﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Tan, CS
   Lim, LW
   Ngo, WK
   Pannirselvam, P
   See, C
   Chee, WK
   Saxena, N
AF Tan, Colin S.
   Lim, Louis W.
   Ngo, Wei Kiong
   Pannirselvam, Pandiyan
   See, Clarence
   Chee, Wai Kitt
   Saxena, Nakul
TI Predictors of persistent disease activity following anti-VEGF loading
   dose for nAMD patients in Singapore: the DIALS study
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF; Neovascular age related macular degeneration; Polypoidal
   choroidal vasculopathy; Persistent disease activity
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; MACULAR
   DEGENERATION; CONTROLLED-TRIAL; SPECTRAL-DOMAIN; RANIBIZUMAB;
   MANAGEMENT; THERAPY; THICKNESSES; MULTICENTER
AB Background To determine the frequency of persistent disease activity following 3 loading doses of anti- vascular endothelial growth factor (VEGF) agents, and the anatomic and demographic predictors of early persistent disease activity among patients with neovascular age-related macular degeneration (nAMD). Methods In a retrospective real-world cohort study, 281 consecutive patients with nAMD were reviewed at baseline and after 3 anti-VEGF injections for pre-defined indicators of disease activity. Optical coherence tomography (OCT) features such as subretinal fluid, intraretinal cysts and intraretinal fluid were assessed by reading-center certified graders. Multiple logistic regression was performed on demographic and anatomic factors. Results At month 3, 66.1% of patients had persistent disease activity. The best-corrected visual acuity (BCVA) improvement was 0.16 LogMAR for those with no disease activity compared to 0 for patients with persistent activity (p < 0.001). The significant risk factors for persistent activity at 3 months were male gender (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32-0.93,p = 0.025), intraretinal cysts at baseline (OR 2.95, 95% CI 1.67-5.20,p < 0.001) and subretinal fluid at baseline (OR 3.17, 95% CI 1.62-6.18,p = 0.002). At 3 months, 58% of patients had features of activity on OCT. Patients with intraretinal cysts and intraretinal fluid at baseline had worse BCVA at month 3 compared to patients without these OCT features (0.69 vs. 0.43,p < 0.001, and 0.62 vs. 0.43,p < 0.001, respectively). Conclusions In a real-world study, 66.1% of nAMD patients have persistent disease activity after the initial loading dose, with poorer BCVA compared to those without. Baseline OCT features (intraretinal cysts and subretinal fluid) are useful predictors of persistent disease activity at month 3.
C1 [Tan, Colin S.; Lim, Louis W.; Ngo, Wei Kiong] Natl Healthcare Grp Eye Inst, Fundus Image Reading Ctr, Singapore, Singapore.
   [Tan, Colin S.; Lim, Louis W.; Ngo, Wei Kiong; Pannirselvam, Pandiyan; See, Clarence; Chee, Wai Kitt] Tan Tock Seng Hosp, Natl Healthcare Grp, Eye Inst, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
   [Tan, Colin S.; Pannirselvam, Pandiyan; See, Clarence] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
   [Tan, Colin S.] Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
   [Saxena, Nakul] Novartis Singapore Private Ltd, Singapore, Singapore.
C3 Tan Tock Seng Hospital; Nanyang Technological University & National
   Institute of Education (NIE) Singapore; Nanyang Technological
   University; National University of Singapore
RP Tan, CS (通讯作者)，Natl Healthcare Grp Eye Inst, Fundus Image Reading Ctr, Singapore, Singapore.; Tan, CS (通讯作者)，Tan Tock Seng Hosp, Natl Healthcare Grp, Eye Inst, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.; Tan, CS (通讯作者)，Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.; Tan, CS (通讯作者)，Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
EM Colintan_eye@yahoo.com
RI Tan, Colin S/K-8972-2012
OI Tan, Colin S/0000-0003-3088-5690
FU National Medical Research Council [NMRC/TA/0039/2015] Funding Source:
   Medline; NMRC Centre Grant Programme [CGAug16M012] Funding Source:
   Medline
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NR 24
TC 1
Z9 1
U1 0
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD AUG 6
PY 2020
VL 20
IS 1
AR 324
DI 10.1186/s12886-020-01582-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NC3LF
UT WOS:000561115700002
PM 32762659
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Linetsky, M
   Guo, J
   Udeigwe, E
   Ma, D
   Chamberlain, AS
   Yu, AO
   Solovyova, K
   Edgar, E
   Salomon, RG
AF Linetsky, Mikhail
   Guo, Junhong
   Udeigwe, Emeka
   Ma, Duoming
   Chamberlain, Amanda S.
   Yu, Annabelle O.
   Solovyova, Kseniya
   Edgar, Elise
   Salomon, Robert G.
TI 4-Hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone induces apoptosis in
   retinal pigment epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Apoptosis; Free radical-induced lipid oxidation;
   4-Hydroxy-7-oxo-5-heptenoic acid lactone; Oxidative stress; Retinal
   pigment epithelial cells; Age-related macular degeneration
ID POLYUNSATURATED FATTY-ACIDS; OXIDATIVE STRESS; PATHOGENESIS; SENESCENCE;
   EXPRESSION; PROTEINS; ARPE-19; PHOSPHOLIPIDS; INFLAMMATION; METABOLISM
AB Retinal pigment epithelial (RPE) cell dysfunction and death play vital roles in age -related macular degeneration (AMD) pathogenesis. Previously we showed that oxidative cleavage of docosahexenoate (DHA) phospholipids generates an ?,?-unsaturated aldehyde, 4-hydroxy-7-oxohept-4-enoic acid (HOHA) lactone, that forms ?-car- boxyethylpyrrole (CEP) derivatives through adduction to proteins and ethanolamine phospholipids. CEP deri- vatives and autoantibodies accumulate in the retinas and blood plasma of individuals with AMD and are a biomarker of AMD. They promote the choroidal neovascularization of ?wet AMD?. Immunization of mice with CEP -modified mouse serum albumin induces ?dry AMD?-like lesions in their retinas as well as interferon -gamma and interleukin-17 production by CEP -specific T cells that promote inflammatory M1 polarization of macro- phages. The present study confirms that oxidative stress or inflammatory stimulus produces CEP in both the primary human ARPE-19 cell line and hRPE cells. Exposure of these cells to HOHA lactone fosters production of reactive oxygen species. Thus, HOHA lactone participates in a vicious cycle, promoting intracellular oxidative stress leading to oxidative cleavage of DHA to produce more HOHA lactone. We now show that HOHA lactone is cytotoxic, inducing apoptotic cell death through activation of the intrinsic pathway. This suggests that ther- apeutic interventions targeting HOHA lactone-induced apoptosis may prevent the loss of RPE cells during the early phase of AMD. We also discovered that ARPE-19 cells are more susceptible than hRPE cells to HOHA lactone cytotoxicity. This is consistent with the view that, compared to normal RPE cells, ARPE-19 cells exhibit a diseased RPE phenotype that also includes elevated expression of the mesenchymal indicator vimentin, ele- vated integrin a5 promotor strength and deficient secretion of the anti -VEGF molecule pigment -epithelium - derived factor fostering weaker tight junctions.
C1 [Linetsky, Mikhail; Guo, Junhong; Udeigwe, Emeka; Ma, Duoming; Edgar, Elise; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Chamberlain, Amanda S.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
   [Yu, Annabelle O.] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA.
   [Linetsky, Mikhail; Salomon, Robert G.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Solovyova, Kseniya] Cleveland State Univ, Dept Chem, Cleveland, OH 44115 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; Case Western Reserve University; University
   System of Ohio; Cleveland State University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@case.edu
FU NIH [R01-EY016813, P30 EY011373]
FX This work was supported by NIH Grant R01-EY016813 (to R.G.S.) and Core
   Grant P30 EY011373 (to Case Visual Sciences Research Center).
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NR 54
TC 4
Z9 4
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 MAY 20
PY 2020
VL 152
BP 280
EP 294
DI 10.1016/j.freeradbiomed.2020.03.017
PG 15
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA MB9WV
UT WOS:000542949100007
PM 32222470
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Fayed, AE
   Fawzi, AA
AF Fayed, Alaa E.
   Fawzi, Amani A.
TI Projection resolved optical coherence tomography angiography to
   distinguish flow signal in retinal angiomatous proliferation from flow
   artifact
SO PLOS ONE
LA English
DT Article
ID HYPERREFLECTIVE FOCI; QUANTITATIVE-ANALYSIS; OCT ANGIOGRAPHY;
   NEOVASCULARIZATION; PLEXUSES
AB Purpose
   To investigate whether hyperreflective foci (HRF) exhibit flow projection artifact on OCTA, and study the efficacy of commercial projection artifact removal software (PAR-OCTA, Optovue, Inc), and a custom projection resolved OCTA (PR-OCTA) in distinguishing artifacts from true flow in retinal angiomatous proliferation (RAP).
   Methods
   The study included five eyes with HRF representing pigment migration in dry age-related macular degeneration (AMD), five eyes with leaking treatment-naive RAP, and ten eyes with diabetic hard exudates. We examined flow signal on OCTA cross-sections using PAR, and performed PR-OCTA to study the effect of increasingly stringent projection removal thresholds. Flow signal intensity was analyzed and quantified using imageJ (NIH, Bethesda, MD, USA), by calculating the percentage of red pixels (R) representing flow, compared to green (G) and blue (B) pixels.
   Results
   PAR-OCTA cross sections revealed persistent flow signal in all HRF, including RAP, hard exudates and pigment migration. In RAP, PR-OCTA detected intransigent flow, irrespective of the flow removal threshold. Mean R in the five RAP lesions remained higher than mean G and B at the most stringent PR-OCTA threshold (40.96% vs 29.52 and 29.52%, respectively), denoting persistence of flow. In contrast, increasing the PR-OCTA threshold in pigment migration and hard exudates removed the flow signal, with a statistically significant decrease in mean R with increasing threshold. (p = 0.017 and 0.0029, respectively)
   Conclusion
   Commercial PAR-OCTA is not completely effective at removing artifactual flow in hard exudates and HRF related to pigment migration. Custom built PR-OCTA, using a sliding scale of threshold, allowed us to distinguish true flow in RAP from artifactual flow in avascular HRF. Further studies are needed to validate the optimum threshold for projection artifact removal, which would preserve true flow in RAP and the small intraretinal capillaries.
C1 [Fayed, Alaa E.; Fawzi, Amani A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Fayed, Alaa E.] Cairo Univ, Kasr Al Ainy Sch Med, Dept Ophthalmol, Cairo, Egypt.
C3 Northwestern University; Feinberg School of Medicine; Egyptian Knowledge
   Bank (EKB); Cairo University
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 NIH [DP3DK108248]
FX This work was funded in part by NIH grants DP3DK108248 (A.A.F.) and
   research instrument support by Optovue, Inc., Fremont, California, USA.
   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 29
TC 8
Z9 8
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 MAY 15
PY 2019
VL 14
IS 5
AR e0217109
DI 10.1371/journal.pone.0217109
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HY2KH
UT WOS:000467949100063
PM 31091288
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Cheng, YS
   Linetsky, M
   Gu, XL
   Ayyash, N
   Gardella, A
   Salomon, RG
AF Cheng, Yu-Shivan
   Linetsky, Mikhail
   Gu, Xilin
   Ayyash, Naji
   Gardella, Anthony
   Salomon, Robert G.
