barany, F (通讯作者)，Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
EM barany@med.cornell.edu
OI Shia, Jinru/0000-0002-4351-2511; Kirchhoff, Tomas/0000-0002-9055-2364;
   Giardina, Sarah/0000-0002-8879-9384; Bacolod, Manny/0000-0002-2085-4877
FU EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN
   DEVELOPMENT [P2CHD047879] Funding Source: NIH RePORTER; NATIONAL CANCER
   INSTITUTE [P01CA065930] Funding Source: NIH RePORTER; NCI NIH HHS
   [P01-CA65930, P01 CA065930] Funding Source: Medline
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NR 50
TC 42
Z9 43
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2008
VL 68
IS 8
BP 2610
EP 2621
DI 10.1158/0008-5472.CAN-07-5250
PG 12
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 290CM
UT WOS:000255100500011
PM 18375840
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Pegaz, B
   Debefve, E
   Borle, F
   Ballini, JP
   van den Bergh, H
   Kouakou-Konan, YN
AF Pegaz, B
   Debefve, E
   Borle, F
   Ballini, JP
   van den Bergh, H
   Kouakou-Konan, YN
TI Encapsulation of porphyrins and chlorins in biodegradable nanoparticles:
   The effect of dye lipophilicity on the extravasation and the
   photothrombic activity. A comparative study
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE photodynamic therapy; nanoparticles; photosensitizer; lipophilicity;
   extravasation; chick embryo; porphyrins; chlorins; verteporfin; CAM
   model
ID PHOTODYNAMIC THERAPY; CHOROIDAL NEOVASCULARIZATION; MACULAR
   DEGENERATION; VERTEPORFIN; PARAMETERS; MECHANISMS; DELIVERY; STERILE
AB In the present work, we performed a preclinical inter-comparison study using several photosensitizers with the goal of optimizing photodynamic therapy (PDT) for the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration. The tested molecules were the porphyrins meso-tetraphenylporphyrin (TPP) and meso-tetra-(4-carboxyphenyl)-porphyrin (TCPP), and the chlorins pheophorbide-a (Pheo-a) and chlorin e(6) (Ce-6). Each of these molecules was entrapped in biodegradable nanoparticles (NP) based on poly(D,L-lactic acid). The influence of the degree of lipophilicity on the incorporation efficiency of the drug in the NPs, and on the dye leakage from blood vessels as well as on the photothrombic efficiency was investigated using the chick chorioallantoic membrane (CAM) as in vivo model. NP characterization showed that the dye was more effectively entrapped in the polymeric matrix when its degree of lipophilicity increased. While less lipophilic compounds (TCPP, Ce6) extravasate rather easily, the more lipophilic dyes (TPP, Pheo-a) tend to remain inside the blood vessels. After injection of a drug dose of 1 mg/kg body weight and a drug-light application interval of 1 min, irradiation with light doses ranging from 5 to 20 J/cm(2) led to the highest photothrombic efficiency when using the NPs loaded with the most lipophilic molecule (TPP). The latter induced vascular damage, which was significantly higher than that observed with the other molecules tested. Thus, in addition to minimal leakage from blood vessels, the TPP in NP formulation exhibited photothrombic efficiency similar to Visudyne (R) which was also tested in the CAM model. (c) 2005 Elsevier B.V. All rights reserved.
C1 Ecole Polytech Fed Lausanne, EPFL ENAC LPAS, CH-1015 Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique
   Federale de Lausanne
RP van den Bergh, H (通讯作者)，Ecole Polytech Fed Lausanne, EPFL ENAC LPAS, Stn 6, CH-1015 Lausanne, Switzerland.
EM hubert.vandenbergh@epfl.ch
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NR 26
TC 45
Z9 48
U1 0
U2 33
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 1
PY 2005
VL 80
IS 1
BP 19
EP 27
DI 10.1016/j.jphotobiol.2005.02.003
PG 9
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 941MW
UT WOS:000230219900003
PM 15963434
DA 2022-11-30
ER

PT J
AU Chen, L
   Wu, W
   Dentchev, T
   Zeng, Y
   Wang, JH
   Tsui, I
   Tobias, JW
   Bennett, J
   Baldwin, D
   Dunaief, JL
AF Chen, L
   Wu, W
   Dentchev, T
   Zeng, Y
   Wang, JH
   Tsui, I
   Tobias, JW
   Bennett, J
   Baldwin, D
   Dunaief, JL
TI Light damage induced changes in mouse retinal gene expression
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE photooxidation; antioxidants; age-related macular degeneration; retina;
   gene expression; apoptosis
ID PHOTORECEPTOR CELL-DEATH; PIGMENT EPITHELIAL-CELLS; PHOTIC INJURY;
   INDUCED APOPTOSIS; MACULAR DEGENERATION; MICROARRAY ANALYSIS; CHLORIDE
   CHANNEL; ALBINO-RATS; METALLOTHIONEIN; PROTEINS
AB Oxidative stress plays a role in the light damage model of retinal degeneration as well as in age-related macular degeneration. The purpose of this study is to identify retinal genes induced by acute photo-oxidative stress, which may function as mediators of apoptosis or as survival factors. To accomplish this, Balb/c mice were exposed to bright cool white fluorescent light for 7 hr. Retinas were then isolated for total RNA preparation followed by Affymetrix DNA microarray analysis to compare gene expression in light damaged mice to unexposed controls. Three independent light damage experiments were carried out and statistical filters were applied to detect genes with expression changes averaging at least two-fold. Quantitative PCR was carried out to confirm altered gene expression. Seventy genes were upregulated at least two-fold immediately following light damage. QPCR confirmed upregulation of all 10 genes tested. The upregulated genes fall into several categories including antioxidants: ceruloplasmin, metallothionein, and heme oxygenase; antiapoptotic gene: bag3, chloride channels: clic1 and clic4; transcription factors: c-fos, fra1, junB, stall, krox-24 and c/ebp; secreted signaling molecules: chitinase 3-like protein I and osteopontin; inflammation related genes: MCP-1 and ICAM1 and others. Upregulation of five interferon-gamma responsive genes suggests elevated interferon levels after light damage. Upregulation of three components of the AP-1 transcription factor is consistent with previous evidence implicating AP-1 in light damage pathogenesis. Four copper or iron binding proteins were upregulated, suggesting that photo-oxidative stress may affect metal homeostasis. The genes found upregulated by light damage may affect the survival of photoreceptors subjected to photo-oxidative stress. (C) 2004 Elsevier Ltd. All rights reserved.
C1 Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   Univ Penn, Penn Microarray Facil, Philadelphia, PA 19104 USA.
   Univ Penn, Biomed Informat Facil, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; University of Pennsylvania
RP Dunaief, JL (通讯作者)，Univ Penn, Stellar Chance Labs 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768
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NR 47
TC 129
Z9 133
U1 2
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2004
VL 79
IS 2
BP 239
EP 247
DI 10.1016/j.exer.2004.05.002
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 845CG
UT WOS:000223212700011
PM 15325571
DA 2022-11-30
ER

PT J
AU Montesel, A
   Gigon, A
   Mosinska, A
   Apostolopoulos, S
   Ciller, C
   De Zanet, S
   Mantel, I
AF Montesel, Andrea
   Gigon, Anthony
   Mosinska, Agata
   Apostolopoulos, Stefanos
   Ciller, Carlos
   De Zanet, Sandro
   Mantel, Irmela
TI Automated foveal location detection on spectral-domain optical coherence
   tomography in geographic atrophy patients
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Foveal location; Algorithm; Optical coherence tomography; Age-related
   macular degeneration; Geographic atrophy
ID MACULAR THICKNESS MEASUREMENTS; RETINAL LAYERS; SCANNING DENSITY;
   VISUAL-ACUITY; EYES; SEGMENTATION; DEGENERATION; IMPACT
AB Purpose To develop a fully automated algorithm for accurate detection of fovea location in atrophic age-related macular degeneration (AMD), based on spectral-domain optical coherence tomography (SD-OCT) scans.
   Methods Image processing was conducted on a cohort of patients affected by geographic atrophy (GA). SD-OCT images (cube volume) from 55 eyes (51 patients) were extracted and processed with a layer segmentation algorithm to segment Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL). Their en face thickness projection was convolved with a 2D Gaussian filter to find the global maximum, which corresponded to the detected fovea. The detection accuracy was evaluated by computing the distance between manual annotation and predicted location.
   Results The mean total location error was 0.101 +/- 0.145mm; the mean error in horizontal and vertical en face axes was 0.064 +/- 0.140mm and 0.063 +/- 0.060mm, respectively. The mean error for foveal and extrafoveal retinal pigment epithelium and outer retinal atrophy (RORA) was 0.096 +/- 0.070mm and 0.107 +/- 0.212mm, respectively. Our method obtained a significantly smaller error than the fovea localization algorithm inbuilt in the OCT device (0.313+0.283mm, p <.001) or a method based on the thinnest central retinal thickness (0.843 +/- 1.221, p <.001). Significant outliers are depicted with the reliability score of the method.
   Conclusion Despite retinal anatomical alterations related to GA, the presented algorithm was able to detect the foveal location on SD-OCT cubes with high reliability. Such an algorithm could be useful for studying structural-functional correlations in atrophic AMD and could have further applications in different retinal pathologies.
C1 [Montesel, Andrea; Gigon, Anthony; Mantel, Irmela] Univ Lausanne, Jules Gonin Eye Hosp, Fdn Asile des Aveugles, Dept Ophthalmol, 15 Ave France,CP 5143, CH-1004 Lausanne, Switzerland.
   [Mosinska, Agata; Apostolopoulos, Stefanos; Ciller, Carlos; De Zanet, Sandro] RetinAI Med AG, Bern, Switzerland.
C3 University of Lausanne
RP Mantel, I (通讯作者)，Univ Lausanne, Jules Gonin Eye Hosp, Fdn Asile des Aveugles, Dept Ophthalmol, 15 Ave France,CP 5143, CH-1004 Lausanne, Switzerland.
EM irmela.mantel@fa2.ch
FU University of Lausanne
FX Open access funding provided by University of Lausanne.
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NR 27
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2022
VL 260
IS 7
BP 2261
EP 2270
DI 10.1007/s00417-021-05520-6
EA JAN 2022
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2H0GI
UT WOS:000744375400001
PM 35044505
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Sultan, F
   Parkin, ET
AF Sultan, Fatima
   Parkin, Edward T.
TI The Amyloid Precursor Protein Plays Differential Roles in the UVA
   Resistance and Proliferation of Human Retinal Pigment Epithelial Cells
SO PROTEIN AND PEPTIDE LETTERS
LA English
DT Article
DE Amyloid precursor protein; ultraviolet; resistance; proliferation;
   retinal; pigment; epithelial
ID MACULAR DEGENERATION; ULTRAVIOLET-RADIATION; SECRETED FORMS;
   BETA-PEPTIDE; DRUSEN; APP; ACTIVATION; EXPOSURE; NEURONS; DAMAGE
AB Background: Age-related macular degeneration (AMD) can be characterised by degeneration of retinal pigment epithelial (RPE) cells and the accumulation, in retinal drusen deposits, of amyloid beta-peptides proteolytically derived, by secretases, from the amyloid precursor protein (APP). Ultraviolet (UV) light exposure is a risk factor for the development of AMD. Objectives: In the current study, we investigated whether APP and/or its proteolysis are linked to the UVA resistance or proliferation of ARPE-19 human RPE cells. Methods: Cell viability was determined, following UVA exposure, with prior small interfering RNA-mediated APP depletion or secretase inhibitor treatments. APP levels/proteolysis were analysed by immunoblotting. Cells were also grown in the presence/absence of secretase inhibitors to assess their effects on longer-term culture growth. Finally, the effects of APP proteolytic fragments on ARPE-19 cell proliferation were monitored following co-culture with human embryonic kidney cells stably over-expressing these fragments. Results: Endogenous APP was depleted following UVA irradiation and beta-secretase, but not alpha-secretase, the processing of the protein was reduced. Experimental APP depletion or gamma-secretase (but not alpha- or beta-secretase) inhibition ablated the detrimental effect of UVA on cell viability. In contrast, alpha-secretase, and possibly gamma-secretase but not beta-secretase activity, appeared to promote the longer-term proliferation of ARPE-19 cells in the absence of UVA irradiation. Conclusion: There are clear but differential links between APP expression/proteolysis and the proliferation and UVA resistance of ARPE-19 cells indicating that the protein should be investigated further in relation to the identification of possible drug targets for the treatment of AMD.
C1 [Sultan, Fatima; Parkin, Edward T.] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England.
C3 Lancaster University
RP Parkin, ET (通讯作者)，Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England.
EM e.parkin@lancaster.ac.uk
OI Parkin, Edward/0000-0003-3270-3184
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NR 52
TC 0
Z9 0
U1 3
U2 3
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8665
EI 1875-5305
J9 PROTEIN PEPTIDE LETT
JI Protein Pept. Lett.
PY 2022
VL 29
IS 4
BP 313
EP 327
DI 10.2174/0929866529666220217124152
PG 15
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 2W3MQ
UT WOS:000824432500005
PM 35176974
DA 2022-11-30
ER

PT J
AU Magonio, F
AF Magonio, Fabrizio
TI REM phase: An ingenious mechanism to enhance clearance of metabolic
   waste from the retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE REM phase; Glymphatic system; Astrocytes; Muller cells; Retina; Vitreous
   humor; Age-related macular degeneration; glaucoma
ID GLYMPHATIC SYSTEM; SLEEP; FLUID; EYE
AB The Rapid Eye Movement (REM) phase of sleep, also known as "active sleep" because of physiological similarities to waking state, is characterized by intense cerebral electrical activity, propensity to dream vividly and suppression of skeletal muscle activity (atonia) except for the extraocular muscles which give rise to the so-called REM. In 1998 David Maurice, an ophthalmologist, proposed that REM sleep was associated with an eye function: it would be required to stir the anterior chamber and bath it with aqueous humor to prevent corneal anoxia during sleep. However, potential metabolic problems could arise in the outer retinal layers which lack a direct blood supply. New research lends support to the hypothesis that a para-vascular transport system, the so-called "glymphatic", is present in the eye analogous to the one recently discovered in the brain. It is a functional waste clearance pathway which promotes elimination of interstitial solutes from the brain along para-vascular channels. Glymphatic function increases during sleep and just as a "brain pump" moves fluids in the central nervous system, a "vitreous pump" moves them into the eyeballs during REM phase. A number of similarities between Alzheimer's disease and several retinal degenerations have been described, particularly with respect to either age-related macular degeneration and chronic open-angle glaucoma. Impairment of this mechanism in some disease states and in the normal aging process could have serious consequences for visual function. In this manuscript I propose a new hypothesis regarding the role of REM phase on physio-pathology of the human eye: it would be an ingenious mechanism to enhanced clearance of metabolic waste from the retina.
C1 [Magonio, Fabrizio] Igea Private Hosp, Dept Ophthalmol, Via Marcona 69, I-20129 Milan, Italy.
RP Magonio, F (通讯作者)，Igea Private Hosp, Dept Ophthalmol, Via Marcona 69, I-20129 Milan, Italy.
EM fabrizio.magonio@alice.it
OI , fabrizio/0000-0002-6126-8436
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NR 31
TC 0
Z9 0
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2022
VL 214
AR 108860
DI 10.1016/j.exer.2021.108860
EA DEC 2021
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XW2LY
UT WOS:000735458600002
PM 34843744
DA 2022-11-30
ER

PT J
AU Gallagher, D
   Kalra, G
   Rasheed, MA
   Vupparaboina, KK
   Singh, SR
   Chhablani, J
AF Gallagher, Denise
   Kalra, Gagan
   Rasheed, Mohammed Abdul
   Vupparaboina, Kiran Kumar
   Singh, Sumit Randhir
   Chhablani, Jay
TI Long-term retinal changes in progressive geographic atrophy
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Retinal thickness assessment; geographic atrophy; long-term retinal
   thickness changes; progressive retinal atrophy
ID NERVE-FIBER LAYER; MACULAR DEGENERATION; FUNDUS AUTOFLUORESCENCE; AGE;
   THICKNESS
AB Background: Age-related macular degeneration (AMD) is one of the leading causes of blindness with loss of retinal layers over long term. We aim to evaluate these changes in eyes with progressive non-exudative AMD with geographic atrophy (GA). Methods: This retrospective study included patients with GA with a minimum of 4 years follow up. Retinal layers on spectral domain optical coherence tomography (SD-OCT) were segmented based on their reflectivity patterns using validated semi-automated segmentation algorithm. The thickness of the segmented retinal layers was measured. Horizontal length of GA at baseline and last follow-up were also measured. Regression analysis was performed to correlate changes in RPE layer thickness with other retinal layers and the length of GA on OCT. Results: A total of 351-line scans including 17 foveal scans showing presence of GA at final visit that is, a total of 2457 retinal layer bands were analyzed. Outer nuclear layer (ONL) (p = 0.02), outer segment layers (OSL) (p = 0.01), and retinal pigment epithelium (RPE) (p = 0.01) showed a statistically significant variation between baseline and final visit. Regression analysis showed the change in ONL (r = 0.72; p = 0.01) and OSL (r = 0.93, p < 0.01) correlated significantly with change in RPE thickness whereas rest of the layers failed to show significant correlation. Conclusion: Outer retinal layers (ONL and OSL) show more significant and widespread changes in retinal thickness and correlated most significantly with RPE thickness changes in eyes with GA due to AMD. Assessment of various retinal layer bands can be used as surrogate quantitative parameters to study eyes with GA.
C1 [Gallagher, Denise; Vupparaboina, Kiran Kumar; Chhablani, Jay] Univ Pittsburgh, UPMC Eye Ctr, 203 Lothrop St, Pittsburgh, PA 15213 USA.
   [Kalra, Gagan] Govt Med Coll & Hosp, Dept Ophthalmol, Chandigarh, India.
   [Rasheed, Mohammed Abdul] Univ Waterloo, Sch Optometry & Vis Sci, Waterloo, ON, Canada.
   [Singh, Sumit Randhir] Univ Calif San Diego, Shiley Eye Inst, Jacobs Retina Ctr, La Jolla, CA 92093 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; University of Waterloo; University of California System;
   University of California San Diego
RP Chhablani, J (通讯作者)，Univ Pittsburgh, UPMC Eye Ctr, 203 Lothrop St, Pittsburgh, PA 15213 USA.
EM jay.chhablani@gmail.com
RI Kalra, Gagan/AAV-3465-2020
OI Kalra, Gagan/0000-0002-3367-3047
CR Chen L, 2020, RETINA-J RET VIT DIS, V40, P618, DOI 10.1097/IAE.0000000000002657
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NR 26
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD MAY
PY 2022
VL 32
IS 3
BP 1687
EP 1693
AR 11206721211035636
DI 10.1177/11206721211035636
EA JUL 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1G7SZ
UT WOS:000678262200001
PM 34308667
DA 2022-11-30
ER

PT J
AU Potapenko, I
   Kristensen, M
   Thiesson, B
   Ilginis, T
   Sorensen, TL
   Hajari, JN
   Fuchs, J
   Hamann, S
   la Cour, M
AF Potapenko, Ivan
   Kristensen, Mads
   Thiesson, Bo
   Ilginis, Tomas
   Lykke Sorensen, Torben
   Nouri Hajari, Javad
   Fuchs, Josefine
   Hamann, Steffen
   la Cour, Morten
TI Detection of oedema on optical coherence tomography images using deep
   learning model trained on noisy clinical data
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age related macular degeneration; deep learning; inter&#8208; grader
   agreement; retinal oedema; training label noise
ID QUANTIFICATION; FLUID
AB Purpose To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling.
   Methods A total of 50 439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema.
   Results Moderate inter-grader agreement on presence of oedema in the relabelled data was found (76.4%). Despite different training and validation labels, the CNN performed on par with inter-grader agreement in detecting oedema on OCT images (AUC 0.97, accuracy 90.9%) and previously published models based on relabelled datasets.
   Conclusion The level of performance shown by the current model might make it valuable in detecting disease activity in automated AMD patient follow-up systems. Our approach demonstrates that high accuracy is not necessarily constrained by incongruent training and validation labels. These results might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.
C1 [Potapenko, Ivan; Ilginis, Tomas; Nouri Hajari, Javad; Fuchs, Josefine; Hamann, Steffen; la Cour, Morten] Rigshosp, Dept Ophthalmol, Copenhagen, Denmark.
   [Potapenko, Ivan; Lykke Sorensen, Torben; Hamann, Steffen; la Cour, Morten] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Kristensen, Mads; Thiesson, Bo] Enversion AS, Aarhus, Denmark.
   [Thiesson, Bo] Aarhus Univ, Dept Engn, Aarhus, Denmark.
   [Lykke Sorensen, Torben] Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.
C3 Rigshospitalet; University of Copenhagen; University of Copenhagen;
   Aarhus University
RP Potapenko, I (通讯作者)，Rigshosp, Dept Ophthalmol, Copenhagen, Denmark.; Potapenko, I (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
EM ivan.olegovich.potapenko@regionh.dk
RI Hamann, Steffen/E-2090-2013
OI Hamann, Steffen/0000-0003-4318-2716; Potapenko,
   Ivan/0000-0002-7201-655X; Dornonville de la Cour,
   Morten/0000-0002-7712-9772
CR Adhi M, 2013, CURR OPIN OPHTHALMOL, V24, P213, DOI 10.1097/ICU.0b013e32835f8bf8
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NR 26
TC 2
Z9 2
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD FEB
PY 2022
VL 100
IS 1
BP 103
EP 110
DI 10.1111/aos.14895
EA MAY 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YD6LB
UT WOS:000650618200001
PM 33991170
DA 2022-11-30
ER

PT J
AU Jain, N
   Li, AL
   Yu, YX
   VanderBeek, BL
AF Jain, Nieraj
   Li, Alexa L.
   Yu, Yinxi
   VanderBeek, Brian L.
TI Association of macular disease with long-term use of pentosan
   polysulfate sodium: findings from a US cohort
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE macula; drugs
AB Background/Aims
   A series at a single clinical centre recently demonstrated an association between the interstitial cystitis drug pentosan polysulfate sodium (PPS) and a vision-threatening pigmentary maculopathy. The aim of this study was to determine if an association exists between PPS use and macular disease in a large national cohort.
   Methods
   A retrospective, matched cohort study using data from a large US medical claims database from 2002 to 2016 was performed. A total of 3012 and 1604 PPS users were compared with 15 060 and 8017 matched controls at 5 and 7 years, respectively. The primary outcome measures included (1) any new diagnosis of a hereditary or secondary pigmentary maculopathy (atypical maculopathy outcome), and (2) any new diagnosis of dry age-related macular degeneration (AMD) or drusen in addition to the aforementioned diagnoses (atypical maculopathy+AMD outcome).
   Results
   At the 5-year and 7-year follow-up, 9 (0.3%) and 10 (0.6%) PPS patients progressed to the atypical maculopathy outcome compared with 32 (0.2%) and 25 (0.3%) control patients, respectively. 103 (3.4%) and 87 (5.4%) PPS patients developed the atypical maculopathy+AMD outcome compared with 440 (2.9%) and 328 (4.1%) control patients at 5 and 7 years, respectively. At 5 years, multivariate analysis showed no significant association (p>0.13). At 7 years, PPS users had significantly increased odds of having the atypical maculopathy+AMD outcome (OR=1.41, 95% CI 1.09 to 1.83, p=0.009).
   Conclusions
   PPS exposure was associated with a new diagnosis of macular disease at the 7-year follow-up in a large national cohort.
C1 [Jain, Nieraj; Li, Alexa L.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
   [Yu, Yinxi] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [VanderBeek, Brian L.] Univ Penn, Scheie Eye Inst, Ophthalmol, Philadelphia, PA 19104 USA.
C3 Emory University; University of Pennsylvania; Pennsylvania Medicine;
   University of Pennsylvania; Pennsylvania Medicine
RP Jain, N (通讯作者)，Emory Eye Ctr, Ophthalmol, Atlanta, GA 30322 USA.
EM nieraj.jain@emory.edu
OI Li, Alexa/0000-0002-5235-6741
FU Foundation Fighting Blindness [CD-C-0918-0748-EEC]; NIH [P30 EY006360];
   National Institutes of Health [1K23EY025729-01]; University of
   Pennsylvania Core Grant for Vision Research [2P30EY001583]; Research to
   Prevent Blindness; Paul and Evanina Mackall Foundation
FX Foundation Fighting Blindness (CD-C-0918-0748-EEC) (NJ); NIH Core Grant
   P30 EY006360 (Emory Eye Center); National Institutes of Health K23 Award
   (1K23EY025729-01) (BLVB) and University of Pennsylvania Core Grant for
   Vision Research (2P30EY001583) (BLVB, YY). The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the National Institutes of Health. Additional funding
   was provided by Research to Prevent Blindness and the Paul and Evanina
   Mackall Foundation. Funding from each of the above sources was received
   in the form of block research grants to the Scheie Eye Institute. The
   sponsors or funding organisations had no role in the design or conduct
   of this research.
CR American Urological Association, 2014, DIAGN TREATM INT CYS
   Drugs.com, ELM PRIC COUP PAT AS
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NR 14
TC 35
Z9 35
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 AUG
PY 2020
VL 104
IS 8
BP 1093
EP 1097
DI 10.1136/bjophthalmol-2019-314765
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PK2OA
UT WOS:000602289600012
PM 31694837
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bammidi, S
   Bali, P
   Kalra, J
   Anand, A
AF Bammidi, Sridhar
   Bali, Parul
   Kalra, Jaswinder
   Anand, Akshay
TI Transplantation Efficacy of Human Ciliary Epithelium Cells from Fetal
   Eye and Lin-ve Stem Cells from Umbilical Cord Blood in the Murine
   Retinal Degeneration Model of Laser Injury
SO CELL TRANSPLANTATION
LA English
DT Article
DE subretinal; laser injury; lineage negative stem cells; ciliary
   epithelium cells; umbilical cord blood; retinal degeneration
AB A number of degenerative conditions affecting the neural retina including age-related macular degeneration have no successful treatment, resulting in partial or complete vision loss. There are a number of stem cell replacement strategies for recovery of retinal damage using cells from variable sources. However, literature is still deficit in the comparison of efficacy of types of stem cells. The purpose of the study was to compare the therapeutic efficacy of undifferentiated cells, i.e., lineage negative stem cells (Lin-ve SC) with differentiated neurosphere derived from ciliary epithelium (CE) cells on retinal markers associated with laser-induced retinal injury. Laser-induced photocoagulation was carried out to disrupt Bruch's membrane and retinal pigmented epithelium in C57BL/6 mouse model. Lineage negative cells were isolated from human umbilical cord blood, whereas neurospheres were derived from CE of post-aborted human eyeballs. The cells were then transplanted into subretinal space to study their effect on injury. Markers of neurotropic factors, retina, apoptosis, and proliferation were analyzed after injury and transplantation. mRNA expression was also analyzed by real-time polymerase chain reaction at 1 week, and 3-month immunohistochemistry was evaluated at 1-week time point. CE cell transplantation showed enhanced differentiation of rods and retinal glial cells. However, Lin-ve cells exerted paracrine-dependent modulation of neurotrophic factors, which is possibly mediated by antiapoptotic and proliferative effects. In conclusion, CE transplantation showed superior regenerative outcome in comparison to Lin-ve SC for rescue of artificially injured rodent retinal cells. It is imperative that this source for transplantation may be extensively studied in various doses and additional retinal degeneration models for prospective clinical applications.
C1 [Bammidi, Sridhar; Bali, Parul; Anand, Akshay] Post Grad Inst Med Educ & Res, Neurosci Res Lab, Dept Neurol, Chandigarh 160012, India.
   [Bali, Parul] Post Grad Inst Med Educ & Res, Dept Biophys, Chandigarh, India.
   [Kalra, Jaswinder] Post Grad Inst Med Educ & Res, Dept Obstet & Gynaecol, Chandigarh, India.
C3 Post Graduate Institute of Medical Education & Research (PGIMER),
   Chandigarh; Post Graduate Institute of Medical Education & Research
   (PGIMER), Chandigarh; Post Graduate Institute of Medical Education &
   Research (PGIMER), Chandigarh
RP Anand, A (通讯作者)，Post Grad Inst Med Educ & Res, Neurosci Res Lab, Dept Neurol, Chandigarh 160012, India.
EM akshay1anand@rediffmail.com
OI Anand, Akshay/0000-0001-9003-3532
FU Department of Science and Technology, Science and Engineering Research
   Board, India [EMR/2016/000190]; Department of Biotechnology, India
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: Funding
   was obtained from Department of Science and Technology, Science and
   Engineering Research Board, India (EMR/2016/000190) and Department of
   Biotechnology, India.
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NR 40
TC 4
Z9 4
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-6897
EI 1555-3892
J9 CELL TRANSPLANT
JI Cell Transplant.
PD JAN-DEC
PY 2020
VL 29
AR 0963689720946031
DI 10.1177/0963689720946031
PG 12
WC Cell & Tissue Engineering; Medicine, Research & Experimental;
   Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine; Transplantation
GA PQ5KJ
UT WOS:000606584100052
PM 33023312
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Yeung, AWK
   Abdel-Daim, MM
   Abushouk, AI
   Kadonosono, K
AF Yeung, Andy Wai Kan
   Abdel-Daim, Mohamed M.
   Abushouk, Abdelrahman Ibrahim
   Kadonosono, Kazuaki
TI A literature analysis on anti-vascular endothelial growth factor therapy
   (anti-VEGF) using a bibliometric approach
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Review
DE Anti-VEGF; Bibliometric; Cancer; Macular edema; Web of Science
ID MACULAR DEGENERATION; CLINICAL-TRIALS; BEVACIZUMAB; ANGIOGENESIS;
   RANIBIZUMAB; CANCER; EXPRESSION; EFFICACY; HYPOXIA; CELLS
AB We performed the current study to assess the citation performance of research works on anti-vascular endothelial growth factor (anti-VEGF) therapy. We searched Web of Science (WoS) to identify relevant publications and analyze them with reference to their publication year, journal title, citation count, WoS category, and article type. The bibliometric software (VOSviewer) was used for citation analyses of countries and journals and to generate a term map that visualizes the recurring terms appearing in the titles and abstracts of published articles. The literature search resulted in 7364 articles, with a mean citation count of 26.2. Over half of them (50.2%) were published during the past 5years. Original articles constituted the majority (67.8%). The publications were mainly classified into WoS categories of ophthalmology (43.2%) and oncology (20.6%). The most prolific ophthalmology and cancer journals were Investigative Ophthalmology & Visual Science (7.3%) and Cancer Research (1.4%), respectively. The correlation between journal impact factor and citation count was weak to moderate (for journals with impact factor up to 5 and 10, respectively), and open-access articles had significantly more citations than non-open-access articles (p<0.001). The frequently targeted tumors by anti-VEGF therapy included metastatic colorectal cancer (196; 49.2 citations per article (CPA)), breast cancers (167; 37.2 CPA), and renal cell carcinoma (122; 38.2 CPA). The frequently targeted eye pathologies were age-related macular degeneration (828; 18.2 CPA), diabetic macular edema (466; 10.8 CPA), and diabetic retinopathy (358; 31.9 CPA). These results indicate that anti-VEGF therapy has a wide range of applications and its publications are highly cited.
C1 [Yeung, Andy Wai Kan] Univ Hong Kong, Fac Dent, Appl Oral Sci, Oral & Maxillofacial Radiol, Hong Kong, Peoples R China.
   [Abdel-Daim, Mohamed M.] Suez Canal Univ, Pharmacol Dept, Fac Vet Med, Ismailia 41522, Egypt.
   [Abdel-Daim, Mohamed M.; Kadonosono, Kazuaki] Yokohama City Univ, Dept Ophthalmol & Microtechnol, Yokohama, Kanagawa, Japan.
   [Abushouk, Abdelrahman Ibrahim] Ain Shams Univ, Fac Med, Cairo, Egypt.
C3 University of Hong Kong; Egyptian Knowledge Bank (EKB); Suez Canal
   University; Yokohama City University; Egyptian Knowledge Bank (EKB); Ain
   Shams University
RP Yeung, AWK (通讯作者)，Univ Hong Kong, Fac Dent, Appl Oral Sci, Oral & Maxillofacial Radiol, Hong Kong, Peoples R China.; Abdel-Daim, MM (通讯作者)，Suez Canal Univ, Pharmacol Dept, Fac Vet Med, Ismailia 41522, Egypt.; Abdel-Daim, MM (通讯作者)，Yokohama City Univ, Dept Ophthalmol & Microtechnol, Yokohama, Kanagawa, Japan.
EM Ndyeung@hku.hk; Abdeldaim.m@vet.suez.edu.eg
RI Abdel-Daim, Mohamed M./B-2545-2013; Yeung, Andy Wai Kan/M-4332-2019;
   Abushouk, Abdelrahman Ibrahim/I-9229-2018
OI Abdel-Daim, Mohamed M./0000-0002-4341-2713; Yeung, Andy Wai
   Kan/0000-0003-3672-357X; Abushouk, Abdelrahman
   Ibrahim/0000-0003-1399-6487
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NR 44
TC 10
Z9 10
U1 2
U2 30
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD APR
PY 2019
VL 392
IS 4
BP 393
EP 403
DI 10.1007/s00210-019-01629-y
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HO8LE
UT WOS:000461201900001
PM 30826857
DA 2022-11-30
ER

PT J
AU Schlanitz, F
   Baumann, B
   Sacu, S
   Baumann, L
   Pircher, M
   Hitzenberger, CK
   Schmidt-Erfurth, UM
AF Schlanitz, Ferdinand
   Baumann, Bernhard
   Sacu, Stefan
   Baumann, Lukas
   Pircher, Michael
   Hitzenberger, Christoph K.
   Schmidt-Erfurth, Ursula Margarethe
TI Impact of drusen and drusenoid retinal pigment epithelium elevation size
   and structure on the integrity of the retinal pigment epithelium layer
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE imaging; retina; macula
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; PROGRESSION; EYE
AB Purpose To evaluate the impact of drusen size and structure on retinal pigment epithelium (RPE) and photoreceptor layers in eyes with early to intermediate age-related macular degeneration (AMD) using polarisation-sensitive optical coherence tomography (OCT). Design Retrospective investigation of an observational cross-sectional study. Participants Patients with early to intermediate AMD. Methods Twenty-five eyes of 25 patients with drusen were imaged with polarisation-sensitive OCT using macular volume scans. Each scan was manually graded for six distinct drusen characteristics and the integrity of both the overlying RPE and photoreceptor layer. The central scan of each single druse, as well as its diameter and location, were selected for statistical calculations. Results A total number of 5933 individual drusen including their adjacent RPE and photoreceptor layer were evaluated. 41.3% of all drusen demonstrated an intact overlying RPE; in 28.1% the RPE layer was irregular, but continuous. In 30.6%, the RPE layer signal was discontinuous above the area of drusen. The level of RPE alteration was significantly related to shape (p<0.001), internal reflectivity (p<0.001) and homogeneity (p<0.001) of the drusen and their diameter, with a higher probability for larger drusen to have a discontinuous RPE (OR 3.2, p<0.001). The number of drusen showing overlying foci or an altered photoreceptor layer was too small to be conclusive, but showed a trend towards an altered RPE if present. Conclusions Polarisation-sensitive OCT reveals a correlation between specific drusen characteristics and the integrity of the overlying RPE layer. Drusen diameter and configuration were significantly associated with RPE loss.
C1 [Schlanitz, Ferdinand; Sacu, Stefan; Schmidt-Erfurth, Ursula Margarethe] Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
   [Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Baumann, Lukas] Med Univ Vienna, Sect Med Stat, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna
RP Schmidt-Erfurth, UM (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Baumann, Bernhard/0000-0001-6419-1932; Baumann,
   Lukas/0000-0001-7931-7470; Schmidt-Erfurth, Ursula/0000-0002-7788-7311
FU FWF, Austrian Science Fund, Vienna, Austria [P19624-B02]; European Union
   (FP7 HEALTH, FUN-OCT, Brussels, Belgium) [201880]; Canon (Tokyo, Japan);
   Herzfelder'sche Familienstiftung [AP0044120FF]
FX CKH has received support by an independent scientific grant (FWF grant
   P19624-B02, Austrian Science Fund, Vienna, Austria), the European Union
   (FP7 HEALTH programme grant 201880, FUN-OCT, Brussels, Belgium) and
   Canon (Tokyo, Japan). S-EU has received support from an independent
   scientific grant (Herzfelder'sche Familienstiftung, grant AP0044120FF).
   None of the grantors had any influence on reporting the study data and
   interpretation of the data. All other authors did not receive any
   government or non-governmental fundings.
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NR 24
TC 7
Z9 7
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 FEB
PY 2019
VL 103
IS 2
BP 227
EP 232
AR 061704
DI 10.1136/bjophthalmol-2017-311782
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HL8YJ
UT WOS:000459028400013
PM 29706603
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Krishna, BVS
   Gnanasekaran, T
AF Krishna, B. V. Santhosh
   Gnanasekaran, T.
TI Retinal Vessel Extraction Framework Using Modified Adaboost Extreme
   Learning Machine
SO CMC-COMPUTERS MATERIALS & CONTINUA
LA English
DT Article
DE Extreme learning machine; ophthalmology; segmentation; adaboost; feature
   extraction; supervised; contrast enhancement
ID BLOOD-VESSELS; SEGMENTATION; IMAGES; INFORMATION
AB An explicit extraction of the retinal vessel is a standout amongst the most significant errands in the field of medical imaging to analyze both the ophthalmological infections, for example, Glaucoma, Diabetic Retinopathy (DR), Retinopathy of Prematurity (ROP), Age-Related Macular Degeneration (AMD) as well as non retinal sickness such as stroke, hypertension and cardiovascular diseases. The state of the retinal vasculature is a significant indicative element in the field of ophthalmology. Retinal vessel extraction in fundus imaging is a difficult task because of varying size vessels, moderately low distinction, and presence of pathologies such as hemorrhages, microaneurysms etc. Manual vessel extraction is a challenging task due to the complicated nature of the retinal vessel structure, which also needs strong skill set and training. In this paper, a supervised technique for blood vessel extraction in retinal images using Modified Adaboost Extreme Learning Machine (MAD-ELM) is proposed. Firstly, the fundus image preprocessing is done for contrast enhancement and inhomogeneity correction. Then, a set of core features is extracted, and the best features are selected using "minimal Redundancy-maximum Relevance (mRmR)." Later, using MAD-ELM method vessels and non vessels are classified. DRIVE and DR-HAGIS datasets are used for the evaluation of the proposed method. The algorithm's performance is assessed based on accuracy, sensitivity and specificity. The proposed technique attains accuracy of 0.9619 on the DRIVE database and 0.9519 on DR-HAGIS database, which contains pathological images. Our results show that, in addition to healthy retinal images, the proposed method performs well in extracting blood vessels from pathological images and is therefore comparable with state of the art methods.
C1 [Krishna, B. V. Santhosh] Velammal Inst Technol, Dept Elect & Commun Engn, Chennai 601204, Tamil Nadu, India.
   [Gnanasekaran, T.] RMK Engn Coll, Dept Informat Technol, Chennai 601206, Tamil Nadu, India.
C3 R.M.K. Engineering College
RP Krishna, BVS (通讯作者)，Velammal Inst Technol, Dept Elect & Commun Engn, Chennai 601204, Tamil Nadu, India.
EM santhoshkrishna1987@gmail.com
RI Thangavel, Gnanasekaran/M-7750-2019; B V, santhosh krishna/X-3035-2019
OI Thangavel, Gnanasekaran/0000-0003-4005-6482; B V, santhosh
   krishna/0000-0002-1919-4031
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NR 26
TC 4
Z9 4
U1 0
U2 2
PU TECH SCIENCE PRESS
PI HENDERSON
PA 871 CORONADO CENTER DR, SUTE 200, HENDERSON, NV 89052 USA
SN 1546-2218
EI 1546-2226
J9 CMC-COMPUT MATER CON
JI CMC-Comput. Mat. Contin.
PY 2019
VL 60
IS 3
BP 855
EP 869
DI 10.32604/cmc.2019.07585
PG 15
WC Computer Science, Information Systems; Materials Science,
   Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Materials Science
GA KH2BX
UT WOS:000510452200001
OA gold
DA 2022-11-30
ER

PT J
AU Chalour, N
   Maoui, A
   Rat, P
   Massicot, F
   Dutot, M
   Faussat, AM
   Devevre, E
   Limb, A
   Warnet, JM
   Treton, J
   Dinet, V
   Mascarelli, F
AF Chalour, Naima
   Maoui, Agathe
   Rat, Patrice
   Massicot, France
   Dutot, Melody
   Faussat, Anne-Marie
   Devevre, Estelle
   Limb, Astrid
   Warnet, Jean-Michel
   Treton, Jacques
   Dinet, Virginie
   Mascarelli, Frederic
TI A beta PP-induced UPR Transcriptomic Signature of Glial Cells to
   Oxidative Stress as an Adaptive Mechanism to Preserve Cell Function and
   Survival
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
DE A beta PP; oxidative stress; glial cells; Alzheimer's disease; Age
   related macular degeneration; retina
ID AMYLOID PRECURSOR PROTEIN; ENDOPLASMIC-RETICULUM STRESS; PIGMENT
   EPITHELIAL-CELLS; RETINAL MULLER CELLS; MACULAR DEGENERATION;
   ALZHEIMERS-DISEASE; MOUSE MODEL; LIPID-PEROXIDATION; ARPE-19 CELLS; ER
   STRESS
AB Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2-nonenal (HNE). AMD has been named the AD in the eye. The Muller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration.
   Objectives: We investigated the effects of HNE in human MC.
   Results: HNE induced an increase of the reactive oxygen species associated with mitochondrial dysfunction and apoptosis. HNE induced endoplasmic reticulum (ER) stress (upregulation of GRP78/Bip, and the proapoptotic factor, CHOP). HNE also impaired expression of genes controlling potassium homeostasis (KCNJ10), glutamate detoxification (GS), and the visual cycle (RLBP1). MC adaptive response to HNE included upregulation of amyloid-beta protein precursor (A beta PP). To determine the role of A beta PP, we overexpressed A beta PP in MC. Overexpression of A beta PP induced strong antioxidant and anti-ER stress (PERK downregulation and GADD34 upregulation) responses accompanied by activation of the prosurvival branch of the unfolded protein response. It was also associated with upregulation of major genes involved in MC-controlled retinal homeostasis (KCNJ10, GS, and RLBP1) and protection against HNE-induced apoptosis. Therefore, A beta PP is an ER and oxidative stress responsive molecule, and is able to stimulate the transcription of major genes involved in MC functions impaired by HNE.
   Conclusion: Our study suggests that targeting oxidative and ER stress might be a potential therapeutic strategy against glia impairment in AMD and AD, in light of the common features between the two pathologies.
C1 [Chalour, Naima] Univ Sci & Technol Alger, Lab Neurochim LBPO, FSB USTHB, Algiers, Algeria.
   [Maoui, Agathe; Devevre, Estelle; Treton, Jacques; Dinet, Virginie; Mascarelli, Frederic] Univ Paris 05, Ctr Rech Cordeliers, UMRS1138, F-75006 Paris, France.
   [Maoui, Agathe; Treton, Jacques; Dinet, Virginie; Mascarelli, Frederic] INSERM, U1138, F-75006 Paris, France.
   [Maoui, Agathe; Treton, Jacques; Dinet, Virginie; Mascarelli, Frederic] Univ Paris 06, UMRS 872, F-75006 Paris, France.
   [Rat, Patrice; Massicot, France; Dutot, Melody; Warnet, Jean-Michel] Univ Paris 05, Sorbonne Paris Cite, Fac Pharm Paris, Toxicol Lab UMR CNRS 8638, F-75006 Paris, France.
   [Faussat, Anne-Marie] Inst Rech Sante, IFR65, F-75012 Paris, France.
   [Limb, Astrid] UCL, Inst Ophthalmol, London, England.
   [Limb, Astrid] Moorfields Eye Hosp, London, England.
C3 University Science & Technology Houari Boumediene; Institut National de
   la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; Institut
   National de la Sante et de la Recherche Medicale (Inserm); UDICE-French
   Research Universities; Universite Paris Cite; UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; UDICE-French
   Research Universities; Universite Paris Cite; University of London;
   University College London; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust
RP Chalour, N (通讯作者)，Univ Sci & Technol Alger, Lab Neurochim LBPO, FSB USTHB, Algiers, Algeria.; Mascarelli, F (通讯作者)，Univ Paris 05, Ctr Rech Cordeliers, UMRS1138, F-75006 Paris, France.
EM naima.chalour@gmail.com; frederic.mascarelli@inserm.fr
RI Dutot, Mélody/ABC-7648-2020; Mascarelli, Frederic/L-8916-2018; DUTOT,
   Mélody/A-1796-2017
OI Dutot, Mélody/0000-0003-0964-0664; DUTOT, Mélody/0000-0003-0964-0664
FU Ministere de la Recherche; Agence Nationale de la Recherche
FX Supported by the Ministere de la Recherche (Naima Chalour and Agathe
   Maoui) and the Agence Nationale de la Recherche (P. Rat, F. Massicot, M.
   Dutot, J-M. Warnet, V. Dinet and F. Mascarelli). We thank Drs. I.
   Jaadane and A. Torriglia (Centre de Recherche des Cordeliers, Paris,
   France) for critically reading the manuscript and for stimulating
   discussions.
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NR 70
TC 3
Z9 3
U1 2
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 1567-2050
EI 1875-5828
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PY 2018
VL 15
IS 7
BP 643
EP 654
DI 10.2174/1567205015666180119101832
PG 12
WC Clinical Neurology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA GG9NN
UT WOS:000433027900006
PM 29357794
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Spaniol, K
   Holtmann, C
   Schwinde, JH
   Deffaa, S
   Guthoff, R
   Geerling, G
AF Spaniol, Kristina
   Holtmann, Christoph
   Schwinde, Jan-Hendrik
   Deffaa, Sophia
   Guthoff, Rainer
   Geerling, Gerd
TI Descemet-membrane endothelial keratoplasty in patients with retinal
   comorbidity -a prospective cohort study
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Descemet-membrane endothelial keratoplasty; age-related macular
   degeneration; pars plana vitrectomy
ID PARS-PLANA VITRECTOMY; PENETRATING KERATOPLASTY; OUTCOMES; DYSTROPHY;
   VISION
AB AIM: To investigate indications, surgical challenges, and outcome of Descemet-membrane endothelial keratoplasty (DMEK) in patients with retinal comorbidities (RC).
   METHODS: In a prospective cohort study, 8 eyes of 8 DMEK -patients with known RC were compared to 38 eyes of 38 DMEK -patients without RC. The duration of surgery, the degree of difficulty graded by the surgeon, and the complications through DMEK -surgery were analyzed for each patient. The best-corrected visual acuity (BCVA), the endothelial cell count, the intraocular pressure, and the subjective satisfaction was evaluated after a 6-month follow-up. Data were compared applying the non -parametric Wilcoxon -, Chi -square - and Fisher's-exact-test with P <= 0.05 as level of significance.
   RESULTS: RC-patients had dry age-related macular degeneration (n=4) or history of pars-plana vitrectomy (n=4). The main indication for DMEK was pain due to bullous keratopathy for the RC-patients (n=7, 88%) and visual impairment due to Fuchs endothelial keratoplasty for the non-RC-patients (n=33, 87%). The BCVA increased for both groups (P=0.01, P<0.001) and all corneas cleared. For the RC -patients, the subjective satisfaction improved significantly (P=0.02). Oil-filling and missing support of the vitreous body complicated surgery in vitrectomized eyes.
   CONCLUSION: DMEK is a favorable technique to treat endothelial disorders even if patients suffer from a retinal comorbidity. By enhancing the corneal clarity, it enables retinal examination or intraocular surgery and increases the patients' satisfaction. However, in vitrectomized or silicone-oil filled eyes, the duration of surgery and degree of complexity are increased. An experienced surgeon should perform DMEK in these patients.
C1 [Spaniol, Kristina; Holtmann, Christoph; Schwinde, Jan-Hendrik; Deffaa, Sophia; Guthoff, Rainer; Geerling, Gerd] Univ Eye Hosp Dusseldorf, Moorenstr 5, D-40225 Dusseldorf, Germany.
RP Spaniol, K (通讯作者)，Univ Eye Hosp Dusseldorf, Moorenstr 5, D-40225 Dusseldorf, Germany.
EM kristina.spaniol@med.uni-duesseldorf.de
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NR 23
TC 10
Z9 10
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 MAR 18
PY 2016
VL 9
IS 3
BP 390
EP 394
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DG0KB
UT WOS:000371752600011
PM 27158608
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Nagiel, A
   Freund, KB
   Spaide, RF
   Munch, IC
   Larsen, M
   Sarraf, D
AF Nagiel, Aaron
   Freund, K. Bailey
   Spaide, Richard F.
   Munch, Inger C.
   Larsen, Michael
   Sarraf, David
TI Mechanism of Retinal Pigment Epithelium Tear Formation Following
   Intravitreal Anti-Vascular Endothelial Growth Factor Therapy Revealed by
   Spectral-Domain Optical Coherence Tomography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CLINICOPATHOLOGICAL CORRELATION; BEVACIZUMAB AVASTIN; DETACHMENT;
   PATHOGENESIS; PREDICTORS; PRETEAR; RIP
AB PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT).
   DESIGN: Retrospective observational case series.
   METHODS: OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur in this setting.
   RESULTS: In all eyes, pretear images revealed a vascularized pigment epithelial detachment (PED) containing hyperreflective material consistent with choroidal neovascularization (CNV). This CNV was adherent to the undersurface of the RPE and created contractile folds in the RPE contour. In 6 eyes, contractile neovascular tissue spanned the PED, causing outward bowing of the Bruch membrane and a peaked appearance to the overlying RPE monolayer. RPE tears occurred after the first anti-VEGF injection in 6 of 8 eyes. The posttear OCT images showed a discontinuity in the RPE with the CNV adherent to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in Contact with the CNV or Bruch membrane.
   CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution and contraction of neovascular tissue adherent to the undersurface of the RPE may impart a substantial contractile force that tears this already-strained tissue layer. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Nagiel, Aaron; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Retinal Disorders & Ophthalm Genet Div, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Freund, K. Bailey; Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, Vitreous Retina Macula Consultants New York, New York, NY 10021 USA.
   [Freund, K. Bailey; Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Munch, Inger C.] Roskilde Hosp, Dept Ophthalmol, Roskilde, Denmark.
   [Munch, Inger C.; Larsen, Michael] Univ Copenhagen, Copenhagen, Denmark.
   [Larsen, Michael] Glostrup Cty Hosp, Dept Ophthalmol, Glostrup, Denmark.
   [Sarraf, David] Kaiser Permanente, Dept Ophthalmol, Woodland Hills, CA USA.
   [Sarraf, David] Greater Los Angeles Vet Affairs 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; Manhattan Eye Ear & Throat Hospital; Vitreous
   Retina Macula Consultants of New York; Manhattan Eye Ear & Throat
   Hospital; University of Copenhagen; University of Copenhagen; Kaiser
   Permanente
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Retinal Disorders & Ophthalm Genet Div, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
RI Munch, Inger Christine/E-9652-2010; Larsen, Michael/E-9620-2010; Nagiel,
   Aaron/AAT-8886-2020; Spaide, Richard/ABD-7368-2020; Freund, K.
   Bailey/V-7488-2018
OI Larsen, Michael/0000-0002-5172-5891; Nagiel, Aaron/0000-0001-7275-6980;
   Freund, K. Bailey/0000-0002-7888-9773
FU Genentech; Thrombogenics; Bausch + Lomb; Topcon; GlaxoSmithKline;
   Novartis; Pfizer; Alcon; Eli Lilly; Regeneron; DORC; LuEsther T. Mertz
   Retinal Research Center; Manhattan Eye, Ear and Throat Hospital, New
   York, New York
FX K.B.F. reports consulting fees from Genentech and serves on the
   scientific advisory board of Genentech. RE S. receives consulting fees
   from Thrombogenics, Bausch + Lomb, and Topcon. I.C.M. reports consulting
   fees and research funding from GlaxoSmithKline, Novartis, and Pfizer.
   M.L. receives consulting fees and research support from Novartis, Alcon,
   Eli Lilly;Pfizer, Novo Nordisk, and GlaxoSmithKline. D.S. reports grant
   support from Genentech, Regeneron, DORC, Allergan, and Alcon. The
   authors indicate funding support from LuEsther T. Mertz Retinal Research
   Center, Manhattan Eye, Ear and Throat Hospital, New York, New York.
   Contributions of authors: design of the study (D.S., A.N.); analysis and
   interpretation of the data (A.N., K.B.F., R.F.S., I.C.M., M.L., D.S.);
   and preparation and review of the manuscript (AN., K.B.F., R.F.S.,
   I.O.M., M.L., D.S.).
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NR 24
TC 74
Z9 77
U1 1
U2 6
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 NOV
PY 2013
VL 156
IS 5
BP 981
EP 988
DI 10.1016/j.ajo.2013.06.024
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 250NJ
UT WOS:000326859200017
PM 23972309
DA 2022-11-30
ER

PT J
AU Dobri, N
   Qin, Q
   Kong, J
   Yamamoto, K
   Liu, Z
   Moiseyev, G
   Ma, JX
   Allikmets, R
   Sparrow, JR
   Petrukhin, K
AF Dobri, Nicoleta
   Qin, Qiong
   Kong, Jian
   Yamamoto, Kazunori
   Liu, Zhao
   Moiseyev, Gennadiy
   Ma, Jian-xing
   Allikmets, Rando
   Sparrow, Janet R.
   Petrukhin, Konstantin
TI A1120, a Nonretinoid RBP4 Antagonist, Inhibits Formation of Cytotoxic
   Bisretinoids in the Animal Model of Enhanced Retinal Lipofuscinogenesis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VITAMIN-A; BINDING-PROTEIN; FUNDUS AUTOFLUORESCENCE; SERUM RETINOL;
   VISUAL CYCLE; PIGMENT EPITHELIUM; N-(4-HYDROXYPHENYL)RETINAMIDE;
   FENRETINIDE; ACCUMULATION; APOPTOSIS
AB PURPOSE. Excessive accumulation of lipofuscin is associated with pathogenesis of atrophic age-related macular degeneration (AMD) and Stargardt disease. Pharmacologic inhibition of the retinol-induced interaction of retinol-binding protein 4 (RBP4) with transthyretin (TTR) in the serum may decrease the uptake of serum retinol to the retina and reduce formation of lipofuscin bisretinoids. We evaluated in vitro and in vivo properties of the new nonretinoid RBP4 antagonist, A1120.
   METHODS. RBP4 binding potency, ability to antagonize RBP4-TTR interaction, and compound specificity were analyzed for A1120 and for the prototypic RBP4 antagonist fenretinide. A1120 ability to inhibit RPE65-mediated isomerohydrolase activity was assessed in the RPE microsomes. The in vivo effect of A1120 administration on serum RBP4, visual cycle retinoids, lipofuscin bisretinoids, and retinal visual function was evaluated using a combination of biochemical and electrophysiologic techniques.
   RESULTS. In comparison to fenretinide, A1120 did not act as a RAR alpha agonist, while exhibiting superior in vitro potency in RBP4 binding and RBP4-TTR interaction assays. A1120 did not inhibit isomerohydrolase activity in the RPE microsomes. A1120 dosing in mice induced 75% reduction in serum RBP4, which correlated with reduction in visual cycle retinoids and ocular levels of lipofuscin fluorophores. A1120 dosing did not induce changes in kinetics of dark adaptation.
   CONCLUSIONS. A1120 significantly reduces accumulation of lipofuscin bisretinoids in the Abca4(-/-) animal model. This activity correlates with reduction in serum RBP4 and visual cycle retinoids confirming the mechanism of action for A1120. In contrast to fenretinide, A1120 does not act as a RARa agonist indicating a more favorable safety profile for this nonretinoid compound. (Invest Ophthalmol Vis Sci. 2013; 54: 85-95) DOI: 10.1167/iovs.12-10050
C1 [Dobri, Nicoleta; Qin, Qiong; Kong, Jian; Yamamoto, Kazunori; Liu, Zhao; Allikmets, Rando; Sparrow, Janet R.; Petrukhin, Konstantin] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Allikmets, Rando; Sparrow, Janet R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Moiseyev, Gennadiy; Ma, Jian-xing] Univ Oklahoma, Hlth Sci Ctr, Dept Med Endocrinol, Oklahoma City, OK USA.
   [Ma, Jian-xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK USA.
C3 Columbia University; Columbia University; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; University of Oklahoma
   System; University of Oklahoma Health Sciences Center
RP Petrukhin, K (通讯作者)，Columbia Univ, Med Ctr, Dept Ophthalmol, 630 W 168th St, New York, NY 10032 USA.
EM kep4@columbia.edu
RI Allikmets, Rando/ABD-4533-2021
OI Petrukhin, Konstantin/0000-0002-5545-6924
FU NIH [R21 NS067594, U01 NS074476, R24 EY019861, R01 EY012951, P30
   EY019007]; Research to Prevent Blindness (New York, New York); Burch
   Family Foundation; Mary Jaharis-John Catsimatidis Scholarship Fund;
   Kaplen Foundation; Eye Surgery Fund; NATIONAL EYE INSTITUTE
   [P30EY019007, R01EY012951, R24EY019861, R01EY021163] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM104934]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL
   DISORDERS AND STROKE [U01NS074476, R21NS067594] Funding Source: NIH
   RePORTER
FX Supported by NIH Grants R21 NS067594 (KP), U01 NS074476 (KP), R24
   EY019861 (RA, JRS, KP), R01 EY012951 (JRS), P30 EY019007 (Core Support
   for Vision Res), and unrestricted funds from Research to Prevent
   Blindness (New York, New York) to the Department of Ophthalmology,
   Columbia University, and by The Burch Family Foundation, the Mary
   Jaharis-John Catsimatidis Scholarship Fund, the Kaplen Foundation, and
   the Eye Surgery Fund.
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TC 57
Z9 66
U1 0
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 JAN
PY 2013
VL 54
IS 1
BP 85
EP 95
DI 10.1167/iovs.12-10050
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 081QX
UT WOS:000314338400012
PM 23211825
OA Green Published
DA 2022-11-30
ER

PT J
AU Castet, E
   Crossland, M
AF Castet, Eric
   Crossland, Michael
TI Quantifying Eye Stability During a Fixation Task: A Review of
   Definitions and Methods
SO SEEING AND PERCEIVING
LA English
DT Review
DE Fixation; fixational eye (gaze) stability; eye movements; low vision;
   fixation map
ID SCANNING LASER OPHTHALMOSCOPE; ECCENTRIC FIXATION; RETINAL LOCATION;
   VISUAL FIXATION; MOVEMENTS; MICROSACCADES; LOCUS; MP-1; SCHIZOPHRENIA;
   INSTABILITY
AB Several definitions, measurements, and implicit meanings of 'fixation stability' have been used in clinical vision research, leading to some confusion. One definition concerns eye movements observed within fixations (i.e., within periods separated by saccades) when observing a point target: drift, microsaccades and physiological tremor all lead to some degree of within-fixation instability. A second definition relates to eye position during multiple fixations (and saccades) when patients fixate a point target. Increased between-fixation variability, combined with within-fixation instability, is known to be associated with poorer visual function in people with retinal disease such as age-related macular degeneration. In this review article, methods of eye stability measurement and quantification are summarised. Two common measures are described in detail: the bivariate contour ellipse area (BCEA) and the within-isolines area. The first measure assumes normality of the underlying positions distribution whereas the second does not. Each of these measures can be applied to two fundamentally different kinds of eye position data collected during a period of target observation. In the first case, mean positions of eye fixations are used to obtain an estimate of between-fixation variability. In the second case, often used in clinical vision research, eye position samples recorded by the eyetracker are used to obtain an estimate that confounds within- and between-fixation variability.
   We show that these two methods can produce significantly different values of eye stability, especially when reported as BCEA values. Statistical techniques for describing eye stability when the distribution of eye positions is multimodal and not normally distributed are also reviewed. (C) Koninklijke Brill NV, Leiden, 2012
C1 [Castet, Eric] CNRS, Inst Neurosci Cognit Mediterranee, Marseille, France.
   [Castet, Eric] Aix Marseille Univ, Marseille, France.
   [Crossland, Michael] Moorfields Eye Hosp, London, England.
   [Crossland, Michael] UCL Inst Ophthalmol, London, England.
C3 Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; Aix-Marseille Universite; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London
RP Castet, E (通讯作者)，CNRS, Inst Neurosci Cognit Mediterranee, Marseille, France.
EM eric.castet@univ-amu.fr
RI Crossland, Michael D/B-5600-2008
OI Crossland, Michael D/0000-0001-6833-6043
FU National Institute for Health Research [PDF/01/2008/011]
FX MDC is funded by the National Institute for Health Research grant
   PDF/01/2008/011. This report describes independent research arising from
   a grant supported by the National Institute for Health Research. The
   views expressed in this publication are those of the authors and not
   necessarily those of the NHS, the National Institute for Health Research
   or the Department of Health.
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NR 65
TC 50
Z9 50
U1 3
U2 32
PU BRILL ACADEMIC PUBLISHERS
PI LEIDEN
PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS
SN 1878-4755
EI 1878-4763
J9 SEEING PERCEIVING
JI Seeing Perceiving
PY 2012
VL 25
IS 5
SI SI
BP 449
EP 469
DI 10.1163/187847611X620955
PG 21
WC Biophysics; Psychology; Psychology, Experimental
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Biophysics; Psychology
GA 991FE
UT WOS:000307686100005
PM 22370759
DA 2022-11-30
ER

PT J
AU Fujimoto, T
   Sonoda, KH
   Hijioka, K
   Sato, K
   Takeda, A
   Hasegawa, E
   Oshima, Y
   Ishibashi, T
AF Fujimoto, Takeshi
   Sonoda, Koh-Hei
   Hijioka, Kuniaki
   Sato, Kohta
   Takeda, Atsunobu
   Hasegawa, Eiichi
   Oshima, Yuji
   Ishibashi, Tatsuro
TI Choroidal Neovascularization Enhanced by Chlamydia pneumoniae via
   Toll-like Receptor 2 in the Retinal Pigment Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; INNATE IMMUNITY;
   RISK-FACTORS; IN-VITRO; COMPLEMENT; INFECTION; MODEL; MICE; TLR4
AB PURPOSE. Choroidal neovascularization (CNV) is directly related to visual loss in persons with age-related macular degeneration (AMD) and other macular disorders. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation, is recognized as a risk factor for cardiovascular diseases. In this study, the authors investigated the association between C. pneumoniae infection and AMD using a laser-induced CNV model in mice.
   METHODS. C57BL/6 mice, myeloid differentiation factor (MyD) 88 knockout (KO) mice, Toll-like receptor (TLR) 2 KO mice, and TLR4 KO mice were used. Experimental CNV was induced by rupturing the Bruch's membrane by laser photocoagulation (PC). Seven days after PC, the eyes were enucleated and the areas of CNV were measured in choroidal flat mounts. Cytokine gene expression by quantitative real-time PCR in the primary cultured retinal pigment epithelium (RPE) cells was also examined.
   RESULTS. Vitreous injection of the C. pneumoniae antigen increased the size of CNV. Although lipopolysaccharide stimulation can induce multiple cytokines, cultured mouse RPE cells from C57BL/6 mice expressed IL-6 and VEGF, but not TNF-alpha mRNA, in response to C. pneumoniae antigen. RPE cells from either MyD88 KO mice or TLR2 KO mice did not respond to the C. pneumoniae antigen. TLR2 KO mice did not augment the size increase of experimental CNV by C. pneumoniae antigen in vivo.
   CONCLUSIONS. C. pneumoniae can trigger inflammatory responses in the eye and promote experimental CNV in a TLR2-dependent manner. These data provide experimental evidence to imply persistent C. pneumoniae infection is a risk factor for AMD. (Invest Ophthalmol Vis Sci. 2010; 51: 4694-4702) DOI: 10.1167/iovs.09-4464
C1 [Sonoda, Koh-Hei] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan.
C3 Kyushu University
RP Sonoda, KH (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM sonodak@med.kyushu-u.ac.jp
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NR 52
TC 42
Z9 47
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 SEP
PY 2010
VL 51
IS 9
BP 4694
EP 4702
DI 10.1167/iovs.09-4464
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 645YS
UT WOS:000281502700046
PM 20393111
DA 2022-11-30
ER

PT J
AU Peng, SM
   Adelman, RA
   Rizzolo, LJ
AF Peng, Shaomin
   Adelman, Ron A.
   Rizzolo, Lawrence J.
TI Minimal Effects of VEGF and Anti-VEGF Drugs on the Permeability or
   Selectivity of RPE Tight Junctions
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL
   NEOVASCULARIZATION; INTRAVITREAL INJECTION; CELL MITOGEN; EXPRESSION;
   RESISTANCE; BARRIER; COMPLEX; RANIBIZUMAB
AB PURPOSE. Bevacizumab and ranibizumab are currently used to treat age-related macular degeneration by neutralizing vascular endothelial growth factor (VEGF). In this study, the potential side effects on the outer blood-retinal barrier were examined.
   METHODS. Human fetal RPE (hfRPE) cells were used because they are highly differentiated in culture. The claudin composition of RPE tight junctions was determined by RT-PCR, immunoblot analysis, and immunofluorescence. ELISA assays monitored the secretion and trafficking of VEGF and a fluid-phase marker, methylpolyethylene glycol (mPEG). Tight junction functions were assessed by the conductance of K+ and Na+ (derived from the transepithelial electrical resistance, TER) and the flux of NaCl and mPEG.
   RESULTS. Claudin-3, claudin-10, and claudin-19 were detected in RPE tight junctions. VEGF was secreted in equal amounts across the apical and basolateral membranes, but the apical membrane was more active in endocytosing and degrading VEGF. Exogenous VEGF and mPEG crossed the RPE monolayer by transcytosis, predominantly in the apical-to-basal direction. RPE tight junctions were selective for K+, but did not discriminate between Na+ and Cl-. VEGF, bevacizumab, and ranibizumab had minimal effects on TER, permeation of mPEG, and selectivity for K+, Na+, and Cl-. They had minimal effects on the expression and distribution of the claudins.
   CONCLUSIONS. RPE has mechanisms for maintaining low concentrations of VEGF in the subretinal space that include endocytosis and degradation and fluid-phase transcytosis in the apical-to-basal direction. RPE tight junctions are selective for K+ over Na+ and Cl-. Permeability and selectivity of the junctions are not affected by VEGF, bevacizumab, or ranibizumab. (Invest Ophthalmol Vis Sci. 2010; 51: 3216-3225) DOI:10.1167/iovs.09-4162
C1 [Peng, Shaomin; Rizzolo, Lawrence J.] Yale Univ, Dept Surg, New Haven, CT 06520 USA.
   [Peng, Shaomin; Adelman, Ron A.; Rizzolo, Lawrence J.] Yale Univ, Dept Ophthalmol & Visual Sci, New Haven, CT 06520 USA.
   [Peng, Shaomin] Harbin Univ, Affiliated Hosp 2, Dept Ophthalmol, Harbin, Peoples R China.
C3 Yale University; Yale University; Harbin University
RP Rizzolo, LJ (通讯作者)，Yale Univ, Dept Surg, POB 208062, New Haven, CT 06520 USA.
EM lawrence.rizzolo@yale.edu
OI Rizzolo, Lawrence/0000-0002-2393-8419
FU Yale University [EY000785]; Leir Foundation; National Natural Science
   Foundation of China [NO 30772381]; NATIONAL EYE INSTITUTE [P30EY000785]
   Funding Source: NIH RePORTER
FX Supported in part by the National Eye Institute Vision Core Grant
   EY000785 (Yale University), the Leir Foundation (RA), and the National
   Natural Science Foundation of China Grant NO 30772381 (SP).
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NR 56
TC 47
Z9 48
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2010
VL 51
IS 6
BP 3216
EP 3225
DI 10.1167/iovs.09-4162
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 598OC
UT WOS:000277846500053
PM 20042644
OA Green Published
DA 2022-11-30
ER

PT J
AU Richer, S
   Stiles, W
   Thomas, C
AF Richer, Stuart
   Stiles, William
   Thomas, Carla
TI Molecular medicine in ophthalmic care
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Article
DE RPE lipofuscin; Dietary polyphenols; Resveratrol
ID RETINAL-PIGMENT EPITHELIUM; LIPOFUSCIN ACCUMULATION; CALORIE
   RESTRICTION; DIETARY RESTRICTION; OXIDATIVE STRESS; GENE-EXPRESSION;
   RAT-BRAIN; LIFE-SPAN; VITAMIN-E; AGE
AB BACKGROUND: Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators.
   METHODS: An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 degrees fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function Contrast Sensitivity Function, 6.5 degrees large field tritan threshold, 10 threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later.
   RESULTS: The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin.
   CONCLUSION: To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention. Optometry 2009;80:695-701
C1 [Richer, Stuart; Stiles, William; Thomas, Carla] Dept Vet Affairs Med Ctr, Eye Clin, N Chicago, IL 60064 USA.
   [Richer, Stuart] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA.
C3 Rosalind Franklin University Medical & Science
RP Richer, S (通讯作者)，Dept Vet Affairs Med Ctr, Eye Clin 112E, 3001 Green Bay Rd, N Chicago, IL 60064 USA.
EM Stuart.Richer1@VA.Gov
FU DVA Medical Center, North Chicago, Illinois; Department of Veteran's
   Affairs
FX This material is based upon work supported by the DVA Medical Center,
   North Chicago, Illinois and the Department of Veteran's Affairs. The
   authors thank Kowa Optimed USA (Torrance, California, and Japan
   Corporate Headquarters); Rush Instruments (Gold Beach, Oregon); Stereo
   Optical (Chicago, Illinois), and Zeavision (St. Louis, Missouri) for
   donation of ophthalmic equipment. The OTC dietary supplement (Logevinex
   (R)) was donated by the manufacturer, Resveratrol Partners LLC (Las
   Vegas, Nevada).
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NR 56
TC 11
Z9 14
U1 0
U2 4
PU AMER OPTOMETRIC ASSN INC
PI ST LOUIS
PA 243 N LINDBERGH BLVD, ST LOUIS, MO 63141 USA
SN 1529-1839
EI 1558-1527
J9 OPTOMETRY
JI Optometry
PD DEC
PY 2009
VL 80
IS 12
BP 695
EP 701
DI 10.1016/j.optm.2009.03.018
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V18QM
UT WOS:000208019300007
PM 19932443
DA 2022-11-30
ER

PT J
AU Kelly, U
   Rickman, CB
   Postel, EA
   Hauser, MA
   Hageman, GS
   Arshavsky, VY
   Skiba, NP
AF Kelly, Una
   Rickman, Catherine Bowes
   Postel, Eric A.
   Hauser, Michael A.
   Hageman, Gregory S.
   Arshavsky, Vadim Y.
   Skiba, Nikolai P.
TI Rapid and Sensitive Method for Detection of Y402, H402, I62, and V62
   Variants of Complement Factor H in Human Plasma Samples Using Mass
   Spectrometry
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; POLYMORPHISM; PROTEINS; RISK
AB PURPOSE. Variations in the complement factor H (CFH) gene are tightly associated with age-related macular degeneration (AMD) across diverse populations. Of the many nonsynonymous coding variants in CFH, two are most strongly associated with increased risk of AMD: isoleucine 62 to valine (I62V) and tyrosine 402 to histidine (Y402H). Detection of these variations in a patient's blood is important for a risk assessment of AMD and disease prognosis. However, traditional methods of genetic analysis cannot be used for measuring CFH allotypes in some sources of human plasma and other biological fluids not containing DNA. The purpose was to develop a protein-based method of detecting CFH allotypes.
   METHODS. A combination of a single-step affinity enrichment of CFH, gel separation, and mass spectrometry identification of the CFH peptides spanning amino acids at positions 62 and 402 was used to identify individual CFH allotypes.
   RESULTS. The CFH isoforms V62, I62, H402, and Y402 were reliably detected based on identification of tryptic peptides with masses of 1148.59 Da, 1162.60 Da, 2031.88 Da, and 2057.88 Da, respectively, using MALDI-TOF-TOF. The presence or absence pattern of these peptides in mass spectra of different CFH samples robustly correlated with all nine genotypes of CFH, as a result of variations at positions 62 and 402.
   CONCLUSIONS. A rapid and sensitive method has been developed for detection of V62, I62, H402, and Y402 variants of CFH in human plasma samples using mass spectrometry. This method can be used in clinical laboratories equipped with a basic inexpensive mass spectrometer capable of performing peptide fingerprinting. (Invest Ophthalmol Vis Sci. 2009; 50: 1540-1545) DOI:10.1167/iovs.08-2782
C1 [Skiba, Nikolai P.] Duke Univ, Med Ctr, Albert Eye Res Inst, Dept Ophthalmol, Durham, NC 27710 USA.
   [Rickman, Catherine Bowes] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   [Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Arshavsky, Vadim Y.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Hauser, Michael A.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA.
   [Hageman, Gregory S.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
C3 Duke University; Duke University; Duke University; Duke University; Duke
   University; University of Iowa
RP Skiba, NP (通讯作者)，Duke Univ, Med Ctr, Albert Eye Res Inst, Dept Ophthalmol, Room 5006,Box 3802,Erwin Rd, Durham, NC 27710 USA.
EM nikolai.skiba@duke.edu
OI Bowes Rickman, Catherine/0000-0002-8555-9596
FU The Foundation Fighting Blindness; National Eye Institute [P30 EY005722,
   EY012118]; Research to Prevent Blindness to the Duke Eye Center;
   National Institutes of Health [R24 EY017404]; NATIONAL EYE INSTITUTE
   [R01EY012118, P30EY005722, R01EY011286, R24EY017404, U10EY012118]
   Funding Source: NIH RePORTER
FX Supported by The Foundation Fighting Blindness (CBR); in part by core
   grants from the National Eye Institute (NEI; P30 EY005722) and Research
   to Prevent Blindness to the Duke Eye Center; National Institutes of
   Health Grant R24 EY017404 (GSH); and funds from NEI Grant EY012118
   provided by Margaret Pericak-Vance (University of Miami) and Jonathan
   Haines (Vanderbilt University), which funded a portion of the samples
   used in this work.
CR Abrera-Abeleda MA, 2006, J MED GENET, V43, P582, DOI 10.1136/jmg.2005.038315
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NR 9
TC 6
Z9 9
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2009
VL 50
IS 4
BP 1540
EP 1545
DI 10.1167/iovs.08-2782
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 424CP
UT WOS:000264543400009
PM 19029036
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, X
   Zhu, YJ
   Shi, XQ
   Zuo, J
   Hu, TM
   Wu, H
   Xia, Y
   Shi, W
   Wei, W
AF Chen, Xi
   Zhu, Yujie
   Shi, Xiaoqing
   Zuo, Jing
   Hu, Tianming
   Wu, Hao
   Xia, Ying
   Shi, Wei
   Wei, Wei
TI Ming-Mu-Di-Huang-Pill Activates SQSTM1 via AMPK-Mediated Autophagic
   KEAP1 Degradation and Protects RPE Cells from Oxidative Damage
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID TRANSCRIPTION FACTOR NRF2; STRESS; DEGENERATION; INFLAMMATION; PATHWAY;
   TARGET
AB Oxidative stress and diminished autophagy in the retinal pigment epithelium (RPE) play crucial roles in the pathogenesis of age-related macular degeneration (AMD). Enhancing autophagy has recently been identified as an important strategy to protect RPE cells from oxidative damage. Ming-Mu-Di-Huang-Pill (MMDH pill) is a traditional herbal medicine used to treat AMD, and its molecular mechanism is not well understood. The aim of the present study was to investigate whether the MMDH pill relieved acute oxidative damage by activating autophagy in an in vitro and in vivo model of sodium iodate (NaIO3). The results showed that NaIO3 induced cell death and inhibited proliferation. The MMDH pill increased cell viability, restored the activities of antioxidant enzymes, and reduced reactive oxygen species (ROS) fluorescence intensity. The MMDH pill mediated Kelch-like ECH-associated protein 1 (Keap1) degradation and decreased oxidative damage, which was blocked in autophagy inhibitor (chloroquine) or sequestosome-1 (SQSTM1) siRNA-treated RPE cells. Furthermore, we indicated that the MMDH pill could promote adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and autophagy adaptor-SQSTM1 expression, which could stimulate autophagic degradation of Keap1. In addition, the MMDH pill increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation in a SQSTM1-dependent manner and induced the expression of the downstream antioxidant factors heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). In conclusion, MMDH pill plays a protective role in relieving NaIO3-induced oxidative stress by activating the AMPK/SQSTM1/Keap1 pathway. The MMDH pill may be useful to treat AMD by maintaining redox homeostasis and autophagy.
C1 [Chen, Xi; Zhu, Yujie; Shi, Xiaoqing; Wei, Wei] Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Xi; Zhu, Yujie; Zuo, Jing; Hu, Tianming; Wu, Hao; Xia, Ying; Shi, Wei; Wei, Wei] Nanjing Univ Chinese Med, Dept Ophthalmol, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Xi; Zhu, Yujie; Shi, Xiaoqing] Nanjing Univ Chinese Med, Coll Clin Med 1, Key Lab Metab Dis Chinese Med, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese
   Medicine; Nanjing University of Chinese Medicine
RP Wei, W (通讯作者)，Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing 210029, Jiangsu, Peoples R China.; Shi, W; Wei, W (通讯作者)，Nanjing Univ Chinese Med, Dept Ophthalmol, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China.
EM shiwei-1218@163.com; 13951776603@163.com
FU National Natural Science Foundation of China [81774370]; Jiangsu
   Province Postgraduate Training Innovation Project [KYCX21_1808]
FX This work was supported by the National Natural Science Foundation of
   China (No. 81774370) and Jiangsu Province Postgraduate Training
   Innovation Project (No. KYCX21_1808).
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NR 39
TC 0
Z9 0
U1 5
U2 5
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD MAR 25
PY 2022
VL 2022
AR 5851315
DI 10.1155/2022/5851315
PG 21
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 3P9SF
UT WOS:000837873300002
PM 35378824
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Du, W
   Lee, YC
   Wang, TF
   Cui, HR
   Xu, H
   Bao, X
   Tang, X
   Zhao, MW
AF Du, Wei
   Lee, Yin Chih
   Wang, Tianfu
   Cui, Haoran
   Xu, Hui
   Bao, Xuan
   Tang, Xin
   Zhao, Mingwei
TI Dose-Related Structural Effects of Photodynamic Therapy on Rabbit
   Choroidal Structure
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Photodynamic therapy; Verteporfin; Dose-dependent effects; Choroidal
   structure; Central serous chorioretinopathy
ID CENTRAL SEROUS CHORIORETINOPATHY; INDOCYANINE GREEN ANGIOGRAPHY; OPTICAL
   COHERENCE TOMOGRAPHY; HALF-FLUENCE; VERTEPORFIN; SAFETY;
   NEOVASCULARIZATION; ISCHEMIA; DISEASE
AB Introduction: Photodynamic therapy with verteporfin (vPDT) has been shown to be effective against central serous chorioretinopathy (CSC) and was the preferred therapeutic for CSC treatment. However, alterations in choroidal structure after PDT were reported, and these effects were dose-dependent. This study aimed to compare the changes in choroidal structure after PDT with different doses of verteporfin in rabbits and may provide individualized therapeutic guidance for patients who failed to respond to initial half-dose vPDT. Methods: The full dose of verteporfin used in CSC was 6 mg/m(2), which was used in patients with neovascular age-related macular degeneration. Laser fluence was 50 J/cm(2) (irradiance, 600 mW/cm(2), 83 s). There were 4 different dose groups in this study (100%, 70%, 50%, and 30%). The alterations were examined at 1 day, 1 week, and 1 month after vPDT using color fundus imaging, indocyanine green angiography, and histopathology analysis. Results: Various degrees of choroidal alterations were demonstrated at different dose groups. Examinations on day 1 showed that gradually reduced verteporfin dose tended to decrease photochemical reactions to the choroid in terms of the number of occlusion vessels and area of the lesion. After 1 month, choroid vessel alteration persisted in high-dose groups (100% and 70%); nevertheless, alterations of low-dose groups (50% and 30%) returned to normal. Conclusions: vPDT can induce photochemical reactions of the choroid, high dose causes permanent change, and low dose causes recoverable change. The dose-dependent alterations need to be considered for the individual therapeutic plan according to the situation of a patient with CSC. (c) 2021 The Author(s) Published by S. Karger AG, Basel
C1 [Du, Wei; Lee, Yin Chih; Wang, Tianfu; Cui, Haoran; Xu, Hui; Bao, Xuan; Tang, Xin; Zhao, Mingwei] Peking Univ Peoples Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Du, Wei; Lee, Yin Chih; Wang, Tianfu; Cui, Haoran; Xu, Hui; Bao, Xuan; Tang, Xin; Zhao, Mingwei] Peking Univ Peoples Hosp, Clin Ctr Optometry, Beijing, Peoples R China.
   [Du, Wei; Lee, Yin Chih; Wang, Tianfu; Cui, Haoran; Xu, Hui; Bao, Xuan; Tang, Xin; Zhao, Mingwei] Peking Univ Peoples Hosp, Eye Dis & Optometry Inst, Beijing, Peoples R China.
   [Du, Wei; Lee, Yin Chih; Wang, Tianfu; Cui, Haoran; Xu, Hui; Bao, Xuan; Tang, Xin; Zhao, Mingwei] Beijing Key Lab Diag & Therapy Retinal & Choroid, Beijing, Peoples R China.
   [Du, Wei; Lee, Yin Chih; Wang, Tianfu; Cui, Haoran; Xu, Hui; Bao, Xuan; Tang, Xin; Zhao, Mingwei] Peking Univ, Coll Optometry, Hlth Sci Ctr, Beijing, Peoples R China.
C3 Peking University; Peking University
RP Zhao, MW (通讯作者)，Peking Univ Peoples Hosp, Dept Ophthalmol, Beijing, Peoples R China.; Zhao, MW (通讯作者)，Peking Univ Peoples Hosp, Clin Ctr Optometry, Beijing, Peoples R China.; Zhao, MW (通讯作者)，Peking Univ Peoples Hosp, Eye Dis & Optometry Inst, Beijing, Peoples R China.; Zhao, MW (通讯作者)，Beijing Key Lab Diag & Therapy Retinal & Choroid, Beijing, Peoples R China.; Zhao, MW (通讯作者)，Peking Univ, Coll Optometry, Hlth Sci Ctr, Beijing, Peoples R China.
EM rmykzmw@163.com
FU National Natural Science Foundation of China [81600770]; National Key
   R&D Program of China [2020YFC2008203]; Beijing Municipal Natural Science
   Foundation, China [7164306]; Research Fund for Science and Technology
   Program of Beijing [Z161100000516037]
FX This study was funded by the National Natural Science Foundation of
   China (No. 81600770); National Key R&D Program of China
   (2020YFC2008203); Beijing Municipal Natural Science Foundation, China
   (No. 7164306); and Research Fund for Science and Technology Program of
   Beijing (Z161100000516037).
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NR 42
TC 1
Z9 1
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD DEC
PY 2021
VL 64
IS 6
BP 1037
EP 1047
DI 10.1159/000519328
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZC4VR
UT WOS:000757520400017
PM 34510043
OA hybrid
DA 2022-11-30
ER

PT J
AU El-Darzi, N
   Mast, N
   Dailey, B
   Denker, J
   Li, Y
   Vance, J
   Pikuleva, IA
AF El-Darzi, Nicole
   Mast, Natalia
   Dailey, Brian
   Denker, John
   Li, Yong
   Vance, Joseph
   Pikuleva, Irina A.
TI Characterizations of Hamster Retina as a Model for Studies of Retinal
   Cholesterol Homeostasis
SO BIOLOGY-BASEL
LA English
DT Article
DE hamster; retina; cholesterol; retinal abnormalities; retinal blood
   vessels; diabetes; diabetic retinopathy
ID DIETARY-CHOLESTEROL; CHINESE-HAMSTER; GANGLION-CELLS; METABOLISM;
   EXPRESSION; RAT; ABNORMALITIES; PRODUCT; ACID; CRB1
AB Simple Summary: This work represents a comprehensive evaluation of hamster retina by state-of-the-art methodologies and provides evidence that hamsters may represent a better model for studies of retinal cholesterol maintenance than mice. The latter is an important finding, as disturbances in retinal cholesterol homeostasis are linked to age-related macular degeneration and diabetic retinopathy, which are blinding diseases.<br></p>
   <br></p>
   Cholesterol homeostasis in the retina, a sensory organ in the back of the eye, has been studied in mice but not hamsters, despite the latter being more similar to humans than mice with respect to their whole-body cholesterol maintenance. The goal of this study was to begin to assess hamster retina and conduct initial interspecies comparisons. First, young (3-month old) and mature (6-month old) Syrian (golden) hamsters were compared with 3- and 6-month old mice for ocular biometrics and retinal appearance on optical coherence tomography and fluorescein angiography. Of the 30 evaluated hamsters, seven had retinal structural abnormalities and all had increased permeability of retinal blood vessels. However, hamsters did not carry the mutations causing retinal degenerations 1 and 8, had normal blood glucose levels, and only slightly elevated hemoglobin A1c content. Cholesterol and six other sterols were quantified in hamster retina and compared with sterol profiles in mouse and human retina. These comparisons suggested that cholesterol turnover is much higher in younger than mature hamster retina, and that mature hamster and human retinas share similarities in the ratios of cholesterol metabolites to cholesterol. This study supports further investigations of cholesterol maintenance in hamster retina.</p>
C1 [El-Darzi, Nicole; Mast, Natalia; Dailey, Brian; Denker, John; Li, Yong; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Vance, Joseph] Spect LLC, Durham, NC 27705 USA.
C3 Case Western Reserve University
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM nae20@case.edu; nvm2@case.edu; bxd238@case.edu; jad6@case.edu;
   yxl665@case.edu; jvance@thespectivegroup.com; iap8@case.edu
OI Mast, Natalia/0000-0001-6427-640X; Pikuleva, Irina/0000-0001-9742-6232
FU NIH [R01 EY018383, P30 EY011373]
FX This research was supported in part by NIH grants R01 EY018383 and P30
   EY011373 (I.A.P.). Irina A. Pikuleva is a Carl F. Asseff Professor of
   Ophthalmology.
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NR 56
TC 1
Z9 1
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2079-7737
J9 BIOLOGY-BASEL
JI Biology-Basel
PD OCT
PY 2021
VL 10
IS 10
AR 1003
DI 10.3390/biology10101003
PG 19
WC Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics
GA WO1NS
UT WOS:000712228900001
PM 34681102
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Peixoto, RD
   Krstic, L
   Hill, SCL
   Foss, AJE
AF De Sousa Peixoto, Ricardo
   Krstic, Lazar
   Hill, Sophie C. L.
   Foss, Alexander J. E.
TI Predicting quality of life in AMD patients-insights on the new NICE
   classification and on a bolt-on vision dimension for the EQ-5D
SO EYE
LA English
DT Article
ID WEIGHTS; IMPACT
AB Background/aims Health-related quality of life (HRQoL) in age-related macular degeneration (AMD) is difficult to estimate as most generic tools underestimate vision. Our aim was to measure the effect of AMD on generic and visual quality of life and how it relates to handicap. We also aimed to validate the NG82 NICE AMD classification. Finally, we studied if a bolt-on visual domain increased the EQ-5D sensitivity to AMD.
   Patients and methods Ninety-six patients with AMD participated in this observational cross-sectional study. Visual (VF-14) and generic questionnaires (EQ-5D) with VIS, and the London handicap scale (LHS) was used to quantify HRQoL and handicap. ANOVA and regression analysis were used to identify significant associations.
   Results Visual dysfunction in AMD has a significant effect in VF-14 (P < 0.001), LHS (p < 0.001), and EQ-5D (p = 0.015). The EQ-5D was less sensitive than the VF-14 and LHS and was not significantly correlated with the VIS bolt-on domain (p = 0.608). On the other hand, VIS was significantly associated with visual acuity (p < 0.001), AMD diagnosis (p = 0.005), VF-14 (p < 0.001), and LHS (p < 0.001). The new AMD classification was a good predictor of visual HRQoL and had an excellent association with visual acuity in the best eye.
   Conclusion This article shows that visual impairment is associated with lower HRQoL and with an increased handicap. It also suggests that a visual dimension may increase the EQ-5D sensitivity in AMD. There was a relationship between visual impairment and handicap with the items of the new NICE AMD classification, which supports its use.
C1 [De Sousa Peixoto, Ricardo; Foss, Alexander J. E.] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Ophthalmol & Visual Sci, Nottingham, England.
   [Krstic, Lazar] Univ Nottingham, Dept Med Educ, Nottingham, England.
   [Hill, Sophie C. L.] Greenland Clin Ctr, Dept Ophthalmol, Auckland, New Zealand.
C3 Nottingham University Hospital NHS Trust; University of Nottingham;
   University of Nottingham
RP Peixoto, RD (通讯作者)，Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Ophthalmol & Visual Sci, Nottingham, England.
EM ricardo.peixoto@nhs.net
OI Krstic, Lazar/0000-0002-0305-3111; Peixoto, Ricardo/0000-0002-3428-131X;
   Foss, Alexander/0000-0001-9649-0072
CR [Anonymous], AG REL MAC DEG
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NR 17
TC 3
Z9 3
U1 0
U2 1
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD DEC
PY 2021
VL 35
IS 12
BP 3333
EP 3341
DI 10.1038/s41433-021-01414-3
EA FEB 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XA1VU
UT WOS:000613585900003
PM 33526850
DA 2022-11-30
ER

PT J
AU Altay, L
   Subiras, X
   de Motta, LL
   Schick, T
   Berghold, A
   Hoyng, CB
   den Hollander, AI
   Fauser, S
   Sadda, SR
   Liakopoulos, S
AF Altay, Lebriz
   Subiras, Xavier
   de Motta, Laura Lores
   Schick, Tina
   Berghold, Aileen
   Hoyng, Carel B.
   den Hollander, Anneke I.
   Fauser, Sascha
   Sadda, Srinivas R.
   Liakopoulos, Sandra
TI Genetic and environmental risk factors for extramacular drusen
SO MOLECULAR VISION
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   BEAVER DAM; 5-YEAR INCIDENCE; PERIPHERAL AUTOFLUORESCENCE; SUNLIGHT
   EXPOSURE; 10-YEAR INCIDENCE; IRIS COLOR; DISEASE
AB Purpose: To analyze risk factors for extramacular drusen (EMD) in patients with age-related macular degeneration (AMD) and healthy control individuals.
   Methods: This case-control study included 1,520 patients from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography scans were evaluated for the presence of AMD and EMD. EMD was considered present if ten or fewer drusen including at least one intermediate-sized drusen were detected outside the macula. Association of EMD was evaluated with various genetic and non-genetic risk factors (31 single nucleotide polymorphisms, systemic complement activation, smoking, cardiovascular factors, and sunlight exposure) using logistic regression models adjusted for age, gender, and AMD.
   Results: EMD was found in 608 subjects (40%) and AMD in 763 (50%) of 1,520 participants. EMD was strongly associated with AMD (p = 2.83 x 10-63, odds ratio [OR] 7.63). After adjustment for AMD, age (p = 0.06, OR 1.02), female gender (p = 3.34 x 10-24, OR 4.44), history of sunlight exposure >= 8 h /day (p = 0.0004, OR 1.99), serum complement activation (p = 0.004, OR 1.61), and polymorphisms in ARMS2 (p = 0.00016, OR 1.43) and CFI (p = 0.043, OR 1.20) were identified as risk factors for EMD. The final prediction model including these variants showed an area under the curve of 0.820.
   Conclusions: The comprehensive analysis of various risk factors revealed a common genetic and pathological pathway of EMD with AMD. Future longitudinal studies are needed to evaluate the role of EMD in otherwise healthy subjects as an expanded phenotype of AMD.
C1 [Altay, Lebriz; Subiras, Xavier; Schick, Tina; Fauser, Sascha; Liakopoulos, Sandra] Univ Cologne, Fac Med, Dept Ophthalmol, Cologne, Germany.
   [Altay, Lebriz; Subiras, Xavier; Schick, Tina; Berghold, Aileen; Liakopoulos, Sandra] Univ Hosp Cologne, Cologne, Germany.
   [Subiras, Xavier; Schick, Tina; Berghold, Aileen; Liakopoulos, Sandra] Univ Cologne, Dept Ophthalmol, Cologne Image Reading Ctr, Fac Med, Cologne, Germany.
   [de Motta, Laura Lores; Hoyng, Carel B.; den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands.
   [de Motta, Laura Lores; den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands.
   [Sadda, Srinivas R.] UCLA, Doheny Eye Inst, Los Angeles, CA USA.
   [Schick, Tina] MVZ ADTC Siegburg GmbH, AugenZentrum Siegburg, Siegburg, Germany.
C3 University of Cologne; University of Cologne; University of Cologne;
   Radboud University Nijmegen; Radboud University Nijmegen; Doheny Eye
   Institute; University of California System; University of California Los
   Angeles
RP Liakopoulos, S (通讯作者)，Univ Hosp Cologne, Dept Ophthalmol, Kerpener Str 62, D-50924 Cologne, Germany.
EM sandra.liakopoulos@uk-koeln.de
FU German Research Foundation DFG [FOR 2240]; European Research Council
   under the European Union/ERC [310,644]
FX The research leading to these results was funded from the German
   Research Foundation DFG FOR 2240 and the European Research Council under
   the European Union's Seventh Framework Program (FP/2007-2013)/ERC Grant
   Agreement n. 310,644 (MACULA).
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NR 44
TC 0
Z9 0
U1 1
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 4
PY 2020
VL 26
BP 661
EP 669
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA NW9ZL
UT WOS:000575379200001
PM 33088170
DA 2022-11-30
ER

PT J
AU Tuo, SH
   Liu, HY
   Chen, H
AF Tuo, Shouheng
   Liu, Haiyan
   Chen, Hao
TI Multipopulation harmony search algorithm for the detection of high-order
   SNP interactions
SO BIOINFORMATICS
LA English
DT Article
ID BREAST-CANCER SUSCEPTIBILITY; ANT COLONY OPTIMIZATION; EPISTATIC
   INTERACTIONS; ASSOCIATION; INFERENCE
AB Motivation: Recently, multiobjective swarm intelligence optimization (SIO) algorithms have attracted considerable attention as disease model-free methods for detecting high-order single nucleotide polymorphism (SNP) interactions. However, a strict Pareto optimal set may filter out some of the SNP combinations associated with disease status. Furthermore, the lack of heuristic factors for finding SNP interactions and the preference for discrimination approaches to disease models are considerable challenges for SIO.
   In this study, we propose a multipopulation harmony search (HS) algorithm dedicated to the detection of high-order SNP interactions (MP-HS-DHSI). This method consists of three stages. In the first stage, HS with multipopulation (multiharmony memories) is used to discover a set of candidate high-order SNP combinations having an association with disease status. In HS, multiple criteria [Bayesian network-based K2-score, Jensen-Shannon divergence, likelihood ratio and normalized distance with joint entropy (ND-JE)] are adopted by four harmony memories to improve the ability to discriminate diverse disease models. A novel evaluation criterion named ND-JE is proposed to guide HS to explore clues for high-order SNP interactions. In the second and third stages, the G-test statistical method and multifactor dimensionality reduction are employed to verify the authenticity of the candidate solutions, respectively.
   Results: We compared MP-HS-DHSI with four state-of-the-art SIO algorithms for detecting high-order SNP interactions for 20 simulation disease models and a real dataset of age-related macular degeneration. The experimental results revealed that our proposed method can accelerate the search speed efficiently and enhance the discrimination ability of diverse epistasis models.
C1 [Tuo, Shouheng; Liu, Haiyan; Chen, Hao] Xian Univ Posts & Telecommun, Sch Comp Sci & Technol, Xian 710121, Shaanxi, Peoples R China.
C3 Xi'an University of Posts & Telecommunications
RP Tuo, SH (通讯作者)，Xian Univ Posts & Telecommun, Sch Comp Sci & Technol, Xian 710121, Shaanxi, Peoples R China.
EM tuo_sh@126.com
OI ShouHeng, Tuo/0000-0002-6696-0085
FU Natural Science Foundation of China [61571341]; Ministry of Education of
   Humanities and Social Science Project of China [19YJCZH148]
FX This work was partially supported by the Natural Science Foundation of
   China [61571341]; and the Ministry of Education of Humanities and Social
   Science Project of China [19YJCZH148].
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NR 53
TC 12
Z9 12
U1 5
U2 17
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 AUG 15
PY 2020
VL 36
IS 16
BP 4389
EP 4398
DI 10.1093/bioinformatics/btaa215
PG 10
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 PQ8LE
UT WOS:000606794200002
PM 32227192
OA Bronze
DA 2022-11-30
ER

PT J
AU Chistyakov, DV
   Baksheeva, VE
   Tiulina, VV
   Goriainov, SV
   Azbukina, NV
   Gancharova, OS
   Arifulin, EA
   Komarov, SV
   Chistyakov, VV
   Tikhomirova, NK
   Zamyatnin, AA
   Philippov, PP
   Senin, II
   Sergeeva, MG
   Zernii, EY
AF Chistyakov, Dmitry, V
   Baksheeva, Viktoriia E.
   Tiulina, Veronika V.
   Goriainov, Sergei, V
   Azbukina, Nadezhda, V
   Gancharova, Olga S.
   Arifulin, Eugene A.
   Komarov, Sergey, V
   Chistyakov, Viktor V.
   Tikhomirova, Natalia K.
   Zamyatnin, Andrey A., Jr.
   Philippov, Pavel P.
   Senin, Ivan I.
   Sergeeva, Marina G.
   Zernii, Evgeni Yu
TI Mechanisms and Treatment of Light-Induced Retinal
   Degeneration-Associated Inflammation: Insights from Biochemical
   Profiling of the Aqueous Humor
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE ocular inflammation; light-induced retinal damage; age-related macular
   degeneration; oxidative stress; polyunsaturated fatty acids; oxylipins;
   mitochondria-targeted antioxidant; SkQ1; non-steroidal anti-inflammatory
   drugs; Nepafenac
ID PLATELET-ACTIVATING-FACTOR; MACULAR DEGENERATION; ANTIOXIDANT CAPACITY;
   OCULAR INFLAMMATION; LIPID-PEROXIDATION; OXIDATIVE STRESS;
   VITREOUS-HUMOR; EYE; NEPAFENAC; RELEASE
AB Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.
C1 [Chistyakov, Dmitry, V; Baksheeva, Viktoriia E.; Tiulina, Veronika V.; Gancharova, Olga S.; Arifulin, Eugene A.; Tikhomirova, Natalia K.; Zamyatnin, Andrey A., Jr.; Philippov, Pavel P.; Senin, Ivan I.; Sergeeva, Marina G.; Zernii, Evgeni Yu] Lomonosov Moscow State Univ, Belozersky Inst Phys Chem Biol, Moscow 119992, Russia.
   [Tiulina, Veronika V.; Komarov, Sergey, V] Skryabin Moscow State Acad Vet Med & Biotechnol, Moscow 109472, Russia.
   [Goriainov, Sergei, V; Chistyakov, Viktor V.] SREC PFUR Peoples Friendship Univ Russia, RUDN Univ, Moscow 117198, Russia.
   [Azbukina, Nadezhda, V; Gancharova, Olga S.] Moscow Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119234, Russia.
   [Zamyatnin, Andrey A., Jr.; Zernii, Evgeni Yu] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
C3 Lomonosov Moscow State University; Moscow State Academy of Veterinary
   Medicine & Biotechnology named after K.I. Skryabin; Peoples Friendship
   University of Russia; Lomonosov Moscow State University; Sechenov First
   Moscow State Medical University
RP Chistyakov, DV; Zernii, EY (通讯作者)，Lomonosov Moscow State Univ, Belozersky Inst Phys Chem Biol, Moscow 119992, Russia.; Zernii, EY (通讯作者)，Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
EM chistyakof@gmail.com; vbaksheeva@belozersky.msu.ru;
   tyulina_nika@list.ru; goryainovs@list.ru; ridernadya@gmail.com;
   olgancharova@belozersky.msu.ru; woodruff@belozersky.msthru;
   skomarov1977@mail.ru; chistvic@gmail.com; tikhomir@belozersky.msu.ru;
   zamyat@genebee.msu.ru; ppph@belozersky.msu.ru; senin@belozersky.msu.ru;
   mg.sergeeva@gmail.com; zerni@belozersky.msu.ru
RI Zamyatnin, Andrey A./D-6443-2012; Viktoriia, Baksheeva E/Q-8035-2018;
   Sergeeva, Marina/G-3439-2012; Baksheeva, Viktoriia/AAO-3153-2020;
   Azbukina, Nadezhda/AAN-9006-2020; Zernii, Evgeni Yu./D-9446-2012;
   Chistyakov, Dmitry V/B-6025-2015; Goriainov, Sergei/AAN-4514-2020;
   Gancharova, Olga S/M-9980-2014
OI Zamyatnin, Andrey A./0000-0002-3046-4565; Baksheeva,
   Viktoriia/0000-0002-0445-2667; Azbukina, Nadezhda/0000-0002-2546-2418;
   Zernii, Evgeni Yu./0000-0002-3013-7863; Chistyakov, Dmitry
   V/0000-0003-0137-8585; Goriainov, Sergei/0000-0002-7625-9110;
   Gancharova, Olga S/0000-0001-7441-1062
FU RUSSIAN SCIENCE FOUNDATION [16-15-00255]; Russian Science Foundation
   [19-15-11014] Funding Source: Russian Science Foundation
FX This research was funded by the RUSSIAN SCIENCE FOUNDATION, grant number
   16-15-00255.
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Z9 6
U1 2
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD FEB
PY 2020
VL 21
IS 3
AR 704
DI 10.3390/ijms21030704
PG 23
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KY4PQ
UT WOS:000522551600018
PM 31973128
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhou, B
   Mitchell, TC
   Rusakevich, AM
   Brown, DM
   Wykoff, CC
AF Zhou, Brenda
   Mitchell, Travis C.
   Rusakevich, Alexander M.
   Brown, David M.
   Wykoff, Charles C.
TI Noncompliance in Prospective Retina Clinical Trials: Analysis of Factors
   Predicting Loss to Follow-up
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; VEIN OCCLUSION; PATIENT ADHERENCE; RANIBIZUMAB;
   NONADHERENCE; AFLIBERCEPT; CARE; BARRIERS; OUTCOMES; LASER
AB PURPOSE: Noncompliance during prospective studies can bias results and limit conclusions. The current study retrospectively investigated the relationship between study subject characteristics and rates of noncompliance in interventional trials involving common causes of blindness.
   DESIGN: Retrospective analysis of 10 randomized clinical trials.
   METHODS: Subjects were enrolled in investigatorinitiated trials studying proliferative diabetic retinopathy, neovascular age-related macular degeneration, diabetic macular edema, and retinal venous occlusive disease. Records were reviewed for hypothesized risk factors of noncompliance and rates of noncompliance, which were defined as at least 1 missed visit or exiting the study early. Demographic information, systemic medical history, and ocular medical history, including visual acuity and central retinal thicknesses, were examined retrospectively using Student t test, Pearson chi(2) test, and logistic regression.
   RESULTS: Of 390 subjects included, 212 (54.4%) were compliant with all scheduled study visits and 178 (45.6%) met criteria for noncompliance, with 53 (13.6%) subjects exiting early. Regression models identified 17 variables that were significant in determining subject noncompliance. Among those, distance, comorbidities, diabetic status, concomitant medications, previous clinic visits, length of study, disease under study, and severe adverse events were highly significant risk factors of noncompliance.
   CONCLUSION: The current research identified a substantial proportion of subjects who met the criteria for noncompliance within the trials analyzed. The factors identified in the current work are consistent with published clinical observations and the results of previous clinical trials. These results highlight the importance of considering study design and medical history when designing prospective clinical trials in an attempt to minimize data loss. (C) 2019 Elsevier Inc. All rights reserved.
C1 [Zhou, Brenda; Rusakevich, Alexander M.; Brown, David M.; Wykoff, Charles C.] Retina Consultants Houston, 6560 Fannin St,Suite 750, Houston, TX 77030 USA.
   [Mitchell, Travis C.] Baylor Coll Med, Houston, TX 77030 USA.
   [Brown, David M.; Wykoff, Charles C.] Houston Methodist Hosp, Blanton Eye Inst, Houston, TX 77030 USA.
C3 Baylor College of Medicine; The Methodist Hospital System; The Methodist
   Hospital - Houston
RP Wykoff, CC (通讯作者)，Retina Consultants Houston, 6560 Fannin St,Suite 750, Houston, TX 77030 USA.
EM ccwmd@houstonretina.com
OI Zhou, Brenda/0000-0002-9532-0570; Rusakevich,
   Alexander/0000-0002-0217-3330
CR Blackburn DF, 2013, PATIENT PREFER ADHER, V7, P183, DOI 10.2147/PPA.S30613
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NR 42
TC 7
Z9 8
U1 0
U2 1
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 FEB
PY 2020
VL 210
BP 86
EP 96
DI 10.1016/j.ajo.2019.10.012
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KJ7CQ
UT WOS:000512216200012
PM 31647931
DA 2022-11-30
ER

PT J
AU Chan, CM
   Hsiao, CY
   Li, HJ
   Fang, JY
   Chang, DC
   Hung, CF
AF Chan, Chi-Ming
   Hsiao, Chien-Yu
   Li, Hsin-Ju
   Fang, Jia-You
   Chang, Der-Chen
   Hung, Chi-Feng
TI The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell
   Migration in Choroid-Retina Endothelial Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE gold nanoparticles (AuNPs); vascular endothelial growth factor (VEGF);
   cell migration; Akt; endothelial nitric oxide synthase (eNOS); choroidal
   and retinal neovascularization
ID GROWTH-FACTOR; ANGIOGENESIS; NEOVASCULARIZATION; EXPRESSION; ADHESION;
   PATHWAY; SILVER; VIEW
AB Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. Methods: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. Results: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. Conclusions: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin.
C1 [Chan, Chi-Ming; Li, Hsin-Ju; Hung, Chi-Feng] Fu Jen Catholic Univ, Sch Med, New Taipei 24205, Taiwan.
   [Chan, Chi-Ming] Cardinal Tien Hosp, Dept Ophthalmol, New Taipei 23148, Taiwan.
   [Hsiao, Chien-Yu] Chang Gung Univ Sci & Technol, Dept Nutr & Hlth Sci, Res Ctr Food & Cosmet Safety, Taoyuan 33303, Taiwan.
   [Hsiao, Chien-Yu] Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Coll Human Ecol, Taoyuan 33303, Taiwan.
   [Hsiao, Chien-Yu] Chang Gung Mem Hosp, Dept Dermatol, Aesthet Med Ctr, Taoyuan 33305, Taiwan.
   [Fang, Jia-You] Chang Gung Univ, Grad Inst Nat Prod, Pharmaceut Lab, Taoyuan 33303, Taiwan.
   [Chang, Der-Chen] Georgetown Univ, Dept Math & Stat, Washington, DC 20057 USA.
   [Chang, Der-Chen] Georgetown Univ, Dept Comp Sci, Washington, DC 20057 USA.
   [Hung, Chi-Feng] Fu Jen Catholic Univ, PhD Program Pharmaceut Biotechnol, New Taipei 24205, Taiwan.
   [Hung, Chi-Feng] Fu Jen Catholic Univ, MS Program Transdisciplinary Long Term Care, New Taipei 24205, Taiwan.
C3 Fu Jen Catholic University; Chang Gung University of Science &
   Technology; Chang Gung University of Science & Technology; Chang Gung
   Memorial Hospital; Chang Gung University; Georgetown University;
   Georgetown University; Fu Jen Catholic University; Fu Jen Catholic
   University
RP Hung, CF (通讯作者)，Fu Jen Catholic Univ, Sch Med, New Taipei 24205, Taiwan.; Hung, CF (通讯作者)，Fu Jen Catholic Univ, PhD Program Pharmaceut Biotechnol, New Taipei 24205, Taiwan.; Hung, CF (通讯作者)，Fu Jen Catholic Univ, MS Program Transdisciplinary Long Term Care, New Taipei 24205, Taiwan.
EM chancm@mail.fju.edu.tw; mozart@gw.cgust.edu.tw; sakumanatsumi@gmail.com;
   fajy@mail.cgu.edu.tw; Chang@georgetown.edu; skin@mail.fju.edu.tw
RI Hung, Chi-Feng/AAL-4977-2021; Chan, Chi-Ming/GWZ-3612-2022
OI Hung, Chi-Feng/0000-0003-3478-5451; 
FU National Science Council; Cardinal Tien Hospital, Taipei, Taiwan
   [CTH-102-1-2A30, CTH-104-1-2B05]; United States National Science
   Foundation [DMS-1408839]; McDevitt Endowment Fund at Georgetown
   University
FX This work was supported by the research grants from the National Science
   Council and from Cardinal Tien Hospital, Taipei, Taiwan (CTH-102-1-2A30,
   CTH-104-1-2B05). The fourth author is partially supported by an United
   States National Science Foundation grant DMS-1408839 and a McDevitt
   Endowment Fund at Georgetown University.
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NR 54
TC 16
Z9 16
U1 1
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JAN 1
PY 2020
VL 21
IS 1
AR 109
DI 10.3390/ijms21010109
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KO2KF
UT WOS:000515378000109
PM 31877924
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Fiess, A
   Schuster, AKG
   Nickels, S
   Elflein, HM
   Schulz, A
   Beutel, ME
   Blettner, M
   Pfeiffer, N
AF Fiess, Achim
   Schuster, Alexander Karl-Georg
   Nickels, Stefan
   Elflein, Heike M.
   Schulz, Andreas
   Beutel, Manfred E.
   Blettner, Maria
   Pfeiffer, Norbert
TI Association of low birth weight with myopic refractive error and lower
   visual acuity in adulthood: results from the population-based Gutenberg
   Health Study (GHS)
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PREMATURELY BORN CHILDREN; TERM-FOLLOW-UP; 1ST 10 YEARS; DEVELOPMENTAL
   ORIGINS; PRETERM INFANTS; EYE SIZE; GROWTH; LIFE; AGE; EPIDEMIOLOGY
AB Purpose Low birth weight (BW) is linked to impaired organ development in childhood, including altered ocular morphological and functional development. The aim of this study was to evaluate whether low BW has longterm effects on visual acuity and refraction in adulthood.
   Methods The Gutenberg Health Study is a populationbased, observational cohort study in Germany, including 15 010 participants aged between 35 and 74 years. These participants were divided into three different BW groups (low: < 2500 g; normal: between 2500 and 4000 g; and high: > 4000 g). Best-corrected visual acuity and objective refraction were examined. We used multivariable linear regression models with adjustment for age, sex, socioeconomic status and self-reported glaucoma, age-related macular degeneration, corneal disease and cataract to assess associations between BW and the main outcome measures, best-corrected visual acuity, spherical equivalent and astigmatism.
   Results Overall, 8369 participants reported their BW. In a multivariable analysis, an association for low BW with spherical equivalent (B=-0.28 per dioptre, P=0.005) and best-corrected visual acuity (B=0.02 logarithm of the minimum angle of resolution, P=0.006) compared with normal BW was observed. For participants with high BW, an association was observed with spherical equivalent (B=0.29 per dioptre, P< 0.001), while none with visual acuity.
   Conclusions Our data demonstrated that low BW is linked to visual acuity and refractive long-term outcomes long after childhood. Individuals with low BW are more likely to have lower visual acuity and a higher myopic refractive error in adulthood. Adults with high BW are more likely to have a more hyperopic refractive error.
C1 [Fiess, Achim; Schuster, Alexander Karl-Georg; Nickels, Stefan; Elflein, Heike M.; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany.
   [Schulz, Andreas] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Prevent Cardiol & Prevent Med, Mainz, Germany.
   [Beutel, Manfred E.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Psychosomat Med & Psychotherapy, Mainz, Germany.
   [Blettner, Maria] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat, Mainz, Germany.
C3 Johannes Gutenberg University of Mainz; Johannes Gutenberg University of
   Mainz; Johannes Gutenberg University of Mainz; Johannes Gutenberg
   University of Mainz
RP Fiess, A (通讯作者)，Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany.
EM achim.fiess@gmail.com
RI Pfeiffer, Norbert/AAO-7586-2020
FU government of Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur
   Innovation') [AZ 961-386261/733]; research programme 'Center for
   Translational Vascular Biology (CTVB)' of the Johannes
   Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical
   Systems; research programme 'Wissen schafft Zukunft'
FX The Gutenberg Health Study is funded through the government of
   Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur Innovation',
   contract AZ 961-386261/733), the research programmes 'Wissen schafft
   Zukunft' and 'Center for Translational Vascular Biology (CTVB)' of the
   Johannes Gutenberg-University of Mainz, and its contract with Boehringer
   Ingelheim and PHILIPS Medical Systems, including an unrestricted grant
   for the Gutenberg Health Study.
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NR 45
TC 23
Z9 23
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 JAN
PY 2019
VL 103
IS 1
BP 99
EP 105
DI 10.1136/bjophthalmol-2017-311774
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IC9BI
UT WOS:000471275800017
PM 29545415
DA 2022-11-30
ER

PT J
AU Dolz-Marco, R
   Balaratnasingam, C
   Gattoussi, S
   Ahn, S
   Yannuzzi, LA
   Freund, KB
AF Dolz-Marco, Rosa
   Balaratnasingam, Chandrakumar
   Gattoussi, Sarra
   Ahn, Seungjun
   Yannuzzi, Lawrence A.
   Freund, K. Bailey
TI Long-term Choroidal Thickness Changes in Eyes With Drusenoid Pigment
   Epithelium Detachment
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; DIURNAL-VARIATION;
   CHORIOCAPILLARIS; RPE; VOLUME
AB PURPOSE: To analyze the changes in visual acuity and subfoveal choroidal thickness in patients with non-neovascular age -related macular degeneration (AMD) and drusenoid pigment epithelium detachments (PED).
   DESIGN: Consecutive observational case series.
   METHODS: Observational retrospective review of eyes diagnosed with drusenoid PED in a single clinical setting. Demographic and clinical data included age, sex, laterality, best-corrected visual acuity (BCVA), and subfoveal choroidal thickness measured at baseline. before and after the collapse of the PED, and at the last available follow-up. The presence of geographic atrophy (GA) was also assessed.
   RESULTS: Thirty-seven eyes of 25 patients (18 female) were included in the analysis. Mean age at baseline was 71 +/- 8.4 years. During a mean follow-up period of 4.9 +/- 1.9 years, PED collapse was observed in 25 eyes (68%). Mean BCVA, mean maximum PED height, and mean subfoveal choroidal thickness significantly decreased from baseline to the last available follow-up (P < .001) in patients showing PED collapse. Choroidal thinning was faster during the PED collapse (speed rate of 35.9 mu m/year). From those, 23 eyes (92%) developed GA. A significant correlation between the area of GA and the decrease in choroidal thickness was found (P = .010).
   CONCLUSIONS: Choroidal thickness significantly decreased in eyes showing drusenoid PED collapse, but not in eyes in which the PED persisted. A significant correlation with resultant GA area following PED collapse and the magnitude of choroidal thinning was found. Further studies are warranted to better understand the mechanisms involved in the occurrence of choroidal changes during the life cycle of drusenoid PEDs. (C) 2018 Elsevier Inc. All rights reserved.
C1 [Dolz-Marco, Rosa; Balaratnasingam, Chandrakumar; Gattoussi, Sarra; Yannuzzi, Lawrence A.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
   [Dolz-Marco, Rosa; Balaratnasingam, Chandrakumar; Gattoussi, Sarra; Yannuzzi, Lawrence A.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Dolz-Marco, Rosa] Oftalvist Clin, Unit Macula, Valencia, Spain.
   [Balaratnasingam, Chandrakumar] Univ Western Australia, Lions Eye Inst, Dept Physiol & Pharmacol, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia.
   [Balaratnasingam, Chandrakumar] Sir Charles Gairdner Hosp, Dept Ophthalmol, Perth, WA, Australia.
   [Gattoussi, Sarra] Bordeaux Hosp, Dept Ophthalmol, Bordeaux, France.
   [Ahn, Seungjun] Columbia Univ, Med Ctr, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
   [Ahn, Seungjun] Northwell Hlth, Feinstein Inst Med Res, Biostat Unit, Great Neck, NY USA.
   [Freund, K. Bailey] Columbia Univ Coll Phys & Surg, Edward S Harkness Eye Inst, Dept Ophthalmol, 630 W 168th St, New York, NY 10032 USA.
   [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital; Lions Eye Institute; University of Western Australia;
   University of Western Australia; CHU Bordeaux; Columbia University;
   Northwell Health; Columbia University; New York University
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA.
EM kbfnyf@aol.com
RI ; Freund, K. Bailey/V-7488-2018
OI Gattoussi, Sarra/0000-0002-8905-7112; Freund, K.
   Bailey/0000-0002-7888-9773
FU LUESTHER T. MERTZ RETINAL RESEARCH CENTER, MANHATTAN EYE, Ear, and
   Throat Hospital, New York, New York; Macula Foundation Inc, New York,
   New York
FX THIS WORK WAS SUPPORTED BY THE LUESTHER T. MERTZ RETINAL RESEARCH
   CENTER, MANHATTAN EYE, Ear, and Throat Hospital, New York, New York, and
   The Macula Foundation Inc, New York, New York. The funding organizations
   had no role in the design or execution of this research.
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NR 36
TC 9
Z9 9
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
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUL
PY 2018
VL 191
BP 23
EP 33
DI 10.1016/j.ajo.2018.03.038
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GL7MX
UT WOS:000437387100009
PM 29621509
DA 2022-11-30
ER

PT J
AU Soomro, T
   Talks, J
AF Soomro, T.
   Talks, J.
TI The use of optical coherence tomography angiography for detecting
   choroidal neovascularization, compared to standard multimodal imaging
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; FLUORESCEIN ANGIOGRAPHY; OCT ANGIOGRAPHY; SUBTYPES
AB Purpose To assess OCT angiography (OCTA) effectiveness at detecting choroidal neovascularization (CNV) in cases of suspected neovascular age related macular degeneration (nAMD), chronic central serous retinopathy (cCSR) and pathological myopia compared to FFA and how it compares to a multimodal approach (OCT, FFA and ICGA) for detecting the vascular network.
   Methods This was a retrospective observational cohort study of patients who had clinical and/or OCT findings suggestive of CNV, having further investigation with FFA, with or without ICG, and had same day OCTA using the Heidelberg Spectralis OCT2 beta angiography module. Multimodal imaging interpretation was compared to OCTA images. OCTA images were also analysed for inter-rater reliability (using kappa statistic). The diagnostic accuracy of OCTA was compared to FFA (using Cochran's Q, po0.05). OCTA was also compared to a multimodal approach in defining a vascular network.
   Results Overall sensitivity of OCTA compared to FFA was 71% and specificity of 81% (p= 0.108). Subgroup analysis for OCTA vs FFA for detecting classic nAMD/type II CNV sensitivity was 100% and specificity of 76% (po0.05). OCTA vs FFA for detecting occult nAMD/type-I CNV sensitivity was 47% and specificity of 76%, (p= 0.248). OCTA was better than FFA at defining a vascular network overall, when OCT was suspicious (59% vs 49%).
   Conclusions OCTA was better at detecting classic nAMD/type II CNV compared to FFA and for defining a vascular network in nAMD compared to FFA and ICGA. It was able to aid in making the diagnosis in cases where evidence of CNV was uncertain following FFA/ICGA.
C1 [Soomro, T.; Talks, J.] Royal Victoria Infirm, Newcastle Eye Ctr, Ophthalmol Dept, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
C3 Newcastle University - UK
RP Soomro, T (通讯作者)，Royal Victoria Infirm, Newcastle Eye Ctr, Ophthalmol Dept, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM tnsoomro@gmail.com
OI Talks, James/0000-0001-6126-6476
FU Heidelberg engineering; Bayer
FX Heidelberg engineering and Bayer provided sponsorship to attend
   conferences. Heidelberg engineering gave access to the Heidelberg OCT
   angiography beta software module.
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NR 23
TC 29
Z9 31
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD APR
PY 2018
VL 32
IS 4
BP 662
EP 672
DI 10.1038/eye.2018.2
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GD0XL
UT WOS:000430224300001
PM 29600987
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Arnaoutoglou, NA
   Arnaoutoglou, M
   Nemtsas, P
   Costa, V
   Baloyannis, SJ
   Ebmeier, KP
AF Arnaoutoglou, N. A.
   Arnaoutoglou, M.
   Nemtsas, P.
   Costa, V.
   Baloyannis, S. J.
   Ebmeier, K. P.
TI Color perception differentiates Alzheimer's Disease (AD) from Vascular
   Dementia (VaD) patients
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Article
DE dementia; Alzheimer's Disease (AD); Vascular Dementia (VaD);
   neuropsychological testing; screening
ID MILD COGNITIVE IMPAIRMENT; DIAGNOSTIC-CRITERIA; TASK; PERFORMANCE; BETA;
   EYE
AB Background:Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003).
   Methods:Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on DS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: Ishihara Color Vision Test - 38 Plate.
   Results:The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used.
   Conclusions:Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.
C1 [Arnaoutoglou, N. A.; Ebmeier, K. P.] Univ Oxford, Dept Psychiat, Oxford, England.
   [Arnaoutoglou, M.; Nemtsas, P.; Costa, V.; Baloyannis, S. J.] Aristotle Univ Thessaloniki, AHEPA Hosp, Dept Neurol 1, Thessaloniki, Greece.
C3 University of Oxford; Aristotle University of Thessaloniki; Ahepa
   University Hospital
RP Arnaoutoglou, NA (通讯作者)，Univ Oxford, Warneford Hosp, Dept Psychiat, Warneford Ln, Oxford OX3 7JX, England.
EM nikitas.arnaoutoglou@psych.ox.ac.uk
RI Ebmeier, Klaus Peter/B-4789-2008; J.Baloyannis, Stavros/V-2478-2017;
   Arnaoutoglou, Nikitas/Q-8921-2018
OI Ebmeier, Klaus Peter/0000-0002-5190-7038; J.Baloyannis,
   Stavros/0000-0002-6865-1075; Arnaoutoglou, Nikitas/0000-0003-0840-271X;
   Arnaoutoglou, Marianthi/0000-0001-6476-2651
FU Greek Scholarship Foundation, PhD research project [4893]
FX Dr Arnaoutoglou N.A. was supported by the Greek Scholarship Foundation
   (4893), as part of a PhD research project. The funders had no role in
   the design of the study, the collection, the analysis, and
   interpretation of data.
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NR 44
TC 11
Z9 12
U1 0
U2 25
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
EI 1741-203X
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD AUG
PY 2017
VL 29
IS 8
BP 1355
EP 1361
DI 10.1017/S1041610217000096
PG 7
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
   Psychology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA FA1JG
UT WOS:000405195000013
PM 28325166
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Telegina, DV
   Korbolina, EE
   Ershov, NI
   Kolosova, NG
   Kozhevnikova, OS
AF Telegina, Darya V.
   Korbolina, Elena E.
   Ershov, Nikita I.
   Kolosova, Nataliya G.
   Kozhevnikova, Oyuna S.
TI Identification of functional networks associated with cell death in the
   retina of OXYS rats during the development of retinopathy
SO CELL CYCLE
LA English
DT Article
DE aging; apoptosis; age-related macular degeneration; cell death; OXYS
   rats; retinal transcriptome; RNA-Seq
ID AMD-LIKE RETINOPATHY; MACULAR DEGENERATION; NEURONAL APOPTOSIS;
   ALZHEIMERS-DISEASE; MITOTIC ARREST; DNA-REPAIR; PHOSPHORYLATION;
   PATHWAY; ALPHA; NEURODEGENERATION
AB Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the molecular pathogenesis of early events in AMD is poorly understood. Senescence-accelerated OXYS rats develop AMD-like retinopathy. The aim of this study was to explore the differences in retinal gene expression between OXYS and Wistar (control) rats at age 20d and to identify the pathways of retinal cell death involved in the OXYS retinopathy initiation and progression. Retinal mRNA profiles of 20-day-old OXYS and Wistar rats were generated at the sequencing read depth 40 mln, in triplicate, using Illumina GAIIx. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay was performed to measure the apoptosis level. GeneMANIA was used to construct interaction networks for differentially expressed (DE) apoptosis-related genes at ages 20d and 3 and 18months. Functional analysis was suggestive of a developmental process, signal transduction, and cell differentiation as the most enriched biological processes among 245 DE genes at age 20d An increased level of apoptosis was observed in OXYS rats at age 20d but not at advanced stages. We identified functional clusters in the constructed interaction networks and possible hub genes (Rasa1, cFLAR, Birc3, Cdk1, Hspa1b, Erbb3, and Ntf3). We also demonstrated the significance of the extrinsic apoptotic pathway at preclinical, early, and advanced stages of retinopathy development. Besides the cell death signaling pathways, immune system-related processes and lipid-metabolic processes showed overrepresentation in the clusters of all networks. These characteristics of the expression profile of the genes functionally associated with apoptosis may contribute to the pathogenesis of AMD-like retinopathy in senescence-accelerated OXYS rats.
C1 [Telegina, Darya V.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Nataliya G.; Kozhevnikova, Oyuna S.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Kolosova, Nataliya G.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB
   RAS; Novosibirsk State University
RP Telegina, DV (通讯作者)，Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
EM gorislavna@mail.ru
RI Telegina, Darya/AAQ-6062-2020; Kolosova, Nataliya G/P-3178-2015;
   Kozhevnikova, Oyuna S./H-3588-2016; Kolosova, Nataliya G/AAR-7409-2020;
   Ershov, Nikita/F-7484-2017
OI Telegina, Darya/0000-0001-8096-0519; Kolosova, Nataliya
   G/0000-0003-2398-8544; Kozhevnikova, Oyuna S./0000-0001-6475-4061;
   Kolosova, Nataliya G/0000-0003-2398-8544; Ershov,
   Nikita/0000-0003-3423-3497
FU Russian Foundation for Basic Research [15-04-02195A]; government of the
   Russian Federation [2012-220-03-435, 14.B25.31.0033]
FX This work was supported by the Russian Foundation for Basic Research
   (project # 15-04-02195A) and by grants from the government of the
   Russian Federation ## 2012-220-03-435 and 14.B25.31.0033.
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NR 54
TC 21
Z9 24
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD NOV 17
PY 2015
VL 14
IS 22
BP 3544
EP 3556
DI 10.1080/15384101.2015.1080399
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA CY3PV
UT WOS:000366322900012
PM 26440064
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Shen, WY
   Lee, SR
   Araujo, J
   Chung, SH
   Zhu, L
   Gillies, MC
AF Shen, Weiyong
   Lee, So-Ra
   Araujo, Joana
   Chung, Sook H.
   Zhu, Ling
   Gillies, Mark C.
TI Effect of glucocorticoids on neuronal and vascular pathology in a
   transgenic model of selective Muller cell ablation
SO GLIA
LA English
DT Article
DE neuroprotection; glucocorticoids; retina; photoreceptor; Muller cell;
   blood retinal barrier; microglia
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; ACTIVATED
   PROTEIN-KINASE; INTRAVITREAL TRIAMCINOLONE; PHOTORECEPTOR APOPTOSIS;
   DEPENDENT DEATH; MESSENGER-RNA; TNF-ALPHA; EXPRESSION; MICROGLIA
AB Retinal diseases such as macular telangiectasis type 2 (MacTel), age-related macular degeneration (AMD) and diabetic retinopathy (DR) affect both neurons and blood vessels. Treatments addressing both at the same time might have advantages over more specific approaches, such as vascular endothelial growth factor (VEGF) inhibitors, which are used to treat vascular leak but are suspected to have a neurotoxic effect. Here, we studied the effects of an intravitreal injection of triamcinolone acetonide (TA) in a transgenic model in which patchy Muller cell ablation leads to photoreceptor degeneration, vascular leak, and intraretinal neovascularization. TA was injected 4 days before Muller cell ablation. Changes in photoreceptors, microglia and Muller cells, retinal vasculature, differential expression of p75 neurotrophin receptor (p75(NTR)), tumor necrosis factor-alpha (TNF alpha), the precursor and mature forms of neurotrophin 3 (pro-NT3 and mature NT3) and activation of the p53 and p38 stress-activated protein kinase (p38/SAPK) signaling pathways were examined. We found that TA prevented photoreceptor degeneration and inhibited activation of microglial and Muller cells. TA attenuated Muller cell loss and inhibited overexpression of p75(NTR), TNF alpha, pro-NT, and the activation of p53 and p38/SAPK signaling pathways. TA not only prevented the development of retinal vascular lesions but also inhibited fluorescein leakage from established vascular lesions. TA inhibited overexpression of VEGF in transgenic mice but without affecting its basal level expression in the normal retina. Our data suggest that glucocorticoid treatment may be beneficial for treatment of retinal diseases such as MacTel, AMD, and DR that affect both neurons and the vasculature. GLIA 2014;62:1110-1124
C1 [Shen, Weiyong; Lee, So-Ra; Araujo, Joana; Chung, Sook H.; Zhu, Ling; Gillies, Mark C.] Univ Sydney, Save Sight Inst, Macular Res Grp, Sydney, NSW 2000, Australia.
   [Araujo, Joana] Univ Barcelona, Fac Pharm, Inst Nanosci & Nanotechnol, Dept Phys Chem, E-08007 Barcelona, Spain.
C3 University of Sydney; University of Barcelona
RP Shen, WY (通讯作者)，Univ Sydney, Save Sight Inst, 8 Macquarie St, Sydney, NSW 2000, Australia.
EM weiyong.shen@sydney.edu.au
RI Zhu, Ling/M-3887-2013
OI Zhu, Ling/0000-0003-0776-1630
FU Lowy Medical Research Institute; National Health and Medical Research
   Council [APP1028393, APP1050373]; Ophthalmic Research Institute of
   Australia; Sydney Medical School Foundation
FX Grant sponsor: Lowy Medical Research Institute; Grant sponsor: National
   Health and Medical Research Council; Grant number: APP1028393 and
   APP1050373; Grant sponsor: Ophthalmic Research Institute of Australia;
   Grant sponsor: Sydney Medical School Foundation.
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NR 69
TC 27
Z9 29
U1 0
U2 17
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
EI 1098-1136
J9 GLIA
JI Glia
PD JUL
PY 2014
VL 62
IS 7
BP 1110
EP 1124
DI 10.1002/glia.22666
PG 15
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA AH3DF
UT WOS:000336001100008
PM 24687761
DA 2022-11-30
ER

PT J
AU Yang, X
   Scott, HA
   Ardekani, S
   Williams, M
   Talbot, P
   Ghosh, K
AF Yang, Xiao
   Scott, Harry A.
   Ardekani, Soroush
   Williams, Monique
   Talbot, Prue
   Ghosh, Kaustabh
TI Aberrant Cell and Basement Membrane Architecture Contribute to
   Sidestream Smoke-Induced Choroidal Endothelial Dysfunction
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroid; tobacco smoke; basement membrane; cytoskeleton; endothelial
   cells; AMD
ID ANGIOGENESIS IN-VITRO; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX;
   CIGARETTE-SMOKE; LYSYL OXIDASE; VASCULAR ENDOTHELIUM; OXIDATIVE STRESS;
   TOBACCO-SMOKE; GROWTH-FACTOR; NICOTINE
AB PURPOSE. Environmental tobacco smoke (ETS) is widely regarded as a major modifiable risk factor for age-related macular degeneration (AMD). Yet, precisely how it exerts its pathologic effects is poorly understood. Since early-stage AMD is characterized by choroidal capillary loss, this study examined the effect of sidestream smoke (SS), the major component of ETS, on the viability of choroidal endothelial cells (EC), with an emphasis on the role of aberrant cell and basement membrane (BM) architecture in mediating SS-induced response.
   METHODS. Chorioretinal ECs (RF/6A) were treated with SS, and cell viability and architecture were analyzed by colorimetric assay and actin cytoskeletal organization, respectively. The structure of RF/6A EC-secreted BM was examined by immunofluorescence for collagen IV and immunoblotting for lysyl oxidase (LOX), a collagen-crosslinking enzyme. Finally, fresh RF/6A ECs were cultured on decellularized SS-treated BM to evaluate its active role in EC dysfunction.
   RESULTS. The RF/6A EC viability decreased progressively with increasing SS dose, which correlated strongly with a significant decline in actin cytoskeleton-dependent EC spreading. Sidestream smoke also caused marked disruption of the RF/6A EC-secreted BM that was accompanied by suppression of LOX expression. Further, fresh, non-SS-treated RF/6A ECs exhibited a significant loss in viability and actin cytoskeletal organization when cultured on SS-treated corrupt BM.
   CONCLUSIONS. These findings indicate that aberrant physical cues in the form of EC and BM architecture likely have an important role in choriocapillaris dysfunction seen in SS-associated early AMD and implicate choroidal BM as a potential target for AMD management strategies.
C1 [Yang, Xiao; Scott, Harry A.; Ardekani, Soroush; Ghosh, Kaustabh] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
   [Williams, Monique; Talbot, Prue] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
   [Talbot, Prue; Ghosh, Kaustabh] Univ Calif Riverside, Stem Cell Ctr, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside;
   University of California System; University of California Riverside;
   University of California System; University of California Riverside
RP Ghosh, K (通讯作者)，Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
EM kghosh@engr.ucr.edu
RI Talbot, Prue/AAY-3896-2021
FU University of California-Riverside Bourns College of Engineering
FX Supported by Initial Complement Funds provided by the University of
   California-Riverside Bourns College of Engineering.
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NR 55
TC 5
Z9 5
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 2014
VL 55
IS 5
BP 3140
EP 3147
DI 10.1167/iovs.13-13659
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AL9TP
UT WOS:000339484800041
PM 24713480
DA 2022-11-30
ER

PT J
AU Hunter, A
   Spechler, PA
   Cwanger, A
   Song, Y
   Zhang, Z
   Ying, GS
   Hunter, AK
   deZoeten, E
   Dunaief, JL
AF Hunter, Allan
   Spechler, Paul A.
   Cwanger, Alyssa
   Song, Ying
   Zhang, Zhe
   Ying, Gui-shuang
   Hunter, Anna K.
   deZoeten, Edwin
   Dunaief, Joshua L.
TI DNA Methylation Is Associated with Altered Gene Expression in AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GLUTATHIONE-S-TRANSFERASE; LARYNX CANCER-RISK; MACULAR DEGENERATION;
   OXIDATIVE STRESS; OXYGEN RADICALS; AQUEOUS-HUMOR; HUMAN RETINA;
   IN-VITRO; AGE; DAMAGE
AB PURPOSE. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Evidence suggests oxidative stress plays a role in the disease. To assess the potential contribution of epigenetic regulation of antioxidant genes relevant to AMD pathogenesis, we evaluated DNA methylation, a tissue-specific genetic modulation that affects gene expression.
   METHODS. Using the Infinium HumanMethylation27 Illumina platform, we performed DNA bisulfite sequencing to compare the methylation status in postmortem retina pigment epithelium (RPE)/choroid between patients with AMD and age-matched controls. Gene expression was assessed with the Affymetrix Exon Array. TaqMan gene expression assays were used for relative quantification (RT-PCR) confirmation of the expression array results. Glutathione S-transferase isoform mu1 (GSTM1) and mu5 (GSTM5) promoter methylation was confirmed by CpG island bisulfite pyrosequencing. To assess protein levels and localization, we used Western analysis, immunohistochemistry, and immunofluorescence with murine and human samples.
   RESULTS. The mRNA levels of GSTM1 and GSTM5 were significantly reduced in AMD versus age-matched controls in RPE/choroid and neurosensory retina (NSR), which corresponded to hypermethylation of the GSTM1 promoter. mRNA and protein levels were decreased (RPE to a greater extent than NSR) in AMD postmortem samples, irrespective of age. Immunohistochemistry and immunofluorescence confirm the presence of the enzymes in the NSR and RPE.
   CONCLUSIONS. Comparison of DNA methylation, together with mRNA levels, revealed significant differences between AMD versus normal retinas. The evidence presented suggests that GSTM1 and GSTM5 undergo epigenetic repression in AMD RPE/choroid, which may increase susceptibility to oxidative stress in AMD retinas. (Invest Ophthalmol Vis Sci. 2012;53:2089-2105) DOI:10.1167/iovs.11-8449
C1 [Hunter, Allan; Spechler, Paul A.; Cwanger, Alyssa; Song, Ying; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Zhang, Zhe; Hunter, Anna K.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
   [Ying, Gui-shuang] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
   [deZoeten, Edwin] Childrens Hosp Colorado, Denver, CO USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia;
   University of Pennsylvania; Children's Hospital Colorado
RP Hunter, A (通讯作者)，FM Kirby Ctr, Stellar Chance Labs 303, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM hunter.allan.a@gmail.com
RI Hunter, Allan/AAJ-5848-2020
FU Research to Prevent Blindness [K12 EY015398]; NATIONAL EYE INSTITUTE
   [K12EY015398] Funding Source: NIH RePORTER
FX Supported by unrestricted core grant K12 EY015398 from Research to
   Prevent Blindness.
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NR 80
TC 95
Z9 101
U1 0
U2 16
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 2089
EP 2105
DI 10.1167/iovs.11-8449
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937PC
UT WOS:000303669400046
PM 22410570
OA Green Published
DA 2022-11-30
ER

PT J
AU Charvet, C
   Liao, WL
   Heo, GY
   Laird, J
   Salomon, RG
   Turko, IV
   Pikuleva, IA
AF Charvet, Casey
   Liao, Wei-Li
   Heo, Gun-Young
   Laird, James
   Salomon, Robert G.
   Turko, Illarion V.
   Pikuleva, Irina A.
TI Isolevuglandins and Mitochondrial Enzymes in the Retina MASS
   SPECTROMETRY DETECTION OF POST-TRANSLATIONAL MODIFICATION OF
   STEROL-METABOLIZING CYP27A1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CYTOCHROME P450C27 CYP27; PROTEIN ADDUCTS;
   CEREBROTENDINOUS-XANTHOMATOSIS; MACULAR DEGENERATION;
   DENSITY-LIPOPROTEIN; ISOPROSTANE PATHWAY; LIPID-PEROXIDATION;
   LEVUGLANDIN E(2); 27-HYDROXYLASE; CHOLESTEROL
AB We report the first peptide mapping and sequencing of an in vivo isolevuglandin-modified protein. Mitochondrial cytochrome P450 27A1 (CYP27A1) is a ubiquitous multifunctional sterol C27-hydroxylase that eliminates cholesterol and likely 7-ketocholesterol from the retina and many other tissues. We investigated the post-translational modification of this protein with isolevuglandins, arachidonate oxidation products. Treatment of purified recombinant CYP27A1 with authentic iso[4]levuglandin E-2 (iso[4]LGE(2)) in vitro diminished enzyme activity in a time-and phospholipid-dependent manner. A multiple reaction monitoring protocol was then developed to identify the sites and extent of iso[4]LGE2 adduction. CYP27A1 exhibited only three Lys residues, Lys(134), Lys(358), and Lys(476), that readily interact with iso[4]LGE(2) in vitro. Such selective modification enabled the generation of an internal standard, N-15-labeled CYP27A1 modified with iso[4]LGE(2), for the subsequent analysis of a human retinal sample. Two multiple reaction monitoring transitions arising from the peptide AVLK(358)(-C20H26O3)ETLR in the retinal sample were observed that co-eluted with the corresponding two N-15 transitions from the supplemented standard. These data demonstrate that modified CYP27A1 is present in the retina. We suggest that such protein modification impairs sterol elimination and likely has other pathological sequelae. We also propose that the post-translational modifications identified in CYP27A1 exemplify a general mechanism whereby oxidative stress and inflammation deleteriously affect protein function, contributing, for example, to cholesterol-rich lesions associated with age-related macular degeneration and cardiovascular disease. The proteomic protocols developed in this study are generally applicable to characterization of lipid-derived oxidative protein modifications occurring in vivo, including proteins bound to membranes.
C1 [Turko, Illarion V.] Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA.
   [Liao, Wei-Li; Turko, Illarion V.] Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
   [Laird, James; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Charvet, Casey; Heo, Gun-Young; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 National Institute of Standards & Technology (NIST) - USA; Case Western
   Reserve University; Case Western Reserve University
RP Pikuleva, IA (通讯作者)，2085 Adelbert Rd,Rm 303, Cleveland, OH 44106 USA.
EM iap8@case.edu
RI Salomon, Robert G/C-3463-2008
OI Salomon, Robert/0000-0001-9456-3557; Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health [EY018383, AG024336, GM21249, T32
   EY007157, P30 EY11373]; NATIONAL EYE INSTITUTE [R01EY018383,
   P30EY011373, T32EY007157] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM021249] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON AGING [K02AG024336] Funding Source: NIH
   RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY018383 and AG024336 (to I. A. P.), GM21249 (to R. G.
   S.), Fellowship T32 EY007157 (to C. C.), and Core Grant P30 EY11373 (to
   Case Visual Sciences Research Center).
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NR 53
TC 18
Z9 18
U1 0
U2 11
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 10
PY 2011
VL 286
IS 23
BP 20413
EP 20422
DI 10.1074/jbc.M111.232546
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600029
PM 21498512
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Srivastava, GK
   Martin, L
   Singh, AK
   Fernandez-Bueno, I
   Gayoso, MJ
   Garcia-Gutierrez, MT
   Girotti, A
   Alonso, M
   Rodriguez-Cabello, JC
   Pastor, JC
AF Srivastava, Girish K.
   Martin, Laura
   Singh, Amar K.
   Fernandez-Bueno, Ivan
   Gayoso, Manuel J.
   Garcia-Gutierrez, Maria T.
   Girotti, Alessandra
   Alonso, Matilde
   Rodriguez-Cabello, Jose C.
   Pastor, Jose C.
TI Elastin-like recombinamers as substrates for retinal pigment epithelial
   cell growth
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE regenerative medicine; biomaterial; RPE cells; AMD; elastin-like
   recombinamers
ID MACULAR DEGENERATION; RPE; TRANSPLANTATION; TRANSDIFFERENTIATION;
   NEOVASCULARIZATION; TRANSLOCATION; TRANSITION; EXPRESSION; MATRIX;
   REPAIR
AB The aim of this study is to investigate the use of elastin-like recombinamers (ELRs) as a substrate that can maintain the growth, phenotype, and functional characteristics of retinal pigment epithelial (RPE) cells efficiently and as a suitable carrier for the transplantation of autologous RPE cells for treatment of age-related macular degeneration (AMD). ELR films containing a bioactive sequence, RGD (ELR-RGD), and one with no specific sequence (ELR-IK) as control, were obtained by solvent-casting onto glass and subsequent cross-linking. ARPE19 cells were seeded on sterilized ELR films as well as on the control surfaces. Cells were analysed after 4, 24, 72, and 120 h to study cell adhesion, proliferation, cell viability, morphology, and specificity by staining with Trypan blue, DAPI, Rhodamin-Phalloidin and RPE65, ZO-1 antibodies and observing under fluorescence as well as electron microscope. ARPE19 cells seeded on both ELR films and controls were 100% viable and maintained their morphology and set of characteristics at the different time points studied. Cell proliferation on ELR-RGD was significantly higher than that found on ELR-IK at all time points, although it was less than the growth rate on polystyrene. ARPE19 cells grow well on ELR-RGD maintaining their phenotype. These results should be extended to further studies with fresh human RPE cells and in vivo studies to determine whether this ELR-RGD matrix could be used as a Bruch's membrane prosthesis and carrier for transplantation of RPE cells in patients suffering with AMD. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 97A: 243-250, 2011.
C1 [Srivastava, Girish K.; Singh, Amar K.; Fernandez-Bueno, Ivan; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, Jose C.] Univ Valladolid, Inst Appl Ophthalmobiol IOBA, Valladolid, Spain.
   [Srivastava, Girish K.] Castilla & Leon Regenerat Med & Cell Therapy Netw, Valladolid, Spain.
   [Martin, Laura; Girotti, Alessandra; Alonso, Matilde; Rodriguez-Cabello, Jose C.] Univ Valladolid, GIR BIOFORGE Grp, CIBER BBN, Valladolid, Spain.
C3 Universidad de Valladolid; CIBER - Centro de Investigacion Biomedica en
   Red; CIBERBBN; Universidad de Valladolid
RP Srivastava, GK (通讯作者)，Univ Valladolid, Inst Appl Ophthalmobiol IOBA, Valladolid, Spain.
EM girish@ioba.med.uva.es
RI Fernandez-Bueno, Ivan/H-4201-2015; ALONSO, MATILDE/G-6719-2017; Girotti,
   Alessandra/D-4325-2012; Rodríguez-Cabello, José Carlos/G-6555-2017;
   Martin, Laura/J-9291-2017; Gayoso, Manuel J/L-7270-2017; SINGH,
   AMAR/H-6569-2016; Srivastava, Girish K/L-7608-2014; Girotti,
   Alessandra/AAA-5820-2019; Jimeno, J Carlos Pastor/AAP-1156-2020
OI Fernandez-Bueno, Ivan/0000-0003-3380-4040; ALONSO,
   MATILDE/0000-0002-6853-8427; Girotti, Alessandra/0000-0003-4754-7022;
   Rodríguez-Cabello, José Carlos/0000-0002-3438-858X; Martin,
   Laura/0000-0002-6583-8731; Gayoso, Manuel J/0000-0001-6651-8273; SINGH,
   AMAR/0000-0002-1767-5907; Srivastava, Girish K/0000-0002-9791-4057;
   Girotti, Alessandra/0000-0003-4754-7022; Jimeno, J Carlos
   Pastor/0000-0001-5934-7306
FU Castilla and Leon Regenerative Medicine and Cell Therapy Network Center;
   CIBER-BBN; AECI (Part of the Spanish Ministry of Foreign Affairs); Junta
   de Castilla-Leon; National Plan of I+D+I; Spanish Institute of Health
   Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la
   Investigacion (MICNN) [PS09/00938]
FX Contract grant sponsors: Castilla and Leon Regenerative Medicine and
   Cell Therapy Network Center, CIBER-BBN, AECI (Part of the Spanish
   Ministry of Foreign Affairs), The Junta de Castilla-Leon; Contract grant
   sponsor: National Plan of I+D+I 2008-2011 and Spanish Institute of
   Health Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento
   de la Investigacion (MICNN) with confinantiation FEDER; contract grant
   number: PS09/00938
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NR 44
TC 29
Z9 31
U1 0
U2 16
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1549-3296
EI 1552-4965
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD JUN
PY 2011
VL 97A
IS 3
BP 243
EP 250
DI 10.1002/jbm.a.33050
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 761FQ
UT WOS:000290382700003
PM 21442725
DA 2022-11-30
ER

PT J
AU Chen, LJ
   Lai, TYY
   Tam, POS
   Chiang, SWY
   Zhang, X
   Lam, S
   Lai, RYK
   Lam, DSC
   Pang, CP
AF Chen, Li Jia
   Lai, Timothy Y. Y.
   Tam, Pancy O. S.
   Chiang, Sylvia W. Y.
   Zhang, Xin
   Lam, Shi
   Lai, Ricky Y. K.
   Lam, Dennis S. C.
   Pang, Chi Pui
TI Compound Heterozygosity of Two Novel Truncation Mutations in RP1 Causing
   Autosomal Recessive Retinitis Pigmentosa
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MESSENGER-RNA DECAY; MACULAR DEGENERATION; GENE; PREVALENCE; PROTEIN;
   BLINDNESS; VARIANTS; FAMILIES; REGION; ADRP
AB PURPOSE. To evaluate the phenotypic effects of two novel frameshift mutations in the RP1 gene in a Chinese pedigree of autosomal recessive retinitis pigmentosa (ARRP).
   METHODS. Family members of a proband with ARRP were screened for RP1, RHO, NR2E3, and NRL mutations by direct sequencing. Detected RP1 mutations were genotyped in 225 control subjects. Since one family member with the RP1 deletion mutation in exon 2 was found to have age-related macular degeneration (AMD) but not RP, exons 2 and 3 of RP1 were screened in 120 patients with exudative AMD. Major AMD-associated SNPs in the HTRA1 and CFH genes were also investigated.
   RESULTS. Two novel frameshift mutations in RP1, c.5 6delGT and c. 4941_4942insT, were identified in the pedigree. They were absent in 225 control subjects. Family members who were compound heterozygous for the nonsense mutations had early-onset and severe RP, whereas those with only one mutation did not have RP. No mutations in RHO, NR2E3, and NRL were identified in the pedigree. Subject I: 2 with AMD carried both at-risk genotypes at HTRA1 rs11200638 and CFH rs800292. No mutation in RP1 exons 2 and 3 was identified in 120 AMD patients.
   CONCLUSIONS. This report is the first to associate ARRP with compound heterozygous nonsense mutations in RP1. Identification of the nonsense-mediated mRNA decay (NMD)-sensitive mutation c.5 6delGT provided further genetic evidence that haploinsufficiency of RP1 is not responsible for RP. The authors propose four classes of truncation mutations in the RP1 gene with different effects on the etiology of RP. (Invest Ophthalmol Vis Sci. 2010;51:2236-2242) DOI:10.1167/iovs.09-4437
C1 [Chen, Li Jia; Lai, Timothy Y. Y.; Tam, Pancy O. S.; Chiang, Sylvia W. Y.; Zhang, Xin; Lam, Shi; Lai, Ricky Y. K.; Lam, Dennis S. C.; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, 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, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
RI Pang, Chi P/I-5388-2014; Lai, Timothy Y Y/AAC-2120-2020; Chen, Li
   Jia/I-5078-2014; Lam, Dennis/AAL-1211-2020
OI Lai, Timothy Y Y/0000-0002-7832-6428; Chen, Li Jia/0000-0003-3500-5840; 
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NR 48
TC 41
Z9 42
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2010
VL 51
IS 4
BP 2236
EP 2242
DI 10.1167/iovs.09-4437
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 574ND
UT WOS:000275995800057
PM 19933189
DA 2022-11-30
ER

PT J
AU Kortvely, E
   Hauck, SM
   Duetsch, G
   Gloeckner, CJ
   Kremmer, E
   Alge-Priglinger, CS
   Deeg, CA
   Ueffing, M
AF Kortvely, Elod
   Hauck, Stefanie M.
   Duetsch, Gabriele
   Gloeckner, Christian J.
   Kremmer, Elisabeth
   Alge-Priglinger, Claudia S.
   Deeg, Cornelia A.
   Ueffing, Marius
TI ARMS2 Is a Constituent of the Extracellular Matrix Providing a Link
   between Familial and Sporadic Age-Related Macular Degenerations
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT COMPONENT 2; FACTOR-B BF; FACTOR-H; METALLOPROTEINASES-3
   TIMP-3; TISSUE INHIBITOR; CELL-ADHESION; ASSOCIATION; BINDING; GENE;
   PROTEINS
AB PURPOSE. SNPs in chromosomal region 10q26 harboring PLEKHA1, ARMS2, and Htra1 showed the strongest association with age-related macular degeneration. Recent evidence suggests that in patients homozygous for the risk allele, the lack of synthesis of the poorly characterized ARMS2 is causative of this disorder. The present study was undertaken to gain an understanding of the genuine (patho) physiological role of this protein.
   METHODS. ARMS2-interacting proteins were identified by using a yeast two-hybrid system and validated by coprecipitation. Immunofluorescence was applied to reveal the localization of ARMS2 in transfected cells and in human eyes. Western blot analyses were performed on extra-and intracellular fractions of ARMS2-expressing cells to demonstrate the secretion of ARMS2.
   RESULTS. Contrary to previous reports, this study showed that ARMS2 is a secreted protein that binds several matrix proteins. Notably, ARMS2 directly interacts with fibulin-6 (hemicentin-1). Mutations in the fibulin-6 gene have been demonstrated to cause familial AMD. ARMS2 also interacts with further extracellular proteins, several of which have been implicated in macular dystrophies. Although ARMS2 apparently lacks any classic targeting sequence, it is translocated to the endoplasmic reticulum in cultured cells before secretion. ARMS2 is mostly confined to choroid pillars in human eyes, representing a part of extracellular matrix and corresponding to the principal sites of drusen formation.
   CONCLUSIONS. The pivotal role of the extracellular matrix in the progression of AMD is underlined by the abnormal deposition of extracellular debris in the macula, observed frequently in affected individuals. The results have shown that ARMS2 may be necessary for proper matrix function. (Invest Ophthalmol Vis Sci. 2010; 51: 79-88) DOI: 10.1167/iovs.09-3850
C1 [Kortvely, Elod; Hauck, Stefanie M.; Duetsch, Gabriele; Gloeckner, Christian J.; Ueffing, Marius] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Dept Prot Sci, D-85764 Munich, Germany.
   [Kremmer, Elisabeth] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Mol Immunol, D-85764 Munich, Germany.
   [Duetsch, Gabriele; Ueffing, Marius] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
   [Alge-Priglinger, Claudia S.] Univ Munich, Dept Ophthalmol, Munich, Germany.
   [Deeg, Cornelia A.] Univ Munich, Dept Anim Physiol, Munich, Germany.
   [Alge-Priglinger, Claudia S.] Linz Gen Hosp, Dept Ophthalmol, Linz, Austria.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center
   for Environmental Health; Helmholtz Association; Helmholtz-Center Munich
   - German Research Center for Environmental Health; Technical University
   of Munich; University of Munich; University of Munich; Kepler University
   Hospital
RP Kortvely, E (通讯作者)，Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Dept Prot Sci, Ingolstaedter Landstr 1, D-85764 Munich, Germany.
EM eloed.koertvely@helmholtz-muenchen.de
RI Hauck, Stefanie/B-3300-2013; Deeg, Cornelia/U-4216-2019; Gloeckner,
   Christian Johannes/R-5374-2019; Deeg, Cornelia A/G-4940-2010
OI Hauck, Stefanie/0000-0002-1630-6827; Deeg, Cornelia
   A/0000-0003-0375-3190; Gloeckner, Christian Johannes/0000-0001-6494-6944
FU RETNET [MRTN-CT-2003-504003]; EVI-GENORET [LSHG-CT-2005-512036];
   Interaction Proteome [LSHGCT-2003-505520]; Deutsche
   Forschungsgemeinschaft [SFB 571 A5]
FX Supported by RETNET Grant MRTN-CT-2003-504003 (MU); EVI-GENORET
   (Functional Genomics of the Retina in Health and Disease) Grant
   LSHG-CT-2005-512036 (MU); Interaction Proteome Grant LSHGCT-2003-505520
   (MU); and Deutsche Forschungsgemeinschaft Grant SFB 571 A5 (CD).
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NR 61
TC 91
Z9 98
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 JAN
PY 2010
VL 51
IS 1
BP 79
EP 88
DI 10.1167/iovs.09-3850
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 539OI
UT WOS:000273264200013
PM 19696174
DA 2022-11-30
ER

PT J
AU Topol, EJ
   Smith, J
   Plow, EF
   Wang, QK
AF Topol, Eric J.
   Smith, Jonathan
   Plow, Edward F.
   Wang, Qing K.
TI Genetic susceptibility to myocardial infarction and coronary artery
   disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Review
ID COMPLEMENT FACTOR-H; TRANSCRIPTION FACTOR MEF2A; MACULAR DEGENERATION;
   LINKAGE ANALYSIS; HEART-DISEASE; CONFERS RISK; CARDIAC DYSFUNCTION;
   GENOMEWIDE LINKAGE; PREMATURE DEATH; PLASMA-LEVELS
AB Atherosclerotic involvement in the coronary arteries, which can result in heart attack and sudden death, is a common disease and prototypic of a complex human trait. To understand its genomic basis, eight linkage studies of sibling pairs have been performed. Although there was limited inter-study concordance of important loci, two gene variants in the leukotriene pathway (ALOX5AP and LTA4) have emerged as susceptibility factors for myocardial infarction (MI). Genome-wide association studies have also been undertaken, and the pro-inflammatory cytokine lymphotoxin-alpha (LTA), and its key ligand galectin-2 (LGALS2) have been identified as genes implicated in predisposition for heart attack. By cueing into the genomic basis for low serum LDL cholesterol levels, much work has been done to advance the importance of the serine protease PCSK9, which modulates LDL receptor function. Lifelong lowered LDL cholesterol associated with PCSK9 point mutations in 2-3% of individuals have been shown to provide marked protection from coronary artery disease (CAD). Most of the success in this field has been with the phenotype of MI, which is considerably more restrictive than CAD. Four principal and interdependent processes-lipoprotein handling, endothelial integrity, arterial inflammation, and thrombosis-have been supported as important via the clustering of genes, thus far implicated in CAD susceptibility. Of note, connecting genes in a single pathway (leukotriene), of a protein and its ligand (LTA alpha) or from one disease to another [age-related macular degeneration (AMD); complement factor H (CFH)], or even three disease characterized by inflammation (MHC2) have now been reported. Although the population attributable risk for any of the genes identified to date is limited, such discovery is likely to be accelerated in the future.
C1 Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Genet, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Mol Med, Cleveland, OH 44106 USA.
   Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA.
   Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA.
   Cleveland Clin, Lerner Res Inst, Ctr Cardiovasc Genet, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation; Case
   Western Reserve University; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation; Cleveland Clinic Foundation; Cleveland Clinic
   Foundation
RP Topol, EJ (通讯作者)，Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Genet, BRB 724,10900 Euclid Ave, Cleveland, OH 44106 USA.
EM eric.topol@case.edu
OI Topol, Eric/0000-0002-1478-4729
FU NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL077101] Funding Source:
   NIH RePORTER; NHLBI NIH HHS [P50 HL077101] Funding Source: Medline
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NR 53
TC 124
Z9 160
U1 0
U2 4
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 OCT 15
PY 2006
VL 15
SI 2
BP R117
EP R123
DI 10.1093/hmg/ddl183
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 095SX
UT WOS:000241329700003
PM 16987874
OA hybrid
DA 2022-11-30
ER

PT J
AU Kokkinou, D
   Kasper, HU
   Bartz-Schmidt, KU
   Schraermeyer, U
AF Kokkinou, D
   Kasper, HU
   Bartz-Schmidt, KU
   Schraermeyer, U
TI The pigmentation of human iris influences the uptake and storing of zinc
SO PIGMENT CELL RESEARCH
LA English
DT Article
DE age-related macular degeneration; iris pigmentation; zinc; uptake;
   storing
ID SENILE MACULAR DEGENERATION; AGE-RELATED MACULOPATHY; OCULAR MELANIN;
   DEFICIENCY; COLOR; EYE; EPITHELIUM; AFFINITY; IONS
AB Age-related macular degeneration (AMD) is more prevalent among the elderly Caucasians than in Africans. A significant association between light iris colour, fundus pigmentation and incidence of AMD is reported, suggesting a possible correlation with melanin pigment. Zinc is known to bind to melanin in pigmented tissues and to enhance antioxidant capacity by function as a cofactor or gene expression factor of antioxidant enzymes in the eye. In this in vitro study, we investigated the uptake and storage of zinc in human irides. Irides of blue and brown human eyes were used. The number of melanocytes was measured. Tissues without any treatment served as controls. The irides were incubated with 100 muM zinc chloride in culture medium for 24 h. Specimens of the tissues were stored for the uptake examination. The remained pieces were further incubated for 3 and 7 d to investigate the storage of zinc. The concentration of zinc was measured by inductively coupled plasma mass spectrometry (ICP-MS). Melanocytes count was significantly higher in the brown tissues (P < 0.0001). Zinc concentration of blue coloured irides after 24 h zinc treatment was close to the controls. We did not observe any significant storing. In contrast, the concentration of zinc in brown irides was significantly increased after 24 h (P less than or equal to 0.01) and remained at a high level for 7 d. The uptake of zinc is likely dependent on the amount of pigmentation in human iris. Therefore, we assume that in patients suffering from AMD the degree of pigmentation of the irides and eventually fundi should be under consideration when the patients are treated with zinc supplementation.
C1 Univ Tubingen, Sect Expt Vitreoretinal Surg, D-72076 Tubingen, Germany.
   Univ Cologne, Inst Geol, Geochem Lab, Cologne, Germany.
   Univ Tubingen, Dept Ophthalmol 1, Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; University of Cologne; Eberhard
   Karls University of Tubingen
RP Kokkinou, D (通讯作者)，Univ Tubingen, Sect Expt Vitreoretinal Surg, Schleichstr 12-1, D-72076 Tubingen, Germany.
EM despina.kokkinou@med.uni-tuebingen.de
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NR 36
TC 12
Z9 12
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-5785
J9 PIGM CELL RES
JI Pigm. Cell. Res.
PD OCT
PY 2004
VL 17
IS 5
BP 515
EP 518
DI 10.1111/j.1600-0749.2004.00177.x
PG 4
WC Cell Biology; Dermatology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Dermatology
GA 852IF
UT WOS:000223748300008
PM 15357838
DA 2022-11-30
ER

PT J
AU Jiang, XF
   Mahroo, OA
AF Jiang, Xiaofan
   Mahroo, Omar A.
TI Human retinal dark adaptation tracked in vivo with the
   electroretinogram: insights into processes underlying recovery of cone-
   and rod-mediated vision
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Review
DE cone photoreceptors; dark adaptation; electroretinographyy; retina;
   retinal bipolar cells; rod photoreceptors
ID A-WAVE; B-WAVE; MACULAR DEGENERATION; PIGMENT REGENERATION; LIGHT
   ADAPTATION; ISCEV STANDARD; AGE; PHOTOTRANSDUCTION; PHOTORECEPTORS;
   ACTIVATION
AB The substantial time taken for regaining visual sensitivity (dark adaptation) following bleaching exposures has been investigated for over a century. Psychophysical studies yielded the classic biphasic curve representing recovery of cone-driven and rod-driven vision. The electroretinogram (ERG) permits direct assessment of recovery at the level of the retina (photoreceptors, bipolar cells), with the first report over 70 years ago. Over the last two decades, ERG studies of dark adaptation have generated insights into underlying physiological processes. After large bleaches, rod photoreceptor circulating current, estimated from the rod-isolated bright-flash ERG a-wave, takes 30 min to recover, indicating that products of bleaching, thought to be free opsin (unbound to 11-cis-retinal), continue to activate phototransduction, shutting off rod circulating current. In contrast, cone current, assessed with cone-driven bright-flash ERG a-waves, recovers within 100 ms following similar exposures, suggesting that free opsin is less able to shut off cone current. The cone-driven dim-flash a-wave can be used to track recovery of cone photopigment, showing regeneration is 'rate-limited' rather than first order. Recoveries of the dim-flash ERG b-wave are consistent also with rate-limited rod photopigment regeneration (where free opsin, desensitising the visual system as an 'equivalent background', is removed by rate-limited delivery of 11-cis-retinal). These findings agree with psychophysical and retinal densitometry studies, although there are unexplained points of divergence. Post-bleach ERG recovery has been explored in age-related macular degeneration and in trials of visual cycle inhibitors for retinal diseases. ERG tracking of dark adaptation may prove useful in future clinical contexts.
C1 [Jiang, Xiaofan; Mahroo, Omar A.] UCL, Inst Ophthalmol, Bath St, London EC1V 9EL, England.
   [Jiang, Xiaofan; Mahroo, Omar A.] Moorfields Eye Hosp, Retinal & Genet Serv, London, England.
   [Jiang, Xiaofan; Mahroo, Omar A.] Kings Coll London, Sect Ophthalmol, London, England.
   [Jiang, Xiaofan; Mahroo, Omar A.] Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Hosp Campus, London, England.
   [Mahroo, Omar A.] Univ Cambridge, Physiol Dev & Neurosci, Cambridge, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; King's College London; University of London;
   King's College London; University of Cambridge
RP Mahroo, OA (通讯作者)，UCL, Inst Ophthalmol, Bath St, London EC1V 9EL, England.
EM o.mahroo@ucl.ac.uk
OI Mahroo, Omar/0000-0003-1254-0832
FU Wellcome Trust [206619/Z/17/Z]; Moorfields Eye Charity
FX This work was funded by the Wellcome Trust (206619/Z/17/Z) and
   Moorfields Eye Charity. The funding organisations had no role in the
   design or conduct of the research. Views expressed are those of the
   authors and not the funding organisations.
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NR 76
TC 1
Z9 1
U1 3
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
EI 1469-7793
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD NOV
PY 2022
VL 600
IS 21
BP 4603
EP 4621
DI 10.1113/JP283105
EA JUN 2022
PG 19
WC Neurosciences; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Physiology
GA 5U7IY
UT WOS:000807106800001
PM 35612091
OA Green Published
DA 2022-11-30
ER

PT J
AU Liu, YR
   Bell, BA
   Song, Y
   Zhang, K
   Anderson, B
   Axelsen, PH
   Bohannan, W
   Agbaga, MP
   Park, HG
   James, G
   Brenna, JT
   Schmidt, K
   Dunaief, JL
   Shchepinov, MS
AF Liu, Yingrui
   Bell, Brent A.
   Song, Ying
   Zhang, Kevin
   Anderson, Brandon
   Axelsen, Paul H.
   Bohannan, Whitney
   Agbaga, Martin-Paul
   Park, Hui Gyu
   James, Genevieve
   Brenna, J. Thomas
   Schmidt, Karsten
   Dunaief, Joshua L.
   Shchepinov, Mikhail S.
TI Deuterated docosahexaenoic acid protects against oxidative stress and
   geographic atrophy-like retinal degeneration in a mouse model with iron
   overload
SO AGING CELL
LA English
DT Article
DE age-related macular degeneration; deuterium; docosahexaenoic acid; iron;
   isotope effect; lipid peroxidation; oxidative stress; polyunsaturated
   fatty acid
ID POLYUNSATURATED FATTY-ACIDS; LIPID-PEROXIDATION; RETINITIS-PIGMENTOSA;
   DAMAGE; BIOMARKERS; ACCUMULATION; MITOCHONDRIA; DEATH; CELLS
AB Oxidative stress plays a central role in age-related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes. Oxidation of DHA produces toxic oxidation products including carboxyethylpyrrole (CEP) adducts, which are increased in the retinas of AMD patients. In this study, we hypothesized that deuterium substitution on the bis-allylic sites of DHA in photoreceptor membranes could prevent iron-induced retinal degeneration by inhibiting oxidative stress and lipid peroxidation. Mice were fed with either DHA deuterated at the oxidation-prone positions (D-DHA) or control natural DHA and then given an intravitreal injection of iron or control saline. Orally administered D-DHA caused a dose-dependent increase in D-DHA levels in the neural retina and retinal pigment epithelium (RPE) as measured by mass spectrometry. At 1 week after iron injection, D-DHA provided nearly complete protection against iron-induced retinal autofluorescence and retinal degeneration, as determined by in vivo imaging, electroretinography, and histology. Iron injection resulted in carboxyethylpyrrole conjugate immunoreactivity in photoreceptors and RPE in mice fed with natural DHA but not D-DHA. Quantitative PCR results were consistent with iron-induced oxidative stress, inflammation, and retinal cell death in mice fed with natural DHA but not D-DHA. Taken together, our findings suggest that DHA oxidation is central to the pathogenesis of iron-induced retinal degeneration. They also provide preclinical evidence that dosing with D-DHA could be a viable therapeutic strategy for retinal diseases involving oxidative stress.
C1 [Liu, Yingrui; Bell, Brent A.; Song, Ying; Zhang, Kevin; Anderson, Brandon; Dunaief, Joshua L.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.
   [Axelsen, Paul H.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA USA.
   [Bohannan, Whitney; Agbaga, Martin-Paul] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA.
   [Bohannan, Whitney; Agbaga, Martin-Paul] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA.
   [Bohannan, Whitney; Agbaga, Martin-Paul] Dean McGee Eye Inst, Oklahoma City, OK USA.
   [Park, Hui Gyu; James, Genevieve; Brenna, J. Thomas] Univ Texas Austin, Dell Pediat Res Inst, Austin, TX USA.
   [Schmidt, Karsten; Shchepinov, Mikhail S.] Retrotope Inc, 4300 El Camino Real, Los Altos, CA 94022 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; University of Oklahoma
   System; University of Oklahoma Health Sciences Center; University of
   Texas System; University of Texas Austin
RP Dunaief, JL (通讯作者)，Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.; Shchepinov, MS (通讯作者)，Retrotope Inc, 4300 El Camino Real, Los Altos, CA 94022 USA.
EM jdunaief@pennmedicine.upenn.edu; misha@retrotope.com
OI James, Genevieve/0000-0002-7275-7227
FU Core Grant for Vision Research [P30EY001583]; F. M. Kirby Foundation;
   Paul and Evanina Bell Mackall Foundation Trust; National Institutes of
   Health [EY015240, EY028916, AG057197, S10OD026860]; Research to Prevent
   Blindness
FX Core Grant for Vision Research, Grant/Award Number: P30EY001583; F. M.
   Kirby Foundation; Paul and Evanina Bell Mackall Foundation Trust; A gift
   in memory of Lee F. Mauger; National Institutes of Health, Grant/Award
   Number: EY015240, EY028916, AG057197 and S10OD026860; Research to
   Prevent Blindness
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NR 59
TC 4
Z9 4
U1 1
U2 4
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 APR
PY 2022
VL 21
IS 4
AR e13579
DI 10.1111/acel.13579
EA MAR 2022
PG 15
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 1X1UP
UT WOS:000765733100001
PM 35257475
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ranta-aho, S
   Piippo, N
   Korhonen, E
   Kaarniranta, K
   Hytti, M
   Kauppinen, A
AF Ranta-aho, Sofia
   Piippo, Niina
   Korhonen, Eveliina
   Kaarniranta, Kai
   Hytti, Maria
   Kauppinen, Anu
TI TAS-116, a Well-Tolerated Hsp90 Inhibitor, Prevents the Activation of
   the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE NLRP3; Hsp90; TAS-116; age-related macular degeneration; retinal pigment
   epithelium
ID 1ST-IN-HUMAN PHASE-I; SHOCK-PROTEIN 90; MACULAR DEGENERATION; REDUCES
   INFLAMMATION; THERAPEUTIC INDEX; ARPE-19; CYTOTOXICITY; DEGRADATION;
   INDUCTION; PATHWAYS
AB Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1 beta. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NLRP3 activation in human retinal pigment epithelial (RPE) cells; these are cells which play a central role in the pathogenesis of AMD. In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects, including ocular toxicity. Here, we have tested the effects of a novel Hsp90 inhibitor, TAS-116, on NLRP3 activation using geldanamycin as a reference compound. Using our existing protocol, inflammasome activation was induced in IL-1 alpha-primed ARPE-19 cells with the proteasome and autophagy inhibitors MG-132 and bafilomycin A1, respectively. Intracellular caspase-1 activity was determined using a commercial caspase-1 activity kit and the FLICA assay. The levels of IL-1 beta were measured from cell culture medium samples by ELISA. Cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) measurements. Our findings show that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1 beta. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.
C1 [Ranta-aho, Sofia; Piippo, Niina; Korhonen, Eveliina; Hytti, Maria; Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, Kuopio 70211, Finland.
   [Korhonen, Eveliina] Univ Helsinki, Helsinki Univ Hosp, Dept Clin Chem, Helsinki 00290, Finland.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio 70211, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70211, Finland.
C3 University of Eastern Finland; University of Helsinki; Helsinki
   University Central Hospital; University of Eastern Finland; Kuopio
   University Hospital; University of Eastern Finland
RP Ranta-aho, S; Kauppinen, A (通讯作者)，Univ Eastern Finland, Sch Pharm, Kuopio 70211, Finland.
EM sofia.ranta-aho@uef.fi; niina.piippo@uef.fi; eveliina.korhonen@uef.fi;
   kai.kaarniranta@kuh.fi; maria.hytti@uef.fi; anu.kauppinen@uef.fi
RI Hytti, Maria/AAE-4016-2019
OI Hytti, Maria/0000-0003-2150-6847; Ranta-aho, Sofia/0000-0001-6569-657X;
   Korhonen, Eveliina/0000-0002-5360-7258; Kaarniranta,
   Kai/0000-0003-2600-8679
FU Academy of Finland [297267, 307341, 328443, 296840, 333302]; Emil
   Aaltonen Foundation; Paivikki and Sakari Sohlberg Foundation; Finnish
   Cultural Foundation; North Savo Regional Fund
FX This research was funded by the Academy of Finland (297267, 307341,
   328443, 296840 and 333302), the Emil Aaltonen Foundation, the Paivikki
   and Sakari Sohlberg Foundation, The Finnish Cultural Foundation, and
   North Savo Regional Fund. The APC was funded by the Academy of Finland
   (328443).
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NR 58
TC 5
Z9 5
U1 1
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAY
PY 2021
VL 22
IS 9
AR 4875
DI 10.3390/ijms22094875
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA SC0MY
UT WOS:000650378200001
PM 34062977
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Beck, M
   Joshi, DS
   Berger, L
   Klose, G
   De Zanet, S
   Mosinska, A
   Apostolopoulos, S
   Ebneter, A
   Zinkernagel, MS
   Wolf, S
   Munk, MR
AF Beck, Marco
   Joshi, Devika S.
   Berger, Lieselotte
   Klose, Gerd
   De Zanet, Sandro
   Mosinska, Agata
   Apostolopoulos, Stefanos
   Ebneter, Andreas
   Zinkernagel, Martin S.
   Wolf, Sebastian
   Munk, Marion R.
TI Comparison of Drusen Volume Assessed by Two Different OCT Devices
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE optical coherence tomography; age-related macular degeneration; AMD;
   drusen; drusen volume; segmentation; retinal pigment epithelium;
   spectral-domain OCT; swept-source OCT; retinal imaging analysis;
   segmentation
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; DOMAIN;
   SEGMENTATION; REPRODUCIBILITY; QUANTIFICATION; PERFORMANCE; ATROPHY
AB To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central 1 and 3 mm ETDRS circle drusen volumes were calculated and compared. Drusen segmentation was performed using automated manufacturer algorithms of the two OCT devices. Then, the automated segmentation was manually corrected and compared and finally analyzed using customized software. Though on SD-OCT, there was a significant difference of mean drusen volume prior to and after manual correction (mean difference: 0.0188 +/- 0.0269 mm(3),p< 0.001, corr.p< 0.001, correlation of r = 0.90), there was no difference found on SS-OCT (mean difference: 0.0001 +/- 0.0003 mm(3),p= 0.262, corr.p= 0.524, r = 1.0). Heidelberg-acquired mean drusen volume after manual correction was significantly different from Zeiss-acquired drusen volume after manual correction (mean difference: 0.1231 +/- 0.0371 mm(3),p< 0.001, corr.p< 0.001, r = 0.68). Using customized software, the difference of measurements between both devices decreased and correlation among the measurements improved (mean difference: 0.0547 +/- 0.0744 mm(3),p= 0.02, corr.p= 0.08, r = 0.937). Heidelberg SD-OCT, the Zeiss PlexElite SS-OCT, and customized software all measured significantly different drusen volumes. Therefore, devices/algorithms may not be interchangeable. Third-party customized software helps to minimize differences, which may allow a pooling of data of different devices, e.g., in multicenter trials.
C1 [Beck, Marco; Joshi, Devika S.; Berger, Lieselotte; Ebneter, Andreas; Zinkernagel, Martin S.; Wolf, Sebastian; Munk, Marion R.] Univ Bern, Bern Univ Hosp, Dept Ophthalmol, Inselspital, CH-3010 Bern, Switzerland.
   [Klose, Gerd] Carl Zeiss Meditec Inc, Tokyo 1020083, Japan.
   [De Zanet, Sandro; Mosinska, Agata; Apostolopoulos, Stefanos] RetinAI Med AG, CH-3010 Bern, Switzerland.
   [Wolf, Sebastian; Munk, Marion R.] Univ Bern, Bern Univ Hosp, Bern Photog Reading Ctr, Inselspital, CH-3010 Bern, Switzerland.
C3 University of Bern; University Hospital of Bern; Carl Zeiss AG;
   University of Bern; University Hospital of Bern
RP Munk, MR (通讯作者)，Univ Bern, Bern Univ Hosp, Dept Ophthalmol, Inselspital, CH-3010 Bern, Switzerland.; Munk, MR (通讯作者)，Univ Bern, Bern Univ Hosp, Bern Photog Reading Ctr, Inselspital, CH-3010 Bern, Switzerland.
EM marco.beck@insel.ch; devika.joshi1788@gmail.com;
   lieselotteerika.berger@insel.ch; gerd.klose@zeiss.com;
   sandro@retinai.com; agata@retinai.com; stefanos@retinai.com;
   andreas.ebneter@insel.ch; martin.zinkernagel@insel.ch;
   sebastian.wolf@insel.ch; marion_munk@hotmail.com
RI Ebneter, Andreas/C-5226-2017
OI Ebneter, Andreas/0000-0001-6666-2558; Zinkernagel, Martin
   S./0000-0003-3447-2359; De Zanet, Sandro/0000-0001-8983-4295
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NR 28
TC 2
Z9 2
U1 0
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2077-0383
J9 J CLIN MED
JI J. Clin. Med.
PD AUG
PY 2020
VL 9
IS 8
AR 2657
DI 10.3390/jcm9082657
PG 11
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA NH5AI
UT WOS:000564682200001
PM 32824455
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rai, BB
   Shresthra, MK
   Thapa, R
   Essex, RW
   Paudyal, G
   Maddess, T
AF Rai, Bhim B.
   Shresthra, Mohan K.
   Thapa, Raba
   Essex, Rohan W.
   Paudyal, Govinda
   Maddess, Ted
TI Pattern and Presentation of Vitreo-Retinal Diseases: An Analysis of
   Retrospective Data at a Tertiary Eye Care Center in Nepal
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE AMD; diabetic retinopathy; retinal diseases; laterality; sex differences
ID DIABETIC-RETINOPATHY; MACULAR DEGENERATION; AVOIDABLE BLINDNESS; RETINAL
   DISEASES; RAPID ASSESSMENT; RISK-FACTORS; PREVALENCE; LECTURE; INDIA
AB Purpose: We examined patients presenting in a tertiary eye hospital in Nepal, focusing on information relevant to screening and management programs for vitreo-retinal (VR) disease.
   Design: Retrospective, cross-sectional study.
   Methods: We reviewed all patients presenting for the first time to the VR-clinic over 1 year. We quantified patient demography, symptoms and duration, systemic diseases, ophthalmological examinations, diagnostic investigations, and final diagnoses.
   Results: Of the 1905 cases, 1148 were male (60.3%). The 25th percentile of ages was 29 and 38 years for male and female, respectively; thus, female presented later (P < 0.0001). Hypertension was the commonest systemic disease (40.8%), followed by diabetes (32.5%). Age-related macular degeneration (AMD) and diabetic retinopathy (DR) affected 447 eyes (11.8%) and 416 eyes (10.9%), respectively. Male and female AMD and DR patients did not differ in age or disease duration. Similarly, age or disease duration for DR did not correlate with severity. Asymmetry of disease severity between eyes with AMD and DR was largest in patients with 1 normal eye. Presenting acuity was asymmetric between eyes (P <0.0001) with people more often reporting once their right eyes had acuity of 6/18 or worse.
   Conclusions: The screening of blood pressure and glucose levels combined with fundus photography could prevent many from progressing to life-changing visual impairment and blindness. Later reporting by females began at childbearing age; therefore, education and ocular screening could be usefully coupled in reproductive health programs. Clubbing VR disease screening with other established health programs like diabetes control program, hypertension clinics, school health program, and so on, would provide economical and sustainable approach.
C1 [Rai, Bhim B.; Maddess, Ted] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.
   [Shresthra, Mohan K.; Thapa, Raba; Paudyal, Govinda] Tilganga Inst Ophthalmol, Kathmandu 44600, Nepal.
   [Essex, Rohan W.] ANU Med Sch, ANU Acad Unit Ophthalmol, Canberra, ACT, Australia.
   [Essex, Rohan W.] Canberra Hosp, ACT Hlth, Dept Ophthalmol, Canberra, ACT, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Australian National University; Canberra
   Hospital
RP Paudyal, G (通讯作者)，Tilganga Inst Ophthalmol, Kathmandu 44600, Nepal.
EM govinda.pau-dyal@tilganga.org
RI Bahadur, Bhim/C-2972-2017; Maddess, Teddy L/A-3200-2008
OI Bahadur, Bhim/0000-0003-0748-4581; Maddess, Teddy L/0000-0003-4591-3658;
   Essex, Rohan/0000-0001-5323-0334
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NR 35
TC 4
Z9 4
U1 0
U2 1
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 NOV-DEC
PY 2019
VL 8
IS 6
BP 481
EP 488
DI 10.1097/01.APO.0000604400.50700.2d
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JT1UH
UT WOS:000500782400012
PM 31789651
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Racz, B
   Varadi, A
   Kong, J
   Allikmets, R
   Pearson, PG
   Johnson, G
   Cioffi, CL
   Petrukhin, K
AF Racz, Boglarka
   Varadi, Andras
   Kong, Jian
   Allikmets, Rando
   Pearson, Paul G.
   Johnson, Graham
   Cioffi, Christopher L.
   Petrukhin, Konstantin
TI A non-retinoid antagonist of retinol-binding protein 4 rescues phenotype
   in a model of Stargardt disease without inhibiting the visual cycle
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE drug design; drug development; drug discovery; pharmacokinetics;
   pharmacology; molecular pharmacology; retinoid-binding protein; retinal
   degeneration; retinal metabolism; retina; age-related macular
   degeneration; lipofuscin; RBP4; Stargardt disease; visual cycle
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; VITAMIN-A; COMPLEMENT
   ACTIVATION; FUNDUS AUTOFLUORESCENCE; LIPOFUSCIN ACCUMULATION; POTENTIAL
   TREATMENT; GEOGRAPHIC ATROPHY; NIGHT BLINDNESS; RPE LIPOFUSCIN
AB A primary pathological defect in the heritable eye disorder Stargardt disease is excessive accumulation of cytotoxic lipofuscin bisretinoids in the retina. Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) matches the age-dependent increase in the incidence of the atrophic (dry) form of age-related macular degeneration (AMD) and therefore may be one of several pathogenic factors contributing to AMD progression. Lipofuscin bisretinoid synthesis in the retina depends on the influx of serum retinol from the circulation into the RPE. Formation of the tertiary retinol-binding protein 4 (RBP4)-transthyretin-retinol complex in the serum is required for this influx. Herein, we report the pharmacological effects of the non-retinoid RBP4 antagonist, BPN-14136. BPN-14136 dosing in the Abca4(-/-) mouse model of increased lipofuscinogenesis significantly reduced serum RBP4 levels and inhibited bisretinoid synthesis, and this inhibition correlated with a partial reduction in visual cycle retinoids such as retinaldehydes serving as bisretinoid precursors. BPN-14136 administration at doses inducing maximal serum RBP4 reduction did not produce changes in the rate of the visual cycle, consistent with minimal changes in dark adaptation. Abca4(-/-) mice exhibited dysregulation of the complement system in the retina, and BPN-14136 administration normalized the retinal levels of proinflammatory complement cascade components such as complement factors D and H, C-reactive protein, and C3. We conclude that BPN-14136 has several beneficial characteristics, combining inhibition of bisretinoid synthesis and reduction in retinaldehydes with normalization of the retinal complement system. BPN-14136, or a similar compound, may be a promising drug candidate to manage Stargardt disease and dry AMD.
C1 [Racz, Boglarka; Varadi, Andras; Kong, Jian; Allikmets, Rando; Petrukhin, Konstantin] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Pearson, Paul G.] Pearson Pharma Partners, Westlake Village, CA 91361 USA.
   [Johnson, Graham] NuPharmAdvise LLC, Sanbornton, NH 03269 USA.
   [Cioffi, Christopher L.] Albany Coll Pharm & Hlth Sci, Dept Basic & Clin Sci, Albany, NY 12208 USA.
   [Cioffi, Christopher L.] Albany Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Albany, NY 12208 USA.
C3 Columbia University; Columbia University; Albany College of Pharmacy &
   Health Sciences; Albany College of Pharmacy & Health Sciences
RP Petrukhin, K (通讯作者)，Columbia Univ, Med Ctr, Dept Ophthalmol, 635 West 165th St,Box 27, New York, NY 10032 USA.
EM kep4@cumc.columbia.edu
RI Allikmets, Rando/ABD-4533-2021
OI Petrukhin, Konstantin/0000-0002-5545-6924; Varadi,
   Andras/0000-0001-5591-377X
FU NEI [P30 EY019007]; Research to Prevent Blindness (New York, NY);
   NATIONAL EYE INSTITUTE [P30EY019007, R24EY019861] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
   [U01NS074476] Funding Source: NIH RePORTER
FX We thank Drs. Theresa Swayne and Laura Munteanu for the assistance with
   confocal microscopy. Research facilities were supported by NEI Grant P30
   EY019007 (Core Support for Vision Research) and by unrestricted funds
   from Research to Prevent Blindness (New York, NY) to the Department of
   Ophthalmology, Columbia University.
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NR 71
TC 23
Z9 23
U1 2
U2 8
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 JUL 20
PY 2018
VL 293
IS 29
BP 11574
EP 11588
DI 10.1074/jbc.RA118.002062
PG 15
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA GN8UL
UT WOS:000439449700026
PM 29871924
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Kortum, KU
   Muller, M
   Kern, C
   Babenko, A
   Mayer, WJ
   Kampik, A
   Kreutzer, TC
   Priglinger, S
   Hirneiss, C
AF Kortuem, Karsten U.
   Mueller, Michael
   Kern, Christoph
   Babenko, Alexander
   Mayer, Wolfgang J.
   Kampik, Anselm
   Kreutzer, Thomas C.
   Priglinger, Siegfried
   Hirneiss, Christoph
TI Using Electronic Health Records to Build an Ophthalmologic Data
   Warehouse and Visualize Patients' Data
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID BIG DATA; MACULAR DEGENERATION; TECHNOLOGY; OUTCOMES; SYSTEM
AB PURPOSE: To develop a near-real-time data warehouse (DW) in an academic ophthalmologic center to gain scientific use of increasing digital data from electronic medical records (EMR) and diagnostic devices.
   DESIGN: Database development.
   METHODS: Specific macular clinic user interfaces within the institutional hospital information system were created. Orders for imaging modalities were sent by an EMR-linked picture-archiving and communications system to the respective devices. All data of 325 767 patients since 2002 were gathered in a DW running on an SQL database. A data discovery tool was developed. An exemplary search for patients with age-related macular degeneration, performed cataract surgery, and at least 10 intravitreal (excluding bevacizumab) injections was conducted.
   RESULTS: Data related to those patients (3 142 204 diagnoses [including diagnoses from other fields of medicine], 720 721 procedures [eg, surgery], and 45 416 intravitreal injections) were stored, including 81 274 optical coherence tomography measurements. A web-based browsing tool was successfully developed for data visualization and filtering data by several linked criteria, for example, minimum number of intravitreal injections of a specific drug and visual acuity interval. The exemplary search identified 450 patients with 516 eyes meeting all criteria.
   CONCLUSIONS: A DW was successfully implemented in an ophthalmologic academic environment to support and facilitate research by using increasing EMR and measurement data. The identification of eligible patients for studies was simplified. In future, software for decision support can be developed based on the DW and its structured data. The improved classification of diseases and semiautomatic validation of data via machine learning are warranted. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Kortuem, Karsten U.; Mueller, Michael; Kern, Christoph; Babenko, Alexander; Mayer, Wolfgang J.; Kampik, Anselm; Kreutzer, Thomas C.; Priglinger, Siegfried; Hirneiss, Christoph] Ludwig Maximilians Univ Munchen, Univ Eye Hosp, Mathildenstr 8, D-80336 Munich, Germany.
C3 University of Munich
RP Kortum, KU (通讯作者)，Ludwig Maximilians Univ Munchen, Univ Eye Hosp, Mathildenstr 8, D-80336 Munich, Germany.
EM Karsten.kortuem@med.uni-muenchen.de
RI Mayer, Wolfgang/AAJ-1407-2020
OI Mayer, Wolfgang/0000-0001-8891-4875; Kortuem,
   Karsten/0000-0001-9442-0708
FU State of Bavaria, Germany
FX WORK WAS DONE BY STAFF HIRED BY THE UNIVERSITY EYE HOSPITAL MUNICH,
   WHICH IS FUNDED BY THE State of Bavaria, Germany.
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NR 37
TC 19
Z9 19
U1 0
U2 23
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 JUN
PY 2017
VL 178
BP 84
EP 93
DI 10.1016/j.ajo.2017.03.026
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EW6CB
UT WOS:000402591700010
PM 28365240
DA 2022-11-30
ER

PT J
AU Kimel, M
   Leidy, NK
   Tschosik, E
   Dolan, C
   Souied, EH
   Varma, R
   Bressler, NM
AF Kimel, Miriam
   Leidy, Nancy Kline
   Tschosik, Elizabeth
   Dolan, Chantal
   Souied, Eric H.
   Varma, Rohit
   Bressler, Neil M.
TI Functional Reading Independence (FRI) Index: A New Patient-Reported
   Outcome Measure for Patients With Geographic Atrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE geographic atrophy; functional reading independence; patient-reported
   outcomes; visual function
ID AGE-RELATED MACULOPATHY; VISUAL FUNCTION; PRO INSTRUMENTS; RISK-FACTORS;
   PREVALENCE; SCOTOMAS; DISEASE
AB Purpose: To develop and validate the Functional Reading Independence (FRI) Index, a new patient-reported outcome measure assessing reading activities in individuals with geographic atrophy (GA) due to age-related macular degeneration.
   Methods: The Index was developed through expert consultation and qualitative patient interviews. Reliability, validity, and responsiveness were tested with data from the Mahalo study (NCT01229215) of lampalizumab in patients with GA.
   Results: Qualitative interviews (n = 40) yielded a 10-item FRI Index, which was refined to seven items in quantitative testing (n = 100). Strong internal consistency (marginal reliability = 0.90) and reproducibility (intraclass correlation coefficient = 0.86) were shown. Known-group validity testing for baseline mean FRI Index scores showed differences (mean [SD]) between patients with Minnesota Low-Vision Reading test reading speed >= 80 vs. <80 words per minute (3.0 [0.7] vs. 1.9 [0.7]; P < 0.001), and between patients above vs. below median values on the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) score (2.9 [0.7] vs. 2.1 [0.8]; P < 0.001). Convergent validity with binocular measures was strong (Spearman's correlation = 0.66 for reading speed, 0.72 for NEI-VFQ-25). Analysis of sensitivity to change revealed mean FRI Index score changes for patients with GA lesion size growth >= 2.5 mm(2)/18 months of -0.41 (0.70) vs. -0.13 (0.61) for patients with lesion growth <2.5 mm(2)/18 months (P = 0.07).
   Conclusions: The FRI Index demonstrated good reliability and validity in patients with GA. Further study in a broader GA population is warranted to confirm responsiveness.
C1 [Kimel, Miriam; Leidy, Nancy Kline] Evidera, Bethesda, MD USA.
   [Tschosik, Elizabeth] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
   [Dolan, Chantal] CMD Consulting Inc, Sandy, UT USA.
   [Souied, Eric H.] Ctr Hosp Intercommunal, Creteil, France.
   [Varma, Rohit] Univ Southern Calif, Keck Sch Med, USC Eye Inst, Los Angeles, CA USA.
   [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
C3 Evidera; Roche Holding; Genentech; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; University of
   Southern California; Johns Hopkins University
RP Tschosik, E (通讯作者)，Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM tschosik.elizabeth@gene.com
FU Genentech, Inc. (South San Francisco, CA, USA)
FX Supported by Genentech, Inc. (South San Francisco, CA, USA). Genentech,
   Inc. participated in study design and conduct; and data collection,
   management, and interpretation.
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   World Health Organization, GLOB DAT VIS IMP 201
NR 36
TC 21
Z9 21
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 NOV
PY 2016
VL 57
IS 14
BP 6298
EP 6304
DI 10.1167/iovs.16-20361
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EI3HG
UT WOS:000392380000052
PM 27893095
OA gold
DA 2022-11-30
ER

PT J
AU Xing, L
   Dorrepaal, SJ
   Gale, J
AF Xing, Lin
   Dorrepaal, Stephen J.
   Gale, Jeffrey
TI Survey of intravitreal injection techniques and treatment protocols
   among retina specialists in Canada
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID INTRAOCULAR-PRESSURE CHANGES; OCCLUSION 12-MONTH OUTCOMES; MACULAR
   DEGENERATION; SUSTAINED BENEFITS; PRACTICE PATTERNS; PHASE-III;
   RANIBIZUMAB; ENDOPHTHALMITIS; BEVACIZUMAB; TRIAMCINOLONE
AB Objective: To describe intravitreal injection (IVI) techniques and treatment protocols by retina specialists in Canada from August 1, 2012, to October 1, 2012.
   Design: Cross-sectional survey.
   Participants: All fellowship-trained retina specialists across Canada, as identified from the Canadian Ophthalmological Society directory and the Canadian Retina and Vitreous Society directory.
   Methods: An anonymous 28-question survey was sent to 125 retina specialists across Canada by email. Reminder letters were sent by email, mail, and fax as necessary.
   Results: A total of 75 (63%) retina specialists responded to the survey. Most IVIs were performed in the office. Most surgeons did not use gloves (61%), sterile draping (91%), or surgical mask (71%). Antisepsis was used on conjunctiva by 100% and on periocular skin by 48%. Nearly all specialists used a sterile lid speculum (91%). Common anaesthetics included topical proparacaine or lidocaine drops (90%), topical lidocaine gel (25%), topical pledget (23%), and subconjunctival lidocaine injections (23%). Most (83%) dilate the pupil before IVI. Prophylactic topical antibiotics were used by 43%; 50% of these were started immediately after IVI. Injection location was estimated by visualization by 45%. A majority (63%) inject inferotemporally. Anterior chamber paracentesis was performed routinely by 5%. Optic nerve perfusion was formally assessed by 48%. The most common treatment protocol for age-related macular degeneration was treat and extend. For both diabetic and retinal vein occlusion-related macular edema, the most common protocol was 3 initial monthly injections with PRN follow-up.
   Conclusions: A wide variety of IVI practice patterns exist in terms of aseptic technique, anaesthetics, prophylactic antibiotics, postinjection monitoring, and treatment protocol.
C1 [Xing, Lin; Dorrepaal, Stephen J.; Gale, Jeffrey] Queens Univ, Dept Ophthalmol, Kingston, ON, Canada.
C3 Queens University - Canada
RP Dorrepaal, SJ (通讯作者)，Clar Eye Inst, 8800 Dufferin St,Suite 105, Vaughan, ON, Canada.
EM 11sjd1@queensu.ca
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NR 48
TC 32
Z9 36
U1 0
U2 7
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 JUN
PY 2014
VL 49
IS 3
BP 261
EP 266
DI 10.1016/j.jcjo.2014.03.009
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AI0GE
UT WOS:000336523400016
PM 24862772
DA 2022-11-30
ER

PT J
AU Lange, CAK
   Luhmann, UFO
   Mowat, FM
   Georgiadis, A
   West, EL
   Abrahams, S
   Sayed, H
   Powner, MB
   Fruttiger, M
   Smith, AJ
   Sowden, JC
   Maxwell, PH
   Ali, RR
   Bainbridge, JWB
AF Lange, Clemens A. K.
   Luhmann, Ulrich F. O.
   Mowat, Freya M.
   Georgiadis, Anastasios
   West, Emma L.
   Abrahams, Sabu
   Sayed, Haroon
   Powner, Michael B.
   Fruttiger, Marcus
   Smith, Alexander J.
   Sowden, Jane C.
   Maxwell, Patrick H.
   Ali, Robin R.
   Bainbridge, James W. B.
TI Von Hippel-Lindau protein in the RPE is essential for normal ocular
   growth and vascular development
SO DEVELOPMENT
LA English
DT Article
DE Von Hippel-Lindau factor; Hypoxia-inducible factor 1; Microphthalmia;
   Angiogenesis; Mouse
ID RETINAL-PIGMENT EPITHELIUM; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA;
   TUMOR-SUPPRESSOR; NEURAL RETINA; MI/MI MOUSE; EXPRESSION; OXYGEN; CELL;
   EYE; VEGF
AB Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature.
C1 [Lange, Clemens A. K.; Luhmann, Ulrich F. O.; Mowat, Freya M.; Georgiadis, Anastasios; West, Emma L.; Sayed, Haroon; Smith, Alexander J.; Ali, Robin R.; Bainbridge, James W. B.] UCL, NIHR Biomed Res Ctr Ophthalmol, Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Lange, Clemens A. K.] Univ Eye Hosp Freiburg, D-79106 Freiburg, Germany.
   [Abrahams, Sabu; Powner, Michael B.; Fruttiger, Marcus] UCL, NIHR Biomed Res Ctr Ophthalmol, Inst Ophthalmol, Dept Cell Biol, London EC1V 9EL, England.
   [Maxwell, Patrick H.] UCL, Rayne Inst, Div Med, London WC1E 6JF, England.
   [Sowden, Jane C.] UCL, Inst Child Hlth, Dev Biol Unit, London WC1N 1EH, England.
C3 University of London; University College London; University of Freiburg;
   University of London; University College London; University of London;
   King's College London; University College London; University of London;
   University College London
RP Bainbridge, JWB (通讯作者)，UCL, NIHR Biomed Res Ctr Ophthalmol, Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
EM j.bainbridge@ucl.ac.uk
RI Abraham, Sabu/E-1144-2019; Maxwell, Patrick H/C-5557-2008; Georgiadis,
   Anastasios/G-8777-2012; Powner, Michael/CAG-7455-2022; MOWAT,
   FREYA/AAD-5102-2021; West, Emma L/C-5252-2013; Smith,
   Alexander/A-5142-2009
OI Abraham, Sabu/0000-0002-0916-5827; Maxwell, Patrick
   H/0000-0002-0338-2679; Georgiadis, Anastasios/0000-0001-5079-3588;
   Powner, Michael/0000-0003-4913-1004; Mowat, Freya/0000-0002-8726-8768;
   Ali, Robin/0000-0003-3126-6517; Bainbridge, James/0000-0003-1318-8201;
   West, Emma/0000-0002-7006-3686; Fruttiger, Marcus/0000-0002-6962-5485;
   Sowden, Jane/0000-0003-0937-2479
FU Wellcome Trust [074617/2/04/2]; National Institute for Health Research
   Biomedical Research Centre at Moorfields Eye Hospital; University
   College London Institute of Ophthalmology; Great Ormond Street Hospital
   Children's Charity; National Institute for Health Research
   [NIHR-RP-011-003, NF-SI-0507-10315, NF-SI-0508-10130] Funding Source:
   researchfish; Great Ormond Street Hospital Childrens Charity [V1257,
   V1221] Funding Source: researchfish
FX This work was supported by The Wellcome Trust [074617/2/04/2]. R. R. A.
   and J.W.B.B. are supported by the National Institute for Health Research
   Biomedical Research Centre at Moorfields Eye Hospital and University
   College London Institute of Ophthalmology. J.C.S. is supported by Great
   Ormond Street Hospital Children's Charity. Deposited in PMC for release
   after 6 months.
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NR 45
TC 18
Z9 18
U1 1
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JUL 1
PY 2012
VL 139
IS 13
BP 2340
EP 2350
DI 10.1242/dev.070813
PG 11
WC Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Developmental Biology
GA 954AF
UT WOS:000304915300009
PM 22627278
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Yanai, A
   Hafeli, UO
   Metcalfe, AL
   Soema, P
   Addo, L
   Gregory-Evans, CY
   Po, K
   Shan, XH
   Moritz, OL
   Gregory-Evans, K
AF Yanai, Anat
   Haefeli, Urs O.
   Metcalfe, Andrew L.
   Soema, Peter
   Addo, Lois
   Gregory-Evans, Cheryl Y.
   Po, Kelvin
   Shan, Xianghong
   Moritz, Orson L.
   Gregory-Evans, Kevin
TI Focused Magnetic Stem Cell Targeting to the Retina Using
   Superparamagnetic Iron Oxide Nanoparticles
SO CELL TRANSPLANTATION
LA English
DT Article
DE Magnetic targeting; Retina; Superparamagnetic iron oxide nanoparticles
   (SPIONs)
ID IN-VIVO; INTRAVITREAL INJECTION; STROMAL CELLS; RAT MODEL;
   TRANSPLANTATION; DELIVERY; THERAPY; VITRO; INTEGRATION; TRAFFICKING
AB Developing new ways of delivering cells to diseased tissue will be a key factor in translating cell therapeutics research into clinical use. Magnetically targeting cells enables delivery of significant numbers of cells to key areas of specific organs. To demonstrate feasibility in neurological tissue, we targeted cells magnetically to the upper hemisphere of the rodent retina. Rat mesenchymal stem cells (MSCs) were magnetized using superparamagnetic iron oxide nanoparticles (SPIONs). In vitro studies suggested that magnetization with fluidMAG-D was well tolerated, that cells remained viable, and they retained their differentiation capabilities. FluidMAG-D-labeled MSCs were injected intravitreally or via the tail vein of the S334ter-4 transgenic rat model of retinal degeneration with or without placing a gold-plated neodymium disc magnet within the orbit, but outside the eye. Retinal flatmount and cryosection imaging demonstrated that after intravitreal injection cells localized to the inner retina in a tightly confined area corresponding to the position of the orbital magnet. After intravenous injection, similar retinal localization was achieved and remarkably was associated with a tenfold increase in magnetic MSC delivery to the retina. Cryosections demonstrated that cells had migrated into both the inner and outer retina. Magnetic MSC treatment with orbital magnet also resulted in significantly higher retinal concentrations of anti-inflammatory molecules interleukin-10 and hepatocyte growth factor. This suggested that intravenous MSC therapy also resulted in significant therapeutic benefit in the dystrophic retina. With minimal risk of collateral damage, these results suggest that magnetic cell delivery is the best approach for controlled delivery of cells to the outer retina-the focus for disease in age-related macular degeneration and retinitis pigmentosa.
C1 [Gregory-Evans, Kevin] Univ British Columbia, Dept Ophthalmol & Visual Sci, Ctr Macular Res, Fac Med, Vancouver, BC V5Z 3N9, Canada.
   [Haefeli, Urs O.; Soema, Peter] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V5Z 3N9, Canada.
C3 University of British Columbia; University of British Columbia
RP Gregory-Evans, K (通讯作者)，Univ British Columbia, Dept Ophthalmol & Visual Sci, Ctr Macular Res, Fac Med, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM kge30@eyecarecentre.org
RI Hafeli, Urs O/B-4097-2012; Gregory-Evans, Cheryl Y/G-9550-2011
OI Gregory-Evans, Kevin/0000-0003-3572-3105; Metcalfe,
   Andrew/0000-0001-9292-8778; Hafeli, Urs/0000-0003-0671-4509; Moritz,
   Orson L/0000-0002-6183-6499; Gregory-Evans, Kevin/0000-0002-0104-7893;
   Yanai, Anat/0000-0002-0792-6901
FU Canadian Institutes of Health Research
FX This work was supported by grants from the Canadian Institutes of Health
   Research. The authors declare no conflicts of interest.
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NR 46
TC 100
Z9 103
U1 0
U2 42
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-6897
EI 1555-3892
J9 CELL TRANSPLANT
JI Cell Transplant.
PY 2012
VL 21
IS 6
BP 1137
EP 1148
DI 10.3727/096368911X627435
PG 12
WC Cell & Tissue Engineering; Medicine, Research & Experimental;
   Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine; Transplantation
GA 009OO
UT WOS:000309035300007
PM 22405427
DA 2022-11-30
ER

PT J
AU Giani, A
   Luiselli, C
   Esmaili, DD
   Salvetti, P
   Cigada, M
   Miller, JW
   Staurenghi, G
AF Giani, Andrea
   Luiselli, Cristiano
   Esmaili, Daniel D.
   Salvetti, Paola
   Cigada, Mario
   Miller, Joan W.
   Staurenghi, Giovanni
TI Spectral-Domain Optical Coherence Tomography as an Indicator of
   Fluorescein Angiography Leakage from Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; VISUAL-ACUITY; VERTEPORFIN;
   RANIBIZUMAB; AGREEMENT; TAP; EYE
AB PURPOSE. To evaluate spectral-domain optical coherence tomography (SD-OCT) findings that predict angiographic leakage in choroidal neovascularization (CNV).
   METHODS. SD-OCT and fluorescein angiography (FA) images of 93 eyes of 93 patients were retrospectively analyzed. All patients were previously treated with anti-vascular endothelial growth factor agents for CNV from age-related macular degeneration. FA images were analyzed to assess the presence of leakage. SD-OCT images were analyzed to identify the overall presence of fluid, as well as specific patterns of fluid presentation, including intraretinal cystic spaces (ICS), retinal pigment epithelium detachment (PED), and neurosensory detachment (NSD). The presence of ultrastructural features such as intraretinal hyperreflective flecks and the inherent reflectivity and boundary definition of the subretinal material were evaluated. Both the association and the sensitivity, specificity, and both positive and negative predictive values of SD-OCT findings compared with FA leakage were calculated.
   RESULTS. A statistically significant association between SD-OCT findings and FA leakage was found for eyes that displayed fluid, NSD, intraretinal flecks, and low reflectivity or undefined boundaries from subretinal material, and not for PED or ICS. Sensitivity and specificity for SD-OCT findings were, respectively: 94% and 27% for fluid; 68% and 88% for NSD; 81% and 83% for intraretinal flecks; 63% and 92% for undefined boundaries of subretinal material; and 94% and 87% for low reflectivity from subretinal material.
   CONCLUSIONS. The evidence of fluid on SD-OCT is sensitive but nonspecific in identifying FA leaky CNV. The assessment of neurosensory detachment as well as other ultrastructural elements may increase the specificity of analysis. (Invest Ophthalmol Vis Sci. 2011; 52: 5579-5586) DOI: 10.1167/iovs.10-6617
C1 [Staurenghi, Giovanni] Univ Milan, Sch Ophthalmol 2, Sacco Hosp, Eye Clin,Dept Clin Sci Luigi Sacco, I-20100 Milan, Italy.
   [Giani, Andrea; Esmaili, Daniel D.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA.
C3 University of Milan; Luigi Sacco Hospital; Harvard University; Harvard
   Medical School; Massachusetts Eye & Ear Infirmary
RP Staurenghi, G (通讯作者)，Univ Milan, Sch Ophthalmol 2, Sacco Hosp, Eye Clin,Dept Clin Sci Luigi Sacco, Via GB Grassi 74, I-20100 Milan, Italy.
EM giovanni.staurenghi@unimi.it
RI ; Staurenghi, Giovanni/K-4388-2017; Giani, Andrea/L-5926-2017
OI Miller, Joan/0000-0003-2046-3996; Staurenghi,
   Giovanni/0000-0002-2299-5251; Salvetti, Anna Paola/0000-0002-5513-2241;
   Giani, Andrea/0000-0003-0682-1945
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NR 28
TC 54
Z9 54
U1 0
U2 0
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 5579
EP 5586
DI 10.1167/iovs.10-6617
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800QC
UT WOS:000293377400074
PM 21693602
DA 2022-11-30
ER

PT J
AU Lee, PP
   Cunningham, WE
   Nakazono, TT
   Hays, RD
AF Lee, Paul P.
   Cunningham, William E.
   Nakazono, Terry T.
   Hays, Ron D.
TI Associations of Eye Diseases and Symptoms with Self-Reported Physical
   and Mental Health
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; FUNCTIONAL STATUS; RATED VISION; GLAUCOMA; OUTCOMES;
   QUESTIONNAIRE; HEARING
AB PURPOSE: To study the associations of eye diseases and visual symptoms with the most widely used health-related quality-of,life (HRQOL) generic profile measure.
   DESIGN: HRQOL was assessed using the short form-36 (SF,36) version I survey administered to a sample of patients receiving care provided by a physician group practice association.
   METHODS: Eye diseases, ocular symptoms, and general health were assessed in a sample of patients from 48 physician groups. A total of 18,480 surveys were mailed out and 7,093 returned; 5,021 of these had complete data. Multiple linear regression models were used to examine the decrements in self-reported physical and mental health associated with eye diseases and symptoms, including trouble seeing and blurred vision.
   RESULTS: Nine percent of the respondents had cataracts, 2% had age,related macular degeneration, 2% glaucoma, 8% blurred vision, and 13% trouble seeing. Trouble seeing and blurred vision both had statistically unique associations with worse scores on the SF,36 mental health summary score. Only trouble seeing had a significant association with the SF-36 physical health summary score. While these ocular symptoms were significantly associated with SF-36 scores, having an eye disease (cataracts, glaucoma, and macular degeneration) was not, after adjusting for other variables in the model.
   CONCLUSIONS: Our results suggest an important link between visual symptoms and general HRQOL. The study extends the findings of prior research to show that both trouble seeing and blurred vision have independent, measurable associations with HRQOL, while the presence of specific eye diseases may not. (Am J Ophthal, mol 2009;148:804-808. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 [Cunningham, William E.; Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
   [Cunningham, William E.; Nakazono, Terry T.; Hays, Ron D.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90024 USA.
   [Lee, Paul P.; Cunningham, William E.; Hays, Ron D.] RAND Corp, Hlth Sci Program, Santa Monica, CA USA.
   [Lee, Paul P.] Duke Eye Ctr, Durham, NC USA.
C3 University of California System; University of California Los Angeles;
   University of California System; University of California Los Angeles;
   RAND Corporation; Duke University
RP Hays, RD (通讯作者)，Univ Calif Los Angeles, Dept Med, 911 Broxton Ave, Los Angeles, CA 90024 USA.
EM drhays@ucla.edu
RI Hays, Ronald/D-5629-2013
OI Hays, Ronald/0000-0001-6697-907X; Lee, Paul/0000-0002-3338-136X
FU RESEARCH TO PREVENT BLINDNESS, NEW YORK, NEW YORK; UCLA Resource Center
   for Minority Aging Research/Center for Health Improvement in Minority
   Elderly (RCMAR/CHIME), NIH/NIA, Bethesda, Maryland [P30AG021684];
   UCLA/DREW Project EXPORT, NCMHD [P20MD000148, P20MD000182]; Allergan,
   Irvine, California; NATIONAL CENTER ON MINORITY HEALTH AND HEALTH
   DISPARITIES [P20MD000148] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [P30AG021684] Funding Source: NIH RePORTER; National
   Institute on Minority Health and Health Disparities [P20MD000182]
   Funding Source: NIH RePORTER
FX THIS STUDY WAS SUPPORTED IN PART BY RESEARCH TO PREVENT BLINDNESS, NEW
   YORK, NEW YORK (DR LEE IS A RECIPIENT OF the Lew Wasserinan Merit Award,
   New York, New York) and a grant front the Medical Quality Commission,
   Seal Beach, California to RAND (Dr Hays). Drs Cunningham and Hays were
   supported in part by the UCLA Resource Center for Minority Aging
   Research/Center for Health Improvement in Minority Elderly
   (RCMAR/CHIME), NIH/NIA, Bethesda, Maryland Grant Award No. P30AG021684,
   and the UCLA/DREW Project EXPORT, NCMHD, P20MD000148 and P20MD000182. Dr
   Hays has received support from Allergan, Irvine, California for lectures
   and as an investigator on a project to develop a health-related quality
   of life preference-based measure. Involved in design of study (P.P.L.,
   R.D.H.); conduct of study (P.P.L., W.E.C., R.D.H.); collection,
   management, analysis, and interpretation of data (P.P.L., W.E.C.,
   T.T.N., R.D.H.); and preparation, review, and approval of manuscript
   (P.P.L., W.E.C., T.T.N., R.D.H.). The study was approved by the RAND
   Institutional Review Board. Julie Brown (RAND) oversaw the survey data
   collection.
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NR 13
TC 13
Z9 14
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
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD NOV
PY 2009
VL 148
IS 5
BP 804
EP 808
DI 10.1016/j.ajo.2009.06.021
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 518DA
UT WOS:000271669300025
PM 19712923
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Armstrong, ME
   Gantier, M
   Li, LL
   Chung, WY
   McCann, A
   Baugh, JA
   Donnelly, SC
AF Armstrong, Michelle E.
   Gantier, Michael
   Li, Lili
   Chung, Wen Y.
   McCann, Amanda
   Baugh, John A.
   Donnelly, Seamas C.
TI Small interfering RNAs induce macrophage migration inhibitory factor
   production and proliferation in breast cancer cells via a
   double-stranded RNA-dependent protein kinase-dependent mechanism
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INNATE IMMUNE-RESPONSE; NF-KAPPA-B; FACTOR MIF; MAMMALIAN-CELLS;
   REGULATORY ROLE; UP-REGULATION; PKR; ACTIVATION; SIRNAS; EXPRESSION
AB Small interfering RNAs (siRNAs) represent a novel tool to induce gene silencing in mammalian cells and clinical trials are currently ongoing to assess the therapeutic efficacy of siRNAs in various human diseases, including age-related macular degeneration and respiratory syncytial virus infection. However, previously reported off-target, nonspecific effects of siRNAs, including activation of type I IFNs and proinflammatory cytokines, remain an outstanding concern regarding use of these agents in vivo. Macrophage-migration inhibitory factor (MIF) is a pleiotropic cytokine with well-described roles in cell proliferation, tumorigenesis, and angiogenesis and represents a target gene for siRNA-based therapy in the treatment of breast cancer. However, in this study we describe an increase in MIF production from mammary adenocarcinoma (MCF-7) cells following transfection with MIF siRNA and various control siRNAs. This effect was shown to be dose-dependent and was attenuated in the presence of a double-stranded RNA-dependent protein kinase inhibitor, 2-aminopurine. Furthermore, treatment of MCF-7 cells with poly(I:C) also stimulated a PKR-dependent increase in MIF production from MCF-7 cells. The biological consequence of the siRNA-induced increase in MIF production from MCF-7 cells was a PKR-dependent increase in proliferation of breast cancer cells. Furthermore, in cDNAs prepared from a primary human breast cancer cohort;. we demonstrated a significant correlation (Spearman rank correlation coefficient, r = 0.50, p < 0.0001, n = 63) between PKR- and MIF-mRNA expression. in conclusion, this study highlights the potential biological consequences of off-target, nonspecific effects of siRNAs and underlines the safety concerns regarding the use of siRNAs in the treatment of human diseases, such as cancer.
C1 [Armstrong, Michelle E.; Gantier, Michael; Li, Lili; Chung, Wen Y.; McCann, Amanda; Baugh, John A.; Donnelly, Seamas C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Coll Life Sci, Sch Med & Med Sci, Dublin 4, Ireland.
C3 University College Dublin
RP Donnelly, SC (通讯作者)，Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Coll Life Sci, Sch Med & Med Sci, Dublin 4, Ireland.
EM seamas.donnelly@ued.ie
RI Gantier, Michael/H-7954-2019; Gantier, Michael/B-7512-2011
OI Gantier, Michael/0000-0003-3740-698X; Gantier,
   Michael/0000-0003-3740-698X; McCann, Amanda/0000-0003-1911-3307;
   Donnelly, Seamas/0000-0001-7145-1843; Chung, Wen
   Yuan/0000-0003-0970-0639; Armstrong, Michelle E./0000-0001-7729-755X
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NR 56
TC 30
Z9 32
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2008
VL 180
IS 11
BP 7125
EP 7133
DI 10.4049/jimmunol.180.11.7125
PG 9
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 324GX
UT WOS:000257507300008
PM 18490711
OA Bronze
DA 2022-11-30
ER

PT J
AU Lowe, J
   Araujo, J
   Yang, JH
   Reich, M
   Oldendorp, A
   Shiu, V
   Quarmby, V
   Lowman, H
   Lien, S
   Gaudreault, J
   Maia, M
AF Lowe, John
   Araujo, James
   Yang, Jihong
   Reich, Mike
   Oldendorp, Amy
   Shiu, Vanessa
   Quarmby, Valerie
   Lowman, Henry
   Lien, Samantha
   Gaudreault, Jacques
   Maia, Mauricio
TI Ranibizumab inhibits multiple forms of biologically active vascular
   endothelial growth factor in vitro and in vivo
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE ranibizumab; vascular endothelial growth factor; age-related macular
   degeneration
ID MACULAR DEGENERATION; CRYSTAL-STRUCTURE; VEGF; MEMBRANES; ANTIBODY;
   AFFINITY; COMPLEX; FAB
AB Neovascular age-related macular degeneration (AMD) is the leading cause of blindness in older adults in the Western world. Ranibizumab (Lucentis (R)), a humanized antibody fragment directed against vascular endothelial growth factor (VEGF-A), was recently approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. The objective of this study was to characterize the binding affinity and pharmacological activity of ranibizumab for 3 biologically active forms of VEGF-A: VEGF(165), VEGF(121), and VEGF(110). The apparent equilibrium binding affinity of ranibizumab for VEGF-A molecules was determined by Biacore (R) analysis; the biological activity of VEGF-A was demonstrated in a human umbilical vein endothelial cell (HUVEC proliferation-inhibition assay. Inhibition of VEGF-A-induced vascular permeability by ranibizumab was assessed in vivo using hairless guinea pigs and a modified Miles assay. Ranibizumab was capable of binding to recombinant human VEGF(165), VEGF(121), and VEGF(110) (K-D <= 192 pM), inhibiting VEGF-A-induced HUVEC proliferation in a concentration-dependent manner. Ranibizumab also exerted potent dose-dependent inhibition IC50 of 0.4-1.2 nM) of the vascular permeability-enhancing activity of VEGF(165), VEGF(121), and VEGF(110) in the Miles assay. In conclusion, these results show that ranibizumab is capable of binding to and specifically inhibiting the activities of 3 biologically active forms of VEGF-A. As VEGF-A plays a pivotal role in the pathogenesis of neovascular AMD, ranibizumab activity, as demonstrated in this study, supports its clinical utility in the treatment of this disease. (C) 2007 Elsevier Ltd. All rights reserved.
C1 Genentech Inc, Dept BioAnalyt R&D, San Francisco, CA 94080 USA.
   Genentech Inc, In Vivo Grp, San Francisco, CA 94080 USA.
   Dept Pharmacokinet Pharmacodynam & Bioanalyt Sci, San Francisco, CA 94080 USA.
   Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Roche Holding;
   Genentech
RP Lowe, J (通讯作者)，Genentech Inc, Dept BioAnalyt R&D, MS38,1 DNA Way, San Francisco, CA 94080 USA.
EM lowe.john@gene.com
RI Maia, Mauricio/I-5892-2015
OI Maia, Mauricio/0000-0002-7034-8091
CR *AD DRUG PROF, 2002, DRUGS R D, V3, P40
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NR 18
TC 112
Z9 118
U1 0
U2 17
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2007
VL 85
IS 4
BP 425
EP 430
DI 10.1016/j.exer.2007.05.008
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 228FM
UT WOS:000250713000002
PM 17714704
DA 2022-11-30
ER

PT J
AU Lamoureux, EL
   Pallant, JF
   Pesudovs, K
   Rees, G
   Hassell, JB
   Keeffe, JE
AF Lamoureux, Ecosse L.
   Pallant, Julie F.
   Pesudovs, Konrad
   Rees, Gwyn
   Hassell, Jennifer B.
   Keeffe, Jill E.
TI The effectiveness of low-vision rehabilitation on participation in daily
   living and quality of life
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VISUAL DISABILITY VARIABLES; MACULAR DEGENERATION; IMPAIRMENT
   QUESTIONNAIRE; IMPACT; OUTCOMES; SAMPLE; PERFORMANCE; INSTRUMENT;
   DEPRESSION; DIFFICULTY
AB PURPOSE. To evaluate the effectiveness of a multidisciplinary low-vision rehabilitation program on quality of life evaluated by the Impact of Vision Impairment (IVI) instrument.
   METHODS. First-time referrals to low-vision clinics were assessed before and after rehabilitation (3-6 months). Rasch analysis was used to estimate the three IVI subscale and overall values on an interval scale. A mixed between-within subjects ANOVA was used to identify whether presenting visual acuity had an interaction effect with rehabilitation change. Cohen d values were used to estimate the magnitude of the change and the standardized response mean (SRM) procedure was selected to determine the clinical significance of the rehabilitation-induced changes.
   RESULTS. One hundred twenty-four women and 68 men (mean age, 80.3 years) completed the rehabilitation. Most had age-related macular degeneration (62%, 119) and were moderately to severely vision impaired (< 6/18; 78%, 149). After rehabilitation, significant improvements were recorded for the overall IVI score (P = 0.006) and two subscales: reading and accessing information and emotional well-being (P = 0.007 and 0.009, respectively). No significant improvement was found on the mobility and independence subscale (P = 0.07). The magnitude of the postintervention improvement was found to be relatively moderate (Cohen d = 0.17-0-30) and clinically modest (SRM = 0.22-0.42).
   CONCLUSIONS. Significant improvements in overall quality of life and two specific areas of daily living in people with low vision were found, although the magnitude and clinical significance of the rehabilitation-induced gains were modest. Further investigation in other models of low-vision rehabilitation is needed to optimize quality of life gains in people with low vision.
C1 Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Melbourne, Vic 8002, Australia.
   Swinburne Univ Technol, Fac Life & Social Sci, Melbourne, Vic, Australia.
   Flinders Univ S Australia, NH&MRC, Ctr Clin Eye Res, Bedford Pk, SA 5042, Australia.
   Flinders Med Ctr, Bedford Pk, SA, Australia.
   Vis CRC, Sydney, NSW, Australia.
C3 Centre for Eye Research Australia; University of Melbourne; Swinburne
   University of Technology; Flinders University South Australia; Flinders
   Medical Centre
RP Lamoureux, EL (通讯作者)，Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Locked Bag 8, Melbourne, Vic 8002, Australia.
EM ecosse@unimelb.edu.au
RI Lamoureux, Ecosse/Z-5482-2019; Pesudovs, Konrad/T-9403-2019
OI Pesudovs, Konrad/0000-0002-6322-9369
CR Andrich D, 2003, RUMM 2020
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NR 57
TC 123
Z9 129
U1 1
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 APR
PY 2007
VL 48
IS 4
BP 1476
EP 1482
DI 10.1167/iovs.06-0610
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 153CB
UT WOS:000245408200007
PM 17389474
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Mozaffarieh, M
   Heinzl, H
   Sacu, S
   Wedrich, A
AF Mozaffarieh, Maneli
   Heinzl, Harald
   Sacu, Stefan
   Wedrich, Andreas
TI In-patient management and treatment satisfaction after intravitreous
   plasminogen activator injection
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE intravetreous injection; plasminogen activator injection; subretinal
   hemmorhage; age-related macular degeneration; patients' satisfaction
ID MACULAR DEGENERATION; SUBRETINAL HEMORRHAGE; PATIENT SATISFACTION;
   SUBMACULAR HEMORRHAGE; NATURAL-HISTORY; CARE; QUALITY; IMPROVEMENT;
   OUTCOMES; SURGERY
AB Aims: To assess patient satisfaction after intravitreous plasminogen activator injections for subretinal hemorrhages secondary to age-related macular degeneration (AMD) and to analyse how it relates to the patients' postoperative visual and functional abilities. Further, to suggest ways to improve in-patient management and thereby treatment satisfaction. Methods: A consecutive series of 101 patients with a subretinal hemorrhage of at least one disk diameter were enrolled in this longitudinal prospective study conducted during 2001-2004. After complete preoperative eye examination all patients were treated with intravitreal injection of 25 mu g recombinant tissue plasminogen activator (rTPA) and 0.5 ml sulphur hexafluoride gas (SF6), followed by face-down positioning for 1 week. Patient satisfaction was assessed using standardised questionnaires administered postoperatively at 4 and 12 months. Outcome measures were: (1) responses to the patient satisfaction survey, (2) degree of satisfaction with in-patient management, (3) subjective change in the patients' functional status, and (4) visual acuity results. Results: Whereas the patients' actual functional status deteriorated from a median value of 2.4 at 4 months to 3.4 at 12 months, their recall of their preoperative functional status shifted from a median value of 4.2 to to 2.3, consecutively. Twelve months after treatment, 75% of patients reported an improved visual acuity, however, only 12% reported satisfaction with treatment. 67.4-87% of patients were dissatisfied with various areas of in-patient management. Conclusions: Satisfaction with plasminogen activator injection treatment is low even though patients experience an improved visual and functional status at 12 months. This suggests that the current system requires improvement in certain areas such as in-patient management.
C1 Med Univ Graz, Dept Ophthalmol, A-8036 Graz, Austria.
   Med Univ Vienna, Dept Ophthalmol, Vienna, Austria.
   Med Univ Vienna, Core Unit Med Stat & Informat, Vienna, Austria.
C3 Medical University of Graz; Medical University of Vienna; Medical
   University of Vienna
RP Wedrich, A (通讯作者)，Med Univ Graz, Dept Ophthalmol, Auenbruggerpl 4, A-8036 Graz, Austria.
EM andreas.wedrich@meduni-graz.at
RI Wedrich, Andreas/AAE-9171-2020
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NR 34
TC 7
Z9 7
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD NOV
PY 2006
VL 244
IS 11
BP 1421
EP 1428
DI 10.1007/s00417-005-0232-z
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 103PL
UT WOS:000241899100007
PM 16596407
DA 2022-11-30
ER

PT J
AU Ray, R
   Stinnett, SS
   Jaffe, GJ
AF Ray, R
   Stinnett, SS
   Jaffe, GJ
TI Evaluation of image artifact produced by optical coherence tomography of
   retinal pathology
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; THICKNESS; DEGENERATION; DISEASE
AB PURPOSE: To determine the frequency and type of optical coherence tomography (OCT) fast macular thickness map (FMTM) scan artifacts, and whether these artifacts depend on patient diagnosis, demographics, and ocular therapy.
   DESIGN: Retrospective observational case series.
   METHODS: Records from patients who underwent an ophthalmologic evaluation by a member of the Duke University Eye Center vitreoretinal faculty and had an OCT scan produced by the FMTM protocol between July 7, 2003 and July 31, 2003 were reviewed. The relationships between OCT scan artifacts and ocular diagnosis, ocular treatment, and patient demographics were deter, mined. Logistic regression was used to relate OCT scan artifacts simultaneously with ocular diagnosis and treatment.
   RESULTS: Scans from 171 eyes were analyzed. Retinal scan artifacts, though not observed in normal eyesi were identified frequently in eyes with macular pathology (P = .049). Artifacts were observed in 43.2% of all scans, and of these, an erroneous retinal thickness measurement was obtained in 62.2%. Six types of OCT surface map artifacts were observed. Of these, inner and outer retinal misidentification, degraded image artifact, and "off center" artifact were significantly associated with central thickness calculation errors (P < .001). Neovascular age-related macular degeneration (AMD), full-thickness macular hole, and photodynamic therapy were all associated with in, creased artifact (P = .002,.022, and < .001, respectively).
   CONCLUSION: Optical coherence tomography scan artifacts are seen surprisingly frequently, adversely affect retinal thickness measurements in a high proportion of cases, and are diagnosis-dependent. Recognition of these artifacts will improve retinal thickness measurement accuracy, and will prevent faulty treatment decisions that are based on inaccurate retinal thickness measurements. (C) 2005 by Elsevier Inc. All rights reserved.
C1 Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
C3 Duke University
RP Jaffe, GJ (通讯作者)，Duke Univ, Ctr Eye, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM jaffe00l@mc.duke.edu
OI Stinnett, Sandra/0000-0001-7192-0195
FU NATIONAL EYE INSTITUTE [R21EY011725] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY11725] Funding Source: Medline
CR Browning DJ, 2003, AM J OPHTHALMOL, V136, P555, DOI 10.1016/S0002-9394(03)00387-8
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   [No title captured]
NR 16
TC 151
Z9 155
U1 1
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 JAN
PY 2005
VL 139
IS 1
BP 18
EP 29
DI 10.1016/j.ajo.2004.07.050
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 885XW
UT WOS:000226191700003
PM 15652824
DA 2022-11-30
ER

PT J
AU Bartolomei, F
   Biagini, I
   Sato, G
   Falchini, E
   Di Simone, A
   Mastrantuono, C
   Micarelli, S
   Virgili, G
AF Bartolomei, Federico
   Biagini, Ilaria
   Sato, Giovanni
   Falchini, Elisabetta
   Di Simone, Alessia
   Mastrantuono, Chiara
   Micarelli, Silvia
   Virgili, Gianni
TI Low-vision rehabilitation in Italy: Cross-sectional data from the Device
   and Aids Registry (DARe)
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Retina; age-related macular degeneration; glaucoma; retina; retinal
   pathology; research; genetics; optics; refraction; instruments
AB Objectives We are reporting on the characteristics of low-vision adults attending large rehabilitation services which provide data to D.A.Re (Devices & Aids REgister) in Italy. D.A.Re aims to gather information about low-vision aids owned by Italian patients with visual impairment. Methods We included consecutive patients attending low-vision rehabilitation centres providing data to D.A.Re from 2019 to July 2021. Demographic features, self-reported use of technology and aids, vision performance, and the Instrumental Activity of Daily Living (IADL) score were collected. Results 720 patients were included in the D.A.Re. About half of the patients were affected by Age-related Macular Degeneration (389, 54.9%). Patients reported a long interval between onset of vision disability and access to low-vision rehabilitation, which was over two years in almost 30% of cases. Blindness registration status was almost complete when reported, but almost 40% were unable to report on this. IADL scores were higher for younger people and those with better visual acuity and critical print size (CPS), and lower for visual field restriction (p < 0.01 for all predictors). Of interest, better IADL scores were recorded for those with computer knowledge who used optical aids and software in univariate analyses and multivariate analyses, adjusting for level of visual disability and employment status (p < 0.01 for all predictors). Conclusions We report on the profile of low-vision patients using rehabilitation services in Italy. Longitudinal data during and after vision rehabilitation were collected. Our results support the validity of the D.A.Re to monitor the use of low-vision devices in Italy.
C1 [Bartolomei, Federico] Ist Cavazza, Bologna, Italy.
   [Biagini, Ilaria; Virgili, Gianni] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Largo Brambilla 3, I-50134 Florence, Italy.
   [Biagini, Ilaria; Virgili, Gianni] AOU Careggi, Largo Brambilla 3, I-50134 Florence, Italy.
   [Sato, Giovanni] Ctr Oculist S Paolo Hosp, S Antonio Padova, Italy.
   [Falchini, Elisabetta] AOU Careggi, Ctr Integrato Riabilitaz Visiva Carlo Monti, Florence, Italy.
   [Di Simone, Alessia] CERVi UICI, Enna, Italy.
   [Mastrantuono, Chiara] Ctr Officina Sensi, Ascoli Piceno, Italy.
   [Micarelli, Silvia] Azienda Serv Persona Disabile Visiva S Alessio Ma, Rome, Italy.
   [Virgili, Gianni] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
C3 University of Florence; University of Florence; Azienda Ospedaliero
   Universitaria Careggi; University of Florence; Azienda Ospedaliero
   Universitaria Careggi; Queens University Belfast
RP Biagini, I (通讯作者)，Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Largo Brambilla 3, I-50134 Florence, Italy.; Biagini, I (通讯作者)，AOU Careggi, Largo Brambilla 3, I-50134 Florence, Italy.
EM ilaria.biagini@unifi.it
RI ; Virgili, Gianni/P-6607-2014
OI Bartolomei, Federico/0000-0001-6007-5096; Virgili,
   Gianni/0000-0002-9960-2989; BIAGINI, ILARIA/0000-0003-1263-7183; sato,
   giovanni/0000-0003-1492-5306
CR [Anonymous], 2019, WORLD REPORT VISION
   Binns AM, 2012, SURV OPHTHALMOL, V57, P34, DOI 10.1016/j.survophthal.2011.06.006
   BRAMER G R, 1988, World Health Statistics Quarterly, V41, P32
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NR 11
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JUL
PY 2022
VL 32
IS 4
BP 1942
EP 1946
AR 11206721221091367
DI 10.1177/11206721221091367
EA APR 2022
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3B9CF
UT WOS:000777936900001
PM 35369783
OA Green Published
DA 2022-11-30
ER

PT J
AU Bulut, MN
   Sonmez, HS
   Gokce, G
   Agackesen, A
   Bulut, K
   Hacisalihoglu, A
   Arsan, A
   Simsek, S
AF Bulut, Muhammed Nurullah
   Sonmez, Hatice Selen
   Gokce, Gizem
   Agackesen, Anil
   Bulut, Kezban
   Hacisalihoglu, Aynur
   Arsan, Aysu
   Simsek, Saban
TI The impact of delayed anti-vascular endothelial growth factor treatment
   for retinal diseases during the COVID-19 lockdown
SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY
LA English
DT Article
DE Diabetic retinopathy; Anti-VEGF; Delaying; COVID-19; Loading dose;
   Treatment delay; OCT
ID DIABETIC MACULAR EDEMA; RANIBIZUMAB; AFLIBERCEPT; OUTCOMES
AB Purpose: : To assess the clinical status of treatment-naive patients who had to delay 3-dose loading anti-VEGF (anti-vascular endothelial growth factor) injections during the COVID-19 lockdown, and to evaluate the effect of the delayed visual acuity treatment on spectral domain optical coherence tomography (SD-OCT) parameters.
   Method:: A total of 55 eyes of 46 patients who were received in the study period participated in this retrospective study, including 28 patients (37 eyes) with diabetic macular edema (DME), 11 patients (11 eyes) with retinal vein occlusion (RVO), and 7 patients (7 eyes) with wet age-related macular degeneration (wet-AMD). The patients were diagnosed with DME, RVO, or wet-AMD in February 2020 and had planned 3-dose loading injections in March, April, and May 2020, but could not be injected due to the COVID-19 pandemic.
   Results: : From the patients' initial examination in February 2020, the mean best corrected visual acuity (BCVA) was 0.72 +/- 59 logMAR. After the patients' lockdown visit in July 2020, the mean BCVA was 0.76 +/- 64 logMAR. BCVA was stable in 11 eyes, decreased in 12 eyes, and increased in 14 eyes for patients with DME. BCVA was stable in 6, decreased in 3, and increased in 2 eyes for patients with RVO, and it was stable in 4 eyes and decreased in 3 eyes for patients with wet-AMD.
   Conclusion: : We concluded that 6-month delay in treatment of DME patients with non-proliferative DRP had no adverse effect on the visual acuity. However, the loading dose in wet-AMD and RVO patients should be applied as soon as possible.
C1 [Bulut, Muhammed Nurullah; Sonmez, Hatice Selen; Gokce, Gizem; Agackesen, Anil; Bulut, Kezban; Hacisalihoglu, Aynur; Arsan, Aysu; Simsek, Saban] Univ Hlth Sci, Kartal Dr Lutfi Kirdar Training & Res Hosp, Eye Dept, Istanbul, Turkey.
C3 Istanbul Kartal Dr Lutfi Kirdar Training & Research Hospital; University
   of Health Sciences Turkey
RP Bulut, MN (通讯作者)，Univ Hlth Sci, Kartal Dr Lutfi Kirdar Training & Res Hosp, Eye Dept, Istanbul, Turkey.
EM muhammednurullah.bulut@sbu.edu.tr
OI Agackesen, Anil/0000-0003-4694-4683
CR American Academy of Ophthalmology, 2020, IMP COR UPD OPHTH
   Bakri SJ, 2019, OPHTHALMOLOGY, V126, P55, DOI 10.1016/j.ophtha.2018.07.028
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   Deutsche Opthalmologische Gesellschaft, 2020, COR COVID 19
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NR 19
TC 3
Z9 3
U1 2
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1572-1000
EI 1873-1597
J9 PHOTODIAGN PHOTODYN
JI Photodiagnosis Photodyn. Ther.
PD SEP
PY 2021
VL 35
AR 102449
DI 10.1016/j.pdpdt.2021.102449
EA AUG 2021
PG 4
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA UR4QR
UT WOS:000696736400012
PM 34314862
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Franzone, F
   Nebbioso, M
   Pergolizzi, T
   Attanasio, G
   Musacchio, A
   Greco, A
   Limoli, P
   Artico, M
   Spandidos, D
   Taurone, S
   Agostinelli, E
AF Franzone, Federica
   Nebbioso, Marcella
   Pergolizzi, Tiziano
   Attanasio, Giuseppe
   Musacchio, Angela
   Greco, Antonio
   Limoli, Paolo
   Artico, Marco
   Spandidos, Demetrios
   Taurone, Samanta
   Agostinelli, Enzo
TI Anti-inflammatory role of curcumin in retinal disorders (Review)
SO EXPERIMENTAL AND THERAPEUTIC MEDICINE
LA English
DT Review
DE curcumin; ROS; protein kinases; epidermal growth factor; DR; polymeric
   micelles
ID DIABETIC-RETINOPATHY; GROWTH-FACTOR; IN-VITRO; FORMULATION; EXPRESSION;
   MANAGEMENT; PROFILE; AGENT
AB Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: I kappa B alpha, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-alpha. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.
C1 [Franzone, Federica; Nebbioso, Marcella; Pergolizzi, Tiziano; Attanasio, Giuseppe; Musacchio, Angela; Greco, Antonio; Artico, Marco; Agostinelli, Enzo] Sapienza Univ Rome, Fac Med & Dent, Dept Sensory Organs, I-00161 Rome, Italy.
   [Limoli, Paolo] Low Vis Res Ctr Milan, I-20145 Milan, Italy.
   [Spandidos, Demetrios] Univ Crete, Med Sch, Lab Clin Virol, Iraklion 71003, Greece.
   [Taurone, Samanta] IRCCS Fdn Bietti, I-00198 Rome, Italy.
   [Agostinelli, Enzo] Int Polyamines Fdn ETS ONLUS, I-00159 Rome, Italy.
C3 Sapienza University Rome; University of Crete; IRCCS - Fondazione "G.B.
   Bietti" per lo Studio e la Ricerca in Oftalmologia
RP Agostinelli, E (通讯作者)，Sapienza Univ Rome, Policlin Umberto I, Fac Med & Dent, Dept Sensory Organs, Viale Policlin 155, I-00161 Rome, Italy.
EM enzo.agostinelli@uniroma1.it
RI Nebbioso, Marcella/K-6878-2018
OI Nebbioso, Marcella/0000-0002-5512-0849
FU Ministry of Health [RC 2765943]; Fondazione Roma
FX This paper was financially supported by Ministry of Health (grant no. RC
   2765943) and Fondazione Roma.
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NR 69
TC 6
Z9 7
U1 5
U2 18
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 JUL
PY 2021
VL 22
IS 1
AR 790
DI 10.3892/etm.2021.10222
PG 7
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA SH5QO
UT WOS:000654190800001
PM 34055089
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Calzetti, G
   Mora, P
   Favilla, S
   Ottonelli, G
   Devincenzi, G
   Carta, A
   Tedesco, S
   Mursch-Edlmayr, A
   Garhofer, G
   Gandolfi, S
   Schmetterer, L
AF Calzetti, Giacomo
   Mora, Paolo
   Favilla, Stefania
   Ottonelli, Giorgia
   Devincenzi, Giulia
   Carta, Arturo
   Tedesco, Salvatore
   Mursch-Edlmayr, Anna
   Garhoefer, Gerhard
   Gandolfi, Stefano
   Schmetterer, Leopold
TI Assessment of Choroidal Neovascularization Perfusion: A Pilot Study With
   Laser Speckle Flowgraphy
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE laser speckle flowgraphy; imaging; choroid; age-related macular
   degeneration; anti-VEGF
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; INDOCYANINE GREEN ANGIOGRAPHY; OCULAR
   BLOOD-FLOW; MACULAR DEGENERATION; INTRAVITREAL BEVACIZUMAB;
   QUANTITATIVE-ANALYSIS; RANIBIZUMAB; CIRCULATION; INJECTION; VASCULOPATHY
AB Purpose: The purpose of this study was to quantify perfusion in the area of choroidal neovascularization (CNV) using laser speckle flowgraphy (LSFG) before and after intravitreal anti-vascular endothelial growth factor (VEGF) injection.
   Methods: Retrospective case series. Fifteen eyes of 15 patients with treatment-naive CNV due to age-related macular degeneration (AMD) and with available LSFG images were included. The main outcome was the mean blur rate (MBR) quantified as a measure of perfusion within the CNV area observed on indocyanine green angiography. Twelve patients had available longitudinal data until one month after the injection, used to evaluate changes in perfusion, central macular thickness (CMT), visual acuity, and ocular perfusion pressure. Reproducibility of LSFG measurements was investigated at each time point from two images taken within five minutes.
   Results: Intraclass correlation coefficients for LSFG measurements were higher than 0.8 indicating excellent reproducibility. There was a significant decrease in perfusion after one week (-26.4 +/- 14.4%; P= 0.027), whereas, after one month, perfusion was no longer significantly different from baseline (P = 0.121). CMT showed a progressive decrease over the follow-up period. Changes in perfusion were strongly correlated with changes in CMT after one week, but not thereafter.
   Conclusions: This pilot study suggests a method to select a region in the CNV area to quantify perfusion using LSFG. MBR could represent a parameter possibly related to regrowth of the CNV after anti-VEGF treatment. Large-scale studies are needed to assess the usefulness of LSFG in defining re-treatment criteria for neovascular AMD.
   Translational Relevance: LSFG technology to quantify perfusion could provide useful biomarkers for therapeutic management of CNV.
C1 [Calzetti, Giacomo; Mora, Paolo; Ottonelli, Giorgia; Devincenzi, Giulia; Carta, Arturo; Tedesco, Salvatore; Gandolfi, Stefano] Univ Hosp Parma, Ophthalmol Unit, Parma, Italy.
   [Mursch-Edlmayr, Anna] Kepler Univ Clin, Johannes Kepler Univ, Dept Ophthalmol, Linz, Austria.
   [Garhoefer, Gerhard; Schmetterer, Leopold] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
   [Schmetterer, Leopold] Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
   [Schmetterer, Leopold] Nanyang Technol Univ, Singapore, Singapore.
   [Schmetterer, Leopold] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Schmetterer, Leopold] Inst Ophthalmol, Basel, Switzerland.
C3 University of Parma; University Hospital of Parma; Johannes Kepler
   University Linz; Kepler University Hospital; Medical University of
   Vienna; National University of Singapore; Singapore National Eye Center;
   Nanyang Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; National University of
   Singapore; Medical University of Vienna
RP Schmetterer, L (通讯作者)，Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM leopold.schmetterer@seri.com.sg
RI Calzetti, Giacomo/AAO-7409-2021; carta, arturo/AAA-4260-2021
OI Calzetti, Giacomo/0000-0003-1391-9510; Schmetterer,
   Leopold/0000-0002-7189-1707
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NR 38
TC 6
Z9 6
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 APR
PY 2020
VL 9
IS 5
AR 9
DI 10.1167/tvst.9.5.9
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MJ6XV
UT WOS:000548232200009
PM 32821481
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Rasti, R
   Mehridehnavi, A
   Rabbani, H
   Hajizadeh, F
AF Rasti, Reza
   Mehridehnavi, Alireza
   Rabbani, Hossein
   Hajizadeh, Fedra
TI Automatic diagnosis of abnormal macula in retinal optical coherence
   tomography images using wavelet-based convolutional neural network
   features and random forests classifier
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE classification; convolutional neural networks; feature learning; macular
   disease; retinal optical coherence tomography; spatial-frequency
   information
ID OCT IMAGES; LAYER SEGMENTATION; EDEMA; DEGENERATION; BOUNDARIES; AMD
AB The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein] Isfahan Univ Med Sci, Sch Adv Technol Med, Isfahan Dept Biomed Engn, Esfahan, Iran.
   [Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein] Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Esfahan, Iran.
   [Hajizadeh, Fedra] Noor Eye Hosp, Noor Ophthalmol Res Ctr, Tehran, Iran.
C3 Isfahan University Medical Science; Isfahan University Medical Science
RP Mehridehnavi, A (通讯作者)，Isfahan Univ Med Sci, Sch Adv Technol Med, Isfahan Dept Biomed Engn, Esfahan, Iran.; Mehridehnavi, A (通讯作者)，Isfahan Univ Med Sci, Med Image & Signal Proc Res Ctr, Esfahan, Iran.
EM mehri@med.mui.ac.ir
RI Rabbani, Hossein/H-7515-2014; Rasti, Reza/AAQ-1323-2021; Rabbani,
   Hossein/O-4987-2019
OI Rabbani, Hossein/0000-0002-0551-3636; Rabbani,
   Hossein/0000-0002-0551-3636; Rasti, Reza/0000-0003-0010-788X; Hajizadeh,
   Fedra/0000-0002-2661-5439
FU Isfahan University of Medical Sciences [395645]
FX This work was supported in part by the Isfahan University of Medical
   Sciences, vice-chancellor of Research and Technology under Grant No.
   395645.
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NR 50
TC 22
Z9 22
U1 1
U2 18
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 MAR
PY 2018
VL 23
IS 3
AR 035005
DI 10.1117/1.JBO.23.3.035005
PG 10
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 GB7IT
UT WOS:000429248800012
PM 29564864
OA gold
DA 2022-11-30
ER

PT J
AU Ratanasukon, M
   Tongsomboon, J
   Bhurayanontachai, P
   Jirarattanasopa, P
AF Ratanasukon, Mansing
   Tongsomboon, Jongjit
   Bhurayanontachai, Patama
   Jirarattanasopa, Pichai
TI The Impact of Vision Impairment (IVI) Questionnaire; Validation of the
   Thai-Version and the Implementation on Vision-Related Quality of Life in
   Thai Rural Community
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; PREVALENCE; POPULATION
AB The objective of this study is to validate the Thai-version of the impact of vision impairment (IVI) questionnaire and to evaluate its impact on vision-related quality of life (VRQoL) in southern Thailand. The IVI questionnaire was translated into Thai according to WHO translation guidelines. In addition to the routine ophthalmological examinations, a Thai version of the IVI questionnaire was administered to all participants. A total of 120 patients with visual impairment who presented at Songklanagarind hospital, Songkhla province, were enrolled in the study; 30 had age-related macular degeneration (AMD), 30 had cataract, 30 had diabetic retinopathy, 30 had glaucoma, and 30 non-visually impaired individuals comprised the control group. Statistical analysis demonstrated the Thai-version IVI questionnaire is valid and reliable to evaluate the VRQoL of the Thai patients through three subscales: (i) mobility and independence, (ii) reading and accessing information, and (iii) emotional well-being. The results demonstrated high consistency in all subscales with Cronbach's alpha ranging from 0.787 to 0.849. Rasch analysis revealed the validity of the Thai-version IVI to assess VRQoL through all three subscales. Test-retest reliability was also high (intraclass correlation coefficient = 0.96). The composite score of the IVI was significantly higher in participants with visual impairment compared with healthy participants. Moreover, the subscale scores of reading and accessing information, and emotional well-being were highest in participants with AMD. While the subscale scores of mobility and independence were highest among those with either cataracts or diabetic retinopathy. The symptoms of the common vision impairment diseases are associated with an adverse impact on VRQoL in a clinic-based population as demonstrated in this study.
C1 [Ratanasukon, Mansing; Bhurayanontachai, Patama; Jirarattanasopa, Pichai] Prince Songkla Univ, Fac Med, Dept Ophthalmol, Hat Yai, Songkhla, Thailand.
   [Tongsomboon, Jongjit] Prince Songkla Univ, Fac Med, Dept Nursing, Hat Yai, Songkhla, Thailand.
C3 Prince of Songkla University; Prince of Songkla University
RP Ratanasukon, M (通讯作者)，Prince Songkla Univ, Fac Med, Dept Ophthalmol, Hat Yai, Songkhla, Thailand.
EM mratanasukon@yahoo.com
OI Jirarattanasopa, Pichai/0000-0003-0584-5101
FU Novartis
FX The authors received funding from Novartis for this work. 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 22
TC 12
Z9 12
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 MAY 18
PY 2016
VL 11
IS 5
AR e0155509
DI 10.1371/journal.pone.0155509
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DM3ZU
UT WOS:000376286100059
PM 27191960
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Shibagaki, K
   Okamoto, K
   Katsuta, O
   Nakamura, M
AF Shibagaki, Keiichi
   Okamoto, Kazuyoshi
   Katsuta, Osamu
   Nakamura, Masatsugu
TI Beneficial protective effect of pramipexole on light-induced retinal
   damage in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Light-induced retinal damage;
   Apoptosis; Pramipexole; Antioxidant
ID FREE-RADICAL SCAVENGER; MACULAR DEGENERATION; OXIDATIVE STRESS;
   IN-VITRO; ANTIPARKINSONIAN DRUGS; LIPID-PEROXIDATION; PIGMENT
   EPITHELIUM; CYTOCHROME-C; EDARAVONE; INJURY
AB We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/ kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h). Electrophysiological and morphologic studies were performed to evaluate the effects of the pramipexole on light-induced retinal damage in mice. Pramipexole significantly prevented the reduction of the a- and b-wave electroretinogram (ERG) amplitudes caused by light exposure in a dose-dependent manner. In parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors, loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light exposure were notably ameliorated by pramipexole. Additionally, pramipexole suppressed H(2)O(2-)induced ARPE-19 cell death in vitro in a concentration-dependent manner. The effect of pramipexole was significant at concentrations of 10(-6) M or higher. Pramipexole also significantly prevented H2O2-induced activation of caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS) in a concentration-dependent manner ranging from 10(-5) to 10(-3) M. Furthermore, pramipexole increased the scavenging activity toward a hydroxyl radical generated from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects against light-induced retinal damage as an antioxidant and that it may be a novel and effective therapy for retinal degenerative disorders, such as dry age-related macular degeneration. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Shibagaki, Keiichi; Katsuta, Osamu; Nakamura, Masatsugu] Santen Pharmaceut Co Ltd, Div Res & Dev, Kita Ku, Osaka 5308552, Japan.
   [Shibagaki, Keiichi] Nara Inst Sci & Technol, Grad Sch Biol Sci, Ikoma, Nara 6300192, Japan.
   [Okamoto, Kazuyoshi] Santen Pharmaceut Co Ltd, Corp Dev Div, Kita Ku, Osaka 5308552, Japan.
C3 Santen Pharmaceutical Co Ltd; Nara Institute of Science & Technology;
   Santen Pharmaceutical Co Ltd
RP Shibagaki, K (通讯作者)，Santen Pharmaceut Co Ltd, Div Res & Dev, Kita Ku, 4-20 Ofuka Cho, Osaka 5308552, Japan.
EM keiichi.shibagaki@santen.co.jp
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NR 56
TC 19
Z9 20
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 OCT
PY 2015
VL 139
BP 64
EP 72
DI 10.1016/j.exer.2015.07.007
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CS0VW
UT WOS:000361781300006
PM 26213307
DA 2022-11-30
ER

PT J
AU Imamura, T
   Hirayama, T
   Tsuruma, K
   Shimazawa, M
   Nagasawa, H
   Hara, H
AF Imamura, Tomoyo
   Hirayama, Tasuku
   Tsuruma, Kazuhiro
   Shimazawa, Masamitsu
   Nagasawa, Hideko
   Hara, Hideaki
TI Hydroxyl radicals cause fluctuation in intracellular ferrous ion levels
   upon light exposure during photoreceptor cell death
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Light-induced retinal damage; Ferrous;
   Iron; Hydroxyl radical
ID LABILE IRON; DEGENERATION; STRESS; ERYTHROPOIESIS; INVOLVEMENT;
   EXPRESSION; PROTECTS
AB Iron accumulation is a potential pathogenic event often seen in age-related macular degeneration (AMD) patients. In this study, we focused on the relationship between AMD pathology and concentrations of ferrous ion, which is a highly reactive oxygen generator in biological systems. Murine cone-cells-derived 661W cells were exposed to white florescence light at 2500 lx for 1, 3, 6, or 12 h. Levels of ferrous ions, reactive oxygen species (ROS), and hydroxyl radicals were detected by RhoNox-1, a novel fluorescent probe for the selective detection of ferrous ion, 5-(and-6)-chloromethy1-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H(2)DCFDA), and 3'-p-(aminophenyl) fluorescein, respectively. Reduced glutathione, total iron levels and photoreceptor cell death were also measured. Two genes related to iron metabolism, transferrin receptor 1 (TfR1) and H ferritin (HFt), were quantified by RT-PCR. The effects of ferrous ion on cell death and hydroxyl radical production were determined by treatment with a ferrous ion chelating agent, 2,2'-bipyridyl. We found that the ferrous ion level decreased with light exposure in the short time frame, whereas it was upregulated during a 6-h light exposure. Total iron, ROS, cell death rate, and expression of TfR and HFt genes were significantly increased in a time-dependent manner in 661W cells exposed to light. Chelation with 2,2'-bipyridyl reduced the level of hydroxyl radicals and protected against light-induced cell death. These results suggest that light exposure decreases ferrous ion levels and enhances iron uptake in photoreceptor cells. Ferrous ion may be involved in light-induced photoreceptor cell death through production of hydroxyl radicals. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Imamura, Tomoyo; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan.
   [Hirayama, Tasuku; Nagasawa, Hideko] Gifu Pharmaceut Univ, Dept Organ & Med Chem, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University; Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
FU Grants-in-Aid for Scientific Research [25702050] Funding Source: KAKEN
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NR 33
TC 18
Z9 19
U1 1
U2 23
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2014
VL 129
BP 24
EP 30
DI 10.1016/j.exer.2014.10.019
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AX4HJ
UT WOS:000346893800005
PM 25447561
DA 2022-11-30
ER

PT J
AU Yang, J
   Li, Y
   Chan, L
   Tsai, YT
   Wu, WH
   Nguyen, HV
   Hsu, CW
   Li, XR
   Brown, LM
   Egli, D
   Sparrow, JR
   Tsang, SH
AF Yang, Jin
   Li, Yao
   Chan, Lawrence
   Tsai, Yi-Ting
   Wu, Wen-Hsuan
   Nguyen, Huy V.
   Hsu, Chun-Wei
   Li, Xiaorong
   Brown, Lewis M.
   Egli, Dieter
   Sparrow, Janet R.
   Tsang, Stephen H.
TI Validation of genome-wide association study (GWAS)-identified disease
   risk alleles with patient-specific stem cell lines
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; POLYUNSATURATED FATTY-ACIDS; OXIDATIVE
   STRESS; MACULAR DEGENERATION; INDUCED APOPTOSIS; RPE LIPOFUSCIN; AGE
   PIGMENT; MODEL; FOXO; A2E
AB While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.
C1 [Yang, Jin; Li, Yao; Chan, Lawrence; Tsai, Yi-Ting; Wu, Wen-Hsuan; Nguyen, Huy V.; Hsu, Chun-Wei; Tsang, Stephen H.] Columbia Univ, Coll Phys & Surg, Dept Ophthalmol Pathol & Cell Biol, Barbara & Donald Jonas Lab Stem Cells & Regenerat, New York, NY 10032 USA.
   [Yang, Jin; Li, Yao; Chan, Lawrence; Tsai, Yi-Ting; Wu, Wen-Hsuan; Nguyen, Huy V.; Hsu, Chun-Wei; Sparrow, Janet R.; Tsang, Stephen H.] Columbia Univ, Edward S Harkness Eye Inst, New York, NY 10032 USA.
   [Yang, Jin; Li, Xiaorong] Tianjin Med Univ, Hosp Eye, Tianjin 300384, Peoples R China.
   [Brown, Lewis M.] Columbia Univ, Dept Biol Sci, Quantitat Prote Ctr, New York, NY 10027 USA.
   [Egli, Dieter] New York Stem Cell Fdn Lab, New York, NY 10032 USA.
   [Tsang, Stephen H.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Tianjin Medical University;
   Columbia University; The New York Stem Cell Foundation; Columbia
   University; NewYork-Presbyterian Hospital
RP Tsang, SH (通讯作者)，New York Presbyterian Columbia Univ, Med Ctr, Edward S Harkness Eye Inst, 160 Ft Washington Ave Res Annex,Room 513, New York, NY 10032 USA.
EM sht2@columbia.edu
FU National Institute of Health Core [5P30EY019007]; National Cancer
   Institute Core [5P30CA013696]; Research to Prevent Blindness, New York,
   NY, USA; Tistou and Charlotte Kerstan Foundation; National Institute of
   Health [R01EY018213]; Research to Prevent Blindness Physician-Scientist
   Award, Association for Research in Vision and Ophthalmology (ARVO)
   Foundation, Macular Society, Retina Research Foundation Cox Macular
   Research Project; Bernard and Shirlee Brown Family Fund; Schneeweiss
   Stem Cell Fund, New York State [N09G-302]; Foundation Fighting Blindness
   New York Regional Research Center Grant [C-NY05-0705-0312]; Joel Hoffman
   Fund; Professor Gertrude Rothschild Stem Cell Foundation; Gebroe Family
   Foundation; Research to Prevent Blindness Medical Student Fellowship;
   NATIONAL CANCER INSTITUTE [P30CA013696] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY018213, P30EY019007, R01EY012951] Funding
   Source: NIH RePORTER
FX This work was supported by the National Institute of Health Core
   (5P30EY019007), National Cancer Institute Core (5P30CA013696) and
   unrestricted funds from Research to Prevent Blindness, New York, NY,
   USA. S. H. T. is a member of the RD-CURE Consortium and is supported by
   the Tistou and Charlotte Kerstan Foundation, the National Institute of
   Health (R01EY018213), the Research to Prevent Blindness
   Physician-Scientist Award, Association for Research in Vision and
   Ophthalmology (ARVO) Foundation, Macular Society, Retina Research
   Foundation Cox Macular Research Project, the Bernard and Shirlee Brown
   Family Fund, the Schneeweiss Stem Cell Fund, New York State (N09G-302),
   the Foundation Fighting Blindness New York Regional Research Center
   Grant (C-NY05-0705-0312), the Joel Hoffman Fund, the Professor Gertrude
   Rothschild Stem Cell Foundation and the Gebroe Family Foundation. H.V.N.
   is supported by the Research to Prevent Blindness Medical Student
   Fellowship.
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   WOLF G, 1993, NUTR REV, V51, P348
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   Zhang SW, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0080342
NR 38
TC 73
Z9 73
U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL
PY 2014
VL 23
IS 13
BP 3445
EP 3455
DI 10.1093/hmg/ddu053
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AK0ST
UT WOS:000338126300008
PM 24497574
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Barleon, L
   Wahl, J
   Morfeld, P
   Deters, C
   Lichtmess, A
   Haas-Braahler, S
   Muller, U
   Breitstadt, R
   Pfeiffer, N
AF Barleon, Lorenz
   Wahl, Jochen
   Morfeld, Peter
   Deters, Claudia
   Lichtmess, Andrea
   Haas-Braehler, Sibylle
   Mueller, Uta
   Breitstadt, Rolf
   Pfeiffer, Norbert
TI The Evonik-Mainz-Eye-Care-Study (EMECS): Design and Execution of the
   Screening Investigation
SO PLOS ONE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; COST-EFFECTIVENESS; DIABETIC-RETINOPATHY; VISUAL
   IMPAIRMENT; POPULATION; PREVALENCE; WORLDWIDE; WORK
AB Purpose: To determine if screening for major ophthalmological diseases is feasible within the frame of routine occupational medicine examinations in a large working population.
   Methods: 13037 employees of Evonik Industries aged 40 to 65 years were invited to be screened for major ophthalmological diseases (glaucoma, age related macular degeneration and diabetic retinopathy between June 2007 and March 2008 within an extended setting of occupational medicine. Ophthalmological examinations consisted of visual acuity, objective refraction, pachymetry, tonometry, perimetry (frequency doubling technology), confocal scanning laser ophthalmoscopy and digital fundus photography. Participants responded to a questionnaire addressing history of ocular and general diseases and social history.
   Results: 4183 participants (961 female and 3222 male) were examined at 13 different sites. Response rates for eligible persons at those sites ranged from 17.9 to 60.5% but were in part limited by availability of examination slots. Average age of participants was 48.4 +/- 5.4 years (mean +/- SD). 4147 out of 4183 subjects (99.1%) had a visual acuity >= 0.5 in the better eye and 3665 out of 4183 (87.6%) subjects had a visual acuity >= 0.8 in the better eye. 1629 participants (38.9%) had previously not been seen by an ophthalmologist at all or not within the last three years.
   Conclusion: This article describes the study design and basic characteristics of study participants within a large occupational medicine based screening study for ophthalmological diseases. Response rates exceeded expectations and were limiting examination capacity. Meaningful data could be obtained for almost all participants. We reached participants who previously had not received ophthalmic care. Thus, ophthalmological screening appears to be feasible within the frame of routine occupational medicine examinations.
C1 [Barleon, Lorenz; Wahl, Jochen; Deters, Claudia; Lichtmess, Andrea; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, D-55122 Mainz, Germany.
   [Morfeld, Peter] Univ Cologne, Inst Occupat Med Environm Med & Prevent Res, D-50931 Cologne, Germany.
   [Morfeld, Peter] Inst Occupat Epidemiol & Risk Assessment Evonik I, Essen, Germany.
   [Haas-Braehler, Sibylle] Evonik Ind, Occupat Hlth, Hanau, Germany.
   [Mueller, Uta; Breitstadt, Rolf] Evonik Ind, Occupat Hlth, Essen, Germany.
C3 Johannes Gutenberg University of Mainz; University of Cologne; Evonik
   Industries; Evonik Industries; Evonik Industries
RP Barleon, L (通讯作者)，Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, D-55122 Mainz, Germany.
EM L.Barleon@diak-ka.de
RI Pfeiffer, Norbert/AAO-7586-2020
FU Evonik Industries
FX This investigation was sponsored by a grant from Evonik Industries. 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 4
Z9 4
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 10
PY 2014
VL 9
IS 6
AR e98538
DI 10.1371/journal.pone.0098538
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AN9SD
UT WOS:000340947700024
PM 24915063
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Juel, HB
   Faber, C
   Svendsen, SG
   Vallejo, AN
   Nissen, MH
AF Juel, Helene B.
   Faber, Carsten
   Svendsen, Signe G.
   Vallejo, Abbe N.
   Nissen, Mogens H.
TI Inflammatory Cytokines Protect Retinal Pigment Epithelial Cells from
   Oxidative Stress-Induced Death
SO PLOS ONE
LA English
DT Article
ID C-REACTIVE PROTEIN; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   MOLECULAR-MECHANISMS; POSSIBLE INVOLVEMENT; INDUCED APOPTOSIS; DRUSEN
   FORMATION; POTENTIAL ROLE; ARPE-19 CELLS; GROWTH-FACTOR
AB Purpose: To investigate the effects of inflammatory factors and oxidative stress on cell survival of the human retinal pigment epithelial (RPE) cell line, ARPE-19.
   Methods: Confluent RPE cells were treated with peripheral blood mononuclear cells-conditioned medium (PCM), H2O2, NaIO3, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, or combinations of these. Cell viability was determined by viability assays and by light microscopy. Effector molecules of cell death were investigated by immunofluorescence microscopy and flow cytometry. Microarrays were performed to screen for differential expression of anti-oxidative enzymes, and protein expression was validated by immunoblotting.
   Results: Viability of RPE cells was reduced by exposure to inflammatory agents (PCM, IFN gamma+/-TNF alpha) or to oxidative agents (H2O2 or NaIO3). Unexpectedly, cells treated with either H2O2 or NaIO3 were partially protected from cell death by the addition of PCM. This protection was conferred, at least in part, by IFN gamma and TNF alpha. Cell death induced by H2O2 or NaIO3 was preceded by mitochondrial dysfunction and by p62 upregulation, both of which were attenuated by PCM and/or by IFN gamma+TNF alpha. RPE cells co-cultured with activated T cells, or treated with cytokines showed increased expression of antio-xidative genes, with upregulation of superoxide dismutase 2 protein following PCM treatment.
   Conclusion: Oxidative stress-induced cell death was reduced by concomitant inflammatory stress. This is likely due to the cytokine-mediated induction of the anti-oxidative stress response, upregulating protective anti-oxidant pathway(s). These findings suggest caution for the clinical use of anti-inflammatory agents in the management of immune-associated eye diseases such as age-related macular degeneration.
C1 [Juel, Helene B.; Faber, Carsten; Svendsen, Signe G.; Nissen, Mogens H.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Eye Res Unit, Copenhagen, Denmark.
   [Vallejo, Abbe N.] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Dept Pediat,Dept Immunol,Pittsburgh Canc Inst, Pittsburgh, PA 15261 USA.
   [Vallejo, Abbe N.] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Pittsburgh, PA USA.
C3 University of Copenhagen; Pennsylvania Commonwealth System of Higher
   Education (PCSHE); University of Pittsburgh; Magee-Womens Research
   Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE);
   University of Pittsburgh
RP Juel, HB (通讯作者)，Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Eye Res Unit, Copenhagen, Denmark.
EM hjuel@sund.ku.dk
RI Nissen, Mogens/B-4825-2008; Faber, Carsten/I-4150-2013; Faber,
   Carsten/N-3210-2019; Juel, Helene/AAD-2843-2020
OI Nissen, Mogens/0000-0001-7729-8667; Faber, Carsten/0000-0002-2517-7270;
   Faber, Carsten/0000-0002-2517-7270; Juel, Helene B/0000-0002-5763-8545;
   Svendsen, Signe Goul/0000-0003-1618-5604
FU Velux Fonden; Vaern om Synet; Synoptikfonden; Candy Foundation; NATIONAL
   INSTITUTE ON AGING [R01AG030734] Funding Source: NIH RePORTER
FX This work was funded by research grants from Velux Fonden
   (veluxfonden.dk); Vaern om Synet (www.vos.dk); Synoptikfonden
   (www.synoptik-fonden.dk); and the Candy Foundation. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 72
TC 26
Z9 27
U1 0
U2 21
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 21
PY 2013
VL 8
IS 5
AR e64619
DI 10.1371/journal.pone.0064619
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 149OK
UT WOS:000319330200155
PM 23705001
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Campochiaro, PA
   Channa, R
   Berger, BB
   Heier, JS
   Brown, DM
   Fiedler, U
   Hepp, J
   Stumpp, MT
AF Campochiaro, Peter A.
   Channa, Roomasa
   Berger, Brian B.
   Heier, Jeffrey S.
   Brown, David M.
   Fiedler, Ulrike
   Hepp, Julia
   Stumpp, Michael T.
TI Treatment of Diabetic Macular Edema With a Designed Ankyrin Repeat
   Protein That Binds Vascular Endothelial Growth Factor: A Phase I/II
   Study
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RANIBIZUMAB; SAFETY; LASER
AB PURPOSE: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein.
   DESIGN: Phase I/II, open-label, multicenter dose-escalation trial.
   METHODS: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial.
   RESULTS: Median aqueous concentration of MP0112 was 555 nM 1 week and > 10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61%) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation.
   CONCLUSIONS: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial. (Am J Ophthalmol 2013;155:697-704. (C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Campochiaro, Peter A.; Channa, Roomasa] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Berger, Brian B.] Retina Res Ctr, Austin, TX USA.
   [Heier, Jeffrey S.] Ophthalm Consultants Boston, Boston, MA USA.
   [Brown, David M.] Retina Consultants Houston, Houston, TX USA.
   [Fiedler, Ulrike; Hepp, Julia; Stumpp, Michael T.] Mol Partners AG, Zurich, Switzerland.
C3 Johns Hopkins University; Johns Hopkins Medicine; Ophthalmic Consultants
   of Boston
RP Campochiaro, PA (通讯作者)，Johns Hopkins Sch Med, Wilmer Eye Inst, 719 Maumenee,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
RI C, Roomasa/AAK-5176-2020
FU Aerpio; Genentech; GlaxoSmithKline; Regeneron; Advanced Cell Technology;
   Elan; Gene Signal; Noryox; Genzyme; Oxford Biomedica; Molecular
   Partners; Allergan; Alcon; Iconic Therapeutics; LPath Inc; Lux
   Biosciences; Neovista Pharmaceuticals; Pfizer Inc; Thrombo genics;
   Alimera Sciences; Bausch and Lomb; Acucel; Bayer; Forsight; Fovea;
   Neovista; Oraya; Paloma; QLT; Quark; Neurotech; Novartis; Ophthotech;
   Regeneron/Bayer; Genentech/Roche; Alimera; Eli Lilly
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST. The authors have the following
   financial disclosures: Peter Campochiaro: Grant to institution from
   Molecular Partners. Relevant financial activities outside the submitted
   work: (1) consultancies with fee going to institution: Aerpio,
   Genentech, GlaxoSmithKline, and Regeneron; (2) consultancies with
   personal remuneration: Advanced Cell Technology, Elan, Gene Signal, and
   Noryox, (3) grants to institution: Genentech, Genzyme, GlaxoSmithKline,
   Oxford Biomedica; (4) co-inventor of "Treatment of ocular diseases with
   polymer/antracycline particles" (this has not produced income and if it
   does it will be divided between other inventor and the University); (5)
   Equity in Graybug. Brian Berger: Grant to institution from Molecular
   Partners and support from Molecular Partners for travel to a meeting.
   Relevant financial activities outside the submitted work: (1) grants to
   institution: Allergan, Alcon, GlaxoSmithKline, Iconic Therapeutics,
   LPath Inc, Lux Biosciences, Genentech, Neovista Pharmaceuticals, Pfizer
   Inc, Thrombo genics; (2) payment for lectures including service on
   speakers bureaus: Allergan, Alimera Sciences, Lux Biosciences, Bausch
   and Lomb. Jeffery Heier: Grant to institution from Molecular Partners.
   Relevant financial activities outside the submitted work: (1)
   consultancies: Acucel, Allergan, Bayer, Forsight, Fovea, Genentech,
   Genzyme, GlaxoSmithKline, LPath, Neovista, Oraya, Paloma, QLT, Quark,
   Regeneron; (2) grants to institution: Allergan, Alcon, GlaxoSmithKline,
   Fovea, Genentech, Genzyme, Neovista Pharmaceuticals, Neurotech,
   Novartis, Ophthotech, Paloma, Regeneron. David Brown: Grant to
   institution from Molecular Partners and consultancy fee from Molecular
   Partners. Support from Molecular Partners for travel to a meeting.
   Relevant financial activities outside the submitted work: (1)
   consultancies: Allergan, Regeneron/Bayer, Genentech/Roche, Alimera,
   Novartis; (2) grants to institution: Allergan, Alcon, Alimera, Eli
   Lilly, Genentech/Roche, Regeneron/Bayer, Novartis; (3) payment for
   lectures including service on speakers bureaus: Genentech/Roche. Ulrike
   Fiedler: Employee of Molecular Partners. Julia Hepp: Employee of
   Molecular Partners and stock options. Michael Stumpp: Employee of
   Molecular Partners and stock options. Molecular Partners AG, Zurich,
   Switzerland provided support for the study and participated in study
   design; conducted the study; and provided data collection, management,
   and interpretation. Author contributions: involved in design of the
   clinical trial, directing clinical trial, entering and evaluating
   patients, analyzing data, and writing first draft of the manuscript
   (P.C.); compiling and analyzing data and editing the manuscript (R.C.);
   entering patients in the clinical trial and evaluating them throughout
   the trial, and contributing to the editing of the manuscript (B.B.B.,
   J.S.H., D.M.B.); design, performance, and evaluation of the ocular
   pharmacokinetics data (U.F., J.H.); design of the clinical study and
   editing of the manuscript (M.T.S.).
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NR 13
TC 86
Z9 93
U1 0
U2 13
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 2013
VL 155
IS 4
BP 697
EP 704
DI 10.1016/j.ajo.2012.09.032
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 118JS
UT WOS:000317022400012
PM 23218689
DA 2022-11-30
ER

PT J
AU Uchiki, T
   Weikel, KA
   Jiao, WW
   Shang, F
   Caceres, A
   Pawlak, D
   Handa, JT
   Brownlee, M
   Nagaraj, R
   Taylor, A
AF Uchiki, Tomoaki
   Weikel, Karen A.
   Jiao, Wangwang
   Shang, Fu
   Caceres, Andrea
   Pawlak, Dorota
   Handa, James T.
   Brownlee, Michael
   Nagaraj, Ram
   Taylor, Allen
TI Glycation-altered proteolysis as a pathobiologic mechanism that links
   dietary glycemic index, aging, and age-related disease (in nondiabetics)
SO AGING CELL
LA English
DT Article
DE age-related macular degeneration; aging; glycemic index; proteolysis;
   ubiquitin
ID UBIQUITIN-PROTEASOME PATHWAY; CHAPERONE-MEDIATED AUTOPHAGY;
   END-PRODUCTS; OXIDATIVE STRESS; MACULAR DEGENERATION;
   PROTEIN-DEGRADATION; GLYOXALASE-I; HUMAN LENS; LIFE-SPAN;
   UBIQUITIN/PROTEASOME SYSTEM
AB Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains the salutary effect is a barrier to implementing dietary practices that capture the benefits of consuming lower GI diets. We established a simple murine model of age-related retinal lesions that precede AMD (hereafter called AMD-like lesions). We found that consuming a higher GI diet promotes these AMD-like lesions. However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (P < 0.02) and severity (P < 0.05) of hallmark age-related retinal lesions such as basal deposits. Consuming higher GI diets was associated with > 3 fold higher accumulation of advanced glycation end products (AGEs) in retina, lens, liver, and brain in the age-matched mice, suggesting that higher GI diets induce systemic glycative stress that is etiologic for lesions. Data from live cell and cell-free systems show that the ubiquitinproteasome system (UPS) and lysosome/autophagy pathway [lysosomal proteolytic system (LPS)] are involved in the degradation of AGEs. Glycatively modified substrates were degraded significantly slower than unmodified substrates by the UPS. Compounding the detriments of glycative stress, AGE modification of ubiquitin and ubiquitin-conjugating enzymes impaired UPS activities. Furthermore, ubiquitin conjugates and AGEs accumulate and are found in lysosomes when cells are glycatively stressed or the UPS or LPS/autophagy are inhibited, indicating that the UPS and LPS interact with one another to degrade AGEs. Together, these data explain why AGEs accumulate as glycative stress increases.
C1 [Uchiki, Tomoaki; Weikel, Karen A.; Jiao, Wangwang; Shang, Fu; Caceres, Andrea; Taylor, Allen] Tufts Univ, Lab Nutr & Vis Res, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Pawlak, Dorota] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA.
   [Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
   [Brownlee, Michael] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
   [Nagaraj, Ram] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 Tufts University; United States Department of Agriculture (USDA);
   Harvard University; Boston Children's Hospital; Harvard Medical School;
   Johns Hopkins University; Johns Hopkins Medicine; Yeshiva University;
   Albert Einstein College of Medicine; Case Western Reserve University
RP Taylor, A (通讯作者)，Tufts Univ, Lab Nutr & Vis Res, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM allen.taylor@tufts.edu
OI Weikel, Karen/0000-0003-0317-7891
FU USDA [1950-510000-060-01A]; Johnson and Johnson Focused Giving; NIH [RO1
   EY 13250, RO1 EY 21212]; NATIONAL EYE INSTITUTE [R01EY014005,
   R01EY013250, R01EY019904, R01EY021212] Funding Source: NIH RePORTER
FX The authors are indebted to Jacqueline Nguyen and Nori Nagai for
   initiating the histology, Dr Mary Rayborn for electron microscopy, Drs
   John Baynes and Susan Thorpe for gifts of the CML antibody, A-M Cuervo
   for help in isolation of lysosomes. Dr David Ludwig contributed tissues
   from 129SvPas mice. We appreciate contributions of carbohydrates from
   National Starch. We thank Dr Obin for critical review of this
   manuscript. NIH RO1 13250, RO1 21212, USDA 1950-510000-060-01A. Funding
   from USDA 1950-510000-060-01A, Johnson and Johnson Focused Giving, NIH
   RO1 EY 13250, RO1 EY 21212 is gratefully acknowledged.
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NR 110
TC 129
Z9 132
U1 0
U2 20
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2012
VL 11
IS 1
BP 1
EP 13
DI 10.1111/j.1474-9726.2011.00752.x
PG 13
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 875LN
UT WOS:000299031500001
PM 21967227
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Simon, E
   Bardet, B
   Gregoire, S
   Acar, N
   Bron, AM
   Creuzot-Garcher, CR
   Bretillon, L
AF Simon, Emilie
   Bardet, Bertrand
   Gregoire, Stephane
   Acar, Niyazi
   Bron, Alain M.
   Creuzot-Garcher, Catherine R.
   Bretillon, Lionel
TI Decreasing dietary linoleic acid promotes long chain omega-3 fatty acid
   incorporation into rat retina and modifies gene expression
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE lipid; nutrition; retina; retinal pigment epithelium; gene expression
ID POLYUNSATURATED FATTY-ACIDS; MACULAR DEGENERATION; DOCOSAHEXAENOIC ACID;
   N-3; DEFICIENCY; BRAIN; PUFA; ELECTRORETINOGRAM; ASSOCIATIONS; RESPONSES
AB Age-related macular degeneration (AMD) may be partially prevented by dietary habits privileging the consumption of omega 3 long chain polyunsaturated fatty acids (omega 3s) while lowering linoleic acid (LA) intake. The present study aimed to document whether following these epidemiological guidelines would enrich the neurosensory retina and RPE with omega 3s and modulate gene expression in the neurosensory retina. Rat progenitors and pups were fed with diets containing low or high LA, and low or high omega 3s. After scotopic single flash and 8-Hz-Flicker electroretinography, rat pups were euthanized at adulthood. The fatty acid profile of the neurosensory retina, RPE, liver, adipose tissue and plasma was analyzed using gas chromatography. Gene expression was analyzed with real-time PCR in the neurosensory retina. Diets rich in omega 3s efficiently improved the incorporation of Os into the organs and tissues. This raising effect was magnified by lowering LA intake. Compared to a diet with high LA and low omega 3s, low LA diets significantly upregulated LDL-receptor gene expression. Similar but not significant upregulation of CD36, ABCA1, ALOX5 and ALOX12 gene expression was observed in rats fed with low LA. No effect was observed on retinal function. Increasing the intake in omega 3s and lowering LA improved the enrichment with omega 3s of the tissues, including the neurosensory retina and RPE, and upregulated genes involved in lipid trafficking in the neurosensory retina. Those results consistently reinforced the beneficial role of omega 3s in the prevention of AMD, especially when the diet contained low levels of LA, as suggested from epidemiological data. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Simon, Emilie; Bardet, Bertrand; Gregoire, Stephane; Acar, Niyazi; Bron, Alain M.; Creuzot-Garcher, Catherine R.; Bretillon, Lionel] Univ Burgundy, Ctr Sci Gout & Alimentat, UMR INRA 1324, CNRS 6265,Eye & Nutr Res Grp, F-21065 Dijon, France.
   [Bron, Alain M.; Creuzot-Garcher, Catherine R.] Univ Hosp, Dept Ophthalmol, Dijon, France.
C3 INRAE; Institut Agro; AgroSup Dijon; Centre National de la Recherche
   Scientifique (CNRS); Universite de Bourgogne; CHU Dijon Bourgogne
RP Bretillon, L (通讯作者)，Univ Burgundy, Ctr Sci Gout & Alimentat, UMR INRA 1324, CNRS 6265,Eye & Nutr Res Grp, 17 Rue Sully,BP86510, F-21065 Dijon, France.
EM lionel.bretillon@dijon.inra.fr
RI Simon, Emilie/B-1194-2009; Bron, Alain/AAP-8010-2020
OI Bron, Alain/0000-0002-7265-931X; Bretillon, Lionel/0000-0002-6957-100X
FU INRA (Human Nutrition Department, France); Laboratoires Horus Pharma
   (Saint Laurent du Var, France) [29000305]; Regional Council of Burgundy
   (France) [29000362]
FX Financial support was provided by INRA (Human Nutrition Department,
   France), Laboratoires Horus Pharma (Saint Laurent du Var, France, grant
   no. 29000305), and the Regional Council of Burgundy (France) (PhD
   fellowship for ES, grant no. 29000362).
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NR 46
TC 16
Z9 17
U1 0
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 NOV
PY 2011
VL 93
IS 5
BP 628
EP 635
DI 10.1016/j.exer.2011.07.016
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 855AK
UT WOS:000297535700009
PM 21821023
DA 2022-11-30
ER

PT J
AU Cao, JT
   Zhao, LA
   Li, YW
   Liu, Y
   Xiao, WH
   Song, Y
   Luo, LY
   Huang, DQ
   Yancopoulos, GD
   Wiegand, SJ
   Wen, R
AF Cao, Jingtai
   Zhao, Lian
   Li, Yiwen
   Liu, Yang
   Xiao, Weihong
   Song, Ying
   Luo, Lingyu
   Huang, Deqiang
   Yancopoulos, George D.
   Wiegand, Stanley J.
   Wen, Rong
TI A Subretinal Matrigel Rat Choroidal Neovascularization (CNV) Model and
   Inhibition of CNV and Associated Inflammation and Fibrosis by VEGF Trap
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; MEDIATED EXPRESSION; BASEMENT-MEMBRANE; NATURAL-HISTORY;
   BRUCHS MEMBRANE; ANGIOGENESIS; RABBIT; MACROPHAGES
AB PURPOSE. The exudative, or the wet form of age-related macular degeneration(AMD) is characterized by choroidal neovascularization (CNV). A subretinal Matrigel(BD Biosciences, Bedford MA) model of CNV is described here, along with the effects of vascular endothelial growth factor(VEGF) neutralization on the development of CNV and associated inflammation and fibrosis.
   METHODS. CNV was induced in adult Sprague-Dawley rats by subretinal injection of Matrigel. CNV growth and associated leukocyte infiltration and collagen deposition were examined. VEGF Trap(Regeneron Pharmaceuticals, Tarrytown, NY), a recombinant protein that comprises portions of the extracellular domains of VEGF receptors 1 and 2 and that binds all isoforms of VEGF-A as well as placental growth factor with high affinity, was administered subcutaneously.
   RESULTS. Initiation of CNV was detected 4 days after Matrigel injection and then increased progressively in size. Systemic administration of VEGF Trap beginning on day 2 and 6 completely prevented development of CNV. When CNV was allowed to develop for 10 days before treatment was initiated, VEGF Trap not only prevented its further progression, but also induced substantial regression of existing lesions. In addition, VEGF Trap treatment reduced the total lesion volume and largely prevented the progressive leukocyte infiltration and fibrosis associated with CNV.
   CONCLUSIONS. The subretinal Matrigel CNV model provides a convenient tool for the study of the diverse components of complex CNV lesions. The data not only confirm the critical roles of VEGF in the development and maintenance of CNV, but further demonstrate that VEGF and other VEGF receptor 1 ligands promote CNV-associated inflammation and fibrosis. (Invest Ophthalmol Vis Sci.2010;51:6009-6017) DOI:10.1167/iovs.09-4956
C1 [Li, Yiwen; Luo, Lingyu; Huang, Deqiang; Wen, Rong] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Cao, Jingtai; Liu, Yang; Xiao, Weihong; Yancopoulos, George D.; Wiegand, Stanley J.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
   [Zhao, Lian; Song, Ying] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Regeneron; University
   of Pennsylvania
RP Wen, R (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 506 McKnight Bldg,1638 NW 10th Ave, Miami, FL 33136 USA.
EM rwen@med.miami.edu
FU NIH [R01EY015289, R01EY018586, P30EY014801]; James and Esther King
   Biomedical Research Program of the State of Florida; U.S. Department of
   Defense [08192003]; Karl Kirchgessner Foundation; Foundation Fighting
   Blindness; Research to Prevent Blindness Inc.; NATIONAL EYE INSTITUTE
   [R01EY015289, P30EY014801, R01EY018586] Funding Source: NIH RePORTER
FX Supported by NIH Grants R01EY015289 (RW) and R01EY018586 (RW); a grant
   from the James and Esther King Biomedical Research Program of the State
   of Florida (YL); Grant USAMRMC NO: 08192003 from the U.S. Department of
   Defense (RW); the Karl Kirchgessner Foundation (RW); the Foundation
   Fighting Blindness; and by NIH Core Grant P30EY014801 and an
   unrestricted grant from Research to Prevent Blindness Inc. to Bascom
   Palmer Eye Institute.
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NR 51
TC 67
Z9 81
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 NOV
PY 2010
VL 51
IS 11
BP 6009
EP 6017
DI 10.1167/iovs.09-4956
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 672BQ
UT WOS:000283558400077
PM 20538989
OA Green Published
DA 2022-11-30
ER

PT J
AU Messias, A
   Zrenner, E
   Tzekov, R
   McGee, D
   Peters, T
   Wilhelm, B
   Baryluk, A
   Kubota, R
   Gekeler, F
AF Messias, Andre
   Zrenner, Eberhart
   Tzekov, Radouil
   McGee, David
   Peters, Tobias
   Wilhelm, Barbara
   Baryluk, Aneta
   Kubota, Ryo
   Gekeler, Florian
TI Single doses of all-trans-N-retinylacetamide slow down the ERG amplitude
   recovery after bleaching in rats
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Visual cycle; Electroretinography; Rats; Dark adaptation; Rods; Cones;
   Retinoid
ID MACULAR DEGENERATION; VISUAL CYCLE; FUNDUS AUTOFLUORESCENCE; LIPOFUSCIN
   ACCUMULATION; RETINOID CYCLE; INHIBITORS; DYSTROPHY; POTENT; GENE; ABCR
AB To assess the safety and to quantify the effects of a single application of all-trans-N-retinylacetamide on the rat retina measured by electroretinography (ERG). Brown Norway rats were assigned to either a control group (n = 13) or to one of the three groups treated with a single intra-peritoneal dose of all-trans-N-retinylacetamide: 20 (n = 8), 5 (n = 7), or 1 mg/kg (n = 8). Full-field ERGs were performed 7 days before (baseline) and 12 h after treatment. Intensity-response relationship of b-wave amplitudes were evaluated in dark-adapted conditions using white stimuli (0.000003-0.3 cd.s/m(2)). Fast dynamics of rod sensitivity was assessed by a paired-flash paradigm; recovery dynamics of b-wave amplitudes after bleaching was followed for 70 min. Light-adapted ERGs were recorded for cone evaluation. No effects were found on either dark-adapted sensitivity or on fast rod recovery. However, drug treatment at 5 and 20 mg/kg significantly delayed ERG amplitude recovery after bleaching: 60 min after bleaching the b-wave amplitude was 21 +/- A 9% (P < 0.05) and 66 +/- A 10% (P < 0.05), respectively, compared to baseline. Recovery rates returned to normal 8 weeks after treatment. There were no changes in light-adapted ERG in any group. Systemic administration of a single dose of the visual cycle modulator all-trans-N-retinylacetamide reversibly delayed recovery of dark-adapted ERG amplitudes after bleaching, leaving other functions unchanged. This finding could make the compound potentially useful in experimental conditions or in specific diseases where the visual cycle is involved, such as retinitis pigmentosa or age-related macular degeneration.
C1 [Messias, Andre; Zrenner, Eberhart; Baryluk, Aneta; Gekeler, Florian] Univ Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   [Messias, Andre] USP, Sch Med Ribeirao Preto, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Ribeirao Preto, Brazil.
   [Tzekov, Radouil; McGee, David; Kubota, Ryo] Acucela Inc, Bothell, WA USA.
   [Zrenner, Eberhart; Peters, Tobias; Wilhelm, Barbara] Steinbeis Transfer Ctr Biomed Opt & Funct Testing, Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Universidade de Sao Paulo
RP Messias, A (通讯作者)，Univ Tubingen, Ctr Ophthalmol, Schleichstr 12-16, D-72076 Tubingen, Germany.
EM amessias@hotmail.com
RI Messias, Andre/H-5801-2012; Messias, Andre MV/C-1560-2012
OI Messias, Andre/0000-0002-5328-9608; Messias, Andre
   MV/0000-0002-5328-9608; Tzekov, Radouil/0000-0002-3662-9818
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NR 19
TC 6
Z9 7
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0012-4486
J9 DOC OPHTHALMOL
JI Doc. Ophthalmol.
PD APR
PY 2010
VL 120
IS 2
BP 165
EP 174
DI 10.1007/s10633-009-9209-2
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 568MP
UT WOS:000275526800005
PM 20012154
DA 2022-11-30
ER

PT J
AU Hillenkamp, J
   Surguch, V
   Framme, C
   Gabel, VP
   Sachs, HG
AF Hillenkamp, Jost
   Surguch, Vladimir
   Framme, Carsten
   Gabel, Veit-Peter
   Sachs, Helmut G.
TI Management of submacular hemorrhage with intravitreal versus subretinal
   injection of recombinant tissue plasminogen activator
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Retinal arterial macroaneurysma;
   Recombinant tissue plasminogen activator; Submacular hemorrhage
ID MACULAR DEGENERATION; PNEUMATIC DISPLACEMENT; NATURAL-HISTORY; EXPANSILE
   GAS; BEVACIZUMAB; REMOVAL; SURGERY; RABBITS
AB To compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas.
   Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea.
   Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A.
   ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.
C1 [Hillenkamp, Jost] Univ Med Ctr Schleswig Holstein, Dept Ophthalmol, D-24105 Kiel, Germany.
   [Surguch, Vladimir; Framme, Carsten; Gabel, Veit-Peter; Sachs, Helmut G.] Univ Regensburg, Regensburg, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Regensburg
RP Hillenkamp, J (通讯作者)，Univ Med Ctr Schleswig Holstein, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
EM hillenka@hotmail.com
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NR 29
TC 87
Z9 90
U1 0
U2 2
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 JAN
PY 2010
VL 248
IS 1
BP 5
EP 11
DI 10.1007/s00417-009-1158-7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 527IJ
UT WOS:000272360400002
PM 19669780
OA Green Published
DA 2022-11-30
ER

PT J
AU Lai, JY
   Lin, PK
   Hsiue, GH
   Cheng, HY
   Huang, SJ
   Li, YT
AF Lai, Jui-Yang
   Lin, Po-Kang
   Hsiue, Ging-Ho
   Cheng, Hsiao-Yun
   Huang, Shu-Jung
   Li, Ya-Ting
TI Low Bloom Strength Gelatin as a Carrier for Potential Use in Retinal
   Sheet Encapsulation and Transplantation
SO BIOMACROMOLECULES
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; IN-VITRO; CONTROLLED-RELEASE;
   MECHANICAL-PROPERTIES; PHOTORECEPTOR CELLS; MOLECULAR-WEIGHT;
   GROWTH-FACTOR; MOUSE RETINA; TISSUE; FILMS
AB Retinal transplantation aims to restore vision for patients suffering from retinitis pigmentosa and age-related macular degeneration. Because the retinal sheets are fragile in nature, it is difficult to maintain graft integrity during surgical manipulation and after transplantation. In the present work, we report the feasibility of applying sandwichlike gelatin membranes as encapsulating carriers for retinal sheet transplantation applications. The relationship between the Bloom index of gelatin and the functionality of carrier membranes was studied by determinations of mechanical property, dissolution degree, melting point, cytocompatibility, biocompatibility, and transplant transfer and encapsulation efficiency. Irrespective of their Bloom strength, the gelatin membranes had a thickness sufficient to provide mechanical support for retinal sheets and would be beneficial to overcome the fragility of transplants during intraocular delivery. It was found that the lower the Bloom value of gelatin, the lower melting point of membranes. This allowed for easy fabrication of a stable sandwich-like encapsulating structure at 37 degrees C. The gelatins with lower Bloom strengths could possibly be dissolved to an extent required for the establishment of close contact between the retinal grafts and defective tissues. In addition, the carrier membranes made from the gelatins with low Bloom values showed a relatively higher cytocompatibility and biocompatibility as well as a higher transfer and encapsulation efficiency as compared to those with high Bloom values. It is concluded that the effect of Bloom index of gelatin plays a significant role in the membrane functionality and the gelatins with low Bloom values have substantial potential to be further developed as effective encapsulating carriers for the intraocular delivery of retinal sheets.
C1 [Lai, Jui-Yang; Huang, Shu-Jung; Li, Ya-Ting] Chang Gung Univ, Inst Biochem & Biomed Engn, Tao Yuan 33302, Taiwan.
   [Lai, Jui-Yang] Chang Gung Univ, Biomed Engn Res Ctr, Tao Yuan 33302, Taiwan.
   [Lai, Jui-Yang; Cheng, Hsiao-Yun] Chang Gung Univ, Mol Med Res Ctr, Tao Yuan 33302, Taiwan.
   [Lin, Po-Kang] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 11217, Taiwan.
   [Hsiue, Ging-Ho] Natl Tsing Hua Univ, Dept Chem Engn, Hsinchu 30013, Taiwan.
C3 Chang Gung University; Chang Gung University; Chang Gung University;
   Taipei Veterans General Hospital; National Tsing Hua University
RP Lai, JY (通讯作者)，Chang Gung Univ, Inst Biochem & Biomed Engn, Tao Yuan 33302, Taiwan.
EM jylai@mail.cgu.edu.tw; ghhsiue@mx.nthu.edu.tw
RI Lai, Jui-Yang/I-1166-2017
OI Lai, Jui-Yang/0000-0002-9227-8549
FU National Science Council of Republic of China [NSC97-2221-E-182-003];
   Chang Gung Memorial Hospital [CMRPD160392]; National Tsing Hua
   University [NTHU97N2551E1]
FX This work was supported financially by Grant NSC97-2221-E-182-003 from
   the National Science Council of Republic of China, Grant CMRPD160392
   from Chang Gung Memorial Hospital, and Grant NTHU97N2551E1 from National
   Tsing Hua University.
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NR 56
TC 55
Z9 56
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
EI 1526-4602
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD FEB
PY 2009
VL 10
IS 2
BP 310
EP 319
DI 10.1021/bm801039n
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 405LM
UT WOS:000263226300015
PM 19063667
DA 2022-11-30
ER

PT J
AU Janoria, KG
   Gunda, S
   Boddu, SH
   Mitra, AK
AF Janoria, Kumar G.
   Gunda, Sriram
   Boddu, Sai Hs
   Mitra, Ashim K.
TI Novel approaches to retinal drug delivery
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
ID LIPOSOME-ENCAPSULATED GANCICLOVIR; BIODEGRADABLE SCLERAL IMPLANT;
   INTRAVITREAL CONTROLLED-RELEASE; AMINO-ACID TRANSPORTER; CYTOMEGALOVIRUS
   RETINITIS; SUSTAINED-RELEASE; PROLIFERATIVE VITREORETINOPATHY; POSTERIOR
   SEGMENT; P-GLYCOPROTEIN; MACULAR EDEMA
AB Research into treatment modalities affecting vision is rapidly progressing due to the high incidence of diseases such as diabetic macular edema, proliferative vitreoretinopathy, wet and dry age-related macular degeneration and cytomegalovirus retinitis. The unique anatomy and physiology of eye offers many challenges to developing effective retinal drug delivery systems. Historically, drugs have been administered to the eye as liquid drops instilled in the cul-de-sac. However retinal drug delivery is a challenging area. The transport of molecules between the vitreous/retina and systemic circulation is restricted by the blood-retinal barrier, which is made up of retinal pigment epithelium and endothelial cells of the retinal blood vessels. An increase in the understanding of drug absorption mechanisms into the retina from local and systemic administration has led to the development of various drug delivery systems, such as biodegradable and non-biodegradable implants, microspheres, nanoparticles and liposomes, gels and transporter-targeted prodrugs. Such diversity in approaches is an indication that there is still a need for an optimized noninvasive or minimally invasive drug delivery system to the eye. A number of large molecular weight compounds (i.e., oligonucleotides, RNA aptamers, peptides and monoclonal antibodies) have been and continue to be introduced as new therapeutic entities. However, for high molecular weight polar compounds the mechanism of epithelial transport is primarily through the tight junctions in the retinal pigment epithelium, as these agents undergo limited transcellular diffusion. Delivery and administration of these new drugs in a safe and effective manner is still a major challenge facing pharmaceutical scientists. In this review article, the authors discuss various drug delivery strategies, devices and challenges associated with drug delivery to the retina.
C1 [Janoria, Kumar G.; Gunda, Sriram; Boddu, Sai Hs; Mitra, Ashim K.] Univ Missouri, Sch Pharm, Dept Pharmaceut Sci, Kansas City, MO 64110 USA.
C3 University of Missouri System; University of Missouri Kansas City
RP Janoria, KG (通讯作者)，Univ Missouri, Sch Pharm, Dept Pharmaceut Sci, Kansas City, MO 64110 USA.
RI Boddu, Sai Hanuman Sagar/E-7777-2012; Sanguansri, Luz/B-6630-2011
OI Sanguansri, Luz/0000-0003-1908-7604; BODDU, SAI HS/0000-0003-2513-5879
FU NATIONAL EYE INSTITUTE [R01EY009171, R01EY010659] Funding Source: NIH
   RePORTER; NEI NIH HHS [R01 EY10659-10, R01 EY09171-12] Funding Source:
   Medline
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NR 193
TC 134
Z9 167
U1 2
U2 42
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD JUL
PY 2007
VL 4
IS 4
BP 371
EP 388
DI 10.1517/17425247.4.4.371
PG 18
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 258GS
UT WOS:000252857000006
PM 17683251
DA 2022-11-30
ER

PT J
AU Kanan, Y
   Moiseyev, G
   Agarwal, N
   Ma, JX
   Al-Ubaidi, MR
AF Kanan, Yogita
   Moiseyev, Gennadiy
   Agarwal, Neeraj
   Ma, Jian-Xing
   Al-Ubaidi, Muayyad R.
TI Light induces programmed cell death by activating multiple independent
   proteases in a cone photoreceptor cell line
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID STRESS-INDUCED APOPTOSIS; INHERITED RETINAL DEGENERATIONS; STARGARDT
   MACULAR DYSTROPHY; RETINITIS-PIGMENTOSA; VISUAL PIGMENT; KAPPA-B;
   OXIDATIVE STRESS; BINDING PROTEIN; TRANSGENIC MICE; ABCA4 ABCR
AB PURPOSE. Although the apoptotic death of photoreceptor cells in retinal degenerative disorders is well documented, the molecular mechanism is not understood. The objective of this study was to determine the molecular events leading to the death of photoreceptor cells.
   METHODS. An assay was developed wherein 661W cells, a cone photoreceptor cell line, were stressed with light and percentage of surviving cells was determined. The degree of cell death was established using the MTT assay. Western blot analysis was used to confirm the activation of multiple proteases. Amounts of retinaldehydes were determined by extraction and HPLC.
   RESULTS. 661W cells were more susceptible to light stress only in the presence of the chromophore 9-cis retinal for 4 hours. On exposure to light, 9-cis retinal was converted to all-trans retinal, which was found to be toxic to cells in the presence of light. However, all-trans retinol, which is the product of action by the enzyme retinol dehydrogenase on all-trans retinal, was not toxic. The sensitivity to light increased with serum deprivation. Light stress activated caspases, calpain 2, and cathepsin D independently and led to the demise of the cell. The mitochondria-dependent apoptotic pathway was also activated after the truncation of Bid, the pre-proapoptotic protein. Truncation of Bid led to the release of cytochrome c from the mitochondria and the activation of caspase 9.
   CONCLUSIONS. The activation of multiple proteases by light-induced stress is a relevant finding for studies conducted to investigate the use of pharmaceutical agents to retard or cure the loss of cone photoreceptors observed in age-related macular degeneration and other degenerative retinal diseases.
C1 Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   Univ Oklahoma, Hlth Sci Ctr, Dept Med & Endocrinol, Oklahoma City, OK 73104 USA.
   Univ Texas, Hlth Sci Ctr, Dept Cell Biol & Genet, Ft Worth, TX USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Texas System; University of Texas
   Arlington
RP Al-Ubaidi, MR (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, BMSB 781,940 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
EM muayyad-al-ubaidi@ouhsc.edu
RI Agarwal, Neeraj/AAP-2676-2021
FU NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017703] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R33EY015650, R01EY014052, R01EY012231,
   R21EY015650, P30EY012190] Funding Source: NIH RePORTER; NCRR NIH HHS
   [RR017703] Funding Source: Medline; NEI NIH HHS [EY14052, EY015650,
   EY012231, EY012190] Funding Source: Medline
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NR 54
TC 58
Z9 65
U1 0
U2 8
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 JAN
PY 2007
VL 48
IS 1
BP 40
EP 51
DI 10.1167/iovs.06-0592
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 124GC
UT WOS:000243355100007
PM 17197514
DA 2022-11-30
ER

PT J
AU Shields, JA
   Mashayekhi, A
   Ra, S
   Shields, CL
AF Shields, Jerry A.
   Mashayekhi, Arman
   Ra, Seong
   Shields, Carol L.
TI Pseudomelanomas of the posterior uveal tract - The 2006 Taylor R. Smith
   Lecture
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; CONGENITAL HYPERTROPHY; CLINICAL
   MANIFESTATIONS; CHOROIDAL MELANOMA; SCLEROCHOROIDAL CALCIFICATION;
   TUMORS; LESIONS; GROWTH; THE-1998-ALBERT-RUEDEMANN-SR-MEMORIAL-LECTURE;
   ADENOCARCINOMA
AB Purpose: To determine the types and frequency of lesions that clinically simulate choroidal or ciliary body melanoma (posterior uveal melanoma; PUM).
   Patients and Methods: A review was conducted on cases of patients referred to the ocular oncology service from October 1978 through September 2003 with the diagnosis of possible PUM but who were subsequently diagnosed by the authors to have a simulating lesion rather than PUM. The type and percent of pseudomelanomas were tabulated and compared with findings of a similar study from our service on data collected before 1978.
   Results: There were approximate to 12,000 patients referred because of a lesion believed to be a PUM during the 25 years included in the data collection. Of these patients, 1,739 (14%) were found to have a simulating condition. There were 54 different conditions that simulated melanoma. The most frequent condition was choroidal nevus, accounting for 851 cases (49%) of the pseudomelanomas. This was followed by peripheral exudative hemorrhagic chorioretinopathy (139 cases; 8%), congenital hypertrophy of the retinal pigment epithelium (108 cases; 6%), hemorrhagic detachment of the retina or pigment epithelium (86 cases; 5%), circumscribed choroidal hemangioma (79 cases; 5%) and age-related macular degeneration (76 cases; 4%). Compared with the 1980 report, the rate of pseudomelanomas diagnosed as choroidal nevus increased from 26% to 49%.
   Conclusion: A variety of lesions can simulate PUM. Suspicious choroidal nevus is still the lesion most difficult to differentiate from PUM. Most other pseudomelanomas account for a lower percent compared with findings from the prior study, suggesting that clinicians are now more familiar with the other pseudomelanomas and less likely to refer them to rule out PUM.
C1 Thomas Jefferson Univ, Wills Eye Hosp, Oncol Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Shields, JA (通讯作者)，Wills Eye Hosp & Res Inst, Ocular Oncol Serv, 840 Walnut St, Philadelphia, PA 19107 USA.
EM jerry.shields@shieldsoncology.com
RI Mashayekhi, Arman/I-3703-2019
OI Mashayekhi, Arman/0000-0002-1739-1322
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NR 43
TC 63
Z9 66
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2005
VL 25
IS 6
BP 767
EP 771
DI 10.1097/00006982-200509000-00013
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 100QU
UT WOS:000241684500013
PM 16141866
DA 2022-11-30
ER

PT J
AU Chu, ZD
   Wang, L
   Zhou, X
   Shi, YY
   Cheng, YX
   Laiginhas, R
   Zhou, H
   Shen, MX
   Zhang, QQ
   de Sisternes, L
   Lee, AY
   Gregori, G
   Rosenfeld, PJ
   Wang, RK
AF Chu, Zhongdi
   Wang, Liang
   Zhou, Xiao
   Shi, Yingying
   Cheng, Yuxuan
   Laiginhas, Rita
   Zhou, Hao
   Shen, Mengxi
   Zhang, Qinqin
   de Sisternes, Luis
   Lee, Aaron Y.
   Gregori, Giovanni
   Rosenfeld, Philip J.
   Wang, Ruikang K.
TI Automatic geographic atrophy segmentation using optical attenuation in
   OCT scans with deep learning
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID MACULAR DEGENERATION; COHERENCE TOMOGRAPHY; NATURAL-HISTORY;
   PROGRESSION; GROWTH; CHORIOCAPILLARIS; COEFFICIENTS; ENLARGEMENT;
   PREVALENCE; SECONDARY
AB A deep learning algorithm was developed to automatically identify, segment, and quantify geographic atrophy (GA) based on optical attenuation coefficients (OACs) calculated from optical coherence tomography (OCT) datasets. Normal eyes and eyes with GA secondary to age-related macular degeneration were imaged with swept-source OCT using 6 x 6 mm scanning patterns. OACs calculated from OCT scans were used to generate customized composite en face OAC images. GA lesions were identified and measured using customized en face sub-retinal pigment epithelium (subRPE) OCT images. Two deep learning models with the same U-Net architecture were trained using OAC images and subRPE OCT images. Model performance was evaluated using DICE similarity coefficients (DSCs). The GA areas were calculated and compared with manual segmentations using Pearson's correlation and Bland-Altman plots. In total, 80 GA eyes and 60 normal eyes were included in this study, out of which, 16 GA eyes and 12 normal eyes were used to test the models. Both models identified GA with 100% sensitivity and specificity on the subject level. With the GA eyes, the model trained with OAC images achieved significantly higher DSCs, stronger correlation to manual results and smaller mean bias than the model trained with subRPE OCT images (0.940 +/- 0.032 vs 0.889 +/- 0.056, p = 0.03, paired t-test, r = 0.995 vs r = 0.959, mean bias = 0.011 mm vs mean bias = 0.117 mm). In summary, the proposed deep learning model using composite OAC images effectively and accurately identified, segmented, and quantified GA using OCT scans. (C) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
C1 [Chu, Zhongdi; Zhou, Xiao; Cheng, Yuxuan; Zhou, Hao; Zhang, Qinqin; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
   [Wang, Liang; Shi, Yingying; Laiginhas, Rita; Shen, Mengxi; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Bascom Palmer Eye Inst, Dept Ophthalmol, Miller Sch Med, Miami, FL 33136 USA.
   [de Sisternes, Luis] Carl Zeiss Meditec Inc, Res & Dev, Dublin, CA USA.
   [Lee, Aaron Y.; Wang, Ruikang K.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Bascom
   Palmer Eye Institute; University of Miami; Carl Zeiss AG; University of
   Washington; University of Washington Seattle
RP Wang, RK (通讯作者)，Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.; Wang, RK (通讯作者)，Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
EM wangrk@uw.edu
RI Shen, Mengxi/ABC-6941-2021; Wang, Ruikang/L-3889-2019; Zhou,
   Hao/U-7850-2017
OI Wang, Ruikang/0000-0001-5169-8822; Shen, Mengxi/0000-0002-1336-1695;
   Zhou, Hao/0000-0003-0068-5102
FU Research to Prevent Blindness; Carl Zeiss Meditec Inc; National Eye
   Institute [K23EY029246, P30EY014801, R01EY028753]
FX Research to Prevent Blindness; Carl Zeiss Meditec Inc; National Eye
   Institute (K23EY029246, P30EY014801, R01EY028753).
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NR 43
TC 6
Z9 6
U1 0
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 MAR 1
PY 2022
VL 13
IS 3
BP 1328
EP 1343
DI 10.1364/BOE.449314
PG 16
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 ZN1UQ
UT WOS:000764828300005
PM 35414972
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gnanaguru, G
   Mackey, A
   Choi, EY
   Arta, A
   Rossato, FA
   Gero, TW
   Urquhart, AJ
   Scott, DA
   D'Amore, PA
   Ng, YSE
AF Gnanaguru, Gopalan
   Mackey, Ashley
   Choi, Eun Young
   Arta, Anthoula
   Rossato, Franco Aparecido
   Gero, Thomas W.
   Urquhart, Andrew J.
   Scott, David A.
   D'Amore, Patricia A.
   Ng, Yin Shan E.
TI Discovery of sterically-hindered phenol compounds with potent
   cytoprotective activities against ox-LDL-induced retinal pigment
   epithelial cell death as a potential pharmacotherapy
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; Oxidized
   lipids; Lysosomes; Hindered phenol compounds; Cytoprotection
ID NLRP3 INFLAMMASOME ACTIVATION; LOW-DENSITY LIPOPROTEINS; ANTIOXIDANTS;
   ATHEROSCLEROSIS; CHOLESTEROL; OXLDL; NEK7
AB Late-stage dry age-related macular degeneration (AMD) or geographic atrophy (GA) is an irreversible blinding condition characterized by degeneration of retinal pigment epithelium (RPE) and the associated photoreceptors. Clinical and genetic evidence supports a role for dysfunctional lipid processing and accumulation of harmful oxidized lipids in the pathogenesis of GA. Using an oxidized low-density lipoprotein (ox-LDL)-induced RPE death assay, we screened and identified sterically-hindered phenol compounds with potent protective activities for RPE. The phenol-containing PPAR gamma agonist, troglitazone, protected against ox-LDL-induced RPE cell death, whereas other more potent PPAR gamma agonists did not protect RPE cells. Knockdown of PPAR gamma did not affect the protective activity of troglitazone in RPE, confirming the protective function is not due to the thiazolidine (TZD) group of troglitazone. Prototypical hindered phenol trolox and its analogs potently protected against ox-LDL-induced RPE cell death whereas potent antioxidants without the phenol group failed to protect RPE. Hindered phenols preserved lysosomal integrity against ox-LDL-induced damage and FITC-labeled trolox was localized to the lysosomes in RPE cells. Analogs of tmlox inhibited reactive oxygen species (ROS) formation induced by ox-LDL uptake in a dose-dependent fashion and were effective at sub-micmmolar concentrations. Treatment with tmlox analog 2,2,5,7,8-pentamethyl-6-chromanol (PMC) significantly induced the expression of the lysosomal protein NPC-1 and reduced intracellular cholesterol level upon ox-LDL uptake. Our data indicate that the lysosomal-localized hindered phenols are uniquely potent in protecting the RPE against the toxic effects of ox-LDL, and may represent a novel pharmacotherapy to preserve the vision in patients with GA.
C1 [Gnanaguru, Gopalan; Mackey, Ashley; Choi, Eun Young; Arta, Anthoula; Rossato, Franco Aparecido; D'Amore, Patricia A.; Ng, Yin Shan E.] Massachusetts Eye & Ear, Schepens Eye Res Inst, Harvard Ophthalmol, Boston, MA 02114 USA.
   [Arta, Anthoula; Urquhart, Andrew J.] Inst Sundhedsteknol, Dept Hlth Technol, Lyngby, Denmark.
   [Gero, Thomas W.; Scott, David A.] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute; Harvard University; Dana-Farber Cancer Institute
RP Ng, YSE (通讯作者)，Massachusetts Eye & Ear, Schepens Eye Res Inst, Harvard Ophthalmol, Boston, MA 02114 USA.
EM eric_ng@meei.harvard.edu
RI Gnanaguru, Gopalan/AAJ-9336-2021; Rossato, Franco Aparecido/K-7981-2014;
   Urquhart, Andrew/B-8194-2014
OI Rossato, Franco Aparecido/0000-0002-4132-2271; Scott,
   David/0000-0003-3243-528X; Urquhart, Andrew/0000-0002-5322-0002
FU Boston Foundation; Edwin S. Webster Foundation research grant;
   Grimshaw-Gudewicz Foundation AMD research grant; NIH Na-tional Eye
   Institute Core grant [P30EY003790]
FX We thank Dhanesh Amarnani of the Schepens Eye Research Institute (SERI)
   for assisting with the LDH cell death assay, Lynn Zehbe for validating
   the ox-LDL-induced cell death assay in ARPE-19 cells. Dr. Magali
   Saint-Geniez for her assistance with human primary RPE cells isolation
   and culture. G.G., A.M., E.Y.C., A.A., F.A.R., T.W.G, and Y.S.E.N.
   performed the experiments, collected and analyzed the data, and
   generated the figures. G.G., A.M., E.Y.C., A.A., F.A.R., T.W.G., D.S.,
   and A.J.U. designed ex-periments and interpreted data, and performed
   literature searches. Y.S. E.N. and P.A.D. conceived the study, designed
   experiments, and inter-preted data, generated figures, and performed
   literature searches. All authors wrote and approved the manuscript.
   Y.S.E.N. and P.A.D. are the guarantors of this work and, as such, had
   full access to all data in the study. They take responsibility for the
   integrity of the data and the ac-curacy of the data analysis. Supported
   by May J. Wikstrom Fund via the Boston Foundation (P.A. D.) , Edwin S.
   Webster Foundation research grant (Y.S.E.N.) , Grimshaw-Gudewicz
   Foundation AMD research grant (Y.S.E.N.) , and the NIH Na-tional Eye
   Institute Core grant P30EY003790.
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NR 55
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JAN
PY 2022
VL 178
BP 360
EP 368
DI 10.1016/j.freeradbiomed.2021.11.026
EA DEC 2021
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA XV4CI
UT WOS:000734891400003
PM 34843917
DA 2022-11-30
ER

PT J
AU Fan, JG
   Rajapakse, D
   Peterson, K
   Lerner, J
   Parsa, S
   Ponduri, A
   Sagar, V
   Duncan, T
   Dong, LJ
   Wistow, G
AF Fan, Jianguo
   Rajapakse, Dinusha
   Peterson, Katherine
   Lerner, Joshua
   Parsa, Shabnam
   Ponduri, Arjun
   Sagar, Vatsala
   Duncan, Todd
   Dong, Lijin
   Wistow, Graeme
TI Retbindin mediates light-damage in mouse retina while its absence leads
   to premature retinal aging
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retina; Aging; Photoreceptors; Retinal pigment epithelium; Retinal
   ganglion cells; Light damage
ID SEQUENCE TAG ANALYSIS; BINDING-PROTEIN; MACULAR DEGENERATION; RPE65;
   GENE; BIOINFORMATICS; MICROGLIA; NEIBANK; PROJECT; VISION
AB Vision requires the transport and recycling of the pigment 11-cis retinaldehyde (retinal) between the retinal pigment epithelium (RPE) and photoreceptors. 11-cis retinal is also required for light-mediated photoreceptor death in dark-adapted mouse eye, probably through overstimulation of rod cells adapted for low light. Retbindin is a photoreceptor-specific protein, of unclear function, that is localized between the RPE and the tips of the photoreceptors. Unexpectedly, young Rtbdn-KO mice, with targeted deletion (KO) of retbindin, showed delayed regeneration of retinal function after bleaching and were strongly resistant to light-induced photoreceptor death. Furthermore, bio-layer interferometry binding studies showed recombinant retbindin had significant affinity for retinoids, most notably 11-cis retinal. This suggests that retbindin mediates light damage, probably through a role in transport of 11-cis retinal. In Rtbdn-KO mice, retinal development was normal, as were amplitudes of rod and cone electroretinograms (ERG) up to 4 months, although implicit times and c-waves were affected. However, with aging, both light- and dark-adapted ERG amplitudes declined significantly and photoreceptor outer segments became disordered, However, in contrast to other reports, there was little retinal degeneration or drop in flavin levels. The RPE developed vacuoles and lipid, protein and calcium deposits reminiscent of age-related macular degeneration. Other signs of premature aging included loss of OPN4+ retinal ganglion cells and activation of microglia. Thus, retbindin plays an unexpected role in the mammalian visual cycle, probably as an adaptation for vision in dim light. It mediates light damage in the dark-adapted eye, but also plays a role in lightadapted responses and in long term retinal homeostasis.
C1 [Fan, Jianguo; Rajapakse, Dinusha; Peterson, Katherine; Lerner, Joshua; Parsa, Shabnam; Ponduri, Arjun; Sagar, Vatsala; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bldg 6,Room 106, Bethesda, MD 20892 USA.
   [Duncan, Todd] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD USA.
   [Dong, Lijin] NEI, Genet Engn Facil, NIH, Bethesda, MD 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)
RP Wistow, G (通讯作者)，NEI, Sect Mol Struct & Funct Genom, NIH, Bldg 6,Room 106, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
OI Lerner, Joshua/0000-0001-5055-1247; Duncan, Todd/0000-0003-2901-6340;
   Parsa, Shabnam/0000-0001-7646-1098
FU Intramural Program of the National Eye Institute
FX This work was supported by the Intramural Program of the National Eye
   Institute.
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NR 55
TC 1
Z9 1
U1 2
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 2021
VL 209
AR 108698
DI 10.1016/j.exer.2021.108698
EA JUL 2021
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WJ8QU
UT WOS:000709303900007
PM 34228964
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Lee, EK
   Kim, YJ
   Shon, WJ
   Yu, HG
AF Lee, Eun Kyoung
   Kim, Young Joo
   Shon, Won-Jun
   Yu, Hyeong Gon
TI A telomerase-derived peptide vaccine inhibits laser-induced choroidal
   neovascularization in a rat model
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID ISCHEMIA-REPERFUSION INJURY; NF-KAPPA-B; MACULAR DEGENERATION;
   PANCREATIC-CANCER; PHASE-I/II; GV1001; ACTIVATION; TRIAL
AB GV1001, a novel peptide derived from human telomerase reverse transcriptase, reportedly has anticancer and anti-inflammatory effects. Choroidal neovascularization (CNV) is a complex pathogenic process that involves angiogenesis, inflammation, cellular immunity, and other factors. This study was aimed at investigating the effect of GV1001 on laser-induced CNV in a rat model. Brown Norway rats were subcutaneously administered GV1001 (0.1 nM, 1 nM, and 10 nM) daily, beginning 3 days prior, and ending 14 days after laser photocoagulation. Optical coherence tomography, fluorescein angiography, choroidal flat mount, and histologic analysis were performed to analyze CNV. The protein level of I kappa B-alpha and nuclear translocation of nuclear factor kappa B (NF-kappa B) was analyzed via immunohistochemistry of p65. Multiplex immunoassay was performed to evaluate the interleukin (IL)-1 beta, IL-6, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and tumor necrosis factor-alpha levels. The GV1001-treated group had significantly lower CNV thickness, smaller CNV area, and lower proportion of CNV lesions with clinically significant fluorescein leakage than vehicle-treated group. GV1001 treatment inhibited I kappa B-alpha degradation and NF-kappa B p65 nuclear translocation. At 1 nM concentration, GV1001 had highest inhibitory effect on CNV and NF-kappa B signaling activation; moreover, it suppressed the levels of IL-1 beta, IL-6, and VEGF significantly. The present study demonstrates that GV1001 treatment led to significant suppression of laser-induced CNV, alongside inhibition of inflammatory processes including NF-kappa B activation and subsequent upregulation of proinflammatory cytokines. Therefore, this provides molecular evidence of potential validity of GV1001 treatment as a therapeutic strategy for neovascular age-related macular degeneration.
C1 Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Ophthalmol, Seoul, South Korea.
   Seoul Natl Univ Hosp, Biomed Res Inst, Dept Ophthalmol, Seoul, South Korea.
   Seoul Natl Univ, Sch Dent, Dept Conservat Dent, Seoul, South Korea.
C3 Seoul National University (SNU); Seoul National University Hospital;
   Seoul National University (SNU); Seoul National University Hospital;
   Seoul National University (SNU)
RP Yu, HG (通讯作者)，Seoul Natl Univ Hosp, Dept Ophthalmol, 101 Daehak Ro, Seoul 110744, South Korea.
EM hgonyu@snu.ac.kr
OI Yu, Hyeong Gon/0000-0002-1795-202X
FU Protein Immunology Core Facility Center for Medical Innovation,
   Biomedical Research Institute, Seoul National University Hospital;
   GemVax KAEL [800-20130362]; Korea Health Technology R&D Project through
   the Korea Health Industry Development Institute (KHIDI) - Ministry of
   Health & Welfare, Republic of Korea [HI14C1277]
FX The authors thank Ms. Hee Sun Park for her technical assistance. The
   authors also gratefully acknowledge support from Protein Immunology Core
   Facility Center for Medical Innovation, Biomedical Research Institute,
   Seoul National University Hospital. GemVax & KAEL provided the GV1001
   peptide and a research grant (grant number: 800-20130362). GemVax & KAEL
   did not play any role in the study design, conduct of the study, or the
   collection, management, analysis, and interpretation of the data. This
   work was also supported in part 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 number: HI14C1277).
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NR 36
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 1931-5244
EI 1878-1810
J9 TRANSL RES
JI Transl. Res.
PD FEB
PY 2020
VL 216
BP 30
EP 42
DI 10.1016/j.trsl.2019.10.001
PG 13
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Medical Laboratory Technology; General & Internal Medicine; Research &
   Experimental Medicine
GA KE3YH
UT WOS:000508494500003
PM 31655029
DA 2022-11-30
ER

PT J
AU Sun, ZW
   Chen, C
   Wang, L
   Li, YD
   Hu, ZL
AF Sun, Z-W
   Chen, C.
   Wang, L.
   Li, Y-D
   Hu, Z-L
TI S-allyl cysteine protects retinal pigment epithelium cells from
   hydroquinone-induced apoptosis through mitigating cellular response to
   oxidative stress
SO EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; Apoptosis;
   S-allyl cysteine; Oxidative stress
ID MACULAR DEGENERATION; ALLYLCYSTEINE; PATHOGENESIS; ACTIVATION; EFFICACY
AB OBJECTIVE: Retinal pigment epithelium (RPE) degenerative death is an evident hallmark of advanced age-related macular degeneration (AMD). The present study aims to evaluate the protective effects of S-allyl L-cysteine (SAC), a bioactive component from aged garlic extracts, on the oxidative stress-related apoptosis of RPE cells and to investigate the potential underlying mechanisms.
   MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were performed to evaluate the effects of SAC on the hydroquinone-treated human ARPE19 cells. The Reactive Oxygen Species (ROS) production was measured by virtue of flow cytometry or determined under an inverted fluorescence microscope. Furthermore, the expression of antioxidant factor Nrf2, as well as downstream antioxidant genes, including NQO1, SOD1, SOD2, and HO1 was assessed in hydroquinone stimulated ARPE19 cells, in the presence or absence of SAC pretreatment.
   RESULTS: Hydroquinone incitement contributed to a marked decrease in cell viability, but enhanced cell apoptosis, whereas SAC addition did not cause significant alterations. When cells were pre-treated with SAC, cell proliferation was dramatically enhanced whereas apoptosis was mitigated, and the ROS generation induced by hydroquinone was also significantly suppressed. indicating a prominent function of SAC in preventing ARPE19 cells from oxidant-related apoptosis. The elevated expression levels of Nrf2 and other antioxidant genes driven by hydroquinone were downregulated by SAC addition.
   CONCLUSIONS: These data suggest that SAC can effectively attenuate hydroquinone-induced oxidative damage in human RPE cells. Our work is the first to demonstrate that SAC modulates oxidative stress-induced RPE apoptosis, thereby potentially proving new insights into the treatment of AMD.
C1 [Sun, Z-W; Chen, C.; Wang, L.; Li, Y-D; Hu, Z-L] Kunming Med Univ, Peoples Hosp Yunnan Prov 2, Affiliated Hosp 4, Dept Ophthalmol, Kunming, Yunnan, Peoples R China.
   [Sun, Z-W; Chen, C.; Wang, L.; Li, Y-D; Hu, Z-L] Yunnan Eye Inst, Kunming, Yunnan, Peoples R China.
   [Sun, Z-W; Chen, C.; Wang, L.; Li, Y-D; Hu, Z-L] Ocular Dis & Clin Med Res Ctr Yunnan Prov, Kunming, Yunnan, Peoples R China.
   [Sun, Z-W; Chen, C.; Wang, L.; Li, Y-D; Hu, Z-L] Ocular Dis Clin Med Ctr Yunnan Prov, Kunming, Yunnan, Peoples R China.
C3 Kunming Medical University
RP Chen, C; Hu, ZL (通讯作者)，Kunming Med Univ, Peoples Hosp Yunnan Prov 2, Affiliated Hosp 4, Dept Ophthalmol, Kunming, Yunnan, Peoples R China.
EM chenchenmd@aliyun.com; HZL77@263.net
OI Chen, Chen/0000-0001-6741-7036
FU National Natural Science Foundation of China (NSFC) [81660167]; Science
   and Technology Project of Yunnan Province [2017FB114]; Key Laboratory of
   Yunnan Province for the Prevention and Treatment of Ophthalmology
   [2017DG008]; Technical Research for the Prevention and Treatment of
   Important Ocular Surface Diseases [2018ZF009]; Provincial Innovation
   Team for Cataract and Ocular Fundus Disease, The Second People's
   Hospital of Yunnan Province [2017HC010]; Expert Workstation of Yao Ke
   [2017IC064]; Graduate Innovation Fund of Kunming Medical University
   [2019S197]
FX The authors wish to thank Dr Zhulin Hu and Dr Chen Chen for their
   experimental design and technology help. This work was financially
   supported by the National Natural Science Foundation of China (NSFC,
   Grant Number 81660167); the Science and Technology Project of Yunnan
   Province (Grant Number 2017FB114); Key Laboratory of Yunnan Province for
   the Prevention and Treatment of Ophthalmology (2017DG008); Technical
   Research for the Prevention and Treatment of Important Ocular Surface
   Diseases (2018ZF009); Provincial Innovation Team for Cataract and Ocular
   Fundus Disease, The Second People's Hospital of Yunnan Province
   (2017HC010); and Expert Workstation of Yao Ke (2017IC064) and Graduate
   Innovation Fund of Kunming Medical University (2019S197).
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NR 35
TC 3
Z9 3
U1 2
U2 4
PU VERDUCI PUBLISHER
PI ROME
PA VIA GREGORIO VII, ROME, 186-00165, ITALY
SN 1128-3602
J9 EUR REV MED PHARMACO
JI Eur. Rev. Med. Pharmacol. Sci.
PD FEB
PY 2020
VL 24
IS 4
BP 2120
EP 2128
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA KT1IP
UT WOS:000518765300060
PM 32141582
DA 2022-11-30
ER

PT J
AU McGill, TJ
   Osborne, L
   Lu, B
   Stoddard, J
   Huhn, S
   Tsukamoto, A
   Capela, A
AF McGill, Trevor J.
   Osborne, Linda
   Lu, Bin
   Stoddard, Jonathan
   Huhn, Stephen
   Tsukamoto, Ann
   Capela, Alexandra
TI Subretinal Transplantation of Human Central Nervous System Stem Cells
   Stimulates Controlled Proliferation of Endogenous Retinal Pigment
   Epithelium
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE cell transplantation; RPE; proliferation; neural stem cells; age related
   macular degeneration
ID RCS RATS; VISUAL FUNCTION; FUNCTIONAL RESCUE; ROYAL-COLLEGE;
   SCHWANN-CELLS; HUMAN RPE; PRESERVATION; VISION; PHAGOCYTOSIS; ROD
AB Purpose: The loss of retinal pigment epithelial (RPE) cells is a feature common to age-related macular degeneration (AMD) and retinitis pigmentosa (RP) and multiple early phase clinical trials are underway testing the safety of RPE cell replacement for these diseases. We examined whether transplantation of human neural stem cells into the subretinal space could enhance the endogenous proliferative capacity of the host RPE cell to regenerate.
   Methods: Human central nervous system stem cells (HuCNS-SC) were isolated from enzymatically treated brain tissue using flow cytometry. Pigmented dystrophic Royal College of Surgeons (RCS) and S334ter-4 rats treated with oral bromodeoxyuridine (BrdU) received a unilateral subretinal injection of 1.0 x 10(5) HuCNS-SC cells at either postnatal day 21 or 60. Animals were sacrificed at 90, 120, and 150 days of age. Eyes were fixed processed for cryostat sectioning. Sections were immunostained with Stem101, Ku80, RPE65, OTX1/2, BrdU, and CRALBP antibodies and analyzed via confocal microscopy.
   Results: RCS rats that received transplantation of HuCNS-SC had significantly more (approximately 3-fold) Ki67-positive or BrdU-labelled host RPE cells adjacent to the HuCNS-SC graft than controls. Significantly increased host RPE cell proliferation as a result of HuCNS-SC transplantation also was confirmed in S334ter-line 4 transgenic rats with higher proliferation observed in animals with longer posttransplantation periods.
   Conclusions: These results suggest that controlled proliferation of endogenous RPE by HuCNS-SC may provide another mechanism by which RPE cell diseases could be treated.
   Translational Relevance: Engaging the capacity for endogenous RPE cell regeneration in atrophic diseases may be a novel therapeutic strategy for degenerative diseases of the RPE and retina.
C1 [McGill, Trevor J.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA.
   [McGill, Trevor J.; Stoddard, Jonathan] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA.
   [Osborne, Linda; Huhn, Stephen; Tsukamoto, Ann; Capela, Alexandra] StemCells Inc, Newark, CA USA.
   [Lu, Bin] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
   [Tsukamoto, Ann] BOCO Silicon Valley, Palo Alto, CA USA.
C3 Oregon Health & Science University; Oregon Health & Science University;
   Oregon National Primate Research Center; Cedars Sinai Medical Center
RP McGill, TJ (通讯作者)，Oregon Hlth & Sci Univ, 505 Nw 185th Ave, Beaverton, OR 97006 USA.
EM mcgilltr@ohsu.edu
FU StemCells, Inc.; National Institutes of Health [P30 EY010572]; Research
   to Prevent Blindness
FX This work was supported by StemCells, Inc., the National Institutes of
   Health core grant P30 EY010572 to Casey Eye Institute, and by an
   unrestricted grant to the Casey Eye Institute from the Research to
   Prevent Blindness.
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NR 41
TC 13
Z9 14
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAY
PY 2019
VL 8
IS 3
AR 43
DI 10.1167/tvst.8.3.43
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IE9SF
UT WOS:000472716200012
PM 31245172
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shadforth, AMA
   Suzuki, S
   Theodoropoulos, C
   Richardson, NA
   Chirila, TV
   Harkin, DG
AF Shadforth, Audra M. A.
   Suzuki, Shuko
   Theodoropoulos, Christina
   Richardson, Neil A.
   Chirila, Traian V.
   Harkin, Damien G.
TI A Bruch's membrane substitute fabricated from silk fibroin supports the
   function of retinal pigment epithelial cells in vitro
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE retinal pigment epithelium; Bruch's membrane; Bombyx mori; silk fibroin;
   biomaterial; cell culture
ID MACULAR DEGENERATION; DIFFERENTIATION; TRANSPLANTATION; BIOMATERIALS;
   SCAFFOLDS; CULTURE; ARPE-19; TISSUE; LAYERS; LINE
AB Silk fibroin provides a promising biomaterial for ocular tissue reconstruction, including the damaged outer blood-retinal barrier of patients afflicted with age-related macular degeneration (AMD). The aim of the present study was to evaluate the function of retinal pigment epithelial (RPE) cells in vitro, when grown on fibroin membranes manufactured to a thickness similar to that of Bruch's membrane (3 mu m). Confluent cultures of RPE cells (ARPE-19) were established on fibroin membranes and maintained under conditions designed to promote maturation over 4months. Control cultures were grown on polyester cell culture well inserts (Transwell((R))). Cultures established on either material developed a cobblestone morphology, with partial pigmentation, within 12weeks. Immunocytochemistry at 16weeks revealed a similar distribution pattern between cultures for F-actin, ZO-1, ezrin, cytokeratin pair 8/18, RPE-65 and Na+/K+-ATPase. Electron microscopy revealed that cultures grown on fibroin displayed a rounder apical surface with a more dense distribution of microvilli. Both cultures avidly ingested fluorescent microspheres coated with vitronectin and bovine serum albumin (BSA), but not controls coated with BSA alone. VEGF and PEDF were detected in the conditioned media collected from above and below the two membrane types. Levels of PEDF were significantly higher than for VEGF on both membranes and a trend was observed towards larger amounts of PEDF in apical compartments. These findings demonstrated that RPE cell functions on fibroin membranes are equivalent to those observed for standard test materials (polyester membranes). As such, these studies support advancement to studies of RPE cell implantation on fibroin membranes in a preclinical model. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Shadforth, Audra M. A.; Richardson, Neil A.; Harkin, Damien G.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
   [Shadforth, Audra M. A.; Theodoropoulos, Christina; Richardson, Neil A.; Harkin, Damien G.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld, Australia.
   [Shadforth, Audra M. A.; Suzuki, Shuko; Theodoropoulos, Christina; Richardson, Neil A.; Chirila, Traian V.; Harkin, Damien G.] Queensland Eye Inst, 140 Melbourne St, South Brisbane, Qld, Australia.
   [Chirila, Traian V.] Univ Queensland, Fac Hlth Sci, Herston, Qld, Australia.
   [Chirila, Traian V.] Queensland Univ Technol, Fac Sci & Engn, Brisbane, Qld, Australia.
   [Chirila, Traian V.] Univ Queensland, Australian Inst Bioengn & Nanotechnol, St Lucia, Qld, Australia.
   [Chirila, Traian V.] Univ Western Australia, Fac Sci, Crawley, WA, Australia.
C3 Queensland University of Technology (QUT); Queensland University of
   Technology (QUT); Queensland Eye Institute; University of Queensland;
   Queensland University of Technology (QUT); University of Queensland;
   University of Western Australia
RP Shadforth, AMA (通讯作者)，Queensland Eye Inst, 140 Melbourne St, South Brisbane, Qld, Australia.
EM audra.shadforth@qei.org.au
RI Shadforth, Audra/S-9859-2017
OI Shadforth, Audra/0000-0001-8857-0742; Harkin, Damien/0000-0002-7358-7987
FU Macular Disease Foundation Australia; Dora Lush Biomedical Research
   Postgraduate Scholarship (National Health and Biomedical Research
   Council of Australia)
FX This project was supported in part by a grant received from the Macular
   Disease Foundation Australia, with additional assistance from the
   Queensland Eye Institute Foundation (formerly the Prevent Blindness
   Foundation). A.M.A.S. was supported by a Dora Lush Biomedical Research
   Postgraduate Scholarship (National Health and Biomedical Research
   Council of Australia). The study was performed under ethics approval
   granted by the Queensland University of Technology Ethics Committee.
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NR 30
TC 16
Z9 16
U1 1
U2 11
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 JUN
PY 2017
VL 11
IS 6
BP 1915
EP 1924
DI 10.1002/term.2089
PG 10
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 EX1MO
UT WOS:000402988100021
PM 26449636
DA 2022-11-30
ER

PT J
AU Natoli, R
   Fernando, N
   Madigan, M
   Chu-Tan, JA
   Valter, K
   Provis, J
   Rutar, M
AF Natoli, Riccardo
   Fernando, Nilisha
   Madigan, Michele
   Chu-Tan, Joshua A.
   Valter, Krisztina
   Provis, Jan
   Rutar, Matt
TI Microglia- derived IL-1 beta promotes chemokine expression by Muller
   cells and RPE in focal retinal degeneration
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
DE Retinal degeneration; Microglia; Interleukin-1 beta; IL-1 beta;
   Chemokines; RPE; Muller cells; Macrophages; Age-related macular
   degeneration; AMD
ID SENILE MACULAR DEGENERATION; PANCREATIC BETA-CELLS; PHOTORECEPTOR
   DEGENERATION; RAT RETINA; MEDIATED INFLAMMATION; PIGMENT EPITHELIUM;
   KAPPA-B; RECRUITMENT; MACROPHAGES; ACTIVATION
AB Background: Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1 beta (IL-1 beta) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors.
   Methods: Inhibition of retinal IL-1 beta expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage. Changes in the expression and localisation of Il-1 beta, Ccl2, Cxcl1 and Cxcl10 genes were assessed using qPCR and in situ hybridisation, while the recruitment of retinal macrophages was detected using immunohistochemistry for IBA1. Levels of photoreceptor cell death were determined using TUNEL.
   Results: Photo-oxidative damage elevated the expression of Il-1 beta and inflammasome-related genes, and IL-1 beta protein was detected in microglia infiltrating the outer retina. This was associated with increased expression of Ccl2, Cxcl1, and Cxcl10. Intravitreal IL-1 beta inhibitors suppressed chemokine expression following damage and reduced macrophage accumulation and photoreceptor death. Moreover, in Muler and RPE cell cultures, and in vivo, Ccl2, Cxcl1 and Cxcl10 were variously upregulated when stimulated with IL-1 beta, with increased macrophage accumulation detected in vivo.
   Conclusions: IL-1 beta is produced by retinal microglia and macrophages and promotes chemokine expression by Muler cells and RPE in retinal degeneration. Targeting IL-1 beta may prove efficacious in broadly suppressing chemokine-mediated inflammation in retinal dystrophies such as AMD.
C1 [Natoli, Riccardo; Fernando, Nilisha; Chu-Tan, Joshua A.; Valter, Krisztina; Provis, Jan; Rutar, Matt] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, 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.
   [Rutar, Matt] Univ Melbourne, Parkville, Vic, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; University of Sydney; University of New
   South Wales Sydney; University of Melbourne
RP Provis, J (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.; Provis, J (通讯作者)，Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
EM jan.provis@anu.edu.au
RI Valter, Krisztina/L-3015-2016; Chu-Tan, Joshua A/A-9728-2019; Provis,
   Jan/C-9529-2009
OI Valter, Krisztina/0000-0002-2033-0408; Provis, Jan/0000-0002-6405-2868;
   Fernando, Nilisha/0000-0002-8488-1348; Natoli,
   Riccardo/0000-0002-9350-0439; Rutar, Matthew/0000-0002-8893-5120;
   Chu-Tan, Joshua/0000-0001-7936-8972
FU Gordon and Gretel Bootes Foundation; Ophthalmic Research Institute of
   Australia (ORIA); Retina Australia; Australian Government Research
   Training Program (RTP) Scholarship
FX This study was supported by grants from The Gordon and Gretel Bootes
   Foundation, the Ophthalmic Research Institute of Australia (ORIA), and
   Retina Australia. This research was supported by an Australian
   Government Research Training Program (RTP) Scholarship.
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NR 55
TC 69
Z9 69
U1 1
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD APR 24
PY 2017
VL 12
AR 31
DI 10.1186/s13024-017-0175-y
PG 11
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA EU7DZ
UT WOS:000401196700002
PM 28438165
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Chriqui, E
   Law, C
   Kergoat, MJ
   Leclerc, BS
   Kergoat, H
AF Chriqui, Estefania
   Law, Caroline
   Kergoat, Marie-Jeanne
   Leclerc, Bernard-Simon
   Kergoat, Helene
TI Visual impairment in older institutionalised Canadian seniors with
   dementia
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE dementia; long-term care facilities; visual acuity; visual impairment
ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; EYE CARE SERVICES;
   CATARACT-SURGERY; VISION; IMPACT; HALLUCINATIONS; DEPRESSION; ACUITY;
   INTERVENTION
AB Purpose: To estimate the prevalence of visual impairment (VI) in a sub-population of Canadian long-term care facilities, i. e. residents affected by dementia.
   Methods: This study was conducted in the long-term care facility units at the Institut universitaire de geriatrie de Montreal. All residents = 65 years old (y. o.), having a clinical diagnosis of dementia, and able to understand French or English, were eligible for participation in the study. All residents participating in the study received a complete eye exam by an experienced optometrist. For the purpose of the study, VI was defined as a distance visual acuity (VA) < 6/12 (0.30 logMAR, 20/40) in the better seeing eye.
   Results: One hundred and fifty residents, 68-102 y. o. took part into the study. All participants had a diagnosis of dementia recorded in their clinical chart. VI was present in 37.3% (95% CI: 29.1-46.1%) (n = 50) of residents in whom monocular VA could be measured. Ocular refraction for their better seeing eye improved the VA to = 6/12 (0.30 logMAR, 20/40) in 40% (n = 20) of those 50 residents. When VI remained after refraction, it was due in order of frequency to cataract, age-related macular degeneration, and primary open angle glaucoma.
   Conclusions: Our data showed that an appreciable proportion (37.3%) of older residents with dementia also have VI, and that VI can be corrected in many by updating their refraction. Others could potentially be helped through cataract surgery. It is therefore important to offer regular eye care services to those residents, knowing that many are not able to express their visual needs.
C1 [Chriqui, Estefania; Law, Caroline; Kergoat, Helene] Univ Montreal, Ecole Optometrie, Montreal, PQ, Canada.
   [Chriqui, Estefania; Law, Caroline; Kergoat, Marie-Jeanne; Leclerc, Bernard-Simon; Kergoat, Helene] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Kergoat, Marie-Jeanne] Univ Montreal, Fac Med, Montreal, PQ, Canada.
   [Leclerc, Bernard-Simon] Univ Montreal, Med Sociale & Prevent, Ecole Sante Publ, Montreal, PQ, Canada.
   [Leclerc, Bernard-Simon] CIUSSS Nord Ill Montreal, Ctr Rech InterAct, Montreal, PQ, Canada.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal;
   Universite de Montreal
RP Kergoat, H (通讯作者)，Univ Montreal, Ecole Optometrie, Montreal, PQ, Canada.; Kergoat, H (通讯作者)，Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
EM helene.kergoat@umontreal.ca
FU Alzheimer Society of Canada
FX This study was funded by a research grant from the Alzheimer Society of
   Canada. The authors wish to thank the Ethics committee and Genevieve
   Ducharme (Site coordinator) for facilitating the implementation of this
   project within the IUGM, as well as all participants and their families
   for their generous contribution to this project.
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NR 46
TC 11
Z9 11
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD MAR
PY 2017
VL 37
IS 2
BP 225
EP 233
DI 10.1111/opo.12358
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA EP3LJ
UT WOS:000397283500012
PM 28211177
DA 2022-11-30
ER

PT J
AU Bernstein, PS
   Ahmed, F
   Liu, AH
   Allman, S
   Sheng, XM
   Sharifzadeh, M
   Ermakov, I
   Gellermann, W
AF Bernstein, Paul S.
   Ahmed, Faisal
   Liu, Aihua
   Allman, Susan
   Sheng, Xiaoming
   Sharifzadeh, Mohsen
   Ermakov, Igor
   Gellermann, Werner
TI Macular Pigment Imaging in AREDS2 Participants: An Ancillary Study of
   AREDS2 Subjects Enrolled at the Moran Eye Center
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RESONANCE RAMAN DETECTION; BETA-CAROTENE; DOCOSAHEXAENOIC ACID;
   OPTICAL-DENSITY; BINDING PROTEIN; LUNG-CANCER; VITAMIN-C; LUTEIN;
   DEGENERATION; ZEAXANTHIN
AB PURPOSE. Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions.
   METHODS. All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy.
   RESULTS. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements.
   CONCLUSIONS. Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.) (Invest Ophthalmol Vis Sci. 2012;53:6178-6186) DOI: 10.1167/iovs.12-10275
C1 [Bernstein, Paul S.; Ahmed, Faisal; Liu, Aihua; Allman, Susan] Univ Utah, Sch Med, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Sheng, Xiaoming] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84132 USA.
   [Sharifzadeh, Mohsen; Ermakov, Igor; Gellermann, Werner] Univ Utah, Dept Phys & Astron, Salt Lake City, UT 84132 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; Utah System of Higher Education;
   University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Sch Med, Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
OI Ahmed, Faisal/0000-0003-1294-5274
FU Foundation Fighting Blindness (Columbia, MD); Research to Prevent
   Blindness (New York, NY); National Eye Institute [EY-11600]; NATIONAL
   EYE INSTITUTE [R01EY011600, P30EY014800, R29EY011600] Funding Source:
   NIH RePORTER
FX Supported by Foundation Fighting Blindness (Columbia, MD); Research to
   Prevent Blindness (New York, NY); and National Eye Institute Grant
   EY-11600 (PSB).
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NR 41
TC 29
Z9 31
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 SEP
PY 2012
VL 53
IS 10
BP 6178
EP 6186
DI 10.1167/iovs.12-10275
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 016NQ
UT WOS:000309526200026
PM 22879423
OA Green Published
DA 2022-11-30
ER

PT J
AU Jaouni, T
   Averbukh, E
   Burstyn-Cohen, T
   Grunin, M
   Banin, E
   Sharon, D
   Chowers, I
AF Jaouni, Tareq
   Averbukh, Edward
   Burstyn-Cohen, Tal
   Grunin, Michelle
   Banin, Eyal
   Sharon, Dror
   Chowers, Itay
TI Association of Pattern Dystrophy With an HTRA1 Single-Nucleotide
   Polymorphism
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; VITELLIFORM MACULAR DETACHMENT; RETINAL
   DEGENERATION; PERIPHERIN/RDS GENE; CUTICULAR DRUSEN; BEST-DISEASE; VMD2
   GENE; RDS GENE; MUTATIONS; RISK
AB Objective: To evaluate if adult-onset foveomacular vitelliform dystrophy (AOFVD) and butterfly-shaped pigment dystrophy (BSPD) are associated with risk single-nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD).
   Methods: This was a tertiary referral center-based cross-sectional study including 35 consecutive patients with BSPD and AOFVD, 317 patients with AMD, and 159 unaffected individuals. Demographics, clinical information, and ophthalmic imaging studies were collected. Sequencing was performed for the peripherin/RDS and BEST1 genes, and genotyping was performed for SNPs in the genes for complement factor H (CFH) (rs1061170), HTRA1 (rs11200638), and complement component 3 (C3) (rs2231099).
   Results: Adult-onset foveomacular vitelliform dystrophy and BSPD were diagnosed in 24 (68.6%) and 11 (31.4%) of the 35 patients, respectively. The mean (SD) age of patients with pattern dystrophy (PD) was 75.3 (10) years and median visual acuity was 0.7. Pattern dystrophy was associated with the HTRA1 risk allele compared with unaffected individuals (odds ratio, 1.72; 95% CI, 1.11-2.66; P=.03). The HTRA1 SNP showed similar prevalence in patients with AMD and PD. The CFH risk allele was significantly less common in patients with PD compared with patients with AMD(odds ratio, 0.47; 95% CI, 0.28-0.76; P=.002). No mutations in peripherin/RDS or BEST1 were detected.
   Conclusions: The AOFVD and BSPD phenotypes are associated with an HTRA1 risk SNP. These phenotypes often present in elderly individuals who do not carry peripherin/RDS gene mutations and are associated with retinal pigment epithelium alterations and increased risk for choroidal neovascularization. Further research is required to evaluate if AOFVD and BSPD phenotypes in aged individuals are associated with AMD.
C1 [Jaouni, Tareq; Averbukh, Edward; Grunin, Michelle; Banin, Eyal; Sharon, Dror; Chowers, Itay] Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, Israel.
   [Burstyn-Cohen, Tal] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hadassah University Medical Center;
   Hebrew University of Jerusalem
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; Sharon, Dror/P-4539-2015; Burstyn-Cohen,
   Tal/K-8846-2012
OI Grunin, Michelle/0000-0002-3155-2858; Sharon, Dror/0000-0002-1789-5811;
   Burstyn-Cohen, Tal/0000-0002-2324-2921
FU Israel Science Foundation; Hadassah Medical Center
FX The study was supported by a grant from the Israel Science Foundation
   (Dr Chowers) and by the Hadassah Medical Center (Dr Jaouni).
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   Zhuk S, 2006, MOL VIS, V12, P811
NR 30
TC 12
Z9 14
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD AUG
PY 2012
VL 130
IS 8
BP 987
EP 991
DI 10.1001/archophthalmol.2012.1483
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 987YU
UT WOS:000307455800003
PM 22893068
OA Bronze
DA 2022-11-30
ER

PT J
AU Amissah-Arthur, KN
   Panneerselvam, S
   Narendran, N
   Yang, YC
AF Amissah-Arthur, K. N.
   Panneerselvam, S.
   Narendran, N.
   Yang, Y. C.
TI Optical coherence tomography changes before the development of choroidal
   neovascularization in second eyes of patients with bilateral wet macular
   degeneration
SO EYE
LA English
DT Article
DE wet AMD; fellow eye risk; second eye involvement; OCT appearance; OCT
   progression
ID RANIBIZUMAB
AB Aim To describe the frequency of neovascular age-related macular degeneration (nAMD) in second eyes of patients undergoing ranibizumab therapy in their first eye and to evaluate the patterns of optical coherence tomography (OCT) abnormalities in fellow eyes before nAMD.
   Method Patients who developed choroidal neovascularization (CNV) in the second eye while on treatment for the first eye were identified. OCT scans of the second eyes, performed before the onset of CNV, were retrospectively examined and graded. Frequency of second eye involvement was estimated and patterns of progression of OCT abnormalities were described and classified.
   Results In all, 65 out of 749 consecutive patients required ranibizumab in their second eye for treatment-naive nAMD over a 2-year period. The mean interval from commencement of ranibizumab in first eye to conversion in second eye was 12 months (2-35.5 months). There were three patterns of CNV development: group A (12%, n=8) had no OCT abnormalities in the second eye just before developing CNV; group B (38%, n=25) had no abnormalities at baseline but developed OCT changes more than one visit before conversion and group C (50%, n=32) had OCT changes from baseline, which did not progress until just before conversion.
   Conclusion Patients with retinal pigment epithelial elevation without sub-retinal fluid on OCT in their fellow eyes have a high risk of progression to require therapy within a 2-year period. An anticipatory approach may be warranted, but a small group with completely normal OCT appearances can still develop lesions between visits. Eye (2012) 26, 394-399; doi: 10.1038/eye.2011.335; published online 23 December 2011
C1 [Amissah-Arthur, K. N.] City Hosp, Birmingham & Midland Eye Ctr, Birmingham B18 7QH, W Midlands, England.
   [Amissah-Arthur, K. N.; Panneerselvam, S.; Narendran, N.; Yang, Y. C.] New Cross Hosp, Wolverhampton Eye Infirm, Wolverhampton, England.
C3 University of Birmingham; New Cross Hospital
RP Amissah-Arthur, KN (通讯作者)，City Hosp, Birmingham & Midland Eye Ctr, Dudley Rd, Birmingham B18 7QH, W Midlands, England.
EM kaarthur@doctors.net.uk
OI Amissah-Arthur, Kwesi Nyan/0000-0003-2018-2043
CR Barbazetto IA, 2010, AM J OPHTHALMOL, V149, P939, DOI 10.1016/j.ajo.2010.01.007
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NR 17
TC 22
Z9 23
U1 0
U2 2
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 MAR
PY 2012
VL 26
IS 3
BP 394
EP 399
DI 10.1038/eye.2011.335
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 907PD
UT WOS:000301428900006
PM 22193875
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Iwama, D
   Hangai, M
   Ooto, S
   Sakamoto, A
   Nakanishi, H
   Fujimura, T
   Domalpally, A
   Danis, RP
   Yoshimura, N
AF Iwama, Daisuke
   Hangai, Masanori
   Ooto, Sotaro
   Sakamoto, Atsushi
   Nakanishi, Hideo
   Fujimura, Takashi
   Domalpally, Amitha
   Danis, Ronald P.
   Yoshimura, Nagahisa
TI Automated Assessment of Drusen Using Three-Dimensional Spectral-Domain
   Optical Coherence Tomography
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; SIGNAL STRENGTH; SEVERITY
   SCALE; NATURAL COURSE; SD-OCT; RISK; SEGMENTATION; PERFORMANCE;
   PATHOLOGY
AB PURPOSE. To compare automated assessment of macular drusen delineated by the authors' originally developed algorithm on three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) with the assessment by certified graders on color fundus photographs in nonneovascular age-related macular degeneration (AMD).
   METHODS. Automated assessment of macular drusen was performed using raster scan by 3D OCT scans in 18 eyes with nonneovascular AMD with at least one large druse (>= 125 mu m) and predominantly soft indistinct drusen. Drusen was defined as the regions that have the distance between the retinal pigment epithelium and calculated Bruch's membrane lines > predefined threshold distances. The agreement was assessed on maximum drusen size and drusen area within grid between 3D SD-OCT and color fundus photographs, and false-negative and false-positive drusen at each threshold distance.
   RESULTS. There was agreement or agreement within one step in all eyes in maximum drusen size, and 15 (83.3%) of the eyes in the drusen area, except 6 pixels, regardless of threshold distances. However, the number of eyes with exact agreement in the drusen area increased when the threshold distances were smaller than 4 pixels. In the three cases with disagreement in the drusen area, false-negative drusen on 3D SD-OCT were characterized by being small in area and height.
   CONCLUSIONS. Automated assessment of drusen parameters based on the authors' algorithm on 3D SD-OCT, which was limited by the poor detection ability of small drusen, showed good agreement with the assessment by certified graders on color fundus photography in these subjects. (Invest Ophthalmol Vis Sci. 2012;53:1576-1583) DOI:10.1167/iovs.11-8103
C1 [Hangai, Masanori] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Kyoto 6068507, Japan.
   [Fujimura, Takashi] Topcon Corp, Tokyo, Japan.
   [Domalpally, Amitha; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Fundus Photograph Reading Ctr, Madison, WI USA.
C3 Kyoto University; Topcon Corporation; University of Wisconsin System;
   University of Wisconsin Madison
RP Hangai, M (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan.
EM hangai@kuhp.kyoto-u.ac.jp
RI Domalpally, Amitha/B-2367-2015
OI Domalpally, Amitha/0000-0002-8145-9619
FU Japan Society for the Promotion of Science, Tokyo, Japan [21249084];
   Japanese National Society for the Prevention of Blindness
FX Supported in part by Grant-in-Aid for Scientific Research 21249084,
   Japan Society for the Promotion of Science, Tokyo, Japan; and the
   Japanese National Society for the Prevention of Blindness.
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NR 39
TC 18
Z9 18
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 MAR
PY 2012
VL 53
IS 3
BP 1576
EP 1583
DI 10.1167/iovs.11-8103
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 925VT
UT WOS:000302790700066
PM 22297491
DA 2022-11-30
ER

PT J
AU Mast, N
   Reem, R
   Bederman, I
   Huang, S
   DiPatre, PL
   Bjorkhem, I
   Pikuleva, IA
AF Mast, Natalia
   Reem, Rachel
   Bederman, Ilya
   Huang, Suber
   DiPatre, Pier Luigi
   Bjorkhem, Ingemar
   Pikuleva, Irina A.
TI Cholestenoic Acid Is an Important Elimination Product of Cholesterol in
   the Retina: Comparison of Retinal Cholesterol Metabolism with That in
   the Brain
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID LIPOPROTEIN-LIKE PARTICLES; STEROL 27-HYDROXYLASE; MACULAR DEGENERATION;
   CEREBROTENDINOUS-XANTHOMATOSIS; ALCOHOL-DEHYDROGENASE; SCAVENGER
   RECEPTORS; PIGMENT EPITHELIUM; VERTEBRATE RETINA; HUMAN CIRCULATION;
   CDNA CLONING
AB PURPOSE. Accumulating evidence indicates a link between cholesterol and age-related macular degeneration. Yet, little is known about cholesterol elimination from the retina and retinal pigment epithelium (RPE), the two layers that are damaged in this blinding disease. Several different pathways of enzymatic cholesterol removal exist in extraocular tissues. The authors tested whether metabolites from these pathways could also be quantified in the bovine and human retina and RPE. For comparison, they measured cholesterol oxidation products in two regions of the bovine and human brain and in the bovine liver and adrenal glands.
   METHODS. Sterol quantification was carried out by isotope dilution gas chromatography-mass spectrometry. Bovine tissues were used first to optimize analytical procedures and to investigate postmortem changes in oxysterol concentrations. Then human specimens were analyzed for oxysterol concentrations.
   RESULTS. Qualitatively, oxysterol profiles were similar in the bovine and human tissues. In the human retina and RPE, the authors could not detect 27-hydroxycholesterol but unexpectedly found that its oxidation product, 5-cholestenoic acid, is the most abundant oxysterol, varying up to threefold in different persons. 24S-Hydroxysterol and pregnenolone were also present in the retina, but at much lower quantities and without significant interindividual variability. In the brain, the predominant oxysterol was 24S-hydroxycholesterol.
   CONCLUSIONS. The oxysterol profile of the retina suggests that all known pathways of cholesterol elimination in extraocular organs are operative in the retina and that they likely vary depending on specific cell type. However, overall oxidation to 5-cholestenoic acid appears to be the predominant mechanism for cholesterol elimination from this organ. ( Invest Ophthalmol Vis Sci. 2011;52:594-603) DOI:10.1167/iovs.10-6021
C1 [Mast, Natalia; Reem, Rachel; Huang, Suber; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Mast, Natalia; Reem, Rachel; Huang, Suber; Pikuleva, Irina A.] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
   [Bederman, Ilya] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
   [DiPatre, Pier Luigi] Univ Texas, Med Branch, Dept Pathol, Galveston, TX USA.
   [Bjorkhem, Ingemar] Karolinska Inst, Dept Lab Med, Div Clin Chem, Stockholm, Sweden.
C3 Case Western Reserve University; University Hospitals of Cleveland; Case
   Western Reserve University; University of Texas System; University of
   Texas Medical Branch Galveston; Karolinska Institutet
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM iap8@case.edu
OI Pikuleva, Irina/0000-0001-9742-6232; Bjorkhem,
   Ingemar/0000-0001-6087-9190; Bjorkhem, Ingemar/0000-0002-0575-9425
FU National Institutes of Health [EY018383, AG024336]; Swedish Science
   Council, Brain Power; National Eye Institute; Visual Sciences Training
   Program [T32 EY07157]; Research to Prevent Blindness Foundation;
   NATIONAL EYE INSTITUTE [T32EY007157, R01EY018383] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON AGING [K02AG024336] Funding Source: NIH
   RePORTER
FX Supported in part by National Institutes of Health Grants EY018383 and
   AG024336 (IAP), the Swedish Science Council, Brain Power (IB), and
   National Eye Institute Postdoctoral Research Training Fellowship T32
   EY07157 from the Visual Sciences Training Program (RR). IAP is a
   recipient of the Jules and Doris Stein Professorship from the Research
   to Prevent Blindness Foundation.
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NR 63
TC 65
Z9 65
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 JAN
PY 2011
VL 52
IS 1
BP 594
EP 603
DI 10.1167/iovs.10-6021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 718CL
UT WOS:000287097400032
PM 20881306
OA Green Published
DA 2022-11-30
ER

PT J
AU George, S
   Cooke, C
   Chakravarthy, U
AF George, S.
   Cooke, C.
   Chakravarthy, U.
TI Exudative AMD subtypes and eligibility for treatment with ranibizumab
SO EYE
LA English
DT Article
DE age-related macular degeneration; choroidal neovascular membrane;
   fluorescein angiogram; analysis; anti-VEGF; eligibility
ID RETINAL ANGIOMATOUS PROLIFERATION; SUBFOVEAL CHOROIDAL
   NEOVASCULARIZATION; MACULAR DEGENERATION; INTRAVITREAL RANIBIZUMAB;
   PHOTODYNAMIC THERAPY; VERTEPORFIN THERAPY; NATURAL-HISTORY
AB Purpose To ascertain the proportion of patients with neovascular age-related macular degeneration (AMD) eligible for intravitreal treatment with monoclonal antibodies to vascular endothelial growth factor, on the basis of inclusion criteria used in pivotal clinical trials.
   Methods We scrutinised an imaging database and extracted all fluorescein angiograms (FAs) captured between 1 January and 31 December 2001. Of the 1083 FA, we found 184 where features of AMD in one or both eyes that were observed. In 130 eyes with neovascular AMD, we measured the area of choroidal neovascularisation (CNV) and retinal angiomatous proliferation (RAP). If contiguous to the area of neovascularisation, any areas of blood, exudate, blocked fluorescence, fibrosis, and atrophy were also measured. Descriptive statistics on lesion location, size, and composition were generated and chi(2)-tests were used to test for associations.
   Results Of 130 eyes with neovascular AMD, a subfoveal CNV was present in over 75%. Overall, 24.6% were wholly or predominantly classic, and the remainder minimally classic or occult. Of this latter group, RAPs constituted nearly a third and were significantly associated with co-existent pigment epithelial detachment (PED). Using MARINA and ANCHOR study criteria, less than 50% would have been eligible for clinical trials for antiangiogenic therapy.
   Conclusions The majority of CNV were ineligible for treatment with antiangiogenic therapies when assessed solely on angiographic features. RAPs accounted for some one-third of lesions classified as minimally classic or occult at presentation, and the majority of these would have been ineligible for inclusion in the pivotal randomized control trials. Eye (2010) 24, 1247-1251; doi:10.1038/eye.2009.301; published online 18 December 2009
C1 [George, S.; Cooke, C.] Royal Grp Hosp, Eye & Ear Clin, Dept Ophthalmol, Belfast BT12 6BA, Antrim, North Ireland.
   [Chakravarthy, U.] Queens Univ Belfast, Ctr Vis Sci, Belfast, Antrim, North Ireland.
C3 Queens University Belfast
RP George, S (通讯作者)，Royal Grp Hosp, Eye & Ear Clin, Dept Ophthalmol, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM sonja_AC@yahoo.com
OI Chakravarthy, Usha/0000-0002-2606-3734
CR [Anonymous], MAC DEG AG REL RAN P
   [Anonymous], 1999, ARCH OPHTHALMOL, V117, P1329
   Arnold J, 2001, AM J OPHTHALMOL, V131, P541
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NR 17
TC 13
Z9 13
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD JUL
PY 2010
VL 24
IS 7
BP 1247
EP 1251
DI 10.1038/eye.2009.301
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 626OT
UT WOS:000279976000019
PM 20019764
OA Bronze
DA 2022-11-30
ER

PT J
AU Vejux, A
   Malvitte, L
   Lizard, G
AF Vejux, A.
   Malvitte, L.
   Lizard, G.
TI Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and
   phospholipidosis
SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
LA English
DT Review
DE apoptosis; atherosclerosis; inflammation; oxysterols; phospholipidosis
ID MYELIN FIGURE FORMATION; 7-KETOCHOLESTEROL-INDUCED APOPTOSIS;
   ENDOTHELIAL-CELLS; ENDOPLASMIC-RETICULUM; OXIDIZED CHOLESTEROL;
   UP-REGULATION; INDUCTION; DEATH; RAT; 7-BETA-HYDROXYCHOLESTEROL
AB Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7 beta-hydroxycholesterol, to trigger cell death, activate inflammation, and modulate lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols, it is important to determine their biological activities and identify their signaling pathways, when they are used either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures has been observed with cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of phospholipidosis. This basic knowledge about oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since oxysterols have a number of biological activities, and as oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation, inflammation, and phospholipidosis).
C1 [Vejux, A.] Univ Nice Sophia Antipolis, Unite Transporter Imaging & Radiotherapy Oncol, Fac Med, Commissariat Energie Atom, Nice, France.
   [Malvitte, L.] CHU Dijon, Hop Gen, Serv Ophtalmol, F-21004 Dijon, France.
   [Lizard, G.] Univ Bourgogne, INSERM, Equipe Biochim Metab & Nutr, U866,Fac Sci Gabriel,Ctr Rech, F-21000 Dijon, France.
C3 CEA; UDICE-French Research Universities; Communaute Universite Grenoble
   Alpes; Universite Grenoble Alpes (UGA); Universite Cote d'Azur;
   Universite de Franche-Comte; CHU Dijon Bourgogne; Institut Agro; AgroSup
   Dijon; Institut National de la Sante et de la Recherche Medicale
   (Inserm); Universite de Bourgogne
RP Lizard, G (通讯作者)，Univ Bourgogne, INSERM, Equipe Biochim Metab & Nutr, U866,Fac Sci Gabriel,Ctr Rech, 6 Bd Gabriel, F-21000 Dijon, France.
EM gerard.lizard@u-bourgogne.fr
RI Lizard, Gerard/B-2439-2012; VEJUX, Anne/C-1509-2019
OI VEJUX, Anne/0000-0002-4063-9680
FU INSERM; Ligue Contre Le Cancer (Comite de Cote d'Or); University
   Hospital of Dijon; Conseil Regional de Bourgogne
FX Research supported by grants from the INSERM, the Ligue Contre Le Cancer
   (Comite de Cote d'Or), the University Hospital of Dijon, and the Conseil
   Regional de Bourgogne.
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NR 60
TC 132
Z9 133
U1 0
U2 14
PU ASSOC BRAS DIVULG CIENTIFICA
PI RIBEIRAO PRETO
PA FACULDADE MEDICINA, CASA 10, 14049 RIBEIRAO PRETO, RIBEIRAO PRETO, SP
   14049, BRAZIL
SN 0100-879X
EI 1414-431X
J9 BRAZ J MED BIOL RES
JI Brazilian J. Med. Biol. Res.
PD JUL
PY 2008
VL 41
IS 7
BP 545
EP 556
DI 10.1590/S0100-879X2008000700001
PG 12
WC Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Research & Experimental
   Medicine
GA 350AZ
UT WOS:000259326100001
PM 18719735
OA Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Sengupta, N
   Caballero, S
   Mames, RN
   Timmers, AM
   Saban, D
   Grant, MB
AF Sengupta, N
   Caballero, S
   Mames, RN
   Timmers, AM
   Saban, D
   Grant, MB
TI Preventing stem cell incorporation into choroidal neovascularization by
   targeting homing and attachment factors
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; TRANSENDOTHELIAL MIGRATION; CHEMOKINE
   SDF-1; CD34(+) CELLS; TUMOR-GROWTH; CADHERIN; MOBILIZATION;
   ANGIOGENESIS; CXCR4; RECRUITMENT
AB PURPOSE. The primary cause of vision loss in people more than 50 years of age in developed nations is age-related macular degeneration (ARMD). The wet form of ARMD is characterized by choroidal neovascularization (CNV). A prior study has shown that adult hematopoietic stem cells (HSCs) contribute to approximately 50% of newly formed vasculature in CNV. Stromal-derived factor (SDF)-1 is involved with homing of HSCs from bone marrow to target tissue. Vascular endothelial cadherin (VE-cadherin, or CD144) is involved in endothelial cell adhesion. Preventing homing and/or adhesion of progenitor cells to damaged choroid could reduce CNV.
   METHODS. Adult C57BL/6J mice were lethally irradiated, and then received a transplant of purified c-kit (+) Sca-1(+) HSCs from the bone marrow of green fluorescent protein (gfp) homozygous donor mice. Bruch's membrane rupture by laser photocoagulation was used to induce CNV. Animals were injected subretinally with anti-SDF-1, anti-CD144, or control, before or after laser photocoagulation. The eyes were enucleated, and the neural retinas were separated from the RPE/choroid/sclera complex. All tissues were flatmounted and qualitatively and quantitatively assessed by fluorescence microscopy.
   RESULTS. CNV lesions from eyes treated with anti-CD144 showed significantly less incorporation of gfp (+) cells compared with those treated with anti-SDF-1. Antibody treatment generally reduced the degree of gfp (+) stem cell recruitment and incorporation into the CNV lesions, compared with the control. Treatment with either antibody also significantly reduced the size of the CNV lesions.
   CONCLUSIONS. These results indicate that homing and adhesion of progenitor cells to CNV may be targeted differentially or in combination to prevent CNV.
C1 Univ Florida, Dept Pharmacol & Therapeut, Program Stem Cell Biol, Gainesville, FL 32510 USA.
   Retina Ctr, Gainesville, FL USA.
C3 State University System of Florida; University of Florida
RP Grant, MB (通讯作者)，Univ Florida, Dept Pharmacol & Therapeut, Program Stem Cell Biol, POB 1200267, Gainesville, FL 32510 USA.
EM grantma@pharmacology.ufl.edu
FU NEI NIH HHS [EY012601, EY07739] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY012601, R01EY007739, R29EY007739] Funding Source: NIH
   RePORTER
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NR 43
TC 58
Z9 70
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 JAN
PY 2005
VL 46
IS 1
BP 343
EP 348
DI 10.1167/iovs.04-0153
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 889UV
UT WOS:000226469100050
PM 15623794
DA 2022-11-30
ER

PT J
AU Berglin, L
   Sarman, S
   van der Ploeg, I
   Steen, B
   Ming, Y
   Itohara, S
   Seregard, S
   Kvanta, A
AF Berglin, L
   Sarman, S
   van der Ploeg, I
   Steen, B
   Ming, Y
   Itohara, S
   Seregard, S
   Kvanta, A
TI Reduced choroidal neovascular membrane formation in matrix
   metalloproteinase-2-deficient mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS; EXPRESSION; ACTIVATOR;
   DEFICIENT; DISRUPTION; INVASION; TYPE-1; CANCER; CELLS
AB PURPOSE. Findings in studies have suggested a role for matrix metalloproteinase (MMP)-2 in angiogenesis, including choroidal neovascularization (CNV). To investigate further, the current study was conducted to observe the formation of experimental CNV in MMP-2-deficient mice.
   METHODS. CNV was induced in wild-type and MMP-2-deficient mice by krypton laser photocoagulation of the fundus. The time-course of expression of MMP-2 mRNA after laser treatment was determined by in situ hybridization with anti-sense and sense cRNA probes. MMP-2 protein distribution was determined by immunohistochemistry. Ten days after treatment, the extent of CNV was evaluated on hematoxylin-eosin stained serial sections. The maximum height of the CNV lesions was calculated by image analysis of digitized histologic images.
   RESULTS. Expression of MMP-2 mRNA was detected in the CNV lesions at day 3 after laser treatment and peaked at day 5, after which it slowly declined. MMP-2 mRNA expression appeared to be highest at the margins of the membrane. Immunostaining for MMP-2 confirmed the presence of MMP-2 protein in the CNV lesions. The CNV lesions of MMP-2-deficient mice showed that relative thickness was reduced by 31% compared with wild-type mice (P = 0.006).
   CONCLUSIONS. The present study demonstrated that MMP-2 mRNA and protein are upregulated during experimental CNV in the mouse. The marked difference in thickness of the CNV membrane between wild-type and MMP-2-deficient mice shows that MMP-2 is involved in the formation of experimental CNV in the mouse. These results suggest that pharmacologic targeting of MMPs, including MMP-2, may reduce formation of CNV in conditions such as age-related macular degeneration.
C1 Karolinska Inst, Dept Ophthalmol, Stockholm, Sweden.
   Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
   Riken Brain Sci Inst, Wako, Saitama, Japan.
C3 Karolinska Institutet; Karolinska Institutet; RIKEN
RP Kvanta, A (通讯作者)，St Eriks Eye Hosp, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
EM anders.kvanta@sankterik.se
RI Itohara, Shigeyoshi/I-8769-2012
OI Itohara, Shigeyoshi/0000-0002-2410-9989
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NR 31
TC 78
Z9 86
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JAN
PY 2003
VL 44
IS 1
BP 403
EP 408
DI 10.1167/iovs.02-0180
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 631EZ
UT WOS:000180156300057
PM 12506102
DA 2022-11-30
ER

PT J
AU Yang, JY
   Lu, B
   Feng, Q
   Alfaro, JS
   Chen, PH
   Loscalzo, J
   Wei, WB
   Zhang, YY
   Lu, SJ
   Wang, SM
AF Yang, Jing-Yan
   Lu, Bin
   Feng, Qiang
   Alfaro, Jorge S.
   Chen, Po-Hsuen
   Loscalzo, Joseph
   Wei, Wen-Bin
   Zhang, Ying-Yi
   Lu, Shi-Jiang
   Wang, Shaomei
TI Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M
   and Ciliary Neurotrophic Factor Into Rodent Models of Retinal
   Degeneration
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE neuroprotection; trophic factors; intravitreal drug delivery
ID CELL INTRAOCULAR IMPLANTS; RETINITIS-PIGMENTOSA; GENE-THERAPY;
   LONG-TERM; PHOTORECEPTOR DEGENERATION; ANIMAL-MODELS; RAT RETINA; RPE65
   MUTATIONS; GROWTH-FACTORS; CNTF
AB Purpose: Retinitis pigmentosa (RP) is caused by mutations in more than 60 genes. Mutation-independent approaches to its treatment by exogeneous administration of neurotrophic factors that will preserve existing retinal anatomy and visual function are a rational strategy. Ciliary neurotrophic factor (CNTF) and oncostatin M (OSM) are two potent survival factors for neurons. However, growth factors degrade rapidly if administered directly. A sustained delivery of growth factors is required for translating their potential therapeutic benefit into patients. Methods: Stable and biocompatible nanoparticles (NP) that incorporated with CNTF and OSM (CNTF- and OSM-NP) were formulated. Both NP-trophic factors were tested in vitro using photoreceptor progenitor cells (PPC) and retinal ganglion progenitor cells (RGPC) derived from induced pluripotent stem cells and in vivo using an optic nerve crush model for glaucoma and the Royal College of Surgeons rat, model of RP (n = 8/treatment) by intravitreal delivery. Efficacy was evaluated by electroretinography and optokinetic response. Retinal histology and a whole mount analysis were performed at the end of experiments. Results: Significant prosurvival and pro-proliferation effects of both complexes were observed in both photoreceptor progenitor cells and RGPC in vitro. Importantly, significant RGC survival and preservation of vision and photoreceptors in both complextreated animals were observed compared with control groups. Conclusions: These results demonstrate that NP-trophic factors are neuroprotective both in vitro and in vivo. A single intravitreal delivery of both NP-trophic factors offered neuroprotection in animal models of retinal degeneration. Translational Relevance: Sustained nanoparticle delivery of neurotrophic factors may offer beneficial effects in slowing down progressive retinal degenerative conditions, including retinitis pigmentosa, age-related macular degeneration, and glaucoma.
C1 [Yang, Jing-Yan; Lu, Bin; Alfaro, Jorge S.; Wang, Shaomei] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA USA.
   [Feng, Qiang; Chen, Po-Hsuen; Lu, Shi-Jiang] NanoNeuron Therapeut & HebeCell Corp, Natick, MA USA.
   [Loscalzo, Joseph; Zhang, Ying-Yi] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA.
   [Yang, Jing-Yan; Wei, Wen-Bin] Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China.
C3 Cedars Sinai Medical Center; Harvard University; Brigham & Women's
   Hospital; Harvard Medical School; Capital Medical University
RP Wang, SM (通讯作者)，Cedars Sinai Med Ctr, Regenerat Med Inst, SSB, 8700 Beverly Blvd,3rd Floor, Los Angeles, CA 90048 USA.
EM shaomei.wang@cshs.org
RI Loscalzo, Joseph/ABD-8980-2021
FU NanoNeuron Therapeutics; HebeCell Corp; Regenerative Medicine Institute
   at Cedars-Sinai Medical Center
FX Supported by NanoNeuron Therapeutics and HebeCell Corp and the
   Regenerative Medicine Insti-tute at Cedars-Sinai Medical Center.
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NR 67
TC 2
Z9 2
U1 0
U2 6
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 AUG
PY 2021
VL 10
IS 9
AR 6
DI 10.1167/tvst.10.9.6
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TY5GW
UT WOS:000683813800004
PM 34347033
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ishii, M
   Beeson, G
   Beeson, C
   Rohrer, B
AF Ishii, Masaaki
   Beeson, Gyda
   Beeson, Craig
   Rohrer, Barbel
TI Mitochondrial C3a Receptor Activation in Oxidatively Stressed Epithelial
   Cells Reduces Mitochondrial Respiration and Metabolism
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE mitochondria; complement C3a receptor; translocation; endosomal
   targeting; calcium imaging; oxidative phosphorylation
AB Complement component 3 fragment C3a is an anaphylatoxin involved in promoting cellular responses important in immune response and host defense. Its receptor (C3a receptor, C3aR) is distributed on the plasma membrane; however, lysosomal localization in immune cells has been reported. Oxidative stress increases intracellular reactive oxygen species (ROS), and ROS activate complement signaling in immune cells and metabolic reprogramming. Here we tested oxidative stress and intracellular complement in mitochondrial dysfunction in RPE cells using high resolution live-cell imaging, and metabolism analysis in isolated mitochondria using Seahorse technology. While C3aR levels were unaffected by oxidative stress, its cell membrane levels decreased and mitochondrial (mt) localization increased. Trafficking was dependent on endocytosis, utilizing endosomal-to-mitochondrial cargo transfer. H2O2-treatment also increased C3a-mtC3aR co-localization dose-dependently. In isolated mitochondria from H2O2-treated cells C3a increased mitochondrial Ca2+ uptake, that could be inhibited by C3aR antagonism (SB290157), mitochondrial Ca2+ uniporter blocker (Ru360), and G alpha i-protein inhibition (pertussis toxin, PTX); and inhibited mitochondrial repiration in an SB290157- and PTX-dependent manner. Specifically, mtC3aR activation inhibited state III ADP-driven respiration and maximal respiratory capacity. Mitochondria from control cells did not respond to C3a. Furthermore, transmitochondrial cybrid ARPE-19 cells harboring J haplogroup mitochondria that confer risk for age-related macular degeneration, showed high levels of mtC3aR and reduced ATP production upon C3a stimulation. Our findings suggest that oxidative stress increases mtC3aR, leading to altered mitochondrial calcium uptake and ATP production. These studies will have important implication in our understanding on the balance of extra- and intracellular complement signaling in controlling cellular health and dysfunction.
C1 [Ishii, Masaaki; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Beeson, Gyda; Beeson, Craig] Med Univ South Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
   [Rohrer, Barbel] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 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; Medical
   University of South Carolina
RP Ishii, M; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.; Rohrer, B (通讯作者)，Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
EM ishiim@musc.edu; rohrer@musc.edu
FU National Institutes of Health (NIH) [R01EY019320, R01EY024581];
   Department of Veterans Affairs [IK6BX004858, RX000444, BX003050]; South
   Carolina SmartState Endowment
FX This study was supported by the National Institutes of Health (NIH)
   (R01EY019320, R01EY024581), the Department of Veterans Affairs
   (IK6BX004858, RX000444, and BX003050), and the South Carolina SmartState
   Endowment.
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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 MAR 5
PY 2021
VL 12
AR 628062
DI 10.3389/fimmu.2021.628062
PG 16
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA QY9HJ
UT WOS:000630346300001
PM 33746964
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Maqsood, S
   Damasevivius, R
   Shah, FM
   Maskeliunas, R
AF Maqsood, Sarmad
   Damasevivius, Robertas
   Shah, Faisal Mehmood
   Maskeliunas, Rytis
TI DETECTION OF MACULA AND RECOGNITION OF AGED-RELATED MACULAR DEGENERATION
   IN RETINAL FUNDUS IMAGES
SO COMPUTING AND INFORMATICS
LA English
DT Article
DE Medical image processing; contrast enhancement; macula detection;
   retinal fundus image; blood vessels segmentation
ID DIABETIC-RETINOPATHY; VESSEL SEGMENTATION; EXTRACTION
AB In aged people, the central vision is affected by Age-Related Macular Degeneration (AMD). From the digital retinal fundus images, AMD can be recognized because of the existence of Drusen, Choroidal Neovascularization (CNV), and Geographic Atrophy (GA). It is time-consuming and costly for the ophthalmologists to monitor fundus images. A monitoring system for automated digital fundus photography can reduce these problems. In this paper, we propose a new macula detection system based on contrast enhancement, top-hat transformation, and the modified Kirsch template method. Firstly, the retinal fundus image is processed through an image enhancement method so that the intensity distribution is improved for finer visualization. The contrast-enhanced image is further improved using the top-hat transformation function to make the intensities level differentiable between the macula and different sections of images. The retinal vessel is enhanced by employing the modified Kirsch's template method. It enhances the vasculature structures and suppresses the blob-like structures. Furthermore, the OTSU thresholding is used to segment out the dark regions and separate the vessel to extract the candidate regions. The dark region and the background estimated image are subtracted from the extracted blood vessels image to obtain the exact location of the macula. The proposed method applied on 1349 images of STARE, DRIVE, MESSIDOR, and DIARETDB1 databases and achieved the average sensitivity, specificity, accuracy, positive predicted value, F1 score, and area under curve of 97.79 %, 97.65 %, 97.60 %, 97.38 %, 97.57 %, and 96.97 %, respectively. Experimental results reveal that the proposed method attains better performance, in terms of visual quality and enriched quantitative analysis, in comparison with eminent state-of-the-art methods.
C1 [Maqsood, Sarmad; Damasevivius, Robertas] Kaunas Univ Technol, Dept Software Engn, LT-51386 Kaunas, Lithuania.
   [Shah, Faisal Mehmood] Pakistan Space & Upper Atmosphere Res Commiss, Karachi 75270, Pakistan.
   [Maskeliunas, Rytis] Silesian Tech Univ, Fac Appl Math, PL-44100 Gliwice, Poland.
C3 Kaunas University of Technology; Silesian University of Technology
RP Maqsood, S (通讯作者)，Kaunas Univ Technol, Dept Software Engn, LT-51386 Kaunas, Lithuania.
EM sarmad.maqsood@ktu.edu; robertas.damasevicius@ktu.lt;
   shahfaisal94@gmail.com; rytis.maskeliunas@polsl.pl
RI Maqsood, Sarmad/AAH-8414-2020; Maskeliunas, Rytis/J-7173-2017;
   Damaševičius, Robertas/E-1387-2017
OI Maskeliunas, Rytis/0000-0002-2809-2213; Damaševičius,
   Robertas/0000-0001-9990-1084
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NR 58
TC 2
Z9 2
U1 1
U2 6
PU SLOVAK ACAD SCIENCES INST INFORMATICS
PI BRATISLAVA
PA DUBRAVSKA CESTA 9, 84237 BRATISLAVA, SLOVAKIA
SN 1335-9150
J9 COMPUT INFORM
JI Comput. Inform.
PY 2021
VL 40
IS 5
BP 957
EP 987
DI 10.31577/cai_2021_5_957
PG 31
WC Computer Science, Artificial Intelligence
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science
GA YT7LZ
UT WOS:000751537900001
OA Bronze
DA 2022-11-30
ER

PT J
AU Ghanchi, FD
   Fulcher, C
   Madanat, Z
   Mdanat, F
AF Ghanchi, Faruque D.
   Fulcher, Corinne
   Madanat, Zeid
   Mdanat, Faris
TI Optical coherence tomography angiography for identifying choroidal
   neovascular membranes: a masked study in clinical practice
SO EYE
LA English
DT Article
ID DOUBLE-LAYER SIGN; MACULAR DEGENERATION; FLUORESCEIN ANGIOGRAPHY
AB Background/objectives Optical coherence tomography angiography (OCT-A) allows non-invasive imaging of chorio-retinal vasculature, and is a potential alternative to fluorescein angiography (FA). Sensitivity and specificity of OCT-A for detecting choroidal neovascularisation (CNV) in treatment-naive neovascular age-related macular degeneration (nAMD) patients is examined, using the Heidelberg Spectralis in a 'real world' setting. Subject/methods Overall, 43 eyes from 26 patients were included in the study. Spectral domain OCT (SD-OCT), OCT-A and FA images were obtained at baseline. Each of the three retinal image modalities was systematically assessed by three masked clinicians. Decisions about the presence/absence of CNV were recorded using an automated segmentation for OCT-A, a manual method, and using both OCT-A and SD-OCT in conjunction. Additional information about the presence of sub-retinal hyper-reflective material (SHRM) and the 'double layer sign' (DLS) were recorded. Results The average sensitivity and specificity of the OCT-A for the detection of CNV in treatment naive AMD was 89% and 87% for the combined SD-OCT and OCT-A, 76% and 91% for the automated segmentation and 84% and 85% for the manual segmentation, respectively. Inter-clinician agreement was 0.59-65 kappa. In patients without CNV, SHRM was present in only 6% while DLS was present in 28%. Sensitivity and specificity was >78% for both SHRM and DLS. Conclusions OCT-A provides a reliable tool for detecting CNV in treatment naive nAMD patients, with high sensitivity and specificity. Combined use of SD-OCT images and SHRM as an additional bio-marker, OCT-A could become an alternative to FA in routine clinical practice.
C1 [Ghanchi, Faruque D.; Fulcher, Corinne; Madanat, Zeid; Mdanat, Faris] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England.
RP Ghanchi, FD (通讯作者)，Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England.
EM Faruque.Ghanchi@bthft.nhs.uk
OI Ghanchi, Faruque/0000-0002-4448-8162; Fulcher,
   Corinne/0000-0002-6668-2396
CR Bearelly S, 2009, CAN J OPHTHALMOL, V44, P444, DOI 10.3129/i09-068
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NR 33
TC 1
Z9 1
U1 0
U2 3
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 134
EP 141
DI 10.1038/s41433-020-01285-0
EA NOV 2020
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI7BU
UT WOS:000592543900002
PM 33235335
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Isumi, Y
   Hayashi, S
   Inoue, T
   Yoshigae, Y
   Sato, T
   Hasegawa, J
   Agatsuma, T
AF Isumi, Yoshitaka
   Hayashi, Shinko
   Inoue, Tatsuya
   Yoshigae, Yasushi
   Sato, Toshiyuki
   Hasegawa, Jun
   Agatsuma, Toshinori
TI DS-7080a, a Selective Anti-ROBO4 Antibody, Shows Anti-Angiogenic
   Efficacy with Distinctly Different Profiles from Anti-VEGF Agents
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE ROBO4; antibody; choroidal neovascularization; vascular endothelial
   growth factor; age-related macular degeneration
ID MACULAR DEGENERATION; PATHOLOGICAL ANGIOGENESIS; ROBO4; GROWTH;
   RANIBIZUMAB; EXPRESSION; TRAP; VERTEPORFIN; STABILIZES; MECHANISMS
AB Purpose: Neovascular age-related macular degeneration (nAMD) results from choroidal neovascularization (CNV) and causes severe vision loss. Intravitreal anti-vascular endothelial growth factor (VEGF) therapies have significantly improved therapeutic outcomes; however, a substantial number of patients experience disease progression. Roundabout 4 (ROBO4) has been reported to be a vascular-specific protein that stabilizes vasculature in ocular pathological angiogenesis. To explore ROBO4 targeting as a novel treatment against neovascularization, we generated a humanized anti-human ROBO4 antibody, DS-7080a, and evaluated its efficacy.
   Methods: ROBO4 mRNA in human whole eye cross-sections was examined by in situ hybridization. Human umbilical vein endothelial cell (HUVEC) migration was measured in the presence of VEGF, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), or conditioned medium of primary human retinal pigment epithelial (HRPE) cells. CNV was induced in cynomolgus monkeys by laser irradiation. Vascular leakage was measured by fluorescein angiography, and pathological changes were determined by histology.
   Results: ROBO4 mRNA was detected in choroidal vessels of nAMD patients. DS-7080a suppressed HGF- or bFGF-induced HUVEC migration in addition to that induced by VEGF. Further, HUVEC migration induced by HRPE-conditioned medium was inhibited by either DS-7080a or ranibizumab in a similar manner, and the combination of these showed further inhibition. In a laser-induced CNV monkey model, single intravitreous administration of 1.1mg/eye ofDS-7080a reduced the incidence of grade 4 leakage from 44.45% in control eyes to 1.85% (P < 0.05 by Dunnett's test).
   Conclusions: Anti-ROBO4 antibody DS-7080a suppressed HUVEC migration in a distinctly different fashion from anti-VEGF agents and improved laser-induced CNV in non-human primates.
C1 [Isumi, Yoshitaka; Hayashi, Shinko; Agatsuma, Toshinori] Daiichi Sankyo Co Ltd, R&D Div, Oncol Funct, Oncol Res Labs 1, Tokyo, Japan.
   [Inoue, Tatsuya] Daiichi Sankyo Co Ltd, R&D Div, Res Funct, Specialty Med Res Labs 1, Tokyo, Japan.
   [Yoshigae, Yasushi] Daiichi Sankyo Co Ltd, R&D Div, Res Funct, Res Planning Grp, Tokyo, Japan.
   [Sato, Toshiyuki] Daiichi Sankyo Co Ltd, R&D Div, Res Funct, Specialty Med Res Labs 2, Tokyo, Japan.
   [Hasegawa, Jun] Daiichi Sankyo Co Ltd, Biol Div, Modal Res Labs, Tokyo, Japan.
C3 Daiichi Sankyo Company Limited; Daiichi Sankyo Company Limited; Daiichi
   Sankyo Company Limited; Daiichi Sankyo Company Limited; Daiichi Sankyo
   Company Limited
RP Isumi, Y (通讯作者)，Daiichi Sankyo Co Ltd, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan.
EM isumi.yoshitaka.hi@daiichisankyo.co.jp
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NR 37
TC 1
Z9 1
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 AUG
PY 2020
VL 9
IS 9
AR 7
DI 10.1167/tvst.9.9.7
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OH9SL
UT WOS:000582929100007
PM 32879763
OA gold, Green Published
DA 2022-11-30
ER

PT J
CA ICNIRP
TI Light-Emitting Diodes (LEDS): Implications for Safety
SO HEALTH PHYSICS
LA English
DT Article
DE International Commission on Non Ionizing Radiation Protection; health
   effects; safety standards; radiation; non-ionizing
ID AGE-RELATED MACULOPATHY; INDUCED RETINAL DAMAGE; MACULAR DEGENERATION;
   SUNLIGHT EXPOSURE; OPTICAL RADIATION; ACTION SPECTRUM; SUN EXPOSURE;
   RISK-FACTORS; SENSITIVITY; THRESHOLDS
AB Since the original ICNIRP Statement was published in 2000, there have been significant improvements in the efficiency and radiance (i.e., optical radiation emission) of LEDs. The most important improvement is the development of 'white' LEDs that can be used as general lighting sources, which are more efficient than traditional lighting sources. LEDs emitting in the ultraviolet wavelength region have also become available and have made their way into consumer products. All these changes have led to a rise in concern for the safety of the optical radiation emissions from LEDs. Several in vitro and animal studies have been conducted, which indicate that blue and white LEDs can potentially cause retinal cell damage under high irradiance and lengthy exposure conditions. However, these studies cannot be directly extrapolated to normal exposure conditions for humans, and equivalent effects can also be caused by the optical radiation from other light sources under extreme exposure conditions. Acute damage to the human retina from typical exposure to blue or white LEDs has not been demonstrated. Concern for potential long-term effects, e.g. age-related macular degeneration (AMD), remains based on epidemiological studies indicating a link between high levels of exposure to sunlight and AMD. When evaluating the optical radiation safety of LEDs, it has now been established that published safety standards for lamps, not lasers, should be applied. Thus far, the only clear, acute adverse health effects from LEDs are those due to temporal light modulation (including flicker). Glare can also create visual disturbances when LED light fixtures are not properly designed. Further research is needed on potential health effects from short- and long-term exposure to new and emerging lighting technologies.
RI Hirata, Akimasa/I-8245-2012; Röösli, Martin/A-2658-2008
OI Hirata, Akimasa/0000-0001-8336-1140; Röösli, Martin/0000-0002-7475-1531;
   Croft, Rodney/0000-0002-5986-9136
FU EU funds
FX Sharon A Miller, ICNIRP; John O'Hagan, ICNIRP SEG and Public Health
   England, United Kingdom; Tsutomu Okuno, ICNIRP; Karl Schulmeister,
   ICNIRP SEG and Seibersdorf Laboratories, ICNIRP and Australian Centre
   for Electromagnetic Bioeffects Research, Illawarra Health & Medical
   Research Institute, University of Wollongong, Australia; Maria
   Feychting, ICNIRP and Karolinska Institutet, Sweden; Adele C Green,
   ICNIRP and QIMR Berghofer Medical Research Institute, Brisbane,
   Australia and CRUK Manchester Institute, University of Manchester,
   Manchester, UK; Akimasa Hirata, ICNIRP and Nagoya Institute of
   Technology, Japan; Guglielmo d'Inzeo, ICNIRP and La Sapienza University
   Rome, Italy; Carmela Marino, ICNIRP and Agency forNewTechnologies,
   Energy and Sustainable Economic Development, Italy; Gunnhild Oftedal,
   ICNIRP and Norwegian University of Science and Technology; Eric van
   Rongen, ICNIRP and Health Council, The Netherlands; Martin Roosli,
   ICNIRP and Swiss Tropical and Public Health Institute, Basel,
   Switzerland; Zenon Sienkiewicz, ICNIRP; Soichi Watanabe, ICNIRP and
   National Institute of Information and Communications Technology, Japan.;
   The views expressed by the collaborators in this publication do not
   necessarily reflect the views or policies of the organizations they are
   professionally affiliated with. The mention of commercial products,
   their sources, or their use in connection with material reported herein
   is not to be construed as either an actual or implied endorsement of
   such products by ICNIRP or any of the organizations with which the
   ICNIRP members are affiliated.; The support received by the German
   FederalMinistry for the Environment (BMU), the European Union Programme
   for Employment and Social Innovation "EaSI" (2014-2020), the
   International Radiation Protection Association (IRPA), the Australian
   Radiation Protection and Nuclear Safety Agency (ARPANSA), and the New
   Zealand Ministry of Health is gratefully acknowledged. In regard to the
   EU funds, for further information please consult:
   http://ec.europa.eu/social/easi.The information contained in this
   publication does not necessarily reflect the official position of the
   European Commission, or any other donors. All information concerning the
   support received by ICNIRP is available at www.icnirp.org.
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NR 92
TC 11
Z9 11
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD MAY
PY 2020
VL 118
IS 5
BP 549
EP 561
DI 10.1097/HP.0000000000001259
PG 13
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
   Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
   Medical Imaging
GA LP5EX
UT WOS:000534341800006
PM 32251083
OA hybrid
DA 2022-11-30
ER

PT J
AU Tufail, A
   Margaron, P
   Guerin, T
   Larsen, M
AF Tufail, Adnan
   Margaron, Philippe
   Guerin, Tadhg
   Larsen, Michael
TI Visual benefit versus visual gain: what is the effect of baseline
   covariants in the treatment arm relative to the control arm? A pooled
   analysis of ANCHOR and MARINA
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE retina; vision
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; MACULAR DEGENERATION;
   INTRAVITREAL RANIBIZUMAB; SUBGROUP ANALYSIS; THERAPY; OUTCOMES;
   VERTEPORFIN; REGIMEN; TRIAL; BEVACIZUMAB
AB Background
   This study aimed to elucidate visual benefits of ranibizumab in patients with neovascular age-related macular degeneration (nAMD) compared with control arms and identify factors affecting response.
   Methods
   This is a post-hoc pooled analysis of two phase III studies, ANCHOR and MARINA, of ranibizumab for the treatment of nAMD. ANCHOR included 83 international sites. MARINA included 96 sites in the USA. Analysis included patients (control, n=323; ranibizumab, n=332) with nAMD and a baseline best-corrected visual acuity (BCVA) of >= 35- Results
   Patients receiving ranibizumab achieved an adjusted mean BCVA superiority of 18.9 and 21.2 letters over 12 and 24 months, respectively, compared with control. Ranibizumab treatment, higher baseline BCVA, lower age and smaller lesion size were positively associated with the ability to achieve BCVA >69 letters. Patients with the highest baseline BCVA had lowest BCVA gains. Ranibizumab treatment, lower baseline BCVA, lower age and smaller lesion size were identified as significant predictors of BCVA gain from baseline at month 24 (all p<0.0001). However, the difference in mean BCVA gains at month 24 between treatment and control groups was similar for all baseline BCVA subgroups (>= 35-<55 letters, 21.9 letters; >= 55-<70 letters, 25.2 letters; >= 70-<85 letters, 19.3 letters).
   Conclusions
   Higher baseline BCVA is associated with lower BCVA gains but a greater likelihood of achieving good final BCVA >69 letters due to smaller gains needed to achieve response. Visual benefits, including maintenance of visual acuity (VA), final VA achieved and relative gain compared with natural disease progression, should be considered when assessing treatment response in nAMD.
C1 [Tufail, Adnan] Moorfields Eye Hosp, Med Retina, London, England.
   [Tufail, Adnan] UCL, Inst Ophthalmol, London, England.
   [Margaron, Philippe] Novartis Pharmaceut, Basel, Switzerland.
   [Guerin, Tadhg] Theravance Biopharma, Dublin, Ireland.
   [Larsen, Michael] Univ Copenhagen, Rigshosp, Dept Ophthalmol, Copenhagen, Denmark.
   [Larsen, Michael] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Novartis; Rigshospitalet; University of Copenhagen; University of
   Copenhagen
RP Tufail, A (通讯作者)，Moorfields Eye Hosp, London EC1V 2PD, England.
EM adnan.tufail@moorfields.nhs.uk
RI Larsen, Michael/E-9620-2010
OI Larsen, Michael/0000-0002-5172-5891; Tufail, Adnan/0000-0001-6131-7640
FU Department of Health's NIHR Biomedical Research Centre for Ophthalmology
   at Moorfields Eye Hospital and UCL Institute of Ophthalmology
FX Dr Tufail has received a proportion of his funding from the Department
   of Health's NIHR Biomedical Research Centre for Ophthalmology at
   Moorfields Eye Hospital and UCL Institute of Ophthalmology. The views
   expressed in the publication are those of the author and not necessarily
   those of the Department of Health.
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NR 38
TC 7
Z9 7
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAY
PY 2020
VL 104
IS 5
BP 672
EP 677
DI 10.1136/bjophthalmol-2018-313682
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LL2KF
UT WOS:000531384100014
PM 31562118
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Dwight, JG
   Weng, CY
   Pawlowski, ME
   Tkaczyk, TS
AF Dwight, Jason G.
   Weng, Christina Y.
   Pawlowski, Michal E.
   Tkaczyk, Tomasz S.
TI A Dye-Free Analog to Retinal Angiography Using Hyperspectral Unmixing to
   Retrieve Oxyhemoglobin Abundance
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE hyperspectral imaging; spectral unmixing; retinal imaging; oxygen
   abundance in tissue; dye-free analog to angiography
ID OPTICAL COHERENCE TOMOGRAPHY; FLUORESCEIN ANGIOGRAPHY;
   OXYGEN-SATURATION; OXIMETRY; METABOLISM; VESSELS
AB Purpose: Retinal angiography evaluates retinal and choroidal perfusion and vascular integrity and is used to manage many ophthalmic diseases, such as age-related macular degeneration. The most common method, fluorescein angiography (FA), is invasive and can lead to untoward effects. As an emerging replacement, noninvasive OCT angiography (OCTA) is used regularly as a dye-free substitute with superior resolution and additional depth-sectioning abilities; however, general trends in FA as signified by varying intensity in images are not always reproducible in the fine structural detail in an OCTA image stack because of the source of their respective signals, OCT speckle decorrelation versus fluorescein emission.
   Methods: We present a noninvasive/dye-free analog to angiography imaging using retinal hyperspectral imaging with a nonscanning spectral imager, the image mapping spectrometer (IMS), to reproduce perfusion-related data based on the abundance of oxyhemoglobin (HbO(2)) in the retina. With a new unmixing procedure of the IMS-acquired spectral data cubes (350 x 350 x 43), we produced noninvasive HbO(2) maps unmixed from reflectance spectra.
   Results: Here, we present 15 HbO(2) maps from seven healthy and eight diseased retinas and compare these maps with corresponding FA and OCTA results with a discussion of each technique.
   Conclusions: Our maps showed visual agreement with hypo- and hyperfluorescence trends in venous phase FA images, suggesting that our method provides a new use for hyperspectral imaging as a noninvasive angiography-analog technique and as a complementary technique to OCTA.
   Translational Relevance: The application of hyperspectral imaging and spectral analysis can potentially improve/broaden retinal disease screening and enable a noninvasive technique, which complements OCTA.
C1 [Dwight, Jason G.; Pawlowski, Michal E.; Tkaczyk, Tomasz S.] Rice Univ, Dept Bioengn, Houston, TX 77005 USA.
   [Weng, Christina Y.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
C3 Rice University; Baylor College of Medicine
RP Tkaczyk, TS (通讯作者)，Rice Univ, Dept Bioengn, Houston, TX 77005 USA.
EM ttkaczyk@rice.edu
RI Pawlowski, Michal/ABG-3922-2020
FU National Institutes of Health (NIH) [R01CA186132]; Institute of
   Biosciences and Bioengineering (IBB) Medical Innovation Grant; NATIONAL
   CANCER INSTITUTE [R01CA186132] Funding Source: NIH RePORTER
FX Supported by grant R01CA186132 from the National Institutes of Health
   (NIH) and the Institute of Biosciences and Bioengineering (IBB) Medical
   Innovation Grant.
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NR 43
TC 2
Z9 2
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAY
PY 2019
VL 8
IS 3
AR 44
DI 10.1167/tvst.8.3.44
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IE9SF
UT WOS:000472716200013
PM 31259089
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kadkhodaeian, HA
   Salati, A
   Lashay, A
AF Kadkhodaeian, Hamid Aboutaleb
   Salati, Amir
   Lashay, Alireza
TI High efficient differentiation of human adipose-derived stem cells into
   retinal pigment epithelium-like cells in medium containing small
   molecules inducers with a simple method
SO TISSUE & CELL
LA English
DT Article
DE Human adipose stem cells; Retinal pigmented epithelium cells;
   Age-related macular degeneration
ID MARROW STROMAL CELLS; IN-VITRO DIFFERENTIATION; GROWTH-FACTOR; NEURAL
   CELLS; RPE; THERAPY; CULTURE; PROLIFERATION; DEGENERATION; EXPRESSION
AB Background: The induction of retinal pigmented epithelium cells (RPE) is one of the most important objectives in research focused on treating retinal degenerative diseases. The present study aims to differentiate human adipose stem cells (hADSCs) into RPE cells for replacement therapies in cases of retinal degenerative diseases.
   Methods: Lipoaspirate-derived human adipose stem cells (LA-hADSCs) were obtained from abdominal samples and examined by immunocytochemistry for the expression of mesenchymal adipose stem cell markers. RPE cells were also obtained from human samples and cultured to be used as control after being examined for the expression of their designated markers. hADSCs differentiated into RPE cells after 80 days using chemical inducers in one steps. The differentiated cells were then compared to control cells in marker expression. The differentiated cells were also examined under a scanning electron microscope for the presence of apical microvilli and cell connection.
   Results: Cultured hADSCs at the fourth passage was shown to express the surface markers CD90 (98 +/- 2%), CD11b (96 +/- 3%), and CD105 (95 +/- 4%). The RPE cells obtained from human samples expressed the marker RPE65 quite well. 80 days after differentiation, the previously hADSCs expressed both RPE65 (100%) and CRALBP (96 +/- 1%) and were thus significantly similar to the RPE cells obtained from human samples. Morphologically, differentiated cells appeared to have epithelial and cytoplasmic pigment granules. Observations using a scanning electron microscope recorded clear connections among the differentiated RPE cells and revealed apical microvilli.
   Conclusion: Human adipose stem cells can differentiate into retinal pigmented epithelium cells, which can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration (AMD) as well as retinitis pigmentosa (RP).
C1 [Kadkhodaeian, Hamid Aboutaleb; Salati, Amir] Semnan Univ Med Sci, Nervous Syst Stem Cells Res Ctr, Semnan, Iran.
   [Kadkhodaeian, Hamid Aboutaleb] Semnan Univ Med Sci, Dept Anat Sci, Fac Med, Semnan, Iran.
   [Salati, Amir] Semnan Univ Med Sci, Dept Tissue Engn & Appl Cell Sci, Fac Med, Semnan, Iran.
   [Lashay, Alireza] Univ Tehran Med Sci, Farabi Eye Inst, Tehran, Iran.
C3 Semnan University of Medical Sciences; Semnan University of Medical
   Sciences; Semnan University of Medical Sciences; Tehran University of
   Medical Sciences
RP Lashay, A (通讯作者)，Univ Tehran Med Sci, Farabi Eye Res Ctr, Tehran, Iran.
EM habootaleb@semums.ac.ir; Lashay@tums.ac.ir
RI kadkhodaeian, Hamid Aboutaleb/K-7997-2017
OI kadkhodaeian, Hamid Aboutaleb/0000-0002-9736-9722
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NR 72
TC 5
Z9 5
U1 1
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0040-8166
J9 TISSUE CELL
JI Tissue Cell
PD FEB
PY 2019
VL 56
BP 52
EP 59
DI 10.1016/j.tice.2018.12.003
PG 8
WC Anatomy & Morphology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Anatomy & Morphology; Cell Biology
GA HK8XM
UT WOS:000458273000007
PM 30736904
DA 2022-11-30
ER

PT J
AU Seddon, JM
   Rosner, B
AF Seddon, Johanna M.
   Rosner, Bernard
TI AOS THESIS Validated Prediction Models for Macular Degeneration
   Progression and Predictors of Visual Acuity Loss Identify High-Risk
   Individuals
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H;
   GENETIC SUSCEPTIBILITY; RARE VARIANTS; FACTOR-I; CFH; EYE; PREVALENCE;
   DISEASE
AB PURPOSE: To determine predictive factors and risk scores for conversion to overall advanced age-related macular degeneration (AMD), geographic atrophy (GA), neovascular disease (NV), and loss of vision, and to validate the model for AMD in an external cohort.
   METHODS: Progression to advanced AMD was evaluated using stepwise survival analysis. Risk scores including genetic, demographic, behavioral, and ocular factors were derived for 3 AMD endpoints and were validated and calibrated in a large independent cohort. Vision loss of 15 or more letters was evaluated as a new endpoint in genetic analyses.
   RESULTS: Eight common and rare variants in genes CFH, C3, ARMS2, COL8A1, and HSPH1/B3GALTL conferred a significantly higher risk of transition to advanced AMD. Three loci (C2, CFB, RAD51B) were associated with lower rate of progression. A protective effect was suggested for CTRB1 and PELI3. The age-adjusted area under the curve (AUC) for the composite model including 13 loci model was 0.900 over 12 years (0.896 in the validation cohort). Generally, progressors had a higher risk category and nonprogressors had a lower risk category when genetic factors were considered. Furthermore, there was heterogeneity between models for GA and NV. The model was calibrated in the validation cohort. Determinants of visual loss included age, education, body mass index, smoking, and several common and rare genetic variants.
   CONCLUSION: Eyes with the same baseline macular grade had a wide range of estimated probability of subsequent progression and visual loss based on the validated risk score. Identifying high-risk individuals at an earlier stage using predictive modeling could lead to improved preventive and therapeutic strategies in the era of precision medicine. ((C) 2018 Elsevier Inc. All rights reserved.)
C1 [Seddon, Johanna M.] Univ Massachusetts, Sch Med, Dept Ophthalmol & Visual Sci, Worcester, MA USA.
   [Rosner, Bernard] Harvard Med Sch, Dept Med, Channing Div Network Med, Boston, MA USA.
C3 University of Massachusetts System; University of Massachusetts
   Worcester; Harvard University; Harvard Medical School
RP Seddon, JM (通讯作者)，POB 120065, Boston, MA 02112 USA.
EM johanna.seddon@umassmed.edu
FU NATIONAL EYE INSTITUTE/NAtional Institutes of Health, Bethesda,
   Massachusetts, USA [R01-EY011309, R01-EY022445]; Massachusetts Lions Eye
   Research Fund, Belmont, Massachusetts, USA; American Macular
   Degeneration Foundation, Northampton, Massachusetts, USA; NATIONAL EYE
   INSTITUTE [R01EY022445, R01EY011309] Funding Source: NIH RePORTER
FX THE RESEARCH REPORTED HEREIN WAS SUPPORTED BY THE FOLLOWING: NATIONAL
   EYE INSTITUTE/NAtional Institutes of Health R01-EY011309 (J.M.S.) and
   R01-EY022445 (B.R.), Bethesda, Massachusetts, USA; Massachusetts Lions
   Eye Research Fund, Belmont, Massachusetts, USA; and American Macular
   Degeneration Foundation, Northampton, Massachusetts, USA.
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Z9 25
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD FEB
PY 2019
VL 198
BP 223
EP 261
DI 10.1016/j.ajo.2018.10.022
PG 39
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HK6MT
UT WOS:000458095500027
PM 30389371
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Salomao, GHA
   Fernandes, AU
   Baptista, MS
   Tardivo, JP
   Gianssante, S
   Veridiano, JM
   Toledo, OMS
   Petri, G
   Christofolini, DM
   Correa, JA
AF Salomao, Gustavo H. A.
   Fernandes, Adjaci U.
   Baptista, Mauricio S.
   Tardivo, Joao Paulo
   Gianssante, Stella
   Veridiano, Juliana Mora
   Toledo, Olga Maria S.
   Petri, Giuliana
   Christofolini, Denise Maria
   Correa, Joao Antonio
TI A new Chlorin formulation promotes efficient photodynamic action in
   choriocapillaris of rabbit's eyes
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Age-related macular degeneration; Choroidal vascular diseases; Choroidal
   neovascularization; PDT; Liposome; Photosensitizer; Chlorin
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   THERAPY; BENZOPORPHYRIN; PHOTOSENSITIZERS; AGGREGATION; VERTEPORFIN
AB Age-related macular degeneration (AMD) as well as other choroidal diseases, demand novel therapeutic methods. Photodynamic therapy (PDT), which uses light and photosensitizer (PS) to cause specific vascular occlusion in the macula, is an interesting alternative. The only drug approved for the PDT treatment of AMD (Verteporfin) has a natural tendency to aggregate, demanding an expensive separation procedure during purification. We report a novel and affordable PS that is intrinsically protected against aggregation, the Monomeric Chlorin at High Concentration (MCHC-Chlorin), whose liposomal formulation was developed to provoke effective photodynamic action on the choroidal vasculature. Our report starts by stablishing the conditions to allow the efficient synthesis of MCHC-Chlorin in high yields (92%). We then tested the light stimulated occlusion of choriocapillary vessels in rabbit's eyes induced by the two MCHCChlorin isomers, which are directly obtained from the synthetic route. The PS formulation was infused in the rabbit's ear vein and eyes were immediately irradiated at 650 nm. Indirect ophthalmoscopy, fundus photography, fluorescein angiography and histopathological evaluations were used to evaluate levels of photo-thrombosis and collateral damage. Choriocapillary occlusion was achieved in all treated rabbits' eyes, while retina and sclera were completely preserved. There was no photochemical reaction in none of the eyes that received LASER without PS. Both MCHC-Chlorin isomers were separately tested and exhibited similar positive results with no systemic toxicity. Therefore, PDT occurred equally well in all treated eyes and none of the controls showed any effect in the ophthalmological exams. MCHC-Chlorin offers great potential and should be further studied as an alternative drug for choroidal diseases. (C) 2018 Elsevier Ltd. All rights reserved.
C1 [Salomao, Gustavo H. A.; Tardivo, Joao Paulo; Veridiano, Juliana Mora; Toledo, Olga Maria S.; Petri, Giuliana; Christofolini, Denise Maria; Correa, Joao Antonio] Fac Med ABC, Sao Paulo, Brazil.
   [Fernandes, Adjaci U.; Gianssante, Stella] Univ Anhembi Morumbi, Sao Paulo, Brazil.
   [Fernandes, Adjaci U.; Baptista, Mauricio S.; Gianssante, Stella] Univ Sao Paulo, Inst Quim, Dept Biochem, AV Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP, Brazil.
C3 Faculdade de Medicina do ABC; Universidade Anhembi Morumbi; Universidade
   de Sao Paulo
RP Baptista, MS (通讯作者)，Univ Sao Paulo, Inst Quim, Dept Biochem, AV Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP, Brazil.
EM baptista@iq.usp.br
RI Baptista, Mauricio S/AAO-5749-2021; Baptista, Mauricio S/A-5140-2008;
   Christofolini, Denise Maria/H-6984-2012; Fernandes,
   adjaci/ABR-0663-2022; Petri, Giuliana/S-8444-2019; CHRISTOFOLINI, DENISE
   MARIA/AAS-5648-2021
OI Baptista, Mauricio S/0000-0001-7079-7666; Baptista, Mauricio
   S/0000-0001-7079-7666; Fernandes, adjaci/0000-0002-6915-9971; Petri,
   Giuliana/0000-0002-6078-9184; 
FU FAPESP [2013/07937-8]; CNPq
FX FAPESP (2013/07937-8) and CNPq are acknowledge to provide funds for this
   research.
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NR 25
TC 2
Z9 2
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 1
PY 2018
VL 28
IS 10
BP 1870
EP 1873
DI 10.1016/j.bmcl.2018.04.007
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Chemistry
GA GG5IM
UT WOS:000432729000035
PM 29661534
DA 2022-11-30
ER

PT J
AU Bonfiglio, V
   Reibaldi, M
   Fallico, M
   Russo, A
   Pizzo, A
   Fichera, S
   Rapisarda, C
   Macchi, I
   Avitabile, T
   Longo, A
AF Bonfiglio, Vincenza
   Reibaldi, Michele
   Fallico, Matteo
   Russo, Andrea
   Pizzo, Alessandra
   Fichera, Stefano
   Rapisarda, Carlo
   Macchi, Iacopo
   Avitabile, Teresio
   Longo, Antonio
TI Widening use of dexamethasone implant for the treatment of macular edema
SO DRUG DESIGN DEVELOPMENT AND THERAPY
LA English
DT Review
DE macular edema; dexamethasone; intravitreal; implant; corticosteroids
ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; RETINAL VEIN OCCLUSION;
   IRVINE-GASS SYNDROME; ENDOTHELIAL GROWTH-FACTOR; PROTON-BEAM THERAPY;
   RETINITIS-PIGMENTOSA; COATS-DISEASE; CHOROIDAL MELANOMA; RADIATION
   MACULOPATHY; NONVITRECTOMIZED EYES
AB Sustained-release intravitreal 0.7 mg dexamethasone (DEX) implant is approved in Europe for the treatment of macular edema related to diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion, and non-infectious uveitis. The implant is formulated in a biodegradable copolymer to release the active ingredient within the vitreous chamber for up to 6 months after an intravitreal injection, allowing a prolonged interval of efficacy between injections with a good safety profile. Various other ocular pathologies with inflammatory etio-pathogeneses associated with macular edema have been treated by DEX implant, including neovascular age-related macular degeneration, Irvine-Gass syndrome, vasoproliferative retinal tumors, retinal telangiectasia, Coats' disease, radiation maculopathy, retinitis pigmentosa, and macular edema secondary to scleral buckling and pars plana vitrectomy. We undertook a review to provide a comprehensive collection of all of the diseases that benefit from the use of the sustained-release DEX implant, alone or in combination with concomitant therapies. A MEDLINE search revealed lack of randomized controlled trials related to these indications. Therefore we included and analyzed all available studies (retrospective and prospective, comparative and non-comparative, randomized and nonrandomized, single center and multicenter, and case report). There are reports in the literature of the use of DEX implant across a range of macular edema-related pathologies, with their clinical experience supporting the use of DEX implant on a case-by-case basis with the aim of improving patient outcomes in many macular pathologies. As many of the reported macular pathologies are difficult to treat, a new treatment option that has a beneficial influence on the clinical course of the disease may be useful in clinical practice.
C1 [Bonfiglio, Vincenza; Reibaldi, Michele; Fallico, Matteo; Russo, Andrea; Pizzo, Alessandra; Fichera, Stefano; Rapisarda, Carlo; Macchi, Iacopo; Avitabile, Teresio; Longo, Antonio] Univ Catania, Dept Ophthalmol, Via S Sofia 76, I-95100 Catania, Italy.
C3 University of Catania
RP Bonfiglio, V (通讯作者)，Univ Catania, Dept Ophthalmol, Via S Sofia 76, I-95100 Catania, Italy.
EM enzabonfiglio@gmail.com
RI Fallico, Matteo/AAC-5284-2022; Reibaldi, Michele/AAL-1113-2021; Longo,
   Antonio/AAC-6092-2022; Russo, Andrea/AAC-5349-2022; Avitabile,
   Teresio/AAC-6076-2022
OI Russo, Andrea/0000-0002-7725-5971; LONGO, Antonio/0000-0002-9525-1800;
   FALLICO, MATTEO/0000-0003-2639-1321
FU Allergan
FX We thank Ray Hill, an independent medical writer, who provided
   English-language editing and journal styling before submission on behalf
   of Health Publishing & Services Srl. Technical editing and publication
   fees for this manuscript were supported by Allergan.
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NR 86
TC 27
Z9 28
U1 1
U2 5
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1177-8881
J9 DRUG DES DEV THER
JI Drug Des. Dev. Ther.
PY 2017
VL 11
BP 2359
EP 2372
DI 10.2147/DDDT.S138922
PG 14
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA FL6SJ
UT WOS:000414376200001
PM 28860707
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Fisichella, V
   Giurdanella, G
   Platania, CBM
   Romano, GL
   Leggio, GM
   Salomone, S
   Drago, F
   Caraci, F
   Bucolo, C
AF Fisichella, Vincenzo
   Giurdanella, Giovanni
   Platania, Chiara Bianca Maria
   Romano, Giovanni Luca
   Leggio, Gian Marco
   Salomone, Salvatore
   Drago, Filippo
   Caraci, Filippo
   Bucolo, Claudio
TI TGF-beta 1 prevents rat retinal insult induced by amyloid-beta (1-42)
   oligomers
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Macular degeneration; Retina; Alzheimer's disease; TGF-beta 1
ID ALZHEIMERS-DISEASE; MACULAR DEGENERATION; TGF-BETA; PHOSPHATIDYLINOSITOL
   3-KINASE; DRUSEN DEPOSITS; MOLECULAR-BASIS; IN-VIVO; KAPPA-B; PATHWAYS;
   ACTIVATION
AB To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-beta (A beta) oligomers, and assess the effect of TGF-beta 1. Sprague-Dawley male rats were used. Human A beta(1-42) oligomers were intravitreally (ITV) injected (10 mu M) in the presence or in the absence of recombinant human TGF-beta 1 (1 ng/mu l ITV injected). After 48 h, the animals were sacrificed and the eyes removed and dissected. The apoptotic markers Bax and Bcl-2 were assessed by western blot analysis in retina lysates. Gene-pathway network analysis was carried out in order to identify pathways involved in AMD. Treatment with A beta oligomers induced a strong increase in Bax protein level (about 4-fold; p < 0.01) and a significant reduction in Bcl-2 protein level (about 2-fold; p < 0.05). Co-injection of TGF-beta 1 triggered a significant reduction of Bax protein induced by A beta oligomers. Bioinformatic analysis revealed that Bcl-2 and PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer disease (AD). Overall, these data indicate that ITV injection of A beta(1-42) oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of A beta oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF-beta 1 can prevent retinal damage elicited by A beta oligomers. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Fisichella, Vincenzo; Giurdanella, Giovanni; Platania, Chiara Bianca Maria; Romano, Giovanni Luca; Leggio, Gian Marco; Salomone, Salvatore; Drago, Filippo; Bucolo, Claudio] Univ Catania, Sch Med, Dept Biomed & Biotechnol Sci, Catania, Italy.
   [Caraci, Filippo] Univ Catania, Dept Drug Sci, Catania, Italy.
   [Caraci, Filippo] IRCSS Assoc Oasi Maria SS, Inst Res Mental Retardat & Brain Aging, Troina, Italy.
C3 University of Catania; University of Catania; IRCCS Oasi Maria SS
RP Bucolo, C (通讯作者)，Univ Catania, Sch Med, Pharmacol Sect, Dept Biomed & Biotechnol Sci, Via S Sofia 64, I-95125 Catania, Italy.
EM claudio.bucolo@unict.it
RI Caraci, Filippo/K-2262-2016; Drago, Filippo/AAC-5090-2022; Platania,
   Chiara BM/AHE-1140-2022; Drago, Francesco/H-7563-2019; Leggio, Gian
   Marco/AHE-1151-2022; Romano, Giovanni Luca/AAS-9208-2020; Giurdanella,
   Giovanni/AAY-9734-2021
OI Caraci, Filippo/0000-0002-9867-6054; Leggio, Gian
   Marco/0000-0002-7280-4871; Romano, Giovanni Luca/0000-0002-8722-7835;
   Platania, Chiara Bianca Maria/0000-0002-8630-5993; GIURDANELLA,
   Giovanni/0000-0002-4855-8615; Bucolo, Claudio/0000-0002-4879-4140
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NR 36
TC 39
Z9 39
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
EI 1879-0712
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD SEP 15
PY 2016
VL 787
SI SI
BP 72
EP 77
DI 10.1016/j.ejphar.2016.02.002
PG 6
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA DW0EX
UT WOS:000383314800009
PM 26845696
DA 2022-11-30
ER

PT J
AU Basavarajappa, HD
   Lee, B
   Fei, X
   Lim, D
   Callaghan, B
   Mund, JA
   Case, J
   Rajashekhar, G
   Seo, SY
   Corson, TW
AF Basavarajappa, Halesha D.
   Lee, Bit
   Fei, Xiang
   Lim, Daesung
   Callaghan, Breedge
   Mund, Julie A.
   Case, Jamie
   Rajashekhar, Gangaraju
   Seo, Seung-Yong
   Corson, Timothy W.
TI Synthesis and Mechanistic Studies of a Novel Homoisoflavanone Inhibitor
   of Endothelial Cell Growth
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; RETINAL NEOVASCULARIZATION; PROTEIN-KINASE;
   GENE-TRANSCRIPTION; ANGIOGENESIS; ACTIVATION; EXPRESSION; THERAPY;
   INTERLEUKIN-8; RANIBIZUMAB
AB Preventing pathological ocular angiogenesis is key to treating retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. At present there is no small molecule drug on the market to target this process and hence there is a pressing need for developing novel small molecules that can replace or complement the present surgical and biologic therapies for these neovascular eye diseases. Previously, an antiangiogenic homoisoflavanone was isolated from the bulb of a medicinal orchid, Cremastra appendiculata. In this study, we present the synthesis of a novel homoisoflavanone isomer of this compound. Our compound, SH-11052, has antiproliferative activity against human umbilical vein endothelial cells, and also against more ocular disease-relevant human retinal microvascular endothelial cells ( HRECs). Tube formation and cell cycle progression of HRECs were inhibited by SH-11052, but the compound did not induce apoptosis at effective concentrations. SH-11052 also decreased TNF-alpha induced p38 MAPK phosphorylation in these cells. Intriguingly, SH-11052 blocked TNF-a induced IkB-a degradation, and therefore decreased NF-kappa B nuclear translocation. It decreased the expression of NF-kappa B target genes and the pro-angiogenic or pro-inflammatory markers VCAM-1, CCL2, IL8, and PTGS2. In addition SH-11052 inhibited VEGF induced activation of Akt but not VEGF receptor autophosphorylation. Based on these results we propose that SH-11052 inhibits inflammation induced angiogenesis by blocking both TNF-alpha and VEGF mediated pathways, two major pathways involved in pathological angiogenesis. Synthesis of this novel homoisoflavanone opens the door to structure-activity relationship studies of this class of compound and further evaluation of its mechanism and potential to complement existing antiangiogenic drugs.
C1 [Basavarajappa, Halesha D.; Callaghan, Breedge; Rajashekhar, Gangaraju; Corson, Timothy W.] Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
   [Basavarajappa, Halesha D.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
   [Lee, Bit; Fei, Xiang; Lim, Daesung; Seo, Seung-Yong] Gachon Univ, Coll Pharm, Inchon, South Korea.
   [Mund, Julie A.; Case, Jamie] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
   [Mund, Julie A.; Case, Jamie; Corson, Timothy W.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
   [Rajashekhar, Gangaraju] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA.
   [Corson, Timothy W.] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
C3 Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington; Gachon University;
   Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University-Purdue University Indianapolis;
   Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington
RP Seo, SY (通讯作者)，Gachon Univ, Coll Pharm, Inchon, South Korea.
EM syseo@gachon.ac.kr; tcorson@iupui.edu
RI Basavarajappa, Halesha Dhurvigere/V-2038-2019; Corson, Timothy
   W./B-6851-2009; Gangaraju, Rajashekhar/I-7852-2019; Fei,
   Xiang/D-6670-2014
OI Basavarajappa, Halesha Dhurvigere/0000-0002-2840-5937; Corson, Timothy
   W./0000-0002-1402-7875; Gangaraju, Rajashekhar/0000-0002-6664-8286;
   Case, Jamie/0000-0002-6721-0307; Fei, Xiang/0000-0001-9637-1989
FU International Retinal Research Foundation; Carl Marshall and Mildred
   Almen Reeves Foundation; Ralph W. and Grace M. Showalter Research Trust;
   Retina Research Foundation; Basic Science Research Program through the
   National Research Foundation of Korea (NRF) - Ministry of Education
   [NRF-2013R1A1A2007151]; Cryptic Masons Medical Research Foundation;
   Ausich Graduate Scholarship from Kemin Health; National Institutes of
   Health, National Center for Advancing Translational Sciences, Clinical
   and Translational Sciences Award [KL2 TR000163]; NATIONAL CENTER FOR
   ADVANCING TRANSLATIONAL SCIENCES [UL1TR001108, KL2TR000163, UL1TR002529]
   Funding Source: NIH RePORTER
FX This work was supported by grants from the International Retinal
   Research Foundation, Carl Marshall and Mildred Almen Reeves Foundation,
   Ralph W. and Grace M. Showalter Research Trust, and Retina Research
   Foundation to TWC, a grant from the Basic Science Research Program
   through the National Research Foundation of Korea (NRF) funded by the
   Ministry of Education (NRF-2013R1A1A2007151) to S-YS, a grant from the
   Cryptic Masons Medical Research Foundation to GR, and the Ausich
   Graduate Scholarship from Kemin Health to HDB. This publication was also
   made possible in part by grant number KL2 TR000163 (A. Shekhar, PI) from
   the National Institutes of Health, National Center for Advancing
   Translational Sciences, Clinical and Translational Sciences Award to TWC
   and GR. 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 65
TC 23
Z9 23
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 21
PY 2014
VL 9
IS 4
AR e95694
DI 10.1371/journal.pone.0095694
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AG2DX
UT WOS:000335227400102
PM 24752613
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Giacomelli, G
   Virgili, G
   Giansanti, F
   Sato, G
   Cappello, E
   Cruciani, F
   Varano, M
   Menchini, U
AF Giacomelli, Giovanni
   Virgili, Gianni
   Giansanti, Fabrizio
   Sato, Giovanni
   Cappello, Ezio
   Cruciani, Filippo
   Varano, Monica
   Menchini, Ugo
TI Clinical and Microperimetric Predictors of Reading Speed in Low Vision
   Patients: A Structural Equation Modeling Approach
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE low vision; reading
ID MACULAR DEGENERATION; CONTRAST SENSITIVITY; FIXATION STABILITY; RETINAL
   LOCUS; PSYCHOPHYSICS; SCOTOMA; PERFORMANCE; TEXT; DISEASE; DESIGN
AB PURPOSE. To investigate the simultaneous association of several psychophysical measures with reading ability in patients with mild and moderate low vision attending rehabilitation services.
   METHODS. Standard measurements of reading ability (Minnesota Reading [MNREAD] charts), visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] charts), contrast sensitivity (Pelli-Robson charts), reading contrast threshold (Reading Explorer [REX] charts), retinal sensitivity, and fixation stability and localization (Micro Perimeter 1 [MP1] fundus perimetry) were obtained in 160 low vision patients with better eye visual acuity ranging from 0.3 to 1.0 logarithm of the minimum angle of resolution and affected by either age-related macular degeneration or diabetic retinopathy.
   RESULTS. All variables were moderately associated with reading performance measures (MNREAD reading speed and reading acuity and REX reading contrast threshold), as well as among each other. In a structural equation model, REX reading contrast threshold was highly associated with MNREAD reading speed (standardized coefficient, 0.63) and moderately associated with reading acuity (standardized coefficient, -0.30). REX test also mediated the effects of Pelli-Robson contrast sensitivity (standardized coefficient, 0.44), MP1 fixation eccentricity (standardized coefficient, 0.19), and the mean retinal sensitivity (standardized coefficient, 0.23) on reading performance. The MP1 fixation stability was associated with both MNREAD reading acuity (standardized coefficient, -0.24) and MNREAD reading speed (standardized coefficient, 0.23), while ETDRS visual acuity only affected reading acuity (standardized coefficient, 0.44).
   CONCLUSIONS. Fixation instability and contrast sensitivity loss are key factors limiting reading performance of patients with mild or moderate low vision. REX charts directly assess the impact of text contrast on letter recognition and text navigation and may be a useful aid in reading rehabilitation.
C1 [Giacomelli, Giovanni; Virgili, Gianni; Giansanti, Fabrizio; Menchini, Ugo] Univ Florence, Dept Ophthalmol, I-50134 Florence, Italy.
   [Sato, Giovanni] St Paul Ophthalm Ctr Padua, Low Vis Ctr, Padua, Italy.
   [Cappello, Ezio] San Bassiano Hosp, Dept Ophthalmol, Bassano Del Grappa, Italy.
   [Cruciani, Filippo] Natl Pole Blindness Prevent & Low Vis Rehabil Res, Rome, Italy.
   [Varano, Monica] GB Bietti Fdn, Ist Ricovero & Cura Carattere Sci, Rome, Italy.
C3 University of Florence; ULSS 7 Pedemontana; Ospedale San Bassiano; IRCCS
   - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in Oftalmologia
RP Giacomelli, G (通讯作者)，Univ Florence, Dept Ophthalmol, Viale Morgagni 85, I-50134 Florence, Italy.
EM giovanni.giacomelli@unifi.it
RI Varano, Monica/K-8573-2016; giacomelli, giovanni/ABC-6173-2020; Virgili,
   Gianni/P-6607-2014
OI Virgili, Gianni/0000-0002-9960-2989; Varano, Monica/0000-0002-6530-1563
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NR 30
TC 13
Z9 14
U1 3
U2 17
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 2013
VL 54
IS 6
BP 4403
EP 4408
DI 10.1167/iovs.12-10734
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 173YW
UT WOS:000321120700075
PM 23722392
DA 2022-11-30
ER

PT J
AU Li, TQ
   Lewallen, M
   Chen, SY
   Yu, W
   Zhang, N
   Xie, T
AF Li, Tianqing
   Lewallen, Michelle
   Chen, Shuyi
   Yu, Wei
   Zhang, Nian
   Xie, Ting
TI Multipotent stem cells isolated from the adult mouse retina are capable
   of producing functional photoreceptor cells
SO CELL RESEARCH
LA English
DT Article
DE retinal stem cells; photoreceptor cells
ID CILIARY EPITHELIAL-CELLS; PROGENITOR CELLS; MAMMALIAN RETINA; NEURAL
   REGENERATION; ROD PHOTORECEPTORS; GLIAL-CELLS; MULLER GLIA; IN-VITRO;
   EYE; TRANSPLANTATION
AB Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptor-deficient mice, but there is still some concern of tumor formation. In this study, we have successfully cultured Nestin(+)Sox2(+)Pax6(+) multipotent retinal stem cells (RSCs) from the adult mouse retina, which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation. After they have been expanded for over 35 passages in the presence of FGF and EGF, the cultured RSCs still maintain stable proliferation and differentiation potential. Under proper differentiation conditions, they can differentiate into all the major retinal cell types found in the adult retina. More importantly, they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions. Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes, RSC-derived photoreceptor cells integrate into the retina, morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons. When transplanted into eyes of photoreceptor-deficient rd1 mutant mice, a RP model, RSC-derived photoreceptors can partially restore light response, indicating that those RSC-derived photoreceptors are functional. Finally, there is no evidence for tumor formation in the photoreceptor-transplanted eyes. Therefore, this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.
C1 [Li, Tianqing; Lewallen, Michelle; Chen, Shuyi; Yu, Wei; Zhang, Nian; Xie, Ting] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Xie, Ting] Univ Kansas, Sch Med, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; University of Kansas; University
   of Kansas Medical Center
RP Xie, T (通讯作者)，Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA.
EM tgx@stowers.org
RI yu, WEI/F-2826-2014
FU Stowers Institute for Medical research
FX We would like to thank the Xie laboratory members for stimulating
   discussions, the Laboratory Animal Services Facility at SIMR for
   maintaining our mouse strains, and C Flournoy for administrative
   assistance. This work was supported by a fund from Stowers Institute for
   Medical research (T Xie).
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   Yang P, 2002, EXP NEUROL, V177, P326, DOI 10.1006/exnr.2002.7955
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NR 50
TC 33
Z9 36
U1 1
U2 45
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD JUN
PY 2013
VL 23
IS 6
BP 788
EP 802
DI 10.1038/cr.2013.48
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 156FL
UT WOS:000319807100010
PM 23567557
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Varshney, N
   Jain, A
   Chan, V
   Yu, L
   Sarraf, D
AF Varshney, Neeta
   Jain, Atul
   Chan, Vicki
   Yu, Le
   Sarraf, David
TI Anti-VEGF response in macular hemorrhage and incidence of retinal
   pigment epithelial tears
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; INTRAVITREAL BEVACIZUMAB INJECTION;
   CARDIOVASCULAR RISK-FACTORS; SUBMACULAR HEMORRHAGE; CHOROIDAL
   NEOVASCULARIZATION; PNEUMATIC DISPLACEMENT; RANIBIZUMAB INJECTION;
   DEGENERATION; MANAGEMENT; DISEASE
AB Objective: To study the visual and anatomic outcomes of serial anti-vascular endothelial growth factor (anti-VEGF) therapy for severe macular hemorrhage in eyes with exudative age-related macular degeneration (AMD).
   Design: Consecutive retrospective analysis.
   Participants: Twenty eyes from 20 patients with severe macular hemorrhage (greater than 50% blockage with formal fluorescein angiography [FA]) secondary to wet AMD were studied.
   Methods: We performed a chart review of patients at a single centre from May 2006 to September 2009. Presenting visual acuity and diameter of hemorrhage were recorded as well as number of injections, time by which no hemorrhage was remaining, and final anatomic outcome. Cardiovascular risk factors and use of antiplatelet medication or anticoagulation were noted.
   Results: Average presenting visual acuity was 1.55 (20/710), and number of injections needed for resolution of hemorrhage was 4. Visual acuity significantly improved from 1.55 (20/710) to 0.70 (20/100) after injections. Thirty-five percent of eyes were found to have an associated retinal pigment epithelial (RPE) tear, and these eyes were found to have received more injections. Final visual acuity was not significantly different in eyes with RPE tears compared with nontear eyes. Eighty-one percent of patients had associated cardiovascular risk factors; antiplatelet therapy and anticoagulation were not found to play a role in hemorrhage size.
   Conclusions: RPE tears are found in a significant number of individuals with large macular hemorrhages secondary to exudative macular degeneration, but with continued treatment with anti-VEGF therapy, visual acuity can significantly improve even in the presence of these tears. Eyes with severe macular hemorrhage thus should be considered candidates for anti-VEGF therapy.
C1 [Varshney, Neeta; Chan, Vicki; Yu, Le; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Jain, Atul] San Diego Retina Associates, San Diego, CA USA.
   [Sarraf, David] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA.
   [Sarraf, David] Kaiser Permanente, Woodland Hills, CA USA.
C3 University of California System; University of California Los Angeles;
   US Department of Veterans Affairs; Veterans Health Administration (VHA);
   VA Greater Los Angeles Healthcare System; Kaiser Permanente
RP Sarraf, D (通讯作者)，Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
FU Karl Kirchgessner Foundation
FX This work was supported by grants from Karl Kirchgessner Foundation
   (D.S.).
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NR 39
TC 7
Z9 7
U1 0
U2 2
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 JUN
PY 2013
VL 48
IS 3
BP 210
EP 215
DI 10.1016/j.jcjo.2013.01.023
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AA5OD
UT WOS:000331148400025
PM 23769784
DA 2022-11-30
ER