TI Light-induced generation and toxicity of docosahexaenoate-derived
   oxidation products in retinal pigmented epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Carboxyethylpyrrole; A2E;
   Mitochondrial membrane potential; Lipid oxidation; Lysosome
ID POLYUNSATURATED FATTY-ACIDS; BLUE-LIGHT; MITOCHONDRIAL-MEMBRANE; INDUCED
   DAMAGE; FUNDUS AUTOFLUORESCENCE; MACULAR DEGENERATION;
   BETA-GALACTOSIDASE; RPE CELLS; LIPOFUSCIN FLUOROPHORE; PHOTOCHEMICAL
   DAMAGE
AB Oxidative cleavage of docosahexaenoate (DHA) in retinal pigmented epithelial (RPE) cells produces 4-hydroxy-7-oxohept-5-enoic acid (HOHA) esters of 2-lysophosphatidylcholine (PC). HOHA-PC spontaneously releases a membrane-permeant HOHA lactone that modifies primary amino groups of proteins and ethanolamine phospholipids to produce 2-(omega-carboxyethyl)pyrrole (CEP) derivatives. CEPs have significant pathological relevance to age-related macular degeneration (AMD) including activation of CEP-specific T-cells leading to inflammatory M1 polarization of macrophages in the retina involved in "dry AMD" and TLR2-dependent induction of angiogenesis that characterizes "wet AMD". RPE cells accumulate DHA from shed rod photoreceptor outer segments through phagocytosis and from plasma lipoproteins secreted by the liver through active uptake from the choriocapillaris. As a cell model of light-induced oxidative damage of DHA phospholipids in RPE cells, ARPE19 cells were supplemented with DHA, with or without the lipofuscin fluorophore A2E. In this model, light exposure, in the absence of A2E, promoted the generation HOHA lactone-glutathione (GSH) adducts, depletion of intracellular GSH and a competing generation of CEPs. While DHA-rich RPE cells exhibit an inherent proclivity toward light-induced oxidative damage, photosensitization by A2E nearly doubled the amount of lipid oxidation and expanded the spectral range of photosensitivity to longer wavelengths. Exposure of ARPE-19 cells to 1 mu M HOHA lactone for 24 h induced massive (50%) loss of lysosomal membrane integrity and caused loss of mitochondrial membrane potential. Using senescence-associated beta-galactosidase (SA beta-gal) staining that detects lysosomal beta-galactosidase, we determined that exposure to HOHA lactone induces senescence in ARPE-19 cells. The present study shows that products of light-induced oxidative damage of DHA phospholipids in the absence of A2E can lead to RPE cell dysfunction. Therefore, their toxicity may be especially important in the early stages of AMD before RPE cells accumulate lipofuscin fluorophores.
C1 [Cheng, Yu-Shivan; Linetsky, Mikhail; Gu, Xilin; Ayyash, Naji; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Gardella, Anthony; Salomon, Robert G.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@case.edu
OI Cheng, Yu-Shiuan/0000-0002-7408-7888
FU National Institutes of Health from the National Eye Institute
   [R01EY016813, P30 EY11373]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER
FX This research was supported by National Institutes of Health grant
   R01EY016813 from the National Eye Institute and Core Grant P30 EY11373
   (to Case Visual Sciences Research Center). We thank Dr. Geeng-Fu Jang
   and Dr. John Crabb for assistance with LC-MS/MS analyses at the
   Cleveland Clinic.
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NR 152
TC 14
Z9 16
U1 0
U2 18
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2019
VL 181
BP 325
EP 345
DI 10.1016/j.exer.2018.09.012
PG 21
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HT5TJ
UT WOS:000464625900040
PM 30296412
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Yanai, R
   Chen, S
   Uchi, SH
   Nanri, T
   Connor, KM
   Kimura, K
AF Yanai, Ryoji
   Chen, Shang
   Uchi, Sho-Hei
   Nanri, Tomoaki
   Connor, Kip M.
   Kimura, Kazuhiro
TI Attenuation of choroidal neovascularization by dietary intake of omega-3
   long-chain polyunsaturated fatty acids and lutein in mice
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; CLINICAL-TRIAL; VITAMIN-E; N-3
   PUFA; OMEGA-3-FATTY-ACIDS; BIOAVAILABILITY; ZEAXANTHIN; CELLS;
   CAROTENOIDS
AB Dietary omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of omega-3 LCPUFAs and lutein supplementation in a mouse model of AMD. Mice were assigned to four groups: (1) a control group fed an omega-3 LCPUFA +/- free diet, (2) a lutein group fed an omega-3 LCPUFA +/- free diet with oral administration of lutein, (3) an omega-3 group fed an omega-3 LCPUFA +/- supplemented diet, and (4) an omega-3 + lutein group fed an omega-3 LCPUFA +/- supplemented diet with oral administration of lutein. Mice were fed the defined diets beginning 2 weeks before, and received lutein with an oral gavage needle beginning 1 week before, induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations was significantly reduced in mice fed omega-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both omega-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed omega-3 LCPUFAs or lutein, but no additive effect was apparent. The generation of reactive oxygen species (ROS) in chorioretinal lesions revealed by dihydroethidium staining as well as the expression of NADPH oxidase 4 (Nox4) in the retina revealed by immunohistofluorescence and immunoblot analyses were attenuated by omega-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of omega-3 LCPUFAs and lutein attenuated CNV in an additive manner and in association with suppression of inflammatory mediator production, ROS generation, and Nox4 expression. Dietary supplementation with both omega-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.
C1 [Yanai, Ryoji; Chen, Shang; Uchi, Sho-Hei; Kimura, Kazuhiro] Yamaguchi Univ, Dept Ophthalmol, Grad Sch Med, Ube, Yamaguchi, Japan.
   [Nanri, Tomoaki] Santen Pharmaceut Co Ltd, Osaka, Japan.
   [Connor, Kip M.] Harvard Med Sch, Dept Ophthalmol, Angiogenesis Lab, Massachusetts Eye & Ear Infirm, Cambridge, MA USA.
C3 Yamaguchi University; Santen Pharmaceutical Co Ltd; Harvard University;
   Massachusetts Eye & Ear Infirmary
RP Yanai, R (通讯作者)，Yamaguchi Univ, Dept Ophthalmol, Grad Sch Med, Ube, Yamaguchi, Japan.
EM yanai@yamaguchi-u.ac.jp
OI Yanai, Ryoji/0000-0002-0265-9760; Connor, Kip/0000-0002-2048-9080
FU Santen Pharmaceutical Co., Ltd., Osaka, Japan; Japan Society for the
   Promotion of Science [15K10869]
FX This was an investigator-industry collaborative study, funded by Santen
   Pharmaceutical Co., Ltd., Osaka, Japan. Tomoaki Nanri is an employee of
   Santen Pharmaceutical Co. Ltd. The funding organization provided support
   in the form of salary for author TN. Japan Society for the Promotion of
   Science (15K10869) supported Dr. Ryoji Yanai. The funding organization
   participated in the design of the study, interpretation of the data,
   review and approval of the manuscript, and had no role in the conduct of
   the study, data collection, or analysis of data derived from this study.
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NR 43
TC 19
Z9 19
U1 1
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 APR 25
PY 2018
VL 13
IS 4
AR e0196037
DI 10.1371/journal.pone.0196037
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GD8ZI
UT WOS:000430802400057
PM 29694386
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Guthrie, MJ
   Osswald, CR
   Valio, NL
   Mieler, WF
   Kang-Mieler, JJ
AF Guthrie, Micah J.
   Osswald, Christian R.
   Valio, Nicole L.
   Mieler, William F.
   Kang-Mieler, Jennifer J.
TI Objective area measurement technique for choroidal neovascularization
   from fluorescein angiography
SO MICROVASCULAR RESEARCH
LA English
DT Article
ID TREATED RAT MODEL; MACULAR DEGENERATION; INTRAVITREAL TRIAMCINOLONE;
   SUBRETINAL NEOVASCULARIZATION; ACETONIDE; RANIBIZUMAB; INHIBITION;
   ALGORITHM; THERAPY
AB The purpose of this study was to develop a non-biased method of quantitatively measuring choroidal neovascularization (CNV) areas based on late-phase fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans rats by laser disruption of the Bruch's membrane. FA was performed weekly for 5 weeks. Multi-Otsu thresholding (MOT) was used to quantify CNV in late-phase FA images from both experimental rodent CNV and wet age-related macular degeneration (wAMD) patients. Images were automatically thresholded into three levels based on the image histogram, with the highest level containing CNV. To determine the technique's ability to quantify CNV areas, rats were given either triamcinolone acetonide or dexamethasone sodium phosphate to treat CNV and compared to untreated rats. The rat CNV lesion areas measured from 5-week histology sections from each treatment group were compared to areas measured from the corresponding FA images. MOT was able to detect statistical decreases in rodent CNV area in the treatment groups versus control from weeks 3 through 5. The ratio of CNV area measured from histology to area measured from FA images was not statistically different between groups. Finally, to determine the usefulness of MOT on pathological morphologies of CNV, MOT was performed on late-phase FA images from patients with classic and diffuse CNV. The technique was able to segment classical CNV in wAMD patients, but performed poorly with diffuse CNV. MOT provides a robust, objective, and quantifiable area measurement of CNV lesion area in both experimentally-induced and pathological CNV. The results indicate that MOT could be a useful research tool in helping evaluate the effects of therapeutics on CNV growth. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Guthrie, Micah J.; Osswald, Christian R.; Kang-Mieler, Jennifer J.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
   [Valio, Nicole L.] IIT, Dept Biol & Chem Sci, Chicago, IL 60616 USA.
   [Mieler, William F.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
C3 Illinois Institute of Technology; Illinois Institute of Technology;
   University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital
RP Kang-Mieler, JJ (通讯作者)，IIT, Dept Biomed Engn, 3255 South Dearborn St,Wishnick Hall Room 314, Chicago, IL 60616 USA.
EM kang-mieler@iit.edu
OI Kang-Mieler, Jennifer/0000-0002-2844-5066
FU Northwestern University Mouse Histology and Phenotyping Laboratory;
   Cancer Center Support Grant [NCI CA060553]; NATIONAL CANCER INSTITUTE
   [P30CA060553] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R15EY020807] Funding Source: NIH RePORTER
FX Histology presented in this work was supported by the Northwestern
   University Mouse Histology and Phenotyping Laboratory and a Cancer
   Center Support Grant (NCI CA060553).
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NR 31
TC 11
Z9 11
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0026-2862
EI 1095-9319
J9 MICROVASC RES
JI Microvasc. Res.
PD JAN
PY 2014
VL 91
BP 1
EP 7
DI 10.1016/j.mvr.2013.11.005
PG 7
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 296BY
UT WOS:000330161300001
PM 24316422
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Woodell, A
   Coughlin, B
   Kunchithapautham, K
   Casey, S
   Williamson, T
   Ferrell, WD
   Atkinson, C
   Jones, BW
   Rohrer, B
AF Woodell, Alex
   Coughlin, Beth
   Kunchithapautham, Kannan
   Casey, Sarah
   Williamson, Tucker
   Ferrell, W. Drew
   Atkinson, Carl
   Jones, Bryan W.
   Rohrer, Baerbel
TI Alternative Complement Pathway Deficiency Ameliorates Chronic
   Smoke-Induced Functional and Morphological Ocular Injury
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; FACTOR-H
   POLYMORPHISM; CAUSES OXIDATIVE DAMAGE; MACULAR DEGENERATION;
   CIGARETTE-SMOKE; BRUCHS MEMBRANE; FACTOR-B; CHOROIDAL
   NEOVASCULARIZATION; MITOCHONDRIAL DYSFUNCTION
AB Background: Age-related macular degeneration (AMD), a complex disease involving genetic variants and environmental insults, is among the leading causes of blindness in Western populations. Genetic and histologic evidence implicate the complement system in AMD pathogenesis; and smoking is the major environmental risk factor associated with increased disease risk. Although previous studies have demonstrated that cigarette smoke exposure (CE) causes retinal pigment epithelium (RPE) defects in mice, and smoking leads to complement activation in patients, it is unknown whether complement activation is causative in the development of CE pathology; and if so, which complement pathway is required.
   Methods: Mice were exposed to cigarette smoke or clean, filtered air for 6 months. The effects of CE were analyzed in wildtype (WT) mice or mice without a functional complement alternative pathway (AP; CFB-/-) using molecular, histological, electrophysiological, and behavioral outcomes.