PT J
AU Biesalski, HK
   Aggett, PJ
   Anton, R
   Bernstein, PS
   Blumberg, J
   Heaney, RP
   Henry, J
   Nolan, JM
   Richardson, DP
   van Ommen, B
   Witkamp, RF
   Rijkers, GT
   Zollner, I
AF Biesalski, Hans Konrad
   Aggett, Peter J.
   Anton, Robert
   Bernstein, Paul S.
   Blumberg, Jeffrey
   Heaney, Robert P.
   Henry, Jeya
   Nolan, John M.
   Richardson, David P.
   van Ommen, Ben
   Witkamp, Renger F.
   Rijkers, Ger T.
   Zoellner, Iris
TI 26th Hohenheim Consensus Conference, September 11, 2010 Scientific
   substantiation of health claims: Evidence-based nutrition
SO NUTRITION
LA English
DT Article
DE Nutrition; Clinical trials; Health claim; Micronutrients; Regulation
ID GLYCEMIC INDEX; BETA-CAROTENE; MACULAR DEGENERATION; LUNG-CANCER;
   RISK-FACTOR; VITAMIN-E; BIOMARKERS; GLUCOSE; FOLATE; ASSOCIATION
AB Objective: The objective was to define the term evidence based nutrition on the basis of expert discussions and scientific evidence.
   Methods and procedures: The method used is the established Hohenheim Consensus Conference. The term "Hohenheim Consensus Conference" defines conferences dealing with nutrition-related topics. The major aim of the conference is to review the state of the art of a given topic with experts from different areas (basic science, clinicians, epidemiologists, etc.). Based on eight to 12 questions, the experts discuss short answers and try to come to a consensus. A scientifically based text is formulated that justifies the consensus answer. To discuss the requirements for the scientific substantiation of claims, the 26th Hohenheim Consensus Conference gathered the views of many academic experts in the field of nutritional research and asked these experts to address the various aspects of a claims substantiation process and the possibilities and limitations of the different approaches.
   Results: The experts spent a day presenting and discussing their views and arrived at several consensus statements that can serve as guidance for bodies performing claims assessments in the framework of regulatory systems.
   Conclusion: The 26th Hohenheim Consensus Conference addresses some general aspects and describes the current scientific status from the point of view of six case studies to illustrate specific areas of scientific interest: carotenoids and vitamin A in relation to age-related macular degeneration, the quality of carbohydrates (as expressed by the glycemic index) in relation to health and well-being, probiotics in relation to intestinal and immune functions, micronutrient intake and maintenance of normal body functions, and food components with antioxidative properties and health benefits. (C) 2011 Published by Elsevier Inc.
C1 [Biesalski, Hans Konrad] Univ Hohenheim, Inst Biol Chem & Nutr, D-7000 Stuttgart, Germany.
   [Aggett, Peter J.] Univ Lancaster, Parbold, England.
   [Anton, Robert] Univ Strasbourg, Strasbourg, France.
   [Bernstein, Paul S.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   [Blumberg, Jeffrey] Tufts Univ, Friedman Sch Nutr Sci & Policy, Jean Mayer USDA Human Nutr Res Ctr Aging, Antioxidants Res Lab, Boston, MA 02111 USA.
   [Heaney, Robert P.] Creighton Univ, Omaha, NE 68178 USA.
   [Henry, Jeya] Oxford Brookes Univ, Funct Food Ctr, Oxford OX3 0BP, England.
   [Nolan, John M.] Waterford Inst Technol, Dept Chem & Life Sci, MPRG, Waterford, Ireland.
   [Nolan, John M.] Whitfield Clin, Inst Vis Res, Waterford, Ireland.
   [Richardson, David P.] DPR Nutr Ltd, Surrey, England.
   [van Ommen, Ben] TNO, NL-3700 AJ Zeist, Netherlands.
   [Witkamp, Renger F.] Wageningen Univ, Div Human Nutr, Dept Pharmacol & Nutr, Wageningen, Netherlands.
   [Rijkers, Ger T.] Univ Med Ctr, Dept Surg, Utrecht, Netherlands.
   [Rijkers, Ger T.] St Antonius Hosp, Lab Med Microbiol & Immunol, Nieuwegein, Netherlands.
   [Zoellner, Iris] Baden Wuerttemberg State Hlth Off, Stuttgart, Germany.
C3 University Hohenheim; Lancaster University; University of Kent;
   UDICE-French Research Universities; Universites de Strasbourg
   Etablissements Associes; Universite de Strasbourg; Utah System of Higher
   Education; University of Utah; Tufts University; United States
   Department of Agriculture (USDA); Creighton University; Oxford Brookes
   University; South East Technological University (SETU); Netherlands
   Organization Applied Science Research; Wageningen University & Research;
   Utrecht University; Utrecht University Medical Center; St. Antonius
   Hospital Utrecht
RP Biesalski, HK (通讯作者)，Univ Hohenheim, Inst Biol Chem & Nutr, Garbenstr 30, D-7000 Stuttgart, Germany.
EM biesal@uni-hohenheim.de
RI Blumberg, Jeffrey/ABH-7888-2020; Rijkers, Ger/AAW-6143-2020; Witkamp,
   Renger/I-7622-2012; Henry, Christiani Jeyakumar/AHB-2632-2022; Rijkers,
   Ger/R-7236-2019; Nolan, John/N-4921-2014
OI Witkamp, Renger/0000-0002-7935-8261; Henry, Christiani
   Jeyakumar/0000-0002-1602-0140; Rijkers, Ger/0000-0001-6948-6123; Nolan,
   John/0000-0002-5503-7084
FU European Responsible Nutrition Alliance; NATIONAL EYE INSTITUTE
   [P30EY014800] Funding Source: NIH RePORTER
FX This work was financially supported by the European Responsible
   Nutrition Alliance.
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NR 79
TC 52
Z9 55
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0899-9007
EI 1873-1244
J9 NUTRITION
JI Nutrition
PD OCT
PY 2011
VL 27
IS 10
SU S
BP S1
EP S20
DI 10.1016/j.nut.2011.04.002
PG 20
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 833DN
UT WOS:000295862100001
PM 21700425
OA Green Published
DA 2022-11-30
ER

PT J
AU Geruschat, DR
   Fujiwara, K
   Emerson, RSW
AF Geruschat, Duane R.
   Fujiwara, Kyoko
   Emerson, Robert S. Wall
TI Traffic Gap Detection for Pedestrians with Low Vision
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE orientation and mobility; low vision; pedestrian; street crossing; gap
   detection; time to contact
ID BLIND PEDESTRIANS; ROUNDABOUTS; IMPAIRMENT
AB Purpose. Pedestrians with low vision have identified crossing the street as a difficult task. With the increasing complexity of the crossing environment (actuated signals and roundabouts), the challenges are increasing. The purpose of this study was to evaluate the effect of two types of vision loss (central or peripheral) on the ability to detect gaps in traffic.
   Methods. Forty-one subjects participated with 14 being fully sighted (FS), 10 having central vision loss from age-related macular degeneration (AMD), and 17 having peripheral vision loss from either retinitis pigmentosa or glaucoma. Standing at entry and exit lanes of a roundabout, subjects depressed a handheld trigger to indicate when there was a sufficient gap in traffic to cross the street. A total of twelve 2-min intervals were completed including four of those intervals with occluded hearing.
   Results. No difference was found in the ability of the three subject groups to identify crossable or short gaps. There were significant differences in latency and safety margin. The AMD subjects did not perform as well as the FS or the subjects with retinitis pigmentosa/glaucoma. When hearing was occluded, the two vision loss groups did not show a change in sensitivity but the FS group did, being more sensitive when hearing was occluded.
   Conclusions. The purpose of this study was to evaluate the effect of low vision on the ability to detect crossable gaps in traffic. The findings suggest that subjects with AMD have an increased risk because they show significant latency in their identification of gaps and this in turn results in a reduction of safety margin. (Optom Vis Sci 2011; 88:208-216)
C1 [Geruschat, Duane R.] Salus Univ, Philadelphia, PA USA.
   [Fujiwara, Kyoko] Johns Hopkins Univ, Baltimore, MD USA.
   [Emerson, Robert S. Wall] Western Michigan Univ, Kalamazoo, MI 49008 USA.
C3 Johns Hopkins University; Western Michigan University
RP Geruschat, DR (通讯作者)，Lions Vis Res & Rehabil Ctr, 550 N Broadway,6th Floor, Baltimore, MD 21205 USA.
EM dgeruschat@jhmi.edu
FU National Eye Institute, National Institute of Health [R01EY12894];
   NATIONAL EYE INSTITUTE [R01EY012894] Funding Source: NIH RePORTER
FX This project was supported by grant R01EY12894 from the National Eye
   Institute, National Institute of Health.
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NR 18
TC 10
Z9 10
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD FEB
PY 2011
VL 88
IS 2
BP 208
EP 216
DI 10.1097/OPX.0b013e3182045988
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 711IV
UT WOS:000286584900009
PM 21131877
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Smith, RT
   Sohrab, MA
   Pumariega, NM
   Mathur, K
   Haans, R
   Blonska, A
   Uy, K
   Despriet, D
   Klaver, C
AF Smith, R. Theodore
   Sohrab, Mahsa A.
   Pumariega, Nicole M.
   Mathur, Kanika
   Haans, Raymond
   Blonska, Anna
   Uy, Karl
   Despriet, Dominiek
   Klaver, Caroline
TI Drusen Analysis in a Human-Machine Synergistic Framework
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DRUSEN; GEOGRAPHIC ATROPHY;
   AUTOFLUORESCENCE CHARACTERISTICS; FUNDUS PHOTOGRAPHS; IMAGE-ANALYSIS;
   SEGMENTATION; RECONSTRUCTION; ABNORMALITIES; PROGNOSIS
AB Objectives: To demonstrate how human-machine intelligence can be integrated for efficient image analysis of drusen in age-related macular degeneration and to validate the method in 2 large, independently graded, population- based data sets.
   Methods: We studied 358 manually graded color slides from the Netherlands Genetic Isolate Study. All slides were digitized and analyzed with a user-interactive drusen detection algorithm for the presence and quantity of small, intermediate, and large drusen. A graphic user interface was used to preprocess the images, choose a region of interest, select appropriate corrective filters for images with photographic artifacts or prominent choroidal pattern, and perform drusen segmentation. Weighted kappa statistics were used to analyze the initial concordance between human graders and the drusen detection algorithm; discordant grades from 177 left-eye slides were subjected to exhaustive analysis of causes of disagreement and adjudication. To validate our method further, we analyzed a second data set from our Columbia Macular Genetics Study.
   Results: The graphical user interface decreased the time required to process images in commercial software by 60.0%. After eliminating borderline size disagreements and applying corrective filters for photographic artifacts and choroidal pattern, the weighted kappa values were 0.61, 0.62, and 0.76 for small, intermediate, and large drusen, respectively. Our second data set demonstrated a similarly high concordance.
   Conclusions: Drusen identification performed by our user-interactive method presented fair to good agreement with human graders after filters for common sources of error were applied. This approach exploits a synergistic relationship between the intelligent user and machine computational power, enabling fast and accurate quantitative retinal image analysis.
C1 [Smith, R. Theodore; Sohrab, Mahsa A.; Pumariega, Nicole M.; Mathur, Kanika; Haans, Raymond; Blonska, Anna; Uy, Karl] Columbia Univ, Harkness Eye Inst, Dept Ophthalmol, New York, NY 10032 USA.
   [Smith, R. Theodore; Pumariega, Nicole M.] Columbia Univ, Dept Biomed Engn, Fu Fdn Sch Engn & Appl Sci, New York, NY 10032 USA.
   [Despriet, Dominiek] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
   [Klaver, Caroline] Erasmus MC, Dept Biostat & Ophthalmol, Rotterdam, Netherlands.
C3 Columbia University; Columbia University; Erasmus University Rotterdam;
   Erasmus MC; Erasmus University Rotterdam; Erasmus MC
RP Smith, RT (通讯作者)，Columbia Univ, Harkness Eye Inst, Dept Ophthalmol, 160 Ft Washington Ave,Room 509C, New York, NY 10032 USA.
EM rts1@columbia.edu
RI Klaver, Caroline C.W./A-2013-2016
OI smith, theodore/0000-0002-1693-943X
FU New York Community Trust (New York, New York); National Eye Institute
   (Bethesda, Maryland) [R01 EY015520]; Research to Prevent Blindness (New
   York, New York); NATIONAL EYE INSTITUTE [R01EY015520] Funding Source:
   NIH RePORTER
FX This study was supported by grants from The New York Community Trust
   (New York, New York), National Eye Institute grant R01 EY015520
   (Bethesda, Maryland), and unrestricted funds from Research to Prevent
   Blindness (New York, New York).
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NR 35
TC 6
Z9 6
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JAN
PY 2011
VL 129
IS 1
BP 40
EP 47
DI 10.1001/archophthalmol.2010.328
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 704MI
UT WOS:000286056700005
PM 21220627
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zeiler, F
   Povazay, B
   Glittenberg, C
   Hermann, B
   Hagen, S
   Lie, S
   Drexler, W
   Binder, S
AF Zeiler, F.
   Povazay, B.
   Glittenberg, C.
   Hermann, B.
   Hagen, S.
   Lie, S.
   Drexler, W.
   Binder, S.
TI Comparison of UHR-OCT versus Stratus-OCT for definition of early retinal
   changes after intravitreal Bevacizumab (Avastin(A (R))) application in
   patients with AMD
SO SPEKTRUM DER AUGENHEILKUNDE
LA English
DT Article
DE Optical coherence tomography; bevacizumab; neovascular AMD
ID OPTICAL COHERENCE TOMOGRAPHY; ULTRAHIGH-RESOLUTION; PATHOLOGY; ACUITY
AB PURPOSE: To investigate and demonstrate early structural changes of the retina/pigmentepithelial/choriocapillaris (RPECC) complex before and 10 +/- 3 days after intravitreal application of bevacizumab (Avastin(A (R))) in patients with neovascular age related macular degeneration (nAMD) by comparison of standard Stratus Optical Coherence Tomography (S-OCT) and Ultra High Resolution (UHR-OCT) imaging systems. METHODS: Six patients with nAMD were examined in a consecutive case series with UHR-OCT and Stratus OCT one day before and 10 +/- 3 days after intravitreal application of 1.25 mg (0.125 ml) bevacizumab (Avastin(A (R))). Maximum central retinal thickness (CRT) was measured with the retinal thickness program and calliper measuring function of S-OCT and by the measuring tool of Adobe Photoshop 5.0 in UHR-OCT pictures. RESULTS: In three of six cases residual fluid after treatment was only visible with UHR-OCT but not with the S-OCT. A decrease of maximum CRT could be shown in all cases in UHR-OCT pictures but only in half of the cases (6/3) in S-OCT pictures. In 2/6 cases vitreoretinal adhesions were demonstrable with UHR-OCT but not seen with the S-OCT, irregularities in the photoreceptor layer could be revealed clearly by UHR-OCT in 2/6 cases. CONCLUSION: After anti-VEGF treatment, UHR-OCT gives more accurate information about residual fluid and intraretinal damage than S-OCT and offers more precise measurements of maximum CRT. These factors may influence further decision of therapy and give us a better explanation and correlation with unsatisfactory visual acuities than with the S-OCT.
C1 [Zeiler, F.; Hagen, S.; Lie, S.; Binder, S.] Rudolf Fdn Clin, Dept Ophthalmol, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, A-1030 Vienna, Austria.
   [Povazay, B.; Hermann, B.; Drexler, W.] Cardiff Univ, Dept Optometry & Vis Sci, Biomed Imaging Grp, Cardiff, Wales.
C3 Ludwig Boltzmann Institute; Cardiff University
RP Zeiler, F (通讯作者)，Rudolf Fdn Clin, Dept Ophthalmol, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Juchgasse 25, A-1030 Vienna, Austria.
EM Florian.Zeiler@wienkav.at
RI Považay, Boris/F-6258-2012
OI Povazay, Boris/0000-0001-5571-5116; Drexler,
   Wolfgang/0000-0002-3557-6398
CR *AM NAT STAND I, 1993, SAF US LAS
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NR 19
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0930-4282
EI 1613-7523
J9 SPEKTRUM AUGENHEILKD
JI Spektrum Augenheilkd.
PD MAR
PY 2009
VL 23
IS 1
BP 30
EP 35
DI 10.1007/s00717-009-0313-1
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 438OK
UT WOS:000265564700007
DA 2022-11-30
ER

PT J
AU Ke, KM
   Montgomery, AM
   Stevenson, M
   O'Neill, C
   Chakravarthy, U
AF Ke, Kathleen M.
   Montgomery, Anne-Marie
   Stevenson, Michael
   O'Neill, Ciaran
   Chakravarthy, Usha
TI Formal and informal care utilisation amongst elderly persons with visual
   impairment
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; MACULAR DEGENERATION; DEPRESSION; VISION
AB Objective: To examine the determinants of formal and informal care utilisation amongst persons with age-related macular degeneration (AMD).
   Design: Cross-sectional hospital-based study.
   Setting: Hospital eye clinic in Northern Ireland.
   Participants: 284 persons aged >= 50 years. Main outcome measures: Participants were questioned about their care, living arrangements, eyesight-related ability to self-care, and eyesight-related need to be more careful whilst undertaking everyday tasks.
   Results: The percentage of older persons receiving formal and informal care rose with the level of visual impairment. 34.9% and 37.3% of those with no visual impairment received formal and informal care, respectively, compared with 51.6% and 69.9% of those with moderate visual impairment and 55.6% and 88.9% of those with severe visual impairment. Three factors ( age, best corrected distance visual acuity in the better eye and living alone) were significant predictors (p < 0.05) of care utilisation. The likelihood of someone utilising formal care rose with increasing age, severity of visual impairment and living alone. There is an approximate one-to-one trade-off between age and visual acuity such that a difference of one line of vision is equivalent to approximately 1 year of life to the affected individual as regards its impact on the probability of care utilisation.
   Conclusions: Care utilisation is predicted by age, visual acuity in the better eye and living arrangement. These findings question the validity of the current practice of defining the need for statutory services on the basis of visual acuity alone. These data may have implications for cost utility analyses of new therapeutic developments in macular degeneration.
C1 Queens Univ Belfast, Royal Victoria Hosp, Ctr Ophthalmol & Vis Sci, Inst Clin Sci, Belfast BT12 6BA, Antrim, North Ireland.
   Queens Univ, Sch Med & Dent, Belfast, Antrim, North Ireland.
   Queens Univ Belfast, Royal Grp Hosp, Ctr Ophthalmol & Vis Sci, Inst Clin Sci, Belfast, Antrim, North Ireland.
   Queens Univ Belfast, Sch Med & Dent, Dept Epidemiol & Publ Hlth, Belfast, Antrim, North Ireland.
   Queens Univ Belfast, Sch Dent, Belfast, Antrim, North Ireland.
C3 Queens University Belfast; Queens University Belfast; Queens University
   Belfast; Queens University Belfast; Queens University Belfast
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Royal Victoria Hosp, Ctr Ophthalmol & Vis Sci, Inst Clin Sci, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Chakravarthy, Usha/0000-0002-2606-3734; Ke, Kathleen
   Melissa/0000-0002-2670-2188
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   Wang JJ, 2003, OPHTHALMIC EPIDEMIOL, V10, P3, DOI 10.1076/opep.10.1.3.13773
   Wang LH, 2001, COGNITIVE BRAIN RES, V12, P19, DOI 10.1016/S0926-6410(01)00022-2
NR 14
TC 18
Z9 18
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 OCT
PY 2007
VL 91
IS 10
BP 1279
EP 1281
DI 10.1136/bjo.2006.113142
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 214AH
UT WOS:000249707900011
PM 17360732
OA Green Published
DA 2022-11-30
ER

PT J
AU Grassi, MA
   Folk, JC
   Scheetz, TE
   Taylor, CM
   Sheffield, VC
   Stone, EM
AF Grassi, Michael A.
   Folk, James C.
   Scheetz, Todd E.
   Taylor, Christine M.
   Sheffield, Val C.
   Stone, Edwin M.
TI Complement factor H polymorphism p.Tyr402His and cuticular drusen
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID GLOMERULONEPHRITIS TYPE-II; BASAL LAMINAR DRUSEN; VITELLIFORM MACULAR
   DETACHMENT; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; DEGENERATION;
   COMPLICATIONS; SUBSTRUCTURE; DEFICIENCY; ACTIVATION; FIBULIN-5
AB Objective: To determine the histidine frequency in patients with the cuticular drusen phenotype of age-related macular degeneration (AMD).
   Methods: Fifty individuals were identified who met the criteria for the cuticular drusen phenotype using a standard threshold photograph. We genotyped DNA samples using a polymerase chain reaction-based restriction digest assay. Seven hundred individuals with typical AMD and 252 controls were also genotyped. Fisher exact test was used to analyze the significance of allele frequency differences.
   Results: The histidine variant was present in 70% (frequency +/- SE, 0.70 +/- 0.05) of the cuticular cohort, 55% (frequency +/- SE, 0.55 +/- 0.01) of the more typical AMD cases, and 34% (frequency +/- SE, 0.34 +/- 0.02) of controls. The association between the cuticular drusen phenotype and the histidine allele was highly significant (P = .003; odds ratio, 2.0; 95% confidence interval, 1.21-3.07; vs AMD cases P < .001; odds ratio 4.54; 95% confidence interval, 2.79-7.50; vs controls). Genotype distribution between the 3 groups was similarly significant (P < .001).
   Conclusion: The cuticular drusen phenotype is highly associated with the Tyr402His variant of the complement factor H (CFH) gene. The significantly higher histidine allele frequency in this group compared with the typical AMD cohort suggests that the complement cascade may play a greater role in the pathogenesis of the cuticular drusen subtype than in AMD as a whole.
   Clinical Relevance: The c. 1204T > C, p. Tyr402His allelic variant in the CFH gene is associated with a 3-fold increased risk for AMD. A high frequency of the histidine allele has also been noted in patients with membranoproliferative glomerulonephritis type II.
C1 Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
   Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA.
   Heed Ophthalm Fdn, Cleveland, OH USA.
   Ctr Bioinformat & Comp Biol, Iowa City, IA USA.
   Howard Hughes Med Inst, Chevy Chase, MD USA.
   Carver Family Ctr Macular Degenerat, Iowa City, IA USA.
C3 University of Iowa; University of Iowa; Howard Hughes Medical Institute
RP Stone, EM (通讯作者)，Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, 200 Hawkins Dr, Iowa City, IA 52242 USA.
EM edwin-stone@uiowa.edu
OI Folk, James/0000-0002-6271-2906; Scheetz, Todd/0000-0002-1965-5811;
   Stone, Edwin M./0000-0003-3343-4414; Sheffield, Val/0000-0002-6282-0835
FU NATIONAL EYE INSTITUTE [R01EY016822] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY016822] Funding Source: Medline
CR BUFFONE GJ, 1985, CLIN CHEM, V31, P164
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NR 26
TC 37
Z9 37
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JAN
PY 2007
VL 125
IS 1
BP 93
EP 97
DI 10.1001/archopht.125.1.93
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 123ZQ
UT WOS:000243336800014
PM 17210858
OA Bronze
DA 2022-11-30
ER

PT J
AU Krieglstein, TR
   Kampik, A
   Ulbig, M
AF Krieglstein, T. R.
   Kampik, A.
   Ulbig, M.
TI Intravitreal triamcinolone and laser photocoagulation for retinal
   angiomatous proliferation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SURGICAL ABLATION; MACULAR DEGENERATION; ANASTOMOSES
AB Background: Recently, the entity of retinal angiomatous proliferation (RAP) as a subtype of exudative age-related macular degeneration was described, but no treatment options have been established as yet. The only two therapeutic modalities being discussed are surgical lysis of the feeding arteriole and draining venule, and the use of photodynamic therapy combined with intravitreal triamcinolone injection.
   Aim: To examine focal laser treatment of early extrafoveal intraretinal neovascularisation of RAP.
   Methods: Prospective case series. We included 13 consecutive patients with an extrafoveal RAP stage I lesion. All patients underwent a complete ophthalmic examination, including fluorescein angiography and optical coherence tomography (OCT) III before treatment and at 2 weeks, 1, 2 and 4 months afterwards. In cases with marked macular oedema (>= 350 mm retinal thickening in OCT III, r = 12), intravitreal injection of 4 mg triamcinolone was given before focal laser treatment to reduce the oedema.
   Results: This case series indicates anatomical improvement or stabilisation in patients with an extrafoveal RAP lesion after treatment. Initial visual acuity ranged from 0.1 to 0.6 on the Snellen chart. By calculating logarithmic values, visual acuity was seen to be improved in five cases (2 to 5 log lines), deteriorated in four cases ( 22 to 5 log lines) and stabilised in four cases (-1 to + 1 log line change). Exudation on fluorescein angiography was stopped in II cases.
   Conclusions: This preliminary case series suggests laser photocoagulation combined with prior intravitreal triamcinolone injection as a viable treatment option for RAP stage I. In cases with marked macular oedema, intravitreal triamcinolone injection improved visual acuity. For long-term stabilisation, additional laser treatment is mandatory. These preliminary results warrant a more detailed prospective clinical trial.
C1 Univ Munich, Dept Ophthalmol, D-80336 Munich, Germany.
C3 University of Munich
RP Krieglstein, TR (通讯作者)，Univ Munich, Dept Ophthalmol, Mathildenstr 8, D-80336 Munich, Germany.
EM Tina.Krieglstein@med.uni-muenchen.de
CR Borrillo JL, 2003, ARCH OPHTHALMOL-CHIC, V121, P558, DOI 10.1001/archopht.121.4.558
   Boscia F, 2005, EUR J OPHTHALMOL, V15, P513, DOI 10.1177/112067210501500418
   BOTTONI F, 2006, GRAEFES ARCH CLIN EX
   Ghazi NG, 2005, GRAEF ARCH CLIN EXP, V243, P493, DOI 10.1007/s00417-004-1034-4
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NR 12
TC 21
Z9 22
U1 0
U2 0
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 NOV
PY 2006
VL 90
IS 11
BP 1357
EP 1360
DI 10.1136/bjo.2006.092536
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 097FJ
UT WOS:000241432100011
PM 16885191
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Foot, B
   Foy, R
   Chakravarthy, U
   Wormald, R
AF Foot, B
   Foy, R
   Chakravarthy, U
   Wormald, R
TI A new health technology: where is the consensus on a clinically
   worthwhile benefit?
SO EYE
LA English
DT Article
DE access; photodynamic therapy; service provision; health technology
AB Aim New therapies are often introduced into the NHS prior to full evaluation, leading to inequities in provision. Uncertainty exists regarding the value of photodynamic therapy in the treatment of neovascular age-related macular degeneration. We ascertained the availability of this treatment and the information used to inform clinical policy.
   Methods A postal survey of all clinical directors/lead consultants in the UK sought data on which (if any) patients were referred or treated with PDT by their unit, the sources of evidence informing clinical policy and the threshold of clinical benefit at which respondents would support the use of PDT. Results 123/152 questionnaires were returned. 42% of units make some provision for PDT on the NHS, including routine provision by 9%. 14.5% of units offer the option of care in the private sector, whilst 26.5% treated or referred no patients. The threshold at which respondents considered introduction of PDT would be justifiable varied widely.
   Respondents cited local literature review, advice from clinicians, guidance from the Royal College and information from the pharmaceutical industry as most influential in determining current policy. However, the National Institute for Clinical Excellence (NICE) and the Cochrane Library were anticipated as playing a greater role in shaping future practice.
   Conclusions Substantial variation exists in the availability of PDT. Advocates of PDT may interpret our data as an indication of the NHS failing to provide an effective therapy equitably, whilst others may deduce that patients are receiving an under-evaluated treatment in routine clinical practice. The differing thresholds at which clinicians believe treatment would be justified may further exacerbate variations and the priority given to PDT.
C1 Royal Coll Ophthalmologists, London, England.
   Univ Edinburgh, Dept Reprod & Dev Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
   Queens Univ Hosp, Belfast, Antrim, North Ireland.
   Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland.
   Moorfields Eye Hosp, London, England.
C3 University of Edinburgh; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust
RP Foot, B (通讯作者)，Royal Coll Ophthalmologists, London, England.
OI Foy, Robbie/0000-0003-0605-7713; Chakravarthy, Usha/0000-0002-2606-3734
CR Bressler NM, 1999, ARCH OPHTHALMOL-CHIC, V117, P1329
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   MOWATT G, 1997, HEALTH TECHNOL ASSES, V1, P1
   Steel N, 2000, BRIT MED J, V320, P1446, DOI 10.1136/bmj.320.7247.1446
   WORMALD R, 2001, COCHRANE LIB, V1
NR 5
TC 8
Z9 8
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 JUL
PY 2002
VL 16
IS 4
BP 469
EP 471
DI 10.1038/sj.eye.6700024
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 583AK
UT WOS:000177383200020
PM 12101457
OA Bronze
DA 2022-11-30
ER

PT J
AU Ollila, T
   Silvennoinen, J
   Joshi, A
   Liu, J
   Kulathinal, S
   Immonen, I
AF Ollila, Terhi
   Silvennoinen, Juuso
   Joshi, Ashwini
   Liu, Jia
   Kulathinal, Sangita
   Immonen, Ilkka
TI Analysing Subgroups and Treatment Discontinuation in a Finnish Cohort of
   Patients with Neovascular AMD
SO OPHTHALMOLOGICA
LA English
DT Article
DE Neovascular age-related macular degeneration; Anti-VEGF treatment;
   Visual acuity; Real-world studies
ID MACULAR DEGENERATION; INTRAVITREAL RANIBIZUMAB; OPEN-LABEL; OUTCOMES;
   MULTICENTER
AB Purpose: We aimed to study the regional detailed visual outcome and treatment discontinuation of neovascular age-related macular degeneration (nAMD). Methods: Clinical records of 110 patients treated for nAMD at the sole referral centre in the Helsinki region were analysed retrospectively. The follow-up was up to the fourth year. Results: The mean visual acuity (VA) at baseline was 56.3 (SD 16.2) letters. The mean last VA at the first year was 59.7 (20.2), and the corresponding values for the second, third, and fourth years were 60.8 (20.6), 60.0 (19.0), and 59.7 (19.3). The mean difference from baseline was +3.39 (SD 14.6), +3.59 (17.6), +0.08 (18.9), and +3.08 (14.3). The number of patients declined each year, with only 51% of the patients being in treatment until the fourth year. The patients with shorter duration of follow-up tended to have a lower baseline VA, lesser gains, and an earlier decline in VA. The VA levels at the last visit were poorer in the shorter follow group. The initial VA response predicted later VA, whereas VA at baseline, age, or sex had no effect. However, the effect vanished with a longer time in treatment. Conclusions: Long-term VA stabilization was obtained in a regional material. Patients with neovascular AMD consist of cohorts with varying visual outcome and treatment time. Many of the patients benefit from the treatment for some time, however. When comparing real-world results, the outcome of the different follow-up time cohorts should be considered. This calls for new methods for analysing real-world nAMD treatment results.
C1 [Ollila, Terhi; Immonen, Ilkka] Helsinki Univ Hosp, Dept Ophthalmol, Helsinki, Finland.
   [Silvennoinen, Juuso; Joshi, Ashwini; Liu, Jia; Kulathinal, Sangita] Univ Helsinki, Dept Math & Stat, Helsinki, Finland.
   [Liu, Jia] Australian Natl Univ, Biol Data Sci Inst, Canberra, ACT, Australia.
C3 University of Helsinki; Helsinki University Central Hospital; University
   of Helsinki; Australian National University
RP Ollila, T (通讯作者)，Helsinki Univ Hosp, Dept Ophthalmol, Helsinki, Finland.
EM terhi.ollila@hus.fi
OI LIU, JIA/0000-0001-9206-7576; Ollila, Terhi/0000-0002-1864-079X
FU Finnish Eye Foundation, Helsinki, Finland; Eye and Tissue Bank
   Foundation, Helsinki, Finland; Finnish Ophthalmological Society,
   Helsinki, Finland; Evald and Hilda Nissi Foundation, Helsinki, Finland;
   Helsinki University Hospital (HUS) research funds; Academy of Finland;
   Professor Sangita Kulathinal's start-up grant
FX Supported by grants from the Finnish Eye Foundation, Helsinki, Finland
   (Ollila); the Eye and Tissue Bank Foundation, Helsinki, Finland
   (Ollila); Finnish Ophthalmological Society, Helsinki, Finland (Ollila);
   the Evald and Hilda Nissi Foundation, Helsinki, Finland (Ollila,
   Silvennoinen, Immonen); Helsinki University Hospital (HUS) research
   funds (Immonen, Liu, Silvennoinen); Academy of Finland, Research
   Mobility Grant (Joshi), and Professor Sangita Kulathinal's start-up
   grant (Silvennoinen).
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NR 23
TC 1
Z9 1
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
PD AUG
PY 2022
VL 245
IS 4
BP 358
EP 367
DI 10.1159/000524848
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3N5ZL
UT WOS:000836226400007
PM 35613545
DA 2022-11-30
ER

PT J
AU Aggarwal, R
   Sounderajah, V
   Martin, G
   Ting, DSW
   Karthikesalingam, A
   King, D
   Ashrafian, H
   Darzi, A
AF Aggarwal, Ravi
   Sounderajah, Viknesh
   Martin, Guy
   Ting, Daniel S. W.
   Karthikesalingam, Alan
   King, Dominic
   Ashrafian, Hutan
   Darzi, Ara
TI Diagnostic accuracy of deep learning in medical imaging: a systematic
   review and meta-analysis
SO NPJ DIGITAL MEDICINE
LA English
DT Review
ID CONVOLUTIONAL NEURAL-NETWORK; DIABETIC-RETINOPATHY;
   ARTIFICIAL-INTELLIGENCE; ANALYSIS-SOFTWARE; BREAST-CANCER; BIG DATA;
   IMAGES; CLASSIFICATION; PERFORMANCE; VALIDATION
AB Deep learning (DL) has the potential to transform medical diagnostics. However, the diagnostic accuracy of DL is uncertain. Our aim was to evaluate the diagnostic accuracy of DL algorithms to identify pathology in medical imaging. Searches were conducted in Medline and EMBASE up to January 2020. We identified 11,921 studies, of which 503 were included in the systematic review. Eighty-two studies in ophthalmology, 82 in breast disease and 115 in respiratory disease were included for meta-analysis. Two hundred twenty-four studies in other specialities were included for qualitative review. Peer-reviewed studies that reported on the diagnostic accuracy of DL algorithms to identify pathology using medical imaging were included. Primary outcomes were measures of diagnostic accuracy, study design and reporting standards in the literature. Estimates were pooled using random-effects meta-analysis. In ophthalmology, AUC's ranged between 0.933 and 1 for diagnosing diabetic retinopathy, age-related macular degeneration and glaucoma on retinal fundus photographs and optical coherence tomography. In respiratory imaging, AUC's ranged between 0.864 and 0.937 for diagnosing lung nodules or lung cancer on chest X-ray or CT scan. For breast imaging, AUC's ranged between 0.868 and 0.909 for diagnosing breast cancer on mammogram, ultrasound, MRI and digital breast tomosynthesis. Heterogeneity was high between studies and extensive variation in methodology, terminology and outcome measures was noted. This can lead to an overestimation of the diagnostic accuracy of DL algorithms on medical imaging. There is an immediate need for the development of artificial intelligence-specific EQUATOR guidelines, particularly STARD, in order to provide guidance around key issues in this field.
C1 [Aggarwal, Ravi; Sounderajah, Viknesh; Martin, Guy; Karthikesalingam, Alan; King, Dominic; Ashrafian, Hutan; Darzi, Ara] Imperial Coll London, Inst Global Hlth Innovat, London, England.
   [Ting, Daniel S. W.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
C3 Imperial College London; National University of Singapore; Singapore
   National Eye Center
RP Ashrafian, H (通讯作者)，Imperial Coll London, Inst Global Hlth Innovat, London, England.
EM h.ashrafian@imperial.ac.uk
OI Ashrafian, Hutan/0000-0003-1668-0672; Sounderajah,
   Viknesh/0000-0002-4595-8402; Ting, Daniel Shu Wei/0000-0003-2264-7174;
   Martin, Guy/0000-0002-5759-962X; Bidwai, Pooja
   Vishal/0000-0002-3077-4395
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NR 139
TC 76
Z9 76
U1 45
U2 94
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2398-6352
J9 NPJ DIGIT MED
JI npj Digit. Med.
PD APR 7
PY 2021
VL 4
IS 1
AR 65
DI 10.1038/s41746-021-00438-z
PG 23
WC Health Care Sciences & Services; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; Medical Informatics
GA RJ7DO
UT WOS:000637760900001
PM 33828217
OA gold, Green Published
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Baba, T
   Miura, G
   Tatsumi, T
   Sakurai, M
   Yamamoto, S
AF Baba, Takayuki
   Miura, Gen
   Tatsumi, Tomoaki
   Sakurai, Madoka
   Yamamoto, Shuichi
TI Characteristics and surgical outcomes of rhegmatogenous retinal
   detachments that develop after intravitreal injections
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Rhegmatogenous retinal detachment; Anti-vascular endothelial growth
   factor drug; Intravitreal injection; Complications
AB Purpose To determine the frequency and characteristics of rhegmatogenous retinal detachments (RRDs) that develop after an intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. Study design A retrospective review of the medical charts. Methods The charts of patients who received intravitreal injections for age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), or myopic choroidal neovascularization (mCNV) between 2013 and 2020 were reviewed. We included the RRD cases that developed within 90 days of the most recent intravitreal injection. The baseline characteristics and surgical outcomes were analyzed. Results A total of 3040 patients received 28,190 intravitreal injections. Seven eyes of 7 cases developed a RRD. There were 6 cases of AMD and one of DME, with an incidence of one in 4027 injections (0.025%). The retinal break was in the superior quadrants in 5 eyes (71%), and in the inferior quadrants in 2 eyes. All eyes had a posterior vitreous detachment. The average number of injections before the development of RRD was 14.1 (range: 2-39). Four eyes were treated by vitrectomy, and 3 by scleral buckling. The primary success rate was 86%, and the final reattachment rate was 100%. The best-corrected visual acuity was 0.41 +/- 0.26 logarithm of minimal angle of resolution (logMAR) units before developing the RRD, 0.78 +/- 0.78 logMAR units before the surgery for RRD, and 0.45 +/- 0.47 logMAR units at the final visit. Conclusions The incidence of RRD after an intravitreal injection is very low (0.025%), and it can be reattached with recovery of the visual acuity.
C1 [Baba, Takayuki; Miura, Gen; Tatsumi, Tomoaki; Sakurai, Madoka; Yamamoto, Shuichi] Chiba Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Chuo Ku, 1-8-1 Inohana, Chiba 2600856, Japan.
C3 Chiba University
RP Baba, T (通讯作者)，Chiba Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Chuo Ku, 1-8-1 Inohana, Chiba 2600856, Japan.
EM babatakayuki@nifty.com
OI Miura, Gen/0000-0001-6288-8840
CR Baumal CR, 2020, OPHTHALMOLOGY, V127, P1345, DOI 10.1016/j.ophtha.2020.04.017
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NR 18
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD JUL
PY 2021
VL 65
IS 4
BP 492
EP 496
DI 10.1007/s10384-021-00834-8
EA MAR 2021
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SW0GG
UT WOS:000630979000001
PM 33745092
DA 2022-11-30
ER

PT J
AU Kremlacek, J
   Nekolova, J
   Stredova, M
   Langrova, J
   Szanyi, J
   Kuba, M
   Kubova, Z
   Vit, F
   Voda, P
   Vesela, M
   Jiraskova, N
AF Kremlacek, Jan
   Nekolova, Jana
   Stredova, Marketa
   Langrova, Jana
   Szanyi, Jana
   Kuba, Miroslav
   Kubova, Zuzana
   Vit, Frantisek
   Voda, Petr
   Vesela, Martina
   Jiraskova, Nad'a
TI Vision before and after scharioth macular lens implantation in patients
   with AMD: an electrophysiological study
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Scharioth macular lens; Maculopathy; Age-related macular degeneration;
   Oddball ERPs; Motion-onset VEPs; Pattern-reversal VEPs; P3b
ID MOTION-ONSET VEPS; VISUAL-EVOKED-POTENTIALS; QUALITY-OF-LIFE;
   INTRAOCULAR-LENS; DEGENERATION; PATTERN
AB Background For patients with age-related macular degeneration (AMD), a special intraocular lens implantation partially compensates for the loss in the central part of the visual field. For six months, we evaluated changes in neurophysiological parameters in patients implanted with a "Scharioth macula lens" (SML; a center near high add + 10 D and peripheral plano carrier bifocal lens designed to be located between the iris and an artificial lens). Methods Fourteen patients (5 M, 9 F, 63-87 years) with dry AMD were examined prior to and at 3 days after, as well as 1, 2, and 6 months after, implantation using pattern-reversal, motion-onset, and cognitive evoked potentials, psychophysical tests evaluating distant and near visual acuity, and contrast sensitivity. Results Near visual acuity without an external aid was significantly better six months after implantation than before implantation (Jaeger table median (lower; upper quartile): 4 (1; 6) vs. 15 (13; 17)). Distant visual acuity was significantly altered between the pre- (0.7 (0.5; 0.8) logMAR) and last postimplantation visits (0.8 (0.7; 0.8) logMAR), which matched prolongation of the P100 peak time (147 (135; 151) ms vs. 161 (141; 166) ms) of 15 arc min pattern-reversal VEPs and N2 peak time (191.5 (186.5; 214.5) ms vs. 205 (187; 218) ms) of peripheral motion-onset VEPs. Conclusion SML implantation significantly improved near vision. We also observed a slight but significant decrease in distant and peripheral vision. The most efficient electrophysiological approach to test patients with SML was the peripheral motion-onset stimulation, which evoked repeatable and readable VEPs.
C1 [Kremlacek, Jan; Voda, Petr] Charles Univ Prague, Fac Med Hradec Kralove, Dept Med Biophys, Simkova 870, Hradec Kralove 50038, Czech Republic.
   [Kremlacek, Jan; Langrova, Jana; Szanyi, Jana; Kuba, Miroslav; Kubova, Zuzana; Vit, Frantisek] Charles Univ Prague, Fac Med Hradec Kralove, Dept Pathol Physiol, Prague, Czech Republic.
   [Nekolova, Jana; Stredova, Marketa; Vesela, Martina; Jiraskova, Nad'a] Charles Univ Prague, Univ Hosp Hradec Kralove, Fac Med Hradec Kralove, Dept Ophthalmol, Prague, Czech Republic.
C3 Charles University Prague; Charles University Prague; Charles University
   Prague
RP Kremlacek, J (通讯作者)，Charles Univ Prague, Fac Med Hradec Kralove, Dept Med Biophys, Simkova 870, Hradec Kralove 50038, Czech Republic.
EM jan.kremlacek@lfhk.cuni.cz
RI Kremlacek, Jan/A-4313-2008; Nekolová, Jana/I-6031-2017; Nekolová,
   Jana/AAX-3663-2021; Langrova, Jana/E-1827-2017; Voda, Petr/A-6754-2017;
   Stredova, Marketa/K-2753-2017; Kuba, Miroslav/D-8252-2017; Kubova,
   Zuzana/H-1328-2015
OI Kremlacek, Jan/0000-0001-8641-4287; Nekolová, Jana/0000-0002-0662-8662;
   Nekolová, Jana/0000-0002-0662-8662; Langrova, Jana/0000-0002-3639-764X;
   Voda, Petr/0000-0003-2751-0062; Stredova, Marketa/0000-0001-7713-9025;
   Kuba, Miroslav/0000-0003-2525-0463; Vi-t, Frantisek/0000-0001-9834-1273;
   Kubova, Zuzana/0000-0002-8470-3218
FU Ministry of Health of the Czech Republic; AZV [NV18-06-00484, PROGRES
   Q40/07]
FX This work was supported by Ministry of Health of the Czech Republic,
   grant nr. AZV NV18-06-00484 and project PROGRES Q40/07. The sponsor
   provided financial support in the form of salaries and consumables and
   had no role in the design or conduct of this research.
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NR 37
TC 1
Z9 1
U1 0
U2 1
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 AUG
PY 2021
VL 143
IS 1
BP 17
EP 31
DI 10.1007/s10633-020-09814-8
EA JAN 2021
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TG4IH
UT WOS:000604483100002
PM 33392893
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Xi, XM
   Meng, XJ
   Qin, ZY
   Nie, XS
   Yin, YL
   Chen, XJ
AF Xi, Xiaoming
   Meng, Xianjing
   Qin, Zheyun
   Nie, Xiushan
   Yin, Yilong
   Chen, Xinjian
TI IA-net: informative attention convolutional neural network for choroidal
   neovascularization segmentation in OCT images
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SPARSE AUTOENCODER; REPRESENTATION
AB Choroidal neovascularization (CNV) is a characteristic feature of wet age-related macular degeneration (AMD). Quantification of CNV is useful to clinicians in the diagnosis and treatment of CNV disease. Before quantification, CNV lesion should be delineated by automatic CNV segmentation technology. Recently, deep learning methods have achieved significant success for medical image segmentation. However, some CNVs are small objects which are hard to discriminate, resulting in performance degradation. In addition, it's difficult to train an effective network for accurate segmentation due to the complicated characteristics of CNV in OCT images. In order to tackle these two challenges, this paper proposed a novel Informative Attention Convolutional Neural Network (IA-net) for automatic CNV segmentation in OCT images. Considering that the attention mechanism has the ability to enhance the discriminative power of the interesting regions in the feature maps, the attention enhancement block is developed by introducing the additional attention constraint. It has the ability to force the model to pay high attention on CNV in the learned feature maps, improving the discriminative ability of the learned CNV features, which is useful to improve the segmentation performance on small CNV. For accurate pixel classification, the novel informative loss is proposed with the incorporation of an informative attention map. It can focus training on a set of informative samples that are difficult to be predicted. Therefore, the trained model has the ability to learn enough information to classify these informative samples, further improving the performance. The experimental results on our database demonstrate that the proposed method outperforms traditional CNV segmentation methods. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Xi, Xiaoming; Nie, Xiushan] Shandong Jianzhu Univ, Sch Comp Sci & Technol, Jinan 250101, Shandong, Peoples R China.
   [Meng, Xianjing] Shandong Univ Finance & Econ, Sch Comp Sci & Technol, Jinan 250014, Shandong, Peoples R China.
   [Qin, Zheyun; Yin, Yilong] Shandong Univ, Sch Software, Jinan 250101, Shandong, Peoples R China.
   [Chen, Xinjian] Soochow Univ, Sch Elect & Informat Engn, Suzhou 215006, Peoples R China.
C3 Shandong Jianzhu University; Shandong University of Finance & Economics;
   Shandong University; Soochow University - China
RP Yin, YL (通讯作者)，Shandong Univ, Sch Software, Jinan 250101, Shandong, Peoples R China.
EM ylyin@sdu.edu.cn; xjchen@suda.edu.cn
OI Chen, Xinjian/0000-0002-0871-293X
FU National Key Research and Development Program of China [2018YFC0830100,
   2018YFC0830102]; National Natural Science Foundation of China [61701280,
   61801263, 61876098]
FX National Key Research and Development Program of China (2018YFC0830100,
   2018YFC0830102); National Natural Science Foundation of China (61701280,
   61801263, 61876098).
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NR 45
TC 6
Z9 6
U1 4
U2 17
PU Optica Publishing Group
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD NOV 1
PY 2020
VL 11
IS 11
BP 6122
EP 6136
DI 10.1364/BOE.400816
PG 15
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 OI6HG
UT WOS:000583376400006
PM 33282479
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Fleissig, E
   Appenbrick, E
   Brock, G
   Barr, CC
AF Fleissig, Efrat
   Appenbrick, Eddie
   Brock, Guy
   Barr, Charles C.
TI Lighting conditions and perceived visual function in ophthalmic
   conditions
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Visual acuity; Luminance; Contrast sensitivity; Age-related macular
   degeneration; Retinal disease
ID CONTRAST-SENSITIVITY FUNCTION; RETINAL-IMAGE QUALITY; LUMINANCE; ACUITY;
   STRAYLIGHT
AB Purpose To determine the influence of different lighting conditions on perceived visual function in patients of different age, gender, race, and in various ophthalmic diseases. Methods A prospective study. A survey given to patients seen in general ophthalmic and retina clinics. Patients were asked four questions: Is your vision better, worse, or the same in (1) bright light vs dim light, (2) indoors or outdoors, (3) beginning or end of the day, and (4) sunny or cloudy day? Parameters tested were age, race, gender, visual acuity, and a variety of ophthalmic conditions. Multivariable models for each question were fit using multinomial regression. Association was considered significant ifp< 0.05. Results A total of 722 patients were enrolled in the study. Patients with lower vision (LogMAR >= 0.3) were more likely to indicate they either had better vision indoors or outdoors compared with better vision patients (LogMAR < 0.1). Patients with pseudophakia were also more likely to indicate they had better vision on a cloudy day (OR = 1.9). White patients had double the odds of selecting bright light compared with others. Males were less likely than females to indicate better vision indoors (OR = 0.62). There were no significant associations with age-related macular degeneration (AMD) in the multivariable model. Conclusions Most patients did not note any difference in lighting conditions, and although there is explanatory rational for some of the findings in this study, those questions concerning lighting conditions or time of day are not useful for screening of disease. Gender and ethnicity were found to have associations with lighting preferences which needs to be further studied.
C1 [Fleissig, Efrat; Appenbrick, Eddie; Barr, Charles C.] Univ Louisville, Dept Ophthalmol & Visual Sci, 301 E Muhammad Ali Blvd, Louisville, KY 40202 USA.
   [Fleissig, Efrat] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Dept Ophthalmol, Tel Aviv, Israel.
   [Brock, Guy] Univ Louisville, Dept Bioinformat & Biostat, Louisville, KY 40292 USA.
C3 University of Louisville; Tel Aviv University; Sackler Faculty of
   Medicine; University of Louisville
RP Barr, CC (通讯作者)，Univ Louisville, Dept Ophthalmol & Visual Sci, 301 E Muhammad Ali Blvd, Louisville, KY 40202 USA.
EM ccbarr01@louisville.edu
OI Barr, Charles/0000-0003-3145-1202
FU Research to Prevent Blindness
FX Supported by an unrestricted grant from Research to Prevent Blindness.
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NR 19
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2021
VL 259
IS 3
BP 723
EP 732
DI 10.1007/s00417-020-04960-w
EA OCT 2020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QM0ZA
UT WOS:000578655200002
PM 33043387
DA 2022-11-30
ER

PT J
AU Annamalai, B
   Nicholson, C
   Parsons, N
   Stephenson, S
   Atkinson, C
   Jones, B
   Rohrer, B
AF Annamalai, Balasubramaniam
   Nicholson, Crystal
   Parsons, Nathaniel
   Stephenson, Sarah
   Atkinson, Carl
   Jones, Bryan
   Rohrer, Barbel
TI Immunization Against Oxidized Elastin Exacerbates Structural and
   Functional Damage in Mouse Model of Smoke-Induced Ocular Injury
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE smoke-induced ocular pathology; elastin; immune response; complement
   activation; electron microscopy
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; OXIDATIVE STRESS;
   CIGARETTE-SMOKING; VITAMIN-C; AGE; COMPLEMENT; ANTIBODIES; PROTEIN;
   PATHWAY
AB PURPOSE. Age-related macular degeneration (AMD) is the leading cause of blindness in Western populations. While an overactive complement system has been linked to pathogenesis, mechanisms contributing to its activation are largely unknown. In aged and AMD eyes, loss of the elastin layer (EL) of Bruch's membrane (BrM) has been reported. Elastin antibodies are elevated in patients with AMD, the pathogenic significance of which is unclear. Here we assess the role of elastin antibodies using a mouse model of smokeinduced ocular pathology (SIOP), which similarly demonstrates EL loss.
   METHODS. C57BL/6J mice were immunized with elastin or elastin peptide oxidatively modified by cigarette smoke (ox-elastin). Mice were then exposed to cigarette smoke or air for 6 months. Visual function was assessed by optokinetic response, retinal morphology by spectral-domain optical coherence tomography and electron microscopy, and complement activation and antibody deposition by Western blot.
   RESULTS. Ox-elastin IgG and IgM antibodies were elevated in ox-elastin immunized mice following 6 months of smoke, whereas elastin immunization had a smaller effect. Oxelastin immunization exacerbated smoke-induced vision loss, with thicker BrM and more damaged retinal pigment epithelium (RPE) mitochondria compared with mice immunized with elastin or nonimmunized controls. These changes were correlated with increased levels of IgM, IgG2, IgG3, and complement activation products in RPE/choroid.
   CONCLUSIONS. These data demonstrate that SIOP mice generate elastin-specific antibodies and that immunization with ox-elastin exacerbates ocular pathology. Elastin antibodies represented complement fixing isotypes that, together with the increased presence of complement activation seen in immunized mice, suggest that elastin antibodies exert pathogenic effects through mediating complement activation.
C1 [Annamalai, Balasubramaniam; Nicholson, Crystal; Parsons, Nathaniel; Rohrer, Barbel] Med Univ South Carolina, Div Res, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Stephenson, Sarah; Atkinson, Carl] Med Univ South Carolina, Div Res, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
   [Jones, Bryan] Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA.
   [Rohrer, Barbel] Med Univ South Carolina, Dept Neurosci, Div Res, 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; 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
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 [R01EY019320, R01HL091944, R01EY015128,
   R01EY028927, P30EY014800]; Department of Veterans Affairs [RX000444,
   BX003050]; South Carolina SmartState Endowment; Research to Prevent
   Blindness, New York
FX Supported by the National Institutes of Health R01EY019320 (BR),
   R01HL091944 (CA), R01EY015128 (BJ), R01EY028927 (BJ), and P30EY014800
   (BJ); the Department of Veterans Affairs RX000444 and BX003050 (BR); the
   South Carolina SmartState Endowment (BR); and an Unrestricted Research
   Grant from Research to Prevent Blindness, New York, to the Department of
   Ophthalmology & Visual Sciences, University of Utah.
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NR 67
TC 10
Z9 11
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 MAR
PY 2020
VL 61
IS 3
AR 45
DI 10.1167/iovs.61.3.45
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LA8BU
UT WOS:000524168000045
PM 32207814
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kawczynski, MG
   Bengtsson, T
   Dai, J
   Hopkins, JJ
   Gao, SS
   Willis, JR
AF Kawczynski, Michael G.
   Bengtsson, Thomas
   Dai, Jian
   Hopkins, J. Jill
   Gao, Simon S.
   Willis, Jeffrey R.
TI Development of Deep Learning Models to Predict Best-Corrected Visual
   Acuity from Optical Coherence Tomography
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE deep learning; ocular imaging; tele-ophthalmology; public health
   ophthalmology; neovascular age-related macular degeneration
ID 2.0 MG RANIBIZUMAB; MACULAR DEGENERATION; MORPHOLOGY; EFFICACY; VISION;
   SAFETY; VIEW
AB Purpose: To develop deep learning (DL) models to predict best-corrected visual acuity (BCVA) from optical coherence tomography (OCT) images from patients with neovascular age-related macular degeneration (nAMD).
   Methods: Retrospective analysis of OCT images and associated BCVA measurements from the phase 3 HARBOR trial (NCT00891735). DL regression models were developed to predict BCVA at the concurrent visit and 12 months from baseline using OCT images. Binary classification models were developed to predict BCVA of Snellen equivalent of <20/40, <20/60, and <= 20/200 at the concurrent visit and 12 months from baseline.
   Results: The regression model to predict BCVA at the concurrent visit had R-2 = 0.67 (root-mean-square error [RMSE] = 8.60) in study eyes and R-2 = 0.84 (RMSE = 9.01) in fellow eyes. The best classification model to predict BCVA at the concurrent visit had an area under the receiver operating characteristic curve (AUC) of 0.92 in study eyes and 0.98 in fellow eyes. The regression model to predict BCVA at month 12 using baseline OCT had R-2 = 0.33 (RMSE = 14.16) in study eyes and R-2 = 0.75 (RMSE = 11.27) in fellow eyes. The best classification model to predict BCVA at month 12 had AUC = 0.84 in study eyes and AUC = 0.96 in fellow eyes.
   Conclusions: DL shows promise in predicting BCVA from OCTs in nAMD. Further research should elucidate the utility of models in clinical settings.
   Translational Relevance: DL models predicting BCVA could be used to enhance understanding of structure-function relationships and develop more efficient clinical trials.
C1 [Kawczynski, Michael G.; Bengtsson, Thomas; Dai, Jian; Hopkins, J. Jill; Gao, Simon S.; Willis, Jeffrey R.] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech
RP Willis, JR (通讯作者)，Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM willis.jeffrey@gene.com
OI Gao, Simon/0000-0002-7020-037X
FU Genentech, Inc.
FX The authors thank Anh Duong and Alex de Crespigny for project guidance;
   Elizabeth Li, Justin Lee, and Priya Ponnapalli for technical support and
   scientific discussions; and Mary K. Durbin, Archana Kolli, and Paolo
   Pochendorfer from Carl Zeiss Meditec, Inc. for technical support.
   Additional writing and editorial assistance was provided by Amy Lindsay,
   PhD, of Envision Pharma Group (funded by Genentech, Inc.).; Funding was
   provided by Genentech, Inc., a member of the RocheGroup, for the study.
   Genentech, Inc. supported and contributed to all aspects of the study,
   including the study design, analyses, data interpretation, report
   writing, and decision to submit the manuscript for publication.
CR American Foundation for the Blind, STAT SNAPSH AM FDN B
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NR 26
TC 8
Z9 8
U1 3
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 JAN
PY 2020
VL 9
IS 2
AR 51
DI 10.1167/tvst.9.2.51
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PG1FX
UT WOS:000599489500037
PM 32974088
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Muftuoglu, IK
   Lin, TZ
   Freeman, WR
AF Muftuoglu, Ilkay Kilic
   Lin, Tiezhu
   Freeman, William R.
TI Inner retinal thickening in newly diagnosed choroidal neovascularization
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Ganglion cell layer; Neovascular AMD; Choroidal neovascularization; OCT;
   Segmentation; Ganglion cell complex; GCC
ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; GANGLION-CELL COMPLEX;
   MACULAR DEGENERATION; PLEXIFORM LAYER
AB PurposeAutomated segmentation of retinal layers by spectral-domain optical coherence tomography (SD-OCT) is usually erroneous in the presence of retinal diseases. The purpose of this study is to report the changes in ganglion cell complex (GCC) comprising retina nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in neovascular age-related macular degeneration (AMD) patients by manually correcting the automated segmentation errors.MethodsThirty eyes of 30 patients with new-onset choroidal neovascularization secondary to neovascular AMD and 30 eyes of 30 healthy subjects were included. The inner retinal thicknesses were measured using early treatment diabetic retinopathy circle in the central 1mm (fovea) and surrounding 3mm diameter (parafovea) after checking the accuracy of automated segmentation lines. Manual segmentation was done to ensure the accurate segmentation, when needed.ResultsNeovascular AMD patients had thicker mean RNFL, GCL, IPL, and GCC thicknesses within the fovea compared to healthy eyes (p=0.04, p=0.001, p=0.032, and p=0.005, respectively). In the parafoveal area, among the thickness-related measurements, the only significant difference was a thicker mean RNFL (p=0.002).ConclusionDiffuse thickening of inner retinal layers in neovascular AMD may overestimate actual GCC thickness within fovea. This pseudo-increase in GCC thickness and inner retinal layers in general likely does not reflect more cells or tissue, but rather diffuse edema which leads to a falsely increased reading of layer thickness. Such false readings may also make the assessment of other conditions that lead to reduced inner retinal layer thickness such as glaucoma, optic nerve disease, or retinovascular occlusions more difficult.
C1 [Muftuoglu, Ilkay Kilic; Lin, Tiezhu; Freeman, William R.] Univ Calif San Diego, Shiley Eye Inst, Dept Ophthalmol, Jacobs Retina Ctr, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
   [Muftuoglu, Ilkay Kilic] Istanbul Training & Res Hosp, Dept Ophthalmol, Istanbul, Turkey.
C3 University of California System; University of California San Diego;
   Istanbul Training & Research Hospital
RP Freeman, WR (通讯作者)，Univ Calif San Diego, Shiley Eye Inst, Dept Ophthalmol, Jacobs Retina Ctr, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM wrfreeman@ucsd.edu
RI lin, Tiezhu/AAY-1971-2020
FU National Eye Institute [P30 EY022589]; Research to Prevent Blindness,
   NY; NATIONAL EYE INSTITUTE [P30EY022589] Funding Source: NIH RePORTER
FX Supported in part by a core grant from the National Eye Institute P30
   EY022589 (WRF) and an unrestricted grant from Research to Prevent
   Blindness, NY (WRF). The funding organizations had no role in the design
   or conduct of this research. The funding organizations had no role in
   the design or conduct of this research.
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NR 16
TC 3
Z9 3
U1 1
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 NOV
PY 2018
VL 256
IS 11
BP 2035
EP 2040
DI 10.1007/s00417-018-4093-7
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GX8NF
UT WOS:000448042400003
PM 30094716
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Koh, JEW
   Acharya, UR
   Hagiwara, Y
   Raghavendra, U
   Tan, JH
   Sree, SV
   Bhandary, SV
   Rao, AK
   Sivaprasad, S
   Chua, KC
   Laude, A
   Tong, L
AF Koh, Joel E. W.
   Acharya, U. Rajendra
   Hagiwara, Yuki
   Raghavendra, U.
   Tan, Jen Hong
   Sree, S. Vinitha
   Bhandary, Sulatha V.
   Rao, A. Krishna
   Sivaprasad, Sobha
   Chua, Kuang Chua
   Laude, Augustinus
   Tong, Louis
TI Diagnosis of retinal health in digital fundus images using continuous
   wavelet transform (CWT) and entropies
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Continuous wavelet transform; Age-related macular degeneration; Diabetic
   retinopathy; Fundus; Glaucoma
ID COMPUTER-AIDED DIAGNOSIS; DECISION-SUPPORT-SYSTEM; MACULAR DEGENERATION;
   DIABETIC-RETINOPATHY; AUTOMATED DIAGNOSIS; FEATURES; IDENTIFICATION;
   EXTRACTION
AB Vision is paramount to humans to lead an active personal and professional life. The prevalence of ocular diseases is rising, and diseases such as glaucoma, Diabetic Retinopathy (DR) and Age-related Macular Degeneration (AMD) are the leading causes of blindness in developed countries. Identifying these diseases in mass screening programmes is time-consuming, labor-intensive and the diagnosis can be subjective. The use of an automated computer aided diagnosis system will reduce the time taken for analysis and will also reduce the inter-observer subjective variabilities in image interpretation. In this work, we propose one such system for the automatic classification of normal from abnormal (DR, AMD, glaucoma) images. We had a total of 404 normal and 1082 abnormal fundus images in our database. As the first step, 2D-Continuous Wavelet Transform (CWT) decomposition on the fundus images of two classes was performed. Subsequently, energy features and various entropies namely Yager, Renyi, Kapoor, Shannon, and Fuzzy were extracted from the decomposed images. Then, adaptive synthetic sampling approach was applied to balance the normal and abnormal datasets. Next, the extracted features were ranked according to the significances using Particle Swarm Optimization (PSO). Thereupon, the ranked and selected features were used to train the random forest classifier using stratified 10-fold cross validation. Overall, the proposed system presented a performance rate of 92.48%, and a sensitivity and specificity of 89.37% and 95.58% respectively using 15 features. This novel system shows promise in detecting abnormal fundus images, and hence, could be a valuable adjunct eye health screening tool that could be employed in polyclinics, and thereby reduce the workload of specialists at hospitals.
C1 [Koh, Joel E. W.; Acharya, U. Rajendra; Hagiwara, Yuki; Tan, Jen Hong; Chua, Kuang Chua] Ngee Ann Polytech, Dept Elect & Comp Engn, Singapore 599489, Singapore.
   [Acharya, U. Rajendra] SIM Univ, Sch Sci & Technol, Dept Biomed Engn, Singapore 599491, Singapore.
   [Acharya, U. Rajendra] Univ Malaya, Dept Biomed Engn, Fac Engn, Kuala Lumpur 50603, Malaysia.
   [Raghavendra, U.] Manipal Univ, Manipal Inst Technol, Dept Instrumentat & Control Engn, Manipal 576104, Karnataka, India.
   [Sree, S. Vinitha] Global Biomed Technol, Roseville, CA USA.
   [Bhandary, Sulatha V.; Rao, A. Krishna] Kasturba Med Coll & Hosp, Dept Ophthalmol, Manipal 576104, India.
   [Sivaprasad, Sobha] NIHR Moorfields Biomed Res Ctr, London, England.
   [Laude, Augustinus] Tan Tock Seng Hosp, Natl Healthcare Grp Eye Inst, Singapore 308433, Singapore.
   [Tong, Louis] Singapore Eye Res Inst, Ocular Surface Res Grp, Singapore, Singapore.
   [Tong, Louis] Singapore Natl Eye Ctr, Cornea & External Eye Dis Dept, Singapore, Singapore.
   [Tong, Louis] Duke Natl Univ Singapore, Grad Med Sch, Singapore, Singapore.
   [Tong, Louis] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore.
C3 Singapore University of Social Sciences (SUSS); Universiti Malaya;
   Manipal Academy of Higher Education (MAHE); Manipal Academy of Higher
   Education (MAHE); Kasturba Medical College, Manipal; Tan Tock Seng
   Hospital; National University of Singapore; Singapore National Eye
   Center; Singapore National Eye Center; National University of Singapore;
   National University of Singapore
RP Acharya, UR (通讯作者)，Ngee Ann Polytech, Dept Elect & Comp Engn, Singapore 599489, Singapore.
EM aru@np.edu.sg
RI Sivaprasad, S./D-6876-2015; Tan, Jenhong/AAD-3664-2020; Acharya,
   Rajendra U/E-3791-2010; Tan, Jen Hong/ABE-6525-2020
OI Sivaprasad, S./0000-0001-8952-0659; Acharya, Rajendra
   U/0000-0003-2689-8552; Hagiwara, Yuki/0000-0002-5418-738X; Bhandary,
   Sulatha/0000-0002-3150-707X
FU Social Innovation Research Fund [16S2111T01]; National Medical Research
   Council, Singapore [NMRC/CSA/045/2012]
FX Authors would like to thank Social Innovation Research Fund (Project ID:
   16S2111T01), and National Medical Research Council (NMRC/CSA/045/2012),
   Singapore, for providing a grants for this research. We would also like
   to express our sincere thanks to Manipal University, Manipal, India for
   providing the images for this study.
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NR 68
TC 46
Z9 47
U1 0
U2 12
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 MAY 1
PY 2017
VL 84
BP 89
EP 97
DI 10.1016/j.compbiomed.2017.03.008
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 EU9RQ
UT WOS:000401377700010
PM 28351716
DA 2022-11-30
ER

PT J
AU Hytti, M
   Szabo, D
   Piippo, N
   Korhonen, E
   Honkakoski, P
   Kaarniranta, K
   Petrovski, G
   Kauppinen, A
AF Hytti, Maria
   Szabo, Dora
   Piippo, Niina
   Korhonen, Eveliina
   Honkakoski, Paavo
   Kaarniranta, Kai
   Petrovski, Goran
   Kauppinen, Anu
TI Two dietary polyphenols, fisetin and luteolin, reduce inflammation but
   augment DNA damage-induced toxicity in human RPE cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Dietary polyphenols; Fisetin; Luteolin; DNA damage; Inflammation;
   Age-related macular degeneration
ID NF-KAPPA-B; PIGMENT EPITHELIAL-CELLS; OXIDATIVE-STRESS; MACULAR
   DEGENERATION; IN-VITRO; ANTIINFLAMMATORY ACTIVITY; VASCULAR
   INFLAMMATION; INSULIN-RESISTANCE; MICE; INHIBITION
AB Plant-derived polyphenols are known to possess anti-inflammatory and antioxidant effects. In recent years, several studies have investigated their potential benefits for treating chronic diseases associated with prolonged inflammation and excessive oxidative stress, such as age-related macular degeneration (AMD). Previously, two polyphenols, fisetin and luteolin, have been reported to increase the survival of retinal pigment epithelial (RPE) cells suffering from oxidative stress as well as decreasing inflammation but the benefits of polyphenol therapy seem to depend on the model system used.
   Our aim was to analyze the effects of fisetin and luteolin on inflammation and cellular viability in a inodel of nonoxidative DNA damage -induced cell death in human RPE (hRPE) cells. Pretreatment of ARPE-19 or primary hRPE cells with the polyphenols augmented etoposide-induced cell death as measured by the lactate dehydrogenase and 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. However, the treatment was able to reduce the release of two proinflammatory cytokines, IL-6 and IL-8, which were determined by enzyme-linked Immunosorbent assay. Analyses of caspase 3 activity, p53 acetylation and SIRT1 protein levels revealed the apoptotic nature of etoposide-evoked cell death and that fisetin and luteolin augmented the etoposide-induced acetylation of p53 and decreased SIRT1 levels. Taken together, our findings suggest that the cytoprotective effects of fisetin and luteolin depend on the stressor they need to combat, whereas their anti-inflammatory potential is sustained over a variety of model systems. Careful consideration of disease pathways will be necessary before fisetin or luteolin can be recommended as therapeutic agents for inflammatory diseases in general and specifically AMD. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, POB 1627, Kuopio 70211, Finland.
   [Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Kaarniranta, Kai] Univ Eastern Finland, Sch Med, Dept Ophthalmol, Kuopio, Finland.
   [Szabo, Dora; Petrovski, Goran] Univ Szeged, Fac Med, Dept Ophthalmol, Stem Cells & Eye Res Lab, Szeged, Hungary.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
   [Petrovski, Goran] Univ Oslo, Ctr Eye Res, Dept Ophthalmol, Oslo, Norway.
   [Petrovski, Goran] Univ Oslo, Norwegian Ctr Stem Cell Res, Oslo Univ Hosp, Oslo, Norway.
C3 University of Eastern Finland; University of Eastern Finland; Szeged
   University; Kuopio University Hospital; University of Eastern Finland;
   University of Oslo; University of Oslo
RP Kauppinen, A (通讯作者)，Univ Eastern Finland, Sch Pharm, POB 1627, Kuopio 70211, Finland.
EM maria.hytti@uef.fi; szabo.julia.dora@gmail.com; niina.e.laakso@uef.fi;
   eveliina.korhonen@uef.fi; paavo.honkakoski@uef.fi;
   kai.kaarniranta@uef.fi; goran.petrovski@medisin.uio.no;
   anu.kauppinen@uef.fi
RI Honkakoski, Paavo/AAJ-1278-2020; Hytti, Maria/AAE-4016-2019
OI Honkakoski, Paavo/0000-0002-4332-3577; Hytti, Maria/0000-0003-2150-6847;
   Petrovski, Goran/0000-0003-2905-9252; Korhonen,
   Eveliina/0000-0002-5360-7258
FU Finnish Cultural Foundation - both central and Northern Savo Regional
   Fund; Silma-ja Kudospankkisaatio; Emil Aaltonen Foundation; Alfred
   Kordelin Foundation; Silmasaatio; Sokeain Ystavat ry; Academy of
   Finland; Kuopio University Hospital; National Brain Research Program
   [KTIA_NAP_13-A_III/9]; European Union [GINOP-23.2-15-2016-00006];
   European Regonal Development Fund
FX The authors warmly acknowledge Dr. Ewen MacDonald for the language
   revision and Res. Dir. Emeritus Antero Salminen for his valuable
   collaboration and critical review of the manuscript. This work was
   financially supported by the Finnish Cultural Foundation - both central
   and Northern Savo Regional Fund, the Silma-ja Kudospankkisaatio, the
   Emil Aaltonen Foundation, the Alfred Kordelin Foundation, Silmasaatio,
   Sokeain Ystavat ry, the Academy of Finland and the Kuopio University
   Hospital. GP and the Stem Cells and Eye Research Laboratory, Department
   of Ophthalmology, Faculty of Medicine, University of Szeged, Hungary,
   have been supported by the National Brain Research Program
   (KTIA_NAP_13-A_III/9), as well as the GINOP-23.2-15-2016-00006 project
   co-financed by the European Union and the European Regonal Development
   Fund.
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NR 47
TC 29
Z9 29
U1 0
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD APR
PY 2017
VL 42
BP 37
EP 42
DI 10.1016/j.jnutbio.2016.12.014
PG 6
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA EQ3YT
UT WOS:000398010600005
PM 28113103
DA 2022-11-30
ER

PT J
AU Campa, C
   Gallenga, CE
   Bolletta, E
   Perri, P
AF Campa, C.
   Gallenga, C. E.
   Bolletta, E.
   Perri, P.
TI The Role of Gene Therapy in the Treatment of Retinal Diseases: A Review
SO CURRENT GENE THERAPY
LA English
DT Review
DE Gene therapy; Eye; Retina; Viral vectors; Administration route;
   Distrophy
ID RECOMBINANT ADENOASSOCIATED VIRUS; EPITHELIUM-DERIVED FACTOR;
   ENDOTHELIAL GROWTH-FACTOR; DOMINANT RETINITIS-PIGMENTOSA; LONG-TERM
   TRANSDUCTION; X-LINKED RETINOSCHISIS; MOUSE MODEL; LENTIVIRAL VECTOR;
   IN-VIVO; OCULAR NEOVASCULARIZATION
AB Background: Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field.
   Objective: The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques.
   Method: Research was performed on PubMed, ClinicalTrials. gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications.
   Results: We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy.
   Conclusion: Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies.
C1 [Campa, C.; Gallenga, C. E.; Bolletta, E.; Perri, P.] S Anna Univ Hosp, Dept Ophthalmol, Via A Moro 8, I-44100 Ferrara, Italy.
C3 University of Ferrara; Arcispedale Sant'Anna
RP Campa, C (通讯作者)，S Anna Univ Hosp, Dept Ophthalmol, Via A Moro 8, I-44100 Ferrara, Italy.
EM claudio.campa@yahoo.com
OI Gallenga, Carla Enrica/0000-0002-7426-8603
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NR 190
TC 19
Z9 19
U1 0
U2 26
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1566-5232
EI 1875-5631
J9 CURR GENE THER
JI Curr. Gene Ther.
PY 2017
VL 17
IS 3
BP 194
EP 213
DI 10.2174/1566523217666171116170040
PG 20
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA FQ1CL
UT WOS:000418093600002
PM 29149824
DA 2022-11-30
ER

PT J
AU Li, LG
   Wei, W
   Zhang, YF
   Tu, G
   Zhang, YM
   Yang, J
   Xing, YQ
AF Li, Langen
   Wei, Wei
   Zhang, Yufeng
   Tu, Gerile
   Zhang, Yanmei
   Yang, Jia
   Xing, Yiqiao
TI SirT1 and STAT3 protect retinal pigmented epithelium cells against
   oxidative stress
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE signal transducer and activator of transcription 3; sirtuin 1; oxidative
   stress; age-related macular degeneration; ophthalmology
ID NF-KAPPA-B; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   ENDOTHELIAL-CELLS; ARPE-19 CELLS; UP-REGULATION; IN-VITRO; ACTIVATION;
   DAMAGE; RPE
AB It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments. However, whether or not there is crosstalk between these two molecules during oxidative stress, and what mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the protection of which may delay the process of age-related macular degeneration (AMD), has required further elucidation. The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress. The rates of proliferation and apoptosis, levels of intracellular reactive oxygen species and cell senescence of RPEs, induced by oxidants [ H2O2 and oxidized low density lipoprotein (oxLDL)], were evaluated. The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress. Further investigation indicated that SirT1 protected RPEs from oxidative stress-induced damage. Furthermore, gain-and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1. Additionally, the protective effects of STAT3 had no association with the modulation of cell senescence during oxidative stress. In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress. However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs. These results therefore suggested that there was an equilibrium mechanism between SirT1 and STAT3 against oxidative stress, meaning that an equilibrium mechanism is required to be considered when combined application of STAT3 and SirT1 were performed to treat AMD.
C1 [Li, Langen; Xing, Yiqiao] Wuhan Univ, Dept Ophthalmol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China.
   [Wei, Wei; Zhang, Yufeng; Tu, Gerile] Inner Mongolia Peoples Hosp, Dept Ophthalmol, Hohhot 010017, Inner Mongolia, Peoples R China.
   [Zhang, Yanmei] Inner Mongolia Peoples Hosp, Dept Neurol, Hohhot 010017, Inner Mongolia, Peoples R China.
   [Yang, Jia] Inner Mongolia Med Univ, Affiliated Hosp, Dept Neurol, Hohhot 010017, Inner Mongolia, Peoples R China.
C3 Wuhan University; Inner Mongolia Medical University
RP Xing, YQ (通讯作者)，Wuhan Univ, Dept Ophthalmol, Renmin Hosp, 99 Zhangzhidong Rd, Wuhan 430060, Hubei, Peoples R China.
EM yqxingwh@sohu.com
RI Zhang, Yufeng/GZL-1973-2022
FU Renmin Hospital of Wuhan University (Wuchang, China); Inner Mongolia
   People's Hospital (Hohhot, China)
FX The authors would like to thank Professor J Li (Beijing Institute of
   Microbiology and Epidemiology, Beijing, China) for valuable suggestions
   and advice. The present study was supported by the Renmin Hospital of
   Wuhan University (Wuchang, China) and Inner Mongolia People's Hospital
   (Hohhot, China).
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NR 43
TC 11
Z9 14
U1 1
U2 8
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 AUG
PY 2015
VL 12
IS 2
BP 2231
EP 2238
DI 10.3892/mmr.2015.3570
PG 8
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA CN8GR
UT WOS:000358678600087
PM 25847123
OA Bronze
DA 2022-11-30
ER

PT J
AU Told, R
   Schmidl, D
   Palkovits, S
   Boltz, A
   Gouya, G
   Wolzt, M
   Witkowska, KJ
   Popa-Cherecheanu, A
   Werkmeister, RM
   Garhofer, G
   Schmetterer, L
AF Told, Reinhard
   Schmidl, Doreen
   Palkovits, Stefan
   Boltz, Agnes
   Gouya, Ghazaleh
   Wolzt, Michael
   Witkowska, Katarzyna J.
   Popa-Cherecheanu, Alina
   Werkmeister, Rene M.
   Garhoefer, Gerhard
   Schmetterer, Leopold
TI Antioxidative Capacity of a Dietary Supplement on Retinal Hemodynamic
   Function in a Human Lipopolysaccharide (LPS) Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinal hemodynamic function; retinal blood flow; dietary supplements;
   endotoxin model; young healthy subjects; red blood cell flow; white
   blood cell flow
ID ENDOTOXIN-INDUCED MODEL; COMPLEMENT FACTOR-H; OCULAR BLOOD-FLOW;
   OXIDATIVE STRESS; HYPOREACTIVITY; HYPEROXIA; VELOCITY; TAURINE; RISK;
   VASOCONSTRICTION
AB PURPOSE. Beneficial effects of dietary supplements in age-related macular degeneration (AMD) are related to antioxidative properties. In the Age-Related Eye Disease Study 1 (AREDS 1), a reduced progression to late stage AMD was found using vitamin C, E, zinc, and beta-carotene. We showed previously that the AREDS 1 formulation restores the O-2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (lipopolysaccharide [LPS]) model.
   METHODS. We hypothesized that the abnormal O-2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (vitamin C, E, and zinc, lutein/zeaxanthin, selenium, taurine, Aronia extract, and omega-3 free fatty acids). A total of 43 healthy subjects was included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity, and flow to 100% O-2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14-day period of daily dietary supplement intake.
   RESULTS. The decrease in retinal arterial diameter, RBC velocity, and flow during 100% O-2 breathing was diminished significantly after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O-2 after LPS administration. This effect was significant for retinal arterial diameter (P = 0.03 between groups), and RBC velocity and flow (each P < 0.01 between groups).
   CONCLUSIONS. The present data indicate restoring of the RBC flow response to 100% O-2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology.
C1 [Told, Reinhard; Schmidl, Doreen; Palkovits, Stefan; Boltz, Agnes; Gouya, Ghazaleh; Wolzt, Michael; Witkowska, Katarzyna J.; Garhoefer, Gerhard; Schmetterer, Leopold] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria.
   [Told, Reinhard; Schmidl, Doreen; Boltz, Agnes; Werkmeister, Rene M.; Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
   [Popa-Cherecheanu, Alina] Emergency Univ Hosp, Dept Ophthalmol, Bucharest, Romania.
C3 Medical University of Vienna; Medical University of Vienna
RP Schmetterer, L (通讯作者)，Med Univ Vienna, Dept Clin Pharmacol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM leopold.schmetterer@meduniwien.ac.at
OI Schmidl, Doreen/0000-0001-5664-7768; Wolzt, Michael/0000-0001-6049-1890;
   Popa-Cherecheanu, Alina/0000-0003-4189-6571; Schmetterer,
   Leopold/0000-0002-7189-1707; Told, Reinhard/0000-0003-2046-7081
FU URSAPHARM, Saarbruecken, Germany
FX Supported by an unrestricted research grant from URSAPHARM,
   Saarbruecken, Germany.
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NR 48
TC 5
Z9 6
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 JAN
PY 2015
VL 56
IS 1
BP 403
EP 411
DI 10.1167/iovs.14-15581
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE0TQ
UT WOS:000351519800044
PM 25525163
DA 2022-11-30
ER

PT J
AU Feigl, B
   Zele, AJ
AF Feigl, Beatrix
   Zele, Andrew J.
TI Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion
   Cells in Retinal Disease
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Review
DE melanopsin-containing intrinsically photosensitive retinal ganglion
   cells; pupil light reflex; age-related macular degeneration; ipRGC; PIPR
ID ILLUMINATION PUPIL RESPONSE; AGE-RELATED MACULOPATHY; LIGHT REFLEX;
   SUPRACHIASMATIC NUCLEUS; ASSESSING ROD; CONE; PHOTORECEPTORS;
   PROJECTIONS; PHOTOENTRAINMENT; CONNECTIVITY
AB Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are a class of photoreceptors with established roles in non-image-forming processes. Their contributions to image-forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. Intrinsically photosensitive retinal ganglion cells can be divided into five ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioral marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma, and hereditary optic neuropathy. We briefly review the anatomical distributions, projections, and basic physiological mechanisms of ipRGCs and their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the PLR can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction.
C1 [Feigl, Beatrix; Zele, Andrew J.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Med Retina & Visual Sci Labs, Brisbane, Qld 4059, Australia.
C3 Queensland University of Technology (QUT)
RP Feigl, B (通讯作者)，Queensland Univ Technol, Inst Hlth & Biomed Innovat, Med Retina & Visual Sci Labs, 60 Musk Ave, Brisbane, Qld 4059, Australia.
EM b.feigl@qut.edu.au
OI Zele, Andrew/0000-0003-0291-9929; Feigl, Beatrix/0000-0001-7198-7373
FU Australian Research Council [ARC-DP140100333]
FX This work was supported by Australian Research Council Discovery
   Projects (ARC-DP140100333 to BF and AJZ). We thank Daniel S. Joyce,
   Michelle L. Maynard, and Prakash Adhikari for contributions to data
   collection.
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NR 80
TC 66
Z9 66
U1 1
U2 32
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 894
EP 903
DI 10.1097/OPX.0000000000000284
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN4KL
UT WOS:000340556500013
PM 24879087
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Diniz, B
   Ribeiro, RM
   Rodger, DC
   Maia, M
   Sadda, S
AF Diniz, Bruno
   Ribeiro, Ramiro M.
   Rodger, Damien C.
   Maia, Mauricio
   Sadda, SriniVas
TI Drusen detection by confocal aperture-modulated infrared scanning laser
   ophthalmoscopy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; VISUAL IMPAIRMENT; EYE
   DISEASE; LESIONS
AB Aim To evaluate the efficiency of drusen detection by scanning laser ophthalmoscopy (SLO) using various infrared confocal apertures and differential contrast (DC) strategies.
   Methods 11 eyes with non-neovascular age-related macular degeneration (AMD) underwent infrared imaging with a Nidek F-10 confocal SLO using multiple confocal apertures: central, ring, aperture on the right side (AR) and left side (AL), with and without use of the DC. A conventional colour fundus photograph was also obtained. Images were exported into a certified grading tool and all visible drusen were manually outlined by two graders. For each image type, the number of drusen and total drusen area were calculated, and the measurements obtained by the two graders were averaged. Intergrader reliability was evaluated, and paired t tests compared measurements between the various aperture/DC modes and the colour image.
   Results Agreement between graders was high (r=0.93-0.98). Drusen number values obtained with the AR (121.0, p=0.01) mode were higher than for the colour photographs (69.1). Area measurements were also significantly higher in the AR (1.93 mm(2); p=0.04) and AL modes (1.41 mm(2); p=0.03) when compared with the colour photographs (1.24 mm(2)). The addition of the DC did not seem to improve drusen detection compared with the unmodified infrared images.
   Conclusions In this pilot study, drusen number and area grades were significantly higher using the AR and AL in which the laterally scattered light is captured (retromode). Use of the lateral confocal aperture may highlight subclinical drusen and aid in monitoring disease progression and response to emerging non-neovascular AMD therapies.
C1 [Diniz, Bruno; Ribeiro, Ramiro M.; Rodger, Damien C.; Sadda, SriniVas] Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Diniz, Bruno; Maia, Mauricio] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil.
   [Ribeiro, Ramiro M.] Hosp Evangel Curitiba, Curitiba, Parana, Brazil.
   [Sadda, SriniVas] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
C3 Doheny Eye Institute; Universidade Federal de Sao Paulo (UNIFESP);
   University of Southern California
RP Diniz, B (通讯作者)，Doheny Eye Inst, Dept Ophthalmol, 1355 San Pablo St,DVRC 121, Los Angeles, CA 90033 USA.
EM dinizb@me.com
RI Rodger, Damien C./A-7866-2009; Maia, Mauricio/Z-1042-2019; Maia,
   Mauricio/I-5892-2015
OI Rodger, Damien C./0000-0002-1583-5946; Maia,
   Mauricio/0000-0002-7034-8091; Maia, Mauricio/0000-0002-7034-8091
FU NEI; Beckman Institute for Macular Research; CAPES Foundation (Brasilia,
   Brazil); NATIONAL EYE INSTITUTE [P30EY003040] Funding Source: NIH
   RePORTER
FX Supported in part by the NEI grant for basic research EY03040, the
   Beckman Institute for Macular Research, Research to Prevent Blindness, a
   Research to Prevent Blindness Physician Scientist Award, and the CAPES
   Foundation (Brasilia, Brazil). The authors thank Laurie Dustin for
   statistical analysis and Susan Clarke for text review.
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Z9 16
U1 0
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2013
VL 97
IS 3
BP 285
EP 290
DI 10.1136/bjophthalmol-2012-302575
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 092ZW
UT WOS:000315162500010
PM 23264545
DA 2022-11-30
ER

PT J
AU Schmitz-Valckenberg, S
   Lara, D
   Nizari, S
   Normando, EM
   Guo, L
   Wegener, AR
   Tufail, A
   Fitzke, FW
   Holz, FG
   Cordeiro, MF
AF Schmitz-Valckenberg, Steffen
   Lara, David
   Nizari, Shereen
   Normando, Eduardo M.
   Guo, Li
   Wegener, Alfred R.
   Tufail, Adnan
   Fitzke, Fred W.
   Holz, Frank G.
   Cordeiro, M. Francesca
TI Localisation and significance of in vivo near-infrared autofluorescent
   signal in retinal imaging
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID FUNDUS AUTOFLUORESCENCE; PIGMENT EPITHELIUM; GEOGRAPHIC ATROPHY;
   FLUORESCENCE; LIPOFUSCIN; PATTERNS; DEGENERATION
AB Aim To evaluate near-infrared (NIR) autofluorescence (AF) in patients with geographic atrophy (GA) secondary to age-related macular degeneration and to investigate the origin of the signal by in vivo and histological analysis in rats and in a human donor eye.
   Methods Confocal scanning laser ophthalmoscopy in vivo imaging, including blue (excitation: 488 nm, emission 500-700 nm) and NIR (excitation: 790 nm, emission >810 nm) AF was performed in 21 eyes of 18 GA patients. Pigmented and albino rats underwent with the same device both in vivo and post-mortem imaging. For the latter, cryostat prepared retinal cross-sections were imaged using an additional customised magnification lens. Finally, cross-sections of a 49-year old human donor eye were recorded.
   Results Atrophic areas in GA were characterised by low NIR AF intensities. In the junctional zone of atrophy, focal areas of increased intensity were seen which appeared to seldom correlate to blue AF findings. Confocal live scanning in pigmented rats identified the maximum of the NIR AF signal in the outer retina, with histological confirmation of the signal origin localised to the retinal pigment epithelium and sclera in both animals and human donor eye. No NIR AF was found in the retina of young non-pigmented rats.
   Discussion This study further underscores the assumption that melanin is the main source of NIR AF in the healthy retina. Increased NIR AF intensities in the junctional zone in GA may represent accumulation of melanolipofuscin, which may reflect disease activity and thus may allow for early identification of patients at high-risk of GA enlargement.
C1 [Schmitz-Valckenberg, Steffen; Wegener, Alfred R.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Schmitz-Valckenberg, Steffen; Lara, David; Nizari, Shereen; Normando, Eduardo M.; Guo, Li; Fitzke, Fred W.; Cordeiro, M. Francesca] UCL, Inst Ophthalmol, London, England.
   [Schmitz-Valckenberg, Steffen; Tufail, Adnan] Moorfields Eye Hosp, Med Retina Serv, London, England.
   [Lara, David] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, London, England.
   [Cordeiro, M. Francesca] Western Eye Hosp, London, England.
C3 University of Bonn; University of London; University College London;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; Imperial College London
RP Schmitz-Valckenberg, S (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM steffen.schmitz-valckenberg@ukb.uni-bonn.de
RI Lara, David/C-3242-2008
OI Cordeiro, Maria Francesca/0000-0001-8663-6525; Normando, Eduardo
   Maria/0000-0002-5774-8082; Guo, Li/0000-0002-3124-4505; Tufail,
   Adnan/0000-0001-6131-7640
FU Sharp-Eye Research Fellowship; European Commission [HPRN-CT-2002-00301];
   Foundation Fighting Blindness; Wellcome Trust
FX Supported by Sharp-Eye Research Fellowship, European Commission FP5,
   HPRN-CT-2002-00301, Foundation Fighting Blindness and Wellcome Trust.
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NR 28
TC 39
Z9 39
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 2011
VL 95
IS 8
BP 1134
EP 1139
DI 10.1136/bjo.2010.189498
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 793ST
UT WOS:000292844100020
PM 20881028
DA 2022-11-30
ER

PT J
AU Grey, AC
   Crouch, RK
   Koutalos, Y
   Schey, KL
   Ablonczy, Z
AF Grey, Angus C.
   Crouch, Rosalie K.
   Koutalos, Yiannis
   Schey, Kevin L.
   Ablonczy, Zsolt
TI Spatial Localization of A2E in the Retinal Pigment Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID LIPOFUSCIN FLUOROPHORE; TISSUE; PROTEINS; BRAIN; BIOSYNTHESIS;
   ACCUMULATION; FLUORESCENCE; PRECURSOR; OXIDATION; PRODUCTS
AB PURPOSE. Lipofuscin, a fluorescent lysosomal pigment made of lipophilic molecules, is associated with age-related pathophysiological processes in the retinal pigment epithelium (RPE). The best-characterized components of lipofuscin are A2E and its oxides, but a direct spatial correlation with lipofuscin has not previously been possible.
   METHODS. Lipofuscin fluorescence was mapped across the RPE of Abca4(-/-) and Sv129 (background strain control) mice. In the same tissues, they determined the spatial distribution of A2E and its oxides by using the high molecular specificity of matrix-assisted laser desorption-ionization imaging mass spectrometry (MALDI-IMS). The fluorescence and tandem mass spectra taken directly from the tissue were compared with those of synthetic A2E standard.
   RESULTS. In 2-month-old mice, A2E was found in the center of the retinal pigment epithelial tissue; with age, A2E increased across the tissue. With high levels of A2E, there was a marked correlation between A2E and lipofuscin, but with low levels this correlation diminished. The distributions of the oxidized forms of A2E were also determined. The amount of oxidation on A2E remained constant over 6 months, implying that A2E does not become increasingly oxidized with age in this time frame.
   CONCLUSIONS. This report is the first description of the spatial imaging of a specific retinoid from fresh tissue and the first description of a direct correlation of A2E with lipofuscin. The molecule-specific imaging of lipofuscin components from the RPE suggests wide applicability to other small molecules and pharmaceuticals for the molecular characterization and treatment of age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2011;52:3926-3933) DOI:10.1167/iovs.10-7020
C1 [Crouch, Rosalie K.; Koutalos, Yiannis; Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, Charleston, SC 29425 USA.
   [Grey, Angus C.] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand.
   [Schey, Kevin L.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
C3 Medical University of South Carolina; University of Auckland; Vanderbilt
   University
RP Ablonczy, Z (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, 167 Ashley Ave, Charleston, SC 29425 USA.
EM ablonczy@musc.edu
RI Grey, Angus/O-3473-2019; Grey, Gus/J-7024-2015
OI Grey, Angus/0000-0002-1540-1080; Grey, Gus/0000-0002-1540-1080
FU National Institutes of Health [R21 EY020661, R01 EY004939, R01 EY014850,
   R01 EY013462, R24 EY14793 (MUSC vision core)]; Foundation Fighting
   Blindness, Inc.; Research to Prevent Blindness; National Institutes of
   Health from National Center for Research Resources [C06 RR015455];
   NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY014850, R01EY013462, R21EY020661,
   R01EY019065, R01EY004939, R24EY014793] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grants R21 EY020661 (ZA,
   RKC), R01 EY004939 (RKC), R01 EY014850 (YK), R01 EY013462 (KS), and R24
   EY14793 (MUSC vision core); Foundation Fighting Blindness, Inc. (RKC);
   and unrestricted awards to the Department of Ophthalmology at the
   Medical University of South Carolina from Research to Prevent Blindness.
   RKC is a Research to Prevent Blindness Senior Scientific Investigator.
   This work was conducted in a facility constructed with support from
   National Institutes of Health Grant C06 RR015455 from the Extramural
   Research Facilities Program of the National Center for Research
   Resources.
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NR 39
TC 46
Z9 46
U1 0
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2011
VL 52
IS 7
BP 3926
EP 3933
DI 10.1167/iovs.10-7020
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800BP
UT WOS:000293332500002
PM 21357388
OA Green Published
DA 2022-11-30
ER

PT J
AU Shastry, BS
AF Shastry, Barkur S.
TI Common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes may
   not influence the intra-familial variability of X-linked juvenile
   retinoschisis
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE degeneration; gene; juvenile; retinoschisis
ID MUTATIONS; PHENOTYPE; GENOTYPE
AB X-linked juvenile retinoschisis (XLRS) is the leading cause of juvenile macular degeneration in males and is rare in females. Previous studies have shown that there is a marked intra- and inter-familial variation in disease severity and progression. This suggests that additional factors, such as genetic modifiers and environmental elements, influence disease severity. In order to understand the contribution of genetic modifiers, we aimed to ascertain whether common variants of the CFH, LOC 387715/ARMS2 and HTRA1 genes, which are major risk factors in age-related macular degeneration, contribute to the phenotypic variability of the XLRS disorder. Two unrelated XLRS families were selected, one harboring the missense mutation and the second a nonsense mutation in the RS gene. Both families exhibited variations in clinical phenotype. Genomic DNA from family members were analyzed for the above three genes using the polymerase chain reaction-based restriction fragment length polymorphism method. Our analyses revealed that both families were wild-type with respect to the LOC 387715/ARMS2 and HTRA1 genes. In one family (but not the other), the most severely affected and unaffected individuals were heterozygous for the CFH polymorphisms, while the less severely affected individual was wild-type. However, this alteration did not necessarily influence disease severity. Although we cannot completely rule out the role of the above genes in determining the phenotypic variability of the disorder, and though the statistical significance of the results could not be assessed due to the small scale of the study, it is unlikely that common polymorphisms of the CFH, LOC 387715/ARMS2 and HTRA1 genes serve as disease modifiers of the XLRS disorder.
C1 Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA.
C3 Oakland University
RP Shastry, BS (通讯作者)，Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA.
EM shastry@oakland.edu
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NR 16
TC 2
Z9 2
U1 0
U2 0
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 MAY-JUN
PY 2010
VL 3
IS 3
BP 469
EP 471
DI 10.3892/mmr_00000282
PG 3
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA 590TN
UT WOS:000277251000016
PM 21472264
OA Bronze
DA 2022-11-30
ER

PT J
AU Fu, L
   Garland, D
   Yang, Z
   Shukla, D
   Rajendran, A
   Pearson, E
   Stone, EM
   Zhang, K
   Pierce, EA
AF Fu, Li
   Garland, Donita
   Yang, Zhenglin
   Shukla, Dhananjay
   Rajendran, Anand
   Pearson, Erik
   Stone, Edwin M.
   Zhang, Kang
   Pierce, Eric A.
TI The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits
   in mice
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID COMPLEMENT FACTOR-H; PHOTORECEPTOR DEGENERATION; ABERRANT ACCUMULATION;
   RETINAL DEGENERATION; MALATTIA LEVENTINESE; MACULAR DEGENERATION; TISSUE
   INHIBITOR; BRUCHS MEMBRANE; TRANSGENIC MICE; ANIMAL-MODEL
AB Age-related macular degeneration (AMD) is the most common cause of vision loss in developed countries. A defining characteristic of this disorder is the accumulation of material between Bruch's membrane and the retinal pigment epithelium (RPE), first as microscopic basal deposits and later as clinically evident drusen. The pathogenesis of these deposits remains to be defined. Biochemical and genetic studies have suggested that inflammation and complement activation may play roles in AMD. Several lines of evidence also suggest that alterations to the extracellular matrix (ECM) of the RPE and choroid contribute to the development of AMD. The inherited macular degeneration Doyne honeycomb retinal dystrophy/Malattia Leventinese is thought to be caused by an R345W mutation in the EFEMP1 gene ( also called fibulin-3). The pathogenicity of this mutation has been questioned because all individuals identified to date with the R345W mutation have shared a common haplotype. We investigated the pathogenicity of this mutation in families with early-onset macular degeneration and by generating Efemp1-R345W knockin mice. Genetic studies show that one of the identified families with the R345W mutation has a novel haplotype. The mutant Efemp1-R345W mice develop deposits of material between Bruch's membrane and the RPE, which resemble basal deposits in patients with AMD. These basal deposits contain Efemp1 and Timp3, an Efemp1 interacting protein. Evidence of complement activation was detected in the RPE and Bruch's membrane of the mutant mice. These results confirm that the R345W mutation in EFEMP1 is pathogenic. Further, they suggest that alterations in the ECM may stimulate complement activation, demonstrating a potential connection between these two etiologic factors in macular degeneration.
C1 Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Stellar Chance Labs 305, Philadelphia, PA 19104 USA.
   Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Program Human Mol Biol, Salt Lake City, UT USA.
   Aravind Eye Hosp, Madurai, Tamil Nadu, India.
   Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India.
   Univ Iowa, Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA.
   Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Utah System of Higher
   Education; University of Utah; Utah System of Higher Education;
   University of Utah; Howard Hughes Medical Institute; University of Iowa;
   University of Iowa
RP Pierce, EA (通讯作者)，Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Stellar Chance Labs 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM epierce@mail.med.upenn.edu
RI Zhang, Kang/Y-2740-2019
OI Zhang, Kang/0000-0002-4549-1697; Stone, Edwin M./0000-0003-3343-4414;
   Pierce, Eric/0000-0002-2354-4102
FU NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000064] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY016822, R01EY014428, R01EY014448,
   P30EY014800] Funding Source: NIH RePORTER; NCRR NIH HHS [M01-RR00064]
   Funding Source: Medline; NEI NIH HHS [P30EY014800, R01EY14428,
   R01EY14448, R01-EY016822-02] Funding Source: Medline
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NR 53
TC 91
Z9 98
U1 1
U2 3
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 OCT 15
PY 2007
VL 16
IS 20
BP 2411
EP 2422
DI 10.1093/hmg/ddm198
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 227SP
UT WOS:000250678400003
PM 17666404
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Kanis, MJ
   Berendschot, TTJM
   van Norren, D
AF Kanis, Martijn J.
   Berendschot, Tos T. J. M.
   van Norren, Dirk
TI Influence of macular pigment and melanin on incident early AMD in a
   white population
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE AMD; macular pigment; melanin; antioxidant; fundus reflectance
ID AGE-RELATED MACULOPATHY; BLUE-MOUNTAINS EYE; BEAVER DAM EYE;
   RISK-FACTORS; CIGARETTE-SMOKING; VISUAL IMPAIRMENT; 5-YEAR INCIDENCE;
   OPTICAL-DENSITY; PRIMATE RETINAS; DEGENERATION
AB Background The protective effect of macular pigment (MP) and melanin against age-related macular degeneration (AMD) is still controversial from cross-sectional studies. In an attempt to clarify this issue, we performed a population-based longitudinal study.
   Methods MP optical density (MPOD) and melanin optical density (MOD) data were collected during the second follow-up phase of the Rotterdam Study in 1999 in a random subset of 435 participants. Data from 419 participants (98% white) was available for analysis. AMD diagnosis was based on standardized fundus photographs according to the International Classification System, and AMD cases were subdivided into five mutually exclusive stages. In the three follow-up phases, incident AMD (iAMD), defined as absence of any AMD at baseline and the presence of stage 2 or higher at follow-up, was determined. We used Cox regression analysis to study the effect of an assumedly stable MPOD and MOD on early iAMD.
   Results During a mean follow-up of 9.82 years, 13 male and 17 female participants developed early iAMD and two male participants late iAMD. Because only two participants developed late iAMD, we had to restrict our analyses to early iAMD. Cox regression analysis adjusted for age and gender showed no significant effect of MPOD [hazard ratio (HR) 0.37; 95% confidence interval (CI) 0.04, 3.57] and MOD (HR 0.56; 95% CI 0.09, 3.60) on early iAMD. Additional adjustment for smoking did not change these associations.
   Conclusions This unique but quantitatively limited material leads to the conclusion that no major protective effect of MPOD or MOD was seen on early iAMD.
C1 Univ Utrecht, Ctr Med, Dept Ophthalmol, NL-3508 GA Utrecht, Netherlands.
   Univ Maastricht, Eye Clin, NL-6202 AZ Maastricht, Netherlands.
C3 Utrecht University; Maastricht University
RP Kanis, MJ (通讯作者)，Univ Utrecht, Ctr Med, Dept Ophthalmol, AZU E03-136,POB 85500, NL-3508 GA Utrecht, Netherlands.
EM M.J.Kanis@umcutrecht.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X
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NR 55
TC 26
Z9 28
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2007
VL 245
IS 6
BP 767
EP 773
DI 10.1007/s00417-006-0478-0
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 169LP
UT WOS:000246594000001
PM 17119995
DA 2022-11-30
ER

PT J
AU Yang, M
   Tsui, MG
   Tsang, JKW
   Goit, RK
   Yao, KM
   So, KF
   Lam, WC
   Lo, ACY
AF Yang, Ming
   Tsui, Michelle Grace
   Tsang, Jessica Kwan Wun
   Goit, Rajesh Kumar
   Yao, Kwok-Ming
   So, Kwok-Fai
   Lam, Wai-Ching
   Lo, Amy Cheuk Yin
TI Involvement of FSP1-CoQ(10)-NADH and GSH-GPx-4 pathways in retinal
   pigment epithelium ferroptosis
SO CELL DEATH & DISEASE
LA English
DT Article
ID SODIUM IODATE; OXIDATIVE STRESS; MOUSE MODEL; CELL-DEATH;
   ULTRASTRUCTURE; DEGENERATION; SHEEP; IRON; THERAPY
AB Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative diseases. Glutathione peroxidase 4 (GPx-4) and ferroptosis suppressor protein 1 (FSP1) have been proposed to be two main regulators of ferroptosis in these diseases; yet, their roles in RPE degeneration remain elusive. Here, we report that both FSP1-CoQ(10)-NADH and GSH-GPx-4 pathways inhibit retinal ferroptosis in sodium iodate (SIO)-induced retinal degeneration pathologies in human primary RPE cells (HRPEpiC), ARPE-19 cell line, and mice. GSH-GPx-4 signaling was compromised after a toxic injury caused by SIO, which was aggravated by silencing GPx-4, and ferroptosis inhibitors robustly protected RPE cells from the challenge. Interestingly, while inhibition of FSP1 caused RPE cell death, which was aggravated by SIO exposure, overexpression of FSP1 effectively protected RPE cells from SIO-induced injury, accompanied by a significant down-regulation of CoQ(10)/NADH and lipid peroxidation. Most importantly, in vivo results showed that Ferrostatin-1 not only remarkably alleviated SIO-induced RPE cell loss, photoreceptor death, and retinal dysfunction but also significantly ameliorated the compromised GSH-GPx-4 and FSP1-CoQ(10)-NADH signaling in RPE cells isolated from SIO-induced RPE degeneration. These data describe a distinct role for ferroptosis in controlling RPE cell death in vitro and in vivo and may provide a new avenue for identifying treatment targets for RPE degeneration.
C1 [Yang, Ming; Tsang, Jessica Kwan Wun; Goit, Rajesh Kumar; So, Kwok-Fai; Lam, Wai-Ching; Lo, Amy Cheuk Yin] Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.
   [Tsui, Michelle Grace; Yao, Kwok-Ming] Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Fac Med, Hong Kong, Peoples R China.
   [So, Kwok-Fai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China.
   [So, Kwok-Fai] Jinan Univ, GHM Inst CNS Regenerat, Guangzhou, Peoples R China.
C3 University of Hong Kong; University of Hong Kong; University of Hong
   Kong; Jinan University
RP So, KF; Lam, WC; Lo, ACY (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Hong Kong, Peoples R China.; So, KF (通讯作者)，Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China.; So, KF (通讯作者)，Jinan Univ, GHM Inst CNS Regenerat, Guangzhou, Peoples R China.
EM hrmaskf@hku.hk; waichlam@hku.hk; amylo@hku.hk
RI Lo, Amy C. Y./C-1195-2009; /C-4457-2009
OI Lo, Amy C. Y./0000-0003-4239-6851; /0000-0002-5923-0869; So,
   Kwok-Fai/0000-0003-4039-4246; Yang, Ming/0000-0001-8600-4325; Tsang,
   Jessica Kwan Wun/0000-0002-4345-1990
FU Health and Medical Research Fund, the Food and Health Bureau, The
   Government of the Hong Kong Special Administrative Region [05163526,
   06171516]; General Research Fund, Research Grants Council; Government of
   the Hong Kong Special Administrative Region [17112919]; Albert
   Bing-Ching Young Professorship Endowment in Ophthalmology
FX The authors would like to thank Prof. Peter D. Adams (Sanford Burnham
   Prebys Medical Discovery Institute) for his generous guidance and
   suggestions on revision of this manuscript, the Faculty Core Facility,
   LKS Faculty of Medicine, The University of Hong Kong for providing the
   AI 680 machine and LSM 800 confocal microscopy and Electron Microscopy
   Unit, Queen Mary Hospital. This study was supported by Health and
   Medical Research Fund, the Food and Health Bureau, The Government of the
   Hong Kong Special Administrative Region (05163526, 06171516) and General
   Research Fund, Research Grants Council, The Government of the Hong Kong
   Special Administrative Region (17112919) to ACYL; Albert Bing-Ching
   Young Professorship Endowment in Ophthalmology to WCL.
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NR 51
TC 2
Z9 2
U1 11
U2 12
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAY 18
PY 2022
VL 13
IS 5
AR 468
DI 10.1038/s41419-022-04924-4
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 1I9OI
UT WOS:000797556400003
PM 35585057
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU DelGuidice, CE
   Ismaiel, OA
   Mylott, WR
   Halquist, MS
AF DelGuidice, Catherine E.
   Ismaiel, Omnia A.
   Mylott, William R., Jr.
   Halquist, Matthew S.
TI Optimization and method validation for the quantitative analysis of a
   monoclonal antibody and its related fab fragment in human plasma after
   intravitreal administration, using LC - MS/MS
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
   AND LIFE SCIENCES
LA English
DT Article
DE Bevacizumab; Ranibizumab; VEGF; LC-MS; MS; Bioanalytical method
   validation; Monoclonal antibody
AB As biologic based drugs become an increasingly important sector of the pharmaceutical industry, accurate and precision techniques for bioanalysis are required to support clinical trials and beyond. Ranibizumab, a fab therapeutic, is an FDA approved drug to treat wet age-related macular degeneration (AMD), as well as other eye related diseases. Ranibizumab's mAb counterpart, bevacizumab, is often also used off-label to treat wet AMD. Ranibizumab and bevacizumab target circulating VEGF-A in the eye, reducing unwanted angiogenesis. Since these drugs are designed for local intravitreal administration, concentration levels in human plasma are expected to be significantly lower compared to vitreous fluid concentrations, presenting bioanalytical challenges. However, this is important for assessment of drug toxicity. In this manuscript, we describe the development, optimization, and validation of an LC-MS/MS method designed for quantitative bioanalysis of ranibizumab and bevacizumab in human plasma following intravitreal administration. In order to fully develop this method, evaluations were conducted to optimize the conditions, including selection of the surrogate peptide by in-silico experiments, optimizations of the immunocapture, denaturation, reduction, alkylation, and digestion extraction steps, as well as optimization of the LC-MS/MS conditions, and evaluation of a dissociation step to determine if there was interference from VEGF or ADAs. Once the method was fully optimized, it was then validated, following the 2018 FDA guidance on bioanalytical method validations. This method is now available for use during clinical trials and precision medicine, for the quantitative evaluation of systemic exposure of ranibizumab or bevacizumab in human plasma after intravitreal administration, with a linear calibration range of 0.300-100 ng/mL.
C1 [DelGuidice, Catherine E.; Halquist, Matthew S.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA.
   [DelGuidice, Catherine E.; Ismaiel, Omnia A.; Mylott, William R., Jr.] PPD Labs, Richmond, VA USA.
   [Ismaiel, Omnia A.] Zagazig Univ, Dept Analyt Chem, Fac Pharm, Zagazig, Egypt.
C3 Virginia Commonwealth University; Egyptian Knowledge Bank (EKB); Zagazig
   University
RP DelGuidice, CE; Halquist, MS (通讯作者)，2244 Dabney Rd, Richmond, VA 23230 USA.
EM delguidicece@mymail.vcu.edu; halquistms@vcu.edu
OI Ismaiel, Omnia/0000-0003-3680-621X
FU Virginia Commonwealth University School of Pharmacy and Pharmaceutical
   Product Development's Bio-analytical Laboratories in Richmond, VA
FX This study was supported by Virginia Commonwealth University School of
   Pharmacy and Pharmaceutical Product Development's Bio-analytical
   Laboratories in Richmond, VA. The authors would like to thank them for
   both their financial support as well as their academic expertise.
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NR 26
TC 2
Z9 2
U1 2
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1570-0232
EI 1873-376X
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD FEB 1
PY 2021
VL 1164
DI 10.1016/j.jchromb.2020.122474
EA JAN 2021
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QR1GU
UT WOS:000624966000001
PM 33508760
DA 2022-11-30
ER

PT J
AU Ying, GS
   Maguire, MG
   Glynn, RJ
   Rosner, B
AF Ying, Gui-Shuang
   Maguire, Maureen G.
   Glynn, Robert J.
   Rosner, Bernard
TI Tutorial on Biostatistics: Longitudinal Analysis of Correlated
   Continuous Eye Data
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Linear regression models; correlated data; inter-eye correlation;
   longitudinal correlation; fixed effects model; mixed effects model;
   generalized estimating equations
ID MODELS
AB Purpose: To describe and demonstrate methods for analyzing longitudinal correlated eye data with a continuous outcome measure. Methods: We described fixed effects, mixed effects and generalized estimating equations (GEE) models, applied them to data from the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) and the Age-Related Eye Disease Study (AREDS). In CAPT (N = 1052), we assessed the effect of eye-specific laser treatment on change in visual acuity (VA). In the AREDS study, we evaluated effects of systemic supplement treatment among 1463 participants with AMD category 3. Results: In CAPT, the inter-eye correlations (0.33 to 0.53) and longitudinal correlations (0.31 to 0.88) varied. There was a small treatment effect on VA change (approximately one letter) at 24 months for all three models (p= .009 to 0.02). Model fit was better with the mixed effects model than the fixed effects model (p< .001). In AREDS, there was no significant treatment effect in all models (p> .55). Current smokers had a significantly greater VA decline than non-current smokers in the fixed effects model (p= .04) and the mixed effects model with random intercept (p= .0003), but marginally significant in the mixed effects model with random intercept and slope (p= .08), and GEE models (p= .054 to 0.07). The model fit was better with the fixed effects model than the mixed effects model (p< .0001). Conclusion: Longitudinal models using the eye as the unit of analysis can be implemented using available statistical software to account for both inter-eye and longitudinal correlations. Goodness-of-fit statistics may guide the selection of the most appropriate model.
C1 [Ying, Gui-Shuang; Maguire, Maureen G.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
   [Glynn, Robert J.; Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
   [Glynn, Robert J.; Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Harvard University;
   Brigham & Women's Hospital; Harvard University; Brigham & Women's
   Hospital
RP Ying, GS (通讯作者)，Univ Penn, Dept Ophthalmol, Perelman Sch Med, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
EM gsying@pennmedicine.upenn.edu
FU National Eye Institute, National Institutes of Health, Department of
   Health and Human Services [R01EY022445, P30 EY01583-26]
FX Supported by grants [R01EY022445 and P30 EY01583-26] from the National
   Eye Institute, National Institutes of Health, Department of Health and
   Human Services.
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NR 14
TC 7
Z9 7
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 JAN 2
PY 2021
VL 28
IS 1
BP 3
EP 20
DI 10.1080/09286586.2020.1786590
EA AUG 2020
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PH8YM
UT WOS:000555176800001
PM 32744149
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Shah, A
   Zhou, LX
   Abramoff, MD
   Wu, XD
AF Shah, Abhay
   Zhou, Leixin
   Abramoff, Michael D.
   Wu, Xiaodong
TI Multiple surface segmentation using convolution neural nets: application
   to retinal layer segmentation in OCT images
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID GRAPH; FRAMEWORK; MODEL
AB Automated segmentation of object boundaries or surfaces is crucial for quantitative image analysis in numerous biomedical applications. For example, retinal surfaces in optical coherence tomography (OCT) images play a vital role in the diagnosis and management of retinal diseases. Recently, graph based surface segmentation and contour modeling have been developed and optimized for various surface segmentation tasks. These methods require expertly designed, application specific transforms, including cost functions, constraints and model parameters. However, deep learning based methods are able to directly learn the model and features from training data. In this paper, we propose a convolutional neural network (CNN) based framework to segment multiple surfaces simultaneously. We demonstrate the application of the proposed method by training a single CNN to segment three retinal surfaces in two types of OCT images normal retinas and retinas affected by intermediate age-related macular degeneration (AMD). The trained network directly infers the segmentations for each B-scan in one pass. The proposed method was validated on 50 retinal OCT volumes (3000 B-scans) including 25 normal and 25 intermediate AMD subjects. Our experiment demonstrated statistically significant improvement of segmentation accuracy compared to the optimal surface segmentation method with convex priors (OSCS) and two deep learning based UNET methods for both types of data. The average computation time for segmenting an entire OCT volume (consisting of 60 B-scans each) for the proposed method was 12.3 seconds, demonstrating low computation costs and higher performance compared to the graph based optimal surface segmentation and UNET based methods. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Shah, Abhay; Zhou, Leixin; Abramoff, Michael D.; Wu, Xiaodong] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
   [Abramoff, Michael D.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
   [Abramoff, Michael D.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Wu, Xiaodong] Univ Iowa, Dept Radiat Oncol, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa; University of Iowa; University
   of Iowa
RP Wu, XD (通讯作者)，Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.; Wu, XD (通讯作者)，Univ Iowa, Dept Radiat Oncol, Iowa City, IA 52242 USA.
EM xiaodong-wu@uiowa.edu
RI Abramoff, Michael D/A-5836-2009
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NR 52
TC 62
Z9 64
U1 2
U2 25
PU Optica Publishing Group
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD SEP 1
PY 2018
VL 9
IS 9
BP 4509
EP 4526
DI 10.1364/BOE.9.004509
PG 18
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 GS1SZ
UT WOS:000443313700038
PM 30615698
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Foot, B
   MacEwen, C
AF Foot, B.
   MacEwen, C.
TI Surveillance of sight loss due to delay in ophthalmic treatment or
   review: frequency, cause and outcome
SO EYE
LA English
DT Review
ID AGE
AB Purpose To determine the frequency of patients suffering harm due to delay in ophthalmic care in the UK over a 12-month period.
   Methods Patients with deterioration in vision in at least one eye of 3 lines of Snellen acuity or 15 letters on ETDRS chart or deterioration in visual field deviation of 3 decibels due to health service initiated delay in review or care were ascertained through the BOSU using prospective active surveillance involving all UK consultant ophthalmologists. Demographic details, diagnosis, cause and length of delay, and vision loss were then sought by questionnaire.
   Results 238 cases reported between March 2015 and February 2016. 197/238 questionnaires were returned (83%). Twenty-eight reports were out of the study period or did not meet the case definition. Median age was 76 years (range: 1 to 98 years). Median delay was 22 weeks (range: 2 days to 5 1/2 years). Seventy two per cent experienced permanent reduction in visual acuity, 23% permanent deterioration in visual field. Main diagnoses were Glaucoma 42%, Age-related Macular Degeneration (AMD) 23%, and Diabetic Retinopathy (DR) 16%. Eighteen patients were eligible for Severely Sight Impaired (SSI) or Sight Impaired (SI) registration. Main causes were delayed follow-up (76%), lost referral (7%), and delayed treatment (8%).
   Conclusion Patients are suffering preventable harm due to health service initiated delay leading to permanently reduced vision. This is occurring in patients of all ages, but most consistently in those with chronic conditions. Delayed follow-up or review is the cause in the majority of cases indicating a lack of capacity within the hospital eye service.
C1 [Foot, B.] Royal Coll Ophthalmologists, British Ophthalmol Surveillance Unit, 18 Stephenson Way, London NW1 2HD, England.
   [MacEwen, C.] Ninewells Med Sch, Dept Ophthalmol, Dundee, Scotland.
C3 University of Dundee
RP Foot, B (通讯作者)，Royal Coll Ophthalmologists, British Ophthalmol Surveillance Unit, 18 Stephenson Way, London NW1 2HD, England.
EM Barny.Foot@rcophth.ac.uk
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NR 13
TC 74
Z9 74
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAY
PY 2017
VL 31
IS 5
BP 771
EP 775
DI 10.1038/eye.2017.1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EU4YF
UT WOS:000401036900017
PM 28128796
OA Green Submitted, Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Liew, G
   Lee, AY
   Zarranz-Ventura, J
   Stratton, I
   Bunce, C
   Chakravarthy, U
   Lee, CS
   Keane, PA
   Sim, DA
   Akerele, T
   McKibbin, M
   Downey, L
   Natha, S
   Bailey, C
   Khan, R
   Antcliff, R
   Armstrong, S
   Varma, A
   Kumar, V
   Tsaloumas, M
   Mandal, K
   Egan, C
   Johnston, RL
   Tufail, A
AF Liew, G.
   Lee, A. Y.
   Zarranz-Ventura, J.
   Stratton, I.
   Bunce, C.
   Chakravarthy, U.
   Lee, C. S.
   Keane, P. A.
   Sim, D. A.
   Akerele, T.
   McKibbin, M.
   Downey, L.
   Natha, S.
   Bailey, C.
   Khan, R.
   Antcliff, R.
   Armstrong, S.
   Varma, A.
   Kumar, V.
   Tsaloumas, M.
   Mandal, K.
   Egan, C.
   Johnston, R. L.
   Tufail, A.
CA UK AMD EMR Users Grp
TI The UK Neovascular AMD Database Report 3: inter-centre variation in
   visual acuity outcomes and establishing real-world measures of care
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB; BEVACIZUMAB; THERAPY; BLINDNESS;
   TRIAL; EYES
AB Purpose International variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intracountry inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and intercentre regional variations in outcomes for treatment of nAMD.
   Patients and methods Prospective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.
   Results Mean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.
   Conclusion There are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.
C1 [Liew, G.; Bunce, C.; Keane, P. A.; Sim, D. A.; Egan, C.; Tufail, A.] Moorfields Eye Hosp NHS Trust, 162 City Rd, London EC1V 2PD, England.
   [Liew, G.] Univ Sydney, Westmead Inst Med Res, Ctr Vis Res, Sydney, NSW, Australia.
   [Lee, A. Y.; Lee, C. S.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   [Zarranz-Ventura, J.; Stratton, I.; Johnston, R. L.] Gloucestershire Hosp NHS Fdn Trust, Gloucester, Glos, England.
   [Chakravarthy, U.] Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland.
   [Akerele, T.] Hinchingbrooke Hlth Care NHS Trust, Hinchingbrooke, England.
   [McKibbin, M.] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England.
   [Downey, L.] Hull & East Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England.
   [Natha, S.] Wrightington Wigan & Leigh NHS Fdn Trust, Wrightington, England.
   [Bailey, C.] Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England.
   [Khan, R.] Calderdale & Huddersfield NHS Fdn Trust, Calderdale, England.
   [Antcliff, R.] Royal United Hosp Bath NHS Trust, Bath, Avon, England.
   [Armstrong, S.] Countess Chester Hosp NHS Trust, Chester, Cheshire, England.
   [Varma, A.] Mid Yorkshire Hosp NHS Trust, Wakefield, England.
   [Kumar, V.] Wirral Univ Teaching Hosp NHS Fdn Trust, Wirral, Merseyside, England.
   [Tsaloumas, M.] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England.
   [Mandal, K.] Warrington & Halton Hosp NHS Fdn Trust, Warrington, Cheshire, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Sydney; Westmead Institute for
   Medical Research; University of Washington; University of Washington
   Seattle; Gloucestershire Hospitals NHS Foundation Trust; University of
   Leeds; University of Bristol; University of Birmingham
RP Tufail, A (通讯作者)，Moorfields Eye Hosp NHS Trust, 162 City Rd, London EC1V 2PD, England.
EM Adnan.Tufail@moorfields.nhs.uk
RI Zarranz-Ventura, Javier/AAB-5390-2021; stratton, irene/AAZ-3627-2020;
   Liew, Gerald/AAB-6870-2022; Keane, Pearse/AAE-5709-2019; Lee,
   Aaron/AAT-2839-2020
OI Zarranz-Ventura, Javier/0000-0003-2338-8143; stratton,
   irene/0000-0003-1172-7865; Keane, Pearse/0000-0002-9239-745X; McKibbin,
   Martin/0000-0003-4388-243X; Chakravarthy, Usha/0000-0002-2606-3734; Lee,
   Aaron/0000-0002-7452-1648; Bunce, Catey/0000-0002-0935-3713; Tufail,
   Adnan/0000-0001-6131-7640
FU Department of Health's NIHR Biomedical Research Centre for Ophthalmology
   at Moorfields Eye Hospital; UCL Institute of Ophthalmology; NIH/NEI
   grant [NIH/NEI K23EY024921]; NATIONAL EYE INSTITUTE [K23EY024921]
   Funding Source: NIH RePORTER; National Institute for Health Research
   [CS-2014-14-023, CL-2010-18-004] Funding Source: researchfish
FX This study group has received a proportion of its funding from the
   Department of Health's NIHR Biomedical Research Centre for Ophthalmology
   at Moorfields Eye Hospital and UCL Institute of Ophthalmology. CSL is
   funded by NIH/NEI grant NIH/NEI K23EY024921. The views expressed in the
   publication are those of the authors and not necessarily those of the
   Department of Health. The funding sources had no role in the design and
   conduct of the study; collection, management, analysis, and
   interpretation of the data; preparation, review, or approval of the
   manuscript; and decision to submit the manuscript for publication. We
   acknowledge Paul Donachie, Gloucestershire Hospitals NHS Foundation
   Trust, for providing statistical advice on the manuscript.
CR Arnold JJ, 2015, OPHTHALMOLOGY, V122, P1212, DOI 10.1016/j.ophtha.2015.02.009
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NR 20
TC 14
Z9 14
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD NOV
PY 2016
VL 30
IS 11
BP 1462
EP 1468
DI 10.1038/eye.2016.149
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EC4RD
UT WOS:000388120200013
PM 27419839
OA Bronze, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Gliem, M
   Muller, PL
   Birtel, J
   Hendig, D
   Holz, FG
   Issa, PC
AF Gliem, Martin
   Mueller, Philipp L.
   Birtel, Johannes
   Hendig, Doris
   Holz, Frank G.
   Issa, Peter Charbel
TI Frequency, Phenotypic Characteristics and Progression of Atrophy
   Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE pseudoxanthoma elasticum; Bruch's membrane; atrophy; phenotype;
   progression
ID OPTICAL COHERENCE TOMOGRAPHY; ONSET RETINAL DEGENERATION; SORSBY FUNDUS
   DYSTROPHY; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; GEOGRAPHIC
   ATROPHY; RETICULAR PSEUDODRUSEN; MORPHOMETRIC-ANALYSIS; PIGMENT
   EPITHELIUM; 5-YEAR INCIDENCE
AB PURPOSE. To characterize atrophy of the outer retina and the retinal pigment epithelium in patients with pseudoxanthoma elasticum (PXE).
   METHODS. In this retrospective cross-sectional study, the frequency and phenotypic characteristics of manifest atrophy were investigated in 276 eyes of 139 patients using color fundus photography, fundus autofluorescence (AF) imaging, and spectral domain optical coherence tomography. Progression rates of atrophy were quantified in eyes with longitudinal AF recordings.
   RESULTS. Atrophy was present in 90 eyes (32%; mean age, 60; range, 32-88 years). In 19 eyes (7%; mean age, 56; range, 37-77 years) atrophy occurred without any signs for an active or fibrotic choroidal neovascularization (CNV). The frequency of both, atrophy and CNV, increased with age. In those > 60 years of age, atrophy and/or CNV were almost universally present but varied considerably in severity. Eyes with emerging pure atrophy (n = 13, no signs of CNV) showed pattern dystrophy-like changes (100%), reticular pseudodrusen (82%), and reduced choroidal thickness. Advanced atrophy was multifocal, reached beyond the arcades, and was present nasal to the optic disc. The average expansion rate of atrophy was 3.3 +/- 1.3 and 1.6 +/- 1.1 mm(2)/year (mean +/- SD), in those without or with signs for CNV, respectively.
   CONCLUSIONS. Atrophy of the outer retina and the retinal pigment epithelium is a common finding in PXE patients characterized by early onset and fast progression with subsequent visual loss independent from CNV. This suggests that atrophy is the natural endpoint of Bruch's membrane disease. Phenotypic similarities with multifactorial geographic atrophy in age-related macular degeneration suggest common pathogenic pathways at the level of Bruch's membrane.
C1 [Gliem, Martin; Mueller, Philipp L.; Birtel, Johannes; Holz, Frank G.; Issa, Peter Charbel] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
   [Gliem, Martin; Mueller, Philipp L.; Birtel, Johannes; Holz, Frank G.; Issa, Peter Charbel] Univ Hosp Bonn, Ctr Rare Dis Bonn ZSEB, Bonn, Germany.
   [Hendig, Doris] Ruhr Univ Bochum, Univ Hosp, Ctr North Rhine Westphalia, Inst Lab & Transfus Med Heart & Diabet, Bad Oeynhausen, Germany.
C3 University of Bonn; University of Bonn; Ruhr University Bochum
RP Issa, PC (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM peter.issa@ukb.uni-bonn.de
RI Müller, Philipp L./P-3350-2019; Hendig, Doris/F-1112-2013; Issa, Peter
   Charbel/O-2580-2019; Issa, Peter Charbel/E-8935-2018
OI Hendig, Doris/0000-0002-3660-6923; Issa, Peter
   Charbel/0000-0002-0351-6673; Issa, Peter Charbel/0000-0002-0351-6673
FU BONFOR research program of the University of Bonn, Bonn, Germany;
   Heidelberg Engineering; ProRetina Deutschland, Aachen, Germany
FX Supported by the ProRetina Deutschland, Aachen, Germany and the BONFOR
   research program of the University of Bonn, Bonn, Germany. The
   Department of Ophthalmology, University of Bonn, receives research
   support from Heidelberg Engineering. The authors alone are responsible
   for the content and writing of the paper.
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NR 44
TC 39
Z9 39
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 JUN
PY 2016
VL 57
IS 7
BP 3323
EP 3330
DI 10.1167/iovs.16-19388
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DT8GA
UT WOS:000381726600050
PM 27367499
OA gold
DA 2022-11-30
ER

PT J
AU De Novelli, FJ
   Preti, RC
   Monteiro, MLR
   Pelayes, DE
   Nobrega, MJ
   Takahashi, WY
AF De Novelli, Fernando Jose
   Preti, Rony Carlos
   Ribeiro Monteiro, Mario Luiz
   Pelayes, David E.
   Nobrega, Mario Junqueira
   Takahashi, Walter Yukihiko
TI Autologous Internal Limiting Membrane Fragment Transplantation for
   Large, Chronic, and Refractory Macular Holes
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Macular hole; Refractory macular hole; Internal limiting membrane
   transplantation; Traumatic macular hole; Chronic macular hole; Secondary
   macular hole
ID OPTICAL COHERENCE TOMOGRAPHY; GAS TAMPONADE; SILICONE OIL; SURGERY;
   OUTCOMES; VITRECTOMY; SERUM; CLOSURE; TRIAL
AB Objective: To evaluate a technique of autologous internal limiting membrane (ILM) fragment transplantation for the treatment of large, chronic, and/or refractory macular holes (MH). Design: This was a 6-month prospective interventional case series. Method: Ten eyes of 10 patients with MH underwent pars plana vitretomy (PPV) and ILM peeling followed by transplantation of an autologous ILM fragment to the MH. Six patients had primary MH with an internal diameter greater than 500 mu m and a duration of more than 18 months, including 1 patient with nonproliferative diabetic retinopathy previously treated with panretinal photocoagulation. Four eyes with MH had previously been submitted to PPV (i.e. 1 for retinal detachment and 3 to attempt to close large MH). One of the latter also displayed juxtapapillary choroidal neovascularization due to age-related macular degeneration. The primary and secondary outcomes were MH closure and improvement of the best corrected visual acuity (BCVA), respectively. Results: Complete MH closure was achieved in all cases. A statistically significant improvement in the average BCVA was observed after 6 months of follow-up (p = 0.018; paired t test). The BCVA improved in 8 eyes (80%), and in 6 of those eyes it improved by = 15 letters. In 1 patient, the BCVA remained unchanged after the surgery, but the visual field reportedly improved. One patient experienced a slight worsening (0.16 logMAR). Two cases developed atrophy of the retinal pigment epithelium despite MH closure and BCVA improvement. Conclusion: Treatment with autologous ILM fragment transplantation seems to be an efficient alternative for large, chronic, and refractory MH. (C) 2015 S. Karger AG, Basel
C1 [De Novelli, Fernando Jose; Preti, Rony Carlos; Ribeiro Monteiro, Mario Luiz; Takahashi, Walter Yukihiko] Univ Sao Paulo, Sch Med, Div Ophthalmol, Sao Paulo, Brazil.
   [Nobrega, Mario Junqueira] Univ Regiao Joinville, Ophthalmol, Joinville, Brazil.
   [Pelayes, David E.] Univ Buenos Aires, Area Ophthalmol, Buenos Aires, DF, Argentina.
   [Pelayes, David E.] Maimonides Univ, Ctr Appl Res & High Complex Ophthalmol, Buenos Aires, DF, Argentina.
C3 Universidade de Sao Paulo; Universidade da Regiao de Joinville;
   University of Buenos Aires
RP De Novelli, FJ (通讯作者)，Rua Camborui 35, BR-89216222 Joinville, SC, Brazil.
EM fernando.novelli@gmail.com
RI Preti, Rony Carlos/N-4584-2013; MONTEIRO, MARIO L R/C-8891-2012
OI Preti, Rony Carlos/0000-0002-4395-6761; MONTEIRO, MARIO L
   R/0000-0002-7281-2791
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NR 24
TC 43
Z9 43
U1 1
U2 19
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2016
VL 55
IS 1
BP 45
EP 52
DI 10.1159/000440767
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CY3VE
UT WOS:000366337200006
PM 26569390
DA 2022-11-30
ER

PT J
AU Spaide, RF
AF Spaide, Richard F.
TI COLOCALIZATION OF PSEUDODRUSEN AND SUBRETINAL DRUSENOID DEPOSITS USING
   HIGH-DENSITY EN FACE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; drusen; pseudodrusen; subretinal
   drusenoid deposits
ID RETICULAR PSEUDODRUSEN; MACULAR DEGENERATION; PREVALENCE; IMAGE; MODEL;
   EYES
AB Purpose: To determine if pseudodrusen seen in fundus photography, particularly infrared scanning laser ophthalmoscopy, colocalize with subretinal drusenoid deposits imaged by optical coherence tomography.
   Methods: The patients were scanned with spectral domain optical coherence tomography having an A-scan spacing of 5.9 mu m and a B-scan spacing of 11 mu m. En face slabs were derived from this data set at distances 50 mu m to 90 mu m above the Bruch membrane reference plane to image the subretinal drusenoid deposit and also 6 mu m below Bruch membrane to image the level of the choriocapillaris. The corresponding infrared scanning laser ophthalmoscopy image was registered to the optical coherence tomography data by aligning the retinal blood vessels in each imaging modality through elastic warping.
   Results: All ten eyes of nine consecutively imaged patients showed a concordance between the pseudodrusen and the subretinal drusenoid deposit in every case. At their more internal aspects, subretinal drusenoid deposits were generally isolated foci of reflectivity and with decreasing distances above the reference plane appeared to become broader, reaching confluence with neighboring deposits analogous to a topographical map of mountains. In contrast to previous reports based on optical coherence tomography, and in keeping with histologic evaluation, no patient was seen to have widespread abnormalities in choriocapillaris imaging.
   Conclusion: This study, using an unprecedented scan density, showed that pseudodrusen appearance can be attributed to subretinal drusenoid deposits. The results of this study have widespread applicability in the understanding of age-related macular degeneration and the associations of the lesions with other structures in the outer retinal neurovascular unit.
C1 [Spaide, Richard F.] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Spaide, Richard F.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA.
C3 Vitreous Retina Macula Consultants of New York; Manhattan Eye Ear &
   Throat Hospital
RP Spaide, RF (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA.
EM rick.spaide@gmail.com
RI Spaide, Richard/ABD-7368-2020
FU Macula Foundation, New York, NY; Topcon Medical Systems
FX Supported in part by the Macula Foundation, New York, NY.; R. F. Spaide
   is a consultant to and received royalty payments from Topcon Medical
   Systems; and consultant to TEVA Pharmaceutical.
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NR 18
TC 28
Z9 28
U1 0
U2 1
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 2336
EP 2345
DI 10.1097/IAE.0000000000000377
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AU9KK
UT WOS:000345911300009
PM 25380066
DA 2022-11-30
ER

PT J
AU Rudolf, M
   Mohi, A
   Dettbarn, MC
   Miura, Y
   Aherrahrou, Z
   Ranjbar, M
   Mutus, B
   Knobloch, JKM
AF Rudolf, Martin
   Mohi, Armin
   Dettbarn, Marie C.
   Miura, Yoko
   Aherrahrou, Zouhair
   Ranjbar, Mahdy
   Mutus, Bulent
   Knobloch, Johannes K. M.
TI Detection of Esterified Cholesterol in Murine Bruch's Membrane
   Wholemounts With a Perfringolysin O-Based Cholesterol Marker
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE Bruch's membrane; lipids; aging; mouse model; cholesterol marker
ID ULTRASTRUCTURAL-CHANGES; DEPENDENT CYTOLYSINS; ACCUMULATION; BINDING;
   PROBE; MICE; AGE; DEGENERATION; MICRODOMAINS; PREVALENCE
AB PURPOSE. To investigate the effects of Bruch's membrane (BrM) neutral lipid deposition in mouse models and its significance to aging and age-related macular degeneration, it is essential to reliably detect small quantities of neutral lipids including esterified cholesterol (EC). In chorioretinal sections and BrM wholemounts, we tested a novel fluorescent cholesterol marker based on the bacterial toxin perfringolysin O (PFO) and compared results with those obtained with the classic cholesterol dye filipin.
   METHODS. An engineered plasmid containing the specific cholesterol binding domain (D4) of PFO fused to green fluorescent protein (GFP) was expressed in cultured E. coli, isolated, purified, and concentrated. A total of 150 BrM-choroid wholemounts and chorioretinal sections of 11- to 13-month-old ApoE(null) mice were prepared and stained with PFO/D4-GFP or filipin for EC. Samples were examined by epifluorescence microscopy.
   RESULTS. The fluorescence intensity of PFO/D4-GFP was strong, stable, and, if small quantities of EC were present, superior to filipin. In all specimens, we could sharply locate the PFO/D4GFP signal to BrM. A semiquantitative evaluation of BrM lipid deposition is possible by measuring PFO/D4-GFP fluorescence intensity.
   CONCLUSIONS. The use of PFO/D4-GFP allowed a robust and direct detection of EC in aged murine BrM. In wholemount samples, its strong and stable fluorescence facilitated a semiquantitative evaluation of BrM-EC content over a large area. The patterns of EC deposition in murine BrM wholemounts are comparable with findings in human BrM wholemounts. Perfringolysin O/D4-GFP could be an important tool for investigating the effects of BrM lipid deposition in mouse models.
C1 [Rudolf, Martin; Mohi, Armin; Dettbarn, Marie C.; Miura, Yoko; Ranjbar, Mahdy] Univ Lubeck, Dept Ophthalmol, D-23538 Lubeck, Germany.
   [Aherrahrou, Zouhair] Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany.
   [Mutus, Bulent] Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada.
   [Knobloch, Johannes K. M.] Univ Lubeck, Inst Med Microbiol & Hyg, D-23538 Lubeck, Germany.
C3 University of Lubeck; University of Lubeck; University of Windsor;
   University of Lubeck
RP Rudolf, M (通讯作者)，Univ Lubeck, Univ Eye Hosp Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM mirudolf@aol.com
RI Knobloch, Johannes K./D-6456-2011; Miura, Yoko/B-5588-2015
OI Knobloch, Johannes K./0000-0002-2591-6387; Aherrahrou,
   Zouhair/0000-0002-1241-8733
FU International Retinal Research Foundation (USA); Jackstadt-Stiftung
   (Germany); AMD-Forderpreis der Deutschen Ophthalmologischen Gesellschaft
   (Germany)
FX Supported by the International Retinal Research Foundation (USA),
   Jackstadt-Stiftung (Germany), and the AMD-Forderpreis der Deutschen
   Ophthalmologischen Gesellschaft 2009 (Germany).
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NR 34
TC 4
Z9 4
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 AUG
PY 2014
VL 55
IS 8
BP 4759
EP 4767
DI 10.1167/iovs.14-14311
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ9DV
UT WOS:000343145500010
PM 24985479
DA 2022-11-30
ER

PT J
AU Gliem, M
   Fimmers, R
   Muller, PL
   Brinkmann, CK
   Finger, RP
   Hendig, D
   Holz, FG
   Issa, PC
AF Gliem, Martin
   Fimmers, Rolf
   Mueller, Philipp L.
   Brinkmann, Christian K.
   Finger, Robert P.
   Hendig, Doris
   Holz, Frank G.
   Issa, Peter Charbel
TI Choroidal Changes Associated With Bruch Membrane Pathology in
   Pseudoxanthoma Elasticum
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; CENTRAL SEROUS CHORIORETINOPATHY; MACULAR
   DEGENERATION; MORPHOMETRIC-ANALYSIS; THICKNESS; EYES; UPDATE; ABCC6;
   CHORIOCAPILLARIS; REGION
AB PURPOSE: To investigate the impact of Bruch membrane pathology on the choroid in pseudoxanthoma elasticum (PXE).
   DESIGN: Monocenter cross-sectional prospective case series.
   METHODS: The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy, genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1); eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy only (Group 3). Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT).
   RESULTS: Compared to controls (331 mu m 24; mean 95% CI), mean subfoveal choroidal thickness in eyes of patients with PXE was significantly reduced within all 3 groups (Group 1: 243 mu m 29; Group 2: 184 mu m 28; Group 3: 104 mu m 28; P < 0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was largest close to the optic disc and approximated the level of controls toward the periphery. Within the PXE subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least reduction of choroidal thickness, while it was most pronounced in Group 3.
   CONCLUSIONS: The results indicate that changes of Bruch membrane can be associated with choroidal alterations, which are most pronounced in the presence of advanced disease. A role of Bruch membrane in choroidal homeostasis may reflect a possible contribution of Bruch membrane alterations to CNV and geographic atrophy development in age-related macular degeneration. (C) 2014 by Elsevier Inc. All rights reserved.
C1 [Gliem, Martin; Mueller, Philipp L.; Brinkmann, Christian K.; Finger, Robert P.; Holz, Frank G.; Issa, Peter Charbel] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Fimmers, Rolf] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany.
   [Finger, Robert P.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Hendig, Doris] Ruhr Univ Bochum, Univ Hosp, Ctr North Rhine Westphalia, Inst Lab & Transfus Med, Bad Oeynhausen, Germany.
C3 University of Bonn; University of Bonn; Centre for Eye Research
   Australia; Royal Victorian Eye & Ear Hospital; University of Melbourne;
   Ruhr University Bochum
RP Issa, PC (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM peter.issa@ukb.uni-bonn.de
RI Müller, Philipp L./P-3350-2019; Issa, Peter Charbel/E-8935-2018; Issa,
   Peter Charbel/O-2580-2019; Hendig, Doris/F-1112-2013
OI Issa, Peter Charbel/0000-0002-0351-6673; Issa, Peter
   Charbel/0000-0002-0351-6673; Hendig, Doris/0000-0002-3660-6923; Finger,
   Robert P/0000-0003-4253-7597
FU Pro Retina Deutschland, Aachen, Germany; BONFOR research program of the
   Faculty of Medicine, University of Bonn, Bonn, Germany [O.137.0018];
   National Health and Medical Research Council Centre for Clinical
   Research Excellence, Canberra, Australia [529923]
FX This work was supported by the Pro Retina Deutschland, Aachen, Germany;
   the BONFOR research program of the Faculty of Medicine, University of
   Bonn (grant #O.137.0018), Bonn, Germany; and the National Health and
   Medical Research Council Centre for Clinical Research Excellence grant
   529923, Canberra, Australia. The Department of Ophthalmology, University
   of Bonn, receives imaging devices from Heidelberg Engineering; the
   Centre for Eye Research Australia receives Operational Infrastructure
   Support from the Victorian Government. FGH is a consultant for
   Heidelberg Engineering; all other coauthors have no financial
   disclosures. Design and conduct of study (M.G., P.L.M., P.C.I.);
   Collection, management, analysis, and interpretation of data (M.G.,
   C.K.B., P.L.M., R.P.F., D.H., P.C.I.); Preparation of manuscript (M.G.,
   P.C.I.); Review and final approval of manuscript (M.G., C.K.B., P.L.M.,
   R.P.F., R.P.F., D.H., F.G.H., P.C.I.).
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NR 40
TC 24
Z9 24
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUL
PY 2014
VL 158
IS 1
BP 198
EP 207
DI 10.1016/j.ajo.2014.04.005
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AK0IY
UT WOS:000338097300027
PM 24727260
DA 2022-11-30
ER

PT J
AU Salinaro, AT
   Cornelius, C
   Koverech, G
   Koverech, A
   Scuto, M
   Lodato, F
   Fronte, V
   Muccilli, V
   Reibaldi, M
   Longo, A
   Uva, MG
   Calabrese, V
AF Salinaro, Angela Trovato
   Cornelius, Carolin
   Koverech, Guido
   Koverech, Angela
   Scuto, Maria
   Lodato, Francesca
   Fronte, Vincenzo
   Muccilli, Vera
   Reibaldi, Michele
   Longo, Antonio
   Uva, Maurizio G.
   Calabrese, Vittorio
TI Cellular stress response, redox status, and vitagenes in glaucoma: a
   systemic oxidant disorder linked to Alzheimer's disease
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE free radicals; stress response; vitagenes; hormesis; antioxidants
ID OXIDATIVE STRESS; OPTIC-NERVE; THIOREDOXIN SUPERFAMILY; PROTEINS;
   APOPTOSIS; SIRT1; DEGENERATION; DEPOSITION; SIRTUINS; HORMESIS
AB Amyloid deposits, constituted of amyloid beta (A beta) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer's, mild cognitive impairment and Parkinson's disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of A beta characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer's disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-soprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies.
C1 [Salinaro, Angela Trovato; Koverech, Guido; Koverech, Angela; Scuto, Maria; Lodato, Francesca; Fronte, Vincenzo; Muccilli, Vera; Calabrese, Vittorio] Univ Catania, Sch Med, Dept Biomed Sci, I-95100 Catania, Italy.
   [Cornelius, Carolin] Univ Catania, Sch Med, Dept Chem, I-95100 Catania, Italy.
   [Reibaldi, Michele; Longo, Antonio; Uva, Maurizio G.] Univ Catania, Sch Med, Dept Ophthalmol, I-95100 Catania, Italy.
C3 University of Catania; University of Catania; University of Catania
RP Calabrese, V (通讯作者)，Univ Catania, Sch Med, Dept Biomed Sci, Viale Andrea Doria 6, I-95100 Catania, Italy.
EM calabres@unict.it
RI Reibaldi, Michele/AAL-1113-2021; Muccilli, Vera/L-3644-2017; Longo,
   Antonio/AAC-6092-2022; MUCCILLI, Vera/AAC-7569-2022; Calabrese,
   Vittorio/AAC-8157-2021; Trovato Salinaro, Angela/AAC-1326-2022
OI Muccilli, Vera/0000-0002-6212-5154; MUCCILLI, Vera/0000-0002-6212-5154;
   Calabrese, Vittorio/0000-0002-0478-985X; TROVATO SALINARO,
   Angela/0000-0003-2377-858X; LONGO, Antonio/0000-0002-9525-1800;
   Reibaldi, Michele/0000-0003-1368-6729
FU MIUR, FIRB [RBRN07BMCT]
FX Work from the authors' laboratories was supported by grants from MIUR,
   FIRB RBRN07BMCT
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NR 48
TC 42
Z9 42
U1 0
U2 16
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD JUN 6
PY 2014
VL 5
AR 129
DI 10.3389/fphar.2014.00129
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AX7LR
UT WOS:000347098000001
PM 24936186
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Loughman, J
   Hewitt, C
   Judge, C
   Martin, L
   Moulds, C
   Davison, PA
AF Loughman, James
   Hewitt, Ciara
   Judge, Claire
   Martin, Louise
   Moulds, Claire
   Davison, Peter A.
TI Clinical applicability of the Macular Degeneration Detection Device
   (MDD-2): a novel photostress recovery measurement device
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE age-related macular degeneration; macula; MDD-2; photostress recovery
   time
ID VISUAL IMPAIRMENT; INTRAOCULAR STRAYLIGHT; CONTRAST SENSITIVITY; RETINAL
   FUNCTION; RANIBIZUMAB; RETINOPATHY; POPULATION; NYCTOMETRY; PREVALENCE;
   PIGMENT
AB Background Diseases affecting the macula, such as age-related macular degeneration (AMD), diabetic retinopathy and central serous retinopathy can result in impaired photostress recovery time (PSRT) despite normal visual acuity and fundoscopic appearance. The MDD-2 Macular Degeneration Detection Device is a novel flash photostress recovery device. In this study, we examine the repeatability of the MDD-2 in a normal population and its suitability for incorporation into routine clinical practice. Methods One hundred (60 female) subjects (mean age 35 +/- 8 years; range 18 to 66 years) were recruited to partake in this study. The photostress recovery time was measured using the MDD-2 on three occasions in the dominant eye and one final occasion in the non-dominant eye to assess measurement repeatability. All subjects were in good ocular health. Visual acuity and iris colour were recorded for each participant. Results Repeated measures analysis of variance revealed a statistically significant learning effect on intra-measurement repeatability (p < 0.01). Although paired t-test analysis revealed statistically significant differences between repeated measures both within and between eyes (p < 0.05 for all) the correlation between repeat measurements is statistically significant (p < 0.05 for all), and the coefficient of repeatability reaches clinically acceptable levels once the initial photostress recovery time, which demonstrated increased variability and latency compared to all subsequent measures, is excluded. Conclusion The MDD-2 provides highly repeatable measurements of photostress recovery time among young naive subjects, following verbal explanation of the task and only one practise' measurement. The measurement is also highly repeatable between eyes, providing a potential immediate clinical biomarker of ocular health.
C1 [Loughman, James; Hewitt, Ciara; Judge, Claire; Martin, Louise; Moulds, Claire; Davison, Peter A.] Dublin Inst Technol, Coll Sci & Hlth, Dept Optometry, Dublin, Ireland.
   [Loughman, James] Univ KwaZulu Natal, Fac Hlth Sci, African Vis Res Inst, Durban, South Africa.
C3 Technological University Dublin; University of Kwazulu Natal
RP Loughman, J (通讯作者)，Dublin Inst Technol, Coll Sci & Hlth, Dept Optometry, Dublin, Ireland.
EM james.loughman@dit.ie
OI Loughman, James/0000-0003-3130-8991
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NR 39
TC 4
Z9 4
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD MAY
PY 2013
VL 96
IS 3
BP 272
EP 277
DI 10.1111/j.1444-0938.2012.00813.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 140AQ
UT WOS:000318627000004
PM 23106424
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Granner, T
   Maloney, S
   Antecka, E
   Correa, JA
   Burnier, MN
AF Granner, Tamara
   Maloney, Shawn
   Antecka, Emilia
   Correa, Jose A.
   Burnier, Miguel N., Jr.
TI 3,4 dihydroxyphenyl ethanol reduces secretion of angiogenin in human
   retinal pigment epithelial cells
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PROLIFERATIVE DIABETIC-RETINOPATHY; GROWTH-FACTOR EXPRESSION; OLIVE OIL;
   MACULAR DEGENERATION; HYDROXYTYROSOL PROTECTS; ENDOTHELIAL-CELLS; COBALT
   CHLORIDE; IN-VITRO; BEVACIZUMAB; HYPOXIA
AB Background Age-related macular degeneration (AMD) is currently the leading cause of blindness in developed countries. Bevacizumab is a widely used anti-VEGF agent that is a commonly applied therapy for neovascular AMD; however, a consequence of bevacizumab therapy may be the activation of compensatory angiogenic signalling. Combination of bevacizumab with 3,4 dihydroxyphenyl ethanol (DPE) may attenuate this compensatory signalling. The goal of the study was to investigate this therapeutic option in a human retinal pigment epithelial cell line (ARPE-19).
   Methods ARPE-19 cells were incubated under both normoxic and hypoxic conditions. The cells were treated as follows: control, 100 mu M DPE, 0.25 mg/ml bevacizumab, the combination of DPE and bevacizumab. Media was harvested after 24 h for sandwich ELISA-based angiogenesis assays. The secretion of the following 10 pro-angiogenic cytokines was measured: angiogenin, ANG2, EGF, bFGF, HB-EGF, PDGF-BB, Leptin, PIGF, HGF, and VEGF-A.
   Results Treatment of ARPE-19 cells with bevacizumab significantly increased the secretion of angiogenin. Secretion of angiogenin and VEGF-A were significantly reduced following treatment with DPE under both normoxia and hypoxia. In addition, angiogenin secretion was significantly reduced following treatment with the combination of DPE and bevacizumab compared to bevacizumab alone.
   Conclusions Compensatory angiogenic signalling may occur in neovascular AMD following treatment with bevacizumab. Here we show that DPE, both alone and in combination with bevacizumab, can reduce the secretion of angiogenin, a cytokine that has been upregulated following treatment with bevacizumab in RPE cells. Therefore, DPE may represent a possible therapeutic agent to be used in combination with bevacizumab for the treatment of neovascular AMD.
C1 [Granner, Tamara; Maloney, Shawn; Antecka, Emilia; Burnier, Miguel N., Jr.] McGill Univ, Henry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2B4, Canada.
   [Correa, Jose A.] McGill Univ, Dept Math & Stat, Montreal, PQ H3A 2B4, Canada.
C3 McGill University; McGill University
RP Granner, T (通讯作者)，McGill Univ, Henry C Witelson Ocular Pathol Lab, 3775 Rue Univ,Room 216, Montreal, PQ H3A 2B4, Canada.
EM tamara.granner@mail.mcgill.ca
OI Burnier, Miguel/0000-0002-2335-7470
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NR 25
TC 11
Z9 11
U1 0
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2013
VL 97
IS 3
BP 371
EP 374
DI 10.1136/bjophthalmol-2012-302002
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 092ZW
UT WOS:000315162500026
PM 23292926
DA 2022-11-30
ER

PT J
AU Harms, NV
   Toris, CB
AF Harms, Nathan V.
   Toris, Carol B.
TI Current status of unoprostone for the management of glaucoma and the
   future of its use in the treatment of retinal disease
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE docosanoid; dry age-related macular degeneration; glaucoma; intraocular
   pressure; neuroprotection; ocular blood flow; ocular hypertension;
   prostaglandin; prostanoids; retinitis pigmentosa; unoprostone
ID OPTIC-NERVE HEAD; NORMAL-TENSION GLAUCOMA; HUMAN TRABECULAR MESHWORK;
   OPEN-ANGLE GLAUCOMA; PROSTAGLANDIN ANALOGS; ISOPROPYL UNOPROSTONE;
   INTRAOCULAR-PRESSURE; BLOOD-FLOW; TOPICAL UNOPROSTONE; OCULAR
   CIRCULATION
AB Introduction: Optic nerve and retinal diseases such as glaucoma, age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are significant public health concerns and have a momentous impact on patients' functional status and quality of life. These diseases are among the most common causes of visual impairment worldwide and account for billions of dollars in healthcare expenditures and lost productivity. The importance of adequate treatment of these conditions and the need for efficacious therapeutic drugs cannot be overstated. Unoprostone continues to be developed as a potential treatment for these debilitating diseases.
   Areas covered: This review provides background information on unoprostone isopropyl (unoprostone), a prostanoid and synthetic docosanoid approved for the treatment of open-angle glaucoma and ocular hypertension, and recapitulates safety and efficacy data as it relates to this indication. Additionally, this review describes potential new uses of unoprostone as therapy for dry AMD and RP. A literature search of peer-reviewed publications was performed utilizing PubMed. Searches were last updated on 10 September 2012.
   Expert opinion: Current data indicate that unoprostone does significantly lower intraocular pressure (IOP) and has a favorable safety and tolerability profile. However, the IOP-lowering effects of unoprostone do not compare with other commercially available prostanoids and it has the disadvantage of a twice-daily rather than once-daily dosing regimen. Nonetheless, recent data suggest that unoprostone may improve neuronal survival and increase ocular blood flow, indicating that it may have some value as a therapy for glaucoma, RP and dry AMD. Further studies are needed to confirm whether unoprostone provides any clinically significant advantage over the other commercially available prostanoids.
C1 [Harms, Nathan V.; Toris, Carol B.] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA.
C3 University of Nebraska System; University of Nebraska Medical Center
RP Toris, CB (通讯作者)，Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA.
EM ctoris@unmc.edu
FU Allergan; Alcon
FX CB Toris received funding for unrelated projects from Allergan and
   Alcon.
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NR 98
TC 8
Z9 8
U1 0
U2 9
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD JAN
PY 2013
VL 14
IS 1
BP 105
EP 113
DI 10.1517/14656566.2013.748038
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 059LC
UT WOS:000312705800011
PM 23199345
DA 2022-11-30
ER

PT J
AU Bhattacharya, S
   Chaum, E
   Johnson, DA
   Johnson, LR
AF Bhattacharya, Sujoy
   Chaum, Edward
   Johnson, Dianna A.
   Johnson, Leonard R.
TI Age-Related Susceptibility to Apoptosis in Human Retinal Pigment
   Epithelial Cells Is Triggered by Disruption of p53-Mdm2 Association
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID DOUBLE-STRAND BREAKS; HUMAN RPE CELLS; MACULAR DEGENERATION; DNA-DAMAGE;
   P53 ACETYLATION; CELLULAR SENESCENCE; OXIDATIVE STRESS; BETA-CATENIN;
   ACTIVATION; PROTEIN
AB PURPOSE. Relatively little is known about the contribution of p53/Mdm2 pathway in apoptosis of retinal pigment epithelial (RPE) cells or its possible link to dysfunction of aging RPE or to related blinding disorders such as age-related macular degeneration (AMD).
   METHODS. Age-associated changes in p53 activation were evaluated in primary RPE cultures from human donor eyes of various ages. Apoptosis was evaluated by activation of caspases and DNA fragmentation. Gene-specific small interfering RNA was used to knock down expression of p53.
   RESULTS. We observed that the basal rate of p53-dependent apoptosis increased in an age-dependent manner in human RPE. The age-dependent increase in apoptosis was linked to alterations in several aspects of the p53 pathway. p53 phosphorylation Ser15 was increased through the stimulation of ATM-Ser1981. p53 acetylation Lys379 was increased through the inhibition of SIRT1/2. These two posttranslational modifications of p53 blocked the sequestration of p53 by Mdm2, thus resulting in an increase in free p53 and of p53 stimulation of apoptosis through increased expression of PUMA (p53 upregulated modulator of apoptosis) and activation of caspase-3. Aged RPE also had reduced expression of antiapoptotic Bcl-2, which contributed to the increase in apoptosis. Of particular interest in these studies was that pharmacologic treatments to block p53 phosphorylation, acetylation, or expression were able to protect RPE cells from apoptosis.
   CONCLUSIONS. Our studies suggest that aging in the RPE leads to alterations of specific checkpoints in the apoptotic pathway, which may represent important molecular targets for the treatment of RPE-related aging disorders such as AMD. (Invest Ophthalmol Vis Sci. 2012;53:8350-8366) DOI:10.1167/iovs.12-10495
C1 [Bhattacharya, Sujoy; Johnson, Leonard R.] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
   [Chaum, Edward; Johnson, Dianna A.] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center
RP Bhattacharya, S (通讯作者)，Univ Tennessee, Ctr Hlth Sci, Dept Physiol, 894 Union Ave, Memphis, TN 38163 USA.
EM sbhatta3@uthsc.edu
RI Chaum, Edward/AAR-1512-2021; Bhattacharya, Sujoy/AAD-2253-2022
OI Bhattacharya, Sujoy/0000-0003-4443-9691; Chaum,
   Edward/0000-0003-3542-8376
FU William Webster Endowment Fund in Neurosciences Grant [R073037299];
   National Institute of Diabetes and Digestive and Kidney Diseases Grant
   [DK-16505]; Research to Prevent Blindness (New York, New York); Plough
   Foundation (Memphis, Tennessee); NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [R37DK016505, R01DK016505] Funding Source:
   NIH RePORTER
FX Supported by William Webster Endowment Fund in Neurosciences Grant
   R073037299, National Institute of Diabetes and Digestive and Kidney
   Diseases Grant DK-16505, an unrestricted grant from Research to Prevent
   Blindness (New York, New York), and the Plough Foundation (Memphis,
   Tennessee). The authors alone are responsible for the content and
   writing of the paper.
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NR 75
TC 53
Z9 55
U1 0
U2 16
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 2012
VL 53
IS 13
BP 8350
EP 8366
DI 10.1167/iovs.12-10495
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EX
UT WOS:000313056000059
PM 23139272
OA Green Published
DA 2022-11-30
ER

PT J
AU Kijlstra, A
   Tian, Y
   Kelly, ER
   Berendschot, TTJM
AF Kijlstra, Aize
   Tian, Yuan
   Kelly, Elton R.
   Berendschot, Tos T. J. M.
TI Lutein: More than just a filter for blue light
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Lutein; Macular pigment; Age related macular degeneration; SR-B1;
   Inflammation; Immune response
ID NF-KAPPA-B; PIGMENT OPTICAL-DENSITY; MACULAR PIGMENT; DIETARY LUTEIN;
   BETA-CAROTENE; INTESTINAL-ABSORPTION; OXIDATIVE STRESS; ZEAXANTHIN
   SUPPLEMENTATION; NUTRITIONAL MANIPULATION; LIPID-PEROXIDATION
AB Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Kijlstra, Aize] Univ Hosp Maastricht, Eye Res Inst Maastricht, Dept Ophthalmol, NL-6202 AZ Maastricht, Netherlands.
   [Kijlstra, Aize; Tian, Yuan; Kelly, Elton R.; Berendschot, Tos T. J. M.] Univ Eye Clin Maastricht, Maastricht, Netherlands.
   [Tian, Yuan] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China.
   [Tian, Yuan] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing, Peoples R China.
C3 Maastricht University; Maastricht University Medical Centre (MUMC);
   Maastricht University; Maastricht University Medical Centre (MUMC);
   Chongqing Medical University; Chongqing Medical University
RP Kijlstra, A (通讯作者)，Univ Hosp Maastricht, Eye Res Inst Maastricht, Dept Ophthalmol, POB 5800, NL-6202 AZ Maastricht, Netherlands.
EM aize.kijlstra@wur.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X; Tian, Yuan/0000-0002-9551-9061
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NR 140
TC 215
Z9 230
U1 6
U2 108
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 JUL
PY 2012
VL 31
IS 4
BP 303
EP 315
DI 10.1016/j.preteyeres.2012.03.002
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 960IF
UT WOS:000305380500002
PM 22465791
DA 2022-11-30
ER

PT J
AU McGreal, RS
   Kantorow, WL
   Chauss, DC
   Wei, JN
   Brennan, LA
   Kantorow, M
AF McGreal, Rebecca S.
   Kantorow, Wanda Lee
   Chauss, Daniel C.
   Wei, Jianning
   Brennan, Lisa A.
   Kantorow, Marc
TI alpha beta-crystallin/sHSP protects cytochrome c and mitochondrial
   function against oxidative stress in lens and retinal cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Cytochrome c; Oxidation; alpha B-crystallin; Small heat shock protein;
   Mitochondrion
ID HEAT-SHOCK-PROTEIN; SULFOXIDE-REDUCTASE-A; DESMIN-RELATED MYOPATHY;
   NON-LENTICULAR TISSUES; B-CRYSTALLIN; EPITHELIAL-CELLS; MOLECULAR
   CHAPERONE; PIGMENT EPITHELIUM; INDUCED APOPTOSIS; IN-VIVO
AB Background: alpha B-crystallin/sHSP protects cells against oxidative stress damage. Here, we mechanistically examined its ability to preserve mitochondrial function in lens and retinal cells and protect cytochrome c under oxidative stress conditions.
   Methods: alpha B-crystallin/sHSP was localized in human lens (HLE-B3) and retinal (ARPE-19) cells. alpha B-crystallin/sHSP was stably over-expressed and its ability to preserve mitochondrial membrane potential under oxidative stress conditions was monitored. Interactions between alpha B-crystallin/sHSP and cytochrome c were examined by fluorescent resonance energy transfer (FRET) and by co-immune precipitation. The ability of alpha B-crystallin/sHSP to protect cytochrome c against methionine-80 oxidation was monitored.
   Results: alpha B-crystallin/sHSP is present in the mitochondria of lens and retinal cells and is translocated to the mitochondria under oxidative conditions. alpha B-crystallin/sHSP specifically interacts with cytochrome c in vitro and in vivo and its overexpression preserves mitochondrial membrane potential under oxidative stress conditions. alpha B-crystallin/sHSP directly protects cytochrome c against oxidation.
   General significance: These data demonstrate that alpha B-crystallin/sHSP maintains lens and retinal cells under oxidative stress conditions at least in part by preserving mitochondrial function and by protecting cytochrome c against oxidation. Since oxidative stress and loss of mitochondrial function are associated with eye lens cataract and age-related macular degeneration, loss of these alpha B-crystallin/sHSP functions likely plays a key role in the development of these diseases.
   alpha B-crystallin/sHSP is expressed throughout the body and its ability to maintain mitochondrial function is likely important for the prevention of multiple degenerative diseases. (C) 2012 Elsevier B.V. All rights reserved.
C1 [McGreal, Rebecca S.; Kantorow, Wanda Lee; Chauss, Daniel C.; Wei, Jianning; Brennan, Lisa A.; Kantorow, Marc] Florida Atlantic Univ, Dept Biomed Sci, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA.
C3 State University System of Florida; Florida Atlantic University
RP Kantorow, M (通讯作者)，Florida Atlantic Univ, Dept Biomed Sci, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA.
EM mkantoro@fau.edu
OI Chauss, Daniel/0000-0002-8343-0860; McGreal, Rebecca/0000-0002-6069-1566
FU [EY13022]; NATIONAL EYE INSTITUTE [R01EY013022] Funding Source: NIH
   RePORTER
FX We wish to thank Mason Posner for alpha B-crystallin pET20-b(+) vector.
   This work was funded by the award grant EY13022 to MK.
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NR 79
TC 44
Z9 47
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUL
PY 2012
VL 1820
IS 7
BP 921
EP 930
DI 10.1016/j.bbagen.2012.04.004
PG 10
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 960CR
UT WOS:000305366100016
PM 22521365
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nag, TC
   Wadhwa, S
AF Nag, Tapas Chandra
   Wadhwa, Shashi
TI Ultrastructure of the human retina in aging and various pathological
   states
SO MICRON
LA English
DT Review
DE Retina; Photoreceptors; Aging; Pathology; Ultrastructure
ID MULLER GLIAL-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ROD OUTER SEGMENT;
   PARAPAPILLARY CHORIORETINAL ATROPHY; PIGMENT EPITHELIAL ABNORMALITIES;
   BASEMENT-MEMBRANE CHANGES; AGE-RELATED MACULOPATHY; BASAL LAMINAR
   DEPOSIT; MORPHOMETRIC-ANALYSIS; MACULAR DEGENERATION
AB Vision is hampered in aging and diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and glaucoma. This review collates the fine structural alterations of the human retina in aging and various pathological situations and their links to the disease pathogenesis. It transpires that most changes occur at the level of the retinal pigment epithelium -Bruch's membrane and the photoreceptor layer, causing visual problems to the sufferers. These changes include loss of normal, essential features of these cells and their gradual disappearance. It is important to understand in depth the selective vulnerability of this retinal region to alterations in aging and diseases. Evidence indicates that some of these changes may be mediated by the effects of oxidative stress, inflammation, and chronic light exposure. There are changes also in the inner retinal layers, wherein hypertension, auto-immunity, hypoxia and ischemia could play significant roles in disease pathogenesis. Results of extensive research utilizing animal models have broadened our idea about photoreceptor pathology. However, equivalent knowledge on various changes in aging human retina and in dystrophies that affect the macula is not complete. Since cone photoreceptor and ganglion cell death are a potential problem, it is imperative to know about the basic facts on how they are affected and the mechanisms involved in their death. Thus, prevention of cone and ganglion cell loss should be the target of choice. This review also highlights the significant role played by electron microscopy in understanding such ultrastructural changes and future strategies utilizing it and other techniques to fill some of the existing lacunae and advance our knowledge. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Nag, Tapas Chandra] All India Inst Med Sci, Dept Anat, Neurobiol Lab, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi
RP Nag, TC (通讯作者)，All India Inst Med Sci, Dept Anat, Neurobiol Lab, New Delhi 110029, India.
EM tapas_nag@yahoo.com
RI NAG, TAPAS CHANDRA/R-6285-2019
OI NAG, TAPAS CHANDRA/0000-0002-6962-0844
FU AIIMS [F.1-6-Para-Med/Acad]; Department of Biotechnology, Government of
   India [BT/PR10195/BRB/10/589/2007]
FX The study was carried out following the tenets of the Declaration of
   Helsinki and approved by the Institute research ethics committee (IHEC
   approval no. A-01: 02/05/2005; A-59/24.03. 2008 and As-207/2008). We
   appreciate the gestures of all relatives of the donors who provided with
   written consent for our use of the donor eyes in research. We thank the
   authorities of the National Eye Bank, especially to Prof. Radhika
   Tandon, Dr Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS for
   providing us the eyeballs as well as the donor history from time to time
   during this investigation. We also thank the anonymous reviewers for
   their constructive criticisms on our initial draft of the manuscript.
   Thanks are also due to all vision researchers who significantly
   contributed to this field, but whose papers could not be cited, which is
   inadvertent. The work was financially supported from the Institute
   research grant, AIIMS (F.1-6-Para-Med/Acad, 2002, 2004, 2006; TCN) and
   Department of Biotechnology, Government of India
   (BT/PR10195/BRB/10/589/2007; TCN). The electron microscope work was done
   at the Sophisticated Analytical Instrumentation Facility (DST), AIIMS.
   We are grateful to our staffs for their patience in carrying out this
   tedious job.
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NR 312
TC 64
Z9 66
U1 1
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-4328
J9 MICRON
JI Micron
PD JUL
PY 2012
VL 43
IS 7
BP 759
EP 781
DI 10.1016/j.micron.2012.01.011
PG 23
WC Microscopy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Microscopy
GA 945QG
UT WOS:000304290500001
PM 22445096
DA 2022-11-30
ER

PT J
AU Zheng, WC
   Reem, RE
   Omarova, S
   Huang, S
   DiPatre, PL
   Charvet, CD
   Curcio, CA
   Pikuleva, IA
AF Zheng, Wenchao
   Reem, Rachel E.
   Omarova, Saida
   Huang, Suber
   DiPatre, Pier Luigi
   Charvet, Casey D.
   Curcio, Christine A.
   Pikuleva, Irina A.
TI Spatial Distribution of the Pathways of Cholesterol Homeostasis in Human
   Retina
SO PLOS ONE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; OUTER SEGMENT MEMBRANES; AGE-RELATED
   MACULOPATHY; CENTRAL-NERVOUS-SYSTEM; SCAVENGER RECEPTOR BI; MACULAR
   DEGENERATION; IN-VIVO; VERTEBRATE RETINA; BRUCHS MEMBRANE; ACID
   SYNTHESIS
AB Background: The retina is a light-sensitive tissue lining the inner surface of the eye and one of the few human organs whose cholesterol maintenance is still poorly understood. Challenges in studies of the retina include its complex multicellular and multilayered structure; unique cell types and functions; and specific physico-chemical environment.
   Methodology/Principal Findings: We isolated specimens of the neural retina (NR) and underlying retinal pigment epithelium (RPE)/choroid from six deceased human donors and evaluated them for expression of genes and proteins representing the major pathways of cholesterol input, output and regulation. Eighty-four genes were studied by PCR array, 16 genes were assessed by quantitative real time PCR, and 13 proteins were characterized by immunohistochemistry. Cholesterol distribution among different retinal layers was analyzed as well by histochemical staining with filipin. Our major findings pertain to two adjacent retinal layers: the photoreceptor outer segments of NR and the RPE. We demonstrate that in the photoreceptor outer segments, cholesterol biosynthesis, catabolism and regulation via LXR and SREBP are weak or absent and cholesterol content is the lowest of all retinal layers. Cholesterol maintenance in the RPE is different, yet the gene expression also does not appear to be regulated by the SREBPs and varies significantly among different individuals.
   Conclusions/Significance: This comprehensive investigation provides important insights into the relationship and spatial distribution of different pathways of cholesterol input, output and regulation in the NR-RPE region. The data obtained are important for deciphering the putative link between cholesterol and age-related macular degeneration, a major cause of irreversible vision loss in the elderly.
C1 [Zheng, Wenchao; Reem, Rachel E.; Omarova, Saida; Huang, Suber; Charvet, Casey D.; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Huang, Suber] Univ Hosp, Cleveland, OH USA.
   [DiPatre, Pier Luigi] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 Case Western Reserve University; University Hospitals of Cleveland;
   University of Texas System; University of Texas Medical Branch
   Galveston; University of Alabama System; University of Alabama
   Birmingham
RP Zheng, WC (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM iap8@case.edu
OI Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health [EY018383, AG024336, EY06109, T32 EY07157,
   P30 EY11373]; Research to Prevent Blindness Foundation; Ohio Lions Eye
   Research Foundation; NATIONAL EYE INSTITUTE [P30EY011373, R01EY006109,
   T32EY007157, R01EY018383] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [K02AG024336] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants EY018383
   and AG024336 (IAP), EY06109 (CAC), T32 EY07157 (pre- and post-doctoral
   research training fellowships for CDC and RER, respectively), P30
   EY11373 (to support the Visual Sciences Research Center Core
   Facilities), Jules and Doris Stein Professorship from the Research to
   Prevent Blindness Foundation (IAP), the Ohio Lions Eye Research
   Foundation. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
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NR 74
TC 72
Z9 73
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 22
PY 2012
VL 7
IS 5
AR e37926
DI 10.1371/journal.pone.0037926
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 959VQ
UT WOS:000305345300084
PM 22629470
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Lichtlen, P
   Lam, TT
   Nork, TM
   Streit, T
   Urech, DM
AF Lichtlen, Peter
   Lam, Tim T.
   Nork, T. Michael
   Streit, Tim
   Urech, David M.
TI Relative Contribution of VEGF and TNF-alpha in the Cynomolgus
   Laser-Induced CNV Model: Comparing the Efficacy of Bevacizumab,
   Adalimumab, and ESBA105
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL GROWTH-FACTOR; SINGLE-CHAIN ANTIBODY;
   MACULAR DEGENERATION; RETINAL NEOVASCULARIZATION; INTRAVITREAL
   INFLIXIMAB; POSTERIOR SEGMENT; PHARMACOKINETICS; RANIBIZUMAB;
   ANTAGONISTS
AB PURPOSE. To compare the relative contribution of VEGF and TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in monkeys and to exploit the feasibility of topical use of suitable antibody fragments for the prevention of experimental CNV.
   METHODS. To induce experimental CNV, small high-energy laser spots were used to treat several areas of the macula in the retinas of cynomolgus monkeys according to previously published protocols. To prevent abnormalities, bevacizumab (a potent VEGF inhibitor) and adalimumab or ESBA105 (potent TNF-alpha inhibitors) were given by intravitreal injection 1 week before and 1 week and 3 weeks after laser treatment. ESBA105 was also applied topically in a separate group. Control animals were treated with either intravitreal or topical saline. Eyes were monitored by ophthalmic examination, color photography, and fluorescein angiography.
   RESULTS. Inhibition of VEGF by bevacizumab completely blocked the formation of CNV. Both TNF-alpha inhibitors also significantly reduced laser-induced CNV abnormalities after intravitreal administration. Most important, topical use of the anti-TNF-alpha single-chain antibody fragment ESBA105 also reduced the formation of CNV.
   CONCLUSIONS. TNF-alpha contributes to laser-induced CNV formation, and its inhibition can be a new therapeutic target for CNV. This study suggests TNF-alpha as another therapeutic target for the prevention and treatment of CNV and adds to the emerging clinical data suggesting the therapeutic value of TNF-alpha inhibitors in age-related macular degeneration (AMD). Further, this study shows that topical therapy with suitable antibody fragments has the potential of being introduced to retinal disease treatment regimens. (Invest Ophthalmol Vis Sci. 2010;51:4738-4745) DOI:10.1167/iovs.09-4890
C1 [Lichtlen, Peter; Urech, David M.] ESBA Tech, CH-8952 Schlieren, Switzerland.
   [Lam, Tim T.; Streit, Tim] Covance Labs Inc, Madison, WI USA.
   [Nork, T. Michael] Univ Wisconsin, Sch Med & Publ Hlth, Comparat Ophthalm Res Labs, Madison, WI USA.
C3 Covance; University of Wisconsin System; University of Wisconsin Madison
RP Urech, DM (通讯作者)，ESBA Tech, Wagistr 21, CH-8952 Schlieren, Switzerland.
EM david.urech@esbatech.com
OI Lam, Tim/0000-0003-2444-360X
FU ESBA Tech, an Alcon Biomedical Research Unit, Schlieren, Switzerland
FX Supported by ESBA Tech, an Alcon Biomedical Research Unit, Schlieren,
   Switzerland.
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NR 52
TC 64
Z9 84
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 2010
VL 51
IS 9
BP 4738
EP 4745
DI 10.1167/iovs.09-4890
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 645YS
UT WOS:000281502700052
PM 20393113
DA 2022-11-30
ER

PT J
AU Sainz-Gomez, C
   Fernandez-Robredo, P
   Salinas-Alaman, A
   Montanes, JM
   Berasategui, JME
   Guillen-Grima, F
   Ruiz-Moreno, JM
   Garcia-Layana, A
AF Sainz-Gomez, Carmen
   Fernandez-Robredo, Patricia
   Salinas-Alaman, Angel
   Moreno Montanes, Javier
   Escudero Berasategui, Jose Maria
   Guillen-Grima, Francisco
   Maria Ruiz-Moreno, Jose
   Garcia-Layana, Alfredo
TI Prevalence and causes of bilateral blindness and visual impairment among
   institutionalized elderly people in Pamplona, Spain
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Blindness; Causes; Institutionalized elderly; Prevalence; Visual
   impairment
ID NURSING-HOME RESIDENTS; SALISBURY EYE EVALUATION; BLUE-MOUNTAINS-EYE;
   VISION; POPULATION; ACUITY; AUSTRALIANS; BALTIMORE; DISEASE; SYSTEM
AB PURPOSE. To estimate the prevalence and causes of bilateral blindness and visual impairment in an urban institutionalized population aged 65 years and older.
   METHODS. A total of 392 nursing home residents completed a standardized eye examination, including measurement of visual acuity (VA), intraocular pressure, lens opacity grading, indirect ophthalmoscopy, and photography of the macular area. The major causes of vision loss identified for all participants were blindness and visual impairment.
   RESULTS. The average subject age was 82 years (65-97); women outnumbered men 263 to 129. The prevalence of bilateral blindness (VA >= 1.0 logarithm of the minimum angle of resolution [logMAR]) was 14.9% (43/288); the prevalence of visual impairment (VA >= 0.5 and 1.0 logMAR) was 31.9% (92/288). Blindness and visual impairment increased significantly with age (p<0.05), odds ratio (OR) 1.047 and 1.088, respectively. Cataract was the most common cause of bilateral blindness and visual impairment (27.9% and 44.6%, respectively) followed by pathologic myopia (23.3%) and age-related macular degeneration (AMD) (20.9%) for blindness, and by AMD (27.2%) and pathologic myopia (12%) for visual impairment. Fifty percent of subjects with visual loss had the potential for improved vision with medical or surgical intervention.
   CONCLUSIONS. Although the prevalences were high, these data are important since it is difficult for epidemiologic studies to include aged, institutionalized individuals, although their numbers are increasing. Recognition of the predominant causes of visual loss dependent on age is fundamental for early diagnosis and treatment of ocular diseases. Many cases of low vision can be treated with appropriate ophthalmologic care. (Eur J Ophthalmol 2010; 20: 442-50)
C1 [Sainz-Gomez, Carmen; Fernandez-Robredo, Patricia; Salinas-Alaman, Angel; Moreno Montanes, Javier; Garcia-Layana, Alfredo] Univ Navarra Clin, Dept Ophthalmol, Pamplona 31008, Spain.
   [Escudero Berasategui, Jose Maria] Hosp Navarra, Unidad Hospitalizac Domicilio, Pamplona, Spain.
   [Guillen-Grima, Francisco] Univ Navarra Clin, Div Prevent Med, Pamplona 31008, Spain.
   [Maria Ruiz-Moreno, Jose] Univ Castilla La Mancha, Dept Ophthalmol, Albacete, Spain.
C3 University of Navarra; Servicio Navarro de Salud - Osasunbidea;
   University of Navarra; Universidad de Castilla-La Mancha
RP Garcia-Layana, A (通讯作者)，Univ Navarra Clin, Dept Ophthalmol, Av Pio XII 36, Pamplona 31008, Spain.
EM aglayana@unav.es
RI Ruiz-Moreno, José M/E-4644-2016; Guillen-Grima, Francisco/H-3359-2012
OI Guillen-Grima, Francisco/0000-0001-9749-8076; Ruiz-Moreno, Jose
   M/0000-0001-9636-0788
FU Ortiz de Landazuri; ISCIII, Ministerio de Ciencia e Innovacion, Spain
   [RD07/0062]
FX The authors thank the participants and the staff of the Casa of
   Misericordia, Pamplona, for their roles in the study. This study was
   supported in part by unrestricted grants from the government of Navarra.
   The present work was partially funded by a Ortiz de Landazuri Grant and
   partially supported by RETICS (RD07/0062) from ISCIII, Ministerio de
   Ciencia e Innovacion, Spain".
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NR 26
TC 24
Z9 25
U1 0
U2 6
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 MAR-APR
PY 2010
VL 20
IS 2
BP 442
EP 450
DI 10.1177/112067211002000228
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 611ED
UT WOS:000278793200028
PM 20213621
DA 2022-11-30
ER

PT J
AU Costa, R
   Carneiro, A
   Rocha, A
   Pirraco, A
   Falcao, M
   Vasques, L
   Soares, R
AF Costa, Raquel
   Carneiro, Angela
   Rocha, Ana
   Pirraco, Ana
   Falcao, Manuel
   Vasques, Luisa
   Soares, Raquel
TI Bevacizumab and Ranibizumab on Microvascular Endothelial Cells: A
   Comparative Study
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE BEVACIZUMAB; RANIBIZUMAB; ANGIOGENESIS; ENDOTHELIAL CELLS; VEGF
   SIGNALING
ID GROWTH-FACTOR THERAPY; ANGIOGENESIS; PEGAPTANIB; DISEASE; MECHANISMS;
   LUCENTIS; MACUGEN
AB Given its broad effects in endothelium, vascular endothelial growth factor (VEGF) represents the primary rate-limiting step of angiogenesis. Therefore, VEGF targeting therapies were soon developed. Bevacizumab and ranibizumab are two of these therapeutic agents already in clinical use. Bevacizumab was first used for cancer treatment, whereas ranibizumab was designed to target choroidal neovascularization, the main cause of blindness in age-related macular degeneration. The present study aims to compare the multiple effects of bevacizumab and ranibizumab in human microvascular endothelial cells (HMECs). HMEC cultures were established and treated during 24 h with the anti-VEGF agents within the intravitreal-established concentration range or excipients. Analyses of VEGF content in cell media and VEGF receptor-2 (VEGFR-2) expression in cell lysates were performed. No cell cytotoxicity (MTS assay) was found in anti-VEGF-treated cultures at any concentration. Apoptosis (TUNEL assay) was significantly increased and cell proliferation (BrdU assay), migration (transwell assay) and assembly into vascular structures were significantly reduced by incubation with both agents at the two doses used. These findings were accompanied by a strong decrease in VEGF release, and in phosphorylated VEGFR-2 and Akt expression for both agents at the clinical concentration. Interestingly, phosphorylated Erk was only significantly reduced upon bevacizumab treatment. In addition, proliferation was more affected by ranibizumab, whereas migration, capillary formation, and phosphorylated VEGFR2 expression were significantly reduced by bevacizumab as compared to ranibizumab. Therefore, although both agents presented anti-angiogenic actions, distinct effects were exerted by the two molecules in HMEC. These findings suggest that a careful confirmation of these effects in clinical settings is mandatory. J. Cell. Biochem. 108: 1410-1417, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Costa, Raquel; Rocha, Ana; Pirraco, Ana; Vasques, Luisa; Soares, Raquel] Univ Porto, Fac Med, Dept Biochem, FCT U38, P-4200319 Oporto, Portugal.
   [Carneiro, Angela; Falcao, Manuel] Univ Porto, Sao Joao Hosp, Fac Med, Dept Ophthalmol, P-4200319 Oporto, Portugal.
C3 Universidade do Porto; Sao Joao Hospital; Universidade do Porto
RP Soares, R (通讯作者)，Univ Porto, Fac Med, Dept Biochem, FCT U38, Al Prof Hernani Monteiro, P-4200319 Oporto, Portugal.
EM raqsoa@med.up.pt
RI Soares, Raquel/L-2349-2013; Costa, Raquel/C-2045-2012; Carneiro,
   Angela/N-9680-2013; Falcao/AAQ-8509-2020
OI Soares, Raquel/0000-0002-9157-5541; Carneiro,
   Angela/0000-0002-3370-7243; Falcao/0000-0003-4718-0910; Costa,
   Raquel/0000-0002-9245-4565
FU FCT [SFRH/BD/36658/2007, PTDC/EME-PME/70155/2006]; European Advisory
   Board (ERAB) [EA0641]
FX This work was supported by FCT (SFRH/BD/36658/2007 and
   PTDC/EME-PME/70155/2006), and grants from European Advisory Board (ERAB)
   (EA0641). The authors would also like to thank Professor Joao Nuno
   Moreira, Center for Neurosciences and Cell Biology, Coimbra University,
   Portugal) for providing the cell cultures.
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NR 27
TC 34
Z9 35
U1 0
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD DEC 15
PY 2009
VL 108
IS 6
BP 1410
EP 1417
DI 10.1002/jcb.22378
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 531FU
UT WOS:000272649900018
PM 19859900
DA 2022-11-30
ER

PT J
AU Kurz, T
   Karlsson, M
   Brunk, UT
   Nilsson, SE
   Frennesson, C
AF Kurz, Tino
   Karlsson, Markus
   Brunk, Ulf T.
   Nilsson, Sven Erik
   Frennesson, Christina
TI ARPE-19 retinal pigment epithelial cells are highly resistant to
   oxidative stress and exercise strict control over their lysosomal
   redox-active iron
SO AUTOPHAGY
LA English
DT Article
DE age-related macular degeneration; hydrogen peroxide; iron; iron
   chelation; lipofuscin; lysosomal stability; lysosomes; macrophage;
   oxidative stress; retinal pigment epithelial cells
ID INDUCED DNA-DAMAGE; CHAPERONE-MEDIATED AUTOPHAGY; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; LIPOFUSCIN ACCUMULATION;
   INTRALYSOSOMAL IRON; APOPTOSIS; DESTABILIZATION; PREVALENCE; MECHANISMS
AB Normal retinal pigment epithelial (RPE) cells are postmitotic, long-lived and basically not replaced. Daily, they phagocytose substantial amounts of lipid-rich material (photoreceptor outer segment discs), and they do so in the most oxygenated part of the body-the retina. One would imagine that this state of affairs should be associated with a rapid formation of the age pigment lipofuscin (LF). However, LF accumulation is slow and reaches significant amounts only late in life when, if substantial, it often coincides with or causes age-related macular degeneration. LF formation occurs inside the lysosomal compartment as a result of iron-catalyzed peroxidation and polymerization. This process requires phagocytosed or autophagocytosed material under degradation, but also the presence of redox-active low mass iron and hydrogen peroxide. To gain some information on how RPE cells are able to evade LF formation, we investigated the response of immortalized human RPE cells (ARPE-19) to oxidative stress with/without the protection of a strong iron-chelator. The cells were found to be extremely resistant to hydrogen peroxide-induced lysosomal rupture and ensuing cell death. This marked resistance to oxidative stress was not explained by enhanced degradation of hydrogen peroxide, but to a certain extent further increased by the potent lipophilic iron chelator STH. The cells were also able to survive, and even replicate, at high concentrations of SIH and showed a high degree of basal autophagic flux. We hypothesize that RPE cells have a highly developed capacity to keep lysosomal iron in a nonredox-active form, perhaps by pronounced autophagy of iron-binding proteins in combination with an ability to rapidly relocate low mass iron from the lysosomal compartment.
C1 [Kurz, Tino; Brunk, Ulf T.] Linkoping Univ, Fac Hlth Sci, Div Pharmacol, Linkoping, Sweden.
   [Karlsson, Markus; Nilsson, Sven Erik; Frennesson, Christina] Linkoping Univ, Fac Hlth Sci, Div Ophthalmol, Linkoping, Sweden.
C3 Linkoping University; Linkoping University
RP Kurz, T (通讯作者)，Linkoping Univ Hosp, Fac Hlth Sci, Dept Pharmacol, S-58185 Linkoping, Ostergotland, Sweden.
EM tino.kurz@imv.liu.se
OI Karlsson, Markus/0000-0003-1183-2526
FU Crown Princess Margareta's Foundation; Edvin Jordan Foundation;
   Linkoping University Hospital Research Fund (ALF)
FX The productive discussions with Professor John W, Eaton, University of
   Louisville, Louisville Kentucky, several very helpful suggestions by the
   editors and reviewers, the excellent linguistic editing by Stephen
   Hampson, and 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) are gratefully acknowledged.
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NR 47
TC 52
Z9 52
U1 1
U2 5
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 MAY 16
PY 2009
VL 5
IS 4
BP 494
EP 501
DI 10.4161/auto.5.4.7961
PG 8
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 446JW
UT WOS:000266118900007
PM 19223767
OA Bronze
DA 2022-11-30
ER

PT J
AU Kim, YH
   He, S
   Kase, S
   Kitamura, M
   Ryan, SJ
   Hinton, DR
AF Kim, Yeong Hoon
   He, Shikun
   Kase, Satoru
   Kitamura, Mizuki
   Ryan, Stephen J.
   Hinton, David R.
TI Regulated secretion of complement factor H by RPE and its role in RPE
   migration
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE AMD; Complement factor H; Migration; Retinal pigment epithelium;
   Interferon-gamma
ID PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; INTERFERON-GAMMA; DRUSEN
   FORMATION; GLOMERULONEPHRITIS; PATHOGENESIS; INFLAMMATION; ACTIVATION
AB Variants in the gene for complement factor H (CFH) have been implicated as a major risk factor for the development of age-related macular degeneration (AMD). Little is known, however, about the factors regulating local expression and secretion of CFH by retinal pigment epithelial cells (RPE).
   Cultured human early passage RPE cells, highly differentiated, polarized human RPE cultures, and bovine RPE explants were incubated in the presence or absence of recombinant human or bovine interferon-gamma (IFN-gamma; 25 ng/ml). CFH expression in cell lysates, and secretion into culture supernatants were examined by Western blot. CHF expression and localization was analyzed by confocal microscopy. Migration assay was performed in a modified Boyden chamber with early passage human RPE cells after stimulation with recombinant CFH protein (1-100 ng/ml).
   CFH was expressed in the cell lysates of RPE cells, and this expression was significantly upregulated by IFN-gamma. Immunoreactivity for CFH was detected in RPE cells of bovine explants and highly differentiated human RPE monolayers, and the level of immunoreactivity increased after IFN-gamma stimulation. Confocal microscopy revealed that CFH was predominantly localized in the apical cytoplasm of polarized human RPE. Western blot confirmed that IFN-gamma increased CFH secretion into RPE supernatants. Dose-dependent RPE cell chemotactic migration was induced by CFH.
   IFN-gamma promotes CFH expression in the apical compartment of RPE cells and increases secretion of CFH into RPE culture supernatants. Furthermore, CFH promotes chemotactic migration of RPE. This study suggests that interactions between CFH and IFN-gamma have the potential to play a role in the pathogenesis of AMD.
C1 [He, Shikun; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
   [Kim, Yeong Hoon; He, Shikun; Ryan, Stephen J.; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Kim, Yeong Hoon; He, Shikun; Kase, Satoru; Kitamura, Mizuki; Ryan, Stephen J.; Hinton, David R.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
C3 University of Southern California; University of Southern California;
   Doheny Eye Institute; University of Southern California
RP Hinton, DR (通讯作者)，Univ So Calif, Keck Sch Med, Dept Pathol, 1355 San Pablo St,DVRC213, Los Angeles, CA 90033 USA.
EM dhinton@hsc.usc.edu
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768
FU Arnold and Mabel Beckman Foundation; National Institutes for Health
   [EY01545, EY03040]; NATIONAL EYE INSTITUTE [R01EY001545, P30EY003040]
   Funding Source: NIH RePORTER
FX This work was supported by the Arnold and Mabel Beckman Foundation and
   by National Institutes for Health grant EY01545 and core grant EY03040.
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NR 41
TC 51
Z9 53
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 MAY
PY 2009
VL 247
IS 5
BP 651
EP 659
DI 10.1007/s00417-009-1049-y
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 428NQ
UT WOS:000264855600010
PM 19214553
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhou, H
   Liu, JRY
   Laiginhas, R
   Zhang, QQ
   Cheng, YX
   Zhang, Y
   Shi, YY
   Shen, MX
   Gregori, G
   Rosenfeld, PJ
   Wang, RK
AF Zhou, Hao
   Liu, Jeremy
   Laiginhas, Rita
   Zhang, Qinqin
   Cheng, Yuxuan
   Zhang, Yi
   Shi, Yingying
   Shen, Mengxi
   Gregori, Giovanni
   Rosenfeld, Philip J.
   Wang, Ruikang K.
TI Depth-resolved visualization and automated quantification of
   hyperreflective foci on OCT scans using optical attenuation coefficients
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; COHERENCE TOMOGRAPHY; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; SEGMENTATION; PROGRESSION; CHORIOCAPILLARIS;
   THICKNESS
AB An automated depth-resolved algorithm using optical attenuation coefficients (OACs) was developed to visualize, localize, and quantify hyperreflective foci (HRF) seen on OCT imaging that are associated with macular hyperpigmentation and represent an increased risk of disease progression in age related macular degeneration. To achieve this, we first transformed the OCT scans to linear representation, which were then contrasted by OACs. HRF were visualized and localized within the entire scan by differentiating HRF within the retina from HRF along the retinal pigment epithelium (RPE). The total pigment burden was quantified using the en face sum projection of an OAC slab between the inner limiting membrane (ILM) to Bruch's membrane (BM). The manual total pigment burden measurements were also obtained by combining manual outlines of HRF in the B-scans with the total area of hypotransmission defects outlined on sub-RPE slabs, which was used as the reference to compare with those obtained from the automated algorithm. 6x6 mm swept-source OCT scans were collected from a total of 49 eyes from 42 patients with macular HRF. We demonstrate that the algorithm was able to automatically distinguish between HRF within the retina and HRF along the RPE. In 24 test eyes, the total pigment burden measurements by the automated algorithm were compared with measurements obtained from manual segmentations. A significant correlation was found between the total pigment area measurements from the automated and manual segmentations (P < 0.001). The proposed automated algorithm based on OACs should be useful in studying eye diseases involving HRF.(c) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
C1 [Zhou, Hao; Zhang, Qinqin; Cheng, Yuxuan; Zhang, Yi; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98105 USA.
   [Liu, Jeremy; Laiginhas, Rita; Shi, Yingying; Shen, Mengxi; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Bascom Palmer Eye Inst, Dept Ophthalmol, Miller Sch Med, Miami, FL 33136 USA.
   [Wang, Ruikang K.] Univ Washington, Karalis Johnson Retina Ctr, Dept Ophthalmol, Seattle, WA 98105 USA.
C3 University of Washington; University of Washington Seattle; Bascom
   Palmer Eye Institute; University of Miami; University of Washington;
   University of Washington Seattle
RP Wang, RK (通讯作者)，Univ Washington, Dept Bioengn, Seattle, WA 98105 USA.; Wang, RK (通讯作者)，Univ Washington, Karalis Johnson Retina Ctr, Dept Ophthalmol, Seattle, WA 98105 USA.
EM wangrk@uw.edu
RI ; Zhou, Hao/U-7850-2017
OI Liu, Jeremy/0000-0003-2395-3536; Zhou, Hao/0000-0003-0068-5102; Shen,
   Mengxi/0000-0002-1336-1695
FU Carl Zeiss Meditec inc; Salah Foundation; Research to Prevent Blindness;
   National Eye Institute [P30EY014801, R01EY028753]
FX Carl Zeiss Meditec inc; Salah Foundation; Research to Prevent Blindness;
   National Eye Institute (P30EY014801, R01EY028753).
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NR 46
TC 1
Z9 1
U1 1
U2 1
PU Optica Publishing Group
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD AUG 1
PY 2022
VL 13
IS 8
BP 4175
EP 4189
DI 10.1364/BOE.467623
PG 15
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 5W4WJ
UT WOS:000877915900006
PM 36032584
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Feng, JH
   Dong, XW
   Yu, HL
   Shen, W
   Lv, XY
   Wang, R
   Cheng, XX
   Xiong, F
   Hu, XL
   Wang, H
AF Feng, Jia-Hao
   Dong, Xiao-Wei
   Yu, Hao-Li
   Shen, Wei
   Lv, Xian-Yu
   Wang, Rong
   Cheng, Xue-Xiang
   Xiong, Fei
   Hu, Xiao-Long
   Wang, Hao
TI Cynaroside protects the blue light-induced retinal degeneration through
   alleviating apoptosis and inducing autophagy in vitro and in vivo
SO PHYTOMEDICINE
LA English
DT Article
DE Cynaroside; Retinal degeneration; Blue light; Autophagy; NF-kappa B;
   NLRP3 inflammasome
ID PIGMENT EPITHELIUM; CELLS; LIPOFUSCIN; ACTIVATION; PATHWAYS; DEATH
AB Background: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear.
   Purpose: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo.
   Study design/methods: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn.
   Results: Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 mu g/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-kappa B and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo.
   Conclusion: Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.
C1 [Feng, Jia-Hao; Dong, Xiao-Wei; Shen, Wei; Lv, Xian-Yu; Wang, Rong; Hu, Xiao-Long; Wang, Hao] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCMs Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Peoples R China.
   [Yu, Hao-Li; Xiong, Fei] Southeast Univ, Jiangsu Lab Biomat & Devices, State Key Lab Bioelect, Nanjing 210009, Peoples R China.
   [Cheng, Xue-Xiang] Hubei Fenghuang Baiyunshan Pharmaceut Co Ltd, Macheng 438300, Peoples R China.
C3 China Pharmaceutical University; Southeast University - China
RP Hu, XL; Wang, H (通讯作者)，China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCMs Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Peoples R China.
EM huxiaolong@cpu.edu.cn; wanghao@cpu.edu.cn
FU National Natural Science Foundation of China [81973206, 82073804]; China
   Postdoctoral Science Foundation [2019M662006, 2019TQ0357]; Major
   National Science and Technology Projects of the Chinese thirteen
   five-year Plan [2017ZX09309024]; National College Student Innovation
   Project for the R&D of Novel Drugs [201710316100]; Jiangsu Province
   Graduate Student Training Innovation Project [KYLX16_1208]
FX This work was financially supported by the National Natural Science
   Foundation of China (No. 81973206, 82073804), the China Postdoctoral
   Science Foundation (No. 2019M662006, 2019TQ0357), the Major National
   Science and Technology Projects of the Chinese thirteen five-year Plan
   (No. 2017ZX09309024), the National College Student Innovation Project
   for the R&D of Novel Drugs (No. 201710316100), and the Jiangsu Province
   Graduate Student Training Innovation Project (No. KYLX16_1208)
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NR 28
TC 6
Z9 5
U1 8
U2 30
PU ELSEVIER GMBH
PI MUNICH
PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY
SN 0944-7113
EI 1618-095X
J9 PHYTOMEDICINE
JI Phytomedicine
PD JUL 15
PY 2021
VL 88
AR 153604
DI 10.1016/j.phymed.2021.153604
EA JUN 2021
PG 14
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 SS4OC
UT WOS:000661732400014
PM 34130054
DA 2022-11-30
ER

PT J
AU Madheswaran, G
   Ramesh, SV
   Pardhan, S
   Sapkota, R
   Raman, R
AF Madheswaran, Gopinath
   Ramesh, S. Ve
   Pardhan, Shahina
   Sapkota, Raju
   Raman, Rajiv
TI Impact of living with a bilateral central vision loss due to geographic
   atrophy-qualitative study
SO BMJ OPEN
LA English
DT Article
DE qualitative research; ophthalmology; vetreoretinal
ID MACULAR DEGENERATION; LIVED EXPERIENCE
AB Objective Geographic atrophy (GA), a type of dry age-related macular degeneration, affects vision as central vision loss (CVL). The challenges faced due to bilateral CVL in activities of daily living and strategies taken to overcome those challenges are not very well understood in the Indian population. This qualitative study aims to understand the impact on everyday life activities and related adaptive and coping strategies in people with long-standing bilateral CVL due to GA in India. Design, participants, setting and methods A qualitative study using a semistructured face-to-face interview was conducted on 10 people with bilateral CVL after obtaining written informed consent. The interviews were audio-recorded, and were transcribed verbatim. Thematic analysis was carried out to understand the challenges faced and adaptive methods due to the impact of CVL. Results Ten participants (50% male) with a median age (IQR) of 72 (70, 74) years were interviewed. All the participants had best-corrected visual acuity of <= 6/60 in the better eye and reported an absolute central scotoma with the home Amsler chart. Qualitative thematic analysis identified four main themes: challenges in everyday living (difficulty in face identification, reading), challenges with lifestyle and socialisation (driving, cooking, reading for a longer duration, watching TV, socially inactive), psychological implications (depression, poor self-esteem, fear due to poor vision) and strategies to overcome the challenges (voice identification, technology support). Conclusion GA has a severe negative impact on the quality of life in people with CVL. Inability to recognise faces was the main reason for dependency on others and being socially disconnected. The findings will help clinicians in providing improved rehabilitative care.
C1 [Madheswaran, Gopinath; Ramesh, S. Ve] Manipal Acad Higher Educ, Manipal Coll Hlth Profess, Dept Optometry, Manipal, Karnataka, India.
   [Pardhan, Shahina; Sapkota, Raju] Anglia Ruskin Univ, Sch Med, Vis & Eye Res Inst VERI, Cambridge, England.
   [Raman, Rajiv] Shri Bhagwan Mahavir Vitreoretinal Serv, Sankara Nethralaya, Chennai, Tamil Nadu, India.
C3 Manipal Academy of Higher Education (MAHE); Anglia Ruskin University;
   University of Cambridge
RP Raman, R (通讯作者)，Shri Bhagwan Mahavir Vitreoretinal Serv, Sankara Nethralaya, Chennai, Tamil Nadu, India.
EM rajivpgraman@gmail.com
RI Madheswaran, Gopinath/Q-2318-2017
OI Madheswaran, Gopinath/0000-0003-4670-329X; S Ve,
   Ramesh/0000-0002-7592-9151
CR [Anonymous], 2021, DED VERS 8 3 47 WEB
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NR 29
TC 0
Z9 0
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2021
VL 11
IS 7
AR e047861
DI 10.1136/bmjopen-2020-047861
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA UK2US
UT WOS:000691830700012
PM 34326049
OA Green Accepted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Ju, YH
   Tang, ZM
   Dai, XC
   Gao, HQ
   Zhang, J
   Liu, Y
   Yang, YN
   Ni, N
   Zhang, DD
   Wang, YY
   Sun, N
   Yin, LQ
   Luo, M
   Zhang, JH
   Gu, P
AF Ju, Yahan
   Tang, Zhimin
   Dai, Xiaochan
   Gao, Huiqin
   Zhang, Jing
   Liu, Yan
   Yang, Yanan
   Ni, Ni
   Zhang, Dandan
   Wang, Yuyao
   Sun, Na
   Yin, Luqiao
   Luo, Min
   Zhang, Jianhua
   Gu, Ping
TI Protection against light-induced retinal degeneration via dual
   anti-inflammatory and anti-angiogenic functions of thrombospondin-1
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE angiogenesis; blue light; inflammation; retinal degeneration;
   thrombospondin&#8208; 1
ID GROWTH-FACTOR VEGF; BLUE-LIGHT; TRIAMCINOLONE ACETONIDE; PIGMENT
   EPITHELIUM; OXIDATIVE STRESS; CONCISE GUIDE; INTRAVITREAL TRIAMCINOLONE;
   UP-REGULATION; PROTEIN; DAMAGE
AB Background and Purpose Retinal photodamage is a high-risk factor for age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide. However, both the pathogenesis and effective therapies for retinal photodamage are still unclear and debated.
   Experimental Approach The anti-inflammatory effects of thrombospondin-1 on blue light-induced inflammation in ARPE-19 cells and in retinal inflammation were evaluated. Furthermore, the anti-angiogenic effects of thrombospondin-1 on human microvascular endothelial cells (hMEC-1 cells) and a laser-induced choroidal neovascularisation (CNV) mouse model were evaluated. in vitro experiments, including western blotting, immunocytochemistry, migration assays and tube formation assays, as well as in vivo experiments, including immunofluorescence, visual electrophysiology, spectral-domain optical coherence tomography, and fluorescein angiography, were employed to evaluate the anti-inflammatory and anti-angiogenic effects of thrombospondin-1.
   Key Results Specific effects of blue light-induced retinal inflammation and pathological angiogenesis were reflected by up-regulation of pro-inflammatory factors and activation of angiogenic responses, predominantly regulated by the NF-kappa B and VEGFR2 pathways respectively. During the blue light-induced pathological progress, THBS-1 derived from retinal pigment epithelium down-regulated proteomics and biological assays. Thrombospondin-1 treatment also suppressed inflammatory infiltration and neovascular leakage. The protective effect of Thrombospondin-1 was additionally demonstrated by a substantial rescue of visual function. Mechanistically, thrombospondin-1 reversed blue light-induced retinal inflammation and angiogenesis by blocking the activated NF-kappa B and VEGFR2 pathways, respectively.
   Conclusion and Implications Thrombospondin-1, with dual anti-inflammatory and anti-neovascularisation properties, is a promising agent for protection against blue light-induced retinal damage and retinal degenerative disorders which are pathologically associated with inflammatory and angiogenic progress.
C1 [Ju, Yahan; Tang, Zhimin; Dai, Xiaochan; Gao, Huiqin; Zhang, Jing; Liu, Yan; Ni, Ni; Zhang, Dandan; Wang, Yuyao; Sun, Na; Luo, Min; Gu, Ping] Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Dept Ophthalmol, Shanghai 200011, Peoples R China.
   [Ju, Yahan; Tang, Zhimin; Dai, Xiaochan; Gao, Huiqin; Zhang, Jing; Liu, Yan; Ni, Ni; Zhang, Dandan; Wang, Yuyao; Sun, Na; Luo, Min; Gu, Ping] Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai, Peoples R China.
   [Yang, Yanan; Yin, Luqiao; Zhang, Jianhua] Shanghai Univ, Key Lab Adv Display & Syst Applicat, Minist Educ, Shanghai 200072, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai University
RP Luo, M; Gu, P (通讯作者)，Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Dept Ophthalmol, Shanghai 200011, Peoples R China.; Zhang, JH (通讯作者)，Shanghai Univ, Key Lab Adv Display & Syst Applicat, Minist Educ, Shanghai 200072, Peoples R China.
EM luomin621124@hotmail.com; jhzhang@oa.shu.edu.cn; guping2009@126.com
FU National Natural Science Foundation of China [81870687]; Shanghai
   Municipal Education Commission-Gaofeng Clinical Medicine Grant Support
   [20161316]; Key Program of Shanghai Science and Technology Commission
   [19JC1415503]; National Key RAMP;D Program of China [2018YFC1106100]
FX National Natural Science Foundation of China, Grant/Award Number:
   81870687; Shanghai Municipal Education Commission-Gaofeng Clinical
   Medicine Grant Support, Grant/Award Number: 20161316; Key Program of
   Shanghai Science and Technology Commission, Grant/Award Number:
   19JC1415503; National Key R&D Program of China, Grant/Award Number:
   2018YFC1106100
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NR 88
TC 7
Z9 7
U1 3
U2 21
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 MAY
PY 2022
VL 179
IS 9
BP 1938
EP 1961
DI 10.1111/bph.15303
EA DEC 2020
PG 24
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 0F8WF
UT WOS:000599731200001
PM 33125704
DA 2022-11-30
ER

PT J
AU Shi, YY
   Chu, ZD
   Wang, L
   Zhang, QQ
   Feuer, W
   De Sisternes, L
   Durbin, MK
   Gregori, G
   Wang, RK
   Rosenfeld, PJ
AF Shi, Yingying
   Chu, Zhongdi
   Wang, Liang
   Zhang, Qinqin
   Feuer, William
   De Sisternes, Luis
   Durbin, Mary K.
   Gregori, Giovanni
   Wang, Ruikang K.
   Rosenfeld, Philip J.
TI Validation of a Compensation Strategy Used to Detect Choriocapillaris
   Flow Deficits Under Drusen With Swept Source OCT Angiography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SPECTRAL-DOMAIN; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; MORPHOMETRIC-ANALYSIS; GEOGRAPHIC ATROPHY;
   FEATURES; EYES
AB PURPOSE: A compensation strategy that was developed to measure the choriocapillaris (CC) flow deficits (FDs) under drusen was tested in eyes with large drusen from age-related macular degeneration (AMD) before and after the drusen spontaneously resolved without evidence of disease progression.
   DESIGN: Prospective, observational consecutive case series.
   METHODS: Patients with AMD were enrolled in a prospective swept-source optical coherence tomography (SS-OCT) imaging study. Consecutive eyes with large drusen were followed, and eyes that underwent spontaneous collapse of drusen without evidence of disease progression were identified retrospectively. The drusen-resolved regions were manually outlined. CC FDs were measured using a previously published compensation strategy that adjusted for the decreased signal intensity underlying drusen. Both the percentage of FDs (FD%) and the mean FD sizes (MFDSs) were measured before and after drusen resolution.
   RESULTS: Resolution of drusen was identified in 8 eyes from 8 patients. The average interval between the 2 visits was 7.8 months. The average drusen volumes measured between visits were 0.23 and 0.04 mm(3), respectively. After the drusen resolved, the average follow-up time without evidence of disease progression was 10.1 months. When the 2 visits were compared, there were no statistically significant differences in any of the CC parameters within the drusen resolved regions once the compensation strategy was applied (all P values > .22).
   CONCLUSIONS: In this naturally occurring experiment in which drusen collapsed without evidence of disease progression, the CC parameters were similar once our compensation strategy was applied both before and after the drusen resolved. ((C) 2020 Elsevier Inc. All rights reserved.)
C1 [Shi, Yingying; Wang, Liang; Feuer, William; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Chu, Zhongdi; Zhang, Qinqin; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 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 Wang, Ruikang/L-3889-2019
OI Wang, Ruikang/0000-0001-5169-8822; Feuer, William/0000-0002-9442-3076;
   Rosenfeld, Philip/0000-0002-4068-6671
FU NATIONAL EYE INSTITUTE [R01EY024158, R01EY028753]; Carl Zeiss Meditec,
   Inc (Dublin, California, USA); Salah Foundation; Research to Prevent
   Blindness, Inc, New York, NY; National Eye Institute Center Core Grant
   [P30EY014801]
FX THIS RESEARCH WAS SUPPORTED BY GRANTS FROM THE NATIONAL EYE INSTITUTE
   (R01EY024158, R01EY028753), Carl Zeiss Meditec, Inc (Dublin, California,
   USA), the Salah Foundation, an unrestricted grant from the Research to
   Prevent Blindness, Inc, New York, NY, and the National Eye Institute
   Center Core Grant (P30EY014801) to the Department of Ophthalmology,
   University of Miami Miller School of Medicine. The funding organizations
   had no role in the design or conduct of this research.
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NR 52
TC 7
Z9 7
U1 0
U2 1
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 DEC
PY 2020
VL 220
BP 115
EP 127
DI 10.1016/j.ajo.2020.06.033
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PG2ZX
UT WOS:000599610200025
PM 32621895
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Haris, EM
   McGraw, PV
   Webb, BS
   Chung, STL
   Astle, AT
AF Haris, Elizabeth M.
   McGraw, Paul V.
   Webb, Ben S.
   Chung, Susana T. L.
   Astle, Andrew T.
TI The Effect of Perceptual Learning on Face Recognition in Individuals
   with Central Vision Loss
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; central vision loss; perceptual
   learning; face recognition; ARMD
ID PREFERRED RETINAL LOCUS; MACULAR DEGENERATION; AGE; IDENTIFICATION;
   DISCRIMINATION; AMBLYOPIA; FIXATION; PATTERNS; PEOPLE; IMAGE
AB PURPOSE. To examine whether perceptual learning can improve face discrimination and recognition in older adults with central vision loss.
   METHODS. Ten participants with age-related macular degeneration (ARMD) received 5 days of training on a face discrimination task (mean age, 78 +/- 10 years). We measured the magnitude of improvements (i.e., a reduction in threshold size at which faces were able to be discriminated) and whether they generalized to an untrained face recognition task. Measurements of visual acuity, fixation stability, and preferred retinal locus were taken before and after training to contextualize learning-related effects. The performance of the ARMD training group was compared to nine untrained age-matched controls (8 = ARMD, 1 = juvenile macular degeneration; mean age, 77 +/- 10 years).
   RESULTS. Perceptual learning on the face discrimination task reduced the threshold size for face discrimination performance in the trained group, with a mean change (SD) of -32.7% (+15.9%). The threshold for performance on the face recognition task was also reduced, with a mean change (SD) of -22.4% (+2.31%). These changes were independent of changes in visual acuity, fixation stability, or preferred retinal locus. Untrained participants showed no statistically significant reduction in threshold size for face discrimination, with a mean change (SD) of -8.3% (+10.1%), or face recognition, with a mean change (SD) of +2.36% (-5.12%).
   CONCLUSIONS. This study shows that face discrimination and recognition can be reliably improved in ARMD using perceptual learning. The benefits point to considerable perceptual plasticity in higher-level cortical areas involved in face-processing. This novel finding highlights that a key visual difficulty in those suffering from ARMD is readily amenable to rehabilitation.
C1 [Haris, Elizabeth M.; McGraw, Paul V.; Webb, Ben S.; Astle, Andrew T.] Univ Nottingham, Sch Psychol, Visual Neurosci Grp, Nottingham, England.
   [Chung, Susana T. L.] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
C3 University of Nottingham; University of California System; University of
   California Berkeley
RP Haris, EM (通讯作者)，Univ New South Wales, Sch Psychol, Sydney, NSW 2052, Australia.
EM e.haris@unsw.edu.au
OI Chung, Susana/0000-0003-2729-1808; Haris, Elizabeth/0000-0002-5323-3516
FU National Institute for Health Research (NIHR) Postdoctoral Fellowship
   (London, UK)
FX Supported by a National Institute for Health Research (NIHR)
   Postdoctoral Fellowship (London, UK; ATA). This report presents
   independent research funded by the NIHR. The views expressed are those
   of the authors and not necessarily those of the National Health Service,
   the NIHR, or the Department of Health.
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NR 68
TC 2
Z9 2
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 JUL
PY 2020
VL 61
IS 8
AR 2
DI 10.1167/iovs.61.8.2
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA MS8BL
UT WOS:000554499000002
PM 32609296
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Mohanty, V
   Pinto, SM
   Subbannayya, Y
   Najar, MA
   Murthy, KB
   Prasad, TSK
   Murthy, KR
AF Mohanty, Varshasnata
   Pinto, Sneha M.
   Subbannayya, Yashwanth
   Najar, Mohd. Altaf
   Murthy, Kalpana Babu
   Prasad, Thottethodi Subrahmanya Keshava
   Murthy, Krishna R.
TI Digging Deeper for the Eye Proteome in Vitreous Substructures: A
   High-Resolution Proteome Map of the Normal Human Vitreous Base
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Article
DE eye proteome; visual health; omics technology; ophthalmology; LC-MS; MS;
   protein network
ID UBIQUITIN-PROTEASOME PATHWAY; HEAT-SHOCK PROTEINS; AQUEOUS-HUMOR;
   ENDOPLASMIC-RETICULUM; VISUAL PIGMENTS; OPTIC-NERVE; TNF-ALPHA;
   HISTAMINE; KINASE; STRESS
AB Mapping the normal eye proteome in healthy persons is essential to unravel the molecular basis of diseases impacting visual health. The vitreous occupies a large portion of the human eye between the lens and the retina and plays a significant role in vitreoretinal diseases as well as maintaining clarity in the visual field, providing nutrition to the lens, and protecting the eye from mechanical shocks. It comprises four distinct anatomical regions, namely the vitreous core, vitreous cortex, vitreous base, and anterior hyaloid. Among these, the vitreous is attached to other substructures in the eye by the vitreous base, which is its strongest point of attachment. Alterations in vitreous substructures have been reported in several vitreoretinal disorders, including vitreomacular traction, vitreoretinopathies, and age-related macular degeneration. There has been limited knowledge on proteomics variations at a resolution of vitreous substructures, including the functionally and pathophysiologically significant vitreous base. We report here new findings on the proteome map of the vitreous base in normal healthy tissue. We employed a global, unbiased proteomic profiling approach resulting in the identification of 6511 proteins. Of these, 302 proteins were involved in metabolic processes essential for energy utilization. Moreover, we identified several structural and nutrient transport proteins. Notably, the identified proteome repertoire indicates that the vitreous base might possess additional physiological functions and may not be a passive structure. This study constitutes the most extensive catalog of vitreous base proteins to our knowledge and offers novel insights as a baseline for future studies on the pathobiology of various eye diseases. These data also invite us to consider a potentially more active functional role for the vitreous base in eye physiology and visual health.
C1 [Mohanty, Varshasnata; Pinto, Sneha M.; Subbannayya, Yashwanth; Najar, Mohd. Altaf; Prasad, Thottethodi Subrahmanya Keshava] Yenepoya Deemed Univ, Yenepoya Res Ctr, Ctr Syst Biol & Mol Med, Mangalore 575018, India.
   [Murthy, Kalpana Babu; Murthy, Krishna R.] Vittala Int Inst Ophthalmol, Dept Vitreo Retina, Bangalore 560085, Karnataka, India.
   [Murthy, Kalpana Babu; Murthy, Krishna R.] Prabha Eye Clin & Res Ctr, Dept Vitreo Retina, Bangalore, Karnataka, India.
   [Murthy, Krishna R.] Inst Bioinformat, Int Technol Pk, Bangalore, Karnataka, India.
   [Murthy, Krishna R.] Manipal Acad Higher Educ, Manipal, India.
C3 Yenepoya (Deemed to be University); Manipal Academy of Higher Education
   (MAHE)
RP Prasad, TSK (通讯作者)，Yenepoya Deemed Univ, Yenepoya Res Ctr, Ctr Syst Biol & Mol Med, Mangalore 575018, India.; Murthy, KR (通讯作者)，Vittala Int Inst Ophthalmol, Dept Vitreo Retina, Bangalore 560085, Karnataka, India.
EM keshav@yenepoya.edu.in; krmjr2000@gmail.com
RI Prasad, Keshava/F-7631-2010; Subbannayya, Yashwanth/A-7796-2012
OI Prasad, Keshava/0000-0002-6206-2384; Subbannayya,
   Yashwanth/0000-0002-3885-3514; MOHANTY, VARSHASNATA/0000-0002-1520-7974
FU Karnataka Biotechnology and Information Technology Services (KBITS),
   Government of Karnataka [BiSEP GO ITD 02 MDA 2017]; Department of
   Science and Technology (DST), Government of India; DST, Government of
   India; University Grants Commission (UGC), Government of India
FX We thank Karnataka Biotechnology and Information Technology Services
   (KBITS), Government of Karnataka, for the support to the Center for
   Systems Biology and Molecular Medicine at Yenepoya (Deemed to be
   University) under the Biotechnology Skill Enhancement Programme in
   Multiomics Technology (BiSEP GO ITD 02 MDA 2017). We thank Yenepoya
   (Deemed to be University) for access to instrumentation. Varshasnata
   Mohanty is a recipient of the Women Scientist-A award from the
   Department of Science and Technology (DST), Government of India. Sneha
   M. Pinto is a recipient of INSPIRE Faculty Award from DST, Government of
   India. Mohd Altaf Najar is a recipient of the Senior Research Fellowship
   from University Grants Commission (UGC), Government of India.
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NR 60
TC 4
Z9 4
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
EI 1557-8100
J9 OMICS
JI OMICS
PD JUN 1
PY 2020
VL 24
IS 6
BP 379
EP 389
DI 10.1089/omi.2020.0020
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA LV5UP
UT WOS:000538500200001
PM 32496972
DA 2022-11-30
ER

PT J
AU Karimi, S
   Mosavi, SA
   Jadidi, K
   Nikkhah, H
   Kheiri, B
AF Karimi, Saeed
   Mosavi, Seyed Aliasghar
   Jadidi, Khosrow
   Nikkhah, Homayoun
   Kheiri, Bahareh
TI Which quadrant is less painful for intravitreal injection? A prospective
   study
SO EYE
LA English
DT Article
ID NERVE-ENDINGS; CORNEAL SENSITIVITY; BEVACIZUMAB AVASTIN; OCULAR PAIN;
   ANESTHESIA; AGE; RANIBIZUMAB; INTENSITY; RETINA
AB Purpose: To evaluate the relationship between injection site and pain severity following intravitreal injection of bevacizumab (IVB).
   Design: Prospective, randomized, four-armed, clinical trial.
   Methods: The present study was a prospective, randomized, four-armed clinical trial, which included 1004 eyes from 1004 patients. Patients receiving IVB were randomly assigned into four groups: superotemporal (ST); superonasal (SN); inferotemporal (IT); and inferonasal (IN) injections. The visual analog scale (VAS) was used to assess pain. Primary study variables were the relationship between pain severity and injection site, number of previous injections, age, sex, and indication for injection. Secondary variables included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes 1 month post IVB.
   Results: Overall mean pain score was 2.86 +/- 2.2. Indications for injection were diabetic macular edema (84.1%), neovascular age-related macular degeneration (7.7%), and macular edema secondary to retinal vein occlusion (8.2%). The mean VAS scores in the SN, IN, ST, and IT groups were 1.5 +/- 1.7, 3 +/- 2.3, 4 +/- 2, and 3 +/- 2.1, respectively. Pain severity was significantly correlated with injection site (p < 0.001) and sex (p < 0.001); females showed higher pain scores. A negative correlation existed between pain score and number of previous injections (p = 0.03). Pain severity was not associated with age (p = 0.659), lens status (p = 0.478), vitreous reflux (p = 0.648), or indication for injection (p = 0.390). No significant complications were observed.
   Conclusions: ST quadrant was the most painful and SN quadrant was the least painful sites for IVB. Pain severity score was significantly associated with injection site, number of injections, and sex.
C1 [Karimi, Saeed; Mosavi, Seyed Aliasghar; Nikkhah, Homayoun; Kheiri, Bahareh] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran.
   [Jadidi, Khosrow] Baqiyatallah Univ Med Sci, Dept Ophthalmol, Tehran, Iran.
C3 Shahid Beheshti University Medical Sciences; Baqiyatallah University of
   Medical Sciences (BMSU)
RP Mosavi, SA (通讯作者)，Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran.
EM a.a.mosavi@gmail.com
RI Jadidi, khosrow/W-3338-2019; Karimi, Saeed/AAW-4905-2020; Nikkhah,
   Homayoun/AAW-4663-2020
OI Jadidi, khosrow/0000-0002-2503-3322; Nikkhah,
   Homayoun/0000-0002-2414-4661; kheiri, bahareh/0000-0001-9448-8104
CR AMOAKU W, 2009, GUIDELINES INTRAVITR
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NR 42
TC 6
Z9 7
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2019
VL 33
IS 2
BP 304
EP 312
DI 10.1038/s41433-018-0208-y
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HK5MG
UT WOS:000458009500019
PM 30202072
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Gong, XM
   Draper, CS
   Allison, GS
   Marisiddaiah, R
   Rubin, LP
AF Gong, Xiaoming
   Draper, Christian S.
   Allison, Geoffrey S.
   Marisiddaiah, Raju
   Rubin, Lewis P.
TI Effects of the Macular Carotenoid Lutein in Human Retinal Pigment
   Epithelial Cells
SO ANTIOXIDANTS
LA English
DT Article
DE xanthophyll; lutein; lycopene; carotenoids; retinal pigment epithelium;
   hypoxia; oxidative stress; tBHP
ID PROTECTS ARPE-19 CELLS; OXIDATIVE STRESS; BETA-CAROTENE; EYE DISEASE;
   ZEAXANTHIN; DAMAGE; LYCOPENE; DEGENERATION; EXPRESSION; MECHANISM
AB Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the pathogenesis of age-related macular degeneration and neovascular retinopathies (e.g., retinopathy of prematurity, diabetic retinopathy). The xanthophyll carotenoids, lutein and zeaxanthin, are selectively taken up by the RPE, preferentially accumulated in the human macula, and transferred to photoreceptors. These macular xanthophylls protect the macula (and the broader retina) via their antioxidant and photo-protective activities. This study was designed to investigate effects of various carotenoids (beta-carotene, lycopene, and lutein) on RPE cells subjected to either hypoxia or oxidative stress, in order to determine if there is effect specificity for macular pigment carotenoids. Using human RPE-derived ARPE-19 cells as an in vitro model, we exposed RPE cells to various concentrations of the specific carotenoids, followed by either graded hypoxia or oxidative stress using tert-butyl hydroperoxide (tBHP). The results indicate that lutein and lycopene, but not beta-carotene, inhibit cell growth in undifferentiated ARPE-19 cells. Moreover, cell viability was decreased under hypoxic conditions. Pre-incubation of ARPE-19 cells with lutein or lycopene protected against tBHP-induced cell loss and cell co-exposure of lutein or lycopene with tBHP essentially neutralized tBHP-dependent cell death at tBHP concentrations up to 500 mu M. Our findings indicate that lutein and lycopene inhibit the growth of human RPE cells and protect the RPE against oxidative stress-induced cell loss. These findings contribute to the understanding of the protective mechanisms attributable to retinal xanthophylls in eye health and retinopathies.
C1 [Gong, Xiaoming; Rubin, Lewis P.] Texas Tech Univ, Paul L Foster Sch Med, Dept Pediat, Hlth Sci Ctr, El Paso, TX 79905 USA.
   [Draper, Christian S.; Allison, Geoffrey S.] Texas Tech Univ, Paul L Foster Sch Med, Hlth Sci Ctr, El Paso, TX 79905 USA.
   [Marisiddaiah, Raju] All Childrens Res Inst, St Petersburg, FL 33701 USA.
   [Rubin, Lewis P.] Texas Tech Univ, Paul L Foster Sch Med, Dept Biomed Sci, Hlth Sci Ctr, El Paso, TX 79905 USA.
C3 Texas Tech University System; Texas Tech University; Texas Tech
   University System; Texas Tech University; Texas Tech University System;
   Texas Tech University
RP Rubin, LP (通讯作者)，Texas Tech Univ, Paul L Foster Sch Med, Dept Pediat, Hlth Sci Ctr, El Paso, TX 79905 USA.; Rubin, LP (通讯作者)，Texas Tech Univ, Paul L Foster Sch Med, Dept Biomed Sci, Hlth Sci Ctr, El Paso, TX 79905 USA.
EM Xiaoming.gong@ttuhsc.edu; christian.draper@ttuhsc.edu;
   christian.draper@ttuhsc.edu; hmraju@gmail.com; lprprb@gmail.com
OI Gong, Xiaoming/0000-0003-1560-5611
FU Texas Tech University Health Sciences Center El Paso
FX We thank Jerzy Sarosiek and Sean Connery in Department of Internal
   Medicine, Texas Tech University Health Sciences Center El Paso for their
   kind assistance with cell culture. This work was partly supported by a
   seed grant to Xiaoming Gong from Texas Tech University Health Sciences
   Center El Paso.
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   Yan WM, 2001, GENOMICS, V72, P193, DOI 10.1006/geno.2000.6476
NR 49
TC 30
Z9 31
U1 1
U2 19
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD DEC
PY 2017
VL 6
IS 4
AR 100
DI 10.3390/antiox6040100
PG 13
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 FR7KQ
UT WOS:000419247200028
PM 29207534
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Schnabolk, G
   Stauffer, K
   O'Quinn, E
   Coughlin, B
   Kunchithapautham, K
   Rohrer, B
AF Schnabolk, Gloriane
   Stauffer, Kimberly
   O'Quinn, Elizabeth
   Coughlin, Beth
   Kunchithapautham, Kannan
   Rohrer, Baerbel
TI A comparative analysis of C57BL/6J and 6N substrains; chemokine/cytokine
   expression and susceptibility to laser-induced choroidal
   neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE rd8 mutation; Choroidal neovascularization; Age-related macular
   degeneration; Para-inflammation; Pre-conditioning
ID DIET-INDUCED OBESITY; MACULAR DEGENERATION; MOUSE MODEL; MUTATION; GENE;
   INFLAMMATION; COMPLEMENT; THERAPY; RETINA; CELLS
AB Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly. To study potential underlying mechanisms of AMD, animal models are utilized, focusing mostly on mice. Recently, genomic and phenotypic differences between the so-called control substrains, C57BL/6J and C57BL/6N, have been described in models of ocular and non-ocular diseases. In particular, the rd8 mutation of the Crb 1 gene present in the C57BL/6N has been shown to impact certain ocular phenotypes and appears to augment phenotypes generally associated with inflammation. Here, we investigated angiogenic factor and cytokine expression using pathway arrays as well as the susceptibility to laser-induced choroidal neovascularization (CNV), a model of wet AMD, in the two substrains. Age-matched 3-month-old C57BL/ 6J and C57BL/6N animals differed in gene expression levels for angiogenic factors and cytokines, with 6N animals expressing higher levels of inflammatory markers than 6Js. Yet laser-induced CNV was comparable in size between the two substrains. This lack of difference in CNV size was correlated with a gene expression profile that was comparable between the two substrains, due to the fact that the degree of change in gene expression of inflammatory markers after CNV was blunted in 6N mice. In summary, significant gene expression differences exist between C57BL/6J and C57BL/6N animals, reinforcing the notion that appropriate litter-mate controls or genetic background controls need to be used. Contrary to our expectation, CNV was not augmented in 6N animals, suggesting that low chronic inflammation in the RPE might provide a level of pre-conditioning and protection against stress. Published by Elsevier Ltd.
C1 [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA.
   [Stauffer, Kimberly; O'Quinn, Elizabeth; Coughlin, Beth; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Ralph H Johnson VA Medical Center; Medical University of South Carolina
RP Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
RI Alexander, Kim/AFU-2460-2022
FU National Institutes of Health (NIH) [R01EY019320]; Department for
   Veteran Affairs [RX000444]; Beckman Initiative for Macular Research
   [1202]; Research to Prevent Blindness (PRB), New York, NY,; Foundation
   Fighting Blindness, Columbia, MD; Wofford College to K.S. (John Rampey
   Fund); NIH [C06RR015455]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY019320] Funding Source: NIH RePORTER; Veterans Affairs
   [I01RX000444] Funding Source: NIH RePORTER
FX We thank Luanna Bartholomew for critical review. This work was supported
   in the laboratory of B.R. in part by the National Institutes of Health
   (NIH R01EY019320), a Department for Veteran Affairs merit award
   RX000444, the Beckman Initiative for Macular Research (1202), an
   unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New
   York, NY, Foundation Fighting Blindness, Columbia, MD, and a summer
   undergraduate stipend from Wofford College to K.S. (John Rampey Fund).
   Animal studies were conducted in a facility constructed with support
   from the NIH C06RR015455.
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NR 29
TC 15
Z9 15
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 DEC
PY 2014
VL 129
BP 18
EP 23
DI 10.1016/j.exer.2014.10.005
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AX4HJ
UT WOS:000346893800004
PM 25305577
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kim, YJ
   Sung, KR
   Lee, KS
   Joe, SG
   Lee, JY
   Kim, JG
   Yoon, YH
AF Kim, Yoon Jeon
   Sung, Kyung Rim
   Lee, Kyoung Sub
   Joe, Soo Geun
   Lee, Joo Yong
   Kim, June-Gone
   Yoon, Young Hee
TI Long-Term Effects of Multiple Intravitreal Antivascular Endothelial
   Growth Factor Injections on Intraocular Pressure
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RANIBIZUMAB; BEVACIZUMAB; PEGAPTANIB
AB PURPOSE: To evaluate long-term effects of multiple intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure (IOP) in eyes with neovascular age-related macular degeneration (AMD) or retinal vein occlusion (RVO).
   DESIGN: Retrospective cohort study.
   METHODS: This study enrolled patients who underwent multiple (more than 3) intravitreal anti-VEGF injections and who were followed for more than 12 months after their last injection. IOP elevation was defined as an increase of 5 mm Hg over the baseline measurement on 2 consecutive visits. The frequency of IOP elevation was determined. A hazard ratio of each putative risk factor for IOP elevation was calculated using the Cox proportional hazard model for all participants, incorporating underlying disease as a covariate, as well as for each cohort.
   RESULTS: Included in the analysis were 629 eyes with neovascular AMD and 95 eyes with RVO. Twenty eyes with neovascular AMD (3.0%) and 7 eyes with RVO (7.4%) experienced IOP elevation after multiple anti-VEGF injections, with an overall incidence of 3.7%. In the Cox proportional hazard analysis of total participants, a diagnosis of RVO (3.424, P = 0.005), a history of glaucoma (8.441, P = 0.001), and low baseline IOP (0.865, P = 0.040) were all significant risk factors for IOP elevation after multiple anti-VEGF injections.
   CONCLUSION: A history of multiple intravitreal anti-VEGF injections was not a significant risk factor for IOP elevation in our study. IOP elevation was more common in eyes with RVO than with AMD after anti-VEGF injection. (C) 2014 by Elsevier Inc. All rights reserved.
C1 [Kim, Yoon Jeon; Sung, Kyung Rim; Lee, Kyoung Sub; Joe, Soo Geun; Lee, Joo Yong; Kim, June-Gone; Yoon, Young Hee] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Ophthalmol, Seoul 138736, South Korea.
C3 University of Ulsan; Asan Medical Center
RP Yoon, YH (通讯作者)，Univ Ulsan, Coll Med, Asan Med Ctr, Dept Ophthalmol, 88 Olymp Ro,43 Gil, Seoul 138736, South Korea.
EM yhyoon@amc.seoul.kr
RI Kim, Yoon Jeon/GZA-3765-2022
OI Kim, Yoon Jeon/0000-0003-4293-9641
FU Ministry of Science, Information and Communication Technology, and
   Future Planning, South Korea [2013R1A2A2A01068457]; Alcon; Bayer;
   Allergan
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST, and the following were reported.
   This study was supported by grant Number 2013R1A2A2A01068457 from
   Ministry of Science, Information and Communication Technology, and
   Future Planning, South Korea. Dr Yoon has served on a consultant for
   Alcon, Bayer, and Allergan and has received consultancy fees from these
   companies. She has received payments for lectures from Alcon, Bayer and
   Allergan. Design and conduct of study (Y.J.K., Y.H.Y., K.R.S.);
   Collection of data (Y.J.K., K.S.L.); Management, analysis and
   interpretation of data (Y.J.K., Y.H.Y., KR.S.); writing of article and
   literature search (Y.J.K., Y.H.Y.); and Preparation, review and final
   approval of article (Y.J.K., Y.H.Y., K.R.S., K.S.L., S.G.J., J.Y.L.,
   J.G.K.).
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NR 18
TC 28
Z9 31
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUN
PY 2014
VL 157
IS 6
BP 1266
EP 1271
DI 10.1016/j.ajo.2014.02.035
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AJ4KF
UT WOS:000337644400021
PM 24561173
DA 2022-11-30
ER

PT J
AU Bola, C
   Bartlett, H
   Eperjesi, F
AF Bola, Christina
   Bartlett, Hannah
   Eperjesi, Frank
TI Resveratrol and the eye: activity and molecular mechanisms
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Age-relatedmacular degeneration; Alcohol; Diabetic retinopathy;
   Polyphenols; Red wine; Resveratrol; Retinopathy of prematurity
ID WINE POLYPHENOL RESVERATROL; PIGMENT EPITHELIAL-CELLS; FACTOR-KAPPA-B;
   OXIDATIVE STRESS; RED WINE; DIABETIC-RETINOPATHY; ACTIVATOR PROTEIN-1;
   IN-VIVO; EXPRESSION; APOPTOSIS
AB Alcohol consumption is inversely correlated with the incidence of cardiovascular disease. It is thought that red wine is specifically responsible for these cardiovascular benefits, due to its ability to reduce vascular inflammation, facilitate vasorelaxation, and inhibit angiogenesis. This is because of its high polyphenolic content. Resveratrol is the main biologically active polyphenol within red wine. Owing to its vascular-enhancing properties, resveratrol may be effective in the microcirculation of the eye, thereby helping prevent ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Such conditions are accountable for worldwide prevalence of visual loss.
   A review of the relevant literature was conducted on the ScienceDirect, Web of Science, and PubMed databases. Key words used to carry out the searches included 'red wine', 'polyphenols', 'resveratrol', 'eye' and 'ocular'. Articles relating to the effects of resveratrol on the eye were reviewed.
   The protective effects of resveratrol within the eye are extensive. It has been demonstrated to have anti-oxidant, anti-apoptotic, anti-tumourogenic, anti-inflammatory, anti-angiogenic and vasorelaxant properties. There are potential benefits of resveratrol supplementation across a wide range of ocular diseases. The molecular mechanisms underlying these protective actions are diverse.
   Evidence suggests that resveratrol may have potential in the treatment of several ocular diseases. However, while there are many studies indicating plausible biological mechanisms using animal models and in-vitro retinal cells there is a paucity of human research. The evidence base for the use of resveratrol in the management of ocular diseases needs to be increased before recommendations can be made for the use of resveratrol as an ocular supplement.
C1 [Bola, Christina; Bartlett, Hannah; Eperjesi, Frank] Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
C3 Aston University
RP Eperjesi, F (通讯作者)，Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
EM f.eperjesi@aston.ac.uk
OI Bartlett Eperjesi, Hannah E/0000-0002-7531-6902; Eperjesi,
   Frank/0000-0003-4358-0095
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NR 89
TC 59
Z9 61
U1 2
U2 39
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 2014
VL 252
IS 5
BP 699
EP 713
DI 10.1007/s00417-014-2604-8
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AG8HS
UT WOS:000335660000001
PM 24652235
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Dhamodaran, K
   Subramani, M
   Ponnalagu, M
   Shetty, R
   Das, D
AF Dhamodaran, Kamesh
   Subramani, Murali
   Ponnalagu, Murugeswari
   Shetty, Reshma
   Das, Debashish
TI Ocular stem cells: a status update!
SO STEM CELL RESEARCH & THERAPY
LA English
DT Review
ID TRABECULAR MESHWORK CELLS; EPITHELIAL-CELLS; HUMAN LIMBAL; RETINAL
   REPAIR; STEM/PROGENITOR CELLS; MACULAR DEGENERATION; PIGMENT-EPITHELIUM;
   PROGENITOR CELLS; PRECURSOR CELLS; CILIARY BODY
AB Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine.
C1 [Dhamodaran, Kamesh; Subramani, Murali; Ponnalagu, Murugeswari; Shetty, Reshma; Das, Debashish] Narayana Hlth City, Narayana Nethralaya, Narayana Nethralaya Fdn, Stem Cell Res Lab, Bangalore 560099, Karnataka, India.
   [Dhamodaran, Kamesh] Univ Vellore, Vellore Inst Technol, Sch Biosci & Technol, Vellore 632014, Tamil Nadu, India.
C3 Vellore Institute of Technology
RP Shetty, R (通讯作者)，Narayana Hlth City, Narayana Nethralaya, Narayana Nethralaya Fdn, Stem Cell Res Lab, 258-A Bommasandra Ind Area,Hosur Rd, Bangalore 560099, Karnataka, India.
EM reshmashetty@narayananethralaya.com
RI Das, Debashish/ABB-4272-2020
OI Das, Debashish/0000-0002-9171-656X
FU Department of Science and Technology
FX The authors would like to convey their sincere gratitude to Dr K Bhujang
   Shetty, Dr Rohit Shetty and Dr Himanshu Matalia. The authors would like
   to thank the Narayana Nethralaya Foundation, India, Department of
   Science and Technology, Government of India and the Discovery Eye
   Foundation/National Keratoconus Foundation, USA, for providing all the
   necessary support for this review. KD is supported by the Department of
   Science and Technology for Senior Research Fellowship. We would also
   like to thank Neeraj Bhas for work on the figures.
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NR 83
TC 38
Z9 39
U1 1
U2 25
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD APR 22
PY 2014
VL 5
AR 56
DI 10.1186/scrt445
PG 11
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA AF3VM
UT WOS:000334640400001
PM 25158127
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kelly, ER
   Plat, J
   Haenen, GRMM
   Kijlstra, A
   Berendschot, TTJM
AF Kelly, Elton R.
   Plat, Jogchum
   Haenen, Guido R. M. M.
   Kijlstra, Aize
   Berendschot, Tos T. J. M.
TI The Effect of Modified Eggs and an Egg-Yolk Based Beverage on Serum
   Lutein and Zeaxanthin Concentrations and Macular Pigment Optical
   Density: Results from a Randomized Trial
SO PLOS ONE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; LIPOPROTEIN CHOLESTEROL; BETA-CAROTENE;
   VITAMIN-E; SUPPLEMENTATION; DEGENERATION; INCREASES; BIOAVAILABILITY;
   ANTIOXIDANTS; TOXICITY
AB Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P<0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements.
C1 [Kelly, Elton R.; Kijlstra, Aize; Berendschot, Tos T. J. M.] Maastricht Univ, Univ Eye Clin Maastricht, Maastricht, Netherlands.
   [Plat, Jogchum] Maastricht Univ, Dept Human Biol, Maastricht, Netherlands.
   [Haenen, Guido R. M. M.] Maastricht Univ, Dept Pharmacol & Toxicol, Maastricht, Netherlands.
C3 Maastricht University; Maastricht University Medical Centre (MUMC);
   Maastricht University; Maastricht University
RP Berendschot, TTJM (通讯作者)，Maastricht Univ, Univ Eye Clin Maastricht, Maastricht, Netherlands.
EM t.berendschot@maastrichtuniversity.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X; Haenen,
   Guido/0000-0001-6986-290X
FU Newtricious (Oirlo, The Netherlands); OP-Zuid grant
FX The study was financially supported by Newtricious (Oirlo, The
   Netherlands) and an OP-Zuid grant. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 43
TC 34
Z9 37
U1 0
U2 19
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 27
PY 2014
VL 9
IS 3
AR e92659
DI 10.1371/journal.pone.0092659
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AE0SW
UT WOS:000333677500031
PM 24675775
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Yan, LL
   Chaqour, B
AF Yan, Lulu
   Chaqour, Brahim
TI Cysteine-rich protein 61 (CCN1) and connective tissue growth factor
   (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease
   therapy
SO JOURNAL OF CELL COMMUNICATION AND SIGNALING
LA English
DT Review
DE CCN1; CCN2; Extracellular matrix; Neovascularization; Retinopathy;
   Ischemia
AB The vasculature forms a highly branched network investing every organ of vertebrate organisms. The retinal circulation, in particular, is supported by a central retinal artery branching into superficial arteries, which dive into the retina to form a dense network of capillaries in the deeper retinal layers. The function of the retina is highly dependent on the integrity and proper functioning of its vascular network and numerous ocular diseases including diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity are caused by vascular abnormalities culminating in total and sometimes irreversible loss of vision. CCN1 and CCN2 are inducible extracellular matrix (ECM) proteins which play a major role in normal and aberrant formation of blood vessels as their expression is associated with developmental and pathological angiogenesis. Both CCN1 and CCN2 achieve disparate cell-type and context-dependent activities through modulation of the angiogenic and synthetic phenotype of vascular and mesenchymal cells respectively. At the molecular level, CCN1 and CCN2 may control capillary growth and vascular cell differentiation by altering the composition or function of the constitutive ECM proteins, potentiating or interfering with the activity of various ligands and/or their receptors, physically interfering with the ECM-cell surface interconnections, and/or reprogramming gene expression driving cells toward new phenotypes. As such, these proteins emerged as important prognostic markers and potential therapeutic targets in neovascular and fibrovascular diseases of the eye. The purpose of this review is to highlight our current knowledge and understanding of the most recent data linking CCN1 and CCN2 signaling to ocular neovascularization bolstering the potential value of targeting these proteins in a therapeutic context.
C1 [Yan, Lulu; Chaqour, Brahim] SUNY, Eye Inst Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
   [Yan, Lulu; Chaqour, Brahim] SUNY, Eye Inst Downstate Med Ctr, Dept Ophthalmol, Brooklyn, NY 11203 USA.
C3 State University of New York (SUNY) System; SUNY Maritime College; State
   University of New York (SUNY) System; SUNY Maritime College
RP Chaqour, B (通讯作者)，SUNY, Eye Inst Downstate Med Ctr, Dept Cell Biol, 450 Clarkson Ave,Box 5, Brooklyn, NY 11203 USA.
EM bchaqour@downstate.edu
RI Chaqour, Brahim/AEH-1314-2022
OI Chaqour, Brahim/0000-0002-8516-4324
FU National Eye Institute of the National Institutes of Health
   [EY022091-01]; Research for the Prevention of Blindness Foundation;
   NATIONAL EYE INSTITUTE [R01EY022091] Funding Source: NIH RePORTER
FX This work was supported by grant from the National Eye Institute of the
   National Institutes of Health EY022091-01 and Research for the
   Prevention of Blindness Foundation.
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NR 92
TC 26
Z9 29
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1873-9601
EI 1873-961X
J9 J CELL COMMUN SIGNAL
JI J. Cell Commun. Signal
PD DEC
PY 2013
VL 7
IS 4
BP 253
EP 263
DI 10.1007/s12079-013-0206-6
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA V39OS
UT WOS:000209420900004
PM 23740088
OA Green Published
DA 2022-11-30
ER

PT J
AU Winnik, S
   Lohmann, C
   Siciliani, G
   von Lukowicz, T
   Kuschnerus, K
   Kraenkel, N
   Brokopp, CE
   Enseleit, F
   Michels, S
   Ruschitzka, F
   Luscher, TF
   Matter, CM
AF Winnik, Stephan
   Lohmann, Christine
   Siciliani, Giovanni
   von Lukowicz, Tobias
   Kuschnerus, Kira
   Kraenkel, Nicolle
   Brokopp, Chad E.
   Enseleit, Frank
   Michels, Stephan
   Ruschitzka, Frank
   Luescher, Thomas F.
   Matter, Christian M.
TI Systemic VEGF inhibition accelerates experimental atherosclerosis and
   disrupts endothelial homeostasis - implications for cardiovascular
   safety
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Angiogenesis inhibitors; Adverse effects; Cardiovascular diseases;
   Patient safety
ID ARTERIAL THROMBOEMBOLIC EVENTS; GROWTH-FACTOR; GENE-TRANSFER;
   CLINICAL-APPLICATIONS; NITRIC-OXIDE; BEVACIZUMAB; RANIBIZUMAB;
   PROGRESSION; PHARMACOKINETICS; METAANALYSIS
AB Objectives: This study sought to examine the effects and underlying mechanisms of systemic VEGF inhibition in experimental atherosclerosis and aortic endothelial cells.
   Background: Pharmacological inhibition of vascular endothelial growth factor (VEGF), a major mediator of angiogenesis, has become a widely applied treatment of certain cancers and multiple ocular diseases including age-related macular degeneration. However, recent clinical trials raise concern for systemic vascular adverse effects, prompting the Food and Drug Administration to revoke the approval of bevacizumab for metastatic breast cancer.
   Methods: Eight-week old apolipoprotein E knockout mice received a high-cholesterol diet (1.25% cholesterol) for 24 weeks and were exposed to a systemic pan-VEGF receptor inhibitor (PTK787/ZK222584, 50 mg/kg/d) or placebo (gavage) for the last 10 weeks. Atherosclerotic lesions were characterized in thoraco-abdominal aortae and aortic arches. Mechanistic analyses were performed in cultured human aortic endothelial cells.
   Results: Systemic VEGF inhibition increased atherosclerotic lesions by 33% whereas features of plaque vulnerability (i.e. necrotic core size, fibrous cap thickness) remained unchanged compared with controls. Aortic eNOS expression was decreased (trend). In human endothelial cells VEGF inhibition induced a dose-dependent increase in mitochondrial superoxide generation with an uncoupling of eNOS, resulting in reduced NO availability and decreased proliferation.
   Conclusion: Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. Cardiovascular safety profiles of currently applied anti-angiogenic regimens should be determined to improve patient selection for therapy and allow close monitoring of patients at increased cardiovascular risk. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Winnik, Stephan; Enseleit, Frank; Ruschitzka, Frank; Luescher, Thomas F.; Matter, Christian M.] Univ Zurich Hosp, Div Cardiol, CH-8091 Zurich, Switzerland.
   [Winnik, Stephan; Lohmann, Christine; Siciliani, Giovanni; Kuschnerus, Kira; Kraenkel, Nicolle; Brokopp, Chad E.; Ruschitzka, Frank; Luescher, Thomas F.; Matter, Christian M.] Univ Zurich, Inst Physiol, Zurich, Switzerland.
   [von Lukowicz, Tobias] Univ Lubeck, Dept Cardiol, Lubeck, Germany.
   [Brokopp, Chad E.; Michels, Stephan] Stadtspital Triemli, Dept Ophthalmol, Zurich, Switzerland.
   [Luescher, Thomas F.; Matter, Christian M.] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland.
C3 University of Zurich; University Zurich Hospital; University of Zurich;
   University of Lubeck; Triemli Hospital; University of Zurich; Zurich
   Center Integrative Human Physiology (ZIHP)
RP Matter, CM (通讯作者)，Univ Zurich Hosp, Div Cardiol, Raemistr 100, CH-8091 Zurich, Switzerland.
EM christian.matter@uzh.ch
OI Kraenkel, Nicolle/0000-0002-9363-1770; Winnik,
   Stephan/0000-0002-1277-5132
FU Swiss National Science Foundation [310030-130626/1]; Swiss Heart
   Foundation; Foundation for Cardiovascular Research, Zurich, Switzerland
FX This work was funded by the Swiss National Science Foundation
   310030-130626/1 (CMM), the Swiss Heart Foundation (CMM) and the
   Foundation for Cardiovascular Research, Zurich, Switzerland.
   PTK787/ZK222584 was a provided by Novartis. All authors take
   responsibility for all aspects of the reliability and freedom from bias
   of the data presented and their discussed interpretation.
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NR 47
TC 63
Z9 67
U1 3
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD OCT 3
PY 2013
VL 168
IS 3
BP 2453
EP 2461
DI 10.1016/j.ijcard.2013.03.010
PG 9
WC Cardiac & Cardiovascular Systems
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 241RF
UT WOS:000326184400118
PM 23561917
OA hybrid
DA 2022-11-30
ER

PT J
AU Schoenberger, SD
   Agarwal, A
AF Schoenberger, Scott D.
   Agarwal, Anita
TI Geographic Chorioretinal Atrophy in Pseudoxanthoma Elasticum
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; FUNDUS AUTOFLUORESCENCE; PATTERN DYSTROPHY; AREA;
   PROGRESSION; PREVALENCE; DISEASE; UPDATE
AB PURPOSE: To describe a series of patients with geographic atrophy independent of choroidal neovascularization (CNV) in pseudoxanthoma elasticum and to report progression over time.
   DESIGN: Retrospective observational case series.
   METHODS: Records of all Vanderbilt Eye Institute patients with pseudoxanthoma elasticum and at least 1 set of color fundus photographs were reviewed (41 eyes of 21 patients). Fluorescein angiography, fundus auto-fluorescence, and optical coherence tomography images were reviewed, when available. In patients with geographic atrophy and at least 1 year of follow-up, atrophy was measured using fundus photographs. Main outcome measures included incidence of geographic atrophy, progression over time, and macular features associated with development or progression of geographic atrophy.
   RESULTS: Eight eyes (20%) of 5 patients had geographic atrophy independent of CNV. Progression was documented in 6 eyes of 4 patients followed for at least 1 year (mean 3.5 years). Mean initial and final area was 2.9 and 9.5 mm(2), respectively, and growth rate was 1.7 mm(2) per year. Of the 6 eyes, 3 had a final visual acuity of 20/20 and the other 3 ranged from 20/150 to 20/400. All 8 eyes had pattern dystrophy, and 5 had linear pigment deposits that appeared to predict development or growth of atrophy.
   CONCLUSIONS: Isolated geographic atrophy independent of CNV can develop in pseudoxanthoma elasticum, causing significant vision loss. Linear pigmented pattern dystrophy appears to predate geographic atrophy. Progression is similar to age-related macular degeneration. Recognition of this feature is important, especially if therapies to slow or reverse geographic atrophy become available. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Schoenberger, Scott D.; Agarwal, Anita] Vanderbilt Univ, Sch Med, Vanderbilt Eye Inst, Nashville, TN 37212 USA.
C3 Vanderbilt University
RP Agarwal, A (通讯作者)，Vanderbilt Eye Inst, 2311 Pierce Ave, Nashville, TN 37232 USA.
EM anita.agarwal@vanderbilt.edu
FU Research to Prevent Blindness
FX BOTH AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF Interest. The authors report no financial
   disclosures. This work was supported in part by an unrestricted grant
   from Research to Prevent Blindness to the Vanderbilt University School
   of Medicine Department of Ophthalmology and Visual Sciences. Author
   contributions: conception and design (S.D.S., A.A.); analysis and
   interpretation (S.D.S., A.A.); writing the article (S.D.S.); critical
   revision of the article (A.A.); final approval of the article (S.D.S.,
   A.A.); data collection (S.D.S., A.A.); provision of materials, patients,
   or resources (AA); obtaining funding (A.A.); literature search (S.D.S.);
   and administrative, technical, or logistical support (A.A.).
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NR 30
TC 7
Z9 9
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 OCT
PY 2013
VL 156
IS 4
BP 715
EP 723
DI 10.1016/j.ajo.2013.05.034
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 231VT
UT WOS:000325447200010
PM 23891334
DA 2022-11-30
ER

PT J
AU Shahid, K
   Kolomeyer, AM
   Nayak, NV
   Salameh, N
   Pelaez, G
   Khouri, AS
   Eck, TT
   Szirth, B
AF Shahid, Khadija
   Kolomeyer, Anton M.
   Nayak, Natasha V.
   Salameh, Nura
   Pelaez, Gina
   Khouri, Albert S.
   Eck, Thomas T.
   Szirth, Ben
TI Ocular Telehealth Screenings in an Urban Community
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE telehealth; non-mydriatic camera; vision-threatening disease; diabetes;
   glaucoma; soup kitchen population
ID VISUAL IMPAIRMENT; DISEASES; CARE
AB The current U.S. economic recession has resulted in a loss of income, housing, and healthcare coverage. Our major goal in this socioeconomic setting was to provide ophthalmic remote health screenings for urban soup kitchen and homeless populations in order to identify and refer undetected vision-threatening disease (VTD). We assessed visual acuity, blood pressure, pulse/oxygen saturation, body mass index, and intraocular pressure for 341 participants at soup kitchens as part of the homeless outreach program in Newark, NJ. History of diabetes, hypertension, and smoking, last ocular examination, and ocular history were noted. Imaging was performed with an 8.2 megapixel nonmydriatic retinal camera with high-speed Internet ready for off-site second opinion image evaluation. Positive VTD findings were identified in 105 participants (31%) (mean age, 53.6 years), of whom 78% were African American, 73% males, and 62% smokers. We detected glaucoma in 34 participants (32%), significant cataract in 22 (21%), diabetic retinopathy in 5 (5%), optic atrophy in 1 (1%), age-related macular degeneration in 1 (1%), and other retinal findings in 43 (41%). The incidence of VTDs was higher among this cohort than among study groups in previous screenings (31% vs. 12%). This finding shows an increase in ocular morbidity in a younger, at-risk population with elevated rates of hypertension, diabetes, and smoking. Functional visual impairment was 2.5 times higher than the national average (16% vs. 6.4%). Comprehensive, community-based screenings can provide more sensitive detection of VTDs in high-risk groups with low access to ophthalmic care and can be an integral part of recession solutions for improving healthcare.
C1 [Shahid, Khadija; Szirth, Ben] Univ Med & Dent New Jersey, Inst Ophthalmol & Visual Sci, Newark, NJ 07101 USA.
   [Shahid, Khadija; Kolomeyer, Anton M.; Nayak, Natasha V.; Salameh, Nura; Khouri, Albert S.; Eck, Thomas T.; Szirth, Ben] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07101 USA.
   [Pelaez, Gina] Rutgers State Univ, Newark, NJ 07102 USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center; Rutgers State University New Brunswick; Rutgers State University
   Medical Center; Rutgers State University Newark; Rutgers State
   University New Brunswick
RP Szirth, B (通讯作者)，Univ Med & Dent New Jersey, Inst Ophthalmol & Visual Sci, 90 Bergen St,Suite 6100,POB 1709, Newark, NJ 07101 USA.
EM szirthgone@aol.com
OI Shahid, Khadija/0000-0003-0028-3883; Khouri, Albert/0000-0002-0806-0898
FU Research for the Prevention of Blindness; Grotta Foundation, Inc.;
   Friends of the Congressional Glaucoma Caucus Foundation
FX The authors wish to thank Sister Alma Pukel and Mr. Larry Crawford, the
   on-site coordinators of the St. John's and St. Anne's soup kitchens in
   Newark, NJ, for their tireless work. This outreach effort was funded by
   the Research for the Prevention of Blindness, the Grotta Foundation,
   Inc., and the Friends of the Congressional Glaucoma Caucus Foundation.
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NR 19
TC 28
Z9 28
U1 0
U2 7
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 MAR
PY 2012
VL 18
IS 2
BP 95
EP 100
DI 10.1089/tmj.2011.0067
PG 6
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA 902MB
UT WOS:000301041200004
PM 22283358
DA 2022-11-30
ER

PT J
AU Takeuchi, A
   Takeuchi, M
   Oikawa, K
   Sonoda, KH
   Usui, Y
   Okunuki, Y
   Takeda, A
   Oshima, Y
   Yoshida, K
   Usui, M
   Goto, H
   Kuroda, M
AF Takeuchi, Aya
   Takeuchi, Masaru
   Oikawa, Kosuke
   Sonoda, Koh-hei
   Usui, Yoshihiko
   Okunuki, Yoko
   Takeda, Atsunobu
   Oshima, Yuji
   Yoshida, Keiichi
   Usui, Masahiko
   Goto, Hiroshi
   Kuroda, Masahiko
TI Effects of Dioxin on Vascular Endothelial Growth Factor (VEGF)
   Production in the Retina Associated with Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; SIDESTREAM CIGARETTE-SMOKE;
   DIBENZO-P-DIOXINS; MACULAR DEGENERATION; AH-RECEPTOR; PIGMENT
   EPITHELIUM; SIGNALING PATHWAYS; EYE DISEASE; EXPRESSION; ANGIOGENESIS
AB PURPOSE. Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects of dioxins on the eye remain elusive. In this study, the authors examined the association between dioxins and neovascularization in the eye.
   METHODS. C57BL/6 mice were injected intraperitoneally with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every other day for 14 days. Messenger RNA expression of cytochrome P450 (CYP) 1A1, CYP1B1, vascular endothelial growth factor (VEGF)-A and VEGF-B, and VEGF production were examined in the eyes of TCDD-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to TCDD. In addition, CNV was induced by photocoagulation in mice injected with TCDD, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount.
   RESULTS. TCDD injected intraperitoneally increased CYP1A1 mRNA expression in the iris/ciliary body and retina, indicating that TCDD acts directly on ocular tissues through the aryl hydrocarbon receptor (AhR) to promote the transcription of target genes. TCDD also promoted VEGF-A mRNA expression in the retina and the retinal pigment epithelium. TCDD- induced VEGF production at the molecular level was also observed in vivo by immunohistochemistry and in vitro using ARPE-19. Moreover, the injection of TCDD significantly exacerbated photocoagulation-induced CNV in mice.
   CONCLUSIONS. The authors demonstrate that dioxins are among the factors inducing abnormal vascularization in the eye through VEGF production mediated by AhR signaling. (Invest Ophthalmol Vis Sci. 2009;50:3410-3416) DOI:10.1167/iovs.08-2299
C1 [Takeuchi, Masaru] Tokyo Med Univ, Dept Ophthalmol, Shinjuku Ku, Tokyo 1600023, Japan.
   [Oikawa, Kosuke; Kuroda, Masahiko] Tokyo Med Univ, Dept Pathol, Tokyo 1600023, Japan.
   [Sonoda, Koh-hei; Takeda, Atsunobu; Oshima, Yuji] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan.
   [Yoshida, Keiichi] Chiba Univ, Grad Sch Med, Dept Anat & Dev Biol, Chiba, Japan.
C3 Tokyo Medical University; Tokyo Medical University; Kyushu University;
   Chiba University
RP Takeuchi, M (通讯作者)，Tokyo Med Univ, Dept Ophthalmol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan.
EM takeuchi@tokyo-med.ac.jp
RI Okunuki, Yoko/ABE-8090-2020; /AAD-1824-2020
OI Okunuki, Yoko/0000-0002-1612-7925; 
FU Japan Society for the Promotion of Science [18591935, 19791294,
   18590349, 18590382]; Ministry of Health, Labour and Welfare of Japan;
   Japan Health Sciences Foundation; Yamaguchi Endocrine Research
   Association
FX Supported by Grants-in-Aid 18591935, 19791294, 18590349, and 18590382
   for Scientific Research from the Japan Society for the Promotion of
   Science; a Grant-in-Aid for Cancer Research from the Ministry of Health,
   Labour and Welfare of Japan; a grant of Research on Publicly Essential
   Drugs and Medical Devices from the Japan Health Sciences Foundation; and
   a grant from Yamaguchi Endocrine Research Association.
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NR 44
TC 23
Z9 27
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2009
VL 50
IS 7
BP 3410
EP 3416
DI 10.1167/iovs.08-2299
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 461SP
UT WOS:000267292100049
PM 19182260
DA 2022-11-30
ER

PT J
AU Lynch, SS
   Cheng, CM
AF Lynch, Shalini S.
   Cheng, Christine M.
TI Bevacizumab for neovascular ocular diseases
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE intravitreal bevacizumab; macular; retinopathy
ID PIGMENT EPITHELIAL TEAR; ANTI-VEGF ANTIBODY; INTRAVITREAL BEVACIZUMAB;
   CHOROIDAL NEOVASCULARIZATION; AVASTIN TREATMENT; INJECTION; SECONDARY;
   THERAPY; SAFETY; PERSISTENT
AB OBJECTIVE: To review the efficacy and safety of off-label use of bevacizumab for neovascular ocular diseases.
   DATA SOURCES: A PubMed (1966-January 2007) search was conducted using the terms human, intravitreal, bevacizumab, macular, and retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina Society, Macula Society, and Association for Research in Vision and Ophthalmology were reviewed.
   STUDY SELECTION AND DATA EXTRACTION: Controlled studies, unpublished reports involving 100 or more subjects, and published reports describing 5 or more subjects were reviewed. Only English-language articles were considered
   DATA SYNTHESIS: Intravitreal bevacizumab has been evaluated in 133 patients in unpublished controlled studies. Over 3500 patients have been evaluated in open-label studies with duration of follow-up ranging from 3 months to 1 year. The most common use was neovascular age-related macular degeneration (AMD). Other conditions studied included diabetic retinopathy, pathological myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein occlusion, or uveitis. Statistically significant improvements in visual acuity, as well as decreases in retinal thickness and the extent of choroidal neovascularization, were noted. Intravitreal bevacizumab was well tolerated over the short term. In a registry compiling adverse experiences of 7113 intravitreal injections, rates of adverse events were less than or equal to 0.21% .
   CONCLUSIONS: Uncontrolled studies support a benefit of intravitreal bevacizumab in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of bevacizumab. Patients should discuss the potential risks and benefits of intravitreal bevacizumab and other available therapies with their physicians I before receiving treatment. Controlled trials are needed to characterize the safety 1 and efficacy of intravitreal bevacizumab and determine the optimal treatment regimen.
C1 Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco
RP Lynch, SS (通讯作者)，Univ Calif San Francisco, Dept Clin Pharm, Box 0622,C-152,521 Parnassua Ave, San Francisco, CA 94143 USA.
EM lynchs@pharmacy.ucsf.edu
OI Lynch, Shalini/0000-0002-2569-7532
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   *US DEP HHS NIH NA, 2003, AG REL MAC DEG WHAT
   WITKOWSKI W, GENENTECH SHARES RIS
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   2005, THOMSON HLTH CARE RE, V24, P42
NR 67
TC 115
Z9 126
U1 0
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 APR
PY 2007
VL 41
IS 4
BP 614
EP 625
DI 10.1345/aph.1H316
PG 12
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 158BA
UT WOS:000245764700010
PM 17355998
DA 2022-11-30
ER

PT J
AU Jang, YP
   Matsuda, H
   Itagaki, Y
   Nakanishi, K
   Sparrow, JR
AF Jang, YP
   Matsuda, H
   Itagaki, Y
   Nakanishi, K
   Sparrow, JR
TI Characterization of peroxy-A2E and furan-A2E photooxidation products and
   detection in human and mouse retinal pigment epithelial cell lipofuscin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIGHT-INDUCED DAMAGE; FUNDUS FLAVIMACULATUS; STARGARDTS-DISEASE; SINGLET
   OXYGEN; A2E; FLUOROPHORE; RPE; PHENOTYPE; ENDOPEROXIDES; MECHANISMS
AB The nondegradable pigments that accumulate in retinal pigment epithelial ( RPE) cells as lipofuscin constituents are considered to be responsible for the loss of RPE cells in recessive Stargardt disease, a blindness macular disorder of juvenile onset. This autofluorescent material may also contribute to the etiology of age-related macular degeneration. The best characterized of these fluorophores is A2E, a compound consisting of two retinoid-derived side arms extending from a pyridinium ring. Evidence indicates that photochemical mechanisms initiated by excitation from the blue region of the spectrum may contribute to the adverse effects of A2E accumulation, with the A2E photooxidation products being damaging intermediates. By studying the oxidation products ( oxo-A2E) generated using oxidizing agents that add one or two oxygens at a time, together with structural analysis by heteronuclear single quantum correlation-NMR spectroscopy, we demonstrated that the oxygen-containing moieties generated within photooxidized A2E include a 5,8-monofuranoid and a cyclic 5,8-monoperoxide. We have shown that the oxidation sites can be assigned to the shorter arm of A2E, to the longer arm, or to both arms by analyzing changes in the UV-visible spectrum of A2E, and we have observed a preference for oxidation on the shorter arm. By liquid chromatography-mass spectrometry, we have also detected both monofuran-A2E and monoperoxy-A2E in aged human RPE and in eye cups of Abca4/Abcr(-/-) mice, a model of Stargardt disease. Because the cytotoxicity of endoperoxide moieties is well known, the production of endoperoxide-containing oxo-A2E may account, at least in part, for cellular damage ensuing from A2E photooxidation.
C1 Columbia Univ, Dept Chem, New York, NY 10027 USA.
   Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   Columbia Univ, Dept Pathol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Nakanishi, K (通讯作者)，Columbia Univ, Dept Chem, New York, NY 10027 USA.
EM kn5@columbia.edu; jrs88@columbia.edu
RI Jang, Young Pyo/AAJ-8782-2020
OI Jang, Young Pyo/0000-0001-5865-9228
FU NATIONAL EYE INSTITUTE [R01EY012951] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM034509,
   R37GM034509] Funding Source: NIH RePORTER; NEI NIH HHS [EY 12951]
   Funding Source: Medline; NIGMS NIH HHS [GM 34509] Funding Source:
   Medline
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NR 40
TC 97
Z9 104
U1 0
U2 5
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 DEC 2
PY 2005
VL 280
IS 48
BP 39732
EP 39739
DI 10.1074/jbc.M504933200
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 986PD
UT WOS:000233461300010
PM 16186115
OA hybrid
DA 2022-11-30
ER

PT J
AU Jeising, S
   Geerling, G
   Guthoff, R
   Hanggi, D
   Sabel, M
   Rapp, M
   Nickel, AC
AF Jeising, Sebastian
   Geerling, Gerd
   Guthoff, Rainer
   Haenggi, Daniel
   Sabel, Michael
   Rapp, Marion
   Nickel, Ann-Christin
TI In-Vitro Use of Verteporfin for Photodynamic Therapy in Glioblastoma
SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY
LA English
DT Article
DE Verteporfin; Benzoporphyrin derivative; Visudyne; Photodynamic therapy;
   Glioblastoma
ID 5-AMINOLEVULINIC ACID; BRAIN-TUMORS; TEMOZOLOMIDE; LANDSCAPE
AB Background: Stummer et al. established fluorescence-guided surgery (FGS) for glioblastoma (GBM) using 5-ami-nolevulinic acid (5-ALA). Its metabolite, protoporphyrin IX (PPIX), is also a photosensitizer and can be used for photodynamic therapy (PDT) using a laser beam of 635 nm. The porphyrin derivate verteporfin (VP) was discovered to have properties to penetrate the brain, pharmacologically target glioma cells, and is approved for PDT of choroidal neovascularization in wet age-related macular degeneration at 689 nm. Objective: To elucidate whether GBM cell lines are susceptible to PDT with second-generation photosensitizer VP. Methods: Human glioma cell lines LN229, HSR-GBM1, and a low-passage patient-derived GBM cell line P1 were treated with variable concentrations of VP for 24 h, followed by PDT at 689 nm using a diode laser light. Cell viability was measured using the MTT assay and VP uptake was measured using a desktop cytometer. Results: Significantly higher cell death following PDT with VP compared to VP treatment alone or no treatment was detected in all cell models (LN229, HSR-GBM1, P1). Flowcytometric measurements revealed a concentration-dependent cellular uptake of VP after 24 h incubation up to 99% at 10 mu M (HSR-GBM1). Conclusion: This study demonstrates that PDT with VP causes cell death in GBM cells at marginal concentrations. Additionally, red spectrum fluorescence was detected at therapeutic concentrations in all cell lines, validating the cellular uptake of VP in GBM cells. VP, therefore, is not only a potential drug for targeting GBM pharmaco-logically but can be used as an optical imaging dye in surgery and photosensitizer to make GBM susceptible to PDT.
C1 [Jeising, Sebastian; Haenggi, Daniel; Sabel, Michael; Rapp, Marion; Nickel, Ann-Christin] Univ Hosp Dusseldorf, Dept Neurosurg, D-40225 Dusseldorf, Germany.
   [Geerling, Gerd; Guthoff, Rainer] Univ Hosp Dusseldorf, Dept Ophthalmol, Dusseldorf, Germany.
C3 Heinrich Heine University Dusseldorf; Heinrich Heine University
   Dusseldorf Hospital; Heinrich Heine University Dusseldorf; Heinrich
   Heine University Dusseldorf Hospital
RP Jeising, S (通讯作者)，Univ Hosp Dusseldorf, Dept Neurosurg, D-40225 Dusseldorf, Germany.
EM sebastian.jeising@hhu.de; Geerling@med.uni-duesseldorf.de;
   Rainer.Guthoff@med.uni-duesseldorf.de;
   Daniel.Haenggi@med.uni-duesseldorf.de;
   Michael.Sabel@med.uni-duesseldorf.de;
   Marion.Rapp@med.uni-duesseldorf.de; ann-christin.nickel@hhu.de
OI Jeising, Sebastian/0000-0002-2130-7082
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NR 34
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1572-1000
EI 1873-1597
J9 PHOTODIAGN PHOTODYN
JI Photodiagnosis Photodyn. Ther.
PD DEC
PY 2022
VL 40
AR 103049
DI 10.1016/j.pdpdt.2022.103049
PG 7
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 5R5HL
UT WOS:000874541500005
PM 35932958
OA hybrid
DA 2022-11-30
ER

PT J
AU Kaushik, M
   Nawaz, S
   Mufti, H
   Qureshi, T
AF Kaushik, Madhurima
   Nawaz, Shah
   Mufti, Haniyaa
   Qureshi, TariqSyed
TI Etiological spectrum of irreversible blindness in Kashmir in North India
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Diabetic retinopathy; glaucoma; India; irreversible blindness; Kashmir;
   ocular trauma
ID MODERATE VISUAL IMPAIRMENT; VISION IMPAIRMENT; GLOBAL PREVALENCE;
   URBAN-POPULATION; GLAUCOMA; BURDEN; PROJECTIONS
AB Purpose: To determine the etiological spectrum of irreversible blindness in Kashmir Valley in India. Methods: Patients presenting to a tertiary care hospital in Kashmir, India, with unilateral or bilateral blindness from April 2019 to March 2020 were included in this cross-sectional study. Blindness was defined using the World Health Organization (WHO) criteria. All subjects had a complete ophthalmologic examination and information was gathered regarding their demographic profile, nature of ocular disorder whether primary or secondary and laterality, if the ocular involvement was unilateral. Results: 248 patients were enrolled in the study. The mean age of the patients was 57.17 years. The male: female ratio was 2.17:1. The commonest cause of unilateral or bilateral blindness was glaucoma (22.58%) followed by diabetic retinopathy (DR) (17.74%). Unilateral blindness was seen in 78.62% of the patients. Unilateral blindness occurred mainly due to glaucoma (16.41%), DR (14.87%), age-related macular degeneration (13.33%), and trauma (pellet injury: 10.76%, non-pellet injury: 10.25%). The major causes of bilateral blindness were glaucoma (45.28%), DR (28.30%), and hereditary/congenital retinal diseases (16.98%). Socioeconomic status and educational status were significantly associated (P < 0.05 each) while age, gender, place of residence, and occupation were not significantly associated (P > 0.05 each) with the number of eyes affected by blindness. Conclusion: Glaucoma and DR are the foremost causes of irreversible blindness in Kashmir. Public health plans aimed at encouraging good health education of patients should be developed in this region. Moreover, patients should be screened effectively for glaucoma and diabetes at the level of primary health care facilities.
C1 [Kaushik, Madhurima; Nawaz, Shah; Mufti, Haniyaa; Qureshi, TariqSyed] Govt Med Coll, Dept Ophthalmol, Srinagar 190010, Jammu & Kashmir, India.
RP Kaushik, M (通讯作者)，Govt Med Coll, Dept Ophthalmol, Srinagar 190010, Jammu & Kashmir, India.
EM madhurima0105@gmail.com
OI Kaushik, Madhurima/0000-0001-8402-9094
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NR 34
TC 1
Z9 1
U1 1
U2 1
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, Maharashtra, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD OCT
PY 2021
VL 69
IS 10
BP 2630
EP +
DI 10.4103/ijo.IJO_3818_20
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YY0HY
UT WOS:000754475500014
PM 34571602
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Macnamara, A
   Chen, CL
   Schinazi, VR
   Saredakis, D
   Loetscher, T
AF Macnamara, Anne
   Chen, Celia
   Schinazi, Victor R.
   Saredakis, Dimitrios
   Loetscher, Tobias
TI Simulating Macular Degeneration to Investigate Activities of Daily
   Living: A Systematic Review
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE age-related macular degeneration; vision impairment; simulation;
   activities of daily living; rehabilitation
ID LOW-VISION; VISUAL IMPAIRMENT; VIRTUAL-REALITY; OLDER-ADULTS;
   EPIDEMIOLOGY; RECOGNITION; ADAPTATION; PERCEPTION; DEPRESSION; BLINDNESS
AB Purpose: Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation strategies. One way to do this is through visual impairment simulations. The aim of this review is to synthesize and assess the types of simulation methods that have been used to simulate age-related macular degeneration (AMD) in normally sighted participants, during activities of daily living (e.g., reading, cleaning, and cooking). Methods: We conducted a systematic literature search in five databases and a critical analysis of the advantages and disadvantages of various AMD simulation methods (following PRISMA guidelines). The review focuses on the suitability of each method for investigating activities of daily living, an assessment of clinical validation procedures, and an evaluation of the adaptation periods for participants. Results: Nineteen studies met the criteria for inclusion. Contact lenses, computer manipulations, gaze contingent displays, and simulation glasses were the main forms of AMD simulation identified. The use of validation and adaptation procedures were reported in approximately two-thirds and half of studies, respectively. Conclusions: Synthesis of the methodology demonstrated that the choice of simulation has been, and should continue to be, guided by the nature of the study. While simulations may never completely replicate vision loss experienced during AMD, consistency in simulation methodology is critical for generating realistic behavioral responses under vision impairment simulation and limiting the influence of confounding factors. Researchers could also come to a consensus regarding the length and form of adaptation by exploring what is an adequate amount of time and type of training required to acclimatize participants to vision impairment simulations.
C1 [Macnamara, Anne; Saredakis, Dimitrios; Loetscher, Tobias] Univ South Australia, Cognit Ageing & Impairment Neurosci Lab, UniSA Justice & Soc, Adelaide, SA, Australia.
   [Chen, Celia] Flinders Univ S Australia, Coll Med & Publ Hlth, Flinders Med Ctr, Adelaide, SA, Australia.
   [Schinazi, Victor R.] Bond Univ, Fac Soc & Design, Dept Psychol, Gold Coast, Qld, Australia.
   [Schinazi, Victor R.] Campus Res Excellence & Technol Enterprise CREATE, Future Hlth Technol, Singapore ETH Ctr, Singapore, Singapore.
C3 University of South Australia; Flinders Medical Centre; Flinders
   University South Australia; Bond University
RP Macnamara, A (通讯作者)，Univ South Australia, Cognit Ageing & Impairment Neurosci Lab, UniSA Justice & Soc, Adelaide, SA, Australia.
EM anne.macnamara@mymail.unisa.edu.au
RI Macnamara, Anne/AAZ-6383-2021
OI Macnamara, Anne/0000-0002-6589-2826; Loetscher,
   Tobias/0000-0003-1967-2926
FU Australian Government Research Training Program Scholarship - National
   Health and Medical Research Council (NHMRC) Dementia Research Leadership
   Fellowship [GNT1136269]
FX Funding. AM and DS were supported by the Australian Government Research
   Training Program Scholarship and TL was funded by a National Health and
   Medical Research Council (NHMRC) Dementia Research Leadership Fellowship
   (GNT1136269).
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NR 86
TC 3
Z9 3
U1 3
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD AUG 13
PY 2021
VL 15
AR 663062
DI 10.3389/fnins.2021.663062
PG 15
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Neurosciences & Neurology
GA XG2NE
UT WOS:000724594000001
PM 34483815
OA gold, Green Submitted, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Lee, SJ
   Kim, SJ
   Jo, DH
   Park, KS
   Kim, JH
AF Lee, Seok Jae
   Kim, Soo-Jin
   Jo, Dong Hyun
   Park, Kyu-Sang
   Kim, Jeong Hun
TI Blockade of mTORC1-NOX signaling pathway inhibits TGF-beta 1-mediated
   senescence-like structural alterations of the retinal pigment epithelium
SO FASEB JOURNAL
LA English
DT Article
DE epithelial&#8208; mesenchymal transition; retinal pigment epithelium;
   senescence; TGF&#8208; &#946; 1; mTORC1&#8208; NOX signaling
AB The retinal pigment epithelium (RPE) undergoes characteristic structural changes and epithelial-mesenchymal transition (EMT) during normal aging, which are exacerbated in age-related macular degeneration (AMD). Although the pathogenic mechanisms of aging and AMD remain unclear, transforming growth factor-beta 1 (TGF-beta 1) is known to induce oxidative stress, morphometric changes, and EMT as a senescence-promoting factor. In this study, we examined whether intravitreal injection of TGF-beta 1 into the mouse eye elicits senescence-like morphological alterations in the RPE and if this can be prevented by suppressing mammalian target of rapamycin complex 1 (mTORC1) or NADPH oxidase (NOX) signaling. We verified that intravitreal TGF-beta 1-induced stress fiber formation and EMT in RPE cells, along with age-associated morphometric changes, including increased variation in cell size and reduced cell density. In RPE cells, exogenous TGF-beta 1 increased endogenous expression of TGF-beta 1 and upregulated Smad3-ERK1/2-mTORC1 signaling, increasing reactive oxygen species (ROS) production and EMT. We demonstrated that inhibition of the mTORC1-NOX4 pathway by pretreatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-dependent protein kinase, or GKT137831, a NOX1/4 inhibitor, decreased ROS generation, prevented stress fiber formation, attenuated EMT, and improved the regularity of the RPE structure in vitro and in vivo. These results suggest that intravitreal TGF-beta 1 injection could be used as a screening model to investigate the aging-related structural and functional changes to the RPE. Furthermore, the regulation of TGF-beta-mTORC1-NOX signaling could be a potential therapeutic target for reducing pathogenic alterations in aged RPE and AMD.
C1 [Lee, Seok Jae; Kim, Jeong Hun] Seoul Natl Univ Hosp, Clin Res Inst, Fight Angiogenesis Related Blindness FARB Lab, Seoul 03080, South Korea.
   [Lee, Seok Jae; Kim, Jeong Hun] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea.
   [Kim, Soo-Jin; Park, Kyu-Sang] Yonsei Univ, Dept Physiol, Wonju Coll Med, Wonju 220701, Gangwon Do, South Korea.
   [Jo, Dong Hyun] Seoul Natl Univ, Dept Anat & Cell Biol, Coll Med, Seoul, South Korea.
   [Kim, Jeong Hun] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Kim, Jeong Hun] Korea Res Inst Biosci & Biotechnol, Adv Biomed Res Ctr, Daejeon, South Korea.
C3 Seoul National University (SNU); Seoul National University Hospital;
   Seoul National University (SNU); Yonsei University; Seoul National
   University (SNU); Seoul National University (SNU); Korea Research
   Institute of Bioscience & Biotechnology (KRIBB)
RP Kim, JH (通讯作者)，Seoul Natl Univ Hosp, Clin Res Inst, Fight Angiogenesis Related Blindness FARB Lab, Seoul 03080, South Korea.; Park, KS (通讯作者)，Yonsei Univ, Dept Physiol, Wonju Coll Med, Wonju 220701, Gangwon Do, South Korea.
EM qsang@yonsei.ac.kr; steph25@snu.ac.kr
OI Kim, Jeong Hun/0000-0003-2957-1766; Lee, Seok Jae/0000-0003-1523-0012
FU Creative Materials Discovery Program through the National Research
   Foundation of Korea (NRF) - Ministry of Science and ICT
   [2018M3D1A1058826]; National Research Foundation of Korea (NRF)
   [2015M3A7B6027946]; Development of Platform Technology for Innovative
   Medical Measurements - Korea Research Institute of Standards and Science
   [KRISS-2020-GP2020-0004]; Medical Research Center Program - Ministry of
   Science and ICT [2017R1A5A2015369]
FX This research was supported by the Creative Materials Discovery Program
   through the National Research Foundation of Korea (NRF) funded by the
   Ministry of Science and ICT (2018M3D1A1058826 to JHK), the National
   Research Foundation of Korea (NRF) Grants (2015M3A7B6027946 to JHK), the
   Development of Platform Technology for Innovative Medical Measurements
   funded by Korea Research Institute of Standards and Science
   (KRISS-2020-GP2020-0004 to JHK), and the Medical Research Center Program
   funded by the Ministry of Science and ICT (2017R1A5A2015369 to K.-S.P).
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NR 47
TC 3
Z9 3
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAR
PY 2021
VL 35
IS 3
AR e21403
DI 10.1096/fj.202001939RR
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA QX8EV
UT WOS:000629576700028
PM 33559185
DA 2022-11-30
ER

PT J
AU Chakravarthy, U
   Havilio, M
   Syntosi, A
   Pillai, N
   Wilkes, E
   Benyamini, G
   Best, C
   Sagkriotis, A
AF Chakravarthy, Usha
   Havilio, Moshe
   Syntosi, Annie
   Pillai, Natasha
   Wilkes, Emily
   Benyamini, Gidi
   Best, Catherine
   Sagkriotis, Alexandros
TI Impact of macular fluid volume fluctuations on visual acuity during
   anti-VEGF therapy in eyes with nAMD
SO EYE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; RETINA SPECIALISTS; DEGENERATION;
   AFLIBERCEPT; GUIDELINES
AB Objectives To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD).
   Methods Data were extracted from electronic medical records of 381 nAMD patients, aged >= 50 years; baseline VA >= 33 and <= 73 letters; >= 24 months' follow-up and >= 2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression.
   Results By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: -12.9 to -6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0-0.7] versus 0.8 [0.5-1.0]; SRF: 0.0 [0.0-0.5] versus 0.6 [0.3-1.0]).
   Conclusions Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.
C1 [Chakravarthy, Usha] Queens Univ Belfast, Inst Clin Sci, Ctr Expt Med, Belfast, Antrim, North Ireland.
   [Havilio, Moshe; Benyamini, Gidi] Notal Vis Ltd, Tel Aviv, Israel.
   [Syntosi, Annie; Best, Catherine; Sagkriotis, Alexandros] Novartis Pharma AG, Basel, Switzerland.
   [Pillai, Natasha] IQVIA, Basel, Switzerland.
   [Wilkes, Emily] IQVIA, London, England.
C3 Queens University Belfast; Novartis; IQVIA; IQVIA
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Inst Clin Sci, Ctr Expt Med, Belfast, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Chakravarthy, Usha/0000-0002-2606-3734
FU Novartis; Novartis Pharma AG, Basel, Switzerland
FX IQVIA and Notal Vision received funding from Novartis to conduct the
   study. Novartis Pharma AG, Basel, Switzerland, sponsored the study. The
   sponsor had a role in the study design, data collection, data analysis
   and manuscript preparation.
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NR 23
TC 23
Z9 25
U1 0
U2 1
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD NOV
PY 2021
VL 35
IS 11
BP 2983
EP 2990
DI 10.1038/s41433-020-01354-4
EA JAN 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WJ3DG
UT WOS:000605863200002
PM 33414525
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU You, S
   Kim, H
   Jung, HY
   Kim, B
   Lee, EJ
   Kim, JW
   Kim, Y
AF You, Suyeon
   Kim, Hyoungtai
   Jung, Hye-youn
   Kim, Boram
   Lee, Eun Jung
   Kim, Jin Woo
   Kim, Yoonkyung
TI Tuning surface functionalities of sub-10 nm-sized nanocarriers to target
   outer retina in designing drug delivery agents for intravitreal
   administration
SO BIOMATERIALS
LA English
DT Article
DE Age-related macular degeneration; Dendrimers; Intravitreal injection;
   Nanomedicine; Retinal drug delivery; Surface functional groups
ID OCULAR DELIVERY; DENDRIMERS; EYE; NANOPARTICLES; ANGIOGENESIS; POLYMERS;
   THERAPY; PHARMACOKINETICS; NANOMATERIALS; PERFORMANCE
AB Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness, generally affecting people over 50 years of age in industrialized countries. Despite the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy in attenuating the growth of new blood vessels, substantial visual improvements are rare with this complex disease. Furthermore, the current regimen of repeated monthly intravitreal injections of drugs can result in serious side effects. Combination therapies-to complement antiVEGF alone-with a prolonged therapeutic effect and efficient delivery to the intended site are urgently needed, which could be realized through the use of carefully designed nanocarriers. To understand the physicochemical effects (e.g., size, charge, geometry) of intravitreally administered nanocarriers on their bioavailability, distribution, and targeting efficiency across multiple layers of the retina, here we prepared seven different types of surface-functionalized water-soluble dendritic nanocarriers with hydrodynamic sizes mostly under 5 nm. A similar stoichiometric amount of fluorophore was covalently attached to each of these biocompatible nanocarriers for quantitative analyses by confocal microscopy of cryosectioned healthy mouse eyes. Interestingly, at 24 h post-injection, the nanocarrier with multiple copies of glucosamine on the surface (D-NSG) accumulated predominantly in the photoreceptor layer and the retinal pigment epithelium (RPE), which are speculated to be associated with AMD pathogenesis (i.e., target sites). Furthermore, extended residence at these outer retinal layers was demonstrated by D-NSG, which appeared to gradually turn into micron-scale particles potentially through aggregation. Our systematic findings may provide useful guidelines for the rational design of intravitreal nanocarriers to treat vision-threatening retinal diseases, including AMD.
C1 [You, Suyeon; Jung, Hye-youn; Kim, Boram; Kim, Yoonkyung] Korea Res Inst Biosci & Biotechnol, Div Biomed Sci, Daejeon 34141, South Korea.
   [Kim, Hyoungtai; Lee, Eun Jung; Kim, Jin Woo] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea.
C3 Korea Research Institute of Bioscience & Biotechnology (KRIBB); Korea
   Advanced Institute of Science & Technology (KAIST)
RP Kim, Y (通讯作者)，Korea Res Inst Biosci & Biotechnol, Div Biomed Sci, Daejeon 34141, South Korea.; Kim, H (通讯作者)，Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea.
EM insurgen@naver.com; ykim@kribb.re.kr
FU National Research Foundation of Korea - Ministry of Science and ICT
   [NRF-2017R1A2B2008284, NRF-2017R1A2B3002862, NRF-2012M3A 9B2028334,
   WISET-2019-560]; KRIBB Research Initiative Program
FX This work was supported by the National Research Foundation of Korea
   funded by the Ministry of Science and ICT (NRF-2017R1A2B2008284,
   NRF-2017R1A2B3002862, NRF-2012M3A 9B2028334, and WISET-2019-560) and the
   KRIBB Research Initiative Program. We thank Dr. Young Joo Lee
   (University of Hamburg) for the assistance with preparing some figures.
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NR 82
TC 3
Z9 3
U1 3
U2 30
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD OCT
PY 2020
VL 255
AR 120188
DI 10.1016/j.biomaterials.2020.120188
PG 18
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA MU5DQ
UT WOS:000555693800029
PM 32652402
DA 2022-11-30
ER

PT J
AU Tahir, NAM
   Saffian, SM
   Islahudin, FH
   Gafor, AHA
   Othman, H
   Manan, HA
   Makmor-Bakry, M
AF Mohd Tahir, Nor Asyikin
   Mohd Saffian, Shamin
   Islahudin, Farida Hanim
   Abdul Gafor, Abdul Halim
   Othman, Hanita
   Abdul Manan, Hamizah
   Makmor-Bakry, Mohd
TI Effects of CST3 Gene G73A Polymorphism on Cystatin C in a Prospective
   Multiethnic Cohort Study
SO NEPHRON
LA English
DT Article
DE Cystatin C; Gene polymorphism; Glomerular filtration rate; Kidney
   function
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; ALZHEIMERS-DISEASE;
   RENAL-FUNCTION; ASSOCIATION; EQUATION; VARIANT; VALUES; GFR; AGE
AB Background/Aims: G73A polymorphism in the CST3 gene of cystatin C has been associated with Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. However, studies investigating the influence of this genetic variability on serum cystatin C and cystatin-based renal function estimate are limited. Therefore, the aim of this study is to investigate the possible association of single-nucleotide polymorphism (rs1064039) of the CST3 gene on the serum cystatin C level and cystatin C-based estimated glomerular filtration rate (eGFR). Methods: Study subjects include patients with various levels of renal function recruited from the nephrology clinic and wards of a tertiary hospital. The blood samples collected were analyzed for serum cystatin C and creatinine levels by particle-enhanced turbidimetric immunoassay and kinetic alkaline picrate method, respectively. DNA was extracted using a commercially available kit. -Polymerase chain reaction results were confirmed by direct DNA Sanger sequencing. Results: The genotype percentage (G/G = 73%, G/A = 24.1%, and A/A = 2.9%) adhere to the Hardy-Weinberg equilibrium. The dominant allele found in our population was CST3 73G allele (85%). The regression lines' slope of serum cystatin C against creatinine and cystatin C-based eGFR against creatinine-based eGFR, between G and A allele groups, showed a statistically significant difference (z-score = 3.457, p < 0.001 and z-score = 2.158, p = 0.015, respectively). Patients with A allele had a lower serum cystatin C level when the values were extrapolated at a fixed serum creatinine value, suggesting the influence of genetic factor. Conclusion: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.
C1 [Mohd Tahir, Nor Asyikin; Mohd Saffian, Shamin; Islahudin, Farida Hanim; Makmor-Bakry, Mohd] Univ Kebangsaan Malaysia, Fac Pharm, Kuala Lumpur, Malaysia.
   [Abdul Gafor, Abdul Halim] Univ Kebangsaan Malaysia, Dept Med, Nephrol Unit, Med Ctr, Kuala Lumpur, Malaysia.
   [Othman, Hanita; Abdul Manan, Hamizah] Univ Kebangsaan Malaysia, Med Ctr, Dept Pathol, Kuala Lumpur, Malaysia.
C3 Universiti Kebangsaan Malaysia; Universiti Kebangsaan Malaysia;
   Universiti Kebangsaan Malaysia
RP Makmor-Bakry, M (通讯作者)，Univ Kebangsaan Malaysia, Fac Pharm, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
EM mohdclinpharm@ukm.edu.my
RI Saffian, Shamin Mohd/Z-1392-2019; Gafor, Abdul Halim Abdul/L-4405-2017;
   Makmor-Bakry, Mohd/AAA-8591-2019; Tahir, Nor Asyikin Mohd/ABC-1172-2020
OI Saffian, Shamin Mohd/0000-0001-6243-6975; Gafor, Abdul Halim
   Abdul/0000-0003-3950-2844; Tahir, Nor Asyikin Mohd/0000-0002-7330-7148;
   Makmor Bakry, Mohd/0000-0002-0592-0645
FU Fundamental Research Grant Scheme, Ministry of Education, Malaysia
   [1/2016/SKK09/UKM/02/3]
FX This study was funded by the Fundamental Research Grant Scheme, Ministry
   of Education, Malaysia (Fundamental Research Grant
   Scheme/1/2016/SKK09/UKM/02/3). The financial resources provided were
   used to purchase materials and related services required for the
   experimental work.
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NR 52
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U1 1
U2 2
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1660-8151
EI 2235-3186
J9 NEPHRON
JI Nephron
PD APR
PY 2020
VL 144
IS 4
BP 204
EP 212
DI 10.1159/000505296
PG 9
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA LE7GW
UT WOS:000526892000008
PM 32050196
DA 2022-11-30
ER

PT J
AU Bolme, S
   Morken, TS
   Follestad, T
   Sorensen, TL
   Austeng, D
AF Bolme, Stine
   Morken, Tora Sund
   Follestad, Turid
   Sorensen, Torben Lykke
   Austeng, Dordi
TI Task shifting of intraocular injections from physicians to nurses: a
   randomized single-masked noninferiority study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; intraocular injections; noninferior;
   nurse training; randomized controlled trial; task shifting
ID MACULAR DEGENERATION; RANIBIZUMAB; BEVACIZUMAB; SAFETY
AB Purpose To test if task shifting of intraocular injections to nurses in a real-world setting can result in similar visual function outcome with equal safety profile.
   Method All patients with either age-related macular degeneration, retinal vein occlusion or diabetic macular oedema remitted to intraocular injections at a tertiary ophthalmology department in Norway between March 2015 and May 2017, were asked to participate. The participants were randomized to either nurse- or physician-administered intraocular injections of anti-vascular endothelial growth factor. The primary outcome measure was change in best-corrected visual acuity from baseline to 1-year follow-up. The mean difference in the primary outcome between the groups was analysed by a noninferiority test with a margin of three letters in disfavour of the nurse group. Adverse events were recorded.
   Results Three hundred and forty-two patients entered the study. Two hundred and fifty-nine completed the 1-year follow-up and were included in the study sample for the analysis of the primary outcome. Nurse-administered intraocular injections were noninferior to physician-administered injections with 0.7 and 1.6 letters gained, respectively (95% CI of the mean difference, -2.9 to 1.0; p = 0.019, one-sided t-test). Two thousand and seventy-seven injections and three ocular adverse events were recorded.
   Conclusion Task shifting of intraocular injections to nurses can be performed without increased risk to visual function. Such a task shift can alleviate the burden of performing intraocular injections in ophthalmology departments. To our knowledge, this is the first RCT on task shifting of a surgical procedure from physicians to nurses in a high-income country.
C1 [Bolme, Stine; Morken, Tora Sund; Austeng, Dordi] Trondheim Reg & Univ Hosp, Olavs Hosp, Dept Ophthalmol, St, Trondheim, Norway.
   [Bolme, Stine; Morken, Tora Sund; Austeng, Dordi] Norwegian Univ Sci, Dept Neuromedicine, Technology, Movement Sci, Trondheim, Norway.
   [Follestad, Turid] Norwegian Univ Sci, Dept Publ Hlth, Technology, Nursing, Trondheim, Norway.
   [Sorensen, Torben Lykke] Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.
   [Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth, Med Sciences, Copenhagen, Denmark.
   Trondheim Reg & Univ Hosp, St, N-7006 Trondheim, Norway.
C3 Norwegian University of Science & Technology (NTNU); Norwegian
   University of Science & Technology (NTNU); Norwegian University of
   Science & Technology (NTNU); University of Copenhagen; Norwegian
   University of Science & Technology (NTNU)
RP Austeng, D (通讯作者)，Trondheim Reg & Univ Hosp, Olavs Hosp, Dept Ophthalmol, St, Trondheim, Norway.
EM dordi.austeng@ntnu.no
OI Bolme, Stine/0000-0002-2540-9545; Austeng, Dordi/0000-0001-9782-576X
FU Central Norway Regional Health Authority Funding Source: Medline;
   Norwegian University of Science and Technology Funding Source: Medline
CR Austeng D, 2016, BMC OPHTHALMOL, V16, DOI 10.1186/s12886-016-0348-4
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   United Nations Department of Economic and Social Affairs Population Division, 2017, ESAPWP248 UN POP DIV
NR 16
TC 7
Z9 7
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAR
PY 2020
VL 98
IS 2
BP 139
EP 144
DI 10.1111/aos.14184
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KS3BI
UT WOS:000518184100007
PM 31267688
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Mahmoudian-Sani, MR
   Forouzanfar, F
   Asgharzade, S
   Ghorbani, N
AF Mahmoudian-Sani, Mohammad-Reza
   Forouzanfar, Fatemeh
   Asgharzade, Samira
   Ghorbani, Nilufar
TI Overexpression of MiR-183/96/182 Triggers Retina-Like Fate in Human Bone
   Marrow-Derived Mesenchymal Stem Cells (hBMSCs) in Culture
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIFFERENTIATION; DELETION; CRX; PHOTORECEPTORS; FIBROBLASTS; MATURATION;
   EPITHELIUM; MICRORNAS; MIR-182; PROTEIN
AB Retinal degeneration is considered as a condition ensued by different blinding disorders such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy, which can cause loss of photoreceptor cells and also lead to significant vision deficiencies. Although there is no efficient treatment in this domain, transplantation of stem cells has been regarded as a therapeutic approach for retinal degeneration. Thus, the purpose of this study was to analyze the potential of human bone marrow-derived mesenchymal stem cells (hBMSCs) to differentiate into photoreceptor cells via transfection of microRNA (miRNA) in vitro for regenerative medicine purposes. To this end, miR-183/96/182 cluster was transfected into hBMSCs; then, qRT-PCR was performed to measure the expression levels of miR-183/96/182 cluster and some retina-specific neuronal genes such as OTX2, NRL, PKC alpha, and recoverin. CRX and rhodopsin (RHO) levels were also measured through qRT-PCR and immunocytochemistry, and subsequently, cellular change morphology was detected. The findings showed no changes in the morphology of the given cells, and the expression of the neuroretinal genes such as OTX2, NRL, and PKC alpha. Moreover, recoverin was upregulated upon miR-183/-96/-182 overexpression in cultured hBMSCs. Ectopic overexpression of the miR-183 cluster could further increase the expression of CRX and RHO at the messenger RNA (mRNA) and protein levels. Furthermore, the data indicated that the miR-183 cluster could serve as a crucial function in photoreceptor cell differentiation. In fact, miRNAs could be assumed as potential targets to exploit silent neuronal differentiation. Ultimately, it was suggested that in vitro overexpression of miR-183 cluster could trigger reprogramming of the hBMSCs to retinal neuron fate, especially photoreceptor cells.
C1 [Mahmoudian-Sani, Mohammad-Reza] Ahvaz Jundishapur Univ Med Sci, Hlth Res Inst, Thalassemia & Hemoglobinopathy Res Ctr, Ahvaz, Iran.
   [Forouzanfar, Fatemeh] Mashhad Univ Med Sci, Neurosci Res Ctr, Mashhad, Razavi Khorasan, Iran.
   [Forouzanfar, Fatemeh] Mashhad Univ Med Sci, Fac Med, Dept Neurosci, Mashhad, Razavi Khorasan, Iran.
   [Asgharzade, Samira; Ghorbani, Nilufar] Shahrekord Univ Med Sci, Basic Hlth Sci Inst, Cellular & Mol Res Ctr, Shahrekord, Iran.
C3 Ahvaz Jundishapur University of Medical Sciences (AJUMS); Mashhad
   University Medical Science; Mashhad University Medical Science;
   Shahrekord University Medical Sciences
RP Asgharzade, S (通讯作者)，Shahrekord Univ Med Sci, Basic Hlth Sci Inst, Cellular & Mol Res Ctr, Shahrekord, Iran.
EM samiraasgharzade29@gmail.com
FU Shahrekord University of Medical Sciences [3529]
FX This research was supported by the Research Deputy of Shahrekord
   University of Medical Sciences (grant number 3529).
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NR 32
TC 7
Z9 8
U1 0
U2 6
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD DEC 11
PY 2019
VL 2019
AR 2454362
DI 10.1155/2019/2454362
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JY2KR
UT WOS:000504250200002
PM 31885884
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Tran, MTN
   Khalid, MKNM
   Pebay, A
   Cook, AL
   Liang, HH
   Wong, RCB
   Craig, JE
   Liu, GS
   Hung, SS
   Hewitt, AW
AF Minh Thuan Nguyen Tran
   Khalid, Mohd Khairul Nizam Mohd
   Pebay, Alice
   Cook, Anthony L.
   Liang, Helena H.
   Wong, Raymond C. B.
   Craig, Jamie E.
   Liu, Guei-Sheung
   Hung, Sandy S.
   Hewitt, Alex W.
TI Screening of CRISPR/Cas base editors to target the AMD high-risk Y402H
   complement factor H variant
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; GENOMIC DNA; RNA; POLYMORPHISM; CLEAVAGE;
   IMMUNITY; DESIGN; CELLS
AB Purpose: To evaluate the efficacy of using a CRISPR/Cas-mediated strategy to correct a common high-risk allele that is associated with age-related macular degeneration (AMD; rs1061170; NM_000186.3:c.1204T>C; NP_ 000177.2:p. His402Tyr) in the complement factor H (CFH) gene.
   Methods: A human embryonic kidney cell line (HEK293A) was engineered to contain the pathogenic risk variant for AMD (HEK293A-CFH). Several different base editor constructs (BE3, SaBE3, SaKKH-BE3, VQR-BE3, and TargetAID) and their respective single-guide RNA (sgRNA) expression cassettes targeting either the pathogenic risk variant allele in the CFH locus or the LacZ gene, as a negative control, were evaluated head-to-head for the incidence of a cytosine-to-thymine nucleotide correction. The base editor construct that showed appreciable editing activity was selected for further assessment in which the base-edited region was subjected to next-generation deep sequencing to quantify on-target and off-target editing efficacy.
   Results: The tandem use of the Target-AID base editor and its respective sgRNA demonstrated a base editing efficiency of facilitating a cytosine-to-thymine nucleotide correction in 21.5% of the total sequencing reads. Additionally, the incidence of insertions and deletions (indels) was detected in only 0.15% of the sequencing reads with virtually no off-target effects evident across the top 11 predicted off-target sites containing at least one cytosine in the activity window (n = 3, pooled amplicons).
   Conclusions: CRISPR-mediated base editing can be used to facilitate a permanent and stably inherited cytosine-tothymine nucleotide correction of the rs1061170 SNP in the CFH gene with minimal off-target effects.
C1 [Minh Thuan Nguyen Tran; Khalid, Mohd Khairul Nizam Mohd; Liu, Guei-Sheung; Hewitt, Alex W.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7000, Australia.
   [Pebay, Alice; Liang, Helena H.; Wong, Raymond C. B.; Hung, Sandy S.; Hewitt, Alex W.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
   [Pebay, Alice; Wong, Raymond C. B.; Liu, Guei-Sheung; Hung, Sandy S.; Hewitt, Alex W.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
   [Cook, Anthony L.] Univ Tasmania, Wicking Dementia Res & Educ Ctr, Hobart, Tas 7000, Australia.
   [Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Flinders Med Ctr, Bedford Pk, SA, Australia.
   [Pebay, Alice] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia.
C3 University of Tasmania; Menzies Institute for Medical Research; Centre
   for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; University of Tasmania; Flinders Medical
   Centre; Flinders University South Australia; University of Melbourne
RP Hewitt, AW (通讯作者)，Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7000, Australia.
EM hewitt.alex@gmail.com
RI Liu, Guei-Sheung/Q-6472-2018; Cook, Anthony/K-9489-2018; Mohd Khalid,
   Mohd Khairul Nizam/F-3821-2016
OI Liu, Guei-Sheung/0000-0003-3379-724X; Craig, Jamie/0000-0001-9955-9696;
   Cook, Anthony/0000-0003-1770-7910; Mohd Khalid, Mohd Khairul
   Nizam/0000-0001-7200-3102; Pebay, Alice/0000-0002-7408-9453; Hung,
   Sandy/0000-0002-7496-7092; Wong, Raymond Ching-Bong/0000-0002-8092-9455
FU Ophthalmic Research Institute of Australia; Macular Disease Foundation
   of Australia; Australian National Health and Medical Research Council
   (NHMRC) Centres of Research Excellence (CRE) [1023911, APP1123329];
   NHMRC; ARC
FX This work was supported by the Ophthalmic Research Institute of
   Australia and the Macular Disease Foundation of Australia. Financial
   support was also obtained from an Australian National Health and Medical
   Research Council (NHMRC) Centres of Research Excellence (CRE) #1023911
   and Project Grant (APP1123329). JEC and AWH are supported by NHMRC
   Fellowships, while AP is supported by an ARC Future Fellowship. The
   Centre for Eye Research Australia (CERA) receives Operational
   Infrastructure Support from the Victorian Government. The contents of
   the published material are solely the responsibility of the
   Administering Institution, a Participating Institution or individual
   authors and do not reflect the views of the NHMRC. We gratefully thank
   Vikrant Singh for helping with the matlab scripts for base calling and
   indel formation.
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NR 47
TC 8
Z9 8
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 MAR 16
PY 2019
VL 25
BP 174
EP 182
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA HS8PF
UT WOS:000464130900001
PM 30996586
DA 2022-11-30
ER

PT J
AU Miere, A
   Butori, P
   Cohen, SY
   Semoun, O
   Capuano, V
   Jung, C
   Souied, EH
AF Miere, Alexandra
   Butori, Pauline
   Cohen, Salomon Y.
   Semoun, Oudy
   Capuano, Vittorio
   Jung, Camille
   Souied, Eric H.
TI VASCULAR REMODELING OF CHOROIDAL NEOVASCULARIZATION AFTER ANTI-VASCULAR
   ENDOTHELIAL GROWTH FACTOR THERAPY VISUALIZED ON OPTICAL COHERENCE
   TOMOGRAPHY ANGIOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE anti-vascular endothelial growth factor; choroidal neovascularization;
   age-related macular degeneration; flow remodeling; high-flow network;
   optical coherence tomography angiography
ID RETINAL ANGIOMATOUS PROLIFERATION; INDOCYANINE GREEN ANGIOGRAPHY;
   MACULAR DEGENERATION; TYPE-2 NEOVASCULARIZATION; CLASSIFICATION; PHASE
AB Purpose: To describe the qualitative and quantitative changes in choroidal neovascula-rization (CNV) flow pattern after anti-vascular endothelial growth factor therapy, by optical coherence tomography angiography (OCTA).
   Methods: Consecutive patients with neovascular age-related macular degeneration underwent multimodal imaging, including OCTA at initial examination and at last visit. High-flow networks in the choriocapillaris segmentation of OCTA were qualitatively and quantitatively analyzed at baseline and at follow-up, to characterize vascular flow changes after anti-vascular endothelial growth factor treatment and to correlate these changes with final exudation signs on spectral domain optical coherence tomography.
   Results: Seventeen eyes were included. Mean follow-up was of 11.7 +/- 3.3 months. Baseline images showed six medusa pattern (35.3%), four seafan pattern (23.5%), and seven indistinct network patterns (41.2%). Mean CNV area at baseline was 1.58 +/- 1.72 mm(2). Final OCTA images revealed a decrease in CNV total area of 21.6%. In 6/17 eyes, the baseline neovascular pattern was unchanged; these cases were associated with exudation at the final spectral domain optical coherence tomography examination (P = 0.034) and a decrease in CNV area of 34.1%. Conversely, in 11/17 eyes (64.7%), the initial pattern had changed to a pruned vascular tree pattern, with variable exudative status on spectral domain optical coherence tomography at the final visit and a decrease in total CNV area of 0.07%.
   Conclusion: The vascular flow remodeling induced by recurrent anti-vascular endothelial growth factor treatment can be assessed by OCTA. Optical coherence tomography angiography may help to accurately evaluate treatment response and to recognize patterns usually associated with recurrent exudative activity.
C1 [Miere, Alexandra; Butori, Pauline; Cohen, Salomon Y.; Semoun, Oudy; Capuano, Vittorio; Souied, Eric H.] Univ Pads Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
   [Cohen, Salomon Y.; Jung, Camille; Souied, Eric H.] Ctr Hosp Intercommunal Creteil, GRC Macula, Clin Res Ctr, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Souied, EH (通讯作者)，Univ Pads Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM eric.souied@chicreteil.fr
RI Miere, Alexandra/AIC-4074-2022
OI Miere, Alexandra/0000-0003-4123-8210; JUNG, Camille/0000-0001-8486-8939
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NR 29
TC 37
Z9 38
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2019
VL 39
IS 3
BP 548
EP 557
DI 10.1097/IAE.0000000000001964
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IQ4SF
UT WOS:000480740100014
PM 29210939
DA 2022-11-30
ER

PT J
AU Corbelli, E
   Sacconi, R
   Rabiolo, A
   Mercuri, S
   Carnevali, A
   Querques, L
   Bandello, F
   Querques, G
AF Corbelli, Eleonora
   Sacconi, Riccardo
   Rabiolo, Alessandro
   Mercuri, Stefano
   Carnevali, Adriano
   Querques, Lea
   Bandello, Francesco
   Querques, Giuseppe
TI Optical Coherence Tomography Angiography in the Evaluation of Geographic
   Atrophy Area Extension
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; fundus autofluorescence; en face
   optical coherence tomography; geographic atrophy; optical coherence
   tomography angiography
ID QUIESCENT CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; PROGRESSION; EYE
AB PURPOSE. To investigate the application of optical coherence tomography angiography (OCT-A) in evaluation of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
   METHODS. Patients with GA were prospectively enrolled and studied with blue fundus autofluorescence (FAF), en face structural OCT, and OCT-A. OCT-A images were acquired using a slab of whole choroid, whereas en face structural OCT images were obtained at the ellipsoid zone (EZ), at the choroidal (CH) level, and at the scleral (SC) level. Three readers independently measured the GA extension areas and evaluated the foveal sparing in each examination. Intraobserver/interobserver agreements and agreement between each couple of imaging techniques were assessed.
   RESUJLTS. A total of 47 eyes (26 patients, mean age 76 +/- 7 years) with GA (mean area using FAF: 8.77 +/- 5.00 mm(2)) were included. Intraobserver and interobserver agreement was excellent for all imaging techniques (intraclass correlation coefficient [ICC] > 0.985), even if en face EZ structural OCT revealed the poorest quality agreement limits. Considering the analysis between each couple of imaging techniques, ICC was excellent between OCT-A compared with FAF (ICC: 0.995), followed by en face structural OCT at CH level (ICC: 0.992), at SC level (ICC: 0.986), and at EZ level (ICC: 0.973). No differences were detected between multifocal and monofocal GA lesions. Considering the evaluation of foveal involvement, lower agreements were disclosed between FAF and all other imaging techniques.
   CONCLUSIONS. OCT-A is a reliable technique for easily visualizing and quantifying GA with the advantages, compared to current imaging techniques, of offering together both structural and blood flow information regarding retinal and choroidal layers and excluding choroidal neovascularization.
C1 [Corbelli, Eleonora; Sacconi, Riccardo; Rabiolo, Alessandro; Mercuri, Stefano; Carnevali, Adriano; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, IRCCS, Dept Ophthalmol, Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
   [Sacconi, Riccardo] Univ Verona, Dept Neurol Biomed & Movement Sci, Eye Clin, Verona, Italy.
   [Carnevali, Adriano] Magna Graecia Univ Catanzaro, Dept Ophthalmol, Catanzaro, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   University of Verona; Magna Graecia University of Catanzaro
RP Querques, G (通讯作者)，Univ Vita Salute, IRCCS, Dept Ophthalmol, Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Rabiolo, Alessandro/J-2831-2019; Corbelli, Eleonora/AAA-3186-2019;
   bandello, francesco/AAH-2405-2019
OI Corbelli, Eleonora/0000-0003-1658-1922; bandello,
   francesco/0000-0003-3238-9682; Rabiolo, Alessandro/0000-0002-7772-5929;
   Querques, Giuseppe/0000-0002-3292-9581; Sacconi,
   Riccardo/0000-0003-2891-2012
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NR 24
TC 25
Z9 26
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 OCT
PY 2017
VL 58
IS 12
BP 5201
EP 5208
DI 10.1167/iovs.17-22508
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FL5JN
UT WOS:000414272100019
PM 29049720
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gianesini, C
   Hiragaki, S
   Laurent, V
   Hicks, D
   Tosini, G
AF Gianesini, Coralie
   Hiragaki, Susumu
   Laurent, Virginie
   Hicks, David
   Tosini, Gianluca
TI Cone Viability Is Affected by Disruption of Melatonin Receptors
   Signaling
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE melatonin; viability; photoreceptors
ID SEROTONIN N-ACETYLTRANSFERASE; RETINAL DEGENERATION MOUSE; CIRCADIAN
   CLOCK; MACULAR DEGENERATION; RAT RETINA; PHOTORECEPTOR DEGENERATION;
   MAMMALIAN RETINA; XENOPUS-LAEVIS; CELL-DEATH; IN-VIVO
AB PURPOSE. Previous studies have demonstrated that melatonin has an important role in the modulation of photoreceptor viability during aging and may be involved in the pathogenesis of age-related macular degeneration. This hormone exerts its influence by binding to G-protein coupled receptors named melatonin receptor 1 (MT1) and 2 (MT2). Melatonin receptors 1 and 2 activate a wide variety of signaling pathways.
   METHODS. Melatonin-proficient mice (C3H/f(+/+)) and melatonin-proficient mice lacking MT1 or MT2 receptors (MT1-/- and MT2-/-) were used in this study. Mice were killed at the ages of 3 and 18 months, and photoreceptor viability was determined by counting nuclei number in the outer nuclear layer (ONL). Cones were identified by immunohistochemistry using peanut agglutinin (PNA) and green/red and blue opsin antibodies. Protein kinase B (AKT) and forkhead box O (FOXO1) were assessed by Western blotting and immunohistochemistry.
   RESULTS. The number of nuclei in the ONL was significantly reduced in C3Hf(+/+), MT1-/-, and MT2-/- mice at 18 months of age with respect to 3-month-old animals. In 18-month-old MT1-/- and MT2-/- mice, but not in C3H/f(+/+), the number of cones was significantly reduced with respect to young MT1-/- and MT2-/- mice or age-matched C3H/f(+/+). In C3H/f(+/+), activation of the AKT-FOXO1 pathway in the photoreceptors showed a significant difference between night and day.
   CONCLUSIONS. Our data indicate that disruption of MT1/MT2 heteromer signaling induces a reduction in the number of photoreceptors during aging and also suggest that the AKT-FOXO1 survival pathway may be involved in the mechanism by which melatonin protects photoreceptors.
C1 [Gianesini, Coralie; Hiragaki, Susumu; Tosini, Gianluca] Morehouse Sch Med, Dept Pharmacol & Toxicol, 720 Westview Dr, Atlanta, GA 30310 USA.
   [Gianesini, Coralie; Hiragaki, Susumu; Tosini, Gianluca] Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA.
   [Gianesini, Coralie; Laurent, Virginie; Hicks, David] Ctr Natl Rech Sci, Unite Propres Rech 3212, Inst Cellular & Integrat Neurosci, Strasbourg, France.
C3 Morehouse School of Medicine; Morehouse School of Medicine; Centre
   National de la Recherche Scientifique (CNRS)
RP Tosini, G (通讯作者)，Morehouse Sch Med, Dept Pharmacol & Toxicol, 720 Westview Dr, Atlanta, GA 30310 USA.
EM gtosini@msm.edu
OI tosini, gianluca/0000-0003-3645-4533
FU National Institutes of Health (Bethesda, MD, USA) [EY022216, EY020821]; 
   [5U54NS083932];  [S21MD000101];  [G12-RR03034];  [U54RR026137]; NATIONAL
   CENTER FOR RESEARCH RESOURCES [U54RR026137, G12RR003034] Funding Source:
   NIH RePORTER; NATIONAL EYE INSTITUTE [R01EY022216, P30EY006360,
   R21EY020821] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   NEUROLOGICAL DISORDERS AND STROKE [U54NS083932] Funding Source: NIH
   RePORTER; National Institute on Minority Health and Health Disparities
   [S21MD000101] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health (Bethesda, MD, USA) Grants
   EY022216 and EY020821 (GT), and by Grants 5U54NS083932, S21MD000101,
   G12-RR03034, U54RR026137 to Morehouse School of Medicine.
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NR 56
TC 27
Z9 27
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 JAN
PY 2016
VL 57
IS 1
BP 94
EP 104
DI 10.1167/iovs.15-18235
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DI6DN
UT WOS:000373589500011
PM 26780313
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Zhou, JL
   Ueda, K
   Zhao, J
   Sparrow, JR
AF Zhou, Jilin
   Ueda, Keiko
   Zhao, Jin
   Sparrow, Janet R.
TI Correlations between Photodegradation of Bisretinoid Constituents of
   Retina and Dicarbonyl Adduct Deposition
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GLYCATION END-PRODUCTS; PIGMENT EPITHELIAL-CELLS; HUMAN BRUCHS MEMBRANE;
   MACULAR DEGENERATION; OXIDATIVE STRESS; MATRIX METALLOPROTEINASES;
   CROSS-LINKING; MOUSE MODEL; FUNDUS AUTOFLUORESCENCE; LIPOFUSCIN PIGMENTS
AB Non-enzymatic collagen cross-linking and carbonyl adduct deposition are features of Bruch's membrane aging in the eye, and disturbances in extracellular matrix turnover are considered to contribute to Bruch's membrane thickening. Because bisretinoid constituents of the lipofuscin of retinal pigment epithelial (RPE) cells are known to photodegrade to mixtures of aldehyde-bearing fragments and small dicarbonyls (glyoxal (GO) and methylglyoxal (MG)), we investigated RPE lipofuscin as a source of the reactive species that covalently modify protein side chains. Abca4(-/-) and Rdh8(-/-)/Abca4(-/-) mice that are models of accelerated bisretinoid formation were studied and pre-exposure of mice to 430 nm light enriched for dicarbonyl release by bisretinoid photodegradation. MG protein adducts were elevated in posterior eyecups of mutant mice, whereas carbonylation of an RPE-specific protein was observed in Abca4(-/-) but not in wild-type mice under the same conditions. Immunolabeling of cryostat-sectioned eyes harvested from Abca4(-/-) mice revealed that carbonyl adduct deposition in Bruch's membrane was accentuated. Cell-based assays corroborated these findings in mice. Moreover, the receptor for advanced glycation end products that recognizes MG and GO adducts and glyoxylase 1 that metabolizes MG and GO were up-regulated in Abca4(-/-) mice. Additionally, in acellular assays, peptides were cross-linked in the presence of A2E (adduct of two vitamin A aldehyde and ethanolamine) photodegradation products, and in a zymography assay, reaction of collagen IV with products of A2E photodegradation resulted in reduced cleavage by the matrix metalloproteinases MMP2 and MMP9. In conclusion, these mechanistic studies demonstrate a link between the photodegradation of RPE bisretinoid fluorophores and aging changes in underlying Bruch's membrane that can confer risk of age-related macular degeneration.
C1 [Zhou, Jilin; Ueda, Keiko; Zhao, 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, Dept Ophthalmol, 635 W 165th St, New York, NY 10032 USA.
EM jrs88@columbia.edu
RI Regan, Clinton/E-6250-2012
FU National Institutes of Health [EY12951, P30EY019007]; Foundation
   Fighting Blindness; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [R01EY012951, P30EY019007] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health Grants EY12951
   and P30EY019007, Foundation Fighting Blindness, and a grant from
   Research to Prevent Blindness (to the Dept. of Ophthalmology, Columbia
   University). The authors declare that they have no conflicts of interest
   with the contents of this article.
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NR 90
TC 18
Z9 18
U1 0
U2 13
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 NOV 6
PY 2015
VL 290
IS 45
BP 27215
EP 27227
DI 10.1074/jbc.M115.680363
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CW2AS
UT WOS:000364794000030
PM 26400086
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Schaal, KB
   Legarreta, AD
   Gregori, G
   Legarreta, JE
   Cheng, QQ
   Stetson, PF
   Cai, M
   Laron, M
   Durbin, M
   Rosenfeld, PJ
AF Schaal, Karen B.
   Legarreta, Andrew D.
   Gregori, Giovanni
   Legarreta, John E.
   Cheng, Qianqian
   Stetson, Paul F.
   Cai, Ming
   Laron, Michal
   Durbin, Mary
   Rosenfeld, Philip J.
TI Widefield En Face Optical Coherence Tomography Imaging of Subretinal
   Drusenoid Deposits
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID RETICULAR PSEUDODRUSEN; GEOGRAPHIC-ATROPHY; MACULAR DEGENERATION;
   CHOROIDAL THICKNESS; RISK-FACTOR; EYES; PREVALENCE; PROGRESSION;
   ASSOCIATION
AB BACKGROUND AND OBJECTIVE: To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans.
   PATIENTS AND METHODS: Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SSOCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 mu m and positioned at distances up to 55 mu m above the retinal pigment epithelium (RPE). A montage of 6 x 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 x 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images.
   RESULTS: A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-mu m thick slab with boundaries from 35 to 55 mu m above the RPE.
   CONCLUSION: Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future.
C1 [Schaal, Karen B.; Legarreta, Andrew D.; Gregori, Giovanni; Legarreta, John E.; Cheng, Qianqian; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Stetson, Paul F.; Cai, Ming; Laron, Michal; Durbin, Mary] Carl Zeiss Meditec, Dept Res & Dev, Dublin, CA USA.
C3 Bascom Palmer Eye Institute; University of Miami; Carl Zeiss AG
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@med.miami.edu
RI Legarreta, Andrew/GRY-0710-2022
OI Cheng, Qianqian/0000-0003-0671-025X
FU Carl Zeiss Meditec; Macula Vision Research Foundation; National Eye
   Institute Center [P30EY014801]; Research to Prevent Blindness; Feig
   Family Foundation; Emma Clyde Hodge Memorial Foundation; German Research
   Foundation (DFG); Acucela; Advanced Cell Technology; GlaxoSmithKline;
   NATIONAL EYE INSTITUTE [P30EY014801] Funding Source: NIH RePORTER
FX Supported by a grant from Carl Zeiss Meditec, the Macula Vision Research
   Foundation, core grant P30EY014801 from the National Eye Institute
   Center, an unrestricted grant from the Research to Prevent Blindness,
   the Feig Family Foundation, and the Emma Clyde Hodge Memorial
   Foundation.; Dr. Schaal received funding from the German Research
   Foundation (DFG).; Dr. Gregori received research support from Carl Zeiss
   Meditec and co-owns a patent that is licensed to Carl Zeiss Meditec. Dr.
   Rosenfeld received research support from Carl Zeiss Meditec, Acucela,
   Advanced Cell Technology, and GlaxoSmithKline and is a consultant for
   Acucela, Alcon, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotech,
   Genentech, Healios K.K., Merck, Oraya, Roche, Sanofi/Genzyme, and
   Xcovery Vision. Drs. Stetson, Cai, Laron, and Durbin are employees of
   Carl Zeiss Meditec. The remaining authors report no relevant financial
   disclosures.
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NR 45
TC 18
Z9 19
U1 0
U2 4
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD MAY
PY 2015
VL 46
IS 5
BP 550
EP 559
DI 10.3928/23258160-20150521-06
PG 10
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA CO6UQ
UT WOS:000359292500006
PM 26057758
DA 2022-11-30
ER

PT J
AU Yehoshua, Z
   Garcia, CAD
   Nunes, RP
   Gregori, G
   Penha, FM
   Moshfeghi, AA
   Sadda, S
   Feuer, W
   Rosenfeld, PJ
AF Yehoshua, Zohar
   de Amorim Garcia Filho, Carlos Alexandre
   Nunes, Renata Portella
   Gregori, Giovanni
   Penha, Fernando M.
   Moshfeghi, Andrew A.
   Sadda, SriniVas
   Feuer, William
   Rosenfeld, Philip J.
TI Comparison of Geographic Atrophy Growth Rates Using Different Imaging
   Modalities in the COMPLETE Study
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; FUNDUS AUTOFLUORESCENCE IMAGES; SCANNING
   LASER OPHTHALMOSCOPY; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   JUNCTIONAL ZONE; EYE DISEASE; HIGH-RESOLUTION; PROGRESSION; PIGMENT
AB BACKGROUND AND OBJECTIVE: To compare the measurements and growth rates of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) obtained using different imaging modalities.
   PATIENTS AND METHODS: Thirty patients with AMD and GA measuring from 1.25 mm(2) to 18 mm(2) based on spectral-domain optical coherence tomography (SD-OCT) fundus imaging were enrolled. Imaging was performed at baseline and at follow-up months 3, 6, 9, and 12, including autofluorescence (AF) imaging with a fundus camera-based flash system (TRC-50DX; Topcon Medical Systems, Oakland, NJ; AF excitation.: 535-585 nm; detection lambda: 605-715 nm), AF and fluorescein angiography (FA) imaging with a confocal scanning laser ophthalmoscopy (SLO) system (Spectralis; Heidelberg Engineering, Heidelberg, Germany; AF excitation lambda: 488 nm; detection lambda: > 500 nm), and SD-OCT en face imaging (Cirrus; Carl Zeiss Meditec, Dublin, CA).
   RESULTS: Average baseline square root measurements and enlargement rates of square root areas appeared similar across all modalities; 0.2 mm was the largest difference between any pair of measurement means. The intraclass correlation coefficients (ICC) were essentially equal to 1 for all comparisons of area measurements but were lower for growth rates than area measurements. Comparison of 26-week average enlargement rates showed no significant difference between the SLO AF image and enhanced SD-OCT en face image (mean difference: 0.01 mm; SD: 0.10; P = .70).
   CONCLUSION: Agreement among all imaging modalities in measuring the areas of GA at baseline diminished when the growth rates of GA were compared over 26 weeks, likely because each imaging technique identifies different anatomic features along the border of GA, which may appear similar but change at different rates.
C1 [Yehoshua, Zohar; de Amorim Garcia Filho, Carlos Alexandre; Nunes, Renata Portella; Gregori, Giovanni; Penha, Fernando M.; Moshfeghi, Andrew A.; Feuer, William; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [de Amorim Garcia Filho, Carlos Alexandre; Penha, Fernando M.] Univ Fed Sao Paulo, UNIFESP, Dept Ophthalmol, Sao Paulo, Brazil.
   [Sadda, SriniVas] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Universidade Federal
   de Sao Paulo (UNIFESP); Doheny Eye Institute; University of Southern
   California
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@med.miami.edu
FU Alexion Pharmaceuticals; Macula Vision Research Foundation; Carl Zeiss
   Meditec; Research to Prevent Blindness, NEI [P30 EY014801,
   W81XWH-09-1-0675]; Jerome A. Yavitz Charitable Foundation; Emma Clyde
   Hodge Memorial Foundation; Florman, Family Foundation; Gemcon Family
   Foundation; Acucela; Advanced Cell Technology; GlaxoSmithKline; NATIONAL
   EYE INSTITUTE [P30EY014801] Funding Source: NIH RePORTER
FX Supported by Alexion Pharmaceuticals, the Macula Vision Research
   Foundation, Carl Zeiss Meditec, an unrestricted grant from Research to
   Prevent Blindness, NEI core center grant P30 EY014801 to the University
   of Miami, Department of Defense (DOD Grant W81XWH-09-1-0675), the Jerome
   A. Yavitz Charitable Foundation, the Emma Clyde Hodge Memorial
   Foundation, the Florman, Family Foundation, and the Gemcon Family
   Foundation.; Dr. Rosenfeld received research support from Alexion
   Pharmaceuticals, Acucela, Advanced Cell Technology, and GlaxoSmithKline
   and is a consultant for Acucela, Alcon, Bayer, Boehringer Ingelheim,
   Chengdu Kanghong Biotech, Merck, Oraya, Roche, and Sanogi/Genzyme. Drs.
   Yehoshua, Garcia Filho, Gregori, Rosenfeld, Penha, and Sadda received
   research support from Carl Zeiss Meditec. Dr. Gregori and the University
   of Miami co-own a patent that is licensed to Carl Zeiss Meditec. Dr.
   Sadda is a consultant to Optos and Carl Zeiss Meditec. Dr. Moshfeghi is
   a consultant to Allergan, Alcon, Genentech/Roche, Valeant, Bayer, and
   Regeneron. The remaining authors report no relevant financial
   disclosures.
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NR 54
TC 36
Z9 37
U1 0
U2 5
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD APR
PY 2015
VL 46
IS 4
BP 413
EP 422
DI 10.3928/23258160-20150422-03
PG 10
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA CO6UP
UT WOS:000359292300003
PM 25970861
DA 2022-11-30
ER

PT J
AU Thompson, RB
   Reffatto, V
   Bundy, JG
   Kortvely, E
   Flinn, JM
   Lanzirotti, A
   Jones, EA
   McPhail, DS
   Fearn, S
   Boldt, K
   Ueffing, M
   Ratu, SGS
   Pauleikhoff, L
   Bird, AC
   Lengyel, I
AF Thompson, Richard B.
   Reffatto, Valentina
   Bundy, Jacob G.
   Kortvely, Elod
   Flinn, Jane M.
   Lanzirotti, Antonio
   Jones, Emrys A.
   McPhail, David S.
   Fearn, Sarah
   Boldt, Karsten
   Ueffing, Marius
   Ratu, Savanjeet Guy Singh
   Pauleikhoff, Laurenz
   Bird, Alan C.
   Lengyel, Imre
TI Identification of hydroxyapatite spherules provides new insight into
   subretinal pigment epithelial deposit formation in the aging eye
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE hydroxyapatite; age-related macular degeneration; retinal pigment
   epithelium; drusen; calcium
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   GEOGRAPHIC ATROPHY; ESTERIFIED CHOLESTEROL; COMPLEMENT ACTIVATION;
   ELECTRON-MICROSCOPY; DRUSEN; BONE; ATHEROSCLEROSIS
AB Accumulation of protein-and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 mu m in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.
C1 [Thompson, Richard B.] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA.
   [Reffatto, Valentina; Ratu, Savanjeet Guy Singh; Pauleikhoff, Laurenz; Bird, Alan C.; Lengyel, Imre] UCL, Inst Ophthalmol, London EC1Y 8TB, England.
   [Bundy, Jacob G.; Jones, Emrys A.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
   [McPhail, David S.; Fearn, Sarah] Univ London Imperial Coll Sci Technol & Med, Dept Mat, London SW7 2AZ, England.
   [Kortvely, Elod; Boldt, Karsten; Ueffing, Marius] Univ Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   [Flinn, Jane M.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
   [Lanzirotti, Antonio] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60439 USA.
C3 University System of Maryland; University of Maryland Baltimore;
   University of London; University College London; Imperial College
   London; Imperial College London; Eberhard Karls University of Tubingen;
   Eberhard Karls University Hospital; George Mason University; University
   of Chicago
RP Lengyel, I (通讯作者)，UCL, Inst Ophthalmol, London EC1Y 8TB, England.
EM i.lengyel@ucl.ac.uk
RI Lengyel, Imre/B-5217-2009; Bundy, Jacob G/C-2131-2008; Fearn,
   Sarah/N-7748-2017
OI Lengyel, Imre/0000-0001-7467-2174; Bundy, Jacob G/0000-0002-1164-8465;
   Jones, Emrys/0000-0001-9834-217X; Lanzirotti,
   Antonio/0000-0002-7597-5924; Fearn, Sarah/0000-0002-9798-8398
FU Bill Brown Charitable Trust Senior Research Fellowship; Moorfields Eye
   Hospital Special Trustees; Mercer Fund from Fight for Sight; Bright
   Focus Foundation; Engineering and Physical Sciences Research Council,
   United Kingdom [EP/H006060/1]; Natural Environment Research Council,
   United Kingdom [NE/J013382/1]; National Synchrotron Light Source (NSLS),
   Brookhaven National Laboratory; US Department of Energy (DOE)
   Geosciences [DE-FG02-92ER14244]; DOE, Office of Science, Office of Basic
   Energy Sciences [DE-AC02-98CH10886]; National Institute for Health
   Research; Engineering and Physical Sciences Research Council
   [EP/H006060/1] Funding Source: researchfish; Natural Environment
   Research Council [NE/J013382/1] Funding Source: researchfish; EPSRC
   [EP/H006060/1] Funding Source: UKRI; NERC [NE/J013382/1] Funding Source:
   UKRI
FX We thank Profs. Philip J. Luthert, Jonathan Knowles, and Frederik Van
   Kuijk for their help and advice; Lajos Csincsik and Robert Tripon for
   technical assistance; and Krystyna Grycynska and Anne Thompson for some
   of the drawings. The research was supported by the Bill Brown Charitable
   Trust Senior Research Fellowship, Moorfields Eye Hospital Special
   Trustees, and Mercer Fund from Fight for Sight (to I. L.) and by a grant
   from Bright Focus Foundation (to R. B. T. and I. L.). The TOF-SIMS
   analysis was funded by the Engineering and Physical Sciences Research
   Council, United Kingdom (Grant EP/H006060/1) and by the Natural
   Environment Research Council, United Kingdom (Grant NE/J013382/1).
   Portions of this work were performed at Beamline X26A [National
   Synchrotron Light Source (NSLS), Brookhaven National Laboratory] under a
   general user grant (to J. M. F.). Beamline X26A is supported, in part,
   by the US Department of Energy (DOE) Geosciences (Grant
   DE-FG02-92ER14244) to The University of Chicago (Centre for Advanced
   Radiation Sources). Use of the NSLS was supported by the DOE, Office of
   Science, Office of Basic Energy Sciences, under Contract
   DE-AC02-98CH10886. Tissue for this project was provided by the
   University College London Institute of Ophthalmology and Moorfields Eye
   Hospital Eye Tissue Repository supported by National Institute for
   Health Research funding.
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NR 47
TC 69
Z9 71
U1 2
U2 54
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 3
PY 2015
VL 112
IS 5
BP 1565
EP 1570
DI 10.1073/pnas.1413347112
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700078
PM 25605911
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Semeraro, F
   Morescalchi, F
   Duse, S
   Gambicorti, E
   Cancarini, A
   Costagliola, C
AF Semeraro, Francesco
   Morescalchi, Francesco
   Duse, Sarah
   Gambicorti, Elena
   Cancarini, Anna
   Costagliola, Ciro
TI Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After
   Intravitreal Injection
SO CURRENT DRUG METABOLISM
LA English
DT Article
DE Aflibercept; age-related macular degeneration; anti-VEGF; bevacizumab;
   metabolism; pharmacokinetics; pegaptanib; ranibizumab
ID ENDOTHELIAL GROWTH-FACTOR; THROMBOEMBOLIC ADVERSE EVENTS; NEONATAL
   FC-RECEPTOR; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   INTRAOCULAR PHARMACOKINETICS; PHOTODYNAMIC THERAPY; BEVACIZUMAB AVASTIN;
   IMMUNE-COMPLEXES; TYROSINE KINASE
AB Subretinal neovascularization and pathologic ocular angiogenesis are common causes of progressive, irreversible impairment of central vision, and dramatically affect quality of life. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the quality of life for many patients with age-related macular degeneration, diabetic retinopathy, and other ocular diseases involving neovascularization and edema. In these pathologies, the inhibition of intraocular VEGF is the only therapy that can preserve vision. Four anti-VEGF drugs are currently used to treat ocular neovascularization; pegaptanib, ranibizumab, and aflibercept have been approved for this condition, while bevacizumab can be used off-label. Anti-VEGF therapy is administered regularly for many months or years because its suspension or discontinuation may cause recurrence of neovascularization. On the other hand, VEGF is necessary for the survival of retinal and choroidal endothelial cells. Experimental studies in animal models have shown that local inhibition of VEGF causes thinning and atrophy of the choriocapillaris and degeneration of photoreceptors, primarily cones. These studies combined with clinical experience indicated that prolonged VEGF inhibition could impair retinal function. Moreover, anti-VEGF compounds can cross the blood-retina barrier, enter the systemic circulation, and inhibit serum VEGF. Since circulating VEGF protects blood vessel integrity, prolonged anti-VEGF treatment could induce thromboembolic adverse events from vascular causes such as heart attack and stroke, and even death. The ocular dosing regimen and systemic toxicity of anti-VEGF compounds are therefore central concerns. A better understanding of this topic requires knowledge of the metabolism, tissue distribution, and clearance of anti-VEGF compounds. This manuscript reviews the properties of anti-VEGF compounds following intravitreal administration.
C1 [Semeraro, Francesco; Morescalchi, Francesco; Duse, Sarah; Gambicorti, Elena; Cancarini, Anna] Univ Brescia, Ophthalmol Clin, Dept Med & Surg Specialties Radiol Specialties &, Brescia, Italy.
   [Costagliola, Ciro] Univ Molise, Eye Clin, Dept Hlth Sci, Campobasso, Italy.
C3 University of Brescia; University of Molise
RP Duse, S (通讯作者)，Spedali Civil Brescia, Ophthalmol Clin, Piazzale Spedali Civili 1, I-25123 Brescia, Italy.
RI Costagliola, Ciro/G-5707-2012; Semeraro, Francesco fs/K-8667-2016
OI Costagliola, Ciro/0000-0001-8477-6188; Semeraro, Francesco
   fs/0000-0002-2275-4917
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NR 139
TC 33
Z9 35
U1 0
U2 22
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1389-2002
EI 1875-5453
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PY 2015
VL 16
IS 7
BP 572
EP 584
DI 10.2174/1389200216666151001120831
PG 13
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA CX3UA
UT WOS:000365623700006
PM 26424177
DA 2022-11-30
ER

PT J
AU Blumenkranz, MS
AF Blumenkranz, Mark S.
TI The Evolution of Laser Therapy in Ophthalmology: A Perspective on the
   Interactions Between Photons, Patients, Physicians, and Physicists: The
   LXX Edward Jackson Memorial Lecture
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL PHOTOCOAGULATION LESIONS; PATTERN SCAN LASER; FEMTOSECOND LASER;
   CATARACT-SURGERY; DIABETIC-RETINOPATHY; MACULAR EDEMA; PANRETINAL
   PHOTOCOAGULATION; SELECTIVE PHOTOCOAGULATION; REFRACTIVE SURGERY; PULSE
   DURATION
AB PURPOSE: To present the evolution of laser therapy in modern ophthalmic practice.
   DESIGN: Review of published experimental and clinical studies.
   METHODS: A review was undertaken of the work of multiple investigators leading to the invention of the laser, its biophysical effects on ocular tissues from which it derives its name (light-amplified stimulation of emitted radiation), and the development of various laser-based devices and methods to treat common ophthalmologic disorders, with particular emphasis on new and emerging retinal and anterior segment applications.
   RESULTS: Because the eye is optimized for the transmission of light and its transduction into neural signals, lasers are particularly well suited for ophthalmic therapy. This fact and the high demands for precision in therapy have inspired the development of highly sophisticated laser systems that have impacted the treatment of common diseases. These include diabetic retinopathy, age-related macular degeneration, retinal venous occlusive disease, retinopathy of prematurity, and optical aberrations including ametropia, cataract, and glaucoma, among others. Recent developments in scanning laser systems, including image-guided systems with eye tracking, real-time feedback, and ultra-short pulse durations, have enabled increased selectivity, precision, and safety in ocular therapy. However, improved outcomes have been associated with increased cost of medical care, and attention to and optimization of their cost effectiveness will continue to be required in the future.
   CONCLUSIONS: The invention and evolution of modern ophthalmic lasers have enhanced therapeutic options and can serve as a heuristic model for better understanding the process of innovation, including the societal benefits and also unintended consequences, including increased costs. (C) 2014 by Elsevier Inc. All rights reserved.
C1 Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Palo Alto, CA 94303 USA.
C3 Stanford University
RP Blumenkranz, MS (通讯作者)，Stanford Univ, Byers Eye Inst, Dept Ophthalmol, 2452 Watson Court, Palo Alto, CA 94303 USA.
EM mark.blumenkranz@stanford.edu
FU Homgren Family Fund
FX Mark Blumenkranz has board membership on the following: Optimedica,
   Avalanche Biotechnologies, Oculeve, Vantage Surgical, Digisight,
   Presbia, and Peak Surgical. This work was supported in part by an
   unrestricted gift by the Homgren Family Fund. Mark Blumenkranz, as sole
   author, is responsible for all aspects of preparation of this
   manuscript.
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NR 84
TC 16
Z9 17
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 JUL
PY 2014
VL 158
IS 1
BP 12
EP 25
DI 10.1016/j.ajo.2014.03.013
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AK0IY
UT WOS:000338097300004
PM 24699157
OA Bronze
DA 2022-11-30
ER

PT J
AU Ananth, S
   Gnana-Prakasam, JP
   Bhutia, YD
   Veeranan-Karmegam, R
   Martin, PM
   Smith, SB
   Ganapathy, V
AF Ananth, Sudha
   Gnana-Prakasam, Jaya P.
   Bhutia, Yangzom D.
   Veeranan-Karmegam, Rajalakshmi
   Martin, Pamela M.
   Smith, Sylvia B.
   Ganapathy, Vadivel
TI Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in
   retina in hemochromatosis and by the endogenous siderophore
   2,5-dihydroxybenzoic acid
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Article
DE Cholesterol transport; Hemochromatosis; Mammalian siderophore;
   beta-Hydroxybutyrate dehydrogenase-2; Retinal pigment epithelial cells
ID PIGMENT EPITHELIUM; OXIDATIVE STRESS; IRON HOMEOSTASIS; BRUCHS MEMBRANE;
   GANGLION-CELLS; EXPRESSION; DEGENERATION; GENE; HDL; SUSCEPTIBILITY
AB Hypercholesterolemia and polymorphisms in the cholesterol exporter ABCA1 are linked to age-related macular degeneration (AMD). Excessive iron in retina also has a link to AMD pathogenesis. Whether these findings mean a biological/molecular connection between iron and cholesterol is not known. Here we examined the relationship between retinal iron and cholesterol using a mouse model (Hfe(-/-)) of hemochromatosis, a genetic disorder of iron overload. We compared the expression of the cholesterol efflux transporters ABCA1 and ABCG1 and cholesterol content in wild type and Hfe(-/-) mouse retinas. We also investigated the expression of Bdh2, the rate-limiting enzyme in the synthesis of the endogenous siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA) in wild type and Hfe(-/-) mouse retinas, and the influence of this siderophore on ABCA1/ABCG1 expression in retinal pigment epithelium. We found that ABCA1 and ABCG1 were expressed in all retinal cell types, and that their expression was decreased in Hfe(-/-) retina. This was accompanied with an increase in retinal cholesterol content. Bdh2 was also expressed in all retinal cell types, and it expression was decreased in hemochromatosis. In ARPE-19 cells, 2,5-DHBA increased ABCA1/ABCG1 expression and decreased cholesterol content. This was not due to depletion of free iron because 2,5-DHBA (a siderophore) and deferiprone (an iron chelator) had opposite effects on transferrin receptor expression and ferritin levels. We conclude that iron is a regulator of cholesterol homeostasis in retina and that removal of cholesterol from retinal cells is impaired in hemochromatosis. Since excessive cholesterol is pro-inflammatory, hemochromatosis might promote retinal inflammation via cholesterol in AMD. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Ananth, Sudha; Gnana-Prakasam, Jaya P.; Bhutia, Yangzom D.; Veeranan-Karmegam, Rajalakshmi; Martin, Pamela M.; Ganapathy, Vadivel] Georgia Regents Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
   [Smith, Sylvia B.] Georgia Regents Univ, Dept Cellular Biol & Anat, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University
RP Ganapathy, V (通讯作者)，Georgia Regents Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
EM vganapat@gru.edu
OI Gnana-Prakasam, Jaya P/0000-0003-2259-9213
FU National Institutes of Health [EY 019672]; NATIONAL EYE INSTITUTE
   [R01EY022704, R01EY012830, R01EY014560, R01EY019672] Funding Source: NIH
   RePORTER
FX This work was supported by the National Institutes of Health grant EY
   019672.
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NR 51
TC 32
Z9 33
U1 1
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 1879-260X
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD APR
PY 2014
VL 1842
IS 4
BP 603
EP 612
DI 10.1016/j.bbadis.2014.01.010
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AD8JC
UT WOS:000333511300008
PM 24462739
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Podbielski, DW
   Reyes, SV
   Markowitz, SN
AF Podbielski, Dominik W.
   Reyes, Sophia V.
   Markowitz, Samuel N.
TI The worse eye is not as bad as it seems to be in A D cases
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID MACULAR DEGENERATION; VISUAL-ACUITY
AB Objective: It is the aim of this study to review residual vision in the less used eye of patients with age-related macular degeneration (AMD) using modern concepts for residual visual functions in addition to traditional methods for assessing visual acuity.
   Design: The study was designed as a retrospective, nonrandomized, observational case series.
   Participants: Consecutive cases tested with microperimetry instruments were identified from archives. Included were cases with diagnosed AMD of all age groups and all visual acuity levels.
   Methods: In all cases, microperimetric technology was used to assess residual visual function. Outcome measures selected for analysis were visual acuity, preferred retinal loci (PRL) topography, fixation stability, and PRL span.
   Results: Data were collected and analyzed for both eyes from 51 patients with AMD low vision. There were 23 males and 28 females whose mean age was 84 (+/- 7) years. Within the group the difference in visual acuity estimates between the better seeing and the less used eye was statistically significant (p = 0.001). Similar positive statistical significant differences were noticed at all spatial frequencies (except at 6 cycles/degree) when testing contrast sensitivity. All other measurements were not statistically different between the better seeing and the poorer eye. This applies to the fixation stability and PRL span estimates. Almost half (49%) of the cases showed retinal noncorrespondence of PRLs between the 2 eyes.
   Conclusions: Visual acuity estimates are not a reliable measure for residual vision. The less used eye in AMD cases has much better residual vision than thought before according to modern outcome measures. This new concept should be taken into account by all practitioners and be applied during all low vision rehabilitation interventions.
C1 [Podbielski, Dominik W.; Reyes, Sophia V.; Markowitz, Samuel N.] Univ Toronto, Dept Ophthalmol & Vis Sci, Low Vis Serv Univ Hlth Network Hosp, Toronto, ON, Canada.
C3 University of Toronto; University Health Network Toronto
RP Markowitz, SN (通讯作者)，1225 Davenport Rd, Toronto, ON M6H 2H1, Canada.
EM snm1@rogers.com
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NR 12
TC 4
Z9 4
U1 1
U2 5
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
EI 1715-3360
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD OCT
PY 2013
VL 48
IS 5
BP 381
EP 385
DI 10.1016/j.jcjo.2013.04.004
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AA5OM
UT WOS:000331149300022
PM 24093184
DA 2022-11-30
ER

PT J
AU Zhong, YS
   Wang, J
   Liu, WM
   Zhu, YH
AF Zhong, Yi-Sheng
   Wang, Jing
   Liu, Wang-Min
   Zhu, Yi-Hua
TI Potassium ion channels in retinal ganglion cells
SO MOLECULAR MEDICINE REPORTS
LA English
DT Review
DE retinal ganglion cells; potassium ion channels; electrical property;
   neuroprotection
ID K+-CHANNEL; FUNCTIONAL EXPRESSION; CURRENT-DENSITY; AXON EXTENSION;
   RECTIFYING K+; CALCIUM; ATP; LOCALIZATION; CONDUCTANCES; NEURONS
AB Retinal ganglion cells (RGCs) consolidate visual processing and constitute the last step prior to the transmission of signals to higher brain centers. RGC death is a major cause of visual impairment in optic neuropathies, including glaucoma, age-related macular degeneration, diabetic retinopathy, uveoretinitis and vitreoretinopathy. Discharge patterns of RGCs are primarily determined by the presence of ion channels. As the most diverse group of ion channels, potassium (K+) channels play key roles in modulating the electrical properties of RGCs. Biochemical, molecular and pharmacological studies have identified a number of K+ channels in RGCs, including inwardly rectifying K+ (K-ir), ATP-sensitive K+ (K-ATP), tandem-pore domain K+ (T-ASK), voltage-gated K+ (K-v), ether-a-go-go (Eag) and Ca2+-activated K+ (K-Ca) channels. K-ir channels are important in the maintenance of the resting membrane potential and controlling RGC excitability. K-ATP channels are involved in RGC survival and neuroprotection. T-ASK channels are hypothesized to contribute to the regulation of resting membrane potentials and firing patterns of RGCs. K-v channels are important regulators of cellular excitability, functioning to modulate the amplitude, duration and frequency of action potentials and subthreshold depolarizations, and are also important in RGC development and protection. Eag channels may contribute to dendritic repolarization during excitatory postsynaptic potentials and to the attenuation of the back propagation of action potentials. K-Ca channels have been observed to contribute to repetitive firing in RGCs. Considering these important roles of K+ channels in RGCs, the study of K+ channels may be beneficial in elucidating the pathophysiology of RGCs and exploring novel RGC protection strategies.
C1 [Zhong, Yi-Sheng; Wang, Jing] Shanghai Jiao Tong Univ, Dept Ophthalmol, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China.
   [Liu, Wang-Min] Hubei Prov Ctr Dis Control & Prevent, Wuhan 430079, Hubei, Peoples R China.
   [Zhu, Yi-Hua] Fujian Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Fuzhou 350005, Fujian, Peoples R China.
C3 Shanghai Jiao Tong University; Fujian Medical University
RP Liu, WM (通讯作者)，Hubei Prov Ctr Dis Control & Prevent, Bldg 13,6 North Zhuodaoquan Rd, Wuhan 430079, Hubei, Peoples R China.
EM lwm662006@126.com; zhuyihua889@hotmail.com
FU Shanghai Leading Academic Discipline Project [S30205]; Shanghai 'Science
   and Technology Innovation Action Plan' Basic Research Key Project
   [11JC1407700, 11JC1407701]
FX This study was funded by the Shanghai Leading Academic Discipline
   Project (no. S30205) and the Shanghai 'Science and Technology Innovation
   Action Plan' Basic Research Key Project (nos. 11JC1407700 and
   11JC1407701).
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NR 106
TC 12
Z9 14
U1 2
U2 23
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 AUG
PY 2013
VL 8
IS 2
BP 311
EP 319
DI 10.3892/mmr.2013.1508
PG 9
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA 190XS
UT WOS:000322377400001
PM 23732984
OA Bronze
DA 2022-11-30
ER

PT J
AU Kannan, R
   Sreekumar, PG
   Hinton, DR
AF Kannan, Ram
   Sreekumar, Parameswaran G.
   Hinton, David R.
TI Novel roles for alpha-crystallins in retinal function and disease
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE alpha B-Crystallin; Angiogenesis; Apoptosis; Chaperone; Exosomes;
   Retinal pigment epithelium
ID HEAT-SHOCK-PROTEIN; CHAPERONE-LIKE ACTIVITY; LENS EPITHELIAL-CELLS;
   AMYLOID FIBRIL FORMATION; GLYCATION-INDUCED INACTIVATION; DESMIN-RELATED
   CARDIOMYOPATHY; RESONANCE ENERGY-TRANSFER; GUILLAIN-BARRE-SYNDROME;
   NON-LENTICULAR TISSUES; SMALL STRESS-PROTEINS
AB alpha-Crystallins are key members of the superfamily of small heat shock proteins that have been studied in detail in the ocular lens. Recently, novel functions for alpha-crystallins have been identified in the retina and in the retinal pigmented epithelium (RPE). alpha B-Crystallin has been localized to multiple compartments and organelles including mitochondria, golgi apparatus, endoplasmic reticulum and nucleus. alpha-Crystallins are regulated by oxidative and endoplasmic reticulum stress, and inhibit apoptosis-induced cell death. alpha-Crystallins interact with a large number of proteins that include other crystallins, and apoptotic, cytoskeletal, inflammatory, signaling, angiogenic, and growth factor molecules. Studies with RPE from alpha B-crystallin deficient mice have shown that aB-crystallin supports retinal and choroidal angiogenesis through its interaction with vascular endothelial growth factor. alpha B-Crystallin has also been shown to have novel functions in the extracellular space. In RPE, alpha B-crystallin is released from the apical surface in exosomes where it accumulates in the interphotoreceptor matrix and may function to protect neighboring cells. In other systems administration of exogenous recombinant aB-crystallin has been shown to be anti-inflammatory. Another newly described function of alpha B-crystallin is its ability to inhibit beta-amyloid fibril formation. alpha-Crystallin minichaperone peptides have been identified that elicit anti-apoptotic function in addition to being efficient chaperones. Generation of liposomal particles and other modes of nanoencapsulation of these minipeptides could offer great therapeutic advantage in ocular delivery for a wide variety of retinal degenerative, inflammatory and vascular diseases including age-related macular degeneration and diabetic retinopathy. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Hinton, David R.] Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90089 USA.
   [Kannan, Ram; Sreekumar, Parameswaran G.; Hinton, David R.] Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, Los Angeles, CA 90033 USA.
   [Kannan, Ram; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
C3 University of Southern California; Doheny Eye Institute; University of
   Southern California
RP Hinton, DR (通讯作者)，Univ So Calif, Dept Pathol, Keck Sch Med, 2011 Zonal Ave,HMR 209, Los Angeles, CA 90089 USA.
EM dhinton@usc.edu
RI kannan, ram/ABB-7154-2020
OI kannan, ram/0000-0002-1583-3414; /0000-0002-9425-3986
FU National Eye Institute [EY03040, EY01545]; Research to Prevent
   Blindness; Arnold and Mabel Beckman Foundation; NATIONAL CENTER FOR
   ADVANCING TRANSLATIONAL SCIENCES [UL1TR000130] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY001545, P30EY003040] Funding
   Source: NIH RePORTER
FX This work was supported by Grants EY03040 and EY01545 from the National
   Eye Institute; and funds from Research to Prevent Blindness; and the
   Arnold and Mabel Beckman Foundation. We thank Christine Spee for able
   technical assistance and Ernesto Barron and Eric Barron for preparation
   of the figures.
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NR 328
TC 89
Z9 95
U1 1
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD NOV
PY 2012
VL 31
IS 6
BP 576
EP 604
DI 10.1016/j.preteyeres.2012.06.001
PG 29
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 035IV
UT WOS:000310940900003
PM 22721717
OA Green Accepted
DA 2022-11-30
ER

PT J
AU van de Ven, JPH
   Boon, CJF
   Fauser, S
   Hoefsloot, LH
   Smailhodzic, D
   Schoenmaker-Koller, F
   Klevering, BJ
   Klaver, CCW
   den Hollander, AI
   Hoyng, CB
AF van de Ven, Johannes P. H.
   Boon, Camiel J. F.
   Fauser, Sacha
   Hoefsloot, Lies H.
   Smailhodzic, Dzenita
   Schoenmaker-Koller, Frederieke
   Klevering, B. Jeroen
   Klaver, Caroline C. W.
   den Hollander, Anneke I.
   Hoyng, Carel B.
TI Clinical Evaluation of 3 Families With Basal Laminar Drusen Caused by
   Novel Mutations in the Complement Factor H Gene
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; POLYPOIDAL CHOROIDAL VASCULOPATHY;
   GLOMERULONEPHRITIS TYPE-II; MACULAR DEGENERATION; MEMBRANOPROLIFERATIVE
   GLOMERULONEPHRITIS; INHIBITOR ECULIZUMAB; PROTEIN BETA-1H;
   KIDNEY-DISEASE; CFH GENE; FACTOR-B
AB Objectives: To identify novel complement factor H (CFH) gene mutations and to specify the clinical characteristics in patients with basal laminar drusen (BLD), a clinical subtype of age-related macular degeneration.
   Methods: Twenty-one probands with BLD were included in this study. The ophthalmic examination included nonstereoscopic 30 degrees color fundus photography, fluorescein angiography, and high-resolution spectral-domain optical coherence tomography. Renal function was tested by measurement of serum creatinine and urea nitrogen levels. Venous blood samples were drawn for genomic DNA, and all coding exons and splice junctions of the CFH gene were analyzed by direct sequencing.
   Results: In 3 families, we identified novel heterozygous mutations in the CFH gene: p.Ile184fsX, p.Lys204fsX, and c.1697-17_-8del. Ten of 13 mutation carriers displayed the BLD phenotype with a wide variety in clinical presentation, ranging from limited macular drusen to extensive drusen in the posterior pole as well as the peripheral retina. Two patients with BLD developed end-stage kidney disease as a result of membranoproliferative glomerulonephritis type II.
   Conclusions: The early-onset BLD phenotype can be caused by heterozygous mutations in the CFH gene. Because some patients with BLD are at risk to develop membranoproliferative glomerulonephritis type II, we recommend that patients with extensive BLD undergo screening for renal dysfunction.
   Clinical Relevance: Elucidation of the clinical BLD phenotype will facilitate identification of individuals predisposed to developing disease-related comorbidity, such as membranoproliferative glomerulonephritis type II. Moreover, with upcoming treatment modalities targeting specific components of the complement system, early identification of patients with BLD and detection of the genetic defect become increasingly important.
C1 [van de Ven, Johannes P. H.; Boon, Camiel J. F.; Smailhodzic, Dzenita; Schoenmaker-Koller, Frederieke; Klevering, B. Jeroen; den Hollander, Anneke I.; Hoyng, Carel B.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6525 EX Nijmegen, Netherlands.
   [Hoefsloot, Lies H.; den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 EX Nijmegen, Netherlands.
   [Fauser, Sacha] Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50931 Cologne, Germany.
   [Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; University of
   Cologne; Erasmus University Rotterdam; Erasmus MC; Erasmus University
   Rotterdam; Erasmus MC
RP van de Ven, JPH (通讯作者)，Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6525 EX Nijmegen, Netherlands.
EM j.vandeven@ohk.umcn.nl
RI Hollander, Anneke den/N-4911-2014; Klevering, B.J./L-4434-2015; Hoyng,
   C.B./H-8050-2014; Klaver, Caroline C.W./A-2013-2016; Boon,
   CJF/P-7534-2014
OI Boon, CJF/0000-0002-6737-7932; Klaver, Caroline/0000-0002-2355-5258
FU Netherlands Organization for Scientific Research [016.096.309]
FX This study was supported by grant 016.096.309 from the Netherlands
   Organization for Scientific Research.
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NR 49
TC 28
Z9 28
U1 0
U2 7
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 AUG
PY 2012
VL 130
IS 8
BP 1038
EP 1047
DI 10.1001/archophthalmol.2012.265
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 987YU
UT WOS:000307455800012
PM 22491393
OA Bronze
DA 2022-11-30
ER

PT J
AU Kernt, M
   Walch, A
   Neubauer, AS
   Hirneiss, C
   Haritoglou, C
   Ulbig, MW
   Kampik, A
AF Kernt, Marcus
   Walch, Axel
   Neubauer, Aljoscha S.
   Hirneiss, Christoph
   Haritoglou, Christos
   Ulbig, Michael W.
   Kampik, Anselm
TI Filtering blue light reduces light-induced oxidative stress, senescence
   and accumulation of extracellular matrix proteins in human retinal
   pigment epithelium cells
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE ageing; senescence; age-related macular degeneration; cataract surgery;
   cytoprotection; yellow intraocular lens
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; ENDOTHELIAL GROWTH-FACTOR;
   MACULAR DEGENERATION; INTRAOCULAR-LENS; 10-YEAR INCIDENCE; HUMAN SKIN;
   IN-VITRO; SUNLIGHT; METALLOPROTEINASES
AB Background: Cumulative light exposure is significantly associated with ageing and the progression of age-related macular degeneration. To prevent the retina from blue-light damage in pseudophakia, blue light-absorbing intraocular lenses have been developed. This study compares the possible protective effects of a blue light-absorbing intraocular lens to an untinted ultraviolet-absorbing intraocular lens with regard to light-induced oxidative stress and senescence of human retinal pigment epithelium.
   Methods: As primary human retinal pigment epithelium cells were exposed to white light, either an ultraviolet-and blue light-absorbing intraocular lens or ultraviolet-absorbing intraocular lens was placed in the light beam. After 60 min of irradiation, cells were investigated by electron microscopy for viability, induction of intracellular reactive oxygen species, and senescence-associated beta-galactosidase activity. Expression and secretion of matrix metalloproteinases 1 and 3 and their mRNA were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay.
   Results: Light exposure induced structural damage, decreased retinal pigment epithelium cell viability, and increased reactive oxygen species, senescence-associated b-galactosidase activity and matrix metalloproteinases 1 and 3 expression and secretion. Although both types of intraocular lens significantly reduced these effects, the protective effects of the ultraviolet- and blue light-absorbing intraocular lens were significantly stronger than those of the ultraviolet-absorbing intraocular lens.
   Conclusions: The ultraviolet-and blue light-absorbing intraocular lens demonstrated significantly better protection against light-induced oxidative stress, senescence and structural damage than the ultraviolet-absorbing intraocular lens. These in vitro findings support the hypothesis that the ultraviolet-and blue light-absorbing intraocular lens may prevent retinal damage in clinical use.
C1 [Kernt, Marcus; Neubauer, Aljoscha S.; Hirneiss, Christoph; Haritoglou, Christos; Ulbig, Michael W.; Kampik, Anselm] Univ Munich, Dept Ophthalmol, D-80336 Munich, Germany.
   [Walch, Axel] GSF Natl Res Ctr Environm & Hlth, Neuherberg, Germany.
C3 University of Munich; Helmholtz Association; Helmholtz-Center Munich -
   German Research Center for Environmental Health
RP Kernt, M (通讯作者)，Univ Munich, Dept Ophthalmol, Mathilden St 8, D-80336 Munich, Germany.
EM marcus.kernt@med.uni-muenchen.de
RI Walch, Axel/B-4554-2012
OI Walch, Axel/0000-0001-5578-4023
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NR 36
TC 17
Z9 19
U1 0
U2 18
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 FEB
PY 2012
VL 40
IS 1
BP E87
EP E97
DI 10.1111/j.1442-9071.2011.02620.x
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 888JW
UT WOS:000300000800011
PM 21668780
DA 2022-11-30
ER

PT J
AU Hanlon, J
   Firpo, M
   Chell, E
   Moshfeghi, DM
   Bolch, WE
AF Hanlon, Justin
   Firpo, Michael
   Chell, Erik
   Moshfeghi, Darius M.
   Bolch, Wesley E.
TI Stereotactic Radiosurgery for AMD: A Monte Carlo-Based Assessment of
   Patient-Specific Tissue Doses
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; PROTON-BEAM IRRADIATION; MACULAR
   DEGENERATION; RADIATION-THERAPY; PLAQUE RADIOTHERAPY; RANIBIZUMAB;
   DOSIMETRY; BRACHYTHERAPY; BEVACIZUMAB; TOLERANCE
AB PURPOSE. To define the radiation doses to nontargeted ocular and adnexal tissues with Monte-Carlo simulation using a stereotactic low-voltage x-ray irradiation system for the treatment of wet age-related macular degeneration.
   METHODS. Thirty-two right/left eye models were created from three-dimensional reconstructions of 1-mm computed tomography images of the head and orbital region. The resultant geometric models were voxelized and imported to the MCNPX 2.5.0 radiation transport code for Monte Carlo-based simulations of AMD treatment. Clinically, treatment is delivered noninvasively by three divergent 100-kVp photon beams entering through the sclera and overlapping on the macula cumulating in a therapeutic dose. Tissue-averaged doses, localized point doses, and color-coded dose contour maps are reported from Monte Carlo simulations of x-ray energy deposition for several tissues of interest, including the lens, optic nerve, macula, brain, and orbital bone.
   RESULTS. For all eye models in this study (n = 32), tissues at risk did not receive tissue-averaged doses over the generally accepted thresholds for serious complication, specifically the formation of cataracts or radiation-induced optic neuropathy. Dose contour maps are included for three patients, each from separate groups defined by coherence to clinically realistic treatment setups. Doses to the brain and orbital bone were found to be insignificant.
   CONCLUSIONS. The computational assessment performed indicates that a previously established therapeutic dose can be delivered effectively to the macula with the scheme described so that the potential for complications to nontargeted radiosensitive tissues might be reduced. (Invest Ophthalmol Vis Sci. 2011;52:2334-2342) DOI: 10.1167/iovs.10-6421
C1 [Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol Engn, Adv Lab Radiat Dosimetry Studies ALRADS, Gainesville, FL 32611 USA.
   [Bolch, Wesley E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
   [Firpo, Michael; Chell, Erik] Oraya Therapeut Inc, Newark, CA USA.
   [Moshfeghi, Darius M.] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida; Stanford University
RP Bolch, WE (通讯作者)，Univ Florida, Dept Nucl & Radiol Engn, Adv Lab Radiat Dosimetry Studies ALRADS, Gainesville, FL 32611 USA.
EM wbolch@ufl.edu
OI Moshfeghi, Darius Mohammad/0000-0003-2254-292X
FU Oraya Therapeutics, Inc. [ORAYA-001-2007]
FX Supported by Oraya Therapeutics, Inc. Grant ORAYA-001-2007.
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NR 40
TC 17
Z9 17
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 2011
VL 52
IS 5
BP 2334
EP 2342
DI 10.1167/iovs.10-6421
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 746XK
UT WOS:000289282600034
PM 21087954
DA 2022-11-30
ER

PT J
AU Hashemi, H
   KhabazKhoob, M
   Yekta, A
   Mohammad, K
   Fotouhi, A
AF Hashemi, Hassan
   KhabazKhoob, Mehdi
   Yekta, AbbasAli
   Mohammad, Kazem
   Fotouhi, Akbar
TI Distribution of Iris Colors and its Association with Ocular Disorder in
   the Tehran Eye Study
SO IRANIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Iris Color; Ocular Disorder; Cross-Sectional Study
ID BLUE MOUNTAINS EYE; AGE-RELATED MACULOPATHY; SKIN SUN SENSITIVITY;
   SENILE MACULAR DEGENERATION; INTRAOCULAR-PRESSURE; UVEAL MELANOMA; HAIR
   COLOR; PIGMENTATION; RISK; PROGRESSION
AB Purpose: To determine the distribution of iris colors in the population of Tehran and to assess possible associations between iris color and Ocular disorder
   Methods: Through a stratified random cluster sampling approach, 160 clusters were selected in different municipality districts of Tehran, and the approached households were invited to a clinic. After the initial interview, all participants had complete eye examinations and their iris color was categorized as grey/blue, yellow/green, light brown, medium brown, and dark. Distributions were determined in percentages and possible correlations with race, refractive errors, visual impairment, cataracts, age-related macular degeneration (AMD). Intraocular pressure (IOP) was also examined.
   Results: Out of 4230 participants aged 7 years or more, the iris color was determined in 4200 people; in 54.09% [95% confidence interval (CI) 51.74% to 56.44%] the iris color was medium brown as the most prevalent color, and in 1.96% (95% CI: 1.43% to 2.48%) the color was grey/blue as the least prevalent color. The inter-gender difference in iris color was not statistically significant (P=0.288). AMD showed the highest prevalence in light brown iris colors (P<0.001). Nuclear cataract and posterior subcapsular cataract (PSC) was significantly correlated with iris color, with higher risks of cataract among medium brown, light brown and yellow/green iris colors (P<0.001).
   Conclusion: The most prevalent iris color in the population of Tehran was medium brown. In light of the observed correlation between the iris color and certain conditions such as cataract and AMD with lighter eye colors, further studies are recommended to investigate the probable associations.
C1 [Mohammad, Kazem; Fotouhi, Akbar] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran.
   [Hashemi, Hassan] Univ Tehran Med Sci, Farabi Eye Hosp, Eye Res Ctr, Tehran, Iran.
   [Yekta, AbbasAli] Mashhad Univ Med Sci, Dept Optometry, Mashhad, Iran.
C3 Tehran University of Medical Sciences; Tehran University of Medical
   Sciences; Mashhad University Medical Science
RP Fotouhi, A (通讯作者)，Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran.
EM afotouhi@tums.ac.ir
RI Fotouhi, Akbar/F-5618-2011; Khabazkhoob, Mehdi/Q-4537-2017; Hashemi,
   Hassan/N-2293-2019; Yekta, Abbasali/A-7810-2017
OI Yekta, Abbasali/0000-0003-4356-9064; Fotouhi, Akbar/0000-0002-6438-6833;
   Hashemi, Hassan/0000-0002-6086-1537; Khabazkhoob,
   Mehdi/0000-0003-0801-8793
FU Noor Ophthalmology Research Center; Iranian National Research Center for
   Medical Sciences
FX This project was funded in part by the Noor Ophthalmology Research
   Center and a grant from the Iranian National Research Center for Medical
   Sciences. The selection of clusters was based on block enumeration of
   the National Census of 1996 by the Iranian Statistics Center.
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NR 25
TC 2
Z9 3
U1 0
U2 8
PU IRANIAN SOC OPHTHALMOLOGY
PI TEHRAN
PA NORTH KARGAR AVE, 2ND FLR, NO 4, HOMA ALLEY, TEHRAN, 1418654743, IRAN
SN 1735-4153
J9 IRAN J OPHTHALMOL
JI Iran. J. Ophthalmol.
PY 2010
VL 22
IS 1
BP 7
EP 14
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 602BP
UT WOS:000278113400003
DA 2022-11-30
ER

PT J
AU Ma, WX
   Zhao, L
   Fontainhas, AM
   Fariss, RN
   Wong, WT
AF Ma, Wenxin
   Zhao, Lian
   Fontainhas, Aurora M.
   Fariss, Robert N.
   Wong, Wai T.
TI Microglia in the Mouse Retina Alter the Structure and Function of
   Retinal Pigmented Epithelial Cells: A Potential Cellular Interaction
   Relevant to AMD
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; SUBRETINAL
   MICROGLIA; FRACTALKINE RECEPTOR; UNITED-STATES; IMMUNE-SYSTEM;
   NITRIC-OXIDE; IN-VITRO; DRUSEN; INFLAMMATION
AB Background: Age-related macular degeneration (AMD) is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE) layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.
   Methodology/Principal Findings: In this study, we examined the effects of retinal microglia on RPE cells using 1) an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2) an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1) changes in RPE structure and distribution, 2) increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3) increased extent of in vivo choroidal neovascularization in the subretinal space.
   Conclusions/Significance: These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.
RP Ma, WX (通讯作者)，NEI, Unit Neuron Glia Interact Retinal Dis, NIH, 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
FU NATIONAL EYE INSTITUTE [ZICEY000459, ZIAEY000463] Funding Source: NIH
   RePORTER; Intramural NIH HHS Funding Source: Medline
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NR 61
TC 152
Z9 159
U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 20
PY 2009
VL 4
IS 11
AR e7945
DI 10.1371/journal.pone.0007945
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 522NL
UT WOS:000272004800021
PM 19936204
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Meri, S
AF Meri, Seppo
TI Loss of self-control in the complement system and innate autoreactivity
SO AUTOIMMUNITY, PART A: BASIC PRINCIPLES AND NEW DIAGNOSTIC TOOLS
SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; FACTOR-H
   DEFICIENCY; C-REACTIVE PROTEIN; THROMBOTIC THROMBOCYTOPENIC PURPURA;
   GLOMERULONEPHRITIS TYPE-II; DECAY-ACCELERATING FACTOR; HEPARIN-BINDING
   DOMAIN; SHORT CONSENSUS REPEAT; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
AB The complement system performs effective antimicrobial and clean-up functions to keep the body clear from invading microbes and accumulating debris. From its about 35 components many regulate complement activity to prevent self-attack. Our work has focused on regulator defects and dysfunctions that cause autoreactivity, that is, inflammation and damage against self-tissues ("innate autoreactivity"). The major complement regulator, factor H (FH), protects host cells and keeps excessive amplification under control. Mutations and polymorphisms in FH predispose to four different diseases: membranoproliferative glomerulonephritis type II (MPGN II), partial lipodystrophy (PLD), recurrent atypical hemolytic uremic syndrome (aHUS), and age-related macular degeneration (AMD). Loss of the complement regulatory activity (cofactor activity for C3b inactivation and decay accelerating activity) in the N terminus of FH leads to PLD and MPGN II, the latter of which is characterized by C3b and MAC deposition on the glomerular basement membranes of kidneys. Polymorphism in the SCR7-domain in the middle part of FH predisposes to AMD, which is the most common cause of vision loss in elderly people. This polymorphism influences the ability of FH to bind to C-reactive protein (CRP) and to target phagocytic clearance of debris (e.g., eye pigment) and control local inflammation. Finally, the loss of the ability of the FH C terminus to recognize C3b molecules deposited on self-structures predisposes to aHUS, where blood cells, platelets, and endothelial cells, particularly in kidneys, become targets for repeated complement attacks and increased procoagulant activity. The pathogenetic mechanisms of these diseases are being increasingly understood, which in the future will help in designing new therapies.
C1 Univ Helsinki, Haartman Inst, Dept Backeriol & Immunol, FIN-00014 Helsinki, Finland.
C3 University of Helsinki
RP Meri, S (通讯作者)，Univ Helsinki, Haartman Inst, Dept Backeriol & Immunol, PO Box 21,Haartmaninkatu 3, FIN-00014 Helsinki, Finland.
EM seppo.nieri@helsinki.fi
OI Meri, Seppo/0000-0001-9142-501X
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NR 65
TC 25
Z9 27
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND
SN 0077-8923
J9 ANN NY ACAD SCI
JI Ann.NY Acad.Sci.
PY 2007
VL 1109
BP 93
EP 105
DI 10.1196/annals.1398.011
PG 13
WC Immunology; Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Science & Technology - Other Topics
GA BGP77
UT WOS:000249589100012
PM 17785294
DA 2022-11-30
ER

PT J
AU Cashman, SM
   Bowman, L
   Christofferson, J
   Kumar-Singh, R
AF Cashman, Siobhan M.
   Bowman, Lisa
   Christofferson, Jason
   Kumar-Singh, Rajendra
TI Inhibition of choroidal neovascularization by adenovirus-mediated
   delivery of short hairpin RNAs targeting VEGF as a potential therapy for
   AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; GENE-TRANSFER; OCULAR NEOVASCULARIZATION; INTRAVITREAL
   INJECTION; INCREASED EXPRESSION; NONHUMAN PRIMATE; VECTOR; MEMBRANES
AB PURPOSE. Choroidal neovascularization ( CNV) is the leading cause of blindness in age-related macular degeneration ( AMD). Several lines of evidence implicate increased levels of vascular endothelial growth factor ( VEGF) in retinal pigment epithelium ( RPE) from patients with AMD. Current approaches to attenuate VEGF or its receptors, including the use of small interfering ( si) RNA, show significant promise, but still have limited efficacy and require repeat administrations, using procedures associated with multiple complications. The goal of this study was to develop an approach for long-term endogenous expression of short hairpin ( sh) RNA that would significantly attenuate VEGF and hence act as a potential therapy for AMD.
   METHODS. Several shRNAs expressed from recombinant adenovirus were developed. These shRNAs were expressed in human RPE cells in the presence of adenovirus vectors overexpressing VEGF, and the amount of VEGF attenuation was evaluated. Adenovirus vectors expressing VEGF were subsequently injected into the subretinal space of mice, and induction of CNV was measured in the presence of adenovirus vectors expressing shRNA targeting VEGF.
   RESULTS. Potent shRNA sequences were identified that were able to silence VEGF in human RPE cells. When expressed from adenovirus backbones, these shRNA constructs silenced VEGF by 94% at a 1: 5 molar ratio ( VEGF to shRNA) and 64% at a 1: 0.05 molar ratio. Adenovirus vectors expressing high levels of VEGF could induce CNV in mice within 5 days. Co-injection of VEGF-expressing viruses into mice with shRNA targeting VEGF led to a substantial ( 84%) reduction in CNV.
   CONCLUSIONS. shRNA targeting VEGF from adenovirus vectors allows potent attenuation of VEGF and prevents CNV. This approach shows promise as a therapy for AMD.
C1 Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
   Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA.
C3 Tufts University; Utah System of Higher Education; University of Utah
RP Kumar-Singh, R (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, 136 Harrison Ave,Jaharis 714, Boston, MA 02111 USA.
EM rajendra.kumar-singh@tufts.edu
OI Kumar-Singh, Rajendra/0000-0002-7754-0713
FU NEI NIH HHS [EY014991, EY013837] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY014991, R01EY013837] Funding Source: NIH RePORTER
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NR 46
TC 53
Z9 62
U1 0
U2 8
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 2006
VL 47
IS 8
BP 3496
EP 3504
DI 10.1167/iovs.05-1610
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 069JC
UT WOS:000239441200038
PM 16877421
DA 2022-11-30
ER

PT J
AU Gade, SS
   Pentlavalli, S
   Mishra, D
   Vora, LK
   Waite, D
   Alvarez-Lorenzo, CI
   Vanrell, MRH
   Laverty, G
   Larraneta, E
   Donnelly, RF
   Thakur, RRS
AF Gade, Shilpkala Shankar
   Pentlavalli, Sreekanth
   Mishra, Deepakkumar
   Vora, Lalitkumar K.
   Waite, David
   Alvarez-Lorenzo, Carmen Isabel
   Vanrell, Maria Roccio Herrero
   Laverty, Garry
   Larraneta, Eneko
   Donnelly, Ryan F.
   Thakur, Raghu Raj Singh
TI Injectable Depot Forming Thermoresponsive Hydrogel for Sustained
   Intrascleral Delivery of Sunitinib Using Hollow Microneedles
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE thermoresponsive hydrogel; sunitinib; age-related macular degeneration;
   chitosan; grafting; poly(n-isopropylacrylamide)
ID DRUG-DELIVERY; HUMAN SCLERA; RELEASE; THICKNESS; IMPLANTS; SU11248;
   GROWTH
AB Purpose: Age-related macular degeneration is a vision-threatening disorder affecting the posterior segment of the eye. Drug delivery to the posterior segment is challenging owing to the complex anatomical and physiological structure, necessitating monthly injections of antivascular endothelial growth factors. Thermoresponsive hydrogels provide sustained drug delivery and ease of injection, due to their sol-gel transition. Poly (N-isopropyl acrylamide) (PNIPAAm) is a widely researched thermoresponsive hydrogel; however, insufficient wet strength and a wide mesh network make it inept for the entrapment of small molecules.Methods: A novel approach of grafting PNIPAAm with chitosan is exploited. A chitosan concentration altered in 10%, 30%, and 50% compared to PNIPAAm is investigated for entrapment of a small-molecular weight, hydrophilic drug, sunitinib (SUN), a multiple tyrosine kinase receptor inhibitor. Furthermore, these hydrogels were characterized using H-1-NMR, FTIR, differential scanning calorimetry (DSC), and thermogravimetric analysis for chemical characterization and viscosity, swellability, syringeability, degradation, and In-vitro permeation using Franz-diffusion cell.Results: In-vitro drug release kinetics suggested that the release of SUN could be controlled with the percentage of chitosan grafting; however, gel strength (3%-5% w/v) of 30% Cs-g-PNIPAAm did not significantly affect percentage drug release. Sustained release of SUN was observed for 1 month. In-vitro permeation studies on porcine sclera suggested that a thermoresponsive gel of chitosan grafted PNIPAAm (Cs-g-PNIPAAm) was able to sustain the drug release by 40%, compared to SUN solution.Conclusions: The study indicates that the synthesized Cs-g-NIPAAm hydrogel has the potential to serve as a tailorable injectable platform for intrascleral drug delivery applications.
C1 [Gade, Shilpkala Shankar; Pentlavalli, Sreekanth; Mishra, Deepakkumar; Vora, Lalitkumar K.; Waite, David; Laverty, Garry; Larraneta, Eneko; Donnelly, Ryan F.; Thakur, Raghu Raj Singh] Queens Univ Belfast, Med Biol Ctr, Sch Pharm, Belfast, North Ireland.
   [Alvarez-Lorenzo, Carmen Isabel] Univ Santiago De Compostela, Fac Farm, Dept Farm & Tecnol Farmaceut, Santiago De Compostela, Spain.
   [Vanrell, Maria Roccio Herrero] Univ Complutense Madrid, Fac Farm, Departmento Farm Galen & Technol Alimmentatia, Madrid, Spain.
   [Thakur, Raghu Raj Singh] Queens Univ Belfast, Med Biol Ctr, Sch Pharm, 97 Lisburn Rd, Belfast BT9 7BL, North Ireland.
C3 Queens University Belfast; Universidade de Santiago de Compostela;
   Complutense University of Madrid; Queens University Belfast
RP Thakur, RRS (通讯作者)，Queens Univ Belfast, Med Biol Ctr, Sch Pharm, 97 Lisburn Rd, Belfast BT9 7BL, North Ireland.
EM r.thakur@qub.ac.uk
OI Vora, Lalitkumar/0000-0001-8106-9066
FU European Unions Horizon2020 research and innovation programme under the
   MarieSklodowska-Curie Actions [813440]
FX This project is funded by the European Unions Horizon2020 research and
   innovation programme under the MarieSklodowska-Curie Actions (grant
   agreement No 813440).
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NR 62
TC 0
Z9 0
U1 9
U2 9
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 AUG 1
PY 2022
VL 38
IS 6
BP 433
EP 448
DI 10.1089/jop.2022.0016
PG 16
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 3L2TY
UT WOS:000834619900007
PM 35914241
DA 2022-11-30
ER

PT J
AU Wykoff, CC
   Hershberger, V
   Eichenbaum, D
   Henry, E
   Younis, HS
   Chandra, P
   Yuan, N
   Solloway, M
   DePaoli, A
AF Wykoff, Charles C.
   Hershberger, Vrinda
   Eichenbaum, David
   Henry, Erin
   Younis, Husam S.
   Chandra, Priya
   Yuan, Nancy
   Solloway, Mark
   DePaoli, Alex
TI Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621:
   Phase 1 Dose-Escalation Study Results
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; SECONDARY; PATHWAY; PROGRESSION; PREVALENCE;
   ACTIVATION; BURDEN; INNATE
AB PURPOSE: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential.
   DESIGN: Multicenter, open-label, single-and multiple dose phase 1 study.
   METHODS: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age related macular degeneration, lesion size >= 2.5 mm(2), best corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments.
   RESULTS: All 15 participants completed the 12-week study. There were no serious adverse events, no drug related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points.
   CONCLUSIONS: In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg. ((C) 2021 The Authors. Published by Elsevier Inc.)
C1 Retina Consultants Amer, Retina Consultants Texas, Houston, TX USA.
   Houston Methodist Hosp, Blanton Eye Inst, Houston, TX 77030 USA.
   Florida Eye Associates, Melbourne, FL USA.
   Univ S Florida, Retina Vitreous Associates Florida, Tampa, FL USA.
   Univ S Florida, Morsani Coll Med, Tampa, FL 33620 USA.
   NGM Biopharmaceut Inc, San Francisco, CA USA.
C3 The Methodist Hospital System; The Methodist Hospital - Houston; State
   University System of Florida; University of South Florida; State
   University System of Florida; University of South Florida
RP Wykoff, CC (通讯作者)，Retina Consultants Texas, 4460 Bissonnet St,Ste 200, Bellaire, TX 77401 USA.
EM charleswykoff@gmail.com
OI Wykoff, Charles/0000-0001-7756-5091; Eichenbaum,
   David/0000-0003-0654-0668; SOLLOWAY, MARK/0000-0003-0589-3437
FU NGM Biopharmaceuticals, Inc.
FX NGM Biopharmaceuticals, Inc.
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NR 28
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAR
PY 2022
VL 235
BP 131
EP 142
DI 10.1016/j.ajo.2021.08.018
EA DEC 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XO6PM
UT WOS:000730304900009
PM 34509438
OA hybrid
DA 2022-11-30
ER

PT J
AU Schmidt-Erfurth, U
   Bogunovic, H
   Grechenig, C
   Bui, P
   Fabianska, M
   Waldstein, S
   Reiter, GS
AF Schmidt-Erfurth, Ursula
   Bogunovic, Hrvoje
   Grechenig, Christoph
   Bui, Patricia
   Fabianska, Maria
   Waldstein, Sebastian
   Reiter, Gregor S.
TI Role of Deep Learning-Quantified Hyperreflective Foci for the Prediction
   of Geographic Atrophy Progression
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; FUNDUS AUTOFLUORESCENCE; EYE DISEASE; AGE; SEGMENTATION;
   FLUID; DETACHMENT; MORPHOLOGY
AB PURPOSE: To quantitatively measure hyperreflective foci (HRF) during the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using deep learning (DL) and investigate the association with local and global growth of GA.
   METHODS: Eyes with GA were prospectively included. Spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence images were acquired every 6 months. A 500-mu m-wide junctional zone adjacent to the GA border was delineated and HRF were quantified using a validated DL algorithm. HRF concentrations in progressing and nonprogressing areas, as well as correlations between HRF quantifications and global and local GA progression, were assessed.
   RESULTS: A total of 491 SDOCT volumes from 87 eyes of 54 patients were assessed with a median followup of 28 months. Two-thirds of HRF were localized within a millimeter adjacent to the GA border. HRF concentration was positively correlated with GA progression in unifocal and multifocal GA (all P < .001) and de novo GA development (P = .037). Local progression speed correlated positively with local increase of HRF (P value range <.001-.004). Global progression speed, however, did not correlate with HRF concentrations (P > .05). Changes in HRF over time did not have an impact on the growth in GA (P > .05).
   CONCLUSION: Advanced artificial intelligence (AI) methods in high-resolution retinal imaging allows to identify, localize, and quantify biomarkers such as HRF. Increased HRF concentrations in the junctional zone and future macular atrophy may represent progressive migration and loss of retinal pigment epithelium. Al-based biomarker monitoring may pave the way into the era of individualized risk assessment and objective decision-making processes. (C) 2020 The Author(s). Published by Elsevier Inc.
C1 [Schmidt-Erfurth, Ursula; Bogunovic, Hrvoje; Grechenig, Christoph; Bui, Patricia; Fabianska, Maria; Waldstein, Sebastian; Reiter, Gregor S.] Med Univ Vienna, Vienna Reading Ctr, Dept Ophthalmol & Optometry, Christian Doppler Lab Ophthalm Image Anal, Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Reiter, Gregor/0000-0001-7661-4015; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Bui, Patricia Thao-An/0000-0001-5625-1755
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NR 75
TC 21
Z9 21
U1 2
U2 5
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 AUG
PY 2020
VL 216
BP 257
EP 270
DI 10.1016/j.ajo.2020.03.042
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NU2AU
UT WOS:000573444200036
PM 32277942
OA hybrid
DA 2022-11-30
ER

PT J
AU Zhao, X
   Liu, LL
   Jiang, YZ
   Silva, M
   Zhen, XC
   Zheng, WH
AF Zhao, Xia
   Liu, Linlin
   Jiang, Yizhou
   Silva, Marta
   Zhen, Xuechu
   Zheng, Wenhua
TI Protective Effect of Metformin against Hydrogen Peroxide-Induced
   Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by
   Enhancing Autophagy through Activation of AMPK Pathway
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID STRESS; APOPTOSIS; DEGENERATION; MECHANISMS; RAPAMYCIN; PROMOTES; DEATH
AB Age-related macular degeneration (AMD) is a leading cause of blindness with limited effective treatment. Although the pathogenesis of this disease is complex and not fully understood, the oxidative damage caused by excessive reactive oxygen species (ROS) in retinal pigment epithelium (RPE) has been considered as a major cause. Autophagy is essential for the degradation of cellular components damaged by ROS, and its dysregulation has been implicated in AMD pathogenesis. Therefore, strategies aiming to boost autophagy could be effective in protecting RPE cells from oxidative damage. Metformin is the first-line anti-type 2 diabetes drug and has been reported to stimulate autophagy in many tissues. We therefore hypothesized that metformin may be able to protect RPE cells against H2O2-induced oxidative damage by autophagy activation. In the present study, we found that metformin attenuated H2O2-induced cell viability loss, apoptosis, elevated ROS levels, and the collapse of the mitochondria membrane potential in D407 cells. Autophagy was stimulated by metformin, and inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) or knockdown of Beclin1 and LC3B blocked the protective effects of metformin. In addition, we showed that metformin could activate the AMPK pathway, whereas both pharmacological and genetic inhibitions of AMPK blocked the autophagy-stimulating and protective effects of metformin. Metformin conferred a similar protection against H2O2-induced oxidative damage in primary cultured human RPE cells. Taken together, these results demonstrate that metformin could protect RPE cells from H2O2-induced oxidative damage by stimulating autophagy via the activation of the AMPK pathway, supporting its potential use in the prevention and treatment of AMD.
C1 [Zhao, Xia; Liu, Linlin; Jiang, Yizhou; Silva, Marta; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Madhya Pradesh, Peoples R China.
   [Zhao, Xia; Liu, Linlin; Jiang, Yizhou; Silva, Marta; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Madhya Pradesh, Peoples R China.
   [Zhen, Xuechu] Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis, Suzhou 215123, Jiangsu, Peoples R China.
   [Zhen, Xuechu] Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Jiangsu, Peoples R China.
C3 University of Macau; University of Macau; Soochow University - China;
   Soochow University - China
RP Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Madhya Pradesh, Peoples R China.; Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Madhya Pradesh, Peoples R China.
EM yb77625@um.edu.mo; yb67622@um.edu.mo; yb77642@um.edu.mo;
   martas@um.edu.mo; zhenxuechu@suda.edu.cn; wenhuazheng@um.edu.mo
OI zhen, xuechu/0000-0001-7458-2566
FU National Natural Science Foundation of China [31771128]; Science and
   Technology Development Fund, Macau SAR [0127/2019/A3, 0044/2019/AGJ,
   0113/2018/A3]; University of Macau [MYRG2018-00134-FHS]
FX This research was supported by the National Natural Science Foundation
   of China (No. 31771128), the Science and Technology Development Fund,
   Macau SAR (File Nos. 0127/2019/A3, 0044/2019/AGJ, and 0113/2018/A3), and
   the University of Macau (File No. MYRG2018-00134-FHS). We are grateful
   to UM-FHS and core facilities for the equipment and administrative
   support for this study.
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NR 48
TC 16
Z9 16
U1 2
U2 7
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD JUL 25
PY 2020
VL 2020
AR 2524174
DI 10.1155/2020/2524174
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA MZ4ZH
UT WOS:000559133200003
PM 32774666
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kim, KT
   Lee, H
   Kim, JY
   Lee, S
   Chae, JB
   Kim, DY
AF Kim, Kyung Tae
   Lee, Hwanho
   Kim, Jin Young
   Lee, Suhwan
   Chae, Ju Byung
   Kim, Dong Yoon
TI Long-Term Visual/Anatomic Outcome in Patients with Fovea-Involving
   Fibrovascular Pigment Epithelium Detachment Presenting Choroidal
   Neovascularization on Optical Coherence Tomography Angiography
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE anti-vascular endothelial growth factor; choroidal neovascularization;
   exudative age-related macular degeneration; fibrovascular pigment
   epithelial detachment
ID MACULAR DEGENERATION; SUBGROUP ANALYSIS; 7-YEAR OUTCOMES; VISUAL-ACUITY;
   RANIBIZUMAB; VEGF; ATROPHY; ANCHOR; MARINA; GROWTH
AB Background: To evaluate long-term visual/anatomic outcome after anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with fovea-involving fibrovascular pigment epithelium detachment (PED) presenting with choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA). Methods: Patients with fibrovascular PED or subretinal CNV confirmed by OCTA who were treated by a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. The best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) before and after anti-VEGF injection were analyzed. Furthermore, changes in photoreceptor layer (PRL) thickness and outer retinal bands in the fovea after injection were evaluated. Results: A total of 31 eyes with fibrovascular PED and 24 eyes with subretinal CNV were included. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST were improved, and the PRL thickness was decreased significantly. There were no differences in BCVA, CST, changes in PRL thickness, or the status of outer retinal bands between the groups. However, the difference in the amount of decrease in PRL thickness between the two groups was increased at 2 years, and the slope tended to be steeper in the subretinal CNV group. Conclusions: Exudative age-related macular degeneration (AMD) with fibrovascular PED or subretinal CNV showed good visual/anatomic outcomes after anti-VEGF treatment, regardless of the CNV type. By 2 years, fibrovascular PED did not have an additional protective effect on the outer retina, compared with subretinal CNV over 2 years. Further follow-up study might be needed to conclude that fibrovascular PED has a protective effect on the surrounding photoreceptor area.
C1 [Kim, Kyung Tae] Univ Ulsan, Gangneung Asan Hosp, Coll Med, Dept Ophthalmol, Kangnung 25440, South Korea.
   [Lee, Hwanho; Chae, Ju Byung; Kim, Dong Yoon] Chungbuk Natl Univ, Chungbuk Natl Univ Hosp, Coll Med, Dept Ophthalmol, Cheongju 28644, South Korea.
   [Kim, Jin Young] Jeju Natl Univ, Jeju Natl Univ Hosp, Sch Med, Dept Ophthalmol, Jeju 63241, South Korea.
   [Lee, Suhwan] Kangwon Natl Univ, Kangwon Natl Univ Hosp, Grad Sch Med, Dept Ophthalmol, Chunchon 24289, South Korea.
C3 University of Ulsan; Chungbuk National University; Chungbuk National
   University Hospital; Jeju National University; Kangwon National
   University; Kangwon National University Hospital
RP Kim, DY (通讯作者)，Chungbuk Natl Univ, Chungbuk Natl Univ Hosp, Coll Med, Dept Ophthalmol, Cheongju 28644, South Korea.
EM kkt400@gmail.com; brolaril@naver.com; umuse7@gmail.com;
   saga2407@naver.com; cjbmed@naver.com; umlover9@gmail.com
OI Kim, Dong Yoon/0000-0002-6058-0145; Chae, Ju Byung/0000-0002-5233-0373;
   Kim, Kyung Tae/0000-0003-0495-930X; Kim, Jin Young/0000-0001-6204-9537;
   Lee, Hwanho/0000-0001-6259-6485; Lee, Suhwan/0000-0002-7065-8735
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NR 48
TC 5
Z9 5
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2077-0383
J9 J CLIN MED
JI J. Clin. Med.
PD JUN
PY 2020
VL 9
IS 6
AR 1863
DI 10.3390/jcm9061863
PG 14
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA ML3HC
UT WOS:000549360300001
PM 32549235
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dervenis, N
   Coleman, AL
   Harris, M
   Wilson, MR
   Yu, F
   Anastasopoulos, E
   Founti, P
   Pappas, T
   Kilintzis, V
   Topouzis, F
AF Dervenis, Nikolaos
   Coleman, Anne L.
   Harris, Mon
   Wilson, M. Roy
   Yu, Fei
   Anastasopoulos, Eleftherios
   Founti, Panayiota
   Pappas, Theofanis
   Kilintzis, Vassilis
   Topouzis, Fotis
TI Factors Associated With Retinal Vessel Diameters in an Elderly
   Population: the Thessaloniki Eye Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinal vasculature; hypertension; epidemiology; population-based; aging
ID OPEN-ANGLE GLAUCOMA; CARDIOVASCULAR RISK-FACTORS; DIASTOLIC
   BLOOD-PRESSURE; ATHEROSCLEROSIS RISK; MICROVASCULAR ABNORMALITIES;
   VASCULAR CALIBER; DIABETIC-RETINOPATHY; OLDER PERSONS; ARTERIOLAR; SIGNS
AB PURPOSE. To identify the factors associated with retinal vessel diameters in the population of the Thessaloniki Eye Study.
   METHODS. Cross-sectional population-based study (age >= 60 years). Subjects with glaucoma, late age-related macular degeneration, and diabetic retinopathy were excluded from the analyses. Retinal vessel diameters were measured using the IVAN software, and measurements were summarized to central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole to venule ratio (AVR).
   RESULTS. The analysis included 1614 subjects. The hypertensive group showed lower values of CRAE (P = 0.033) and AVR (P = 0.0351) compared to the normal blood pressure (BP) group. On the contrary, the group having normal BP under antihypertensive treatment did not have different values compared to the normal BP group. Diastolic BP (per mm Hg) was negatively associated with CRAE (P < 0.0001) and AVR (P < 0.0001), while systolic BP (per mm Hg) was positively associated with CRAE (P = 0.001) and AVR (P = 0.0096). Other factors significantly associated included age, sex, alcohol, smoking, cardiovascular disease history, ophthalmic medication, weight, and IOP; differences were observed in a stratified analysis based on BP medication use.
   CONCLUSIONS. Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.
C1 [Dervenis, Nikolaos; Anastasopoulos, Eleftherios; Founti, Panayiota; Pappas, Theofanis; Kilintzis, Vassilis; Topouzis, Fotis] Aristotle Univ Thessaloniki, Sch Med, Dept Ophthalmol, Lab Res & Clin Applicat Ophthalmol LARCAO, Kiriakidi 1, Thessaloniki 54621, Greece.
   [Coleman, Anne L.] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Harris, Mon] Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
   [Wilson, M. Roy] Wayne State Univ, Detroit, MI USA.
   [Yu, Fei] UCLA, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA.
   [Founti, Panayiota] Moorfields Eye Hosp NHS Fdn Trust, Glaucoma Unit, London, England.
C3 Aristotle University of Thessaloniki; University of California System;
   University of California Los Angeles; University of California Los
   Angeles Medical Center; David Geffen School of Medicine at UCLA; Indiana
   University System; Indiana University Bloomington; Wayne State
   University; University of California System; University of California
   Los Angeles; University of London; University College London; Moorfields
   Eye Hospital NHS Foundation Trust
RP Topouzis, F (通讯作者)，Aristotle Univ Thessaloniki, Sch Med, Dept Ophthalmol, Lab Res & Clin Applicat Ophthalmol LARCAO, Kiriakidi 1, Thessaloniki 54621, Greece.
EM ftopou12@otenet.gr
RI Dervenis, Nikolaos/AAK-2376-2020
OI Dervenis, Nikolaos/0000-0002-7269-2785; Kilintzis,
   Vassilis/0000-0002-9783-6757; Topouzis, Fotis/0000-0002-8966-537X
FU International Glaucoma Association (London, UK); UCLA Center for Eye
   Epidemiology (Los Angeles, CA, USA); Health Future Foundation; Creighton
   University (Omaha, NE, USA); Texas Tech University Health Sciences
   Center (Lubbock, TX, USA); Pfizer, Inc. (New York, NY, USA); Merck &
   Co., Inc. (Whitehouse Station, NJ, USA); Pharmacia Hellas (Athens,
   Greece)
FX Supported by the International Glaucoma Association (London, UK), UCLA
   Center for Eye Epidemiology (Los Angeles, CA, USA), Health Future
   Foundation, Creighton University (Omaha, NE, USA), Texas Tech University
   Health Sciences Center (Lubbock, TX, USA); Pfizer, Inc. (New York, NY,
   USA); Merck & Co., Inc. (Whitehouse Station, NJ, USA); and Pharmacia
   Hellas (Athens, Greece).
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NR 33
TC 11
Z9 12
U1 2
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2019
VL 60
IS 6
BP 2208
EP 2217
DI 10.1167/iovs.18-26276
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HZ6RS
UT WOS:000468980600046
PM 31108551
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Qiu, CX
   Ding, J
   Sigurdsson, S
   Fisher, DE
   Zhang, Q
   Eiriksdottir, G
   Klein, R
   van Buchem, MA
   Gudnason, V
   Cotch, MF
   Launer, LJ
AF Qiu, Chengxuan
   Ding, Jie
   Sigurdsson, Sigurdur
   Fisher, Diana E.
   Zhang, Qian
   Eiriksdottir, Gudny
   Klein, Ronald
   van Buchem, Mark A.
   Gudnason, Vilmundur
   Cotch, Mary Frances
   Launer, Lenore J.
TI Differential associations between retinal signs and CMBs by location:
   The AGES-Reykjavik Study
SO NEUROLOGY
LA English
DT Article
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; CEREBRAL MICROBLEEDS; MACULAR
   DEGENERATION; MICROVASCULAR SIGNS; ALZHEIMERS-DISEASE; AMYLOID-BETA;
   ATHEROSCLEROSIS RISK; COGNITIVE DECLINE; BRAIN; ABNORMALITIES
AB ObjectiveTo test the hypothesis that age-related macular degeneration (AMD) and retinal microvascular signs are differentially associated with lobar and deep cerebral microbleeds (CMBs).MethodsCMBs in lobar regions indicate cerebral amyloid angiopathy (CAA). -Amyloid deposits are implicated in both CAA and AMD. Deep CMBs are associated with hypertension, a major risk factor for retinal microvascular damage. This population-based cohort study included 2,502 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who undertook binocular digital retinal photographs at baseline (2002-2006) to assess retinal microvascular signs and AMD and brain MRI scan at both baseline and follow-up (2007-2011) to assess CMBs. We assessed retinal microvascular lesion burden by counting the 3 retinal microvascular signs (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) concurrently present in the participant. We used multiple logistic models to examine the association of baseline retinal pathology to incident CMBs detected at follow-up.ResultsDuring an average 5.2 years of follow-up, 461 people (18.3%) developed new CMBs, including 293 in exclusively lobar regions and 168 in deep regions. Pure geographic atrophy was significantly associated with strictly lobar CMBs (multivariable-adjusted odds ratio 2.59, 95% confidence interval [CI] 1.01-6.65) but not with deep CMBs. Concurrently having 2 retinal microvascular signs was associated with a 3-fold (95% CI 1.73-5.20) increased likelihood for deep CMBs but not exclusively lobar CMBs.ConclusionsRetinal microvascular signs and pure geographic atrophy may be associated with deep and exclusively lobar CMBs, respectively, in older people. These results have implications for further research to define the role of small vessel disease in cognitive impairment.
C1 [Qiu, Chengxuan; Ding, Jie; Zhang, Qian; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
   [Qiu, Chengxuan] Stockholm Univ, Karolinska Inst, Dept Neurobiol Care Sci & Soc, Aging Res Ctr, Stockholm, Sweden.
   [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
   [Fisher, Diana E.; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
   [Klein, Ronald] Univ Wisconsin Madison, Ophthalmol & Visual Sci, Madison, WI USA.
   [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
   [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on
   Aging (NIA); Karolinska Institutet; Stockholm University; Icelandic
   Heart Association; National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI); University of Wisconsin System; University
   of Wisconsin Madison; Leiden University; Leiden University Medical
   Center (LUMC); Leiden University - Excl LUMC; University of Iceland
RP Qiu, CX; Launer, LJ (通讯作者)，NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.; Qiu, CX (通讯作者)，Stockholm Univ, Karolinska Inst, Dept Neurobiol Care Sci & Soc, Aging Res Ctr, Stockholm, Sweden.
EM chengxuan.qiu@ki.se; LaunerL@nia.nih.gov
RI Gudnason, Vilmundur/AAE-7126-2019; van Buchem, Mark/AAC-9843-2022
OI Gudnason, Vilmundur/0000-0001-5696-0084; van Buchem,
   Mark/0000-0003-1881-1998; Cotch, Mary Frances/0000-0002-2046-4350
FU NIH [N01-AG-12100]; Intramural Research Program of the National
   Institute on Aging, NIH [ZIAEY000401]; National Eye Institute, NIH
   [ZIAEY000401]; Icelandic Heart Association; Icelandic Parliament;
   NATIONAL EYE INSTITUTE [ZIAEY000401] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [ZIAAG007420, ZIAAG007380, ZIAAG007480]
   Funding Source: NIH RePORTER
FX The AGES-Reykjavik Study was funded by the NIH (contract N01-AG-12100);
   the Intramural Research Program of the National Institute on Aging and
   the National Eye Institute (ZIAEY000401), NIH; and the Icelandic Heart
   Association and the Icelandic Parliament. None of the funding
   organizations or sponsors were involved in study design; in the
   collection, analysis, or interpretation of data; in writing of the
   report; or in the decision to submit the manuscript for publication.
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   Wieberdink RG, 2011, STROKE, V42, P2138, DOI 10.1161/STROKEAHA.111.616359
NR 39
TC 8
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JAN 9
PY 2018
VL 90
IS 2
BP E142
EP E148
DI 10.1212/WNL.0000000000004792
PG 7
WC Clinical Neurology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA FZ7QZ
UT WOS:000427797300007
PM 29237799
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Gobel, AP
   Fleckenstein, M
   Heeren, TFC
   Holz, FG
   Schmitz-Valckenberg, S
AF Goebel, Arno P.
   Fleckenstein, Monika
   Heeren, Tjebo F. C.
   Holz, Frank G.
   Schmitz-Valckenberg, Steffen
TI In-vivo mapping of drusen by fundus autofluorescence and spectral-domain
   optical coherence tomography imaging
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Drusen; Geographic atrophy; Fundus
   autofluorescence; Scanning laser ophthalmoscope; Spectral-domain optical
   coherence tomography
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY;
   HIGH-RESOLUTION; APPEARANCE
AB Purpose To determine fundus autofluorescence (FAF) signal variations and corresponding microstructural alterations on spectral-domain optical coherence tomography (SD-OCT) in areas of funduscopically visible drusen associated with age-related macular degeneration (AMD).
   Methods Thirty eyes from 22 patients with geographic atrophy (GA) secondary to AMD (median age 74, range 64-87 years), who had undergone retinal imaging including color fundus photography (CFP), FAF and SD-OCT (Spectralis HRA+OCT; Heidelberg Engineering GmbH, Heidelberg, Germany) were retrospectively analyzed. In each eye, at least one druse (>= 63 mu m) in the perilesional zone of GA recorded on CFP was analyzed. Relative FAF intensities and alterations in SD-OCT bands at the site of each druse were evaluated.
   Results A total of 73 drusen were analyzed, which were associated with heterogeneous corresponding alterations on FAF and SD-OCT. The FAF signal was normal, increased, decreased or not evaluable in 32 (44 %), 27 (37 %), 12 (16 %), and 2 (3 %) drusen, respectively. Focal hyperreflectivity overlying drusen was most frequently spatially confined to increased FAF (present in 9 (33 %) of 27 drusen with increased FAF). Outer nuclear layer thinning and choroidal hyperreflectivity were associated with decreased FAF (present in 7 [58 %] of 12 and 6 [50 %] of 12 drusen with decreased FAF, respectively).
   Conclusions The appearance of soft drusen on CFP does not allow for differentiation between preserved and markedly compromised outer retinal integrity, including incipient atrophy and focal neurosensory alterations of reflectivity overlying extracellular sub-retinal pigment epithelium (RPE) deposits. Multimodal imaging reveals a broad spectrum of microstructural changes, which may reflect different stages in the evolution of drusen.
C1 [Goebel, Arno P.; Fleckenstein, Monika; Heeren, Tjebo F. C.; Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
C3 University of Bonn
RP Schmitz-Valckenberg, S (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM steffen.schmitz-valckenberg@ukb.uni-bonn.de
RI Heeren, Tjebo/R-5055-2019
OI Heeren, Tjebo/0000-0001-5297-2301; Fleckenstein,
   Monika/0000-0001-8321-8037
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NR 23
TC 10
Z9 10
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JAN
PY 2016
VL 254
IS 1
BP 59
EP 67
DI 10.1007/s00417-015-3012-4
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DD5ZT
UT WOS:000370004200009
PM 25904296
DA 2022-11-30
ER

PT J
AU Zetterberg, M
AF Zetterberg, Madeleine
TI Age-related eye disease and gender
SO MATURITAS
LA English
DT Review
DE Age-related macular degeneration; Aging; Blindness; Cataract; Diabetic
   retinopathy; Estrogen; Eye disease; Gender; Glaucoma; Visual impairment
ID OPEN-ANGLE GLAUCOMA; FEMALE REPRODUCTIVE FACTORS; HORMONE REPLACEMENT
   THERAPY; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; VISUAL IMPAIRMENT;
   CLOSURE GLAUCOMA; LENS OPACITIES; RISK-FACTORS; EXFOLIATION GLAUCOMA
AB Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Zetterberg, Madeleine] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil Ophthalmol, Gothenburg, Sweden.
   [Zetterberg, Madeleine] Sahlgrens Univ Hosp, Dept Ophthalmol, Molndal, Sweden.
C3 University of Gothenburg; Sahlgrenska University Hospital
RP Zetterberg, M (通讯作者)，Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil Ophthalmol, Gothenburg, Sweden.
EM madeleine.zetterberg@gu.se
FU Sahlgrenska University Hospital [ALFGBG-441721]; Goteborg Medical
   Society; Marianne and Marcus Wallenberg Foundation; Dr Reinhard Marcuses
   Foundation; Konung Gustaf V:s och Drottning Victorias
   Frimurarestiftelse; Hjalmar Svensson Foundation; Greta Andersson
   Foundation; Herman Svensson Foundation; Ogonfonden; De Blindas Vanner;
   Kronprinsessan Margaretas Arbetsnamnd for Synskadade
FX This work was supported by grants from the Sahlgrenska University
   Hospital ("Agreement concerning research and education of doctors";
   ALFGBG-441721), Goteborg Medical Society, Marianne and Marcus Wallenberg
   Foundation, Dr Reinhard Marcuses Foundation, Konung Gustaf V:s och
   Drottning Victorias Frimurarestiftelse, Hjalmar Svensson Foundation,
   Greta Andersson Foundation, Herman Svensson Foundation, Ogonfonden, De
   Blindas Vanner and Kronprinsessan Margaretas Arbetsnamnd for Synskadade.
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NR 120
TC 75
Z9 78
U1 0
U2 28
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0378-5122
EI 1873-4111
J9 MATURITAS
JI Maturitas
PD JAN
PY 2016
VL 83
BP 19
EP 26
DI 10.1016/j.maturitas.2015.10.005
PG 8
WC Geriatrics & Gerontology; Obstetrics & Gynecology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA CZ0GT
UT WOS:000366783800005
PM 26508081
DA 2022-11-30
ER

PT J
AU Dev, MK
   Paudel, N
   Joshi, ND
   Shah, DN
   Subba, S
AF Dev, Mahesh Kumar
   Paudel, Nabin
   Joshi, Niraj Dev
   Shah, Dev Narayan
   Subba, Shishir
TI Impact of Visual Impairment on Vision-Specific Quality of Life among
   Older Adults Living in Nursing Home
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Blindness; kathmandu; nursing home; prevalence; quality of life; visual
   impairment
ID CATARACT-SURGERY; PREVALENCE; RESIDENTS; PEOPLE; DEPRESSION
AB Background: Visual impairment (VI) has a significant negative impact on quality of life (QoL) amongst older people living in nursing homes. The purpose of this study was to determine the prevalence of VI and blindness and to explore the association between severity of VI and vision-specific QoL among older people living in nursing homes of Kathmandu, Nepal.
   Methods: This cross-sectional study involved 158 residents aged 60 years or older residing in seven nursing homes of Kathmandu Valley, Nepal. Near acuity, presenting and the best corrected distance visual acuity (VA) were assessed in each eye and considered in the better eye after adequate refraction. A complete anterior and posterior segment examination was carried out. Face-to-face interviews were conducted using a 57-item Nursing Home Vision-Targeted Health-Related Quality of Life (NHVQoL) questionnaire.
   Results: The mean age of residents was 75.60 +/- 7.12 years and the majority were female (66.46%). The prevalence of VI and blindness was 45.57% and its leading cause was cataract, which was followed by age-related macular degeneration, corneal opacity, glaucoma and macular scar. The mean composite score of NHVQoL questionnaire was 52.22 +/- 12.49. There was a consistent overall deterioration in the mean composite score as well as each subscale score of NHVQoL questionnaire with a worsening of VA.
   Conclusion: VI and blindness are highly prevalent among older people living in nursing homes. VI has a significant negative impact on vision-specific QoL. Vision-specific QoL is reduced, and the reduction in the QoL bears a positive association with severity of VI among older people living in nursing homes.
C1 [Dev, Mahesh Kumar; Paudel, Nabin; Joshi, Niraj Dev; Shah, Dev Narayan] Tribhuvan Univ, Inst Med, Dept Ophthalmol, BP Koirala Lions Ctr Ophthalm Studies, Kathmandu, Nepal.
   [Subba, Shishir] Tribhuvan Univ, Cent Dept Psychol, Kathmandu, Nepal.
   [Paudel, Nabin] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand.
C3 Tribhuvan University; Institute of Medicine (IoM) - Nepal; Tribhuvan
   University; University of Auckland
RP Dev, MK (通讯作者)，Tribhuvan Univ, Inst Med, Dept Ophthalmol, BP Koirala Lions Ctr Ophthalm Studies, Kathmandu, Nepal.
EM maheshdev2002@gmail.com
RI Paudel, Nabin/W-3265-2019; Dev, Mahesh Kumar/T-9113-2019
OI Paudel, Nabin/0000-0003-1583-9856; Dev, Mahesh Kumar/0000-0003-1339-8727
FU Social Inclusion Research Fund (SIRF), Secretariat SNV, Bakhundole,
   Lalitpur, Nepal
FX This research was supported by Social Inclusion Research Fund (SIRF),
   Secretariat SNV, Bakhundole, Lalitpur, Nepal, as Matthias Moyersoen
   research apprenticeship grant.
CR American Academy of Ophthalmology Preferred Practice Patterns Committee, 2005, OPHTHALMOLOGY
   American Optometric Association Consensus Panel on Comprehensive Adult Eye and Vision Examination, 2005, VISION
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NR 25
TC 26
Z9 26
U1 0
U2 14
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 MAR
PY 2014
VL 39
IS 3
BP 232
EP 238
DI 10.3109/02713683.2013.838973
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA AD1YS
UT WOS:000333030200002
PM 24144491
DA 2022-11-30
ER

PT J
AU Minor, EA
   Court, BL
   Dubovy, S
   Wang, GF
AF Minor, Emily A.
   Court, Brenda L.
   Dubovy, Sander
   Wang, Gaofeng
TI AMD-Associated Variants at the Chromosome 10q26 Locus and the Stability
   of ARMS2 Transcripts
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; ARMS2; variants; gene expression;
   transcript stability
ID MACULAR DEGENERATION; MESSENGER-RNA; RISK-FACTORS; HTRA1;
   SUSCEPTIBILITY; LOC387715; GENE; POLYMORPHISM; EXPRESSION; CFH
AB PURPOSE. To analyze the effect of variants including age-related macular degeneration (AMD)-associated combinative insertion/deletion polymorphism (indel) at 3'UTR of ARMS2 and possibly associated R38X on the stability of ARMS2 transcripts.
   METHODS. ARMS2 transcription from minigene vectors carrying different alleles at variants R38X and the indel were assessed in mouse embryonic fibroblasts (MEFs). Dual luciferase assays were applied to evaluate the effect of the indel on gene expression. RT-PCR and quantitative RT-PCR (qRT-PCR) were used to measure the two ARMS2 transcripts (isoform A and isoform B) in MEFs and human retina-RPE-choroid samples (n = 83).
   RESULTS. Allele X at variant R38X decreased exogenous ARMS2 transcripts in MEFs compared to allele R. In contrast, the indel did not change the level of exogenous ARMS2 transcripts. After blocking transcription by actinomycin D, R38X appeared to accelerate the degradation of ARMS2 transcripts, while the indel did not obviously affect the stability of ARMS2 transcripts compared to the wild-type (WT) allele. Dual luciferase assays further indicated that the indel did not influence gene expression. Quantitative RT-PCR results showed that there was no significant difference in two ARMS2 transcript splice isoforms among retina-RPE-choroid samples carrying different genotypes at variants R38X and the indel.
   CONCLUSIONS. Variant R38X, not the indel, decreases the stability of ARMS2 transcripts in vitro. However, genotypes at R38X and the indel do not obviously affect the level of ARMS2 transcripts in retina-RPE-choroid samples. These results suggest that variants R38X and the indel are less likely to play a pathogenic role in AMD by changing the level of ARMS2 transcripts.
C1 [Minor, Emily A.; Court, Brenda L.; Wang, Gaofeng] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Dr John T Macdonald Fdn,Dept Human Genet, Miami, FL 33136 USA.
   [Dubovy, Sander] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
C3 University of Miami; Bascom Palmer Eye Institute; University of Miami
RP Wang, GF (通讯作者)，Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Dr John T Macdonald Fdn,Dept Human Genet, 1501 NW 10th Ave, Miami, FL 33136 USA.
EM gwang@med.miami.edu
FU BrightFocus Foundation [M2012048]
FX Supported by BrightFocus Foundation Grant M2012048 (GW).
CR Bergeron-Sawitzke J, 2009, EUR J HUM GENET, V17, P1190, DOI 10.1038/ejhg.2009.23
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NR 22
TC 11
Z9 11
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2013
VL 54
IS 8
BP 5913
EP 5919
DI 10.1167/iovs.13-12273
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 228EA
UT WOS:000325167200096
PM 23942973
DA 2022-11-30
ER

PT J
AU Finger, RP
   Fenwick, E
   Pesudovs, K
   Marella, M
   Lamoureux, EL
   Holz, FG
AF Finger, Robert P.
   Fenwick, Eva
   Pesudovs, Konrad
   Marella, Manjula
   Lamoureux, Ecosse L.
   Holz, Frank G.
TI Rasch Analysis Reveals Problems with Multiplicative Scoring in the
   Macular Disease Quality of Life Questionnaire
SO OPHTHALMOLOGY
LA English
DT Article
ID INDIVIDUALIZED MEASURE; VISION; IMPACT; DEGENERATION; PARTICIPATION;
   RELIABILITY; OUTCOMES; MACDQOL; SCALE
AB Purpose: To evaluate validity and psychometric characteristics of the Macular Disease Quality of Life questionnaire (MacDQoL), a multiplicative rating scale designed to measure vision-related quality of life (VRQoL) in macular diseases and age-related macular degeneration (AMD).
   Design: Cross-sectional study.
   Participants: We included 108 patients with neovascular AMD at baseline before ranibizumab treatment.
   Methods: The psychometric properties of the MacDQoL were assessed using Rasch analysis, exploring key indices such as response category functioning, instrument unidimensionality, discriminant ability, and targeting of item difficulty to patient ability.
   Main Outcome Measures: Measurement characteristics of the MacDQoL.
   Results: In the MacDQoL's native form, the majority of response categories were underutilized and thresholds disordered. This could not be remedied without eliminating the importance ratings owing to the ambiguous nature of the response categories. Scaling problems were resolved by using the impairment rating scale only and collapsing response categories to 4. However, the MacDQoL was multidimensional, necessitating the omission of a number of items and splitting it into an activity limitation and mobility and a socioemotional well-being scale. This improved the psychometric parameters of the revised MacDQoL, although no correlation with clinical measures such as visual acuity was found.
   Conclusions: The multiplicative rating scale of the MacDQoL is flawed and does not provide scientific measurement of VRQoL. Measurement can be restored with a series of revisions to the instrument. This study reinforces the importance of considering rating scale design when choosing patient reported outcomes instruments for healthcare research.
   Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2012;119:2351-2357 (C) 2012 by the American Academy of Ophthalmology.
C1 [Finger, Robert P.; Fenwick, Eva; Marella, Manjula; Lamoureux, Ecosse L.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia.
   [Finger, Robert P.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Pesudovs, Konrad] Flinders Med Ctr, NHMRC Ctr Clin Eye Res, Discipline Optometry & Vis Sci, Adelaide, SA, Australia.
   [Pesudovs, Konrad] Flinders Univ S Australia, Adelaide, SA, Australia.
   [Lamoureux, Ecosse L.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; University of Bonn; Flinders Medical Centre;
   Flinders University South Australia; National University of Singapore;
   Singapore National Eye Center
RP Finger, RP (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Dept Ophthalmol, Royal Victorian Eye & Ear Hosp, Level 1,32 Gisborne St, Melbourne, Vic 3002, Australia.
EM robertfinger@gmx.net
RI Pesudovs, Konrad/T-9403-2019; Lamoureux, Ecosse/Z-5482-2019; Marella,
   Majula/AAN-2488-2021
OI Pesudovs, Konrad/0000-0002-6322-9369; Marella,
   Majula/0000-0002-1877-7956; Finger, Robert P/0000-0003-4253-7597
FU German Research Council [DFG FI 1540/5-1]; Novartis Pharma GmbH, Germany
FX Funded by the German Research Council grant (DFG FI 1540/5-1) to RPF.
   CERA receives Operational Infrastructure Support from the Victorian
   Government. This study was supported by Novartis Pharma GmbH, Germany.
CR Berdeaux G, 2011, VALUE HEALTH, V14, P110, DOI 10.1016/j.jval.2010.10.027
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   Denny F, 2007, INVEST OPHTH VIS SCI, V48, P1976, DOI 10.1167/iovs.06-0135
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   Scheibler F, 2010, OPHTHALMOLOGE, V107, P235, DOI 10.1007/s00347-009-2037-7
NR 31
TC 23
Z9 24
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2012
VL 119
IS 11
BP 2351
EP 2357
DI 10.1016/j.ophtha.2012.05.031
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 030OH
UT WOS:000310579500023
PM 22968142
DA 2022-11-30
ER

PT J
AU Mendrinos, E
   Petropoulos, IK
   Pournaras, CJ
AF Mendrinos, E.
   Petropoulos, I. K.
   Pournaras, C. J.
TI Retinal Angiomatous Proliferations: When Should We Suspect Them and How
   Should We Detect Them?
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE retinal angiomatous proliferation; hard exudates; pigment epithelium
   detachment; hot spot; video-angiography
ID INDOCYANINE GREEN ANGIOGRAPHY; INTRAVITREAL TRIAMCINOLONE;
   NEOVASCULARIZATION; ABLATION
AB Background: The aim of this study was to identify the clinical and angiographic features of retinal angiomatous proliferations (RAPs) in patients with age-related macular degeneration.
   Patients and Methods: 26 eyes of 24 patients with RAPs were retrospectively reviewed. All patients had colour and red-free photographs, and fluorescein (FA) and indocyanine-green angiography (ICGA). The biomicroscopic and angiographic characteristics were evaluated and video-angiograms were analysed for staging the RAPs.
   Results: The total number of RAPs was 29. Stage 1 was present in 3/29, stage 2 in 3/29 and stage 3 in 23/29 with a chorio-retinal anastomosis identified in 21 of these 23 eyes. The total number of retinal vessels involved were 83, 35 were arteries and 48 were veins. RAPs were seen in ICGA as hot spots in all but one case where it appeared as a plaque. A retinal pigment epithelial detachment (PED) was observed in 22/26 eyes. Cystoid macular oedema was observed in 13/26 eyes in FA and intraretinal ICG leakage in 6/26 eyes. Hard exudates were present in 21/26 eyes. Retinal haemorrhages were present in 23/26 eyes; all but one were intraretinal and had a size of less than half of the optic disc diameter. The RAP was bilateral in 2/24 patients.
   Conclusions: Clinicians should suspect the diagnosis of RAP when hard exudates, small intraretinal haemorrhages, PED or a hot spot in ICGA are present. Both fluorescein and ICG video-angiography provide adequate temporal resolution and vascular flow examination leading to easier RAP staging and identification of the anastomosis.
C1 [Mendrinos, E.; Petropoulos, I. K.; Pournaras, C. J.] Univ Hosp Geneva, Dept Ophthalmol, CH-1211 Geneva 14, Switzerland.
C3 University of Geneva
RP Pournaras, CJ (通讯作者)，Univ Hosp Geneva, Dept Ophthalmol, 22 Rue Alcide Jentzer, CH-1211 Geneva 14, Switzerland.
EM constantin.pournaras@hcuge.ch
CR Bearelly S, 2008, BRIT J OPHTHALMOL, V92, P191, DOI 10.1136/bjo.2007.118760
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   Yannuzzi LA, 2001, RETINA-J RET VIT DIS, V21, P416, DOI 10.1097/00006982-200110000-00003
NR 12
TC 2
Z9 2
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0023-2165
EI 1439-3999
J9 KLIN MONATSBL AUGENH
JI Klinische Monatsblat. Augenheilkunde
PD APR
PY 2009
VL 226
IS 4
BP 284
EP 288
DI 10.1055/s-0028-1109311
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 441CW
UT WOS:000265747900017
PM 19384784
DA 2022-11-30
ER

PT J
AU Jordan, JF
   Semkova, I
   Kociok, N
   Welsandt, GR
   Krieglstein, GK
   Schraermeyer, U
AF Jordan, JF
   Semkova, I
   Kociok, N
   Welsandt, GR
   Krieglstein, GK
   Schraermeyer, U
TI Iris pigment epithelial cells transplanted into the vitreous accumulate
   at the optic nerve head
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID RETINAL GANGLION-CELLS; NEUROTROPHIC FACTOR; RAT; SURVIVAL; DEATH;
   PROLIFERATION; DEGENERATION; EXPRESSION; DAMAGE
AB Background: Iris pigment epithelial (IPE) cells have mainly been investigated in the past for their proposed potential to rescue or even replace degenerated retinal pigment epithelial (RPE) cells after subretinal transplantation in patients with age-related macular degeneration (AMD). More recent reports have characterised the IPE cell as a potent source of trophic factors and cytokines. In our study we investigated the spatial distribution of IPE cells that were injected into the vitreous instead of being injected subretinally. Methods: IPE cells from Long Evans rats were isolated and injected into the vitreous cavity of Wistar rats without preculturing. Free melanin granules were injected into the vitreous in the same manner. After a period of 2 months, eyes were prepared for histological analysis. Localisation of the injected IPE cells was defined by topographical mapping of the analysed sections. Results: PVR was not observed in any eye. In 8 of 10 injected eyes, IPE cells had accumulated in the prepapillary region. In 2 of 10 eyes, no IPE cells could be detected. The injected melanin granules also accumulated at the optic nerve head, indicating that this is most likely a passive process. In sections of the papillary region containing retinal vessels, the IPE cells seemed to have migrated into the superficial tissue of the optic nerve head. Conclusion: Our results demonstrate a way to access the optic nerve head easily and securely without the danger of damaging its fragile structure. This could have important implications for new therapeutic strategies in ocular neurodegenerative diseases like glaucoma. New prospects in gene therapy will require further characterisation of the potential of the IPE cell to produce neuroprotective trophic factors at the optic nerve head.
C1 Univ Cologne, Eye Clin, D-50931 Cologne, Germany.
C3 University of Cologne
RP Jordan, JF (通讯作者)，Univ Cologne, Eye Clin, Joseph Stelzmann Str 9, D-50931 Cologne, Germany.
EM j.jordan@uni-koeln.de
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NR 27
TC 6
Z9 9
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAY
PY 2002
VL 240
IS 5
BP 403
EP 407
DI 10.1007/s00417-002-0436-4
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 564TQ
UT WOS:000176330000011
PM 12073064
DA 2022-11-30
ER

PT J
AU Thomson, K
   Karouta, C
   Sabeti, F
   Anstice, N
   Leung, M
   Jong, T
   Maddess, T
   Morgan, IG
   Game, J
   Ashby, R
AF Thomson, Kate
   Karouta, Cindy
   Sabeti, Faran
   Anstice, Nicola
   Leung, Myra
   Jong, Tina
   Maddess, Ted
   Morgan, Ian G.
   Game, Jeremy
   Ashby, Regan
TI The safety and tolerability of levodopa eye drops for the treatment of
   ocular disorders: A randomized first-in-human study
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
ID PARKINSONS-DISEASE; PATTERN ELECTRORETINOGRAM; L-DOPA; MYOPIA
AB Myopia is the leading cause of low vision worldwide and can lead to significant pathological complications. Therefore, to improve patient outcomes, the field continues to develop novel interventions for this visual disorder. Accordingly, this first-in-human study reports on the safety profile of a novel dopamine-based ophthalmic treatment for myopia, levodopa/carbidopa eye drops. This phase I, first-in-human, monocenter, placebo-controlled, double-blind, paired-eye, multidose, randomized clinical trial was undertaken in healthy adult males aged 18-30 years (mean age 24.9 +/- 2.7) at the University of Canberra Eye Clinic, Australia. Participants were randomly assigned to receive either a low (1.4 levodopa:0.34 carbidopa [mu moles/day], n = 14) or standard dose (2.7 levodopa:0.68 carbidopa [mu moles/day], n = 15) of levodopa/carbidopa eye drops in one eye and placebo in the fellow eye once daily for 4 weeks (28 days). Over this 4-week trial, and after a 4-month follow-up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non-ocular adverse events. These results indicate that topical levodopa/carbidopa is safe and tolerable to the eye, paving the way for future studies on the efficacy of this novel ophthalmic formulation in the treatment of human myopia. The findings of this study have implications not only for the treatment of myopia, but in a number of other visual disorders (i.e., amblyopia, diabetic retinopathy, and age-related macular degeneration) in which levodopa has been identified as a potential clinical intervention.
C1 [Thomson, Kate; Karouta, Cindy; Game, Jeremy; Ashby, Regan] Univ Canberra, Fac Sci & Technol, Univ Dr, Canberra, ACT, Australia.
   [Sabeti, Faran; Leung, Myra; Jong, Tina] Univ Canberra, Fac Hlth, Discipline Optometry, Canberra, ACT, Australia.
   [Sabeti, Faran; Maddess, Ted] Australian Natl Univ, John Curtin Sch Med Res JCSMR, Canberra, ACT, Australia.
   [Anstice, Nicola] Flinders Univ S Australia, Coll Nursing & Hlth Sci, Optometry & Vis Sci, Adelaide, SA, Australia.
   [Morgan, Ian G.] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia.
C3 University of Canberra; University of Canberra; Australian National
   University; John Curtin School of Medical Research; Flinders University
   South Australia; Australian National University
RP Thomson, K (通讯作者)，Univ Canberra, Fac Sci & Technol, Univ Dr, Canberra, ACT, Australia.
EM kate.thomson@canberra.edu.au
RI Morgan, Ian G/D-1190-2009
OI Morgan, Ian G/0000-0002-4548-3574; Karouta, Cindy/0000-0003-1157-2840;
   Thomson, Kate/0000-0002-2272-2800; Anstice, Nicola/0000-0003-1999-5274;
   Leung, Myra/0000-0003-3116-4481
FU University of Canberra; ANU Connect Ventures [DTF 216]
FX This work was supported by internal funding from the University of
   Canberra and a Discovery Translation Fund grant from ANU Connect
   Ventures (DTF 216). The University of Canberra acted as the trial
   sponsor, while ANU Connect Ventures played no role in trial activities.
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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 1752-8054
EI 1752-8062
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD NOV
PY 2022
VL 15
IS 11
BP 2673
EP 2684
DI 10.1111/cts.13392
EA OCT 2022
PG 12
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 6C2KJ
UT WOS:000866134000001
PM 36221799
OA Green Published
DA 2022-11-30
ER

PT J
AU Minnella, AM
   Centini, C
   Gambini, G
   Savastano, MC
   Pagliei, V
   Falsini, B
   Rizzo, S
   Ciasca, G
   Maceroni, M
AF Minnella, Angelo Maria
   Centini, Chiara
   Gambini, Gloria
   Savastano, Maria Cristina
   Pagliei, Valeria
   Falsini, Benedetto
   Rizzo, Stanislao
   Ciasca, Gabriele
   Maceroni, Martina
TI Choroidal Thickness Changes After Intravitreal Aflibercept Injections in
   Treatment-Naive Neovascular AMD
SO ADVANCES IN THERAPY
LA English
DT Article
DE Aflibercept; Anti-VEGF; Choroid; Choroidal thickness; Macular
   neovascularization (MNV); Neovascular age-related macular degeneration;
   Optical coherence tomography (OCT)
ID MACULAR DEGENERATION RANIBIZUMAB; OPTICAL COHERENCE TOMOGRAPHY; OCULAR
   BLOOD-FLOW; GEOGRAPHIC ATROPHY; 2-YEAR OUTCOMES; EXTEND REGIMEN;
   SUBFOVEAL; EYES; THERAPY; GROWTH
AB Introduction Choroidal thickness (CT) plays an important role in the pathogenesis of various ocular diseases, including neovascular age-related macular degeneration (nAMD). Previous studies evaluated the CT variations after anti-vascular endothelial growth factor (VEGF) injections in patients with nAMD, but the results are still controversial. The present study aimed to evaluate the CT at different times (15, 30, 60, 90, and 365 days) after intravitreal aflibercept injections and its correlation with the baseline CT in treatment-naive patients with nAMD. Secondly, the study evaluated the correlation between CT variation at 365 days and the number of intravitreal injections received. Methods This was a prospective, open-label, single-arm pilot study. Twenty-one treatment-naive nAMD eyes were enrolled. The study population underwent three monthly aflibercept injections (loading phase) and additional injections as needed (pro re nata regimen). A complete ophthalmological examination, including optical coherence tomography (OCT) was performed at each visit. CT was measured manually by two independent observers. All patients were evaluated at baseline and at 15, 30, 60, 90, and 365 days after the first intravitreal injection. Results CT showed a statistically significant reduction at days 15, 90, and 365 in comparison to baseline. However, the major reduction of CT was observed at day 15 and in eyes with a thicker choroid at baseline. No significant correlation between CT variation and the number of injections performed was found. Conclusion Our findings contribute to clarifying the role of aflibercept injections in choroidal vasculature, confirming its effect after the first 2 weeks. Moreover, CT can be considered as a potential biomarker, as it reflects the pharmacological effect of anti-VEGF drugs.
C1 [Minnella, Angelo Maria; Savastano, Maria Cristina; Falsini, Benedetto; Rizzo, Stanislao; Ciasca, Gabriele; Maceroni, Martina] Univ Cattolica Sacro Cuore, Rome, Italy.
   [Minnella, Angelo Maria; Gambini, Gloria; Savastano, Maria Cristina; Falsini, Benedetto; Rizzo, Stanislao] Fdn Policlin Univ A Gemelli IRCCS, UOC Oftalmol, Rome, Italy.
   [Ciasca, Gabriele] Fdn Policlin Univ A Gemelli IRCCS, Largo Agostino Gemelli 8, I-00168 Rome, RM, Italy.
   [Pagliei, Valeria] Univ Aquila, Dipartimento Biotecnol & Sci Clin Appl, Laquila, Italy.
   [Centini, Chiara] Univ Politecn Marche, Ancona, Italy.
C3 Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli;
   Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli;
   Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli;
   University of L'Aquila; Marche Polytechnic University
RP Centini, C (通讯作者)，Univ Politecn Marche, Ancona, Italy.
EM aminnella59@gmail.com; cent.chiara@gmail.com; gambini.gloria@gmail.com;
   mariacristina.savastano@unicatt.it; valeria.pagliei@gmail.com;
   benedetto.falsini@unicatt.it; stanislao.rizzo@policlinicogemelli.it;
   gabriele.ciasca@unicatt.it; maceronimartina@gmail.com
RI Savastano, Maria Cristina/I-5355-2015
OI Savastano, Maria Cristina/0000-0003-1397-4333; Centini,
   Chiara/0000-0002-8355-1611
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NR 39
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0741-238X
EI 1865-8652
J9 ADV THER
JI Adv. Ther.
PD JUL
PY 2022
VL 39
IS 7
BP 3248
EP 3261
DI 10.1007/s12325-022-02129-x
EA MAY 2022
PG 14
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 2O4KV
UT WOS:000799697700002
PM 35597837
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Zhu, JM
   Su, T
   Wang, ML
   Li, M
   Liu, L
   Wang, F
AF Zhu, Juming
   Su, Tu
   Wang, Minli
   Li, Min
   Liu, Lin
   Wang, Fang
TI Highly Expressed Amyloid Beta-42 Of Aqueous Humor In Patients With
   Neovascular Macular Degeneration
SO SEMINARS IN OPHTHALMOLOGY
LA English
DT Article
DE Neovascular macular degeneration; Cognitive function; Amyloid beta-42;
   Aqueous humor
AB Background: Age-related macular degeneration (AMD) is a type of macular degeneration disease, and amyloid beta (a beta) is the main component of vitreous warts in AMD patients. Neovascular AMD (nAMD) is the most serious type of AMD, but its pathogenesis remains unclear. The aim of this study was to detect the expression of a beta 42 in the aqueous humor of nAMD patients and to evaluate whether a beta 42 expression of aqueous humor is correlated with cognitive function in these patients.
   Methods: A total of 70 patients were enrolled in this study, including 50 nAMD patients (nAMD group) and 20 patients with cataract (control group). The cognitive function of the patients was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment Scale, and based on their scores, 50 patients with nAMD were divided into two subgroups: the p-nAMD group (18 nAMD patients with normal cognition) and the ci-nAMD group (32 nAMD patients with cognitive impairment). An immunofluorescence microsphere probe technique was used to detect the a beta 42 expression of aqueous humor in all patients. Pearson correlation analysis was used.
   Results: The a beta 42 expression of aqueous humor was significantly higher in the nAMD group (124.56 +/- 41.93 pg/mL) as compared with the control group (82.94 +/- 33.75 pg/mL; P < .01). There was no significant difference in a beta 42 expression of aqueous humor between the p-nAMD group (136.42 +/- 51.68 pg/mL) and ci-nAMD group (117.90 +/- 34.46 pg/mL; P = .14).
   Conclusion: In nAMD patients, a beta 42 was highly expressed in the aqueous humor but was not correlated with cognitive function.
C1 [Zhu, Juming] Nantong Univ, Yancheng 1 Peoples Hosp, Dept Ophthalmol, Affiliated Hosp 4, Nanjing, Jiangsu, Peoples R China.
   [Su, Tu; Wang, Minli; Li, Min; Liu, Lin; Wang, Fang] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.
C3 Nantong University; Tongji University
RP Wang, F (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Ophthalmol, Shanghai 200072, Peoples R China.
EM wangfang7527@163.com
FU National Natural Science Foundation of China [81770939]; Yancheng
   medical science and technology development [2020008]
FX This work was supported by the National Natural Science Foundation of
   China under Grant [No. 81770939], and Yancheng medical science and
   technology development (grant no. 2020008).
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NR 35
TC 1
Z9 1
U1 1
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0882-0538
EI 1744-5205
J9 SEMIN OPHTHALMOL
JI Semin. Ophthalmol.
PD FEB 17
PY 2021
VL 36
IS 1-2
BP 9
EP 13
DI 10.1080/08820538.2021.1883679
EA FEB 2021
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RH9VX
UT WOS:000618284200001
PM 33587673
DA 2022-11-30
ER