   Results: CE in WT mice exhibited a significant reduction in function of both rods and cones as determined by electroretinography and contrast sensitivity measurements, concomitant with a thinning of the nuclear layers as measured by SD-OCT imaging and histology. Gene expression analyses suggested that alterations in both photoreceptors and RPE/choroid might contribute to the observed loss of function, and visualization of complement C3d deposition implies the RPE/Bruch's membrane (BrM) complex as the target of AP activity. RPE/BrM alterations include an increase in mitochondrial size concomitant with an apical shift in mitochondrial distribution within the RPE and a thickening of BrM. CFB-/- mice were protected from developing these CE-mediated alterations.
   Conclusions: Taken together, these findings provide clear evidence that ocular pathology generated in CE mice is dependent on complement activation and requires the AP. Identifying animal models with RPE/BrM damage and verifying which aspects of pathology are dependent upon complement activation is essential for developing novel complement-based treatment approaches for the treatment of AMD.
C1 [Woodell, Alex; Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA.
   [Coughlin, Beth; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Casey, Sarah; Williamson, Tucker; Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
   [Ferrell, W. Drew; Jones, Bryan W.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA.
   [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; 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
RP Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA.
EM rohrer@musc.edu
OI Jones, Bryan/0000-0001-5527-6643
FU Department for Veterans Affairs [RX000444]; Research to Prevent
   Blindness (RPB), New York, NY; Foundation Fighting Blindness, Columbia,
   MD; NIH NHLBI [RO1 091944]; NIH [C06RR015455]; NATIONAL CENTER FOR
   RESEARCH RESOURCES [C06RR015455] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [R01EY019320] Funding Source: NIH RePORTER; NATIONAL
   HEART, LUNG, AND BLOOD INSTITUTE [R01HL091944] Funding Source: NIH
   RePORTER; Veterans Affairs [I01RX000444] Funding Source: NIH RePORTER
FX This work was supported in part by a Department for Veterans Affairs
   merit award RX000444 (BR), unrestricted grant to MUSC from Research to
   Prevent Blindness (RPB), New York, NY and Foundation Fighting Blindness,
   Columbia, MD, and NIH NHLBI RO1 091944 (CA). Animal studies were
   conducted in a facility constructed with support from the NIH
   (C06RR015455). The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
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   Zhang HB, 2008, J NEUROSCI, V28, P4008, DOI 10.1523/JNEUROSCI.0317-08.2008
   ZHU BQ, 1995, AM HEART J, V130, P1270, DOI 10.1016/0002-8703(95)90154-X
NR 93
TC 38
Z9 38
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 JUN 25
PY 2013
VL 8
IS 6
AR e67894
DI 10.1371/journal.pone.0067894
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 175IB
UT WOS:000321223000122
PM 23825688
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Hefner, L
   Riese, J
   Gerding, H
AF Hefner, L.
   Riese, J.
   Gerding, H.
TI Three Years Follow-up Results of Ranibizumab Treatment for Choroidal
   Neovascularization Secondary to Pathologic Myopia
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE choroidal neovascularization (CNV); pathologic myopia (PM); Ranibizumab;
   anti-VEGF; Lucentis
ID INTRAVITREAL RANIBIZUMAB; PHOTODYNAMIC THERAPY; ANTI-VEGF; BEVACIZUMAB
AB Background: Choroidal neovascularization (CNV) secondary to pathological myopia (PM) is one of the main causes of severe visual impairment in patients younger than 50 years. In this analysis we want to demonstrate the long-term results of Ranibizumab treating CNV secondary to PM.
   Patients and Methods: We retrospectively analysed 15 treatment naive eyes of 13 patients (10 women, 3 men, mean age: 61.5, SD 11.6, range: 41-80) with visual impairment due to CNV secondary to PM, which were treated with ranibizumab. Criteria for re-treatment were reduction of visual acuity and/or activity in OCT or fluorescence angiography.
   Results: We applied a mean of 3 injections (standard deviation [SD] 2.5, range: 1-8) ranibizumab during a mean period of 39.6 months (SD 5.3, range: 31-52). The spherical equivalent was -12.4 diopters +/- 4.1 (range -7.5 to -20.5 diopters). Before the first injection mean visual acuity (logMAR) was 0.69 +/- 0.26. After one month visual acuity improved to 0.39 +/- 0.23 (p = 0.002), after 3 months to 0.30 +/- 0.22 (p = 0.002) and after 6 months up to 0.30 +/- 0.22 (p = 0.002). After 12 months visual acuity was 0.30 +/- 0.22 (p = 0.001) and after 24 months 0.30 +/- SD 0.24 (p = 0.001). 11 patients reached a follow-up of at least 36 months and visual acuity was 0.30 +/- 0.13 (p = 0,001).
   Conclusions: Treating CNV secondary to PM with ranibizumab during a follow-up of 36 months, we found considerable improvement of visual acuity. Compared to treatment of CNV secondary to exudative age-related macular degeneration, CNVs secondary to PM seem to respond faster to ranibizumab treatment and less injections are neccessary to reach stabilization.
C1 [Hefner, L.; Riese, J.; Gerding, H.] Klin Pallas, Dept Retinol, CH-4600 Olten, Switzerland.
   [Gerding, H.] Univ Munster, Dept Ophthalmol, Munster, Germany.
C3 University of Munster
RP Hefner, L (通讯作者)，Klin Pallas, Augenzentrum, Abt Retinol, Louis Giroud Str 20, CH-4600 Olten, Switzerland.
EM lars.hefner@klinik-pallas.ch
RI Gerding, Heinrich/M-2363-2019
OI Gerding, Heinrich/0000-0003-3968-5601
CR Blinder KJ, 2003, OPHTHALMOLOGY, V110, P667, DOI 10.1016/S0161-6420(02)01998-X
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NR 20
TC 15
Z9 15
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0023-2165
EI 1439-3999
J9 KLIN MONATSBL AUGENH
JI Klinische Monatsblat. Augenheilkunde
PD APR
PY 2013
VL 230
IS 4
BP 401
EP 404
DI 10.1055/s-0032-1328366
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 134OO
UT WOS:000318222000025
PM 23629791
DA 2022-11-30
ER

PT J
AU Goldacre, MJ
   Wotton, CJ
   Keenan, TDL
AF Goldacre, Michael J.
   Wotton, Clare J.
   Keenan, Tiarnan D. L.
TI Risk of selected eye diseases in people admitted to hospital for
   hypertension or diabetes mellitus: record linkage studies
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID POSTERIOR VITREOUS DETACHMENT; RETINAL VEIN OCCLUSION; OPEN-ANGLE
   GLAUCOMA; SYSTEMIC HYPERTENSION; CATARACTS
AB Aims Associations among hypertension, diabetes mellitus and some ophthalmic diseases are well established; associations with others are more equivocal. The aim was to quantify associations accurately using large epidemiological datasets.
   Methods Analysis of the Oxford Record Linkage Study (ORLS), 1963-1998, and English linked hospital episode statistics (LHES), 1999-2010; calculation of rate ratios of eye disease in a hypertension cohort and a diabetes cohort, compared with a reference cohort as control.
   Results Risk of cataract following hypertension was marginally elevated (rate ratio ORLS 1.15, 95% CI 1.00 to 1.31; LHES 1.06, 1.01 to 1.10), as was risk of glaucoma (LHES 1.07, 1.00 to 1.14) and age-related macular degeneration (AMD) (LHES 1.14, 1.02 to 1.27). Risk of retinal vein or artery occlusion was elevated three-to fivefold in both populations. Risk of retinal detachment was elevated in LHES at 1.52 (1.43 to 1.73). Risk of cataract in diabetes was high in ORLS and LHES at, respectively, 2.95 (2.75 to 3.16) and 2.30 (2.24 to 2.35), as was risk of glaucoma: 2.47 (2.14 to 2.84) and 2.23 (2.15 to 2.30). Risks were high for AMD (10.3, 8.1 to 13.1, and 3.46, 3.35 to 3.58) and retinal detachment (3.41, 2.71 to 4.25, and 7.96, 7.63 to 8.30), and very high for retinal vein and artery occlusion.
   Conclusions With the exception of retinal vascular occlusion, elevations of risk of the ophthalmic diseases studied in hypertension were modest. By contrast, there were significant and substantial increases of risk for each eye disease in people with diabetes.
C1 [Keenan, Tiarnan D. L.] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PT, Lancs, England.
   [Keenan, Tiarnan D. L.] Manchester Royal Eye Hosp, Manchester M13 9WH, Lancs, England.
   [Goldacre, Michael J.; Wotton, Clare J.] Univ Oxford, Dept Publ Hlth, Unit Hth Care Epidemiol, Oxford, England.
C3 University of Manchester; Manchester Royal Eye Hospital; University of
   Oxford
RP Keenan, TDL (通讯作者)，Univ Manchester, Fac Med & Human Sci, AV Hill Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
EM tiarnan.keenan@doctors.org.uk
RI Wotton, Clare J/L-8863-2018; Wotton, Clare/L-8863-2018
OI Wotton, Clare J/0000-0002-7173-1009; Wotton, Clare/0000-0002-5753-907X
FU English National Institute for Health Research; Fight For Sight through
   a Clinical Fellowship; Fight for Sight [1865/66] Funding Source:
   researchfish
FX The Unit of Health-Care Epidemiology is funded by the English National
   Institute for Health Research to analyse the linked data. The views
   expressed in this paper do not necessarily reflect those of the funding
   body. TDLK is funded by Fight For Sight through a Clinical Fellowship.
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NR 25
TC 16
Z9 16
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 JUN
PY 2012
VL 96
IS 6
BP 872
EP 876
DI 10.1136/bjophthalmol-2012-301519
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 946IX
UT WOS:000304346300022
PM 22493039
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Kehler, AK
   Andersen, C
   Andreasen, JR
   Vohra, R
   Junker, N
   Poulsen, KA
   Kolko, M
AF Kehler, Anne Katrine
   Andersen, Cammilla
   Andreasen, Jens Rovelt
   Vohra, Rupali
   Junker, Nanna
   Poulsen, Kristian Arild
   Kolko, Miriam
TI Interaction between VEGF and Calcium-Independent Phospholipase A(2) in
   Proliferation and Migration of Retinal Pigment Epithelium
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium; VEGF; iPLA2-VIA; proliferation; migration
ID ENDOTHELIAL GROWTH-FACTOR; ARACHIDONIC-ACID RELEASE; MACULAR
   DEGENERATION; P388D(1) MACROPHAGES; SUICIDE INHIBITION; CELLS;
   ACTIVATION; LEUKOTRIENE; EXPRESSION; MEMBRANES
AB Purpose: Inhibition of VEGF in the eye is an important treatment modality for reducing proliferation and migration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). Additionally, previous studies suggest calcium-independent phospholipase A(2) group VIA (iPLA(2)-VIA) to be a potential regulator of cell proliferation and migration, and evidence show abundant expression of iPLA(2)-VIA in RPE cells. The aim of the present study was to evaluate the potential role of iPLA(2)-VIA in VEGF-induced proliferation and migration of RPE cells.
   Materials and methods: The human RPE cell line, ARPE-19, was used in all assays. To explore the role of iPLA(2)-VIA in VEGF-induced RPE proliferation and migration, iPLA(2)-VIA inhibition by the iPLA(2)-VIA specific inhibitor, bromoenol lactone, was done. RPE cell proliferation and migration were evaluated by measurements of incorporated radioactive thymidine in DNA and by a Boyden chamber technique, respectively. A luciferase assay monitored the VEGF-induced iPLA(2)-VIA transcriptional activity. Western blot analysis and an activity assay were used to detect the protein levels and activity of iPLA(2)-VIA respectively after treatment with VEGF.
   Results: RPE cells treated with VEGF showed significant increased proliferation and migration. Furthermore, inhibition of iPLA(2)-VIA significantly reduced the spontaneous proliferation and migration as well as the VEGF-induced proliferation and migration. Finally, inhibition of iPLA(2)-VIA reduced the VEGF-induced iPLA(2)-VIA-activity, -protein level, and-promoter activity.