PT J
AU Gao, C
   Cao, X
   Huang, LL
   Bao, YQ
   Li, T
   Di, Y
   Wu, LC
   Song, Y
AF Gao, Chuang
   Cao, Xin
   Huang, Lili
   Bao, Yueqi
   Li, Tao
   Di, Yue
   Wu, Liucheng
   Song, Yu
TI Pirfenidone Alleviates Choroidal Neovascular Fibrosis through
   TGF-beta/Smad Signaling Pathway
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
AB Background. Transforming growth factor-beta (TGF-beta) plays a major role in CNV. However, the mechanism is unclear. This study investigates the effect of Pirfenidone (PFD) on TGF-beta/Smad signaling pathway on the development of choroidal neovascular fibrosis in choroidal neovascularization (CNV) mouse model. C57BL/6J male mice (aged from 6 to 8 weeks) received intravitreal injections of phosphate-buffered saline (PBS)/PFD solution on 14 days after laser injury. Mice were anesthetized by intraperitoneal injection of 4% pentobarbital (0.05 mg/g body weight). Optical Coherence Tomography (OCT), Fundus Fluorescein angiography (FFA), and hematoxylin-eosin (HE) were used to assess CNV formation. The fibrosis area was monitored by staining the collagen type I (Col-I). Western blotting was used to analyze the expression of TGF-beta 2, Smad 2/3, phosphorylated Smad 2/3 (p-Smad 2/3), and alpha-smooth muscle actin (alpha-SMA). Terminal deoxynucleotidy1 transferase dUTP nick-end labelling (TUNEL) assay was performed on cryosections of mouse eyes to detect apoptosis. Our data showed PFD inhibited areas of fibrosis during day 21 to day 28. We also found that the levels of TGF-beta 2 protein expressions increasingly reached the peak till the 3rd week during the CNV development. The protein levels of Smad 2/3, p-Smad 2/3, and alpha-SMA also increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-beta inhibitor PFD. The results of this study suggest that TGF-beta 2 represents a target to prevent or treat choroidal neovascular fibrosis, and PFD may provide an alternative to traditional methods for Wet Age-related macular degeneration (wAMD) treatment.
C1 [Gao, Chuang; Cao, Xin; Huang, Lili; Li, Tao; Di, Yue; Song, Yu] Nantong Univ, Affiliated Hosp 2, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
   [Gao, Chuang] Nantong Univ, Tongzhou Peoples Hosp, Dept Ophthalmol, Nantong 226300, Jiangsu, Peoples R China.
   [Bao, Yueqi] Wuxi Childrens Hosp, Dept Ophthalmol, Wuxi 214002, Jiangsu, Peoples R China.
   [Wu, Liucheng] Nantong Univ, Lab Anim Ctr, Nantong 226001, Jiangsu, Peoples R China.
C3 Nantong University; Nantong University; Nantong University
RP Song, Y (通讯作者)，Nantong Univ, Affiliated Hosp 2, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
EM 17160257@stmail.ntu.edu.cn; caoxin512@163.com; lily03128@163.com;
   ophthal_byq@163.com; 894624986@qq.com; 997580179@qq.com;
   hnwulc@ntu.edu.cn; songyueye@ntu.edu.cn
OI Bao, Yueqi/0000-0002-6589-3845; Wu, Liucheng/0000-0002-8053-1340
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NR 31
TC 1
Z9 1
U1 4
U2 7
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD FEB 10
PY 2021
VL 2021
AR 8846708
DI 10.1155/2021/8846708
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QM5US
UT WOS:000621844800002
PM 33628482
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Walek, E
   Przeidziecka-Dolyk, J
   Helemejko, I
   Misiuk-Hojlo, M
AF Walek, Ewa
   Przeidziecka-Dolyk, Joanna
   Helemejko, Iwona
   Misiuk-Hojlo, Marta
TI Efficacy of postoperative management with 5-fluorouracil injections
   after XEN Gel Stent implantation
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Glaucoma; XEN; 5-Fluorouracil; Minimally invasive glaucoma surgery;
   Stent
ID REVISION; SURGERY
AB Purpose To evaluate the efficacy of postoperative management with 5-fluorouracil injections after XEN Gel Stent implantation. Methods Prospective real-world evidence study included 39 eyes (of 36 patients) with primary open-angle glaucoma without previous glaucoma surgery and with uncontrolled intraocular pressure (IOP), glaucoma progression, or intolerance to IOP-lowering therapy. Patients underwent mitomycin C-augmented XEN implantation either as a stand-alone procedure or combined with cataract extraction. 5-Fluorouracil subconjunctival injections were a first-choice therapy for bleb failure and were administered according to predetermined criteria (analogous to pro re nata regimen in age-related macular degeneration treatment). Primary outcome was unqualified success, defined as postoperative IOP < 18 mmHg and > 20% reduction from medicated baseline without any antiglaucoma medications and no detected glaucoma progression. Results At median follow-up of 8 months (range 3-24 months), IOP decreased from a medicated baseline value of 23 mmHg (95% CI 21-24 mmHg) to 13 mmHg (95% CI 12-15 mmHg) and number of medications decreased from 3 (95% CI 2-3) to 0 (p < 0.0001 for both). Median number of 5-fluorouracil injections per eye was 3 (95% CI 2-3), and median time to first injection was 0.5 months (95% CI 0.25-3 months) after surgery. Thirteen eyes (33.3%) underwent >= 1 needling, and surgical revision was performed in three cases (7.7%). The primary outcome measure, which allows performing additional procedures, was achieved in 27 eyes (69%). Conclusions 5-Fluorouracil subconjunctival injections are safe and effective in postoperative management of bleb failure after XEN implantation and represent a viable alternative to other methods.
C1 [Walek, Ewa; Przeidziecka-Dolyk, Joanna; Helemejko, Iwona; Misiuk-Hojlo, Marta] Wroclaw Med Univ, Dept Ophthalmol, Borowska 213, Wroclaw, Poland.
   [Przeidziecka-Dolyk, Joanna] Wroclaw Univ Sci & Technol, Fac Fundamental Problems Technol, Dept Opt & Photon, Wroclaw, Poland.
C3 Wroclaw Medical University; Wroclaw University of Science & Technology
RP Walek, E (通讯作者)，Wroclaw Med Univ, Dept Ophthalmol, Borowska 213, Wroclaw, Poland.
EM ewka.walek@gmail.com
RI Przeździecka-Dołyk, Joanna Wiktoria/ABG-8843-2021
OI Przeździecka-Dołyk, Joanna Wiktoria/0000-0002-1099-4876; Walek,
   Ewa/0000-0002-9103-2141; Misiuk - Hojlo, Marta/0000-0002-4020-3203
FU Wroclaw Medical University Grant for Young Researchers
   [STM.C240.17.037]; Allergan plc. (Irvine, CA) [PG-2018-10478]
FX The study was performed with financial support of Wroclaw Medical
   University Grant for Young Researchers (No: STM.C240.17.037). Editorial
   support was funded by Allergan plc. (Irvine, CA)-publication Grant No:
   PG-2018-10478. The authors maintained complete control over the content
   of the paper. No payment was received for authorship of the document.
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NR 21
TC 7
Z9 7
U1 0
U2 1
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 JAN
PY 2020
VL 40
IS 1
BP 235
EP 246
DI 10.1007/s10792-019-01168-8
EA OCT 2019
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KO8TH
UT WOS:000488918000001
PM 31578662
OA hybrid
DA 2022-11-30
ER

PT J
AU Choi, AJ
   Nivison-Smith, L
   Phu, J
   Zangerl, B
   Khuu, SK
   Jones, BW
   Pfeiffer, RL
   Marc, RE
   Kalloniatis, M
AF Choi, AgnesY J.
   Nivison-Smith, Lisa
   Phu, Jack
   Zangerl, Barbara
   Khuu, Sieu K.
   Jones, Bryan W.
   Pfeiffer, Rebecca L.
   Marc, Robert E.
   Kalloniatis, Michael
TI Contrast sensitivity isocontours of the central visual field
SO SCIENTIFIC REPORTS
LA English
DT Article
ID STANDARD AUTOMATED PERIMETRY; PATTERN-RECOGNITION ANALYSIS; AMINO-ACID
   SIGNATURES; MACULAR DEGENERATION; FLICKER PERIMETRY; SPATIAL SUMMATION;
   FULL-THRESHOLD; GLAUCOMA; STIMULI; MATRIX
AB Standard automated perimetry (SAP), the most common form of perimetry used in clinical practice, is associated with high test variability, impacting clinical decision making and efficiency. Contrast sensitivity isocontours (CSIs) may reduce test variability in SAP by identifying regions of the visual field with statistically similar patterns of change that can be analysed collectively and allow a point (disease)-to-CSI (normal) comparison in disease assessment as opposed to a point (disease)-to-point (normal) comparison. CSIs in the central visual field however have limited applicability as they have only been described using visual field test patterns with low, 6 degrees spatial sampling. In this study, CSIs were determined within the central 20 degrees visual field using the 10-2 test grid paradigm of the Humphrey Field Analyzer which has a high 2 degrees sampling frequency. The number of CSIs detected in the central 20 degrees visual field was greater than previously reported with low spatial sampling and stimulus size dependent: 6 CSIs for GI, 4 CSIs for GII and GIII, and 3 CSIs for GIV and GV. CSI number and distribution were preserved with age. Use of CSIs to assess visual function in age-related macular degeneration (AMD) found CSI guided analysis detected a significantly greater deviation in sensitivity of AMD eyes from normal compared to a standard clinical pointwise comparison (-1.40 +/- 0.15 dB vs -0.96 +/- 0.15 dB; p < 0.05). This work suggests detection of CSIs within the central 20 degrees is dependent on sampling strategy and stimulus size and normative distribution limits of CSIs can indicate significant functional deficits in diseases affecting the central visual field such as AMD.
C1 [Choi, AgnesY J.; Nivison-Smith, Lisa; Phu, Jack; Zangerl, Barbara; Kalloniatis, Michael] Univ New South Wales, Ctr Eye Hlth, Kensington, NSW, Australia.
   [Choi, AgnesY J.; Nivison-Smith, Lisa; Phu, Jack; Zangerl, Barbara; Khuu, Sieu K.; Kalloniatis, Michael] Univ New South Wales, Sch Optometry & Vis Sci, Kensington, NSW, Australia.
   [Jones, Bryan W.; Pfeiffer, Rebecca L.; Marc, Robert E.] Univ Utah, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT USA.
C3 University of New South Wales Sydney; University of New South Wales
   Sydney; Utah System of Higher Education; University of Utah
RP Kalloniatis, M (通讯作者)，Univ New South Wales, Ctr Eye Hlth, Kensington, NSW, Australia.; Kalloniatis, M (通讯作者)，Univ New South Wales, Sch Optometry & Vis Sci, Kensington, NSW, Australia.
EM m.kalloniatis@unsw.edu.au
RI Choi, Agnes Yiu Jeung/AAZ-3484-2020; Phu, Jack/AAO-6855-2020
OI Nivison-Smith, Lisa/0000-0001-6677-1949; Phu, Jack/0000-0002-9933-6780;
   Khuu, Sieu/0000-0003-1850-0225; Kalloniatis, Michael/0000-0002-5264-4639
FU University of New South Wales; National Health and Medical Research
   Council (NHMRC) [1033224]; National Institutes of Health [EY015128,
   EY02576, EY014800]; Research to Prevent Blindness; Vision Core; NATIONAL
   EYE INSTITUTE [R01EY002576, R01EY015128, P30EY014800, T32EY024234,
   R01EY028927] Funding Source: NIH RePORTER
FX The authors would like to thank Dr Bang Bui and Cornelia Zangerl for
   technical assistance. This work was supported, in part, by grants and
   awards from the University of New South Wales (Research Training Program
   PhD Scholarship), the National Health and Medical Research Council
   (NHMRC; #1033224), National Institutes of Health (EY015128, EY02576,
   EY014800); Vision Core; and an unrestricted grant from Research to
   Prevent Blindness to the Moran Eye Center. The Centre for Eye Health is
   an initiative between UNSW Australia and Guide Dogs NSW/ACT. Guide Dogs
   NSW/ACT is also a partner on the NHMRC grant and provides a
   supplementary PhD scholarship for AC and support for LN-S and BZ.
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NR 53
TC 6
Z9 6
U1 0
U2 2
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 AUG 12
PY 2019
VL 9
AR 11603
DI 10.1038/s41598-019-48026-2
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IP9QH
UT WOS:000480384500019
PM 31406197
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Migacz, JV
   Gorczynska, I
   Azimipour, M
   Jonnal, R
   Zawadzki, RJ
   Werner, JS
AF Migacz, Justin, V
   Gorczynska, Iwona
   Azimipour, Mehdi
   Jonnal, Ravi
   Zawadzki, Robert J.
   Werner, John S.
TI Megahertz-rate optical coherence tomography angiography improves the
   contrast of the choriocapillaris and choroid in human retinal imaging
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID BLOOD-FLOW; AMPLITUDE-DECORRELATION; MACULAR DEGENERATION; OCT
   ANGIOGRAPHY; VARIANCE; VELOCITY; IMAGES; SPEED
AB Angiographic imaging of the human eye with optical coherence tomography (OCT) is becoming an increasingly important tool in the scientific investigation and clinical management of several blinding diseases, including age-related macular degeneration and diabetic retinopathy. We have observed that OCT angiography (OCTA) of the human choriocapillaris and choroid with a 1.64 MHz A-scan rate swept-source laser yields higher contrast images as compared to a slower rate system operating at 100 kHz. This result is unexpected because signal sensitivity is reduced when acquisition rates are increased, and the incident illumination power is kept constant. The contrast of angiography images generated by acquiring multiple sequential frames and calculating the variation caused by blood flow, however, appears to be improved significantly when lower-contrast images are taken more rapidly. To demonstrate that the acquisition rate plays a role in the quality improvement, we have imaged five healthy subjects with a narrow field of view (1.2 mm) OCTA imaging system using two separate swept-source lasers of different A-line rates and compared the results quantitatively using the radially-averaged power spectrum. The average improvement in the contrast is 23.0% (+/-7.6%). Although the underlying cause of this enhancement is not explicitly determined here, we speculate that the higher-speed system suppresses the noise contribution from eye motion in subjects and operates with an inter-scan time that better discriminates the flow velocities present in the choroid and choriocapillaris. Our result informs OCT system developers on the merits of ultrahigh-speed acquisition in functional imaging applications. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Migacz, Justin, V; Gorczynska, Iwona; Azimipour, Mehdi; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Vison Sci & Adv Retinal Imaging Lab, Sacramento, CA 95817 USA.
   [Gorczynska, Iwona] Nicolaus Copernicus Univ Torun, Fac Phvs Astron & Informat, Inst Phys, Grudziadzka 5, PL-87100 Torun, Poland.
C3 University of California System; University of California Davis;
   Nicolaus Copernicus University
RP Migacz, JV (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Vis Sci, Vison Sci & Adv Retinal Imaging Lab, Sacramento, CA 95817 USA.
EM jvmigacz@ucdavis.edu
RI Gorczynska, Iwona M./P-9367-2015; Zawadzki, Robert J./S-3236-2019
OI Gorczynska, Iwona M./0000-0002-6120-8791; Zawadzki, Robert
   J./0000-0002-9574-156X
FU National Eye Institute (NEI) [R01 EY024239, P30 EY012576, T32 EY15387];
   NATIONAL EYE INSTITUTE [T32EY015387] Funding Source: NIH RePORTER
FX National Eye Institute (NEI) (R01 EY024239, P30 EY012576, T32 EY15387).
CR American National Standards Institute, 2014, AM NAT STAND SAF US
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NR 41
TC 30
Z9 31
U1 0
U2 6
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 JAN 1
PY 2019
VL 10
IS 1
BP 50
EP 65
DI 10.1364/BOE.10.000050
PG 16
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 HF3ZQ
UT WOS:000454173400004
PM 30775082
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Vu, KT
   Hulleman, JD
AF Vu, Khiem T.
   Hulleman, John D.
TI An inducible form of Nrf2 confers enhanced protection against acute
   oxidative stresses in RPE cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID MANGANESE SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION; RETINAL
   ABNORMALITIES; ANTIOXIDANT RESPONSE; LIPID-PEROXIDATION; POOLED
   FINDINGS; RISK-FACTORS; ASSOCIATION; DYSFUNCTION; MECHANISMS
AB Increasing evidence suggests that overt oxidative stress within the retina plays an important role in the progression of age-related retinal decline, and in particular, in the disease age-related macular degeneration (AMD). Nuclear factor erythroid 2-like 2 (Nrf2) is a master transcription factor that upregulates numerous of antioxidant/detoxification genes. Nrf2(-/-) mice develop progressive retinal degeneration that includes the formation of drusen-like deposits, lipofuscin, and sub-retinal pigment epithelium (RPE) deposition of inflammatory proteins. Furthermore, strategies that promote Nrf2 activation have shown promise for the treatment of cone/rod dystrophies and other forms of retinal degeneration. Herein we explored whether utilizing a small molecule-inducible version of Nrf2 confers additional protection against oxidative stresses when compared to a constitutively expressed version of Nrf2. Stable populations of human ARPE-19 cells were generated that express either constitutive FLAG-tagged (FT) Nrf2 (FT cNrf2) or doxycycline (dox)-inducible FT Nrf2 (FT iNrf2) at low levels (similar to 4.5 fold vs. endogenous). Expression of either FT cNRF2 or FT iNrf2 upregulated canonical antioxidant genes (e.g., NQO1, GCLC). Both FT cNrf2 and FT iNrf2 ARPE-19 cells were protected from cigarette smoke extract-induced nitric oxide generation to similar extents. However, only FT iNrf2 cells demonstrated enhanced resistance to doxorubicin and cumene hydroperoxide-mediated increases in mitochondrial superoxide and lipid peroxidation, respectively, and did so in a dox-dependent manner. These results suggest that therapeutic approaches which conditionally control Nrf2 activity may provide additional protection against acute oxidative stresses when compared to constitutively expressed Nrf2 strategies. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Vu, Khiem T.; Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
   [Hulleman, John D.] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical
   Center Dallas; University of Texas System; University of Texas
   Southwestern Medical Center Dallas
RP Hulleman, JD (通讯作者)，Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM John.Hulleman@UTSouthwestern.edu
RI Hulleman, John D./AAV-8242-2020
OI Hulleman, John/0000-0001-8149-656X
FU Roger and Dorothy Hirl Research Fund; Karl Kirchgessner Foundation;
   National Eye Institute Visual Science Core Grant [EY020799]; Research to
   Prevent Blindness (RPB); RPB; NATIONAL EYE INSTITUTE [P30EY020799]
   Funding Source: NIH RePORTER
FX This work was funded in part by an endowment from the Roger and Dorothy
   Hirl Research Fund (JDH), a vision research grant from the Karl
   Kirchgessner Foundation (JDH), a National Eye Institute Visual Science
   Core Grant (EY020799), an unrestricted grant from Research to Prevent
   Blindness (RPB), a Career Development Award from RPB (JDH), and a
   Medical Student Research Fellowship from RPB (KTV).
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NR 47
TC 18
Z9 18
U1 0
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 NOV
PY 2017
VL 164
BP 31
EP 36
DI 10.1016/j.exer.2017.08.001
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FJ9XJ
UT WOS:000413134500004
PM 28782506
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bose, K
   Lakshminarasimhan, H
   Sundar, K
   Kathiresan, T
AF Bose, Karthikeyan
   Lakshminarasimhan, Harini
   Sundar, Krishnan
   Kathiresan, Thandavarayan
TI Cytotoxic effect of ZnS nanoparticles on primary mouse retinal pigment
   epithelial cells
SO ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
LA English
DT Article
DE Akt kinase; cytotoxicity; mouse retinal pigment epithelial cells;
   reactive oxygen species; ZnS-NPs
ID YTTRIUM-OXIDE NANOPARTICLES; OPTICAL-PROPERTIES; ZINC; COPPER;
   ACTIVATION; APOPTOSIS; KINASE; PROLIFERATION; DEFICIENCY; POLARITY
AB The multiple properties of zinc sulphide nanoparticles (ZnS-NPs) are attracting great attention in the field of chemical and biological research. ZnS-NPs also find their application in biosensor and photocatalysis. Zinc is an important metal ion in retina and its deficiency leads to age-related macular degeneration. As of now, not much research is available on bio-interaction of ZnS as nanoform with retinal pigment epithelial (RPE) cells. RPE cells in the retina help in maintaining normal photoreceptor function and vision. To begin with, ZnS-NPs were synthesized and characterized using UV-visible spectra, X-ray diffraction, Fourier transform infrared spectrum, transmission electron microscopy and dynamic light scattering. Followed by the confirmation of nanoparticles, our study extended to investigate the impact of ZnS-NPs in primary mouse RPE (MRPE) cells at different concentrations. ZnS-NPs showed dose-dependent cytotoxicity in MRPE cells and no changes were observed in cells' tight intactness at minimal concentration. In addition, exposure to ZnS-NPs increased cellular permeability in dose- and time-dependent manner in MRPE cells. The findings from DCFH-DA analysis revealed that ZnS-NPs-treated cells had elevated level of reactive oxygen species and partial activation of cell apoptosis was identified after exposure to ZnS-NPs at higher concentration. Furthermore, pre-treatment of the primary MRPE cells with ZnS-NPs led to phosphorylation of Akt (Ser 473), which indicates the crucial role of ZnS-NPs in regulating cell survival at minimal concentration. Altogether, this study enumerates requisite dose of using ZnS-NPs to maintain healthy RPE cells and contributes to future studies in development of therapeutic drug and drug carrier for ocular-related disorders.
C1 [Bose, Karthikeyan; Lakshminarasimhan, Harini; Sundar, Krishnan; Kathiresan, Thandavarayan] Kalasalingam Univ, Dept Biotechnol, Krishnankoil 626126, Tamil Nadu, India.
   [Sundar, Krishnan; Kathiresan, Thandavarayan] Kalasalingam Univ, Int Res Ctr, Krishnankoil, 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.
EM t.kathiresan@klu.ac.in
RI Sundar, Krishnan/E-2748-2015; Bose, Karthikeyan/GRN-8684-2022
OI Sundar, Krishnan/0000-0001-7156-1057
FU Department of Science and Technology (SERB) of India
   [SB/FT/LS-204/2012]; Kalasalingam academy of research and education
   (KARE); Council of Scientific and Industrial Research (CSIR), India
   [09/1012 (0005) 2K11 - 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) and
   Kalasalingam academy of research and education (KARE) to T.K. B.K. is
   the recipient of senior research fellowship (09/1012 (0005) 2K11 - EMR -
   I) from the Council of Scientific and Industrial Research (CSIR), India.
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NR 55
TC 8
Z9 9
U1 1
U2 18
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 2169-1401
EI 2169-141X
J9 ARTIF CELL NANOMED B
JI Artif. Cell. Nanomed. Biotechnol.
PD NOV
PY 2016
VL 44
IS 7
BP 1764
EP 1773
DI 10.3109/21691401.2015.1102739
PG 10
WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials
   Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Engineering; Materials Science
GA DV5GT
UT WOS:000382955900022
PM 26523428
DA 2022-11-30
ER

PT J
AU Sturrock, BA
   Xie, J
   Holloway, EE
   Hegel, M
   Casten, R
   Mellor, D
   Fenwick, E
   Rees, G
AF Sturrock, Bonnie A.
   Xie, Jing
   Holloway, Edith E.
   Hegel, Mark
   Casten, Robin
   Mellor, David
   Fenwick, Eva
   Rees, Gwyneth
TI Illness Cognitions and Coping Self-Efficacy in Depression Among Persons
   With Low Vision
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE illness cognitions; coping self-efficacy; low vision; depression;
   acceptance
ID IMPAIRED OLDER-ADULTS; PRIMARY-CARE; LATER LIFE; VISUAL IMPAIRMENT;
   VALIDATION; VALIDITY; PHQ-9; REHABILITATION; PARTICIPATION; PREVALENCE
AB PURPOSE: To investigate the mediating role of coping self-efficacy (CSE) between two types of illness cognitions (i.e., acceptance and helplessness) and depressive symptoms in persons with low vision.
   METHODS: This was a single-group, cross-sectional study. Patients with visual acuity < 6/12 in the better eye and at least minimal depressive symptoms (>= 5 on the Patient Health Questionnaire-9 [PHQ-9]) were recruited from vision rehabilitation services and participated in telephone-administered structured interviews at one time point. Measures were the PHQ-9, CSE Scale, and Illness Cognition Questionnaire. Structural equation modeling (SEM) devised the causal flow of illness cognitions and their observed indirect effects on depressive symptoms via the CSE mediators: problem focused, emotion focused, and social support.
   RESULTS: The study comprised 163 patients (mean age 62 years; 61% female), most with age-related macular degeneration (26%) and moderate vision impairment (44%, <6/18-6/60). Structural equation modeling indices indicated a perfect fit (chi(2) < 0.001, P = 1.00), accounting for 55% of the variance in depressive symptoms. Lower levels of acceptance and higher levels of helplessness illness cognitions were associated with lower self-efficacy in problem-focused coping (beta = 0.38, P < 0.001, beta = -0.28, P < 0.01, respectively), which in turn was associated with greater depressive symptom severity (beta = -0.54, P < 0.001).
   CONCLUSIONS: Lack of acceptance and greater helplessness relating to low vision led to a lack of perceived capability to engage in problem-focused coping, which in turn promoted depressive symptoms. Third-wave cognitive-behavioral treatments that focus on acceptance may be efficacious in this population.
C1 [Sturrock, Bonnie A.; Xie, Jing; Holloway, Edith E.; Fenwick, Eva; Rees, Gwyneth] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Hegel, Mark] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA.
   [Casten, Robin] Thomas Jefferson Univ, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA.
   [Mellor, David] Deakin Univ, Sch Psychol, Bundoora, Vic, Australia.
   [Fenwick, Eva] Singapore Eye Res Inst, Singapore, Singapore.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Dartmouth College; Jefferson University; Deakin
   University; National University of Singapore; Singapore National Eye
   Center
RP Rees, G (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Behav Res Ophthalmol, Locked Bag 8, East Melbourne, Vic 8002, Australia.
EM grees@unimelb.edu.au
RI xie, jing/GRY-1689-2022
OI /0000-0001-6694-3587
FU Australian Research Council's Linkage Projects scheme [LP110200035];
   NHMRC Postgraduate Scholarship; Australian Rotary Health Ian Scott
   Mental Health Scholarship top-up; Vision Australia; beyondblue: The
   national depression and anxiety initiatives
FX Supported under the Australian Research Council's Linkage Projects
   scheme (LP110200035). Vision Australia and beyondblue: The national
   depression and anxiety initiatives are partner organizations that
   contributed to funding. GR was a National Health and Medical Research
   Council (NHMRC) Translating Research Into Practice Fellow for 2012-2014.
   EH was a recipient of the NHMRC Postgraduate Scholarship (2013-2015) and
   the Australian Rotary Health Ian Scott Mental Health Scholarship top-up
   (2013-2015). CERA receives Operational Infrastructure Support from the
   Victorian Government.
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NR 41
TC 10
Z9 10
U1 3
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 JUN
PY 2016
VL 57
IS 7
BP 3032
EP 3038
DI 10.1167/iovs.16-19110
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA DT8GA
UT WOS:000381726600016
PM 27281268
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Jin, HL
   Jeong, KW
AF Jin, Hong Lan
   Jeong, Kwang Won
TI Regulation of aryl hydrocarbon receptor-mediated transcription in human
   retinal pigmented epithelial cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Aryl hydrocarbon receptor; ARPE-19; BRG1; AMD
ID AH RECEPTOR; ACTIVATION; COACTIVATORS; INVOLVEMENT; INDUCTION; PROTEIN
AB The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with pleiotropic effects in normal physiology or vascular development, xenobiotic metabolism, and cancer. A previous study has reported that BRG1, a component of the SWI/SNF complex, is a coactivator for AHR and is recruited to the promoter region of the CYP1A1 gene in mouse hepatocytes. Recent data suggest that AHR is also expressed in human retinal pigment epithelial cells (ARPE-19), which play a crucial role in retinal physiology and the visual cycle. Multiple studies have shown that the AHR plays an important role in the pathogenesis of retinal diseases including age-related macular degeneration. However, the mechanism of AHR transcriptional activation in retinal pigment cells has not been reported. Here, we demonstrate that the AHR signaling pathway is active in ARPE-19 cells, as in hepatocytes, but with different target gene specificity. We also found that chromatin remodeling by the BRG1-containing SWI/SNF complex is required for the AHR-mediated expression of target genes in ARPE-19 cells. We identified a novel enhancer region (-12 kb) of the CYP1A1 gene in ARPE-19 cells, to which both AHR and BRG1 are recruited in a ligand-dependent manner. BRG1 is associated with the AHR in ARPE-19 cells, and the C-terminal activation domain of the AHR directly interacts with BRG1. Furthermore, depletion of BRG1 caused a reduction in chromatin accessibility at the CYP1A1 enhancer. These results suggest that ARPE-19 cells possess an AHR-mediated transcription pathway with different target gene specificity, and that BRG1 is required for AHR-mediated transcription in ARPE-19 cells. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Jin, Hong Lan; Jeong, Kwang Won] Gachon Univ, Coll Pharm, Gachon Inst Pharmaceut Sci, 191 Hambakmoero, Inchon 406799, South Korea.
C3 Gachon University
RP Jeong, KW (通讯作者)，Gachon Univ, Coll Pharm, Gachon Inst Pharmaceut Sci, 191 Hambakmoero, Inchon 406799, South Korea.
EM kwjeong@gachon.ac.kr
FU Basic Science Research Program through the National Research Foundation
   of Korea - Ministry of Education [2014R1A1A2056066]
FX This research was supported by Basic Science Research Program through
   the National Research Foundation of Korea funded by the Ministry of
   Education (2014R1A1A2056066).
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NR 24
TC 10
Z9 10
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD APR 1
PY 2016
VL 472
IS 2
BP 366
EP 372
DI 10.1016/j.bbrc.2016.03.006
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA DI1JB
UT WOS:000373251300012
PM 26966070
DA 2022-11-30
ER

PT J
AU Chen, WS
   Cao, ZY
   Krishnan, C
   Panjwani, N
AF Chen, Wei-Sheng
   Cao, Zhiyi
   Krishnan, Chandrasekharan
   Panjwani, Noorjahan
TI Verteporfin without light stimulation inhibits YAP activation in
   trabecular meshwork cells: Implications for glaucoma treatment
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Verteporfin; YAP; Glaucoma; Trabecular meshwork
ID PROTEIN-KINASE INHIBITOR; AQUEOUS-HUMOR OUTFLOW; MECHANOTRANSDUCERS YAP;
   SUBSTRATUM STIFFNESS; PHOTODYNAMIC THERAPY; RHO-KINASE; CANCER; Y-27632;
   TAZ; EXPRESSION
AB Verteporfin, a photosensitizer, is used in photodynamic therapy to treat age-related macular degeneration. In a glaucoma mouse model, Verteporfin without light stimulation has been shown to reduce intraocular pressure (IOP) but the mechanism is unknown. Recent studies have shown that Verteporfin inhibits YAP without light stimulation in cancer cells. Additionally, YAP has emerged as an important molecule in the pathogenesis of glaucoma. We hypothesize that YAP inactivation by Verteporfin in trabecular meshwork (TM) may be related to the reduced MP observed in vivo. As contractility of TM tissues is associated with IOP, collagen gel contraction assay was used to assess the effect of Verteporfin on contractility of TM cells. Human TM cells were embedded in collagen gel and treated with Verteporfin for 48 h. Areas of collagen gel sizes were quantified by ImageJ. To assess the effect of Verteporfin on the expression of YAP, human TM cells were treated with Verteporfin for 24 h and the expression of YAP was determined by Western blotting. To determine the cytotoxic effect of Verteporfin, human TM cells were treated with Verteporfin for 24 h, and then the cell viability was assessed by WST-1. We demonstrated here that Verteporfin (i) abolishes TM cell-mediated collagen gel contraction in a dose-dependent manner, (ii) attenuates expression of YAP and CTGE (connective tissue growth factor, a direct YAP target gene) in a dose-dependent manner, and (iii) has no significant cytotoxicity below 2 mu M. Taken together, Verteporfin may facilitate aqueous humor outflow through the conventional outflow system and reduce IOP by inactivating YAP. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Chen, Wei-Sheng; Panjwani, Noorjahan] Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA.
   [Chen, Wei-Sheng; Cao, Zhiyi; Krishnan, Chandrasekharan; Panjwani, Noorjahan] Tufts Univ, New England Eye Ctr, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts University; Tufts University
RP Panjwani, N (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, 136 Harrison Ave, Boston, MA 02111 USA.
EM Noorjahan.Panjwani@tufts.edu
FU Mass Lions Eye Research fund; Research to Prevent Blindness; Glenn/AFAR
   Scholarship for Research In the Biology of Aging
FX This work was supported by Mass Lions Eye Research fund, and an
   unrestricted award from Research to Prevent Blindness to the Department
   of Ophthalmology, Tufts University; and Glenn/AFAR Scholarship for
   Research In the Biology of Aging to WSC.
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NR 33
TC 25
Z9 26
U1 0
U2 18
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 OCT 16
PY 2015
VL 466
IS 2
BP 221
EP 225
DI 10.1016/j.bbrc.2015.09.012
PG 5
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA CT2CY
UT WOS:000362610800013
PM 26361148
DA 2022-11-30
ER

PT J
AU Zehetner, C
   Bechrakis, NE
   Stattin, M
   Kirchmair, R
   Ulmer, H
   Kralinger, MT
   Kieselbach, GF
AF Zehetner, Claus
   Bechrakis, Nikolaos E.
   Stattin, Martin
   Kirchmair, Rudolf
   Ulmer, Hanno
   Kralinger, Martina T.
   Kieselbach, Gerhard F.
TI Systemic Counterregulatory Response of Placental Growth Factor Levels to
   Intravitreal Aflibercept Therapy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aflibercept; ranibizumab; bevacizumab; age-related macular degeneration
   (AMD); VEGF-A; VEGF-B; placental growth factor (PlGF)
ID NEONATAL FC-RECEPTOR; VEGF-TRAP; ANTIANGIOGENIC THERAPY; MACULAR
   DEGENERATION; PLASMA-LEVELS; FACTOR-B; BEVACIZUMAB; RANIBIZUMAB;
   EXPRESSION; ANGIOGENESIS
AB PURPOSE. Placental growth factor (PlGF) has been implicated as a contributor to resistance against anti-VEGF therapy. The purpose of the present study was to analyze the systemic levels of PlGF, VEGF-A, and VEGF-B in patients with neovascular age-related macular degeneration (AMD) after treatment with aflibercept, ranibizumab, or bevacizumab.
   METHODS. Totals of 19 patients were treated with intravitreal aflibercept, 19 with ranibizumab, and 18 with bevacizumab. The cytokine levels were measured by ELISA just before the injection, and 7 days and 1 month thereafter. Age-and sex-matched participants (n = 22) served as controls.
   RESULTS. The median PlGF plasma concentration at baseline was < 12.0 pg/mL in the control group as well as in all three anti-VEGF treatment cohorts. After intravitreal aflibercept injection, a significant upregulation of systemic PlGF could be observed in all treated patients (38.0 [31.0-44.0] pg/mL after 1 week [P < 0.001] and 16.0 [0.0-19.0] pg/mL [P = 0.005] after 4 weeks). No significant effects on plasma PlGF concentrations could be detected in those treated with ranibizumab and bevacizumab. The systemic VEGF-A levels were significantly reduced 1 and 4 weeks after intravitreal aflibercept (P < 0.001, P < 0.001) and bevacizumab (P < 0.001, P < 0.01) injections. No significant effects on plasma cytokine concentrations could be observed in the ranibizumab cohort. No significant effects on systemic VEGF-B could be observed in any of the treatment groups.
   CONCLUSIONS. In this study, we report a significant systemic upregulation of the proangiogenic cytokine PlGF after intravitreal administration of aflibercept. This might represent a counter-regulatory response to antiangiogenic therapy.
C1 [Zehetner, Claus; Bechrakis, Nikolaos E.; Stattin, Martin; Kralinger, Martina T.; Kieselbach, Gerhard F.] Med Univ Innsbruck, Dept Ophthalmol, A-6020 Innsbruck, Austria.
   [Kirchmair, Rudolf] Med Univ Innsbruck, Dept Internal Med, A-6020 Innsbruck, Austria.
   [Ulmer, Hanno] Med Univ Innsbruck, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
C3 Medical University of Innsbruck; Medical University of Innsbruck;
   Medical University of Innsbruck
RP Zehetner, C (通讯作者)，Med Univ Innsbruck, Dept Ophthalmol, Anichstr 35, A-6020 Innsbruck, Austria.
EM claus.zehetner@i-med.ac.at
RI Ulmer, Hanno/S-6615-2019
OI Ulmer, Hanno/0000-0001-5911-1002; Zehetner, Claus/0000-0003-1405-7457
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NR 34
TC 13
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 MAY
PY 2015
VL 56
IS 5
BP 3279
EP 3286
DI 10.1167/iovs.15-16686
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CK7UJ
UT WOS:000356439200062
PM 26024110
DA 2022-11-30
ER

PT J
AU Vessey, KA
   Greferath, U
   Jobling, AI
   Phipps, JA
   Ho, T
   Waugh, M
   Fletcher, EL
AF Vessey, Kirstan A.
   Greferath, Ursula
   Jobling, Andrew I.
   Phipps, Joanna A.
   Ho, Tracy
   Waugh, Michelle
   Fletcher, Erica L.
TI Ccl2/Cx3cr1 Knockout Mice Have Inner Retinal Dysfunction but Are Not an
   Accelerated Model of AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; MICROGLIAL CELLS; RAT RETINA;
   ACTIVATED MICROGLIA; ANIMAL-MODEL; RETINOPATHY; MOUSE; ROD; ACCUMULATION
AB PURPOSE. The chemokine, Ccl2, and the fractalkine receptor, Cx3cr1, have both been implicated in the pathogenesis of age related macular degeneration (AMD), with mice lacking both genes exhibiting features of AMD by 3 months of age. However, recent reports indicate that this ascribed phenotype is due to the presence of a retinal degeneration mutation (crb1(rd8/rd8), rd8) on the background strain. Our aim was to characterize the retinal effects of lack of Ccl2 and Cx3cr1 (Ccl2(-/-)/Cx3cr1(EGFP/EGFP), CDKO-mice), in mice without the rd8 mutation.
   METHODS. Nine-month-old, CDKO and wildtype C57blk6J mice were investigated for retinal fundus appearance and histology. The function of the rod and cone pathways was assessed using the ERG.
   RESULTS. The CDKO mice did not develop lesions in the retinal fundus, and the ultrastructure of Bruch's membrane and the RPE were similar to that of C57blk6J mice. From the ERG, there was no change in the amplitude of the rod photoreceptor response, or in the rod or cone post-photoreceptor b-wave. However, the rod and cone ERG oscillatory potentials were significantly reduced in the CDKO animals, a phenotype apparent in Cx3cr1(EGFP/EGFP)- but not Ccl2(-/-)-founder lines. This correlated with aberrant amacrine cell morphology in the CDKO mice. In addition, Muller cells were gliotic and microglial morphology subtly altered, indicative of retinal stress.
   CONCLUSIONS. These results suggest that in the absence of the rd8 mutation, the CDKO-mouse has a mild inner retinal phenotype characterized by altered amacrine cell function, but that it is not an accelerated model of AMD. (Invest Ophthalmol Vis Sci. 2012;53:7833-7846) DOI:10.1167/iovs.12-10650
C1 [Vessey, Kirstan A.; Greferath, Ursula; Jobling, Andrew I.; Phipps, Joanna A.; Ho, Tracy; Waugh, Michelle; Fletcher, Erica L.] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia.
C3 University of Melbourne
RP Fletcher, EL (通讯作者)，Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia.
EM elf@unimelb.edu.au
RI ; Jobling, Andrew/C-8221-2015; Fletcher, Erica/E-6364-2012
OI Ho, Tracy/0000-0002-9277-7823; Jobling, Andrew/0000-0002-7827-3135;
   Fletcher, Erica/0000-0001-9412-9523; Vessey, Kirstan/0000-0003-1031-1964
FU NHMRC [566814, 1021918]; American Health Assistance Foundation; Macular
   Degeneration Research grant; Victoria's Science Agenda grant
FX Supported by the NHMRC project Grants 566814 and 1021918 (ELF); by the
   American Health Assistance Foundation; Macular Degeneration Research
   grant (ELF); and a Victoria's Science Agenda grant (ELF).
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NR 44
TC 42
Z9 43
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2012
VL 53
IS 12
BP 7833
EP 7846
DI 10.1167/iovs.12-10650
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EE
UT WOS:000313053500058
PM 23074204
DA 2022-11-30
ER

PT J
AU Yu, MZ
   Zou, WL
   Peachey, NS
   McIntyre, TM
   Liu, JB
AF Yu, Minzhong
   Zou, Weilin
   Peachey, Neal S.
   McIntyre, Thomas M.
   Liu, Jinbo
TI A Novel Role of Complement in Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; ROD BIPOLAR CELLS; MACULAR DEGENERATION;
   RETINITIS-PIGMENTOSA; EPITHELIAL-CELLS; C3A RECEPTOR; FACTOR-B; C5A;
   ACTIVATION; ANAPHYLATOXIN
AB PURPOSE. The association of single nucleotide polymorphisms of components of the complement alternative pathway with the risk of age-related macular degeneration (AMD) indicates that complement signaling plays an important role in retinal physiology. How genetic variation leads to retinal degeneration is unknown. It has been assumed that complement activation augments immune responses, which in turn initiate AMD pathogenesis. To better understand the relationship between complement and the outer retina, we examined mice lacking the main complement component C3 and the receptors for complement activation fragments C3a (C3aR) and/or C5a (C5aR).
   METHODS. Complement mutant mice were studied along with wild-type (WT) littermates from 6 weeks to 14 months of age. Strobe flash electroretinography (ERG) was used to examine outer retinal function and a dc-ERG technique was used to measure ERG components generated by the retinal pigment epithelium. Retinas were examined by histology, immunohistochemistry, and biochemistry.
   RESULTS. Mice lacking C3aR and/or C5aR developed early onset and progressive retinal degeneration, accompanied by cleaved caspase-3 upregulation. Genetic deletion of C3aR and/or C5aR led to cell-specific defects that matched the cellular localization of these receptors in the WT retina. Compared to WT, C3aR(-/-) and C3aR(-/-) C5aR(-/-) mice showed increased retinal dysfunction upon light exposure. C3aR(-/-) C5aR(-/-) mice immunized with 4-hydroxynonenal-adducted protein developed severe retinal impairment unrelated to immune response.
   CONCLUSIONS. C3aR- and C5aR-mediated signaling was necessary to maintain normal retinal function and structure. These receptors may be important biomarkers for predicting retinal degeneration including AMD. (Invest Ophthalmol Vis Sci. 2012;53:7684-7692) DOI:10.1167/iovs.12-10069
C1 [Yu, Minzhong; Peachey, Neal S.] Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalm Res, Cleveland, OH 44195 USA.
   [Zou, Weilin; McIntyre, Thomas M.; Liu, Jinbo] Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Peachey, Neal S.] Cleveland VA Med Ctr, Res Serv, Cleveland, OH USA.
   [Peachey, Neal S.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Ophthalmol, Cleveland, OH 44106 USA.
   [McIntyre, Thomas M.; Liu, Jinbo] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Mol Med, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; US Department
   of Veterans Affairs; Veterans Health Administration (VHA); Case Western
   Reserve University; Louis Stokes Cleveland Veterans Affairs Medical
   Center; Case Western Reserve University; Cleveland Clinic Foundation;
   Case Western Reserve University; Cleveland Clinic Foundation
RP Liu, JB (通讯作者)，Cleveland Clin, Dept Cell Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM Liuj6@ccf.org
RI Peachey, Neal/G-5533-2010
OI Peachey, Neal/0000-0002-4419-7226
FU American Health Assistance Foundation [M2008-063]; Foundation Fighting
   Blindness Center grant; Research to Prevent Blindness; VA Medical
   Research Service; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
   [UL1TR000439] Funding Source: NIH RePORTER
FX Supported by American Health Assistance Foundation Award M2008-063;
   Foundation Fighting Blindness Center grant; Research to Prevent
   Blindness; VA Medical Research Service.
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   Zipfel PF, 2010, ADV EXP MED BIOL, V703, P9, DOI 10.1007/978-1-4419-5635-4_2
NR 57
TC 40
Z9 40
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 NOV
PY 2012
VL 53
IS 12
BP 7684
EP 7692
DI 10.1167/iovs.12-10069
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EE
UT WOS:000313053500036
PM 23074214
OA Green Published
DA 2022-11-30
ER

PT J
AU Zheng, G
   Yuan, A
   Jeffries, N
AF Zheng, Gang
   Yuan, Ao
   Jeffries, Neal
TI Hybrid Bayes factors for genome-wide association studies when a robust
   test is used
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
DE Bayesian model averaging; Bayes factors; Genetic models; Genome-wide
   scan and ranking; Posterior weighted likelihood; Profile likelihood
ID GENETIC ASSOCIATION; SAMPLE-SIZE; RISK LOCI; MODELS; SCANS
AB Bayes factor (BF) is often used to measure evidence against the null hypothesis in Bayesian hypothesis testing. In the analysis of genome-wide association (GWA) studies, extreme BF values support the associations detected based on significant p-values. Results from recent GWA studies are presented, which show that existing BFs may not be consistent with p-values when a robust test is used due to using different genetic models in the BF and p-value approaches and this may result in misleading conclusions. Two hybrid BFs, which combine the advantages of both the frequentist and Bayesian methods, are then proposed for the markers showing at least moderate associations (p-value < 10(-5)) based on a robust test. One is Bayesian model averaging using a posterior weighted likelihood and the other is the maximum BF using a profile likelihood. The proposed hybrid BFs and p-values of robust tests do not depend on a single genetic model, but instead, consolidate information over a set of models. We compare the hybrid BFs with two existing BF approaches, including an existing Bayesian model averaging method, in terms of false and true positive rates by simulations. The results show that, for markers showing at least moderate associations, both the hybrid BFs have higher true positive rates than the two existing BFs, while all false positive rates are similar. Applications of the two hybrid BFs to the markers associated with bipolar disorder, type 2 diabetes and age-related macular degeneration are presented. Our hybrid BFs provide better and more robust measures to compare significantly associated markers within and across GWA studies. Published by Elsevier B.V.
C1 [Zheng, Gang; Jeffries, Neal] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
   [Yuan, Ao] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung &
   Blood Institute (NHLBI); Howard University
RP Zheng, G (通讯作者)，NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
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NR 16
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
EI 1872-7352
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD SEP 1
PY 2011
VL 55
IS 9
BP 2698
EP 2711
DI 10.1016/j.csda.2011.03.021
PG 14
WC Computer Science, Interdisciplinary Applications; Statistics &
   Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematics
GA 781FN
UT WOS:000291916100013
DA 2022-11-30
ER

PT J
AU Barakat, MR
   Shusterman, M
   Moshfeghi, D
   Danis, R
   Gertner, M
   Singh, RP
AF Barakat, Mark R.
   Shusterman, Mark
   Moshfeghi, Darius
   Danis, Ronald
   Gertner, Michael
   Singh, Rishi P.
TI Pilot Study of the Delivery of Microcollimated Pars Plana External Beam
   Radiation in Porcine Eyes
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; RADIOTHERAPY; TRIAL;
   IRRADIATION; INJECTION
AB Objective: To investigate the effects of a novel stereotactic radiosurgical system for pars plana delivery of microcollimated x-rays to the retina and determine the retinal radiological dose response and toxicity threshold in a pig model.
   Methods: The x-rays were delivered through the pars plana to the maculae of Yucatan miniswine to verify the targeting and safety of a cornea-scleral, stabilized, office-based delivery system. Twelve eyes were randomized to receive 0, 16, 24, 42, 60, or 90 Gy in a single dose to the retina. Eye examinations, fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography were obtained at days 7, 30, 60, and 90. Indocyanine green angiography was done at day 90.
   Results: Through day 90 interim analysis, no abnormalities of external structures were noted. A small cortical lens opacity was noted in the 60-Gy group. Fundus evaluation revealed no abnormalities at 16 or 24 Gy. Beginning at day 30, circular pale retinal lesions with sharp margins were noted in the maculae of the eyes that received 42, 60, and 90 Gy. Higher-dose lesions showed late staining on fluorescein angiography, choroidal hypoperfusion on indocyanine green angiography, and defined photoreceptor loss and retinal thinning on spectral-domain optical coherence tomography.
   Conclusion: Transscleral stereotactic radiation dosing of porcine eyes demonstrates no apparent clinical abnormalities in doses less than 24 Gy. Doses of 42 Gy or higher led to focal choroidal and retinal damage within the target area.
   Clinical Relevance Radiation can induce small-blood vessel closure and thereby has therapeutic potential in neovascular diseases such as age-related macular degeneration.
C1 [Barakat, Mark R.; Singh, Rishi P.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Shusterman, Mark; Gertner, Michael] Oraya Therapeut, Newark, CA USA.
   [Moshfeghi, Darius] Stanford Univ, Palo Alto, CA 94304 USA.
   [Danis, Ronald] Univ Wisconsin, Madison, WI 53706 USA.
C3 Cleveland Clinic Foundation; Stanford University; University of
   Wisconsin System; University of Wisconsin Madison
RP Singh, RP (通讯作者)，9500 Euclid Ave,I-32, Cleveland, OH 44195 USA.
EM singhr@ccf.org
OI Moshfeghi, Darius Mohammad/0000-0003-2254-292X
FU Oraya Therapeutics, California
FX This study was supported by Oraya Therapeutics, California.
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NR 15
TC 8
Z9 8
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAY
PY 2011
VL 129
IS 5
BP 628
EP 632
DI 10.1001/archophthalmol.2011.99
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 761XU
UT WOS:000290437100013
PM 21555617
DA 2022-11-30
ER

PT J
AU Huber, G
   Heynen, S
   Imsand, C
   vom Hagen, F
   Muehlfriedel, R
   Tanimoto, N
   Feng, Y
   Hammes, HP
   Grimm, C
   Peichl, L
   Seeliger, MW
   Beck, SC
AF Huber, Gesine
   Heynen, Severin
   Imsand, Coni
   vom Hagen, Franziska
   Muehlfriedel, Regine
   Tanimoto, Naoyuki
   Feng, Yuxi
   Hammes, Hans-Peter
   Grimm, Christian
   Peichl, Leo
   Seeliger, Mathias W.
   Beck, Susanne C.
TI Novel Rodent Models for Macular Research
SO PLOS ONE
LA English
DT Article
ID RETINAL DEGENERATION; GANGLION-CELLS; ANIMAL-MODELS; MOUSE MODELS;
   PHOTORECEPTORS; COEXPRESSION; PATHOGENESIS; ARRANGEMENT; PREVALENCE;
   PHENOTYPE
AB Background: Many disabling human retinal disorders involve the central retina, particularly the macula. However, the commonly used rodent models in research, mouse and rat, do not possess a macula. The purpose of this study was to identify small laboratory rodents with a significant central region as potential new models for macular research.
   Methodology/Principal Findings: Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli, laboratory rodents less commonly used in retinal research, were subjected to confocal scanning laser ophthalmoscopy (cSLO), fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT) using standard equipment (Heidelberg Engineering HRA1 and Spectralis (TM)) adapted to small rodent eyes. The existence of a visual streak-like pattern was assessed on the basis of vascular topography, retinal thickness, and the topography of retinal ganglion cells and cone photoreceptors. All three species examined showed evidence of a significant horizontal streak-like specialization. cSLO angiography and retinal wholemounts revealed that superficial retinal blood vessels typically ramify and narrow into a sparse capillary net at the border of the respective area located dorsal to the optic nerve. Similar to the macular region, there was an absence of larger blood vessels in the streak region. Furthermore, the thickness of the photoreceptor layer and the population density of neurons in the ganglion cell layer were markedly increased in the visual streak region.
   Conclusions/Significance: The retinal specializations of Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli resemble features of the primate macula. Hence, the rodents reported here may serve to study aspects of macular development and diseases like age-related macular degeneration and diabetic macular edema, and the preclinical assessment of therapeutic strategies.
C1 [Huber, Gesine; Muehlfriedel, Regine; Tanimoto, Naoyuki; Seeliger, Mathias W.; Beck, Susanne C.] Univ Tubingen, Inst Ophthalm Res, Ctr Ophthalmol, Div Ocular Neurodegenerat, Tubingen, Germany.
   [Heynen, Severin; Imsand, Coni; Grimm, Christian] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Zurich, Switzerland.
   [vom Hagen, Franziska; Feng, Yuxi; Hammes, Hans-Peter] Heidelberg Univ, Univ Med Mannheim, Dept Med 5, D-6800 Mannheim, Germany.
   [Peichl, Leo] Max Planck Inst Brain Res, D-60496 Frankfurt, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; University of Zurich; Ruprecht Karls University Heidelberg;
   Max Planck Society
RP Huber, G (通讯作者)，Univ Tubingen, Inst Ophthalm Res, Ctr Ophthalmol, Div Ocular Neurodegenerat, Tubingen, Germany.
EM Susanne.Beck@med.uni-tuebingen.de
OI Peichl, Leo/0000-0002-8141-0911; Grimm, Christian/0000-0001-9318-4352
FU Deutsche Forschungsgemeinschaft (DFG) [Se837/5-2, Se837/6-1, Se837/7-1];
   German Ministry of Education and Research (BMBF) [0314106]; European
   Union [EU HEALTH-F2-2008-200234, EU MEST-CT-2005-020235]; Kerstan
   Foundation; Swiss National Science Foundation [3100A0-117760, GRK880, Ha
   1755/8-1]
FX This work was supported by Deutsche Forschungsgemeinschaft (DFG, grants
   Se837/5-2, Se837/6-1, Se837/7-1), the German Ministry of Education and
   Research (BMBF, grant 0314106), and the European Union grants EU
   HEALTH-F2-2008-200234, EU MEST-CT-2005-020235, Kerstan Foundation, Swiss
   National Science Foundation Grant 3100A0-117760, GRK880, Ha 1755/8-1.
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the mansucript.
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NR 36
TC 37
Z9 38
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 15
PY 2010
VL 5
IS 10
AR e13403
DI 10.1371/journal.pone.0013403
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 665NX
UT WOS:000283043700008
PM 20976212
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ganesan, AK
   Ho, H
   Bodemann, B
   Petersen, S
   Aruri, J
   Koshy, S
   Richardson, Z
   Le, LQ
   Krasieva, T
   Roth, MG
   Farmer, P
   White, MA
AF Ganesan, Anand K.
   Ho, Hsiang
   Bodemann, Brian
   Petersen, Sean
   Aruri, Jayavani
   Koshy, Shiney
   Richardson, Zachary
   Le, Lu Q.
   Krasieva, Tatiana
   Roth, Michael G.
   Farmer, Pat
   White, Michael A.
TI Genome-Wide siRNA-Based Functional Genomics of Pigmentation Identifies
   Novel Genes and Pathways That Impact Melanogenesis in Human Cells
SO PLOS GENETICS
LA English
DT Article
ID ALDEHYDE DEHYDROGENASE; MELANOSOME BIOGENESIS; CULTURED MELANOCYTES;
   PARKINSONS-DISEASE; SKIN PIGMENTATION; TYROSINASE; AUTOPHAGY; PROTEIN;
   ENDOSOMES; HAIR
AB Melanin protects the skin and eyes from the harmful effects of UV irradiation, protects neural cells from toxic insults, and is required for sound conduction in the inner ear. Aberrant regulation of melanogenesis underlies skin disorders (melasma and vitiligo), neurologic disorders (Parkinson's disease), auditory disorders (Waardenburg's syndrome), and opthalmologic disorders (age related macular degeneration). Much of the core synthetic machinery driving melanin production has been identified; however, the spectrum of gene products participating in melanogenesis in different physiological niches is poorly understood. Functional genomics based on RNA-mediated interference (RNAi) provides the opportunity to derive unbiased comprehensive collections of pharmaceutically tractable single gene targets supporting melanin production. In this study, we have combined a high-throughput, cell-based, one-well/one-gene screening platform with a genome-wide arrayed synthetic library of chemically synthesized, small interfering RNAs to identify novel biological pathways that govern melanin biogenesis in human melanocytes. Ninety-two novel genes that support pigment production were identified with a low false discovery rate. Secondary validation and preliminary mechanistic studies identified a large panel of targets that converge on tyrosinase expression and stability. Small molecule inhibition of a family of gene products in this class was sufficient to impair chronic tyrosinase expression in pigmented melanoma cells and UV-induced tyrosinase expression in primary melanocytes. Isolation of molecular machinery known to support autophagosome biosynthesis from this screen, together with in vitro and in vivo validation, exposed a close functional relationship between melanogenesis and autophagy. In summary, these studies illustrate the power of RNAi-based functional genomics to identify novel genes, pathways, and pharmacologic agents that impact a biological phenotype and operate outside of preconceived mechanistic relationships.
C1 [Ganesan, Anand K.; Aruri, Jayavani; Koshy, Shiney; Richardson, Zachary] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA.
   [Ganesan, Anand K.; Ho, Hsiang] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA.
   [Bodemann, Brian; White, Michael A.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Petersen, Sean; Roth, Michael G.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Le, Lu Q.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA.
   [Krasieva, Tatiana] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92717 USA.
   [Farmer, Pat] Univ Calif Irvine, Dept Chem, Irvine, CA 92717 USA.
C3 University of California System; University of California Irvine;
   University of California System; University of California Irvine;
   University of Texas System; University of Texas Southwestern Medical
   Center Dallas; University of Texas System; University of Texas
   Southwestern Medical Center Dallas; University of Texas System;
   University of Texas Southwestern Medical Center Dallas; University of
   California System; University of California Irvine; University of
   California System; University of California Irvine
RP Ganesan, AK (通讯作者)，Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA.
EM aganesan@uci.edu; michael.white@utsouthwestern.edu
RI Farmer, Patrick J/J-3757-2019
OI Farmer, Patrick J/0000-0001-9911-999X; Roth, Michael/0000-0002-9056-332X
FU National Institutes of Health [CA71443]; Robert Welch Foundation
   [I-1414]; Mary K. Ash Cheritable Foundation [076-06]; National Cancer
   Institute [P30CA62203]; Galderma Laboratories; Laser Microbeam Program
   (LAMMP); University of California, Irvine [P41-RR01192]; DoD
   [W81XWH060749]; NATIONAL CANCER INSTITUTE [R01CA071443, P30CA062203]
   Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCES
   [P41RR001192] Funding Source: NIH RePORTER
FX This work was supported by the National Institutes of Health (CA71443),
   the Robert Welch Foundation (I-1414), the Mary K. Ash Cheritable
   Foundation (076-06), the National Cancer Institute (P30CA62203), and a
   pilot and feasibility grant from Galderma Laboratories. This research
   was performed with support from the Laser Microbeam Program (LAMMP), A
   NIH Biomedical Technology Resource, grant # P41-RR01192 at the
   University of California, Irvine. BB is supported by DoD (W81XWH060749).
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NR 43
TC 112
Z9 124
U1 1
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD DEC
PY 2008
VL 4
IS 12
AR e1000298
DI 10.1371/journal.pgen.1000298
PG 12
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 411RO
UT WOS:000263667900013
PM 19057677
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Caicedo, A
   Espinosa-Heidmann, DG
   Pina, Y
   Hernandez, EP
   Cousins, SW
AF Caicedo, A
   Espinosa-Heidmann, DG
   Pina, Y
   Hernandez, EP
   Cousins, SW
TI Blood-derived macrophages infiltrate the retina and activate Muller
   glial cells under experimental choroidal neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE mouse; VCAM 1; ICAM 1; PECAM; microglia; macrophages; choroidal
   neovascularization; age-related macular degeneration
ID FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ARGON-LASER
   PHOTOCOAGULATION; ISCHEMIA-REPERFUSION INJURY; RAT RETINA; MACULAR
   DEGENERATION; RABBIT RETINA; WOUND REPAIR; EXPRESSION; MICROGLIA
AB Inflammation is a major mechanism in the pathogenesis of age-related macular degeneration, the most important cause of blindness in the elderly. Previous studies have focused on the role of macrophages in regulating the growth of pathological new vessels over the retina, called choroidal neovascularization (CNV). However, no research has been done to evaluate the role of inflammation as a mechanism of vision loss and retinal degeneration in the retina underlying CNV. In other neuropathological conditions, hematogenous macrophages and/or resident microglia contribute to neurodegeneration. We have combined laser-induced CNV in mice and bone marrow transplantation with GFP-labeled bone marrow to determine the relative role of recruited blood-derived macrophages versus resident microglia in the retina associated with CNV. Using these chimeric mice, we have found that many GFP-labeled cells infiltrated the retina underlying CNV but not the retina unaffected by CNV. Immunostaining for the cell adhesion molecules VCAM 1, ICAM 1, and PECAM was strongly upregulated in retinal blood vessels under CNV. All GFP-labeled cells were immunoreactive for the macrophage marker F4/80. Most (70%) of the F4/80 immunoreactive cells were GFP-labeled under CNV. The density of resident microglia did not increase. Most GFP-labeled cells were found in close proximity to activated Muller cells. Depleting circulating macrophages with clodronic acid diminished the density of F4/80 immunoreactive cells as well as the density of pERK immunoreactive Muller cells in the retina under CNV. Thus, recruitment of blood-derived macrophages more than resident microglia seems to be associated with CNV. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami
RP Caicedo, A (通讯作者)，Univ Miami, Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
RI Caicedo, Alejandro/F-1202-2010; Caicedo, Alejandro/AAC-8544-2020
FU NATIONAL EYE INSTITUTE [P30EY014801, R01EY013318] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION
   DISORDERS [R03DC004525] Funding Source: NIH RePORTER; NEI NIH HHS [EY/AI
   13318, P30 EY14801] Funding Source: Medline; NIDCD NIH HHS [DC 4525]
   Funding Source: Medline
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NR 59
TC 120
Z9 133
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 JUL
PY 2005
VL 81
IS 1
BP 38
EP 47
DI 10.1016/j.exer.2005.01.013
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 943VW
UT WOS:000230383900006
PM 15978253
DA 2022-11-30
ER

PT J
AU Zou, R
   Feng, YF
   Xu, YH
   Shen, MQ
   Zhang, X
   Yuan, YZ
AF Zou, Rong
   Feng, Yi-Fan
   Xu, Ya-Hui
   Shen, Min-Qian
   Zhang, Xi
   Yuan, Yuan-Zhi
TI Yes-associated protein promotes endothelial-to-mesenchymal transition of
   endothelial cells in choroidal neovascularization fibrosis
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE endothelial-to-mesenchymal transition; Yes-associated protein;
   hypoxia-inducible factor-1 alpha; choroidal neovascularization;
   age-related macular degeneration
ID YAP PROMOTES; LUNG-CANCER; CHEMORESISTANCE; CONTRIBUTES; INHIBITION;
   SNAIL
AB AIM: To reveal whether and how Yes-associated protein (YAP) promotes the occurrence of subretinal fibrosis in age-related macular degeneration (AMD).
   METHODS: Cobalt chloride (CoCl2) was used in primary human umbilical vein endothelial cells (HUVECs) to induce hypoxia in vitro. Eigrit-week-old male C57BL/6J mice weighing 19-25 g were used for a choroidal neovascularization (CNV) model induced by laser photocoagulation in vivo. Expression levels of YAP, phosphorylated YAP, mesenchymal markers [alpha smooth muscle actin (alpha-SMA), vimentin, and Snail], and endothelial cell markers (CD31 and zonula occludens 1) were measured by Western blotting, quantitative real-time PCR, and immunofluorescence microscopy. Small molecules YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor 1 alpha), CA3 (CIL56, an inhibitor of YAP), and XMU-MP-1 (an inhibitor of Hippo kinase MST1/2, which activates YAP) were used to explore the underlying mechanism.
   RESULTS: CoCl2 increased expression of mesenchymal markers, decreased expression of endothelial cell markers, and enhanced the ability of primary HUVECs to proliferate and migrate. YC-1 suppressed hypoxia-induced endothelialto-mesenchymal transition (EndMT). Moreover, hypoxia promoted total expression, inhibited phosphorylation, and enhanced the transcriptional activity of YAP. XMU-MP-1 enhanced hypoxia-induced EndMT, whereas CA3 elicited the opposite effect. Expression of YAP, alpha-SMA, and vimentin were upregulated in the laser-induced CNV model. However, silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these changes.
   CONCLUSION: The findings reveal a critical role of the hypoxia-inducible factor-1 alpha (HIF-1 alpha)/YAP signaling axis in EndMT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.
C1 [Zou, Rong; Feng, Yi-Fan; Xu, Ya-Hui; Shen, Min-Qian; Zhang, Xi; Yuan, Yuan-Zhi] Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, Shanghai 200032, Peoples R China.
   [Yuan, Yuan-Zhi] Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, Xiamen Branch, Xiamen 361015, Fujian, Peoples R China.
C3 Fudan University; Fudan University
RP Feng, YF (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, Shanghai 200032, Peoples R China.
EM yktgyx2019@163.com
FU National Natural Science Foundation of China [81970817, 81873680]
FX Foundations: Supported by the National Natural Science Foundation of
   China (No.81970817; No.81873680) .
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NR 42
TC 0
Z9 0
U1 3
U2 3
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD MAY 18
PY 2022
VL 15
IS 5
BP 701
EP 710
DI 10.18240/ijo.2022.05.03
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1O2XK
UT WOS:000801201700003
PM 35601164
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, HH
   Xie, J
   Zeng, JW
   Wu, J
   Zhou, J
   Zhao, W
AF Li, Honghui
   Xie, Jun
   Zeng, Junwen
   Wu, Juan
   Zhou, Jin
   Zhao, Wei
TI VEGF gene polymorphisms regulate human retinal vascular endothelial cell
   proliferation and apoptosis through ASF/SF2-associated alternative
   splicing
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE VEGF; VEGF(165b); SNP; human retinal vascular endothelial cells
ID MIGRATION
AB This study investigated the effects of single nucleotide polymorphisms (SNPs) of the VEGF (vascular endothelial growth factor? gene, which are associated with susceptibility to age-related macular degeneration (AMD), on the expression of VEGF proteins (VEGF(165) and VEGF(165b)) and their role in cell proliferation and apoptosis in human retinal vascular endothelial cells (hRVECs). Cell viability and VEGF(165) and VEGF(165b) expressions were evaluated in hRVECs transfected with VEGF genes containing different SNPs (rs3025039, rs3025033, and rs10434). The Cell Counting Kit 8 assay, quantitative real-time PCR, western blotting, TUNEL assay, and enzyme-linked immunosorbent assay were used to examine the effects of VEGF gene SNPs on cell viability, VEGF(165) and VEGF(165b) expressions, and cell apoptosis in hRVECs. The interaction and localization of the RNA-binding protein alternative splicing factor/splicing factor 2 (ASF/SF2) were assessed using RNA pull-down. Although VEGF(165) expression decreased, VEGF(165b) levels increased significantly in hRVECs transfected with rs3025039, which decreased cell viability and induced apoptosis. The SNPs rs3025033 and rs10434 had no significant effects on VEGF(165b) protein production and apoptosis; however, they promoted cell proliferation. SNPs affected the interaction between RNA and ASF/SF2, a splicing factor for intron retention. Insulin-like growth factor-1 treatment induced the expression of VEGF(165), but not VEGF(165b), whereas SRPIN340 treatment, an inhibitor of ASF/SF2, increased VEGF(165b) protein levels. VEGF gene sequence variations affected hRVEC proliferation and apoptosis via alternative gene splicing. Thus, the regulation of splicing via ASF/SF2 could be a potential strategy in treating pathological neovascularization in patients with AMD.
C1 [Li, Honghui; Xie, Jun; Zhou, Jin] Chengdu Aier Eye Hosp, Chengdu, Peoples R China.
   [Zeng, Junwen; Wu, Juan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China.
   [Zhao, Wei] City Univ Hong Kong, Dept Biomed Sci, Tat Chee Ave, Hong Kong, Peoples R China.
C3 Sun Yat Sen University; City University of Hong Kong
RP Zhao, W (通讯作者)，City Univ Hong Kong, Dept Biomed Sci, Tat Chee Ave, Hong Kong, Peoples R China.; Zhou, J (通讯作者)，Chengdu Aier Eye Hosp, Dept Ophthalmol & Optometry, Chengdu, Peoples R China.
EM drzhoujin321@163.com; zw198626520@126.com
RI Zhao, Wei/AAC-6849-2020
OI Zhao, Wei/0000-0003-2421-7311
FU Department of Science and Technology of Sichuan Province [2018RZ0095]
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This work
   was supported by the Department of Science and Technology of Sichuan
   Province (grant number 2018RZ0095).
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NR 27
TC 1
Z9 1
U1 1
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP
PY 2022
VL 32
IS 5
BP 2726
EP 2734
AR 11206721211058000
DI 10.1177/11206721211058000
EA NOV 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3S5GW
UT WOS:000726641800001
PM 34825587
DA 2022-11-30
ER

PT J
AU Xie, TH
   Cai, JP
   Yao, Y
   Sun, C
   Yang, Q
   Wu, ML
   Xu, ZF
   Sun, XD
   Wang, XL
AF Xie, Tianhua
   Cai, Jiping
   Yao, Yong
   Sun, Chao
   Yang, Qian
   Wu, Meili
   Xu, Zifan
   Sun, Xiaodong
   Wang, Xiaolu
TI LXA4 protects against blue-light induced retinal degeneration in human
   A2E-laden RPE cells and Balb-c mice
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Age-related macular degeneration (AMD); retinal degeneration; lipoxin A4
   (LXA4); blue light; oxidative stress
ID MACULAR DEGENERATION; OXIDATIVE STRESS; LIPOXIN A(4); PIGMENT;
   PREVALENCE; ACTIVATION; MECHANISMS; PEPTIDE; ASPIRIN; DAMAGE
AB Background: Age-related macular degeneration (AMD) is one of the leading causes of permanent visual impairment in the elderly. Blue light (BL) has been reported to cause retinal damage and contribute to the onset and development of severe AMD. N-retinylidene-N-retinylethanolamine (A2E), a lipofuscin fluorophore, accumulates with ageing in the retinal pigment epithelium (RPE) cells. Once exposed to BL, A2E easily oxidizes to A2E-epoxides, causing oxidative-stress injury to the retina. Lipoxin A4 (LXA4), an endogenous anti-antioxidant lipid, plays a key role in multiple organs by binding to the formyl-peptide receptor-like 1 (FPRL1). This study examined the protective effects of LXA4 on oxidative-stress injury induced by BL exposure, and clarified the underlying mechanisms in cultured RPE cells and Balb-c mice. Methods: LXA4 diluent was orally administered to mice before retinal degeneration was established. Optical coherence tomography, retinal histology, and RPE cell injury were assessed. Results: LXA4 administration significantly ameliorated retinal damage as evidenced by the thicknesses of the retinal layers and the tight junctions of RPE cells in vivo. LXA4 inhibited BL-induced reactive oxygen species (ROS) production, reduced tight junctions, and the death of A2E-laden RPE cells. LXA4 also potently increased the expression of haem oxygenase-1 (HO1) and NAD(P)H quinone oxidoreductase 1 (NQO1), probably by decreasing the association between nuclear factor erythroid 2-related factor 2 (NRF2) and Kelch-like ECH (Epichlorohydrin)-associated protein 1 (Keap1), and ameliorating NRF2 nuclear translocation and the antioxidant response element (ARE) deoxyribonucleic acid (DNA) binding activity. Conclusions: Our results showed that LXA4 ameliorated retinal degeneration, and should be considered in the prevention and treatment of AMD.
C1 [Xie, Tianhua; Sun, Xiaodong] Nanjing Med Univ, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai 200080, Peoples R China.
   [Xie, Tianhua; Cai, Jiping; Yao, Yong; Sun, Chao; Yang, Qian; Xu, Zifan] Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Dept Ophthalmol, Wuxi, Jiangsu, Peoples R China.
   [Wu, Meili; Wang, Xiaolu] Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Ctr Clin Res, 299 Qingyang Rd, Wuxi 214023, Jiangsu, Peoples R China.
C3 Nanjing Medical University; Nanjing Medical University; Nanjing Medical
   University
RP Sun, XD (通讯作者)，Nanjing Med Univ, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai 200080, Peoples R China.; Wang, XL (通讯作者)，Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Ctr Clin Res, 299 Qingyang Rd, Wuxi 214023, Jiangsu, Peoples R China.
EM xdsun@sjtu.edu.cn; xlwang@njmu.edu.cn
OI Wang, Xiaolu/0000-0001-8089-6473
FU National Natural Science Foundation of China [81800845, 81770941];
   Technology Development Fund [CSE12N1701]; Wuxi Taihu Lake Talent Plan,
   Supports for Leading Talents in Medical and Health Profession
   [2020-THRCTD-1]; Top Talent Support Program for Young and Middle-Aged
   People of the Wuxi Health Committee [HB2020004, HB2020022]
FX This work was supported by the National Natural Science Foundation of
   China (grant numbers: 81800845, 81770941), the Technology Development
   Fund (grant number: CSE12N1701), the Wuxi Taihu Lake Talent Plan,
   Supports for Leading Talents in Medical and Health Profession (grant
   numbers: 2020-THRCTD-1, THRCDJ-1) and the Top Talent Support Program for
   Young and Middle-Aged People of the Wuxi Health Committee (grant
   numbers: HB2020004, HB2020022).
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NR 45
TC 2
Z9 2
U1 1
U2 9
PU AME PUBL CO
PI SHATIN
PA FLAT-RM C 16F, KINGS WING PLAZA 1, NO 3 KWAN ST, SHATIN, HONG KONG
   00000, PEOPLES R CHINA
SN 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD AUG
PY 2021
VL 9
IS 15
DI 10.21037/atm-21-3390
EA AUG 2021
PG 17
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA UA8PU
UT WOS:000684466700001
PM 34532386
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hou, X
   Du, HJ
   Zhou, J
   Hu, D
   Wang, YS
   Li, XR
AF Hou, Xu
   Du, Hong-Jun
   Zhou, Jian
   Hu, Dan
   Wang, Yu-Sheng
   Li, Xuri
TI Role of Junctional Adhesion Molecule-C in the Regulation of Inner
   Endothelial Blood-Retinal Barrier Function
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE junctional adhesion molecule-C; blood-retinal barrier; retinal capillary
   endothelial cell; vascular endothelial growth factor; platelet-derived
   growth factor-C
ID PROTEIN-KINASE-C; TRANSENDOTHELIAL MIGRATION; JAM-C; EXPRESSION; CELLS;
   CALCIUM; IDENTIFICATION; ANGIOGENESIS; PERMEABILITY; CHANNELS
AB Although JAM-C is abundantly expressed in the retinae and upregulated in choroidal neovascularization (CNV), it remains thus far poorly understood whether it plays a role in the blood-retinal barrier, which is critical to maintain the normal functions of the eye. Here, we report that JAM-C is highly expressed in retinal capillary endothelial cells (RCECs), and VEGF or PDGF-C treatment induced JAM-C translocation from the cytoplasm to the cytomembrane. Moreover, JAM-C knockdown in RCECs inhibited the adhesion and transmigration of macrophages from wet age-related macular degeneration (wAMD) patients to and through RCECs, whereas JAM-C overexpression in RCECs increased the adhesion and transmigration of macrophages from both wAMD patients and healthy controls. Importantly, the JAM-C overexpression-induced transmigration of macrophages from wAMD patients was abolished by the administration of the protein kinase C (PKC) inhibitor GF109203X. Of note, we found that the serum levels of soluble JAM-C were more than twofold higher in wAMD patients than in healthy controls. Mechanistically, we show that JAM-C overexpression or knockdown in RCECs decreased or increased cytosolic Ca2+ concentrations, respectively. Our findings suggest that the dynamic translocation of JAM-C induced by vasoactive molecules might be one of the mechanisms underlying inner endothelial BRB malfunction, and inhibition of JAM-C or PKC in RCECs may help maintain the normal function of the inner BRB. In addition, increased serum soluble JAM-C levels might serve as a molecular marker for wAMD, and modulating JAM-C activity may have potential therapeutic value for the treatment of BRB malfunction-related ocular diseases.
C1 [Hou, Xu; Du, Hong-Jun; Zhou, Jian; Hu, Dan; Wang, Yu-Sheng] Fourth Mil Med Univ, Dept Ophthalmol, Eye Inst Chinese PLA, Xijing Hosp, Xian, Peoples R China.
   [Li, Xuri] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
C3 Air Force Military Medical University; Sun Yat Sen University
RP Hou, X (通讯作者)，Fourth Mil Med Univ, Dept Ophthalmol, Eye Inst Chinese PLA, Xijing Hosp, Xian, Peoples R China.; Li, XR (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
EM hxfmmu@163.com; lixr6@mail.sysu.edu.cn
FU National Natural Science Foundation of China [81371034, 81470654]; Key
   Project of the Natural Science Foundation of Shaanxi Province
   [2017JZ025]; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic
   Center, Sun Yat-sen University, Guangzhou, China; Key Program of
   Guangzhou Scientific Research Plan [201804020010]
FX This study was funded by the National Natural Science Foundation of
   China (Nos. 81371034 and 81470654), the Key Project of the Natural
   Science Foundation of Shaanxi Province (No. 2017JZ025), the State Key
   Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
   University, Guangzhou, China, and the Key Program of Guangzhou
   Scientific Research Plan (No. 201804020010).
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NR 48
TC 2
Z9 2
U1 2
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-634X
J9 FRONT CELL DEV BIOL
JI Front. Cell. Dev. Biol.
PD JUN 7
PY 2021
VL 9
AR 695657
DI 10.3389/fcell.2021.695657
PG 12
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA SW1ZG
UT WOS:000664318500001
PM 34164405
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Muller, PL
   Maloca, P
   Webster, A
   Egan, C
   Tufail, A
AF Mueller, Philipp L.
   Maloca, Peter
   Webster, Andrew
   Egan, Catherine
   Tufail, Adnan
TI Structural Features Associated With the Development and Progression of
   RORA Secondary to Maternally Inherited Diabetes and Deafness
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL-COHERENCE-TOMOGRAPHY; INTRARETINAL HYPERREFLECTIVE FOCI; OUTER
   RETINAL TUBULATION; AGE-RELATED CATARACT; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; DRUSEN VOLUME; END-POINTS; MITOCHONDRIA; PHENOTYPES
AB PURPOSE: To investigate the development and progression of retinal pigment epithelial and outer retinal atrophy (RORA) secondary to maternally inherited diabetes and deafness (MIDD).
   DESIGN: Retrospective observational case series.
   METHODS: Thirty-six eyes of 18 patients (age range, 22.4-71.6 years) with genetically proven MIDD and serial optical coherence tomography (OCT) images were included. As proposed reference standard to diagnose and stage atrophy, OCT images were longitudinally evaluated and analyzed for presence and precursors of RORA. RORA was defined as an area of (1) hypertransmission, (2) disruption of the retinal pigment epithelium, (3) photoreceptor degeneration, and (4) absence of other signs of a retinal pigment epithelial tear.
   RESULTS: The majority of patients revealed areas of RORA in a circular area around the fovea of between 5 degrees and 15 degrees eccentricity. Over the observation time (range, 0.5-8.5 years), evidence for a consistent sequence of OCT features from earlier disease stages to the end stage of RORA could be found, starting with loss of ellipsoid zone and subretinal deposits, followed by loss of external limiting membrane and loss of retinal pigment epithelium with hypertransmission of OCT signal into the choroid, and leading to loss of the outer nuclear layer bordered by hyporeflective wedges. Outer retinal tabulations seemed to develop in regions of coalescent areas of RORA.
   CONCLUSIONS: The development and progression of RORA could be tracked in MIDD patients using OCT images, allowing potential definition of novel surrogate markers. Similarities to OCT features in age-related macular degeneration, where mitochondrial dysfunction has been implicated in the pathogenesis, support wide-ranging benefits from proof-of-concept studies in MIDD. (C) 2020 Elsevier Inc. All rights reserved.
C1 [Mueller, Philipp L.; Maloca, Peter; Webster, Andrew; Egan, Catherine; Tufail, Adnan] Moorfields Eye Hosp NHS Fdn Trust, 162 City Rd, London EC1V 2PD, England.
   [Mueller, Philipp L.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Mueller, Philipp L.] Univ Bonn, Ctr Rare Dis, Bonn, Germany.
   [Maloca, Peter] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Maloca, Peter] Inst Mol & Clin Ophthalmol Basel, Basel, Switzerland.
   [Webster, Andrew] UCL, Inst Ophthalmol, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Bonn; University of Bonn; University
   of Basel; University of London; University College London
RP Tufail, A (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, 162 City Rd, London EC1V 2PD, England.
EM adnan.tufail@nhs.net
RI Maloca, Peter/N-4908-2018
OI Maloca, Peter/0000-0002-4794-5859; Tufail, Adnan/0000-0001-6131-7640
FU GERMAN RESEARCH FOUNDATION [MU4279/2-1]; United Kingdom's National
   Institute for Health Research of Health's Biomedical Research Centre for
   Ophthalmology at Moorfields Eye Hospital; UCL Institute of Ophthalmology
FX THIS WORK WAS SUPPORTED BY THE GERMAN RESEARCH FOUNDATION (GRANT
   MU4279/2-1 TO PLM), THE United Kingdom's National Institute for Health
   Research of Health's Biomedical Research Centre for Ophthalmology at
   Moorfields Eye Hospital and UCL Institute of Ophthalmology. The views
   expressed are those of the authors, not necessarily those of the
   Department of Health. The funder had no role in study design, data
   collection, analysis, or interpretation, or the writing of the report.
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NR 49
TC 5
Z9 5
U1 0
U2 1
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 2020
VL 218
BP 136
EP 147
DI 10.1016/j.ajo.2020.05.023
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NW3OL
UT WOS:000574919700015
PM 32446735
DA 2022-11-30
ER

PT J
AU Cho, HJ
   Jung, SH
   Cho, S
   Han, JO
   Park, S
   Kim, JW
AF Cho, Han Joo
   Jung, Seong Heon
   Cho, Suyeon
   Han, Jae Ook
   Park, Saemi
   Kim, Jong Woo
TI Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for
   Pachychoroid Neovasculopathy
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   pachychoroid neovasculopathy; vascular endothelial growth factor
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; MACULAR DEGENERATION; GEOGRAPHIC
   ATROPHY; AFLIBERCEPT THERAPY; AGE; RISK; NEOVASCULARIZATION;
   RANIBIZUMAB; ANGIOGRAPHY; THICKNESS
AB Purpose: To compare the effectiveness of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD). Methods: Twenty-two eyes with pachychoroid neovasculopathy and 183 eyes with neovascular AMD were retrospectively included for analysis. All patients were treatment naive and received an initial series of 3 monthly loading injections of anti-VEGF, followed by further injections as required. The visual and anatomical outcomes after treatment were evaluated at 12 months from baseline. Results: The pachychoroid neovasculopathy group showed a significant improvement in the mean best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution) from 0.50 +/- 0.32 (Snellen equivalent; 20/63) to 0.31 +/- 0.28 (20/85, P = 0.021), and a decrease in the mean central foveal thickness from 373 +/- 184 mu m to 195 +/- 137 mu m at 12 months (P < 0.001). No significant intergroup difference in the achieved improvement of BCVA and decrease of central foveal thickness was observed. However, compared with the neovascular AMD group, the pachychoroid neovasculopathy group showed lower proportions of patients requiring retreatment during the maintenance phase (59.1% vs. 80.9%, P = 0.018), longer treatment-free period after loading injections (6.1 vs. 4.3 months, P = 0.006), and fewer number of injections (4.2 vs. 4.9, P = 0.031). Conclusions: Anti-VEGF treatment for pachychoroid neovasculopathy showed a similar efficacy to anti-VEGF treatment for neovascular AMD in improving visual acuity during 12 months. However, eyes with pachychoroid neovasculopathy had a significantly lesser need for retreatment during the maintenance phase and longer retreatment-free period, while requiring fewer injections.
C1 [Cho, Han Joo; Jung, Seong Heon; Cho, Suyeon; Han, Jae Ook; Park, Saemi; Kim, Jong Woo] Konyang Univ, Coll Med, Myung Gok Eye Res Inst, Dept Ophthalmol,Kims Eye Hosp, Seoul 07301, South Korea.
C3 Konyang University
RP Cho, HJ (通讯作者)，Konyang Univ, Coll Med, Myung Gok Eye Res Inst, Dept Ophthalmol,Kims Eye Hosp, Seoul 07301, South Korea.
EM chojoo@kimeye.com
OI Cho, Han Joo/0000-0001-7336-5762
CR Adatia FA, 2015, SURV OPHTHALMOL, V60, P204, DOI 10.1016/j.survophthal.2014.10.002
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NR 24
TC 21
Z9 21
U1 0
U2 1
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 APR 1
PY 2019
VL 35
IS 3
BP 174
EP 181
DI 10.1089/jop.2018.0107
PG 8
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA HS4DC
UT WOS:000463811100006
PM 30807236
DA 2022-11-30
ER

PT J
AU Head, T
   Dau, P
   Duffort, S
   Daftarian, P
   Joshi, PM
   Vazquez-Padron, R
   Deo, SK
   Daunert, S
AF Head, Trajen
   Dau, Peter
   Duffort, Stephanie
   Daftarian, Pirouz
   Joshi, Pratibha M.
   Vazquez-Padron, Roberto
   Deo, Sapna K.
   Daunert, Sylvia
TI An enhanced bioluminescence-based Annexin V probe for apoptosis
   detection in vitro and in vivo
SO CELL DEATH & DISEASE
LA English
DT Article
ID PROTEIN SECONDARY STRUCTURE; PROGRAMMED CELL-DEATH; CIRCULAR-DICHROISM
   SPECTRA; PHOSPHATIDYLSERINE EXPOSURE; RENILLA LUCIFERASE; SODIUM IODATE;
   STAUROSPORINE; PURIFICATION; EXPRESSION; PATHWAYS
AB The process of controlled cellular death known as apoptosis has an important central role not only in normal homeostatic maintenance of tissues, but also in numerous diseases such as cancer, neurodegenerative, autoimmune, and cardiovascular diseases. As a result, new technologies with the capability to selectively detect apoptotic cells represent a central focus of research for the study of these conditions. We have developed a new biosensor for the detection of apoptotic cells, incorporating the targeted selectivity for apoptotic cells from Annexin V with the sensitivity of bioluminescence signal generation from a serum-stable mutant of Renilla luciferase (RLuc8). Our data presents a complete characterization of the structural and biochemical properties of this new Annexin-Renilla fusion protein (ArFP) construct, as well as a validation of its ability to detect apoptosis in vitro. Moreover, this work represents the first report of a bioluminescent Annexin V apoptosis sensor utilized in vivo. With this new construct, we examine apoptosis within disease-relevant animal models of surgery-induced ischemia/reperfusion, corneal injury, and retinal cell death as a model of age-related macular degeneration. In each of these experiments, we demonstrate successful application of the ArFP construct for detection and bioluminescence imaging of apoptosis within each disease or treatment model. ArFP represents an important new tool in the continuously growing kit of technologies for apoptosis detection, and our results from both in vitro and in vivo experiments suggest a diverse range of potential clinically relevant applications including cancer therapeutic screening and efficacy analysis, atherosclerosis and cardiovascular disease detection, and the monitoring of any number of other conditions in which apoptosis has a central role.
C1 [Head, Trajen; Dau, Peter; Joshi, Pratibha M.; Deo, Sapna K.; Daunert, Sylvia] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, 1011 NW 15th St,Gautier Bldg Room 239DA, Miami, FL 33136 USA.
   [Duffort, Stephanie] Univ Miami, Miller Sch Med, Dept Ophthalmol, Miami, FL 33136 USA.
   [Daftarian, Pirouz] NGM Biopharmaceut Inc, San Francisco, CA 94080 USA.
   [Vazquez-Padron, Roberto] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA.
C3 University of Miami; University of Miami; University of Miami
RP Daunert, S (通讯作者)，Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, 1011 NW 15th St,Gautier Bldg Room 239DA, Miami, FL 33136 USA.
EM SDaunert@miami.edu
FU National Institutes of Health [1R01GM114321, R01GM047915]; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM047915, R01GM114321] Funding
   Source: NIH RePORTER
FX This work was supported in part by grants from the National Institutes
   of Health (1R01GM114321 and R01GM047915). Dr. Sylvia Daunert is grateful
   to the Miller School of Medicine of the University of Miami for the
   Lucille P. Markey Chair in the Department of Biochemistry and Molecular
   Biology. We would like to thank Dr. Oscar Alcazar, Dr. Luis Alberto
   Radames Escobar Carrasquero, and Dr. Yuntao Wei for their assistance
   with animal experiments.
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NR 49
TC 19
Z9 20
U1 2
U2 14
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 2017
VL 8
AR e2826
DI 10.1038/cddis.2017.141
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA EW0QG
UT WOS:000402195700021
PM 28542141
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Naga, SHA
   Dithmer, M
   Chitadze, G
   Kabelitz, D
   Lucius, R
   Roider, J
   Klettner, A
AF Naga, Shereen Hassan Aboul
   Dithmer, Michaela
   Chitadze, Guranda
   Kabelitz, Dieter
   Lucius, Ralph
   Roider, Johann
   Klettner, Alexa
TI Intracellular pathways following uptake of bevacizumab in RPE cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Bevacizumab; Actin-filament; Myosin7a; Exosomes; Retinal pigment
   epithelium
ID PIGMENT EPITHELIAL-CELLS; RECEPTOR-MEDIATED ENDOCYTOSIS; MACULAR
   DEGENERATION; VEGF-ANTAGONISTS; OXIDATIVE STRESS; TIGHT JUNCTION; OUTER
   SEGMENTS; 1B PROTEIN; IN-VITRO; EXOSOMES
AB The anti-VEGF antibody bevacizumab is widely used off-label for the treatment of various ocular diseases, most commonly in age-related macular degeneration and diabetic macular edema. Bevacizumab is able to penetrate the retina and is found in the choroid after intravitreal injection in a time dependent manner. It has previously been shown to be taken up by the retinal pigment epithelium (RPE). In this study, we have investigated the intracellular pathway following uptake of bevacizumab in RPE cells, tested both in primary porcine RPE cells and in the human cell line ARPE19. Bevacizumab displays a characteristic, time-dependent pattern of intracellular distribution, as detected by immunofluorescence and pulse chase experiments. In both primary cells and the cell line, intracellular bevacizumab can be found after seven days, as detected by immunofluorescence and Western blotting. Immediately after application, bevacizumab partially colocalizes with Rab5, indicating some uptake in early endosomes. Intracellularly, bevacizumab is detected in the cytoskeletal fraction, aligning with actin filaments, as revealed by subcellular fractioning and immunofluorescence. Bevacizumab seems to travel along actin filaments by myosin7a, as determined by triple staining immunofluorescence. Interestingly, over a period of seven days, bevacizumab seems to accumulate in certain storage areas, as observed by immunofluorescence. Furthermore, results obtained with immunocytochemistry, Western blotting and flow cytometry indicate that bevacizumab may be released from the RPE cells via exosomes. In conclusion, bevacizumab is taken up by and transported in the retinal pigment epithelial cells in a characteristic, time-dependent manner, where it seems to move along actin filaments by myosin7a and seem to be partially released from the cells via exosomes. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Naga, Shereen Hassan Aboul; Dithmer, Michaela; Roider, Johann; Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, D-24105 Kiel, Germany.
   [Naga, Shereen Hassan Aboul] Cairo Univ, Kasr Al Aini Fac Med, Cairo, Egypt.
   [Chitadze, Guranda; Kabelitz, Dieter] Univ Kiel, Univ Med Ctr, Inst Immunol, D-24105 Kiel, Germany.
   [Lucius, Ralph] Univ Kiel, Inst Anat, D-24105 Kiel, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; Egyptian
   Knowledge Bank (EKB); Cairo University; University of Kiel; Schleswig
   Holstein University Hospital; University of Kiel
RP Klettner, A (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3, D-24105 Kiel, Germany.
EM aklettner@auge.uni-kiel.de
RI Lucius, Ralph/B-1614-2010; Kabelitz, Dieter/A-2757-2010; Klettner, Alexa
   Karina/M-8344-2018; Hassan M. Aboul Naga, Shereen/GXV-8898-2022;
   Chitadze, Guranda/ABA-4545-2020; Kabelitz, Dieter/AAB-4199-2021
OI Chitadze, Guranda/0000-0001-9609-4643; Klettner,
   Alexa/0000-0002-2709-1059; H. Aboul Naga, Shereen/0000-0002-7167-0795
FU Deutsche Forschungsgemeinschaft [KL-2425/2-1]; Herrman-Wacker
   Foundation; DAAD Scholarship; Novartis Pharma
FX This study was financially supported by the Deutsche
   Forschungsgemeinschaft (KL-2425/2-1). AK is financed by the
   Herrman-Wacker Foundation. SHAN was a recipient of a DAAD Scholarship.
   Independently of this study, AK has been a consultant for and received
   research grants and lecture fees from Novartis Pharma. Parts of the data
   presented here were presented at the ARVO meeting 2013, the Norddeutsche
   Arztetagung 2013 and the DOG 2013.
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NR 53
TC 27
Z9 27
U1 0
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2015
VL 131
BP 29
EP 41
DI 10.1016/j.exer.2014.12.010
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CA5VA
UT WOS:000348974700004
PM 25533679
DA 2022-11-30
ER

PT J
AU Simader, C
   Sayegh, RG
   Montuoro, A
   Azhary, M
   Koth, AL
   Baratsits, M
   Sacu, S
   Prunte, C
   Kreil, DP
   Schmidt-Erfurth, U
AF Simader, Christian
   Sayegh, Ramzi G.
   Montuoro, Alessio
   Azhary, Malek
   Koth, Anna Lucia
   Baratsits, Magdalena
   Sacu, Stefan
   Pruente, Christian
   Kreil, David P.
   Schmidt-Erfurth, Ursula
TI A Longitudinal Comparison of Spectral-Domain Optical Coherence
   Tomography and Fundus Autofluorescence in Geographic Atrophy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; VISUAL IMPAIRMENT; CLASSIFICATION; RANIBIZUMAB;
   PATTERNS
AB PURPOSE: To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to monitor disease progression in geographic atrophy attributable to age-related macular degeneration (AMID) compared with lesion size determination based on fundus autofluorescence (FAF).
   DESIGN: Prospective longitudinal observational study.
   METHODS: SETTING: Institutional. STUDY POPULATION: A total of 48 eyes in 24 patients with geographic atrophy. OBSERVATION PROCEDURES: Eyes with geographic atrophy were included and examined at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were analyzed using the region overlay device. Planimetric measurements in SD OCT, including alterations or loss of outer retinal layers and " the RPE, as well as choroidal signal enhancement, were performed with the OCT Toolkit. MAIN OUTCOME MEASURES: Areas of interest in patients with geographic atrophy measured from baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF.
   RESULTS: Geographic atrophy lesion size increased from 8.88 mm(2) to 11.22 mm(2) based on quantitative FAF evaluation. Linear regression analysis demonstrated that results similar to FAF planimetry for determining lesion progression can be obtained by measuring the areas of outer plexiform layer thinning (adjusted R-2 = 0.93), external limiting membrane loss (adjusted R-2 = 0.89), or choroidal signal enhancement (R-2 = 0.93) by SD OCT.
   CONCLUSIONS: SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic AMD. (C) 2014 by Elsevier Inc. All rights reserved.
C1 [Simader, Christian; Sayegh, Ramzi G.; Montuoro, Alessio; Azhary, Malek; Koth, Anna Lucia; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Vienna Reading Ctr, Vienna, Austria.
   [Simader, Christian; Sayegh, Ramzi G.; Baratsits, Magdalena; Sacu, Stefan; Pruente, Christian; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Vienna, Austria.
   [Kreil, David P.] Univ Nat Resources & Life Sci, Dept Biotechnol, Vienna, Austria.
   [Kreil, David P.] Univ Warwick, Sch Life Sci, Coventry CV4 7AL, W Midlands, England.
C3 Medical University of Vienna; Medical University of Vienna; University
   of Natural Resources & Life Sciences, Vienna; University of Warwick
RP Sayegh, RG (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, Vienna, Austria.
EM ramzi.sayegh@meduniwien.ac.at
RI Kreil, D/O-1783-2013
OI Kreil, D/0000-0001-7538-2056; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311
FU Angioblast Systems; Bayer; Bohringer Ingelheim; Novartis; Alcon
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST. None of the authors have a propriety
   interest in any of the products mentioned in this study. The authors
   indicate the following financial disclosures: C.S. is director of the
   Vienna Reading Center at the Medical University of Vienna. The Vienna
   Reading Center receives money for data evaluations (money to
   institution): Angioblast Systems, Bayer, Bohringer Ingelheim, Novartis.
   C.P.: Consultancy (money to institution): Alcon, Bayer, Novartis;
   Grant/grants pending (money to institution): Bayer, Novartis; Payment
   for lectures including service on speakers bureaus (money to
   institution): Bayer, Novartis. U.S-E.: Consultancy: Alcon, Bayer,
   Bohringer Ingelheim, Novartis; Payment for lectures including service on
   speakers bureaus: Bayer, Novartis. The authors indicate no funding
   support. Contributions of authors: design and conduct of the study
   (C.S., R.S., S.S., C.P., D.K., U.S.-E.); collection, management,
   analysis, and interpretation of the data (C.S., R.S., A.M., M.A., A.K.,
   M.B., S.S., C.P., D.K., U.S.-E.); preparation, review, or approval of
   the manuscript (C.S., R.S., A.M., S.S., C.P., D.K., U.S.-E.).
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NR 26
TC 34
Z9 35
U1 0
U2 3
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 SEP
PY 2014
VL 158
IS 3
BP 557
EP 566
DI 10.1016/j.ajo.2014.05.026
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO2CZ
UT WOS:000341124400020
PM 24879944
DA 2022-11-30
ER

PT J
AU Bonnet, C
   Querques, G
   Zerbib, J
   Oubraham, H
   Garavito, RB
   Puche, N
   Souied, EH
AF Bonnet, Clemence
   Querques, Giuseppe
   Zerbib, Jennyfer
   Oubraham, Hassiba
   Garavito, Rocio B.
   Puche, Nathalie
   Souied, Eric H.
TI HYPERREFLECTIVE PYRAMIDAL STRUCTURES ON OPTICAL COHERENCE TOMOGRAPHY IN
   GEOGRAPHIC ATROPHY AREAS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; ghost drusen; soft
   drusen; retinal pigment epithelium; spectral domain optical coherence
   tomography
ID AGE-RELATED MACULOPATHY; SUBRETINAL DRUSENOID DEPOSITS; MACULAR
   DEGENERATION; RETICULAR PSEUDODRUSEN; BASAL DEPOSITS; UNESTERIFIED
   CHOLESTEROL; FUNDUS AUTOFLUORESCENCE; 10-YEAR INCIDENCE; SEVERITY SCALE;
   EYE DISEASE
AB Purpose: We observed hyperreflective dome-shaped or pyramidal structures (HPS) on spectral domain optical coherence tomography (SD-OCT) in patients affected with geographic atrophy (GA). Our purpose was to describe the multimodal imaging features of HPS identified in areas of GA in patients with age-related macular degeneration.
   Methods: This is a retrospective case series of patients with GA harboring HPS in atrophic areas. Multimodal imaging examination including infrared reflectance, fundus autofluorescence, and SD-OCT, was performed for each patient. Infrared and fundus autofluorescence appearance and mean SD-OCT height of HPS in GA were analyzed.
   Results: A total of 36 eyes of 25 patients (20 women; mean age, 82.3 +/- 5.9 years, range, 73-92 years) with GA were included. A total of 96 HPS in GA were analyzed by SD-OCT. In all HPS (96/96, 100%), the peripheral part was hyperreflective. In 66 of 96 HPS (69%), the center was heterogeneously hyperreflective, whereas in 30 of 96 HPS (31%), the center was hyporeflective. On infrared reflectance images, HPS in GA appeared as hyporeflective lesions surrounded by hyperreflective halos, within an area of background hyperreflectivity because of GA in all eyes. On fundus autofluorescence, 39 of 96 HPS (41%) were heterogeneously hyperautofluorescent, whereas 57 of 96 HPS (59%) were hypoautofluorescent. Mean height of HPS was 91 +/- 50.9 mu m in the foveal scan (range, 42-291 mu m).
   Conclusion: We describe a multimodal imaging of distinctive lesions that presented as hyperreflective pyramidal structures on SD-OCT. We suggest the name "ghost drusen" because these HPS appear in GA areas, and because of their pyramidal or dome-shaped aspect on SD-OCT.
C1 [Bonnet, Clemence; Querques, Giuseppe; Zerbib, Jennyfer; Oubraham, Hassiba; Garavito, Rocio B.; Puche, Nathalie; Souied, Eric H.] Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Souied, EH (通讯作者)，Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM eric.souied@chicreteil.fr
OI Querques, Giuseppe/0000-0002-3292-9581
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NR 44
TC 18
Z9 18
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 AUG
PY 2014
VL 34
IS 8
BP 1524
EP 1530
DI 10.1097/IAE.0000000000000165
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AM7ZE
UT WOS:000340086600011
PM 24736463
DA 2022-11-30
ER

PT J
AU Ha, JH
   Shil, PK
   Zhu, P
   Gu, LW
   Li, QH
   Chung, S
AF Ha, Jung-Heun
   Shil, Pollob Kumar
   Zhu, Ping
   Gu, Liwei
   Li, Qiuhong
   Chung, Soonkyu
TI Ocular Inflammation and Endoplasmic Reticulum Stress Are Attenuated by
   Supplementation with Grape Polyphenols in Human Retinal Pigmented
   Epithelium Cells and in C57BL/6 Mice
SO JOURNAL OF NUTRITION
LA English
DT Article
ID PROLIFERATIVE DIABETIC-RETINOPATHY; EXPERIMENTAL AUTOIMMUNE UVEITIS;
   ENDOTOXIN-INDUCED UVEITIS; FACTOR-KAPPA-B; MACULAR DEGENERATION;
   OXIDATIVE STRESS; VITIS ROTUNDIFOLIA; TIGHT JUNCTIONS; AQUEOUS-HUMOR;
   AGE
AB Inflammation and endoplasmic reticulum (ER) stress are common denominators for vision-threatening diseases such as diabetic retinopathy and age-related macular degeneration. Based on our previous study, supplementation with muscadine grape polyphenols (MGPs) alleviated systemic insulin resistance and proinflammatory responses. In this study, we hypothesized that MGPs would also be effective in attenuating ocular inflammation and ER stress. We tested this hypothesis using the human retinal pigmented epithelium (ARPE-19) cells and C57BL/6 mice. In ARPE-19 cells, tumor necrosis factor-a induced proinflammatory gene expression of interleukin (IL)-1 beta, IL-6, and monocyte chemotactic protein-1 was decreased by 35.0%, 68.8%, and 62.5%, respectively, with MGP pretreatment, which was primarily due to the diminished mitogen-activated protein kinase activation and subsequent reduction of nuclear factor kappa-B activation. Consistently, acute ocular inflammation and leukocyte infiltration were almost completely dampened (>95%) by MGP supplementation (100-200 mg/kg body weight) in C57BL/6 mice. Moreover, MGPs reduced inflammation-mediated loss of tight junctions and retinal permeability. To further investigate the protective roles of MGPs against ER stress, ARPE-19 cells were stimulated with thapsigargin. Pretreatment with MGPs significantly decreased the following: 1) ER stress-mediated vascular endothelial growth factor secretion (3.47 +/- 0.06 vs. 1.58 +/- 0.02 mu g/L, P < 0.0001), 2) unfolded protein response, and 3) early apoptotic cell death (64.4 +/- 6.85 vs. 33.7 +/- 4.32%, P = 0.0003). Collectively, we have demonstrated that MOP is effective in attenuating ocular inflammation and ER stress. Our work also suggests that MGP may provide a novel dietary strategy to prevent vision-threatening retinal diseases.
C1 [Ha, Jung-Heun; Gu, Liwei; Chung, Soonkyu] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA.
   [Shil, Pollob Kumar; Zhu, Ping; Li, Qiuhong] Univ Florida, Dept Ophthalmol, Gainesville, FL USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida
RP Chung, S (通讯作者)，Univ Nebraska, Dept Nutr & Hlth Sci, 316G Leverton Hall, Lincoln, NE 68583 USA.
EM schung4@unl.edu
OI Chung, Soonkyu/0000-0001-6279-7017; Shil, Pollob/0000-0002-3440-0059
FU Institute of Food and Agricultural Science (IFAS) at the University of
   Florida (USDA-Hatch); Florida Department of Agriculture and Consumer
   Service, Viticulture Research Program; NATIONAL EYE INSTITUTE
   [R01EY021752] Funding Source: NIH RePORTER
FX Supported by the Institute of Food and Agricultural Science (IFAS) at
   the University of Florida (USDA-Hatch) and partly by the Florida
   Department of Agriculture and Consumer Service, Viticulture Research
   Program.
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NR 54
TC 20
Z9 21
U1 0
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2014
VL 144
IS 6
BP 799
EP 806
DI 10.3945/jn.113.186957
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA AH9LZ
UT WOS:000336465200003
PM 24699803
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Homma, K
   Okamoto, S
   Mandai, M
   Gotoh, N
   Rajasimha, HK
   Chang, YS
   Chen, S
   Li, W
   Cogliati, T
   Swaroop, A
   Takahashi, M
AF Homma, Kohei
   Okamoto, Satoshi
   Mandai, Michiko
   Gotoh, Norimoto
   Rajasimha, Harsha K.
   Chang, Yi-Sheng
   Chen, Shan
   Li, Wei
   Cogliati, Tiziana
   Swaroop, Anand
   Takahashi, Masayo
TI Developing Rods Transplanted into the Degenerating Retina of
   Crx-Knockout Mice Exhibit Neural Activity Similar to Native
   Photoreceptors
SO STEM CELLS
LA English
DT Article
DE Retinal photoreceptors; Induced pluripotent stem cells; Cell
   transplantation; Calcium flux
ID PLURIPOTENT STEM-CELLS; NA+ ACTION-POTENTIALS; IN-VITRO; VISUAL
   FUNCTION; BIPOLAR CELLS; H-CURRENT; GENERATION; CHANNELS; CONE;
   DIFFERENTIATION
AB Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild-type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with green fluorescent protein (GFP) driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (I-h) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When trans-planted into the subretinal space of wild-type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wildtype mouse retina and exhibit Ca2+ responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within 2 weeks after transplantation into the retina of Crx-knockout mice and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter-driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell-replacement therapy.
C1 [Homma, Kohei; Okamoto, Satoshi; Mandai, Michiko; Takahashi, Masayo] RIKEN, Ctr Dev Biol, Lab Retinal Regenerat, Kobe, Hyogo, Japan.
   [Homma, Kohei; Gotoh, Norimoto; Rajasimha, Harsha K.; Chang, Yi-Sheng; Cogliati, Tiziana; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Chen, Shan; Li, Wei] NEI, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Chang, Yi-Sheng] Natl Cheng Kung Univ & Hosp, Dept Ophthalmol, Tainan, Taiwan.
C3 RIKEN; National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); National Institutes of Health (NIH) - USA; NIH National
   Eye Institute (NEI); National Cheng Kung University; National Cheng Kung
   University Hospital
RP Homma, K (通讯作者)，NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA.
EM kohei.homma@nih.gov
RI Okamoto, Satoshi/F-7309-2013; Homma, Kohei/AAF-6716-2021
OI Okamoto, Satoshi/0000-0003-4071-9696; Homma, Kohei/0000-0002-6253-8047;
   Swaroop, Anand/0000-0002-1975-1141
FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT);
   Ministry of Health Labor and Welfare; Japan Society for the Promotion of
   Science (JSPS); JSPS Postdoctoral Fellowships for Research Abroad
   (Kaitoku-NIH); National Eye Institute, National Institutes of Health,
   Bethesda, MD, USA; NATIONAL EYE INSTITUTE [ZIAEY000474] Funding Source:
   NIH RePORTER
FX We thank Itaru Arai and Masao Tachibana (University of Tokyo) for help
   in patch-clamp recording, Robert Farris (Biological Imaging Core,
   National Eye Institute) for Ca<SUP>2+</SUP> imaging, Linn Gieser for
   Affymetrix Chip analysis, Juthaporn Assawachananont for retinal
   differentiation culture, Kyoko Iseki, Chie Ishigami, and Chikako Yamada
   for technical support, and lab colleagues for helpful discussions. We
   are grateful to Takahisa Furukawa (Osaka Bioscience Institute) for
   providing Crx-knockout mice. This work was supported by Ministry of
   Education, Culture, Sports, Science, and Technology (MEXT), Ministry of
   Health Labor and Welfare, a grant-in-aid for Young Scientists (B) from
   Japan Society for the Promotion of Science (JSPS) (to KH), JSPS
   Postdoctoral Fellowships for Research Abroad (Kaitoku-NIH) (to KH), and
   by intramural research program of the National Eye Institute, National
   Institutes of Health, Bethesda, MD, USA.
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NR 63
TC 73
Z9 76
U1 0
U2 27
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 JUN
PY 2013
VL 31
IS 6
BP 1149
EP 1159
DI 10.1002/stem.1372
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 149QD
UT WOS:000319335200012
PM 23495178
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Blaha, M
   Kostal, M
   Lanska, M
   Blaha, V
   Foralova, I
   Filip, S
   Kubisova, M
   Maly, J
AF Blaha, M.
   Kostal, M.
   Lanska, M.
   Blaha, V.
   Foralova, I.
   Filip, S.
   Kubisova, M.
   Maly, J.
TI The decrease of mean platelet volume after extracorporeal
   LDL-cholesterol elimination
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Article
DE Mean platelet volume; Familial hyperlipoproteinemia; LDL-apheresis;
   Extracorporeal elimination; Therapeutic hemapheresis; Rheohemapheresis
ID CORONARY-ARTERY-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; THERAPY;
   APHERESIS; DIAGNOSIS; CHILDREN; DENSITY; SIZE
AB Objective: Mean platelet volume is arousing increasing interest as a new independent cardiovascular risk factor. Large platelets are likely to be more reactive. If mean platelet volume would drop after LDL-lowering therapy, decreased MPV could be one of the markers of successful therapy. Therefore, we investigated mean platelet volume after extracorporeal LDL-cholesterol elimination.
   Methods: Mean platelet volume was investigated in patients with severe familial hypercholesterolemia long-term treated (3-12 years) by LDL-apheresis (immunoapheresis) or cascade filtration. Plasma was obtained by centrifugation. Adsorbers Lipopak 400 were used for immunoapheresis and filters Evaflux 4A were used for cascade filtration. 95 pair samples were measured (before and after the procedures) in a group of 12 patients - each patient 8 times in 4 years.
   Results: Mean platelet volume before the procedures was 10.891 fl, CI 10.25-11.53. Mean platelet volume after the procedures decreased - 10.478 fl, CI 09.84-11.11. The difference is statistically significant (p = 0.036). Mean platelet volume did not correlate with age, sex, platelet count, duration of therapy. At the same time, we used rheohemapheresis in the therapy of 40 patients with age-related macular degeneration. But mean platelet volume was not changed.
   Conclusion: Mean platelet volume is easily available and is often disregarded, and sometimes may suggest the need for a careful assessment in patients with familial hypercholesterolemia. Mean platelet volume could be one of the markers of therapeutic efficacy in patients with familial hypercholesterolemia treated by extracorporeal LDL-cholesterol elimination that is simple and inexpensive. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Blaha, M.; Kostal, M.; Lanska, M.; Foralova, I.; Maly, J.] Charles Univ Prague, Sch Med, Dept Internal Med 2, Hradec Kralove, Czech Republic.
   [Blaha, M.; Kostal, M.; Lanska, M.; Blaha, V.; Foralova, I.; Kubisova, M.; Maly, J.] Teaching Hosp, Hradec Kralove, Czech Republic.
   [Blaha, V.; Kubisova, M.] Charles Univ Prague, Sch Med, Dept Gerontol & Metab, Hradec Kralove, Czech Republic.
   [Filip, S.] Charles Univ Prague, Sch Med, Dept Radiotherapy & Oncol, Hradec Kralove, Czech Republic.
C3 Charles University Prague; University Hospital Hradec Kralove; Charles
   University Prague; Charles University Prague
RP Blaha, M (通讯作者)，Dept Med 2, Sokolskast 408, Hradec Kralove 50005, Czech Republic.
EM blaham@email.cz
RI Filip, Stanislav/AAU-9160-2020; Kostal, Milan/S-8157-2018; Blaha,
   Vladimir/C-1151-2016; Kostal, Milan/ABE-3938-2020; Maly,
   Jaroslav/P-6660-2017; Blaha, Milan/H-8955-2016; Kostal,
   Milan/GRS-9847-2022; Filip, Stanislav/D-4908-2017
OI Kostal, Milan/0000-0002-0686-5852; Blaha, Vladimir/0000-0001-8088-9919;
   Maly, Jaroslav/0000-0003-4889-5504; Blaha, Milan/0000-0003-2330-5838;
   Kostal, Milan/0000-0002-0686-5852; Filip, Stanislav/0000-0002-8567-0745
FU Ministry of Health, CZ [NT/12287-5]
FX The study was supported by a grant from the Ministry of Health, CZ, No.
   NT/12287-5.
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NR 26
TC 8
Z9 8
U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JAN
PY 2013
VL 14
IS 1
BP 77
EP 81
DI 10.1016/j.atherosclerosissup.2012.10.019
PG 5
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 089BX
UT WOS:000314885000014
PM 23357146
DA 2022-11-30
ER

PT J
AU DeCarlo, DK
   McGwin, G
   Searcey, K
   Gao, LY
   Snow, M
   Waterbor, J
   Owsley, C
AF DeCarlo, Dawn K.
   McGwin, Gerald, Jr.
   Searcey, Karen
   Gao, Liyan
   Snow, Marsha
   Waterbor, John
   Owsley, Cynthia
TI Trial Frame Refraction versus Autorefraction among New Patients in a
   Low-Vision Clinic
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VISUAL-ACUITY; EYE
AB PURPOSE. To determine the relationship between refractive error as measured by autorefraction and that measured by trial frame refraction among a sample of adults with vision impairment seen in a university-based low-vision clinic and to determine if autorefraction might be a suitable replacement for trial frame refraction.
   METHODS. A retrospective chart review of all new patients 19 years or older seen over an 18-month period was conducted and the following data collected: age, sex, primary ocular diagnosis, entering distance visual acuity, habitual correction, trial frame refraction, autorefraction, and distance visual acuity measured after trial frame refraction. Trial frame refraction and autorefraction were compared using paired t-tests, intraclass correlations, and Bland-Altman plots.
   RESULTS. Final analyses included 440 patients for whom both trial frame refraction and autorefraction data were available for the better eye. Participants were mostly female (59%) with a mean age of 68 years (SD = 20). Age-related macular degeneration was the most common etiology for vision impairment (44%). Values for autorefraction and trial frame refraction were statistically different, but highly correlated for the spherical equivalent power (r = 0.92), the cylinder power (r = 0.80) and overall blurring strength (0.89). Although the values of the cross-cylinders J(0) and J(45) were similar, they were poorly correlated (0.08 and 0.15, respectively). The range of differences in spherical equivalent power was large (-8.6 to 4.9).
   CONCLUSIONS. Autorefraction is highly correlated with trial frame refraction. Differences are sometimes substantial, making autorefraction an unsuitable substitute for trial frame refraction. (Invest Ophthalmol Vis Sci. 2013; 54: 19-24) DOI: 10.1167/iovs.12-10508
C1 [DeCarlo, Dawn K.; McGwin, Gerald, Jr.; Searcey, Karen; Gao, Liyan; Owsley, Cynthia] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
   [DeCarlo, Dawn K.; Snow, Marsha] Univ Alabama Birmingham, Dept Optometry, Sch Optometry, Birmingham, AL USA.
   [McGwin, Gerald, Jr.; Waterbor, John] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Dept Surg, Sect Trauma Burns & Surg Crit Care, Div Gen Surg,Sch Med, 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;
   University of Alabama System; University of Alabama Birmingham
RP DeCarlo, DK (通讯作者)，CEFH 405,700 18th St S, Birmingham, AL 35233 USA.
EM ddecarlo@uab.edu
OI DeCarlo, Dawn/0000-0001-9078-9882
FU National Eye Institute [NEI K 23 EY018864]; EyeSight Foundation of
   Alabama; Research to Prevent Blindness; Able Trust; Alfreda J. Schueler
   Trust; NATIONAL EYE INSTITUTE [K23EY018864] Funding Source: NIH RePORTER
FX Supported by Grant NEI K 23 EY018864 from the National Eye Institute,
   and the EyeSight Foundation of Alabama, Research to Prevent Blindness,
   Able Trust, and Alfreda J. Schueler Trust.
CR American National Standards Institute (ANSI) Z80 Committee on Ophthalmic Optics, 2010, Z8012010 ANSI COMM O
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NR 24
TC 3
Z9 4
U1 1
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 JAN
PY 2013
VL 54
IS 1
BP 19
EP 24
DI 10.1167/iovs.12-10508
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 081QX
UT WOS:000314338400004
PM 23188726
OA Green Published
DA 2022-11-30
ER

PT J
AU Song, DL
   Song, Y
   Hadziahmetovic, M
   Zhong, Y
   Dunaief, JL
AF Song, Delu
   Song, Ying
   Hadziahmetovic, Majda
   Zhong, Yong
   Dunaief, Joshua L.
TI Systemic administration of the iron chelator deferiprone protects
   against light-induced photoreceptor degeneration in the mouse retina
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Deferiprone; Iron; Light damage; Retinal degeneration; Chelator
ID MACULAR DEGENERATION; OXIDATIVE DAMAGE; PIGMENT EPITHELIUM; POTENTIAL
   FACTOR; BRUCHS MEMBRANE; CERULOPLASMIN; THALASSEMIA; THERAPY;
   INFLAMMATION; ANTIOXIDANT
AB Oxidative stress plays a key role in a light-damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). Since iron can promote oxidative stress, the iron chelator deferiprone (DFP) was tested for protection against light-induced retinal degeneration. To accomplish this, A/J mice were treated with or without oral DFP and then were placed in constant bright white fluorescent light (10,000 lx) for 20 h. Retinas were evaluated at several time points after light exposure. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal degeneration was assessed by histology 10 days after exposure to damaging white light. Two genes upregulated by oxidative stress, heme oxygenase 1 (Hmox1) and ceruloplasmin (Cp), as well as complement component 3 (C3) were quantified by RT-qPCR. Cryosections were immunolabeled for an oxidative stress marker (nitrotyrosine), a microglial marker (Iba1), as well as both heavy (H) and light (L) ferritin. Light exposure resulted in substantial photoreceptor-specific cell death. Dosing with DFP protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of oxidative stress-related genes and C3 were upregulated following light exposure and diminished by DFP treatment. Immunostaining for nitrotyrosine indicated that DFP reduced the nitrative stress caused by light exposure. Robust H/L-ferritin-containing microglial activation and migration to the outer retina occurred after light exposure and DFP treatment reduced microglial invasion. DFP is protective against light-induced retinal degeneration and has the potential to diminish oxidative stress in the retina. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Song, Delu; Song, Ying; Hadziahmetovic, Majda; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Song, Delu; Zhong, Yong] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing 100730, Peoples R China.
   [Song, Delu; Zhong, Yong] Peking Union Med Coll, Beijing 100021, Peoples R China.
C3 University of Pennsylvania; Pennsylvania Medicine; Chinese Academy of
   Medical Sciences - Peking Union Medical College; Peking Union Medical
   College Hospital; Chinese Academy of Medical Sciences - Peking Union
   Medical College; Peking Union Medical College
RP Dunaief, JL (通讯作者)，Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Perelman Sch Med, 305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
FU NIH [R01 EY 015240]; Research to Prevent Blindness, State Scholarship
   Fund of the China Scholarship Council in the Ministry of Education of
   the P.R. China [2010621116]; F.M. Kirby Foundation; Paul and Evanina
   Bell Mackall Foundation Trust; ApoPharma, Inc.; ApoPharma; NATIONAL EYE
   INSTITUTE [R01EY015240] Funding Source: NIH RePORTER
FX We acknowledge the help of Dr. Gui-shuang Ying for biostatistics
   analysis. This work was supported by NIH R01 EY 015240, unrestricted
   funding from Research to Prevent Blindness, State Scholarship Fund (File
   no. 2010621116) of the China Scholarship Council in the Ministry of
   Education of the P.R. China, the F.M. Kirby Foundation, a gift in memory
   of Dr. Lee F. Mauger, the Paul and Evanina Bell Mackall Foundation
   Trust, and an unrestricted grant from ApoPharma, Inc. Dr. Dunaief and
   ApoPharma have a patent pending on the use of DFP for AMD, and Dr.
   Dunaief's lab receives research funding from ApoPharma.
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NR 60
TC 62
Z9 63
U1 3
U2 16
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 JUL 1
PY 2012
VL 53
IS 1
BP 64
EP 71
DI 10.1016/j.freeradbiomed.2012.04.020
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 966SJ
UT WOS:000305857400008
PM 22579919
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Schweitzer, D
   Jentsch, S
   Dawczynski, J
   Hammer, M
   Wolf-Schnurrbusch, UEK
   Wolf, S
AF Schweitzer, Dietrich
   Jentsch, Susanne
   Dawczynski, Jens
   Hammer, Martin
   Wolf-Schnurrbusch, Ute E. K.
   Wolf, Sebastian
TI Simple and objective method for routine detection of the macular pigment
   xanthophyll
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE macular pigment xanthophyll; objective detection; stray light; blue
   light; reflection; age-related macular degeneration; pseudophakic eye
ID EPITHELIAL-CELLS; SINGLET OXYGEN; LUTEIN; DEGENERATION; LIPOFUSCIN;
   ZEAXANTHIN; DENSITY; QUANTIFICATION; SPECTROMETRY; ANTIOXIDANTS
AB A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, mean-ODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R-2 = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491 +/- 0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615 +/- 0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610 +/- 0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674 +/- 0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3526358]
C1 [Schweitzer, Dietrich; Jentsch, Susanne; Dawczynski, Jens; Hammer, Martin] Univ Jena, Augenklin, D-07743 Jena, Germany.
   [Wolf-Schnurrbusch, Ute E. K.; Wolf, Sebastian] Univ Bern, Univ Eye Clin, Inselspital, Klin Augenheilkunde, CH-3010 Bern, Switzerland.
C3 Friedrich Schiller University of Jena; University of Hamburg; University
   Medical Center Hamburg-Eppendorf; University of Bern; University
   Hospital of Bern
RP Schweitzer, D (通讯作者)，Univ Jena, Augenklin, Bachstr 18, D-07743 Jena, Germany.
EM Dietrich.schweitzer@med.uni-jena.de
RI Wolf, Sebastian/B-8782-2008
OI Wolf, Sebastian/0000-0002-7467-7028
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NR 49
TC 33
Z9 34
U1 0
U2 11
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 NOV-DEC
PY 2010
VL 15
IS 6
AR 061714
DI 10.1117/1.3526358
PG 10
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 719AI
UT WOS:000287171100021
PM 21198162
OA Bronze
DA 2022-11-30
ER

PT J
AU Radtke, ND
   Aramant, RB
   Petry, HM
   Green, PT
   Pidwell, DJ
   Seiler, MJ
AF Radtke, Norman D.
   Aramant, Robert B.
   Petry, Heywood M.
   Green, Parke T.
   Pidwell, Diane J.
   Seiler, Magdalene J.
TI Vision improvement in retinal degeneration patients by implantation of
   retina together with retinal pigment epithelium
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GANGLION-CELL RESPONSES; GEOGRAPHIC ATROPHY; PHOTORECEPTOR DEGENERATION;
   MORPHOMETRIC ANALYSIS; VISUAL FUNCTION; TRANSPLANTATION; LIGHT; THERAPY;
   SHEETS; RESCUE
AB PURPOSE: To demonstrate efficacy and safety of the implantation of neural retinal progenitor cell layers (sheets) with its retinal pigment epithelium (RPE) in retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD) patients with 20/200 or worse vision in the surgery eye.
   DESIGN: Interventional nonrandomized clinical trial.
   METHODS: Ten patients (six RP, four AMD) received retinal implants in one eye and were followed in a phase II trial conducted in a clinical practice setting. Early Treatment Diabetic Retinopathy Study (EDTRS) was the prig mary outcome measure. All implant recipients and nine of 10 tissue donors were deoxyribonucleic acids typed.
   RESULTS: Seven patients (three RP, four AMD) showed improved EDTRS visual acuity (VA) scores. Three of these patients (one RP, two AMD) showed improvement in both eyes to the same extent. Vision in one RP patient remained the same, while vision in two RP patients de, creased. One RP patient has maintained an improvement in vision from 20/800 to 20/200 ETDRS for more than five years; at the six-year examination, it was still maintained at 20/320 while the nonsurgery eye had deteriorated to hand motion vision. This patient also showed a 22.72% increase in light sensitivity at five years compared to microperimetry results at two years; the other patients showed no improved sensitivity. Although no match was found between donors and recipients, no rejection of the implanted tissue was observed clinically.
   CONCLUSIONS: Seven (70%) of 10 patients showed improved VA. This outcome provides clinical evidence of the safety and beneficial effect of retinal implants and corroborates results in animal models of retinal degeneration.
C1 [Radtke, Norman D.] Univ Louisville, Retina Vitreous Resource Ctr, Louisville, KY 40217 USA.
   [Aramant, Robert B.; Seiler, Magdalene J.] Univ So Calif, Dept Ophthalmol, Doheny Retina Inst, Los Angeles, CA 90089 USA.
   [Aramant, Robert B.; Seiler, Magdalene J.] Univ Calif Irvine, Irvine, CA USA.
   [Green, Parke T.] Nidek Inc, Fremont, CA USA.
   [Pidwell, Diane J.] Jewish Hosp, Louisville, KY USA.
   [Pidwell, Diane J.] Cleveland Clin, Transplantat Ctr, Cleveland, OH 44106 USA.
C3 University of Louisville; University of Southern California; University
   of California System; University of California Irvine; Nidek Co., Ltd;
   Cleveland Clinic Foundation
RP Radtke, ND (通讯作者)，Univ Louisville, Retina Vitreous Resource Ctr, 240 Audubon Med Plaza, Louisville, KY 40217 USA.
EM nradtke@rvrc.com
RI Seiler, Magdalene J./I-2942-2019
OI Seiler, Magdalene J./0000-0002-0869-9923
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NR 47
TC 167
Z9 178
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD AUG
PY 2008
VL 146
IS 2
BP 172
EP 182
DI 10.1016/j.ajo.2008.04.009
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 333CD
UT WOS:000258128700005
PM 18547537
OA Green Published
DA 2022-11-30
ER

PT J
AU Foy, JWD
   Rittenhouse, K
   Modi, M
   Patel, M
AF Foy, Jeffrey W. -D.
   Rittenhouse, Kay
   Modi, Marlene
   Patel, Manju
TI Local tolerance and systemic safety of pegaptanib sodium in the dog and
   rabbit
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB AVASTIN; MACULAR
   DEGENERATION; FACTOR APTAMER; ANGIOGENESIS; RANIBIZUMAB; PHASE; TRIAL;
   NEOVASCULARIZATION; SURVIVAL
AB Purpose: To evaluate the local tolerance, systemic toxicity, and toxicokinetics in dogs and rabbits of pegaptanib sodium, an aptamer that targets vascular endothelial growth factor (VEGF(165))
   Methods: Dogs received biweekly, bilateral, intravitreous (IVT) injections of pegaptanib sodium for 9 months at doses of 0.3 (n = 10), 1 (n = 10), or 3 mg (n = 14); 14 control dogs received phosphate-buffered saline (PBS). In rabbits, pegaptanib sodium was administered by IVT injection biweekly for 6 months at doses of 0.2 (n = 14), 0.67 (n = 14), or 2 mg (n = 18); 18 rabbits; received PBS. The systemic and ocular safety of pegaptanib sodium was assessed. Assessments in both dogs and rabbits included complete ophthalmologic examinations, serum chemistry, hematology, urinalysis, and coagulation assessments, as well as gross and microscopic pathologic examination. In addition, dogs were assessed by electroretinography and electrocardiography. In a cardiovascular safety study, loading intravenous boluses and maintenance infusions of pegaptanib sodium or PBS were administered to dogs (n = 4) in an ascending dose design, with each dose level separated by 2-3 days. The pegaptanib dosing regimens were designed to achieve pegaptanib plasma concentrations of approximately 90, 270, or 900 ng/mL.
   Results: There were no pegaptanib sodium-associated clinical ophthalmologic, pathologic, or cardiovascular abnormalities at doses of pegaptanib that achieved systemic and ocular exposure levels in excess of those associated with the recommended pegaptanib IVT dosing regimen of 0.3 mg per study eye in patients with age-related macular degeneration.
   Conclusion: These studies, together with data from clinical trials, provide strong evidence that inhibition of VEGF(165) by pegaptanib in the eye is a safe therapy for the treatment of ocular neovascular disease.
C1 OSI Pharmaceut, Boulder, CO 80301 USA.
   Pfizer Inc, San Diego, CA USA.
   MWM Consulting Grp, Princeton, NJ USA.
   Pfizer Inc, New London, CT USA.
C3 Astellas Pharmaceuticals; OSI Pharmaceuticals; Pfizer; Pfizer
RP Foy, JWD (通讯作者)，OSI Pharmaceut, 2860 Wilderness Pl, Boulder, CO 80301 USA.
EM jfoy@osip.com
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NR 24
TC 34
Z9 37
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 OCT
PY 2007
VL 23
IS 5
BP 452
EP 466
DI 10.1089/jop.2006.0149
PG 15
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 221EP
UT WOS:000250210500005
PM 17900226
DA 2022-11-30
ER

PT J
AU Chen, X
   Xu, MH
   Zhang, XM
   Barnstable, CJ
   Li, XR
   Tombran-Tink, J
AF Chen, Xin
   Xu, Manhong
   Zhang, Xiaomin
   Barnstable, Colin J.
   Li, Xiaorong
   Tombran-Tink, Joyce
TI Deletion of the Pedf gene leads to inflammation, photoreceptor loss and
   vascular disturbances in the retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Vascular leakage; Inflammation; Apoptosis; Glia activation; Pedf(-/-)
ID EPITHELIUM-DERIVED FACTOR; PIGMENT EPITHELIUM; DIABETIC-RETINOPATHY;
   VEIN OCCLUSION; MACULAR EDEMA; EXPRESSION; PROTECTS; NEURONS
AB Retinal diseases are often accompanied by inflammation, vascular abnormalities, and neurodegeneration that decrease vision. Treatment with exogenous PEDF is widely shown to alleviate these conditions leading us to hypothesize that loss of function of the PEDF gene disrupts these pathways and leads to visual loss.
   Measurements were carried out by detailed phenotyping of PEDF null mice to assess expression of immuno-modulators, glia activation, systemic inflammation, vascular disturbances, and visual sensitivity often associated with retinal pathologies.
   With a deletion of the Pedf gene, there was increased expression of several immune modulators in Pedf(-/-) retinas and serum with IL-2 and GM-CSF upregulated in both. Increases in retina glia activation and macrophage infiltration, levels of serum c-reactive protein (CRP), numbers of white and red blood cells and platelets and decreased blood glucose levels were all features associated with PEDF null mice. With PEDF gene deletion, there was also a notable increase in apoptosis in early developing retinas (PN3), reduced thickness of the photoreceptor layer, swelling of the inner plexiform layer, reduced retinal sensitivity and steady-state reduced activation of Erk and Akt, two signaling pathways used by PEDF.
   There is a substantial body of animal data emphasizing utility of PEDF treatment in homeostatic regulation of retinal diseases, including diabetic retinopathy and age-related macular degeneration but there is little agreement or evidence on the role of endogenous PEDF in retinal diseases. Our findings strongly support the concept that a deletion of the PEDF gene makes the retina vulnerable to diseases, and argue that endogenous PEDF plays a critical role in limiting pathological events in the retina.
C1 [Chen, Xin; Xu, Manhong; Zhang, Xiaomin; Barnstable, Colin J.; Li, Xiaorong; Tombran-Tink, Joyce] Tianjin Med Univ Eye Hosp, Eye Inst, Tianjin Branch Natl Clin Res Ctr Ocular Dis, Tianjin Key Lab Retinal Funct & Dis, Tianjin 300384, Peoples R China.
   [Zhang, Xiaomin; Li, Xiaorong; Tombran-Tink, Joyce] Tianjin Med Univ Eye Hosp, Sch Optometry, Tianjin 300384, Peoples R China.
   [Barnstable, Colin J.; Tombran-Tink, Joyce] Penn State Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA.
   [Tombran-Tink, Joyce] Tianjin Med Univ Eye Hosp, Eye Inst, Penn State Coll Med Tianjin Key Lab Retinal Funct, Tianjin Branch Natl Clin Res Ctr Ocular Dis, Tianjin 300384, Peoples R China.
C3 Tianjin Medical University; Tianjin Medical University; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Pennsylvania State
   University; Penn State Health; Tianjin Medical University
RP Zhang, XM; Li, XR; Tombran-Tink, J (通讯作者)，Tianjin Med Univ Eye Hosp, Eye Inst, Tianjin Branch Natl Clin Res Ctr Ocular Dis, Tianjin Key Lab Retinal Funct & Dis, Tianjin 300384, Peoples R China.; Zhang, XM; Li, XR; Tombran-Tink, J (通讯作者)，Tianjin Med Univ Eye Hosp, Sch Optometry, Tianjin 300384, Peoples R China.; Tombran-Tink, J (通讯作者)，Tianjin Med Univ Eye Hosp, Eye Inst, Penn State Coll Med Tianjin Key Lab Retinal Funct, Tianjin Branch Natl Clin Res Ctr Ocular Dis, Tianjin 300384, Peoples R China.
EM xiaomzh@126.com; xiaorli@163.com; jttink@aol.com
OI Xu, Manhong/0000-0003-0548-6305
FU National Natural Science Foundation of China [81870675]; Tianjin
   Postgraduate Research Innovation Project [2021YJSB271]
FX This work was supported by the National Natural Science Foundation of
   China (82171085) , the Tianjin Postgraduate Research Innovation Project
   (2021YJSB271) , and the National Natural Science Foundation of China
   (81870675) .
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NR 53
TC 0
Z9 0
U1 3
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 SEP
PY 2022
VL 222
AR 109171
DI 10.1016/j.exer.2022.109171
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4Y9NW
UT WOS:000861849000001
PM 35809620
DA 2022-11-30
ER

PT J
AU Mahlumba, P
   Kumar, P
   du Toit, LC
   Poka, MS
   Ubanako, P
   Choonara, YE
AF Mahlumba, Pakama
   Kumar, Pradeep
   du Toit, Lisa C.
   Poka, Madan S.
   Ubanako, Philemon
   Choonara, Yahya E.
TI Fabrication and Characterisation of a Photo-Responsive, Injectable
   Nanosystem for Sustained Delivery of Macromolecules
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE zein; macromolecules; photo-responsive; nanospheres; sustained release;
   biodegradable; injectable; hydrogel
AB The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of >= 80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.
C1 [Mahlumba, Pakama; Kumar, Pradeep; du Toit, Lisa C.; Ubanako, Philemon; Choonara, Yahya E.] Univ Witwatersrand, Wits Adv Drug Delivery Platform Res Unit, Dept Pharm & Pharmacol, Sch Therapeut Sci,Fac Hlth Sci, 7 York Rd, ZA-2193 Parktown, South Africa.
   [Poka, Madan S.] Sefako Makgatho Hlth Sci Univ, Sch Pharm, Div Pharmaceut Sci, ZA-0208 Pretoria, South Africa.
C3 University of Witwatersrand; Sefako Makgatho Health Sciences University
RP Choonara, YE (通讯作者)，Univ Witwatersrand, Wits Adv Drug Delivery Platform Res Unit, Dept Pharm & Pharmacol, Sch Therapeut Sci,Fac Hlth Sci, 7 York Rd, ZA-2193 Parktown, South Africa.
EM pakama.mahlumba@students.wits.ac.za; pradeep.kumar@wits.ac.za;
   lisa.dutoit1@wits.ac.za; madan.poka@smu.ac.za;
   philemon.ubanako@wits.ac.za; yahya.choonara@wits.ac.za
RI Kumar, Pradeep/GQA-7930-2022; Choonara, Yahya E./B-2955-2013; Kumar,
   Pradeep/GQV-5790-2022; Kumar, Pradeep/C-9424-2013
OI Choonara, Yahya E./0000-0002-3889-1529; Kumar,
   Pradeep/0000-0002-8640-4350; POKA, MADAN SAI/0000-0001-7289-3408;
   Ubanako, Philemon/0000-0002-3281-8697
FU National Research Foundation (NRF) of South Africa
FX This research was funded by the National Research Foundation (NRF) of
   South Africa.
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NR 57
TC 3
Z9 3
U1 4
U2 30
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD APR
PY 2021
VL 22
IS 7
AR 3359
DI 10.3390/ijms22073359
PG 21
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA RL0DD
UT WOS:000638654200001
PM 33805969
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kawasaki, R
   Bauer, M
   Bezlyak, V
   Ogura, Y
AF Kawasaki, Ryo
   Bauer, Melissa
   Bezlyak, Vladimir
   Ogura, Yuichiro
TI Treatment patterns for retinal diseases in patients newly-treated with
   anti-VEGF agents: A retrospective analysis of claims data from the Japan
   Medical Data Center database
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anti-vascular endothelial growth factor agents; Diabetic macular edema;
   Japan medical data center; Neovascular age-related macular degeneration;
   Retinal vein occlusion
ID OCCLUSION 12-MONTH OUTCOMES; MACULAR EDEMA; SUSTAINED BENEFITS;
   RANIBIZUMAB; DEGENERATION; EFFICACY; REGIMEN; SAFETY; LASER
AB Purpose To describe treatment patterns in patients diagnosed with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), or diabetic macular edema (DME), newly-treated with anti-vascular endothelial growth factor (anti-VEGF) agents as recorded in the Japanese Medical Data Center (JMDC) database. Study design This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged >= 21 and <= 75 years at index date (anti-VEGF treatment initiation). Methods Patients with minimum one claim in JMDC database with a diagnosis code for nAMD, RVO, or DME between October 2007-May 2015 and with minimum of one claim for anti-VEGF agents on or after the date of diagnosis were included. Frequency and proportion of claims submitted for anti-VEGF injections were assessed during 12 months post-index date. Results The median (interquartile range) number of claims for anti-VEGF injections during 12 months post-index date were 3 (1, 4) for nAMD (n = 255), 2 (1, 3) for RVO (n = 223) and 2 (1, 4) for DME (n = 125) patients. Frequencies of nAMD, RVO and DME patients with one or more claims for a retinal disease treatment other than an anti-VEGF agent were 4 (1.57%), 59 (26.46%) and 68 (54.40%) during the 12 months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12 months post-index date, respectively. Conclusions The median number of anti-VEGF injections per patient was lower than those reported in clinical trials. Although various pre- and concomitant treatments were used in RVO and DME, anti-VEGF monotherapy was the first-line treatment in > 90% of nAMD patients.
C1 [Kawasaki, Ryo] Osaka Univ, Grad Sch Med, Dept Vis Informat, Osaka, Japan.
   [Bauer, Melissa] Novartis Global Serv Ctr, Real World Data Analyt, Dublin, Ireland.
   [Bezlyak, Vladimir] Novartis Pharma AG, Basel, Switzerland.
   [Ogura, Yuichiro] Nagoya City Univ, Dept Visual Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
C3 Osaka University; Novartis; Nagoya City University
RP Ogura, Y (通讯作者)，Nagoya City Univ, Dept Visual Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
EM ogura.yuichiro@me.com
RI Kawasaki, Ryo/B-7266-2009
OI Kawasaki, Ryo/0000-0002-7492-6303
FU Novartis Pharma, K.K., Tokyo, Japan
FX The study was sponsored by Novartis Pharma, K.K., Tokyo, Japan. The
   sponsor participated in the design of the study, conducting the study,
   data collection, data management, data analysis, interpretation of the
   data, preparation, review and approval of the manuscript.
CR Bernard AG, 2017, MACULART M PAR
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NR 30
TC 2
Z9 2
U1 1
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAR
PY 2021
VL 65
IS 2
BP 215
EP 226
DI 10.1007/s10384-020-00802-8
EA JAN 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QZ0AH
UT WOS:000606467400002
PM 33420855
DA 2022-11-30
ER

PT J
AU Achberger, K
   Probst, C
   Haderspeck, J
   Bolz, S
   Rogal, J
   Chuchuy, J
   Nikolova, M
   Cora, V
   Antkowiak, L
   Haq, W
   Shen, N
   Schenke-Layland, K
   Ueffing, M
   Liebau, S
   Loskill, P
AF Achberger, Kevin
   Probst, Christopher
   Haderspeck, Jasmin
   Bolz, Sylvia
   Rogal, Julia
   Chuchuy, Johanna
   Nikolova, Marina
   Cora, Virginia
   Antkowiak, Lena
   Haq, Wadood
   Shen, Nian
   Schenke-Layland, Katja
   Ueffing, Marius
   Liebau, Stefan
   Loskill, Peter
TI Merging organoid and organ-on-a-chip technology to generate complex
   multi-layer tissue models in a human retina-on-a-chip platform
SO ELIFE
LA English
DT Article
ID CHLOROQUINE RETINOPATHY; OCULAR TOXICITY; NEURAL RETINA; PHOTORECEPTORS;
   PROTEIN
AB The devastating effects and incurable nature of hereditary and sporadic retinal diseases such as Stargardt disease, age-related macular degeneration or retinitis pigmentosa urgently require the development of new therapeutic strategies. Additionally, a high prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. Ophthalmologic drug development, to date, largely relies on animal models, which often do not provide results that are translatable to human patients. Hence, the establishment of sophisticated human tissue-based in vitro models is of upmost importance. The discovery of self-forming retinal organoids (ROs) derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) is a promising approach to model the complex stratified retinal tissue. Yet, ROs lack vascularization and cannot recapitulate the important physiological interactions of matured photoreceptors and the retinal pigment epithelium (RPE). In this study, we present the retina-on-achip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell types derived from hiPSCs. It provides vasculature-like perfusion and enables, for the first time, the recapitulation of the interaction of mature photoreceptor segments with RPE in vitro. We show that this interaction enhances the formation of outer segment-like structures and the establishment of in vivo-like physiological processes such as outer segment phagocytosis and calcium dynamics. In addition, we demonstrate the applicability of the RoC for drug testing, by reproducing the retinopathic side-effects of the anti-malaria drug chloroquine and the antibiotic gentamicin. The developed hiPSC-based RoC has the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases.
C1 [Achberger, Kevin; Haderspeck, Jasmin; Nikolova, Marina; Cora, Virginia; Antkowiak, Lena; Liebau, Stefan] Eberhard Karls Univ Tubingen, INDB, Tubingen, Germany.
   [Probst, Christopher; Rogal, Julia; Chuchuy, Johanna; Haq, Wadood; Loskill, Peter] Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.
   [Bolz, Sylvia; Ueffing, Marius] Eberhard Karls Univ Tubingen, Ctr Ophthalmol, Inst Ophthalm Res, Tubingen, Germany.
   [Rogal, Julia; Chuchuy, Johanna; Shen, Nian; Schenke-Layland, Katja; Loskill, Peter] Eberhard Karls Univ Tubingen, Res Inst Womens Hlth, Dept Womens Hlth, Tubingen, Germany.
   [Schenke-Layland, Katja] Nat & Med Sci Inst NMI, Reutlingen, Germany.
   [Schenke-Layland, Katja] David Geffen Sch Med, Dept Med Cardiol, Cardiovasc Res Labs, Los Angeles, CA USA.
C3 Eberhard Karls University of Tubingen; Fraunhofer Gesellschaft; Eberhard
   Karls University of Tubingen; Eberhard Karls University Hospital;
   Eberhard Karls University of Tubingen; University of California System;
   University of California Los Angeles; University of California Los
   Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Liebau, S (通讯作者)，Eberhard Karls Univ Tubingen, INDB, Tubingen, Germany.; Loskill, P (通讯作者)，Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.; Loskill, P (通讯作者)，Eberhard Karls Univ Tubingen, Res Inst Womens Hlth, Dept Womens Hlth, Tubingen, Germany.
EM stefan.liebau@uni-tuebingen.de; peter.loskill@igb.fraunhofer.de
RI Schenke-Layland, Katja/E-5940-2013; Loskill, Peter/AAU-8978-2020;
   Loskill, Peter/D-9252-2013
OI Schenke-Layland, Katja/0000-0001-8066-5157; Nikolova, Marina
   Tsvetomilova/0000-0002-8212-049X; Loskill, Peter/0000-0002-5000-0581;
   Probst, Christopher/0000-0002-1380-0117
FU Fraunhofer-Gesellschaft
FX Fraunhofer-Gesellschaft Peter Loskill; Deutsche Forschungsgemeinschaft
   Katja Schenke-Layland Stefan Liebau; Horizon 2020 Framework Programme
   Peter Loskill; Ministerium fur Wissenschaft, Forschung und Kunst
   Baden-Wurttemberg Katja Schenke-Layland Peter Loskill; National Centre
   for the Replacement, Refinement and Reduction of Animals in Research
   Stefan Liebau Peter Loskill Hector Fellow Academy Wadood Haq; The
   funders had no role in study design, data collection and interpretation,
   or the decision to submit the work for publication.
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NR 49
TC 137
Z9 139
U1 22
U2 69
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD AUG 27
PY 2019
VL 8
AR e46188
DI 10.7554/eLife.46188
PG 26
WC Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics
GA JC0ZD
UT WOS:000489007400001
PM 31451149
OA Green Submitted, gold, Green Published
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Louer, EMM
   Lores-Motta, L
   Ion, AM
   Den Hollander, AI
   Deen, PMT
AF Louer, Elja M. M.
   Lores-Motta, Laura
   Ion, Ana Madalina
   Den Hollander, Anneke, I
   Deen, Peter M. T.
TI Single nucleotide polymorphism rs13079080 is associated with
   differential regulation of the succinate receptor 1 (SUCNR1) gene by
   miRNA-4470
SO RNA BIOLOGY
LA English
DT Article
DE SUCNR1; micro-RNA; gene expression; AMD; oxidative stress; retina
ID MACULAR DEGENERATION; GPR91; DATABASE; DRUSEN
AB Oxidative stress is a feature of many common diseases. It leads to excessive formation and subsequent release of the mitochondrial metabolite succinate, which acts as a signalling molecule through binding the succinate receptor (SUCNR1). Recently, a potential role for SUCNR1 was proposed in age-related macular degeneration (AMD), a common cause of vision loss in the elderly associated with increased oxidative stress. Here, we evaluated the potential effect of genetic variants in SUCNR1 on its expression through differential micro-RNA (miRNA) binding to target mRNA, and investigated the relevance of altered SUCNR1 expression in AMD pathogenesis. We analysed common SUCNR1 SNPs for potential miRNA binding sites and identified rs13079080, located in the 3MODIFIER LETTER PRIME-UTR and binding site for miRNA-4470. Both miRNA-4470 and SUCNR1 were found to be expressed in human retina. Moreover, using a luciferase reporter assay, a 60% decrease in activity was observed when miRNA-4470 was co-expressed with the C allele compared to the T allele of rs13079080. Finally, genotyping rs13079080 in an AMD case-control cohort revealed a protective effect of the TT genotype on AMD compared to the CC genotype (p = 0.007, odds ratio = 0.66). However, the association was not confirmed in the case-control study of the International AMD Genomics Consortium. Our study demonstrates that the T allele of rs13079080 in SUCNR1 disrupts a binding site for miRNA-4470, potentially increasing SUCNR1 expression and consequently increasing the capacity of sensing and dealing with oxidative stress. Therefore, it would be worthwhile assessing the relevance of rs13079080 in other oxidative stress-associated diseases in future studies.
C1 [Louer, Elja M. M.; Ion, Ana Madalina; Deen, Peter M. T.] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Physiol, Med Ctr, Nijmegen, Netherlands.
   [Louer, Elja M. M.; Lores-Motta, Laura; Ion, Ana Madalina; Den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands.
   [Den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Human Genet, Med Ctr, Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen
RP Deen, PMT (通讯作者)，Radboud Univ Nijmegen, Dept Physiol, Med Ctr, 286,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM Peter.Deen@radboudumc.nl
RI Louer, Elja M. M./R-1011-2017
OI Lores-Motta, Laura/0000-0002-2423-9126
FU RadboudUMC/RIMLS
FX We acknowledge the financial support of the RadboudUMC/RIMLS to PMTD and
   AdH for making this study possible.
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NR 33
TC 3
Z9 5
U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD NOV 2
PY 2019
VL 16
IS 11
BP 1547
EP 1554
DI 10.1080/15476286.2019.1643100
EA JUL 2019
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA JA7RN
UT WOS:000480863100001
PM 31304868
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Lee, CS
   Larson, EB
   Gibbons, LE
   Latimer, CS
   Rose, SE
   Hellstern, LL
   Keene, CD
   Crane, PK
AF Lee, Cecilia S.
   Larson, Eric B.
   Gibbons, Laura E.
   Latimer, Caitlin S.
   Rose, Shannon E.
   Hellstern, Leanne L.
   Keene, C. Dirk
   Crane, Paul K.
CA Adult Changes Thought ACT Study
TI Ophthalmology-Based Neuropathology Risk Factors: Diabetic Retinopathy is
   Associated with Deep Microinfarcts in a Community-Based Autopsy Study
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Alzheimer's disease; diabetic retinopathy; glaucoma; macular
   degeneration; neuropathology
ID GANGLION-CELL LOSSES; VISUAL-FIELD DEFECTS; ALZHEIMERS-DISEASE;
   COGNITIVE IMPAIRMENT; MACULAR DEGENERATION; NATIONAL INSTITUTE;
   GRAY-MATTER; DEMENTIA; AGE; PATHOLOGY
AB Background: The aging eye offers unique opportunities to study and understand the aging brain, in particular related to Alzheimer's disease (AD) and dementia. However, little is known about relationships between eye diseases and dementia-related neurodegeneration.
   Objective: To determine the potential association between three age-related eye diseases and AD and dementia-related neuropathology.
   Methods: We reviewed autopsy data from the prospective longitudinal Adult Changes in Thought (ACT) cohort. ICD-9 codes were used to identify diagnoses of diabetic retinopathy, glaucoma, and age-related macular degeneration. Multivariate regression models were used to determine odds ratios (OR) of neuropathology features associated with dementia, including Braak stage, Consortium to Establish a Registry for AD (CERAD score), Lewy bodies, hippocampal sclerosis, and microvascular brain injury, in addition to quantitative paired helical filament (PHF)-tau levels for people with and without each eye condition. We also evaluated interactions between eye conditions and dementia related neuropathologic findings were evaluated.
   Results: 676 autopsies were included. Diabetic retinopathy was significantly associated with increased risk of deep cerebral microinfarcts (OR = 1.91 [95% confidence interval (CI) 1.11, 3.27], p = 0.02). No other significant association or interaction between eye diseases and neuropathology was found. When PHF-tau quantity was evaluated in 124 decedents, the OR for the association between PHF-tau in the occipital cortex and glaucoma was 1.36 (95% CI 0.91, 2.03, p = 0.13). No statistical correction was made for multiple comparisons.
   Conclusion: Increased risk of deep cerebral microinfarcts was found in participants diagnosed with diabetic retinopathy. Eye diseases such as glaucoma may increase susceptibility to neurofibrillary tangles in the occipital cortex.
C1 [Lee, Cecilia S.] Univ Washington, Dept Ophthalmol, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA.
   [Larson, Eric B.] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
   [Gibbons, Laura E.; Crane, Paul K.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
   [Latimer, Caitlin S.; Rose, Shannon E.; Hellstern, Leanne L.; Keene, C. Dirk] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Kaiser
   Permanente; University of Washington; University of Washington Seattle;
   University of Washington; University of Washington Seattle
RP Lee, CS (通讯作者)，Univ Washington, Dept Ophthalmol, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA.
EM leecs2@uw.edu
RI Melief, Erica/M-6436-2019
FU NIH/NEI [K23EY02 492]; NIH/NIA [AG U01 0006781, P50 AG05136]; Research
   to Prevent Blindness; Nancy and Buster Alvord Endowment (CDK); NATIONAL
   EYE INSTITUTE [K23EY024921] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [P50AG005136, U01AG006781] Funding Source: NIH
   RePORTER
FX This work was supported by NIH/NEI K23EY02 492; NIH/NIA AG U01 0006781,
   P50 AG05136, Unrestricted Grant from Research to Prevent Blindness,
   Nancy and Buster Alvord Endowment (CDK) and Royalties from UpToDate. The
   sponsors/funding organizations had no role in the design or conduct of
   this research.S
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NR 47
TC 5
Z9 6
U1 2
U2 2
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 1387-2877
EI 1875-8908
J9 J ALZHEIMERS DIS
JI J. Alzheimers Dis.
PY 2019
VL 68
IS 2
BP 647
EP 655
DI 10.3233/JAD-181087
PG 9
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA HR1FP
UT WOS:000462875000021
PM 30883356
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chen, X
   Han, RF
   Hao, P
   Wang, LM
   Liu, MX
   Jin, MH
   Kong, DX
   Li, X
AF Chen, Xi
   Han, Ruifang
   Hao, Peng
   Wang, Liming
   Liu, Meixin
   Jin, Meihua
   Kong, Dexin
   Li, Xuan
TI Nepetin inhibits IL-1 beta induced inflammation via NF-kappa B and MAPKs
   signaling pathways in ARPE-19 cells
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE Nepetin; Inflammation; ARPE-19; NF-kappa B; MAPK
ID RETINAL-PIGMENT EPITHELIUM; CYTOKINE PRODUCTION; MACULAR EDEMA;
   EXPRESSION; EUPAFOLIN; IL-6; AGE; KERATINOCYTES; INTERLEUKIN-6;
   ACTIVATION
AB Backgrounds: Chronic inflammation in retinal pigment epithelial (RPE) cells is related to the pathogenesis of retinal inflammatory blind causing diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Nepetin, a natural flavonoid compound, has shown potent anti-inflammatory activities but has not been studied on ocular resident cells yet. Here, we assess the ability of Nepetin to alleviate the inflammatory responses of ARPE-19 cells induced by interleukin (IL)-1 beta.
   Methods: The secretion and mRNA expression of inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by IL-1 beta are measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) respectively. To clarify the underlying action mechanism, we examine the effect of Nepetin on activation of nuclear factor of kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways using Western blot.
   Results: Nepetin can significantly decrease the three inflammatory mediators at both protein and mRNA level in a dose-dependent manner. Western blot results show that Nepetin can decrease the nuclear translocation of p65 through suppressing phosphorylation of inhibitor of nuclear factor kappa B (I kappa B) and I.B kinase (IKK). Also, Nepetin can decrease the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, c-Jun N-terminal kinase (JNK) and p38 MAPK.
   Conclusions: Taken together, Nepetin abolishes IL-1 beta-induced IL-6, IL-8 and MCP-1 secretion and mRNA expression by repressing the activation of NF-kappa B and MAPKs. These results indicate that Nepetin shows potential to be used for prevention and treatment of inflammatory retinal diseases or as a lead compound.
C1 [Chen, Xi; Han, Ruifang; Hao, Peng; Wang, Liming; Liu, Meixin; Li, Xuan] Tianjin Eye Hosp, Tianjin Eye Inst, Tianjin Key Lab Ophthalmol & Visual Sci, Tianjin 300020, Peoples R China.
   [Chen, Xi; Han, Ruifang; Hao, Peng; Wang, Liming; Liu, Meixin; Li, Xuan] Tianjin Med Univ, Clin Coll Ophthalmol, Tianjin 300020, Peoples R China.
   [Chen, Xi; Han, Ruifang; Hao, Peng; Wang, Liming; Liu, Meixin; Li, Xuan] Nankai Univ, Affiliated Eye Hosp, Tianjin 300020, Peoples R China.
   [Chen, Xi; Jin, Meihua; Kong, Dexin] Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China.
   [Kong, Dexin] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China.
C3 Tianjin Medical University; Tianjin Medical University; Nankai
   University; Tianjin Medical University; Tianjin Medical University
RP Li, X (通讯作者)，Tianjin Eye Hosp, Tianjin Eye Inst, Tianjin Key Lab Ophthalmol & Visual Sci, Tianjin 300020, Peoples R China.
EM xuanli08@yahoo.com
FU National Natural Science Foundation of China [81170828, 81670837];
   Tianjin Science & Technology Foundation [15JCZDJC35300]; Tianjin Health
   and Family Planning Communication Foundation [14KG133]; Youth Project of
   Tianjin Applied Basic Research and Cuttingedge Technology Research
   Programs [15JCQNJC45000, 15JCQNJC11000]
FX This work was supported by grants from the National Natural Science
   Foundation of China (81170828; 81670837), the Tianjin Science &
   Technology Foundation (15JCZDJC35300), the Tianjin Health and Family
   Planning Communication Foundation (14KG133) and the Youth Project of
   Tianjin Applied Basic Research and Cuttingedge Technology Research
   Programs (15JCQNJC45000, 15JCQNJC11000).
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NR 51
TC 37
Z9 40
U1 0
U2 16
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 2018
VL 101
BP 87
EP 93
DI 10.1016/j.biopha.2018.02.054
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA GC2BG
UT WOS:000429586400010
PM 29477475
DA 2022-11-30
ER

PT J
AU Reiner, A
   Fitzgerald, MEC
   Del Mar, N
   Li, CY
AF Reiner, Anton
   Fitzgerald, Malinda E. C.
   Del Mar, Nobel
   Li, Chunyan
TI Neural control of choroidal blood flow
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Ciliary ganglion; Pterygopalatine ganglion; Superior cervical ganglion;
   Parasympathetic; Sympathetic; Choroidal blood flow; Ocular blood flow;
   Uvea
ID VASOACTIVE INTESTINAL POLYPEPTIDE; NITRIC-OXIDE SYNTHASE; HYPOTHALAMIC
   PARAVENTRICULAR NUCLEUS; EDINGER-WESTPHAL NUCLEUS; PARASYMPATHETIC
   PREGANGLIONIC NEURONS; ENDOTHELIUM-DEPENDENT REGULATION; CHICKEN
   SUPRACHIASMATIC NUCLEI; PEPTIDE IMMUNOREACTIVE NERVES; SUPERIOR
   SALIVATORY NUCLEUS; CENTRAL RETINAL ARTERY
AB The choroid is richly innervated by parasympathetic, sympathetic and trigeminal sensory nerve fibers that regulate choroidal blood flow in birds and mammals, and presumably other vertebrate classes as well. The parasympathetic innervation has been shown to vasodilate and increase choroidal blood flow, the sympathetic input has been shown to vasoconstrict and decrease choroidal blood flow, and the sensory input has been shown to both convey pain and thermal information centrally and act locally to vasodilate and increase choroidal blood flow. As the choroid lies behind the retina and cannot respond readily to retinal metabolic signals, its innervation is important for adjustments in flow required by either retinal activity, by fluctuations in the systemic blood pressure driving choroidal perfusion, and possibly by retinal temperature. The former two appear to be mediated by the sympathetic and parasympathetic nervous systems, via central circuits responsive to retinal activity and systemic blood pressure, but adjustments for ocular perfusion pressure also appear to be influenced by local autoregulatory myogenic mechanisms. Adaptive choroidal responses to temperature may be mediated by trigeminal sensory fibers. Impairments in the neural control of choroidal blood flow occur with aging, and various ocular or systemic diseases such as glaucoma, age-related macular degeneration (AMD), hypertension, and diabetes, and may contribute to retinal pathology and dysfunction in these conditions, or in the case of AMD be a precondition. The present manuscript reviews findings in birds and mammals that contribute to the above summarized understanding of the roles of the autonomic and sensory innervation of the choroid in controlling choroidal blood flow, and in the importance of such regulation for maintaining retinal health.
C1 [Reiner, Anton; Fitzgerald, Malinda E. C.; Del Mar, Nobel; Li, Chunyan] Univ Tennessee, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA.
   [Reiner, Anton; Fitzgerald, Malinda E. C.] Univ Tennessee, Dept Ophthalmol, 855 Monroe Ave, Memphis, TN 38163 USA.
   [Fitzgerald, Malinda E. C.] Christian Bros Univ, Dept Biol, Memphis, TN USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center
RP Reiner, A (通讯作者)，Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA.
EM areiner@uthsc.edu
RI Reiner, Anton/AAG-8860-2020
OI Reiner, Anton/0000-0002-2146-5232
FU Methodist Hospitals Endowed Professorship in Neuroscience; University of
   Tennessee Neuroscience Institute; Department of Ophthalmology of the
   University of Tennessee Health Science Center (MECF); Research to
   Prevent Blindness (MECF);  [NIH-EY-05298]; NATIONAL EYE INSTITUTE
   [P30EY003039, R01EY005298] Funding Source: NIH RePORTER
FX Special thanks to Rebeca-Ann Weinstock, Raven Babcock, Amanda Valencia,
   Aminah Henderson, Marion Joni, Ting Wong, Julia Jones, Felicia
   Covington, Karen Hanks, Shani Bell, Christy Loggins, Dr. Christopher
   Meade, Dr. Yun Jiao, and Dr. Seth Jones for assistance and/ or advice
   during the course of our studies. Our work has been supported by
   NIH-EY-05298 (AR), The Methodist Hospitals Endowed Professorship in
   Neuroscience (AR), the University of Tennessee Neuroscience Institute
   (CL), and the Department of Ophthalmology of the University of Tennessee
   Health Science Center (MECF), and an unrestricted grant from Research to
   Prevent Blindness (MECF).
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   Zhang J, 2000, J PHYSIOL-LONDON, V529, P431, DOI 10.1111/j.1469-7793.2000.00431.x
NR 369
TC 73
Z9 74
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAY
PY 2018
VL 64
BP 96
EP 130
DI 10.1016/j.preteyeres.2017.12.001
PG 35
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GK9AV
UT WOS:000436529700006
PM 29229444
OA hybrid, Green Accepted
DA 2022-11-30
ER

PT J
AU Szabo, D
   Sandor, GL
   Toth, G
   Pek, A
   Lukacs, R
   Szalai, I
   Toth, GZ
   Papp, A
   Nagy, ZZ
   Limburg, H
   Nemeth, J
AF Szabo, Dorottya
   Sandor, Gabor Laszlo
   Toth, Gabor
   Pek, Anita
   Lukacs, Regina
   Szalai, Iren
   Toth, Georgina Zsofia
   Papp, Andras
   Nagy, Zoltan Zsolt
   Limburg, Hans
   Nemeth, Janos
TI Visual impairment and blindness in Hungary
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE avoidable blindness; epidemiology; rapid assessment; visual impairment
ID DIABETIC-RETINOPATHY; AVOIDABLE BLINDNESS; RAPID ASSESSMENT; PREVALENCE;
   PROGRAM
AB AimThe aim of this study was to estimate the prevalence and causes of blindness, severe visual impairment (SVI), moderate visual impairment (MVI), and early visual impairment (EVI) and its causes in an established market economy of Europe.
   DesignA cross-sectional population-based survey.
   MethodsA sample size of 3675 was calculated using the standard Rapid Assessment of Avoidable Blindness (RAAB) software in Hungary. A total of 105 clusters of 35 people aged 50years or older were randomly selected with probability proportionate to size by the Hungarian Central Statistical Office. Households within the clusters were selected using compact segment sampling. Visual acuity (VA) was assessed with a Snellen tumbling E-chart with or without a pinhole in the households.
   ResultsThe adjusted prevalences of bilateral blindness, SVI, MVI and EVI were 0.9% (95% CI: 0.6-1.2), 0.5% (95% CI: 0.2-0.7), 5.1% (95% CI: 4.3-5.9) and 6.9% (95% CI: 5.9-7.9), respectively. The major causes of blindness in Hungary were age-related macular degeneration (AMD; 27.3%) and other posterior segment diseases (27.3%), cataract (21.2%) and glaucoma (12.1%). Cataract was the main cause of SVI, MVI and EVI. Cataract surgical coverage (CSC) was 90.7%. Of all bilateral blindness in Hungary, 45.5% was considered avoidable.
   ConclusionThis study proved that RAAB methodology can be successfully conducted in industrialized countries, which often lack reliable epidemiologic data. The prevalence of blindness was relatively low, with AMD and other posterior segment diseases being the leading causes, and cataract is still a significant cause of visual impairment.
C1 [Szabo, Dorottya; Sandor, Gabor Laszlo; Toth, Gabor; Pek, Anita; Lukacs, Regina; Szalai, Iren; Toth, Georgina Zsofia; Papp, Andras; Nagy, Zoltan Zsolt; Nemeth, Janos] Semmelweis Univ, Dept Ophthalmol, 39 Maria Str, H-1085 Budapest, Hungary.
   [Pek, Anita] Petz Aladar Hosp, Dept Ophthalmol, Gyor, Hungary.
   [Lukacs, Regina] Flor Ferenc Hosp, Dept Ophthalmol, Budapest, Hungary.
   [Limburg, Hans] Hlth Informat Serv, Grootebroek, Netherlands.
C3 Semmelweis University
RP Nemeth, J (通讯作者)，Semmelweis Univ, Dept Ophthalmol, 39 Maria Str, H-1085 Budapest, Hungary.
EM nemeth.janos@med.semmelweis-univ.hu
RI Sandor, Gabor Laszlo/P-9924-2019
OI Sandor, Gabor Laszlo/0000-0002-2484-9848; Toth,
   Gabor/0000-0002-9176-9442; Nemeth, Janos/0000-0001-8575-4888
FU Lions Clubs International Foundation; National Institute of the Blind;
   Hungarian Lions Clubs; Hungarian Central Statistical Office; Hungarian
   Diabetes Society; 77 Elektronika Co
FX This research project was made possible with a SightFirst research grant
   from the Lions Clubs International Foundation. We also like to thank the
   National Institute of the Blind, the Hungarian Lions Clubs, the
   Hungarian Central Statistical Office, the Hungarian Diabetes Society,
   and 77 Elektronika Co for their active support during the planning and
   implementation of this study. We also thank to Serge Resnikoff for his
   important comments. The results were partially presented as a poster in
   the ARVO 2016 Meeting in Seattle, USA. Ethics committee approval: The
   study was approved by Semmelweis University Regional and Institutional
   Committee of Science and Research Ethics.
CR Al Ghamdi AH, 2012, BRIT J OPHTHALMOL, V96, P1168, DOI 10.1136/bjophthalmol-2012-301874
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NR 22
TC 15
Z9 16
U1 0
U2 9
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAR
PY 2018
VL 96
IS 2
BP 168
EP 173
DI 10.1111/aos.13542
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FW5PL
UT WOS:000425369200043
PM 28834193
DA 2022-11-30
ER

PT J
AU Boopathy, GTK
   Kulkarni, M
   Ho, SY
   Boey, A
   Chua, EWM
   Barathi, VA
   Carney, TJ
   Wang, XM
   Hong, WJ
AF Boopathy, Gandhi T. K.
   Kulkarni, Madhura
   Ho, Sze Yuan
   Boey, Adrian
   Chua, Edmond Wei Min
   Barathi, Veluchamy A.
   Carney, Tom J.
   Wang, Xiaomeng
   Hong, Wanjin
TI Cavin-2 regulates the activity and stability of endothelial nitric-oxide
   synthase (eNOS) in angiogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OXYGEN-INDUCED RETINOPATHY; PATHOLOGICAL ANGIOGENESIS;
   DIABETIC-RETINOPATHY; VASCULAR DEVELOPMENT; IN-VIVO; CAVEOLAE;
   MICROPARTICLES; MEMBRANE; CELLS; ACTIVATION
AB Angiogenesis is a highly regulated process for formation of new blood vessels from pre-existing ones. Angiogenesis is dysregulated in various pathologies, including age-related macular degeneration, arthritis, and cancer. Inhibiting pathological angiogenesis therefore represents a promising therapeutic strategy for treating these disorders, highlighting the need to study angiogenesis in more detail. To this end, identifying the genes essential for blood vessel formation and elucidating their function are crucial for a complete understanding of angiogenesis. Here, focusing on potential candidate genes for angiogenesis, we performed a morpholino-based genetic screen in zebrafish and identified Cavin-2, a membrane-bound phosphatidylserine-binding protein and critical organizer of caveolae (small microdomains in the plasma membrane), as a regulator of angiogenesis. Using endothelial cells, we show that Cavin-2 is required for in vitro angiogenesis and also for endothelial cell proliferation, migration, and invasion. We noted a high level of Cavin-2 expression in the neovascular tufts in the mouse model of oxygen-induced retinopathy, suggesting a role for Cavin-2 in pathogenic angiogenesis. Interestingly, we also found that Cavin-2 regulates the production of nitric oxide (NO) in endothelial cells by controlling the stability and activity of the endothelial nitric-oxide synthase (eNOS) and that Cavin-2 knockdown cells produce much less NO than WT cells. Also, mass spectrometry, flow cytometry, and electron microscopy analyses indicated that Cavin-2 is secreted in endothelial microparticles (EMPs) and is required for EMP biogenesis. Taken together, our results indicate that in addition to its function in caveolae biogenesis, Cavin-2 plays a critical role in endothelial cell maintenance and function by regulating eNOS activity.
C1 [Boopathy, Gandhi T. K.; Boey, Adrian; Chua, Edmond Wei Min; Carney, Tom J.; Wang, Xiaomeng; Hong, Wanjin] ASTAR, IMCB, 61 Biopolis Dr, Singapore 138673, Singapore.
   [Kulkarni, Madhura; Ho, Sze Yuan; Carney, Tom J.; Wang, Xiaomeng] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
   [Barathi, Veluchamy A.; Wang, Xiaomeng] SERI, 20 Coll Rd, Singapore 169856, Singapore.
   [Barathi, Veluchamy A.] Duke NUS Grad Med Sch, Ophthalmol & Visual Sci Acad Clin Program, 8 Coll Rd, Singapore 169857, Singapore.
   [Barathi, Veluchamy A.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Boopathy, Gandhi T. K.; Barathi, Veluchamy A.; Carney, Tom J.; Wang, Xiaomeng; Hong, Wanjin] SERI IMCB, SERI IMCB Programme Retinal Angiogen Dis SIPRAD, Singapore, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of
   Molecular & Cell Biology (IMCB); Nanyang Technological University &
   National Institute of Education (NIE) Singapore; Nanyang Technological
   University; National University of Singapore; National University of
   Singapore
RP Boopathy, GTK; Hong, WJ (通讯作者)，ASTAR, IMCB, 61 Biopolis Dr, Singapore 138673, Singapore.
EM gandhibtk@imcb.a-star.edu.sg; mcbhwj@imcb.a-star.edu.sg
RI Boey, Adrian/AAC-4239-2022; Carney, Tom J/H-4389-2011; Carney, Tom
   James/ACF-9214-2022; Wang, Xiaomeng/F-9504-2015
OI Carney, Tom J/0000-0003-2371-1924; Carney, Tom
   James/0000-0003-2371-1924; T. K. Boopathy, Gandhi/0000-0002-1821-9540;
   Boey, Adrian/0000-0003-2835-6159; Wang, Xiaomeng/0000-0002-1036-2764
FU Agency for Science, Technology and Research (A*STAR); SERI-IMCB
   Programme in Retinal Angiogenic Diseases (SIPRAD)
FX This work was supported by Agency for Science, Technology and Research
   (A*STAR) funds (to W. H.) and the SERI-IMCB Programme in Retinal
   Angiogenic Diseases (SIPRAD). The authors declare that they have no
   conflicts of interest with the contents of this article.
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NR 64
TC 22
Z9 23
U1 1
U2 4
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 OCT 27
PY 2017
VL 292
IS 43
BP 17760
EP 17776
DI 10.1074/jbc.M117.794743
PG 17
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA FL1ZL
UT WOS:000414013000015
PM 28912276
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Mrowicka, M
   Mrowicki, J
   Szaflik, JP
   Szaflik, M
   Ulinska, M
   Szaflik, J
   Majsterek, I
AF Mrowicka, Malgorzata
   Mrowicki, Jerzy
   Szaflik, Jacek Pawel
   Szaflik, Marta
   Ulinska, Magdalena
   Szaflik, Jerzy
   Majsterek, Ireneusz
TI Analysis of antioxidative factors related to AMD risk development in the
   polish patients
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; antioxidant enzyme; genetic
   polymorphism; the polish population
ID MANGANESE SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION;
   GENETIC-POLYMORPHISM; CHINESE PATIENTS; PROSTATE-CANCER;
   ENZYME-ACTIVITY; BREAST-CANCER; GPX ACTIVITY; ASSOCIATION; PEROXIDASE
AB PurposeAge-related macular degeneration (AMD) is a major cause of blindness in developed countries. Oxidative mechanisms may play a key role in the aetiology of AMD. The main aim of this study was to investigate antioxidative markers in the pathogenesis of AMD.
   MethodsA total of 510 subjects including 240 patients with AMD (mean age 77.98.5year) and 270 controls (mean age 74.010.4year) were allowed in this study. We measured activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and examined their association with the SNPs of respective genes (SOD1+35A/C, CAT C-262T and GPx Pro197Leu). Restriction fragment length polymorphism (RFLP) technique was used to determine the selected gene polymorphisms. Sixty subjects including 30 patients with AMD (mean age 69.4 +/- 9.3) and 30 controls (mean age 64.6 +/- 8.2) were enrolled to determine the activity of antioxidant enzymes by spectrometry method.
   ResultsA significant decrease in enzymes, SOD (p=0.011), CAT (p=0.002) and GPx (p0.001) in AMD patients compared to controls, was indicated. The risk of susceptibility to AMD was significantly higher in patients with AMD who had Pro197Leu C/T genotype of GPx (OR=2.78; 95% CI=1.78-4.35). The A/C genotype and the C allele frequencies of A/C polymorphism of SOD1 gene significantly reduce the risk of AMD (OR=0.48; 95% CI 0.27; 0.85).
   ConclusionIn conclusion, our data showed that insufficient antioxidant capacity may have an important role in age-related macular degeneration. The polymorphism of GPx Pro197Leu may reduce the ability to scavenge free radicals in retina and contribute to the development of AMD.
C1 [Mrowicka, Malgorzata; Mrowicki, Jerzy; Majsterek, Ireneusz] Med Univ Lodz, Dept Clin Chem & Biochem, Hallera 1 Sq, PL-90647 Lodz, Poland.
   [Szaflik, Jacek Pawel; Ulinska, Magdalena; Szaflik, Jerzy] Med Univ Warsaw, Dept Ophthalmol, SPKSO Ophthalm Hosp, Warsaw, Poland.
   [Szaflik, Marta] Med Univ, Dept Ophthalmol, Fac Med 1, Ophthalmol Ctr Laser, Warsaw, Poland.
C3 Medical University Lodz; Medical University of Warsaw
RP Mrowicka, M (通讯作者)，Med Univ Lodz, Dept Clin Chem & Biochem, Hallera 1 Sq, PL-90647 Lodz, Poland.
EM malgorzata.mrowicka@umed.lodz.pl
RI Mrowicka, Malgorzata/S-6633-2016
OI Szaflik, Jerzy/0000-0002-7601-1326; Ulinska,
   Magdalena/0000-0001-9252-9996; Majsterek, Ireneusz/0000-0001-6231-3334;
   Mrowicka, Malgorzata/0000-0003-1018-730X
FU Medical University of Lodz [503/5-108-05/503-51-001]
FX This work was supported by Medical University of Lodz
   (503/5-108-05/503-51-001).
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NR 36
TC 12
Z9 12
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD AUG
PY 2017
VL 95
IS 5
BP 530
EP 536
DI 10.1111/aos.13289
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FA4BJ
UT WOS:000405388500032
PM 27935234
DA 2022-11-30
ER

PT J
AU Lopez-Perrote, A
   Harrison, RES
   Subias, M
   Alcorlo, M
   de Cordoba, SR
   Morikis, D
   Llorca, O
AF Lopez-Perrote, Andres
   Harrison, Reed E. S.
   Subias, Marta
   Alcorlo, Martin
   Rodriguez de Cordoba, Santiago
   Morikis, Dimitrios
   Llorca, Oscar
TI Ionic tethering contributes to the conformational stability and function
   of complement C3b
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Complement; C3b; S-variant; F-variant; Polymorphisms; Electron
   microscopy
ID HEMOLYTIC-UREMIC SYNDROME; ELECTRON-MICROSCOPY; ACTIVATION; CONVERTASE;
   INSIGHTS; PROTEIN; ASSOCIATION; REGULATORS; MUTATIONS; MECHANISM
AB C3b, the central component of the alternative pathway (AP) of the complement system, coexists as a mixture of conformations in solution. These conformational changes can affect interactions with other proteins and complement regulators. Here we combine a computational model for electrostatic interactions within C3b with molecular imaging to study the conformation of C3b. The computational analysis shows that the TED domain in C3b is tethered ionically to the macroglobulin (MG) ring. Monovalent counterion concentration affects the magnitude of electrostatic forces anchoring the TED domain to the rest of the C3b molecule in a thermodynamic model. This is confirmed by observing NaCl concentration dependent conformational changes using single molecule electron microscopy (EM). We show that the displacement of the TED domain is compatible with C3b binding to Factor B (FB), suggesting that the regulation of the C3bBb convertase could be affected by conditions that promote movement in the TED domain. Our molecular model also predicts mutations that could alter the positioning of the TED domain, including the common R102G polymorphism, a risk variant for developing age-related macular degeneration. The common C3b isoform, C3bS, and the risk isoform, C3bF, show distinct energetic barriers to displacement in the TED that are related to a network of electrostatic interactions at the interface of the TED and MG-ring domains of Ob. These computational predictions agree with experimental evidence that shows differences in conformation observed in C3b isoforms purified from homozygous donors. Altogether, we reveal an ionic, reversible attachment of the TED domain to the MG ring that may influence complement regulation in some mutations and polymorphisms of C3b. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Lopez-Perrote, Andres; Subias, Marta; Alcorlo, Martin; Rodriguez de Cordoba, Santiago; Llorca, Oscar] CSIC, Ctr Invest Biol, Madrid, Spain.
   [Harrison, Reed E. S.; Morikis, Dimitrios] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
   [Subias, Marta; Rodriguez de Cordoba, Santiago] Ctr Invest Biomed Enfermedades Raras, Madrid, Spain.
   [Alcorlo, Martin] CSIC, Inst Phys Chemistry Rocasolano, Dept Crystal & Struct Biol, Madrid, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de
   Investigaciones Biologicas (CIB); University of California System;
   University of California Riverside; CIBER - Centro de Investigacion
   Biomedica en Red; CIBERER; Consejo Superior de Investigaciones
   Cientificas (CSIC)
RP de Cordoba, SR; Llorca, O (通讯作者)，CSIC, Ctr Invest Biol, Madrid, Spain.; Morikis, D (通讯作者)，Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.; de Cordoba, SR (通讯作者)，Ctr Invest Biomed Enfermedades Raras, Madrid, Spain.
EM srdecordoba@cib.csic.es; dmorikis@ucr.edu; ollorca@cib.csic.es
RI Llorca, Oscar/K-1144-2014; Llorca, Oscar/P-2784-2019; Morikis,
   Dimitrios/L-8527-2013; Rodriguez de Cordoba, Santiago/K-6727-2014
OI Llorca, Oscar/0000-0001-5705-0699; Llorca, Oscar/0000-0001-5705-0699;
   Morikis, Dimitrios/0000-0003-0083-4665; Rodriguez de Cordoba,
   Santiago/0000-0001-6401-1874; Harrison, Reed/0000-0003-2512-4344
FU Spanish Ministry of Economy and Competitiveness [SAF2011-26583,
   SAF2014-52301-R]; Fundacion Renal Inigo Alvarez de Toledo; Seventh
   Framework Programme European Union Project EURenOmics [305608];
   Autonomous Region of Madrid [52010/BMD-2316]
FX Work in this report has been funded by the Spanish Ministry of Economy
   and Competitiveness (SAF2011-26583 to SRC and SAF2014-52301-R to OL),
   the Fundacion Renal Inigo Alvarez de Toledo and the Seventh Framework
   Programme European Union Project EURenOmics (305608) to SRC. In
   addition, this work has been supported by a grant from the Autonomous
   Region of Madrid (52010/BMD-2316) to SRC and OL.
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NR 37
TC 3
Z9 3
U1 0
U2 9
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 MAY
PY 2017
VL 85
BP 137
EP 147
DI 10.1016/j.molimm.2016.12.015
PG 11
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA EU0RO
UT WOS:000400719200016
PM 28254726
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Zhang, YH
   Wang, XL
   Rivero, EB
   Clark, ME
   Witherspoon, CD
   Spaide, RF
   Girkin, CA
   Owsley, C
   Curcio, CA
AF Zhang, Yuhua
   Wang, Xiaolin
   Rivero, Ernesto Blanco
   Clark, Mark E.
   Witherspoon, Clark Douglas
   Spaide, Richard F.
   Girkin, Christopher A.
   Owsley, Cynthia
   Curcio, Christine A.
TI Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as
   Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETICULAR PSEUDODRUSEN; MACULAR DEGENERATION; CHOROIDAL THICKNESS;
   GEOGRAPHIC ATROPHY; HIGH-RISK; EYES; AUTOFLUORESCENCE; PREVALENCE;
   REFLECTANCE; SENSITIVITY
AB PURPOSE: To describe the microscopic structure of photoreceptors impacted by subretinal drusenoid deposits, also called pseudodrusen, an extracellular lesion associated with age-related macular degeneration (AMD), using adaptive optics scanning laser ophthalmoscopy (AOSLO).
   DESIGN: Observational case series.
   METHODS: We recruited 53 patients with AMD and 10 age-similar subjects who had normal retinal health. All subjects underwent color fundus photography, infrared reflectance, red-free reflectance, autofluorescence, and spectral-domain optical coherence tomography (OCT). Subretinal drusenoid deposits were classified by a 3-stage OCT-based grading system. Lesions and surrounding photoreceptors were examined by AOSLO.
   RESULTS: Subretinal drusenoid deposits were found in 26 eyes of 13 patients with AMD and imaged by AOSLO and spectral-domain OCT in 18 eyes (n = 342 lesions). Spectral-domain OCT showed subretinal drusenoid deposits as highly reflective material accumulated internal to the retinal pigment epithelium. AOSLO revealed that photoreceptor reflectivity was qualitatively reduced by stage 1 subretinal drusenoid deposits and was greatly reduced by stage 2. AOSLO presented a distinct structure in stage 3, a hyporeflective annulus consisting of deflected, degenerated or absent photoreceptors. A central core with a reflectivity superficially resembling photoreceptors is formed by the lesion material itself. A hyporeflective gap in the photoreceptor ellipsoid zone on either side of this core shown in spectral-domain OCT corresponded to the hyporeflective annulus seen by AOSLO.
   CONCLUSIONS: AOSLO and multimodal imaging of subretinal drusenoid deposits indicate solid, space-filling lesions in the subretinal space. Associated retinal reflectivity changes are related to lesion stages and are consistent with perturbations to photoreceptors, as suggested by histology. (C) 2014 by Elsevier Inc. All rights reserved.
C1 [Zhang, Yuhua; Wang, Xiaolin; Rivero, Ernesto Blanco; Clark, Mark E.; Witherspoon, Clark Douglas; Girkin, Christopher A.; Owsley, Cynthia; Curcio, Christine A.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA.
   [Spaide, Richard F.] Vitreous Retina Macula Consultants New York, New York, NY USA.
C3 University of Alabama System; University of Alabama Birmingham; Vitreous
   Retina Macula Consultants of New York
RP Zhang, YH (通讯作者)，Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Volker Hall 390C,1670 Univ Blvd, Birmingham, AL 35294 USA.
EM zhanghua@uab.edu
RI Spaide, Richard/ABD-7368-2020
OI Girkin, Christopher/0000-0002-5781-7682; Witherspoon,
   Clark/0000-0003-4456-9437
FU Topcon; Bausch Lomb; EyeSight Foundation of Alabama; International
   Retinal Research Foundation [5R21EY021903]; Songs for Sight; Buck Trust
   of Alabama;  [R01AG04212];  [R01EY06109]; NATIONAL EYE INSTITUTE
   [R01EY006109, R21EY021903, P30EY003039] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [R01AG004212] Funding Source: NIH RePORTER
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST. Dr Spaide receives consultant and
   royalty payment support from Topcon and receives consultant payment
   support from Bausch & Lomb. This project was supported in part by the
   EyeSight Foundation of Alabama (Y.Z.); the International Retinal
   Research Foundation (Y.Z.), 5R21EY021903 (YZ); Songs for Sight (C.A.G.);
   the Buck Trust of Alabama (C.A.G.); R01A004212 (C.O.); R01EY06109
   (C.C.); and institutional support from Research to Prevent Blindness,
   EyeSight Foundation of Alabama, Buck Trust of Alabama, and National
   Institutes of Health P30 EY003039. A part of this work was presented at
   the ARVO 2013 annual meeting. Conception and design of study (Y.Z.,C.O.,
   C.A.C.); Analysis and interpretation of data (Y.Z., X.W., C.A.C.);
   Writing of manuscript (Y.Z.); Critical revision of manuscript (Y.Z.,
   C.A.G., R.F.S., C.O., C.A.C.); Final approval of manuscript (Y.Z., X.W.,
   E.B.R., M.E.C.,C.D.W., R.F.S., C.A.G., CO., C.A.C.); Data collection
   (Y.Z., X.W., E.B.R., M.E.C.); Obtaining of funding (Y.Z., C.A.G., C.O.,
   C.A.C.); Literature search (Y.Z., R.F.S., C.A.C.); Technical support and
   clinical supervision (C.D.W.).
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NR 66
TC 72
Z9 92
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2014
VL 158
IS 3
BP 584
EP 596
DI 10.1016/j.ajo.2014.05.038
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO2CZ
UT WOS:000341124400023
PM 24907433
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Pauly, D
   Nagel, BM
   Reinders, J
   Killian, T
   Wulf, M
   Ackermann, S
   Ehrenstein, B
   Zipfel, PF
   Skerka, C
   Weber, BHF
AF Pauly, Diana
   Nagel, Benedikt M.
   Reinders, Joerg
   Killian, Tobias
   Wulf, Matthias
   Ackermann, Susanne
   Ehrenstein, Boris
   Zipfel, Peter F.
   Skerka, Christine
   Weber, Bernhard H. F.
TI A Novel Antibody against Human Properdin Inhibits the Alternative
   Complement System and Specifically Detects Properdin from Blood Samples
SO PLOS ONE
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; IMMUNE-COMPLEXES; FACTOR-H; IN-VITRO;
   FACTOR-B; ACTIVATION; PATHWAY; DEFICIENCY; CONVERTASE; PROTEINS
AB The complement system is an essential part of the innate immune system by acting as a first line of defense which is stabilized by properdin, the sole known positive regulator of the alternative complement pathway. Dysregulation of complement can promote a diversity of human inflammatory diseases which are treated by complement inhibitors. Here, we generated a novel blocking monoclonal antibody (mAb) against properdin and devised a new diagnostic assay for this important complement regulator. Mouse mAb 1340 specifically detected native properdin from human samples with high avidity. MAb 1340 inhibited specifically the alternative complement mediated cell lysis within a concentration range of 110 mg/mL. Thus, in vitro anti-properdin mAb 1340 was up to fifteen times more efficient in blocking the complement system as compared to anti-C5 or anti-Ba antibodies. Computer-assisted modelling suggested a three-dimensional binding epitope in a properdin-C3(H2O)-clusterin complex to be responsible for the inhibition. Recovery of properdin in a newly established sandwich ELISA using mAb 1340 was determined at 80-125% for blood sample dilutions above 1:50. Reproducibility assays showed a variation below 25% at dilutions less than 1:1,000. Systemic properdin concentrations of healthy controls and patients with age-related macular degeneration or rheumatic diseases were all in the range of 13-30 mg/mL and did not reveal significant differences. These initial results encourage further investigation into the functional role of properdin in the development, progression and treatment of diseases related to the alternative complement pathway. Thus, mAb 1340 represents a potent properdin inhibitor suitable for further research to understand the exact mechanisms how properdin
C1 [Pauly, Diana; Nagel, Benedikt M.; Killian, Tobias; Wulf, Matthias; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Reinders, Joerg] Univ Regensburg, Inst Funct Genom, D-93053 Regensburg, Germany.
   [Ackermann, Susanne; Zipfel, Peter F.; Skerka, Christine] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
   [Ehrenstein, Boris] Asklepios Klinikum Bad Abbach, Klin & Poliklin Rheumatol & Klin Immunol, Bad Abbach, Germany.
   [Zipfel, Peter F.] Univ Jena, Dept Infect Biol, Jena, Germany.
C3 University of Regensburg; University of Regensburg; Hans Knoll Institute
   (HKI); Friedrich Schiller University of Jena
RP Pauly, D (通讯作者)，Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
EM Diana.pauly@klinik.uni-regensburg.de; bweb@klinik.uni-regensburg.de
OI Wulf, Matthias/0000-0002-6240-4874; Ackermann,
   Susanne/0000-0001-8179-5201; Weber, Bernhard H.F./0000-0002-8808-7723;
   Reinders, Joerg/0000-0003-1025-7849
FU PRO RETINA foundation; German Research Foundation (DFG) [DFG Sk46/2-1,
   WE1259/18-1, WE1259/19-1]; Ruth and Milton Steinbach Foundation New
   York; Alcon Research Institute
FX This work was supported by a grant from the PRO RETINA foundation
   (http://www.pro-retina.de, DP) and in part by grants from the German
   Research Foundation (DFG, http://www.dfg.de/) DFG Sk46/2-1 (CS)
   WE1259/18-1 (BHFW), WE1259/19-1 (BHFW), The Ruth and Milton Steinbach
   Foundation New York (BHFW) and the Alcon Research Institute
   (http://www.alcon.com/, BHFW). 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 84
TC 32
Z9 32
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 5
PY 2014
VL 9
IS 5
AR e96371
DI 10.1371/journal.pone.0096371
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AI1ZV
UT WOS:000336656000070
PM 24797388
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Iriyama, A
   Oba, M
   Ishii, T
   Nishiyama, N
   Kataoka, K
   Tamaki, Y
   Yanagi, Y
AF Iriyama, Aya
   Oba, Makoto
   Ishii, Takehiko
   Nishiyama, Nobuhiro
   Kataoka, Kazunori
   Tamaki, Yasuhiro
   Yanagi, Yasuo
TI Gene Transfer Using Micellar Nanovectors Inhibits Choroidal
   Neovascularization In Vivo
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; FACTOR RECEPTOR;
   POLYPLEX NANOMICELLES; RANIBIZUMAB; THERAPY; PEGAPTANIB; CELLS; RATS;
   SUPPRESSION
AB Purpose: Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model.
   Methods: The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7.
   Results: Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01).
   Conclusions: Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA.
C1 [Iriyama, Aya] Tokyo Metropolitan Geriatr Hosp, Tokyo 173, Japan.
   [Iriyama, Aya; Tamaki, Yasuhiro; Yanagi, Yasuo] Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 113, Japan.
   [Oba, Makoto] Univ Tokyo, Dept Clin Vasc Regenerat, Grad Sch Med, Bunkyo Ku, Tokyo, Japan.
   [Ishii, Takehiko; Kataoka, Kazunori] Univ Tokyo, Dept Bioengn, Grad Sch Engn, Bunkyo Ku, Tokyo, Japan.
   [Nishiyama, Nobuhiro; Kataoka, Kazunori] Univ Tokyo, Ctr Dis Biol & Integrat Med, Grad Sch Med, Bunkyo Ku, Tokyo, Japan.
   [Kataoka, Kazunori] Univ Tokyo, Dept Mat Engn, Grad Sch Engn, Bunkyo Ku, Tokyo, Japan.
C3 Tokyo Metropolitan Institute of Gerontology; University of Tokyo;
   University of Tokyo; University of Tokyo; University of Tokyo;
   University of Tokyo
RP Iriyama, A (通讯作者)，Tokyo Metropolitan Geriatr Hosp, Tokyo 173, Japan.
EM akagi-tky@umin.ac.jp
RI Yanagi, Yasuo/AAF-2670-2020; Yanagi, Yasuo/AAA-5441-2022; Kataoka,
   Kazunori/K-7108-2012; Nishiyama, Nobuhiro/F-1867-2014
OI Kataoka, Kazunori/0000-0002-8591-413X; Nishiyama,
   Nobuhiro/0000-0002-6886-9357; Oba, Makoto/0000-0002-3691-3608; Yanagi,
   Yasuo/0000-0002-0362-7285
FU Ministry of Education, Science, Sports and Culture of Japan
FX The work is supported in part by a grant-in-aid from the Ministry of
   Education, Science, Sports and Culture of Japan. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. No additional external funding received
   for this study.
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NR 34
TC 9
Z9 10
U1 0
U2 5
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 DEC 5
PY 2011
VL 6
IS 12
AR e28560
DI 10.1371/journal.pone.0028560
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 863NX
UT WOS:000298172800047
PM 22162776
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Li, XQ
   Larsen, M
   Munch, IC
AF Li, Xiao Qiang
   Larsen, Michael
   Munch, Inger Christine
TI Subfoveal Choroidal Thickness in Relation to Sex and Axial Length in 93
   Danish University Students
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; CENTRAL SEROUS CHORIORETINOPATHY;
   REFRACTIVE ERRORS; RISK-FACTORS; PREVALENCE; MYOPIA; EYE; ESTROGEN; AGE;
   HERITABILITY
AB PURPOSE. To investigate the association between subfoveal choroidal thickness and ocular axial length, refractive error, and blood pressure in healthy young women and men.
   METHODS. Cross-sectional observational study of 93 eyes in 93 healthy Danish university students (mean age 24.9 +/- 2.6 years). The submacular choroid was imaged using enhanced-depth imaging spectral domain optical coherence tomography. Subfoveal choroidal thickness was measured by visual inspection and manual fitting of the choroidal borderlines. Study parameters included history, best corrected visual acuity, objective refraction, interferometric ocular axial length, fundus photography, and blood pressure manometry.
   RESULTS. The mean subfoveal choroidal thickness was 342 (+/- 118) mu m, the mean age was 24.9 (+/- 2.6) years and the mean refractive error of participants was -1.43 (+/- 2.9) diopters (D). In a multiple regression model, subfoveal choroidal thickness decreased by 58.2 mu m (95% confidence interval [CI], 42.2-74.2 mu m; P < 0.001) per mm increase in axial length adjusted for age and sex and subfoveal choroidal thickness was 62 mu m (95% CI, 21-104 mu m; P = 0.0039) thicker in men than in women, adjusted for age and axial length. Arterial blood pressure had no statistical effect on subfoveal choroidal thickness.
   CONCLUSIONS. In this study of healthy young participants choroidal thickness was 18% higher in men than in women when adjusting for age and axial length. This observation may help explain the effect of sex in conditions related to choroidal thickness such as myopia, central serous chorioretinopathy, and age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2011;52:8438-8441) DOI:10.1167/iovs.11-8108
C1 [Li, Xiao Qiang; Larsen, Michael; Munch, Inger Christine] Glostrup Cty Hosp, Dept Ophthalmol, DK-2600 Glostrup, Denmark.
   [Li, Xiao Qiang; Larsen, Michael; Munch, Inger Christine] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
   [Larsen, Michael] Kennedy Ctr, Glostrup, Denmark.
C3 University of Copenhagen; University of Copenhagen
RP Li, XQ (通讯作者)，Glostrup Cty Hosp, Dept Ophthalmol, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
EM xlii0005@glo.regionh.dk
RI Munch, Inger Christine/E-9652-2010; Larsen, Michael/E-9620-2010
OI Larsen, Michael/0000-0002-5172-5891
FU Bagenkop-Nielsen Foundation
FX Supported by the Bagenkop-Nielsen Foundation.
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NR 40
TC 199
Z9 206
U1 0
U2 12
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 OCT
PY 2011
VL 52
IS 11
BP 8438
EP 8441
DI 10.1167/iovs.11-8108
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 846MN
UT WOS:000296907700028
PM 21917938
DA 2022-11-30
ER

PT J
AU Jain, N
   Farsiu, S
   Khanifar, AA
   Bearelly, S
   Smith, RT
   Izatt, JA
   Toth, CA
AF Jain, Nieraj
   Farsiu, Sina
   Khanifar, Aziz A.
   Bearelly, Srilaxmi
   Smith, R. Theodore
   Izatt, Joseph A.
   Toth, Cynthia A.
TI Quantitative Comparison of Drusen Segmented on SD-OCT versus Drusen
   Delineated on Color Fundus Photographs
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; GEOGRAPHIC ATROPHY; GRADING SYSTEM; RISK;
   AUTOFLUORESCENCE; RECONSTRUCTION; EYES
AB PURPOSE. Spectral domain-optical coherence tomography (SD-OCT) may be useful for efficient measurement of drusen in patients with age-related macular degeneration (AMD). Areas identified as drusen from semiautomated segmentation of drusen on SD-OCT were compared to those identified from review of digital color fundus photographs (CFPs).
   METHODS. Twelve eyes with nonneovascular AMD were prospectively imaged with digital CFP and SD-OCT. For each eye, areas on CFP in which at least two of three retina specialists agreed on drusen presence produced the composite CFP drusen map. Automated image analysis produced another CFP map. Areas identified as drusen by segmentation on SD-OCT B-scans were plotted as the SD-OCT drusen map. The CFP and SD-OCT maps were compared and agreement was quantified. Disagreement was characterized into distinct types, and the frequency of each type was quantified.
   RESULTS. There was general agreement between CFP and SD-OCT in identifying presence and absence of drusen, with mean agreement in 82% +/- 9% of total image pixels. Most disagreement (80% +/- 15%) occurred at drusen margins. There was a trend toward greater detection of drusen with SD-OCT in eyes with larger drusen and with hyperpigmentation. There was a trend toward greater detection of smaller drusen by CFP.
   CONCLUSIONS. Good agreement was demonstrated in drusen detection between CFP and SD-OCT. Areas of disagreement underscore limitations of CFP-based measurement of drusen, particularly in the sizing of large, soft drusen. SD-OCT shows great promise as an adjunctive tool for assessing drusen burden in AMD. (ClinicalTrials.gov number, NCT00734487.) (Invest Ophthalmol Vis Sci. 2010;51:4875-4883) DOI:10.1167/iovs.09-4962
C1 [Jain, Nieraj; Farsiu, Sina; Khanifar, Aziz A.; Bearelly, Srilaxmi; Izatt, Joseph A.; Toth, Cynthia A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
   [Farsiu, Sina; Izatt, Joseph A.; Toth, Cynthia A.] Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC 27710 USA.
   [Bearelly, Srilaxmi; Smith, R. Theodore] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
C3 Duke University; Duke University; Columbia University
RP Toth, CA (通讯作者)，DUMC, Duke Eye Ctr, Box 3802, Durham, NC 27710 USA.
EM toth0004@mc.duke.edu
RI toth, cynthia a/F-5614-2011; Izatt, Joseph/C-9067-2014; Toth,
   Cynthia/L-5534-2019
OI Izatt, Joseph/0000-0003-1993-2249; Toth, Cynthia/0000-0002-2324-0854;
   Farsiu, Sina/0000-0003-4872-2902; smith, theodore/0000-0002-1693-943X
FU Alcon Laboratories, National Institutes of Health [R21 EY017393, K23
   EY018895]; Genentech; North Carolina Biotechnology Center Collaborative
   [2007-CFG-8005]; National Institutes of Health; NATIONAL EYE INSTITUTE
   [K23EY018895, R01EY015520, R21EY017393] Funding Source: NIH RePORTER
FX Supported in part by Alcon Laboratories, National Institutes of Health
   Grants R21 EY017393 and K23 EY018895, Genentech, and The North Carolina
   Biotechnology Center Collaborative Funding Grant 2007-CFG-8005 with
   Bioptigen (all in support of The Duke Advanced Research in SDOCT Imaging
   [DARSI] Laboratory). SB receives research support from the National
   Institutes of Health.
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NR 29
TC 76
Z9 76
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 OCT
PY 2010
VL 51
IS 10
BP 4875
EP 4883
DI 10.1167/iovs.09-4962
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 655UI
UT WOS:000282275500002
PM 20393117
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Pescina, S
   Ferrari, G
   Govoni, P
   Macaluso, C
   Padula, C
   Santi, P
   Nicoli, S
AF Pescina, Silvia
   Ferrari, Giulio
   Govoni, Paolo
   Macaluso, Claudio
   Padula, Cristina
   Santi, Patrizia
   Nicoli, Sara
TI In-vitro permeation of bevacizumab through human sclera: effect of
   iontophoresis application
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
DE bevacizumab; fluorescein isothiocyanate; iontophoresis; transscleral
   permeation
ID DRUG-DELIVERY; FLUORESCEIN-ISOTHIOCYANATE; BARRIERS; MODEL
AB Objectives
   Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used in ophthalmology (off-label) for the treatment of neovascularization in diseases such as diabetic retinopathy and age-related macular degeneration (wet form). Bevacizumab is currently administrated by repeated intravitreal injection, which can cause severe complications; a non-invasive delivery route is therefore desirable. The passive permeation of bevacizumab through isolated human sclera was evaluated and the iontophoretic technique was explored as a method to enhance its transscleral transport in vitro.
   Methods
   Bevacizumab was fluorescently labelled using fluorescein isothiocyanate (FITC). Permeation experiments were conducted for 2 h in Franz-type diffusion cells using human sclera as the barrier. The donor compartment contained FITC-bevacizumab (2.5 mg/ml) in phosphate-buffered saline at pH 7.4. In the iontophoretic experiments, a current intensity of 2.3 mA (current density 3.8 mA/cm2) was applied. The permeation samples were analysed with a fluorescence detector (excitation and emission wavelengths were 490 and 520 nm, respectively). The stability of FITC-bevacizumab conjugate was checked by thin layer chromatography.
   Key findings
   The main finding of this work is that anodal iontophoresis can significantly enhance bevacizumab transport through isolated human sclera (enhancement factor 7.5), even though the drug is essentially uncharged. Due to the relatively constant characteristics of antibodies, these results can probably be extended to other molecules of the same family.
   Conclusions
   Preliminary results indicate that anodal iontophoresis could be a promising strategy to non-invasively deliver bevacizumab through the sclera. The presence in the eye of other barriers, both static and dynamic, necessitates further evaluation of the technique on more complex ex-vivo and in-vivo models.
C1 [Pescina, Silvia; Padula, Cristina; Santi, Patrizia; Nicoli, Sara] Univ Parma, Dept Pharm, I-43100 Parma, Italy.
   [Ferrari, Giulio; Macaluso, Claudio] Univ Parma, Dept Ophthalmol, I-43100 Parma, Italy.
   [Govoni, Paolo] Univ Parma, Dept Expt Med, I-43100 Parma, Italy.
C3 University of Parma; University of Parma; University of Parma
RP Nicoli, S (通讯作者)，Univ Parma, Dept Pharm, Viale Usberti 27-A, I-43100 Parma, Italy.
EM sara.nicoli@unipr.it
RI PESCINA, SILVIA/J-8524-2014; Macaluso, Claudio/G-8997-2013; ferrari,
   giulio/AAR-8261-2021; Padula, Cristina/K-6372-2017; Padula,
   Cristina/AAL-3536-2021; Santi, Patrizia/G-8601-2011; ferrari,
   giulio/J-9260-2016; Ferrari, Giulio/AAT-1970-2021; Nicoli,
   Sara/J-5199-2012
OI ferrari, giulio/0000-0001-6474-9908; Padula,
   Cristina/0000-0003-1024-524X; Santi, Patrizia/0000-0001-7601-7894;
   ferrari, giulio/0000-0001-6474-9908; Nicoli, Sara/0000-0001-6955-0957;
   PESCINA, SILVIA/0000-0002-6131-4375
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NR 26
TC 31
Z9 32
U1 2
U2 14
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3573
EI 2042-7158
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD SEP
PY 2010
VL 62
IS 9
BP 1189
EP 1194
DI 10.1111/j.2042-7158.2010.01153.x
PG 6
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 635HO
UT WOS:000280646400014
PM 20796199
DA 2022-11-30
ER

PT J
AU Semkova, I
   Peters, S
   Welsandt, G
   Janicki, H
   Jordan, J
   Schraermeyer, U
AF Semkova, I
   Peters, S
   Welsandt, G
   Janicki, H
   Jordan, J
   Schraermeyer, U
TI Investigation of laser-induced choroidal neovascularization in the rat
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BLOOD-FLOW; PIGMENT EPITHELIUM; ANGIOGRAPHY; MICROSCOPY; DEXTRANS; CASTS
AB PURPOSE. Choroidal neovascularization plays an important role in pathogenesis of age-related macular degeneration. Induction of neovascularization by laser photocoagulation in the rat fundus is an established animal model in which the effects of new therapeutic approaches are assessed. The purpose of this study was to compare different detection methods of laser-induced neovascularization in the rat.
   METHODS. Laser spots were applied to the fundus of Long-Evans rats. Ten days after, four different methods were used to detect laser-induced neovascularization: (1) high-resolution angiography with fluorescein isothiocyanate-dextran, (2) immunohistochemical visualization of platelet endothelial cell adhesion molecule (PECAM)-1, (3) visualization of intravascular lumens by peroxidase perfusion in the living rat with subsequent histologic analysis, and (4) histochemical representation of alkaline phosphatase in endothelial cells.
   RESULTS. At the rim of the laser scars vessel-forming endothelial cells with intravasal dextran and peroxidase were present. Cross-sections demonstrated that these vessels originated from the retina. The center of the scars contained homogenous endothelial cells of choroidal origin, which was confirmed by immunohistochemistry and electron microscopy. In laser-treated eves without FITC-dextran perfusion, scars showed unspecific fluorescence, making differentiation from specific FITC-dextran-associated fluorescence difficult.
   CONCLUSIONS. In the rat model of laser-induced neovascularization, newly developed endothelial cells originate from the retina and the choroid. Whereas ring-like surrounding vessels come from the retina, flat endothelial cells in deeper layers are of choroidal origin or may originate from circulating endothelial precursor cells. Dextran angiography has to be regarded critically for visualizing the choriocapillaris and CNV in laser scars. PECAM-1 immunohistochemistry is best for detection and quantification of neovascularization in laser scars.
C1 Univ Cologne, Dept Vitreo Retinal Surg, Ctr Ophthalmol, D-50931 Cologne, Germany.
   Univ Ulm, Div Gene Therapy, Ulm, Germany.
   Univ Tubingen, Dept Expt Vitreo Retinal Surg, Tubingen, Germany.
C3 University of Cologne; Ulm University; Eberhard Karls University of
   Tubingen
RP Semkova, I (通讯作者)，Univ Cologne, Dept Vitreo Retinal Surg, Ctr Ophthalmol, Joseph Stelzmann Str 9, D-50931 Cologne, Germany.
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NR 23
TC 33
Z9 35
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 DEC
PY 2003
VL 44
IS 12
BP 5349
EP 5354
DI 10.1167/iovs.02-0732
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 747JJ
UT WOS:000186801200041
PM 14638737
DA 2022-11-30
ER

PT J
AU Kwak, J
   Han, JY
   Moon, SY
   Nam, S
   Kim, JY
   Tchah, H
   Lee, H
AF Kwak, Jiehoon
   Han, Jung Yeob
   Moon, Su Young
   Nam, Sanghyu
   Kim, Jae Yong
   Tchah, Hungwon
   Lee, Hun
TI Relationship Between Tamsulosin Use and Surgical Complications of
   Cataract Surgery in Elderly Patients: Population-Based Cohort Study
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE cataract surgery; tamsulosin; surgical complication; KNHIS-Senior
   cohort; cataract (senile)
ID FLOPPY IRIS SYNDROME; ASSOCIATION; MORTALITY; IFIS
AB PurposeAlthough several previous studies have investigated the relationship between tamsulosin use and surgical complications of cataract surgery, no population-based cohort study has been conducted for the Asian population. We aimed to investigate the relationship between tamsulosin use and surgical complications of cataract surgery in the Korean elderly population. MethodsThis nationwide population-based retrospective cohort study included elderly patients (>= 60 years) who had undergone cataract surgery in the period from 2003 to 2015. Baseline characteristics were age, sex, income, residence, and systemic, and ocular comorbidities (glaucoma, myopia, eye trauma, diabetes mellitus with ophthalmic manifestations, severe cataract, age-related macular degeneration). The exposure of interest was tamsulosin use within 1 year before cataract surgery. Logistic regression model was used to evaluate the relationship of tamsulosin use with surgical complications of cataract surgery. ResultsThe rate of surgical complications of cataract surgery was 0.88% (375/42,539) in the non-tamsulosin group and 0.83% (71/8,510) in the tamsulosin group. The groups showed no significant difference in the risk of surgical complications of cataract surgery in the unadjusted model [odds ratio (OR) = 0.946; 95% confidence interval (CI):0.733-1.220; P = 0.669]. Additionally, tamsulosin use was not significantly associated with surgical complications of cataract surgery in the fully adjusted model accounting for age, income, residence, and systemic and ocular comorbidities (OR = 0.997; 95% CI: 0.749-1.325; P = 0.981). ConclusionsThe rate or risk of surgical complications of cataract surgery does not change with tamsulosin use. We suggest that better surgical techniques and surgeons' cognizance of the patient's tamsulosin use could improve surgical outcomes, without increasing surgical complications.
C1 [Kwak, Jiehoon; Han, Jung Yeob; Moon, Su Young; Nam, Sanghyu; Kim, Jae Yong; Tchah, Hungwon; Lee, Hun] Univ Ulsan, Asan Med Ctr, Dept Ophthalmol, Coll Med, Seoul, South Korea.
C3 University of Ulsan; Asan Medical Center
RP Kim, JY; Lee, H (通讯作者)，Univ Ulsan, Asan Med Ctr, Dept Ophthalmol, Coll Med, Seoul, South Korea.
EM jykim2311@amc.seoul.kr; yhun777@gmail.com
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NR 27
TC 0
Z9 0
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD MAY 19
PY 2022
VL 9
AR 882131
DI 10.3389/fmed.2022.882131
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 1U6WI
UT WOS:000805550000001
PM 35665322
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cai, BX
   Liao, CY
   He, DX
   Chen, JM
   Han, JH
   Lu, JY
   Qin, KQ
   Liang, WX
   Wu, XL
   Liu, ZG
   Wu, YL
AF Cai, Binxiang
   Liao, Chunyan
   He, Danxue
   Chen, Jingmeng
   Han, Jiahuai
   Lu, Jiaying
   Qin, Kaiqi
   Liang, Wenxu
   Wu, Xiaoling
   Liu, Zuguo
   Wu, Yalin
TI Gasdermin E mediates photoreceptor damage by all-trans-retinal in the
   mouse retina
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOMAIN-LIKE PROTEIN; INFLAMMATORY CASPASES; CELL-DEATH; PYROPTOSIS;
   APOPTOSIS; RETINOPATHY; METABOLISM; CLEAVAGE; DISEASE; ROD
AB The breakdown of all-trans-retinal (atRAL) clearance is closely associated with photoreceptor cell death in dry age related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its mechanisms remain elusive. Here, we demonstrate that activation of gasdermin E (GSDME) but not gasdermin D promotes atRAL-induced photoreceptor damage by activating pyroptosis and aggravating apoptosis through a mitochondria-mediated caspase-3-dependent signaling pathway. Activation of c-Jun N-terminal kinase was identified as one of the major causes of mitochondrial membrane rupture in atRAL-loaded photoreceptor cells, resulting in the release of cytochrome c from mitochondria to the cytosol, where it stimulated caspase-3 activation required for cleavage of GSDME. Aggregation of the N-terminal fragment of GSDME in the mitochondria revealed that GSDME was likely to penetrate mitochondrial membranes in photoreceptor cells after atRAL exposure. ABC (subfamily A, member 4) and all-trans-retinol dehydrogenase 8 are two key proteins responsible for clearing atRAL in the retina. Abca4(-/-)Rdh8(-/-) mice exhibit serious defects in atRAL clearance upon light exposure and serve as an acute model for dry AMD and STGD1. We found that N-terminal fragment of GSDME was distinctly localized in the photoreceptor outer nuclear layer of light-exposed Abca4(-/-)Rdh8(-/-)mice. Of note, degeneration and caspase-3 activation in photoreceptors were significantly alleviated in Abca4(-/-)Rdh8(-/-)Gsdme(-/-) mice after exposure to light. The results of this study indicate that GSDME is a common causative factor of photoreceptor pyroptosis and apoptosis arising from atRAL overload, suggesting that repressing GSDME may represent a potential treatment of photoreceptor atrophy in dry AMD and STGD1.
C1 [Cai, Binxiang; Liao, Chunyan; He, Danxue; Lu, Jiaying; Qin, Kaiqi; Liang, Wenxu; Wu, Xiaoling; Liu, Zuguo; Wu, Yalin] Xiamen Univ, Fujian Prov Key Lab Ophthalmol & Visual Sci, Eye Inst,Dept Ophthalmol, Fujian Engn & Res Ctr Eye Regenerat Med,Xiangan H, Xiamen, Fujian, Peoples R China.
   [Chen, Jingmeng] Xiamen Univ, Sch Med, Xiamen, Fujian, Peoples R China.
   [Han, Jiahuai] Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Biol, Sch Life Sci, Xiamen, Fujian, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Xiamen Eye Ctr, Sch Med, Xiamen, Fujian, Peoples R China.
   [Wu, Yalin] Xiamen Univ, Shenzhen Res Inst, Shenzhen, Guangdong, Peoples R China.
C3 Xiamen University; Xiamen University; Xiamen University; Xiamen
   University; Xiamen University
RP Wu, YL (通讯作者)，Xiamen Univ, Fujian Prov Key Lab Ophthalmol & Visual Sci, Eye Inst,Dept Ophthalmol, Fujian Engn & Res Ctr Eye Regenerat Med,Xiangan H, Xiamen, Fujian, Peoples R China.; Wu, YL (通讯作者)，Xiamen Univ, Xiamen Eye Ctr, Sch Med, 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 China National Natural Science Foundation [82171064, 81870671];
   Guangdong Basic and Applied Basic Research Foundation [2021A1515011391];
   Basic Research Program of Shenzhen [JCYJ20180306173025004]; XMU Training
   Program of Innovation and Entrepreneurship for Undergraduates
FX This work was supported in part by grants from China National Natural
   Science Foundation (grant nos.: 82171064 and 81870671 to Y. W.),
   Guangdong Basic and Applied Basic Research Foundation (grant no.:
   2021A1515011391 to Y. W.), the Basic Research Program of Shenzhen (grant
   no.: JCYJ20180306173025004 to Y. W.), and XMU Training Program of
   Innovation and Entrepreneurship for Undergraduates.
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NR 39
TC 3
Z9 3
U1 3
U2 16
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB
PY 2022
VL 298
IS 2
AR 101553
DI 10.1016/j.jbc.2021.101553
PG 17
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA ZI1NP
UT WOS:000761395300008
PM 34973334
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kerr, H
   Herbert, AP
   Makou, E
   Abramczyk, D
   Malik, TH
   Lomax-Browne, H
   Yang, Y
   Pappworth, IY
   Denton, H
   Richards, A
   Marchbank, KJ
   Pickering, MC
   Barlow, PN
AF Kerr, Heather
   Herbert, Andrew P.
   Makou, Elisavet
   Abramczyk, Dariusz
   Malik, Talat H.
   Lomax-Browne, Hannah
   Yang, Yi
   Pappworth, Isabel Y.
   Denton, Harriet
   Richards, Anna
   Marchbank, Kevin J.
   Pickering, Matthew C.
   Barlow, Paul N.
TI Murine Factor H Co-Produced in Yeast With Protein Disulfide Isomerase
   Ameliorated C3 Dysregulation in Factor H-Deficient Mice
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE complement system; factor H; C3 glomerulonephritis mouse model;
   therapeutic protein; C3 glomerulonephritis; chaperonin; Pichia pastoris;
   protein disulfide isomerase (PDI)
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; ASSOCIATIONS; EXPRESSION
AB Recombinant human factor H (hFH) has potential for treating diseases linked to aberrant complement regulation including C3 glomerulopathy (C3G) and dry age-related macular degeneration. Murine FH (mFH), produced in the same host, is useful for pre-clinical investigations in mouse models of disease. An abundance of FH in plasma suggests high doses, and hence microbial production, will be needed. Previously, Pichia pastoris produced useful but modest quantities of hFH. Herein, a similar strategy yielded miniscule quantities of mFH. Since FH has 40 disulfide bonds, we created a P. pastoris strain containing a methanol-inducible codon-modified gene for protein-disulfide isomerase (PDI) and transformed this with codon-modified DNA encoding mFH under the same promoter. What had been barely detectable yields of mFH became multiple 10s of mg/L. Our PDI-overexpressing strain also boosted hFH overproduction, by about tenfold. These enhancements exceeded PDI-related production gains reported for other proteins, all of which contain fewer disulfide-stabilized domains. We optimized fermentation conditions, purified recombinant mFH, enzymatically trimmed down its (non-human) N-glycans, characterised its functions in vitro and administered it to mice. In FH-knockout mice, our de-glycosylated recombinant mFH had a shorter half-life and induced more anti-mFH antibodies than mouse serum-derived, natively glycosylated, mFH. Even sequential daily injections of recombinant mFH failed to restore wild-type levels of FH and C3 in mouse plasma beyond 24 hours after the first injection. Nevertheless, mFH functionality appeared to persist in the glomerular basement membrane because C3-fragment deposition here, a hallmark of C3G, remained significantly reduced throughout and beyond the ten-day dosing regimen.
C1 [Kerr, Heather; Richards, Anna] Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
   [Kerr, Heather; Herbert, Andrew P.; Makou, Elisavet; Abramczyk, Dariusz; Barlow, Paul N.] Univ Edinburgh, Sch Chem, Edinburgh, Midlothian, Scotland.
   [Malik, Talat H.; Lomax-Browne, Hannah; Pickering, Matthew C.] Imperial Coll London, Ctr Inflammatory Dis, London, England.
   [Yang, Yi; Pappworth, Isabel Y.; Denton, Harriet; Marchbank, Kevin J.] Newcastle Univ, Translat & Clin Res Inst, Newcastle, NSW, Australia.
   [Yang, Yi; Pappworth, Isabel Y.; Denton, Harriet; Marchbank, Kevin J.] Royal Victoria Infirm, Natl Renal Complement Therapeut Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
   [Barlow, Paul N.] Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland.
C3 University of Edinburgh; University of Edinburgh; Imperial College
   London; University of Newcastle; Newcastle University - UK; University
   of Edinburgh
RP Barlow, PN (通讯作者)，Univ Edinburgh, Sch Chem, Edinburgh, Midlothian, Scotland.; Barlow, PN (通讯作者)，Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland.
EM paul.barlow@ed.ac.uk
OI marchbank, kevin james/0000-0003-1312-5411
FU MRC [G1001971]; Wellcome Trust [212252/Z/18/Z, WT085226]; Northern
   Counties Kidney Research Fund; Kidney Research UK [RP7/2015,
   RP_006_20170301]; IBioIC [2019-1-6/2017-166B]
FX HK was an MRC (G1001971) Clinical Training Fellow. MP is a Wellcome
   Trust Senior Fellow in Clinical Science (212252/Z/18/Z). KM was funded
   by the Northern Counties Kidney Research Fund and Kidney Research UK
   project grants (RP7/2015 & RP_006_20170301). DA is funded by IBioIC
   (2019-1-6/2017-166B). AR was a Wellcome Trust Intermediate Clinical
   Fellow (WT085226; 2009-2014).
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NR 91
TC 3
Z9 3
U1 0
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD MAY 12
PY 2021
VL 12
AR 681098
DI 10.3389/fimmu.2021.681098
PG 17
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA SH6AJ
UT WOS:000654216800001
PM 34054871
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Teo, KYC
   Nguyen, V
   Barthelmes, D
   Arnold, JJ
   Gillies, MC
   Cheung, CMG
AF Teo, Kelvin Yi Chong
   Nguyen, Vuong
   Barthelmes, Daniel
   Arnold, Jennifer J.
   Gillies, Mark C.
   Cheung, Chui Ming Gemmy
TI Extended intervals for wet AMD patients with high retreatment needs:
   informing the risk during COVID-19, data from real-world evidence
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB TREATMENT; CLINICAL-PRACTICE; VISUAL
   OUTCOMES; SAFETY; TREAT; REGIMENS; EFFICACY; THERAPY; CHINA
AB Background/Objective Some clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. Methods We compared eyes with active disease despite <= 6 weekly injections whose next injection was extended to >= 7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) <= 6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) >12 weeks (5%). Results There was a significant loss in VA in eyes extended to >12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): <= 6 weeks, 0.4 (-1.5 to 2.2), versus >12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing >= 15 letters (absolute risk (14% versus 4%, p < 0.01)). Conclusion Mean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19.
C1 [Teo, Kelvin Yi Chong; Cheung, Chui Ming Gemmy] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Teo, Kelvin Yi Chong; Cheung, Chui Ming Gemmy] Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
   [Teo, Kelvin Yi Chong; Nguyen, Vuong; Barthelmes, Daniel; Gillies, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW, Australia.
   [Barthelmes, Daniel] Univ Zurich, Univ Hosp Zurich, Zurich, Switzerland.
   [Arnold, Jennifer J.] Marsden Eye Specialist, Sydney, NSW, Australia.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; University of Sydney; University of
   Zurich; University Zurich Hospital
RP Cheung, CMG (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.; Cheung, CMG (通讯作者)，Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
EM gemmy.cheung.c.m@singhealth.com.sg
OI Teo, Kelvin/0000-0002-7458-7081
FU Royal Australian NZ College of Ophthalmologists Eye Foundation
   (2007-2009); National Health and Medical Research Council, Australia,
   (NHMRC 2010-2012); Macula Disease Foundation, Australia; NHMRC
   practitioner fellowship; Walter and Gertrud Siegenthaler Foundation
   Zurich, Switzerland; Swiss National Foundation; National Medical
   Research Council Open Fund Large Collaborative grant [NMRC/LCG/0042018]
FX Supported by a grant from the Royal Australian NZ College of
   Ophthalmologists Eye Foundation (2007-2009), a grant from the National
   Health and Medical Research Council, Australia, (NHMRC 2010-2012) and a
   grant from the Macula Disease Foundation, Australia. MCG is a Sydney
   Medical Foundation Fellow and is supported by an NHMRC practitioner
   fellowship. DB was supported by the Walter and Gertrud Siegenthaler
   Foundation Zurich, Switzerland, and the Swiss National Foundation. CMGC
   is supported grant by a grant from the National Medical Research Council
   Open Fund Large Collaborative grant no: NMRC/LCG/0042018).
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NR 37
TC 11
Z9 11
U1 0
U2 0
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD OCT
PY 2021
VL 35
IS 10
BP 2793
EP 2801
DI 10.1038/s41433-020-01315-x
EA NOV 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UT9UR
UT WOS:000592570400003
PM 33239765
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Mehta, N
   Lee, CS
   Mendonca, LSM
   Raza, K
   Braun, PX
   Duker, JS
   Waheed, NK
   Lee, AY
AF Mehta, Nihaal
   Lee, Cecilia S.
   Mendonca, Luisa S. M.
   Raza, Khadija
   Braun, Phillip X.
   Duker, Jay S.
   Waheed, Nadia K.
   Lee, Aaron Y.
TI Model-to-Data Approach for Deep Learning in Optical Coherence Tomography
   Intraretinal Fluid Segmentation
SO JAMA OPHTHALMOLOGY
LA English
DT Article
AB IMPORTANCE Amid an explosion of interest in deep learning in medicine, including within ophthalmology, concerns regarding data privacy, security, and sharing are of increasing importance. A model-to-data approach, in which the model itself is transferred rather than data, can circumvent many of these challenges but has not been previously demonstrated in ophthalmology.
   OBJECTIVE To determine whether a model-to-data deep learning approach (ie, validation of the algorithm without any data transfer) can be applied in ophthalmology.
   DESIGN, SETTING, AND PARTICIPANTS This single-center cross-sectional study included patients with active exudative age-related macular degeneration undergoing optical coherence tomography (OCT) at the New England Eye Center from August 1, 2018, to February 28, 2019. Data were primarily analyzed from March 1 to June 20, 2019.
   MAIN OUTCOMES AND MEASURES Training of the deep learning model, using a model-to-data approach, in recognizing intraretinal fluid (IRF) on OCT B-scans.
   RESULTS The model was trained (learning curve Dice coefficient, >80%) using 400 OCT B-scans from 128 participants (69 female [54%] and 59 male [46%]; mean [SD] age, 77.5 [9.1] years). In comparing the model with manual human grading of IRF pockets, no statistically significant difference in Dice coefficients or intersection over union scores was found (P >.05).
   CONCLUSIONS AND RELEVANCE A model-to-data approach to deep learning applied in ophthalmology avoided many of the traditional hurdles in large-scale deep learning, including data sharing, security, and privacy concerns. Although the clinical relevance of these results is limited at this time, this proof-of-concept study suggests that such a paradigm should be further examined in larger-scale, multicenter deep learning studies.
C1 [Mehta, Nihaal; Mendonca, Luisa S. M.; Raza, Khadija; Braun, Phillip X.; Duker, Jay S.; Waheed, Nadia K.] Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA.
   [Mehta, Nihaal] Brown Univ, Warren Alpert Med Sch, Providence, RI USA.
   [Lee, Cecilia S.; Lee, Aaron Y.] Univ Washington, Dept Ophthalmol, 325 Ninth Ave,POB 359608, Seattle, WA 98104 USA.
   [Mendonca, Luisa S. M.] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil.
   [Braun, Phillip X.] Yale Univ, Sch Med, New Haven, CT USA.
C3 Tufts Medical Center; Brown University; University of Washington;
   University of Washington Seattle; Universidade Federal de Sao Paulo
   (UNIFESP); Yale University
RP Lee, AY (通讯作者)，Univ Washington, Dept Ophthalmol, 325 Ninth Ave,POB 359608, Seattle, WA 98104 USA.
EM leeay@uw.edu
OI Lee, Aaron/0000-0002-7452-1648
FU Macula Vision Research Foundation; Massachusetts Lions Clubs; National
   Institutes of Health [5-R01-EY011289-31, K23-EY029246,
   R01-AG060942-01A1]; Air Force Office of Scientific Research
   [FA9550-15-1-0473]; Champalimaud Vision Award; Beckman-Argyros Award in
   Vision Research; Yale School of Medicine Medical Student Fellowship;
   CAPES Foundation-Ministry of Education Brazil [88887.369769/2019-00];
   Research to Prevent Blindness
FX This study was supported by the Macula Vision Research Foundation; the
   Massachusetts Lions Clubs; grants 5-R01-EY011289-31, K23-EY029246, and
   R01-AG060942-01A1 from the National Institutes of Health; grant
   FA9550-15-1-0473 from the Air Force Office of Scientific Research; the
   Champalimaud Vision Award; the Beckman-Argyros Award in Vision Research;
   the Yale School of Medicine Medical Student Fellowship; a scholarship
   provided by the CAPES Foundation-Ministry of Education Brazil, as part
   of the CAPES-PrInt program (process 88887.369769/2019-00); and an
   unrestricted grant from Research to Prevent Blindness.
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NR 40
TC 17
Z9 18
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD OCT
PY 2020
VL 138
IS 10
BP 1017
EP 1024
DI 10.1001/jamaophthalmol.2020.2769
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PO1YX
UT WOS:000604967700006
PM 32761143
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Giannaccare, G
   Pellegrini, M
   Sebastiani, S
   Bernabei, F
   Moscardelli, F
   Iovino, C
   Napoli, PE
   Campos, E
AF Giannaccare, Giuseppe
   Pellegrini, Marco
   Sebastiani, Stefano
   Bernabei, Federico
   Moscardelli, Fabiana
   Iovino, Claudio
   Napoli, Pietro E.
   Campos, Emilio
TI CHOROIDAL VASCULARITY INDEX QUANTIFICATION IN GEOGRAPHIC ATROPHY USING
   BINARIZATION OF ENHANCED-DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHIC
   SCANS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; choroidal
   vascularity index; optical coherence tomography
ID MACULAR DEGENERATION; BLOOD-FLOW; THICKNESS; EYES; SECONDARY
AB Purpose: To evaluate choroidal structural changes occurring over time in geographic atrophy (GA) secondary to age-related macular degeneration using choroidal vascularity index (CVI). Methods: Enhanced-depth imaging optical coherence tomography scans of 34 patients with GA and 32 control subjects were retrospectively analyzed. Data were collected at baseline and after a mean follow-up of 18.3 +/- 8.3 months. Choroidal images were binarized using the ImageJ software, and the luminal area and stromal area were segmented. Choroidal vascularity index was defined as the ratio of luminal area to total choroid area. Results: Patients with GA showed significantly lower values of CVI, total choroid area, luminal area, and subfoveal choroidal thickness compared to control subjects (65.83 +/- 3.95 vs. 69.33 +/- 3.11, P < 0.001; 0.400 +/- 0.239 mm(2) vs. 0.491 +/- 0.132, P = 0.006; 0.263 +/- 0.152 mm(2) vs. 0.340 +/- 0.094, P = 0.002; 185.2 +/- 79.8 mu m vs. 216.8 +/- 58.8 mu m, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = -0.509; P = 0.002). During the follow-up period in patients with GA, subfoveal choroidal thickness decreased from 185.2 +/- 79.8 to 152.2 +/- 73.1 (P = 0.001), stromal area increased from 0.138 +/- 0.090 mm(2) to 0.156 +/- 0.068 (P = 0.028), and CVI decreased from 65.83 +/- 3.95 to 62.24 +/- 3.63 (P < 0.001). Conclusion: This study showed for the first time that CVI is reduced in patients with GA, and that this metric further worsened during the follow-up period.
C1 [Giannaccare, Giuseppe; Pellegrini, Marco; Sebastiani, Stefano; Bernabei, Federico; Moscardelli, Fabiana; Campos, Emilio] Univ Bologna, S Orsola Malpighi Univ Hosp, Ophthalmol Unit, Via Palagi 9, Bologna 40138, Italy.
   [Iovino, Claudio; Napoli, Pietro E.] Univ Cagliari, Dept Surg Sci, Eye Clin, Cagliari, Italy.
C3 IRCCS Azienda Ospedaliero-Universitaria di Bologna; University of
   Bologna; University of Cagliari
RP Pellegrini, M (通讯作者)，Univ Bologna, S Orsola Malpighi Univ Hosp, Ophthalmol Unit, Via Palagi 9, Bologna 40138, Italy.
EM marco.pellegrini@hotmail.it
RI Iovino, Claudio/O-7680-2019; Napoli, Pietro/AAP-8423-2020; Bernabei,
   Federico/AAC-2293-2019; Pellegrini, Marco/T-3694-2019
OI Iovino, Claudio/0000-0003-1984-0555; Pellegrini,
   Marco/0000-0002-6419-6941; Napoli, Pietro Emanuele/0000-0001-7020-0823
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NR 33
TC 39
Z9 39
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2020
VL 40
IS 5
BP 960
EP 965
DI 10.1097/IAE.0000000000002459
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LL2HK
UT WOS:000531376000022
PM 30676528
DA 2022-11-30
ER

PT J
AU Loyet, KM
   Hass, PE
   Sandoval, WN
   Morando, A
   Liu, P
   Shatz, W
   Dickmann, L
   Kenrick, M
   Good, J
   Davancaze, T
   Morimoto, AM
   Kelley, RF
   Scheer, JM
AF Loyet, Kelly M.
   Hass, Philip E.
   Sandoval, Wendy N.
   Morando, Ashley
   Liu, Peter
   Shatz, Whitney
   Dickmann, Leslie
   Kenrick, Margaret
   Good, Jeremy
   Davancaze, Teresa
   Morimoto, Alyssa M.
   Kelley, Robert F.
   Scheer, Justin M.
TI In Vivo Stability Profiles of Anti-factor D Molecules Support
   Long-Acting Delivery Approaches
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE age-related macular degeneration; anti factor D; aqueous humor;
   geographic atrophy; human; lampalizumab; long-acting delivery;
   pharmacokinetics; rabbit; stability; target binding; vitreous humor
ID AQUEOUS-HUMOR LEVELS; MACULAR DEGENERATION; INTRAVITREAL INJECTION;
   COMPLEMENT ACTIVATION; ALTERNATIVE PATHWAY; VITREOUS LEVELS;
   PHARMACOKINETICS; DRUSEN; LAMPALIZUMAB; RANIBIZUMAB
AB The collection of aqueous humor (phase 1b/2 Mahalo study) from patients dosed intravitreally with anti-factor D (AFD; FCFD4514S, lampalizumab), a humanized antibody fragment previously under investigation to treat geographic atrophy (GA) secondary to age-related macular degeneration, presented a unique opportunity to examine AFD properties in clinical samples. We investigated AFD stability and target-binding characteristics to set up strategies for engineering and evaluating optimized molecules that enable less frequent dosing. Two variants, AFD.v8 and AFD.v14, were evaluated as alternatives to AFD for longer-acting treatments. Mass spectrometry, surface plasmon resonance, and immunoassay were used to assess AFD stability and binding activity in aqueous humor samples from Mahalo patients. In vitro stability and binding activity of AFD, AFD.v8, and AFD.v14 were assessed in human vitreous humor versus buffer at 37 degrees C over 16 weeks and in vivo in rabbits over 28 days along with pharmacokinetic determinations. In human aqueous humor, AFD specific binding was >85% through 30 days, and deamidation was <3% through 60 days, consistent with the AFD stability and binding activity in vitreous humor from humans in vitro and rabbits in vivo. Target binding, stability, and rabbit pharmacokinetic parameters of AFD.v8 and AFD.v14 were similar to those of AFD. Physiological stability and activity of AFD translated across in vitro and in vivo studies in humans and rabbits. The two variants AFD.v8 and AFD.v14 demonstrated comparable potency and pharmacokinetics. These findings, along with previously demonstrated improved solubility of AFD.v8 and AFD.v14, provide proof-of-concept for developing other similar long-acting therapeutic variants.
C1 [Loyet, Kelly M.; Morando, Ashley] Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
   [Hass, Philip E.; Shatz, Whitney] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Sandoval, Wendy N.; Liu, Peter] Genentech Inc, Dept Microchem Prote & Lipid, San Francisco, CA 94080 USA.
   [Dickmann, Leslie; Kenrick, Margaret] Genentech Inc, Dept Preclin & Translat Pharmacokinet, San Francisco, CA 94080 USA.
   [Good, Jeremy; Davancaze, Teresa; Morimoto, Alyssa M.] Genentech Inc, Dept Assay Dev & Technol, San Francisco, CA 94080 USA.
   [Kelley, Robert F.] Genentech Inc, Dept Drug Delivery, San Francisco, CA 94080 USA.
   [Morando, Ashley] Alector Inc, 151 Oyster Point Blvd,Suite 300, San Francisco, CA 94080 USA.
   [Kenrick, Margaret] NanoString Technol Inc, 530 Fairview Ave N, Seattle, WA 98109 USA.
   [Morimoto, Alyssa M.] Genentech Inc, Dept OMNI Biomarker Dev, San Francisco, CA 94080 USA.
   [Scheer, Justin M.] Boehringer Ingelheim GmbH & Co KG, 900 Ridgebury Rd, Ridgefield, CT 06877 USA.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Roche Holding;
   Genentech; Roche Holding; Genentech; Roche Holding; Genentech; Roche
   Holding; Genentech; Roche Holding; Genentech; Boehringer Ingelheim
RP Loyet, KM (通讯作者)，Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
EM loyet.kelly@gene.com
RI Loyet, Kelly/AAD-7544-2021
OI Shatz-Binder, Whitney/0000-0003-2996-501X; Loyet, Kelly
   M./0000-0002-3733-099X
FU Genentech, Inc.
FX The authors thank Vladimir Bantseev, Laetitia Comps-Agrar, Jason Gow,
   Yichin Liu, Karthik Rajagopal, and Menno van Lookeren Campagne for
   critical review of the manuscript. Third-party writing assistance for
   this manuscript was provided by Shirley Teng, PhD, CMPP, of Envision
   Pharma Group and funded by Genentech, Inc.
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NR 49
TC 3
Z9 3
U1 0
U2 11
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 JAN
PY 2019
VL 16
IS 1
BP 86
EP 95
DI 10.1021/acs.molpharmaceut.8b00871
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA HG8WZ
UT WOS:000455288900007
PM 30444371
DA 2022-11-30
ER

PT J
AU Reid, CA
   Nettesheim, ER
   Connor, TB
   Lipinski, DM
AF Reid, Christopher A.
   Nettesheim, Emily R.
   Connor, Thomas B.
   Lipinski, Daniel M.
TI Development of an inducible anti-VEGF rAAV gene therapy strategy for the
   treatment of wet AMD
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; EXPRESSION; VECTOR;
   SAFETY; TRIAL; INJECTION; SYSTEM; RETINA; MODEL
AB Vascular endothelial growth factor (VEGF) is a key mediator in the development and progression of choroidal neovascularization (CNV) in patients with wet age-related macular degeneration (AMD). As a consequence, current treatment strategies typically focus on the administration of anti-VEGF agents, such as Aflibercept (Eylea), that inhibit VEGF function. While this approach is largely successful at counteracting CNV progression, the treatment can require repetitive (i.e. monthly) intravitreal injections of the anti-VEGF agent throughout the patient's lifetime, imposing a substantial financial and medical burden on the patient. Moreover, repetitive injection of anti-VEGF agents over a period of years may encourage progression of retinal and choroidal atrophy in patients with AMD, leading to a decrease in visual acuity. Herein, we have developed a single-injection recombinant adeno-associated virus (rAAV)-based gene therapy treatment for wet AMD that prevents CNV formation through inducible over-expression of Eylea. First, we demonstrate that by incorporating riboswitch elements into the rAAV expression cassette allows protein expression levels to be modulated in vivo through oral supplementation on an activating ligand (e.g. tetracycline). We subsequently utilized this technology to modulate the intraocular concentration of Eylea following rAAV delivery, leading to nearly complete (p = 0.0008) inhibition of clinically significant CNV lesions in an established mouse model of wet AMD. The results shown in this study pave the way for the development of a personalized gene therapy strategy for the treatment of wet AMD that is substantially less invasive and more clinically adaptable than the current treatment paradigm of repetitive bolus injections of anti-VEGF agents.
C1 [Reid, Christopher A.; Nettesheim, Emily R.; Connor, Thomas B.; Lipinski, Daniel M.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
   [Lipinski, Daniel M.] Univ Oxford, Nuffield Lab Ophthalmol, Oxford, England.
C3 Medical College of Wisconsin; University of Oxford
RP Lipinski, DM (通讯作者)，Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.; Lipinski, DM (通讯作者)，Univ Oxford, Nuffield Lab Ophthalmol, Oxford, England.
EM dlipinski@mcw.edu
OI Reid, Christopher/0000-0001-9816-7244
FU Foundation for Fighting Blindness Individual Investigator Award; NIH/NEI
   [P30 EY001931-37]; Research Training Program in Vision Science [T32
   EY014537-11]; Robert A. Brandt Macular Degeneration Fund; NATIONAL EYE
   INSTITUTE [P30EY001931, T32EY014537] Funding Source: NIH RePORTER
FX D.M.L. is funded through an intra-mural endowment, a Foundation for
   Fighting Blindness Individual Investigator Award and additionally
   receives support through a NIH/NEI Core Grant for Vision Research (P30
   EY001931-37) and Research Training Program in Vision Science (T32
   EY014537-11). This work was also funded through a generous donation from
   the Robert A. Brandt Macular Degeneration Fund.
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NR 48
TC 27
Z9 28
U1 0
U2 7
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 AUG 6
PY 2018
VL 8
AR 11763
DI 10.1038/s41598-018-29726-7
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GP3VG
UT WOS:000440782000050
PM 30082848
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Qureshi, MA
   Robbie, SJ
   Tabernero, J
   Artal, P
AF Qureshi, Muhammad A.
   Robbie, Scott J.
   Tabernero, Juan
   Artal, Pablo
TI Injectable intraocular telescope: Pilot study
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID MACULAR DEGENERATION; SURGERY; DISEASE; SYSTEM; ACUITY; RISK; END
AB PURPOSE: To assess the feasibility of a new injectable telescopic intraocular lens (IOL).
   SETTING: London Eye Hospital, London, United Kingdom.
   DESIGN: Prospective interventional pilot study.
   METHOD: Eyes with bilateral, intermediate, or advanced dry age-related macular degeneration (AMD); preoperative decimal corrected distance visual acuity (CDVA) of 0.25 or less; and improvement with extraocular simulation of the intervention had implantation of 2 IOLs designed for use together in a Galilean telescope configuration (iolAMD). Patients were followed for 4 months. Safety was assessed by monitoring visual acuity, intraocular pressure, specular microscopy, and anterior segment and macular optical coherence tomographies. Fixation stability and macular sensitivity were determined using microperimetry in some eyes.
   RESULTS: There were no significant intraoperative or postoperative complications. In 1 eye, an anterior sulcus IOL was replaced; there were no sequelae. The mean endothelial cell density was reduced by 18%. The mean decimal CDVA improved from 0.12 preoperatively to 0.20 at 4 months, a 67% gain. The mean change in spherical equivalent after implantation was -1.5 diopters (D) with 0.5 D of induced astigmatism. Microperimetric testing indicated a magnification effect and a deviation of the retinal image by up to 5 degrees, with improved fixation stability.
   CONCLUSIONS: This injectable intraocular miniature telescope appears safe in the short to medium term and capable of improving visual function. No significant issues were encountered regarding candidate eye selection or patient retention and cooperation. Further work is needed to evaluate the safety and efficacy of the device, particularly with respect to daily-living activities and the range of indications. (C) 2015 ASCRS and ESCRS
C1 [Qureshi, Muhammad A.] London Eye Hosp, London W1G 9PB, England.
   [Qureshi, Muhammad A.; Robbie, Scott J.] London Eye Hosp Pharma, London, England.
   [Tabernero, Juan] Univ Murcia, Lab Opt, Murcia, Spain.
C3 University of Murcia
RP Qureshi, MA (通讯作者)，London Eye Hosp, 4 Harley St, London W1G 9PB, England.
EM admin@londoneyehospital.com
RI Tabernero, Juan/D-1120-2014; Artal, Pablo/AAG-4485-2020; Artal,
   Pablo/AGV-7547-2022; Tabernero, Juan/AAO-9855-2020
OI Tabernero, Juan/0000-0002-5149-8350; Artal, Pablo/0000-0003-1284-6591;
   Artal, Pablo/0000-0003-1284-6591; 
FU London Eye Hospital
FX Supported by London Eye Hospital.
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NR 21
TC 16
Z9 17
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
EI 1873-4502
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD OCT
PY 2015
VL 41
IS 10
BP 2125
EP 2135
DI 10.1016/j.jcrs.2015.03.021
PG 11
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA DA0QW
UT WOS:000367503200014
PM 26703288
DA 2022-11-30
ER

PT J
AU Saraf, SS
   Ryu, CL
   Ober, MD
AF Saraf, Steven S.
   Ryu, Christina L.
   Ober, Michael D.
TI The Effects of Cataract Surgery on Patients With Wet Macular
   Degeneration
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB; CHOROIDAL NEOVASCULARIZATION;
   CONTROLLED-TRIAL; RANIBIZUMAB; RISK; EXTRACTION; KETOROLAC; OUTCOMES;
   THERAPY; ANCHOR
AB PURPOSE: To explore whether cataract surgery contributes to the progression of wet age-related macular degeneration (wet AMD).
   DESIGN: Retrospective cohort study.
   METHODS: Retrospective review was performed of consecutive patients with wet AMD who underwent cataract surgery at the midpoint of a 1-year study window. A control arm included wet AMD eyes treated with antivascular endothelial growth factor (VEGF) injections that did not undergo cataract surgery for a 1-year period. Best-corrected visual acuity (BCVA), number of anti-VEGF injections, and optical coherence tomography (OCT) features were compared between the 2 arms.
   RESULTS: Forty eyes in the surgical group and 42 in the nonsurgical group were included. BCVA was equivalent in the first half of the study, and became significantly better in the surgical group vs the nonsurgical group (0.23 +/- 0.65 vs 0.11 +/- 0.59 logMAR improvement, P=.049). There was no change in the number of injections given 6 months before vs after the midpoint in the surgical group (P=.921). The mean OCT central retinal thickness became greater in postsurgical eyes compared to nonsurgical eyes (265.4 +/- 98.4 mu m vs 216.4 +/- 58.3 mu m, P=.011). Surgical eyes were more likely to develop new or worse cystoid changes after the study midpoint (13 surgical eyes [54.2%] vs 9 nonsurgical eyes [28.1%], P=.048).
   CONCLUSIONS: Cataract surgery leads to vision improvement and does not appear to contribute to worsening of wet AMD. However, anatomic changes based on OCT analysis suggest a subclinical susceptibility to postoperative cystoid macular edema or exacerbation of choroidal neovascularization. (C) 2015 by Elsevier Inc. All rights reserved.
C1 [Saraf, Steven S.; Ryu, Christina L.] Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI USA.
   [Ober, Michael D.] Retina Consultants Michigan, Southfield, MI USA.
C3 Henry Ford Health System; Henry Ford Hospital
RP Ober, MD (通讯作者)，29201 Telegraph Rd,Suite 606, Southfield, MI 48034 USA.
EM obermike@gmail.com
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NR 28
TC 23
Z9 23
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 SEP
PY 2015
VL 160
IS 3
BP 487
EP 492
DI 10.1016/j.ajo.2015.06.006
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CP6AG
UT WOS:000359966100013
PM 26095263
DA 2022-11-30
ER

PT J
AU Qiu, M
   Wang, SY
   Singh, K
   Lin, SC
AF Qiu, Mary
   Wang, Sophia Y.
   Singh, Kuldev
   Lin, Shan C.
TI Racial Disparities in Uncorrected and Undercorrected Refractive Error in
   the United States
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE ethnic disparities; healthcare access; NHANES; racial disparities;
   refractive error
ID SCHOOL-AGE-CHILDREN; VISUAL IMPAIRMENT PROJECT; URBAN-POPULATION;
   SOUTHERN CHINA; PREVALENCE; BLINDNESS; AUSTRALIA; VISION; EYE; DISTRICT
AB PURPOSE. To identify risk factors for inadequately corrected refractive error in the United States.
   METHODS. This cross-sectional study included 12,758 participants 12 years of age and older from the 2005 to 2008 National Health and Nutrition Examination Survey. The primary outcome was the proportion of individuals with inadequate refractive correction for whom refractive correction would result in a visual acuity of 20/40 or better. The primary predictor was race/ethnicity. Secondary predictors included age, sex, annual household income, education, insurance, type of refractive error, current corrective lens use, presenting and best corrected visual acuity, cataract surgery, glaucoma, and age-related macular degeneration.
   RESULTS. Overall, 50.6% of subjects had a refractive error which was correctable to 20/40 or better with refraction. The percentage of subjects with correctable refractive error who were inadequately corrected was 11.7%. Odds of inadequate refractive correction were significantly greater in Mexican Americans and non-Hispanic blacks than in their non-Hispanic white counterparts in all age groups, with the greatest disparity in the 12-to 19-year-old group. Other risk factors associated with inadequate refractive correction in adults but not in teenagers included low annual household income, low education, and lack of health insurance.
   CONCLUSIONS. Racial disparities in refractive error correction were most pronounced in those under 20 years of age, as well as in adults with low annual household income, low education level, and lack of health insurance. Targeted efforts to provide culturally appropriate education, accessible vision screening, appropriate refractive correction, and routine follow-up to these medically underserved groups should be pursued as a public health strategy.
C1 [Qiu, Mary; Wang, Sophia Y.; Lin, Shan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA.
   [Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 University of California System; University of California San Francisco;
   Stanford University
RP Lin, SC (通讯作者)，10 Koret St,Room K301, San Francisco, CA 94143 USA.
EM lins@vision.ucsf.edu
OI Wang, Sophia/0000-0003-0916-9403
FU National Eye Institute core grant [EY002162]; Man May See, Inc.;
   Research to Prevent Blindness; National Center for Advancing
   Translational Sciences; National Institutes of Health through University
   of California San Francisco CTSI Grant [TL1 TR000144]; NATIONAL EYE
   INSTITUTE [P30EY002162] Funding Source: NIH RePORTER
FX Supported by National Eye Institute core grant EY002162, That Man May
   See, Inc., Research to Prevent Blindness, and National Center for
   Advancing Translational Sciences, National Institutes of Health, through
   University of California San Francisco CTSI Grant TL1 TR000144. The
   contents are solely the responsibility of the authors and do not
   necessarily represent the official views of the funding agencies. The
   authors have no financial disclosures to report.
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NR 37
TC 39
Z9 39
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 OCT
PY 2014
VL 55
IS 10
DI 10.1167/iovs.13-12662
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AT1ZS
UT WOS:000344730500049
PM 25249602
OA Green Published
DA 2022-11-30
ER

PT J
AU Guymer, RH
   Brassington, KH
   Dimitrov, P
   Makeyeva, G
   Plunkett, M
   Xia, W
   Chauhan, D
   Vingrys, A
   Luu, CD
AF Guymer, Robyn H.
   Brassington, Kate H.
   Dimitrov, Peter
   Makeyeva, Galina
   Plunkett, Malcolm
   Xia, Wie
   Chauhan, Devinder
   Vingrys, Algis
   Luu, Chi D.
TI Nanosecond-laser application in intermediate AMD: 12-month results of
   fundus appearance and macular function
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE AMD; macula; nanosecond laser; perimetry
ID AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; FOVEAL FLICKER
   SENSITIVITY; 3-NANOSECOND PULSE LASER; CONVENTIONAL PHOTOCOAGULATOR;
   VISUAL FUNCTION; CLINICAL-TRIAL; RETINAL LASER; FELLOW EYE; HIGH-RISK
AB Background: A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported.
   Design: Prospective non-randomised, pilot intervention study.
   Participants or Samples: Subjects with bilateral intermediate AMD (n = 50, aged 50-75 years).
   Methods: Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 mu m diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient.
   Main Outcome Measures: Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser.
   Results: Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3 degrees was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect > 15 dB), seven improved sufficiently to be taken out of this high-risk category.
   Conclusions: A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD.
C1 [Guymer, Robyn H.; Brassington, Kate H.; Dimitrov, Peter; Makeyeva, Galina; Chauhan, Devinder; Luu, Chi D.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Australia.
   [Plunkett, Malcolm; Xia, Wie] Ellex R&D Pty Ltd, Adelaide, SA, Australia.
   [Vingrys, Algis] Univ Melbourne, Carlton, Vic 3053, Australia.
C3 Centre for Eye Research Australia; University of Melbourne; University
   of Melbourne
RP Guymer, RH (通讯作者)，Ctr Eye Res Australia, Level 1,32 Gisborne St, East Melbourne, Vic 3002, Australia.
EM rhg@unimelb.edu.au
RI Chauhan, Devinder/W-8069-2019
OI Luu, Chi/0000-0002-7604-7097; Guymer, Robyn/0000-0002-9441-4356;
   Vingrys, Algis/0000-0001-5920-4604
FU Victorian State Government; Ellex R&D Pty Ltd, Adelaide; National Health
   and Medical Research Council (NHMRC) [529905]; NHMRC Centre for Clinical
   Research Excellence [529923]
FX This work was supported by a grant to the Centre for Eye Research
   Australia, from the Victorian State Government under the Victoria's
   Science Agenda Investment Fund and from Ellex R&D Pty Ltd, Adelaide. RHG
   receives a National Health and Medical Research Council (NHMRC)
   practitioner fellowship (#529905). CERA is supported by a NHMRC Centre
   for Clinical Research Excellence #529923 award and receives operational
   infrastructure from the Victorian Government. The funding organizations
   had no role in the design or conduct of this research.
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NR 39
TC 52
Z9 52
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD JUL
PY 2014
VL 42
IS 5
BP 466
EP 479
DI 10.1111/ceo.12247
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AM6DM
UT WOS:000339952400011
PM 24118741
DA 2022-11-30
ER

PT J
AU Lai, FHP
   Lok, JYC
   Chow, PPC
   Young, AL
AF Lai, Frank H. P.
   Lok, Julie Y. C.
   Chow, Prudence P. C.
   Young, Alvin L.
TI Clinical Outcomes of Cataract Surgery in Very Elderly Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cataract surgery; elderly; visual outcome; morbidity; risk factor
ID ELECTRONIC MULTICENTER AUDIT; PREVALENCE; COMPLICATIONS; IMPAIRMENT;
   CHINESE; IMPACT; OLDER; LENS; AGE
AB ObjectivesTo investigate the clinical outcomes of cataract surgery elderly adults.
   DesignRetrospective cohort study.
   SettingTwo clustered hospitals.
   ParticipantsTwo hundred seven individuals aged 90 and older who underwent cataract surgery for primary senile cataracts.
   MeasurementsBest-corrected preoperative and postoperative Snellen visual acuity, type of cataract, surgical techniques, preoperative systemic or ocular comorbidities, and intraoperative and postoperative complications were assessed. Improvement of visual acuity was defined as a decrease in logMAR acuity of 0.1. Factors associated with visual outcome within 6months after surgery were identified using logistic regression modeling. The duration of postoperative survival was calculated.
   ResultsIn the 207 participants (mean age 92.02.1), 79.7% achieved visual improvement after cataract surgery. Forty-eight percent (mean age 97.4 +/- 2.8) were alive on December 31, 2012. The most common systemic comorbidities were hypertension (66.2%), diabetes mellitus (25.1%), and myocardial infarction (19.8%). Age-related macular degeneration (AMRD) (15.9%), glaucoma (10.6%), and myopic degeneration (5.3%) were the three most common ocular comorbidities. Uncomplicated cataract surgery was performed in 87.0% cases. The most common complications were vitreous loss (8.2%), posterior capsular rupture (7.2%), and zonular rupture (4.8%). Participants with AMRD (P=.001, odds ratio (OR)=4.77, 95% confidence interval (CI)=1.86-12.26) and vitreous loss (P=.001, OR=12.86, 95% CI=2.71-61.10) were less likely to achieve postoperative visual improvement.
   ConclusionDespite a high prevalence of systemic and ocular comorbidities in very elderly adults, good clinical outcomes of cataract surgery were attainable. ARMD and vitreous loss were associated with a lower chance of postoperative visual improvement.
C1 [Lai, Frank H. P.; Lok, Julie Y. C.; Chow, Prudence P. C.; Young, Alvin L.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Shatin, Hong Kong, Peoples R China.
C3 Chinese University of Hong Kong
RP Young, AL (通讯作者)，Chinese Univ Hong Kong, Prince Wales Hosp, Dept Ophthalmol & Visual Sci, Shatin, Hong Kong, Peoples R China.
EM youngla@ha.org.hk
OI Lai, Hiu Ping/0000-0002-4446-3790
CR [Anonymous], 2000, Community Eye Health, V13, P17
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NR 30
TC 22
Z9 23
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2014
VL 62
IS 1
BP 165
EP 170
DI 10.1111/jgs.12590
PG 6
WC Geriatrics & Gerontology; Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA 292AS
UT WOS:000329874600023
PM 24279708
DA 2022-11-30
ER

PT J
AU Makou, E
   Herbert, AP
   Barlow, PN
AF Makou, Elisavet
   Herbert, Andrew P.
   Barlow, Paul N.
TI Functional Anatomy of Complement Factor H
SO BIOCHEMISTRY
LA English
DT Article
ID REGULATOR FACTOR-H; TRANSLATIONAL MINIREVIEW SERIES; HEMOLYTIC-UREMIC
   SYNDROME; POLYANION BINDING-SITE; SHORT CONSENSUS REPEAT; C-REACTIVE
   PROTEIN; MACULAR DEGENERATION; ALTERNATIVE PATHWAY; STRUCTURAL BASIS;
   SEQUENCE VARIATIONS
AB Factor H (FH) is a soluble regulator of the proteolytic cascade at the core of the evolutionarily ancient vertebrate complement system. Although FH consists of a single chain of similar protein modules, it has a demanding job description. Its chief role is to prevent complement-mediated injury to healthy host cells and tissues. This entails recognition of molecular patterns on host surfaces combined with control of one of nature's most dangerous examples of a positive-feedback loop. In this way, FH modulates, where and when needed, an amplification process that otherwise exponentially escalates the production of the pro-inflammatory, pro-phagocytic, and pro-cytolytic cleavage products of complement proteins C3 and C5. Mutations and single-nucleotide, polymorphisms in the FH gene an autoantibodies against FH predispose individuals to diseases, including age-related macular degeneration, dense-deposit disease, and atypical hemolytic uremic syndrome. Moreover, deletions or variations of genes for FH-related proteins also influence the risk of disease. Numerous pathogens hijack FH and use it for self-defense. As reviewed herein, a molecular understanding of FH function is emerging. While its functional oligomeric status remains uncertain, progress has been achieved in characterizing its three-dimensional architecture and, to a lesser extent, its intermodular flexibility. Models are proposed, based on the reconciliation of older data with a wealth of recent evidence, in which a latent circulating form of FH is activated by its principal target, C3b tethered to a self-surface. Such models suggest hypotheses linking sequence variations to pathophysiology, but improved, more quantitative, functional assays and rigorous data analysis are required to test these ideas.
C1 [Makou, Elisavet; Herbert, Andrew P.; Barlow, Paul N.] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Barlow, Paul N.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JJ, Midlothian, Scotland.
C3 University of Edinburgh; University of Edinburgh
RP Barlow, PN (通讯作者)，Univ Edinburgh, Sch Biol Sci, Joseph Black Chem Bldg,West Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM paul.barlow@ed.ac.uk
RI Herbert, Andrew P/C-4755-2008; Herbert, Andy P/F-6693-2010
OI Herbert, Andrew P/0000-0002-4549-6965; Herbert, Andy
   P/0000-0002-4549-6965
FU BBSRC [BB/I007946]; Biotechnology and Biological Sciences Research
   Council [BB/I007946/1] Funding Source: researchfish; Medical Research
   Council [G0001089] Funding Source: researchfish; Chief Scientist Office
   [CZB/4/763] Funding Source: researchfish; BBSRC [BB/I007946/1] Funding
   Source: UKRI; MRC [G0001089] Funding Source: UKRI
FX Supported by BBSRC Grant BB/I007946.
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NR 108
TC 86
Z9 89
U1 0
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 11
PY 2013
VL 52
IS 23
BP 3949
EP 3962
DI 10.1021/bi4003452
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 165LO
UT WOS:000320485600001
PM 23701234
DA 2022-11-30
ER

PT J
AU Kemp, A
   Preen, DB
   Morlet, N
   Clark, A
   McAllister, IL
   Briffa, T
   Sanfilippo, FM
   Ng, JQ
   McKnight, C
   Reynolds, W
   Gilles, MC
AF Kemp, Anna
   Preen, David B.
   Morlet, Nigel
   Clark, Antony
   McAllister, Ian L.
   Briffa, Tom
   Sanfilippo, Frank M.
   Ng, Jonathon Q.
   McKnight, Charlotte
   Reynolds, Wayne
   Gilles, Mark C.
TI MYOCARDIAL INFARCTION AFTER INTRAVITREAL VASCULAR ENDOTHELIAL GROWTH
   FACTOR INHIBITORS A Whole Population Study
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE adverse events; age-related macular degeneration; bevacizumab; choroidal
   neovascularization; postmarketing surveillance; ranibizumab
ID MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; WESTERN-AUSTRALIA;
   RANIBIZUMAB; VERTEPORFIN; EVENTS; MORTALITY; THERAPY; STROKE
AB Purpose: To determine the risk of thromboembolic and gastrointestinal bleeding events in the 12 months after injections of bevacizumab or ranibizumab compared with photodynamic therapy and a nontreated community sample.
   Methods: Hospital and death records were examined for 1,267 patients treated with vascular endothelial growth factor inhibitor and 399 patients treated with photodynamic therapy attending Western Australian eye clinics from 2002 to 2008, and 1,763 community controls, aged >= 50 years. Hospital records from 1995 to 2009 were analyzed for history of myocardial infarction (MI), stroke, and gastrointestinal bleeding before treatment. Records were searched for evidence of these events in the 12 months after treatment.
   Results: The 12-month MI rate was higher for vascular endothelial growth factor inhibitor patients than photodynamic therapy patientsand the community group (1.9/100 vs. 0.8 and 0.7, respectively). No differences were observed between patients treated with bevacizumab and ranibizumab. The adjusted MI rate was 2.3 times greater than the community group (95% confidence interval, 1.2-4.5) and photodynamic therapy rate (95% confidence interval, 0.7-7.7). The 12-month MI risk did not increase with the number of injections administered (hazard ratio, 0.9; 95% confidence interval, 0.5-1.5). Stroke and gastrointestinal bleeding did not differ between any exposure groups.
   Conclusion: Although all the adverse events examined were rare, patients treated with vascular endothelial growth factor inhibitors were significantly more likely to experience fatal or nonfatal MI than the community group. This increased risk may be related to the underlying age-related macular degeneration or vascular endothelial growth factor inhibitor use itself. RETINA 33: 920-927, 2013
C1 [Kemp, Anna; Preen, David B.] Univ Western Australia, Sch Populat Hlth, Ctr Hlth Serv Res, Perth, WA 6009, Australia.
   [Kemp, Anna] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia.
   [Morlet, Nigel; Clark, Antony; McAllister, Ian L.; McKnight, Charlotte; Reynolds, Wayne] Royal Perth Hosp, Dept Ophthalmol, Perth, WA, Australia.
   [Clark, Antony] Curtin Univ, Curtin Hlth Innovat Res Inst, Bentley, WA, Australia.
   [McAllister, Ian L.; McKnight, Charlotte] Univ Western Australia, Sch Populat Hlth, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia.
   [Briffa, Tom; Sanfilippo, Frank M.] Univ Western Australia, Sch Populat Hlth, Cardiovasc Res Grp, Perth, WA 6009, Australia.
   [Ng, Jonathon Q.] Univ Western Australia, Sch Populat Hlth, Eye & Vis Epidemiol Res Grp, Perth, WA 6009, Australia.
   [Gilles, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
C3 University of Western Australia; University of Wollongong; Royal Perth
   Hospital; University of Western Australia; Curtin University; Lions Eye
   Institute; University of Western Australia; University of Western
   Australia; University of Western Australia; University of Sydney
RP Kemp, A (通讯作者)，Univ Western Australia, Sch Populat Hlth, Ctr Hlth Serv Res, 35 Stirling Hwy, Perth, WA 6009, Australia.
EM anna.kemp@uwa.edu.au
RI Kemp-Casey, Anna/AAU-7292-2021; Sanfilippo, Frank M/H-9334-2013; Clark,
   Antony/K-7419-2014; Kemp-Casey, Anna/F-1283-2013; Preen, David
   B/H-5663-2014; Clark, Antony/A-2641-2009
OI Kemp-Casey, Anna/0000-0002-0018-962X; Sanfilippo, Frank
   M/0000-0003-3639-0787; Clark, Antony/0000-0001-8393-9870; Kemp-Casey,
   Anna/0000-0002-0018-962X; Preen, David B/0000-0002-2982-2169; Clark,
   Antony/0000-0001-8393-9870; Ng, Jonathon/0000-0002-4731-6673
FU University of Western Australia, Perth, Australia; Save Sight Institute,
   University of Sydney, Sydney, Australia; Medical Research Council
   [MR/K006525/1] Funding Source: researchfish; MRC [MR/K006525/1] Funding
   Source: UKRI
FX Supported by the Research Development Award, The University of Western
   Australia, Perth, Australia, and by the Research Award, Save Sight
   Institute, University of Sydney, Sydney, Australia. The funding
   organizations had no role in the design or conduct of this research.
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NR 37
TC 36
Z9 36
U1 0
U2 7
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 2013
VL 33
IS 5
BP 920
EP 927
DI 10.1097/IAE.0b013e318276e07b
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 131QY
UT WOS:000318011100004
PM 23492942
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 Aging and Cone Dark Adaptation
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE aging; dark adaptation; cones; age-related macular degeneration;
   biomarker
ID AGE-RELATED MACULOPATHY; ERG PHOTOSTRESS TEST; HUMAN OPTIC-NERVE;
   MACULAR DEGENERATION; GOOD ACUITY; OLDER EYES; FELLOW EYE; ROD;
   SENSITIVITIES; REGENERATION
AB Purpose. Following exposure to a bright light that bleaches a significant portion of photopigment, the eyes take several minutes to regain sensitivity. This slow process, known as dark adaptation, is impaired in patients with age-related macular degeneration and is an important candidate biomarker for this disease. The aim of this study was to evaluate the effect of age on cone dark adaptation.
   Methods. Data were obtained from 41 healthy adults aged between 20 and 83 years. Pupils were dilated and 96% of cone photopigment was "bleached," before threshold was monitored continuously for 5 min in the dark, using a 4 diameter achromatic spot centered on the fovea. Threshold recovery data were modeled, and the time constant of cone recovery (tau), initial cone thresholds, and final cone thresholds were determined. Regression analysis was used to determine the relationship between age and cone dark adaptation parameters.
   Results. Cone tau increased by 16.4 s/decade of life, indicating a progressive slowing of dark adaptation with increasing age. This change in cone tau throughout adulthood was significant (p < 0.0005). There was no significant relationship between increasing age and initial cone threshold (p = 0.84) or final cone threshold (p = 0.82).
   Conclusions. Our results provide evidence for age-related slowing of cone dark adaptation after a full bleach in healthy adults, which is likely to contribute to visual difficulties when moving from bright to dim photopic light levels. We propose that the sensitivity and specificity of cone tau as a biomarker for early age-related macular disease could be improved by taking into account the significant age-related decline in this parameter. (Optom Vis Sci 2012;89:1219-1224)
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 Margrain, TH (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Maindy Rd, Cardiff CF24 4LU, 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. We would like to thank Bryn Jones for his
   help with data collection.
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NR 42
TC 15
Z9 21
U1 0
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-5488
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD AUG
PY 2012
VL 89
IS 8
BP 1219
EP 1224
DI 10.1097/OPX.0b013e318263c6b1
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 988GH
UT WOS:000307476600017
PM 22773176
DA 2022-11-30
ER

PT J
AU Rosman, M
   Zheng, Y
   Lamoureux, E
   Saw, SM
   Aung, T
   Tay, WT
   Wang, JJ
   Mitchell, P
   Tai, ES
   Wong, TY
AF Rosman, M.
   Zheng, Y.
   Lamoureux, E.
   Saw, S. M.
   Aung, T.
   Tay, W. T.
   Wang, J. J.
   Mitchell, P.
   Tai, E. S.
   Wong, T. Y.
TI Review of key findings from the Singapore Malay Eye Study (SiMES-1)
SO SINGAPORE MEDICAL JOURNAL
LA English
DT Review
DE eye diseases; prevalence; Singaporean Malays
ID RETINAL VASCULAR CALIBER; RISK-FACTORS; REFRACTIVE ERRORS; ASIAN
   POPULATION; LOW-VISION; PREVALENCE; GLAUCOMA; BLINDNESS; IMPAIRMENT;
   CATARACT
AB INTRODUCTION This study highlights the key epidemiological findings from the Singapore Malay Eye Study (SiMES-1). METHODS SiMES-1 was a cross-sectional, population-based epidemiological study on eye diseases. It was performed on 3,280 randomly selected Malay adults living in the south-western part of Singapore. All study participants underwent various validated questionnaires and detailed eye examinations. A review of all papers published from SiMES-1 was performed.
   RESULTS A total of 24.6% of the study population had myopia, while 35.3% had hyperopia and 39.4% had astigmatism. 20.4% of the population had under-corrected refractive error. 1,338 (45.7%) participants were diagnosed to have cataracts in at least one eye. 8.6% of the study population had undergone cataract surgery in either eye, while 4.7% had bilateral cataract surgery. 150 (4.6%) participants were diagnosed to have glaucoma, of which primary open angle glaucoma was the most common type (3.2% of the study population), followed by secondary glaucoma (0.8%) and primary angle closure glaucoma (0.2%). Pterygium was diagnosed in 508 out of 3,266 study participants, giving a prevalence rate of 15.6%. The presence of diabetic retinopathy was observed in 421 (12.9%) out of 3,265 study participants. 183 (5.6%) study participants had some degree of age-related macular degeneration (AMD), of which 23 (0.7%) were classified as having late AMD.
   CONCLUSION This paper provides a summary of the prevalence of common eye diseases among the Singaporean adult Malay population and provides data useful for public health education and disease prevention.
C1 [Rosman, M.; Zheng, Y.; Lamoureux, E.; Saw, S. M.; Aung, T.; Tay, W. T.; Wong, T. Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 168751, Singapore.
   [Rosman, M.; Saw, S. M.; Aung, T.; Wong, T. Y.] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Lamoureux, E.; Wang, J. J.; Wong, T. Y.] Univ Melbourne, Ctr Eye Res, Melbourne, Vic 3010, Australia.
   [Saw, S. M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 168751, Singapore.
   [Aung, T.; Wong, T. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 168751, Singapore.
   [Wang, J. J.; Mitchell, P.] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Tai, E. S.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 168751, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   Singapore National Eye Center; University of Melbourne; National
   University of Singapore; National University of Singapore; University of
   Sydney; National University of Singapore
RP Wong, TY (通讯作者)，Natl Univ Singapore, Singapore Eye Res Inst, 11 3rd Hosp Ave,05-00, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
RI Mitchell, Paul/P-1498-2014; Tai, E Shyong/J-9831-2013; wang,
   jie/GRS-0942-2022; Lamoureux, Ecosse/Z-5482-2019; Wong, Tien
   Yin/AAC-9724-2020; Wang, Jie Jin/P-1499-2014
OI Wong, Tien Yin/0000-0002-8448-1264; Wang, Jie Jin/0000-0001-9491-4898;
   Tai, E Shyong/0000-0003-2929-8966
FU National Medical Research Council [0796/2003]; Biomedical Research
   Council [501/1/25-5]
FX This study was supported by the National Medical Research Council Grants
   No. 0796/2003 and Biomedical Research Council Grant No 501/1/25-5.
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NR 31
TC 20
Z9 21
U1 0
U2 8
PU SINGAPORE MEDICAL ASSOC
PI SINGAPORE
PA 2985 JALAN BUKIT MERAH, #02-2C, SMF BUILDING, SINGAPORE, SINGAPORE
SN 0037-5675
J9 SINGAP MED J
JI Singap. Med. J.
PD FEB
PY 2012
VL 53
IS 2
BP 82
EP 87
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 922XU
UT WOS:000302582800009
PM 22337179
DA 2022-11-30
ER

PT J
AU Veurink, M
   Stella, C
   Tabatabay, C
   Pournaras, CJ
   Gurny, R
AF Veurink, Marieke
   Stella, Cinzia
   Tabatabay, Cyrus
   Pournaras, Constantin J.
   Gurny, Robert
TI Association of ranibizumab (Lucentis (R)) or bevacizumab (Avastin (R))
   with dexamethasone and triamcinolone acetonide: An in vitro stability
   assessment
SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
LA English
DT Article
DE Monoclonal antibodies; Asymmetrical flow field-flow fractionation;
   Aggregation state; Anti-inflammatory drugs; Neovascular age-related
   macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; INTRAVITREAL
   BEVACIZUMAB; PROTEIN AGGREGATION; CLINICAL-TRIAL; DEGENERATION;
   ANTIBODY; THERAPY; IMMUNOGLOBULIN; FORMULATION
AB The in vitro stability of monoclonal antibodies used for age-related macular degeneration, ranibizumab and bevacizumab, was investigated. The aggregation profile of the antibodies was compared, alone and after association with dexamethasone sodium phosphate or triamcinolone acetonide. Commercial formulations of ranibizumab and bevacizumab were dialysed into three different buffers. After dialysis, samples were stored at 4 degrees C, 25 degrees C and 40 degrees C during 35 days, alone and in combination with dexamethasone sodium phosphate, triamcinolone acetonide phosphate solution or triamcinolone acetonide suspension. Combined formulations based on both commercial formulations were investigated as well. The aggregation state of the antibodies was measured by multi-angle light scattering (MALS) after separation by asymmetrical flow field-flow fractionation (AFFF) or size-exclusion chromatography (SEC). Ranibizumab results to be more stable than bevacizumab, alone and in combination with dexamethasone sodium phosphate or triamcinolone acetonide. Elevation in concentration, pH and temperature causes a decrease in stability of both antibodies. The association of triamcinolone acetonide phosphate solution with either ranibizumab or bevacizumab is observed to be the least stable combination of all samples tested. Dexamethasone sodium phosphate was shown to have a stabilizing effect on bevacizumab, although this is not the case for its combination with the commercial formulation Avastin (R). The results demonstrate that the in vitro association of either ranibizumab or bevacizumab with dexamethasone sodium phosphate or triamcinolone acetonide suspension does not decrease the stability of these antibodies. Although ranibizumab is more stable than bevacizumab in vitro, further research has to point out how this affects their mechanism of action in vivo. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Veurink, Marieke; Stella, Cinzia; Gurny, Robert] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, Dept Pharmaceut & Biopharmaceut, CH-1211 Geneva 4, Switzerland.
   [Tabatabay, Cyrus; Pournaras, Constantin J.] Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland.
C3 University of Geneva; University of Lausanne; University of Geneva
RP Gurny, R (通讯作者)，Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, Dept Pharmaceut & Biopharmaceut, CH-1211 Geneva 4, Switzerland.
EM Robert.Gurny@unige.ch
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NR 26
TC 16
Z9 19
U1 0
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0939-6411
J9 EUR J PHARM BIOPHARM
JI Eur. J. Pharm. Biopharm.
PD JUN
PY 2011
VL 78
IS 2
SI SI
BP 271
EP 277
DI 10.1016/j.ejpb.2010.12.018
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 771TQ
UT WOS:000291184000012
PM 21172437
DA 2022-11-30
ER

PT J
AU London, NJS
   Chiang, A
   Haller, JA
AF London, Nikolas J. S.
   Chiang, Allen
   Haller, Julia A.
TI The Dexamethasone Drug Delivery System: Indications and Evidence
SO ADVANCES IN THERAPY
LA English
DT Review
DE age-related macular degeneration; corticosteroids; dexamethasone;
   diabetic retinopathy; intraocular; intravitreal triamcinolone acetonide;
   macular edema; Ozurdex; retinal vein occlusion; uveitis
ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; DIABETIC MACULAR EDEMA;
   INTRAOCULAR CONCENTRATION; CORTICOSTEROIDS INHIBIT; RETINAL TOXICITY;
   VISUAL-ACUITY; STANDARD-CARE; RABBIT MODEL; INJECTION; PHARMACOKINETICS
AB Introduction: The Ozurdex (R) (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 mu g of preservative-free dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options. Methods: Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed. Results: The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management. Conclusions: The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.
C1 [Haller, Julia A.] Wills Eye Hosp & Res Inst, Philadelphia, PA 19107 USA.
   [London, Nikolas J. S.; Chiang, Allen; Haller, Julia A.] Thomas Jefferson Univ, Wills Eye Inst, Retina Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University; Jefferson University
RP Haller, JA (通讯作者)，Wills Eye Hosp & Res Inst, 840 Walnut St,Suite 1510, Philadelphia, PA 19107 USA.
EM jhaller@willseye.org
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NR 64
TC 104
Z9 110
U1 2
U2 24
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0741-238X
EI 1865-8652
J9 ADV THER
JI Adv. Ther.
PD MAY
PY 2011
VL 28
IS 5
BP 351
EP 366
DI 10.1007/s12325-011-0019-z
PG 16
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 771LQ
UT WOS:000291159600001
PM 21494891
DA 2022-11-30
ER

PT J
AU Jiang, AH
   Gao, H
   Kelley, MR
   Qiao, XX
AF Jiang, Aihua
   Gao, Hua
   Kelley, Mark R.
   Qiao, Xiaoxi
TI Inhibition of APE1/Ref-1 redox activity with APX3330 blocks retinal
   angiogenesis in vitro and in vivo
SO VISION RESEARCH
LA English
DT Article
DE Age-related macular degeneration; RAP-like neovascularization;
   Angiogenesis; APE1/Ref-1; Reduction-oxidation regulation; Redox
   inhibitor; APX3330
ID ENDOTHELIAL GROWTH-FACTOR; SUBRETINAL NEOVASCULARIZATION; PROTEIN
   APE1/REF-1; CANCER CELLS; DNA-REPAIR; REF-1; DIFFERENTIATION;
   SUPPRESSION; EXPRESSION; APOPTOSIS
AB This study examines the role of APE1/Ref-1 in the retina and its potential as a therapeutic target for inhibiting retinal angiogenesis. APE1/Ref-1 expression was quantified by Western blot. The role of APE1/Ref-1 redox function in endothelial cell in vitro angiogenesis was examined by treating retinal vascular endothelial cells (RVECs) with APX3330, a small molecule inhibitor of APE1/Ref-1 redox activity. In vitro methods included a proliferation assay, a transwell migration assay, a Matrigel tube formation assay, and a Real-Time Cell Analysis (RTCA) using the xCELLigence System. In vivo functional studies of APE1/Ref-1 were carried out by treating very low density lipoprotein (VLDL) receptor knockout mice (Vldlr(-/-)) with intravitreal injection of APX3330, and subsequent measurement of retinal angiomatous proliferation (RAP)-like neovascularization for one week. APE1/Ref-1 was highly expressed in the retina and in RVECs and pericytes in mice. APX3330 (1-10 mu M) inhibited proliferation, migration and tube formation of RVECs in vitro in a dose-dependent manner. Vldlr(-/-) RVECs were more sensitive to APX3330 than wild-type RVECs. In Vldlr(-/-) mice, a single intravitreal injection of APX3330 at the onset of RAP-like neovascularization significantly reduced RAP-like neovascularization development. APE1/Ref-1 is expressed in retinal vascular cells. APX3330 inhibits RVEC angiogenesis in vitro and significantly reduces RAP-like neovascularization in Vldlr(-/-) mice. These data support the conclusion that APE1/Ref-1 redox function is required for retinal angiogenesis. Thus, APE1/Ref-1 may have potential as a therapeutic target for treating neovascular age-related macular degeneration and other neovascular diseases. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Gao, Hua; Qiao, Xiaoxi] Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI 48202 USA.
   [Jiang, Aihua] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
   [Kelley, Mark R.] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA.
C3 Henry Ford Health System; Henry Ford Hospital; Harvard University; Beth
   Israel Deaconess Medical Center; Indiana University System; Indiana
   University Bloomington
RP Qiao, XX (通讯作者)，Henry Ford Hlth Syst, Dept Ophthalmol, 1 Ford Pl, Detroit, MI 48202 USA.
EM xqiao1@hfhs.org
FU Fight for Sight; Reeve's Foundation; American Health Assistance
   Foundation; NIH, National Cancer Institute [CA106298, CA114571,
   CA121168]; NIH National Eye Institute [R41 EY019784]; Riley Children's
   Foundation; CTSA [UL1RR025761]; NATIONAL CANCER INSTITUTE [R01CA114571,
   R01CA121168, R01CA106298] Funding Source: NIH RePORTER; NATIONAL CENTER
   FOR RESEARCH RESOURCES [UL1RR025761] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R41EY019784] Funding Source: NIH RePORTER
FX Financial support for this work was provided by a postdoctoral
   fellowship from the Fight for Sight to A.J., research grants from
   Reeve's Foundation, and American Health Assistance Foundation to X.Q.
   and the NIH, National Cancer Institute CA106298, CA114571 and CA121168
   to M.R.K., NIH National Eye Institute R41 EY019784 to both M.R.K. and
   X.Q. and the Riley Children's Foundation (M.R.K.). Additional support
   was provided by pilot funding through TRAC1 of the CTSA UL1RR025761 to
   the IU School of Medicine. The corresponding author had full access to
   all the data in the study and takes responsibility for the integrity of
   the data and the accuracy of the data analysis.
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NR 30
TC 36
Z9 37
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD JAN
PY 2011
VL 51
IS 1
BP 93
EP 100
DI 10.1016/j.visres.2010.10.008
PG 8
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 705RG
UT WOS:000286155000012
PM 20937296
OA Green Accepted, Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Mihaescu, R
   Moonesinghe, R
   Khoury, MJ
   Janssens, ACJW
AF Mihaescu, Raluca
   Moonesinghe, Ramal
   Khoury, Muin J.
   Janssens, A. Cecile J. W.
TI Predictive genetic testing for the identification of high-risk groups: a
   simulation study on the impact of predictive ability
SO GENOME MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; GENOME-BASED PREDICTION; CARDIOVASCULAR EVENTS;
   SCORE; HEALTH; POLYMORPHISMS; ASSOCIATION; PROFILES; UTILITY; COHORT
AB Background: Genetic risk models could potentially be useful in identifying high-risk groups for the prevention of complex diseases. We investigated the performance of this risk stratification strategy by examining epidemiological parameters that impact the predictive ability of risk models.
   Methods: We assessed sensitivity, specificity, and positive and negative predictive value for all possible risk thresholds that can define high-risk groups and investigated how these measures depend on the frequency of disease in the population, the frequency of the high-risk group, and the discriminative accuracy of the risk model, as assessed by the area under the receiver-operating characteristic curve (AUC). In a simulation study, we modeled genetic risk scores of 50 genes with equal odds ratios and genotype frequencies, and varied the odds ratios and the disease frequency across scenarios. We also performed a simulation of age-related macular degeneration risk prediction based on published odds ratios and frequencies for six genetic risk variants.
   Results: We show that when the frequency of the high-risk group was lower than the disease frequency, positive predictive value increased with the AUC but sensitivity remained low. When the frequency of the high-risk group was higher than the disease frequency, sensitivity was high but positive predictive value remained low. When both frequencies were equal, both positive predictive value and sensitivity increased with increasing AUC, but higher AUC was needed to maximize both measures.
   Conclusions: The performance of risk stratification is strongly determined by the frequency of the high-risk group relative to the frequency of disease in the population. The identification of high-risk groups with appreciable combinations of sensitivity and positive predictive value requires higher AUC.
C1 [Mihaescu, Raluca; Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
   [Moonesinghe, Ramal] Ctr Dis Control & Prevent, Off Minor Hlth & Hlth Dispar, Atlanta, GA 30341 USA.
   [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30341 USA.
C3 Erasmus University Rotterdam; Erasmus MC; Centers for Disease Control &
   Prevention - USA; Centers for Disease Control & Prevention - USA
RP Janssens, ACJW (通讯作者)，Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM a.janssens@erasmusmc.nl
RI Moonesinghe, Ramal/W-2534-2019; janssens, cecile c/L-1075-2015
OI Moonesinghe, Ramal/0000-0001-5327-533X; Janssens, A
   Cecile/0000-0002-6153-4976
FU Centre for Medical Systems Biology (CMSB); VIDI grant of the Netherlands
   Organization for Scientific Research (NWO)
FX This study was supported by the Centre for Medical Systems Biology
   (CMSB) in the framework of the Netherlands Genomics Initiative (NGI).
   Furthermore, this project was sponsored by the VIDI grant of the
   Netherlands Organization for Scientific Research (NWO).
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   Seddon JM, 2009, INVEST OPHTH VIS SCI, V50, P2044, DOI 10.1167/iovs.08-3064
   Talmud PJ, 2010, BMJ-BRIT MED J, V340, DOI 10.1136/bmj.b4838
   van der Net JB, 2009, AM J CARDIOL, V103, P375, DOI 10.1016/j.amjcard.2008.09.093
   van Hoek M, 2008, DIABETES, V57, P3122, DOI 10.2337/db08-0425
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   Wray NR, 2010, PLOS GENET, V6, DOI 10.1371/journal.pgen.1000864
NR 30
TC 9
Z9 9
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PY 2011
VL 3
AR 51
DI 10.1186/gm267
PG 8
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA V27QJ
UT WOS:000208627400051
PM 21797996
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Everdell, NL
   Styles, IB
   Calcagni, A
   Gibson, J
   Hebden, J
   Claridge, E
AF Everdell, N. L.
   Styles, I. B.
   Calcagni, A.
   Gibson, J.
   Hebden, J.
   Claridge, E.
TI Multispectral imaging of the ocular fundus using light emitting diode
   illumination
SO REVIEW OF SCIENTIFIC INSTRUMENTS
LA English
DT Article
DE biomedical optical imaging; CCD image sensors; diseases; eye; light
   emitting diodes
ID DISEASES
AB We present an imaging system based on light emitting diode (LED) illumination that produces multispectral optical images of the human ocular fundus. It uses a conventional fundus camera equipped with a high power LED light source and a highly sensitive electron-multiplying charge coupled device camera. It is able to take pictures at a series of wavelengths in rapid succession at short exposure times, thereby eliminating the image shift introduced by natural eye movements (saccades). In contrast with snapshot systems the images retain full spatial resolution. The system is not suitable for applications where the full spectral resolution is required as it uses discrete wavebands for illumination. This is not a problem in retinal imaging where the use of selected wavelengths is common. The modular nature of the light source allows new wavelengths to be introduced easily and at low cost. The use of wavelength-specific LEDs as a source is preferable to white light illumination and subsequent filtering of the remitted light as it minimizes the total light exposure of the subject. The system is controlled via a graphical user interface that enables flexible control of intensity, duration, and sequencing of sources in synchrony with the camera. Our initial experiments indicate that the system can acquire multispectral image sequences of the human retina at exposure times of 0.05 s in the range of 500-620 nm with mean signal to noise ratio of 17 dB (min 11, std 4.5), making it suitable for quantitative analysis with application to the diagnosis and screening of eye diseases such as diabetic retinopathy and age-related macular degeneration. (c) 2010 American Institute of Physics. [doi:10.1063/1.3478001]
C1 [Everdell, N. L.; Hebden, J.] UCL, Dept Med Phys, London WC1E 6BT, England.
   [Styles, I. B.; Calcagni, A.; Claridge, E.] Univ Birmingham, Sch Comp Sci, Birmingham B15 2TT, W Midlands, England.
   [Gibson, J.] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
C3 University of London; University College London; University of
   Birmingham; Aston University
RP Everdell, NL (通讯作者)，UCL, Dept Med Phys, Malet Pl Engn Bldg, London WC1E 6BT, England.
OI Gibson, Jonathan M/0000-0002-9281-5244; Styles,
   Iain/0000-0002-6755-0299; Calcagni, Antonio Salvatore
   Pio/0000-0002-1446-3546
FU Engineering and Physical Sciences Research Council (EPSRC); EPSRC
   [EP/E065104/1, EP/E065236/1] Funding Source: UKRI; Engineering and
   Physical Sciences Research Council [EP/E065236/1, EP/E065104/1] Funding
   Source: researchfish
FX This research was funded by the Engineering and Physical Sciences
   Research Council (EPSRC). Thanks also go to Joe Evans, Erich Herrmann,
   and Rob Cooper for their valuable help.
CR Alabboud I, 2007, PROC SPIE, V6631, DOI 10.1117/12.728535
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NR 17
TC 43
Z9 47
U1 2
U2 19
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
   MELVILLE, NY 11747-4501 USA
SN 0034-6748
J9 REV SCI INSTRUM
JI Rev. Sci. Instrum.
PD SEP
PY 2010
VL 81
IS 9
AR 093706
DI 10.1063/1.3478001
PG 9
WC Instruments & Instrumentation; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Instruments & Instrumentation; Physics
GA 657UK
UT WOS:000282440900017
PM 20886986
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Littarru, GP
   Tiano, L
AF Littarru, GP
   Tiano, L
TI Clinical aspects of coenzyme Q(10): an update
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Article
DE age-related macular degeneration; asthenozoospermia; cardiovascular
   disease; coenzyme-Q(10); migraine; mitochondrial dysfunction;
   neurodegenerative disorders; oxidative stress
ID RANDOMIZED CONTROLLED-TRIAL; HUMAN HEART-DISEASE; OXIDATIVE STRESS;
   PARKINSONS-DISEASE; MITOCHONDRIAL-FUNCTION; MIGRAINE PROPHYLAXIS;
   DEFICIENCY; THERAPY; FAILURE; ASTHENOZOOSPERMIA
AB Purpose of review Coenzyme Q(10) is administered for an ever-widening range of disorders, therefore it is timely to illustrate the latest findings with special emphasis on areas in which this therapeutic approach is completely new. These findings also give further insight into the biochemical mechanisms underlying clinical involvement of coenzyme Q(10).
   Recent findings Cardiovascular properties of coenzyme Q(10) have been further addressed, namely regarding myocardial protection during cardiac surgery, end-stage heart failure, pediatric at cardiomyopathy and in cardiopulmonary resuscitation. The vascular aspects of coenzyme Q(10) addressing the important field of endothelial function are briefly examined. The controversial issue of the statin/coenzyme Q(10) relationship, has been investigated in preliminary studies in which the,two substances were administered simultaneously. Work on different neurological diseases, involving mitochondrial dysfunction and oxidative stress, highlights some of the neuroprotective mechanisms of coenzyme Q(10). A 4-year follow-up on 10 Friedreich's Ataxia patients treated with coenzyme Q(10) and vitamin E showed a substantial improvement in cardiac and skeletal muscle bioenergetics and heart function. Mitochondrial dysfunction likely plays a role in the pathophysiology of migraine as well as age-related macular degeneration and a therapy including coenzyme Q(10) produced significant improvement. Finally, the effect of coenzyme Q(10) was evaluated in the treatment of asthenozoospermia.
   Summary The latest findings highlight the beneficial role of coenzyme Q(10) as coadjuvant in the treatment of syndromes, characterized by impaired mitochondrial bioenergetics and increased oxidative stress, which have a high social impact. Besides their clinical significance, these data give further insight into the biochemical mechanisms of coenzyme Q(10) activity.
C1 Polytech Univ Marche, Inst Biochem, I-60131 Ancona, Italy.
C3 Marche Polytechnic University
RP Littarru, GP (通讯作者)，Polytech Univ Marche, Inst Biochem, Via Ranieri, I-60131 Ancona, Italy.
EM g.littarru@univpm.it
RI Tiano, Luca/ABC-2341-2020
OI Tiano, Luca/0000-0002-7519-7106
CR Balercia G, 2004, FERTIL STERIL, V81, P93, DOI 10.1016/j.fertnstert.2003.05.009
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   Beal MF, 2004, J BIOENERG BIOMEMBR, V36, P381, DOI 10.1023/B:JOBB.0000041772.74810.92
   BELARDINELLI R, 2005, 4 C INT COQ10 ASS LO, P62
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   [No title captured]
NR 37
TC 76
Z9 81
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD NOV
PY 2005
VL 8
IS 6
BP 641
EP 646
DI 10.1097/01.mco.0000171123.60665.16
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 987OK
UT WOS:000233527000010
PM 16205466
DA 2022-11-30
ER

PT J
AU Wang, Z
   Paik, DC
   Del Priore, LV
   Gaillard, ER
   Burch, RL
AF Wang, Z
   Paik, DC
   Del Priore, LV
   Gaillard, ER
   Burch, RL
TI Nitrite-modified extracellular matrix proteins deleteriously affect
   retinal pigment epithelial cell function and viability: A comparison
   study with nonenzymatic glycation mechanisms
SO CURRENT EYE RESEARCH
LA English
DT Article
DE A2E; age-related macular degeneration; collagen cross-linking;
   extracellular matrix proteins; nitrite modified protein; retinal pigment
   epithelial cells
ID AGE-RELATED-CHANGES; BRUCHS MEMBRANE; MACULAR DEGENERATION; IN-VIVO;
   END-PRODUCTS; LIPOFUSCIN; OXIDE; NITRATE; DRUSEN; RPE
AB Purpose: Extracellular matrix (ECM) plays an important role in the regulation of cell function. The aging process may involve chemical modifications to ECM proteins, which may contribute to the aging of the Bruch membrane and pathogenesis of age-related macular degeneration (AMD). The purpose of this study is to investigate nitrite modification of basement membrane-like proteins on RPE cell behavior as a model for the aging of the Bruch membrane in age-related eye diseases. As a comparison, retinal pigment epithelium (RPE) cell behavior on glycolaldehyde-modified matrices (GMM) was also studied. Methods: Growth factor reduced Matrigel was reacted with nitrite or glycolaldehyde for 1 week or 12 hr, respectively. Calf RPE cells were plated on the modified matrices and examined in several ways. Attachment rates, proliferation rates, apoptosis, and necrosis were determined. Cell morphology and cell susceptibility to A2E-mediated damage was also monitored. Results: Nitrite-modified matrices (NMMs) inhibited cell attachment by 65% and proliferation by 33.7% compared to 69.6% and 21.7%, respectively, by GMM. Proliferation inhibition was not significant when cells were plated at high density on GMM (3.47%) but significant on NMM (20.9%). NMM induced cell apoptosis and necrosis, but GMM induced cell apoptosis only. Both modifications inhibited RPE differentiation. RPE cells on both matrices were more susceptible to blue light mediated damage by A2E, but damage was greater on NMM. Conclusions: NMM has significant damaging effects on RPE cell function and viability that is similar to the damaging effects of GMM. These studies may have relevance to the RPE dysfunction observed during the progression of AMD.
C1 No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   Columbia Univ, Dept Ophthalmol, New York, NY 10027 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
FU NATIONAL EYE INSTITUTE [R01EY012344] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [K08AG000863] Funding Source: NIH RePORTER;
   NEI NIH HHS [R01 EY12344] Funding Source: Medline; NIA NIH HHS [K08
   AG000863] Funding Source: Medline
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NR 59
TC 23
Z9 26
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD AUG
PY 2005
VL 30
IS 8
BP 691
EP 702
DI 10.1080/02713680590968259
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 965VA
UT WOS:000231977300011
PM 16109650
DA 2022-11-30
ER

PT J
AU Bailey, TA
   Kanuga, N
   Romero, IA
   Greenwood, J
   Luthert, PJ
   Cheetham, ME
AF Bailey, TA
   Kanuga, N
   Romero, IA
   Greenwood, J
   Luthert, PJ
   Cheetham, ME
TI Oxidative stress affects the junctional integrity of retinal pigment
   epithelial cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID IN-VITRO; GENE-EXPRESSION; BRUCHS MEMBRANE; TIGHT JUNCTIONS;
   BETA-CATENIN; PROTEINS; INCREASE; ADHESION; KINASE; WNT
AB PURPOSE. Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration. The cell line ARPE-19 was therefore examined for response to oxidative stress and its effect on stress protein induction and junctional integrity.
   METHODS. ARPE-19 cell viability after 1 week or 5 weeks in culture was assessed in response to different concentrations of hydrogen peroxide. The response to sublethal doses was assessed by examination of heme oxygenase (HO)-1, Hsp27 and Hsp70 by immunofluorescence and Western blot analysis. Immumofluorescence was used to investigate the localization of the junctional proteins zonula occludens (ZO)-1, occludin, and N-cadherin, and beta-catenin. Subcellular fractionation was used to assess any redistribution of beta-catenin. Monolayer integrity was examined by measurement of flux of rhodamine-conjugated dextrans from the apical to basal aspect of cells.
   RESULTS ARPE-19 cells cultured for 5 weeks were less sensitive to chronic oxidative stress induced by hydrogen peroxide than those cultured for 1 week. The more differentiated ARPE-19 cells had higher steady state levels of Hsp27 and Hsp70. The response to stress also differed with time in culture. The localization of junctional proteins, which became strongly peripheral after 5 weeks in culture, became disrupted after oxidative stress, and cytosolic beta-catenin increased. Chronic oxidative stress also increased paracellular flux across the monolayer.
   CONCLUSIONS. Increased resistance to chronic oxidative stress with differentiation in ARPE-19 cells correlated with higher steady state levels of Hsp27 and Hsp70. Oxidative stress disrupted RPE cell junction and barrier integrity, which may contribute to the pathogenesis of diseases related to RPE through disruption of the blood-retinal barrier.
C1 UCL, Div Pathol, London EC1V 9EL, England.
   UCL, Div Cell Biol, London EC1V 9EL, England.
   UCL, Inst Ophthalmol, London EC1V 9EL, England.
C3 University of London; University College London; University of London;
   University College London; University of London; University College
   London
RP Cheetham, ME (通讯作者)，UCL, Div Pathol, 11-43 Bath St, London EC1V 9EL, England.
EM michael.cheetham@ucl.ac.uk
RI Romero, Ignacio/A-7381-2008; Cheetham, Michael/B-4672-2011
OI Luthert, Philip/0000-0001-7276-6898; Greenwood,
   John/0000-0003-4496-2984; Cheetham, Michael/0000-0001-6429-654X; Romero,
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NR 41
TC 189
Z9 209
U1 0
U2 19
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2004
VL 45
IS 2
BP 675
EP 684
DI 10.1167/iovs.03-0351
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 771CX
UT WOS:000188769000043
PM 14744914
DA 2022-11-30
ER

PT J
AU Rakocz, N
   Chiang, JN
   Nittala, MG
   Corradetti, G
   Tiosano, L
   Velaga, S
   Thompson, M
   Hill, BL
   Sankararaman, S
   Haines, JL
   Pericak-Vance, MA
   Stambolian, D
   Sadda, SR
   Halperin, E
AF Rakocz, Nadav
   Chiang, Jeffrey N.
   Nittala, Muneeswar G.
   Corradetti, Giulia
   Tiosano, Liran
   Velaga, Swetha
   Thompson, Michael
   Hill, Brian L.
   Sankararaman, Sriram
   Haines, Jonathan L.
   Pericak-Vance, Margaret A.
   Stambolian, Dwight
   Sadda, Srinivas R.
   Halperin, Eran
TI Automated identification of clinical features from sparsely annotated
   3-dimensional medical imaging
SO NPJ DIGITAL MEDICINE
LA English
DT Article
ID MACULAR DEGENERATION; DEEP; PROGRESSION; SEGMENTATION; NETWORKS; CNN
AB One of the core challenges in applying machine learning and artificial intelligence to medicine is the limited availability of annotated medical data. Unlike in other applications of machine learning, where an abundance of labeled data is available, the labeling and annotation of medical data and images require a major effort of manual work by expert clinicians who do not have the time to annotate manually. In this work, we propose a new deep learning technique (SLIVER-net), to predict clinical features from 3-dimensional volumes using a limited number of manually annotated examples. SLIVER-net is based on transfer learning, where we borrow information about the structure and parameters of the network from publicly available large datasets. Since public volume data are scarce, we use 2D images and account for the 3-dimensional structure using a novel deep learning method which tiles the volume scans, and then adds layers that leverage the 3D structure. In order to illustrate its utility, we apply SLIVER-net to predict risk factors for progression of age-related macular degeneration (AMD), a leading cause of blindness, from optical coherence tomography (OCT) volumes acquired from multiple sites. SLIVER-net successfully predicts these factors despite being trained with a relatively small number of annotated volumes (hundreds) and only dozens of positive training examples. Our empirical evaluation demonstrates that SLIVER-net significantly outperforms standard state-of-the-art deep learning techniques used for medical volumes, and its performance is generalizable as it was validated on an external testing set. In a direct comparison with a clinician panel, we find that SLIVER-net also outperforms junior specialists, and identifies AMD progression risk factors similarly to expert retina specialists.
C1 [Rakocz, Nadav; Thompson, Michael; Hill, Brian L.; Sankararaman, Sriram; Halperin, Eran] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA.
   [Rakocz, Nadav; Chiang, Jeffrey N.; Sankararaman, Sriram; Halperin, Eran] Univ Calif Los Angeles, Dept Computat Med, Los Angeles, CA 90095 USA.
   [Nittala, Muneeswar G.; Corradetti, Giulia; Tiosano, Liran; Velaga, Swetha; Sadda, Srinivas R.] Doheny Eye Inst, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Corradetti, Giulia; Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Tiosano, Liran; Halperin, Eran] Hebrew Univ Jerusalem, Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, Fac Med, Jerusalem, Israel.
   [Sankararaman, Sriram] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA.
   [Haines, Jonathan L.] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
   [Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Halperin, Eran] Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90024 USA.
   [Halperin, Eran] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California System; University of California Los Angeles;
   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; Hebrew University of
   Jerusalem; University of California System; University of California Los
   Angeles; Case Western Reserve University; University of Miami;
   University of Pennsylvania; Pennsylvania Medicine; University of
   California System; University of California Los Angeles; University of
   California System; University of California Los Angeles
RP Halperin, E (通讯作者)，Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA.; Halperin, E (通讯作者)，Univ Calif Los Angeles, Dept Computat Med, Los Angeles, CA 90095 USA.; Halperin, E (通讯作者)，Hebrew Univ Jerusalem, Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, Fac Med, Jerusalem, Israel.; Halperin, E (通讯作者)，Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90024 USA.; Halperin, E (通讯作者)，Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA 90095 USA.
EM ehalperin@cs.ucla.edu
OI Rakocz, Nadav/0000-0001-5437-9691; Hill, Brian/0000-0002-6881-5770;
   Thompson, Mike/0000-0003-1546-0512; Chiang, Jeffrey/0000-0002-6843-1355
FU NIH [R01EY023164]; National Science Foundation [1705197]; NIH/NHGRI
   [HG010505-02]
FX This project was supported by NIH R01EY023164. This work was also funded
   by the National Science Foundation (Grant No. 1705197), and by NIH/NHGRI
   HG010505-02.
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NR 55
TC 3
Z9 3
U1 0
U2 2
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2398-6352
J9 NPJ DIGIT MED
JI npj Digit. Med.
PD MAR 8
PY 2021
VL 4
IS 1
AR 44
DI 10.1038/s41746-021-00411-w
PG 13
WC Health Care Sciences & Services; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; Medical Informatics
GA QT5XB
UT WOS:000626659400001
PM 33686212
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ni, TM
   Yang, WJ
   Xing, YQ
AF Ni, Timin
   Yang, Wanju
   Xing, Yiqiao
TI Protective effects of delphinidin against H2O2-induced oxidative
   injuries in human retinal pigment epithelial cells
SO BIOSCIENCE REPORTS
LA English
DT Article
ID LIPID-PEROXIDATION; SIGNALING PATHWAY; DAMAGE; ANTHOCYANINS; MECHANISMS;
   EXPRESSION; STRESS; ANGIOGENESIS; ACTIVATION; GROWTH
AB Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 mu g/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2. Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2. Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.
C1 [Ni, Timin; Xing, Yiqiao] Wuhan Univ, Dept Ophthalmol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China.
   [Ni, Timin; Yang, Wanju] Wuhan Cent Hosp, Dept Ophthalmol, Wuhan 430014, Hubei, Peoples R China.
C3 Wuhan University
RP Xing, YQ (通讯作者)，Wuhan Univ, Dept Ophthalmol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China.
EM yiqiaoxingwuhan@gmail.com
OI Yang, Wanju/0000-0002-3071-2805
FU Guidance Project of Wuhan Municipal Health Planning Commission [WX17Z02]
FX This work was supported by the Guidance Project of Wuhan Municipal
   Health Planning Commission [grant number WX17Z02].
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NR 45
TC 18
Z9 20
U1 0
U2 14
PU PORTLAND PRESS LTD
PI LONDON
PA 5TH FLR, 90 HIGH HOLBORN, LONDON WC1V 6LJ, ENGLAND
SN 0144-8463
EI 1573-4935
J9 BIOSCIENCE REP
JI Biosci. Rep.
PD AUG 15
PY 2019
VL 39
AR BSR20190689
DI 10.1042/BSR20190689
PN 8
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA IS9YY
UT WOS:000482505100001
PM 31345961
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Issa, PC
   Gliem, M
   Yusuf, IH
   Birtel, J
   Muller, PL
   Mangold, E
   Downes, SM
   MacLaren, RE
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   Bolz, HJ
AF Issa, Peter Charbel
   Gliem, Martin
   Yusuf, Imran H.
   Birtel, Johannes
   Mueller, Philipp L.
   Mangold, Elisabeth
   Downes, Susan M.
   MacLaren, Robert E.
   Betz, Christian
   Bolz, Hanno J.
TI A Specific Macula-Predominant Retinal Phenotype Is Associated With the
   CDHR1 Variant c.783G > A, a Silent Mutation Leading to In-Frame Exon
   Skipping
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE CDHR1; autofluorescence; OCT; AMD; phenotyping
ID PROTOCADHERIN-21 PCDH21; OUTER SEGMENT; GENE; IDENTIFICATION;
   DEGENERATION; FAMILY; CONE; SPECTRUM; CADHERIN
AB PURPOSE. To report the clinical and molecular findings in patients with retinal dystrophy associated with the c.783G>A variant in CDHR1.
   METHODS. The retinal phenotype of 10 patients with CDHR1-related retinopathy was characterized by multimodal imaging including color fundus photography, optical coherence tomography (OCT), and blue- and near-infrared fundus autofluorescence imaging. Functional testing included electroretinography, visual acuity, and visual field testing.
   RESULTS. Six patients homozygous for the c.783G>A variant in CDHR1 showed a retinal phenotype resembling central areolar choroidal dystrophy (CACD) on multimodal imaging. Retinal function outside an area of slowly progressive macular atrophy remained relatively preserved. In contrast, biallelic severe/truncating CDHR1 mutations result in retina-wide retinal degeneration in addition to macular atrophy, with overall severely reduced retinal function. Patients compound heterozygous for the c.783G>A mutation and a truncating mutation in CDHR1 showed an intermediate phenotype. All patients except one with biallelic severe CDHR1 mutations were asymptomatic in the first four decades of life, irrespective of their individual CDHR1 mutations. Analysis of blood RNA from patients with the c.783G>A variant revealed in-frame skipping of exon 8 in vivo, predicting a partial deletion of CDHR1 ectodomains 2 and 3.
   CONCLUSIONS. Patients with biallelic c.783G>A CDHR1 mutations demonstrate a retinal phenotype consistent with autosomal recessive CACD. The apparently silent dbSNP-annotated c.783G>A CDHR1 variant (rs147346345) has a relatively high minor allele frequency (0.31%), with homozygous individuals annotated in the general population, and it may therefore have been disregarded in many next-generation sequencing (NGS)-based studies. The differential diagnosis includes PRPH2-associated CACD and age-related macular degeneration.
C1 [Issa, Peter Charbel; Gliem, Martin; Yusuf, Imran H.; Downes, Susan M.; MacLaren, Robert E.] Univ Oxford, Oxford Eye Hosp, Oxford Univ Hosp Natl Hlth Serv Fdn Trust, Oxford, England.
   [Issa, Peter Charbel; Gliem, Martin; Yusuf, Imran H.; Downes, Susan M.; MacLaren, Robert E.] Univ Oxford, Nuffield Lab Ophthalmol, Dept Clin Neurosci, Oxford, England.
   [Gliem, Martin; Birtel, Johannes; Mueller, Philipp L.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Mangold, Elisabeth] Univ Bonn, Inst Human Genet, Bonn, Germany.
   [Betz, Christian] Bioscientia Ctr Human Genet, Ingelheim, Germany.
   [Bolz, Hanno J.] Univ Hosp Cologne, Inst Human Genet, Cologne, Germany.
C3 Oxford University Hospitals NHS Foundation Trust; University of Oxford;
   University of Oxford; University of Bonn; University of Bonn; University
   of Cologne
RP Issa, PC (通讯作者)，John Radcliffe Hosp, Oxford Eye Hosp, Oxford OX3 9DU, England.
EM study-enquiry@outlook.com
RI ; Charbel Issa, Peter/E-8935-2018
OI Yusuf, Imran/0000-0002-0424-5852; Charbel Issa,
   Peter/0000-0002-0351-6673
FU National Institute for Health Research (NIHR) Oxford Biomedical Research
   Centre (BRC); ProRetina, Aachen, Germany; German Research Foundation
   [GL920/1-1]; MRC [MR/R000735/1] Funding Source: UKRI
FX Supported by the National Institute for Health Research (NIHR) Oxford
   Biomedical Research Centre (BRC); ProRetina, Aachen, Germany; and the
   German Research Foundation (MG, Grant GL920/1-1; PLM). The views
   expressed are those of the authors and not necessarily those of the NHS,
   the NIHR, or the Department of Health. The authors alone are responsible
   for the content and writing of the paper.
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NR 28
TC 10
Z9 10
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 AUG
PY 2019
VL 60
IS 10
BP 3388
EP 3397
DI 10.1167/iovs.18-26415
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IS2FS
UT WOS:000481969000015
PM 31387115
OA gold
DA 2022-11-30
ER

PT J
AU Osborne, AJ
   Nan, RD
   Miller, A
   Bhatt, JS
   Gor, J
   Perkins, SJ
AF Osborne, Amy J.
   Nan, Ruodan
   Miller, Ami
   Bhatt, Jayesh S.
   Gor, Jayesh
   Perkins, Stephen J.
TI Two distinct conformations of factor H regulate discrete
   complement-binding functions in the fluid phase and at cell surfaces
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE C3b activity; immune system; innate immunity; solution structure;
   analytical ultracentrifugation; complement; molecular modeling; surface
   plasmon resonance (SPR); X-ray scattering; complement regulation; Monte
   Carlo modeling
ID HEMOLYTIC-UREMIC SYNDROME; PROTEIN-PROTEIN INTERACTIONS; MEMBRANE
   COFACTOR PROTEIN; ALTERNATIVE PATHWAY; SELF-ASSOCIATION;
   SEDIMENTATION-VELOCITY; MACULAR DEGENERATION; NEUTRON-SCATTERING;
   HEPARAN-SULFATE; FACTOR-I
AB Factor H (FH) is the major regulator of C3b in the alternative pathway of the complement system in immunity. FH comprises 20 short complement regulator (SCR) domains, including eight glycans, and its Y402H polymorphism predisposes those who carry it to age-related macular degeneration. To better understand FH complement binding and self-association, we have studied the solution structures of both the His-402 and Tyr-402 FH allotypes. Analytical ultracentrifugation revealed that up to 12% of both FH allotypes self-associate, and this was confirmed by small-angle X-ray scattering (SAXS), MS, and surface plasmon resonance analyses. SAXS showed that monomeric FH has a radius of gyration (R-g) of 7.2-7.8 nm and a length of 25 nm. Starting from known structures for the SCR domains and glycans, the SAXS data were fitted using Monte Carlo methods to determine atomistic structures of monomeric FH. The analysis of 29,715 physically realistic but randomized FH conformations resulted in 100 similar best-fit FH structures for each allotype. Two distinct molecular structures resulted that showed either an extended N-terminal domain arrangement with a folded-back C terminus or an extended C terminus and a folded-back N terminus. These two structures are the most accurate to date for glycosylated full-length FH. To clarify FH functional roles in host protection, crystal structures for the FH complexes with C3b and C3dg revealed that the extended N-terminal conformation accounted for C3b fluid-phase regulation, the extended C-terminal conformation accounted for C3d binding, and both conformations accounted for bivalent FH binding to glycosaminoglycans on the target cell surface.
C1 [Osborne, Amy J.; Nan, Ruodan; Miller, Ami; Bhatt, Jayesh S.; Gor, Jayesh; Perkins, Stephen J.] UCL, Dept Struct & Mol Biol, Darwin Bldg,Gower St, London WC1E 6BT, England.
C3 University of London; University College London
RP Perkins, SJ (通讯作者)，UCL, Dept Struct & Mol Biol, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM s.perkins@ucl.ac.uk
OI Perkins, Stephen/0000-0001-9218-9805; Osborne, Amy/0000-0001-6869-1176
FU Alexion; Mizutani Foundation Award [180218]; CCP-SAS Project through
   joint EPSRC [EP/K039121/1]; National Science Foundation [CHE-1265821];
   MRC [G0801724]; EPSRC [EP/K039121/1] Funding Source: UKRI
FX This work was supported in part by a Ph.D. studentship grant from
   Alexion to Complement UK, Mizutani Foundation Award 180218, CCP-SAS
   Project through joint EPSRC Grant EP/K039121/1, National Science
   Foundation Grant CHE-1265821, and MRC Grant G0801724. The authors
   declare that they have no conflicts of interest with the contents of
   this article.
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NR 115
TC 9
Z9 9
U1 2
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI ROCKVILLE
PA 11200 ROCKVILLE PIKE, SUITE 302, ROCKVILLE, MD, UNITED STATES
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 2
PY 2018
VL 293
IS 44
BP 17166
EP 17187
DI 10.1074/jbc.RA118.004767
PG 22
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA GZ5MI
UT WOS:000449466500017
PM 30217822
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Garweg, JG
   Zirpel, JJ
   Gerhardt, C
   Pfister, IB
AF Garweg, Justus G.
   Zirpel, Johanna J.
   Gerhardt, Christin
   Pfister, Isabel B.
TI The fate of eyes with wet AMD beyond four years of anti-VEGF therapy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Intravitreal injections; Long-term treatment; Ranibizumab;
   Wet age-related macular degeneration; wAMD
ID LONG-TERM OUTCOMES; MACULAR DEGENERATION; RANIBIZUMAB TREATMENT; 7-YEAR
   OUTCOMES; FOLLOW-UP; ATROPHY; ANCHOR; BEVACIZUMAB; HORIZON; MARINA
AB Real-life studies on long-term functional outcome of anti-VEGF treatment for wet age-related macular degeneration (wAMD) are limited. We therefore assessed the 10-year outcomes in our patients.
   In this retrospective study, all patients with newly diagnosed wAMD that had received minimally three intravitreal injections between 2007 and 2012 and a follow-up of >= 48 months were included. Primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. For qualitative, quantitative and longitudinal data, Pearson's chi(2) test, the Mann-Whitney U-test and Wilcoxon's signed-rank test were applied at a significance level of p < 0.05.
   Of 267 eyes (219 patients) with newly diagnosed wAMD treated during this period, 104 eyes (104 patients) had been followed for at least 48 months and were included. Fifty-nine eyes (57.8%) after 7 years were still under active treatment, 29 eyes (25.0%) had interrupted treatment [mean follow-up 7.5 years (4.0-10.1; SD 1.6)], whereas 16 patients had died. BCVA stabilized at -7.3 to -11.9 letters after 3-10 years of follow-up with a mean of 2.8 injections (median; 3.0, SD 1.0; 1-5) and 5.1 visits per year. In two thirds of eyes, treatment was switched to aflibercept or corticosteroid combinations without bearing on functional outcomes. Thirty-seven percent (37%) of eyes maintained driving vision for up to 10 years.
   Beyond 3 years of treatment, functional stability was maintained for up to 10 years. Further improvement of long-term outcomes might have required a more intensive treatment in the early phase.
C1 [Garweg, Justus G.; Gerhardt, Christin; Pfister, Isabel B.] Lindenhofspital, Swiss Eye Inst, Rotkreuz & Berner Augenklin, Bremgartenstr 119, CH-3012 Bern, Switzerland.
   [Garweg, Justus G.; Zirpel, Johanna J.; Gerhardt, Christin; Pfister, Isabel B.] Univ Bern, Bern, Switzerland.
C3 University of Bern
RP Garweg, JG (通讯作者)，Lindenhofspital, Swiss Eye Inst, Rotkreuz & Berner Augenklin, Bremgartenstr 119, CH-3012 Bern, Switzerland.; Garweg, JG (通讯作者)，Univ Bern, Bern, Switzerland.
EM Justus.garweg@augenklinik-bern.ch
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NR 32
TC 18
Z9 18
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD APR
PY 2018
VL 256
IS 4
BP 823
EP 831
DI 10.1007/s00417-018-3907-y
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FZ6HS
UT WOS:000427699300021
PM 29397436
OA Green Published
DA 2022-11-30
ER

PT J
AU Sun, YJ
   Pan, YR
   Fan, F
   Li, GY
AF Sun, Ying-Jian
   Pan, Yi-Ran
   Fan, Bin
   Li, Guang-Yu
TI Potential Role of Induced Pluripotent Stem Cells as Regenerative
   Medicine in Retinal Cell Damage
SO JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY
LA English
DT Article
DE embryonic stem; pluripotent stem cells; regenerative medicine; retinal
   pigmented epithelium; retinal cells
ID PIGMENT EPITHELIAL-CELLS; CASEIN KINASE-I; MIDBRAIN
   DOPAMINERGIC-NEURONS; DIRECTED DIFFERENTIATION; VITRO DIFFERENTIATION;
   CONE PHOTORECEPTORS; EYE DEVELOPMENT; OPTIC VESICLE; XENO-FREE; ES CELLS
AB Induced pluripotent stem cells (iPSCs), somatic cells reprogrammed by four overexpressing nuclear transcriptional factors containing Sox2, Klf4, c-myc, and Oct4, are currently a hot topic in research. Their pluripotency, self-renewal capacity, and wide accessibility to donor tissues have made possible the means for modified regenerative medicine. iPSCs are considered a possible basis of healthy tissue to cure diseases such as ophthalmic diseases, degenerative diseases, and age-related macular degeneration (AMD), primarily because of the weakening capability of photoreceptor cells, retinal ganglion cells (RGCs), retinal pigmented epithelium (RPE), or other retinal cells. These retinal cells are unable to regenerate and currently there are no effective treatments to restore sight. iPSCs allow for the in vitro development of numerous varieties of retinal cells and may treat these diseases by retinal transplantation. Although other stem cells could differentiate into retinal cells, iPSC-derived retinal cells might have numerous benefits compared with other stem cell sources including embryonic stem cells (ESCs). Mainly, they would be directly obtained from the patient, therefore eradicating every probable chance of adverse immune responses. Second, making iPSCs just needs somatic cells, thus circumventing the ethical issues that limited the clinical use of ESCs derived from humans. Third, iPSCs are parallel to ESCs in their differentiation ability: they can be expanded in vitro and induced to differentiate into retinal cells, providing a renewable source for therapeutic applications and scientific research. In this review, we discuss the latest progress in the development of retinal cell types from iPSCs, which can assist as a renewable source of cell population relevant to disease for basic and translational studies.
C1 [Sun, Ying-Jian; Pan, Yi-Ran; Fan, Bin; Li, Guang-Yu] Jilin Univ, Hosp 2, Dept Ophthalmol, 218 Ziqiang Rd, Changchun 130041, Jilin, Peoples R China.
C3 Jilin University
RP Li, GY (通讯作者)，Jilin Univ, Hosp 2, Dept Ophthalmol, 218 Ziqiang Rd, Changchun 130041, Jilin, Peoples R China.
EM guangyu.li@yahoo.com
FU National Natural Science Foundation of China [81570864]; Norman Bethune
   Program of Jilin University [2012208]; Natural Science Foundation of
   Jilin Province [20160101004JC, 20160414045GH]
FX This work was supported by the National Natural Science Foundation of
   China (Grant 81570864), the Norman Bethune Program of Jilin University
   (Grant 2012208), and the Natural Science Foundation of Jilin Province
   (Grant 20160101004JC and Grant 20160414045GH).
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NR 93
TC 0
Z9 0
U1 0
U2 13
PU BEGELL HOUSE INC
PI DANBURY
PA 50 NORTH ST, DANBURY, CT 06810 USA
SN 0731-8898
EI 2162-6537
J9 J ENVIRON PATHOL TOX
JI J. Environ. Pathol. Toxicol. Oncol.
PY 2018
VL 37
IS 4
BP 305
EP 316
DI 10.1615/JEnvironPatholToxicolOncol.2018027447
PG 12
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA GX0EC
UT WOS:000447381600003
PM 30806237
DA 2022-11-30
ER

PT J
AU Kennedy, RD
   Hammond, D
   Spafford, MM
   Douglas, O
   Brule, J
   Fong, GT
   Schultz, ASH
AF Kennedy, Ryan David
   Hammond, David
   Spafford, Marlee M.
   Douglas, Ornell
   Brule, Julie
   Fong, Geoffrey T.
   Schultz, Annette S. H.
TI Educating smokers about the risk of blindness - insights to improve
   tobacco product health warning labels
SO TOBACCO INDUCED DISEASES
LA English
DT Article
ID 4 COUNTRY SURVEY; SMOKING
AB Background: Health warning labels (HWL) on tobacco products help educate smokers about the health effects from smoking; however, there is a need to improve HWL content including images and text to increase effectiveness. In Canada, a HWL was created that communicates smoking's causal association with "blindness" from age-related macular degeneration (AMD). This study surveyed Canadian optometrists about their opinions regarding the image and text used in the "blindness" HWL.
   Methods: An online survey was sent to all 4528 registered Canadian optometrists. Respondents were asked if the HWL conveyed important and believable information, and if the picture was appropriate. Optometrists were invited to make open-ended comments about the label which were analyzed using a qualitative analysis framework suitable for health policy evaluation. Frequency distributions were calculated for closed-ended questions.
   Results: The survey was completed by 850 respondents (19 %). Most respondents (90 %) reported the message was believable/somewhat believable; while 35 % felt the picture was "too graphic". Some respondents reported in their open-ended comments that they were concerned the HWL was internally inconsistent because it reports there is "no effective treatment in most cases" for AMD but the image depicts someone undergoing surgery. There was concern that this may discourage patients from seeking needed treatment.
   Conclusion: The majority of Canadian optometrist respondents were in agreement that the new, "RISK OF BLINDNESS" pictorial HWL includes important, believable information. Some optometrists had concerns that the HWL included a confusing message or a message that may discourage some patients from pursuing treatment for AMD. Future development of blindness-related HWL should seek practitioner input.
C1 [Kennedy, Ryan David; Douglas, Ornell] Univ Waterloo, Propel Ctr Populat Hlth Impact, Waterloo, ON N2L 3G1, Canada.
   [Kennedy, Ryan David] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA.
   [Hammond, David] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada.
   [Spafford, Marlee M.] Univ Waterloo, Fac Sci, Waterloo, ON N2L 3G1, Canada.
   [Brule, Julie] Univ Montreal, Ecole Optometrie, Montreal, PQ H3T 1P1, Canada.
   [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada.
   [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Schultz, Annette S. H.] Univ Manitoba, Rady Fac Hlth Sci, Coll Nursing, Winnipeg, MB R3T 2N2, Canada.
C3 University of Waterloo; Johns Hopkins University; Johns Hopkins
   Bloomberg School of Public Health; University of Waterloo; University of
   Waterloo; Universite de Montreal; University of Waterloo; Ontario
   Institute for Cancer Research; University of Toronto; University Toronto
   Affiliates; University of Manitoba
RP Kennedy, RD (通讯作者)，Univ Waterloo, Propel Ctr Populat Hlth Impact, Waterloo, ON N2L 3G1, Canada.; Kennedy, RD (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA.
EM rdkennedy@jhu.edu
RI Fong, Geoffrey T/H-2810-2014; Kennedy, Ryan David/U-3794-2017
OI Fong, Geoffrey T/0000-0001-9098-6472; Kennedy, Ryan
   David/0000-0002-9448-5234; Schultz, Annette/0000-0002-7944-2180
FU Federal Tobacco Control Strategy from Health Canada; Canadian Cancer
   Society Research Initiative (CCSRI) [701019]; Ontario Institute for
   Cancer Research; Canadian Institutes of Health Research New Investigator
   Award; Canadian Cancer Society Research Institute Junior Investigator
   Award
FX This work was funded by a grant from the Federal Tobacco Control
   Strategy from Health Canada. The Propel Centre for Population Health
   Impact is supported from an operating grant from the Canadian Cancer
   Society Research Initiative (CCSRI grant #701019). Geoffrey T. Fong is
   supported by the Ontario Institute for Cancer Research (Senior
   Investigator Award). Additional support was provided from a Canadian
   Institutes of Health Research New Investigator Award and the Canadian
   Cancer Society Research Institute Junior Investigator Award (David
   Hammond).
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NR 22
TC 2
Z9 2
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1617-9625
J9 TOB INDUC DIS
JI Tob. Induc. Dis.
PD AUG 19
PY 2016
VL 14
AR 30
DI 10.1186/s12971-016-0094-7
PG 7
WC Substance Abuse; Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Substance Abuse; Public, Environmental & Occupational Health
GA DW1QR
UT WOS:000383418200001
PM 27547176
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Espinosa-Heidmann, DG
   Malek, G
   Mettu, PS
   Caicedo, A
   Saloupis, P
   Gach, S
   Dunnon, AK
   Hu, P
   Spiga, MG
   Cousins, SW
AF Espinosa-Heidmann, Diego G.
   Malek, Goldis
   Mettu, Priyatham S.
   Caicedo, Alejandro
   Saloupis, Peter
   Gach, Sarah
   Dunnon, Askia K.
   Hu, Peng
   Spiga, Maria-Grazia
   Cousins, Scott W.
TI Bone Marrow Transplantation Transfers Age-Related Susceptibility to
   Neovascular Remodeling in Murine Laser-Induced Choroidal
   Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; experimental choroidal
   neovascularization; bone marrow-derived perivascular precursor cells;
   bone marrow transplantation; neovascular remodeling
ID ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; MACULAR
   DEGENERATION; TISSUE-INJURY; GROWTH-FACTOR; IN-VITRO; VASCULOGENESIS;
   ANGIOGENESIS; MACROPHAGE; EXPRESSION
AB PURPOSE. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow-derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV.
   METHODS. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+).
   RESULTS. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells.
   CONCLUSIONS. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization.
C1 [Espinosa-Heidmann, Diego G.; Mettu, Priyatham S.; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K.; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W.] Duke Eye Ctr, Duke Ctr Macular Dis, Durham, NC 27705 USA.
   [Malek, Goldis] Duke Univ, Dept Ophthalmol, Albert Eye Res Inst, Durham, NC USA.
   [Caicedo, Alejandro] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
C3 Duke University; Duke University; Bascom Palmer Eye Institute;
   University of Miami
RP Cousins, SW (通讯作者)，Duke Eye Ctr, Duke Ctr Macular Dis, 2351 Erwin Rd, Durham, NC 27705 USA.
EM scott.cousins@duke.edu
RI Caicedo, Alejandro/AAC-8544-2020
OI Dunnon, Askia/0000-0003-1440-835X; Malek, Goldis/0000-0003-0026-2388
FU National Institutes of Health [EY018880-01]; NATIONAL EYE INSTITUTE
   [R01EY018880, R01EY020868, P30EY005722] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grant EY018880-01. The
   authors alone are responsible for the content and writing of the paper.
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NR 32
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 NOV
PY 2013
VL 54
IS 12
BP 7439
EP 7449
DI 10.1167/iovs.13-12546
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 265KH
UT WOS:000327949700035
PM 24135751
OA Green Published
DA 2022-11-30
ER

PT J
AU Bernstein, PS
   Sharifzadeh, M
   Liu, AH
   Ermakov, I
   Nelson, K
   Sheng, XM
   Panish, C
   Carlstrom, B
   Hoffman, RO
   Gellermann, W
AF Bernstein, Paul S.
   Sharifzadeh, Mohsen
   Liu, Aihua
   Ermakov, Igor
   Nelson, Kelly
   Sheng, Xiaoming
   Panish, Cynthia
   Carlstrom, Bonnie
   Hoffman, Robert O.
   Gellermann, Werner
TI Blue-Light Reflectance Imaging of Macular Pigment in Infants and
   Children
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE macular pigment; carotenoid; imaging; lutein; zeaxanthin
ID OPTICAL-DENSITY; RAMAN MEASUREMENT; VEGETABLE INTAKE; HUMAN RETINA;
   IN-VIVO; LUTEIN; ZEAXANTHIN; AGE; DEGENERATION; DISTRIBUTIONS
AB PURPOSE. While the role of the macular pigment carotenoids in the prevention of age-related macular degeneration has been extensively studied in adults, comparatively little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital video fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children.
   METHODS. We used blue light reflectance to image the macular pigment in premature babies at the time of retinopathy of prematurity (ROP) screening and in children aged under 7 years who were undergoing examinations under anesthesia for other reasons. We correlated the MPOD with skin carotenoid levels measured by resonance Raman spectroscopy, serum carotenoids measured by HPLC, and dietary carotenoid intake.
   RESULTS. We enrolled 51 infants and children ranging from preterm to age 7 years. MPOD correlated significantly with age (r = 0.36; P = 0.0142), with serum lutein + zeaxanthin (r = 0.44; P = 0.0049) and with skin carotenoid levels (r = 0.42; P = 0.0106), but not with dietary lutein + zeaxanthin intake (r = 0.13; P = 0.50). All premature infants had undetectable macular pigment, and most had unusually low serum and skin carotenoid concentrations.
   CONCLUSIONS. Our most remarkable finding is the undetectable MPOD in premature infants. This may be due in part to foveal immaturity, but the very low levels of serum and skin carotenoids suggest that these infants are carotenoid insufficient as a consequence of low dietary intake and/or severe oxidative stress. The potential value of carotenoid supplementation in the prevention of ROP and other disorders of prematurity should be a fruitful direction for further investigation.
C1 [Bernstein, Paul S.; Liu, Aihua; Nelson, Kelly; Panish, Cynthia; Carlstrom, Bonnie; Hoffman, Robert O.] Univ Utah, Moran Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
   [Sharifzadeh, Mohsen; Ermakov, Igor; Gellermann, Werner] Univ Utah, Dept Phys & Astron, Salt Lake City, UT 84132 USA.
   [Sheng, Xiaoming] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84132 USA.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; Utah System of Higher Education;
   University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
FU National Eye Institute Grant [EY-11600, EY-14800]; Research to Prevent
   Blindness; Abbott Nutrition (Columbus, Ohio); NATIONAL EYE INSTITUTE
   [R01EY011600, P30EY014800, R29EY011600] Funding Source: NIH RePORTER
FX Supported by National Eye Institute Grant EY-11600 and Core Grant
   EY-14800, Research to Prevent Blindness, and Abbott Nutrition (Columbus,
   Ohio).
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NR 31
TC 35
Z9 36
U1 1
U2 21
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 2013
VL 54
IS 6
BP 4034
EP 4040
DI 10.1167/iovs.13-11891
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 173YW
UT WOS:000321120700028
OA Green Published
DA 2022-11-30
ER

PT J
AU Pintea, A
   Rugina, D
   Pop, R
   Bunea, A
   Socaciu, C
   Diehl, HA
AF Pintea, Adela
   Rugina, Dumitrita
   Pop, Raluca
   Bunea, Andrea
   Socaciu, Carmen
   Diehl, Horst A.
TI Antioxidant Effect of Trans-Resveratrol in Cultured Human Retinal
   Pigment Epithelial Cells
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID ACTIVATED POTASSIUM CHANNELS; OXIDATIVE STRESS; MACULAR DEGENERATION;
   PHASE-2 ENZYMES; UP-REGULATION; RED WINE; PROTECTS; DAMAGE;
   PROLIFERATION; INHIBITION
AB Purposec Oxidative damages to the retinal pigment epithelium (RPE) have been suggested to play a key role in the pathogenesis of age-related macular degeneration. trans-Resveratrol (3,4',5-trihydroxystilbene) is a non-flavonoid dietary polyphenol with various pharmacological effects, including antioxidant activity. The purpose of this study was to evaluate the potential protective effect of resveratrol against hydrogen peroxide induced oxidative stress in cultured human RPE cells.
   Methods: Human retinal D407 RPE cells were pretreated with resveratrol at 3 different concentrations (25, 50, and 100 mu M) for 24 h and exposed for 1 h to 500 mu M hydrogen peroxide. Cell viability, cytotoxicity, and the level of intracellular reactive oxygen species (ROS) were determined in basal and oxidative stress conditions. The concentration of reduced glutathione and the activities of catalase, superoxide dismutase, and glutathione peroxidase were also examined under both experimental conditions.
   Results: Resveratrol in culture media had no cytotoxic effect at a concentration of 25-100 mu M but showed a protective effect against hydrogen peroxide-induced cytoxicity. Pretreatment with resveratrol induced a significant, dose-dependent increase of superoxide dismutase, glutathione peroxidase, and catalase activities. Moreover, resveratrol significantly enhanced the level of reduced glutathione under both basal and oxidative stress conditions. The significant inhibition of the intracellular ROS generation supports the hypothesis that resveratrol can also contribute to the antioxidant defense by directly scavenging the ROS in RPE cells.
   Conclusions: Our results indicate that treatment of RPE cells with resveratrol at micromolar concentrations confers a marked protection against oxidative stress. These data suggest that dietary supplementation of resveratrol may contribute to the prevention of RPE degeneration induced by oxidative stress.
C1 [Pintea, Adela; Rugina, Dumitrita; Pop, Raluca; Bunea, Andrea; Socaciu, Carmen] Univ Agr Sci & Vet Med, Dept Chem & Biochem, Cluj Napoca 400372, Romania.
   [Diehl, Horst A.] Univ Bremen, Inst Biophys, Bremen, Germany.
C3 University of Agricultural Sciences & Veterinary Medicine Cluj Napoca;
   University of Bremen
RP Pintea, A (通讯作者)，Univ Agr Sci & Vet Med, Dept Chem & Biochem, Manastur St 3-5, Cluj Napoca 400372, Romania.
EM apintea@usamvcluj.ro
RI Rugina, Dumitrita/C-4780-2011; Pintea, Adela/C-4521-2011; Rugina,
   Dumitrita/AAA-1667-2019; Pop, Raluca Maria/CAG-2449-2022; Socaciu,
   Carmen/AAX-2579-2020; Pop, Raluca Maria/I-4639-2019; Socaciu,
   Carmen/P-8358-2014
OI Pintea, Adela/0000-0002-9914-2070; Pop, Raluca
   Maria/0000-0003-1899-5977; Pop, Raluca Maria/0000-0003-1899-5977; Bunea,
   Andrea/0000-0002-2358-485X; RUGINA, Dumitrita
   Olivia/0000-0003-4881-3273; Socaciu, Carmen/0000-0002-7352-5057
FU PNCD [II ID_854]
FX This study was supported by PNCD II ID_854 Research Grant.
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NR 34
TC 63
Z9 66
U1 0
U2 32
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 2011
VL 27
IS 4
BP 315
EP 321
DI 10.1089/jop.2010.0144
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 800TC
UT WOS:000293388900001
PM 21663493
DA 2022-11-30
ER

PT J
AU Solomon, SD
   Dong, LM
   Haller, JA
   Gilson, MM
   Hawkins, BS
   Bressler, NM
AF Solomon, Sharon D.
   Dong, Li Ming
   Haller, Julia A.
   Gilson, Marta M.
   Hawkins, Barbaro S.
   Bressler, Neil M.
CA SST Res Grp
   SST Adverse Event Review Comm
TI RISK FACTORS FOR RHEGMATOGENOUS RETINAL DETACHMENT IN THE SUBMACULAR
   SURGERY TRIALS SST Report No. 22
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal neovascularization; rhegmatogenous retinal detachment; risk of
   retinal detachment; submacular surgery trials
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; OF-LIFE FINDINGS; OCULAR
   HISTOPLASMOSIS SYNDROME; RANDOMIZED CLINICAL-TRIAL; GROUP-H TRIAL;
   MACULAR DEGENERATION; OPHTHALMIC FINDINGS; SURGICAL REMOVAL; LESIONS
AB Objective: To identify risk factors associated with the development of rhegmatogenous retinal detachment (RRD) in patients enrolled in the Submacular Surgery Trials.
   Methods: One thousand fifteen patients with eligible subfoveal neovascular lesions in the study eye were assigned randomly to observation or to surgery. Eyes were examined at 3 months, 6 months, 12 months, and 24 months after enrollment to assess study outcomes and adverse events, including RRDs. Adverse events also were reported at other times as clinical personnel became aware of them. Potential risk factors for the development of RRD in study eyes were evaluated using recursive partitioning and logistic regression analysis.
   Results: Among 506 eyes assigned to surgery, RRD developed in 44 (8.7%) compared with 4 (0.8%) of 509 eyes assigned to observation. Of the 44 eyes in which RRD developed, 27 had age-related macular degeneration (AMD) and large (>3.5 MPS disk areas) hemorrhagic subfoveal neovascular lesions at baseline and represented 16.1% of all eyes with such lesions assigned to surgery. Eyes with AMD and larger hemorrhagic lesions (>16 MPS disk areas) together with relatively poor visual acuity (best-corrected visual acuity <= 20/1280) had a higher risk of RRD (odds ratio = 6.2, 95% confidence interval: 2.2-16.7) compared with those with smaller lesions and better visual acuity at baseline.
   Conclusion: Poor visual acuity and very large, predominantly hemorrhagic subfoveal neovascular AMD lesion type were the greatest risk factors for RRD after submacular surgery. Submacular surgery should be undertaken in such eyes with full awareness of the risk of RRD during subsequent follow-up. RETINA 29:819-824, 2009
C1 [Solomon, Sharon D.; Hawkins, Barbaro S.; Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Gilson, Marta M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
   [Dong, Li Ming] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
   [Haller, Julia A.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
   [Haller, Julia A.] Wills Eye Inst, Philadelphia, PA USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; State University of New York (SUNY) System; SUNY Community
   College; State University of New York (SUNY) Stony Brook; Jefferson
   University; Jefferson University
RP Solomon, SD (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, 550 N Broadway,Suite 115, Baltimore, MD 21205 USA.
EM sstchairman@jhmi.edu
FU NATIONAL EYE INSTITUTE [U10EY011557, U10EY011547, U10EY011558] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY11557, EY11558, U10 EY11547]
   Funding Source: Medline
CR Breiman L., 1984, CLASSICATION REGRESS
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NR 8
TC 5
Z9 6
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 JUN
PY 2009
VL 29
IS 6
BP 819
EP 824
DI 10.1097/IAE.0b013e3181a0857e
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 464HS
UT WOS:000267496600012
PM 19516120
DA 2022-11-30
ER

PT J
AU Nia, K
   Markowitz, SN
AF Nia, Keon
   Markowitz, Samuel N.
TI Provision and utilization of low-vision rehabilitation services in
   Toronto
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
DE low vision; vision rehabilitation; age-related macular degeneration
ID ACUITY
AB Background: Demographic changes expected to occur in the near future and the need for planning to address them are behind the urgent drive to assess present day provision and utilization of low-vision rehabilitation (LVR) services in the community. Current data available in Canada in this regard are mostly from Canadian National Institute for the Blind (CNIB) sources from clients accessing services, and are therefore incomplete. The purpose of this study, therefore, was to survey the provision and utilization of LVR services as reported by patients identified with low vision (LV) outside the CNIB system, specifically among those attending hospital-based ophthalmology clinics.
   Methods: The study design was a prospective, nonrandomized, observational case series based on interviews with LV patients. Cases with LV identified according to preset criteria were interviewed and tested for best-corrected visual acuity. The interview format included questions on multiple outcome measures of LVR, which provided answers addressing the theme of this study. A separate questionnaire was used to assess quality-of-life measures.
   Results: Thirty-four subjects were recruited for the study, 21 females and 13 males, with a mean age of 74 (SD 16) years. LV had been present for a mean of 8.26 (SD 12.2) years, mostly caused by age-related macular degeneration (44%) and other maculopathies (38%). Patients classified as having LV were referred to LVR services only in 50% of cases and mostly to CNIB offices (47%).The majority of cases (59%) used magnifiers as the most common remedy for LVR. A majority of cases (59%) felt that current rehabilitation services are insufficient and that more LVR interventions were warranted in their case.
C1 Univ Toronto, Low Vis Serv, Univ Hlth Network Hosp, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
C3 University of Toronto; University Health Network Toronto
RP Markowitz, SN (通讯作者)，1225 Davenport Rd, Toronto, ON M6H 2H1, Canada.
EM snm1@rogers.com
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NR 18
TC 15
Z9 16
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 OCT
PY 2007
VL 42
IS 5
BP 698
EP 702
DI 10.3129/i07-124
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 221VW
UT WOS:000250256500008
PM 17823645
DA 2022-11-30
ER

PT J
AU Sall, JW
   Klisovic, DD
   O'Dorisio, MS
   Katz, SE
AF Sall, JW
   Klisovic, DD
   O'Dorisio, MS
   Katz, SE
TI Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal
   pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE choroidal neovascularization; diabetic retinopathy; somatostatin
   receptor; IGF-1R; VEGF; octreotide; macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; ANALOG
   OCTREOTIDE ACETATE; FACTOR-I RECEPTOR; FACTOR EXPRESSION; CHOROIDAL
   NEOVASCULARIZATION; GENE-EXPRESSION; MESSENGER-RNA; LOCALIZATION;
   ANGIOGENESIS
AB Neovascularization stimulated by IGF-1 mediated induction of vascular endothelial growth factor (VEGF) is one of the leading causes of blindness in humans. It plays a central role in the pathogenesis of proliferative diabetic retinopathy (DR), neovascular glaucoma, exudative age-related macular degeneration (AMD) and retinopathy of prematurity. Neovascularization is a multi-step process that involves complex interactions of a variety of mitogenic factors such as VEGF and IGF-1 which are produced locally in the human eye by a variety of cells including retinal pigment epithelial (RPE) cells, retinal capillary pericytes, endothelial cells, Mueller cells and ganglion cells. We hypothesized that somatostatin would inhibit the IGF-1 signal transduction pathway in RPE cells, resulting in decreased VEGF production.
   We have observed expression of somatostatin receptor protein in retinal pigment epithelial (RPE) cells of the human eye using immunohistochemistry and have confirmed expression of somatostatin receptors in cultured human RPE cells using reverse transcriptase-PCR. IGF-1 induced a dose dependent increase in IGF-1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells. Somatostatin and octreotide, a somatostatin analogue, inhibited IGF-1 receptor (IGF-1R) phosphorylation and decreased VEGF production. Both IGF-1R phosphorylation and accumulation of VEGF mRNA were inhibited by physiological levels of somatostatin and octreotide (1 nM). These results demonstrate somatostatin and octreotide mediated attenuation of both IGF-1R signal transduction and VEGF mRNA accumulation via somatostatin receptor type 2 (sst2). Furthermore, these data suggest a rationale for the use of octreotide as a prophylactic and therapeutic option in disease states that cause ocular neovascularization. (C) 2004 Elsevier Ltd. All rights reserved.
C1 Univ Iowa Hosp & Clin, Interdisciplinary Program Neurosci, Iowa City, IA 52242 USA.
   Univ Iowa, Med Sci Training Program, Iowa City, IA USA.
   Ohio State Univ, William H Havener Eye Ctr, Columbus, OH 43210 USA.
C3 University of Iowa; University of Iowa; University System of Ohio; Ohio
   State University
RP O'Dorisio, MS (通讯作者)，Univ Iowa Hosp & Clin, Interdisciplinary Program Neurosci, 200 Hawkins Dr,2520 JCP, Iowa City, IA 52242 USA.
EM sue-odorisio@uiowa.edu
OI O'Dorisio, M Sue/0000-0003-0690-1160
FU NCI NIH HHS [R01 CA 90236] Funding Source: Medline; NATIONAL CANCER
   INSTITUTE [R01CA090236] Funding Source: NIH RePORTER
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NR 77
TC 58
Z9 65
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 OCT
PY 2004
VL 79
IS 4
BP 465
EP 476
DI 10.1016/j.exer.2004.06.007
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 860YF
UT WOS:000224379800003
PM 15381031
DA 2022-11-30
ER

PT J
AU Rohrer, B
   Parsons, N
   Annamalai, B
   Nicholson, C
   Obert, E
   Jones, BW
   Dick, AD
AF Rohrer, Barbel
   Parsons, Nathaniel
   Annamalai, Balasubramaniam
   Nicholson, Crystal
   Obert, Elisabeth
   Jones, Bryan W.
   Dick, Andrew D.
TI Peptide-based immunotherapy against oxidized elastin ameliorates
   pathology in mouse model of smoke-induced ocular injury
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Elastin; Peptide-based immunotherapy;
   Complement; Smoking
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   COMPLEMENT ACTIVATION; PERIPHERAL TOLERANCE; IMMUNE-RESPONSES; CELLS;
   ACCUMULATION; INFLAMMATION; DEGRADATION
AB Purpose: Age-related macular degeneration (AMD), the leading cause of blindness in western populations, is associated with an overactive complement system, and an increase in circulating antibodies against certain epitopes, including elastin. As loss of the elastin layer of Bruch's membrane (BrM) has been reported in aging and AMD, we previously showed that immunization with elastin peptide oxidatively modified by cigarette smoke (oxelastin), exacerbated ocular pathology in the smoke-induced ocular pathology (SIOP) model. Here we asked whether ox-elastin peptide-based immunotherapy (PIT) ameliorates damage.
   Methods: C57BL/6J mice were injected with ox-elastin peptide at two doses via weekly subcutaneous administration, while exposed to cigarette smoke for 6 months. Fc gamma R-/- and uninjected C57BL/6J mice served as controls. Retinal morphology was assessed by electron microscopy, and complement activation, antibody deposition and mechanisms of immunological tolerance were assessed by Western blotting and ELISA.
   Results: Elimination of Fc gamma receptors, preventing antigen/antibody-dependent cytotoxicity, protected against SIOP. Mice receiving PIT with low dose ox-elastin (LD-PIT) exhibited reduced humoral immunity, reduced complement activation and IgG/IgM deposition in the RPE/choroid, and largely a preserved BrM. While there is no direct evidence of ox-elastin pathogenicity, LD-PIT reduced IFN gamma and increased IL-4 within RPE/choroid. High dose PIT was not protective.
   Conclusions: These data further support ox-elastin role in ocular damage in part via elastin-specific antibodies, and support the corollary that PIT with ox-elastin attenuates ocular pathology. Overall, damage is associated with complement activation, antibody-dependent cell-mediated cytotoxicity, and altered cytokine signature.
C1 [Rohrer, Barbel; Parsons, Nathaniel; Annamalai, Balasubramaniam; Nicholson, Crystal; Obert, Elisabeth] Med Univ South Carolina, Dept Ophthalmol, Div Res, Charleston, SC 29425 USA.
   [Rohrer, Barbel; Parsons, Nathaniel; Annamalai, Balasubramaniam; Nicholson, Crystal; Obert, Elisabeth] Med Univ South Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Dept Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA.
   [Jones, Bryan W.] Univ Utah, Dept Ophthalmol, Salt Lake City, UT 84132 USA.
   [Dick, Andrew D.] Univ Bristol, Bristol BS8 1TD, Avon, England.
   [Dick, Andrew D.] UCL, Inst Ophthalmol, London EC1V 9EL, England.
   [Dick, Andrew D.] Moorfields Eye Hosp, Natl Inst Hlth Res Biomed Res Ctr, London EC1V 9EL, England.
C3 Medical University of South Carolina; Medical University of South
   Carolina; Utah System of Higher Education; University of Utah;
   University of Bristol; University of London; University College London;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust
RP Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu; a.dick@bristol.ac.uk
OI Jones, Bryan/0000-0001-5527-6643
FU National Institutes of Health (NIH) [R01EY019320, R01EY015128,
   R01EY028927, P30EY014800]; Department of Veterans Affairs [RX000444,
   BX003050]; South Carolina SmartState Endowment; Research to Prevent
   Blindness, New York, NY; National Institute for Health Research (NIHR)
   Biomedical Research Centre at Moorfields Eye Hospital; University
   College London Institute of Ophthalmology
FX Funding for this project was provided in part by the National Institutes
   of Health (NIH) R01EY019320 (BR), R01EY015128 (BWJ), R01EY028927 (BWJ)
   and P30EY014800 (BWJ), the Department of Veterans Affairs RX000444 and
   BX003050 (BR), the South Carolina SmartState Endowment (BR), and an
   Unrestricted Research Grant from Research to Prevent Blindness, New
   York, NY to the Department of Ophthalmology & Visual Sciences,
   University of Utah. ADD is supported in part through the National
   Institute for Health Research (NIHR) Biomedical Research Centre at
   Moorfields Eye Hospital and University College London Institute of
   Ophthalmology. We would like to thank Carl Atkinson (Medical University
   of South Carolina) for the room air and smoke-exposed Fc gamma R
   <SUP>-/-</SUP> mice.
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NR 69
TC 1
Z9 1
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2021
VL 212
AR 108755
DI 10.1016/j.exer.2021.108755
EA SEP 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WC6AR
UT WOS:000704339400004
PM 34487725
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Annamalai, B
   Parsons, N
   Nicholson, C
   Obert, E
   Jones, B
   Rohrer, B
AF Annamalai, Balasubramaniam
   Parsons, Nathaniel
   Nicholson, Crystal
   Obert, Elisabeth
   Jones, Bryan
   Rohrer, Barbel
TI Subretinal Rather Than Intravitreal Adeno-Associated Virus-Mediated
   Delivery of a Complement Alternative Pathway Inhibitor Is Effective in a
   Mouse Model of RPE Damage
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE complement system; choroidal neovascularization; smoke-induced ocular
   pathology; natural antibody-mediated targeting; alternative pathway
   inhibitor; encapsulated ARPE-19 cells
ID RETINAL-PIGMENT EPITHELIUM; MEMBRANE ATTACK COMPLEX;
   MACULAR-DEGENERATION; TARGETED INHIBITOR; OXIDATIVE STRESS; GENE
   DELIVERY; AAV VECTORS; IN-VITRO; CELLS; TRANSDUCTION
AB PURPOSE. The risk for age-related macular degeneration has been tied to an overactive complement system. Despite combined attempts by academia and industry to develop therapeutics that modulate the complement response, particularly in the late geographic atrophy form of advanced AMD, to date, there is no effective treatment. We have previously demonstrated that pathology in the smoke-induced ocular pathology (SIOP) model, a model with similarities to dry AMD, is dependent on activation of the alternative complement pathway and that a novel complement activation site targeted inhibitor of the alternative pathway can be delivered to ocular tissues via an adeno-associated virus (AAV).
   METHODS. Two different viral vectors for specific tissue targeting were compared: AAV5-VMD2-CR2-fH for delivery to the retinal pigment epithelium (RPE) and AAV2YF-smCBA-CR2-fH for delivery to retinal ganglion cells (RGCs). Efficacy was tested in SIOP (6 months of passive smoke inhalation), assessing visual function (optokinetic responses), retinal structure (optical coherence tomography), and integrity of the RPE and Bruch's membrane (electron microscopy). Protein chemistry was used to assess complement activation, CR2-fH tissue distribution, and CR2-fH transport across the RPE.
   RESULTS. RPE- but not RGC-mediated secretion of CR2-fH was found to reduce SIOP and complement activation in RPE/choroid. Bioavailability of CR2-fH in RPE/choroid could be confirmed only after AAV5-VMD2-CR2-fH treatment, and inefficient, adenosine triphosphate-dependent transport of CR2-fH across the RPE was identified.
   CONCLUSIONS. Our results suggest that complement inhibition for AMD-like pathology is required basal to the RPE and argues in favor of AAV vector delivery to the RPE or outside the blood-retina barrier.
C1 [Annamalai, Balasubramaniam; Parsons, Nathaniel; Nicholson, Crystal; Obert, Elisabeth; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
   [Jones, Bryan] Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA.
   [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC USA.
   [Rohrer, Barbel] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina; Utah System of Higher Education;
   University of Utah; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center; 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 National Institutes of Health [R01EY024581, EY030072]; Department of
   Veterans Affairs [IK6BX004858, RX000444, BX003050]; South Carolina
   SmartState Endowment at the Medical University of South Carolina (MUSC);
   Research to Prevent Blindness (New York);  [R01 EY015128];  [R01
   EY028927];  [P30 EY014800]
FX Supported by the National Institutes of Health (R01EY024581, EY030072),
   the Department of Veterans Affairs (IK6BX004858, RX000444, and
   BX003050), and the South Carolina SmartState Endowment at the Medical
   University of South Carolina (MUSC). In Utah, the following grants are
   acknowledged: R01 EY015128 (BJ), R01 EY028927 (BJ), P30 EY014800 to
   Moran Eye Center Core, and Research to Prevent Blindness (New York)
   Unrestricted Grant to the Department of Ophthalmology & Visual Sciences,
   University of Utah.
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NR 82
TC 4
Z9 4
U1 3
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 2021
VL 62
IS 4
AR 11
DI 10.1167/iovs.62.4.11
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RM2XB
UT WOS:000639527200011
PM 33830174
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gelfman, CM
   Grishanin, R
   Bender, KO
   Nguyen, A
   Greengard, J
   Sharma, P
   Nieves, J
   Kiss, S
   Gasmi, M
AF Gelfman, Claire M.
   Grishanin, Ruslan
   Bender, Kristina Oresic
   Nguyen, Aivan
   Greengard, Judith
   Sharma, Pallavi
   Nieves, Julio
   Kiss, Szilard
   Gasmi, Mehdi
TI Comprehensive Preclinical Assessment of ADVM-022, an Intravitreal
   Anti-VEGF Gene Therapy for the Treatment of Neovascular AMD and Diabetic
   Macular Edema
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE anti-VEGF; adeno-associated virus; gene therapy; neovascular AMD;
   intravitreal
AB Inhibition of vascular endothelial growth factor is the mode of action for several approved therapies, including aflibercept, for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Lack of compliance due to the frequent intravitreal dosing requirements may result in inadequately treated disease, leading to irreversible vision impairment. To date, the majority of gene therapy clinical trials providing sustained anti-VEGF levels in the retina have been limited to subretinal injections requiring a vitrectomy. A single intravitreal injection of a gene therapy product could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, has been optimized for intravitreal delivery and strong protein expression. Long-term expression and efficacy of ADVM-022-derived aflibercept were evaluated in a laser-induced choroidal neovascularization (CNV) model in non-human primates. Ocular safety was evaluated following long-term suppression of VEGF by clinical scoring (inflammatory parameters) as well as optical coherence tomography (OCT) and electroretinography (ERG). Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels in ocular tissues. In addition, ADVM-022 administration 13 months before laser-induced CNV prevented the occurrence of clinically relevant CNV lesions, to the same degree as a bolus of aflibercept delivered at the time of laser. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for nAMD and DME, and may ultimately improve patients' visual outcomes. Clinical trials are currently underway, evaluating safety and efficacy following a single intravitreal injection of ADVM-022.
C1 [Gelfman, Claire M.; Grishanin, Ruslan; Bender, Kristina Oresic; Nguyen, Aivan; Greengard, Judith; Sharma, Pallavi; Nieves, Julio; Gasmi, Mehdi] Adverum Biotechnol Inc, Redwood City, CA 94063 USA.
   [Kiss, Szilard] Weill Cornell Med Coll, Dept Ophthalmol, New York, NY USA.
C3 Cornell University
RP Gelfman, CM (通讯作者)，Adverum Biotechnol Inc, Pharmaceut Dev, 800 Saginaw Dr, Redwood City, CA 94063 USA.
EM cgelfman@adverum.com
OI Kiss, Szilard/0000-0003-3433-8432
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NR 26
TC 5
Z9 6
U1 0
U2 1
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 APR 1
PY 2021
VL 37
IS 3
BP 181
EP 190
DI 10.1089/jop.2021.0001
PG 10
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA RK4YC
UT WOS:000638302700010
PM 33835848
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ahn, JY
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   Cano, M
   Mallick, E
   Rai, U
   Powell, B
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   Witwer, KW
   Handa, JT
   Paulaitis, ME
AF Ahn, J. Y.
   Datta, S.
   Bandeira, E.
   Cano, M.
   Mallick, E.
   Rai, U.
   Powell, B.
   Tian, J.
   Witwer, K. W.
   Handa, J. T.
   Paulaitis, M. E.
TI Release of extracellular vesicle miR-494-3p by ARPE-19 cells with
   impaired mitochondria
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE miRNA; miR-494-3p; Extracellular vesicles; Mitochondria; Retinal pigment
   epithelial cells; Age-related macular degeneration
AB Background: Mitochondrial function in retinal pigmented epithelial (RPE) cells and extracellular vesicle (EV) formation/release are related through the lysosomal and exocytotic pathways that process and eliminate intracellular material, including mitochondrial fragments. We propose that RPE cells with impaired mitochondria will release EVs containing mitochondrial miRNAs that reflect the diminished capacity of mitochondria within these cells.
   Methods: We screened ARPE-19 cells for miRNAs that localize to the mitochondria, exhibit biological activity, and are present in EVs released by both untreated cells and cells treated with rotenone to induce mitochondrial injury. EVs were characterized by vesicle size, size distribution, presence of EV biomarkers: CD81, CD63, and syntenin-1, miRNA cargo, and number concentration of EVs released per cell.
   Results: We found that miR-494-3p was enriched in ARPE-19 mitochondria. Knockdown of miR-494-3p in ARPE-19 cells decreased ATP production and mitochondrial membrane potential in a dose-dependent manner, and decreased basal oxygen consumption rate and maximal respiratory capacity. Increased number of EVs released per cell and elevated levels of miR-494-3p in EVs released from ARPE-19 cells treated with rotenone were also measured.
   Conclusions: ARPE-19 mitochondrial function is regulated by miR-494-3p. Elevated levels of miR-494-3p in EVs released by ARPE-19 cells indicate diminished capacity of the mitochondria within these cells.
   General significance: EV miR-494-3p is a potential biomarker for RPE mitochondrial dysfunction, which plays a central role in non-neovascular age-related macular degeneration, and may be a diagnostic biomarker for monitoring the spread of degeneration to neighboring RPE cells in the retina.
C1 [Ahn, J. Y.; Bandeira, E.; Rai, U.; Paulaitis, M. E.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Nanomed, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Datta, S.; Cano, M.; Handa, J. T.] Johns Hopkins Univ Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD USA.
   [Mallick, E.; Powell, B.; Witwer, K. W.] Johns Hopkins Univ, Sch Med, Mol & Comparat Pathobiol, Baltimore, MD USA.
   [Tian, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Biostat Ctr, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins
   Medicine; Johns Hopkins University; Johns Hopkins University; Johns
   Hopkins Bloomberg School of Public Health
RP Paulaitis, ME (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Nanomed, Wilmer Eye Inst, Baltimore, MD 21205 USA.
EM michaelp@jhmi.edu
RI Witwer, Kenneth W./G-1626-2013; Bandeira, Elga/AAL-1610-2020
OI Witwer, Kenneth W./0000-0003-1664-4233; Bandeira,
   Elga/0000-0002-6098-9071; Ahn, Ju Young/0000-0002-0946-4157; Powell,
   Bonita/0000-0003-1979-6822
FU NIH [NEI EY027691]; NIH1 grant [NEI K99EY029010]; Macular Degeneration
   Foundation; Robert Bond Welch Professorship; NIH Common Fund through the
   Office of Strategic Coordination/Office of the NIH Director
   [UG3CA241694]; NIMH [MH118164]; Research to Prevent Blindness
FX Support of this research from donors of the Macular Degeneration
   Research Program of the BrightFocus Foundation (MEP), NIH grant NEI
   EY027691 (JTH), NIH1 grant NEI K99EY029010 (SD), Macular Degeneration
   Foundation (JTH), Robert Bond Welch Professorship (JTH), a gift from
   Celia Weatherhead, a Research to Prevent Blindness unrestricted grant to
   Wilmer are gratefully acknowledged. This work was also supported in part
   by the NIH Common Fund through the Office of Strategic
   Coordination/Office of the NIH Director (UG3CA241694, MEP and KWW) and
   by NIMH MH118164 (KWW). We also thank Samarjit Das for numerous
   insightful discussions on mitochondrial miRNAs, and Jean-Luc Fraikin for
   his guidance and technical assistance on microfluidic resistive pulse
   sensing measurements.
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NR 78
TC 10
Z9 10
U1 2
U2 8
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD APR
PY 2021
VL 1865
IS 4
SI SI
AR 129598
DI 10.1016/j.bbagen.2020.129598
EA FEB 2021
PG 12
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA RJ1AD
UT WOS:000637333900006
PM 32240720
DA 2022-11-30
ER

PT J
AU Hoffmann, L
   Rossouw, P
   Guichard, MM
   Hatz, K
AF Hoffmann, Laura
   Rossouw, Petra
   Guichard, Maria-Magdalena
   Hatz, Katja
TI Strongest Correlation Between Contrast Sensitivity and Morphological
   Characteristics in Bilateral nAMD
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE contrast sensitivity; age-reated macular degeneration; AMD; visual
   function; OCT; OCTA; geographic atrophy; fundus autofluorecence
ID OPTICAL COHERENCE TOMOGRAPHY; GEOGRAPHIC ATROPHY PROGRESSION; PIGMENT
   EPITHELIAL DETACHMENT; QUALITY-OF-LIFE; MACULAR DEGENERATION; VISUAL
   FUNCTION; NATURAL COURSE; CHOROIDAL NEOVASCULARIZATION; FUNDUS
   AUTOFLUORESCENCE; RETINAL MORPHOLOGY
AB In patients with neovascular age-related macular degeneration (nAMD) there is often an inconsistency between their subjective visual impairment and a still relatively preserved standard Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity. Therefore, in order to better capture the specific functional defects in nAMD, other tests need to be evaluated. In a previous study, we reported contrast sensitivity of the better eye to best correlate with near distance and distance vision related quality of life in patients with bilateral nAMD. Here, we evaluated Pelli-Robson contrast sensitivity, ETDRS visual acuity, low luminance visual acuity and Radner maximum reading speed and correlated them with several morphologic parameters as measured on fundus autofluorescence imaging, optical coherence tomography and optical tomography angiography in 54 patients. A multiple regression analysis was performed which correlated each visual function parameter with the anatomic features. The results showed the strongest correlations between the total area of macular geographic atrophy as well as the percentage of geographic atrophy in the central 1 mm and contrast sensitivity. Further, the regression model selected the total area of macular geographic atrophy, the photoreceptor inner and outer segments interface disruption score, the presence of subretinal fibrosis in the central 1 mm and the central retinal thickness as the variables that explained 71% of the variation in contrast sensitivity when including all eyes. Hence, our results suggest that among the evaluated measures of vision, contrast sensitivity is best correlated with the morphologic impairment in bilateral nAMD. Thus, contrast sensitivity may complement ETDRS visual acuity in clinical trials and serve as a standard diagnostic tool in clinical practice.
C1 [Hoffmann, Laura; Rossouw, Petra; Guichard, Maria-Magdalena; Hatz, Katja] Vista Klin, Binningen, Switzerland.
   [Rossouw, Petra] Univ Aalen, Dept Vis Sci & Optometry, Aalen, Germany.
   [Hatz, Katja] Univ Basel, Fac Med, Basel, Switzerland.
C3 Hochschule Aalen; University of Basel; University of Geneva
RP Hatz, K (通讯作者)，Vista Klin, Binningen, Switzerland.; Hatz, K (通讯作者)，Univ Basel, Fac Med, Basel, Switzerland.
EM katja.hatz@vista.ch
FU Retina Suisse Foundation
FX This study was supported by a grant of Retina Suisse Foundation.
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NR 43
TC 3
Z9 3
U1 0
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD JAN 28
PY 2021
VL 7
AR 622877
DI 10.3389/fmed.2020.622877
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA QF3WE
UT WOS:000616827500001
PM 33585517
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Angermann, R
   Rauchegger, T
   Nowosielski, Y
   Seifarth, C
   Egger, S
   Kralinger, MT
   Kieselbach, GF
   Zehetner, C
AF Angermann, Reinhard
   Rauchegger, Teresa
   Nowosielski, Yvonne
   Seifarth, Christof
   Egger, Stefan
   Kralinger, Martina T.
   Kieselbach, Gerhard F.
   Zehetner, Claus
TI Systemic counterregulatory response of angiopoietin-2 after aflibercept
   therapy for nAMD: a potential escape mechanism
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE aflibercept; age&#8208; related macular degeneration;
   angiopoietin&#8208; 2; escape mechanism; vascular endothelial growth
   factor
ID NEONATAL FC-RECEPTOR; VEGF-TRAP; GROWTH; BEVACIZUMAB; PATHOGENESIS;
   RANIBIZUMAB; EXPRESSION; RESISTANCE; REGRESSION; INJECTION
AB Purpose To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration (nAMD).
   Methods In a prospective, randomized study, aflibercept (2.0 mg/50 mu l) or ranibizumab (0.5 mg/50 mu l) was administered intravitreally to 38 treatment-naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme-linked immunosorbent assay. Twenty-two age- and sex-matched individuals served as controls.
   Results At baseline, there were no significant differences of systemic Ang2 and VEGF-A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262-3099) to 2123 pg/ml (1441-3769; p = 0.011) 7 days after the drug injection and remained non-significantly elevated at 1944 pg/ml (1431-2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF-A levels were significantly reduced from 43 pg/ml (30-57) to 8 pg/ml (8-8; p < 0.0001) 7 days and 16 pg/ml (8-26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF-A and Ang2 levels in the ranibizumab group at any time point following the first injection.
   Conclusion In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy.
C1 [Angermann, Reinhard; Rauchegger, Teresa; Nowosielski, Yvonne; Seifarth, Christof; Kralinger, Martina T.; Kieselbach, Gerhard F.; Zehetner, Claus] Med Univ Innsbruck, Dept Ophthalmol, Anichstr 35, A-6020 Innsbruck, Austria.
   [Egger, Stefan] Paracelsus Med Univ Salzburg, Dept Ophthalmol, Salzburg, Austria.
C3 Medical University of Innsbruck; Paracelsus Private Medical University
RP Zehetner, C (通讯作者)，Med Univ Innsbruck, Dept Ophthalmol, Anichstr 35, A-6020 Innsbruck, Austria.
EM claus.zehetner@i-med.ac.at
RI Rauchegger, Teresa/ABD-3420-2020; Angermann, Reinhard/ABG-1712-2021
OI Rauchegger, Teresa/0000-0003-3439-6333; Angermann,
   Reinhard/0000-0002-1610-4619; Zehetner, Claus/0000-0003-1405-7457
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NR 41
TC 3
Z9 3
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD SEP
PY 2021
VL 99
IS 6
BP E869
EP E875
DI 10.1111/aos.14691
EA DEC 2020
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UO6TY
UT WOS:000598981300001
PM 33326179
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Francisco, SG
   Smith, KM
   Aragones, G
   Whitcomb, EA
   Weinberg, J
   Wang, XD
   Bejarano, E
   Taylor, A
   Rowan, S
AF Francisco, Sarah G.
   Smith, Kelsey M.
   Aragones, Gemma
   Whitcomb, Elizabeth A.
   Weinberg, Jasper
   Wang, Xuedi
   Bejarano, Eloy
   Taylor, Allen
   Rowan, Sheldon
TI Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases
SO NUTRIENTS
LA English
DT Review
DE age-related macular degeneration; cataract; diabetic retinopathy;
   glaucoma; dietary pattern; Mediterranean diet; glycemic index; caloric
   restriction; intermittent fasting
ID RESTRICTION DELAYS CATARACT; RETINAL GANGLION-CELLS; NUCLEAR LENS
   OPACITIES; OPEN-ANGLE GLAUCOMA; CALORIC RESTRICTION; MEDITERRANEAN DIET;
   MACULAR DEGENERATION; GLYCEMIC INDEX; NUTRITIONAL MODULATION; SUBSEQUENT
   PREVALENCE
AB Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries.
C1 [Francisco, Sarah G.; Smith, Kelsey M.; Aragones, Gemma; Whitcomb, Elizabeth A.; Weinberg, Jasper; Wang, Xuedi; Bejarano, Eloy; Taylor, Allen; Rowan, Sheldon] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Smith, Kelsey M.; Taylor, Allen; Rowan, Sheldon] Tufts Univ, Friedman Sch Nutr & Sci Policy, Boston, MA 02111 USA.
   [Taylor, Allen; Rowan, Sheldon] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts University; United States Department of Agriculture (USDA); Tufts
   University; Tufts University
RP Bejarano, E; Taylor, A; Rowan, S (通讯作者)，Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.; Taylor, A; Rowan, S (通讯作者)，Tufts Univ, Friedman Sch Nutr & Sci Policy, Boston, MA 02111 USA.; Taylor, A; Rowan, S (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
EM sarah.francisco@tufts.edu; kelsey.smith@tufts.edu;
   gemma.aragones@tufts.edu; elizabeth.whitcomb@tufts.edu;
   jasper.weinberg@tufts.edu; xuedi.wang@tufts.edu;
   eloy.bejarano@tufts.edu; allen.taylor@tufts.edu; sheldon.rowan@tufts.edu
RI Bejarano, Eloy/AAJ-4708-2021; Aragones, Gemma/A-9693-2013
OI Bejarano, Eloy/0000-0001-8390-1581; Smith, Kelsey/0000-0003-4536-082X;
   Aragones, Gemma/0000-0002-1924-9231; Francisco,
   Sarah/0000-0001-9794-1533
FU NIH [RO1EY028559, RO1EY026979]; USDA (NIFA AT); BrightFocus Foundation;
   Human Nutrition Research Center on Aging; U.S. Department of
   Agriculture-Agricultural Research Service (ARS) [58-1950-4-003]
FX This research was funded by grants from NIH (RO1EY028559 and RO1EY026979
   to AT), USDA (NIFA AT), and BrightFocus Foundation (to SR), and a grant
   from the Human Nutrition Research Center on Aging (to EB). This material
   was based upon work supported by the U.S. Department of
   Agriculture-Agricultural Research Service (ARS), under Agreement No.
   58-1950-4-003.
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NR 113
TC 13
Z9 13
U1 9
U2 14
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD SEP
PY 2020
VL 12
IS 9
AR 2862
DI 10.3390/nu12092862
PG 19
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA OE0HH
UT WOS:000580222500001
PM 32962100
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Tran, TM
   Kim, S
   Lin, KH
   Chung, SH
   Park, S
   Sazhnyev, Y
   Wang, YW
   Cunefare, D
   Farsiu, S
   Thomasy, SM
   Moshiri, A
   Yiu, G
AF Tran, Tu M.
   Kim, Soohyun
   Lin, Kira H.
   Chung, Sook Hyun
   Park, Sangwan
   Sazhnyev, Yevgeniy
   Wang, Yinwen
   Cunefare, David
   Farsiu, Sina
   Thomasy, Sara M.
   Moshiri, Ala
   Yiu, Glenn
TI Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and
   Age-Related Drusen
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE autofluorescence; fundus autofluorescence; lipofuscin; primate; macaque;
   rhesus macaque; maculopathy; age-related macular degeneration; AMD
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL-PIGMENT EPITHELIUM; CHOROIDAL
   THICKNESS MEASUREMENTS; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY;
   PROGRESSION; LIPOFUSCIN; MONKEYS; DENSITY; EYES
AB PURPOSE. To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD).
   METHODS. The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 +/- 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectraldomain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis.
   RESULTS. Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with agematched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R-2 = 0.391, P < 0.001).
   CONCLUSIONS. In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.
C1 [Tran, Tu M.; Chung, Sook Hyun; Sazhnyev, Yevgeniy; Wang, Yinwen; Moshiri, Ala; Yiu, Glenn] Univ Calif Davis, Dept Ophthalmol & Vis Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
   [Kim, Soohyun; Lin, Kira H.; Park, Sangwan; Thomasy, Sara M.] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA.
   [Cunefare, David; Farsiu, Sina] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
C3 University of California System; University of California Davis;
   University of California System; University of California Davis; Duke
   University
RP Yiu, G (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Vis Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
EM gyiu@ucdavis.edu
OI Park, Sangwan/0000-0003-0381-0386
FU California National Primate Research Center [NIH P510D011107]; NIH [K08
   EY026101, R21 EY031108, K08 EY027463, U24 EY029904, R01 EY016134, U01
   ES027288]; E. Matilda Ziegler Foundation for the Blind; Barr Foundation
   for Retinal Research; ARVO Foundation; Macula Society; Fight for Sight
   [SS-19-001]; Unrestricted Research to Prevent Blindness; National
   Institutes of Health Core Grant [P30EY005722]
FX Supported by the California National Primate Research Center pilot grant
   program and base grant NIH P510D011107. Glenn C. Yiu is supported by NIH
   K08 EY026101, NIH R21 EY031108, the E. Matilda Ziegler Foundation for
   the Blind, the Barr Foundation for Retinal Research, ARVO Foundation,
   and the Macula Society. Ala Moshiri is supported by NIH K08 EY027463,
   NIH U24 EY029904, and the Barr Foundation for Retinal Research. Sara M.
   Thomasy is supported by NIH R01 EY016134, NIH U01 ES027288, and NIH U24
   EY029904. Tu M. Tran is supported by Fight for Sight SS-19-001. Sina
   Farsiu is supported in part by the Unrestricted Research to Prevent
   Blindness Grant to Duke University and the National Institutes of Health
   Core Grant, P30EY005722. 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. The authors alone are
   responsible for the content and writing of the article.
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NR 77
TC 5
Z9 5
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 2020
VL 61
IS 8
AR 16
DI 10.1167/iovs.61.8.16
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MS8BL
UT WOS:000554499000018
PM 32663290
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kristiansen, IS
   Braten, RH
   Jorstad, OK
   Moe, MC
   Saether, EM
AF Kristiansen, Ivar Sonbo
   Haugli Braten, Ragnhild
   Jorstad, Oystein Kalsnes
   Moe, Morten Carstens
   Saether, Erik Magnus
TI Intravitreal therapy for retinal diseases in Norway 2011-2015
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE EGFR; intravitreal injection; retinal disease; statistics; wet
   age-related macular degeneration
ID MACULAR DEGENERATION; VEIN OCCLUSION; AFLIBERCEPT INJECTION;
   RANIBIZUMAB; EDEMA; BEVACIZUMAB; PREVALENCE; RATES
AB Purpose During the past decade, intravitreally administered biologic drugs have advanced the treatment of retinal diseases, such as wet age-related macular degeneration (AMD), diabetic macular oedema and retinal venous occlusions. The drugs as well as the necessary disease management imply considerable economic burden on healthcare systems. This Norwegian study documents the rates of use of intravitreal therapies and intercounty variation over a 5-year period.
   Methods We collected data from the Norwegian Patient Register for all episodes of care encompassing intravitreal therapy during the period 2011-2015. For each episode, we received information on patient age, sex, county of residence, diagnosis and name of drug injected.
   Results During the study period, 21 277 patients had in total 236 857 episodes of care. The number of intravitreal injections doubled from 2011 to 2015, reaching 63 601 injections in 2015, of which 77% were for diagnosed wet AMD. In 2015, the age-adjusted number of episodes varied from 19 to 55 per 1000 population aged 50+ across Norway's 19 counties. The age-adjusted number of patients treated per 1000 population aged 50+ varied from 5.22 to 8.35.
   Conclusion The use of intravitreal injections increased rapidly with wet AMD as the most frequent diagnosis and with varying utilization across Norway's 19 counties. The causes of the varying use of intravitreal therapies could not be established but may reflect variation in disease prevalence, treatment capacity, travel distance to the nearest ophthalmic service and lack of national treatment guidelines. The geographic variation in utilization may challenge policy goals of equitable care and warrants further studies.
C1 [Kristiansen, Ivar Sonbo] Univ Oslo, Dept Hlth Management & Hlth Econ, Inst Hlth & Med, POB 1089 Blindern, NO-0317 Oslo, Norway.
   [Kristiansen, Ivar Sonbo; Haugli Braten, Ragnhild; Saether, Erik Magnus] Oslo Econ, Oslo, Norway.
   [Jorstad, Oystein Kalsnes; Moe, Morten Carstens] Oslo Univ Hosp, Dept Ophthalmol, Oslo, Norway.
   [Jorstad, Oystein Kalsnes; Moe, Morten Carstens] Univ Oslo, Inst Clin Med, Oslo, Norway.
C3 University of Oslo; University of Oslo; University of Oslo
RP Kristiansen, IS (通讯作者)，Univ Oslo, Dept Hlth Management & Hlth Econ, Inst Hlth & Med, POB 1089 Blindern, NO-0317 Oslo, Norway.
EM i.s.kristiansen@medisin.uio.no
OI Jorstad, Oystein Kalsnes/0000-0003-1259-0653; Kristiansen, Ivar
   Sonbo/0000-0002-5389-6010
FU Bayer
FX The study was sponsored by Bayer. It was based on the data from the
   Norwegian Patient Register (NPR). No endorsement by the Norwegian
   Patient Registry is intended nor should be inferred. The authors bear
   the sole responsibility for analysis and interpretation of the data. All
   authors have access to the data.
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NR 26
TC 4
Z9 4
U1 0
U2 0
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 2020
VL 98
IS 3
BP 279
EP 285
DI 10.1111/aos.14262
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LH4QT
UT WOS:000528770500012
PM 31587508
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Kim, M
   Iezzi, R
   Shim, BS
   Martin, DC
AF Kim, Minsoo
   Iezzi, Raymond, Jr.
   Shim, Bong Sup
   Martin, David C.
TI Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor
   (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold
   Nanoparticle (Au NP) Composites
SO FRONTIERS IN CHEMISTRY
LA English
DT Article
DE VEGF (Vascular Endotelial Growth Factor); PEDOT (poly(3,
   4-ethylenedioxythiophene)); biosensor; electrochemical deposition;
   impedance spectroscopy
ID IMPEDANCE SPECTROSCOPY; ELECTROCHEMICAL SENSORS; RANIBIZUMAB; LIGANDS;
   DESIGN
AB In advanced forms of diabetic retinopathy, retinal vascular occlusive disease and exudative age-related macular degeneration, vision loss is associated with elevated levels or extravasation of vascular endothelial-derived growth factor (VEGF) into the retina, vitreous, and anterior chamber of the eye. We hypothesize that point-of-care biosensors, capable of rapidly and precisely measuring VEGF levels within the eye will assist clinicians in assessing disease severity, and in establishing individualized dosing intervals for intraocular anti-VEGF injection therapy. An impedance biosensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT)/gold nanoparticle (Au NP) composite was developed for detecting VEGF. PEDOT with Au NP was electrochemically deposited on three different medical electrode sensor designs: free-standing pads, screen printed dots, and interdigitated micro-strip electrodes. Anti-VEGF antibody was covalently immobilized on the surface of the polymer films through attachment to citrate-functionalized Au NPs, and the resulting composites were used to detect VEGF-165 by electrochemical impedance spectroscopy (EIS). The PEDOT-Au NP composite materials were characterized using optical microscopy, SEM/EDS, FIB, TEM, and STEM techniques. Among the different micro-electrodes, the interdigitated strip shape showed the best overall film stability and reproducibility. A linear relationship was established between the charge transfer resistance (R-ct) and VEGF concentration. The detection limit of VEGF was found to be 0.5 pg/mL, with a correlation coefficient of 0.99 +/- 0.064%. These results indicate that the proposed PEDOT/Au NP composites can be used in designing low-cost and accurate VEGF biosensors for applications such as clinical diagnosis of VEGF-mediated eye disease.
C1 [Kim, Minsoo; Shim, Bong Sup; Martin, David C.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
   [Iezzi, Raymond, Jr.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA.
   [Shim, Bong Sup] Inha Univ, Dept Chem Engn, Incheon, South Korea.
C3 University of Delaware; Mayo Clinic; Inha University
RP Martin, DC (通讯作者)，Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
EM milty@udel.edu
RI Martin, David/B-1838-2008; Shim, Bong Sup/A-1348-2019
OI Martin, David/0000-0003-1195-3838; Shim, Bong Sup/0000-0003-3205-6191
FU University of Delaware; National Science Foundation [DMR-1505144,
   DMR-1808048, NRF-2017R1A2B4012736]
FX This research was supported in part by funding from University of
   Delaware and the National Science Foundation (DMR-1505144 and
   DMR-1808048). BS acknowledges funding support from NRF-2017R1A2B4012736.
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SC Chemistry
GA HT4YU
UT WOS:000464570100001
PM 31058131
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cantsilieris, S
   Nelson, BJ
   Huddleston, J
   Baker, C
   Harshman, L
   Penewit, K
   Munson, KM
   Sorensen, M
   Welch, AE
   Dang, V
   Grassmann, F
   Richardson, AJ
   Guymer, RH
   Graves-Lindsay, TA
   Wilson, RK
   Weber, BHF
   Baird, PN
   Allikmets, R
   Eichler, EE
AF Cantsilieris, Stuart
   Nelson, Bradley J.
   Huddleston, John
   Baker, Carl
   Harshman, Lana
   Penewit, Kelsi
   Munson, Katherine M.
   Sorensen, Melanie
   Welch, AnneMarie E.
   Dang, Vy
   Grassmann, Felix
   Richardson, Andrea J.
   Guymer, Robyn H.
   Graves-Lindsay, Tina A.
   Wilson, Richard K.
   Weber, Bernhard H. F.
   Baird, Paul N.
   Allikmets, Rando
   Eichler, Evan E.
TI Recurrent structural variation, clustered sites of selection, and
   disease risk for the complement factor H (CFH) gene family
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE structural variation; CFH gene family; natural selection; age-related
   macular degeneration; AMD
ID HEMOLYTIC-UREMIC SYNDROME; MACULAR DEGENERATION; RARE VARIANTS;
   EVOLUTIONARY INSTABILITY; EARLY-ONSET; MUTATIONS; PROTEINS; DELETION;
   SUSCEPTIBILITY; ACTIVATION
AB Structural variation and single-nucleotide variation of the complement factor H (CFH) gene family underlie several complex genetic diseases, including age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (AHUS). To understand its diversity and evolution, we performed high-quality sequencing of this similar to 360-kbp locus in six primate lineages, including multiple human haplotypes. Comparative sequence analyses reveal two distinct periods of gene duplication leading to the emergence of four CFH-related (CFHR) gene paralogs (CFHR2 and CFHR4 similar to 25-35 Mya and CFHR1 and CFHR3 similar to 7-13 Mya). Remarkably, all evolutionary breakpoints share a common similar to 4.8-kbp segment corresponding to an ancestral CFHR gene promoter that has expanded independently throughout primate evolution. This segment is recurrently reused and juxtaposed with a donor duplication containing exons 8 and 9 from ancestral CFH, creating four CFHR fusion genes that include lineage-specific members of the gene family. Combined analysis of > 5,000 AMD cases and controls identifies a significant burden of a rare missense mutation that clusters at the N terminus of CFH [P = 5.81 x 10(-8), odds ratio (OR) = 9.8 (3.67-Infinity)]. A bipolar clustering pattern of rare nonsynonymous mutations in patients with AMD (P < 10(-3)) and AHUS (P = 0.0079) maps to functional domains that show evidence of positive selection during primate evolution. Our structural variation analysis in >2,400 individuals reveals five recurrent rearrangement breakpoints that show variable frequency among AMD cases and controls. These data suggest a dynamic and recurrent pattern of mutation critical to the emergence of new CFHR genes but also in the predisposition to complex human genetic disease phenotypes.
C1 [Cantsilieris, Stuart; Nelson, Bradley J.; Huddleston, John; Baker, Carl; Harshman, Lana; Penewit, Kelsi; Munson, Katherine M.; Sorensen, Melanie; Welch, AnneMarie E.; Dang, Vy; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Grassmann, Felix; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Richardson, Andrea J.; Guymer, Robyn H.; Baird, Paul N.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Dept Surg Ophthalmol, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.
   [Graves-Lindsay, Tina A.] Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA.
   [Wilson, Richard K.] Nationwide Childrens Hosp, Inst Genom Med, Columbus, OH 43205 USA.
   [Wilson, Richard K.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 93053 USA.
   [Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   [Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA.
C3 University of Washington; University of Washington Seattle; Howard
   Hughes Medical Institute; University of Washington; University of
   Washington Seattle; University of Regensburg; Centre for Eye Research
   Australia; Royal Victorian Eye & Ear Hospital; University of Melbourne;
   Washington University (WUSTL); University System of Ohio; Ohio State
   University; Nationwide Childrens Hospital; University System of Ohio;
   Ohio State University; Columbia University; Columbia University
RP Eichler, EE (通讯作者)，Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.; Eichler, EE (通讯作者)，Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
RI Wilson, Richard K./AAF-4139-2019; Munson, Katherine M/P-2462-2015;
   Allikmets, Rando/ABD-4533-2021
OI Wilson, Richard K./0000-0002-1992-1358; Munson, Katherine
   M/0000-0001-8413-6498; Guymer, Robyn/0000-0002-9441-4356; Grassmann,
   Felix/0000-0003-1390-7528; Sorensen, Melanie/0000-0002-1525-9707; Baird,
   Paul/0000-0002-1305-3502
FU US NIH [R01HG002385, U41HG007635]; National Health and Medical Research
   Council (NHMRC) C. J. Martin Biomedical Fellowship [1073726]; NHMRC
   Senior Research Fellowship [APP1138585]; NIH [R01-EY013435,
   P30-EY019007]; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [P30EY019007, R01EY013435] Funding Source: NIH RePORTER; NATIONAL HUMAN
   GENOME RESEARCH INSTITUTE [U41HG007635, R01HG002385] Funding Source: NIH
   RePORTER
FX We thank T. Brown for assistance with manuscript preparation. This work
   was supported, in part, by grants from the US NIH (Grant R01HG002385 to
   E.E.E. and Grant U41HG007635 to R.K.W. and E.E.E.). S.C. was supported
   by a National Health and Medical Research Council (NHMRC) C. J. Martin
   Biomedical Fellowship (1073726). P.N.B. was supported by an NHMRC Senior
   Research Fellowship (APP1138585). The Centre for Eye Research Australia
   receives operational infrastructure support from the Victorian
   Government. R.A. was supported, in part, by NIH Grants R01-EY013435 and
   P30-EY019007 and by an unrestricted grant from Research to Prevent
   Blindness to the Department of Ophthalmology, Columbia University.
   E.E.E. is an Investigator of the Howard Hughes Medical Institute.
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NR 56
TC 26
Z9 27
U1 0
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 MAY 8
PY 2018
VL 115
IS 19
BP E4433
EP E4442
DI 10.1073/pnas.1717600115
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GF0RQ
UT WOS:000431639100017
PM 29686068
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Rao, RC
   Dedania, VS
   Johnson, MW
AF Rao, Rajesh C.
   Dedania, Vaidehi S.
   Johnson, Mark W.
TI Stem Cells for Retinal Disease: A Perspective on the Promise and Perils
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; GLOBAL PREVALENCE; THERAPY; BURDEN; TRIALS
AB PURPOSE: To summarize key concepts, as well as early safety and efficacy signals from clinical trials, for stem/ progenitor cell-based interventions for retinal disease.
   DESIGN: Interpretive essay.
   METHODS: Review and synthesis of selected recent reports of stem/progenitor cell-based approaches for retinal disease, with interpretation and perspective.
   RESULTS: Stem/progenitor cell-based interventions represent a novel class of potential therapies for retinal diseases, such as age-related macular degeneration and inherited retinal dystrophies, aoong others. Sources include pluripotent stem cells and fetal and postnatal tissues. Two mechanisms of "rescue" have been proposed: regenerative or trophic. Although pluripotent and fetal sourced-cell types have been tested in preclinical animal models of retinal disease, many postnatal stem/progenitor cell populations currently in trial do not have preclinical safety or efficacy data. Some early-phase trials of cell therapies suggest acceptable safety profiles. Other reports, involving some types of autologous, nonocular cell sources, have been linked to severe, blinding complications. Larger trials will be needed to determine short-term and long-term safety and efficacy of these cell-based interventions.
   CONCLUSIONS: Stem/progenitor cell-based interventions have the potential to address blinding retinal diseases that affect hundreds of millions worldwide. Yet no Food and Drug Administration-approved stem cell therapies for retinal disease exist. Although some early-phase trial data are promising, reports of blinding complications from cell interventions remain troubling. It is paramount to apply a strong level of scientific rigor toward a well planned, step-wise sequence of preclinical and clinical studies, to determine whether this class of potential therapies will be safe and effective for individuals with retinal diseases. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Rao, Rajesh C.; Dedania, Vaidehi S.; Johnson, Mark W.] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Rao, Rajesh C.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48105 USA.
   [Rao, Rajesh C.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48105 USA.
   [Rao, Rajesh C.] Univ Michigan, A Alfred Taubman Med Res Inst, Ann Arbor, MI 48105 USA.
   [Rao, Rajesh C.] Vet Adm Ann Arbor Healthcare Syst, Sect Ophthalmol, Surg Serv, Ann Arbor, MI USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan; University of Michigan System;
   University of Michigan; University of Michigan System; University of
   Michigan
RP Rao, RC (通讯作者)，Univ Michigan, WK Kellogg Eye Ctr, Med Sch, 1000 Wall St,Brehm Room 8333, Ann Arbor, MI 48105 USA.
EM rajeshr@med.umich.edu
RI Rao, Rajesh C./N-1107-2017
OI Rao, Rajesh C./0000-0002-5776-8366; Johnson, Mark W/0000-0001-9720-8761
FU THE LEONARD G. MILLER OPHTHALMIC RESEARCH FUND (ANN ARBOR, Michigan,
   USA) at the Kellogg Eye Center; Barbara Dunn Research Fund (Ann Arbor,
   Michigan, USA); Beatrice AMP; Reymont Paul Foundation (Bloomfield Hills,
   Michigan, USA); March Hoops to Beat Blindness (Ann Arbor, Michigan,
   USA); A. Alfred Taubman Medical Research Institute (Ann Arbor, Michigan,
   USA)
FX THIS WORK WAS SUPPORTED BY THE LEONARD G. MILLER OPHTHALMIC RESEARCH
   FUND (ANN ARBOR, Michigan, USA) at the Kellogg Eye Center, Barbara Dunn
   Research Fund (Ann Arbor, Michigan, USA), Beatrice & Reymont Paul
   Foundation (Bloomfield Hills, Michigan, USA), and March Hoops to Beat
   Blindness (Ann Arbor, Michigan, USA) (to R.C.R.). R.C.R. is the Leslie
   H. and Abigail S. Wexner Emerging Scholar of the A. Alfred Taubman
   Medical Research Institute (Ann Arbor, Michigan, USA), which supported,
   in part, this study. None of the sponsors participated in the
   preparation, review, or approval of the manuscript; or the decision to
   submit the manuscript for publication.
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NR 35
TC 7
Z9 7
U1 0
U2 9
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 JUL
PY 2017
VL 179
BP 32
EP 38
DI 10.1016/j.ajo.2017.04.007
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FA0YY
UT WOS:000405163900005
PM 28428049
DA 2022-11-30
ER

PT J
AU Pilotto, E
   Guidolin, F
   Convento, E
   Antonini, R
   Stefanon, FG
   Parrozzani, R
   Midena, E
AF Pilotto, Elisabetta
   Guidolin, Francesca
   Convento, Enrica
   Antonini, Rachele
   Stefanon, Francesco Giuseppe
   Parrozzani, Raffaele
   Midena, Edoardo
TI En Face Optical Coherence Tomography to Detect and Measure Geographic
   Atrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE geographic atrophy; age-related macular degeneration; en face optical
   coherence tomography; fundus autofluorescence; near infrared fundus
   autofluorescence
ID NEAR-INFRARED AUTOFLUORESCENCE; MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; PHOTORECEPTOR-LOSS; VISUAL-LOSS; PROGRESSION; OCT;
   RPE; CHORIOCAPILLARIS; DISEASE
AB PURPOSE. To detect and quantify geographic atrophy (GA) secondary to age-related macular degeneration using en face optical coherence tomography (OCT) and to correlate it to GA measured with fundus autofluorescence (FAF).
   METHODS. Twenty-four consecutive patients (27 eyes) were studied with both standard (STD)and enhanced depth imaging (EDI)-OCT. En face OCT images were obtained at the outer retinal layer (OR) and at the choroidal layer (CH) level for both STD-and EDI-OCT. Areas of GA were measured on the en face OCT images and were correlated with the GA areas measured on blue (B)- and near infrared (NIR)-wavelength FAF images.
   RESULTS. The intraoperator agreement in GA measurement was excellent with en face OCT at both OR and CH levels (intraclass correlation coefficient [ICC] = 0.99 in EDI and 0.98 in STD at OR level; 0.99 in EDI and 0.99 in STD at CH level). The interoperator agreement was excellent at OR level (ICC = 0.97 in EDI and 0.98 in STD), good at CH level (ICC = 0.95 in EDI, 0.90 in STD). The geographic atrophy area, at both B-FAF and NIR-FAF, was significantly equivalent to the GA area at OR level (B-FAF versus SDT-OR and EDI-OR: P = 0.0057 and 0.0090, respectively; NIR-FAF versus STD-OR and EDI-OR: P = 0.0131 and 0.0036, respectively), but not at CH level.
   CONCLUSIONS. En face OCT is a reliable method to detect and quantify GA, particularly when analyzed at the OR level, where the photoreceptors' loss creates an abrupt transition in OCT reflectivity.
C1 [Pilotto, Elisabetta; Guidolin, Francesca; Convento, Enrica; Antonini, Rachele; Stefanon, Francesco Giuseppe; Midena, Edoardo] Univ Padua, Inst Ophthalmol, I-35128 Padua, Italy.
   [Parrozzani, Raffaele; Midena, Edoardo] IRCCS, GB Bietti Fdn, Rome, Italy.
C3 University of Padua; IRCCS - Fondazione "G.B. Bietti" per lo Studio e la
   Ricerca in Oftalmologia
RP Midena, E (通讯作者)，Univ Padua, Inst Ophthalmol, Via Giustiniani 2, I-35128 Padua, Italy.
EM edoardo.midena@unipd.it
RI Midena, Edoardo/AAB-6010-2020; Parrozzani, Raffaele/W-3341-2017;
   parrozzani, raffaele/K-2034-2016
OI Parrozzani, Raffaele/0000-0003-0216-727X; parrozzani,
   raffaele/0000-0003-0216-727X
FU Fondazione Roma; Ministry of Health
FX The research contribution by the G.B. Bietti Foundation was supported by
   Fondazione Roma and Ministry of Health.
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NR 35
TC 19
Z9 20
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 DEC
PY 2015
VL 56
IS 13
BP 8120
EP 8124
DI 10.1167/iovs.15-17366
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DB1BU
UT WOS:000368243800064
PM 26720464
OA Green Published
DA 2022-11-30
ER

PT J
AU Salomon, RG
   Bi, WZ
AF Salomon, Robert G.
   Bi, Wenzhao
TI Isolevuglandin Adducts in Disease
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID ALDEHYDE-MODIFIED PHOSPHATIDYLETHANOLAMINES; ENDOPLASMIC-RETICULUM
   STRESS; SCAVENGER RECEPTOR CD36; LOW-DENSITY-LIPOPROTEIN;
   NECROSIS-FACTOR-ALPHA; GAMMA-KETOALDEHYDES; ALZHEIMERS-DISEASE;
   PROSTAGLANDIN ENDOPEROXIDES; PROTEIN ADDUCTS; OXIDIZED PHOSPHOLIPIDS
AB Significance: A diverse family of lipid-derived levulinaldehydes, isolevuglandins (isoLGs), is produced by rearrangement of endoperoxide intermediates generated through both cyclooxygenase (COX) and free radical-induced cyclooxygenation of polyunsaturated fatty acids and their phospholipid esters. The formation and reactions of isoLGs with other biomolecules has been linked to alcoholic liver disease, Alzheimer's disease, age-related macular degeneration, atherosclerosis, cardiac arythmias, cancer, end-stage renal disease, glaucoma, inflammation of allergies and infection, mitochondrial dysfunction, multiple sclerosis, and thrombosis. This review chronicles progress in understanding the chemistry of isoLGs, detecting their production in vivo and understanding their biological consequences. Critical Issues: IsoLGs have never been isolated from biological sources, because they form adducts with primary amino groups of other biomolecules within seconds. Chemical synthesis enabled investigation of isoLG chemistry and detection of isoLG adducts present in vivo. Recent Advances: The first peptide mapping and sequencing of an isoLG-modified protein present in human retina identified the modification of a specific lysyl residue of the sterol C27-hydroxylase Cyp27A1. This residue is preferentially modified by iso[4]LGE(2)in vitro, causing loss of function. Adduction of less than one equivalent of isoLG can induce COX-associated oligomerization of the amyloid peptide A(1-42). Adduction of isoLGE(2) to phosphatidylethanolamines causes gain of function, converting them into proinflammatory isoLGE(2)-PE agonists that foster monocyte adhesion to endothelial cells. Future Directions: Among the remaining questions on the biochemistry of isoLGs are the dependence of biological activity on isoLG isomer structure, the structures and mechanism of isoLG-derived protein-protein and DNA-protein cross-link formation, and its biological consequences. Antioxid. Redox Signal. 22, 1703-1718.
C1 [Salomon, Robert G.; Bi, Wenzhao] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
C3 Case Western Reserve University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@cwru.edu
OI Salomon, Robert/0000-0001-9456-3557
FU National Institute of General Medical Sciences of National Institutes of
   Health [GM021249]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [R01GM021249] Funding Source: NIH RePORTER
FX The portions of this work conducted in the Salomon laboratories were
   supported by grant (GM021249) from the National Institute of General
   Medical Sciences of National Institutes of Health. Dr. Salomon thanks
   his students and collaborators whose names appear in the references for
   their industrious, meticulous, persistent, and thoughtful contributions
   to their studies.
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NR 102
TC 29
Z9 30
U1 0
U2 19
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 JUN 20
PY 2015
VL 22
IS 18
BP 1703
EP 1718
DI 10.1089/ars.2014.6154
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CU9WA
UT WOS:000363895900005
PM 25557218
OA Green Published
DA 2022-11-30
ER

PT J
AU Pennington, BO
   Clegg, DO
   Melkoumian, ZK
   Hikita, ST
AF Pennington, Britney O.
   Clegg, Dennis O.
   Melkoumian, Zara K.
   Hikita, Sherry T.
TI Defined Culture of Human Embryonic Stem Cells and Xeno-Free Derivation
   of Retinal Pigmented Epithelial Cells on a Novel, Synthetic Substrate
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Human embryonic stem cells; Retinal pigmented epithelium; Synthemax
   II-SC substrate; Age-related macular degeneration; Parylene-C
ID PEPTIDE-ACRYLATE SURFACE; FEEDER-FREE; SUBRETINAL IMPLANTATION; MACULAR
   DEGENERATION; SELF-RENEWAL; IN-VIVO; DIFFERENTIATION; MATRIX;
   ADAPTATION; PARYLENE
AB Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by the death of the retinal pigmented epithelium (RPE), which is a monolayer posterior to the retina that supports the photoreceptors. Human embryonic stem cells (hESCs) can generate an unlimited source of RPE for cellular therapies, and clinical trials have been initiated. However, protocols for RPE derivation using defined conditions free of nonhuman derivatives (xeno-free) are preferred for clinical translation. This avoids exposing AMD patients to animal-derived products, which could incite an immune response. In this study, we investigated the maintenance of hESCs and their differentiation into RPE using Synthemax II-SC, which is a novel, synthetic animal-derived component-free, RGD peptide-containing copolymer compliant with good manufacturing practices designed for xeno-free stem cell culture. Cells on Synthemax II-SC were compared with cultures grown with xenogeneic and xeno-free control substrates. This report demonstrates that Synthemax II-SC supports long-term culture of H9 and H14 hESC lines and permits efficient differentiation of hESCs into functional RPE. Expression of RPE-specific markers was assessed by flow cytometry, quantitative polymerase chain reaction, and immunocytochemistry, and RPE function was determined by phagocytosis of rod outer segments and secretion of pigment epithelium-derived factor. Both hESCs and hESC-RPE maintained normal karyotypes after long-term culture on Synthemax II-SC. Furthermore, RPE generated on Synthemax II-SC are functional when seeded onto parylene-C scaffolds designed for clinical use. These experiments suggest that Synthemax II-SC is a suitable, defined substrate for hESC culture and the xeno-free derivation of RPE for cellular therapies.
C1 [Pennington, Britney O.; Clegg, Dennis O.; Hikita, Sherry T.] Univ Calif Santa Barbara, Biomol Sci & Engn Program, Neurosci Res Inst, Ctr Stem Cell Biol & Engn, Santa Barbara, CA 93106 USA.
   [Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Melkoumian, Zara K.] Corning Inc, Corning Life Sci Dev, New York, NY USA.
   [Hikita, Sherry T.] Asterias Biotherapeut Inc, Menlo Pk, CA USA.
C3 University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   Corning Inc; State University of New York (SUNY) System; SUNY Community
   College
RP Clegg, DO (通讯作者)，Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
EM clegg@lifesci.ucsb.edu
FU Richard & Katherine Gee Breaux Fellowship in Vision Research; Garland
   Initiative for Vision; Scientific Research Society Sigma Xi; Wynn-Gund
   Translational Research Acceleration Program; University of California;
   Santa Barbara Institute for Collaborative Biotechnologies from the U.S.
   Army Research Office [W911NF-09-0001]; California Institute for
   Regenerative Medicine [DR1-01444, CL1-00521, TG2-01151, FA1-00616];
   Fight for Sight
FX We thank the staff of the Center for Stem Cell Biology and Engineering,
   as well as the Laboratory for Stem Cell Biology and Engineering. This
   work was supported by the Richard & Katherine Gee Breaux Fellowship in
   Vision Research, the Garland Initiative for Vision, a grant-in-aid for
   research from the Scientific Research Society Sigma Xi, the Wynn-Gund
   Translational Research Acceleration Program, the University of
   California, Santa Barbara Institute for Collaborative Biotechnologies
   through Grant W911NF-09-0001 from the U.S. Army Research Office, and
   California Institute for Regenerative Medicine Grants DR1-01444,
   CL1-00521, TG2-01151, and FA1-00616 (to D.O.C.). Financial support from
   Fight for Sight is gratefully acknowledged. B.O.P. is a fellow of the
   California Institute for Regenerative Medicine. The content of the
   information does not necessarily reflect the position or the policy of
   the U.S. government, and no official endorsement should be inferred.
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NR 74
TC 46
Z9 48
U1 0
U2 17
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD FEB
PY 2015
VL 4
IS 2
BP 165
EP 177
DI 10.5966/sctm.2014-0179
PG 13
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA CA5SK
UT WOS:000348967900007
PM 25593208
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Herbik, A
   Geringswald, F
   Thieme, H
   Pollmann, S
   Hoffmann, MB
AF Herbik, Anne
   Geringswald, Franziska
   Thieme, Hagen
   Pollmann, Stefan
   Hoffmann, Michael B.
TI Prediction of higher visual function in macular degeneration with
   multifocal electroretinogram and multifocal visual evoked potential
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE age-related macular degeneration; contextual cueing; multifocal
   electrophysiology; multifocal electroretinogram; multifocal visual
   evoked potential; visual acuity; visual search; visuospatial working
   memory
ID RETINAL FUNCTION; UNITED-STATES; SEARCH; ATTENTION; CONTEXT;
   ABNORMALITIES; MACULOPATHY; PREVALENCE; DEFOCUS; DAMAGE
AB Objective: Visual search can be guided by past experience of regularities in our visual environment. This search guidance by contextual memory cues is impaired by foveal vision loss. Here we compared retinal and cortical visually evoked responses in their predictive value for contextual cueing impairment and visual acuity.
   Methods: Multifocal electroretinograms to flash stimulation (mfERGs; 103 locations; 55.8 degrees diameter) and visual evoked potentials to pattern-reversal stimulation (mfVEPs; 60 locations; 48.6 degrees diameter) were recorded monocularly in participants with age-related macular degeneration (n = 14 and 16, respectively). Response magnitudes were calculated as the respective signal-to-noise ratios for each eccentricity. Visual acuities (logMAR, range: 0.0-1.2) and contextual cueing effects on visual search (reaction time gain, range: -0.14-0.15) were correlated with the signal-to-noise ratios. A step-wise regression analysis was applied separately to the mfERG- and mfVEP-dataset to determine the eccentricity range and the processing stage that is critical for these visual functions.
   Results: Central mfERGs (1.0-3.2 degrees) were the sole predictor of contextual cueing of visual search (p = 0.006), but they were not significant predictors of visual acuity. In contrast, central mfVEPs (1.3-3.2 degrees) were the sole predictor of visual acuity (p < 0.001), but they were not significant predictors of contextual cueing.
   Conclusions: Contextual cueing is more dependent on parafoveal mfERG magnitude while visual acuity is more dependent on parafoveal mfVEP magnitude. The relation of contextual cueing to parafoveal mfERG magnitudes indicates the predictive value of retinal bipolar cell activity for this advanced level of visual function.
C1 [Herbik, Anne; Thieme, Hagen; Hoffmann, Michael B.] Univ Magdeburg, Dept Ophthalmol, D-39106 Magdeburg, Germany.
   [Geringswald, Franziska; Pollmann, Stefan] Univ Magdeburg, Dept Expt Psychol, D-39106 Magdeburg, Germany.
   [Pollmann, Stefan; Hoffmann, Michael B.] Ctr Behav Brain Sci, Magdeburg, Germany.
C3 Otto von Guericke University; Otto von Guericke University
RP Hoffmann, MB (通讯作者)，Univ Magdeburg, Dept Ophthalmol, D-39106 Magdeburg, Germany.
EM michael.hoffmann@med.ovgu.de
RI Pollmann, Stefan/D-1999-2013; Pollmann, Stefan/AAH-5584-2020; Hoffmann,
   Michael/E-9115-2010
OI Pollmann, Stefan/0000-0001-5840-5658; Pollmann,
   Stefan/0000-0001-5840-5658; Hoffmann, Michael/0000-0002-6452-9638
FU DFG [HO2002/9-1, PO548/8-1, 14-1]
FX We gratefully acknowledge the support by the DFG (HO2002/9-1; PO548/8-1
   and 14-1) and the support by the study participants.
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   World Med Assoc, 2013, JAMA-J AM MED ASSOC, V310, P2191, DOI 10.1001/jama.2013.281053
NR 50
TC 2
Z9 3
U1 0
U2 12
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD SEP
PY 2014
VL 34
IS 5
BP 540
EP 551
DI 10.1111/opo.12152
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO3SB
UT WOS:000341254500006
PM 25160891
DA 2022-11-30
ER

PT J
AU Stein, JD
   Blachley, TS
   Musch, DC
AF Stein, Joshua D.
   Blachley, Taylor S.
   Musch, David C.
TI Identification of Persons With Incident Ocular Diseases Using Health
   Care Claims Databases
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GLAUCOMA; OUTCOMES
AB PURPOSE: To assess the extent to which incidence rates calculated for common ocular diseases by using claims data may be overestimated according to the length of the disease-free look-back period used in the analysis.
   DESIGN: Retrospective longitudinal cohort analysis.
   METHODS: Billing records of 2457 persons continuously enrolled for 11 years in a managed-care network were searched for International Classification of Diseases (ICD-9-CM) diagnoses of cataract, open-angle glaucoma (OAG), nonexudative age-related macular degeneration (ARMD), and nonproliferative diabetic retinopathy (NPDR) at eye-care visits in the first half of 2001, the second half of 2010, and 2011. For each condition, incidence rates calculated by using "look-back" periods ranging from 0.5-9 years were compared with best estimates from a gold-standard period of 9.5 years.
   RESULTS: With a 1-year disease-free look-back period, incidence was overestimated by 260% for cataract, 135% for OAG, 209% for ARMD, and 300% for NPDR. Expanding the disease-free look-back period to 3 years resulted in a reduction of incidence overestimation to 40% for cataract, 14% for OAG, 45% for ARMD, and 100% for NPDR. A 5-year look-back period yielded incidence rates that were overestimated by <30% for all 4 conditions.
   CONCLUSIONS: In our claims-data analysis of 4 common ocular conditions, a disease-free interval 51 year insufficiently distinguished newly diagnosed from pre-existing disease, resulting in grossly overestimated incidence rates. Using look-back periods of 3-5 years, depending on the specific diagnosis, yielded considerably more accurate estimates of disease incidence. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Stein, Joshua D.; Blachley, Taylor S.; Musch, David C.] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan
RP Stein, JD (通讯作者)，Univ Michigan, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM jdstein@med.umich.edu
OI Musch, David/0000-0002-4164-3841; Stein, Joshua/0000-0003-2937-6987
FU National Eye Institute K23 Mentored Clinician Scientist Award, Bethesda,
   Maryland, USA [1K23EY019511-01]; Blue Cross Blue Shield of Michigan
   Foundation, Detroit, Michigan, USA; Michigan Diabetes Research and
   Training Center, Ann Arbor, Michigan, USA; Research to Prevent
   Blindness: Physician Scientist Award, New York, New York, USA; Lew R.
   Wasserman Merit Award; W.K. Kellogg Foundation, Battle Creek, Michigan,
   USA; NATIONAL EYE INSTITUTE [K23EY019511] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
   [P30DK092926] Funding Source: NIH RePORTER
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST and none were reported. Grant
   support: National Eye Institute K23 Mentored Clinician Scientist Award
   (J.D.S.: 1K23EY019511-01), Bethesda, Maryland, USA; Blue Cross Blue
   Shield of Michigan Foundation (J.D.S.), Detroit, Michigan, USA; Michigan
   Diabetes Research and Training Center, Ann Arbor, Michigan, USA;
   Research to Prevent Blindness: Physician Scientist Award (J.D.S.), New
   York, New York, USA and Lew R. Wasserman Merit Award (D.C.M.), and the
   W.K. Kellogg Foundation, Battle Creek, Michigan, USA. All the authors
   had full access to all of the data in the study and take responsibility
   for the integrity of the data and the accuracy of the data analysis.
   Contributions of authors: design of study (J.D.S.); data collection
   (J.D.S.); data management (J.D.S., T.S.B.); data analysis (J.D.S.,
   T.S.B.); interpretation of data (J.D.S., T.S.B., D.C.M.); preparation of
   manuscript (J.D.S.); review of manuscript (T.S.B., D.C.M.); approval of
   manuscript (J.D.S., T.S.B., D.C.M.).
CR Abbas S, 2012, HEALTH SERV RES, V47, P746, DOI 10.1111/j.1475-6773.2011.01325.x
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   [Anonymous], 2006, PHYS INT CLASSIFICAT, V2
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   Wysong A, 2009, ARCH OPHTHALMOL-CHIC, V127, P320, DOI 10.1001/archophthalmol.2008.613
NR 16
TC 17
Z9 17
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2013
VL 156
IS 6
BP 1169
EP 1175
DI 10.1016/j.ajo.2013.06.035
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 261OQ
UT WOS:000327674900014
PM 23972306
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zanon-Moreno, V
   Garcia-Medina, JJ
   Zanon-Viguer, V
   Moreno-Nadal, MA
   Pinazo-Duran, MD
AF Zanon-Moreno, Vicente
   Garcia-Medina, Jose J.
   Zanon-Viguer, Vicente
   Moreno-Nadal, Maria A.
   Pinazo-Duran, Maria D.
TI Smoking, an additional risk factor in elder women with primary
   open-angle glaucoma
SO MOLECULAR VISION
LA English
DT Article
ID ENVIRONMENTAL TOBACCO-SMOKE; C-REACTIVE PROTEIN; CIGARETTE-SMOKE;
   POLY(ADP-RIBOSE) POLYMERASE; MACULAR DEGENERATION; TRABECULAR MESHWORK;
   OXIDATIVE STRESS; LUNG-CANCER; CELL-DEATH; APOPTOSIS
AB Purpose: Smoking is a serious public health problem worldwide. Some authors refer to it as the "silent epidemic of the 20th century." It constitutes an important risk factor for ocular pathologies such as age-related macular degeneration (ARMD), diabetic retinopathy, and neuropathy because the toxic effects of tobacco play a key role in the deterioration of eye tissue. Damage to trabecular meshwork cells (TMC) and retinal ganglion cells (RGC), involving inflammation and apoptosis mechanisms, has been proved in glaucoma. The aim of this study was to determine whether smoking influences the progression of primary open angle glaucoma (POAG) in women.
   Methods: This experimental study involved a sampling of consecutive cases of smokers, ex-smokers and non-smokers women with POAG. One hundred and twenty women with POAG, aged 40-90 years, were enrolled (40 smokers, 40 ex-smokers and 40 non-smokers). Samples of aqueous humor (AH) and plasma from each subject were obtained at the beginning of the surgical procedures. Both inflammation and apoptosis processes in the subjects were studied by means of enzyme immunoassay and western blot procedures respectively. We analyzed the interleukin-6 (IL-6) levels as an inflammation marker and the expression of caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1) as apoptosis markers.
   Results: IL-6, caspase-3, and PARP-1 levels were significantly higher in the smoker women who smoked than in the ex-smoker and non-smoker glaucomatous groups of the same gender (p<0,05).
   Conclusions: Inflammation and apoptosis marker levels increase with smoking in the aqueous humor and plasma samples of POAG women. Smoking could be an important additional risk factor for glaucoma progression in elderly women.
C1 [Zanon-Moreno, Vicente; Garcia-Medina, Jose J.; Moreno-Nadal, Maria A.; Pinazo-Duran, Maria D.] Ophthalmol Res Unit Santiago Grisolia, Valencia 46017, Spain.
   [Zanon-Moreno, Vicente; Pinazo-Duran, Maria D.] Dr Peset Univ Hosp, Biomed Res Ctr, Valencia, Spain.
   [Moreno-Nadal, Maria A.] Dr Peset Univ Hosp, Dept Ophthalmol, Valencia, Spain.
   [Zanon-Viguer, Vicente] Dr Peset Univ Hosp, Dept Prevent Med & Publ Hlth, Valencia, Spain.
   [Garcia-Medina, Jose J.] La Inmaculada Hosp, Dept Ophthalmol, Huercal Overa, Almeria, Spain.
RP Zanon-Moreno, V (通讯作者)，Ophthalmol Res Unit Santiago Grisolia, Gaspar Aguilar 90, Valencia 46017, Spain.
EM zanon_vicmor@gva.es
RI Zanon-Moreno, Vicente/B-8348-2009; Zanon-Moreno, Vicente/ABB-7328-2021
OI Zanon-Moreno, Vicente/0000-0003-1179-1592; Garcia-Medina, Jose
   Javier/0000-0002-6245-7271; Pinazo-Duran, Maria
   Dolores/0000-0002-0118-7837
FU Health Counseling of Valencia - Spain [EVES 005/2008]
FX This study was supported by the Health Counseling of Valencia - Spain
   (project EVES 005/2008). This study has been previously presented at
   2009 Congress of the European Society of Ophthalmology. All authors
   declare that the answer to the questions on the competing interest form
   are all NO and therefore have nothing to declare.
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NR 49
TC 33
Z9 34
U1 0
U2 10
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 31
PY 2009
VL 15
IS 312-14
BP 2953
EP 2959
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 570SS
UT WOS:000275698900002
PM 20057902
DA 2022-11-30
ER

PT J
AU Warburton, S
   Davis, WE
   Southwick, K
   Xin, HJ
   Woolley, AT
   Burton, GF
   Thulin, CD
AF Warburton, Sarah
   Davis, Wayne E.
   Southwick, Katie
   Xin, Huijun
   Woolley, Adam T.
   Burton, Gregory F.
   Thulin, Craig D.
TI Proteomic and phototoxic characterization of melanolipofuscin:
   Correlation to disease and model for its origin
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; HUMAN RPE; AGE PIGMENT; MELANIN;
   MELANOSOMES; LIPOFUSCIN; PROTEINS; PHOTOREACTIVITY; FLUORESCENCE;
   GRANULES
AB PURPOSE: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of both melanosomes and lipofuscin (LF) granules, which accumulates in retinal pigment epithelial (RPE) cells and may contribute to the etiology of age-related macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to more closely reflect the onset of AMD than the accumulation of lipofuscin. In an effort to assess the possible contribution MLF may have to the onset of AMD, we analyzed the phototoxicity and protein composition of MLF and compared those results to that of LF.
   METHODS: Specifically, we observed the accumulation of MLF in human RPE from different decades of life, and assessed the phototoxicity of these granules. We also employed fluorescence spectroscopy, atomic force microscopy, transmission and scanning electron microscopy and proteomic analysis to examine the composition of MLF granules in an effort to ascertain their origin.
   RESULTS: Our results show that MLF granules are phototoxic and their accumulation more closely reflects the onset of AMD than does LF accumulation. Our compositional analysis of MLF has shown that while these granules contain some similarities to LF granules, MLF is substantially different. Of significant interest is the finding that MLF, in contrast to LF, does not contain photoreceptor-specific proteins, suggesting that MLF may not originate from the phagocytosis of photoreceptor outer segments. Instead the presence of RPE- and melanosome-specific proteins would suggest that MLF accumulates as a result of the melanosomal autophagocytosis of RPE cells.
   CONCLUSIONS: Our results provide significant insight into understanding the formation and toxicity of MLF and suggest a possible contribution to the etiology of retinal diseases.
C1 Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
C3 Brigham Young University
RP Thulin, CD (通讯作者)，Brigham Young Univ, Dept Chem & Biochem, Benson Sci Bldg C100, Provo, UT 84602 USA.
EM craig_thulin@byu.edu
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NR 36
TC 44
Z9 47
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 1
PY 2007
VL 13
IS 35-37
BP 318
EP 329
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 151BN
UT WOS:000245263400001
PM 17392682
DA 2022-11-30
ER

PT J
AU Wang, Z
   Keller, LMM
   Dillon, J
   Gaillard, ER
AF Wang, Zhen
   Keller, Lanea M. M.
   Dillon, James
   Gaillard, Elizabeth R.
TI Oxidation of A2E results in the formation of highly reactive aldehydes
   and ketones
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID HUMAN RETINAL LIPOFUSCIN; PIGMENTED EPITHELIAL-CELLS; MACULAR
   DEGENERATION; SINGLET OXYGEN; BETA-CAROTENE; COMPONENT; PRODUCTS; LIGHT;
   PHOTOCHEMISTRY; DAMAGE
AB It has been reported that the photo-oxidation of A2E, a component of human retinal lipofuscin, leads to products that are toxic to cells via dark reactions. Because these compounds have been implicated in the development of various maculopathies such as age-related macular degeneration (AMD), it is important to determine the structures of those deleterious compounds. Both the photo-oxidation and auto-oxidation of A2E lead to the same complex mixture of products, some of which have lower molecular weights than the staring material. Because A2E is homologous to beta-carotene, it was hypothesized that its oxidation would lead to products analogous to those found in oxidized beta-carotene, namely, a series of cleavage products along the acyclic chain with the concomitant formation of aldehydes. This was found to be the case based upon 1) the formation of all of the aldehydes predicted from the oxidation of P-carotene, 2) the loss of 28 amu (carbonyl moiety) from the molecular ion, 3) the facile reaction of the aldehydes with nitrophenylhydrazines to form nitrophenylhydrazones and 4) the subsequent MS/MS cleavage of those derivatives at the N-N bond. If formed in vivo, these aldehydes would have toxic effects on any cell. Finally, the similarity in product mixtures from both the photo-oxidation and auto-oxidation strongly suggests that the intermolecular photo-oxidation of A2E results primarily from a radical process without the involvement of singlet oxygen. Any formation of singlet oxygen most likely arises from sensitization by the aldehyde oxidation products, as this process is well known for aldehydes, in general, and retinal, specifically.
C1 No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY 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 41
TC 53
Z9 54
U1 0
U2 3
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 SEP-OCT
PY 2006
VL 82
IS 5
BP 1251
EP 1257
DI 10.1562/2006-04-01-RA-864
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 097DK
UT WOS:000241426600013
PM 16813456
DA 2022-11-30
ER

PT J
AU Pegaz, B
   Debefve, E
   Ballini, JP
   Wagnieres, G
   Spaniol, S
   Albrecht, V
   Scheglmann, DV
   Nifantiev, NE
   van den Bergh, H
   Konan-Kouakou, Y
AF Pegaz, B
   Debefve, E
   Ballini, JP
   Wagnieres, G
   Spaniol, S
   Albrecht, V
   Scheglmann, DV
   Nifantiev, NE
   van den Bergh, H
   Konan-Kouakou, Y
TI Photothrombic activity of m-THPC-loaded liposomal formulations:
   Pre-clinical assessment on chick chorioallantoic membrane model
SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE photodynamic therapy; meso-tetra(hydroxyphenyl)chlorin; liposomes;
   PEGylation; chick chorioallantoic membrane model; extravasation;
   photothrombic activity; age-related macular degeneration
ID PHOTODYNAMIC THERAPY; DELIVERY; PHOTOSENSITIZERS
AB The objective of this study was to evaluate the ability of meso-tetra (hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100J/cm(2)) higher than with Fospeg (50J/cm(2)). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration. (c) 2006 Elsevier B.V. All rights reserved.
C1 Ecole Polytech Fed Lausanne, ENAC, LPAS, Stn 6, CH-1015 Lausanne, Switzerland.
   Biolitec AG, D-07745 Jena, Germany.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique
   Federale de Lausanne; Biolitec AG
RP van den Bergh, H (通讯作者)，Ecole Polytech Fed Lausanne, ENAC, LPAS, Stn 6, CH-1015 Lausanne, Switzerland.
EM hubert.vandenbergh@epfl.ch
RI Nifantiev, Nikolay E/O-6579-2015
OI Nifantiev, Nikolay E/0000-0002-0727-4050; Wagnieres,
   Georges/0000-0002-9082-3099
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NR 15
TC 60
Z9 62
U1 0
U2 8
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0928-0987
EI 1879-0720
J9 EUR J PHARM SCI
JI Eur. J. Pharm. Sci.
PD MAY
PY 2006
VL 28
IS 1-2
BP 134
EP 140
DI 10.1016/j.ejps.2006.01.008
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 034TP
UT WOS:000236953800016
PM 16504490
DA 2022-11-30
ER

PT J
AU Berendschot, TT
   van Norren, D
AF Berendschot, TT
   van Norren, D
TI On the age dependency of the macular pigment optical density
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE macular pigment; fundus reflectance; autofluorescence; heterochromatic
   flicker photometry; aging; scanning laser ophthalmoscope
ID SPECTRAL REFLECTANCE; SPATIAL-DISTRIBUTION; FUNDUS REFLECTANCE; RAMAN
   MEASUREMENT; CONE SENSITIVITY; IN-VIVO; CAROTENOIDS; LUTEIN;
   DEGENERATION; ZEAXANTHIN
AB Macular pigment may protect against age related macular degeneration (AMD), because of its capability to absorb blue light and scavenge free radicals. Since age is the major risk factor in AMD, a fundamental question to be answered is the possible age dependence of the macular pigment optical density (MPOD) in normal healthy subjects. In this study we used five methods to study a possible age effect: heterochromatic flickerphotometry, two setups for fundus reflectance spectroscopy, a Scanning Laser Ophthalmoscope (SLO) for obtaining reflectance, and the same SLO for autofluorescence maps. MPOD was determined from the reflected light by a full spectral analysis. We also used a new, directional analysis of the reflected light to estimate MPOD. The latter avoids the disturbing influence of stray-light. Digital subtraction at two wavelengths of log reflectance and digital subtraction of log autofluorescence obtained with the SLO provided MPOD maps. Together, all methods of measuring and of analysis provided seven MPOD estimates per subject. A total of 53 subjects, aged 19-76 years, completed all five measurements (and thus seven analyses). An additional 81 subjects, aged 18-70 years, were measured with one setup for fundus reflectance spectroscopy (and thus only two analyses). We could not find any association with age with all the objective techniques. Only MPOD values obtained with heterochromatic flickerphotometry showed a small, but significant decrease with age. This decrease was caused by an increase in the parafoveal data, suggesting that the central MPOD is unchanged with age. The bivariate correlation coefficients between all methods were significant (all p < 0.001). (c) 2005 Elsevier Ltd. All rights reserved.
C1 Univ Maastricht, Eye Clin, NL-6202 AZ Maastricht, Netherlands.
   UMC Utrecht, Dept Ophthalmol, NL-3508 GA Utrecht, Netherlands.
C3 Maastricht University; Utrecht University; Utrecht University Medical
   Center
RP Berendschot, TT (通讯作者)，Univ Maastricht, Eye Clin, POB 5800, NL-6202 AZ Maastricht, Netherlands.
EM tber@soog.dzm.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X
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NR 73
TC 81
Z9 84
U1 0
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2005
VL 81
IS 5
BP 602
EP 609
DI 10.1016/j.exer.2005.03.019
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 993MB
UT WOS:000233957100011
PM 16024015
DA 2022-11-30
ER

PT J
AU Hoeller, U
   Fuisting, B
   Schwartz, R
   Roeper, B
   Richard, G
   Alberti, W
AF Hoeller, U
   Fuisting, B
   Schwartz, R
   Roeper, B
   Richard, G
   Alberti, W
TI Results of radiotherapy of subfoveal neovascularization with 16 and 20
   Gy
SO EYE
LA English
DT Article
DE radiotherapy; ARMD; choroidal neovascularization
ID EXTERNAL-BEAM RADIOTHERAPY; VASCULAR ENDOTHELIAL-CELLS; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; RADIATION-THERAPY; BRUCHS
   MEMBRANE; IRRADIATION; TELETHERAPY; GROWTH; RADIOPROTECTION
AB Purpose In a nonrandomized, prospective study the efficacy of radiotherapy with 16 and 20 Gray (Gy) for subfoveal neovascularization in age-related macular degeneration (ARMD) was analysed.
   Material and Methods From 1996 to 1998, 63 eyes were irradiated with 16 Gy and 38 eyes with 20 Gy for exudative ARMD. A total of 12 eyes had classic ARMD, 89 eyes occult ARMD, median baseline visual acuity (VA) was 6/30 (range: 3/60-6/9.5), median age was 78 years. Risk factors (type of ARMD, baseline VA) were evenly distributed in both groups. Median follow-up was 1.3 years (range: 4 months -4.7 years). VA of 71 line or better and unchanged size and activity of the membrane in fluorescein angiography were defined as stable. Actuarial methods were used.
   Results Median loss of VA was -3 lines (range: -14 to +5), neovascularization remained unchanged or decreased in size and activity in 35 eyes. At 18 months, the probability of stabilized VA was 0.4 (95% confidence interval (CI): 0.3-0.5), at 24 months 0.3 (95% CI: 0.2-0.4). Radiation dose, type of ARMD or baseline VA had no significant impact on outcome of VA and membrane size and activity (P>0.05). Side effects were mild and transient increased tearing.
   Conclusion In this study, the results after radiotherapy were comparable to the natural course of the disease. An impact of radiation dose (16 vs 20 Gy) on stabilizing visual acuity and subfoveal neovascularization could not be shown. The results of studies on dose escalation using very small fields and high radiation doses should be awaited.
C1 Univ Hamburg Hosp, Dept Radiotherapy & Radiooncol, D-2000 Hamburg, Germany.
C3 University of Hamburg; University Medical Center Hamburg-Eppendorf
RP Hoeller, U (通讯作者)，Klinikum Neukoelln, Rudower St 48, D-12351 Berlin, Germany.
EM ulrike.hoeller@vivantes.de
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NR 40
TC 2
Z9 3
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 NOV
PY 2005
VL 19
IS 11
BP 1151
EP 1156
DI 10.1038/sj.eye.6701743
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 982EZ
UT WOS:000233142000003
PM 15543182
OA Bronze
DA 2022-11-30
ER

PT J
AU Khan, AH
   Pierce, CO
   De Salvo, G
   Griffiths, H
   Nelson, M
   Cree, AJ
   Menon, G
   Lotery, AJ
AF Khan, Adnan H.
   Pierce, Charles O.
   De Salvo, Gabriella
   Griffiths, Helen
   Nelson, Marie
   Cree, Angela J.
   Menon, Geeta
   Lotery, Andrew J.
TI The effect of systemic levels of TNF-alpha and complement pathway
   activity on outcomes of VEGF inhibition in neovascular AMD
SO EYE
LA English
DT Article
ID C-REACTIVE PROTEIN; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   FACTOR-I; RISK; ASSOCIATION; ACTIVATION; GENE; EXPRESSION; DISEASE
AB Background/Objectives Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD. Methods Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD. Results A statistically significant difference in VAS was observed for serum levels of TNF-alpha only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS. Conclusions Lower serum TNF-alpha levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.
C1 [Khan, Adnan H.; Pierce, Charles O.; Griffiths, Helen; Cree, Angela J.; Lotery, Andrew J.] Univ Southampton, Fac Med, Div Clin Neurosci Clin & Expt Sci, Southampton, Hants, England.
   [Khan, Adnan H.; De Salvo, Gabriella; Nelson, Marie; Lotery, Andrew J.] Univ Hosp Southampton NHS Fdn Trust, Southampton Eye Unit, Southampton, Hants, England.
   [Menon, Geeta] Frimley Hlth NHS Fdn Trust, Dept Ophthalmol, Frimley Pk Hosp, Camberley, England.
C3 University of Southampton; University of Southampton; University
   Hospital Southampton NHS Foundation Trust
RP Lotery, AJ (通讯作者)，Univ Southampton, Fac Med, Div Clin Neurosci Clin & Expt Sci, Southampton, Hants, England.; Lotery, AJ (通讯作者)，Univ Hosp Southampton NHS Fdn Trust, Southampton Eye Unit, Southampton, Hants, England.
EM A.J.Lotery@soton.ac.uk
RI Khan, Adnan/CAH-3285-2022
OI Khan, Adnan/0000-0001-8153-8002; Nelson, Marie/0000-0002-4772-5418;
   Cree, Angela/0000-0002-1987-8900; Lotery, Andrew/0000-0001-5541-4305
FU Novartis UK
FX This study was supported by an educational grant from Novartis UK.
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NR 54
TC 5
Z9 5
U1 0
U2 1
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD NOV
PY 2022
VL 36
IS 11
BP 2192
EP 2199
DI 10.1038/s41433-021-01824-3
EA NOV 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5L2UH
UT WOS:000715690100002
PM 34750590
OA hybrid, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Brambati, M
   Miere, A
   Costanzo, E
   Capuano, V
   Borrelli, E
   Battista, M
   Parravano, M
   Souied, EH
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Brambati, Maria
   Miere, Alexandra
   Costanzo, Eliana
   Capuano, Vittorio
   Borrelli, Enrico
   Battista, Marco
   Parravano, Mariacristina
   Souied, Eric H.
   Bandello, Francesco
   Querques, Giuseppe
TI Characterisation of macular neovascularisation in geographic atrophy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE imaging; macula; neovascularisation; retina
ID QUIESCENT CHOROIDAL NEOVASCULARIZATION; COHERENCE TOMOGRAPHY
   ANGIOGRAPHY; DEGENERATION; DISEASE; EYE; AMD
AB Aim To characterise macular neovascularisation (MNV) developing in eyes affected by geographic atrophy (GA). Methods In this multicentric longitudinal study involving three retina referral centres, patients previously affected by GA who developed an active MNV were included. Patients were investigated using structural optical coherence tomography (OCT), fundus autofluorescence, OCT-angiography and dye angiographies. Patients were treated with ProReNata antivascular endothelial growth factor (VEGF) injections and were revaluated after treatment. Results Among 512 patients previously diagnosed with GA, 40 eyes of 40 patients (mean age 80.8 +/- 7.9 years, mean GA area 8.73 +/- 7.39 mm(2)) presented with treatment-naive exudative MNV (accounting for an estimated prevalence of 7.81%; 5.49 to 10.13, 95% CIs) and thus were included in the analysis. 67.5% of MNVs were classified as type 2 MNV, 25% as type 1, 2.5% as type 3 and 5% as mixed phenotype. In 92.5% of cases, active MNV in GA showed subretinal hyperreflective material with or without evidence of subretinal/intraretinal hyporeflective exudation. During a mean follow-up of 28 +/- 25 months, patients were treated with 6.6 +/- 6.3 anti-VEGF injections, with 2.9 +/- 1.4 injections in the first year of treatment. No patient developed GA enlargement in the area of MNV. Conclusions MNVs in GA showed different features and therapeutic response in comparison to previously reported features of MNV in age-related macular degeneration (AMD) without GA. For these reasons, the combined phenotype (ie, GA with neovascular AMD) should be considered as a distinct entity in the research and clinical setting.
C1 [Sacconi, Riccardo; Brambati, Maria; Borrelli, Enrico; Battista, Marco; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
   [Sacconi, Riccardo; Brambati, Maria; Borrelli, Enrico; Battista, Marco; Bandello, Francesco; Querques, Giuseppe] IRCCS San Raffaele Sci Inst, Div Head & Neck, Ophthalmol Unit, Milan, Italy.
   [Sacconi, Riccardo] Hosp Intercommunal Creteil, Clin Res Ctr, Creteil, France.
   [Miere, Alexandra; Capuano, Vittorio; Souied, Eric H.] Univ Paris Est Creteil, Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Costanzo, Eliana; Parravano, Mariacristina] Fdn GB Bietti IRCCS, Rome, Italy.
C3 Vita-Salute San Raffaele University; Vita-Salute San Raffaele
   University; IRCCS Ospedale San Raffaele; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; IRCCS - Fondazione
   "G.B. Bietti" per lo Studio e la Ricerca in Oftalmologia
RP Querques, G (通讯作者)，Osped San Raffaele, Dept Ophthalmol, I-20132 Milan, Italy.
EM querques.giuseppe@hsr.it
RI Miere, Alexandra/AIC-4074-2022; Battista, Marco/AAO-3106-2021
OI Miere, Alexandra/0000-0003-4123-8210; Battista,
   Marco/0000-0001-5940-6177; bandello, francesco/0000-0003-3238-9682;
   Sacconi, Riccardo/0000-0003-2891-2012; Querques,
   Giuseppe/0000-0002-3292-9581; Borrelli, Enrico/0000-0003-2815-5031
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NR 36
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2022
VL 106
IS 9
BP 1282
EP 1287
DI 10.1136/bjophthalmol-2021-318820
EA APR 2021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4D0ZF
UT WOS:000726948000001
PM 33836986
DA 2022-11-30
ER