   Conclusions: A significant interaction between VEGF and iPLA(2)-VIA in the regulation of RPE cells appears to be relevant in elucidating the exact mechanisms of action in the proliferative and migratory phenotype of RPE cells in AMD.
C1 [Kehler, Anne Katrine; Andersen, Cammilla; Andreasen, Jens Rovelt; Vohra, Rupali; Poulsen, Kristian Arild; Kolko, Miriam] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark.
   [Kehler, Anne Katrine; Andersen, Cammilla; Andreasen, Jens Rovelt; Vohra, Rupali; Poulsen, Kristian Arild; Kolko, Miriam] Univ Copenhagen, Panum Inst, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark.
   [Junker, Nanna] Univ Copenhagen, Panum Inst, Dept Biomed Sci, DK-2200 Copenhagen, Denmark.
   [Kolko, Miriam] Glostrup Univ Hosp, Dept Ophthalmol, Copenhagen, Denmark.
C3 University of Copenhagen; University of Copenhagen; University of
   Copenhagen; University of Copenhagen
RP Kehler, AK (通讯作者)，Galionsvej 1,2-32, DK-1437 Copenhagen, Denmark.
EM akkehler@yahoo.com; mkolko@dadlnet.dk
OI Kolko, Miriam/0000-0001-8697-0734; Vohra, Rupali/0000-0002-3326-7655;
   Toft-Kehler, Anne Katrine/0000-0003-4402-7101
FU Danish Eye Foundation; Danish Eye Health Society; Lundbeck Foundation
FX The authors thank technician Charlotte Taul Braendstrup, Department of
   International Health, Immunology and Microbiology, University of
   Copenhagen, Denmark for skillful assistance to the study and Michael
   Gelb, Departments of Chemistry and Biochemistry, University of
   Washington, Seattle, for providing the cPLA 2 inhibitors Pyrrolidine and
   Wyeth-1. The study was supported by The Danish Eye Foundation, The
   Danish Eye Health Society, and The Lundbeck Foundation.
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NR 33
TC 8
Z9 8
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0271-3683
J9 CURR EYE RES
JI Curr. Eye Res.
PD JUN
PY 2012
VL 37
IS 6
BP 500
EP 507
DI 10.3109/02713683.2012.663855
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 942RH
UT WOS:000304064200008
PM 22577768
DA 2022-11-30
ER

PT J
AU Glenn, JV
   Mahaffy, H
   Dasari, S
   Oliver, M
   Chen, M
   Boulton, ME
   Xu, H
   Curry, WJ
   Stitt, AW
AF Glenn, J. V.
   Mahaffy, H.
   Dasari, S.
   Oliver, M.
   Chen, M.
   Boulton, M. E.
   Xu, H.
   Curry, W. J.
   Stitt, Alan W.
TI Proteomic profiling of human retinal pigment epithelium exposed to an
   advanced glycation-modified substrate
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Bruch's membrane; RPE; Advanced glycation endproducts; Ubiquitin
   carboxyterminal hydrolase-1
ID PROTEIN-DISULFIDE-ISOMERASE; APOPTOTIC CELL-DEATH; HUMAN RPE CELLS;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; END-PRODUCTS;
   EXTRACELLULAR-MATRIX; GROWTH-FACTOR; UP-REGULATION; AGE
AB The retinal pigment epithelium (RPE) and underlying Bruch's membrane undergo significant modulation during ageing. Progressive, age-related modifications of lipids and proteins by advanced glycation end products (AGEs) at this cell-substrate interface have been implicated in RPE dysfunction and the progression to age-related macular degeneration (AMD). The pathogenic nature of these adducts in Bruch's membrane and their influence on the overlying RPE remains unclear. This study aimed to identify alterations in RPE protein expression in cells exposed to AGE-modified basement membrane (AGE-BM), to determine how this "aged" substrate impacts RPE function and to map the localisation of identified proteins in ageing retina.
   Confluent ARPE-19 monolayers were cultured on AGE-BM and native, non-modified BM (BM). Following 28-day incubation, the proteome was profiled using 2-dimensional gel electrophoresis (2D), densitometry and image analysis was employed to map proteins of interest that were identified by electrospray ionisation mass spectrometry (ESI MS/MS). Immunocytochemistry was employed to localise identified proteins in ARPE-19 monolayers cultured on unmodified and AGE-BM and to analyze aged human retina.
   Image analysis detected altered protein spot densities between treatment groups, and proteins of interest were identified by LC ESI MS/MS which included heat-shock proteins, cytoskeletal and metabolic regulators. Immunocytochemistry revealed deubiquitinating enzyme ubiquitin carboxyterminal hydrolase-1 (UCH-L1), which was upregulated in AGE-exposed RPE and was also localised to RPE in human retinal sections.
   This study has demonstrated that AGE-modification of basement membrane alters the RPE proteome. Many proteins are changed in this ageing model, including UCHL-1, which could impact upon RPE degradative capacity. Accumulation of AGEs at Bruch"s membrane could play a significant role in age-related dysfunction of the RPE.
C1 [Glenn, J. V.; Mahaffy, H.; Dasari, S.; Chen, M.; Xu, H.; Curry, W. J.; Stitt, Alan W.] Queens Univ Belfast, Royal Victoria Hosp, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Glenn, J. V.; Mahaffy, H.; Dasari, S.; Chen, M.; Xu, H.; Curry, W. J.; Stitt, Alan W.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Oliver, M.] Waters MS Technol Ctr, Manchester, Lancs, England.
   [Boulton, M. E.] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL USA.
C3 Queens University Belfast; Queens University Belfast; Waters UK; State
   University System of Florida; University of Florida
RP Stitt, AW (通讯作者)，Queens Univ Belfast, Royal Victoria Hosp, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM a.stitt@qub.ac.uk
RI Xu, Heping/A-4430-2008; Stitt, Alan/A-9842-2009
OI Xu, Heping/0000-0003-4000-931X; Stitt, Alan/0000-0002-8647-9918
FU Wellcome Trust; Medical Research Council (MRC); Action Medical Research;
   NIH [EY019688]; MRC [G0600053] Funding Source: UKRI; NATIONAL EYE
   INSTITUTE [P30EY021721, R01EY019688] Funding Source: NIH RePORTER;
   Medical Research Council [G0600053] Funding Source: researchfish
FX The authors would like to acknowledge financial support from the
   Wellcome Trust, The Medical Research Council (MRC), Action Medical
   Research, and NIH grant EY019688. The authors would like to thank the
   Bristol Eye Bank for their donation of clinical material. AWS holds a
   Royal Society Wolfson Merit Award.
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NR 56
TC 14
Z9 14
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2012
VL 250
IS 3
BP 349
EP 359
DI 10.1007/s00417-011-1856-9
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 902LH
UT WOS:000301039100005
PM 22081232
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Yang, DL
   Elner, SG
   Chen, X
   Field, MG
   Petty, HR
   Elner, VM
AF Yang, Dongli
   Elner, Susan G.
   Chen, Xun
   Field, Matthew G.
   Petty, Howard R.
   Elner, Victor M.
TI MCP-1-Activated Monocytes Induce Apoptosis in Human Retinal Pigment
   Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CYCLIC-ADP-RIBOSE; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION;
   INTERCELLULAR-ADHESION MOLECULE-1; PRO-INFLAMMATORY CYTOKINES; MACULAR
   DEGENERATION; PROLIFERATIVE VITREORETINOPATHY; CHEMOATTRACTANT
   PROTEIN-1; EPIRETINAL MEMBRANES; ENDOTHELIAL-CELLS; PERMEABILITY
   TRANSITION
AB PURPOSE. The inflammatory response in age-related macular degeneration (AMD) is characterized by mononuclear leukocyte infiltration of the outer blood-retina barrier formed by the retinal pigment epithelium (RPE). A key mechanistic element in AMD progression is RPE dysfunction and apoptotic cell loss. The purpose of this study was to evaluate whether monocyte chemoattractant protein (MCP)-1-activated monocytes induce human RPE apoptosis and whether Ca(2+) and reactive oxygen species(ROS) are involved in this process.
   METHODS. A cell-based fluorometric assay was used to measure intracellular Ca(2+) concentrations ([Ca(2+)](i)) in RPE cells loaded with fluorescent Ca(2+) indicator. Intracellular RPE ROS levels were measured by using the 5- and 6-chloromethyl-2',7'-dichlorodihydrofluorescence diacetate acetyl ester(CM-H(2)DCFDA) assay. RPE apoptosis was evaluated by activated caspase-3, Hoechst staining, and apoptosis ELISA.
   RESULTS. MCP-1-activated human monocytes increased [Ca(2+)]i, ROS levels, and apoptosis in RPE cells, all of which were inhibited by 8-bromo-cyclic adenosine diphosphoribosyl ribose (8-Br-cADPR), an antagonist of cADPR. Although the ROS scavengers pyrrolidinedithiocarbamate(PDTC) and N-acetylcysteine (NAC) significantly inhibited ROS production and apoptosis induced by activated monocytes, they did not affect induced Ca(2+) levels. The induced Ca(2+) levels and apoptosis in RPE cells were inhibited by an antibody against cluster of differentiation antigen 14 (CD14), an adhesion molecule expressed by these cells.
   CONCLUSIONS. These results indicate that CD14, Ca(2+), and ROS are involved in activated monocyte-induced RPE apoptosis and that cADPR contributes to these changes. Understanding the complex interactions among CD14, cADPR, Ca(2+), and ROS may provide new insights and treatments of retinal diseases, including AMD.(Invest Ophthalmol Vis Sci. 2011;52:6026-6034) DOI:10.1167/iovs.10-7023
C1 [Elner, Victor M.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Petty, Howard R.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
   [Elner, Victor M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan; University of Michigan System;
   University of Michigan
RP Elner, VM (通讯作者)，Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
EM velner@umich.edu
OI , Howard/0000-0001-8516-3666; Elner, Victor/0000-0001-7708-1898
FU National Institutes of Health [R01EY009441, EY019986, P30EY07003];
   University of Michigan Claude Pepper Older Americans Independence
   Center; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [P30EY007003, R21EY019986, R01EY009441] Funding Source: NIH RePORTER
FX Supported by the National Institutes of Health Grants R01EY009441 (VME),
   EY019986 (HRP) and P30EY07003 (core), and by a pilot grant from the
   University of Michigan Claude Pepper Older Americans Independence Center
   (DY). VME is a recipient of the Senior Scientific Investigator Award
   from Research to Prevent Blindness.
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NR 88
TC 35
Z9 37
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 6026
EP 6034
DI 10.1167/iovs.10-7023
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800QC
UT WOS:000293377400130
PM 21447688
OA Green Published
DA 2022-11-30
ER

PT J
AU Tarita-Nistor, L
   Gonzalez, EG
   Markowitz, SN
   Steinbach, MJ
AF Tarita-Nistor, Luminita
   Gonzalez, Esther G.
   Markowitz, Samuel N.
   Steinbach, Martin J.