PT J
AU Butola, A
   Prasad, DK
   Ahmad, A
   Dubey, V
   Qaiser, D
   Srivastava, A
   Senthilkumaran, P
   Ahluwalia, BS
   Mehta, DS
AF Butola, Ankit
   Prasad, Dilip K.
   Ahmad, Azeem
   Dubey, Vishesh
   Qaiser, Darakhshan
   Srivastava, Anurag
   Senthilkumaran, Paramasivam
   Ahluwalia, Balpreet Singh
   Mehta, Dalip Singh
TI Deep learning architecture "LightOCT" for diagnostic decision support
   using optical coherence tomography images of biological samples
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID DIABETIC MACULAR EDEMA; NONDESTRUCTIVE ANALYSIS; AUTOMOTIVE PAINTS;
   NEURAL-NETWORK; OCT
AB Optical coherence tomography (OCT) is being increasingly adopted as a label-free and non-invasive technique for biomedical applications such as cancer and ocular disease diagnosis. Diagnostic information for these tissues is manifest in textural and geometric features of the OCT images, which are used by human expertise to interpret and triage. However, it suffers delays due to the long process of the conventional diagnostic procedure and shortage of human expertise. Here, a custom deep learning architecture, LightOCT, is proposed for the classification of OCT images into diagnostically relevant classes. LightOCT is a convolutional neural network with only two convolutional layers and a fully connected layer, but it is shown to provide excellent training and test results for diverse OCT image datasets. We show that LightOCT provides 98.9% accuracy in classifying 44 normal and 44 malignant (invasive ductal carcinoma) breast tissue volumetric OCT images. Also, >96% accuracy in classifying public datasets of ocular OCT images as normal, age-related macular degeneration and diabetic macular edema. Additionally, we show similar to 96% test accuracy for classifying retinal images as belonging to choroidal neovascularization, diabetic macular edema, drusen, and normal samples on a large public dataset of more than 100,000 images. The performance of the architecture is compared with transfer learning based deep neural networks. Through this, we show that LightOCT can provide significant diagnostic support for a variety of OCT images with sufficient training and minimal hyper-parameter tuning. The trained LightOCT networks for the three-classification problem will be released online to support transfer learning on other datasets. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Butola, Ankit; Dubey, Vishesh; Mehta, Dalip Singh] Indian Inst Technol Delhi, Dept Phys, Biophoton Lab, New Delhi 110016, India.
   [Prasad, Dilip K.] Nanyang Technol Univ, Sch Comp Sci & Amp, Singapore 639798, Singapore.
   [Prasad, Dilip K.] Nanyang Technol Univ, Engn, Singapore 639798, Singapore.
   [Ahmad, Azeem; Ahluwalia, Balpreet Singh] UiT Arctic Univ Norway, Dept Phys & Technol, Tromso, Norway.
   [Qaiser, Darakhshan; Srivastava, Anurag] All India Inst Med Sci, Dept Surg Disciplines, New Delhi 110029, India.
   [Senthilkumaran, Paramasivam] Indian Inst Technol Delhi, Dept Phys, New Delhi 110016, India.
C3 Indian Institute of Technology System (IIT System); Indian Institute of
   Technology (IIT) - Delhi; Nanyang Technological University & National
   Institute of Education (NIE) Singapore; Nanyang Technological
   University; Nanyang Technological University & National Institute of
   Education (NIE) Singapore; Nanyang Technological University; UiT The
   Arctic University of Tromso; All India Institute of Medical Sciences
   (AIIMS) New Delhi; Indian Institute of Technology System (IIT System);
   Indian Institute of Technology (IIT) - Delhi
RP Ahluwalia, BS (通讯作者)，UiT Arctic Univ Norway, Dept Phys & Technol, Tromso, Norway.
EM balpreet.singh.ahluwalia@uit.no
RI Prasad, Dilip K./B-5838-2009; Ahluwalia, Balpreet S/C-3316-2016
OI Prasad, Dilip K./0000-0002-3693-6973; Butola, Ankit/0000-0001-7847-7173;
   Senthilkumaran, Paramasivam/0000-0002-1015-0710; Ahluwalia, Balpreet
   Singh/0000-0001-7841-6952; Dubey, Vishesh Kumar/0000-0002-2753-0445
FU  [INCP-2014/10024]
FX DIKU (INCP-2014/10024).
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   Venhuizen FG, 2018, BIOMED OPT EXPRESS, V9, P1545, DOI 10.1364/BOE.9.001545
   Vuong B, 2015, BIOMED OPT EXPRESS, V6, P1487, DOI 10.1364/BOE.6.001487
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NR 30
TC 9
Z9 9
U1 1
U2 8
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 SEP 1
PY 2020
VL 11
IS 9
BP 5017
EP 5031
DI 10.1364/BOE.395487
PG 15
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 NZ9YV
UT WOS:000577455500013
PM 33014597
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Lee, MW
   Kim, KM
   Lim, HB
   Jo, YJ
   Kim, JY
AF Lee, Min-Woo
   Kim, Kyeung-Min
   Lim, Hyung-Bin
   Jo, Young-Joon
   Kim, Jung-Yeul
TI Repeatability of vessel density measurements using optical coherence
   tomography angiography in retinal diseases
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INNER PLEXIFORM LAYER; NERVE-FIBER LAYER; FLUORESCEIN ANGIOGRAPHY;
   MICROVASCULAR DENSITY; REPRODUCIBILITY; THICKNESS; GLAUCOMA; IMAGES;
   MACULA
AB Aim To analyse the repeatability of vessel density (VD) measurements using optical coherence tomography angiography (OCTA) in patients with retinal diseases.
   Methods Two consecutive VD measurements using OCTA were analysed prospectively in patients with retinal diseases (diabetic macular oedema (DME), retinal vein occlusion (RVO) with macular oedema, epiretinal membrane (ERM), wet age-related macular degeneration (AMD)). The intraclass correlation coefficient (ICC), coefficient of variation (CV) and test-retest SD of VD measurements were assessed, and linear regression analyses were conducted to identify factors related to repeatability.
   Results A total of 134 eyes were analysed involving 20 eyes with DME, 44 eyes with RVO with macular oedema, 50 eyes with ERM and 20 eyes with wet AMD. The mean age was 64.9 years, and the mean best-corrected visual acuity (BCVA) was 0.24. The mean central macular thickness (CMT) was 391.6 mu m, and the mean ganglion cell-inner plexiform layer (GC-IPL) thickness was 61.4 mu m. In all four diseases, the ICC and CV of the full VD were 0.812 and 6.72%, respectively. Univariate analyses showed that the BCVA (B, 8.553; p= 0.031), signal strength (B, -1.688; p= 0.050), CMT (B, 0.019; p= 0.015) and mean GC-IPL thickness (B, -0.103; p= 0.001) were significant factors that affected the repeatability. Multivariate analyses of these factors showed a significant result for the GC-IPL thickness.
   Conclusions Measurements of the VD using OCTA showed relatively good repeatability for various retinal diseases. The BCVA, signal strength, CMT and GC-IPL thickness affected the repeatability, so these factors should be considered when analysing the VD.
C1 [Lee, Min-Woo; Kim, Kyeung-Min; Jo, Young-Joon; Kim, Jung-Yeul] Chungnam Natl Univ, Dept Ophthalmol, Coll Med, Daejeon, South Korea.
   [Lim, Hyung-Bin] Armed Forces Capital Hosp, Dept Ophthalmol, Seongnam, South Korea.
C3 Chungnam National University
RP Kim, JY (通讯作者)，Chungnam Natl Univ Hosp, Dept Ophthalmol, Daejeon 301721, South Korea.
EM kimjy@cnu.ac.kr
OI Kim, Jung yeul/0000-0003-3679-1310
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NR 23
TC 30
Z9 31
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 MAY
PY 2019
VL 103
IS 5
BP 704
EP 710
DI 10.1136/bjophthalmol-2018-312516
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ID7PB
UT WOS:000471873700022
PM 29973363
OA hybrid
DA 2022-11-30
ER

PT J
AU Jin, ZB
   Gao, ML
   Deng, WL
   Wu, KC
   Sugita, S
   Mandai, M
   Takahashi, M
AF Jin, Zi-Bing
   Gao, Mei-Ling
   Deng, Wen-Li
   Wu, Kun-Chao
   Sugita, Sunao
   Mandai, Michiko
   Takahashi, Masayo
TI Stemming retinal regeneration with pluripotent stem cells
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Retinal degeneration; Pluripotent stem cells; Retinal pigment
   epithelium; Stem cell-derived retinal cell; Retinal tissue;
   Transplantation
ID PIGMENT EPITHELIAL-CELLS; CILIARY NEUROTROPHIC FACTOR; IN-VITRO
   DIFFERENTIATION; ADULT HUMAN FIBROBLASTS; VESICLE-LIKE STRUCTURES;
   OPTIC-NERVE DISEASES; HUMAN IPS CELLS; MACULAR-DEGENERATION;
   GANGLION-CELLS; OPHTHALMOLOGY TREATMENT
AB Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases, such as age related macular degeneration (AMD), Stargardt's disease, retinitis pigmentosa (RP) and glaucoma. These diseases are all characterized by the degeneration of one or two retinal cell types that cannot regenerate spontaneously in humans. Aberrant retinal pigment epithelial (RPE) cells can be observed through optical coherence tomography (OCT) in AMD patients. In RP patients, the morphological and functional abnormalities of RPE and photoreceptor layers are caused by a genetic abnormality. Stargardt's disease or juvenile macular degeneration, which is characterized by the loss of the RPE and photoreceptors in the macular area, causes central vision loss at an early age. Loss of retinal ganglion cells (RGCs) can be observed in patients with glaucoma. Once the retinal cell degeneration is triggered, no treatments can reverse it. Transplantation-based approaches have been proposed as a universal therapy to target patients with various concomitant diseases. Both the replacement of dead cells and neuroprotection are strategies used to rescue visual function in animal models of retinal degeneration. Diverse retinal cell types derived from pluripotent stem cells, including RPE cells, photoreceptors, RGCs and even retinal organoids with a layered structure, provide unlimited cell sources for transplantation. In addition, mesenchymal stem cells (MSCs) are multifunctional and protect degenerating retinal cells. The aim of this review is to summarize current findings from preclinical and clinical studies. We begin with a brief introduction to retinal degenerative diseases and cell death in diverse diseases, followed by methods for retinal cell generation. Preclinical and clinical studies are discussed, and future concerns about efficacy, safety and immunorejection are also addressed.
C1 [Jin, Zi-Bing; Gao, Mei-Ling; Deng, Wen-Li; Wu, Kun-Chao] Wenzhou Med Univ, Natl Ctr Int Res Regenerat Med & Neurogenet, State Key Lab Ophthalmol Optometry & Visual Sci, Inst Stem Cell Res,Div Ophthalm Genet,Eye Hosp,La, Wenzhou 325027, Peoples R China.
   [Sugita, Sunao; Mandai, Michiko; Takahashi, Masayo] RIKEN Ctr Dev Biol, Lab Retinal Regenerat, Kobe, Hyogo 6500047, Japan.
C3 Wenzhou Medical University; RIKEN
RP Jin, ZB (通讯作者)，Wenzhou Med Univ, Natl Ctr Int Res Regenerat Med & Neurogenet, State Key Lab Ophthalmol Optometry & Visual Sci, Inst Stem Cell Res,Div Ophthalm Genet,Eye Hosp,La, Wenzhou 325027, Peoples R China.
EM jinzb@mail.eye.ac.cn
RI Gao, Mei-Ling/GNH-5156-2022; Jin, Zi-Bing/AAE-4106-2019
OI Jin, Zi-Bing/0000-0003-0515-698X
FU National Key R&D Program of China [2017YFA0105300, 2017YFB0403700];
   National Natural Science Foundation of China [81522014, 81700848];
   Zhejiang Provincial Natural Science Foundation of China [LD18H120001LD,
   LQ17H120005]; Zhejiang Provincial Key RD Program [2015C03029]; Wenzhou
   Science and Technology Innovation Team Project [C20150004]; Ministry of
   Education 111 project [D16011]
FX We thank Zhen-Ji Chen for the graphing, and Xue-Bi Cai and Dan Jiang for
   English editing. This work was supported by the National Key R&D Program
   of China (2017YFA0105300 and 2017YFB0403700), National Natural Science
   Foundation of China (81522014 and 81700848), Zhejiang Provincial Natural
   Science Foundation of China (LD18H120001LD and LQ17H120005), Zhejiang
   Provincial Key R&D Program (2015C03029), Wenzhou Science and Technology
   Innovation Team Project (C20150004), Ministry of Education 111 project
   (D16011).
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NR 232
TC 82
Z9 82
U1 5
U2 44
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 38
EP 56
DI 10.1016/j.preteyeres.2018.11.003
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HW1OL
UT WOS:000466452100002
PM 30419340
OA hybrid
DA 2022-11-30
ER

PT J
AU Smith, JR
   David, LL
   Appukuttan, B
   Wilmarth, PA
AF Smith, Justine R.
   David, Larry L.
   Appukuttan, Binoy
   Wilmarth, Phillip A.
TI Angiogenic and Immunologic Proteins Identified by Deep Proteomic
   Profiling of Human Retinal and Choroidal Vascular Endothelial Cells:
   Potential Targets for New Biologic Drugs
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIFFERENTIAL EXPRESSION ANALYSIS; FALSE DISCOVERY RATES; GROWTH-FACTOR;
   MASS-SPECTROMETRY; UNITED-STATES; IN-VIVO; MACULAR DEGENERATION;
   REFRACTORY UVEITIS; INFLIXIMAB THERAPY; VISUAL IMPAIRMENT
AB PURPOSE: Diseases that involve retinal or choroidal vascular endothelial cells are leading causes of vision loss: age-related macular degeneration, retinal ischemic vasculopathies, and noninfectious posterior uveitis. Proteins differentially expressed by these endothelial cell populations are potential drug targets. We used deep proteomic profiling to define the molecular phenotype of human retinal and choroidal endothelial cells at the protein level.
   METHODS: Retinal and choroidal vascular endothelial cells were separately isolated from 5 human eye pairs by selection on CD31. Total protein was extracted and digested, and peptide fractions were analyzed by reverse-phase liquid chromatography tandem mass spectrometry. Peptide sequences were assigned to fragment ion spectra, and proteins were inferred from openly accessible protein databases. Protein abundance was determined by spectral counting. Publicly available software packages were used to identify proteins that were differentially expressed between human retinal and choroidal endothelial cells, and to classify proteins that were highly abundant in each endothelial cell population.
   RESULTS: Human retinal and/or choroidal vascular endothelial cells expressed 5042 nonredundant proteins. Setting the differential expression false discovery rate at 0.05, 498 proteins of 3454 quantifiable proteins (14.4%) with minimum mean spectral counts of 2.5 were differentially abundant in the 2 cell populations. Retinal and choroidal endothelial cells were enriched in angiogenic proteins, and retinal endothelial cells were also enriched in immunologic proteins.
   CONCLUSIONS: This work describes the different protein expression profiles of human retinal and choroidal vascular endothelial cells, and provides multiple candidates for further study as novel treatments or drug targets for posterior eye diseases. NOTE: Publication of this article is sponsored by the American Ophthalmological Society. ((C) 2018 Elsevier Inc. All rights reserved.)
C1 [Smith, Justine R.; David, Larry L.; Appukuttan, Binoy; Wilmarth, Phillip A.] Flinders Univ S Australia, Adelaide, SA, Australia.
   [Smith, Justine R.; David, Larry L.; Appukuttan, Binoy; Wilmarth, Phillip A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
   [Smith, Justine R.; Appukuttan, Binoy] Flinders Univ S Australia, Bedford Pk, SA, Australia.
C3 Flinders University South Australia; Oregon Health & Science University;
   Flinders University South Australia
RP Smith, JR (通讯作者)，Flinders Univ S Australia, Eye & Vis Hlth, Coll Med & Publ Hlth, Flinders Med Ctr, Room 4E-431,Flinders Dr, Bedford Pk, SA 5042, Australia.
EM justine.smith@flinders.edu.au
RI Smith, Justine/Y-9044-2019
OI Smith, Justine/0000-0002-4756-5493
FU National Institutes of Health, Bethesda, Maryland [R01 EY019875, P30
   EY010572]; Australian Research Council, Canberra, Australia
   [FT130101648]; NATIONAL EYE INSTITUTE [P30EY010572, R01EY019875] Funding
   Source: NIH RePORTER
FX THIS WORK WAS SUPPORTED BY GRANT R01 EY019875 (DR SMITH) AND GRANT P30
   EY010572 (DR DAVID) from the National Institutes of Health, Bethesda,
   Maryland; and grant FT130101648 (Dr Smith) from the Australian Research
   Council, Canberra, Australia.
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NR 139
TC 14
Z9 15
U1 0
U2 3
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 SEP
PY 2018
VL 193
BP 197
EP 229
DI 10.1016/j.ajo.2018.03.020
PG 33
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GS9SU
UT WOS:000444068100024
PM 29559410
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Dobo, J
   Kocsis, A
   Gal, P
AF Dobo, Jozsef
   Kocsis, Andrea
   Gal, Peter
TI Be on Target: Strategies of Targeting Alternative and Lectin Pathway
   Components in Complement-Mediated Diseases
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE complement system; lectin pathway; alternative pathway; complement
   inhibitors; complement-related diseases
ID MANNAN-BINDING LECTIN; HEMOLYTIC-UREMIC SYNDROME; PATTERN-RECOGNITION
   MOLECULES; SERINE-PROTEASE (MASP)-1; PAROXYSMAL-NOCTURNAL
   HEMOGLOBINURIA; ISCHEMIA-REPERFUSION INJURY; RARE GENETIC-VARIANTS;
   C-REACTIVE PROTEIN; FACTOR-H; MACULAR DEGENERATION
AB The complement system has moved into the focus of drug development efforts in the last decade, since its inappropriate or uncontrolled activation has been recognized in many diseases. Some of them are primarily complement-mediated rare diseases, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, and atypical hemolytic uremic syndrome. Complement also plays a role in various multifactorial diseases that affect millions of people worldwide, such as ischemia reperfusion injury (myocardial infarction, stroke), age-related macular degeneration, and several neurodegenerative disorders. In this review, we summarize the potential advantages of targeting various complement proteins with special emphasis on the components of the lectin (LP) and the alternative pathways (AP). The serine proteases (MASP-1/2/3, factor D, factor B), which are responsible for the activation of the cascade, are straightforward targets of inhibition, but the pattern recognition molecules (mannose-binding lectin, other collectins, and ficolins), the regulatory components (factor H, factor I, properdin), and C3 are also subjects of drug development. Recent discoveries about cross-talks between the LP and AP offer new approaches for clinical intervention. Mannan-binding lectin-associated serine proteases (MASPs) are not just responsible for LP activation, but they are also indispensable for efficient AP activation. Activated MASP-3 has recently been shown to be the enzyme that continuously supplies factor D (FD) for the AP by cleaving pro-factor D (pro-FD). In this aspect, MASP-3 emerges as a novel feasible target for the regulation of AP activity. MASP-1 was shown to be required for AP activity on various surfaces, first of all on LPS of Gram-negative bacteria.
C1 [Dobo, Jozsef; Kocsis, Andrea; Gal, Peter] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Budapest, Hungary.
C3 Hungarian Academy of Sciences; Hungarian Research Centre for Natural
   Sciences
RP Gal, P (通讯作者)，Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Budapest, Hungary.
EM gal.peter@ttk.mta.hu
RI Gal, Peter/B-5886-2011
OI Dobo, Jozsef/0000-0001-9187-8502
FU National Research, Development and Innovation Office (NKTH) OTKA grants
   [K108642, K119374]; MedInProt program of the Hungarian Academy of
   Sciences
FX The study was supported by the National Research, Development and
   Innovation Office (NKTH) OTKA grants K108642 and K119374, and by the
   MedInProt program of the Hungarian Academy of Sciences.
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NR 205
TC 43
Z9 49
U1 1
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 AUG 8
PY 2018
VL 9
AR 1851
DI 10.3389/fimmu.2018.01851
PG 22
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA GP7FZ
UT WOS:000441061000002
PM 30135690
OA Green Published, Green Accepted, gold
DA 2022-11-30
ER

PT J
AU Gharbiya, M
   Giustolisi, R
   Marchiori, J
   Bruscolini, A
   Mallone, F
   Fameli, V
   Nebbioso, M
   Abdolrahimzadeh, S
AF Gharbiya, Magda
   Giustolisi, Rosalia
   Marchiori, Jessica
   Bruscolini, Alice
   Mallone, Fabiana
   Fameli, Valeria
   Nebbioso, Marcella
   Abdolrahimzadeh, Solmaz
TI Comparison of Short-Term Choroidal Thickness and Retinal Morphological
   Changes after Intravitreal Anti-VEGF Therapy with Ranibizumab or
   Aflibercept in Treatment-Naive Eyes
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; choroidal thickness; optical coherence
   tomography; dry macula; anti-VEGF; ranibizumab; aflibercept
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; AGE; SUBFOVEAL;
   INJECTIONS; EFFICACY; TRAP
AB Purpose: To evaluate choroidal thickness (CT) and retinal morphological changes in eyes with neovascular age-related macular degeneration (nAMD) following ranibizumab or aflibercept intravitreal treatment.
   Materials and methods: This was a prospective, observational, comparative study where 76 eyes of 76 consecutive patients with treatment-naive nAMD were consecutively enrolled and randomized to ranibizumab 0.5 mg or aflibercept 2mg injections. Spectral-domain optical coherence tomography images of the choroid were obtained by enhanced depth imaging modality. CT measurements were made of the subfoveal choroid, and at 500 m from the center of the fovea in the superior, inferior, temporal, and nasal quadrants. Central subfield retinal thickness, intraretinal fluid, subretinal fluid, and pigment epithelium detachment were evaluated. Patients were followed up for 3months.
   Results: Compared with baseline, CT decreased over time in both the ranibizumab and aflibercept group (P = 0.04 and 0.001, respectively). At each location, the decrease in CT was significantly more prominent in aflibercept with respect to ranibizumab-treated eyes (P < 0.05). Among the different choroidal neovascularization subtypes, type 3 lesions showed the greatest CT decrease after anti-vascular endothelial growth factor injections (P = 0.003). Choroidal thinning was significantly greater in type 3 lesions treated with aflibercept compared with ranibizumab (F = 13.6, P = 0.002). Post-treatment incidence of dry macula was higher in aflibercept- versus ranibizumab-treated eyes (50% vs. 76%, P = 0.03).
   Conclusions: CT reduction is greater in aflibercept-treated eyes, and type 3 lesions show the greatest thickness decrease. The post-treatment frequency of dry macula, evaluated by qualitative parameters, is higher in aflibercept-treated eyes, but is not correlated with CT change.
C1 [Gharbiya, Magda; Giustolisi, Rosalia; Marchiori, Jessica; Bruscolini, Alice; Mallone, Fabiana; Fameli, Valeria; Nebbioso, Marcella; Abdolrahimzadeh, Solmaz] Univ Rome Sapienza, Umberto Univ Hosp 1, Ophthalmol Unit, Rome, Italy.
C3 Sapienza University Rome; University Hospital Sapienza Rome
RP Abdolrahimzadeh, S (通讯作者)，Univ Rome Sapienza, Umberto Univ Hosp 1, Viale Policlin 155, I-00161 Rome, Italy.
EM solmazzadeh@gmail.com
RI Bruscolini, Alice/ABA-4275-2020; Nebbioso, Marcella/K-6878-2018;
   Gharbiya, Magda/AAS-1182-2021
OI Bruscolini, Alice/0000-0002-1627-5493; Nebbioso,
   Marcella/0000-0002-5512-0849; Gharbiya, Magda/0000-0002-4991-9689
CR Abdolrahimzadeh S, 2016, RETINA-J RET VIT DIS, V36, P2329, DOI 10.1097/IAE.0000000000001097
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NR 27
TC 19
Z9 19
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2018
VL 43
IS 3
BP 391
EP 396
DI 10.1080/02713683.2017.1405045
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FV2SX
UT WOS:000424419400017
PM 29166140
DA 2022-11-30
ER

PT J
AU Balmer, D
   Bapst-Wicht, L
   Pyakurel, A
   Emery, M
   Nanchen, N
   Bochet, CG
   Roduit, R
AF Balmer, Delphine
   Bapst-Wicht, Linda
   Pyakurel, Aswin
   Emery, Martine
   Nanchen, Natacha
   Bochet, Christian G.
   Roduit, Raphael
TI Bis-Retinoid A2E Induces an Increase of Basic Fibroblast Growth Factor
   via Inhibition of Extracellular Signal-Regulated Kinases 1/2 Pathway in
   Retinal Pigment Epithelium Cells and Facilitates Phagocytosis.2
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE retinal metabolism; A2E; age-related macular degeneration (ARMD);
   ARPE19; retinal pigment epithelium cells (RPE); fibroblast growth factor
   (FGF); mitogen-activated protein kinase (MAPK); extracellular
   signal-regulated kinase (ERK)
ID MACULAR DEGENERATION; ARPE-19 CELLS; OXIDATIVE STRESS; LIPOFUSCIN
   FLUOROPHORE; GENE-EXPRESSION; PROTEIN-KINASE; VISUAL CYCLE; BLUE-LIGHT;
   RPE CELLS; DAMAGE
AB Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known: indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium -specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD.
C1 [Balmer, Delphine; Bapst-Wicht, Linda; Pyakurel, Aswin; Emery, Martine; Nanchen, Natacha; Roduit, Raphael] Inst Res Ophthalmol, Sion, Switzerland.
   [Pyakurel, Aswin; Roduit, Raphael] Univ Lausanne, Jules Gonin Eye Hosp, Fdn Asile Des Aveugles, Dept Ophthalmol, Lausanne, Switzerland.
   [Bochet, Christian G.] Univ Fribourg, Dept Chem, Fribourg, Switzerland.
C3 University of Lausanne; University of Fribourg
RP Roduit, R (通讯作者)，Inst Res Ophthalmol, Sion, Switzerland.
EM raphael.roduit@fa2.ch
RI Roduit, Raphael/AAC-3890-2021
OI Roduit, Raphael/0000-0001-7440-2799; Bochet,
   Christian/0000-0003-4267-0523; , Aswin/0000-0001-8382-5355
FU Gelbert Foundation; Fritz-Tobler Foundation; foundation "Art Vie"
FX RR and AP were supported by the Gelbert Foundation; RR and LB were
   supported by the Fritz-Tobler Foundation. AP was supported by the
   foundation "Art & Vie".
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NR 57
TC 2
Z9 2
U1 0
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
   SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD MAR 1
PY 2017
VL 9
AR 43
DI 10.3389/fnagi.2017.00043
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA EL9MT
UT WOS:000394945100002
PM 28298893
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Pan, JR
   Wang, C
   Yu, QL
   Zhang, S
   Li, B
   Hu, J
AF Pan, Jun-ru
   Wang, Chen
   Yu, Qi-lin
   Zhang, Shu
   Li, Bin
   Hu, Jun
TI Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions
   in ApoE-deficient mice
SO JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL
   SCIENCES
LA English
DT Article
DE methyl-CpG binding domain protein 2; aged-related macular degeneration;
   endothelial dysfunction; intercellular adhesion molecule 1
ID CHOROIDAL BLOOD-FLOW; MACULAR DEGENERATION; APOLIPOPROTEIN-E; BRUCHS
   MEMBRANE; ENDOTHELIAL-CELLS; DNA METHYLATION; EXPRESSION; ICAM-1;
   CHORIOCAPILLARIS; PATHOGENESIS
AB The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse model of age-related macular degeneration (AMD) was investigated. Eight-week-old Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes, experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group) were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group (P > 0.05). Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group (P < 0.05). Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.
C1 [Pan, Jun-ru; Wang, Chen; Li, Bin; Hu, Jun] Huazhong Univ Sci & Technol, Dept Ophthalmol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China.
   [Pan, Jun-ru; Wang, Chen; Yu, Qi-lin; Zhang, Shu; Hu, Jun] Huazhong Univ Sci & Technol, Ctr Biomed Res, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China.
C3 Huazhong University of Science & Technology; Huazhong University of
   Science & Technology
RP Hu, J (通讯作者)，Huazhong Univ Sci & Technol, Dept Ophthalmol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China.
EM panjunru919@gmail.com; hu-jun525@hotmail.com
FU Natural Science Foundation of Hubei Province [2012FFB02304]; Scientific
   Research Foundation of Ministry of Education, China [2013-1792]
FX This study was supported by grants from Natural Science Foundation of
   Hubei Province (No: 2012FFB02304) and Scientific Research Foundation of
   Ministry of Education (No: 2013-1792), China.
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NR 50
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Z9 4
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1672-0733
EI 1993-1352
J9 J HUAZHONG U SCI-MED
JI J. Huazhong Univ. Sci. Tech.-Med.
PD JUN
PY 2014
VL 34
IS 3
BP 408
EP 414
DI 10.1007/s11596-014-1292-2
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AK1WR
UT WOS:000338209800019
PM 24939308
DA 2022-11-30
ER

PT J
AU Sonoda, S
   Sakamoto, T
   Yamashita, T
   Shirasawa, M
   Uchino, E
   Terasaki, H
   Tomita, M
AF Sonoda, Shozo
   Sakamoto, Taiji
   Yamashita, Takehiro
   Shirasawa, Makoto
   Uchino, Eisuke
   Terasaki, Hiroto
   Tomita, Masatoshi
TI Choroidal Structure in Normal Eyes and After Photodynamic Therapy
   Determined by Binarization of Optical Coherence Tomographic Images
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroid; age-related macular degeneration; vessel; EDI-OCT
ID CENTRAL SEROUS CHORIORETINOPATHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; THICKNESS; CHORIOCAPILLARIS; NEOVASCULARIZATION;
   VERTEPORFIN; VASCULATURE; MONKEY; RPE
AB PURPOSE. To determine changes in choroidal structure by binarization of optical coherence tomographic (OCT) images.
   METHODS. Choroidal images were recorded by enhanced depth imaging OCT. The subfoveal choroidal images were analyzed, and the luminal and interstitial areas were converted to binary images by the Niblack method. The interrater, intrarater, and intersession agreements of the binary images were determined for healthy eyes. In eyes with age-related macular degeneration (AMD), the binary images of the choroid before photodynamic therapy (PDT) were compared to those after PDT. The untreated fellow eyes were studied as controls.
   RESULTS. In healthy eyes, the average ratio of the luminal to choroidal area was 65.4%. The interrater agreement rate was high, with intraclass correlation coefficient (ICC) 0.985 and 0.988 for the choroid and luminal areas, respectively. The intrarater ICC was 0.996 for the choroid and 0.997 for the luminal areas. The intersession ICC was 0.993 for the choroid and 0.984 for the luminal areas. In eyes with AMD, the subfoveal choroidal area, the luminal area, and the interstitial areas were thinner 6 months after PDT (all P < 0.01, Wilcoxon signed-rank sum test). The ratio of the luminal to choroidal area was significantly decreased to 62.8% (P < 0.01, Wilcoxon signed-rank sum test). The ratio for the fellow eyes was not significantly changed.
   CONCLUSIONS. The Niblack binarization method can be used to analyze the luminal area of choroid in an OCT image with good repeatability and reproducibility. The change in the subfoveal choroidal area after PDT is due mainly to a decrease in the luminal areas.
C1 [Sonoda, Shozo; Sakamoto, Taiji; Yamashita, Takehiro; Shirasawa, Makoto; Uchino, Eisuke; Terasaki, Hiroto; Tomita, Masatoshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Kagoshima 8908520, Japan.
C3 Kagoshima University
RP Sakamoto, T (通讯作者)，Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan.
EM tsakamot@m3.kufm.kagoshima-u.ac.jp
FU Research Committee on Chorioretinal Degeneration and Optic Atrophy,
   Ministry of Health, Labor, and Welfare, Tokyo, Japan; Ministry of
   Education, Science, and Culture of the Japanese Government
FX Supported by a grant from the Research Committee on Chorioretinal
   Degeneration and Optic Atrophy, Ministry of Health, Labor, and Welfare,
   Tokyo, Japan, and by a Grant-in-Aid for Scientific Research from the
   Ministry of Education, Science, and Culture of the Japanese Government.
   The authors alone are responsible for the content and writing of the
   paper.
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NR 34
TC 196
Z9 200
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2014
VL 55
IS 6
BP 3893
EP 3898
DI 10.1167/iovs.14-14447
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AL9TX
UT WOS:000339485800064
PM 24894395
DA 2022-11-30
ER

PT J
AU Chen, C
   Cano, M
   Wang, JJ
   Li, JM
   Huang, CX
   Yu, Q
   Herbert, TP
   Handa, JT
   Zhang, SX
AF Chen, Chen
   Cano, Marisol
   Wang, Joshua J.
   Li, Jingming
   Huang, Chuangxin
   Yu, Qiang
   Herbert, Terence P.
   Handa, James T.
   Zhang, Sarah X.
TI Role of Unfolded Protein Response Dysregulation in Oxidative Injury of
   Retinal Pigment Epithelial Cells
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; AGE-RELATED MACULOPATHY; ER STRESS;
   CHEMICAL CHAPERONES; MEDIATED APOPTOSIS; SMOKING; ACTIVATION; GENES;
   XBP1; DEGENERATION
AB Aims: Age-related macular degeneration (AMD), a major cause of legal blindness in the elderly, is associated with genetic and environmental risk factors, such as cigarette smoking. Recent evidence shows that cigarette smoke (CS) that contains high levels of potent oxidants preferably targets retinal pigment epithelium (RPE) leading to oxidative damage and apoptosis; however, the mechanisms are poorly understood. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in CS-related RPE apoptosis. Results: ER stress and proapoptotic gene C/EBP homologous protein (CHOP) were induced in the RPE/choroid complex from mice exposed to CS for 2 weeks and in human RPE cells treated with hydroquinone, a potent oxidant found at high concentrations in CS. Suppressing ER stress or inhibiting CHOP activation by pharmacological chaperones or genetic approaches attenuated hydroquinone-induced RPE cell apoptosis. In contrast to enhanced CHOP activation, protein level of active X-box binding protein 1 (XBP1), a major regulator of the adaptive UPR, was reduced in hydroquinone-treated cells. Conditional knockout of XBP1 gene in the RPE resulted in caspase-12 activation, increased CHOP expression, and decreased antiapoptotic gene Bcl-2. Furthermore, XBP1-deficient RPE cells are more sensitive to oxidative damage induced by hydroquinone or NaIO3, a CS-unrelated chemical oxidant. Conversely, overexpressing XBP1 protected RPE cells and attenuated oxidative stress-induced RPE apoptosis. Innovation and Conclusion: These findings provide strong evidence suggesting an important role of ER stress and the UPR in CS-related oxidative injury of RPE cells. Thus, the modulation of the UPR signaling may provide a promising target for the treatment of AMD.
C1 [Chen, Chen; Wang, Joshua J.; Huang, Chuangxin; Zhang, Sarah X.] SUNY Buffalo, Ross Eye Inst, Dept Ophthalmol, Buffalo, NY 14214 USA.
   [Chen, Chen; Wang, Joshua J.; Li, Jingming; Zhang, Sarah X.] Univ Oklahoma, Hlth Sci Ctr, Dept Med & Endocrinol, Oklahoma City, OK USA.
   [Cano, Marisol; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
   [Wang, Joshua J.; Zhang, Sarah X.] SUNY Buffalo, SUNY Eye Inst, Buffalo, NY 14214 USA.
   [Huang, Chuangxin; Yu, Qiang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
   [Herbert, Terence P.] Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
   [Zhang, Sarah X.] SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo; University of Oklahoma System; University of Oklahoma
   Health Sciences Center; Johns Hopkins University; Johns Hopkins
   Medicine; State University of New York (SUNY) System; State University
   of New York (SUNY) Buffalo; Sun Yat Sen University; University of
   Leicester; State University of New York (SUNY) System; State University
   of New York (SUNY) Buffalo
RP Zhang, SX (通讯作者)，SUNY Buffalo, SUNY Eye Inst, Ira G Ross Eye Inst, Dept Ophthalmol, Farber Hall 308, Buffalo, NY 14214 USA.
EM xzhang38@buffalo.edu
OI Chen, Chen/0000-0001-6741-7036; Herbert, Terence/0000-0001-5402-0814
FU National Institutes of Health [EY019949]; American Health Assistance
   Foundation [M2010088]; American Diabetes Association [7-11-BS-182];
   Oklahoma Center for the Advancement of Science and Technology
   [HR10-060]; Harold Hamm Diabetes Center; Research to Prevent Blindness
   [EY14005, EY019004]; Thome Foundation Grant; RPB Senior Scientist Award;
   Robert Bond Welch Professorship; NATIONAL EYE INSTITUTE [R01EY019949,
   R01EY019904, R01EY014005] Funding Source: NIH RePORTER
FX We thank Drs. Laurie Glimcher and Ann-Hwee Lee (Harvard University,
   Boston, MA) for XBP1flox/flox mice; Dr. Luke Szweda (Oklahoma Medical
   Research Foundation) for anticytochrome c antibody; Dr. Jian-xing Ma for
   anti-RPE65 antibody; Louisa J. Williams and Linda S. Boone (Dean A.
   McGee Eye Institute, Oklahoma City, OK) for their help in histology; and
   Diabetes COBRE Histology Core (OUHSC, Oklahoma City, OK) for image
   acquisition. This work was supported by the National Institutes of
   Health grants EY019949, Research Grant M2010088 from the American Health
   Assistance Foundation, Research Award 7-11-BS-182 from the American
   Diabetes Association, Research Grant HR10-060 from the Oklahoma Center
   for the Advancement of Science and Technology, Dr. William Talley
   Research Award from Harold Hamm Diabetes Center, and Unrestricted Grants
   from Research to Prevent Blindness to the Department of Ophthalmology of
   University at Buffalo (S.X.Z); EY14005, EY019004, Thome Foundation
   Grant, RPB Senior Scientist Award, and the Robert Bond Welch
   Professorship (J.T.H.).
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NR 59
TC 47
Z9 48
U1 0
U2 16
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 MAY 10
PY 2014
VL 20
IS 14
BP 2091
EP U19
DI 10.1089/ars.2013.5240
PG 17
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AI9UF
UT WOS:000337284000001
PM 24053669
OA Green Published
DA 2022-11-30
ER

PT J
AU Haller, JA
AF Haller, Julia A.
TI Current Anti-Vascular Endothelial Growth Factor Dosing Regimens Benefits
   and Burden
SO OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; CLINICAL-TRIAL; RANIBIZUMAB; BEVACIZUMAB
AB Topic: To examine the outcomes of clinical trials and case studies that investigated the different dosing regimens used for the 3 intravitreal anti-vascular endothelial growth factor (VEGF) inhibitors that are available currently. The Comparisons of Age-Related Macular Degeneration (AMD) Treatments Trial (CATT) data are discussed briefly here and are reviewed in greater detail in a separate accompanying article.
   Clinical Relevance: Sustained improvement with the 2 most widely used anti-VEGF drugs, bevacizumab and ranibizumab, requires monthly visits, posing a difficulty for patients. Thus, there is a need to evaluate whether individualized treatment regimens may reduce patient burden and improve patient outcomes.
   Methods: Review of clinical trials and case studies presented at recent medical conferences and published in peer-reviewed literature.
   Results: Numerous trials, including the Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization (CNV) Secondary to AMD, Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with Intraocular Ranibizumab, Study of Ranibizumab in Patients with Subfoveal CNV Secondary to AMD, Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects with CNV Secondary to AMD or Macular Edema Secondary to Retinal Vein Occlusion, Safety Assessment of Intravitreal Lucentis for AMD, and CATT, have evaluated alternatives to monthly dosing. Evidence suggests that either a treat-as-needed or, possibly, a treat-and-extend regimen provides a reasonable approach to monthly injections recommended for bevacizumab and ranibizumab, with the caveat that as yet, careful and ongoing surveillance remains a key feature of optical management.
   Conclusions: Individualization of antiangiogenic treatment using data from clinical trials evaluating various dosing regimens against the patient's disease, lifestyle, and economic restrictions continues to evolve.
C1 [Haller, Julia A.] Thomas Jefferson Univ, Wills Eye Inst, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Haller, JA (通讯作者)，Wills Eye Inst, 840 Walnut St,Suite 1510, Philadelphia, PA 19107 USA.
EM jhaller@willseye.org
RI CLIHON, Residencia Medica/K-4896-2013
OI CLIHON, Residencia Medica/0000-0001-6734-2513
FU Regeneron Pharmaceuticals, Inc, Tarrytown, NY
FX Supported by an educational grant from Regeneron Pharmaceuticals, Inc,
   Tarrytown, NY.
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NR 22
TC 73
Z9 75
U1 0
U2 24
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2013
VL 120
IS 5
SU S
BP S3
EP S7
DI 10.1016/j.ophtha.2013.01.057
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 140UW
UT WOS:000318682500002
PM 23642784
DA 2022-11-30
ER

PT J
AU Collier, RJ
   Wang, Y
   Smith, SS
   Martin, E
   Ornberg, R
   Rhoades, K
   Romano, C
AF Collier, Robert J.
   Wang, Yu
   Smith, Sherry S.
   Martin, Elizabeth
   Ornberg, Richard
   Rhoades, Kristina
   Romano, Carmelo
TI Complement Deposition and Microglial Activation in the Outer Retina in
   Light-Induced Retinopathy: Inhibition by a 5-HT1A Agonist
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; RECEPTOR AGONIST; OXIDATIVE
   DAMAGE; KAPPA-B; ASSOCIATION; EXPRESSION; VARIANT; RISK; SUSCEPTIBILITY
AB PURPOSE. Increasing evidence supports a role for complement in the pathogenesis of age-related macular degeneration (AMD). This study evaluated retinal microglia, T-lymphocytes, and complement deposition in a light-induced retinopathy model. The effect of a serotonin (5-hydroxytryptamine, 5-HT1A) agonist on these processes was investigated.
   METHODS. Rats were dark adapted for 24 hours before a 6-hour blue light exposure. Some animals were predosed subcutaneously with AL-8309A. Retinas were evaluated at different times after light exposure. Paraffin sections were stained with antibody for a microglial marker (Iba1), a T-lymphocyte marker (CD3), and complement components C1q, C3, factor B, factor H, and membrane attack complex (MAC).
   RESULTS. Light exposure resulted in substantial photoreceptor and RPE loss. Robust microglia activation and migration to the outer retina occurred rapidly. Substantial T-lymphocyte recruitment did not occur. Complement alternative pathway was strongly activated, resulting in the deposition of C3, factor B, factor H, and MAC in the area of photic lesions. Dosing with AL-8309A prevented retinal lesions and decreased microglia activation/recruitment and complement deposition in the outer retina.
   CONCLUSIONS. In blue light exposed retinas, microglia were activated and migrated toward the outer retina, whereas a T-lymphocyte response was minimal. The innate immune system was markedly activated, with substantial complement deposition in the outer retina after light exposure. This complement deposition was prevented by AL-8309A. This model may be useful in the evaluation of complement inhibitors and other neuroprotectants intended for ocular use. AL-8309 is under evaluation in the clinic and may be useful in the treatment of AMD. (Invest Ophthalmol Vis Sci. 2011;52:8108-8116) DOI: 10.1167/iovs.10-6418
C1 [Collier, Robert J.; Wang, Yu; Smith, Sherry S.; Martin, Elizabeth; Ornberg, Richard; Rhoades, Kristina; Romano, Carmelo] Alcon Res Ltd, Ft Worth, TX 76134 USA.
C3 Novartis; Alcon
RP Romano, C (通讯作者)，Alcon Res Ltd, 6201 S Freeway, Ft Worth, TX 76134 USA.
EM carl.romano@alconlabs.com
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768
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NR 51
TC 59
Z9 62
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 OCT
PY 2011
VL 52
IS 11
BP 8108
EP 8116
DI 10.1167/iovs.10-6418
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 834MY
UT WOS:000295966600043
PM 21467172
DA 2022-11-30
ER

PT J
AU Lee, E
   Rewolinski, D
AF Lee, Edwin
   Rewolinski, David
TI Evaluation of CXCR4 Inhibition in the Prevention and Intervention Model
   of Laser-Induced Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MOLECULAR-CLONING; PROGENITOR CELLS;
   CHEMOKINE SDF-1; STEM-CELLS; RECEPTOR; ANGIOGENESIS; SUPPRESSION;
   ANTAGONIST; EXPRESSION
AB PURPOSE. Endothelial precursor cells (EPCs) derived from hematopoietic stem cells (HSCs) have been shown to contribute to choroidal neovascularization by signaling through the SDF1/CXCR4 axis. In a prevention and treatment/intervention modality of the laser choroidal neovascularization (CNV) model, the efficacy of CXCR4 inhibition on reducing choroidal leakage and angiogenesis was evaluated.
   METHODS. CNV in rats was generated by focal rupture of Bruch's membrane with an 810-nm diode laser. In the prevention mode, a CXCR4 antagonist (AMD3100) was delivered via an osmotic pump 1 day after laser induction. In the intervention mode, AMD3100 delivery commenced 14 days after laser induction. Inhibition of CXCR4 was determined through leukocyte and SDF-1 actin polymerization blood biomarker assays. Leakage was assessed by fluorescein angiography, and CNV lesion size was quantified after isolectin B4 endothelial cell staining. SU14813, an anti-VEGFR, PDGFR-beta, KIT, and FLT3 inhibitor, was also assessed in an intervention study protocol.
   RESULTS. Inhibition of CXCR4 was demonstrated by an increase in the number of blood leukocytes, and diminished SDF-1 induced actin polymerization in whole blood. CNV leakage and neovascularization were inhibited when the dose regimen was initiated 1 day after laser-induced CNV induction. AMD3100 did not show efficacy when administered 14 days after lasering. Treatment with SU14813 significantly decreased CNV leakage and lesion size in an intervention modality.
   CONCLUSIONS. Inhibition of CXCR4 may be useful in preventing neovascularization but does not appear to have an effect on already established angiogenesis. A multiple receptor tyrosine kinase (RTK) inhibitor approach shows promise for the treatment of wet age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2010;51:3666-3672) DOI: 10.1167/iovs.09-3802
C1 [Lee, Edwin; Rewolinski, David] Pfizer Inc, Dept Ocular Biol, San Diego, CA USA.
C3 Pfizer
RP Lee, E (通讯作者)，Care Of Shiue M, Pfizer Inc, PGRD La Jolla, 10646 Sci Ctr Dr, San Diego, CA 92121 USA.
FU Pfizer, Inc.
FX Supported by Pfizer, Inc.
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NR 32
TC 22
Z9 26
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 2010
VL 51
IS 7
BP 3666
EP 3672
DI 10.1167/iovs.09-3802
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 614HX
UT WOS:000279047500046
PM 20042641
DA 2022-11-30
ER

PT J
AU Sheu, SJ
   Liu, NC
   Chen, JL
AF Sheu, Shwu-Jiuan
   Liu, Ni-Chun
   Chen, Jiunn-Liang
TI Resveratrol Protects Human Retinal Pigment Epithelial Cells from
   Acrolein-Induced Damage
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID MITOCHONDRIAL-DNA DAMAGE; MACULAR DEGENERATION; OXIDATIVE DAMAGE;
   CIGARETTE-SMOKE; RISK-FACTORS; FATTY-ACIDS; AGE; SUPPLEMENTATION;
   PHAGOCYTOSIS; CONSUMPTION
AB Purpose: Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells.
   Methods: Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 mu M), zeaxanthin (100 mu M), meclofenamic acid (30 mu M), and resveratrol (10 mM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells.
   Results: Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment.
   Conclusions: Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.
C1 [Sheu, Shwu-Jiuan; Liu, Ni-Chun; Chen, Jiunn-Liang] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung 813, Taiwan.
   [Sheu, Shwu-Jiuan] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
C3 Kaohsiung Veterans General Hospital; National Yang Ming Chiao Tung
   University
RP Sheu, SJ (通讯作者)，Kaohsiung Vet Gen Hosp, Dept Ophthalmol, 386 Ta Chung 1st Rd, Kaohsiung 813, Taiwan.
EM sjsheu@vghks.gov.tw
FU National Science Council [NSC97-2314-B-075B-011]; Kaohsiung Veterans
   General Hospital, Kaohsiung City, Taiwan [VGHKS 99-059]
FX This study was supported by grants from the National Science Council
   (NSC97-2314-B-075B-011) and the Kaohsiung Veterans General Hospital,
   Kaohsiung City, Taiwan (VGHKS 99-059).
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NR 36
TC 47
Z9 51
U1 0
U2 9
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 2010
VL 26
IS 3
BP 231
EP 236
DI 10.1089/jop.2009.0137
PG 6
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 614CW
UT WOS:000279033800002
PM 20565308
DA 2022-11-30
ER

PT J
AU Beltran, WA
   Allore, HG
   Johnson, E
   Towle, V
   Tao, W
   Acland, GM
   Aguirre, GD
   Zeiss, CJ
AF Beltran, William A.
   Allore, Heather G.
   Johnson, Elizabeth
   Towle, Virginia
   Tao, Weng
   Acland, Gregory M.
   Aguirre, Gustavo D.
   Zeiss, Caroline J.
TI CREB1/ATF1 Activation in Photoreceptor Degeneration and Protection
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CILIARY NEUROTROPHIC FACTOR; ELEMENT-BINDING PROTEIN; ROD-CONE
   DYSPLASIA; RETINITIS-PIGMENTOSA; TRANSCRIPTIONAL ACTIVATION; RETINAL
   DEGENERATIONS; MESSENGER-RNA; GENE-TRANSFER; CELL-DEATH; IN-VITRO
AB PURPOSE. The cAMP response element binding protein 1 (CREB1) and activating transcription factor 1 (ATF1) are closely related members of the bZIP superfamily of transcription factors. Both are activated in response to a wide array of stimuli, including cellular stress. This study was conducted to assess the CREB1/ATF1 pathway in photoreceptor disease and protection.
   METHODS. The expression levels of p-CREB1, CREB1, and ATF1 were examined by immunoblot and immunohistochemistry in normal canine retina and retinas of several canine models of retinal degeneration (rcd1, rcd2, erd, prcd, XLPRA1, XLPRA2, T4R RHO). Humans retinas affected with age-related macular degeneration (AMD) were also examined. p-CREB1/ATF1 immunolabeling was assessed in normal and rcd1 dogs treated with ciliary neurotrophic factor (CNTF), to examine the effect of a neuroprotective stimulus on activation of CREB1/ATF1.
   RESULTS. Native CREB1 and ATF1 as well as phosphorylated CREB1/ATF1 was examined in normal canine retina by immunoblot. The p-CREB1 antibody identified phosphorylated CREB1 and ATF1 and labeled the inner retina only in normal dogs. In degenerate canine and human retinas, strong immunolabeling appeared in rod and cone photoreceptors, indicating increased expression of native CREB1 and ATF1, as well as increased phosphorylation of these proteins. Retinal protection by CNTF in rcd1 dogs was accompanied by a significant increase in the number of p-CREB1/ATF1-labeled photoreceptor nuclei.
   CONCLUSIONS. Positive association of CREB1/ATF1 phosphorylation with photoreceptor protection suggests that it may contribute to an innate protective response. These data identify a signaling mechanism in rods and cones of potential importance for therapies of RP and AMD. (Invest Ophthalmol Vis Sci. 2009;50:5355-5363) DOI:10.1167/iovs.09-3741
C1 [Johnson, Elizabeth; Zeiss, Caroline J.] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06510 USA.
   [Beltran, William A.; Aguirre, Gustavo D.] Univ Penn, Sch Vet Med, Sect Ophthalmol, Philadelphia, PA 19104 USA.
   [Allore, Heather G.; Towle, Virginia] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
   [Tao, Weng] Neurotech USA, Lincoln, RI USA.
   [Acland, Gregory M.] Cornell Univ, Coll Vet Med, JA Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
C3 Yale University; University of Pennsylvania; Yale University; Cornell
   University
RP Zeiss, CJ (通讯作者)，Yale Univ, Sch Med, Comparat Med Sect, 375 Congress Ave, New Haven, CT 06510 USA.
EM caroline.zeiss@yale.edu
OI Allore, Heather/0000-0001-7685-8175
FU National Institute of Health [K01 RR1609001A2, EY-06855, EY13132,
   EY17549]; Foundation Fighting Blindness Individual Investigator Award
   and Center; Fight for Sight Nowak family; Claude D. Pepper Older
   Americans Independence Center [P30-AG21342]; Vision Research Center [P30
   EY-001583]; NATIONAL CENTER FOR RESEARCH RESOURCES [K01RR016090] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [P30EY001583, R01EY006855,
   R01EY017549, R01EY013132] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON AGING [P30AG021342] Funding Source: NIH RePORTER
FX Supported by National Institute of Health Grants K01 RR1609001A2,
   EY-06855, EY13132, and EY17549; Foundation Fighting Blindness Individual
   Investigator Award and Center grants; a Fight for Sight Nowak family
   grant; Grant P30-AG21342 from the Claude D. Pepper Older Americans
   Independence Center at Yale University School of Medicine (Mary Tinetti,
   PI); and Vision Research Center Grant P30 EY-001583. Human retinas were
   obtained through the National Retinitis Pigmentosa Foundation Donor
   Program (Hunt Valley, MD, donation numbers 709, 722, and 716). Neurotech
   USA provided the tissue blocks from dogs treated with CNTF encapsulated
   cell implants.
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NR 52
TC 14
Z9 15
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 NOV
PY 2009
VL 50
IS 11
BP 5355
EP 5363
DI 10.1167/iovs.09-3741
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 514XH
UT WOS:000271429200046
PM 19643965
OA Green Published
DA 2022-11-30
ER

PT J
AU Chung, RH
   Schmidt, S
   Martin, ER
   Hauser, ER
AF Chung, Ren-Hua
   Schmidt, Silke
   Martin, Eden R.
   Hauser, Elizabeth R.
TI Ordered-Subset Analysis (OSA) for Family-Based Association Mapping of
   Complex Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE family-based association analysis; linkage; ordered-subset analysis;
   covariate; genetic heterogeneity
ID ONSET PARKINSONS-DISEASE; LINKAGE ANALYSIS; NUCLEAR FAMILIES; MACULAR
   DEGENERATION; TESTS; GENE; AGE; DISEQUILIBRIUM; HETEROGENEITY; RISK
AB Association analysis provides a powerful tool for complex disease gene mapping. However, in the presence of genetic heterogeneity, the power for association analysis can be low since only a fraction of the collected families may carry a specific disease susceptibility allele. Ordered-subset analysis (OSA) is a linkage test that can be powerful in the presence of genetic heterogeneity. OSA uses trait-related covariates to identify a subset of families that provide the most evidence for linkage. A similar strategy applied to genetic association analysis would likely result in increased power to detect association. Association in the presence of linkage (APL) is a family-based association test (FBAT) for nuclear families with multiple affected siblings that properly infers missing parental genotypes when linkage is present. We propose here APL-OSA, which applies the OSA method to the APL statistic to identify a subset of families that provide the most evidence for association. A permutation procedure is used to approximate the distribution of the APL-OSA statistic under the null hypothesis that there is no relationship between the family-specific covariate and the family-specific evidence for allelic association. We performed a comprehensive simulation study to verify that APL-OSA has the correct type I error rate under the null hypothesis. This simulation study also showed that APL-OSA can increase power relative to other commonly used association tests (APL, FBAT and FBAT with covariate adjustment) in the presence of genetic heterogeneity. Finally, we applied APL-OSA to a family study of age-related macular degeneration, where cigarette smoking was used as a covariate. Genet. Epidemiol. 32:627-637, 2008. (C) 2008 Wiley-Liss, Inc.
C1 [Chung, Ren-Hua; Schmidt, Silke; Hauser, Elizabeth R.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA.
   [Martin, Eden R.] Univ Miami, Miller Sch Med, Miami Inst Human Genom, Ctr Genet Epidemiol & Stat Genet, Miami, FL 33136 USA.
C3 Duke University; University of Miami
RP Hauser, ER (通讯作者)，Duke Univ, Med Ctr, Ctr Human Genet, Box 3445, Durham, NC 27710 USA.
EM Elizabeth.Hauser@duke.edu
RI Chung, Ren-Hua/AAB-8364-2019; Chung, Ren-Hua/A-8833-2012
OI Hauser, Elizabeth/0000-0003-0367-9189
FU National Institutes of Health (NIMH) [R01 MH595228]; Neurosciences
   Education and Research Foundation; NATIONAL EYE INSTITUTE [R03EY015216,
   R01EY012118] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF MENTAL
   HEALTH [R01MH059528] Funding Source: NIH RePORTER
FX Contract grant sponsor: National Institutes of Health (NIMH); Contract
   grant number: R01 MH595228; Contract grant sponsor: Neurosciences
   Education and Research Foundation.
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NR 39
TC 8
Z9 8
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 NOV
PY 2008
VL 32
IS 7
BP 627
EP 637
DI 10.1002/gepi.20340
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600005
PM 18473393
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Hatef, E
   Fotouhi, A
   Hashemi, H
   Mohammad, K
   Jalali, KH
AF Hatef, Elham
   Fotouhi, Akbar
   Hashemi, Hassan
   Mohammad, Kazem
   Jalali, Kamran Hodjat
TI Prevalence of retinal diseases and their pattern in Tehran - The Tehran
   Eye Study
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; diabetic retinopathy; retinal disease;
   risk factor; Tehran Eye Study
ID AGE-RELATED MACULOPATHY; POPULATION-BASED ASSESSMENT; COPENHAGEN CITY
   EYE; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; SOUTHERN INDIA;
   RISK-FACTORS; PEOPLE
AB Purpose: To determine the prevalence of retinal diseases and their pattern in Tehran through a population-based study.
   Methods: In 2002, through a stratified random cluster sampling, 6497 citizens representing a cross-section of the population of Tehran were selected from 160 clusters. Eligible people were recruited through a door-to-door household survey in selected clusters and transferred to a clinic for an extensive eye examination and interview.
   Results: The prevalence of retinal diseases was 8.56 per 100 (95% CI, 7.74-9.39). Acquired retinopathies (3.33 per 100) and peripheral retinal lesions (3.29 per 100) were the most common retinal diseases in our population. Cataract (12.47 per 100) was the major ocular comorbidity; high blood pressure (21.14 per 100) and diabetes mellitus (15.99 per 100) were the main systemic comorbidities among 415 patients with retinal diseases. The prevalence of low vision on the basis of best-corrected and presenting visual acuity was 0.63 and 2.87 per 100 in 415 patients with retinal disease. Two patients (0.48 per 100) were blind with corrected and presenting visual acuity. The prevalence of diabetic retinopathy in the studied population was 0.61 per 100 (95% CI, 0.39-0.82) and age-related macular degeneration was detected in 1.95 per 100 (95% CI, 1.55-2.34) of the population.
   Conclusions: These findings reveal a considerable prevalence of retinal diseases in the population. The prevalence might be underestimated due to the lack of fundus photography. The findings could be considered for case finding and planning treatment programs for specific retinal diseases.
C1 [Fotouhi, Akbar; Mohammad, Kazem] Univ Tehran Med Sci, Dept Epidemiol & Biostat, Sch Publ Hlth, Tehran, Iran.
   [Hatef, Elham; Hashemi, Hassan; Jalali, Kamran Hodjat] Noor Vis Correct Ctr, Tehran, Iran.
   [Hashemi, Hassan] Univ Tehran Med Sci, Sch Med, Farabi Eye Hosp, Tehran, Iran.
C3 Tehran University of Medical Sciences; Tehran University of Medical
   Sciences
RP Fotouhi, A (通讯作者)，Univ Tehran Med Sci, Dept Epidemiol & Biostat, Sch Publ Hlth, Postal Box 141556446, Tehran, Iran.
EM afotouhi@tums.ac.ir
RI Fotouhi, Akbar/F-5618-2011; Hashemi, Hassan/N-2293-2019
OI Fotouhi, Akbar/0000-0002-6438-6833; Hashemi, Hassan/0000-0002-6086-1537
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NR 23
TC 26
Z9 26
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2008
VL 28
IS 5
BP 755
EP 762
DI 10.1097/IAE.0b013e3181613463
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 302KQ
UT WOS:000255967600014
PM 18463522
DA 2022-11-30
ER

PT J
AU Johnson, EJ
   Neuringer, M
   Russell, RM
   Schalch, W
   Snodderly, DM
AF Johnson, EJ
   Neuringer, M
   Russell, RM
   Schalch, W
   Snodderly, DM
TI Nutritional manipulation of primate retinas, III: Effects of lutein or
   zeaxanthin supplementation on adipose tissue and retina of
   xanthophyll-free monkeys
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR PIGMENT; CAROTENOIDS; AGE; DEGENERATION; PLASMA; DEATH; SERUM
AB PURPOSE. Macular pigment ( MP) is composed of the xanthophylls lutein ( L) and zeaxanthin ( Z) and may help to prevent age- related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls.
   METHODS. From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 mu mol/ kg per day for 24 to 101 weeks. At baseline and at 4- to 12- week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina ( central 4 mm, 8- mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet.
   RESULTS. Monkeys fed xanthophyll- free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R, 3 ' S- Z ( RSZ or meso- Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula ( central 4 mm). All- trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z.
   CONCLUSIONS. L is the precursor of RSZ, a major component of macular pigment. Xanthophyll- free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.
C1 Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Portland, OR USA.
   Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA.
   Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR USA.
   DSM Nutr Ltd, Basel, Switzerland.
   Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA USA.
   Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
C3 Tufts University; United States Department of Agriculture (USDA); Oregon
   Health & Science University; Oregon National Primate Research Center;
   Oregon Health & Science University; Oregon Health & Science University;
   DSM NV; Harvard University; Harvard Medical School; Schepens Eye
   Research Institute; Harvard University; Harvard Medical School
RP Johnson, EJ (通讯作者)，Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM elizabeth.johnson@tufts.edu
OI Snodderly, Donald/0000-0002-3428-609X
FU NATIONAL CENTER FOR RESEARCH RESOURCES [P51RR000163] Funding Source: NIH
   RePORTER; NCRR NIH HHS [RR-00163] Funding Source: Medline
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NR 31
TC 166
Z9 171
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2005
VL 46
IS 2
BP 692
EP 702
DI 10.1167/iovs.02-1192
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 890WP
UT WOS:000226542100041
PM 15671301
DA 2022-11-30
ER

PT J
AU Arens-Arad, T
   Lender, R
   Farah, N
   Mandel, Y
AF Arens-Arad, Tamar
   Lender, Rivkah
   Farah, Nairouz
   Mandel, Yossi
TI Cortical responses to prosthetic retinal stimulation are significantly
   affected by the light-adaptive state of the surrounding normal retina
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; age-related macular degeneration; photoreceptors;
   dark-adaptation; amacrine cells; GABA
ID ROD BIPOLAR CELLS; LATERAL SPREAD; DARK-ADAPTATION; GANGLION-CELLS;
   ABNORMAL RCS; VISION; GABA; INHIBITION; RATS; MODULATION
AB Objective. Restoration of central vision loss in patients with age-related macular degeneration (AMD) by implanting a retinal prosthesis is associated with an intriguing situation wherein the central prosthetic vision co-exists with natural normal vision. Of major interest are the interactions between the prosthetic and natural vision. Here we studied the effect of the light-adaptive state of the normal retina on the electrical visual evoked potentials (VEPs) arising from the retinal prosthesis. Approach. We recorded electrical VEP elicited by prosthetic retinal stimulation in wild-type rats implanted with a 1 mm photovoltaic subretinal array. Cortical responses were recorded following overnight dark adaption and compared to those recorded following bleaching of the retina by light (520 nm) at various intensities and durations. Main results. Compared to dark-adapted responses, bleaching induced a 2-fold decrease in the prosthetic cortical response, which returned to the dark-adapted baseline within 30 min to several hours, depending on the degree of bleaching. This reduction was neither observed in Royal College of Surgeons (RCS) rats with a degenerated photoreceptor layer nor following intravitreal injection of a GABAa receptor blocker (bicuculine), suggesting the involvement of photoreceptors and a GABAa-mediated mechanism. Significance. These findings show a robust effect of the retinal light-adaptive state on the obtained prosthetic responses. If a similar effect is found in humans, this will have immediate implications on the design of prosthetic devices, where both natural and prosthetic vision co-exist, such as in AMD patients receiving a photovoltaic retinal implant. Similarly, standardization of the retinal light-adaptive state in prosthetic clinical trials should be considered.
C1 [Arens-Arad, Tamar; Lender, Rivkah; Farah, Nairouz; Mandel, Yossi] Bar Ilan Univ, Sch Optometry & Vis Sci, Fac Life Sci, Ramat Gan, Israel.
   [Arens-Arad, Tamar; Lender, Rivkah; Farah, Nairouz; Mandel, Yossi] Bar Ilan Univ, Bar Ilan Inst Nanotechnol & Adv Mat BINA, Ramat Gan, Israel.
   [Mandel, Yossi] Bar Ilan Univ, Gonda Brain Res Ctr, Ramat Gan, Israel.
C3 Bar Ilan University; Bar Ilan University; Bar Ilan University
RP Mandel, Y (通讯作者)，Bar Ilan Univ, Sch Optometry & Vis Sci, Fac Life Sci, Ramat Gan, Israel.; Mandel, Y (通讯作者)，Bar Ilan Univ, Bar Ilan Inst Nanotechnol & Adv Mat BINA, Ramat Gan, Israel.; Mandel, Y (通讯作者)，Bar Ilan Univ, Gonda Brain Res Ctr, Ramat Gan, Israel.
EM yossi.mandel@biu.ac.il
OI Farah, Nairouz/0000-0003-3227-2628
FU Israeli Science Foundation [ISF 157/16]; Israeli -US Binational Science
   Foundation (BSF); ERC starter grant
FX This study was supported by the Israeli Science Foundation research
   grant ISF 157/16 (YM) and the Israeli -US Binational Science Foundation
   (BSF) (YM) and an ERC starter grant (YM).
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NR 55
TC 1
Z9 1
U1 0
U2 5
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 APR
PY 2021
VL 18
IS 2
AR 026024
DI 10.1088/1741-2552/abdd42
PG 12
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA QQ4LU
UT WOS:000624495600001
PM 33470983
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Battista, M
   Borrelli, E
   Miere, A
   Corbelli, E
   Capuano, V
   Querques, L
   Souied, EH
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Battista, Marco
   Borrelli, Enrico
   Miere, Alexandra
   Corbelli, Eleonora
   Capuano, Vittorio
   Querques, Lea
   Souied, Eric H.
   Bandello, Francesco
   Querques, Giuseppe
TI OCT-A characterisation of recurrent type 3 macular neovascularisation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE imaging; macula; retina
AB Purpose
   To investigate optical coherence tomography angiography (OCT-A) findings in recurrent type 3 macular neovascularisation (MNV).
   Methods
   In this retrospective cohort study, consecutive patients with type 3 MNV secondary to age-related macular degeneration underwent OCT-A at three different time points: baseline, after anti-vascular endothelial growth factor treatment with complete resolution of the exudative signs (ie, non-exudative stage) and at the recurrence of exudation (ie, recurrence stage). Demographics and clinical findings were analysed, including OCT-A features of type 3 MNV recurrence.
   Results
   Twelve eyes (12 patients, mean age 78 +/- 7 years) were included. Using OCT-A, at baseline all type 3 MNVs showed the presence of detectable flow downgrowing from the deep vascular complex (DVC) to the retinal pigment epithelium (RPE)/sub-RPE space. 6/12 eyes (50%) showed anomalous flow under the RPE, while the other 6 eyes showed flow reaching the RPE without anomalous flow in the sub-RPE space. At the non-exudative stage (after treatment), BCVA and CMT significantly improved (p=0.004 and p=0.036), and flow inside the retinal lesions reduced; interestingly the connection to the RPE/sub-RPE space regressed. At the time of recurrence, all type 3 MNVs showed the presence of intra/sub-retinal exudation with restoration of the flow deepening from the DVC to the RPE/sub-RPE space.
   Conclusions
   Detectable flow deepening from the DVC to the RPE/sub-RPE space using OCT-A is mandatory to have a new exudation secondary to recurrent type 3 MNV. Early detection of type 3 MNV recurrence by OCT-A characterisation may prompt retreatment and potentially prevent progression to late stages of the disease.
C1 [Sacconi, Riccardo; Battista, Marco; Borrelli, Enrico; Corbelli, Eleonora; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
   [Sacconi, Riccardo; Battista, Marco; Borrelli, Enrico; Corbelli, Eleonora; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] IRCCS San Raffaele Sci Inst, Div Head & Neck, Ophthalmol Unit, Milan, Italy.
   [Miere, Alexandra; Capuano, Vittorio; Souied, Eric H.] Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
C3 Vita-Salute San Raffaele University; Vita-Salute San Raffaele
   University; IRCCS Ospedale San Raffaele; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Querques, G (通讯作者)，Osped San Raffaele, Ophthalmol, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Borrelli, Enrico/AAR-3693-2020; Miere, Alexandra/AIC-4074-2022;
   Battista, Marco/AAO-3106-2021
OI Borrelli, Enrico/0000-0003-2815-5031; Miere,
   Alexandra/0000-0003-4123-8210; Battista, Marco/0000-0001-5940-6177;
   Sacconi, Riccardo/0000-0003-2891-2012; Querques,
   Giuseppe/0000-0002-3292-9581; bandello, francesco/0000-0003-3238-9682
CR Bhavsar Kavita V, 2017, Am J Ophthalmol Case Rep, V8, P53, DOI 10.1016/j.ajoc.2017.10.001
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   Klein ML, 2011, AM J OPHTHALMOL, V151, P161, DOI 10.1016/j.ajo.2010.07.020
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NR 27
TC 15
Z9 15
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD FEB
PY 2021
VL 105
IS 2
BP 222
EP 226
DI 10.1136/bjophthalmol-2020-316054
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QB6HE
UT WOS:000614238600014
PM 32229515
DA 2022-11-30
ER

PT J
AU Hirst, RJ
   Setti, A
   De Looze, C
   Akuffo, KO
   Peto, T
   Kenny, RA
   Newell, FN
AF Hirst, Rebecca J.
   Setti, Annalisa
   De Looze, Celine
   Akuffo, Kwadwo O.
   Peto, Tunde
   Kenny, Rose A.
   Newell, Fiona N.
TI The effect of eye disease, cataract surgery and hearing aid use on
   multisensory integration in ageing
SO CORTEX
LA English
DT Article
DE Sound-induced flash illusion; Multisensory; Ageing; Eye disease; Hearing
   aids
ID INDUCED FLASH ILLUSION; TEMPORAL BINDING WINDOW; MACULAR DEGENERATION;
   SPEECH-PERCEPTION; SUSCEPTIBILITY; PREVALENCE; RESOLUTION; SYNCHRONY;
   PEOPLE; SEE
AB Sensory impairment is common in ageing, as are approaches to treat it. However, the impact of age-related sensory impairment upon multisensory perception remains unexplored, despite the multisensory nature of our environment. Here, we used data from The Irish Longitudinal Study of Ageing (TILDA) to investigate whether common, age-related eye diseases (cataracts, glaucoma and Age-Related Macular Degeneration, ARMD) and clinical intervention to improve sensory function (cataract removal and hearing aids) influence multisensory integration in older adults. Integration was measured using the Sound Induced Flash Illusion (SIFI), and the extent to which identifying two flashes was improved by accompanying auditory information ("visual gain"). Visual gain was not influenced by eye disease or treatment. For the SIFI, participants self-reporting cataracts, ARMD or glaucoma were as susceptible as healthy controls, even when controlling for age, sex, cognition, self-reported vision/hearing and visual acuity. In a second analysis using retinal photographs, glaucoma and ARMD (hard drusen) did not influence susceptibility relative to controls. However, participants with soft drusen ARMD were more susceptible to the illusion at long Stimulus-Onset Asynchronies (SOAs) compared with controls. Following this, we identified groups reporting bilateral cataract removal or hearing aid acquisition 4 years and <2 years prior to assessment, enabling comparison of longer- and shorter- term effects of interventions. Cataract removal groups did not differ from controls. Longer-term hearing aid users were less susceptible to the SIFI at short SOAs compared with controls. Our findings suggest that multisensory integration in ageing might be specifically influenced by ARMD (soft drusen) and hearing aid use. (C) 2020 The Authors. Published by Elsevier Ltd.
C1 [Hirst, Rebecca J.; Newell, Fiona N.] Trinity Coll Dublin, Sch Psychol, Dublin, Ireland.
   [Hirst, Rebecca J.; Newell, Fiona N.] Trinity Coll Dublin, Inst Neurosci, Dublin, Ireland.
   [Hirst, Rebecca J.; Setti, Annalisa; De Looze, Celine; Kenny, Rose A.] Trinity Coll Dublin, Irish Longitudinal Study Ageing, Dublin, Ireland.
   [Setti, Annalisa] Univ Coll Cork, Sch Appl Psychol, Cork, Ireland.
   [Akuffo, Kwadwo O.] Kwame Nkrumah Univ Sci & Technol, Coll Sci, Dept Optometry & Visual Sci, Kumasi, Ghana.
   [Peto, Tunde] Queens Univ Belfast, Dept Ophthalmol, Belfast, Antrim, North Ireland.
   [Kenny, Rose A.] St James Hosp, Mercer Inst Successful Ageing, Dublin, Ireland.
C3 Trinity College Dublin; Trinity College Dublin; Trinity College Dublin;
   University College Cork; Kwame Nkrumah University Science & Technology;
   Queens University Belfast; Trinity College Dublin
RP Hirst, RJ (通讯作者)，Trinity Coll Dublin, Inst Neurosci, Dublin, Ireland.
EM hirstr@tcd.ie
RI Akuffo, Kwadwo Owusu/J-2036-2019; Newell, Fiona/AIE-2422-2022; Peto,
   Tunde/M-2081-2013
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; Newell,
   Fiona/0000-0002-7363-2346; Peto, Tunde/0000-0001-6265-0381; Kenny, Rose
   Anne/0000-0002-9336-8124
FU Health Research Board (HRB), Ireland [ILP-PHR-2017-014]
FX This work was supported by the Health Research Board (HRB), Ireland;
   Grant reference ILP-PHR-2017-014. The authors would like to thank Dr.
   John Newell (School of Mathematics, Statistics and Applied Mathematics,
   National University of Ireland Galway, Ireland) for his feedback on the
   statistical analysis performed within previous versions of this
   manuscript.
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NR 73
TC 3
Z9 3
U1 2
U2 3
PU ELSEVIER MASSON, CORP OFF
PI PARIS
PA 65 CAMILLE DESMOULINS CS50083 ISSY-LES-MOULINEAUX, 92442 PARIS, FRANCE
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD DEC
PY 2020
VL 133
BP 161
EP 176
DI 10.1016/j.cortex.2020.08.030
PG 16
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA PN7NX
UT WOS:000604662800010
PM 33126009
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Chen, SX
   Le, BT
   Chakravarthy, M
   Kosbar, TR
   Veedu, RN
AF Chen, Suxiang
   Le, Bao T.
   Chakravarthy, Madhuri
   Kosbar, Tamer R.
   Veedu, Rakesh N.
TI Systematic evaluation of 2 '-Fluoro modified chimeric antisense
   oligonucleotide-mediated exon skipping in vitro
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LOCKED NUCLEIC-ACID; RNA; DYSTROPHIN; ANALOGS; DESIGN; MDX; THERAPY
AB Antisense oligonucleotide (AO)-mediated splice modulation has been established as a therapeutic approach for tackling genetic diseases. Recently, Exondys51, a drug that aims to correct splicing defects in the dystrophin gene was approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD). However, Exondys51 has relied on phosphorodiamidate morpholino oligomer (PMO) chemistry which poses challenges in the cost of production and compatibility with conventional oligonucleotide synthesis procedures. One approach to overcome this problem is to construct the AO with alternative nucleic acid chemistries using solid-phase oligonucleotide synthesis via standard phosphoramidite chemistry. 2'-Fluoro (2'-F) is a potent RNA analogue that possesses high RNA binding affinity and resistance to nuclease degradation with good safety profile, and an approved drug Macugen containing 2'-F-modified pyrimidines was approved for the treatment of age-related macular degeneration (AMD). In the present study, we investigated the scope of 2'-F nucleotides to construct mixmer and gapmer exon skipping AOs with either 2'-O-methyl (2'-OMe) or locked nucleic acid (LNA) nucleotides on a phosphorothioate (PS) backbone, and evaluated their efficacy in inducing exon-skipping in mdx mouse myotubes in vitro. Our results showed that all AOs containing 2'-F nucleotides induced efficient exon-23 skipping, with LNA/2'-F chimeras achieving better efficiency than the AOs without LNA modification. In addition, LNA/2'-F chimeric AOs demonstrated higher exonuclease stability and lower cytotoxicity than the 2'-OMe/2'-F chimeras. Overall, our findings certainly expand the scope of constructing 2'-F modified AOs in splice modulation by incorporating 2'-OMe and LNA modifications.
C1 [Chen, Suxiang; Le, Bao T.; Chakravarthy, Madhuri; Veedu, Rakesh N.] Murdoch Univ, Ctr Mol Med & Innovat Therapeut, Perth, WA 6150, Australia.
   [Chen, Suxiang; Le, Bao T.; Chakravarthy, Madhuri; Kosbar, Tamer R.; Veedu, Rakesh N.] Perron Inst Neurol & Translat Sci, Perth, WA 6150, Australia.
C3 Murdoch University
RP Veedu, RN (通讯作者)，Murdoch Univ, Ctr Mol Med & Innovat Therapeut, Perth, WA 6150, Australia.; Veedu, RN (通讯作者)，Perron Inst Neurol & Translat Sci, Perth, WA 6150, Australia.
EM R.Veedu@murdoch.edu.au
RI Chen, Suxiang/ABF-3203-2020; Le, Bao/GWU-4979-2022
OI LE, BAO/0000-0003-1881-8153; Chen, Suxiang/0000-0001-6878-9587; Kosbar,
   Tamer/0000-0002-0953-9809
FU McCusker Charitable Foundation; Perron Instiute for Neurological and
   Translational Science; Perron Institute Top-Up Scholarship;
   International Tuition Fee Scholarship scheme from Murdoch University;
   Murdoch International Postgraduate Scholarships scheme
FX RNV acknowledges the financial support from McCusker Charitable
   Foundation and Perron Instiute for Neurological and Translational
   Science. SC thanks the funding from Perron Institute Top-Up Scholarship
   and International Tuition Fee Scholarship scheme from Murdoch
   University. BTL thanks the Murdoch International Postgraduate
   Scholarships scheme. MC thanks Greg and Dale Higham for financial
   support. The authors thank Prithi Raguraman for assistance towards
   experiments, Yanying An and Jessica Cale for help towards figure
   preparation and Kristin West for informative discussion.
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Z9 19
U1 1
U2 12
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 APR 15
PY 2019
VL 9
AR 6078
DI 10.1038/s41598-019-42523-0
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HT3XF
UT WOS:000464495800002
PM 30988454
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Singh, S
   Pardhan, S
   Kulothungan, V
   Swaminathan, G
   Ravichandran, JS
   Ganesan, S
   Sharma, T
   Raman, R
AF Singh, Sumeer
   Pardhan, Shahina
   Kulothungan, Vaitheeswaran
   Swaminathan, Gayathri
   Ravichandran, Janani Surya
   Ganesan, Suganeswari
   Sharma, Tarun
   Raman, Rajiv
TI The prevalence and risk factor for cataract in rural and urban India
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Prevalence of cataract; risk factors; rural-urban
ID AGE-RELATED CATARACT; POSTERIOR SUBCAPSULAR CATARACTS;
   DIABETIC-RETINOPATHY; LIPID-PEROXIDATION; CHINESE POPULATION; REFRACTIVE
   ERRORS; 5-YEAR INCIDENCE; LENS OPACITIES; SOUTHERN INDIA; EPIDEMIOLOGY
AB Purpose: To report the prevalence and risk factors of cataract and its subtypes in older age group. Methods: A total of 6617 subjects were recruited from both rural and urban areas. A detailed history including data on demographic, socioeconomic and ocular history was obtained. Lens opacity was graded according to the Lens Opacity Classification System III (LOCS III). Results: Cataract was present in 1094 of the rural and 649 subjects in the urban population. Monotype subtype cataracts were found in 32% and 25% in rural and urban population and 12.68% and 18.6% were mixed cataracts in the rural and urban groups. In baseline characteristics history of diabetes, alcohol intake and presence of age-related macular degeneration were the risk factors in urban group. On multivariate analysis, the only significant risk factors for any cataract in subjects >= 60 years were increasing age in both rural [odds ratio (OR), 1.07] and urban (OR, 1.08) population, and HbAlc (OR, 1.14) in rural population. Overweight (OR, 0.6) was found to be a protective factor, and lower social economic status (OR, 1.52) a risk factor for cataract in urban population. A significant urban- rural difference was found in the prevalence of cataract and its subtypes (P <= 0.05). Conclusion: We found the risk factors for any cataract in older age group to be increasing age and HbA1c in rural group. Age and lower social economic status were found to be the risk factors in urban arm. A statistically significant difference was found on comparison of the prevalence of cataract and its subtypes between the rural and urban population.
C1 [Singh, Sumeer; Ganesan, Suganeswari; Sharma, Tarun; Raman, Rajiv] Sankara Nethralaya, Shri Bhagwan Mahavir Vitreoretinal Serv, 18 Coll Rd, Chennai 600006, Tamil Nadu, India.
   [Kulothungan, Vaitheeswaran; Swaminathan, Gayathri; Ravichandran, Janani Surya] Sankara Nethralaya, Dept Prevent Ophthalmol, 18 Coll Rd, Chennai, Tamil Nadu, India.
   [Singh, Sumeer; Pardhan, Shahina; Raman, Rajiv] Anglia Ruskin Univ, Vis & Eye Res Unit, Cambridge, England.
C3 Anglia Ruskin University
RP Raman, R (通讯作者)，Sankara Nethralaya, Shri Bhagwan Mahavir Vitreoretinal Serv, 18 Coll Rd, Chennai 600006, Tamil Nadu, India.
EM rajivpgraman@gmail.com
RI Raman, Rajiv/A-7234-2009; Pardhan, Shahina/AAZ-7509-2020
OI Raman, Rajiv/0000-0001-5842-0233; Singh, Sumeer/0000-0003-3519-7037
FU Jamshetji Tata trust, Mumbai
FX Jamshetji Tata trust, Mumbai.
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NR 40
TC 25
Z9 25
U1 2
U2 6
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD APR
PY 2019
VL 67
IS 4
BP 477
EP 483
DI 10.4103/ijo.IJO_1127_17
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HQ5TV
UT WOS:000462476400008
PM 30900578
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, PJ
   Shang, AQ
   Wang, WW
   Yang, JP
AF Chen, Pei-Jun
   Shang, An-Quan
   Wang, Wei-Wei
   Yang, Jian-Ping
TI Astragaloside suppresses tumor necrosis factor receptor-associated
   factor 5 signaling pathway and alleviates neurodegenerative changes in
   retinal pigment epithelial cells induced by isoflurane
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE antioxidant; astragaloside; isoflurane; retial pigment epithelial cells;
   tumor necrosis factor receptor-associated factor 5
ID AMYLOID-BETA; ANESTHETIC NEUROTOXICITY; MACULAR DEGENERATION; APOPTOSIS;
   DEATH; ACTIVATION; SEVOFLURANE; DEMENTIA; PROPOFOL; NEURONS
AB Epidemiological studies showed that isoflurane, a general anesthetic widely used in surgery including those for the children, is associated with impairment of neurodevelopment and neurodegenerative diseases, such as Alzheimer's disease (AD) and age-related macular degeneration (AMD), which are related to the accumulation of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS. Cell cycle re-entry and proapoptosis were seen in retinal pigment epithelium (RPE) cells treated with isoflurane, which was alleviated by pretreatment of AS. Further, tumor necrosis factor receptor-associated factor 5 (TRAF5) and downstream nuclear factor-kappa B (NF-kappa B) were investigated to elucidate the molecular mechanism underlying protective effect of AS. RPE cells exposed to isoflurane expressed higher TRAF5 and NF-kappa B than those pretreated with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM) assay, Sprague-Dawley rats pretreated with AS and then exposed to isoflurane spent less time in swimming to the platform, and their TRAF5 expression was significantly lower than those received anesthesia alone. Further studies on the consequence of forced downregulation or upregulation are warranted that may employ cutting-edge technologies such as optogenetics to overcome the difficulties in manipulating expression of TRAF5. Although the link between TRAF5 and neurodegeneration requires more in-depth investigations, our study provide a novel hint on the pathological mechanism of isoflurane and suggest a potential target for eliminating persistent side effect of anesthesia.
C1 [Chen, Pei-Jun; Yang, Jian-Ping] Soochow Univ, Affiliated Hosp 1, Dept Anesthesiol, 188 Shizi St, Suzhou 215006, Jiangsu, Peoples R China.
   [Chen, Pei-Jun] Sixth Peoples Hosp Yancheng City, Dept Anesthesiol, Yancheng, Peoples R China.
   [Shang, An-Quan] Tongji Univ, Sch Med, Tongji Hosp, Dept Lab Med, Shanghai, Peoples R China.
   [Wang, Wei-Wei] Sixth Peoples Hosp Yancheng City, Dept Pathol, 66 Zhongting Rd, Yancheng 224001, Jiangsu, Peoples R China.
C3 Soochow University - China; Tongji University
RP Yang, JP (通讯作者)，Soochow Univ, Affiliated Hosp 1, Dept Anesthesiol, 188 Shizi St, Suzhou 215006, Jiangsu, Peoples R China.; Wang, WW (通讯作者)，Sixth Peoples Hosp Yancheng City, Dept Pathol, 66 Zhongting Rd, Yancheng 224001, Jiangsu, Peoples R China.
EM lydia_wangweiwei0501@sina.com; 17712661266@163.com
RI Sosudjai, @onanong/AAF-3628-2021; Shang, Anquan/K-7456-2015
OI Shang, Anquan/0000-0003-2820-1982; Yang, Jian-Ping/0000-0002-0665-4924
FU Medical Science and Technology Development Program of Yancheng City
   [YK2017120, YK2017121, YK2017122]; Youth Medical Talent of Jiangsu
   Province [QNRC2016464]
FX Medical Science and Technology Development Program of Yancheng City,
   Grant/Award Numbers: YK2017120, YK2017121, YK2017122; Youth Medical
   Talent of Jiangsu Province, Grant/Award Number: QNRC2016464
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NR 46
TC 9
Z9 12
U1 1
U2 22
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JAN
PY 2019
VL 120
IS 1
BP 1028
EP 1037
DI 10.1002/jcb.27599
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA HB1XP
UT WOS:000450823500092
PM 30277612
DA 2022-11-30
ER

PT J
AU Sant, DW
   Camarena, V
   Nlustafi, S
   Li, YW
   Wilkes, Z
   Van Booven, D
   Wen, R
   Wang, GF
AF Sant, David W.
   Camarena, Vladimir
   Nlustafi, Sushmita
   Li, Yiwen
   Wilkes, Zachary
   Van Booven, Derek
   Wen, Rong
   Wang, Gaofeng
TI Ascorbate Suppresses VEGF Expression in Retinal Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE VEGF; age-related macular degeneration; ascorbate; retinal pigment
   epithelium; 5-hydroxymethylcytosine
ID ENDOTHELIAL GROWTH-FACTOR; VITAMIN-C; MACULAR DEGENERATION; DNA
   DEMETHYLATION; GENE-EXPRESSION; BETA-CAROTENE; 5-HYDROXYMETHYLCYTOSINE;
   GENERATION; ACID; 5-METHYLCYTOSINE
AB PURPOSE. To investigate the impact of ascorbate, via DNA hydroxymethylation, on VEGF expression in retinal pigment epithelial (RPE) cells.
   METHODS. Dot-blot and hydroxymethylated DNA immunoprecipitation sequencing were applied to evaluate the impact of ascorbate on DNA hydroxymethylation in ARPE-19 cells. RNA sequencing (RNA-seq) was carried out to analyze the transcriptome. Quantitative RT-PCR and ELISA were conducted to examine the transcription and secretion of VEGF from cultured cells. Primary human fetal RPE cells and RPE-J cells were used to verify the effect of ascorbate on VEGF expression. ELISA was used to measure VEGF in the vitreous humor of Gulo(-/-) mice, which, like humans, cannot synthesize ascorbate de novo.
   RESULTS. Treatment with ascorbate (50 lM) promoted 5-hydroxymethycytosine (5hmC) generation and changed the genome-wide profiles of 5hmC in ARPE-19 cells. Ascorbate also caused a dramatic shift in the transcriptome-3186 differential transcripts, of which 69.3% are correlated with altered 5hmC in promoters or gene bodies. One of the most downregulated genes was VEGFA, which encodes the VEGF protein. The suppression of VEGF by ascorbate is independent of hypoxia-inducible factor 1-alpha (HIF-1 alpha) but correlates with increased 5hmC in the gene body. The decreased transcription and secretion of VEGF by ascorbate were verified in primary human fetal RPE cells. Furthermore, adding ascorbate in the diet for Gulo(-/-) mice resulted in decreased levels of VEGF in the RPE/choroid and vitreous humor.
   CONCLUSIONS. Ascorbate inhibits VEGF expression in RPE cells likely via DNA hydroxymethylation. Thus, ascorbate could be implicated in the prevention or treatment of diseases such as age-related macular degeneration (AMD).
C1 [Sant, David W.; Camarena, Vladimir; Nlustafi, Sushmita; Wilkes, Zachary; Van Booven, Derek; Wang, Gaofeng] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Dr John T Macdonald Fdn,Dept Human Genet, Miami, FL 33136 USA.
   [Li, Yiwen; Wen, Rong; Wang, Gaofeng] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Wang, Gaofeng] Univ Miami, Miller Sch Med, Dr Nasser Ibrahim Al Rashid Orbital Vis Res Ctr, Miami, FL 33136 USA.
C3 University of Miami; Bascom Palmer Eye Institute; University of Miami;
   University of Miami
RP Wang, GF (通讯作者)，Univ Miami, Miller Sch Med, Dept Human Genet, 1501 NW 10th Ave,BRB Room 608, Miami, FL 33136 USA.
EM gwang@med.miami.edu
FU National Institutes of Health [R01NS089525]; BrightFocus Grant
   [M2017081]; NATIONAL EYE INSTITUTE [T32EY023194] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
   [R01NS089525] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grant R01NS089525 and
   BrightFocus Grant M2017081 (to GW).
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NR 43
TC 15
Z9 16
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2018
VL 59
IS 8
BP 3608
EP 3618
DI 10.1167/iovs.18-24101
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GN7KQ
UT WOS:000439317900010
PM 30025088
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Grossman, TR
   Carrer, M
   Shen, LJ
   Johnson, RB
   Hettrick, LA
   Henry, SP
   Monia, BP
   McCaleb, ML
AF Grossman, Tamar R.
   Carrer, Michele
   Shen, Lijiang
   Johnson, Robert B.
   Hettrick, Lisa A.
   Henry, Scott P.
   Monia, Brett P.
   McCaleb, Michael L.
TI Reduction in ocular complement factor B protein in mice and monkeys by
   systemic administration of factor B antisense oligonucleotide
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; FACTOR-H; ALTERNATIVE PATHWAY; GEOGRAPHIC ATROPHY;
   EPITHELIAL-CELLS; ACTIVATION; RISK; POLYMORPHISM; PHARMACOKINETICS;
   VARIANT
AB Purpose: Age-related macular degeneration (AMD) is the leading cause of permanent vision loss among the elderly in many industrialized countries, and the complement system plays an important role in the pathogenesis of AMD. Inhibition of complement factor B, a key regulator of the alternative pathway, is implicated as a potential therapeutic intervention for AMD. Here we investigated the effect of liver factor B reduction on systemic and ocular factor B levels.
   Methods: Second-generation antisense oligonucleotides (ASOs) targeting mouse and monkey factor B mRNA were administered by subcutaneous injection to healthy mice or monkeys, and the level of factor B mRNA was assessed in the liver and the eye. In addition, the factor B protein level was determined in plasma and whole eyes from the treated animals.
   Results: Mice and monkeys treated with factor B ASOs demonstrated a robust reduction in liver factor B mRNA levels with no change in ocular factor B mRNA levels. Plasma factor B protein levels were significantly reduced in mice and monkeys treated with factor B ASOs, leading to a dramatic reduction in ocular factor B protein, below the assay detection levels.
   Conclusions: The results add to the increasing evidence that the liver is the main source of plasma and ocular factor B protein, and demonstrate that reduction of liver factor B mRNA by an ASO results in a significant reduction in plasma and ocular factor B protein levels. The results suggest that inhibition of liver factor B mRNA by factor B ASOs would reduce systemic alternative complement pathway activation and has potential to be used as a novel therapy for AMD.
C1 [Grossman, Tamar R.; Carrer, Michele; Shen, Lijiang; Johnson, Robert B.; Hettrick, Lisa A.; Henry, Scott P.; Monia, Brett P.; McCaleb, Michael L.] Ionis Pharmaceut Inc, Carlsbad, CA USA.
C3 Ionis Pharmaceuticals, Inc.
RP Grossman, TR (通讯作者)，Ionis Pharmaceut, Antisense Drug Discovery, 2855 Gazelle Court, Carlsbad, CA 92010 USA.
EM tgrossman@ionisph.com
OI Carrer, Michele/0000-0002-6464-9584
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NR 58
TC 15
Z9 15
U1 1
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD AUG 10
PY 2017
VL 23
BP 561
EP 571
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA FD0EA
UT WOS:000407211400002
PM 28855795
DA 2022-11-30
ER

PT J
AU Loeven, MA
   Rops, AL
   Lehtinen, MJ
   van Kuppevelt, TH
   Daha, MR
   Smith, RJ
   Bakker, M
   Berden, JH
   Rabelink, TJ
   Jokiranta, TS
   van der Vlag, J
AF Loeven, Markus A.
   Rops, Angelique L.
   Lehtinen, Markus J.
   van Kuppevelt, Toin H.
   Daha, Mohamed R.
   Smith, Richard J.
   Bakker, Marinka
   Berden, Jo H.
   Rabelink, Ton J.
   Jokiranta, T. Sakari
   van der Vlag, Johan
TI Mutations in Complement Factor H Impair Alternative Pathway Regulation
   on Mouse Glomerular Endothelial Cells in Vitro
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE autoimmune disease; complement system; endothelium; heparan sulfate;
   innate immunity; atypical hemolytic uremic syndrome; complement Factor
   H; endothelial glycocalyx
ID BINDING-SITES; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; C-3 CONVERTASE;
   3RD COMPONENT; BOUND C3B; PROTEIN; PURIFICATION; DOMAINS;
   GLYCOSAMINOGLYCAN; IDENTIFICATION
AB Complement factor H (FH) inhibits complement activation and interacts with glomerular endothelium via its complement control protein domains 19 and 20, which also recognize heparan sulfate (HS). Abnormalities in FH are associated with the renal diseases atypical hemolytic uremic syndrome and dense deposit disease and the ocular disease age-related macular degeneration. Although FH systemically controls complement activation, clinical phenotypes selectively manifest in kidneys and eyes, suggesting the presence of tissue-specific determinants of disease development. Recent results imply the importance of tissue-specifically expressed, sulfated glycosaminoglycans (GAGs), like HS, in determining FH binding to and activity on host tissues. Therefore, we investigated which GAGs mediate human FH and recombinant human FH complement control proteins domains 19 and 20 (FH19-20) binding to mouse glomerular endothelial cells (mGEnCs) in ELISA. Furthermore, we evaluated the functional defects of FH19-20 mutants during complement activation by measuring C3b deposition on mGEnCs using flow cytometry. FH and FH19-20 bound dose-dependently to mGEnCs and TNF- treatment increased binding of both proteins, whereas heparinase digestion and competition with heparin/HS inhibited binding. Furthermore, 2-O-, and 6-O-, but not N-desulfation of heparin, significantly increased the inhibitory effect on FH19-20 binding to mGEnCs. Compared with wild type FH19-20, atypical hemolytic uremic syndrome-associated mutants were less able to compete with FH in normal human serum during complement activation on mGEnCs, confirming their potential glomerular pathogenicity. In conclusion, our study shows that FH and FH19-20 binding to glomerular endothelial cells is differentially mediated by HS but not other GAGs. Furthermore, we describe a novel, patient serum-independent competition assay for pathogenicity screening of FH19-20 mutants.
C1 [Loeven, Markus A.; Rops, Angelique L.; Bakker, Marinka; Berden, Jo H.; van der Vlag, Johan] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands.
   [Lehtinen, Markus J.; Jokiranta, T. Sakari] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00290 Helsinki, Finland.
   [van Kuppevelt, Toin H.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Biochem, NL-6500 HB Nijmegen, Netherlands.
   [Daha, Mohamed R.; Rabelink, Ton J.] Leiden Univ, Med Ctr, Dept Nephrol, NL-2300 RC Leiden, Netherlands.
   [Smith, Richard J.] Univ Iowa, Carver Coll Med, Dept Internal Med & Otolaryngol, Iowa City, IA 52242 USA.
C3 Radboud University Nijmegen; University of Helsinki; Radboud University
   Nijmegen; Leiden University; Leiden University Medical Center (LUMC);
   Leiden University - Excl LUMC; University of Iowa
RP van der Vlag, J (通讯作者)，Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nephrol Res Lab 480,Radboud Inst Mol Life Sci, Geert Grootepl 10, NL-6525 GA Nijmegen, Netherlands.
EM johan.vandervlag@radboudumc.nl
RI Berden, J.H.M./H-8009-2014; van Kuppevelt, A.H.M.S.M./L-4463-2015; Van
   der Vlag, Johan/E-4636-2010; Loeven, Markus/F-7863-2016; Rabelink, Ton
   J./A-5316-2008
OI Van der Vlag, Johan/0000-0001-7843-5918; Rabelink, Ton
   J./0000-0001-6780-5186; Smith, Richard/0000-0003-1201-6731
FU Kidneeds; Dutch Kidney Foundation [KJPB 09.01]; Radboud University
   Medical Center; Sigrid Juselius Foundation; Academy of Finland [128646,
   259793];  [CP09.03]
FX This work was supported by Kidneeds, the Dutch Kidney Foundation, Grants
   KJPB 09.01 and Consortium Grant CP09.03 (GLYCOREN), the Radboud
   University Medical Center, the Sigrid Juselius Foundation, and the
   Academy of Finland (Projects 128646 and 259793). The authors declare
   that they have no conflicts of interest with the contents of this
   article.
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NR 50
TC 15
Z9 15
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 4
PY 2016
VL 291
IS 10
BP 4974
EP 4981
DI 10.1074/jbc.M115.702506
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DF8WF
UT WOS:000371640600013
PM 26728463
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Gordon, KD
AF Gordon, Keith D.
TI Prevalence of visual hallucinations in a national low vision client
   population
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID CHARLES-BONNET-SYNDROME; MACULAR DEGENERATION; BONNETSYNDROME,CHARLES
AB Purpose: To evaluate the prevalence of visual hallucinations (Charles Bonnet syndrome) in a national population undergoing vision rehabilitation.
   Study Design: Cross-sectional survey.
   Participants: Participants were 2565 new clients older than 40 years attending a Canadian National Institute for the Blind (CNIB) vision rehabilitation clinic.
   Methods: Participants were asked the following question: "Many people who come to CNIB tell us that they see things they know are not there. Some see patterns or shapes. Others see images of people or animals. Have you ever experienced this?" Responses were cross-tabulated on the basis of age, sex, eye disease, visual acuity, and whether the clients lived alone. Multivariable logistic regression was used to analyze the responses.
   Results: Overall, 18.8% of people surveyed indicated that they had experienced hallucinations. In the multivariable model, females showed higher odds of hallucinations than males did (odds ratio [OR] 1.32, 95% CI 1.06-1.64, p = 0.02). Clients with greater vision loss had higher chances of experiencing hallucinations than those with the lowest level of vision loss (OR 1.49, 95% CI 1.19-1.88, p = 0.0005). There was no significant difference in the chances of experiencing hallucinations between people with age-related macular degeneration, diabetic retinopathy, and glaucoma, or in older versus younger respondents. People who did not live alone had higher chances of experiencing hallucinations than those who lived alone (OR 1.54, 95% CI 1.19-1.98, p = 0.0009).
   Conclusions: Visual hallucinations are experienced by approximately 1 in 5 patients with vision loss caused by any eye disease, warranting greater awareness of the phenomenon among all vision health professionals and their patients.
C1 [Gordon, Keith D.] Canadian Natl Inst Blind, 1929 Bayview Ave, Toronto, ON M4G 3E8, Canada.
RP Gordon, KD (通讯作者)，Canadian Natl Inst Blind, 1929 Bayview Ave, Toronto, ON M4G 3E8, Canada.
EM keith.gordon@cnib.ca
FU Bayer, Inc.
FX The author would like to acknowledge Dr. Marguerite Ennis for
   statistical assistance, and Bayer, Inc. for providing an educational
   grant.
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NR 10
TC 22
Z9 22
U1 0
U2 11
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 FEB
PY 2016
VL 51
IS 1
BP 3
EP 6
DI 10.1016/j.jcjo.2015.10.006
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA DD5ZQ
UT WOS:000370003900018
PM 26874151
DA 2022-11-30
ER

PT J
AU Feeny, AK
   Tadarati, M
   Freund, DE
   Bressler, NM
   Burlina, P
AF Feeny, Albert K.
   Tadarati, Mongkol
   Freund, David E.
   Bressler, Neil M.
   Burlina, Philippe
TI Automated segmentation of geographic atrophy of the retinal epithelium
   via random forests in AREDS color fundus images
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Automated delineation; Segmentation; Geographic atrophy of the retinal
   pigment epithelium; Age-related macular degeneration; AREDS color fundus
   imagery; Machine learning
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; SD-OCT;
   AUTOFLUORESCENCE; DRUSEN; FEATURES
AB Background: Age-related macular degeneration (AMD), left untreated, is the leading cause of vision loss in people older than 55. Severe central vision loss occurs in the advanced stage of the disease, characterized by either the in growth of choroidal neovascularization (CNV), termed the "wet" form, or by geographic atrophy (GA) of the retinal pigment epithelium (RPE) involving the center of the macula, termed the "dry" form. Tracking the change in GA area over time is important since it allows for the characterization of the effectiveness of GA treatments. Tracking GA evolution can be achieved by physicians performing manual delineation of GA area on retinal fiindus images. However, manual GA delineation is time-consuming and subject to inter-and intra-observer variability.
   Methods: We have developed a fully automated GA segmentation algorithm in color fundus images that uses a supervised machine learning approach employing a random forest classifier. This algorithm is developed and tested using a dataset of images from the NIH-sponsored Age Related Eye Disease Study (AREDS). GA segmentation output was compared against a manual delineation by a retina specialist.
   Results: Using 143 color fundus images from 55 different patient eyes, our algorithm achieved PPV of 0.82 +/- 0.19, and NPV of 0:95 +/- 0.07.
   Discussion: This is the first study, to our knowledge, applying machine learning methods to GA segmentation on color fundus images and using AREDS imagery for testing. These preliminary results show promising evidence that machine learning methods may have utility in automated characterization of GA from color fundus images. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Feeny, Albert K.; Freund, David E.; Burlina, Philippe] Johns Hopkins Univ, Appl Phys Lab, Baltimore, MD 21218 USA.
   [Feeny, Albert K.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
   [Tadarati, Mongkol; Bressler, Neil M.; Burlina, Philippe] Johns Hopkins Univ, Wilmer Eye Inst, Retina Div, Baltimore, MD 21218 USA.
   [Burlina, Philippe] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
   [Tadarati, Mongkol] Rangsit Univ, Coll Med, Rajavithi Hosp, Bangkok, Thailand.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics
   Laboratory; Johns Hopkins University; Johns Hopkins University; Johns
   Hopkins Medicine; Johns Hopkins University; Rajavithi Hospital; Rangsit
   University
RP Burlina, P (通讯作者)，Johns Hopkins Univ, Wilmer Eye Inst, Retina Div, Baltimore, MD 21218 USA.
RI Freund, D.E./AAW-9401-2020
OI Feeny, Albert/0000-0003-3096-8373
FU National Eye Institute of the National Institutes of Health
   [R21EY024310]; James P. Gills Professorship; JHU Whiting School of
   Engineering SPUR program; NATIONAL EYE INSTITUTE [R21EY024310] Funding
   Source: NIH RePORTER
FX Research reported in this publication was supported by the National Eye
   Institute of the National Institutes of Health under award number
   R21EY024310. The content is solely the responsibility of the authors and
   does not necessarily represent the official views of the National
   Institutes of Health. Supported in part by the James P. Gills
   Professorship and unrestricted research funds to the Retina Division for
   macular degeneration and related diseases research. Additional support
   from the JHU Whiting School of Engineering SPUR program is acknowledged.
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NR 46
TC 42
Z9 42
U1 0
U2 16
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 OCT 1
PY 2015
VL 65
BP 124
EP 136
DI 10.1016/j.compbiomed.2015.06.018
PG 13
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
   Engineering; Mathematical & Computational Biology
GA CT5OW
UT WOS:000362860700013
PM 26318113
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Albert, R
   Kristof, E
   Zahuczky, G
   Szatmari-Toth, M
   Vereb, Z
   Olah, B
   Moe, MC
   Facsko, A
   Fesus, L
   Petrovski, G
AF Albert, Reka
   Kristof, Endre
   Zahuczky, Gabor
   Szatmari-Toth, Maria
   Vereb, Zoltan
   Olah, Brigitta
   Moe, Morten C.
   Facsko, Andrea
   Fesues, Laszlo
   Petrovski, Goran
TI Triamcinolone regulated apopto-phagocytic gene expression patterns in
   the clearance of dying retinal pigment epithelial cells. A key role of
   Mertk in the enhanced phagocytosis
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE AMD; Anoikis; Phagocytosis; Triamcinolone; MERTK; Gas6
ID INTRAVITREAL TRIAMCINOLONE; MACULAR DEGENERATION; OUTER SEGMENTS;
   ALPHA-V-BETA-5 INTEGRIN; MOLECULAR-MECHANISMS; MACROPHAGES;
   GLUCOCORTICOIDS; DIFFERENTIATION; INFLAMMATION; BEVACIZUMAB
AB Background: The apopto-phagocytic gene expression patterns during clearance of dying cells in the retina and the effect of triamcinolone (TC) upon these processes have relevance to development of age-related macular degeneration (AMD).
   Methods: ARPE-19 cells and primary human retinal pigment epithelium (hRPE) were induced to undergo cell death by anoikis and the clearance of these cells by living hRPE/ARPE-19 or human monocyte-derived macrophages (HMDMs) in the presence or absence of TC was quantified by flow cytometry. TaqMan low-density gene expression array determining known markers of phagocytosis and loss-of-function studies on selected apopto-phagocytic genes was carried out in HMDM engulfing anoikic cells.
   Results: The glucocorticoid TC had a profound phagocytosis-enhancing effect on HMDM engulfing anoikic ARPE-19 or hRPE cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and thrombospondin-1 (THSB-1). The key role of the MERTK could be demonstrated in HMDM engulfing dying cells using gene silencing as well as blocking antibodies. Similar pathways were found upregulated in living ARPE-19 engulfing anoikic ARPE-19 cells. Gas6 treatment enhanced phagocytosis in TC-treated HMDMs.
   Conclusions: Specific agonists of the Mertk receptor may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy.
   General significance: The use of Gas6 as enhancer of retinal phagocytosis via the MerTK receptor, alone or in combination with other specific ligands of the tyrosine kinase receptors' family may have a potential role in AMD therapy. (C) 2014 Published by Elsevier B.V.
C1 [Albert, Reka; Vereb, Zoltan; Olah, Brigitta; Facsko, Andrea; Petrovski, Goran] Univ Szeged, Dept Ophthalmol, Fac Med, H-6720 Szeged, Hungary.
   [Albert, Reka; Kristof, Endre; Szatmari-Toth, Maria; Vereb, Zoltan; Olah, Brigitta; Fesues, Laszlo; Petrovski, Goran] Univ Debrecen, Stem Cells & Eye Res Lab, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary.
   [Albert, Reka; Kristof, Endre; Szatmari-Toth, Maria; Vereb, Zoltan; Olah, Brigitta; Fesues, Laszlo; Petrovski, Goran] Univ Debrecen, MTA DE Stem Cell Apoptosis & Genom Res Grp, H-4012 Debrecen, Hungary.
   [Zahuczky, Gabor] UD Genomed Ltd, Debrecen, Hungary.
   [Moe, Morten C.] Univ Oslo, Ctr Eye Res, Dept Ophthalmol, Oslo Univ Hosp, Oslo, Norway.
C3 Szeged University; University of Debrecen; University of Debrecen;
   University of Oslo
RP Petrovski, G (通讯作者)，Univ Szeged, Dept Ophthalmol, Koranyi Fasor 10-11, H-6720 Szeged, Hungary.
EM petrovski.goran@med.u-szeged.hu
RI Vereb, Zoltan/AAR-4092-2020; Kristóf, Endre/AGB-5046-2022; Vereb,
   Zoltan/I-6356-2019
OI Kristóf, Endre/0000-0002-2215-6984; Vereb, Zoltan/0000-0002-9518-2155;
   Petrovski, Goran/0000-0003-2905-9252; Olah,
   Brigitta/0000-0002-1795-3890; Szatmari-Toth, Maria/0000-0003-3028-5097
FU Hungarian Scientific Research Fund [OTKA PD 101316]; National Excellence
   Program [TAMOP-4.2.4.A/2-11-1-2012-0001]
FX The study has been funded by a grant from the Hungarian Scientific
   Research Fund (OTKA PD 101316) and TAMOP-4.2.4.A/2-11-1-2012-0001
   'National Excellence Program' provided personal support to E.K. The
   funders had no role in the study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 48
TC 8
Z9 8
U1 0
U2 9
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD FEB
PY 2015
VL 1850
IS 2
BP 435
EP 446
DI 10.1016/j.bbagen.2014.10.026
PG 12
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA AZ5JF
UT WOS:000348256800020
PM 25450174
DA 2022-11-30
ER

PT J
AU Sacca, SC
   Roszkowska, AM
   Izzotti, A
AF Sacca, Sergio C.
   Roszkowska, Anna Maria
   Izzotti, Alberto
TI Environmental light and endogenous antioxidants as the main determinants
   of non-cancer ocular diseases
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Review
DE UV radiations; Oxidative damage; Antioxidant; Eye
ID RETINAL-PIGMENT EPITHELIUM; COMPLEMENT FACTOR-H; MITOCHONDRIAL-DNA
   DAMAGE; OPEN-ANGLE GLAUCOMA; AGE-RELATED MACULOPATHY; XANTHINE
   OXIDOREDUCTASE/XANTHINE OXIDASE; GLUTATHIONE-RELATED ENZYMES;
   AQUEOUS-HUMOR DYNAMICS; TUMOR-NECROSIS-FACTOR; HUMAN VITREOUS BODY
AB The human eye is constantly exposed to sunlight and artificial lighting. Exogenous sources of reactive oxygen species (ROS) such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins contribute to oxidative damage in ocular tissues. Long-term exposure to these insults places the aging eye at considerable risk for pathological consequences of oxidative stress. Furthermore, in eye tissues, mitochondria are an important endogenous source of ROS. Over time, all ocular structures, from the tear film to the retina, undergo oxidative stress, and therefore, the antioxidant defenses of each tissue assume the role of a safeguard against degenerative ocular pathologies. The ocular surface and cornea protect the other ocular tissues and are significantly exposed to oxidative stress of environmental origin. Overwhelming of antioxidant defenses in these tissues clinically manifests as pathologies including pterygium, corneal dystrophies, and endothelial Fuch's dystrophy. The crystalline lens is highly susceptible to oxidative damage in aging because its cells and their intracellular proteins are not turned over or replaced, thus providing the basis for cataractogenesis. The trabecular meshwork, which is the anterior chamber tissue devoted to aqueous humor drainage, has a particular susceptibility to mitochondrial oxidative injury that affects its endothelium and leads to an intraocular pressure increase that marks the beginning of glaucoma. Photo-oxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration involves oxidative stress and death of the retinal pigment epithelium followed by death of the overlying photoreceptors. Accordingly, converging evidence indicates that mutagenic mechanisms of environmental and endogenous sources play a fundamental pathogenic role in degenerative eye diseases. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Sacca, Sergio C.] St Martino Hosp, Ophthalmol unit, Dept Head Neck Pathol, Genoa, Italy.
   [Roszkowska, Anna Maria] Univ Hosp, Ophthalmol Unit, Dept Specialized Surg, Messina, Italy.
   [Izzotti, Alberto] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
C3 AOU Policlinico Gaetano Martino; University of Genoa
RP Izzotti, A (通讯作者)，Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
EM izzotti@unige.it
RI Saccà, Sergio/AAG-3335-2019; roszkowska, anna/X-2998-2019; Sacca,
   Sergio/D-5118-2018
OI Saccà, Sergio/0000-0001-6973-5978; Sacca, Sergio/0000-0001-6973-5978;
   izzotti, alberto/0000-0002-8588-0347; Roszkowska, Anna
   Maria/0000-0002-8083-3437
FU Glaucoma Foundation, New York, USA
FX This study was supported by The Glaucoma Foundation, New York, USA.
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NR 318
TC 52
Z9 54
U1 1
U2 40
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
EI 1388-2139
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD APR-JUN
PY 2013
VL 752
IS 2
BP 153
EP 171
DI 10.1016/j.mrrev.2013.01.001
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 148LM
UT WOS:000319246100008
PM 23337404
DA 2022-11-30
ER

PT J
AU Kim, SJ
   Kim, J
   Lee, J
   Cho, SY
   Kang, HJ
   Kim, KY
   Jin, DK
AF Kim, Sang Jin
   Kim, Jaeryung
   Lee, Jinyoung
   Cho, Sung Yoon
   Kang, Hee Jung
   Kim, Ki-Yong
   Jin, Dong-Kyu
TI Intravitreal human complement factor H in a rat model of laser-induced
   choroidal neovascularisation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PROTEIN BETA-1H; ACTIVATION; PATHOGENESIS;
   INFLAMMATION; POLYMORPHISM; PATHWAY; MICE
AB Purpose To investigate the inhibitory effect of intravitreally administered human complement factor H (CFH) in a rat model of laser-induced choroidal neovascularisation (CNV).
   Methods Analysis of alternative pathway inhibition by human plasma-purified CFH was conducted by measuring C3 deposition on zymosan particles using rat serum. CNV was induced by laser photocoagulation on Day 0 in the eyes of Brown Norway rats. Human plasma-purified CFH (50 mu g/2 mu l) or phosphate buffered saline was injected intravitreally on Day 0 (prevention arm) or Day 7 (treatment arm). Seven days after injection, eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in flat mounts and quantified using an image analysis programme. Flat mounts were also stained for membrane attack complex.
   Results In rat serum, human CFH inhibited activity of alternative pathway in a dose-dependent manner. On Day 3, mean membrane attack complex deposition in laser-treated retina significantly decreased in CFH-treated eyes (p<0.001). In the prevention arm, the mean CNV area in CFH-treated eyes decreased by 27.0% compared with phosphate buffered saline-treated control eyes on Day 7 (p=0.011). In the treatment arm, the mean CNV area in CFH-treated eyes decreased by 38.3% compared with control eyes on Day 14 (p=0.001).
   Conclusions Intravitreal injection of human CFH resulted in the suppression of formation of new, and regression of preformed laser-induced CNV in the rat model. Human CFH may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.
C1 [Kim, Sang Jin; Kim, Jaeryung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul 135710, South Korea.
   [Lee, Jinyoung] Samsung Biomed Res Inst, Clin Res Ctr, Seoul, South Korea.
   [Lee, Jinyoung] Sungkyunkwan Univ, Dept Hlth Sci & Technol, Grad Sch, SAIHST, Seoul 135710, South Korea.
   [Cho, Sung Yoon; Jin, Dong-Kyu] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul 135710, South Korea.
   [Kang, Hee Jung] Hallym Univ, Coll Med, Dept Lab Med, Anyang, South Korea.
   [Kim, Ki-Yong] Green Cross Co, Yongin, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center; Samsung;
   Sungkyunkwan University (SKKU); Samsung Medical Center; Sungkyunkwan
   University (SKKU); Sungkyunkwan University (SKKU); Samsung Medical
   Center; Hallym University; Green Cross Corporation
RP Jin, DK (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, 50 Irwon Dong, Seoul 135710, South Korea.
EM jindk@skku.edu
RI Kim, Jaeryung/AAB-6693-2022
OI Kim, Jaeryung/0000-0002-8003-5849
FU Korea Healthcare Technology RD Project; Ministry of Health, Welfare and
   Family Affairs, Republic of Korea [A080588]; Samsung Biomedical Research
   Institute [C-A9-240-3]; In-Sung Foundation for Medical Research
FX The study was supported by the Korea Healthcare Technology R&D Project
   funded by the Ministry of Health, Welfare and Family Affairs, Republic
   of Korea (grant number A080588), the Samsung Biomedical Research
   Institute (grant number C-A9-240-3) and the In-Sung Foundation for
   Medical Research.
CR Berkowitz BA, 1998, INVEST OPHTH VIS SCI, V39, P391
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NR 25
TC 18
Z9 19
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2013
VL 97
IS 3
BP 367
EP 370
DI 10.1136/bjophthalmol-2012-302307
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 092ZW
UT WOS:000315162500025
PM 23258212
DA 2022-11-30
ER

PT J
AU Haapasalo, K
   Vuopio, J
   Syrjanen, J
   Suvilehto, J
   Massinen, S
   Karppelin, M
   Jarvela, I
   Meri, S
   Kere, J
   Jokiranta, TS
AF Haapasalo, Karita
   Vuopio, Jaana
   Syrjanen, Jaana
   Suvilehto, Jari
   Massinen, Satu
   Karppelin, Matti
   Jarvela, Irma
   Meri, Seppo
   Kere, Juha
   Jokiranta, T. Sakari
TI Acquisition of Complement Factor H Is Important for Pathogenesis of
   Streptococcus pyogenes Infections: Evidence from Bacterial In Vitro
   Survival and Human Genetic Association
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SHORT CONSENSUS REPEAT; C-REACTIVE PROTEIN; MACULAR DEGENERATION;
   ALTERNATIVE PATHWAY; PHAGOCYTOSIS RESISTANCE; REGULATORY DOMAINS;
   BINDING-SITE; POLYMORPHISM; ACTIVATION; IDENTIFICATION
AB Streptococcus pyogenes (or group A streptococcus [GAS]) is a major human pathogen causing infections, such as tonsillitis, erysipelas, and sepsis. Several GAS strains bind host complement regulator factor H (CFH) via its domain 7 and, thereby, evade complement attack and C3b-mediated opsonophagocytosis. Importance of CFH binding for survival of GAS has been poorly studied because removal of CFH from plasma or blood causes vigorous complement activation, and specific inhibitors of the interaction have not been available. In this study, we found that activation of human complement by different GAS strains (n = 38) correlated negatively with binding of CFH via its domains 5-7. The importance of acquisition of host CFH for survival of GAS in vitro was studied next by blocking the binding with recombinant CFH5-7 lacking the regulatory domains 1-4. Using this fragment in full human blood resulted in death or radically reduced multiplication of all of the studied CFH-binding GAS strains. To study the importance of CFH binding in vivo (i.e., for pathogenesis of streptococcal infections), we used our recent finding that GAS binding to CFH is diminished in vitro by polymorphism 402H, which is also associated with age-related macular degeneration. We showed that allele 402H is suggested to be associated with protection from erysipelas (n = 278) and streptococcal tonsillitis (n = 209) compared with controls (n = 455) (p < 0.05). Taken together, the bacterial in vitro survival data and human genetic association revealed that binding of CFH is important for pathogenesis of GAS infections and suggested that inhibition of CFH binding can be a novel therapeutic approach in GAS infections. The Journal of Immunology, 2012, 188: 426-435.
C1 [Haapasalo, Karita; Suvilehto, Jari; Meri, Seppo; Jokiranta, T. Sakari] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00290 Helsinki, Finland.
   [Haapasalo, Karita; Suvilehto, Jari; Meri, Seppo; Jokiranta, T. Sakari] Univ Helsinki, Haartman Inst, Infect Biol Program, FIN-00290 Helsinki, Finland.
   [Haapasalo, Karita; Meri, Seppo] Univ Helsinki, Cent Hosp Lab, HUSLAB, FIN-00290 Helsinki, Finland.
   [Vuopio, Jaana] Natl Inst Hlth & Welf, Dept Infect Dis, FIN-00271 Helsinki, Finland.
   [Syrjanen, Jaana; Karppelin, Matti] Univ Cent Tampere Hosp, Dept Infect Dis, FIN-33521 Tampere, Finland.
   [Syrjanen, Jaana; Karppelin, Matti] Univ Tampere, Sch Med, FIN-33520 Tampere, Finland.
   [Massinen, Satu; Jarvela, Irma; Kere, Juha] Univ Helsinki, Haartman Inst, Dept Med Genet, FIN-00290 Helsinki, Finland.
   [Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, SE-14183 Stockholm, Sweden.
C3 University of Helsinki; University of Helsinki; University of Helsinki;
   Finland National Institute for Health & Welfare; Tampere University;
   Tampere University Hospital; Tampere University; University of Helsinki;
   Karolinska Institutet
RP Haapasalo, K (通讯作者)，Univ Helsinki, Haartman Inst, POB 21, FIN-00014 Helsinki, Finland.
EM karita.haapasalo@helsinki.fi
RI Kere, Juha/AAX-9117-2021; Jarvela, Irma E/L-5836-2013; Kere,
   Juha/A-9179-2008
OI Kere, Juha/0000-0003-1974-0271; Jarvela, Irma E/0000-0002-1770-6187;
   Kere, Juha/0000-0003-1974-0271; Syrjanen, Jaana/0000-0002-7335-573X;
   Haapasalo, Karita/0000-0002-9619-625X; Karppelin,
   Matti/0000-0002-7503-6900; Meri, Seppo/0000-0001-9142-501X
FU Academy of Finland [128646]; Helsinki University Central Hospital;
   Sigrid Juselius Foundation
FX This work was supported by grants from the Academy of Finland (Project
   128646), Helsinki University Central Hospital funds, and the Sigrid
   Juselius Foundation.
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NR 46
TC 29
Z9 29
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JAN 1
PY 2012
VL 188
IS 1
BP 426
EP 435
DI 10.4049/jimmunol.1102545
PG 10
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 869WE
UT WOS:000298628400049
PM 22140259
DA 2022-11-30
ER

PT J
AU Shirasawa, M
   Arimura, N
   Otsuka, H
   Sonoda, S
   Hashiguchi, T
   Sakamoto, T
AF Shirasawa, Makoto
   Arimura, Noboru
   Otsuka, Hiroki
   Sonoda, Shozo
   Hashiguchi, Teruto
   Sakamoto, Taiji
TI Intravitreous VEGF-A in eyes with massive vitreous hemorrhage
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Plasmin; Vitrectomy; Diabetes; Platelet; Thrombin
ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; MACULAR
   EDEMA; BIOACTIVITY; PLATELETS; BINDING
AB Although vascular endothelial growth factor (VEGF) is abundant in serum, the intraocular concentration of VEGF in eyes with massive vitreous hemorrhage (VH) is not well-known. The present study was conducted to elucidate the effects of a massive VH on intravitreous VEGF concentration.
   Vitreous samples were obtained during vitrectomy: 12 samples from eyes with epiretinal membrane without diabetic retinopathy (DR), and nine samples from massive VH with no DR, such as age-related macular degeneration, rhegmatogenous VH, Terson's syndrome and macro-aneurysm rupture. Twelve samples were obtained from proliferative DR. VEGF was measured with an enzyme-linked immunosorbent assay (ELISA). Samples incubated with or without heparin were also examined for the release of VEGF binding to the vitreous body. The localization of VEGF and type II collagen in the vitreous was evaluated from immunohistochemistry.
   The concentration of VEGF was significantly higher in eyes with proliferative DR (821 +/- 949 pg/ml) than in non-DR with massive VH (2.75 +/- 7.5 pg/ml, P < 0.01, chi-square test) or non-DR with no VH (less than detectable level, P < 0.01, chi-square test) There was no statistically significant difference between eyes with massive VH and non-diabetic eyes without VH. Treatment with heparin did not significantly affect the concentration of vitreous VEGF. VEGF was localized mainly in the clot from the results of an immunohistochemical analysis.
   Even with a massive VH, diffusible VEGF does not increase significantly in the liquid phase and is principally present in a clot. VH alone should not be an indication for vitrectomy from the point of view of VEGF-related pathology.
C1 [Shirasawa, Makoto; Arimura, Noboru; Otsuka, Hiroki; Sonoda, Shozo; Sakamoto, Taiji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Fac Med, Kagoshima 8908520, Japan.
   [Hashiguchi, Teruto] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Lab & Vasc Med, Kagoshima 8908520, Japan.
C3 Kagoshima University; Kagoshima University
RP Sakamoto, T (通讯作者)，Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Fac Med, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan.
EM tsakamot@m3.kufm.kagoshima-u.ac.jp
FU Research Committee on Chorioretinal Degeneration and Optic Atrophy,
   Ministry of Health, Labor, and Welfare; Ministry of Education, Science,
   and Culture of the Japanese Government
FX Grant support Supported in part by a Grant from the Research Committee
   on Chorioretinal Degeneration and Optic Atrophy, Ministry of Health,
   Labor, and Welfare; by a Grant-in-Aid for Scientific Research from the
   Ministry of Education, Science, and Culture of the Japanese Government.
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NR 17
TC 5
Z9 5
U1 0
U2 5
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 DEC
PY 2011
VL 249
IS 12
BP 1805
EP 1810
DI 10.1007/s00417-011-1795-5
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 857VK
UT WOS:000297751000010
PM 21853228
DA 2022-11-30
ER

PT J
AU Czoski-Murray, C
   Carlton, J
   Brazier, J
   Young, T
   Papo, NL
   Kang, HK
AF Czoski-Murray, Carolyn
   Carlton, Jill
   Brazier, John
   Young, Tracey
   Papo, Natalie L.
   Kang, Hyong Kwon
TI Valuing Condition-Specific Health States Using Simulation Contact Lenses
SO VALUE IN HEALTH
LA English
DT Article
DE age-related macular degeneration; health-related quality of life;
   quality of life; United Kingdom
ID MACULAR DEGENERATION; UTILITY VALUES; IMPAIRMENT; QUALITY; EUROQOL;
   INDEX; LIFE
AB Objective:
   This article reports on a study that used contact lenses to simulate the effects of a visual impairment caused by age-related macular degeneration (ARMD). The primary objective was to examine the feasibility of using this method of simulation. A secondary objective was to compare the results from this experiment with those obtained from ARMD patients (n = 209) using generic preference-based measures (Health Utilities Index 3 (HUI3) and EUROQOL 5 Dimensions (EQ-5D) and patient time trade-off (TTO).
   Methods:
   Utility values were elicited from healthy participants (n = 108) for three ARMD states simulated using contact lenses.
   Results:
   A significant relationship was found between visual acuity and TTO values elicited from our sample population (n = 108). It was stronger than that found for HUI3, EQ-5D, and own TTO values from patients (n = 209). Our sample values informed by the experience of simulation were found to be significantly different from values from patient TTO and generic preference-based measures obtained from patients for the same level of visual impairment. Sociodemographic characteristics did not significantly affect results, although baseline TTO utility values were positively associated with TTO values for simulated states. Nevertheless, the patient population was significantly older than the sample population.
   Conclusions:
   ARMD has a major impact on our sample values TTO health state values. Differences across four visual health severity groups appear larger than those found for a generic preference-based measure and patient TTO values. For conditions that are difficult to describe and imagine, simulation methods may offer an additional tool when combined with usual methods of description for obtaining better informed general population preferences.
C1 [Czoski-Murray, Carolyn] Univ Sheffield, Sch Hlth & Related Res, Sheffield S1 4DA, S Yorkshire, England.
C3 University of Sheffield
RP Czoski-Murray, C (通讯作者)，Univ Sheffield, Sch Hlth & Related Res, 30 Regent St, Sheffield S1 4DA, S Yorkshire, England.
EM j.e.brazier@shef.ac.uk
RI brazier, john e/B-1936-2008; Carlton, Jill/E-6673-2010; Carlton,
   Jill/N-3225-2019; Young, Tracey A/A-4543-2010
OI Carlton, Jill/0000-0002-9373-7663; Carlton, Jill/0000-0002-9373-7663;
   Czoski Murray, Carolyn/0000-0001-7742-2883; Brazier,
   John/0000-0001-8645-4780; Young, Tracey/0000-0001-8467-0471
FU Novartis UK; MRC [MC_U145080960] Funding Source: UKRI; Medical Research
   Council [MC_U145080960] Funding Source: researchfish
FX Source of financial support: We acknowledge the receipt of a grant from
   Novartis UK to complete this work.
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NR 20
TC 43
Z9 46
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD JUL-AUG
PY 2009
VL 12
IS 5
BP 793
EP 799
DI 10.1111/j.1524-4733.2009.00527.x
PG 7
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 459SR
UT WOS:000267130200021
PM 19490557
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Satofuka, S
   Ichihara, A
   Nagai, N
   Noda, K
   Ozawa, Y
   Fukamizu, A
   Tsubota, K
   Itoh, H
   Oike, Y
   Ishida, S
AF Satofuka, Shingo
   Ichihara, Atsuhiro
   Nagai, Norihiro
   Noda, Kousuke
   Ozawa, Yoko
   Fukamizu, Akiyoshi
   Tsubota, Kazuo
   Itoh, Hiroshi
   Oike, Yuichi
   Ishida, Susumu
TI (Pro)renin Receptor Promotes Choroidal Neovascularization by Activating
   Its Signal Transduction and Tissue Renin-Angiotensin System
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; NONPROTEOLYTIC ACTIVATION; DEFICIENT MICE;
   METABOLIC SYNDROME; PRORENIN; INFLAMMATION; EXPRESSION;
   GLOMERULOSCLEROSIS; NEPHROPATHY; HYPOTENSION
AB The receptor-associated prorenin system (RAPS) refers to pathogenic mechanisms whereby prorenin binding to its receptor activates both the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling pathways. Although we found significant involvement of angiotensin H type 1 receptor (AT1-R)-mediated inflammation in choroidal neovascularization (CNV), a central abnormality of vision-threatening age-related macular degeneration, the association of RAPS with CNV has not been defined. Here, (pro)renin receptor blockade in a murine model of laser-induced CNV led to the significant suppression of CNV together with macrophage infiltration and the up-regulation of intercellular adhesion molecule (ICAM-1), monocyte chemotactic protein (MCP-1), vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2. To clarify the role of signal transduction via the (pro)renin receptor in CNV, we used mice in which renin-angiotensin system was deactivated by either the pharmacological blockade of AT1-R with losartan or the genetic ablation of AT1-R or angiotensinogen. Compared with wild type controls, these mice exhibited significant reduction of CNV and macrophage infiltration, both of which were further suppressed by (pro)renin receptor blockade. The (pro)renin receptor and phosphorylated extracellular signal-regulated kinases (ERK) were co-localized in vascular endothelial cells and macrophages in CNV. (Pro)renin receptor blockade suppressed ERK activation and the production of MCP-1 and VEGF, but not ICAM-1, VEGFR-1, or VEGFR-2, in AT1-R-deficient mice with CNV and in losartan-treated microvascular endothelial cells and macrophages. These results indicate the significant contribution of RAPS to CNV pathogenesis. (Am J Pathol, 2008, 173:1911-1918; DOI: 10.2353/ajpath.2008.080457)
C1 [Ishida, Susumu] Keio Univ, Sch Med, Inaida Endowed Dept Antiaging Ophthalmol, Lab Retinal Cell Biol,Shinjuku Ku, Tokyo 1608582, Japan.
   [Satofuka, Shingo; Nagai, Norihiro; Noda, Kousuke; Ozawa, Yoko; Tsubota, Kazuo; Ishida, Susumu] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo 1608582, Japan.
   [Ichihara, Atsuhiro; Itoh, Hiroshi] Keio Univ, Sch Med, Dept Internal Med, Tokyo 1608582, Japan.
   [Fukamizu, Akiyoshi] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki, Japan.
   [Oike, Yuichi] Kumamoto Univ, Dept Mol Genet, Grad Sch Med Sci, Kumamoto, Japan.
C3 Keio University; Keio University; Keio University; University of
   Tsukuba; Kumamoto University
RP Ishida, S (通讯作者)，Keio Univ, Sch Med, Inaida Endowed Dept Antiaging Ophthalmol, Lab Retinal Cell Biol,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ishidasu@sc.itc.keio.ac.jp
RI ISHIDA, SUSUMU/D-7067-2012; fukamizu, akiyoshi/J-5350-2012; Ozawa,
   Yoko/AAH-9888-2020
OI fukamizu, akiyoshi/0000-0002-8786-6020; 
FU Japanese Ministry of Education, Culture, Sports, Science and Technology
   [18791296]
FX Supported by Grant-in-Aid for Scientific Research of Japanese Ministry
   of Education, Culture, Sports, Science and Technology (No. 18791296 to
   S.S.).
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NR 28
TC 48
Z9 57
U1 0
U2 3
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 2008
VL 173
IS 6
BP 1911
EP 1918
DI 10.2353/ajpath.2008.080457
PG 8
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 377LU
UT WOS:000261253500031
PM 18974301
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhou, JL
   Cai, BL
   Jang, YP
   Pachydaki, S
   Schmidt, AM
   Sparrow, JR
AF Zhou, JL
   Cai, BL
   Jang, YP
   Pachydaki, S
   Schmidt, AM
   Sparrow, JR
TI Mechanisms for the induction of HNE- MDA- and AGE-adducts, RAGE and VEGF
   in retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium;
   lipofuscin; A2E; lipid peroxidation; 4-hydroxynonenal; HNE;
   malondialdhyde; MDA; advanced glycation end products; RAGE; vascular
   endothelial growth factor
ID GLYCATION END-PRODUCTS; ENDOTHELIAL GROWTH-FACTOR; 4-HYDROXYNONENAL
   PROTEIN ADDUCTS; LIPID-PEROXIDATION PRODUCTS; LIGHT-INDUCED DAMAGE;
   LIPOFUSCIN FLUOROPHORE; MACULAR DEGENERATION; RECEPTOR RAGE;
   IMMUNOHISTOCHEMICAL DETECTION; CHOROIDAL NEOVASCULARIZATION
AB Pathological features of age-related macular degeneration such as the formation of extracellular deposits and neovascularization are frequently viewed as outcomes of compromising processes within retinal pigment epithelial cells, but the initiating circumstances are poorly understood. Here we tested the hypothesis that photooxidation events initiated by A2E, a blue light-excitable aging fluorophore of the retinal pigment epithelium, can set the stage for altered cellular signaling and changes in the expression of genes that can impact the extracellular milieu. Proteins modified by lipid peroxidation products (4-hydroxynonenal; malondialdhyde) and advanced glycation end products were detected at sites of blue light irradiation both in association with the cultured A2E-laden retinal pigment epithelial cells and within the fibronectin substrate on which the cells were grown. RAGE, the cell surface receptor that transduces the effects of advanced glycation end products, was also upregulated, and RAGE expression co-localized with the deposition of advanced glycation end products. Blue light triggered alterations in gene expression was also evidenced by elevations in both transcripts and protein for vascular endothelial growth factor, a potent angiogenic and penneability-enhancing factor. These findings indicate that cell associated and extracellular modification of proteins by lipid peroxidation products and advanced glycation end products together with increased expression of RAGE and vascular endothelial growth factor may be induced consequent to blue light illumination of A2E-burdened retinal pigment epithelial cells. Thus, photooxidative events that are not an immediate threat to retinal pigment epithelial cell viability may nevertheless elicit sustained perturbation that could ultimately alter neighboring tissues and impact retinal pigment epithelia] cell function. (c) 2004 Elsevier Ltd. All rights reserved.
C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   Columbia Univ, Dept Chem, New York, NY 10032 USA.
   Columbia Univ, Dept Surg, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Sparrow, JR (通讯作者)，Columbia Univ, Dept Ophthalmol, 630 W 168th St, New York, NY 10032 USA.
EM jrs88@columbia.edu
RI Jang, Young Pyo/AAJ-8782-2020
OI Jang, Young Pyo/0000-0001-5865-9228
FU NATIONAL EYE INSTITUTE [R01EY012951] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY012951-11, EY12951] Funding Source: Medline
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NR 93
TC 93
Z9 108
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 APR
PY 2005
VL 80
IS 4
BP 567
EP 580
DI 10.1016/j.exer.2004.11.009
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 914YN
UT WOS:000228264200013
PM 15781285
DA 2022-11-30
ER

PT J
AU Caicedo, A
   Espinosa-Heidmann, DG
   Hamasaki, D
   Pina, Y
   Cousins, SW
AF Caicedo, A
   Espinosa-Heidmann, DG
   Hamasaki, D
   Pina, Y
   Cousins, SW
TI Photoreceptor synapses degenerate early in experimental choroidal
   neovascularization
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE age-related macular degeneration; macrophages; Muller glial cell;
   electroretinogram; FM1-43
ID ARGON-LASER PHOTOCOAGULATION; TREATED RAT MODEL; MACULAR DEGENERATION;
   GROWTH-FACTOR; INTRAVITREAL TRIAMCINOLONE; PHOTODYNAMIC THERAPY;
   RETINITIS-PIGMENTOSA; RETINAL DEGENERATION; ALZHEIMERS-DISEASE;
   CLINICAL-TRIALS
AB Severe visual loss in patients with age-related macular degeneration is associated with the development of choroidal neovascularization (CNV). The pathogenic mechanisms for CNV formation have been extensively investigated, but remarkably little research has addressed the mechanisms for dysfunction of the retina in CNV. Using laser-induced CNV in mice, we evaluated the mechanisms of retinal dysfunction. At 3 days, 1 week, 2 weeks, and 4 weeks after laser application, retinas under experimental CNV were characterized physiologically (ERG recordings, synaptic uptake of the exocytotic marker FM1-43, and light-induced translocation of transducin), histologically, and immunohistochemically. ERG amplitudes were reduced by 20% at 1 week after CNV. Depolarization-induced FM1-43 uptake in photoreceptor synapses was selectively reduced by 45% at 1 week after CNV. Although photoreceptor outer segments were shortened by 36%, light adaptation as measured by transducin translocation was mostly preserved. Early in CNV (3 days to 1 week), Muller cells demonstrated induction of c-fos and pERK expression. Also, the density of macrophage-like, F4/80 immunoreactive cells increased similar to3-fold. Minimal photoreceptor death occurred during the first week, and was variable thereafter. At later times in CNV formation ( greater than or equal to2 weeks), expression of photoreceptor synaptic markers was reduced in the outer plexiform layer, indicating loss of photoreceptor synaptic terminals. ERG amplitudes, synaptic uptake of FM1-43, and the induction of c-fos and pERK in Muller cells were altered within 1 week of experimental CNV, suggesting that during CNV formation, deficits in retinal function, in particular photoreceptor synaptic function, precede degeneration of photoreceptor terminals and photoreceptor cell death. (C) 2005 Wiley-Liss, Inc.
C1 Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami Beach, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami
RP Caicedo, A (通讯作者)，Univ Miami, Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami Beach, FL 33136 USA.
EM acaicedo@med.miami.edu
RI Caicedo, Alejandro/F-1202-2010; Caicedo, Alejandro/AAC-8544-2020
FU NEI NIH HHS [EY/AI 13318, P30 EY14801] Funding Source: Medline; NIDCD
   NIH HHS [DC 4525] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [P30EY014801, R01EY013318] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [R03DC004525]
   Funding Source: NIH RePORTER
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NR 68
TC 20
Z9 20
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD MAR 14
PY 2005
VL 483
IS 3
BP 263
EP 277
DI 10.1002/cne.20413
PG 15
WC Neurosciences; Zoology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Zoology
GA 893RD
UT WOS:000226736000002
PM 15682400
DA 2022-11-30
ER

PT J
AU Shiose, S
   Hata, Y
   Noda, Y
   Sassa, Y
   Takeda, A
   Yoshikawa, H
   Fujisawa, K
   Kubota, T
   Ishibashi, T
AF Shiose, S
   Hata, Y
   Noda, Y
   Sassa, Y
   Takeda, A
   Yoshikawa, H
   Fujisawa, K
   Kubota, T
   Ishibashi, T
TI Fibrinogen stimulates in vitro angiogenesis by choroidal endothelial
   cells via autocrine VEGF
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID CARDIOVASCULAR RISK-FACTORS; HYPOXIA-INDUCIBLE FACTOR-1; GROWTH-FACTOR;
   MACULAR DEGENERATION; DIABETIC-RETINOPATHY; NEOVASCULAR MEMBRANES; TUMOR
   ANGIOGENESIS; PLASMA-FIBRINOGEN; SIGNALING PATHWAY; FACTOR EXPRESSION
AB Background: The purpose of this study is to investigate the effect of fibrinogen on angiogenesis in vitro formed by cultured bovine choroidal endothelial cells (BCECs) and the involvement of vascular endothelial growth factor (VEGF) in this mechanism. Methods: For in vitro tube formation assay, BCECs were seeded on collagen gel containing fibrinogen (0-1.5 mg/ml). After 3 days of cultivation, the total length of the tubular structure was measured using Macscope Analyzer. Total RNA and conditioned media were collected after fibrinogen treatment and subjected to Northern and Western blot analyses, respectively. Transcription factor HIF-1alpha was also analyzed by Western blot analysis using cytosolic and nuclear fraction of BCECs. Involvement of VEGF in fibrinogen-dependent in vitro tube formation was evaluated using anti-VEGF neutralizing antibody or VEGF receptor 2-selective inhibitor (SU5416). Results: Formation of the tubular structure was enhanced 20similar to50 times in fibrinogen-containing gel in a concentration-dependent manner. The treatment of BCECs with fibrinogen resulted in a significant increase in VEGF gene and protein expression. Accumulation of HIF-1alpha protein in the nuclear fraction was also detected after the treatment with fibrinogen. Finally, fibrinogen-induced tube formation was significantly inhibited in the presence of anti-VEGF-neutralizing antibody (52.0% inhibition at the concentration of 1 mug/ml, P<0.05) or SU5416 (54.8% inhibition at the concentration of 3 mu M, P<0.05). Conclusions: Extravasated fibrinogen might play an important role in the development of choroidal neovascularization associated with age-related macular degeneration, at least in part, through the function of VEGF in an autocrine manner. Transcription factor HIF-1 appears to be involved in fibrinogen-induced VEGF expression.
C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan.
C3 Kyushu University
RP Shiose, S (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM asshy@med.kyushu-u.ac.jp
RI Kubota, Toshiaki/AAN-4334-2021; Sassa, Yukio/H-6339-2012
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NR 44
TC 27
Z9 28
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD SEP
PY 2004
VL 242
IS 9
BP 777
EP 783
DI 10.1007/s00417-004-0910-2
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 862US
UT WOS:000224517300009
PM 15103470
DA 2022-11-30
ER

PT J
AU Wang, YS
   Friedrichs, U
   Eichler, W
   Hoffmann, S
   Wiedemann, P
AF Wang, YS
   Friedrichs, U
   Eichler, W
   Hoffmann, S
   Wiedemann, P
TI Inhibitory effects of triamcinolone acetonide on bFGF-induced migration
   and tube formation in choroidal microvascular endothelial cells
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; MATRIX METALLOPROTEINASES; MACULAR DEGENERATION;
   IN-VITRO; INTRAVITREAL TRIAMCINOLONE; NEOVASCULAR MEMBRANES; EXPRESSION;
   DIFFERENTIATION; CORTICOSTEROIDS; PROLIFERATION
AB Background: Angiostatic drugs might provide desirable modulation of choroidal angiogenesis-related diseases, including histoplasmosis and the exudative form of age-related macular degeneration. However, the precise effects of this class of compounds in the choroidal neovascularization are still unclear. In the present study, we investigated the effects of triamcinolone acetonide (TA), an angiostatic steroid, on choroidal angiogenesis in vitro. Methods: Bovine choroidal endothelial cells (CEC), which are the critical cellular component of choroidal angiogenesis in vivo, were isolated with Lycopersicon esculentum agglutinin-coated Dynabeads and cultured in EGM medium. CEC were treated with basic fibroblast growth factor (bFGF) and TA at various concentrations ranging from 50 to 300 mg/l. The capacities for CEC migration and tube formation were evaluated with the modified Boyden chamber and the Vitrogen collagen assay, respectively. The activities of matrix metalloproteinases (MMP)-2 and -9 were examined using gelatin zymography. Results The stimulation of CEC with 50 ng/ml bFGF resulted in an increase of about 100% in migration activity (P<0.01). Preincubation of CEC with TA at the indicated concentrations for 20 min inhibited the bFGF-stimulated migration in a dose-dependent manner (P<0.01). After 5 days, the bFGF-stimulated tube formation in CEC was inhibited by TA at the concentrations 100, 150 and 300 mg/l (P<0.01). Gelatin zymography of the culture media of CEC showed that the bFGF-induced activation of MMP-2 was attenuated by 300 mg/l TA (P&LT;0.05). Conclusion: Downregulation of the activation of MMPs in CEC could be one of the mechanisms by which angiostatic steroids inhibit choroidal angiogenesis.
C1 Univ Leipzig, Fac Med, Dept Ophthalmol, D-04103 Leipzig, Germany.
   Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Peoples R China.
C3 Leipzig University; Air Force Military Medical University
RP Wiedemann, P (通讯作者)，Univ Leipzig, Fac Med, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
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NR 40
TC 90
Z9 98
U1 0
U2 3
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JAN
PY 2002
VL 240
IS 1
BP 42
EP 48
DI 10.1007/s00417-001-0398-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 528CJ
UT WOS:000174226300009
PM 11954780
DA 2022-11-30
ER

PT J
AU Seebock, P
   Orlando, JI
   Schlegl, T
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   Bogunovic, H
   Klimscha, S
   Langs, G
   Schmidt-Erfurth, U
AF Seebock, Philipp
   Orlando, Jose Ignacio
   Schlegl, Thomas
   Waldstein, Sebastian M.
   Bogunovic, Hrvoje
   Klimscha, Sophie
   Langs, Georg
   Schmidt-Erfurth, Ursula
TI Exploiting Epistemic Uncertainty of Anatomy Segmentation for Anomaly
   Detection in Retinal OCT
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Retina; Uncertainty; Diseases; Anomaly detection; Image segmentation;
   Biomarkers; Training; Weakly supervised learning; anomaly detection;
   biomarker discovery; optical coherence tomography; epistemic uncertainty
ID CLASSIFICATION
AB Diagnosis and treatment guidance are aided by detecting relevant biomarkers in medical images. Although supervised deep learning can perform accurate segmentation of pathological areas, it is limited by requiring a priori definitions of these regions, large-scale annotations, and a representative patient cohort in the training set. In contrast, anomaly detection is not limited to specific definitions of pathologies and allows for training on healthy samples without annotation. Anomalous regions can then serve as candidates for biomarker discovery. Knowledge about normal anatomical structure brings implicit information for detecting anomalies. We propose to take advantage of this property using Bayesian deep learning, based on the assumption that epistemic uncertainties will correlate with anatomical deviations from a normal training set. A Bayesian U-Net is trained on a well-defined healthy environment using weak labels of healthy anatomy produced by existing methods. At test time, we capture epistemic uncertainty estimates of our model using Monte Carlo dropout. A novel post-processing technique is then applied to exploit these estimates and transfer their layered appearance to smooth blob-shaped segmentations of the anomalies. We experimentally validated this approach in retinal optical coherence tomography (OCT) images, using weak labels of retinal layers. Our method achieved a Dice index of 0.789 in an independent anomaly test set of age-related macular degeneration (AMD) cases. The resulting segmentations allowed very high accuracy for separating healthy and diseased cases with late wet AMD, dry geographic atrophy (GA), diabetic macular edema (DME) and retinal vein occlusion (RVO). Finally, we qualitatively observed that our approach can also detect other deviations in normal scans such as cut edge artifacts.
C1 [Seebock, Philipp; Langs, Georg] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Computat Imaging Res Lab, A-1090 Vienna, Austria.
   [Seebock, Philipp; Orlando, Jose Ignacio; Schlegl, Thomas; Waldstein, Sebastian M.; Bogunovic, Hrvoje; Klimscha, Sophie; Langs, Georg; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, A-1090 Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Seebock, P; Langs, G (通讯作者)，Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Computat Imaging Res Lab, A-1090 Vienna, Austria.
EM philipp.seeboeck@meduniwien.ac.at; georg.langs@meduniwien.ac.at
RI Orlando, José Ignacio/AAB-3411-2020; Bogunovic, Hrvoje/J-3445-2014
OI Orlando, José Ignacio/0000-0001-9734-5571; Waldstein,
   Sebastian/0000-0003-2899-6279; Riedl, Sophie/0000-0003-0003-0886;
   Schlegl, Thomas/0000-0003-0706-7876; Bogunovic,
   Hrvoje/0000-0002-9168-0894
FU Christian Doppler Research Association; Austrian Federal Ministry for
   Digital and Economic Affairs; National Foundation for Research,
   Technology, and Development; Austrian Science Fund [FWF I2714-B31]; WWTF
   AugUniWien [FA7464A0249, VRG12-009]
FX This work was support in part by the Christian Doppler Research
   Association, in part by the Austrian Federal Ministry for Digital and
   Economic Affairs, in part by the National Foundation for Research,
   Technology, and Development, and in part by the Austrian Science Fund
   FWF I2714-B31. The work of J. I. Orlando was supported by WWTF
   AugUniWien under Grant FA7464A0249 (Medical University of Vienna) and
   Grant VRG12-009 (University of Vienna).
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NR 47
TC 42
Z9 42
U1 4
U2 31
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 JAN
PY 2020
VL 39
IS 1
BP 87
EP 98
DI 10.1109/TMI.2019.2919951
PG 12
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 KB6BA
UT WOS:000506577100008
PM 31170065
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Bravo-Osuna, I
   Andres-Guerrero, V
   Arranz-Romera, A
   Esteban-Perez, S
   Molina-Martinez, IT
   Herrero-Vanrell, R
AF Bravo-Osuna, Irene
   Andres-Guerrero, Vanessa
   Arranz-Romera, Alicia
   Esteban-Perez, Sergio
   Molina-Martinez, Irene T.
   Herrero-Vanrell, Rocio
TI Microspheres as intraocular therapeutic tools in chronic diseases of the
   optic nerve and retina
SO ADVANCED DRUG DELIVERY REVIEWS
LA English
DT Review
DE Microspheres Protein release; Age-related-macular degeneration (AMD);
   Glaucoma; Diabetic retinopathy (RD); Neuroprotection; Animal models;
   Peptides release
ID ENDOTHELIAL GROWTH-FACTOR; GANGLION-CELL DEATH; NEUROTROPHIC FACTOR
   GDNF; MACULAR DEGENERATION; CONTROLLED-RELEASE; BIODEGRADABLE
   MICROSPHERES; INTRAVITREAL INJECTION; DIABETIC-RETINOPATHY; PLGA
   MICROSPHERES; DRUG-DELIVERY
AB Pathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment. The prevalence of neurodegenerative diseases of the posterior segment is increased as most of them are related with the elderly. Even with the access to different treatments, there are some challenges in managing patients suffering retinal diseases. One of them is the need for frequent interventions. Also, an unpredictable response to therapy has suggested that different pathways may be playing a role in the development of these diseases. The management of these pathologies requires the development of controlled drug delivery systems able to slow the progression of the disease without the need of frequent invasive interventions, typically related with endophthalmitis, retinal detachment, ocular hypertension, cataract, inflammation, and floaters, among other. Biodegradable microspheres are able to encapsulate low molecular weight substances and large molecules such as biotechnological products. Over the last years, a large variety of active substances has been encapsulated in microspheres with the intention of providing neuroprotection of the optic nerve and the retina.
   The purpose of the present review is to describe the use of microspheres in chronic neurodegenerative diseases affecting the retina and the optic nerve. The advantage of microencapsulation of low molecular weight drugs as well as therapeutic peptides and proteins to be used as neuroprotective strategy is discussed. Also, a new use of the micro spheres in the development of animal models of neurodegeneration of the posterior segment is described. (C) 2018 Elsevier B.V. All rights reserved.
C1 [Herrero-Vanrell, Rocio] Univ Complutense Madrid, Sch Pharm, Dept Pharm & Pharmaceut Technol, Madrid, Spain.
   San Carlos Clin Hosp IdISSC, Sanit Res Inst, Madrid, Spain.
   Inst Hlth Carlos III, Ocular Pathol Natl Net OFTARED, Madrid, Spain.
   Univ Complutense Madrid, Sch Pharm, IUFI, Madrid, Spain.
C3 Complutense University of Madrid; Complutense University of Madrid
RP Herrero-Vanrell, R (通讯作者)，Univ Complutense Madrid, Sch Pharm, Dept Pharm & Pharmaceut Technol, Madrid, Spain.
EM rociohv@ucm.es
RI Martínez, Irene Teresa Molina/G-4970-2017; bravo-osuna,
   irene/M-3469-2015; Andrés-Guerrero, Vanessa/K-8077-2015; Pérez, Sergio
   Esteban/K-6400-2017
OI Martínez, Irene Teresa Molina/0000-0002-9157-571X; bravo-osuna,
   irene/0000-0003-3133-7872; Andrés-Guerrero, Vanessa/0000-0003-0157-1932;
   Pérez, Sergio Esteban/0000-0003-4832-0778
FU MINECO/AEI/FEDER, UE [MAT2013-43127-R, MAT2017-83858-C2-1]; Complutense
   University Research Group [UCM-920415]; Red Tematica de Investigacion
   Cooperativa en Oftalmologia RETICS (Oftared) [RD16/0008 ISCIII-FEDER];
   Spanish Fund for Health Research [PI17/00079]
FX MAT2013-43127-R and MAT2017-83858-C2-1 MINECO/AEI/FEDER, UE; Complutense
   University Research Group UCM-920415; Red Tematica de Investigacion
   Cooperativa en Oftalmologia RETICS (Oftared) RD16/0008 ISCIII-FEDER;
   Spanish Fund for Health Research PI17/00079.
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NR 144
TC 20
Z9 21
U1 4
U2 56
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0169-409X
EI 1872-8294
J9 ADV DRUG DELIVER REV
JI Adv. Drug Deliv. Rev.
PD FEB 15
PY 2018
VL 126
BP 127
EP 144
DI 10.1016/j.addr.2018.01.007
PG 18
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GK5MY
UT WOS:000436220400009
PM 29339146
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Freund, KB
   Yannuzzi, LA
   Dolz-Marco, R
   Souied, E
   Capuano, V
   Semoun, O
   Phasukkijwatana, N
   Sarraf, D
   Carnevali, A
   Querques, L
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Freund, K. Bailey
   Yannuzzi, Lawrence A.
   Dolz-Marco, Rosa
   Souied, Eric
   Capuano, Vittorio
   Semoun, Oudy
   Phasukkijwatana, Nopasak
   Sarraf, David
   Carnevali, Adriano
   Querques, Lea
   Bandello, Francesco
   Querques, Giuseppe
TI The Expanded Spectrum of Perifoveal Exudative CD Vascular Anomalous
   Complex
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; RETINAL ANGIOMATOUS PROLIFERATION;
   TYPE-3 NEOVASCULARIZATION; DIABETIC-RETINOPATHY; VEIN OCCLUSION;
   MACROANEURYSMS; CLASSIFICATION; FEATURES
AB PURPOSE: To expand our understanding of the uncommon entity, referred to as perifoveal exudative vascular anomalous complex (PEVAC) by describing multimodal imaging findings, including optical coherence tomography angiography (OCT-A).
   DESIGN: Retrospective cohort study.
   METHODS: Patients diagnosed with PEVAC were identified at 4 retina referral centers worldwide and underwent complete ophthalmologic examination including structural OCT, OCT-A, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Demographics and clinical findings were analyzed at baseline and at available follow-ups.
   RESULTS: Fifteen eyes (15 patients, mean age 73 +/- 13 years) were included. Six of 15 eyes were diagnosed with coincident age-related macular degeneration (AMD) and 2 with myopic macular degeneration. On fundus examination PEVAC presented as a large perifoveal isolated aneurysm, unifocal in 12 of 15 eyes, associated with small retinal hemorrhages and intraretinal exudation. On structural OCT, PEVAC appeared as a round hyperreflective lesion with hyporeflective lumen, typically surrounded by intraretinal cystic spaces. Dye angiography demonstrated a well-defined hyperfluorescent lesion with variable leakage on FA and without leakage on ICGA. OCT-A showed flow signal correlating with the aneurysmal lesion connecting to retinal capillary plexuses. Seven patients were followed for 13.0 +/- 10.5 months with no evidence of functional/anatomic changes. Three patients underwent anti-vascular endothelial growth factor (VEGF) intravitreal injections without improvement. Two eyes were associated with a type 3 neovascularization eccentric to PEVAC.
   CONCLUSIONS: PEVAC is an isolated, perifoveal, aneurysmal abnormality, occurring in otherwise healthy patients who may manifest other macular disease including AMD and myopic macular degeneration. PEVAC did not typically respond to anti-VEGF therapy, and may be associated with type 3 neovascularization. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Sacconi, Riccardo; Carnevali, Adriano; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, Dept Ophthalmol, IRCCS, Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
   [Freund, K. Bailey; Yannuzzi, Lawrence A.; Dolz-Marco, Rosa] Vitreous Retina Macula Consultants New York, New York, NY USA.
   [Souied, Eric; Capuano, Vittorio; Semoun, Oudy] Univ Paris Est Creteil, Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Phasukkijwatana, Nopasak; Sarraf, David] Univ Calif Los Angeles, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA USA.
   [Sacconi, Riccardo] Univ Verona, Dept Neurol & Movement Sci, Eye Clin, Verona, Italy.
   [Carnevali, Adriano] Magna Graecia Univ Catanzaro, Dept Ophthalmol, Catanzaro, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   Vitreous Retina Macula Consultants of New York; Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; University of
   California System; University of California Los Angeles; University of
   Verona; Magna Graecia University of Catanzaro
RP Querques, G (通讯作者)，Univ Vita Salute, Dept Ophthalmol, IRCCS, Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Phasukkijwatana, Nopasak/T-8630-2019; bandello, francesco/AAH-2405-2019;
   Freund, K. Bailey/V-7488-2018
OI bandello, francesco/0000-0003-3238-9682; Querques,
   Giuseppe/0000-0002-3292-9581; Sacconi, Riccardo/0000-0003-2891-2012;
   Freund, K. Bailey/0000-0002-7888-9773
FU Allergan Inc (Irvine, California, USA); Genentech (San Francisco,
   California, USA); Heidelberg (Heidelberg, Germany); Regeneron
   (Tarrytown, New York, USA); Optovue (Fremont, California, USA)
FX K. BAILEY FREUND IS A CONSULTANT FOR Genentech (San Francisco,
   California, USA), Optovue (Fremont, California, USA), Heidelberg
   Engineering (Heidelberg, Germany), Optos (Dunfermline, United Kingdom),
   and Bayer Schering Pharma (Berlin, Germany). Eric Souied is a consultant
   for Allergan Inc (Irvine, California, USA), Bausch and Lomb (Rochester,
   New York, USA), Bayer Schering Pharma (Berlin, Germany), and Novartis
   (Basel, Switzerland). David Sarraf is a consultant for Amgen Inc
   (Thousand Oaks, California, USA), Bayer Schering Pharma (Berlin,
   Germany), Novartis (Basel, Switzerland), Genentech (San Francisco,
   California, USA), and Optovue (Fremont, California, USA) and receives
   research support from Allergan Inc (Irvine, California, USA), Genentech
   (San Francisco, California, USA), Heidelberg (Heidelberg, Germany),
   Regeneron (Tarrytown, New York, USA), and Optovue (Fremont, California,
   USA). Francesco Bandello is a consultant for Alcon (Fort Worth, Texas,
   USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine,
   California, USA), Farmila-Thea (Clermont-Ferrand, France), Bayer
   Schering Pharma (Berlin, Germany), Bausch and Lomb (Rochester, New York,
   USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche
   (Basel, Switzerland), Novagali Pharma (Evry, France), Novartis (Basel,
   Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee,
   Belgium), and Zeiss (Dublin, California, USA). Giuseppe Querques is a
   consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc
   (Irvine, California, USA), Bayer Schering Pharma (Berlin, Germany),
   Heidelberg (Heidelberg, Germany), Novartis (Basel, Switzerland), Sandoz
   (Berlin, Germany), and Zeiss (Dublin, Caifornia, USA). The following
   authors have no financial disclosures: Riccardo Sacconi, Lawrence A.
   Yannuzzi, Rosa Dolz-Marco, Vittorio Capuano, Oudy Semoun, Nopasak
   Phasukkijwatana, Adriano Camevali, and Lea Querques. All authors attest
   that they meet the current ICMJE criteria for authorship.
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NR 25
TC 35
Z9 37
U1 0
U2 3
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 DEC
PY 2017
VL 184
BP 137
EP 146
DI 10.1016/j.ajo.2017.10.009
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FP6ZP
UT WOS:000417776400016
PM 29079450
DA 2022-11-30
ER

PT J
AU Jiang, HY
   Wu, MJ
   Liu, YM
   Song, LP
   Li, SF
   Wang, XW
   Zhang, YF
   Fang, JX
   Wu, SZ
AF Jiang, Haiyan
   Wu, Mengjuan
   Liu, Yimei
   Song, Liping
   Li, Shifeng
   Wang, Xianwei
   Zhang, Yun-feng
   Fang, Junxu
   Wu, Shengzhou
TI Serine racemase deficiency attenuates choroidal neovascularization and
   reduces nitric oxide and VEGF levels by retinal pigment epithelial cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE choroidal flat mount; choroidal neovascularization; d-serine;
   macrophages infiltration; nitric oxide synthase; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; METHYL-D-ASPARTATE;
   NF-KAPPA-B; MACULAR DEGENERATION; MOUSE MODEL; GENE-EXPRESSION; LASER
   PHOTOCOAGULATION; AKT PHOSPHORYLATION; NMDA RECEPTORS
AB Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of vascular endothelial growth factor (VEGF) and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, d-serine, is an endogenous co-agonist of N-methyl-d-aspartate receptor. Activation of the receptor results in production of nitric oxide ((NO)-N-.), a molecule that promotes retinal and choroidal neovascularization. These observations suggest possible roles of SR in CNV. With laser-injured CNV mice, we found that inactivation of SR-coding gene (Srr(null)) significantly reduced CNV volume, neovascular density, and invading macrophages. We exploited the underlying mechanism invivo and exvivo. RPE from wild-type (WT) mice expressed SR. To explore the possible downstream target of SR inactivation, we showed that choroid/RPE homogenates extracted from laser-injured Srr(null) mice contained less inducible nitric oxide synthase and decreased phospho-VEGFR2 compared to amounts in WT mice. In vitro, inflammation-primed WT RPEs expressed more inducible NOS, produced more(.)NO and VEGF than did inflammation-primed Srr(null) RPEs. When co-cultured with inflammation-primed Srr(null) RPE, significantly fewer RF/6A-a cell line of choroidal endothelial cell, migrated to the opposite side of the insert membrane than did cells co-cultured with pre-treated WT RPE. Altogether, SR deficiency reduces RPE response to laser-induced inflammatory stimuli, resulting in decreased production of a cascade of pro-angiogenic cytokines, including(.)NO and VEGF, and reduced macrophage recruitment, which contribute synergistically to attenuated angiogenesis.
C1 [Jiang, Haiyan; Wu, Mengjuan; Liu, Yimei; Song, Liping; Wang, Xianwei; Zhang, Yun-feng; Fang, Junxu; Wu, Shengzhou] Wenzhou Med Univ, Sch Optometry & Ophthalmolgy, Wenzhou 325027, Zhejiang, Peoples R China.
   [Jiang, Haiyan; Wu, Mengjuan; Liu, Yimei; Song, Liping; Wang, Xianwei; Zhang, Yun-feng; Fang, Junxu; Wu, Shengzhou] Wenzhou Med Univ, Hosp Eye, Wenzhou 325027, Zhejiang, Peoples R China.
   [Jiang, Haiyan; Wu, Mengjuan; Liu, Yimei; Song, Liping; Wang, Xianwei; Zhang, Yun-feng; Fang, Junxu; Wu, Shengzhou] State Key Lab Optometry Ophthalmol & Visual Sci, Wenzhou, Zhejiang, Peoples R China.
   [Li, Shifeng] Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University; Chinese Academy
   of Sciences; Shanghai Institutes for Biological Sciences, CAS
RP Wu, SZ (通讯作者)，Wenzhou Med Univ, Sch Optometry & Ophthalmolgy, Wenzhou 325027, Zhejiang, Peoples R China.; Wu, SZ (通讯作者)，Wenzhou Med Univ, Hosp Eye, Wenzhou 325027, Zhejiang, Peoples R China.
EM wszlab@mail.eye.ac.cn
RI Zhang, Yun-Feng/ABD-7464-2020; wu, shengzhou/ABG-8579-2021
OI wu, shengzhou/0000-0003-1154-2369; Jiang, Haiyan/0000-0003-2756-4335;
   Wu, Mengjuan/0000-0002-9558-2159; Zhang, Yun-Feng/0000-0001-6324-4115
FU National Natural Science Foundation of China [81371027]; National
   Natural Science Foundation of China for Youth [81600755]; Wenzhou
   Medical University [QTJ10001]
FX The work is supported by National Natural Science Foundation of China
   (81371027), National Natural Science Foundation of China for Youth
   (81600755) and by Wenzhou Medical University (QTJ10001) as well.
   Shengzhou Wu is an editor with Journal of Neurochemistry. The authors
   declare no competing financial interests.
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NR 74
TC 13
Z9 13
U1 0
U2 9
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 NOV
PY 2017
VL 143
IS 3
BP 375
EP 388
DI 10.1111/jnc.14214
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA FK5OQ
UT WOS:000413550000009
PM 28892569
OA Bronze
DA 2022-11-30
ER

PT J
AU Ryals, RC
   Andrews, MD
   Datta, S
   Coyner, AS
   Fischer, CM
   Wen, YQ
   Pennesi, ME
   McGill, TJ
AF Ryals, Renee C.
   Andrews, Michael D.
   Datta, Shreya
   Coyner, Aaron S.
   Fischer, Cody M.
   Wen, Yuquan
   Pennesi, Mark E.
   McGill, Trevor J.
TI Long-term Characterization of Retinal Degeneration in Royal College of
   Surgeons Rats Using Spectral-Domain Optical Coherence Tomography
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE spectral-domain optical coherence tomography; Royal College of Surgeons
   Rat; animal models; inherited retinal degeneration; MERTK
ID THERAPY RESTORES VISION; EMBRYONIC STEM-CELLS; RCS RAT; PIGMENT
   EPITHELIUM; GENE-THERAPY; PHOTORECEPTOR DEGENERATION; DYSTROPHY; MODEL;
   MERTK; TRANSPLANTATION
AB PURPOSE. Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT).
   METHODS. Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images.
   RESULTS. In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris.
   CONCLUSIONS. Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.
C1 [Ryals, Renee C.; Andrews, Michael D.; Datta, Shreya; Coyner, Aaron S.; Fischer, Cody M.; Pennesi, Mark E.; McGill, Trevor J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Wen, Yuquan] Baylor Univ, Med Ctr, Dallas, TX USA.
   [McGill, Trevor J.] Oregon Hlth & Sci Univ, Dept Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
C3 Oregon Health & Science University; Baylor University; Baylor University
   Medical Center; Oregon Health & Science University; Oregon National
   Primate Research Center
RP Ryals, RC (通讯作者)，Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM ryals@ohsu.edu
RI Coyner, Aaron/W-5592-2019
OI Coyner, Aaron/0000-0003-3261-1909
FU Research to Prevent Blindness (New York, NY, USA); National Institutes
   of Health (Bethesda, MD, USA) [P30 EY010572]; K08 Career Development
   Award [K08 EY021186]; Alcon Young Investigator Award; Foundation
   Fighting Blindness Enhanced Research and Clinical Training Award
   [CD-NMT-0914-0659-OHSU]; Career Development Award from Research to
   Prevent Blindness; Sybil B. Harrington Special Scholar Award from
   Research to Prevent Blindness; Oregon Clinical and Translational
   Research Institute (OCTRI); NATIONAL EYE INSTITUTE [P30EY010572,
   T32EY023211, K08EY021186] Funding Source: NIH RePORTER
FX Supported by unrestricted departmental funding from Research to Prevent
   Blindness (New York, NY, USA), Grant P30 EY010572 from the National
   Institutes of Health (Bethesda, MD, USA), K08 Career Development Award
   (K08 EY021186, MEP), Alcon Young Investigator Award (MEP), Foundation
   Fighting Blindness Enhanced Research and Clinical Training Award
   (CD-NMT-0914-0659-OHSU, MEP), Career Development Award from Research to
   Prevent Blindness (MEP), Sybil B. Harrington Special Scholar Award from
   Research to Prevent Blindness (TJM), Oregon Clinical and Translational
   Research Institute (OCTRI).
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NR 56
TC 35
Z9 35
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 MAR
PY 2017
VL 58
IS 3
BP 1378
EP 1386
DI 10.1167/iovs.16-20363
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EQ4ZA
UT WOS:000398089000003
PM 28253400
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Scherer, KM
   Bisby, RH
   Botchway, SW
   Parker, AW
AF Scherer, Kathrin M.
   Bisby, Roger H.
   Botchway, Stanley W.
   Parker, Anthony W.
TI New Approaches to Photodynamic Therapy from Types I, II and III to Type
   IV Using One or More Photons
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Review
DE Photodynamic therapy (PDT); photosensitizer; two-photon; combretastatin;
   anticancer; Type IV
ID UP-CONVERSION NANOPARTICLES; 5-AMINOLEVULINIC ACID; INDUCED
   FLUORESCENCE; 2-PHOTON EXCITATION; MALIGNANT GLIOMA; PHASE-I;
   CLINICAL-EXPERIENCE; CANCER; HEMATOPORPHYRIN; LIGHT
AB Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty's group dating back to the 1970' s. PDT has significant advantages over surgery or radiation therapy for low lying tumours due to better cosmetic outcome and localised treatment for the patients. However, despite these advantages and significant developments in optical technology that has enabled light penetration to deeper lying tumours, in excess of 5 cm, a lack of phase III clinical trials has slowed down the uptake of PDT by the healthcare sector as a frontline treatment in cancer. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold.
C1 [Scherer, Kathrin M.] UCL, Fac Life Sci, Mol Cell Biol Lab, MRC, London WC1E 6BT, England.
   [Bisby, Roger H.] Univ Salford, Sch Environm & Life Sci, Biomed Sci Res Ctr, Salford, Lancs, England.
   [Botchway, Stanley W.; Parker, Anthony W.] STFC Rutherford Appleton Lab, Cent Laser Facil, Res Complex Harwell, Harwell Campus, Didcot, Oxon, England.
C3 University of London; University College London; University of Salford;
   UK Research & Innovation (UKRI); Science & Technology Facilities Council
   (STFC); STFC Rutherford Appleton Laboratory
RP Scherer, KM; Botchway, SW (通讯作者)，UCL, Fac Life Sci, Mol Cell Biol Lab, MRC, London WC1E 6BT, England.
EM k.scherer@ucl.ac.uk
RI Parker, Anthony W./G-5445-2011; Bisby, Roger/K-3136-2019
OI Parker, Anthony W./0000-0003-3094-9762; Bisby, Roger/0000-0002-5069-0498
FU University of Salford; STFC Futures Programme
FX Author contributions: KMS wrote the manuscript and prepared Figs. 1, 2,
   3 and 7. RHB prepared Figs. 4 and 5 and sought permission for reprints
   of Figs. 6 and 8. RHB, SWB and AWP critically read, drafted and edited
   the manuscript and figures. We acknowledge the University of Salford and
   the STFC Futures Programme for funding.
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NR 156
TC 25
Z9 26
U1 2
U2 84
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1871-5206
EI 1875-5992
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PY 2017
VL 17
IS 2
BP 171
EP 189
DI 10.2174/1871520616666160513131723
PG 19
WC Oncology; Chemistry, Medicinal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pharmacology & Pharmacy
GA EP2YY
UT WOS:000397250800003
PM 27173966
OA Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Chen, Q
   Leng, T
   Zheng, LL
   Kutzscher, L
   De Sisternes, L
   Rubin, DL
AF Chen, Qiang
   Leng, Theodore
   Zheng, Luo Luo
   Kutzscher, Lauren
   De Sisternes, Luis
   Rubin, Daniel L.
TI AN IMPROVED OPTICAL COHERENCE TOMOGRAPHY-DERIVED FUNDUS PROJECTION IMAGE
   FOR DRUSEN VISUALIZATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE drusen; en face fundus images; geographic atrophy; image processing;
   optical coherence tomography; restricted summed-voxel projection;
   retinal pigment epithelium; visualization
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; SEGMENTATION; PATHOLOGY;
   OCT
AB Purpose: To develop and evaluate an improved method of generating en face fundus images from three-dimensional optical coherence tomography images which enhances the visualization of drusen.
   Methods: We describe a novel approach, the restricted summed-voxel projection (RSVP), to generate en face projection images of the retinal surface combined with an image processing method to enhance drusen visualization. The RSVP approach is an automated method that restricts the projection to the retinal pigment epithelium layer neighborhood. Additionally, drusen visualization is improved through an image processing technique that fills drusen with bright pixels. The choroid layer is also excluded when creating the RSVP to eliminate bright pixels beneath drusen that could be confused with drusen when geographic atrophy is present. The RSVP method was evaluated in 46 patients and 3-dimensional optical coherence tomography data sets were obtained from 8 patients, for which 2 readers independently identified drusen as the gold standard. The mean drusen overlap ratio was used as the metric to determine the accuracy of visualization of the RSVP method when compared with the conventional summed-voxel projection technique.
   Results: Comparative results demonstrate that the RSVP method was more effective than the conventional summed-voxel projection in displaying drusen and retinal vessels, and was more useful in detecting drusen. The mean drusen overlap ratios based on the conventional summed-voxel projection method and the RSVP method were 2.1% and 89.3%, respectively.
   Conclusion: The RSVP method was more effective for drusen visualization than the conventional summed-voxel projection method, and it may be useful for macular assessment in patients with nonexudative age-related macular degeneration.
C1 [Chen, Qiang; De Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Sch Med, Dept Radiol & Med Biomed Informat Res, Stanford, CA 94305 USA.
   [Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [Leng, Theodore; Zheng, Luo Luo; Kutzscher, Lauren] Stanford Univ, Sch Med, Byers Eye Inst Stanford, Palo Alto, CA 94304 USA.
C3 Stanford University; Nanjing University of Science & Technology;
   Stanford University
RP Chen, Q (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Xiao Lingwei 200, Nanjing 210094, Jiangsu, Peoples R China.
EM chen2qiang@njust.edu.cn
RI Leng, Theodore/AAQ-7459-2020; chen, qiang/GWZ-7308-2022
OI Leng, Theodore/0000-0002-8461-3562
FU Bio-X Interdisciplinary Initiatives Program of Stanford University;
   National Cancer Institute, National Institutes of Health
   [U01-CA-142555]; Qing Lan Project; NATIONAL CANCER INSTITUTE
   [U01CA142555] Funding Source: NIH RePORTER
FX Supported by a grant from the Bio-X Interdisciplinary Initiatives
   Program of Stanford University; a grant from the National Cancer
   Institute, National Institutes of Health (Grant U01-CA-142555); and
   grants from Qing Lan Project.
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NR 26
TC 7
Z9 8
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 MAY
PY 2014
VL 34
IS 5
BP 996
EP 1005
DI 10.1097/IAE.0000000000000018
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AI8GM
UT WOS:000337148700020
PM 24177190
DA 2022-11-30
ER

PT J
AU Singh, AK
   Srivastava, GK
   Garcia-Gutierrez, MT
   Pastor, JC
AF Singh, Amar K.
   Srivastava, Girish K.
   Garcia-Gutierrez, Maria T.
   Carlos Pastor, J.
TI Adipose derived mesenchymal stem cells partially rescue mitomycin C
   treated ARPE19 cells from death in co-culture condition
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Article
DE Human adipose derived mesenchymal stem cells; Age-related macular
   degeneration; Cell death; ARPE19 cell; Mitomycin C
ID RETINAL-PIGMENT EPITHELIUM; INDUCED APOPTOSIS; TISSUE
AB Age-related macular degeneration is a retinal disease with important damage at the RPE layer. This layer is considered a target for therapeutical approaches. Stem cell transplantation is a promising option for retinal diseases. Adipose derived mesenchymal stem cells secret growth factors which might play a significant role in RPE maintenance. This study aimed to evaluate human AD-MSCs ability to rescue mitomycin C treated dying ARPE19 cells in co-culture condition.
   ARPE19 cells were treated with MMC (50 mu g/ml, 100 mu g/ml and 200 mu g/ml) for 2 hours to induce cell death. These treated cells were co-cultured with hAD-MSCs in indirect co-culture system for 3 days and 3 weeks. Then the viability, growth and proliferation of these ARPE19 cells were evaluated by a cell viability/cytotoxicity assay kit and Alamar Blue (AB) assay. Untreated ARPE19 cells and human skin fibroblasts (HSF) were used as controls.
   MMC blocked ARPE19 cell proliferation significantly in 3 days and cells were almost completely dead after 3 weeks. Cell toxicity of MMC increased significantly with concentration. When these cells were co-cultured with hAD-MSCs, a significant growth difference was observed in treated cells compared to untreated cells. hAD-MSCs rescue capacity was also significantly higher than HSF for treated ARPE19 cells.
   This study showed that hAD-MSCs rescued MMC treated ARPE19 cells from death. It probably occurred due to undefined growth factors secreted by hAD-MSCs in the medium, shared by treated ARPE19 cells in co-culture conditions. This study supports further evaluation of the effect of hAD-MSCs subretinal transplantation over the RPE degeneration process in AMD patients.
C1 [Singh, Amar K.; Srivastava, Girish K.; Garcia-Gutierrez, Maria T.; Carlos Pastor, J.] Univ Valladolid, IOBA Eye Inst, E-47011 Valladolid, Spain.
   [Srivastava, Girish K.; Garcia-Gutierrez, Maria T.] Regenerat Med & Cell Therapy Networking Ctr Casti, Leon, Spain.
   [Srivastava, Girish K.] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Valladolid, Spain.
C3 Universidad de Valladolid; CIBER - Centro de Investigacion Biomedica en
   Red; CIBERBBN
RP Srivastava, GK (通讯作者)，Univ Valladolid, Inst Appl Ophthalmobiol Eye Inst IOBA, Campus Miguel Delibes,Paseo Belen 17, E-47011 Valladolid, Spain.
EM girish@ioba.med.uva.es
RI Srivastava, Girish K/L-7608-2014; Jimeno, J Carlos Pastor/AAP-1156-2020;
   SINGH, AMAR/H-6569-2016
OI Srivastava, Girish K/0000-0002-9791-4057; Jimeno, J Carlos
   Pastor/0000-0001-5934-7306; SINGH, AMAR/0000-0002-1767-5907
FU Castilla and Leon Regenerative Medicine and Cell Therapy Network Center;
   National Plan of I+D+I; ISCIII-Subdireccion General de Evaluacion y
   Fomento de la Investigacion [PS09/00938]; FEDER; JCYL [BIO/39/VA26/10,
   VA386A12-2]; Junta de Castilla y Leon, Spain; AECI, Spanish Ministry of
   Foreign Affairs and Cooperation
FX This work was supported by grants from Castilla and Leon Regenerative
   Medicine and Cell Therapy Network Center, National Plan of I+D+I
   2008-2011 and ISCIII-Subdireccion General de Evaluacion y Fomento de la
   Investigacion (PS09/00938) (MICNN) co-financed by FEDER, JCYL
   BIO/39/VA26/10 and VA386A12-2, Junta de Castilla y Leon, Spain to JCP
   and GKS. A. K. Singh is a Pre-doctoral research scholar supported by
   AECI, Spanish Ministry of Foreign Affairs and Cooperation.
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NR 24
TC 10
Z9 11
U1 0
U2 9
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 DEC
PY 2013
VL 28
IS 12
BP 1577
EP 1583
PG 7
WC Cell Biology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Pathology
GA 250TU
UT WOS:000326879000006
PM 23719745
DA 2022-11-30
ER

PT J
AU Berchuck, JE
   Yang, P
   Toimil, BA
   Ma, Z
   Baciu, P
   Jaffe, GJ
AF Berchuck, Jacob E.
   Yang, Ping
   Toimil, Brett A.
   Ma, Zhe
   Baciu, Peter
   Jaffe, Glenn J.
TI All-trans-Retinal Sensitizes Human RPE Cells to Alternative Complement
   Pathway-Induced Cell Death
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium; oxidative
   damage; alternative complement pathway; all-trans-retinal
ID STARGARDT-DISEASE; GENE ABCR; RETINOPATHY; EXPRESSION
AB PURPOSE. Retinal pigment epithelial (RPE) cell death occurs early in the pathogenesis of age-related macular degeneration (AMD) and Stargardt's disease. Emerging evidence suggests that all-trans-retinal (atRal) and alternative complement pathway (AP) activation contribute to RPE cell death in both of these retinal disorders. The aim of this study was to investigate the combined effect of atRal and AP activation on RPE cell viability.
   METHODS. RPE cells were treated with atRal and then incubated with a complement-fixing antibody followed by stimulation with C1q-depleted serum to activate AP. Cell viability was assessed by tetrazolium salt and lactate dehydrogenase release assays. Changes in cell surface CD46 and CD59 expression were assessed by flow cytometry. Cells were pretreated with the antioxidant resveratrol, and C1q-depleted serum was incubated with an anti-C5 antibody prior to initiating AP attack to determine the protective effects of antioxidant therapy and complement inhibition, respectively.
   RESULTS. Both atRal and AP activation independently caused RPE cell death. When AP attack was initiated following atRal treatment, a synergistic increase in cell death was observed. Following 24-hour atRal treatment, CD46 and CD59 expression decreased, corresponding temporally to increased susceptibility to AP attack. Resveratrol and the anti-C5 antibody both protected against AP-induced cell death following atRal exposure and were most effective when used in combination.
   CONCLUSIONS. atRal sensitizes RPE cells to AP attack, which may be mediated in part by atRal-induced downregulation of CD46 and CD59. Despite increased susceptibility to AP attack following exposure to atRal, resveratrol and anti-C5 antibody effectively prevent AP-mediated cell death.
C1 [Berchuck, Jacob E.] Duke Univ, Sch Med, Durham, NC USA.
   [Yang, Ping; Toimil, Brett A.; Ma, Zhe; Jaffe, Glenn J.] Duke Univ, Dept Ophthalmol, Durham, NC USA.
   [Baciu, Peter] Allergan Pharmaceut Inc, Irvine, CA 92715 USA.
C3 Duke University; Duke University; AbbVie; Allergan
RP Jaffe, GJ (通讯作者)，Duke Eye Ctr, DUMC 3802, Durham, NC 27710 USA.
EM glenn.jaffe@dm.duke.edu
FU Howard Hughes Medical Institute; Foundation Fighting Blindness; Research
   to Prevent Blindness; National Eye Institute [NIH P30 EY-005722];
   NATIONAL EYE INSTITUTE [P30EY005722] Funding Source: NIH RePORTER
FX Supported by funding from Howard Hughes Medical Institute Medical
   Research Fellows Program, Foundation Fighting Blindness, Research to
   Prevent Blindness, and National Eye Institute Core Grant NIH P30
   EY-005722.
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   Yehoshua Z, 2011, CURRENT CLIN TRIALS
NR 28
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 APR
PY 2013
VL 54
IS 4
BP 2669
EP 2677
DI 10.1167/iovs.12-11020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 156KV
UT WOS:000319821700031
PM 23518773
OA Green Published
DA 2022-11-30
ER

PT J
AU Sohrab, M
   Wu, K
   Fawzi, AA
AF Sohrab, Mahsa
   Wu, Katherine
   Fawzi, Amani A.
TI A Pilot Study of Morphometric Analysis of Choroidal Vasculature In Vivo,
   Using En Face Optical Coherence Tomography
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; AXIAL LENGTH; THICKNESS; EYES;
   CHORIOCAPILLARIS; DRUSEN; RPE
AB Purpose: To study the ability of volumetric spectral domain optical coherence tomography (SD-OCT) to perform quantitative measurement of the choroidal vasculature in vivo.
   Methods: Choroidal vascular density and vessel size were quantified using en face choroidal scans from various depths below the retinal pigment epithelium (RPE) in 58 eyes of 58 patients with either epiretinal membranes (ERM), early age-related macular degeneration (AMD), or reticular pseudo-drusen (RPD). For each patient, we used the macular volume scan (666 mm cube) for vessel quantification, while high-definition (HD) cross-section raster scans were used to qualitatively assess vascularity of the choroidal sub-layers, and measure choroidal thickness.
   Results: Of the 58 patients, more were female (66% versus 34% male), of whom 14 (24%) had ERM, 11 (19%) early AMD, and 33 (57%) RPD. Compared to intact choriocapillaris in all ERM (100%), none of the RPD and only 5/11 (45%) early AMD eyes had visible choriocapillaris on either cross section or C-scans (p-value<0.001). When comparing select regions from the most superficial C-scans, early AMD group had lowest vascular density and RPD had highest (p-value 0.04). Qualitative evaluation of C-scans from all three groups revealed a more granular appearance of the choriocapillaris in ERM versus increased stroma and larger vessels in the RPD eyes.
   Conclusions: SD-OCT can be used to qualitatively and quantitatively assess choroidal vascularity in vivo. Our findings correlate to previously reported histopathologic studies. Lack of choriocapillaris on HD cross-sections or C-scans in all RPD and about half of early AMD eyes suggests earlier choroidal involvement in AMD and specifically, RPD.
C1 [Sohrab, Mahsa; Wu, Katherine; Fawzi, Amani A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine
RP Fawzi, AA (通讯作者)，Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
EM Afawzimd@gmail.com
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558
FU National Eye Institute [EY03040, EY021470]; NATIONAL EYE INSTITUTE
   [P30EY003040, R01EY021470] Funding Source: NIH RePORTER
FX This work was supported by the National Eye Institute EY03040 and
   EY021470. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
CR Brown JS, 2009, INVEST OPHTH VIS SCI, V50, P5, DOI 10.1167/iovs.08-1779
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NR 22
TC 85
Z9 86
U1 0
U2 12
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 2012
VL 7
IS 11
AR e48631
DI 10.1371/journal.pone.0048631
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 048RI
UT WOS:000311929800011
PM 23189132
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Popescu, ML
   Boisjoly, H
   Schmaltz, H
   Kergoat, MJ
   Rousseau, J
   Moghadaszadeh, S
   Djafari, F
   Freeman, EE
AF Popescu, Mihaela L.
   Boisjoly, Helene
   Schmaltz, Heidi
   Kergoat, Marie-Jeanne
   Rousseau, Jacqueline
   Moghadaszadeh, Solmaz
   Djafari, Fawzia
   Freeman, Ellen E.
TI Explaining the Relationship between Three Eye Diseases and Depressive
   Symptoms in Older Adults
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; SOCIAL SUPPORT; VISUAL-ACUITY; LATE-LIFE;
   PREVALENCE; COMMUNITY; GLAUCOMA; MOBILITY; RISK; DISABILITY
AB PURPOSE. The purpose of this study is to examine whether patients with age-related eye diseases, like age-related macular degeneration (AMD), glaucoma, or Fuchs corneal dystrophy, are more likely to show signs of depression compared to a control group of older adults with good vision, and to determine whether reduced mobility mediates these relationships.
   METHODS. We recruited 315 eligible patients (81 with AMD, 55 with Fuchs, 91 with glaucoma, and 88 controls) from the ophthalmology clinics of a Montreal hospital from September 2009 until December 2011. Depressive symptoms were assessed using the Geriatric Depression Scale Short Form (GDS-15). Life space was measured using the Life Space Assessment. Logistic regression was used to adjust for demographic, health, and social factors, and mediation was assessed using the methods of Baron and Kenny.
   RESULTS. There were 78 people (25%) meeting the criteria for depression in the cohort. All three groups with eye disease were more likely to be depressed than the control group after adjusting for age, sex, ethnicity, education, cognitive score, limitations in activities of daily living, social support, and lens opacity (P < 0.05). Life space and limited activities due to a fear of falling appeared to mediate the relationship between eye disease and depression.
   CONCLUSIONS. Visually limiting eye disease is associated with depression in older adults. Further research on interventions to prevent depression in patients with eye disease is warranted and should consider strategies to alleviate mobility limitation. Greater attention from families, physicians, and society to the mental health needs and mobility challenges of patients with eye disease is needed. (Invest Ophthalmol Vis Sci. 2012; 53: 2308-2313) DOI:10.1167/iovs.11-9330
C1 [Freeman, Ellen E.] Hop Maison Neuve Rosemont, CSA, RC, Ctr Rech, Montreal, PQ H1T 2M4, Canada.
   [Boisjoly, Helene; Djafari, Fawzia; Freeman, Ellen E.] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Schmaltz, Heidi] Univ Calgary, Dept Geriatr Med, Calgary, AB, Canada.
   [Kergoat, Marie-Jeanne; Rousseau, Jacqueline] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
C3 Universite de Montreal; Universite de Montreal; University of Calgary;
   Universite de Montreal
RP Freeman, EE (通讯作者)，Hop Maison Neuve Rosemont, CSA, RC, Ctr Rech, F131,5415 Blvd Assompt, Montreal, PQ H1T 2M4, Canada.
OI Freeman, Ellen/0000-0002-1403-8427
FU CNIB, Toronto, Canada; Canadian Institutes of Health Research, Ottawa,
   Canada [IAP-98996]; Fonds de Recherche en Sante du Quebec; Fonds de
   recherche en ophtalmologie de l'Universite de Montreal
FX Supported by CNIB New Investigator grant, Toronto, Canada, Canadian
   Institutes of Health Research Grant IAP-98996, Ottawa, Canada, Fonds de
   Recherche en Sante du Quebec salary award (EEF), Fonds de recherche en
   ophtalmologie de l'Universite de Montreal salary award (MLP). The
   funding organizations had no role in the design or conduct of this
   research.
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NR 36
TC 60
Z9 61
U1 0
U2 21
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 2308
EP 2313
DI 10.1167/iovs.11-9330
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 937PC
UT WOS:000303669400070
PM 22427589
DA 2022-11-30
ER

PT J
AU Lucas, RM
AF Lucas, Robyn M.
TI An Epidemiological Perspective of Ultraviolet Exposure-Public Health
   Concerns
SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE
LA English
DT Review
DE Ultraviolet radiation; Vitamin D; Disease burden; Sun exposure policy
ID NONMELANOMA SKIN-CANCER; VITAMIN-D; UVEAL MELANOMA; LIGHT EXPOSURE; LENS
   OPACITIES; AQUEOUS-HUMOR; SUN EXPOSURE; POPULAR ATTITUDES; OCULAR
   EXPOSURE; ACTION SPECTRUM
AB Over the last 30 years, many countries have developed strong sun protection programs, spurred on by rapidly increasing skin cancer incidence and concerns about stratospheric ozone depletion. More recently, considerable concern has arisen about widespread vitamin D insufficiency, creating a "sun exposure dilemma," since in most regions vitamin D predominantly derives from endogenous synthesis in the skin initiated by exposure to ultraviolet (UV) radiation. Little attention has been paid to whether a similar dilemma exists for UV-related eye conditions.
   For the eyes, to our current knowledge, exposure to UV radiation has only adverse effects. There is strong evidence that acute high dose exposure to UV radiation causes photokeratitis and photoconjunctivitis, while even low dose chronic exposure to UV radiation is a risk factor for cataract, pterygium, and squamous cell carcinoma of the cornea and conjunctiva. There is weaker evidence in relation to other conditions, including ocular melanoma and age-related macular degeneration. Ultraviolet radiation-related eye diseases are common, disabling, and cause a considerable disease burden worldwide.
   The "correct" public health message for optimal sun exposure is not clear cut, with too many variables-ambient UV radiation, personal skin type, age, weight, clothing habits, medication, and others-for a blanket sun safety message. In addition, there remain many unknowns, including strong evidence supporting or refuting the very many proposed health benefits of vitamin D. More evidence is required to define disease burdens for UV-induced eye diseases, to evaluate the decrease in disease burden from sun protective measures and to elucidate any beneficial effects of exposure of the eye to UV radiation, to provide appropriate advice to the public.
C1 Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT 0200, Australia.
C3 Australian National University
RP Lucas, RM (通讯作者)，Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, GPO Box 4, Canberra, ACT 0200, Australia.
EM robyn.lucas@anu.edu.au
OI Lucas, Robyn/0000-0003-2736-3541
FU Contact Lens Association of Ophthalmologists
FX Robyn M. Lucas, Ph.D. received a travel stipend from the Contact Lens
   Association of Ophthalmologists.
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NR 77
TC 33
Z9 35
U1 3
U2 27
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 168
EP 175
DI 10.1097/ICL.0b013e31821cb0cf
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 784BJ
UT WOS:000292128300002
PM 21670693
DA 2022-11-30
ER

PT J
AU Sherwin, JC
   Kearns, LS
   Hewitt, AW
   Ma, YL
   Kelly, J
   Griffiths, LR
   Mackey, DA
AF Sherwin, Justin C.
   Kearns, Lisa S.
   Hewitt, Alex W.
   Ma, Yaling
   Kelly, John
   Griffiths, Lyn R.
   Mackey, David A.
TI Prevalence of Chronic Ocular Diseases in a Genetic Isolate: The Norfolk
   Island Eye Study (NIES)
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Blindness; Epidemiology; Genetics; Glaucoma; Macular degeneration;
   Norfolk Island; Pitcairn Island; Population isolates
ID OPEN-ANGLE GLAUCOMA; VISUAL IMPAIRMENT PROJECT; MACULAR DEGENERATION;
   CARDIOVASCULAR-DISEASE; AGE; AUSTRALIA; CARE; POPULATION; CATARACT;
   REGION
AB Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island.
   Methods: All permanent residents of Norfolk Island aged >= a parts per thousand yen 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy.
   Results: We recruited 781 people aged >= a parts per thousand yen 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged >= a parts per thousand yen 40 was 1.5%. Blindness was more common in females (P == 0.049) and less common in people with Pitcairn Island ancestry (P < 0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P < 0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry.
   Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.
C1 [Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Nedlands, WA 6009, Australia.
   [Sherwin, Justin C.; Kearns, Lisa S.; Hewitt, Alex W.; Ma, Yaling; Mackey, David A.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
   [Ma, Yaling] Ningxia Med Univ, Affiliated Hosp, Ningxia, Peoples R China.
   [Griffiths, Lyn R.] Griffith Univ, Griffith Inst Hlth & Med Res, Genom Res Ctr, Southport, Qld 4215, Australia.
   [Mackey, David A.] Univ Tasmania, Royal Hobart Hosp, Dept Ophthalmol, Hobart, Tas, Australia.
C3 Lions Eye Institute; University of Western Australia; Centre for Eye
   Research Australia; Royal Victorian Eye & Ear Hospital; University of
   Melbourne; Ningxia Medical University; Griffith University; Royal Hobart
   Hospital; University of Tasmania
RP Mackey, DA (通讯作者)，Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, 2 Verdun St, Nedlands, WA 6009, Australia.
EM D.Mackey@utas.edu.au
RI Hewitt, Alex W/D-1936-2013; Mackey, David A/H-5340-2014
OI Hewitt, Alex W/0000-0002-5123-5999; Mackey, David A/0000-0001-7914-4709;
   Kearns, Lisa/0000-0001-9432-4054; Griffiths, Lyn/0000-0002-6774-5475
FU RVEEH research committee; Peggy and Leslie Cranbourne Foundation; Pfizer
   Australia
FX We thank the Norfolk Islanders for welcoming us into their community and
   for their participation and assistance in this study. Financial support
   was provided by the RVEEH research committee and the Peggy and Leslie
   Cranbourne Foundation, DAM is a recipient of the Pfizer Australia Senior
   Research Fellowship. We would like to thank Byoung-Sun Chu, Robert
   MacMillan, Julie Barbour and Colleen Wilkinson for helping examine the
   Norfolk Islanders. CERA receives Operational Infrastructure Support from
   the Victorian Government.
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NR 36
TC 9
Z9 10
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD APR
PY 2011
VL 18
IS 2
BP 61
EP 71
DI 10.3109/09286586.2010.545933
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 734IA
UT WOS:000288326600003
PM 21401413
DA 2022-11-30
ER

PT J
AU Silva, RLE
   Shen, JK
   Gong, YY
   Seidel, CP
   Hackett, SF
   Kesavan, K
   Jacoby, DB
   Campochiaro, PA
AF Lima E Silva, Raquel
   Shen, Jikui
   Gong, Yuan Yuan
   Seidel, Christopher P.
   Hackett, Sean F.
   Kesavan, Kamala
   Jacoby, Douglas B.
   Campochiaro, Peter A.
TI Agents That Bind Annexin A2 Suppress Ocular Neovascularization
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TISSUE-PLASMINOGEN ACTIVATOR; CHOROIDAL
   NEOVASCULARIZATION; VASCULAR LEAKAGE; CELL RECEPTOR; ANGIOSTATIN;
   CHLOROTOXIN; EXPRESSION; PHOSPHORYLATION; ANGIOGENESIS
AB TM601 is a synthetic polypeptide with sequence derived from the venom of the scorpion Leiurus quinquestriatus that has anti-neoplastic activity. It has recently been demonstrated to bind annexin A2 on cultured tumor and vascular endothelial cells and to suppress blood vessel growth on chick chorioallantoic membrane. In this study, we investigated the effects of TM601 in models of ocular neovascularization (NV). When administered by intraocular injection, intravenous injections, or periocular injections. TM601 significantly suppressed the development of choroidal NV at rupture sites in Bruch's membrane. Treatment of established choroidal NV with TM601 caused apoptosis of endothelial cells and regression of the NV. TM601 suppressed ischemia-induced and vascular endothelial growth factor-induced retinal NV and reduced excess vascular permeability induced by vascular endothelial growth factor. Immunostaining with an antibody directed against TM601 showed that after intraocular or periocular injection. TM601 selectively bound to choroidal or retinal NV and co-localized with annexin A2, which is undetectable in normal retinal and choroidal vessels, but is upregulated in endothelial cells participating in choroidal or retinal NV. Intraocular injection of plasminogen or tissue plasminogen activator, which like TM601 bind to annexin A2, also suppressed retinal NV. This study supports the hypothesis that annexin A2 is an important target for treatment of neovascular diseases and suggests that TM601, through its interaction with annexin A2, causes suppression and regression of ocular NV and reduces vascular leakage and thus may provide a new treatment for blinding diseases such as neovascular age-related macular degeneration and diabetic retinopathy. J. Cell. Physiol. 225: 855-864, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Lima E Silva, Raquel; Shen, Jikui; Gong, Yuan Yuan; Seidel, Christopher P.; Hackett, Sean F.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol & Neurosci, Baltimore, MD 21287 USA.
   [Kesavan, Kamala; Jacoby, Douglas B.] TransMolecular Inc, King Of Prussia, PA USA.
C3 Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol & Neurosci, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
FU NIH [P30EY1765]; National Eye Institute [EY12609, EY009769];
   TransMolecular, Inc.; NATIONAL EYE INSTITUTE [R01EY009769, P30EY001765,
   R01EY012609] Funding Source: NIH RePORTER
FX The authors thank Jiangxia Wang and Carol B. Thompson of the core
   statistics module of NIH grant P30EY1765 for statistical consultation.
   This work was also supported by National Eye Institute (grant numbers
   EY12609 and EY009769) and TransMolecular, Inc.
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NR 38
TC 23
Z9 30
U1 0
U2 3
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 2010
VL 225
IS 3
BP 855
EP 864
DI 10.1002/jcp.22296
PG 10
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA 679WI
UT WOS:000284191100026
PM 20607799
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Frank-Cannon, TC
   Alto, LT
   McAlpine, FE
   Tansey, MG
AF Frank-Cannon, Tamy C.
   Alto, Laura T.
   McAlpine, Fiona E.
   Tansey, Malu G.
TI Does neuroinflammation fan the flame in neurodegenerative diseases?
SO MOLECULAR NEURODEGENERATION
LA English
DT Review
ID TUMOR-NECROSIS-FACTOR; AMYLOID PRECURSOR PROTEIN;
   AMYOTROPHIC-LATERAL-SCLEROSIS; ANTIINFLAMMATORY DRUG-USE;
   CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; FACTOR-ALPHA; MICROGLIAL
   ACTIVATION; BETA-PEPTIDE; MOUSE MODEL
AB While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells ( microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis ( MS), Alzheimer's disease ( AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.
C1 [Tansey, Malu G.] Emory Univ, Dept Physiol, Sch Med, Atlanta, GA 30322 USA.
   [Frank-Cannon, Tamy C.] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.
   [Alto, Laura T.] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [McAlpine, Fiona E.] Canc Res UK London Res Inst, London WC2A 3PX, England.
C3 Emory University; Texas A&M University System; Texas A&M University
   College Station; University of Texas System; University of Texas
   Southwestern Medical Center Dallas; Cancer Research UK
RP Tansey, MG (通讯作者)，Emory Univ, Dept Physiol, Sch Med, Atlanta, GA 30322 USA.
EM TFrank-Cannon@cvm.tamu.edu; laura.alto@utsouthwestern.edu;
   fiona.mcalpine@cancer.org.uk; malu.tansey@emory.edu
FU NINDS NIH HHS [R01 NS049433, R01 NS049433-04] Funding Source: Medline;
   NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS049433]
   Funding Source: NIH RePORTER
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NR 142
TC 521
Z9 538
U1 4
U2 68
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD NOV 16
PY 2009
VL 4
AR 47
DI 10.1186/1750-1326-4-47
PG 13
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 526JC
UT WOS:000272283300001
PM 19917131
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Browning, AC
   Dua, HS
   Amoaku, WM
AF Browning, A. C.
   Dua, H. S.
   Amoaku, W. M.
TI The effects of growth factors on the proliferation and in vitro
   angiogenesis of human macular inner choroidal endothelial cells
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID IGF-I; NEOVASCULAR MEMBRANES; ADHESION MOLECULES; SIGNALING PATHWAYS;
   MESSENGER-RNA; EXPRESSION; FIBROBLAST; DEGENERATION; BOVINE; INHIBITION
AB Aim: To investigate the effect of VEGF(165), FGF2, IGF-1, PDGF-AA, PDGF-BB and IL-1 beta on the proliferation and angiogenic tube formation of human macular inner choroidal endothelial cells (ICEC).
   Methods: The proliferation of human macular ICECs after exposure to the aforementioned growth factors was determined by using both a WST-1 colorimetric assay and a cell-counting technique. The effect of growth factors on ICEC angiogenesis was assessed by sprout formation using a three-dimensional in vitro Matrigel duplex assay.
   Results: Using both the WST-1 assay and a cell-counting technique, VEGF(165) and FGF2 both significantly increased human macular ICEC proliferation. The effect of equimolar concentrations of VEGF(165) and FGF2 was additive. There was no significant effect for IGF-1, PDGF-AA, PDGF-BB or IL-1 beta on proliferation up to a growth factor concentration of 1000 pmol/l. The angiogenesis assay found a significant effect on sprout formation for VEGF(165) and FGF2. Again, the effect of equimolar concentrations of VEGF(165) and FGF2 was additive. There was no significant effect for IGF-1, PDGF-AA, PDGF-BB or IL-1 beta on sprout formation at 1000 pmol/l.
   Conclusions: Both VEGF(165) and FGF2 significantly increase human macular ICEC proliferation and sprout formation in an angiogenesis assay. When present together, their effect was additive. IGF-1, PDGF-AA, PDGF-BB and IL-1 beta did not have any significant effect on proliferation or sprout formation in vitro. These results suggest that targeting other growth factors such as FGF2, in addition to VEGF, may be beneficial in the treatment of neovascular age-related macular degeneration.
C1 [Browning, A. C.; Dua, H. S.; Amoaku, W. M.] Univ Nottingham Hosp, Queens Med Ctr, Div Ophthalmol & Visual Sci, Eye Ear Nose & Throat Ctr, Nottingham NG7 2UH, England.
C3 University of Nottingham
RP Amoaku, WM (通讯作者)，Univ Nottingham Hosp, Queens Med Ctr, Div Ophthalmol & Visual Sci, Eye Ear Nose & Throat Ctr, Nottingham NG7 2UH, England.
EM wma@nottingham.ac.uk
RI Dua, Harminder S/F-3656-2011
OI Amoaku, Winfried/0000-0001-5028-7984
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NR 66
TC 27
Z9 29
U1 1
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 JUL
PY 2008
VL 92
IS 7
BP 1003
EP 1008
DI 10.1136/bjo.2007.127670
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 318RL
UT WOS:000257109700030
PM 18577655
DA 2022-11-30
ER

PT J
AU Nagaoka, T
   Kuo, L
   Ren, Y
   Yoshida, A
   Hein, TW
AF Nagaoka, Taiji
   Kuo, Lih
   Ren, Yi
   Yoshida, Akitoshi
   Hein, Travis W.
TI C-reactive protein inhibits endothelium-dependent nitric oxide-mediated
   dilation of retinal arterioles via enhanced superoxide production
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; INTERCELLULAR-ADHESION MOLECULE-1; LIPOPROTEIN
   CHOLESTEROL LEVELS; MACULAR DEGENERATION; CORONARY ARTERIOLES;
   MICROVASCULAR COMPLICATIONS; POTASSIUM CHANNELS; ELICITS DILATION;
   XANTHINE-OXIDASE; NAD(P)H OXIDASE
AB PURPOSE. Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP on ocular microvascular reactivity remains unknown. The authors examined whether CRP can affect endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the CRP-mediated effect.
   METHODS. Porcine retinal arterioles (internal diameter, 71 +/- 2 mu m) were isolated and pressurized without flow for in vitro study. Diameter changes were recorded using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production.
   RESULTS. Intraluminal treatment with a clinically relevant concentration of CRP (7 mu g/mL, 60 minutes) significantly attenuated arteriolar dilation to endothelium-dependent NO-mediated agonists bradykinin and A23187 but not to endothelium-independent NO donor sodium nitroprusside. In the presence of superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, simvastatin, or Rho-kinase inhibitor Y-27632, the detrimental effect of CRP on bradykinin-induced dilation was prevented. DHE staining showed that CRP produced TEMPOL-sensitive superoxide production in the arteriolar endothelium.
   CONCLUSIONS. CRP inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase and RhoA/Rho-kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP can potentially facilitate the development of retinal vascular diseases. In addition, statins are beneficial by preserving endothelial function, possibly through inactivation of the RhoA/Rho-kinase pathway.
C1 [Nagaoka, Taiji; Kuo, Lih; Hein, Travis W.] Scott & White Eye Inst, Dept Ophthalmol, Temple, TX USA.
   [Nagaoka, Taiji; Kuo, Lih; Hein, Travis W.] Scott & White Eye Inst, Dept Surg, Temple, TX USA.
   [Nagaoka, Taiji; Yoshida, Akitoshi] Asahikawa Med Coll, Dept Ophthalmol, Asahikawa, Hokkaido, Japan.
   [Kuo, Lih; Ren, Yi] Texas A&M Hlth Sci Ctr, Coll Med, Dept Syst Biol, Temple, TX 76504 USA.
   [Kuo, Lih; Ren, Yi] Texas A&M Hlth Sci Ctr, Coll Med, Dept Translat Med, Temple, TX 76504 USA.
C3 Asahikawa Medical College; Texas A&M University System; Texas A&M
   University College Station; Texas A&M Health Science Center; Texas A&M
   University System; Texas A&M University College Station; Texas A&M
   Health Science Center
RP Nagaoka, T (通讯作者)，Texas A&M Hlth Sci Ctr, Coll Med, Dept Ophthalmol, 702 SW HK Dodgen Loop, Temple, TX 76504 USA.
EM nagaoka@asahikawa-med.ac.jp
RI NAGAOKA, TAIJI/AHD-7407-2022
OI NAGAOKA, TAIJI/0000-0003-3933-1002; Kuo, Lih/0000-0002-4912-6910
FU NEI NIH HHS [R01 EY018420, EY 018420] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R01EY018420] Funding Source: NIH RePORTER
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NR 64
TC 53
Z9 55
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2008
VL 49
IS 5
BP 2053
EP 2060
DI 10.1167/iovs.07-1387
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 292UH
UT WOS:000255291100042
PM 18436840
DA 2022-11-30
ER

PT J
AU Smith, CP
   Sharma, S
   Steinle, JJ
AF Smith, Christopher P.
   Sharma, Sheena
   Steinle, Jena J.
TI Age-related changes in sympathetic neurotransmission in rat retina and
   choroid
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; choroid; adrenergic receptors; aging
ID DOPAMINE-BETA-HYDROXYLASE; EXPRESSION; RECEPTORS; CORTEX
AB While age-related night vision loss and age-related macular degeneration are well characterized, less is known about the normal aging process in the retina and choroid. The purpose of this study was to ascertain whether dopamine beta-hydroxylase (DBH), beta(1)- and beta(2)-adrenergic receptor gene and protein expression are altered in the retina and choroid with age. The retina and choroid were dissected from F344 x BNF1 hybrid rats aged 8, 22, and 32 months. Real-time PCR and Western blot analysis were conducted to determine steady-state mRNA and protein expression. Immunohistochemistry (IHC) was conducted to localize DBH protein expression in the retina. DBH protein expression was substantially decreased with age in the retina, particularly in the outer nuclear layer, with no changes in DBH expression noted in the choroid. There was a significant increase in beta(1)-adrenergic receptor protein expression in retinal samples at 22 months, while beta(2)-adrenergic receptor protein expression was not affected by age. Decreased expression of DBH with age in the retina could lead to reduced production of norepinephrine, potentially resulting in an increase of beta(1)-adrenergic receptor expression due to denervation supersensitivity. Gene expression for DBH, beta(1)- and beta(2)-adrenergic receptors were observed to peak at 22 months and return to baseline levels by 32 months of age in the choroid. Our findings suggest that the retina may be more sensitive to age-related loss of sympathetic neurotransmission than the choroid, which may partially explain normal age-related vision loss in the elderly. (c) 2006 Elsevier Ltd. All rights reserved.
C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA.
C3 Southern Illinois University System; Southern Illinois University
RP Steinle, JJ (通讯作者)，So Illinois Univ, Sch Med, Dept Physiol, 1135 Lincoln Dr,LS III Room 2071, Carbondale, IL 62901 USA.
EM jsteinle@siumed.edu
OI Steinle, Jena/0000-0002-7539-2892
FU NIA NIH HHS [R15AG027827A] Funding Source: Medline
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NR 18
TC 26
Z9 28
U1 0
U2 1
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2007
VL 84
IS 1
BP 75
EP 81
DI 10.1016/j.exer.2006.08.018
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 123JP
UT WOS:000243292500010
PM 17074321
DA 2022-11-30
ER

PT J
AU Choudhary, S
   Xiao, T
   Srivastava, S
   Zhang, W
   Chan, LL
   Vergara, LA
   Van Kuijk, FJGM
   Ansari, NH
AF Choudhary, S
   Xiao, T
   Srivastava, S
   Zhang, W
   Chan, LL
   Vergara, LA
   Van Kuijk, FJGM
   Ansari, NH
TI Toxicity and detoxification of lipid-derived aldehydes in cultured
   retinal pigmented epithelial cells
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE 4-hydroxynonenal; 4-hydroxyhexenal; oxidative stress; retinal pigmented;
   epithelium; apoptosis; age-related macular degeneration
ID MITOCHONDRIAL PERMEABILITY TRANSITION; MACULAR DEGENERATION; INDUCED
   APOPTOSIS; OXIDATIVE STRESS; PEROXIDATION PRODUCT; ALDOSE REDUCTASE;
   OUTER SEGMENTS; HUMAN LENS; METALLOTHIONEIN; PATHOGENESIS
AB Age-related macular degeneration (ARMD) is the leading cause of blindness in the developed world and yet its pathogenesis remains poorly understood. Retina has high levels of polyunsaturated fatty acids (PUFAs) and functions under conditions of oxidative stress. To investigate whether peroxidative products of PUFAs induce apoptosis in retinal pigmented epithelial (RPE) cells and possibly contribute to ARMD, human retinal pigmented epithelial cells (ARPE-19) were exposed to micromolar concentrations of H2O2, 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE). A concentration- and time-dependent increase in H2O2-, HNE-, and HHE-induced apoptosis was observed when monitored by quantifying DNA fragmentation as determined by ELISA, flow cytometry, and Hoechst staining. The broad-spectrum inhibitor of apoptosis Z-VAD inhibited apoptosis. Treatment of RPE cells with a thionein peptide prior to exposure to H2O2 or HNE reduced the formation of protein-HNE adducts as well as alteration in mitochondrial membrane potential and apoptosis. Using 3 H-FINE, various metabolic pathways to detoxify HNE by ARPE-19 cells were studied. The metabolites were separated by HPLC and characterized by ElectroSpray Ionization-Mass Spectrometry (ESI-MS) and gas chromatography-MS. Three main metabolic routes of HNE detoxification were detected: (1) conjugation with glutathione (GSH) to form GS-HNE, catalyzed by glutathione-S-transferase (GST), (2) reduction of GS-HNE catalyzed by aldose reductase, and (3) oxidation of HNE catalyzed by aldehyde dehydrogenase (ALDH). Preventing HNE fort-nation by a combined strategy of antioxidants, scavenging HNE by thionein peptide, and inhibiting apoptosis by caspase inhibitors may offer a potential therapy to limit retinal degeneration in ARMD. (c) 2004 Elsevier Inc. All rights reserved.
C1 Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA.
   Univ Louisville, Dept Med, Div Cardiol, Louisville, KY 40208 USA.
   Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA.
   Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77555 USA.
C3 University of Texas System; University of Texas Medical Branch
   Galveston; University of Louisville; University of Texas System;
   University of Texas Medical Branch Galveston; University of Texas
   System; University of Texas Medical Branch Galveston
RP Ansari, NH (通讯作者)，Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA.
EM nansari@utmb.edu
RI Srivastava, Sanjay/D-3921-2012
OI Choudhary, Sanjeev/0000-0001-8290-7420
FU NEI NIH HHS [EY13104] Funding Source: Medline; NHLBI NIH HHS [HL61618]
   Funding Source: Medline
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NR 54
TC 82
Z9 87
U1 0
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD APR 15
PY 2005
VL 204
IS 2
BP 122
EP 134
DI 10.1016/j.taap.2004.08.023
PG 13
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA 916GF
UT WOS:000228372700003
PM 15808518
DA 2022-11-30
ER

PT J
AU Toth, CA
   Lapolice, DJ
   Banks, AD
   Stinnett, SS
AF Toth, CA
   Lapolice, DJ
   Banks, AD
   Stinnett, SS
TI Improvement in near visual function after macular translocation surgery
   with 360-degree peripheral retinectomy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID RETINOTOMY; PSYCHOPHYSICS; DEGENERATION; SIZE
AB Background: Information is limited on how specific near-vision skills are impacted by therapies such as macular translocation surgery with 360-degree retinectomy (MT360) for age-related macular degeneration (AMD). Methods: Standardized tests of near vision were given to 25 consecutive patients with AMD who met entry criteria for this study, preoperatively and 6 and 12 months after MT360. Tests included: near acuity with the Lighthouse chart, timed reading speed using Sloan cards, contrast sensitivity, and color vision. Distance acuity was measured using Bailey-Lovey charts. Measures of preoperative visual function were analyzed to identify those predictive of visual outcomes. Results: Distance acuity was 20/80 or better in 52% of patients at 12 months after surgery, and mean acuity improved from similar to20/125 preoperatively to similar to20/100 at 12 months. Mean near acuity improved from 3.2 +/- 2.5 M before surgery to 1.5 +/- 1.0 M at 12 months (significant change of -1.5 +/- 2 M, P < 0.001). Gain of greater than five numbers in contrast sensitivity at 12 months was also significant (P < 0.001). Mean reading speed improved from 41 31 words per minute (wpm) before surgery to 67 44 wpm at 12 months (significant gain of 25 +/- 33 wpm, P = 0.001). Preoperative distance acuity, near acuity, and reading speed were each predictors of postoperative near visual function. Conclusion: Standardized testing of near visual function provides important predictive and functional outcome data for MT360. MT360 significantly improved near visual function (including near acuity, reading speed and contrast sensitivity) in patients with subfoveal lesions from AMD in the second eye.
C1 Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27701 USA.
   Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
   Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA.
C3 Duke University; Duke University; Duke University
RP Toth, CA (通讯作者)，Duke Univ, Med Ctr, Dept Ophthalmol, Box 3802, Durham, NC 27701 USA.
EM toth004@mc.duke.edu
RI Toth, Cynthia/L-5534-2019; toth, cynthia a/F-5614-2011
OI Toth, Cynthia/0000-0002-2324-0854; Stinnett, Sandra/0000-0001-7192-0195
CR Abdel-Meguid A, 2003, BRIT J OPHTHALMOL, V87, P615, DOI 10.1136/bjo.87.5.615
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   1998, SUBMACULAR SURG TRIA
NR 25
TC 35
Z9 35
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2004
VL 242
IS 7
BP 541
EP 548
DI 10.1007/s00417-004-0867-1
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 847PN
UT WOS:000223407500002
PM 15185091
DA 2022-11-30
ER