TI Plasticity of fixation in patients with central vision loss
SO VISUAL NEUROSCIENCE
LA English
DT Article
DE Central vision loss; PRL; Fixation stability training; Plasticity of
   ocular motor system
ID PREFERRED RETINAL LOCI; SCANNING LASER OPHTHALMOSCOPE; MACULAR
   DEGENERATION; CENTRAL SCOTOMAS; OPTOKINETIC NYSTAGMUS;
   STARGARDT-DISEASE; VISUAL-CORTEX; READING SPEED; LOCATION;
   REORGANIZATION
AB The aim of this study was to explore the plasticity of fixation in patients with central vision loss. Most of these patients use preferred retinal loci (PRLs) in the healthy eccentric part of the retina to fixate, but fixation stability and retinal location are not always optimal for best visual performance. This Study examined whether fixation stability and a new PRL location can be trained and whether these changes in Ocular motor control transfer into better reading performance. Six patients with age-related macular degeneration participated in the study. Fixation stability measurements, microperimetry, and auditory biofeedback training were performed with the MP-1 microperimeter. The auditory biofeedback was used during five 1-h long training sessions to improve fixation and relocate the PRL. Fixation location and stability were recorded while viewing four different targets: a cross, a letter, a word, and a nine-cycle radial grating. Visual acuity was assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and reading performance with the MNRead test. The results showed that all patients developed a new PRL in an optimal location for reading, and they were able to use it consistently while viewing different targets. Fixation stability improved 53% after training. Learning transferred to the old PRL even though fixation stability at this location was not trained. All these improvements in ocular motor control translated into better reading performance: reading speed improved 38% and reading acuity and critical print size gained two lines. We conclude that the ability of the ocular motor system to fixate is flexible in patients with central vision loss: a new PRL can be trained, fixation stability call be improved, and learning transfers to all untrained location. These gains in Ocular motor control result ill better visual performance. This property can be Successfully used to optimize the residual vision of patients with central vision loss.
C1 [Tarita-Nistor, Luminita; Gonzalez, Esther G.; Steinbach, Martin J.] Toronto Western Res Inst, Vis Sci Res Program, Toronto, ON M5T 2S8, Canada.
   [Gonzalez, Esther G.; Steinbach, Martin J.] York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada.
   [Gonzalez, Esther G.; Markowitz, Samuel N.; Steinbach, Martin J.] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto; York University - Canada; University of Toronto
RP Gonzalez, EG (通讯作者)，Toronto Western Res Inst, Vis Sci Res Program, 399 Bathurst St,FP 6-212, Toronto, ON M5T 2S8, Canada.
EM gonzalez@yorku.ca
FU CNIB EA Baker Applied Research; Natural Sciences and Engineering
   Research Council of Canada [A7664]; Sir Jules Thorn Charitable Trust;
   Krembil Family Foundation; Vision Science Research Program, Toronto
   Western Hospital
FX The authors thank the two anonymous reviewers for their. helpful
   suggestions and Linda Lillakas for her valuable comments on the
   manuscript. The study was supported by the CNIB EA Baker Applied
   Research Grant (E.G.G.); Natural Sciences and Engineering Research
   Council of Canada grant A7664 (M.J.S.); the Sir Jules Thorn Charitable
   Trust (M.J.S.); the Krembil Family Foundation (M.J.S.); Vision Science
   Research Program, Toronto Western Hospital; and an anonymous donor.
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NR 40
TC 78
Z9 84
U1 0
U2 22
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
EI 1469-8714
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PD SEP-DEC
PY 2009
VL 26
IS 5-6
BP 487
EP 494
DI 10.1017/S0952523809990265
PG 8
WC Neurosciences; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology
GA 562CZ
UT WOS:000275028200006
PM 20003597
DA 2022-11-30
ER

PT J
AU Mir, Y
   van Lier, JE
   Allard, JF
   Morris, D
   Houde, D
AF Mir, Youssef
   van Lier, Johan E.
   Allard, Jean-Francois
   Morris, Denis
   Houde, Daniel
TI Two-photon absorption cross section of excited phthalocyanines by a
   femtosecond Ti-sapphire laser
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID PHOTODYNAMIC THERAPY; PHOTOCHEMICAL PROPERTIES; BIOLOGICAL-ACTIVITIES;
   ZINC; FLUORESCENCE; EXCITATION; PHOTOSENSITIZERS; TETRASULFONATE;
   OXYGEN; YIELD
AB In the past few years, photodynamic therapy (PDT) has become a major treatment for neovascular age-related macular degeneration (AMD) in which there is abnormal growth of choroidal neovasculature (CNV) that eventually obscures central vision, leading to blindness. However, one of the main limitations of current PDT is the relatively low specificity of the photosensitizer (PS) and light for pathological tissue which may induce damage to adjacent healthy tissue. An alternative approach to circumvent the specificity limitation is to improve the irradiation process. In particular two photon (2-gamma) excitation promises a more precise illumination of the target tissue. PS are activated by the simultaneous absorption of 2-gamma delivered by ultra-fast pulses of near infrared light. In order to evaluate the efficiency of phthalocyanine (Pc) dyes for 2-gamma absorption we measured 2-gamma absorption cross sections (sigma(2)) of a number of metalated Pc (MPc) dyes at lambda(ex) = 800 nm using a femtosecond laser. The studied Pc molecules vary by the type of the central metal ion (Al or Zn) and the number of peripheral sulfo substituents (MPcS). Each MPc dye of our series shows an improved 2-gamma absorption sigma(2) as compared to that obtained for Photofrin (3.1 +/- 0.1 GM, with 1 GM = 10(-50) cm(4) s photon(-1) mol(-1)), the PS currently approved for 1-gamma PDT. Our data show an 2.5-fold enhancement for AlPcCl, AlPcS2adj and ZnPcS3C9, up to 10-fold (28.6 +/- 0.72 GM) for the ZnPcS4 dye relative to Photofrin. These findings confirm the efficiency of Pc for 2-gamma absorption processes and represent the first detailed comparison study of 2-gamma absorption sigma(2) between Photofrin and Pc dyes.
C1 [Mir, Youssef; van Lier, Johan E.; Allard, Jean-Francois; Houde, Daniel] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med Nucl & Radiobiol, Sherbrooke, PQ J1H 5N4, Canada.
   [Morris, Denis] Univ Sherbrooke, Fac Sci, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
C3 University of Sherbrooke; University of Sherbrooke
RP Houde, D (通讯作者)，Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med Nucl & Radiobiol, Sherbrooke, PQ J1H 5N4, Canada.
EM Daniel.Houde@usherbrooke.ca
RI Mir, Youssef/ABD-8309-2021
OI Mir, Youssef/0000-0002-7421-9545
FU Canadian Institutes of Health Research (CIHR) [MOP-37768]; Canadian
   Institute for Photonics Innovations; Intelligent Materials and Systems
   Institute of the University of Sherbrooke
FX Funding for this research was provided by the Canadian Institutes of
   Health Research (CIHR, grant no MOP-37768) (J. E. v. L.), the Canadian
   Institute for Photonics Innovations ( D. H.) and by the Intelligent
   Materials and Systems Institute of the University of Sherbrooke ( D.
   H.).
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NR 38
TC 20
Z9 20
U1 0
U2 1
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1474-905X
EI 1474-9092
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PY 2009
VL 8
IS 3
BP 391
EP 395
DI 10.1039/b805909h
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA 414FB
UT WOS:000263848200013
PM 19255681
DA 2022-11-30
ER

PT J
AU Zou, YH
   Xu, XR
   Chiou, GCY
AF Zou, YH
   Xu, XR
   Chiou, GCY
TI Effect of interleukin-1 blockers, CK112, and CK116 on rat experimental
   choroidal neovascularization in vivo and endothelial cell cultures in
   vitro
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID CORNEAL FIBROBLAST PROLIFERATION; PREVALENCE; ANTAGONISM; UVEITIS; EYE
AB Purpose: The aim of this study was to investigate the effect of interleukin-1 blockers, CK112 and CK116, on laser-induced experimental choroidal neovascularization (CNV) in rat models in vivo and endothelial cell proliferation in vitro.
   Methods: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. CK112, CK116, and prednisolone were given once-daily through intraperitoneal (i.p.) injection after laser treatment for 4 weeks. The development of CNV was determined by fluorescein angiography performed on weeks 2 and 4. Human umbilical vein endothelial cells (HUVEC) were tested with proliferation assay with CK112, CK116, and prednisolone at different concentrations.
   Results: The intensity of fluorescein leakage from the photocoagulated lesions decreased significantly, compared to the control group (treated with dimethyl sulfoxide [DMSO] only), following CK112, CK116, and prednisolone treatment. Four (4) weeks after administration, CK112, at 10 mg/kg and 30 mg/kg, inhibited CNV development to 75% and 77% of the control group, respectively (P < 0.01). Both CK116, 10 mg/kg, and prednisolone, 5 mg/kg, inhibited the CNV development to 85% of the control group (P < 0.05). All three compounds interfered with the endothelial cell proliferation significantly. The reduction of the endothelial cells was 50.5% (P < 0.01), 28.5% (P < 0.05), and 23.1% (P < 0.05), respectively, in 500 mu g/mL, 300 mu g/mL, and 100 mu g/mL of the CK112-treated group. CK116 inhibited the cell proliferation significantly to 77.2% of the control group at 500 mu g/mL (P < 0.05).
   Conclusions: CK112 and CK116 inhibited the development of CNV in the rat model and interfered with vascular endothelial cell proliferation in vitro. Our results suggest that CK112 and CK116 may be good candidates to inhibit ocular neovascularization related to age-related macular degeneration (ARMD).
C1 Texas A&M Hlth Sci Ctr, Coll Med, Dept Med Pharmacol & Toxicol, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
C3 Texas A&M University System; Texas A&M University College Station; Texas
   A&M Health Science Center
RP Chiou, GCY (通讯作者)，Texas A&M Hlth Sci Ctr, Coll Med, Dept Med Pharmacol & Toxicol, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
EM gchiou@medicine.tamhsc.edu
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NR 21
TC 19
Z9 29
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 FEB
PY 2006
VL 22
IS 1
BP 19
EP 25
DI 10.1089/jop.2006.22.19
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 019DR
UT WOS:000235816300003
PM 16503771
DA 2022-11-30
ER

PT J
AU Cheng, CY
   Chung, WY
   Szeto, YT
   Benzie, IFF
AF Cheng, CY
   Chung, WY
   Szeto, YT
   Benzie, IFF
TI Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry;
   Kei Tze) in a food-based human supplementation trial
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE macular pigment; AMD; zeaxanthin; lutein; Fructus lycii; Kei Tze;
   wolfberry; antioxidant; oxidative stress
ID MACULAR PIGMENT DENSITY; GOU-QI-ZI; PERFORMANCE LIQUID-CHROMATOGRAPHY;
   MASS-SPECTROMETRY; PROTECTIVE ROLE; LUTEIN; DEGENERATION; CAROTENOIDS;
   SERUM; IDENTIFICATION
AB Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) mumol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) mumol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.
C1 Hong Kong Polytech Univ, Fac Hlth & Social Sci, Antioxidant Res Grp, Kowloon, Hong Kong, Peoples R China.
C3 Hong Kong Polytechnic University
RP Benzie, IFF (通讯作者)，Hong Kong Polytech Univ, Fac Hlth & Social Sci, Antioxidant Res Grp, Kowloon, Hong Kong, Peoples R China.
EM hsbenzie@inet.polyu.edu.hk
RI Szeto, Yim Tong/W-6247-2019; SZETO, Yim Tong/G-1074-2011
OI SZETO, Yim Tong/0000-0002-1711-8510; Benzie, Iris/0000-0002-2312-0318
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NR 31
TC 60
Z9 70
U1 1
U2 29
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JAN
PY 2005
VL 93
IS 1
BP 123
EP 130
DI 10.1079/BJN20041284
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 896FI
UT WOS:000226919600018
PM 15705234
OA Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Chen, X
   Hui, L
   Foster, DA
   Drain, CM
AF Chen, X
   Hui, L
   Foster, DA
   Drain, CM
TI Efficient synthesis and photodynamic activity of porphyrin-saccharide
   conjugates: Targeting and incapacitating cancer cells
SO BIOCHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; PHOSPHOLIPASE-D; RAT FIBROBLASTS; IONIC
   CURRENTS; MULTIFUNCTIONALISED PORPHYRINS; REGIOSELECTIVE SYNTHESIS;
   TUMOR PHOTOSENSITIZERS; BIOLOGICAL EVALUATION; CELLULAR UPTAKE;
   LIPID-BILAYERS
AB Since the role of saccharides in cell recognition, metabolism, and cell labeling is well-established, the conjugation of saccharides to drugs is an active area of research. Thus, one goal in the use of saccharide-drug conjugates is to impart a greater specificity toward a given cell type or other targets. Although widely used to treat some cancers and age related macular degeneration, the drugs used in photodynamic therapy (PDT) display poor chemical selectivity toward the intended targets, and uptake by cells most likely arises from passive, diffusional processes. Instead, the specific irradiation of the target tissues, and the formation of the toxic species in situ, are the primary factors that modulate the selectivity in the present mode of PDT. We report herein a two-step method to make nonhydrolyzable saccharide-porphyrin conjugates in high yields using a tetra(pentafluorophenyl)porphyrin and the thio derivative of the sugar. As a demonstration of their properties, the selective uptake (and/or binding) of these compounds to several cancer cell types was examined, followed by an investigation of their photodynamic properties. As expected, different malignant cell types take up one type of saccharide-porphyrin conjugate preferentially over others; for example, human breast cancer cells (MDA-MB-231) absorb a tetraglucose-porphyrin conjugate over the corresponding galactose derivative. Doseametric studies reveal that these saccharide-porphyrin conjugates exhibit varying PDT responses depending on drug concentration and irradiation energy. (1) Using 20 muM conjugate and greater irradiation energy induces cell death by necrosis. (2) When 10-20 muM conjugate and less irradiation energy are used, both necrosis and apoptosis are observed. (3) Using 10 muM and the least irradiation energy, a significant reduction in cell migration is observed, which indicates a reduction in aggressiveness of the cancer cells.
C1 CUNY Hunter Coll, Dept Chem & Biochem, New York, NY 10021 USA.
   CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA.
   CUNY, Grad Ctr, New York, NY 10021 USA.
   Rockefeller Univ, New York, NY 10021 USA.
C3 City University of New York (CUNY) System; Hunter College (CUNY); City
   University of New York (CUNY) System; Hunter College (CUNY); City
   University of New York (CUNY) System; Rockefeller University
RP Drain, CM (通讯作者)，CUNY Hunter Coll, Dept Chem & Biochem, 695 Pk Ave, New York, NY 10021 USA.
EM cdrain@hunter.cuny.edu
RI Drain, Charles Michael/N-9270-2018
OI Drain, Charles Michael/0000-0003-2541-2813
FU NATIONAL CANCER INSTITUTE [R01CA046677, R29CA046677] Funding Source: NIH
   RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCES [G12RR003037] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [S06GM060654] Funding Source: NIH RePORTER; NCI NIH HHS [R01 CA046677,
   CA46677] Funding Source: Medline; NCRR NIH HHS [RR-03037, G12 RR003037]
   Funding Source: Medline; NIGMS NIH HHS [GM60654, S06 GM060654] Funding
   Source: Medline
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NR 64
TC 184
Z9 192
U1 1
U2 57
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 31
PY 2004
VL 43
IS 34
BP 10918
EP 10929
DI 10.1021/bi049272v
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 849ZI
UT WOS:000223580000008
PM 15323552
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zur, D
   Ullman, S
AF Zur, D
   Ullman, S
TI Filling-in of retinal scotomas
SO VISION RESEARCH
LA English
DT Article
DE filling-in; retinal scotoma; density; regularity; cortical mechanism
ID PRIMARY VISUAL-CORTEX; BLIND SPOT; HUMAN VISION; PERCEPTUAL COMPLETION;
   EXPERIENCE; ADAPTATION; DYNAMICS
AB In this study we examined the perception of one- and two-dimensional patterns across central retinal scotomas, caused by age-related macular degeneration. In contrast with previous studies of disrupted visual input that used the blind spot and artificial scotomas, the current study used large central scotomas caused by physical retinal damage. Such damage is associated with atrophy and long-term cortical reorganization, and it was therefore unclear whether perceptual completion in the damaged system will be similar to that reported for artificial scotomas and the blind spot. In addition, the scotomas under study were much larger and more central than artificial scotomas for which perceptual completion has been reported. For 1-D line and grating patterns, we found perceptual completion across large central scotomas (up to radius of 7), which is significantly beyond the range of perceptual completion in artificial scotomas. Gratings completion was better than that of a single line, and increased with bars density. The use of central scotomas allowed us to test the completion of 2-D patterns that are difficult to study in peripheral vision. We found completion of two-dimensional dot arrays over large regions that improved with pattern density and regularity. The results show that in the physically damaged system the range of perceptual completion is increased compared with artificial scotomas, they strongly support the view of an active filling-in process rather than simply ignoring the damaged location, and they show that perceptual completion of physical scotomas is likely to involve cortical processing at multiple levels. We finally discuss implications of the results to the possible use of image enhancement techniques to facilitate the perception of low-vision individuals. (C) 2003 Elsevier Science Ltd. All rights reserved.
C1 Weizmann Inst Sci, Dept Appl Math & Comp Sci, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science
RP Zur, D (通讯作者)，Rockefeller Univ, Neurobiol Lab, 1230 York Ave,RU Box 108, New York, NY 10021 USA.
EM zurd@mail.rockefeller.edu
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NR 39
TC 76
Z9 79
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD APR
PY 2003
VL 43
IS 9
BP 971
EP 982
DI 10.1016/S0042-6989(03)00038-5
PG 12
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 667VH
UT WOS:000182254400002
PM 12676241
OA Bronze
DA 2022-11-30
ER

PT J
AU Houle, JM
   Strong, HA
AF Houle, JM
   Strong, HA
TI Duration of skin photosensitivity and incidence of photosensitivity
   reactions after administration of verteporfin
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE photodynamic therapy; photosensitivity; verteporfin therapy; Visudyne
AB Background: Verteporfin (Visudyne, Novartis AG) is a light-activated drug that reduces the risk of vision loss in patients with certain types of choroidal neovascularization (CNV). Because photosensitivity can occur with photosensitizers, it is important for ophthalmologists providing verteporfin therapy to understand its time course and duration, as well as the incidence of photosensitivity reactions.
   Methods: Data were obtained from three sources: 1) the time course of skin photosensitivity in 17 volunteers by measuring erythema/edema over time after verteporfin, using red light exposure; 2) the duration of skin photosensitivity in 30 patients with skin cancer by exposing skin to simulated solar light and calculating the daily minimal erythematous dose; and 3) the incidences of photosensitivity reactions as recorded in three phase III trials in patients with CNV secondary to age-related macular degeneration or pathologic myopia who received the regimen of verteporfin therapy currently approved by regulatory authorities (infusion of 6 mg/m(2) body surface area).
   Results: 1) Skin photosensitivity was high at the first timepoint of 1.5 hours after dosing and decreased rapidly thereafter; 2) the duration of skin photosensitivity was dose dependent, ranging from 2.0 to 6.7 days at 6 to 20 mg/m(2), respectively (mean of 2 days at a dose of 6 mg/m(2)); and 3) photosensitivity reactions occurred in only 2.2% of,patients in the phase III trials, including two severe events, one secondary to extravasation. All treatment-related reactions in the phase III trials occurred within the first 2 days after dosing, with the exception of two mild reactions and one moderate reaction that occurred 3 days after treatment.
   Conclusions: Verteporfin is associated with short-lived photosensitivity and a low incidence of photosensitivity reactions in clinical trials, most of which could probably have been avoided by adherence to protocol instructions for skin protection.
C1 Jean Marie Houle QLT Inc, Vancouver, BC V5T 4T5, Canada.
RP Houle, JM (通讯作者)，Jean Marie Houle QLT Inc, 887 Great No Way, Vancouver, BC V5T 4T5, Canada.
CR Arnold J, 2001, OPHTHALMOLOGY, V108, P841
   Arnold J, 2001, AM J OPHTHALMOL, V131, P541
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   *TREATM AG REL MAC, 2002, RETINA, V22, P6
   *VERT PHOT THER ST, 2002, UNPUB OPHTHALMOLOGY
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NR 10
TC 28
Z9 30
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 DEC
PY 2002
VL 22
IS 6
BP 691
EP 697
DI 10.1097/00006982-200212000-00002
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 627UQ
UT WOS:000179954900002
PM 12476093
DA 2022-11-30
ER

PT J
AU Trotter, WL
   Miller, KM
AF Trotter, WL
   Miller, KM
TI Outcomes of cataract extraction in functionally monocular patients -
   Case-control study
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
AB Purpose: To compare the ocular comorbidities, visual outcomes, and surgical complications between a series of functionally monocular patients who had phacoemulsification and intraocular lens (10L) implantation and a control group of age- and sex-matched binocular patients.
   Setting: Jules Stein Eye Institute and the Department of Ophthalmology, UCLA School of Medicine, Los Angeles, California, USA.
   Methods: The records of a consecutive series of 100 functionally monocular patients who had phacoemulsification and IOL implantation were reviewed. The records of a control group of binocularly sighted patients who were matched to the monocular patients by age, sex, and date of surgery were also reviewed.
   Results: Thirteen patients in the monocular group were monocular because of surgical complications. The remaining patients (87%) were monocular from medical conditions. Monocular patients had significantly more ocular comorbidity than binocular control patients (P < .0001). Age-related macular degeneration, diabetic retinopathy, and open-angle glaucoma were the most common reasons for monocular status and the most common ocular comorbidities in study eyes. The median preoperative best corrected visual acuity (BCVA) was 20/50 in the monocular group and 20/40 in the binocular group. The median postoperative BCVA was 20/25 and 20/20, respectively. A final BCVA of 20/40 or worse was the result of preexisting macular pathology or glaucoma in every instance. Surgical complications (P = .096) and the number of postoperative procedures (P = .724) were similar between the 2 groups.
   Conclusions: Ocular comorbidity was significantly more prevalent in the eyes of monocular patients. Monocular and binocular patients experienced a 3-line improvement in BCVA after cataract surgery; however, the final median acuity was 20/25 in the monocular group and 20/20 in the binocular group. The 2 groups had a similar complication rate. (C) 2002 ASCRS and ESCRS.
C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   Univ Calif Los Angeles, Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Miller, KM (通讯作者)，Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA.
RI Miller, Kevin/ABB-5906-2021
OI Miller, Kevin/0000-0002-5128-0685
CR *AM AC OPHTH, 2001, CAT AD EY
   Bergwerk KL, 2000, J CATARACT REFR SURG, V26, P1631, DOI 10.1016/S0886-3350(00)00440-5
   MILLER KM, 1994, AM J OPHTHALMOL, V117, P107, DOI 10.1016/S0002-9394(14)73023-5
NR 3
TC 11
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD AUG
PY 2002
VL 28
IS 8
BP 1348
EP 1354
AR PII S0886-3350(01)01320-7
DI 10.1016/S0886-3350(01)01320-7
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 583PW
UT WOS:000177417200018
PM 12160803
DA 2022-11-30
ER

PT J
AU Lai, S
   Perrotta, AM
   Bagordo, D
   Mazzaferro, S
   Mene, P
   Errigo, F
   Tinti, F
   Rotondi, S
   Molfino, A
   Simeoni, M
   Mitterhofer, AP
   Cianci, R
AF Lai, S.
   Perrotta, A. M.
   Bagordo, D.
   Mazzaferro, S.
   Mene, P.
   Errigo, F.
   Tinti, F.
   Rotondi, S.
   Molfino, A.
   Simeoni, M.
   Mitterhofer, A. P.
   Cianci, R.
TI Literature review on the cross-link between ocular and renal disease:
   renin angiotensin aldosterone system is a main actor
SO EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE Eye; Chronic kidney disease; Ocular disease; Oculo-renal syndrome
ID CHRONIC KIDNEY-DISEASE; NUTRITION EXAMINATION SURVEY;
   BARDET-BIEDL-SYNDROME; 3RD NATIONAL-HEALTH; TUBULOINTERSTITIAL
   NEPHRITIS; MACULAR DEGENERATION; VITAMIN-D; OCULOCEREBRORENAL SYNDROME;
   COLOBOMA SYNDROME; CLINICAL FINDINGS
AB OBJECTIVE: Chronic kidney disease (CKD) and ocular disease share several cardiovascular risk factors as well as pathogenetic mechanisms having Renin-Angiotensin-Aldosterone System (RAAS) as main actor. Moreover, kidney and eyes have common genetic and embryonic origin. In this literature review, we present main evidence supporting this association for early identifying diseases affecting both systems and evaluating potential multi-target therapeutic strategies.