PT J
AU Yang, Q
   Cai, WT
   Jin, HZ
   Shen, TY
   Yu, J
AF Yang, Qian
   Cai, Wenting
   Jin, Huizi
   Shen, Tianyi
   Yu, Jing
TI Downregulation of Inflammatory Response via Nrf2/Trx1/TXNIP Axis in
   Oxidative Stress-Induced ARPE-19 Cells and Mouse Model of AMD
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID INHIBITS NLRP3 INFLAMMASOME; DEGENERATION; THIOREDOXIN; ACTIVATION;
   DISEASE
AB Aim. Chronic inflammation is crucial for age-related macular degeneration (AMD) pathogenesis. However, the mechanism involved in activating inflammation remains unclear. This study is aimed at investigating whether nuclear factor erythrocyte-associated factor 2 (Nrf2) negatively regulated the Nod-like receptor protein 3 (NLRP3) inflammasomes through the thioredoxin 1 (Trx1)/thioredoxin interaction protein (TXNIP) complex. Methods. We determined the optimal hydrogen peroxide (H2O2) concentration, time, and changes in reactive oxygen species (ROS) levels. We also constructed animal models using blue LED irradiation. Then, the expression of Nrf2, TXNIP, Trx1, NLRP3, and inflammation-related factors and proteins, along with the changes in retinal thickness and functional status, was analyzed. Results. The oxidative stress model was established after 1 h intervention with 100 mu M H2O2. Nrf2 reduced ROS production, protected the ultrastructure of mitochondria, increased the thickness of the ONL layer, and increased the amplitude of a- and b-wave amplitudes in ERG. Trx1 knockdown increased the production of ROS, damaged the ultrastructure of mitochondria, reduced the thickness of the other ONL layer, and reduced the amplitudes of a- and b-waves in the electroretinogram (ERG). Thus, TXNIP in the cytoplasm activated the inflammasomes. Conclusions. Nrf2 showed antioxidant and anti-inflammatory activity in the H2O2-induced cell stress model and blue LED-induced retinal light damage model. TXNIP transferred from the nucleus to the cytoplasm, activated NLRP3, and aggravated the retinal injury in both the cell stress model and the animal blue LED model. In contrast, Trx1 knockout promoted this process. This study revealed the possible role of the thioredoxin system in developing AMD while also providing newer insights for the future treatment of AMD.
C1 [Yang, Qian; Cai, Wenting; Jin, Huizi; Shen, Tianyi; 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 qyang0918@163.com; caiwentingtj@163.com; huiziking@126.com;
   1831263@tongji.edu.cn; dryujing@aliyun.com
FU Medical Science and Technology Project of Health Commission of Zhejiang
   Province; Natural Science Foundation of Shanghai;  [2019KY643]; 
   [19ZR1439500]
FX AcknowledgmentsFunding for this research was provided by the Medical
   Science and Technology Project of Health Commission of Zhejiang Province
   (2019KY643) and the Natural Science Foundation of Shanghai (No.
   19ZR1439500).
CR [Anonymous], 2015, Int J Nanomedicine, V10, P6657, DOI 10.2147/IJN.S97780
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NR 35
TC 0
Z9 0
U1 3
U2 3
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 AUG 12
PY 2022
VL 2022
AR 1497813
DI 10.1155/2022/1497813
PG 19
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 3X9NB
UT WOS:000843358200002
PM 35993020
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Fujita, K
   Suzukamo, Y
   Murotani, K
   Jinno, A
   Kamei, M
AF Fujita, Kyoko
   Suzukamo, Yoshimi
   Murotani, Kenta
   Jinno, Akiko
   Kamei, Motohiro
TI Impact of low luminance conditions on quality of life for the visually
   impaired: development of the Low Luminance Questionnaire Japanese
   version
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Low Luminance Questionnaire; Low luminance visual acuity; Low luminance
   deficit; Activities of daily living; Quality of life
ID ADAPTATION
AB Purpose This study aimed to develop a Japanese version of the Low Luminance Questionnaire (LLQ-J) and to evaluate its reliability and validity. Study design Cross-sectional study. Methods LLQ-J was developed by standardized methods. A total of 101 patients comprising 55 with age-related macular degeneration, 25 with glaucoma, 15 with regressed proliferative diabetic retinopathy, and 6 with retinitis pigmentosa were included in this study. The patients completed the LLQ-J and Japanese version of the visual function Questionnaire-25 (VFQ-25). Using the LLQ-J data, floor and ceiling effects were computed. To examine internal consistency, some patients completed the LLQ-J a second time 2-4 weeks later and the data were analyzed for Cronbach's alpha and intra-class correlation coefficients (ICCs). Best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) were measured, and low-luminance deficit (LLD) was calculated. Criterion validity was also tested. Results No ceiling or floor effects were present in the LLQ-J data. Cronbach's alfa was 0.88, and ICCs were higher than 0.70 for all subscales. Moderate to high correlation was observed between LLQ-J and VFQ-25 (p < 0.01), confirming concurrent validity. "General dim lighting" and "Peripheral vision" were significantly associated with LLVA in the better eye (p < 0.05). "Mobility", "General dim lighting" and "Peripheral vision" were significantly associated with LLD (p < 0.05). "Emotional distress" was significantly associated with BCVA in the worse eye (p < 0.05). No subscales were associated with BCVA of the better eye. Conclusions The LLQ-J is a valid and reliable questionnaire for assessing QOL under low luminance conditions.
C1 [Fujita, Kyoko; Jinno, Akiko; Kamei, Motohiro] Aichi Med Univ, Dept Ophthalmol, 1-1 Yazakokarimata, Nagakute, Aichi 4801195, Japan.
   [Suzukamo, Yoshimi] Tohoku Univ, Grad Sch Med, Dept Phys Med & Rehabil, Sendai, Miyagi, Japan.
   [Murotani, Kenta] Kurume Med Univ, Dept Biostat, Kurume, Fukuoka, Japan.
C3 Aichi Medical University; Tohoku University; Kurume University
RP Fujita, K (通讯作者)，Aichi Med Univ, Dept Ophthalmol, 1-1 Yazakokarimata, Nagakute, Aichi 4801195, Japan.
EM fujita.kyouko.249@mail.aichi-med-u.ac.jp
FU JSPS KAKENHI [20K02199]
FX This work was supported by JSPS KAKENHI Grant Number 20K02199.
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NR 15
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD JUL
PY 2021
VL 65
IS 4
BP 554
EP 560
DI 10.1007/s10384-021-00838-4
EA MAY 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SW0GG
UT WOS:000650817200001
PM 33991271
DA 2022-11-30
ER

PT J
AU Liu, JF
   Tong, K
   Lin, YH
   Lee, VWH
   So, KF
   Shih, KC
   Lai, JSM
   Chiu, K
AF Liu, Jinfeng
   Tong, Kelvin
   Lin, Youhong
   Lee, Vincent W. H.
   So, Kwok Fai
   Shih, Kendrick Co
   Lai, Jimmy S. M.
   Chiu, Kin
TI Effectiveness of Microcurrent Stimulation in Preserving Retinal Function
   of Blind Leading Retinal Degeneration and Optic Neuropathy: A Systematic
   Review
SO NEUROMODULATION
LA English
DT Review
DE Electrical phosphene threshold; electrical stimulation; neuroprotection;
   retinal degeneration; visual function
ID TRANSCORNEAL ELECTRICAL-STIMULATION; ALTERNATING-CURRENT STIMULATION;
   BLOOD-FLOW-VELOCITY; VISUAL FUNCTION; GANGLION-CELLS; VISION; EFFICACY;
   QUALITY; RESTORATION; EXPRESSION
AB Objectives To systematically identify and summarize the effectiveness and the parameters of electrical stimulation (ES) for the preservation of visual function in major retinal degeneration and optic neuropathy.
   Materials and Methods A systematic review of clinical studies, using ES therapy in patients with blind leading retinal degenerations, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO), retinal artery occlusion (RAO), and optic neuropathy was conducted. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant interventional studies including randomized controlled trials (RCTs) and observational studies.
   Results A total of 10 RCTs and 15 observational studies were included. Transcorneal ES (TcES), transpalpebral ES (TpES), transdermal ES (TdES), and repetitive transorbital alternating current stimulation (rtACS) were used for the treatment of the patients. ES using 20 Hz biphasic pulses with current strength at 150%-200% of individual electrical phosphene threshold (EPT) for RP patients showed improved retinal function detected by visual acuity (VA), visual field (VF), or electrical retinal graphs (ERG). rtACS on patients with optic neuropathy showed significant preservation of VA and VF. Clinical studies on AMD, RAO, and glaucoma indicated promising protective effects of ES on the visual function, though the amount of evidence is limited.
   Conclusions ES treatment has promising therapeutic effects on RP and optic neuropathy. More large-scale RCT studies should be conducted to elucidate the potential of ES, especially on AMD, RAO, and glaucoma. A comparison of the effects by different ES methods in the same disease populations is still lacking. Parameters of the electric current and sensitive detection method should be optimized for the evaluation of ES treatment effects in future studies.
C1 [Liu, Jinfeng; Lin, Youhong; Lee, Vincent W. H.; So, Kwok Fai; Shih, Kendrick Co; Lai, Jimmy S. M.; Chiu, Kin] Univ Hong Kong, LKS Fac Med, Dept Ophthalmol, Room 410,5 Sassoon Rd, Hong Kong, Peoples R China.
   [Tong, Kelvin] Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Peoples R China.
   [So, Kwok Fai; Chiu, Kin] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China.
   [So, Kwok Fai] Guangdong HongKong Macau Inst CNS Regenerat Guang, Guangzhou, Peoples R China.
C3 University of Hong Kong; University of Hong Kong; University of Hong
   Kong
RP Chiu, K (通讯作者)，Univ Hong Kong, LKS Fac Med, Dept Ophthalmol, Room 410,5 Sassoon Rd, Hong Kong, Peoples R China.
EM datwai@hku.hk
RI Shih, Kendrick Co/E-9883-2010; Chiu, Kin/C-4152-2009
OI Shih, Kendrick Co/0000-0001-6255-2941; Chiu, Kin/0000-0001-6581-9007;
   So, Kwok-Fai/0000-0003-4039-4246
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NR 52
TC 4
Z9 4
U1 2
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1094-7159
EI 1525-1403
J9 NEUROMODULATION
JI Neuromodulation
PD AUG
PY 2021
VL 24
IS 6
BP 992
EP 1002
DI 10.1111/ner.13414
EA MAY 2021
PG 11
WC Medicine, Research & Experimental; Clinical Neurology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Neurosciences & Neurology
GA UI1MU
UT WOS:000649853600001
PM 33984873
DA 2022-11-30
ER

PT J
AU Jiang, XS
   Shen, MX
   Wang, L
   de Sisternes, L
   Durbin, MK
   Feuer, W
   Rosenfeld, PJ
   Gregori, G
AF Jiang, Xiaoshuang
   Shen, Mengxi
   Wang, Liang
   de Sisternes, Luis
   Durbin, Mary K.
   Feuer, William
   Rosenfeld, Philip J.
   Gregori, Giovanni
TI Validation of a Novel Automated Algorithm to Measure Drusen Volume and
   Area Using Swept Source Optical Coherence Tomography Angiography
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE swept source optical coherence tomography angiography; spectral domain
   optical coherence tomography; retinal pigment epithelial elevations;
   drusen; volume
ID PIGMENT EPITHELIAL DETACHMENTS; MACULAR DEGENERATION; SD-OCT; NATURAL
   COURSE; SEGMENTATION; RISK; EYES
AB Purpose: The purpose of this study was to validate a novel automated swept source optical coherence tomography angiography (SS-OCTA) algorithm to measure elevations of the retinal pigment epithelium (RPE) in eyes with nonexudative age-related macular degeneration (neAMD).
   Methods: Patients with drusen were enrolled in a prospective optical coherence tomography (OCT) study and underwent both spectral domain OCT (SD-OCT) and SS-OCTA imaging at the same visit using the 6 x 6 mm scan patterns. The RPE elevation measurements (square root area and cube root volume) from the SS-OCTA algorithm were compared with the automated validated SD-OCT algorithm on the instrument. Standard deviations of drusen measurements from four repeated scans of another separate set were also calculated to evaluate the reproducibility of the SS-OCTA algorithm.
   Results: A total of 53 eyes from 28 patients were scanned on both instruments. A very strong correlation was found between the measurements from the two algorithms (all r > 0.95), although the measurements of the drusen area and volume were all larger from the SS-OCTA instrument. The reproducibility of the new SS-OCTA algorithm was analyzed using a sample of 66 eyes from 43 patients. The intraclass correlation coefficient (ICC) was greater than 99% from different macular regions for both the square root area and cube root volume measurements.
   Conclusions: A novel automated SS-OCTA algorithm for the quantitative assessment of drusen was validated against the SD-OCT algorithm and was shown to be highly reproducible.
   Translational Relevance: This novel SS-OCTA algorithm provides a strategy to measure the area and volume of drusen to assess disease progression in neAMD.
C1 [Jiang, Xiaoshuang; Shen, Mengxi; Wang, Liang; Feuer, William; Rosenfeld, Philip J.; Gregori, Giovanni] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Jiang, Xiaoshuang] Sichuan Univ, West China Hosp, Dept Ophthalmol, Chengdu, Peoples R China.
   [de Sisternes, Luis; Durbin, Mary K.] Carl Zeiss Meditec Inc, Res & Dev, Dublin, CA USA.
C3 Bascom Palmer Eye Institute; University of Miami; Sichuan University;
   Carl Zeiss AG
RP Gregori, G (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM ggregori@med.miami.edu
RI Shen, Mengxi/ABC-6941-2021
OI Shen, Mengxi/0000-0002-1336-1695
FU Carl Zeiss Meditec, Inc. (Dublin, CA); Salah Foundation; National Eye
   Institute Center Core Grant [P30EY014801]; Research to Prevent Blindness
FX Supported by Grants from Carl Zeiss Meditec, Inc. (Dublin, CA), the
   Salah Foundation, the National Eye Institute Center Core Grant
   (P30EY014801), and Research to Prevent Blindness (unrestricted Grant) to
   the Department of Ophthalmology, University of MiamiMiller School of
   Medicine. The funding organization had no role in the design or conduct
   of this research.
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Z9 7
U1 1
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD APR
PY 2021
VL 10
IS 4
AR 11
DI 10.1167/tvst.10.4.11
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RW0SI
UT WOS:000646234300005
PM 34003988
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nath, SC
   Harper, L
   Rancourt, DE
AF Nath, Suman C.
   Harper, Lane
   Rancourt, Derrick E.
TI Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor:
   Thoughts for cGMP Compliance
SO FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
LA English
DT Review
DE cell-based therapy; biologics manufacturing; cGMP; genetic engineering;
   integrated bioprocessing; bioreactor
ID PLURIPOTENT STEM-CELLS; MESENCHYMAL STROMAL CELLS; ZINC-FINGER
   NUCLEASES; IN-VITRO EXPANSION; CD8(+) T-CELLS; SCALABLE EXPANSION;
   GENE-THERAPY; HEPATIC DIFFERENTIATION; CLINICAL-APPLICATION; LENTIVIRAL
   VECTOR
AB Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson's disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the "cells are the final products" and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.
C1 [Nath, Suman C.; Harper, Lane; Rancourt, Derrick E.] Univ Calgary, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB, Canada.
   [Nath, Suman C.; Rancourt, Derrick E.] Univ Calgary, Cumming Sch Med, McCaig Inst Bone & Joint Hlth, Calgary, AB, Canada.
C3 University of Calgary; University of Calgary
RP Nath, SC; Harper, L; Rancourt, DE (通讯作者)，Univ Calgary, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB, Canada.; Nath, SC; Rancourt, DE (通讯作者)，Univ Calgary, Cumming Sch Med, McCaig Inst Bone & Joint Hlth, Calgary, AB, Canada.
EM suman.nath1@ucalgary.ca; lane.harper1@ucalgary.ca; rancourt@ucalgary.ca
OI Nath, Suman Chandra/0000-0002-4995-6252
FU Cumming School of Medicine Postdoctoral Fellowship
FX SN is partially supported by a Cumming School of Medicine Postdoctoral
   Fellowship.
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NR 190
TC 9
Z9 9
U1 1
U2 10
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-4185
J9 FRONT BIOENG BIOTECH
JI Front. Bioeng. Biotechnol.
PD NOV 26
PY 2020
VL 8
AR 599674
DI 10.3389/fbioe.2020.599674
PG 16
WC Biotechnology & Applied Microbiology; Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Science & Technology - Other
   Topics
GA PC2GA
UT WOS:000596824500001
PM 33324625
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Gabrielle, PH
   Seydou, A
   Arnould, L
   Acar, N
   Devilliers, H
   Baudin, F
   Ben Ghezala, I
   Binquet, C
   Bron, AM
   Creuzot-Garcher, C
AF Gabrielle, Pierre-Henry
   Seydou, Alassane
   Arnould, Louis
   Acar, Niyazi
   Devilliers, Herve
   Baudin, Florian
   Ben Ghezala, Ines
   Binquet, Christine
   Bron, Alain Marie
   Creuzot-Garcher, Catherine
TI Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study
   (the Montrachet Study)
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE subretinal drusenoid deposits; reticular pseudodrusen; prevalence;
   age-related maculopathy; age-related macular degeneration; optical
   coherence tomography; population-based study
ID AGE-RELATED MACULOPATHY; RETICULAR MACULAR DISEASE; CHOROIDAL THICKNESS;
   GEOGRAPHIC ATROPHY; PSEUDODRUSEN; DEGENERATION; PREVALENCE; PROGRESSION;
   EPIDEMIOLOGY; EYES
AB PURPOSE. The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population.
   METHODS. The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed.
   RESULTS. The mean age of patients was 82.3 +/- 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n = 205) in the subjects with at least one eye interpretable (n = 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8-7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2-2.4; P = 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0-1.5; P = 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3-0.9; P = 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7-0.9; P = 0.002).
   CONCLUSIONS. The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.
C1 [Gabrielle, Pierre-Henry; Arnould, Louis; Baudin, Florian; Ben Ghezala, Ines; Bron, Alain Marie; Creuzot-Garcher, Catherine] Univ Hosp, Dept Ophthalmol, 14 Rue Paul Gaffarel, F-21079 Dijon, France.
   [Gabrielle, Pierre-Henry; Seydou, Alassane; Acar, Niyazi; Bron, Alain Marie; Creuzot-Garcher, Catherine] Burgundy Univ, CSGA, Eye & Nutr Res Grp, UMR 1324,INRA,6265 CNRS, Dijon, France.
   [Seydou, Alassane; Devilliers, Herve; Binquet, Christine] Univ Hosp, Dept Epidemiol, INSERM Unit, Dijon, France.
C3 CHU Dijon Bourgogne; INRAE; Institut Agro; AgroSup Dijon; Centre
   National de la Recherche Scientifique (CNRS); Universite de Bourgogne;
   CHU Dijon Bourgogne; Institut National de la Sante et de la Recherche
   Medicale (Inserm); Universite de Bourgogne
RP Creuzot-Garcher, C (通讯作者)，Univ Hosp, Dept Ophthalmol, 14 Rue Paul Gaffarel, F-21079 Dijon, France.
EM catherine.creuzot-garcher@chu-dijon.fr
RI GABRIELLE, Pierre-Henry/Y-4971-2018; Arnould, Louis/AAG-2207-2021;
   BAUDIN, Florian/AHA-7176-2022; Bron, Alain/AAP-8010-2020; Binquet,
   Christine/E-8953-2018
OI GABRIELLE, Pierre-Henry/0000-0002-9688-4845; Bron,
   Alain/0000-0002-7265-931X; Binquet, Christine/0000-0002-9417-5754;
   Alassane, Seydou/0000-0001-8958-6834; Ben Ghezala,
   Ines/0000-0002-4002-7414
FU interregional grant (PHRC); regional Council of Burgundy; INRA; CNRS;
   Universite de Bourgogne; Regional Council of Burgundy France (PARI
   Agrale 1); FEDER (European Funding for Regional Economic Development);
   French Government grant [ANR-11-LABX-0021-01-LipSTIC Labex]
FX Supported by an interregional grant (PHRC) and the regional Council of
   Burgundy; by INRA, CNRS, Universite de Bourgogne, Regional Council of
   Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional
   Economic Development); and a French Government grant managed by the
   French National Research Agency (ANR) under the "Investissements
   d'Avenir'' program, ANR-11-LABX-0021-01-LipSTIC Labex.
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NR 55
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 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2019
VL 60
IS 14
BP 4838
EP 4848
DI 10.1167/iovs.19-27283
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JS4YT
UT WOS:000500313300034
PM 31747683
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Yang, HJ
   Hu, R
   Sun, H
   Chen, B
   Li, X
   Chen, JB
AF Yang, Hua-jing
   Hu, Rui
   Sun, Hong
   Chen, Bo
   Li, Xia
   Chen, Jian-bin
TI 4-HNE induces proinflammatory cytokines of human retinal pigment
   epithelial cells by promoting extracellular efflux of HSP70
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE 4-Hydroxynonenal; HSP70; Retinal pigment epithelial cells; Inflammation;
   Age-related macular degeneration
ID NF-KAPPA-B; MACULAR DEGENERATION; NLRP3 INFLAMMASOME;
   HEAT-SHOCK-PROTEIN-70; NEUROINFLAMMATION; EXPRESSION; CHAPERONE; DEATH
AB Oxidative stress and subsequent chronic inflammation result in dysfunction of the retinal pigment epithelium (RPE) and represent therapeutic targets in the context of age-related macular degeneration (AMD). However, molecular mechanisms that linked oxidative stress and inflammation still unclear. As an important byproduct of oxidative stress, 4-hydroxynonenal (4-HNE) induces apoptosis and lysosome dysregulation of RPE cells. In the present study, we evaluated cytokines production of RPE cells induced by 4-HNE by using cytokine array and confirmed that 4-HNE induced IL-6, IL-1 beta and TNF-alpha production in a concentration dependent manner. Specifically, 4-HNE also induced IL-10 and TGF-beta production in low concentration. Molecular analysis revealed that intracellular HSP70 inhibited 4-HNE-induced production of pro-inflammatory cytokines, and 4-HNE exerted proinflammatory effects in RPE cells by enhancing extracellular release of HSP70, as efflux inhibitor Methyl-beta-cyclodextrin (MBC) treatment significantly blocked the release of HSP70 and decreased IL-6 production of RPE cells induced by 4-HNE. Meanwhile, HSP70 inducer arimoclomol increased intracellular HSP70 production, but showed no influence on its extracellular level, also performed anti-inflammatory effects in 4-1-ME-stimulated RPE cells. Whereas the anti-inflammatory effects of paeoniflorin, an HSP70 inducer simultaneously promoted its extracellular efflux, was lower than arimoclomol. In addition, we further confirmed that MBC exhibited synergetic effect with both paeoniflorin and arimoclomol to inhibit the production of proinflammatory cytokines induced by 4-HNE. Taken together, these results indicate that HSP70 plays a vital role in regulating inflammation of RPE cells induced by oxidative stress and might be a potential novel target for clinical treatment of AMD.
C1 [Yang, Hua-jing; Chen, Bo; Chen, Jian-bin] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Ophthalomol, Wuhan 430030, Hubei, Peoples R China.
   [Hu, Rui; Sun, Hong] Huazhong Univ Sci & Technol, Wuhan Med & Hlth Ctr Women & Children, Dept Eugen Genet Lab, Wuhan 430016, Hubei, Peoples R China.
   [Li, Xia] Wuhan Univ, Enshi Clin Coll, Cent Hosp Enshi Autonomous Prefecture, Ophthalm Ctr, Enshi 445000, Hubei, Peoples R China.
C3 Huazhong University of Science & Technology; Huazhong University of
   Science & Technology; Wuhan University
RP Chen, JB (通讯作者)，Huazhong Univ Sci & Technol, Tongji Hosp, Dept Ophthalomol, Wuhan 430030, Hubei, Peoples R China.; Li, X (通讯作者)，Wuhan Univ, Enshi Clin Coll, Cent Hosp Enshi Autonomous Prefecture, Ophthalm Ctr, Enshi 445000, Hubei, Peoples R China.
EM lixiaxxx@sina.com.cn; jbchen10@163.com
FU Natural Science Foundation of Hubei Province, China [2009CDB115,
   2012FKB02444, 2018CFB463]; Natural Science Foundation of Health and
   Family Planning Commission of Wuhan Municipality, Hubei Province, China
   [WX18Q03]
FX This project was supported by grants from Natural Science Foundation of
   Hubei Province, China (No. 2009CDB115, 2012FKB02444 and 2018CFB463), and
   Natural Science Foundation of Health and Family Planning Commission of
   Wuhan Municipality, Hubei Province, China (No. WX18Q03).
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   2009, CHIN ECON YEARB, V3, P1
NR 43
TC 13
Z9 13
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 NOV
PY 2019
VL 188
AR 107792
DI 10.1016/j.exer.2019.107792
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JJ9XC
UT WOS:000494503700014
PM 31499034
DA 2022-11-30
ER

PT J
AU Singh, SR
   Oli, A
   Mohan, S
   Goud, A
   Rasheed, MA
   Vupparaboina, KK
   Chhablani, JK
AF Singh, Sumit Randhir
   Oli, Avadhesh
   Mohan, Sashwanthi
   Goud, Abhilash
   Rasheed, Mohammed A.
   Vupparaboina, Kiran K.
   Chhablani, Jay K.
TI Pachydrusen in Indian population: A hospital-based study
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; fluorescein angiography; optical
   coherence tomography; pachydrusen; soft drusen; subretinal drusenoid
   deposits
ID SWEPT-SOURCE OCT; POLYPOIDAL CHOROIDAL VASCULOPATHY; SPECTRAL-DOMAIN
   OCT; MACULAR DEGENERATION; CLINICAL-FEATURES; RURAL-POPULATION;
   THICKNESS; PREVALENCE
AB To report the prevalence of pachydrusen in Indian population and their characteristics in relation to subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI) in comparison to eyes with soft drusen and subretinal drusenoid deposits (SDD) in age-related macular degeneration (AMD). Methods: The study was a retrospective, cross-sectional study involving patients with a diagnosis of dry AMD in at least one eye. The diagnosis of soft drusen, SDD, and pachydrusen was made on the basis of color fundus photograph and optical coherence tomography (OCT). SFCT and CVI was calculated and compared among the different subtypes of drusen. Results: A total of 169 eyes (143 dry and 26 wet AMD) of 85 patients with a mean age of 67.67 +/- 9.57 years were included. In eyes with dry AMD, pachydrusen were seen in 12 eyes (8.4%) with a mean (+/- SD) SFCT of 289.66 +/- 91.01 mu. The difference in SFCT was statistically significant (P = 0.001) using analysis of variance (ANOVA) test. The eyes with pachydrusen had significantly thickened choroid compared to the eyes with SDD (30 eyes; 21.0%) or combination of soft drusen and SDD (29 eyes; 20.3%) but not soft drusen (72 eyes; 50.3%). The difference of CVI in different subgroups was significant (P = 0.03). One eye in wet AMD group had concurrent pachydrusen. Comparison of SFCT and CVI in wet AMD and fellow dry AMD eyes were not significant. Conclusion: In Indian eyes with dry AMD, prevalence of pachydrusen (8.4%) is slightly lower compared to western literature (11.7%) and is associated with thicker choroid and higher CVI.
C1 [Singh, Sumit Randhir; Oli, Avadhesh; Goud, Abhilash; Rasheed, Mohammed A.; Vupparaboina, Kiran K.; Chhablani, Jay K.] LV Prasad Eye Inst, Smt Kanuri Santhamma Ctr Vitreoretinal Dis, Banjara Hills, Hyderabad 34, Telangana, India.
   [Mohan, Sashwanthi] LV Prasad Eye Inst, Acad Eye Care Educ, Hyderabad, Telangana, India.
C3 L. V. Prasad Eye Institute; L. V. Prasad Eye Institute
RP Chhablani, JK (通讯作者)，LV Prasad Eye Inst, Smt Kanuri Santhamma Ctr Vitreoretinal Dis, Banjara Hills, Hyderabad 34, Telangana, India.
EM jay.chhablani@gmail.com
RI OLI, AVADHESH/T-1234-2018
OI Mohan, Sashwanthi/0000-0002-2239-5440; Abdul Rasheed,
   Mohammed/0000-0002-6417-2552; Chhablani, Jay/0000-0003-1772-3558
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NR 28
TC 7
Z9 7
U1 0
U2 1
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD MAR
PY 2019
VL 67
IS 3
BP 371
EP 375
DI 10.4103/ijo.IJO_1173_18
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HM1VD
UT WOS:000459241600013
PM 30777955
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ibrahim, AM
   Elgouhary, SM
   Nassar, MK
   El Batanony, AH
AF Ibrahim, Asmaa Mohamed
   Elgouhary, Sameh Mohamed
   Nassar, Moustafa Kamal
   El Batanony, Ahmed Helmy
TI Changes in Choroidal Thickness after Cataract Surgery
SO SEMINARS IN OPHTHALMOLOGY
LA English
DT Article
DE Central retinal thickness; EDI-OCT; subfoveal choroidal thickness
ID OPTICAL COHERENCE TOMOGRAPHY; INTRAOCULAR-LENS IMPLANTATION; CYSTOID
   MACULAR EDEMA; MYOPIC EYES; DEPTH; EXTRACTION; PRESSURE
AB Objective: The aim of this study is to compare subfoveal choroidal thickness (SFCT) before and after uneventful phacoemulsification using enhanced depth imaging optical coherence tomography (EDI-OCT). Background: Cataract is a major cause of visual impairment in the elderly. Cataract surgery is the most common ophthalmic surgery and is performed simultaneously with glaucoma or vitreous surgery in many cases. However, according to the results in epidemiology studies, cataract surgery is associated with the onset of age-related macular degeneration (AMD) and cataract surgery increases visual acuity in these patients without an increased risk of progression to exudative AMD. Methods: A prospective study was conducted on 53 eyes of 53 patients who had phacoemulsification. Measurements of SFCT were performed preoperatively, 7 days (D7), 1 month (Ml), and 3 months (M3) postoperative using the EDI-OCT technique. Central retinal thickness was also measured at the same time. Results: Twenty-seven male (50.9%) and 26 female (49.1%) with a mean age of 56.43 years +/- 10.34 (SD) were analyzed. The mean choroidal thickness was 199.9 +/- 60.74 mu m. It significantly increased to 228.42 +/- 59.77 mu m at D7, then decreased to 210.78 +/- 59.59 mu m at Ml, and then decreased to 200.63 +/- 61 mu m at M3. The mean retinal thickness was 260.79 +/- 6.12 mu m. It significantly increased to 294.09 +/- 7.20 mu m at D7 and then decreased to 274.70 +/- 6.00 mu m at Ml and 258.92 +/- 5.89 mu m at M3. Conclusion: Mean SFCT increased after cataract surgery. The changes in SFCT return to near the baseline after 3 months.
C1 [Ibrahim, Asmaa Mohamed; Elgouhary, Sameh Mohamed; Nassar, Moustafa Kamal; El Batanony, Ahmed Helmy] Menoufia Univ, Ophthalmol Dept, Fac Med, Shibin Al Kawm, Egypt.
C3 Egyptian Knowledge Bank (EKB); Menofia University
RP Ibrahim, AM (通讯作者)，Menoufia Univ, Ophthalmol, Yaseen Abdel Ghaffar St, Shibin Al Kawm 32511, Egypt.
EM khsemsem@yahoo.com
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NR 26
TC 12
Z9 13
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0882-0538
EI 1744-5205
J9 SEMIN OPHTHALMOL
JI Semin. Ophthalmol.
PY 2018
VL 33
IS 5
BP 664
EP 670
DI 10.1080/08820538.2017.1416410
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GM5CX
UT WOS:000438148800012
PM 29278973
DA 2022-11-30
ER

PT J
AU Zhao, CP
   Boles, NC
   Miller, JD
   Kawola, S
   Temple, S
   Davis, RJ
   Stern, JH
AF Zhao, Cuiping
   Boles, Nathan C.
   Miller, Justine D.
   Kawola, Suzanne
   Temple, Sally
   Davis, Richard J.
   Stern, Jeffrey H.
TI Development of a Refined Protocol for Trans-scleral Subretinal
   Transplantation of Human Retinal Pigment Epithelial Cells into Rat Eyes
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 126; Subretinal injection; trans-sclera route; cell
   transplantation; retinal pigment epithelium; Royal College of Surgeons
   rat; age-related macular degeneration; stem cell therapy
ID STEM-CELL; MACULAR DEGENERATION; RPE MONOLAYERS; MECHANISMS; DISEASE
AB Degenerative retinal diseases such as age-related macular degeneration (AMD) are the leading cause of irreversible vision loss worldwide. AMD is characterized by the degeneration of retinal pigment epithelial (RPE) cells, which are a monolayer of cells functionally supporting and anatomically wrapping around the neural retina. Current pharmacological treatments for the non-neovascular AMD (dry AMD) only slow down the disease progression but cannot restore vision, necessitating studies aimed at identifying novel therapeutic strategies. Replacing the degenerative RPE cells with healthy cells holds promise to treat dry AMD in the future. Extensive preclinical studies of stem cell replacement therapies for AMD involve the transplantation of stem cell-derived RPE cells into the subretinal space of animal models, in which the subretinal injection technique is applied. The approach most frequently used in these preclinical animal studies is through the trans-scleral route, which is made difficult by the lack of direct visualization of the needle end and can often result in retinal damage. An alternative approach through the vitreous allows for direct observation of the needle end position, but it carries a high risk of surgical traumas as more eye tissues are disturbed. We have developed a less risky and reproducible modified trans-scleral injection method that uses defined needle angles and depths to successfully and consistently deliver RPE cells into the rat subretinal space and avoid excessive retinal damage. Cells delivered in this manner have been previously demonstrated to be efficacious in the Royal College of Surgeons (RCS) rat for at least 2 months. This technique can be used not only for cell transplantation but also for delivery of small molecules or gene therapies.
C1 [Zhao, Cuiping; Boles, Nathan C.; Miller, Justine D.; Kawola, Suzanne; Temple, Sally; Davis, Richard J.; Stern, Jeffrey H.] Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
RP Zhao, CP (通讯作者)，Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
EM christinezhao@neuralsci.org
FU NYSTEM [C028504]; NIH [F32EY025931]; NATIONAL EYE INSTITUTE
   [F32EY025931] Funding Source: NIH RePORTER
FX We wish to thank Patty Lederman for her assistance on the surgery and
   Susan Borden for RPE cell preparation. We also acknowledge NYSTEM
   C028504 for the funding for this project. Justine D. Miller is supported
   by NIH grant F32EY025931.
CR Abdelsalam A, 1999, SURV OPHTHALMOL, V44, P1, DOI 10.1016/S0039-6257(99)00072-7
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NR 21
TC 2
Z9 2
U1 0
U2 2
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2017
IS 126
AR e55220
DI 10.3791/55220
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FM8VM
UT WOS:000415369500009
PM 28829422
OA Green Published
DA 2022-11-30
ER

PT J
AU Wu, MX
   Xiong, HB
   Xu, Y
   Xiong, XJ
   Zou, HM
   Zheng, MM
   Wang, XQ
   Zhou, XY
AF Wu, Mingxing
   Xiong, Haibo
   Xu, Yan
   Xiong, Xiaojing
   Zou, Hongmi
   Zheng, Minming
   Wang, Xiuqing
   Zhou, Xiyuan
TI Association between VEGF-A and VEGFR-2 polymorphisms and response to
   treatment of neovascular AMD with anti-VEGF agents: a meta-analysis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; INTRAVITREAL
   RANIBIZUMAB; GENE POLYMORPHISMS; BEVACIZUMAB; THERAPY; PHARMACOGENETICS;
   PUBLICATION; DISEASE; BIAS
AB Aims The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD).
   Methods We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD.
   Results For the single nucleotide polymorphisms (SNPs) within VEGF-A and VEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT: OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT: OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414 to 3.946, p=0.001), particularly for Asians (CC vs TT: OR=2.903, 95% CI 1.150 to 7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In subgroup analysis, rs833061 was more likely to be a predictor of response to anti-VEGF therapy specifically when ranibizumab (RBZ) only regime was adopted or visual acuity (VA) was taken as the standardised assessment of outcome. No association with response to anti-VEGF treatment was detected for the other eight polymorphisms.
   Conclusions Pharmacogenetics of VEGF-A polymorphism rs833061 may play a positive role in response to anti-VEGF therapy for nAMD.
C1 [Wu, Mingxing; Xiong, Haibo; Xu, Yan; Xiong, Xiaojing; Zou, Hongmi; Zheng, Minming; Wang, Xiuqing; Zhou, Xiyuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Chongqing, Peoples R China.
   [Xiong, Haibo] Chongqing Gen Hosp, Dept Ophthalmol, Chongqing, Peoples R China.
C3 Chongqing Medical University
RP Zhou, XY (通讯作者)，74 Linjiang Rd, Chongqing, Peoples R China.
EM zhouxiyuan2002@aliyun.com
FU National Natural Science Foundation of China [81170858, 81401423,
   81501487]
FX This work was supported by grants from the National Natural Science
   Foundation of China (No. 81170858, 81401423, 81501487).
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NR 33
TC 19
Z9 22
U1 1
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2017
VL 101
IS 7
BP 976
EP 984
DI 10.1136/bjophthalmol-2016-309418
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EY6BX
UT WOS:000404068600023
PM 28400373
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Nathan, JR
   Lakshmanan, G
   Michael, FM
   Seppan, P
   Ragunathan, M
AF Nathan, Jhansi Rani
   Lakshmanan, Ganesh
   Michael, Felicia Mary
   Seppan, Prakash
   Ragunathan, Malathi
TI Expression of adenosine receptors and vegf during angiogenesis and its
   inhibition by pentoxifylline-A study using zebrafish model
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE PTX; Angiogenesis; Adenosine receptors; Vertebrate model; Epiboly
ID ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; RETINAL NEOVASCULARIZATION;
   CARDIOVASCULAR-SYSTEM; DOWN-REGULATION; DISEASE; DISCOVERY; ORGANS;
   TUMORS; CELLS
AB Angiogenesis, formation of new blood vessels is an important process involved in neovascular diseases and tumor progression. Understanding and defining novel therapeutic targets of neovascular diseases like retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration have been hindered by a lack of appropriate animal models. Zebrafish provides an excellent vertebrate model to study above disorders since its circulatory system and retinal layers are similar to mammals. Adenosine is a known mediator of angiogenesis in hypoxic condition and adenosine receptor antagonists such as theophylline, theobromine are known to exert antiangiogenic properties. We evaluated the antiangiogenic potential of a methylxanthine pentoxifylline (PTX) with various concentrations (0.1-1 mM) at 50% epiboly stage (5.2 hpf) of zebrafish embryos and studied the mRNA expression of major angiogenic factors like vegfaa and its receptors under normal conditions and when treated with an adenosine analog NECA (5'-N-ethylcarboxamidoadenosine). Upregulation of adenosine receptors, hif-1 alpha and vegfaa by NECA could possibly mimic hypoxic condition, but PTX downregulated vegfaa and other growth factors at 1 mM concentration. Vegfa protein expression was also downregulated by PTX in the retina and the compound did not damage the retinal cells. Embryos treated with PTX generated abnormal phenotypic variants with poor vasculature, tail bending and developmental delay at 1 mM. Survival rates, heart rate and hatching rates were also significantly lower. Targeting the vegf signaling pathway with small molecules inhibiting adenosine receptors in addition to antagonizing vegf might be a promising approach to treat neovascular diseases of the retina and also tumors. (C) 2016 Elsevier Masson SAS. All rights reserved.
C1 [Nathan, Jhansi Rani; Ragunathan, Malathi] Univ Madras, Dr ALM PG IBMS, Dept Genet, Madras 600113, Tamil Nadu, India.
   [Lakshmanan, Ganesh; Michael, Felicia Mary; Seppan, Prakash] Univ Madras, Dr ALM PG IBMS, Dept Anat, Madras 600113, Tamil Nadu, India.
C3 University of Madras; University of Madras
RP Ragunathan, M (通讯作者)，Univ Madras, Dr ALM PG IBMS, Dept Genet, Madras 600113, Tamil Nadu, India.
EM r_malathi@hotmail.com
RI Nathan, Jhansi Rani/I-2327-2013; Ganesh, Lakshmanan/AAF-4287-2019;
   Seppan, Prakash/ABA-2441-2021
OI Seppan, Prakash/0000-0003-0220-1159; Nathan, Jhansi/0000-0002-0855-0088;
   Govindan, Lakshmanan/0000-0002-7503-354X
FU University Grants Commission - Rajiv Gandhi National Fellowship (UGC -
   RGNF)
FX Financial support from University Grants Commission - Rajiv Gandhi
   National Fellowship (UGC - RGNF) is gratefully acknowledged.
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NR 39
TC 18
Z9 19
U1 0
U2 11
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0753-3322
EI 1950-6007
J9 BIOMED PHARMACOTHER
JI Biomed. Pharmacother.
PD DEC
PY 2016
VL 84
BP 1406
EP 1418
DI 10.1016/j.biopha.2016.10.045
PG 13
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA EF6JU
UT WOS:000390438100163
PM 27802896
DA 2022-11-30
ER

PT J
AU Monestam, E
AF Monestam, Eva
TI Long-term outcomes of cataract surgery: 15-year results of a prospective
   study
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID BLUE-MOUNTAINS-EYE; BEAVER-DAM-EYE; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; VISUAL IMPAIRMENT; 2ND EYE; POPULATION; OPACIFICATION;
   ASSOCIATION; PERSPECTIVE
AB PURPOSE: To describe the change over a 15-year period in corrected distance visual acuity (CDVA), subjective visual function, and neodymium:YAG (Nd:YAG) frequency after cataract surgery.
   SETTING: Eye Clinic, Norrlands University Hospital, Umea, Sweden.
   DESIGN: Prospective longitudinal population-based cohort study.
   METHODS: Patients who had cataract surgery during a 1-year period, 15 years previously (1997 to 1998), were included. All patients answered the same Visual Function-14 (VF-14) questionnaire preoperatively, 4 months postoperatively, and 5, 10, and 15 years after surgery. Most patients (88%; 168/190; 74% of survivors) also had an ocular examination. The CDVA was measured with logMAR charts.
   RESULTS: The study included 190 patients (83% of survivors). Fifteen years after surgery, the median CDVA in the operated eye had deteriorated from 20/20 postoperatively to 20/25 (P = .0001). Sixty percent of the patients had worsening of CDVA of less than 0.1 logMAR units compared with postoperatively. Fifty-four percent (103/190) had no deterioration in subjective visual function (VF-14), and 79% (150/190) had 10 points of decline or less. Previous Nd:YAG laser capsulotomy was more common in those younger than 65 years at surgery (49% versus 25%) (P = .002).
   CONCLUSIONS: The study confirms the effectiveness of cataract extraction, offering good long-term visual rehabilitation for the majority of the patients. The most common comorbidity causing large functional loss 15 years after surgery was age-related macular degeneration. Fifteen years after surgery, one half of the patients younger than 65 years at surgery had not required a posterior Nd:YAG laser capsulotomy. (C) 2016 ASCRS and ESCRS
C1 [Monestam, Eva] Umea Univ, Dept Clin Sci Ophthalmol, Fac Med, S-90185 Umea, Sweden.
C3 Umea University
RP Monestam, E (通讯作者)，Umea Univ, Dept Clin Sci Ophthalmol, Fac Med, S-90185 Umea, Sweden.
EM eva.monestam@vll.se
FU Vasterbottens County Council Research Fund, Umea, Sweden; Swedish
   Government ("Agreement concerning Research and Education of Doctors"
   ALF); Swedish Medical Society, Stockholm, Sweden; Capio Medocular,
   Stockholm, Sweden
FX Supported by grants from the Vasterbottens County Council Research Fund,
   Umea, Sweden; the Swedish Government ("Agreement concerning Research and
   Education of Doctors" ALF); the Swedish Medical Society, Stockholm,
   Sweden; and Capio Medocular, Stockholm, Sweden. The sponsor or funding
   organization had no role in the design or conduct of this research.
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NR 28
TC 12
Z9 13
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
EI 1873-4502
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD JAN
PY 2016
VL 42
IS 1
BP 19
EP 26
DI 10.1016/j.jcrs.2015.07.040
PG 8
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA DG5SP
UT WOS:000372139200005
PM 26948774
DA 2022-11-30
ER

PT J
AU Baumann, B
   Schirmer, J
   Rauscher, S
   Fialova, S
   Glosmann, M
   Augustin, M
   Pircher, M
   Groger, M
   Hitzenberger, CK
AF Baumann, Bernhard
   Schirmer, Johannes
   Rauscher, Sabine
   Fialova, Stanislava
   Gloesmann, Martin
   Augustin, Marco
   Pircher, Michael
   Groeger, Marion
   Hitzenberger, Christoph K.
TI Melanin Pigmentation in Rat Eyes: In Vivo Imaging by
   Polarization-Sensitive Optical Coherence Tomography and Comparison to
   Histology
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE optical coherence tomography; polarization sensitive devices; melanin;
   depolarization; retinal pigment epithelium; choroid
ID FUNDUS AUTOFLUORESCENCE; HIGH-SPEED; MACULAR DEGENERATION; OCULAR
   FUNDUS; EPITHELIUM; LIPOFUSCIN; FLUORESCENCE; ATROPHY; RPE
AB PURPOSE. The purpose of this study was to demonstrate polarization-sensitive optical coherence tomography (PS-OCT) for imaging pigmented structures in the posterior eye segments of albino and pigmented rats and to correlate depolarization contrast of the retinal pigment epithelium (RPE) and choroid in in vivo PS-OCT to melanin pigmentation detected in postmortem histologic serial sections.
   METHODS. In vivo three-dimensional PS-OCT imaging was performed in adult albino and pigmented rat eyes at 70-kHz A-line rate. Degree of polarization uniformity (DOPU) fundus maps and radial DOPU profiles were generated. Postmortem histomorphologic analysis was performed in order to investigate melanin pigmentation of the RPE and choroid. Fundus pigmentation maps were extracted from histologic serial sections. Pigmentation profiles were correlated to DOPU profiles of the same eyes.
   RESULTS. Strong depolarization was found in the RPE/choroid complex of pigmented rats, whereas the same structures exhibited uniform polarization in albino rats. The difference between the depolarization characteristics between albino and pigmented animals was statistically significant. In the fundus pigmentation maps, optical pigment density was zero in albino rat eyes. In pigmented rat eyes, a strong negative correlation between optical pigment density and DOPU was observed.
   CONCLUSIONS. This in vivo and ex vivo investigation of posterior rat eyes indicates that melanin is the cause of depolarization in retinal PS-OCT images. It further demonstrates that melanin pigmentation in the RPE and choroid can be quantified via depolarization imaging and therefore suggests that PS-OCT is a useful tool for the noninvasive quantitative assessment of pigmentary changes in vision-threatening diseases such as age-related macular degeneration.
C1 [Baumann, Bernhard; Schirmer, Johannes; Fialova, Stanislava; Augustin, Marco; Pircher, Michael; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
   [Rauscher, Sabine; Groeger, Marion] Med Univ Vienna, Core Facil Imaging, A-1090 Vienna, Austria.
   [Gloesmann, Martin] Univ Vet Med Vienna, Core Facil Res & Technol, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; University
   of Veterinary Medicine Vienna
RP Baumann, B (通讯作者)，Med Univ Vienna, Ctr Med Phys & Biomed Engn, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM bernhard.baumann@meduniwien.ac.at
RI Glösmann, Martin/F-9349-2019
OI Glösmann, Martin/0000-0002-2094-3247; Hitzenberger,
   Christoph/0000-0002-6608-8821; Baumann, Bernhard/0000-0001-6419-1932;
   Augustin, Marco/0000-0002-1019-0907; Michael,
   Pircher/0000-0001-9285-7527
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NR 43
TC 36
Z9 36
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 NOV
PY 2015
VL 56
IS 12
BP 7462
EP 7472
DI 10.1167/iovs.15-17742
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DB0ZS
UT WOS:000368238200058
PM 26595606
DA 2022-11-30
ER

PT J
AU Lee, JE
   Kim, HW
   Lee, SJ
   Lee, JE
AF Lee, Ji Eun
   Kim, Hyun Woong
   Lee, Sang Joon
   Lee, Joo Eun
TI CHANGES OF CHOROIDAL NEOVASCULARIZATION IN INDOCYANINE GREEN ANGIOGRAPHY
   AFTER INTRAVITREAL RANIBIZUMAB INJECTION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   indocyanine angiography; ranibizumab
ID CLINICOPATHOLOGICAL FEATURES; MACULAR DEGENERATION; DOSING REGIMEN;
   TRIALS
AB Purpose: To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography.
   Methods: A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed.
   Results: Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months.
   Conclusion: Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.
C1 [Lee, Ji Eun; Lee, Sang Joon] Pusan Natl Univ, Sch Med, Dept Ophthalmol, Yangsan, South Korea.
   [Lee, Ji Eun] Pusan Natl Univ Hosp, Inst Med, Busan, South Korea.
   [Kim, Hyun Woong; Lee, Joo Eun] Inje Univ, Coll Med, Busan, South Korea.
   [Kim, Hyun Woong] Busan Paik Hosp, Dept Ophthalmol, Busan, South Korea.
   Kosin Univ, Coll Med, Gospel Hosp, Dept Ophthalmol, Busan, South Korea.
   [Lee, Joo Eun] Haeundae Paik Hosp, Dept Ophthalmol, Busan, South Korea.
C3 Pusan National University; Pusan National University Hospital; Pusan
   National University; Pusan National University Hospital; Inje University
RP Lee, JE (通讯作者)，Inje Univ, Haeundae Paik Hosp, Dept Ophthalmol, 1435 Jwa Dong, Busan 612031, South Korea.
EM jooeun2@paik.ac.kr
RI Lee, Sang Joon/AAG-2448-2019
FU Korean Health Technology RAMP;D Project, Ministry of Health and Welfare,
   Republic of Korea [A070001]; Novartis Korea, Seoul, Republic of Korea
FX Supported by a grant of the Korean Health Technology R&D Project,
   Ministry of Health and Welfare, Republic of Korea (A070001), and by
   funding and investigation drugs from Novartis Korea, Seoul, Republic of
   Korea.
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NR 24
TC 3
Z9 3
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 2015
VL 35
IS 5
BP 999
EP 1006
DI 10.1097/IAE.0000000000000432
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CG6KI
UT WOS:000353408900022
PM 25590857
DA 2022-11-30
ER

PT J
AU Finlayson, M
AF Finlayson, Malcolm
TI Modulation of CD44 activity by A6-peptide
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE A6; CD44; HA; CLL; metastasis; recurrence; resistant; ocular
ID UROKINASE PLASMINOGEN-ACTIVATOR; HEPATOCYTE GROWTH-FACTOR;
   UROKINASE/UROKINASE RECEPTOR SYSTEM; LYMPHOCYTIC-LEUKEMIA CELLS;
   CHOROIDAL NEOVASCULARIZATION; HYALURONAN-BINDING; EPITHELIAL OVARIAN;
   PEPTIDE INHIBITOR; TUMOR PROGRESSION; GENE-EXPRESSION
AB Hyaluronan (HA) is a non-sulfated glycosaminoglycan distributed throughout the extracellular matrix that plays a major role in cell adhesion, migration, and proliferation. CD44, a multifunctional cell surface glycoprotein, is a receptor for HA. In addition, CD44 is known to interact with other receptors and ligands, and to mediate a number of cellular functions as well as disease progression. Studies have shown that binding of HA to CD44 in cancer cells activates survival pathways resulting in cancer cell survival. This effect can be blocked by anti-CD44 monoclonal antibodies. A6 is a capped, eight L-amino acid peptide (Ac-KPSSPPEE-NH2) derived from the biologically active connecting peptide domain of the serine protease, human urokinase plasminogen activator (uPA). A6 neither binds to the uPA receptor (uPAR) nor interferes with uPA/uPAR binding. A6 binds to CD44 resulting in the inhibition of migration, invasion, and metastasis of tumor cells, and the modulation of CD44-mediated cell signaling. A6 has been shown to have no dose-limiting toxicity in animal studies. A6 has demonstrated efficacy and an excellent safety profile in Phase 1a, 1b, and 2 clinical trials. In animal models, A6 has also exhibited promising results for the treatment of diabetic retinopathy and wet age-related macular degeneration through the reduction of retinal vascular permeability and inhibition of choroidal neovascularization, respectively. Recently, A6 has been shown to be directly cytotoxic for B-lymphocytes obtained from patients with chronic lymphocytic leukemia expressing the kinase, ZAP-70. This review will discuss the activity of A6, A6 modulation of HA and CD44, and a novel strategy for therapeutic intervention in disease.
C1 Angstrom Pharmaceut Inc, Solana Beach, CA 92075 USA.
RP Finlayson, M (通讯作者)，Angstrom Pharmaceut Inc, 990 Highland Dr,Suite 110V, Solana Beach, CA 92075 USA.
EM mfinlayson@angstrominc.com
FU Angstrom Pharmaceuticals, Inc.
FX The author has a financial relationship with Angstrom Pharmaceuticals,
   Inc.
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NR 74
TC 27
Z9 29
U1 2
U2 17
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 MAR 30
PY 2015
VL 6
BP 1
EP 8
AR 135
DI 10.3389/fimmu.2015.00135
PG 8
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA CI5RV
UT WOS:000354817600001
PM 25870596
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Swaminathan, S
   Li, HL
   Palamoor, M
   de Obarrio, WTL
   Madhura, D
   Meibohm, B
   Jablonski, MM
AF Swaminathan, Shankar
   Li, Huiling
   Palamoor, Mallika
   de Obarrio, Walter T. Luchsinger
   Madhura, Dorababu
   Meibohm, Bernd
   Jablonski, Monica M.
TI Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro
   Stability, Ocular Pharmacokinetic Modeling, and Biodistribution
SO AAPS JOURNAL
LA English
DT Article
DE age-related macular degeneration (AMD); NA3 glycan; pharmacokinetics;
   safety
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; PIGMENT-EPITHELIUM; BRUCHS MEMBRANE; UNITED-STATES;
   PREVALENCE; EXPRESSION; NEOVASCULARIZATION; FORMULATION
AB Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Muller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [H-3]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous>retina>sclera/choroid>aqueous humor>cornea>lens. Area under the curve (0 to infinity) (AUC infinity) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [H-3]NA3 was excreted via urine and feces. NA3 was stable at 37 degrees C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.
C1 [Swaminathan, Shankar; Li, Huiling; Palamoor, Mallika; de Obarrio, Walter T. Luchsinger; Jablonski, Monica M.] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Hamilton Eye Inst, Memphis, TN 38163 USA.
   [Madhura, Dorababu; Meibohm, Bernd] Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Memphis, TN 38163 USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center
RP Jablonski, MM (通讯作者)，Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Hamilton Eye Inst, 930 Madison Ave,Suite 731, Memphis, TN 38163 USA.
EM mjablonski@uthsc.edu
OI Meibohm, Bernd/0000-0003-3923-3648; Swaminathan,
   Shankar/0000-0002-1254-7105
FU March of Dimes; University of Tennessee Research Foundation;
   International Retinal Research Foundation; Research to Prevent
   Blindness; Knights Templar Eye Foundation; Fight for Sight
FX The research work was supported by the following grants: March of Dimes,
   University of Tennessee Research Foundation, International Retinal
   Research Foundation, an unrestricted grant from Research to Prevent
   Blindness, Knights Templar Eye Foundation, and Fight for Sight. The
   authors would like to thank Bob M. Moore, Ph.D. and Vivian S. Loveless,
   Pharm. D. (Department of Pharmaceutical Sciences, UTHSC) for providing
   their expertise in radiolabeling and scintillation counting.
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NR 49
TC 4
Z9 4
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAR
PY 2014
VL 16
IS 2
BP 311
EP 323
DI 10.1208/s12248-014-9563-1
PG 13
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AC1AD
UT WOS:000332225700014
PM 24470212
OA Green Published
DA 2022-11-30
ER

PT J
AU Lin, JC
   Yu, JH
AF Lin, Jen-Chieh
   Yu, Jy-Haw
TI Assessment of quality of life among Taiwanese patients with visual
   impairment
SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
LA English
DT Article
DE EQ-5D; health-related quality of life; VFQ-25; visual acuity; visual
   impairment
ID MACULAR DEGENERATION; FUNCTIONING QUESTIONNAIRE; DIABETIC-RETINOPATHY;
   EYE DISEASE; IMPACT; VISION; ADULTS; DEPRESSION; VALIDATION; VERSION
AB Background/Purpose: This study aims at evaluating the relationship between visual impairment and health-related quality of life (QoL) by identifying factors that affect the EQ-5D index score and Visual Functioning Questionnaire (VFQ) global score, and determining whether the VFQ-25 scores and the European Quality of Life-5 Dimensions (EQ-5D) scores are correlated.
   Methods: This cross-sectional study comprised 318 patients aged 40 years or more presenting with best corrected visual acuity (BCVA) of 20/40 or worse in the better eye. Patients received comprehensive ophthalmologic examinations, and were administered the National Eye Institute VFQ-25 and the EQ-5D instruments. A higher VFQ-25 score indicates a better QoL and, after conversion of the EQ-5D scores to an index score, a higher EQ-5D index score indicates a better QoL.
   Results: On multivariate analysis of the EQ-5D index scores, women and those with arthritis were found to have significantly worse QoL, and the EQ-5D index score was increased by every unit increase in BCVA or mean deviation. Multivariate analysis of the VFQ-25 scores revealed that a history of heart disease, arthritis, and eye diseases, such as age-related macular degeneration or diabetic retinopathy, had significant negative effects on patients' QoL, and VFQ-25 global score was decreased by every unit increase in logMAR. According to this analysis, patients' QoL was improved by each unit increase in BCVA or mean deviation. The correlation between the two questionnaires was only weak to moderate.
   Conclusion: Visual impairment was associated with lower QoL, as assessed by either questionnaire in Taiwanese patients. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
C1 [Lin, Jen-Chieh; Yu, Jy-Haw] Taipei City Hosp, Heping Fuyoy Branch, Dept Ophthalmol, Taipei 10065, Taiwan.
   [Lin, Jen-Chieh] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
C3 Taipei City Hospital; National Taiwan University
RP Lin, JC (通讯作者)，Taipei City Hosp, Heping Fuyoy Branch, Dept Ophthalmol, 33,Sect 2,Chung Hwa Rd, Taipei 10065, Taiwan.
EM jclin54@yahoo.com.tw
CR Anderson Andrew J, 2003, Ophthalmol Clin North Am, V16, P213, DOI 10.1016/S0896-1549(03)00011-7
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NR 26
TC 20
Z9 21
U1 0
U2 8
PU ELSEVIER TAIWAN
PI TAIPEI
PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2,
   TAIPEI, 10449, TAIWAN
SN 0929-6646
J9 J FORMOS MED ASSOC
JI J. Formos. Med. Assoc.
PD OCT
PY 2012
VL 111
IS 10
BP 572
EP 579
DI 10.1016/j.jfma.2011.09.021
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 036CS
UT WOS:000311004600008
PM 23089693
OA Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Mizutani, T
   Yasukawa, T
   Ito, Y
   Takase, A
   Hirano, Y
   Yoshida, M
   Ogura, Y
AF Mizutani, Takeshi
   Yasukawa, Tsutomu
   Ito, Yuya
   Takase, Ayae
   Hirano, Yoshio
   Yoshida, Munenori
   Ogura, Yuichiro
TI Pneumatic displacement of submacular hemorrhage with or without tissue
   plasminogen activator
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Pneumatic displacement; Retinal
   arterial macroaneurysm; Submacular hemorrhage; Sulfur hexafluoride;
   Tissue plasminogen activator (tPA)
ID SUBRETINAL HEMORRHAGE; SURGICAL REMOVAL; RETINAL TOXICITY;
   NATURAL-HISTORY; MANAGEMENT
AB To assess the efficacy and complications of intravitreal injection of sulfur hexafluoride (SF6) gas with/without tissue plasminogen activator (tPA) for displacing submacular hemorrhage.
   The medical records of 53 eyes that underwent pneumatic displacement for submacular hemorrhage were reviewed retrospectively. Submacular hemorrhage was related to exudative age-related macular degeneration (AMD) in 39 eyes and ruptured retinal arterial macroaneurysms in 14 eyes, and treated with intravitreal injection of SF6 gas with or without tPA.
   Compared with preoperatively (mean follow-up, 18.4 months), the final visual acuity (VA) improved by 0.3 or more logMAR unit in 34 eyes (64.2%), stabilized within 0.3 logMAR in 15 eyes (28.3%), and deteriorated in four eyes (7.5%). In eyes with AMD, hemorrhage including vitreous hemorrhage recurred in eight (22.2%) of 36 eyes treated with tPA and one (33.3%) of three eyes not treated with tPA. In eyes with macroaneurysms, hemorrhage recurred in four (100%) of four eyes treated with tPA and in one (10.0%) of ten eyes without tPA (p < 0.005). Eight eyes underwent vitrectomy for recurrent hemorrhage. During follow-up, photodynamic therapy or intravitreal ranibizumab or pegaptanib was administered in 16 (41.0%) of 39 eyes with AMD. Postoperative ocular hypertension persisting over 3 days was not observed.
   Intravitreal SF6 gas plus tPA may be well-accepted, with good visual outcomes and no remarkable complications for treating submacular hemorrhage secondary to AMD. tPA is not recommended for ruptured retinal arterial macroaneurysms, because of a higher incidence of subsequent vitreous hemorrhage. Pneumatic displacement of submacular hemorrhage without tPA may provide good visual outcomes with less re-bleeding.
C1 [Mizutani, Takeshi; Yasukawa, Tsutomu; Ito, Yuya; Takase, Ayae; Hirano, Yoshio; Yoshida, Munenori; Ogura, Yuichiro] Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
C3 Nagoya City University
RP Yasukawa, T (通讯作者)，Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
EM yasukawa@med.nagoya-cu.ac.jp
OI Hirano, Yoshio/0000-0002-9173-0839
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NR 23
TC 36
Z9 37
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2011
VL 249
IS 8
BP 1153
EP 1157
DI 10.1007/s00417-011-1649-1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 804GM
UT WOS:000293642300006
PM 21445629
DA 2022-11-30
ER

PT J
AU Schlanitz, FG
   Baumann, B
   Spalek, T
   Schutze, C
   Ahlers, C
   Pircher, M
   Gotzinger, E
   Hitzenberger, CK
   Schmidt-Erfurth, U
AF Schlanitz, Ferdinand G.
   Baumann, Bernhard
   Spalek, Tobias
   Schuetze, Christopher
   Ahlers, Christian
   Pircher, Michael
   Goetzinger, Erich
   Hitzenberger, Christoph K.
   Schmidt-Erfurth, Ursula
TI Performance of Automated Drusen Detection by Polarization-Sensitive
   Optical Coherence Tomography
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; IN-VIVO; SEVERITY SCALE; SEGMENTATION; PREVALENCE;
   DEPOSITS; FEATURES; DISEASE
AB PURPOSE. To estimate the potential of polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of drusen in patients with early age-related macular degeneration (AMD).
   METHODS. Fifteen eyes from 13 patients presenting drusen consistent with Age-Related Eye Disease Study classifications (grades 2 and 3) were examined ophthalmoscopically, followed by fundus photography, autofluorescence imaging, and three-dimensional scanning using a PS-OCT. For the automated evaluation of drusen location, area, and volume, a novel segmentation algorithm was developed based on the polarization scrambling characteristics of the retinal pigment epithelium (RPE) and applied to each complete data set. Subsequently, the drusen in each individual B-scan were identified by two independent expert graders. Concordance between manual and automated segmentation results was analyzed. Errors in the automated segmentation performance were classified as nonsignificant, moderate, or severe.
   RESULTS. In all, 2355 individual drusen, with a mean of 157 drusen per eye, were analyzed. Of drusen seen in the individual B-scans, 91.4% were detected manually by both expert graders. The automated segmentation algorithm identified 96.5% of all drusen without significant error. The mean difference in manual and automated drusen area (mean, 4.65 mm(2)) was 0.150. The number of detected drusen was significantly higher with automated than that with manual segmentation. PS-OCT segmentation was generally superior to fundus photography (P < 0.001). Particularly in nondetected drusen, a large variability in drusen morphology was noted.
   CONCLUSIONS. Automated drusen detection based on PS-OCT technology allows a fast and accurate determination of drusen location, number, and total area. (Invest Ophthalmol Vis Sci. 2011;51:4571-4579) DOI:10.1167/iovs.10-6846
C1 [Schlanitz, Ferdinand G.; Spalek, Tobias; Schuetze, Christopher; Ahlers, Christian; Schmidt-Erfurth, Ursula] Med Univ, Dept Ophthalmol & Optometry, Vienna, Austria.
   [Baumann, Bernhard; Pircher, Michael; Goetzinger, Erich; Hitzenberger, Christoph K.] Med Univ, Ctr Med Phys & Biomed Engn, Vienna, Austria.
RP Schmidt-Erfurth, U (通讯作者)，Gen Hosp Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Baumann, Bernhard/0000-0001-6419-1932; Hitzenberger,
   Christoph/0000-0002-6608-8821; Michael, Pircher/0000-0001-9285-7527;
   Schmidt-Erfurth, Ursula/0000-0002-7788-7311
FU Herzfeldersche Familienstiftung [AP004120FF]; Austrian Science Fund
   [P19624-B]
FX Supported, in part, by Herzfeldersche Familienstiftung Grant AP004120FF
   and Austrian Science Fund Grant P19624-B.
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   [No title captured]
NR 64
TC 50
Z9 51
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 JUN
PY 2011
VL 52
IS 7
BP 4571
EP 4579
DI 10.1167/iovs.10-6846
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800BP
UT WOS:000293332500085
PM 21474772
DA 2022-11-30
ER

PT J
AU Li, BX
   Vachali, P
   Frederick, JM
   Bernstein, PS
AF Li, Binxing
   Vachali, Preejith
   Frederick, Jeanne M.
   Bernstein, Paul S.
TI Identification of StARD3 as a Lutein-Binding Protein in the Macula of
   the Primate Retina
SO BIOCHEMISTRY
LA English
DT Article
ID RESONANCE RAMAN MEASUREMENT; PIGMENT OPTICAL-DENSITY; LIPID TRANSPORT;
   CAROTENOIDS; ZEAXANTHIN; QUANTIFICATION; DEGENERATION; MEMBRANES;
   ARRESTIN; MLN64
AB Lutein, zeaxanthin, and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum, and macula are associated with a decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provide important insights into the physiology of the human macula in health and disease. GSTP1 is the macular zeaxanthin-binding protein, but the identity of the human macular lutein-binding protein has remained elusive. Prior identification of the silkworm lutein-binding protein (CBP) as a member of the steroidogenic acute regulatory domain (StARD) protein family and selective labeling of monkey photoreceptor inner segments with an anti-CBP antibody provided an important clue for identifying the primate retina lutein-binding protein. The homology of CBP with all 15 human StARD proteins was analyzed using database searches, Western blotting, and immunohistochemistry, and we here provide evidence to identify StARD3 (also known as MLN64) as a human retinal lutein-binding protein. Antibody to StARD3, N-62 StAR, localizes to all neurons of monkey macular retina and especially cone inner segments and axons, but does not colocalize with the Muller cell marker, glutamine synthetase. Further, recombinant StARD3 selectively binds lutein with high affinity (K-D = 0.45 mu M) when assessed by surface plasmon resonance (SPR) binding assays. Our results demonstrate previously unrecognized, specific interactions of StARD3 with lutein and provide novel avenues for exploring its roles in human macular physiology and disease.
C1 [Li, Binxing; Vachali, Preejith; Frederick, Jeanne M.; Bernstein, Paul S.] Univ Utah, Moran Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
C3 Utah System of Higher Education; University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Moran Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
RI Vachali, Preejith/L-8661-2014; Li, Binxing/C-9153-2012; Li,
   Binxing/ABB-7775-2020
OI Vachali, Preejith/0000-0003-3569-1553; Li, Binxing/0000-0002-0715-7495
FU National Institutes of Health (Des Moines, IA) [EY-11600]; Foundation
   Fighting Blindness, Inc. (Columbia, MD); Research to Prevent Blindness,
   Inc. (New York, NY); NATIONAL EYE INSTITUTE [P30EY014800, R29EY011600,
   R01EY011600] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health Grant EY-11600,
   by Kemin Health (Des Moines, IA), the Foundation Fighting Blindness,
   Inc. (Columbia, MD), and by Research to Prevent Blindness, Inc. (New
   York, NY).
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NR 38
TC 129
Z9 133
U1 1
U2 34
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 5
PY 2011
VL 50
IS 13
BP 2541
EP 2549
DI 10.1021/bi101906y
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 742UN
UT WOS:000288970800018
PM 21322544
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Falkenstein, IA
   Cochran, DE
   Azen, SP
   Dustin, L
   Tammewar, AM
   Kozak, I
   Freeman, WR
AF Falkenstein, Iryna A.
   Cochran, Denine E.
   Azen, Stanley P.
   Dustin, Laurie
   Tammewar, Ajay M.
   Kozak, Igor
   Freeman, William R.
TI Comparison of visual acuity in macular degeneration patients measured
   with Snellen and Early Treatment Diabetic Retinopathy Study Charts
SO OPHTHALMOLOGY
LA English
DT Article
ID CONTRAST SENSITIVITY; RELIABILITY; LOGMAR; REPEATABILITY; PROTOCOL;
   CHILDREN
AB Purpose: To compare the measurements of visual acuity (VA)results measured with Snellen and Early Treatment Diabetic Retinopathy Study (ETDRS) charts in eyes with and without age-related macular degeneration (AMD).
   Design: Cross-sectional study.
   Participants: One hundred four participants (190 eyes) selected from a university retina practice; 80 participants (142 eyes) had some degree of AMD.
   Methods: Visual acuity was measured in each patient using standard procedure with both Snellen and ETDRS charts in random order. Statistical analysis of the results was performed.
   Main Outcome Measures: Difference in VA measured by both charts in logarithm of minimal angle of resolution (logMAR) notations.
   Results: Overall, the mean Snellen VA was 0.78 logMAR (= 20/120), and the mean ETDRS VA in the same eye was 0.54 logMAR (= 20/70; P<0.001). In the low vision group (<20/200), represented by patients with AMD, the average difference in number of lines was considerably larger than in the good vision range (>20/30). On average, 20/200 on Snellen was 20/95 on ETDRS (>3 lines difference), and 20/30 on Snellen was 20/25 on ETDRS (<1 line difference).
   Conclusion: Our results show poor agreement between the Snellen and ETDRS charts, and it was more pronounced in the group with poor vision. The ETDRS measurements yielded better VA, particularly in participants with vision <20/200 (representing more advanced AMD patients). We suggest taking these findings into consideration when comparing outcomes in clinical practices (which typically measure VA using standard Snellen charts) with outcomes from clinical trials (which typically measure VA using ETDRS charts).
C1 [Falkenstein, Iryna A.; Cochran, Denine E.; Tammewar, Ajay M.; Kozak, Igor; Freeman, William R.] Univ Calif San Diego, Shiley Eye Ctr, Dept Ophthalmol, Joan & Irwin Jacobs Retina Ctr, La Jolla, CA 92037 USA.
   [Azen, Stanley P.; Dustin, Laurie] Univ So Calif, Dept Prevent Med, Keck Sch Med, Stat Consultat & Res Ctr, Los Angeles, CA 90089 USA.
C3 University of California System; University of California San Diego;
   University of Southern California
RP Freeman, WR (通讯作者)，Univ Calif San Diego, Shiley Eye Ctr, Dept Ophthalmol, Joan & Irwin Jacobs Retina Ctr, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM freeman@eyecenter.ucsd.edu
RI Kozak, Igor/AAC-4645-2019
FU NEI NIH HHS [EY07366, P30 EY003040, EY03040, R01 EY007366, R01
   EY007366-21] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY007366, P30EY003040] Funding Source: NIH RePORTER
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NR 29
TC 85
Z9 93
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2008
VL 115
IS 2
BP 319
EP 323
DI 10.1016/j.ophtha.2007.05.028
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 258AJ
UT WOS:000252840500016
PM 17706288
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhao, L
   Wang, ZF
   Liu, Y
   Song, Y
   Li, YW
   Laties, AM
   Wen, R
AF Zhao, Lian
   Wang, Zhenfang
   Liu, Yun
   Song, Ying
   Li, Yiwen
   Laties, Alan M.
   Wen, Rong
TI Translocation of the retinal pigment epithelium and formation of
   sub-retinal pigment epithelium deposit induced by subretinal deposit
SO MOLECULAR VISION
LA English
DT Article
ID RHODOPSIN MUTATION S334TER; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   BRUCHS MEMBRANE; TRANSGENIC RATS; DRUSEN; PATHOGENESIS; INCREASES;
   VARIANT
AB Purpose: A cardinal pathological feature of age-related macular degeneration (AMD) is the deposition of extracellular material between the retinal pigment epithelium (RPE) and Bruch's membrane, pathologically described as sub-RPE deposits. Both the presence and local organization of these deposits contribute to the clinical manifestations of AMD, including localized deposits clinically recognized as drusen. The biogenesis of sub-RPE deposits remains elusive. This work explores the pathological processes of sub-RPE deposit formation.
   Methods: Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Tissue sections were examined by light or confocal microscopy.
   Results: In the presence of the subretinal deposit of Matrigel, RPE cells leave Bruch's membrane to migrate toward photoreceptors and then form a new layer between the deposit and photoreceptors, resulting in RPE translocation. The new RPE layer displaces the deposit to the sub-RPE location and therefore it becomes a sub-RPE deposit. The RPE mobilization requires the presence of photoreceptors. Bruch's membrane devoid of RPE attachment becomes vulnerable to invasion by new blood vessels from the choroid.
   Conclusions: Our work supports a novel model of sub-RPE deposit formation in which excessive material first accumulates in the subretinal space, disrupting the physical contact between RPE cells and photoreceptors. To restore the contact, RPE cells migrate toward photoreceptors and form a new layer. The subretinal material is consequently displaced to the sub-RPE location and becomes sub-RPE deposit. Our data also provide evidence that the presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane.
C1 Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   Zhongshan Ophthalm Ctr, Dept Eye Trauma, Guangzhou 510060, Guangdong, Peoples R China.
C3 University of Pennsylvania
RP Wen, R (通讯作者)，Univ Penn, Sch Med, Dept Ophthalmol, 603 Richards Bldg, Philadelphia, PA 19104 USA.
EM rwen@mail.med.upenn.edu
FU NATIONAL EYE INSTITUTE [R01EY012727, R01EY015289] Funding Source: NIH
   RePORTER; NEI NIH HHS [R01 EY015289, EY-015289, R01 EY012727, EY-012727]
   Funding Source: Medline
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NR 35
TC 19
Z9 20
U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 14
PY 2007
VL 13
IS 93-95
BP 873
EP 880
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 186PA
UT WOS:000247789400003
PM 17615538
DA 2022-11-30
ER

PT J
AU Ohia, SE
   Opere, CA
   LeDay, AM
AF Ohia, SE
   Opere, CA
   LeDay, AM
TI Pharmacological consequences of oxidative stress in ocular tissues
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Review
DE ocular tissues; oxidative stress; free radicals
ID PEROXIDE-INDUCED POTENTIATION; RETINAL-PIGMENT EPITHELIUM;
   HYDROGEN-PEROXIDE; SYMPATHETIC NEUROTRANSMISSION; LIPID-PEROXIDATION;
   GLUTAMATE RELEASE; FREE-RADICALS; NOREPINEPHRINE RELEASE; AQUEOUS-HUMOR;
   NITRIC-OXIDE
AB The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma. cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior Uvea, both H2O2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior Uvea especially on the sympathetic nerves and smooth Muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H2O2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [3 HI D-aspartate. in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers Such as nitric oxide, prostaglandins and isoprostanes. The ability of H2O2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma. (c) 2005 Elsevier B.V. All rights reserved.
C1 Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77204 USA.
   Creighton Univ, Med Ctr, Dept Pharm Sci, Sch Pharm & Hlth Profess, Omaha, NE 68178 USA.
   Procter & Gamble Pharmaceut Inc, Mason, OH 45040 USA.
C3 University of Houston System; University of Houston; Creighton
   University; Procter & Gamble
RP Ohia, SE (通讯作者)，Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, 141 Sci & Res Bldg 2, Houston, TX 77204 USA.
EM seohia@uh.edu
FU NEI NIH HHS [EY11023, EY12157, EY13967, EY13266] Funding Source:
   Medline; NATIONAL EYE INSTITUTE [R15EY011023, R15EY013967, R15EY012157,
   R15EY013266] Funding Source: NIH RePORTER
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NR 90
TC 113
Z9 130
U1 1
U2 16
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0027-5107
EI 1873-135X
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD NOV 11
PY 2005
VL 579
IS 1-2
BP 22
EP 36
DI 10.1016/j.mrfmmm.2005.03.025
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 985KR
UT WOS:000233376800003
PM 16055157
DA 2022-11-30
ER

PT J
AU Gross, NE
   Aizman, A
   Brucker, A
   Klancnik, JM
   Yannuzzi, LA
AF Gross, Nicole E.
   Aizman, Alexander
   Brucker, Allison
   Klancnik, James M., Jr.
   Yannuzzi, Lawrence A.
TI Nature and risk of neovascularization in the fellow eye of patients with
   unilateral retinal angiomatous proliferation
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID SENILE MACULAR DEGENERATION; AGE-RELATED MACULOPATHY; OCCULT CHOROIDAL
   NEOVASCULARIZATION; BEAVER DAM EYE; 2ND EYE; TELANGIECTASIS; DISEASE;
   DRUSEN; ANASTOMOSES; DETACHMENTS
AB Purpose: To determine the nature and risk of neovascularization in the fellow eyes of patients with unilateral retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration (AMD).
   Methods: A consecutive series of 52 patients diagnosed with unilateral RAP were studied retrospectively. Clinical biomicroscopic examination, fluorescein angiography, and inclocyanine green angiography were used to evaluate all patients for the development of neovascular manifestations in the fellow eye.
   Results: Neovascularization developed in the fellow eye in 52 patients over the follow-up period (range, 2-36 months). All patients developed neovascular manifestations of RAP in the fellow eye. Twenty-one patients (40%) developed a RAP lesion within 1 year; 29 (56%), within 2 years; and 52 (100%), within 3 years. At the time of diagnosis of neovascularization in the fellow eye, 8 patients (15%) had a stage I RAP lesion, 36 (70%) had a stage II RAP lesion, and 8 (15%) had a stage III RAP lesion. Other characteristic findings in these patients included the presence of preretinal, intraretinal, and subretinal hemorrhages in 49 patients (94%) and pigment epithelial detachments in 41 patients (79%).
   Conclusions: In patients diagnosed with unilateral RAP lesions, the form of neovascularization that develops in the fellow eye is virtually always RAP. The annual and accumulative risk of neovascularization in the fellow eye is higher in patients with RAP than in those with other forms of neovascular AMD. These new findings enhance our understanding of the clinical spectrum of RAP in terms of its natural course and visual prognosis and may possibly offer useful information to establish future treatment options.
C1 Manhattan Eye Ear & Throat Hosp, Luesther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
C3 Manhattan Eye Ear & Throat Hospital
RP Yannuzzi, LA (通讯作者)，Manhattan Eye Ear & Throat Hosp, Luesther T Mertz Retinal Res Ctr, 210 E 64th St, New York, NY 10021 USA.
EM vrmny@aol.com
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NR 38
TC 108
Z9 116
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 2005
VL 25
IS 6
BP 713
EP 718
DI 10.1097/00006982-200509000-00005
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 100QU
UT WOS:000241684500005
PM 16141858
DA 2022-11-30
ER

PT J
AU Riusala, AM
   Immonen, IJR
AF Riusala, AM
   Immonen, IJR
TI Predictors of structural findings in old disciform lesions
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION;
   PIGMENT EPITHELIAL DETACHMENTS; SENILE MACULAR DEGENERATION;
   NATURAL-HISTORY; LASER PHOTOCOAGULATION; PHOTODYNAMIC THERAPY; VISUAL
   PROGNOSIS; OCCULT; MEMBRANES
AB PURPOSE: To analyze the baseline findings predictive of the size and type of the late exudative age-related macular degeneration (AMD) lesions.
   DESIGN: Observational case series.
   METHODS: Retrospective study.
   SETTING: University clinic referral practice.
   STUDY POPULATION: The records of 167 consecutive patients initially diagnosed with recent choroidal neovascularization (CNV) related to AMD were analyzed 4.8 to 9.2 (mean 6.8) years after baseline. Of 121 patients still living, 74 attended the reexamination. After exclusions, data from 61 patients were analyzed.
   OBSERVATION PROCEDURES: From the fundus photo, graphs and fluorescein angiographic images taken at baseline and at follow,up the size and components of AMD lesion were measured. The presence of hemorrhage, pigment epithelial detachment (PED), classic CNV, laser treatment, and involvement of the fellow eye were recorded at baseline.
   MAIN OUTCOME MEASURES: Lesion size, increase in lesion size, persistent exudative process, subretinal fibrosis, and chorioretinal anastomosis at the follow,up examination.
   RESULTS: Large lesion (P < .001) and CNV (P = .003) sizes, and the presence of occult, no classic CNV (P = .013) at baseline predict a large lesion at follow-up. Other factors predicting a large lesion were subfoveal (P = .019) and bilateral lesions (P = .017) and the presence of hemorrhage (P = .012) at baseline. A large (P = .040) and bilateral lesion (P = .040) and hemorrhage (P = .011) at baseline were correlated with subretinal fibrosis at follow-up. Occult lesions (P = .002) at baseline were correlated with chorioretinal anastomosis at follow-up.
   CONCLUSION: The type and size of the late AMD lesion can partly be predicted from baseline characteristics. (C) 2004 by Elsevier Inc. All rights reserved.
C1 Univ Helsinki Hosp, Dept Ophthalmol, FIN-00029 Helsinki, Finland.
C3 University of Helsinki; Helsinki University Central Hospital
RP Riusala, AM (通讯作者)，Univ Helsinki Hosp, Dept Ophthalmol, Haartmaninkatu 4 C,JP 220, FIN-00029 Helsinki, Finland.
EM aila.riusala@hus.fi
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NR 25
TC 9
Z9 9
U1 0
U2 1
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 AUG
PY 2004
VL 138
IS 2
BP 245
EP 253
DI 10.1016/j.ajo.2004.03.007
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 844UM
UT WOS:000223186100011
PM 15289134
DA 2022-11-30
ER

PT J
AU Gacina, DL
   Skegro, B
   Jandrokovic, S
   Skegro, I
   Beslic, I
   Bukvic, M
AF Lesin Gacina, Dina
   Skegro, Bernarda
   Jandrokovic, Sonja
   Skegro, Ivan
   Beslic, Iva
   Bukvic, Marija
TI Psychometric properties of the Croatian version of the 25-item National
   Eye Institute Visual Function Questionnaire (NEI VFQ-25)
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Psychometrics; Questionnaires; Visual function; Quality of life; NEI
   VFQ-25; Croatian
ID QUALITY-OF-LIFE; VALIDATION; POPULATION; TRANSLATION; IMPAIRMENT
AB Purpose The purpose of the study was to translate, adapt and validate the Croatian version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in participants with visual impairment. This study also aims at evaluating the relationship between visual impairment and health-related quality of life (HRQoL). Methods The prospective observational study was conducted at the University Hospital Centre Zagreb, Department of Ophthalmology. The sample consisted of 175 patients with four chronic ocular diseases: cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. The translation of the NEI VFQ-25 to Croatian was conducted following the standardised procedure. All participants underwent an ophthalmological examination and completed the NEI VFQ-25 and the Medical Outcomes Study Short Form-36 Questionnaire (SF-36). In order to assess the psychometric properties of the NEI VFQ-25, we calculated Cronbach's alpha coefficient, intraclass correlation coefficient (ICC), convergent and discriminant validity, as well as criterion and concurrent validity. Results Results show high internal consistency (Cronbach alpha range 0.739-0.932) and high test-retest reliability (ICC 0.876-0.975) for all subscales. None of the items had failed either convergent or discriminant validity. Moderate to high Spearman's rho coefficients of correlations were found between best corrected visual acuity and eight subscales in the NEI VFQ-25 (0.430 < rho < 0.631). Moderate correlations were found between comparable domains in the NEI VFQ-25 and in the SF-36 questionnaire (p < 0.01). Conclusion The Croatian version of the NEI VFQ-25 has very good psychometric properties and can be a useful instrument for assessing vision-related quality of life in Croatian population with chronic ophthalmic diseases.
C1 [Lesin Gacina, Dina; Jandrokovic, Sonja; Skegro, Ivan; Beslic, Iva; Bukvic, Marija] Univ Hosp Ctr Zagreb, Dept Ophthalmol, Kispaticeva 12, Zagreb 10000, Croatia.
   [Skegro, Bernarda] Sestre Milosrdnice Univ Hosp Ctr, Dept Rheumatol Phys & Rehabil Med, Zagreb, Croatia.
C3 University of Zagreb; University of Zagreb
RP Gacina, DL (通讯作者)，Univ Hosp Ctr Zagreb, Dept Ophthalmol, Kispaticeva 12, Zagreb 10000, Croatia.
EM dina.lesin@yahoo.com
RI Jandrokovic, Sonja/GZL-0681-2022
OI Jandrokovic, Sonja/0000-0003-0536-1502; Lesin Gacina,
   Dina/0000-0002-2468-2195
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NR 43
TC 2
Z9 2
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 DEC
PY 2021
VL 41
IS 12
BP 4025
EP 4036
DI 10.1007/s10792-021-01975-y
EA JUL 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WS5OU
UT WOS:000679031800003
PM 34312780
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Szeskin, A
   Yehuda, R
   Shmueli, O
   Levy, J
   Joskowicz, L
AF Szeskin, Adi
   Yehuda, Roei
   Shmueli, Or
   Levy, Jaime
   Joskowicz, Leo
TI A column-based deep learning method for the detection and quantification
   of atrophy associated with AMD in OCT scans
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE OCT scan analysis; Retinal atrophy in dry age-related macular
   degeneration; Column-based OCT scattering; CNN deep learning
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; AUTOMATIC SEGMENTATION; FOVEAL
   CENTER; IMAGES
AB The objective quantification of retinal atrophy associated with age-related macular degeneration (AMD) is required for clinical diagnosis, follow-up, treatment efficacy evaluation, and clinical research. Spectral Domain Optical Coherence Tomography (OCT) has become an essential imaging technology to evaluate the macula. This paper describes a novel automatic method for the identification and quantification of atrophy associated with AMD in OCT scans and its visualization in the corresponding infrared imaging (IR) image. The method is based on the classification of light scattering patterns in vertical pixel-wide columns (A-scans) in OCT slices (B-scans) in which atrophy appears with a custom column-based convolutional neural network (CNN). The network classifies individual columns with 3D column patches formed by adjacent neighboring columns from the volumetric OCT scan. Subsequent atrophy columns form atrophy segments which are then projected onto the IR image and are used to identify and segment atrophy lesions in the IR image and to measure their areas and distances from the fovea. Experimental results on 106 clinical OCT scans (5,207 slices) in which cRORA atrophy (the end point of advanced dry AMD) was identified in 2,952 atrophy segments and 1,046 atrophy lesions yield a mean F-1 score of 0.78 (std 0.06) and an AUC of 0.937, both close to the observer variability. Automated computer-based detection and quantification of atrophy associated with AMD using a column-based CNN classification in OCT scans can be performed at expert level and may be a useful clinical decision support and research tool for the diagnosis, follow-up and treatment of retinal degenerations and dystrophies. (C) 2021 Elsevier B.V. All rights reserved.
C1 [Szeskin, Adi; Yehuda, Roei; Joskowicz, Leo] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, Jerusalem, Israel.
   [Shmueli, Or; Levy, Jaime] Hadassah Med Ctr, Dept Ophthalmol, Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem; Hadassah
   University Medical Center
RP Joskowicz, L (通讯作者)，Hebrew Univ Jerusalem, Rachel & Selim Benin Sch Comp Science & Engn, Edmond J Safra Campus, IL-9190401 Jerusalem, Israel.
EM josko@cs.huji.ac.il
RI Shmueli, Or/AHD-0983-2022
OI Shmueli, Or/0000-0003-3718-2664; Szeskin, Adi/0000-0002-3397-7964; Levy,
   Jaime/0000-0003-0043-4354
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NR 23
TC 6
Z9 6
U1 6
U2 11
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 AUG
PY 2021
VL 72
AR 102130
DI 10.1016/j.media.2021.102130
EA JUN 2021
PG 12
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 TP3PA
UT WOS:000677504500001
PM 34198041
DA 2022-11-30
ER

PT J
AU Zarbin, MA
   Hill, L
   Maunz, A
   Gliem, M
   Stoilov, I
AF Zarbin, Marco A.
   Hill, Lauren
   Maunz, Andreas
   Gliem, Martin
   Stoilov, Ivaylo
TI Anti-VEGF-resistant subretinal fluid is associated with better vision
   and reduced risk of macular atrophy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE harbor; neovascular age-related macular degeneration; ranibizumab; treat
   to dry
ID ENDOTHELIAL GROWTH-FACTOR; 2.0 MG RANIBIZUMAB; CHOROIDAL
   NEOVASCULARIZATION; GEOGRAPHIC ATROPHY; EFFICACY; HARBOR; SAFETY; TREAT;
   EYES
AB Background/aim To evaluate relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration (nAMD). Methods This post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg, monthly or as-needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0-50, >50-100 and >100 mu m) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA) was assessed. MA was identified using fluorescein angiograms and colour fundus photographs, as well as SD-OCT. Results Seven hundred eighty-five of 1097 eyes met analysis criteria. In eyes without baseline MA, residual versus no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1% vs 22.1%) and M24 (13.3% vs 31.2%) (both p<0.0001); MA percentages at M12/M24 were similar among patients with residual SRF at M6. Higher baseline SRFV was associated with a lower MA rate. Greater mean BCVA was observed with residual SRF of any thickness (>0-50 mu m, 71.2 letters; >50-100 mu m, 71.3 letters; >100 mu m, 69.2 letters) versus no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6. Conclusion TR-SRF was not detrimental to vision outcomes over 2 years, regardless of thickness. MA rates were significantly higher without TR-SRF.
C1 [Zarbin, Marco A.] Rutgers New Jersey Med Sch, Inst Ophthalmol & Visual Sci, Newark, NJ 07103 USA.
   [Hill, Lauren; Stoilov, Ivaylo] Genentech Inc, Med Affairs Ophthalmol, San Francisco, CA 94080 USA.
   [Maunz, Andreas; Gliem, Martin] Roche Pharma Res & Early Dev, Basel, Switzerland.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center; Roche Holding; Genentech; Roche Holding
RP Zarbin, MA (通讯作者)，Rutgers New Jersey Med Sch, Inst Ophthalmol & Visual Sci, Newark, NJ 07103 USA.
EM zarbin@rutgers.edu
OI Zarbin, Marco/0000-0002-7811-7132
FU Genentech, Inc.
FX Funding was provided by Genentech, Inc., a member of the Roche Group,
   for the study. Genentech, Inc. participated in the design of the HARBOR
   trial. Medical reviewers from Genentech, Inc., were allowed to review
   this manuscript for accurate reporting of the data but did not make
   decisions regarding the final interpretation of the data or overall
   content of this paper. Funding was provided by Genentech, Inc., for
   third--party writing assistance, which was provided by Ray Beck, Jr,
   PhD, and Michelle Kelly, PhD, of Envision Pharma Group.
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NR 31
TC 6
Z9 6
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD NOV
PY 2022
VL 106
IS 11
BP 1561
EP 1566
DI 10.1136/bjophthalmol-2020-318688
EA MAY 2021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5U6TH
UT WOS:000727746100001
PM 34039560
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Rickmann, A
   Paez, LR
   Waizel, MD
   Bisorca-Gassendorf, L
   Schulz, A
   Vandebroek, AC
   Szurman, P
   Januschowski, K
AF Rickmann, Annekatrin
   Paez, Lina R.
   Waizel, Maria della Volpe
   Bisorca-Gassendorf, Lukas
   Schulz, Andre
   Vandebroek, Anne-Cecile
   Szurman, Peter
   Januschowski, Kai
TI Functional and structural outcome after vitrectomy combined with
   subretinal rtPA Injection with or without additional intravitreal
   Bevacizumab injection for submacular hemorrhages
SO PLOS ONE
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; MACULAR DEGENERATION; CO-APPLICATION;
   PNEUMATIC DISPLACEMENT; GAS; AMD; COMPATIBILITY; EFFICACY
AB Background To analyze the functional and anatomical outcome after vitrectomy with subretinal rtPA (recombinant tissue plasminogen activator) combined with or without an intravitreal Bevacizumab injection.
   Patients and methods Retrospective, consecutive case series of 31 pseudophakic patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD) treated with vitrectomy, subretinal rtPA and pneumatic air displacement with or without an additional intravitreal Bevacizumab injection. The primary endpoints were best-corrected visual acuity (BCVA), and central macular thickness (CMT) measured by SD-OCT. The secondary endpoint was a displacement of hemorrhage from the subretinal space three months after surgery.
   Results 31 eyes of 31 patients were treated with vitrectomy and subretinal rtPA. 17/31 were treated simultaneously with an intravitreal Bevacizumab injection (group +B) and 14/31 without (group -B). The mean visual acuity improved significantly in both groups (from 1.37 +/- 0.39 to 1.03 +/- 0.57 logMAR in +B and from 1.48 +/- 0.48 to 1.01 +/- 0.38 logMAR in group -B, p < 0.05). The mean CMT decreased in group +B from 607 +/- 179 mu m to 424 +/- 205 mu m (p = 0.2) and in group -B from 722 +/- 216 mu m to 460 +/- 202 mu m (p < 0.05). A central displacement of the hemorrhage could be achieved in 47% in group +B, whereas in group -B displacement could be achieved in 50% (p = 0.44).
   Conclusions Vitrectomy with subretinal rtPA injection and air tamponade with or without simultaneous intravitreal Bevacizumab injection displaces SMH and improves BCVA effectively. In comparison, the postoperative outcome is comparable regardless of whether or not intravitreal bevacizumab is applied simultaneously.
C1 [Rickmann, Annekatrin; Paez, Lina R.; Bisorca-Gassendorf, Lukas; Schulz, Andre; Vandebroek, Anne-Cecile; Szurman, Peter; Januschowski, Kai] Knappschaft Hosp Saar, Depatment Ophthalmol, Sulzbach, Germany.
   [Waizel, Maria della Volpe] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Januschowski, Kai] Univ Eye Clin Tuebingen, Depatment Ophthalmol, Tubingen, Germany.
C3 University of Basel
RP Rickmann, A (通讯作者)，Knappschaft Hosp Saar, Depatment Ophthalmol, Sulzbach, Germany.
EM annekatrin.rickmann@kksaar.de
RI Bisorca-Gassendorf, Lukas/AAM-4834-2021
OI Bisorca-Gassendorf, Lukas/0000-0002-6863-9439; Vandebroek,
   Anne-Cecile/0000-0002-7629-5525; Ramirez Paez, Lina
   Marcela/0000-0002-0625-5392
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NR 28
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 30
PY 2021
VL 16
IS 4
AR e0250587
DI 10.1371/journal.pone.0250587
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA SW6EM
UT WOS:000664607000018
PM 33930041
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sivaprasad, S
   Tschosik, E
   Kapre, A
   Varma, R
   Bressler, NM
   Kimel, M
   Dolan, C
   Silverman, D
AF Sivaprasad, Sobha
   Tschosik, Elizabeth
   Kapre, Audrey
   Varma, Rohit
   Bressler, Neil M.
   Kimel, Miriam
   Dolan, Chantal
   Silverman, David
TI Reliability and Construct Validity of the NEI VFQ-25 in a Subset of
   Patients With Geographic Atrophy From the Phase 2 Mahalo Study
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; VISUAL FUNCTION
   QUESTIONNAIRE; VISION-RELATED FUNCTION; MACULAR DEGENERATION; AGE;
   RESPONSIVENESS; RANIBIZUMAB; INDEX
AB PURPOSE: Geographic atrophy (GA) is an advanced form of age-related macular degeneration characterized by progressive, irreversible visual function loss. This analysis evaluates the psychometric properties of the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite, near activity, and distance activity scores in patients with GA.
   DESIGN: Reliability and validity study.
   METHODS: Reliability and validity were tested with NEI VFQ-25 data collected from 100 subjects with GA from United States' sites of the phase 2 Mahalo study of lampalizumab (ClinicalTrials.gov identifier: NCT01229215).
   RESULTS: Strong internal consistency and reproducibility were demonstrated for the NEI VFQ-25 composite (Cronbach's alpha, 0.95; intraclass correlation coefficient [ICC], 0.86), near activity (Cronbach's alpha, 0.84; ICC, 0.80), and distance activity (Cronbach's alpha, 0.84; ICC, 0.84) scores. Convergent validity with the binocular measures, Minnesota Low-Vision Reading Test (MNRead) reading speed and Functional Reading Independence (FRI) index score, was demonstrated for baseline NEI VFQ-25 composite (Pearson correlation [r] = 0.61 and 0.69, respectively), near activities (r = 0.69 and 0.73), and distance activities (r = 0.57 and 0.64) scores. Known-group validity testing for baseline mean NEI VFQ-25 scores (composite, near activities, and distance activities) showed differences between patients with mean maximum MNRead reading speed >= 80 vs < 80 words per minute, and between mean FRI index score >= 2.5 vs < 2.5 (all P < .0001).
   CONCLUSIONS: Psychometric evidence supports the NEI VFQ-25 as a reliable and valid cross-sectional measure of the impact of GA on patient visual function and vision-related quality of life. (C) 2018 The Authors. Published by Elsevier Inc.
C1 [Sivaprasad, Sobha] NIHR Moorfields Biomed Res Ctr, London, England.
   [Tschosik, Elizabeth; Kapre, Audrey] Genentech Inc, San Francisco, CA 94080 USA.
   [Varma, Rohit] Univ Southern Calif, Keck Sch Med, USC Eye Inst, Los Angeles, CA 90033 USA.
   [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Kimel, Miriam] Evidera, Bethesda, MD USA.
   [Dolan, Chantal] CMD Consulting Inc, Sandy, UT USA.
   [Silverman, David] Roche Prod Ltd, Welwyn Garden City, Herts, England.
C3 Roche Holding; Genentech; University of Southern California; Johns
   Hopkins University; Evidera; Roche Holding
RP Sivaprasad, S (通讯作者)，Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England.
EM Sobha.Sivaprasad@moorfields.nhs.uk
RI Sivaprasad, S./D-6876-2015
OI Sivaprasad, S./0000-0001-8952-0659; Silverman, David/0000-0003-1842-5739
FU F. HOFFMANN-LA ROCHE LTD.
FX THE STUDY WAS FUNDED BY F. HOFFMANN-LA ROCHE LTD. F. HOFFMANN-LA ROCHE
   LTD PARTICIPATED IN the design and conduct of the studies; data
   collection, analysis, and interpretation of results; preparation,
   review, and approval of the manuscript; and decision to submit the
   manuscript for publication.
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NR 37
TC 26
Z9 26
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUN
PY 2018
VL 190
BP 1
EP 8
DI 10.1016/j.ajo.2018.03.006
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GI1AY
UT WOS:000434102800005
PM 29530781
OA hybrid
DA 2022-11-30
ER

PT J
AU Wei, X
   Zhang, T
   Yao, YQ
   Zeng, SX
   Li, M
   Xiang, HT
   Zhao, CJ
   Cao, GQ
   Li, MH
   Wan, R
   Yang, P
   Yang, JL
AF Wei, Xian
   Zhang, Ting
   Yao, Yuqin
   Zeng, Shaoxue
   Li, Min
   Xiang, Haotian
   Zhao, Chengjian
   Cao, Guiqun
   Li, Minhui
   Wan, Ran
   Yang, Ping
   Yang, Jinliang
TI Efficacy of Lenvatinib, a multitargeted tyrosine kinase inhibitor, on
   laser induced CNV mouse model of neovascular AMD
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Neovascular AMD; Choroidal neovascularization; Lenvatinib; Angiogenesis
   tyrosine kinase inhibitor; LC/MS/MS; Retina
ID MACULAR DEGENERATION; PHASE 1B; VEGF; ANGIOGENESIS; E7080; COMBINATION;
   CARCINOMA; OUTCOMES
AB Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Although intravitreal injection of anti-VEGF antibodies and VEGF Trap have significant clinical benefits, the complications of intravitreal injection, drug resistance and patient compliance still need to be concerned. In this study, the effects of an orally administered multi-targeted tyrosine kinase inhibitor (Lenvatinib, E7080) were evaluated in vitro and in vivo on neovascular AMD mouse model. The results showed that E7080 effectively inhibited the proliferation, migration and tubule formation of human choroidal microvascular endothelial cells (HCMECs), and suppressed the angiogenesis of zebrafish subintestinal vessels without causing malformation. The and-angiogenic effect of E7080 on the laser-induced choroidal neovascularization (CNV) mouse model by oral administration of 10 mg/kg/day was observed. The fluorescein angiography showed CNV leakage area in treatment group vs control group was 3.407 +/- 0.2939 vs 5.202 +/- 0.9001 (P = .0133) at day 7th post laser-induced CNV, 1.138 +/- 0.4334 vs 3.122 +/- 0.3466 (P = .0064) at day 14th, 1.401 +/- 0.6577 vs 2.781 +/- 0.9815 (P = .00262) at day 21th respectively. Moreover, pharmacokinetics analysis in rat retina showed that E7080 rapidly penetrated the blood-retina barrier to retina through oral administration. The T-1/2 in retina was 3.81 +/- 0.77 h, the T-max, was 4.60 +/- 0.73 h, the AU(0-infinity) was 110448.51 +/- 18532.51 h*ng/g after a single dose administration analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In conclusion, our study suggested that orally administered E7080 can be a novel therapeutic strategy for neovascular AMD.
C1 [Wei, Xian; Li, Minhui; Yang, Ping] Chengdu Med Coll, Sch Basic Med Sci, Chengdu, Sichuan, Peoples R China.
   [Zhang, Ting; Li, Min; Zhao, Chengjian] Sichuan Univ, West China Hosp, Canc Ctr, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China.
   [Zhang, Ting; Li, Min; Zhao, Chengjian] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China.
   [Yao, Yuqin] Sichuan Univ, West China Sch Publ Hlth, West China Teaching Hosp 4, Res Ctr Publ Hlth & Prevent Med, Chengdu 610041, Sichuan, Peoples R China.
   [Zeng, Shaoxue; Xiang, Haotian] Sichuan Univ, West China Hosp, Translat Neurosci Ctr, Ophthalm Labs, Chengdu, Sichuan, Peoples R China.
   [Zeng, Shaoxue; Xiang, Haotian] Sichuan Univ, West China Hosp, Translat Neurosci Ctr, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China.
   [Cao, Guiqun] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Mol Med Res Ctr, Chengdu 610041, Sichuan, Peoples R China.
   [Wan, Ran] Liverpool Hosp, Liverpool, NSW 2170, Australia.
   [Yang, Jinliang] Guangdong Zhongsheng Pharmaceut Co Ltd, Shantou, Guangdong, Peoples R China.
C3 Chengdu Medical College; Sichuan University; Sichuan University; Sichuan
   University; Sichuan University; Sichuan University; Liverpool Hospital
RP Yang, P (通讯作者)，Chengdu Med Coll, Sch Basic Med Sci, Chengdu, Sichuan, Peoples R China.; Yao, YQ (通讯作者)，Sichuan Univ, West China Sch Publ Hlth, West China Teaching Hosp 4, Res Ctr Publ Hlth & Prevent Med, Chengdu 610041, Sichuan, Peoples R China.
EM yuqin_yao@scu.edu.cn; yangping1996@cmc.edu.cn
RI Yao, Yuqin/AAG-3879-2020; Zhang, Ting/P-8913-2017
OI Yao, Yuqin/0000-0003-2097-6978; Zhang, Ting/0000-0001-8074-8999
FU Scientific Research Fund of Sichuan Provincial Health Department
   [17PJ591]; Applied Basic Research Programs of Science and Technology
   Department of Sichuan Province [2016JY0074, 2015JY0205]; Guangdong
   Innovative Research Team Program [2011Y073]
FX The work was supported by The Applied Basic Research Programs of Science
   and Technology Department of Sichuan Province (No.2015JY0205,
   2016JY0074); The Scientific Research Fund of Sichuan Provincial Health
   Department (No.17PJ591) and Guangdong Innovative Research Team Program
   (No. 2011Y073).
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NR 38
TC 17
Z9 17
U1 6
U2 27
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 2018
VL 168
BP 2
EP 11
DI 10.1016/j.exer.2017.12.009
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FY2BT
UT WOS:000426620600002
PM 29284110
DA 2022-11-30
ER

PT J
AU Shu, X
   Li, H
   Dong, BQ
   Sun, C
   Zhang, HF
AF Shu, Xiao
   Li, Hao
   Dong, Biqin
   Sun, Cheng
   Zhang, Hao F.
TI Quantifying melanin concentration in retinal pigment epithelium using
   broadband photoacoustic microscopy
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; OCULAR MELANIN;
   HUMAN RPE; EYES; AUTOFLUORESCENCE; REFLECTANCE; ABSORPTION; EUMELANIN;
   FUNDUS
AB Melanin is the dominant light absorber in retinal pigment epithelium (RPE). The loss of RPE melanin is a sign of ocular senescence and is both a risk factor and a symptom of age-related macular degeneration (AMD). Quantifying the RPE melanin concentration provides insight into the pathological role of RPE in ocular aging and the onset and progression of AMD. The main challenge in accurate quantification of RPE melanin concentration is to distinguish this ten-micrometer-thick cell monolayer from the underlying choroid, which also contains melanin but carries different pathognomonic information. In this work, we investigated a three-dimensional photoacoustic microscopic (PAM) method with high axial resolution, empowered by broad acoustic detection bandwidth, to distinguish RPE from choroid and quantify melanin concentrations in the RPE ex vivo. We first conducted numerical simulation on photoacoustic generation in the RPE, which suggested that a PAM system with at least 100-MHz detection bandwidth provided sufficient axial resolution to distinguish the melanin in RPE from that in choroid. Based on simulation results, we integrated a transparent broadband micro-ring resonator (MRR) based detector in a homebuilt PAM system. We imaged ex vivo RPE-choroid complexes (RCCs) from both porcine and human eyes and quantified the absolute melanin concentrations in the RPE and choroid, respectively. In our study, the measured melanin concentrations were 14.7 mg/mL and 17.0 mg/mL in human and porcine RPE, and 12 mg/mL and 61 mg/mL in human and porcine choroid, respectively. This study suggests that broadband PAM is capable of quantifying the RPE melanin concentration from RCCs ex vivo. (C) 2017 Optical Society of America
C1 [Shu, Xiao; Li, Hao; Dong, Biqin; Zhang, Hao F.] Northwestern Univ, Dept Biomed Engn, 2145 Sheridan Rd, Evanston, IL 60201 USA.
   [Dong, Biqin; Sun, Cheng] Northwestern Univ, Dept Mech Engn, 2145 Sheridan Rd, Evanston, IL 60201 USA.
   [Zhang, Hao F.] Northwestern Univ, Dept Ophthalmol, 645 North Michigan Ave, Chicago, IL 60611 USA.
C3 Northwestern University; Northwestern University; Northwestern
   University
RP Zhang, HF (通讯作者)，Northwestern Univ, Dept Biomed Engn, 2145 Sheridan Rd, Evanston, IL 60201 USA.; Zhang, HF (通讯作者)，Northwestern Univ, Dept Ophthalmol, 645 North Michigan Ave, Chicago, IL 60611 USA.
EM hfzhang@northwestern.edu
RI Zhang, Hao F/D-1695-2011; Li, Hao/S-7988-2017; Sun, Cheng/B-7609-2009;
   Zhang, Hao/H-6199-2012
OI Li, Hao/0000-0002-7813-5349; Shu, Xiao/0000-0001-7998-4556
FU National Institutes of Health (NIH) [DP3DK108248, R24EY022883,
   R01EY026078]; National Science Foundation (NSF) [CBET-1055379,
   DBI-1353952]; Illinois Society for the Prevention of Blindness; NATIONAL
   EYE INSTITUTE [R01EY026078] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [DP3DK108248]
   Funding Source: NIH RePORTER
FX National Institutes of Health (NIH) (DP3DK108248, R24EY022883, and
   R01EY026078); National Science Foundation (NSF) (CBET-1055379 and
   DBI-1353952); and Illinois Society for the Prevention of Blindness.
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NR 42
TC 29
Z9 30
U1 2
U2 10
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 JUN 1
PY 2017
VL 8
IS 6
BP 2851
EP 2865
DI 10.1364/BOE.8.002851
PG 15
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 EZ5FA
UT WOS:000404737200006
PM 28663911
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Fernandez-Robredo, P
   Selvam, S
   Powner, MB
   Sim, DA
   Fruttiger, M
AF Fernandez-Robredo, Patricia
   Selvam, Senthil
   Powner, Michael B.
   Sim, Dawn A.
   Fruttiger, Marcus
TI Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation
SO PLOS ONE
LA English
DT Article
ID OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; PATHOLOGICAL ANGIOGENESIS; SPROUTING ANGIOGENESIS;
   VASCULAR-DISEASE; VEGF; MODEL; NRP1; INHIBITION
AB Purpose
   Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a coreceptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1.
   Methods
   Crossing Nrp1 floxed mice with Pdgfb-CreERT2 mice produced tamoxifen-inducible, endothelial specific Nrp1 knock out mice (Nrp1(Delta EC)) and Cre-negative, control littermates. Crerecombinase activity was confirmed in the Ai3(RCL-EYFP) reporter strain. Animals were subjected to laser-induced CNV (532 nm) and spectral domain-optical coherence tomography (SD-OCT) was performed immediately after laser and at day 7. Fluorescein angiography (FA) evaluated leakage and postmortem lectin staining in flat mounted RPE/choroid complexes was also used to measure CNV. Furthermore, retinal neovascularisation in the oxygen induced retinopathy (OIR) model was assessed by immunohistochemistry in retinal flatmounts.
   Results
   In vivo FA, OCT and post-mortem lectin staining showed a statistically significant reduction in leakage (p<0.05), CNV volume (p<0.05) and CNV area (p<0.05) in the Nrp1(Delta EC) mice compared to their Cre-negative littermates. Also the OIR model showed reduced retinal NV in the mutant animals compared to wild types (p<0.001).
   Conclusion
   We have demonstrated reduced choroidal and retinal NV in animals that lack endothelial Nrp1, confirming a role of Nrp1 in those processes. Therefore, Nrp1 may be a promising drug target for neovascular diseases in the eye.
C1 [Fernandez-Robredo, Patricia; Selvam, Senthil; Powner, Michael B.; Sim, Dawn A.; Fruttiger, Marcus] UCL, UCL Inst Ophthalmol, London, England.
   [Fernandez-Robredo, Patricia] Univ Navarra, Sch Med, Expt Ophthalmol Lab, Navarra Inst Hlth Res,IdiSNA, Pamplona, Spain.
   [Powner, Michael B.] City Univ London, Sch Hlth Sci, Div Optometry & Visual Sci, London, England.
   [Sim, Dawn A.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London, England.
C3 University of London; University College London; University of Navarra;
   City University London; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust
RP Fruttiger, M (通讯作者)，UCL, UCL Inst Ophthalmol, London, England.
EM m.fruttiger@ucl.ac.uk
RI Powner, Michael/CAG-7455-2022
OI Powner, Michael/0000-0003-4913-1004; Fruttiger,
   Marcus/0000-0002-6962-5485
FU European Union, 7th Framework Program [331855]; Fight for Sight [1389];
   Wellcome Trust [099173/Z/12/Z]; National Institute for Health Research
   [ACF-2016-18-014] Funding Source: researchfish; Fight for Sight [1987,
   1389/90] Funding Source: researchfish
FX PFR received an FP7-MC-IEF grant (331855) from the European Union, 7th
   Framework Program. The study was also partially funded by grant from
   Fight for Sight (1389) and used imaging equipment that was obtained by a
   multiuser equipment grant from the Wellcome Trust [099173/Z/12/Z].
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NR 38
TC 6
Z9 6
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 20
PY 2017
VL 12
IS 1
AR e0169865
DI 10.1371/journal.pone.0169865
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EI3QC
UT WOS:000392405300048
PM 28107458
OA Green Published, Green Submitted, Green Accepted, gold
DA 2022-11-30
ER

PT J
AU Liu, F
   Ding, XY
   Yang, Y
   Li, JQ
   Tang, M
   Yuan, M
   Hu, ADN
   Zhan, ZY
   Li, ZJ
   Lu, L
AF Liu, Fang
   Ding, Xiaoyan
   Yang, Yu
   Li, Jiaqing
   Tang, Miao
   Yuan, Miner
   Hu, Andina
   Zhan, Zongyi
   Li, Zijing
   Lu, Lin
TI Aqueous humor cytokine profiling in patients with wet AMD
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; DIABETIC-RETINOPATHY;
   EXPRESSION; UVEITIS; CXCL16; ANGIOGENESIS; INFILTRATION; CHEMOTAXIS;
   BIOMARKERS
AB Purpose: To investigate the chemokine expression profiles in the aqueous humor of wet age-related macular degeneration (wet AMD) patients and to correlate their levels with clinical findings.
   Methods: Undiluted aqueous humor samples (100-200 mu l) were obtained from 16 wet AMD eyes and 12 control eyes. Forty chemokines were measured using a multiplex method. A 6x6 mm area of the macular region centered on the fovea was examined using spectral domain optical coherence tomography (SD-OCT).
   Results: The detection rates were 50% or more for 15 chemokines. Compared with the control group, the aqueous humor in wet AMD patients showed a significantly higher expression of CXCL10 (p=0.004), CCL14 (p=0.002), CXCL16 (p=0.013), CXCL7 (p=0.033), and CCL22 (p=0.037), while growth-related oncogene (GRO) was significantly decreased in the wet AMD patients (p=0.001). When compared with treatment-naive patients, the recurrent group had significant upregulation of CXCL10 (p=0.012) and CCL22 (p=0.002). CXCL16 was positively correlated with lesion size, and CCL22 was higher in patients whose OCT images showed intraretinal fluid (IRF) or hyperreflective foci (HF).
   Conclusions: Elevated levels of inflammation-related chemokines, including CXCL10, CCL14, CXCL16, CXCL7, and CCL22, in the aqueous humor of AMD patients may suggest a pathogenic role for inflammation. CXCL10 and CCL22 were more elevated in eyes with recurrent wet AMD than in treatment-naive eyes. CXCL16 was positively correlated with lesion size. The increase in CCL22 was correlated with the presence of IRF or HF. These data may be of interest in the search for biomarkers associated with wet AMD and may potentially indicate different treatment strategies.
C1 [Liu, Fang; Ding, Xiaoyan; Yang, Yu; Li, Jiaqing; Tang, Miao; Yuan, Miner; Hu, Andina; Zhan, Zongyi; Li, Zijing; Lu, Lin] Sun Yat Sen Univ, State Key Lab Ophthalmol, Retina Div, Zhongshan Ophthalm Ctr, 54 Xianlie S Rd, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Lu, L (通讯作者)，Sun Yat Sen Univ, State Key Lab Ophthalmol, Retina Div, Zhongshan Ophthalm Ctr, 54 Xianlie S Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM lulin888@126.com
RI Li, Zijing/ABE-5039-2021
OI Zhan, Zongyi/0000-0002-6621-1172; Fang, Liu/0000-0002-7962-3854; Yuan,
   Miner/0000-0002-8988-3289
FU Fundamental Research Funds of State Key Laboratory of Ophthalmology;
   National Natural Science Foundation of China [81,470,645, 81,500,735];
   Science and Technology Program of Guangdong Province, China
   [2013B020400003]; Science and Technology Program of Guangzhou, China
   [15,570,001]
FX This study was supported by the Fundamental Research Funds of State Key
   Laboratory of Ophthalmology and National Natural Science Foundation of
   China 81,470,645 and 81,500,735 and by Science and Technology Program of
   Guangdong Province, China 2013B020400003 and by Science and Technology
   Program of Guangzhou, China 15,570,001. No authors have any
   financial/conflicting interests to disclose. Involved in design and
   conduct of the study (L.L., D.X.), collection (L.F., L.J., Y.Y.),
   management (L.L., L.J.), analysis (L.L., Y.Y., T.M.), interpretation of
   the data (D.X., L.L.), and preparation and review of the manuscript
   (D.X., L.F., L.L., Y.M., H.A., Z.Z., L.Z.).
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NR 31
TC 34
Z9 35
U1 1
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 22
PY 2016
VL 22
BP 352
EP 361
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA DL5MY
UT WOS:000375682400001
PM 27122966
DA 2022-11-30
ER

PT J
AU Schnabolk, G
   Coughlin, B
   Joseph, K
   Kunchithapautham, K
   Bandyopadhyay, M
   O'Quinn, EC
   Nowling, T
   Rohrer, B
AF Schnabolk, Gloriane
   Coughlin, Beth
   Joseph, Kusumam
   Kunchithapautham, Kannan
   Bandyopadhyay, Mausumi
   O'Quinn, Elizabeth C.
   Nowling, Tamara
   Rohrer, Baerbel
TI Local Production of the Alternative Pathway Component Factor B Is
   Sufficient to Promote Laser-Induced Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE alternative complement pathway; complement factor B; RPE-specific
   transgenic mouse; choroidal neovascularization; age-related macular
   degeneration
ID COMPLEMENT FACTOR-H; PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION;
   OXIDATIVE STRESS; MEDIATED INJURY; LECTIN PATHWAY; MOUSE MODEL; AGE;
   ACTIVATION; RISK
AB PURPOSE. Complement factor B (CFB) is a required component of the alternative pathway (AP) of complement, and CFB polymorphisms are associated with age-related macular degeneration (AMD) risk. Complement factor B is made in the liver, but expression has also been detected in retina and retinal pigment epithelium (RPE)-choroid. We investigated whether production of CFB by the RPE can promote AP activation in mouse choroidal neovascularization (CNV).
   METHODS. Transgenic mice expressing CFB under the RPE65 promoter were generated and crossed onto factor B-deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was investigated using CFB-KO reconstituted with CFB-sufficient serum.
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C1 [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.
   [Coughlin, Beth; Joseph, Kusumam; Kunchithapautham, Kannan; Bandyopadhyay, Mausumi; O'Quinn, Elizabeth C.; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Nowling, Tamara] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
C3 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 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 (NIH) [R01EY019320]; Department for
   Veteran Affairs Merit Award [RX000444]; Beckman Initiative for Macular
   Research; Medical University of South Carolina from Research to Prevent
   Blindness (RPB), New York, New York, United States; NIH [C06RR015455]; 
   [AR053376];  [R03-NIAMS]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY024581, R01EY019320] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
   [R03AR053376] Funding Source: NIH RePORTER; Veterans Affairs
   [I01RX000444] Funding Source: NIH RePORTER
FX Supported in the laboratory of BR in part by the National Institutes of
   Health (NIH R01EY019320); Department for Veteran Affairs Merit Award
   RX000444; the Beckman Initiative for Macular Research; an unrestricted
   grant to the Medical University of South Carolina from Research to
   Prevent Blindness (RPB), New York, New York, United States; and in the
   laboratory of TN by Grant AR053376 (R03-NIAMS). Animal studies were
   conducted in a facility constructed with support from NIH C06RR015455.
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NR 50
TC 29
Z9 29
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2015
VL 56
IS 3
BP 1850
EP 1863
DI 10.1167/iovs.14-15910
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE9BF
UT WOS:000352137600057
PM 25593023
OA Green Published
DA 2022-11-30
ER

PT J
AU Yannuzzi, NA
   Patel, SN
   Bhavsar, KV
   Sugiguchi, F
   Freund, KB
AF Yannuzzi, Nicolas A.
   Patel, Samir N.
   Bhavsar, Kavita V.
   Sugiguchi, Fumitaka
   Freund, K. Bailey
TI Predictors of Sustained Intraocular Pressure Elevation in Eyes Receiving
   Intravitreal Anti-Vascular Endothelial Growth Factor Therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; REPACKAGED BEVACIZUMAB; FACTOR AGENTS; INJECTIONS;
   RANIBIZUMAB; TRIAMCINOLONE; HYPERTENSION; PEGAPTANIB; NEEDLES; IOP
AB PURPOSE: To determine the intravitreal anti-vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and to identify potential factors associated with the development of sustained intraocular pressure (IOP) elevation in patients treated with intravitreal anti-VEGF therapy for neovascular age-related macular degeneration (AMD).
   DESIGN: Cross-sectional physician survey.
   METHODS: Five hundred and thirty retina specialists spanning both private and academic practices were surveyed regarding current anti-VEGF intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP.
   RESULTS: Two hundred ninety-two specialists (55%) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. Of these responses, the most common reported prevalence was 1%-2% (48%), followed by 3%-5% (34%). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. Physicians who injected greater than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation (P = .006, 95% CI 1.64-18.89).
   CONCLUSIONS: Based on physician survey data, serial anti-VEGF injections using higher injection volumes with a rapid injection technique may potentially lead to sustained IOP elevation. The underlying mechanism for this complication may be injury to the trabecular meshwork resulting from rapid elevations in IOP. Further investigation of the relationship between injection techniques and sustained IOP elevation in the form of retrospective or prospective clinical studies is warranted. ((C) 2014 by Elsevier Inc. All rights reserved.)
C1 [Yannuzzi, Nicolas A.; Patel, Samir N.; Sugiguchi, Fumitaka] Weill Cornell Med Coll, New York, NY USA.
   [Yannuzzi, Nicolas A.; Patel, Samir N.; Bhavsar, Kavita V.; Sugiguchi, Fumitaka; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA.
   [Bhavsar, Kavita V.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA.
   [Bhavsar, Kavita V.; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
   Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA.
C3 Cornell University; Manhattan Eye Ear & Throat Hospital; Vitreous Retina
   Macula Consultants of New York; New York University; Columbia University
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, 460 Pk Ave 5, New York, NY 10022 USA.
EM kbfnyf@aol.com
RI Freund, K. Bailey/V-7488-2018
OI Freund, K. Bailey/0000-0002-7888-9773
FU Macula Foundation (New York, New York); LuEsther T. Mertz Retinal
   Research Center (New York, New York)
FX K. Bailey Freund discloses the following: Genentech, Inc: Consultant,
   Honoraria; Heidelberg Engineering: Consultant, Honoraria; Regeneron
   Pharmaceuticals, Inc: Consultant, Honoraria; Bayer Heath Care:
   Consultant, Honoraria. The other authors indicate no disclosures. This
   work was supported by the Macula Foundation (New York, New York) and the
   LuEsther T. Mertz Retinal Research Center (New York, New York).
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NR 27
TC 30
Z9 31
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
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD AUG
PY 2014
VL 158
IS 2
BP 319
EP 327
DI 10.1016/j.ajo.2014.04.029
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN6EB
UT WOS:000340686600016
PM 24814167
DA 2022-11-30
ER

PT J
AU Johnen, S
   Izsvak, Z
   Stocker, M
   Harmening, N
   Salz, AK
   Walter, P
   Thumann, G
AF Johnen, Sandra
   Izsvak, Zsuzsanna
   Stoecker, Michael
   Harmening, Nina
   Salz, Anna Katharina
   Walter, Peter
   Thumann, Gabriele
TI Sleeping Beauty Transposon-Mediated Transfection of Retinal and Iris
   Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; INHIBITS CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL
   GROWTH-FACTOR; MACULAR DEGENERATION; GENE-TRANSFER; INTRAVITREAL
   BEVACIZUMAB; TRANSGENE EXPRESSION; VECTOR; SYSTEM; DELIVERY
AB PURPOSE. Subretinal transplantation of retinal (RPE) or iris (IPE) pigment epithelial cells has been advocated as a treatment for retinal degeneration. However, to our knowledge, in patients with age-related macular degeneration no significant beneficial effects on vision have been shown. Since the transplanted cells did not appear to maintain a healthy avascular and neuroprotective environment, we postulate that it will be necessary to transplant cells that express elevated levels of anti-angiogenic and neuroprotective activities. In our study, we provide a protocol for the efficient stable gene transfer and sustained gene expression of pigment epithelium-derived factor (PEDF), a potent anti-angiogenic and neuroprotective factor, using the nonviral Sleeping Beauty transposon system (SB100X).
   METHODS. Pigment epithelial cells were electroporated with a Venus reporter or a PEDF encoding plasmid, controlled by either CMV or CAGGS promoters. Transfection efficiencies and protein expression stability were evaluated by flow cytometry and immunoblotting. Gene expression profiles were analyzed by RT-PCR.
   RESULTS. SB100X-based delivery resulted in efficiencies of 100% with the Venus gene and 30% with the PEDF gene. Cell sorting enabled establishment of pure PEDF-transfected ARPE-19 populations. Transfected RPE and IPE cells have been shown to maintain stable PEDF secretion for more than 16 and 6 months, respectively.
   CONCLUSIONS. Transfection using the nonviral SB100X vector system avoids complications associated with viral gene delivery. SB100X-mediated transfer allows for stable PEDF gene integration into the cell's genome, ensuring continuous expression and secretion of PEDF. Stable expression of the therapeutic gene is critical for the development of cell-based gene addition therapies for retinal degenerative diseases. (Invest Ophthalmol Vis Sci. 2012;53:4787-4796) DOI: 10.1167/iovs.12-9951
C1 [Walter, Peter; Thumann, Gabriele] Rhein Westfal TH Aachen, Dept Ophthalmol, D-52074 Aachen, Germany.
   [Johnen, Sandra; Harmening, Nina; Salz, Anna Katharina; Thumann, Gabriele] Rhein Westfal TH Aachen, IZKF Aachen, D-52074 Aachen, Germany.
   [Izsvak, Zsuzsanna] Max Delbruck Ctr Mol Med, Berlin, Germany.
   [Stoecker, Michael] Forschungszentrum Julich, Project Management Julich, D-52425 Julich, Germany.
C3 RWTH Aachen University; RWTH Aachen University; Helmholtz Association;
   Max Delbruck Center for Molecular Medicine; Helmholtz Association;
   Research Center Julich
RP Thumann, G (通讯作者)，Rhein Westfal TH Aachen, Dept Ophthalmol, Pauwelsstr 30, D-52074 Aachen, Germany.
EM gthumann@ukaachen.de
RI Harmening, Nina/F-7804-2017; Walter, Peter/L-5982-2018; Johnen,
   Sandra/ABA-9955-2020
OI Walter, Peter/0000-0001-8745-6593; Johnen, Sandra/0000-0003-0028-2557;
   Izsvak, Zsuzsanna/0000-0002-2053-2384
FU Interdisciplinary Center for Clinical Research IZKF Aachen within the
   Faculty of Medicine at the RWTH Aachen University
FX Supported by a grant from the Interdisciplinary Center for Clinical
   Research IZKF Aachen within the Faculty of Medicine at the RWTH Aachen
   University.
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NR 58
TC 33
Z9 34
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 JUL
PY 2012
VL 53
IS 8
BP 4787
EP 4796
DI 10.1167/iovs.12-9951
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400055
PM 22729435
OA Green Published
DA 2022-11-30
ER

PT J
AU Feng, ZH
   Liu, ZB
   Li, XS
   Jia, HQ
   Sun, LJ
   Tian, CA
   Jia, LH
   Liu, JK
AF Feng, Zhihui
   Liu, Zhongbo
   Li, Xuesen
   Jia, Haiqun
   Sun, Lijuan
   Tian, Chuan
   Jia, Lihong
   Liu, Jiankang
TI alpha-Tocopherol is an effective Phase II enzyme inducer: protective
   effects on acrolein-induced oxidative stress and mitochondrial
   dysfunction in human retinal pigment epithelial cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Mitochondrial complex; Protein oxidation; Nuclear factor-E2-related
   factor 2 (Nrf2); Glutamate cysteine ligase (GCL); NAD(P)H:quinone;
   oxidoreductase 1 (NQ01); Glutathione
ID RAT-LIVER MITOCHONDRIA; VITAMIN-E; MACULAR DEGENERATION; GLUTATHIONE
   SYNTHESIS; RESPIRATORY-FUNCTION; TRANSCRIPTION FACTOR;
   PARKINSONS-DISEASE; CELLULAR-RESPONSES; CIGARETTE-SMOKE; LIPOIC ACID
AB Vitamin E has long been identified as a major lipid-soluble chain-breaking antioxidant in mammals. alpha-Tocopherol is a vitamin E component and the major form in the human body. We propose that, besides its direct chain-breaking antioxidant activity, alpha-tocopherol may exert an indirect antioxidant activity by enhancing the cell's antioxidant system as a Phase II enzyme inducer. We investigated alpha-tocopherol's inducing effect on Phase II enzymes and its protective effect on acrolein-induced toxicity in a human retinal pigment epithelial (RPE) cell line, ARPE-19. Acrolein, a major component of cigarette smoke and also a product of lipid peroxidation, at 75 mu mol/L over 24 h, caused significant loss of ARPE-19 cell viability, increased oxidative damage, decreased antioxidant defense, inactivation of the Keap1/Nrf2 pathway, and mitochondrial dysfunction. ARPE-19 cells have been used as a model of smoking- and age-related macular degeneration. Pretreatment with alpha-tocopherol activated the Keap1/Nrf2 pathway by increasing Nrf2 expression and inducing its translocation to the nucleus. Consequently, the expression and/or activity of the following Phase II enzymes increased: glutamate cysteine ligase, NAD(P)H:quinone oxidoreductase 1, hemeoxygenase 1, glutathione S-transferase and superoxide dismutase; total antioxidant capacity and glutathione also increased. This antioxidant defense enhancement protected ARPE-19 cells from an acrolein-induced decrease in cell viability, lowered reactive oxygen species and protein oxidation levels, and improved mitochondria! function. These results suggest that alpha-tocopherol protects ARPE-19 cells from acrolein-induced cellular toxicity, not only as a chain-breaking antioxidant, but also as a Phase II enzyme inducer. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Liu, Jiankang] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mitochondrial Biol & Med, Key Lab Biomed Informat Engn,Minist Engn, Xian 710049, Peoples R China.
   [Feng, Zhihui; Liu, Zhongbo; Li, Xuesen; Jia, Haiqun; Tian, Chuan] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
   [Feng, Zhihui; Liu, Zhongbo; Li, Xuesen; Jia, Haiqun; Tian, Chuan] Chinese Acad Sci, Grad Sch, Beijing 100081, Peoples R China.
   [Sun, Lijuan] E China Normal Univ, Coll Phys Educ & Hlth, Shanghai 200241, Peoples R China.
   [Jia, Lihong] China Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Shenyang 110001, Peoples R China.
C3 Xi'an Jiaotong University; Chinese Academy of Sciences; Shanghai
   Institutes for Biological Sciences, CAS; Chinese Academy of Sciences;
   University of Chinese Academy of Sciences, CAS; East China Normal
   University; China Medical University
RP Liu, JK (通讯作者)，Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mitochondrial Biol & Med, Key Lab Biomed Informat Engn,Minist Engn, Xian 710049, Peoples R China.
EM j.liu@mail.xjtu.edu.cn
RI Liu, Jiankang/A-1610-2011; Jia, Haiqun/B-1305-2012; Liu,
   Zhongbo/U-3004-2017; Feng, Zhihui/E-7408-2011
OI Jia, Haiqun/0000-0003-1606-4861; Feng, Zhihui/0000-0002-2448-6565
FU National Eye Institute, NIH [EY0160101]; Macular Degeneration Research
   (MDR) [2005-038]; Chinese Academy of Sciences [05PG14104]; Xi'an
   Jiaotong University; NIH [5R01 CA119028-05, R01 CA116697, R01 ES015518,
   ES015375]
FX This study was supported by the National Eye Institute, NIH grant
   EY0160101, Macular Degeneration Research (MDR Grant 2005-038), Chinese
   Academy of Sciences grant 05PG14104 and a starting fund of 985 Plan of
   Xi'an Jiaotong University.; This study was partially supported by NIH
   grants, 5R01 CA119028-05, R01 CA116697, R01 ES015518, and ES015375.
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NR 55
TC 89
Z9 93
U1 1
U2 21
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 DEC
PY 2010
VL 21
IS 12
BP 1222
EP 1231
DI 10.1016/j.jnutbio.2009.10.010
PG 10
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 686YJ
UT WOS:000284737800011
PM 20153624
DA 2022-11-30
ER

PT J
AU An, E
   Sen, S
   Park, SK
   Gordish-Dressman, H
   Hathout, Y
AF An, Eunkyung
   Sen, Supti
   Park, Sung Kyu
   Gordish-Dressman, Heather
   Hathout, Yetrib
TI Identification of Novel Substrates for the Serine Protease HTRA1 in the
   Human RPE Secretome
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX;
   AMYLOID-BETA; IN-VITRO; VARIANT; GENE; SUSCEPTIBILITY; POLYMORPHISM;
   EXPRESSION
AB PURPOSE. To define the role of the serine protease HTRA1 in age-related macular degeneration (AMD) by examining its expression level and identifying its potential substrates in the context of primary RPE cell extracellular milieu.
   METHODS. Primary RPE cell cultures were established from human donor eyes and screened for CFH, ARMS2, and HTRA1 risk genotypes by using an allele-discrimination assay. HTRA1 expression in genotyped RPE cells was determined by using real-time PCR and quantitative proteomics. Potential HTRA1 substrates were identified by incubating RPE-conditioned medium with or without human recombinant HTRA1. Selectively cleaved proteins were quantified by using the differential stable isotope labeling by amino acids in cell culture (SILAC) strategy.
   RESULTS. HTRA1 mRNA levels were threefold higher in primary RPE cells homozygous for the HTRA1 promoter risk allele than in RPE cells with the wild-type allele, which translated into a twofold increase in HTRA1 secretion by RPE cells with the risk genotype. A total of 196 extracellular proteins were identified in the RPE secretome, and only 8 were found to be selectively cleaved by the human recombinant HTRA1. These include fibromodulin with 90% cleavage, clusterin (50%), ADAM9 (54%), vitronectin (54%), and alpha 2-macroglobulin (55%), as well as some cell surface proteins including talin-1 (21%), fascin (40%), and chloride intracellular channel protein 1 (51%).
   CONCLUSIONS. Recombinant HTRA1 cleaves RPE-secreted proteins involved in regulation of the complement pathway (clusterin, vitronectin, and fibromodulin) and of amyloid deposition (clusterin, alpha 2-macroglobulin, and ADAM9). These findings suggest a link between HTRA1, complement regulation, and amyloid deposition in AMD pathogenesis. (Invest Ophthalmol Vis Sci. 2010; 51:3379-3386) DOI:10.1167/iovs.09-4853
C1 [An, Eunkyung; Sen, Supti; Gordish-Dressman, Heather; Hathout, Yetrib] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA.
   [An, Eunkyung] George Washington Univ, Program Biochem & Mol Genet, Inst Biomed Sci, Washington, DC USA.
   [Park, Sung Kyu] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Children's National Health System; George Washington University; Scripps
   Research Institute
RP Hathout, Y (通讯作者)，Childrens Natl Med Ctr, Res Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM yhathout@cnmcresearch.org
FU National Institutes of Health/National Eye Institute (NIH/NEI)
   [R21EY016723]; NEI ARRA [R21EY016723-02S109]; National Institute of
   Child Health and Development (NICHD)/NIH [5R24HD050846, 5P30HD040677];
   EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN
   DEVELOPMENT [R24HD050846, P30HD040677] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R21EY016723] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health/National Eye Institute
   (NIH/NEI) Grant R21EY016723, NEI ARRA administrative supplement
   R21EY016723-02S109, and partially by National Institute of Child Health
   and Development (NICHD)/NIH Core Grants 5R24HD050846 and 5P30HD040677.
   Eunkyung An is a predoctoral student in the Biochemistry and Molecular
   Genetics Program of the Institute for Biomedical Sciences at the George
   Washington University. This work is from a dissertation to be presented
   to the above program in partial fulfillment of the requirements of the
   PhD degree.
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NR 50
TC 69
Z9 71
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 JUL
PY 2010
VL 51
IS 7
BP 3379
EP 3386
DI 10.1167/iovs.09-4853
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 614HX
UT WOS:000279047500008
PM 20207970
OA Green Published
DA 2022-11-30
ER

PT J
AU Krishnan, R
   Goverdhan, S
   Lochhead, J
AF Krishnan, Radhika
   Goverdhan, Srinivas
   Lochhead, Jonathan
TI Submacular haemorrhage after intravitreal bevacizumab compared with
   intravitreal ranibizumab in large occult choroidal neovascularization
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE bevacizumab; choroidal neovascularization; occult; ranibizumab;
   submacular haemorrhage
ID PIGMENT EPITHELIUM TEARS; MACULAR DEGENERATION; AVASTIN;
   PHARMACOKINETICS; INJECTION
AB P>Background:
   Submacular haemorrhage may occur following intravitreal bevacizumab injection for large occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD). We report the occurrence of submacular haemorrhage following intravitreal ranibizumab compared with intravitreal bevacizumab for large occult CNV in AMD.
   Methods:
   Retrospective, comparative evaluation of two interventional case series. Evaluation of consecutive patients with occult CNV >= 15 mm(2) treated with intravitreal bevacizumab (n = 14) and intravitreal ranibizumab (n = 22) over a 2-year period within a single institution. Postoperative submacular haemorrhage, Early Treatment Diabetic Retinopathy Study-derived visual acuity, preoperative blood pressure and anticoagulant use were noted. The two groups were compared using Fisher's exact test.
   Results:
   The mean surface area of occult CNV at presentation was 20.9 +/- 5.4 mm(2) in the bevacizumab group and 24.0 +/- 11.0 mm(2) in the ranibizumab group. Fresh submacular haemorrhage was seen in 4 out of 14 patients following bevacizumab compared with 0 out of 22 patients following ranibizumab (P = 0.017, odds ratio = 19.29). Mean preoperative blood pressures were very similar between the groups. 28.6% of patients in the bevacizumab group were on oral anticoagulants compared with 31.8% in the ranibizumab group. None of the patients who developed postoperative haemorrhage were on anticoagulants.
   Conclusions:
   Acute submacular haemorrhages appear to be a significant adverse event following intravitreal bevacizumab in occult CNV >= 15 mm(2). Intravitreal ranibizumab appears to have a significantly lower incidence of postoperative submacular haemorrhage in occult CNV >= 15 mm(2). Larger studies are required to identify the most appropriate agent for the treatment of large occult CNV.
EM radhikrishnan2004@yahoo.co.uk
CR Bakri SJ, 2007, OPHTHALMOLOGY, V114, P2179, DOI 10.1016/j.ophtha.2007.09.012
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NR 13
TC 31
Z9 31
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD MAY-JUN
PY 2009
VL 37
IS 4
BP 384
EP 388
DI 10.1111/j.1442-9071.2009.02043.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 462AQ
UT WOS:000267317800009
PM 19594565
DA 2022-11-30
ER

PT J
AU Bermudez, OI
   Ribaya-Mercado, JD
   Talegawkar, SA
   Tucker, KL
AF Bermudez, OI
   Ribaya-Mercado, JD
   Talegawkar, SA
   Tucker, KL
TI Hispanic and non-Hispanic white elders from Massachusetts have different
   patterns of carotenoid intake and plasma concentrations
SO JOURNAL OF NUTRITION
LA English
DT Article
DE carotenoids; elderly; Hispanic; Puerto Rican; Dominican
ID FOOD FREQUENCY QUESTIONNAIRE; 3RD NATIONAL-HEALTH; BETA-CAROTENE;
   DIETARY CAROTENOIDS; RISK-FACTORS; VITAMIN-C; ALL-TRANS; LYCOPENE;
   DISEASE; CANCER
AB Carotenoids have been linked with protective roles against diseases associated with aging, including cancer, cardiovascular disease, cataracts, and age-related macular degeneration. With data from a serniquantitative, validated FFQ, we examined carotenoid intake of 340 Puerto Ricans, 98 Dominicans, and 146 non-Hispanic whites (> 60 y old) in Massachusetts. Compared with non-Hispanic white men, Hispanic men reported a higher intake of lycopene and lower intakes of a-carotene, lutein + zeaxanthin, beta-carotene (from diet only), and total beta-carotene (diet and supplements) (P < 0.001). Hispanic women reported higher intakes of beta-cryptoxanthin and lycopene but lower intakes of lutein + zeaxanthin (P < 0.001) than non-Hispahic white women. The frequency of consumption of fruit and vegetables was higher among Hispanic women, relative to non-Hispanic white women (P < 0.05). Plasma concentrations of alpha-carotene and lycopene were higher in Hispanic than in non-Hispanic white men and women. For both ethnic groups, higher intakes of carotenoids were associated with higher plasma concentrations of the respective carotenoids, except for lycopene (Hispanics) and lutein + zeaxanthin (nonHispanic whites). Food sources contributing most to total intakes differed among the groups. The major sources of alpha- and beta-carotene were carrots for non-Hispanic whites and winter squash for Hispanics. The major source of lycopene was cooked tomato products for Hispanics, and pasta dishes for non-Hispanic whites. Traditional foods such as beans and plantains were also important contributors of carotenoids for Hispanics. Because of the potential importance of carotenoids as protective factors against chronic diseases, more attention to food-related practices associated with carotenoid intake in differing population groups is warranted.
C1 Tufts Univ, Jean Mayer US Dept Agr Human Nutr, Res Ctr Aging, Boston, MA 02111 USA.
C3 Tufts University
RP Bermudez, OI (通讯作者)，Tufts Univ, Jean Mayer US Dept Agr Human Nutr, Res Ctr Aging, Boston, MA 02111 USA.
EM Odilia.Bermudez@Tufts.edu
RI Tucker, Katherine L/A-4545-2010; Talegawkar, Sameera/ABF-8126-2020
OI Tucker, Katherine/0000-0001-7640-662X
FU NIA NIH HHS [AG10425-05] Funding Source: Medline; NATIONAL INSTITUTE ON
   AGING [R01AG010425] Funding Source: NIH RePORTER
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NR 53
TC 53
Z9 58
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2005
VL 135
IS 6
BP 1496
EP 1502
DI 10.1093/jn/135.6.1496
PG 7
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 933HX
UT WOS:000229620600026
PM 15930459
OA Bronze
DA 2022-11-30
ER

PT J
AU Zhang, K
   Garibaldi, DC
   Li, Y
   Green, WR
   Zack, DJ
AF Zhang, K
   Garibaldi, DC
   Li, Y
   Green, WR
   Zack, DJ
TI Butterfly-shaped pattern dystrophy - A genetic, clinical, and
   histopathological report
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID PERIPHERIN-RDS GENE; DOMINANT RETINITIS-PIGMENTOSA; RETINAL
   DEGENERATION; MACULAR DYSTROPHY; FUNDUS FLAVIMACULATUS; DELETION;
   MUTATION; FAMILY; FOVEA; PRODUCT
AB Objectives: To identify the disease-causing mutation in a large family segregating dominantly inherited butterfly-shaped pattern dystrophy (BPD) and to describe the microscopic pathological changes observed in a member of this family.
   Methods: Seventeen individuals at risk for dominantly inherited BPD in a family were examined and,blood samples obtained. Linkage analysis and mutation screening of the human retinal degeneration slow (RDS)/peripherin locus were performed. Light and electron microscopic examinations were performed on I postmortem eye of I affected individual.
   Results: Four individuals demonstrated macular degenerative changes with diminished visual acuity, and 3 others exhibited early signs of atrophy without visual deficits. Microscopic examination of the left eye of I patient revealed an area of total loss of the retinal pigment epithelium (RPE) and photoreceptor cell layer with intact choriocapillaris and lipofuscin-containing cells in the subretinal space. Outside the area of RPE atrophy, the RPE was greatly distended by lipofuscin. The disease locus in this family was mapped to 6p21.2, the region of the RDS/peripherin gene. Further analysis identified a G-->A change at nucleotide position 637 of RDS/peripherin, predicting a novel Cys213Tyr substitution in all affected members of the family.
   Conclusions: This study describes a new RDS/peripherin mutation for BPD and provides the first combined genetic-pathological study of this condition, to our knowledge.
   Clinical Relevance: Accumulation of lipofuscin in RPE is a prominent feature of several retinal disorders, including age-related macular degeneration. Further elucidation of the cellular and molecular mechanism of BPD may provide insight into pathogenesis and lead to novel treatment approaches for this and other macular degenerations.
C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   Medicine; Johns Hopkins University; Johns Hopkins University
RP Green, WR (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 809 Maumenee,600 N Wolfe St, Baltimore, MD 21287 USA.
RI Zhang, Kang/Y-2740-2019
OI Zhang, Kang/0000-0002-4549-1697; Zack, Don/0000-0002-7966-1973
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NR 23
TC 49
Z9 50
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD APR
PY 2002
VL 120
IS 4
BP 485
EP 490
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 538JU
UT WOS:000174813300008
PM 11934323
DA 2022-11-30
ER

PT J
AU Henning, Y
   Blind, US
   Larafa, S
   Matschke, J
   Fandrey, J
AF Henning, Yoshiyuki
   Blind, Ursula Sarah
   Larafa, Safa
   Matschke, Johann
   Fandrey, Joachim
TI Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton
   reaction
SO CELL DEATH & DISEASE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; LIPID-PEROXIDATION;
   OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; SODIUM-IODATE; RETINAL
   DEGENERATION; IRON ACCUMULATION; CHELATABLE IRON; GENE-EXPRESSION
AB Oxidative stress and hypoxia in the retinal pigment epithelium (RPE) have long been considered major risk factors in the pathophysiology of age-related macular degeneration (AMD), but systematic investigation of the interplay between these two risk factors was lacking. For this purpose, we treated a human RPE cell line (ARPE-19) with sodium iodate (SI), an oxidative stress agent, together with dimethyloxalylglycine (DMOG) which leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. We found that HIF stabilization aggravated oxidative stress-induced cell death by SI and iron-dependent ferroptosis was identified as the main cell death mechanism. Ferroptotic cell death depends on the Fenton reaction where H2O2 and iron react to generate hydroxyl radicals which trigger lipid peroxidation. Our findings clearly provide evidence for superoxide dismutase (SOD) driven H2O2 production fostering the Fenton reaction as indicated by triggered SOD activity upon DMOG + SI treatment as well as by reduced cell death levels upon SOD2 knockdown. In addition, iron transporters involved in non-transferrin-bound Fe2+ import as well as intracellular iron levels were also upregulated. Consequently, chelation of Fe2+ by 2'2-Bipyridyl completely rescued cells. Taken together, we show for the first time that HIF stabilization under oxidative stress conditions aggravates ferroptotic cell death in RPE cells. Thus, our study provides a novel link between hypoxia, oxidative stress and iron metabolism in AMD pathophysiology. Since iron accumulation and altered iron metabolism are characteristic features of AMD retinas and RPE cells, our cell culture model is suitable for high-throughput screening of new treatment approaches against AMD.
C1 [Henning, Yoshiyuki; Blind, Ursula Sarah; Fandrey, Joachim] Univ Duisburg Essen, Univ Hosp Essen, Inst Physiol, Essen, Germany.
   [Larafa, Safa; Matschke, Johann] Univ Duisburg Essen, Univ Hosp Essen, Inst Cell Biol Canc Res, Essen, Germany.
C3 University of Duisburg Essen; University of Duisburg Essen
RP Henning, Y (通讯作者)，Univ Duisburg Essen, Univ Hosp Essen, Inst Physiol, Essen, Germany.
EM yoshiyuki.henning@uni-due.de
RI Matschke, Johann/AAI-9590-2020
OI Matschke, Johann/0000-0003-4878-8741; Henning,
   Yoshiyuki/0000-0002-0166-2204; Larafa, Safa/0000-0001-5245-2373
FU European Union [860245]; Federal Ministry of Education and Research
   (BMBF) [02NUK061B]; Medical Faculty of the University of Duisburg-Essen;
   PRO RETINA foundation; University of Duisburg-Essen
FX The work was supported by grant from European Union's Framework Program
   for Research and Innovation Horizon 2020 (2014-2020) under Marie
   Skodowska-Curie (Grant Agreements No. 860245 (ITN THERADNET) to JM), the
   Federal Ministry of Education and Research (BMBF, 02NUK061B) to JM, the
   intramural WIR-grant of the Medical Faculty of the University of
   Duisburg-Essen to JM and YH, and by the PRO RETINA foundation to prevent
   blindness, Germany, granted to YH (Pro-Re/KP/Henning.09-2021). We thank
   B. Delos-Reyes and C. Padberg for technical assistance, the Institute of
   Medical Psychology for providing access to the FACSCelesta <SUP>TM</SUP>
   Flow Cytometer, V. Matschke for providing the FTH antibody, and Andreas
   Wagner and Markus Hecker (University of Heidelberg) for helpful
   discussions. We acknowledge support by the Open Access Publication Fund
   of the University of Duisburg-Essen.
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NR 93
TC 1
Z9 1
U1 8
U2 8
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUL 29
PY 2022
VL 13
IS 7
AR 662
DI 10.1038/s41419-022-05121-z
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 3I9MW
UT WOS:000833032700001
PM 35906211
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Micera, A
   Balzamino, BO
   Di Zazzo, A
   Dinice, L
   Bonini, S
   Coassin, M
AF Micera, Alessandra
   Balzamino, Bijorn Omar
   Di Zazzo, Antonio
   Dinice, Lucia
   Bonini, Stefano
   Coassin, Marco
TI Biomarkers of Neurodegeneration and Precision Therapy in Retinal Disease
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Review
DE retinal diseases; chronic inflammation; growth factors; angiogenesis;
   precision medicine; neurodegeneration; pharmacological targets
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA;
   PLASMA-LEVELS; MICROVASCULAR COMPLICATIONS; PERSONALIZED MEDICINE;
   DIABETIC-RETINOPATHY; CIGARETTE-SMOKING; GENE-EXPRESSION; PREVALENCE
AB Vision-threatening retinal diseases affect millions of people worldwide, representing an important public health issue (high social cost) for both technologically advanced and new-industrialized countries. Overall RD group comprises the retinitis pigmentosa, the age-related macular degeneration (AMD), the diabetic retinopathy (DR), and idiopathic epiretinal membrane formation. Endocrine, metabolic, and even lifestyles risk factors have been reported for these age-linked conditions that represent a "public priority" also in this COVID-19 emergency. Chronic inflammation and neurodegeneration characterize the disease evolution, with a consistent vitreoretinal interface impairment. As the vitreous chamber is significantly involved, the latest diagnostic technologies of imaging (retina) and biomarker detection (vitreous) have provided a huge input at both medical and surgical levels. Complement activation and immune cell recruitment/infiltration as well as detrimental intra/extracellular deposits occur in association with a reactive gliosis. The cell/tissue aging route shows a specific signal path and biomolecular profile characterized by the increased expression of several glial-derived mediators, including angiogenic/angiostatic, neurogenic, and stress-related factors (oxidative stress metabolites, inflammation, and even amyloid formation). The possibility to access vitreous chamber by collecting vitreous reflux during intravitreal injection or obtaining vitreous biopsy during a vitrectomy represents a step forward for an individualized therapy. As drug response and protein signature appear unique in each single patient, therapies should be individualized. This review addresses the current knowledge about biomarkers and pharmacological targets in these vitreoretinal diseases. As vitreous fluids might reflect the early stages of retinal sufferance and/or late stages of neurodegeneration, the possibility to modulate intravitreal levels of growth factors, in combination to anti-VEGF therapy, would open to a personalized therapy of retinal diseases.
C1 [Micera, Alessandra; Balzamino, Bijorn Omar; Dinice, Lucia] IRCCS Fdn Bietti, Res & Dev Lab Biochem Mol & Cellular Applicat Opt, Rome, Italy.
   [Di Zazzo, Antonio; Bonini, Stefano; Coassin, Marco] Univ Campus Biomed, Ophthalmol Operat Complex Unit, Rome, Italy.
C3 IRCCS - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in
   Oftalmologia; University Campus Bio-Medico - Rome Italy
RP Micera, A (通讯作者)，IRCCS Fdn Bietti, Res & Dev Lab Biochem Mol & Cellular Applicat Opt, Rome, Italy.
EM alessandra.micera@fondazionebietti.it
RI balzamino, bijorn omar/A-4433-2013
OI balzamino, bijorn omar/0000-0002-2254-1647
FU Italian Ministry of Health [5x1000 (2016)]
FX The study was partially supported by the Italian Ministry of Health and
   5x1000 (2016) project to IRCCS-Fondazione Bietti.
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NR 112
TC 9
Z9 9
U1 0
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD JAN 18
PY 2021
VL 11
AR 601647
DI 10.3389/fphar.2020.601647
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA QA0MK
UT WOS:000613145200001
PM 33584278
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Paulsen, AJ
   Pinto, A
   Fischer, ME
   Chen, YJ
   Huang, GH
   Klein, BEK
   Klein, R
   Cruickshanks, KJ
AF Paulsen, Adam J.
   Pinto, Alex
   Fischer, Mary E.
   Chen, Yanjun
   Huang, Guan-Hua
   Klein, Barbara E. K.
   Klein, Ronald
   Cruickshanks, Karen J.
TI Generational Differences in the 10-year Incidence of Impaired Contrast
   Sensitivity
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Epidemiology; Birth Cohort Effect; Contrast Sensitivity; Visual
   Function; Aging
ID MACULAR DEGENERATION; HEARING IMPAIRMENT; VISUAL IMPAIRMENT;
   RISK-FACTORS; PREVALENCE; PERFORMANCE; POPULATION; FRACTURES; ACUITY;
   FALLS
AB Purpose To determine if incidence of contrast sensitivity (CS) impairment differs by generation and identify factors to explain these differences. Methods The Beaver Dam Eye Study (BDES) and Beaver Dam Offspring Study (BOSS) are cohort studies of aging adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 (BDES) and 2005-2008 (BOSS). Follow-up examinations occurred in five-year intervals. CS testing was conducted with Pelli-Robson letter sensitivity charts; Incident impairment was a log CS score <1.55 in either eye at follow-up. Associations of incidence with generation were investigated using estimated hazard ratios (HR) with 95% confidence intervals (CI). Results Participants (N = 3185) had a mean age of 51.9 years at baseline (standard deviation = 9.9) and 51.9% were female. Ten-year cumulative incidence of CS impairment was 40.1%, was higher among women (41.7%) than men (38.8%), and increased by age group. The risk of incident CS impairment decreased by 39% per generation. In multivariable models, the Baby Boom Generation (HR = 0.42, 95%CI = 0.31, 0.58) and Generation X (HR = 0.56, 95%CI = 0.34, 0.91) had a significantly decreased risk of CS impairment compared to the Greatest Generation. Results were similar in sensitivity analyses excluding those with cataract, age-related macular degeneration, or visual acuity impairment. Conclusion The risk of incident CS impairment decreased by birth cohort, with the greatest reduction in the Baby Boom Generation. The difference in risk suggests that there are unknown modifiable risk factors that may help to further explain the etiology of CS impairment and provide potential pathways for prevention in the future.
C1 [Paulsen, Adam J.; Pinto, Alex; Fischer, Mary E.; Chen, Yanjun; Klein, Barbara E. K.; Klein, Ronald; Cruickshanks, Karen J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
   [Huang, Guan-Hua] Natl Chiao Tung Univ, Inst Stat, Hsinchu, Taiwan.
   [Cruickshanks, Karen J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   National Yang Ming Chiao Tung University; University of Wisconsin
   System; University of Wisconsin Madison
RP Paulsen, AJ (通讯作者)，Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
EM paulsen@episense.wisc.edu
FU National Institute on Aging [R37AG011099]; National Eye Institute
   [U10EY06594, R01AG021917]; Research to Prevent Blindness
FX This work was supported by the National Institute on Aging and the
   National Eye Institute under Grant R01AG021917 (Dr. Cruickshanks); the
   National Institute on Aging under Grant R37AG011099 (Dr. Cruickshanks);
   the National Eye Institute under Grant U10EY06594 (Drs. B.E.K. Klein and
   R. Klein); Research to Prevent Blindness under an unrestricted grant to
   the Department of Ophthalmology and Visual Sciences at the University of
   Wisconsin School of Medicine and Public Health
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NR 34
TC 0
Z9 0
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 MAR 4
PY 2021
VL 28
IS 2
BP 175
EP 182
DI 10.1080/09286586.2020.1791909
EA JUL 2020
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RC2XS
UT WOS:000550940200001
PM 32693658
OA Green Accepted
DA 2022-11-30
ER

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   Bazan, NG
AF Do, Khanh V.
   Kautzmann, Marie-Audrey I.
   Jun, Bokkyoo
   Gordon, William C.
   Nshimiyimana, Robert
   Yang, Rong
   Petasis, Nicos A.
   Bazan, Nicolas G.
TI Elovanoids counteract oligomeric beta-amyloid-induced gene expression
   and protect photoreceptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE retinal pigment epithelial cells; age-related macular degeneration;
   senescence gene program; p16; SASP
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; DOCOSAHEXAENOIC ACID;
   ALZHEIMERS-DISEASE; CELL-SURVIVAL; FATTY-ACIDS; NEUROINFLAMMATION; LONG;
   PEPTIDE; ELOVL4
AB The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer's disease) and sight (age-related macular degeneration [AMD]). How neuroinflammation can be counteracted is not known. In AMD, amyloid beta-peptide (A beta) accumulates in subretinal drusen. In the 5xFAD retina, we found early functional deficiencies (ERG) without photoreceptor cell (PRC) death and identified early insufficiency in biosynthetic pathways of prohomeostatic/neuroprotective mediators neuroprotectin D1 (NPD1) and elovanoids (ELVs). To mimic an inflammatory milieu in wild-type mouse, we triggered retinal pigment epithelium (RPE) damage/PRC death by subretinally injected oligomeric beta-amyloid (OA beta) and observed that ELVs administration counteracted their effects, protecting these cells. In addition, ELVs prevented OA beta-induced changes in gene expression engaged in senescence, inflammation, autophagy, extracellular matrix remodeling, and AMD. Moreover, as OA beta targets the RPE, we used primary human RPE cell cultures and demonstrated that OA beta caused cell damage, while ELVs protected and restored gene expression as in mouse. Our data show OA beta activates senescence as reflected by enhanced expression of p16(INK4)(a), MMP1, p53, p21, p27, and Il-6, and of senescence-associated phenotype secretome, followed by RPE and PRC demise, and that ELVs 32 and 34 blunt these events and elicit protection. In addition, ELVs counteracted OA beta-induced expression of genes engaged in AMD, autophagy, and extracellular matrix remodeling. Overall, our data uncovered that ELVs downplay OA beta-senescence program induction and inflammatory transcriptional events and protect RPE cells and PRC, and therefore have potential as a possible therapeutic avenue for AMD.
C1 [Do, Khanh V.; Kautzmann, Marie-Audrey I.; Jun, Bokkyoo; Gordon, William C.; Bazan, Nicolas G.] Louisiana State Univ Hlth New Orleans, Sch Med, Neurosci Ctr Excellence, New Orleans, LA 70112 USA.
   [Nshimiyimana, Robert; Yang, Rong; Petasis, Nicos A.] Univ Southern Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Nshimiyimana, Robert; Yang, Rong; Petasis, Nicos A.] Univ Southern Calif, Loker Hydrocarbon Res Inst, Los Angeles, CA 90089 USA.
C3 Louisiana State University System; Louisiana State University Health
   Sciences Center New Orleans; University of Southern California;
   University of Southern California
RP Bazan, NG (通讯作者)，Louisiana State Univ Hlth New Orleans, Sch Med, Neurosci Ctr Excellence, New Orleans, LA 70112 USA.
EM nbazan@lsuhsc.edu
RI Yang, Rong/ABA-7587-2021; Bazan, Nicolas/AAN-4121-2020
OI Bazan, Nicolas/0000-0002-9243-5444; Yang, Rong/0000-0001-8837-0089; DO,
   KHANH/0000-0001-7834-3781
FU National Institutes of Health/National Eye Institute [R01 EY005121]; Eye
   Ear Nose & Throat Foundation; NATIONAL EYE INSTITUTE [R01EY005121]
   Funding Source: NIH RePORTER
FX This study was supported by the National Institutes of Health/National
   Eye Institute grant R01 EY005121 and the Eye Ear Nose & Throat
   Foundation.
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NR 58
TC 31
Z9 32
U1 2
U2 8
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 26
PY 2019
VL 116
IS 48
BP 24317
EP 24325
DI 10.1073/pnas.1912959116
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA JQ7DI
UT WOS:000499101100064
PM 31712409
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Parravano, M
   Borrelli, E
   Sacconi, R
   Costanzo, E
   Marchese, A
   Manca, D
   Varano, M
   Bandello, F
   Querques, G
AF Parravano, Mariacristina
   Borrelli, Enrico
   Sacconi, Riccardo
   Costanzo, Eliana
   Marchese, Alessandro
   Manca, Daniela
   Varano, Monica
   Bandello, Francesco
   Querques, Giuseppe
TI A Comparison Among Different Automatically Segmented Slabs to Assess
   Neovascular AMD using Swept Source OCT Angiography
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE OCTA; neovascularization; neovascular; AMD
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SUBRETINAL HYPERREFLECTIVE MATERIAL;
   CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; TYPE-2
   NEOVASCULARIZATION; QUANTITATIVE-ANALYSIS; SPECTRAL-DOMAIN
AB Purpose: We systematically compare the intermodality and interreader agreement in age-related macular degeneration(AMD)-associated neovascularization assessment for optical coherence tomography angiography (OCTA) images obtained using different slabs.
   Methods: We collected data from 48 patients (50 eyes) with type 1 or 2 neovascularization (NV) and AMD. Subjects were imaged with a swept source (SS)-OCTA system. For each eye, three OCTA en face images generated from three different slabs were exported: (1) the outer retina to choriocapillaris (ORCC) image, (2) the choriocapillaris (CC) image, and (3) the retinal pigment epithelium (RPE)-RPE fit image. Each image was graded by two readers to assess interreader variability and a single image for each modality was used to assess the intermodality variability.
   Results: In the assessment of type 1 NV, mean absolute interreader difference between measured NV areas was 0.19, 0.30, and 0.16 mm(2) for ORCC, CC, and RPE-RPE fit images, respectively. Similarly, the coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) indicated that the RPE-RPE fit assessment was characterized by the highest interreader reproducibility. Type 1 NV size was 0.58 mm(2) (0.30-1.60 mm(2)) on ORCC images, 0.00 mm(2) (0.00-0.36 mm(2)) on CC images (P = 0.002 vs. ORCC), and 0.62 mm(2) (0.31-2.03 mm(2)) on RPE-RPE fit images (P < 0.0001 vs. CC, P = 0.041 vs. ORCC).
   Conclusions: The RPE-RPE fit OCTA images have the highest interreader agreement and deliver larger measurements in type 1 lesions.
   Translational Relevance: OCTA imaging may be used in ongoing trials of potential novel treatments for NV.
C1 [Parravano, Mariacristina; Costanzo, Eliana; Manca, Daniela; Varano, Monica] IRCCS Fdn Bietti, Rome, Italy.
   [Borrelli, Enrico; Sacconi, Riccardo; Marchese, Alessandro; Bandello, Francesco; Querques, Giuseppe] San Raffaele Univ Hosp, Ophthalmol Dept, Milan, Italy.
   [Borrelli, Enrico] Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalmol Clin, Chieti, Italy.
C3 IRCCS - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in
   Oftalmologia; Vita-Salute San Raffaele University; IRCCS Ospedale San
   Raffaele; G d'Annunzio University of Chieti-Pescara
RP Querques, G (通讯作者)，Univ Vita Salute San Raffaele, Dept Ophthalmol, Via Olgettina 60, Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Borrelli, Enrico/AAR-3693-2020; Costanzo, Eliana/AAA-7690-2020;
   Marchese, Alessandro/AAG-7231-2019; bandello, francesco/AAH-2405-2019
OI Borrelli, Enrico/0000-0003-2815-5031; bandello,
   francesco/0000-0003-3238-9682; Sacconi, Riccardo/0000-0003-2891-2012;
   Varano, Monica/0000-0002-6530-1563; Marchese,
   Alessandro/0000-0001-7716-7261; Querques, Giuseppe/0000-0002-3292-9581
FU Italian Ministry of Health; Fondazione Roma
FX Supported in part by the Italian Ministry of Health and Fondazione Roma.
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NR 24
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 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAR
PY 2019
VL 8
IS 2
AR 8
DI 10.1167/tvst.8.2.8
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HS6SU
UT WOS:000464002400007
PM 30941265
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Doktor, F
   Prager, P
   Wiedemann, P
   Kohen, L
   Bringmann, A
   Hollborn, M
AF Doktor, Fabian
   Prager, Philipp
   Wiedemann, Peter
   Kohen, Leon
   Bringmann, Andreas
   Hollborn, Margrit
TI Hypoxic expression of NLRP3 and VEGF in cultured retinal pigment
   epithelial cells: contribution of P2Y(2) receptor signaling
SO PURINERGIC SIGNALLING
LA English
DT Article
DE Retinal pigment epithelium; P2Y(2); NLRP3; VEGF; Inflammasome; Hypoxia
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; INFLAMMASOME
   ACTIVATION; MACULAR DEGENERATION; OXIDATIVE STRESS; IL-1-BETA;
   INVOLVEMENT; LIPOFUSCIN; INHIBITOR; CASPASE-4
AB Retinal hypoxia is a major condition of the chronic inflammatory disease age-related macular degeneration. Extracellular ATP is a danger signal which is known to activate the NLRP3 inflammasome in various cell systems. We investigated in cultured human retinal pigment epithelial (RPE) cells whether hypoxia alters the expression of inflammasome-associated genes and whether purinergic receptor signaling contributes to the hypoxic expression of key inflammatory (NLRP3) and angiogenic factor (VEGF) genes. Hypoxia and chemical hypoxia were induced by a 0.2%-O-2 atmosphere and addition of CoCl2, respectively. Gene expression was determined with real-time RT-PCR. Cytosolic NLRP3 and (pro-) IL-1 levels, and the extracellular VEGF level, were evaluated with Western blot and ELISA analyses. Cell culture in 0.2% O-2 induced expression of NLRP3 and pro-IL-1 genes but not of the pro-IL-18 gene. Hypoxia also increased the cytosolic levels of NLRP3 and (pro-) IL-1 proteins. Inflammasome activation by lysosomal destabilization decreased the cell viability under hypoxic, but not control conditions. In addition to activation of IL-1 receptors, purinergic receptor signaling mediated by a pannexin-dependent release of ATP and a release of adenosine, and activation of P2Y(2) and adenosine A(1) receptors, was required for the full hypoxic expression of the NLRP3 gene. P2Y(2) (but not A(1)) receptor signaling also contributed to the hypoxic expression and secretion of VEGF. The data indicate that hypoxia induces priming and activation of the NLRP3 inflammasome in cultured RPE cells. The hypoxic NLRP3 and VEGF gene expression and the secretion of VEGF are in part mediated by P2Y(2) receptor signaling.
C1 [Doktor, Fabian; Prager, Philipp; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
   [Doktor, Fabian; Prager, Philipp; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas; Hollborn, Margrit] Univ Leipzig, Eye Hosp, Liebigstr 10-14, D-04103 Leipzig, Germany.
   [Kohen, Leon] Helios Klinikum Aue, Aue, Germany.
C3 Leipzig University; Leipzig University; Helios Kliniken
RP Bringmann, A (通讯作者)，Univ Leipzig, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.; Bringmann, A (通讯作者)，Univ Leipzig, Eye Hosp, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM bria@medizin.uni-leipzig.de
FU Deutsche Forschungsgemeinschaft [KO 1547/7-1]; Geschwister Freter
   Stiftung (Hannover, Germany)
FX This research was supported by grants from the Deutsche
   Forschungsgemeinschaft (KO 1547/7-1 to L.K.) and the Geschwister Freter
   Stiftung (Hannover, Germany) to P.W.
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NR 49
TC 16
Z9 18
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD DEC
PY 2018
VL 14
IS 4
BP 471
EP 484
DI 10.1007/s11302-018-9631-6
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA HF0CH
UT WOS:000453824200014
PM 30415294
OA Green Published
DA 2022-11-30
ER

PT J
AU Rodrigues, GA
   Mason, M
   Christie, LA
   Hansen, C
   Hernandez, LM
   Burke, J
   Luhrs, KA
   Hohman, TC
AF Rodrigues, Gerard A.
   Mason, Matthew
   Christie, Lori-Ann
   Hansen, Candice
   Hernandez, Lisa M.
   Burke, James
   Luhrs, Keith A.
   Hohman, Thomas C.
TI Functional Characterization of Abicipar-Pegol, an Anti-VEGF DARPin
   Therapeutic That Potently Inhibits Angiogenesis and Vascular
   Permeability
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE abicipar; VEGF-A; DARPin; wet AMD; age-related macular degeneration;
   angiogenesis; ophthalmology
ID ENDOTHELIAL GROWTH-FACTOR; ANKYRIN REPEAT PROTEIN; DIABETIC MACULAR
   EDEMA; RETINAL NEOVASCULARIZATION; IN-VITRO; MESSENGER-RNA;
   VISUAL-ACUITY; RABBIT MODEL; RANIBIZUMAB; DEGENERATION
AB PURPOSE. DARPin molecules are a novel class of small proteins that contain engineered ankyrin repeat domain(s) and bind to target proteins with high specificity and affinity. Abicipar-pegol (abicipar), a DARPin molecule targeting vascular endothelial growth factor-A (VEGF-A), is currently under evaluation in patients with age-related macular degeneration. The pharmacodynamic properties of abicipar were characterized using in vivo and in vitro assays.
   METHODS. The binding affinity of abicipar was assessed using a kinetic exclusion assay (KinExA). In vitro assays evaluated abicipar effects on VEGF-A165-induced calcium mobilization and tube formation in human umbilical vein endothelial cells. Abicipar was tested in vivo in a mouse model of corneal neovascularization and a rabbit model of chronic retinal neovascularization. The efficacies of abicipar and ranibizumab were compared in a rabbit model of VEGF-A165-induced retinal vasculopathy.
   RESULTS. Abicipar has a high affinity for the soluble isoforms of VEGF-A; binding affinities for human VEGF-A165 are approximately 100-fold greater than those of ranibizumab and bevacizumab and are similar for rat VEGF-A164 but approximately 20-fold lower for rabbit VEGF-A165. Abicipar was effective in cell-based and in vivo models of angiogenesis and vascular leak, blocking neovascularization in a mouse model of corneal neovascularization and vascular permeability in a rabbit model of chronic neovascularization. In a rabbit model of VEGF-A165-induced vasculopathy, the duration of effect of abicipar was longer than ranibizumab when the two compounds were administered at molar-equivalent doses.
   CONCLUSIONS. These data support the testing of abicipar as a treatment for retinal diseases characterized by neovascularization and vascular leak.
C1 [Rodrigues, Gerard A.; Mason, Matthew; Christie, Lori-Ann; Hansen, Candice; Hernandez, Lisa M.; Burke, James; Luhrs, Keith A.; Hohman, Thomas C.] Allergan Plc, Irvine, CA USA.
C3 AbbVie; Allergan
RP Rodrigues, GA (通讯作者)，Allergan, RD3-2D,2525 Dupont Dr, Irvine, CA 92612 USA.
EM rodrigues_gerry@allergan.com
FU Allergan plc, Dublin, Ireland
FX Sponsored by Allergan plc, Dublin, Ireland.
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NR 59
TC 41
Z9 43
U1 1
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 2018
VL 59
IS 15
BP 5836
EP 5846
DI 10.1167/iovs.18-25307
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HF5EU
UT WOS:000454256200003
PM 30535424
OA gold
DA 2022-11-30
ER

PT J
AU Rasti, R
   Rabbani, H
   Mehridehnavi, A
   Hajizadeh, F
AF Rasti, Reza
   Rabbani, Hossein
   Mehridehnavi, Alireza
   Hajizadeh, Fedra
TI Macular OCT Classification Using a Multi-Scale Convolutional Neural
   Network Ensemble
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE CAD system; classification; macular pathology; Multi-scale Convolutional
   Mixture of Experts (MCME); Optical Coherence Tomography (OCT)
ID OPTICAL COHERENCE TOMOGRAPHY; LAYER SEGMENTATION; MIXTURE; EXPERTS;
   DEGENERATION; RECOGNITION; DIAGNOSIS; BURDEN; FACE
AB Computer-aided diagnosis (CAD) of retinal pathologies is a current active area in medical image analysis. Due to the increasing use of retinal optical coherence tomography (OCT) imaging technique, a CAD system in retinal OCT is essential to assist ophthalmologist in the early detection of ocular diseases and treatment monitoring. This paper presents a novel CAD system based on a multi-scale convolutional mixture of expert (MCME) ensemble model to identify normal retina, and two common types of macular pathologies, namely, dry age-related macular degeneration, and diabetic macular edema. The proposed MCME modular model is a data-driven neural structure, which employs a new cost function for discriminative and fast learning of image features by applying convolutional neural networks on multiple-scale sub-images. MCME maximizes the likelihood function of the training data set and ground truth by considering a mixture model, which tries also to model the joint interaction between individual experts by using a correlated multivariate component for each expert module instead of only modeling the marginal distributions by independent Gaussian components. Two different macular OCT data sets from Heidelberg devices were considered for the evaluation of the method, i.e., a local data set of OCT images of 148 subjects and a public data set of 45 OCT acquisitions. For comparison purpose, we performed a wide range of classification measures to compare the results with the best configurations of the MCME method. With the MCME model of four scale-dependent experts, the precision rate of 98.86%, and the area under the receiver operating characteristic curve (AUC) of 0.9985 were obtained on average.
C1 [Rasti, Reza; Rabbani, Hossein; Mehridehnavi, Alireza] Isfahan Univ Med Sci, Sch Adv Technol Med, Dept Biomed Engn, Med Image & Signal Proc Res Ctr, Esfahan 8174673461, Iran.
   [Hajizadeh, Fedra] Noor Eye Hosp, Noor Ophthalmol Res Ctr, Tehran 1968653111, Iran.
C3 Isfahan University Medical Science
RP Rabbani, H (通讯作者)，Isfahan Univ Med Sci, Sch Adv Technol Med, Dept Biomed Engn, Med Image & Signal Proc Res Ctr, Esfahan 8174673461, Iran.
EM mr.r.rasti@ieee.org; rabbani.h@ieee.org; mehri@med.mui.ac.ir;
   fedra_hajizadeh@yahoo.com
RI Rabbani, Hossein/H-7515-2014; Rabbani, Hossein/O-4987-2019; Rasti,
   Reza/AAQ-1323-2021
OI Rabbani, Hossein/0000-0002-0551-3636; Rabbani,
   Hossein/0000-0002-0551-3636; Rasti, Reza/0000-0003-0010-788X;
   mehridehnavi, alireza/0000-0002-7964-0478; Hajizadeh,
   Fedra/0000-0002-2661-5439
FU Department of Biomedical Engineering, Isfahan University of Medical
   Sciences [395645]
FX This work was supported by the Department of Biomedical Engineering,
   Isfahan University of Medical Sciences, under Grant 395645.
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NR 58
TC 110
Z9 115
U1 8
U2 52
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 APR
PY 2018
VL 37
IS 4
BP 1024
EP 1034
DI 10.1109/TMI.2017.2780115
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 GB2MH
UT WOS:000428886700018
PM 29610079
DA 2022-11-30
ER

PT J
AU Krishnan, AK
   Bedell, HE
AF Krishnan, Arun Kumar
   Bedell, Harold E.
TI Functional changes at the preferred retinal locus in subjects with
   bilateral central vision loss
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Micro-perimetry; Central vision loss; Macular degeneration; Preferred
   retinal locus (PRL); Micro-scotomas
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; STARGARDT-DISEASE;
   FIXATION; MICROPERIMETRY; SENSITIVITY; LOCATION; FUNDUS; DYSFUNCTION;
   SCOTOMAS
AB Subjects with bilateral central vision loss (CVL) use a retinal region called the preferred retinal locus (PRL) for performing various visual tasks. We probed the fixation PRL in individuals with bilateral macular disease, including age-related macular degeneration (AMD) and Stargardt disease (STGD), for localized sensitivity deficits.
   Three letter words at the critical print size were presented in the NIDEK MP-1 microperimeter to determine the fixation PRL and its radial retinal eccentricity from the residual fovea in 29 subjects with bilateral CVL. Fixation stability was defined as the median bivariate contour ellipse area (BCEA) from 3 fixation assessments. A standard 10-2 grid (68 locations, 2A degrees apart) was used to determine central retinal sensitivity for Goldmann size II test spots. Baseline and follow-up supra-threshold screening of the fixation PRL for localized sensitivity deficits was performed using high density (0.2A degrees or 0.3A degrees apart) 0 dB Goldmann size II test spots. Custom MATLAB code and a dual bootstrapping algorithm were used to register test-spot locations from the baseline and follow-up tests. Locations where the 0 dB test spots were not seen on either test were labeled as micro-scotomas (MSs).
   Median BCEA correlated poorly with the radial eccentricity of the fixation PRL. Mean (+/- SD) sensitivity around the PRL from 10-2 testing was 4.93 +/- 4.73 dB. The average percentage of MSs was similar for patients with AMD (25.4%), STGD (20.3%), and other etiologies of CVL (27.1%).
   The fixation PRL in subjects with bilateral CVL frequently includes local regions of sensitivity loss.
C1 [Krishnan, Arun Kumar] Envision Inc, Envision Res Inst, 610 N Main St, Wichita, KS 67203 USA.
   [Krishnan, Arun Kumar; Bedell, Harold E.] Univ Houston, Coll Optometry, Houston, TX 77204 USA.
C3 University of Houston System; University of Houston
RP Krishnan, AK (通讯作者)，Envision Inc, Envision Res Inst, 610 N Main St, Wichita, KS 67203 USA.; Krishnan, AK (通讯作者)，Univ Houston, Coll Optometry, Houston, TX 77204 USA.
EM arunopto@gmail.com
RI Krishnan, Arun Kumar/ABF-7662-2021
OI Krishnan, Arun Kumar/0000-0002-3888-2614
FU Minnie Flaura Turner Memorial Fund for Impaired Vision Research; Fight
   for Sight; University of Houston student vision science grant to advance
   research (SVGR, UHCO); NIH/NEI [P30 EY 07551]
FX This work was supported in part by an award from the Minnie Flaura
   Turner Memorial Fund for Impaired Vision Research; a Fight for Sight -
   summer student fellowship; a University of Houston student vision
   science grant to advance research (SVGR, UHCO) and NIH/NEI Core center
   grant, P30 EY 07551, to UHCO. The sponsors had no role in the design or
   conduct of this research.
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NR 40
TC 7
Z9 7
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 JAN
PY 2018
VL 256
IS 1
BP 29
EP 37
DI 10.1007/s00417-017-3818-3
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FR5WO
UT WOS:000419137400004
PM 28971293
DA 2022-11-30
ER

PT J
AU Shahmoradi, S
   Yazdian, F
   Tabandeh, F
   Soheili, ZS
   Zarami, ASH
   Navaei-Nigjeh, M
AF Shahmoradi, Saleheh
   Yazdian, Fatemeh
   Tabandeh, Fatemeh
   Soheili, Zahra-Soheila
   Zarami, Ashraf Sadat Hatamian
   Navaei-Nigjeh, Mona
TI Controlled surface morphology and hydrophilicity of polycaprolactone
   toward human retinal pigment epithelium cells
SO MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
LA English
DT Article
DE Polycaprolactone; Retinal pigment epithelium; Age-related macular
   degeneration; Retina; Alkaline hydrolysis
ID POLY(EPSILON-CAPROLACTONE) SCAFFOLDS; BIODEGRADABLE POLYESTERS;
   MECHANICAL-PROPERTIES; MACULAR DEGENERATION; NANOFIBER SCAFFOLD;
   STEM-CELLS; IN-VITRO; DIFFERENTIATION; HYDROLYSIS; CULTURE
AB Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nano fibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12 g/mL and 20 kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120 min and 5 M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48 degrees). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistty (ICC), KM' and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8 nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. (C) 2016 Published by Elsevier B.V.
C1 [Shahmoradi, Saleheh; Yazdian, Fatemeh; Zarami, Ashraf Sadat Hatamian] Univ Tehran, Fac New Sci & Technol, Dept Life Sci Engn, Tehran, Iran.
   [Tabandeh, Fatemeh] Natl Inst Genet Engn & Biotechnol, Dept Ind & Environm Biotechnol, Tehran, Iran.
   [Soheili, Zahra-Soheila] Natl Inst Genet Engn & Biotechnol, Dept Mol Med, Tehran, Iran.
   [Navaei-Nigjeh, Mona] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Tissue Engn, Tehran, Iran.
C3 University of Tehran; Tehran University of Medical Sciences
RP Tabandeh, F (通讯作者)，Natl Inst Genet Engn & Biotechnol, Dept Ind & Environm Biotechnol, Tehran, Iran.
EM taban_f@nigeb.ac.ir
RI Navaei-Nigjeh, Mona/S-4352-2019; Soheili, Zahra-Soheila/W-8316-2018
OI Navaei-Nigjeh, Mona/0000-0002-3819-9153; Gholami,
   Mahdi/0000-0002-4085-6095; Soheili, Zahra-Soheila/0000-0003-1292-465X
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NR 57
TC 28
Z9 30
U1 1
U2 63
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0928-4931
EI 1873-0191
J9 MAT SCI ENG C-MATER
JI Mater. Sci. Eng. C-Mater. Biol. Appl.
PD APR 1
PY 2017
VL 73
BP 300
EP 309
DI 10.1016/j.msec.2016.11.076
PG 10
WC Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science
GA EK6VT
UT WOS:000394064800036
PM 28183612
DA 2022-11-30
ER

PT J
AU Bitirgen, G
   Belviranli, S
   Malik, RA
   Kerimoglu, H
   Satirtav, G
   Zengin, N
AF Bitirgen, Gulfidan
   Belviranli, Selman
   Malik, Rayaz A.
   Kerimoglu, Hurkan
   Satirtav, Gunhal
   Zengin, Nazmi
TI Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber
   Layer in Patients Treated with Multiple Intravitreal Ranibizumab
   Injections
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTRAOCULAR-PRESSURE CHANGES; MACULAR
   DEGENERATION; CONFOCAL MICROSCOPY; VEGF; PHARMACOKINETICS; THICKNESS;
   SURVIVAL; BEVACIZUMAB; MACULOPATHY
AB Purpose
   To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD).
   Methods
   Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects.
   Results
   The mean number of ranibizumab injections per eye was 8.9 +/- 5.0 (range 3-20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P=0.237), and the eyes of healthy control subjects (P=0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters.
   Conclusions
   Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.
C1 [Bitirgen, Gulfidan; Belviranli, Selman; Kerimoglu, Hurkan; Satirtav, Gunhal; Zengin, Nazmi] Necmettin Erbakan Univ Meram, Fac Med, Dept Ophthalmol, Konya, Turkey.
   [Malik, Rayaz A.] Weill Cornell Med Qatar, Educ City, Doha, Qatar.
   [Malik, Rayaz A.] Univ Manchester, Cent Manchester Univ, Teaching Hosp Fdn Trust, Manchester, Lancs, England.
   [Malik, Rayaz A.] Univ Manchester, Div Cardiovasc Sci, Manchester, Lancs, England.
C3 Necmettin Erbakan University; Selcuk University; Weill Cornell Medical
   College Qatar; University of Manchester; University of Manchester
RP Bitirgen, G (通讯作者)，Necmettin Erbakan Univ Meram, Fac Med, Dept Ophthalmol, Konya, Turkey.
EM gbitirgen@yahoo.com
RI Bitirgen, Gulfidan/V-7709-2017; Belviranli, Selman/AAM-7262-2020;
   Kerimoglu, Hurkan/A-7857-2016; Satirtav, Gunhal/D-6975-2015; Malik,
   Rayaz/H-9231-2019
OI Bitirgen, Gulfidan/0000-0002-0509-5649; Belviranli,
   Selman/0000-0003-0272-7345; Kerimoglu, Hurkan/0000-0002-5601-2049;
   Satirtav, Gunhal/0000-0003-4157-2876; Malik, Rayaz/0000-0002-7188-8903
FU Scientific Research Fund of the Necmettin Erbakan University [151218003]
FX This work was supported by the Scientific Research Fund of the Necmettin
   Erbakan University (Project Number: 151218003) (GB). 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 35
TC 4
Z9 4
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 13
PY 2017
VL 12
IS 1
AR e0170271
DI 10.1371/journal.pone.0170271
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EH7SJ
UT WOS:000391972600082
PM 28085965
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Oliveira, J
   Pereira, S
   Goncalves, L
   Ferreira, M
   Silva, CA
AF Oliveira, Jorge
   Pereira, Sergio
   Goncalves, Luis
   Ferreira, Manuel
   Silva, Carlos A.
TI Multi-surface segmentation of OCT images with AMD using sparse high
   order potentials
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SD-OCT; AUTOMATIC SEGMENTATION; DRUSEN;
   LAYERS
AB In age-related macular degeneration (AMD), the quantification of drusen is important because it is correlated with the evolution of the disease to an advanced stage. Therefore, we propose an algorithm based on a multi-surface framework for the segmentation of the limiting boundaries of drusen: the inner boundary of the retinal pigment epithelium + drusen complex (IRPEDC) and the Bruch's membrane (BM). Several segmentation methods have been considerably successful in segmenting retinal layers of healthy retinas in optical coherence tomography (OCT) images. These methods are successful because they incorporate prior information and regularization. Nonetheless, these factors tend to hinder the segmentation for diseased retinas. The proposed algorithm takes into account the presence of drusen and geographic atrophy (GA) related to AMD by excluding prior information and regularization just valid for healthy regions. However, even with this algorithm, prior information and regularization still cause the oversmoothing of drusen in some locations. Thus, we propose the integration of local shape prior in the form of a sparse high order potentials (SHOPs) into the algorithm to reduce the oversmoothing of drusen. The proposed algorithm was evaluated in a public database. The mean unsigned errors, relative to the average of two experts, for the inner limiting membrane (ILM), IRPEDC and BM were 2.94 +/- 2.69, 5.53 +/- 5.66 and 4.00 +/- 4.00 mu m, respectively. Drusen areas measurements were evaluated, relative to the average of two expert graders, by the mean absolute area difference and overlap ratio, which were 1579.7 +/- 2106.8 mu m(2) and 0.78 +/- 0.11, respectively. (C) 2016 Optical Society of America
C1 [Oliveira, Jorge; Pereira, Sergio; Silva, Carlos A.] Univ Minho, CMEMS UMinho, P-4800058 Guimaraes, Portugal.
   [Goncalves, Luis] Oftalmocenter, P-4800045 Azurem, Guimaraes, Portugal.
   [Ferreira, Manuel] Univ Minho, Algoritmi Ctr, P-4800058 Guimaraes, Portugal.
   [Ferreira, Manuel] ENERMETER, Parque Ind Celeiros, P-4705025 Braga, Portugal.
C3 Universidade do Minho; Universidade do Minho
RP Oliveira, J (通讯作者)，Univ Minho, CMEMS UMinho, P-4800058 Guimaraes, Portugal.
EM id4327@alunos.uminho.pt; csilva@dei.uminho.pt
RI Ferreira, Manuel Joao/AAC-2201-2020; Silva, Carlos/J-1190-2014; Pereira,
   Sérgio/K-5591-2019
OI Silva, Carlos/0000-0002-1015-5095; Pereira, Sérgio/0000-0002-4298-0903;
   Ferreira, Manuel/0000-0002-4685-5632
FU FCT [UID/EEA/04436/2013]; FEDER funds through COMPETE 2020 - Programa
   Operacional Competitividade e Internacionalizacao (POCI)
   [POCI-01-0145-FEDER-006941]; Portuguese funding institution Fundacao
   Calouste Gulbenkian [126501]; ENERMETER - Sistemas de Medicao, Lda
FX This work is supported by FCT with the reference project
   UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 - Programa
   Operacional Competitividade e Internacionalizacao (POCI) with the
   reference project POCI-01-0145-FEDER-006941. The authors would like to
   thank the questions and suggestions of the anonymous reviewers that
   helped to improve this document. J.O. wishes to acknowledge the
   Portuguese funding institution Fundacao Calouste Gulbenkian for the
   Ph.D. Grant (process 126501) and to ENERMETER - Sistemas de Medicao, Lda
   for their support.
CR Acess Economics Pty Limited, 2010, TECH REP
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NR 26
TC 22
Z9 22
U1 0
U2 7
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 JAN 1
PY 2017
VL 8
IS 1
BP 281
EP 297
DI 10.1364/BOE.8.000281
PG 17
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 EI0ZO
UT WOS:000392204700022
PM 28101418
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Corbelli, E
   Sacconi, R
   De Vitis, LA
   Carnevali, A
   Rabiolo, A
   Querques, L
   Bandello, F
   Querques, G
AF Corbelli, Eleonora
   Sacconi, Riccardo
   De Vitis, Luigi Antonio
   Carnevali, Adriano
   Rabiolo, Alessandro
   Querques, Lea
   Bandello, Francesco
   Querques, Giuseppe
TI Choroidal Round Hyporeflectivities in Geographic Atrophy
SO PLOS ONE
LA English
DT Article
ID OPTICAL-COHERENCE-TOMOGRAPHY; MACULAR DEGENERATION; MORPHOLOGIC
   FEATURES; THICKNESS; ANGIOGRAPHY; DIAMETER; EYES
AB Purpose
   In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A).
   Methods
   Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University VitaSalute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed.
   Results
   Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8 +/- 6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30 +/- 5.74 and 5.57 +/- 4.48mm(2), respectively; p = 0.01).
   Conclusions
   Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.
C1 [Corbelli, Eleonora; Sacconi, Riccardo; De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, IRCCS Osped San Raffaele, Dept Ophthalmol, Milan, Italy.
   [Sacconi, Riccardo] Univ Verona, Univ Hosp Verona, Dept Ophthalmol, Verona, Italy.
   [Carnevali, Adriano] Magna Graecia Univ Catanzaro, Dept Ophthalmol, Catanzaro, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   University of Verona; Azienda Ospedaliera Universitaria Integrata
   Verona; Magna Graecia University of Catanzaro
RP Querques, G (通讯作者)，Univ Vita Salute, IRCCS Osped San Raffaele, Dept Ophthalmol, Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Rabiolo, Alessandro/J-2831-2019; Corbelli, Eleonora/AAA-3186-2019; De
   Vitis, Luigi Antonio/I-1667-2016; bandello, francesco/AAH-2405-2019
OI Corbelli, Eleonora/0000-0003-1658-1922; De Vitis, Luigi
   Antonio/0000-0003-3778-8666; bandello, francesco/0000-0003-3238-9682;
   Sacconi, Riccardo/0000-0003-2891-2012; Querques,
   Giuseppe/0000-0002-3292-9581; Rabiolo, Alessandro/0000-0002-7772-5929
CR Adhi M, 2014, RETINA-J RET VIT DIS, V34, P306, DOI 10.1097/IAE.0b013e3182993e09
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NR 26
TC 7
Z9 7
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 23
PY 2016
VL 11
IS 11
AR e0166968
DI 10.1371/journal.pone.0166968
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA ED5KB
UT WOS:000388889500047
PM 27880806
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Zernii, EY
   Nazipova, AA
   Gancharova, OS
   Kazakov, AS
   Serebryakova, MV
   Zinchenko, DV
   Tikhomirova, NK
   Senin, II
   Philippov, PP
   Permyakov, EA
   Permyakov, SE
AF Zernii, Evgeni Yu
   Nazipova, Aliya A.
   Gancharova, Olga S.
   Kazakov, Alexey S.
   Serebryakova, Marina V.
   Zinchenko, Dmitry V.
   Tikhomirova, Natalya K.
   Senin, Ivan I.
   Philippov, Pavel P.
   Permyakov, Eugene A.
   Permyakov, Sergei E.
TI Light-induced disulfide dimerization of recoverin under ex vivo and in
   vivo conditions
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Photoreceptor; Age-related macular degeneration; Photochemical damage;
   Disulfide dimerization; EF-hand; NCS family; Recoverin; Visual arrestin
ID OXIDATIVE STRESS; RABBIT RETINA; REDOX STATE; DAMAGE; CALCIUM; BINDING;
   MECHANISMS; PROTEINS; CELL; ROD
AB Despite vast knowledge of the molecular mechanisms underlying photochemical damage of photo-receptors, linked to progression of age-related macular degeneration, information on specific protein targets of the light-induced oxidative stress is scarce. Here, we demonstrate that prolonged intense illumination (halogen bulb, 1500 lx, 1-5 h) of mammalian eyes under ex vivo (cow) or in vivo (rabbit) conditions induces disulfide dimerization of recoverin, a Ca2+ -dependent inhibitor of rhodopsin kinase. Western blotting and mass spectrometry analysis of retinal extracts reveals illumination time-dependent accumulation of disulfide homodimers of recoverin and its higher order disulfide cross-linked species, including a minor fraction of mixed disulfides with intracellular proteins (tubulins, etc.). Meanwhile, monomeric bovine recoverin remains mostly reduced. These effects are accompanied by accumulation of disulfide homodimers of visual arrestin. Histological studies demonstrate that the light-induced oxidation of recoverin and arrestin occurs in intact retina (illumination for 2 h), while illumination for 5 h is associated with damage of the photoreceptor layer. A comparison of ex vivo levels of disulfide homodimers of bovine recoverin with redox dependence of its in vitro thiol-disulfide equilibrium (glutathione redox pair) gives the lowest estimate of redox potential in rod outer segments under illumination from -160 to -155 mV. Chemical crosslinking and dynamic light scattering data demonstrate an increased propensity of disulfide dimer of bovine recoverin to multimerization/aggregation. Overall, the oxidative stress caused by the prolonged intense illumination of retina might affect rhodopsin desensitization via concerted disulfide dimerization of recoverin and arrestin. The developed herein models of eye illumination are useful for studies of the light-induced thiol oxidation of visual proteins. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Zernii, Evgeni Yu; Gancharova, Olga S.; Serebryakova, Marina V.; Tikhomirova, Natalya K.; Senin, Ivan I.; Philippov, Pavel P.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Dept Cell Signaling, Moscow 119992, Russia.
   [Nazipova, Aliya A.; Kazakov, Alexey S.; Permyakov, Eugene A.; Permyakov, Sergei E.] Russian Acad Sci, Inst Biol Instrumentat, Prot Res Grp, Pushchino 142290, Moscow Region, Russia.
   [Zinchenko, Dmitry V.] Russian Acad Sci, Branch Shemyakin, Pushchino 142290, Moscow Region, Russia.
   [Zinchenko, Dmitry V.] Russian Acad Sci, Ovchinnikov Inst Bioorgan Chem, Pushchino 142290, Moscow Region, Russia.
   [Permyakov, Eugene A.; Permyakov, Sergei E.] Pushchino State Inst Nat Sci, Dept Biomed Engn, Pushchino 142290, Moscow Region, Russia.
C3 Lomonosov Moscow State University; Russian Academy of Sciences; Russian
   Academy of Sciences; Pushchino Scientific Center for Biological Research
   (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic
   Chemistry of the Russian Academy of Sciences; Russian Academy of
   Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of
   the Russian Academy of Sciences; Institute of Bioorganic Chemistry of
   the Russian Academy of Sciences
RP Zernii, EY (通讯作者)，Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, 1-40 Leninskye Gory, Moscow 119992, Russia.
EM zerni@belozersky.msu.ru
RI Zernii, Evgeni Yu./D-9446-2012; Serebryakova, Marina/E-2986-2012;
   Permyakov, Sergei/O-1386-2019; Gancharova, Olga S/M-9980-2014;
   Permyakov, Sergei E./B-8156-2011; Zinchenko, Dmitry/C-8000-2014;
   Kazakov, Alexey S./M-9129-2014; Permyakov, Eugene A./M-8707-2014
OI Zernii, Evgeni Yu./0000-0002-3013-7863; Serebryakova,
   Marina/0000-0002-5402-8215; Permyakov, Sergei/0000-0003-4086-3137;
   Gancharova, Olga S/0000-0001-7441-1062; Permyakov, Sergei
   E./0000-0003-4086-3137; Zinchenko, Dmitry/0000-0001-7181-6283; Kazakov,
   Alexey S./0000-0002-1586-7649; Permyakov, Eugene A./0000-0002-9099-1148
FU Russian Academy of Sciences "Molecular and Cellular Biology"; Russian
   Foundation for Basic Research [12-04-01045-a, 15-04-07963-a]
FX This work was supported by a grant from the Program of the Russian
   Academy of Sciences "Molecular and Cellular Biology" (E. A.P.) and by a
   grant from the Russian Foundation for Basic Research (E.Yu.Z., No.
   12-04-01045-a and No. 15-04-07963-a). We are indebted to Dr. Andrei P.
   Zhadan (IBI RAS, Pushchino) for chromatographic separation of monomeric
   and dimeric forms of recoverin.
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NR 66
TC 24
Z9 26
U1 1
U2 39
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 JUN
PY 2015
VL 83
BP 283
EP 295
DI 10.1016/j.freeradbiomed.2015.03.001
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CJ6BI
UT WOS:000355577600028
PM 25772009
DA 2022-11-30
ER

PT J
AU Saxena, K
   Rutar, MV
   Provis, JM
   Natoli, RC
AF Saxena, Kartik
   Rutar, Matthew Viktor
   Provis, Jan M.
   Natoli, Riccardo Carlo
TI Identification of miRNAs in a Model of Retinal Degenerations
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; microRNA; light damage; retinal degeneration; noncoding RNA
ID MACULAR DEGENERATION; CELL-PROLIFERATION; LIGHT DAMAGE; EXPRESSION;
   MICRORNAS; GENE; ACTIVATION; PHOTORECEPTORS; MACROPHAGES; MICROGLIA
AB PURPOSE. We investigated the expression profile of and identify all microRNAs (miRNAs) that potentially regulate inflammation in a light-induced model of focal retinal degeneration.
   METHODS. Sprague Dawley (SD) rats aged 90 to 140 postnatal days were exposed to 1000 lux white fluorescent light for 24 hours. At 24 hours, and 3 and 7 days after exposure, the animals were euthanized and retinas processed for RNA. Expression of 750 miRNAs at 24 hours of exposure was assessed using low density array analysis. Significantly modulated miRNAs and their target mRNAs were used to assess the potential biological effects. Expression of seven miRNAs, potentially modulating inflammation, was investigated across a protracted time course after light exposure using quantitative PCR. Photoreceptor cell death was analyzed using TUNEL.
   RESULTS. Intense light exposure for 24 hours led to differential expression of a number of miRNAs, 37 of which were significantly modulated by 2-fold or more. Of those, 19 may potentially regulate the inflammatory immune response observed in the model. MicroRNAs -125-3p, -155, -207, -347, -449a, -351, and -542-3p are all upregulated at 24 hours of exposure along with peak photoreceptor cell death. The MiRNAs -542-3p and -351 reached maximum expression at 7 days after exposure, while -125-3p, -155, -207, -347, and -449 reached a peak expression at 3 days.
   CONCLUSIONS. The results of the study show that miRNAs are modulated in response to light damage (LD). These miRNAs potentially regulate the inflammatory immune response, triggered as a result of the acute retinal damage, which is a key mediator of retinal degeneration in this model and age-related macular degeneration.
C1 [Saxena, Kartik; Rutar, Matthew Viktor; Provis, Jan M.; Natoli, Riccardo Carlo] Australian Natl Univ, Canberra, ACT 0200, Australia.
C3 Australian National University
RP Natoli, RC (通讯作者)，Australian Natl Univ, Sch Med, Coll Med Biol & Environm, GPO Box 4, Canberra, ACT 0200, Australia.
EM riccardo.natoli@anu.edu.au
RI ; Provis, Jan/C-9529-2009
OI Natoli, Riccardo/0000-0002-9350-0439; Rutar,
   Matthew/0000-0002-8893-5120; Provis, Jan/0000-0002-6405-2868
FU Australian Research Council Centres of Excellence Program Grant
   [CE0561903]; National Health and Medical Research Council Grant
   [1049990]
FX Supported by the Australian Research Council Centres of Excellence
   Program Grant CE0561903 and National Health and Medical Research Council
   Grant 1049990.
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NR 59
TC 20
Z9 21
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 MAR
PY 2015
VL 56
IS 3
BP 1820
EP 1829
DI 10.1167/iovs.14-15449
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE9BF
UT WOS:000352137600054
PM 25711632
OA Green Published
DA 2022-11-30
ER

PT J
AU Pollreisz, A
   Afonyushkin, T
   Oskolkova, OV
   Gruber, F
   Bochkov, VN
   Schmidt-Erfurth, U
AF Pollreisz, Andreas
   Afonyushkin, Taras
   Oskolkova, Olga V.
   Gruber, Florian
   Bochkov, Valery N.
   Schmidt-Erfurth, Ursula
TI Retinal pigment epithelium cells produce VEGF in response to oxidized
   phospholipids through mechanisms involving ATF4 and protein kinase CK2
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE oxidized phospholipids; RPE; angiogenesis; unfolded protein response;
   protein kinase CK2
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; AGE; ACTIVATION;
   EXPRESSION; STRESS; TRANSCRIPTION; ANGIOGENESIS; SECRETION; RANIBIZUMAB
AB Oxidized phospholipids (OxPLs) are pleiotropic lipid mediators known to induce proangiogenic and proinflammatory cellular effects that are increasingly recognized to be involved in a number of physiologic and pathologic processes in the retina. Immunohistochemical studies have detected OxPLs in retinal structures, such as retinal pigment epithelium (RPE) or photoreceptor cells. This study analyzed whether OxPLs could play a role in upregulation of VEGF, which is a cause of pathological neovascularization characteristic of eye diseases such as age-related macular degeneration. We confirmed accumulation of OxPLs in the eye using reversed-phase liquid chromatography coupled to mass spectrometry. Multiple species of oxidized phosphatidylcholines (OxPCs) were detected in human vitreous, including biologically active fragmented species POVPC, PGPC, PONPC and PAzPC. In in vitro experiments human fetal RPE and primary RPE cells were stimulated with OxPLs. Primary RPE cells were transfected with small interfering RNAs targeting ATF4. mRNA levels of VEGF in fetal and primary RPE cells were determined by real-time quantitative PCR. VEGF protein concentrations were measured in culture medium by ELISA. We found that OxPCs and other classes of OxPLs upregulated the expression of VEGF in fetal and primary RPE cells, which critically depended on ATF4. In addition, upregulation of VEGF in primary RPE cells was blocked by a chemical inhibitor of protein kinase CK2 known to suppress induction of ATF4 and VEGF by OxPLs. Our data show that different species of OxPLs, which are present in the human eye are capable of stimulating expression of VEGF in fetal and primary RPE cells via ATF4-dependent mechanisms. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Pollreisz, Andreas; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, A-1090 Vienna, Austria.
   [Afonyushkin, Taras; Oskolkova, Olga V.; Bochkov, Valery N.] Med Univ Vienna, Dept Vasc Biol & Thrombosis Res, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria.
   [Gruber, Florian] Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna; Medical
   University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
RI Pollreisz, Andreas/AAJ-1538-2021
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Oskolkova,
   Olga/0000-0001-9443-8705; Gruber, Florian/0000-0003-1094-5641
FU Austrian Science Fund (FWF) [P23016-B11, P22267-B11, S10713-B13];
   Austrian Science Fund (FWF) [P 23016, P 22267] Funding Source:
   researchfish
FX This work was supported by grants from the Austrian Science Fund (FWF):
   P23016-B11 to T.A., P22267-B11 to O.V.O, and S10713-B13 to V.N.B.
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NR 32
TC 20
Z9 20
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 NOV
PY 2013
VL 116
BP 177
EP 184
DI 10.1016/j.exer.2013.08.021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 259YP
UT WOS:000327562500020
PM 24021586
OA Green Published
DA 2022-11-30
ER

PT J
AU Balaiya, S
   Murthy, RK
   Malyapa, R
   Grover, S
   Chalam, KV
AF Balaiya, Sankarathi
   Murthy, Ravi K.
   Malyapa, Robert
   Grover, Sandeep
   Chalam, Kakarla V.
TI Differential Sensitivity of Choroidal Endothelial, Retinal Ganglion, and
   Retinal Pigment Epithelial Cells In Vitro to Proton Radiation
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; BEAM IRRADIATION;
   CONTROLLED-TRIAL; THERAPY; BRACHYTHERAPY; RADIOTHERAPY; VERTEPORFIN
AB PURPOSE: To evaluate the differential sensitivity of choroidal endothelial, retinal pigment epithelial, and retinal ganglion cells to escalating doses of proton beam radiation and to establish a safe dose range for the management of choroidal neovascularization associated with age-related macular degeneration (AMD).
   DESIGN: Laboratory investigation.
   METHODS: Proliferating simian choroidal endothelial cells (RF/6A), differentiated rat retinal ganglion cells (RGC-5), and serum-starved human retinal pigment epithelial cells (ARPE-19) were exposed to 2, 4, 8, and 12 cobalt gray equivalent of proton beam radiation and cell viability was quantified on day 9. Reactive oxygen species levels were analyzed.
   RESULTS: Significant decline of choroidal endothelial cell viability was noted as dose escalated from 4 to 8 cobalt gray equivalent with maximum effect observed at 12 cobalt gray equivalent. RGC-5 and ARPE-19 cell count decreased to 95% and 62.7% at 8 cobalt gray equivalent, respectively. Sub-analysis between 4 and 8 cobalt gray equivalent radiation revealed significant decrease in choroidal endothelial cell viability (43.1% at 7 cobalt gray equivalent and 32.3% at 8 cobalt gray equivalent of radiation). Correspondingly, RGC-5 and ARPE-19 cells did not show decrease in cell count or viability. Reactive oxygen species levels significantly increased in radiation-treated choroidal endothelial cells (8.3%-11.9%).
   CONCLUSIONS: At 6-8 cobalt gray equivalent proton beam radiation, retinal ganglion and retinal pigment epithelial cells are preserved while choroidal endothelial cells are completely inhibited. This dosage offers optimum therapeutic safety window for treatment using proton beam radiation for exudative AMD. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Balaiya, Sankarathi; Murthy, Ravi K.; Grover, Sandeep; Chalam, Kakarla V.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL 32209 USA.
   [Malyapa, Robert] Univ Florida, Proton Therapy Inst, Jacksonville, FL 32209 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida
RP Chalam, KV (通讯作者)，Univ Florida, Coll Med, Dept Ophthalmol, 580 W 8th St,Tower 2, Jacksonville, FL 32209 USA.
EM kchalam@jax.ufl.edu
RI Chalam, kakarla/K-7507-2019
OI Chalam, kakarla/0000-0001-9325-8665; Grover,
   Sandeep/0000-0002-3771-7510; Chalam, K V/0000-0002-0004-9416
CR Avila MP, 2009, BRIT J OPHTHALMOL, V93, P305, DOI 10.1136/bjo.2008.145912
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NR 22
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2013
VL 156
IS 3
BP 444
EP 453
DI 10.1016/j.ajo.2013.04.036
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 214RM
UT WOS:000324153500006
PM 23769193
DA 2022-11-30
ER

PT J
AU Holz, FG
   Bandello, F
   Gillies, M
   Mitchell, P
   Osborne, A
   Sheidow, T
   Souied, E
   Figueroa, MS
AF Holz, Frank G.
   Bandello, Francesco
   Gillies, Mark
   Mitchell, Paul
   Osborne, Aaron
   Sheidow, Tom
   Souied, Eric
   Figueroa, Marta S.
CA LUMINOUS Steering Comm
TI Safety of ranibizumab in routine clinical practice: 1-year retrospective
   pooled analysis of four European neovascular AMD registries within the
   LUMINOUS programme
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Degeneration; Macula; Treatment Medical
ID OCCLUSION 12-MONTH OUTCOMES; MACULAR DEGENERATION; SUSTAINED BENEFITS;
   PHARMACOKINETICS; VERTEPORFIN; BEVACIZUMAB
AB Purpose
   Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice.
   Methods
   The LUMINOUS programme comprises a prospective observational study assessing ranibizumab real-world' safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence.
   Results
   Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0-0.5%).
   Conclusions
   Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in real-life' settings. The 5-year LUMINOUS prospective observational study will address this need.
C1 [Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Bandello, Francesco] Univ Vita Salute Sci Inst, Dept Ophthalmol, Milan, Italy.
   [Gillies, Mark] Univ Sydney, Sydney Eye Hosp, Sydney, NSW 2006, Australia.
   [Mitchell, Paul] Univ Sydney, Dept Ophthalmol, Sydney, NSW 2006, Australia.
   [Osborne, Aaron] Novartis, Dept Ophthalmol, Basel, Switzerland.
   [Sheidow, Tom] Ivey Eye Inst, Dept Ophthalmol, Toronto, ON, Canada.
   [Souied, Eric] Hop Intercommunal Creteil, Serv Ophthalmol, Creteil, France.
   [Figueroa, Marta S.] Ramon & Cajal Univ Hosp, Serv Oftalmol, Madrid, Spain.
C3 University of Bonn; Vita-Salute San Raffaele University; IRCCS Ospedale
   San Raffaele; University of Sydney; University of Sydney; Novartis;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; Hospital
   Universitario Ramon y Cajal
RP Holz, FG (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM Frank.Holz@ukb.uni-bonn.de
RI bandello, francesco/AAH-2405-2019; Mitchell, Paul/P-1498-2014
OI bandello, francesco/0000-0003-3238-9682; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Sheidow, Tom/0000-0001-6370-1857
FU Novartis
FX The four registries reported in this pooled analysis were funded by
   Novartis.
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NR 29
TC 75
Z9 78
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 SEP
PY 2013
VL 97
IS 9
BP 1161
EP 1167
DI 10.1136/bjophthalmol-2013-303232
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 201SO
UT WOS:000323163500017
PM 23850682
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Fong, CSU
   Mitchell, P
   de Loryn, T
   Rochtchina, E
   Hong, T
   Cugati, S
   Wang, JJ
AF Fong, Calvin Sze-un
   Mitchell, Paul
   de Loryn, Tania
   Rochtchina, Elena
   Hong, Thomas
   Cugati, Sudha
   Wang, Jie Jin
TI Long-term outcomes of phacoemulsification cataract surgery performed by
   trainees and consultants in an Australian cohort
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Australian Prospective Cataract Surgery and Age-related Macular
   Degeneration study; cataract surgery; visual acuity
ID VITREOUS LOSS; INTRAOPERATIVE COMPLICATIONS; TOPICAL ANESTHESIA; VISUAL
   OUTCOMES; RESIDENTS; EXTRACTION; RATES; RISK
AB Background: It is unclear whether differences exist in surgical complication rates and long-term visual acuity outcomes between patients whose phacoemulsification cataract surgery was performed by ophthalmological trainees and those performed by consultants.
   Design: Prospective clinical cohort study.
   Participants: 1851 participants of the Cataract Surgery and Age-related Macular Degeneration study, aged >= 64 years, had cataract surgery performed at Westmead Hospital, Sydney.
   Methods: Surgical complication rates and visual acuity at 24-month postoperative visits were compared between patients who were operated on by trainees and those operated on by consultants.
   Main Outcome Measures: Surgical outcomes included operative complications recorded in surgical audit forms and 24-month postoperative visual acuity.
   Results: Of 1851 patients, 1274 (68.8%) were reviewed 24 months after surgery. Of these, 976 had data on the type of surgeon who performed the operation. After excluding 152 challenging cases and three cases operated on by first-year trainees at the beginning of their training, 821 patients were included in this study, of those, 498 were operated on by trainees and 323 by consultants. Habitual visual acuity >= 6/12 was achieved in 77.3% (n = 385/498) and 74.3% (n = 240/323), respectively, of the two groups of patients 24 months postoperatively. Of 514 patients who had surgical audit data, the major complication rate was numerically greater, but not significantly different for the 330 trainee-operated (6.1%) patients, compared with the 184 consultant-operated patients (2.7%, P = 0.091).
   Conclusions: We found relatively comparable complication rates and visual outcomes after 2 years between patients operated on by ophthalmological trainees and those by consultants, in a cataract surgical cohort at Westmead Hospital.
C1 [Fong, Calvin Sze-un; Mitchell, Paul; de Loryn, Tania; Rochtchina, Elena; Hong, Thomas; Wang, Jie Jin] Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Fong, Calvin Sze-un; Mitchell, Paul; de Loryn, Tania; Rochtchina, Elena; Hong, Thomas; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
   [Cugati, Sudha] Flinders Univ S Australia, Flinders Med Ctr, Dept Ophthalmol, Adelaide, SA 5001, Australia.
   [Wang, Jie Jin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
C3 University of Sydney; University of Sydney; Westmead Institute for
   Medical Research; Flinders Medical Centre; Flinders University South
   Australia; Centre for Eye Research Australia; University of Melbourne
RP Wang, JJ (通讯作者)，Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead Millennium Inst, Hawkesbury Rd, Westmead, NSW 2145, Australia.
EM jiejin.wang@sydney.edu.au
RI Mitchell, Paul/P-1498-2014; Cugati, Sudha/ABB-1331-2021; wang,
   jie/GRS-0942-2022; Wang, Jie Jin/P-1499-2014
OI Wang, Jie Jin/0000-0001-9491-4898
FU Australian National Health & Medical Research Council, Canberra,
   Australia [302010]; Retina Australia
FX Australian National Health & Medical Research Council, Canberra,
   Australia (Grant no. 302010, 2004-2006), Retina Australia (2005).
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NR 30
TC 16
Z9 16
U1 0
U2 6
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 AUG
PY 2012
VL 40
IS 6
BP 597
EP 603
DI 10.1111/j.1442-9071.2012.02759.x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 017QF
UT WOS:000309604700011
PM 22300362
DA 2022-11-30
ER

PT J
AU Boyer, NP
   Higbee, D
   Currin, MB
   Blakeley, LR
   Chen, CH
   Ablonczy, Z
   Crouch, RK
   Koutalos, Y
AF Boyer, Nicholas P.
   Higbee, Daniel
   Currin, Mark B.
   Blakeley, Lorie R.
   Chen, Chunhe
   Ablonczy, Zsolt
   Crouch, Rosalie K.
   Koutalos, Yiannis
TI Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in
   Retinal Pigment Epithelium in Absence of Light Exposure THEIR ORIGIN IS
   11-cis-RETINAL
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ABC TRANSPORTER ABCA4; STARGARDT-DISEASE; RPE LIPOFUSCIN; FLUOROPHORE;
   BIOSYNTHESIS; FLUORESCENCE; CELLS; DEGENERATION; GENERATION; SUBSTRATE
AB The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis-and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane.
C1 [Koutalos, Yiannis] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina
RP Koutalos, Y (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM koutalo@musc.edu
FU National Institutes of Health [EY020661, EY004939, EY014850, EY014793];
   Extramural Research Facilities Program of NCRR [C06 RR015455];
   Foundation Fighting Blindness, Inc.; Departments of Ophthalmology at
   Medical University of South Carolina from Research to Prevent Blindness;
   NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R21EY020661, R01EY004939, R24EY014793,
   R01EY019065, R01EY014850] Funding Source: NIH RePORTER
FX This work was conducted in a facility constructed with support from
   National Institutes of Health Grant C06 RR015455 from the Extramural
   Research Facilities Program of NCRR.; This work was supported, in whole
   or in part, by National Institutes of Health Grants EY020661 (to Z. A.
   and R. K. C.), EY004939 (to R. K. C.), EY014850 (to Y. K.), and EY014793
   (to Medical University of South Carolina Vision Core). This work was
   also supported by the Foundation Fighting Blindness, Inc. (to R. K. C.)
   and unrestricted awards to the Departments of Ophthalmology at Medical
   University of South Carolina from Research to Prevent Blindness.
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NR 54
TC 89
Z9 98
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 22
PY 2012
VL 287
IS 26
BP 22276
EP 22286
DI 10.1074/jbc.M111.329235
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 974GH
UT WOS:000306418600065
PM 22570475
OA Green Published, hybrid
DA 2022-11-30
ER

EF