   MATERIALS AND METHODS: We performed a literature review of the current peer- reviewed English-language randomized controlled studies (RCTs), reference lists of nephrology or ophthalmology textbooks, review articles and relevant studies with ocular or eye and kidney or renal diseases as keywords until March 2020. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included.
   RESULTS: We evaluated a total of 683 records, finally selecting 119 articles related to ocular and renal diseases. Records were divided into two areas: chronic and acute kidney disease and ocular or eye diseases. Some of the examined studies were discarded for population biases/intervention or deemed unfit.
   CONCLUSIONS: Based on our results, we conclude that there is evidence of a clear association between kidney and eye diseases, being this cross-link mainly based on RAAS dysregulation. Our review suggests that it may be useful to screen CKD patients for associated ocular diseases, such as cataract, glaucoma, diabetic retinopathy and age- related macular degeneration. A comprehensive study of CKD and proteinuric patients should include careful eye ex- amination. Renal impairment in young patients should prompt a search for ocular disease, such as TUNA syndrome or oculo-renal syndrome, in particular if family history of concurrent ocular and renal disease is present. Anti-RAAS agents are mostly recommended in patients with renal and ocular impairment.
C1 [Lai, S.; Perrotta, A. M.; Bagordo, D.; Mazzaferro, S.; Errigo, F.; Tinti, F.; Rotondi, S.; Mitterhofer, A. P.; Cianci, R.] Sapienza Univ Rome, Dept Translat & Precis Med, Nephrol Unit, Rome, Italy.
   [Mene, P.] Sapienza Univ Rome, St Andrea Univ Hosp, Dept Clin Sci, Div Nephrol, Rome, Italy.
   [Molfino, A.] Sapienza Univ Rome, Dept Translat & Precis Med, Rome, Italy.
   [Simeoni, M.] Univ Campania Luigi Vanvitelli, Translat Med Sci, Naples, Italy.
C3 Sapienza University Rome; Sapienza University Rome; Azienda Ospedaliera
   Sant'Andrea; Sapienza University Rome; Universita della Campania
   Vanvitelli
RP Simeoni, M (通讯作者)，Univ Campania Luigi Vanvitelli, Translat Med Sci, Naples, Italy.
EM mariadelina.simeoni@unicampania.it
OI Bagordo, Domenico/0000-0002-7137-0354
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NR 118
TC 0
Z9 0
U1 2
U2 2
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.
PY 2022
VL 26
IS 13
BP 4774
EP 4788
PG 15
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 3P0VK
UT WOS:000837256500030
PM 35856370
DA 2022-11-30
ER

PT J
AU Ehlers, JP
   Clark, J
   Uchida, A
   Figueiredo, N
   Babiuch, A
   Talcott, KE
   Lunasco, L
   Le, TK
   Meng, XY
   Hu, M
   Reese, J
   Srivastava, SK
AF Ehlers, Justis P.
   Clark, Julie
   Uchida, Atsuro
   Figueiredo, Natalia
   Babiuch, Amy
   Talcott, Katherine E.
   Lunasco, Leina
   Le, Thuy K.
   Meng, Xiangyi
   Hu, Ming
   Reese, Jamie
   Srivastava, Sunil K.
TI Longitudinal Higher-Order OCT Assessment of Quantitative Fluid Dynamics
   and the Total Retinal Fluid Index in Neovascular AMD
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE optical coherence tomography (OCT); fluid feature extraction; retinal
   fluid index; wet age-related macular degeneration (AMD)
ID OPTICAL COHERENCE TOMOGRAPHY; TREAT-AND-EXTEND; MACULAR DEGENERATION;
   VISUAL-ACUITY; RANIBIZUMAB; SEGMENTATION; QUANTIFICATION; MORPHOLOGY;
   OUTCOMES
AB Purpose: The purpose of this study was to evaluate the feasibility of assessing quantita-tive longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD). Methods: A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analy-sis using a machine learning & minus;enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnos -tic), brolucizumab, and aflibercept. Results: Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution assessment of quantitative fluid burden. A greater proportion of brolucizumab participants achieved true zero and minimal fluid (total fluid volume between 0.0001 and 0.001mm3) versus aflibercept participants at week 40. True zero fluid during q12 brolucizumab dosing was achieved in 36.6% to 38.5%, similar to the 25.6% to 38.5% during the corresponding q8 aflibercept cycles. TRFI was significantly reduced from baseline in all groups. Conclusions: Higher-order OCT analysis demonstrates the feasibility of fluid feature extraction and longitudinal volumetric fluid burden and TRFI characterization in nAMD, supporting a unique opportunity for fluid burden assessment and the impact on outcomes. Translational Relevance: Detection and characterization of disease activity is vital for optimal treatment of nAMD. Longitudinal assessment of fluid dynamics and the TRFI provide important proof of concept for future automated tools in characterizing disease activity.
C1 [Ehlers, Justis P.; Uchida, Atsuro; Figueiredo, Natalia; Babiuch, Amy; Talcott, Katherine E.; Lunasco, Leina; Le, Thuy K.; Hu, Ming; Reese, Jamie; Srivastava, Sunil K.] Cleveland Clin, Tony & Leona Campane Ctr Excellence Image Guided, Cleveland, OH 44106 USA.
   [Ehlers, Justis P.; Uchida, Atsuro; Figueiredo, Natalia; Babiuch, Amy; Talcott, Katherine E.; Lunasco, Leina; Le, Thuy K.; Reese, Jamie; Srivastava, Sunil K.] Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,i32, Cleveland, OH 44195 USA.
   [Clark, Julie] Novartis Pharmaceut, E Hanover, NJ USA.
   [Meng, Xiangyi] Novartis Pharmaceut, E Hanover, NJ USA.
   [Hu, Ming] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Novartis;
   Novartis; Cleveland Clinic Foundation
RP Ehlers, JP (通讯作者)，Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,i32, Cleveland, OH 44195 USA.
EM ehlersj@ccf.org
OI Lunasco, Leina/0000-0003-3403-7429
FU Novartis Pharmaceuticals, East Hanover, NJ, USA; NIH/NEI
   [K23-EY022947-01A1]
FX Supported by a research grant provided by Novartis Pharmaceuticals, East
   Hanover, NJ, USA, who participated in the design and conduct of the
   study; data collection, management, and interpretation; and preparation,
   review, and approval of the manuscript. This work was also supported
   through the NIH/NEI K23-EY022947-01A1.
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NR 28
TC 6
Z9 6
U1 1
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAR
PY 2021
VL 10
IS 3
DI 10.1167/tvst.10.3.29
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RI4AK
UT WOS:000636851700008
PM 34003963
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Jacob, J
   Mangelschots, E
   Michez, M
   Sanak, SN
   Leys, A
AF Jacob, Julie
   Mangelschots, Els
   Michez, Marine
   Sanak, Serdal N.
   Leys, Anita
TI Cross-Sectional Study on Vitamin D, Zinc Oxide and Fatty Acid Status in
   a Population with a Moderate to High Risk of AMD Identified by the
   STARS(R) Questionnaire
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Article
DE AMD; Micronutrients; Omega-6; omega-3; Vitamin D; Zinc
AB Introduction A prospective study was carried out in Belgium to determine the proportion of subjects with a moderate to high risk of developing age-related macular degeneration (AMD), identified using the STARS(R) (Simplified Thea AMD Risk-Assessment Scale) questionnaire, who were in need of nutritional supplementation, by assessing the vitamin D, zinc oxide and fatty acid profile status. Methods This multicentre cross-sectional pilot study involved 50 Belgian subjects with no or early AMD, aged > 55 years who were at moderate to high risk for AMD. Subjects were assessed using the STARS(R) questionnaire, visual acuity assessment, an optical coherence tomography scan of the macula and fundus photography. Blood samples were collected, and serum analyses were performed to determine the the omega-6:omega-3 (omega 6:omega 3) ratio and the levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), zinc and cupric oxides and vitamin D. Results Abnormal serum levels for at least one of the micronutrients was detected in 94% of the subjects. Lower than optimal vitamin D levels were found in 76% of the participants, and 68% of the subjects demonstrated at least one abnormal fatty acid profile. The omega 6:omega 3 ratio was above the reference range for normal values in 54% of the subjects; DHA and EPA levels were below the reference range in 60 and 46% of the subjects, respectively; and zinc oxide concentration was below the reference range in 50% of the subjects. Only 12% of the subjects exhibited cupric oxide deficiency. Conclusion In this study, the STARS(R) questionnaire was used for early identification of patients at moderate to high risk of AMD in real life. These patients presented a suboptimal nutritional status. Further research is needed to determine if specific diet modification or micronutrient supplement intake delays the onset or slows down the progression of AMD in these subjects.
C1 [Jacob, Julie; Leys, Anita] Univ Ziekenhuis Leuven UZ Leuven, Dept Ophthalmol, Leuven, Belgium.
   [Mangelschots, Els] Oogartsenpraktijk Alken, Alken, Belgium.
   [Michez, Marine] Univ Catholique Louvain UCLouvain, Clin Univ St Luc, Brussels, Belgium.
   [Sanak, Serdal N.] CHIREC Hop Delta, Dept Ophthalmol, Brussels, Belgium.
C3 Universite Catholique Louvain; Cliniques Universitaires Saint-Luc
RP Jacob, J (通讯作者)，Univ Ziekenhuis Leuven UZ Leuven, Dept Ophthalmol, Leuven, Belgium.
EM Julie.jacob@uzleuven.be
FU Laboratoires Thea, Clermont-Ferrand
FX This study was funded by a grant from Laboratoires Thea, 12 rue
   Louis-Bleriot, 63000 Clermont-Ferrand. The study sponsor also funded the
   journal's Rapid Service Fee.
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NR 50
TC 3
Z9 4
U1 3
U2 5
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-8245
EI 2193-6528
J9 OPHTHALMOL THER
JI OPHTHALMOL. THER.
PD JUN
PY 2021
VL 10
IS 2
BP 299
EP 311
DI 10.1007/s40123-021-00335-4
EA FEB 2021
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RU0LP
UT WOS:000621077500001
PM 33620690
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Keenan, TDL
   Chakravarthy, U
   Loewenstein, A
   Chew, EY
   Schmidt-Erfurth, U
AF Keenan, Tiarnan D. L.
   Chakravarthy, Usha
   Loewenstein, Anat
   Chew, Emily Y.
   Schmidt-Erfurth, Ursula
TI Automated Quantitative Assessment of Retinal Fluid Volumes as Important
   Biomarkers in Degeneration
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; VISUAL-ACUITY;
   IMAGING BIOMARKERS; RANIBIZUMAB; QUANTIFICATION; SEGMENTATION; THERAPY;
   OPHTHALMOLOGISTS; IDENTIFICATION
AB PURPOSE: To evaluate retinal fluid volume data extracted from optical coherence tomography (OCT) scans by artificial intelligence algorithms in the treatment of neovascular age- related macular degeneration (NVAMD).
   DESIGN: Perspective.
   METHODS: A review was performed of retinal image repository datasets from diverse clinical settings.
   SETTINGS: Clinical trial (HARBOR) and trial follow-on (AgeRelated Eye Disease Study 2 10-year Follow-On); realworld (Belfast and Tel-Aviv tertiary centers). PATIENTS: 24,362 scans of 1,095 eyes (HARBOR); 4,673 of 880 (Belfast); 1,470 of 132 (Tel-Aviv); 511 of 511 (AgeRelated Eye Disease Study 2 10-year Follow-On). OBSERVATION PROCEDURES: Vienna Fluid Monitor or Notal OCT Analyzer applied to macular cube scans. OUTCOME MEASURES: Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) volumes.
   RESULTS: The fluid volumes measured in neovascular AMD were expressed efficiently in nanoliters. Large ranges that differed by population were observed at the treatment-naive stage: 0-3,435 nL (IRF), 0-5,018 nL (SRF), and 0-10,022 nL (PED). Mean volumes decreased rapidly and consistently with anti-vascular endothelial growth factor therapy. During maintenance therapy, mean IRF volumes were highest in Tel-Aviv (100 nL), lower in Belfast and HARBOR-Pro Re Nata, and lowest in HARBOR-monthly (21 nL). Mean SRF volumes were low in all: 30 nL (HARBOR-monthly) and 48-49 nL (others).
   CONCLUSIONS: Quantitative measures of IRF, SRF, and PED are important biomarkers in NV-AMD. Accurate volumes can be extracted efficiently from OCT scans by artificial intelligence algorithms to guide the treatment of exudative macular diseases. Automated fluid monitoring identifies fluid characteristics in different NVAMD populations at baseline and during follow-up. For consistency between studies, we propose the nanoliter as a convenient unit. We explore the advantages of using these quantitative metrics in clinical practice and research.
C1 [Keenan, Tiarnan D. L.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [Chakravarthy, Usha] Queens Univ Belfast, Ctr Expt Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
   [Loewenstein, Anat] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Tel Aviv, Israel.
   [Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, Christian Doppler Lab Ophthalm Image Anal OPTIMA, Vienna, Austria.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Queens University Belfast; Tel Aviv University; Sackler Faculty
   of Medicine; Medical University of Vienna
RP Keenan, TDL (通讯作者)，NIH, Bldg 10,CRC,Room 10D45,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM tiarnan.keenan@nih.gov
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Keenan,
   Tiarnan/0000-0002-2253-1772; Chew, Emily/0000-0003-0999-9802
FU National Eye Institute, National Institutes of Health (NIH), Department
   of Health and Human Services, Bethesda, MD
FX This work was supported by intramural program funds from the National
   Eye Institute, National Institutes of Health (NIH), Department of Health
   and Human Services, Bethesda, MD. The funding organization participated
   in the study design; the collection, analysis, and interpretation of
   data; the writing of the report; and the decision to submit the article
   for publication. Financial Disclosures: U.C.: consultancy (Alimera,
   Apellis, Iveric Bio); advisory boards (Bayer, Genentech, Novartis);
   institutional research support (Bayer, Novartis, Roche); A.L.:
   consultancy (Allergan, Bayer, Beyeonics, Notal Vision, Novartis, Roche);
   U.S.-E.: consultancy (Genentech, Kodiak, Novartis, Roche). The rest of
   the authors have no financial disclosures. All authors attest that they
   meet the current ICMJE criteria for authorship.
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NR 60
TC 18
Z9 19
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD APR
PY 2021
VL 224
BP 267
EP 281
DI 10.1016/j.ajo.2020.12.012
EA FEB 2021
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RN7UW
UT WOS:000640559300027
PM 33359681
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Schlecht, A
   Zhang, PP
   Wolf, J
   Thien, A
   Rosmus, DD
   Boneva, S
   Schlunck, G
   Lange, C
   Wieghofer, P
AF Schlecht, Anja
   Zhang, Peipei
   Wolf, Julian
   Thien, Adrian
   Rosmus, Dennis-Dominik
   Boneva, Stefaniya
   Schlunck, Gunther
   Lange, Clemens
   Wieghofer, Peter
TI Secreted Phosphoprotein 1 Expression in Retinal Mononuclear Phagocytes
   Links Murine to Human Choroidal Neovascularization
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE AMD; CNV; Osteopontin; OPN; SPP1; microglia; Cx3cr1(CreERT2)
AB Age-related macular degeneration (AMD) represents the most common cause of blindness in the elderly in the Western world. An impairment of the outer blood-retina barrier and a localized inflammatory microenvironment cause sprouting of choroidal neovascular membranes (CNV) in neovascular AMD that are in intimate contact with surrounding myeloid cells, such as retinal microglia, and ultimately lead to visual impairment. The discovery of novel target molecules to interfere with angiogenesis and inflammation is vital for future treatment approaches in AMD patients. To explore the transcriptional profile and the function of retinal microglia at sites of CNV, we performed a comprehensive RNA-seq analysis of retinal microglia in the mouse model of laser-induced choroidal neovascularization (mCNV). Here, we identified the angiogenic factor Osteopontin (Opn), also known as "secreted phosphoprotein 1" (Spp1), as one of the most highly expressed genes in retinal microglia in the course of CNV formation. We confirmed the presence of SPP1 at the lesion site in recruited retinal microglia in Cx3cr1(CreER):Rosa26-tdTomato reporter mice by confocal microscopy and in whole retinal tissue lysates by ELISA highlighting a massive local production of SPP1. Inhibition of SPP1 by intravitreal injection of an anti-SPP1 antibody significantly increased the lesion size compared to IgG-treated control eyes. In line with our results in rodents, we found an increased SPP1 mRNA expression in surgically extracted human choroidal neovascular (hCNV) membranes by the quantitative RNA-seq approach of massive analysis of cDNA ends (MACE). Numerous IBA1(+)SPP1(+) myeloid cells were detected in human CNV membranes. Taken together, these results highlight the importance of SPP1 in the formation of CNV and potentially offer new opportunities for therapeutic intervention by modulating the SPP1 pathway.
C1 [Schlecht, Anja; Zhang, Peipei; Wolf, Julian; Thien, Adrian; Boneva, Stefaniya; Schlunck, Gunther; Lange, Clemens] Univ Freiburg, Med Fac, Eye Ctr, Med Ctr, Freiburg, Germany.
   [Rosmus, Dennis-Dominik; Wieghofer, Peter] Univ Leipzig, Inst Anat, Leipzig, Germany.
C3 University of Freiburg; Leipzig University
RP Lange, C (通讯作者)，Univ Freiburg, Med Fac, Eye Ctr, Med Ctr, Freiburg, Germany.; Wieghofer, P (通讯作者)，Univ Leipzig, Inst Anat, Leipzig, Germany.
EM clemens.lange@uniklinik-freiburg.de;
   peter.wieghofer@medizin.uni-leipzig.de
RI Wieghofer, Peter/AAV-9572-2020
OI Wolf, Julian/0000-0002-3470-9697; Boneva, Stefaniya/0000-0002-9811-2160;
   Rosmus, Dennis-Dominik/0000-0002-4094-0334
FU  [SFB/TRR167]
FX AS and CL were supported by the SFB/TRR167.
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NR 58
TC 14
Z9 13
U1 0
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 JAN 28
PY 2021
VL 8
AR 618598
DI 10.3389/fcell.2020.618598
PG 12
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA QF4SX
UT WOS:000616886800001
PM 33585455
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhou, Y
   Yusufu, M
   Zhang, T
   Wang, J
AF Zhou, Yang
   Yusufu, Meilibanu
   Zhang, Ting
   Wang, Jing
TI Silencing of miR-23a attenuates hydrogen peroxide (H2O2) induced
   oxidative damages in ARPE-19 cells by upregulating GLS1: an in vitro
   study
SO CYTOTECHNOLOGY
LA English
DT Article
DE Age-related macular degeneration; Oxidative stress; ARPE-19; miR-23a;
   GLS1
ID GLUTAMINE UPTAKE; STRESS; PROLIFERATION; INFLAMMATION; GLIOMA
AB Background Oxidative damages contributes to age-related macular degeneration (AMD) caused vision blindness, but the molecular mechanisms are still largely unknown. Objectives This study managed to investigate this issue by conducting in vitro experiments. Methods Oxidative stress were evaluated by L-012 dye, DHE staining and MDA assay. CCK-8 and colony formation assay were conducted to examine cell proliferation. Cell death was evaluated by trypan blue staining and Annexin V-FITC/PI double staining method through flow cytometry (FCM). The binding sites of miR-23a and GLS1 mRNA were predicted by online miRDB database and validated by dual-luciferase reporter gene system. Real-Time qPCR for miR-23a levels and Western Blot for protein expressions. Results The retinal pigment epithelial (RPE) cells (ARPE-19) were subjected to hydrogen peroxide (H2O2) stimulation to simulate AMD progression in vitro, and we identified a novel miR-23a/glutaminase-1 (GLS1) pathway that regulated H2O2 induced oxidative damages in ARPE-19 cells. Mechanistically, H2O2 induced oxidative stress, inhibited cell proliferation and induced cell death in ARPE-19 cells in a dose- and time-dependent manner. Also, H2O2 stimulation hindered cell invasion, migration and glutamine uptake in ARPE-19 cells. Interestingly, we proved that H2O2 increased miR-23a levels, while downregulated glutaminase-1 (GLS1) in ARPE-19 cells, and miR-23a targeted 3 ' untranslated region (3 ' UTR) of GLS1 mRNA for GLS1 degradation. Finally, our data suggested that silencing miR-23a upregulated GLS1 to reverse the detrimental effects of H2O2 treatment on ARPE-19 cells. Conclusions In general, analysis of the data suggested that miR-23a ablation upregulated GLS1 to attenuate H2O2 stimulation induced oxidative damages in ARPE-19 cells in vitro, and this study broadened our knowledge in this field, which might help to provide novel theranostic signatures for AMD.
C1 [Zhou, Yang; Yusufu, Meilibanu] Xinjiang Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Henan Rd 118, Urumqi 830011, Xinjiang, Peoples R China.
   [Zhang, Ting; Wang, Jing] Qingdao Municipal Hosp Grp, Dept Eye Ctr, Jiaozhou Rd 1, Qingdao 266011, Shandong, Peoples R China.
C3 Xinjiang Medical University; Qingdao Municipal Hospital
RP Wang, J (通讯作者)，Qingdao Municipal Hosp Grp, Dept Eye Ctr, Jiaozhou Rd 1, Qingdao 266011, Shandong, Peoples R China.
EM zhouyangdoctor@sina.com; 95319915@qq.com; zhang_ting442@163.com;
   jing_wang1106@163.com
FU Youth Science and Innovation Research Fund of Xinjiang Province
   [WJWY-202039]
FX This work was supported by the Youth Science and Innovation Research
   Fund of Xinjiang Province (No. WJWY-202039).
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NR 33
TC 1
Z9 1
U1 3
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-9069
EI 1573-0778
J9 CYTOTECHNOLOGY
JI Cytotechnology
PD DEC
PY 2020
VL 72
IS 6
BP 873
EP 884
DI 10.1007/s10616-020-00431-6
EA OCT 2020
PG 12
WC Biotechnology & Applied Microbiology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Cell Biology
GA OX2TR
UT WOS:000585061100001
PM 33123932
OA Green Published
DA 2022-11-30
ER

PT J
AU Luaces-Rodriguez, A
   del Amo, EM
   Mondelo-Garcia, C
   Gomez-Lado, N
   Gonzalez, F
   Ruibal, L
   Gonzalez-Barcia, M
   Zarra-Ferro, I
   Otero-Espinar, FJ
   Fernandez-Ferreiro, A
   Aguiar, P
AF Luaces-Rodriguez, Andrea
   del Amo, Eva M.
   Mondelo-Garcia, Cristina
   Gomez-Lado, Noemi
   Gonzalez, Francisco
   Ruibal, Alvaro
   Gonzalez-Barcia, Miguel
   Zarra-Ferro, Irene
   Otero-Espinar, Francisco J.
   Fernandez-Ferreiro, Anxo
   Aguiar, Pablo
TI PET study of ocular and blood pharmacokinetics of intravitreal
   bevacizumab and aflibercept in rats
SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
LA English
DT Article
DE Aflibercept; Bevacizumab; Pharmacokinetics; Molecular imaging; PET;
   89-Zirconium; Anti-VEGF; AMD
ID ENDOTHELIAL GROWTH-FACTOR; ANIMAL-MODELS; RABBIT; RANIBIZUMAB;
   INJECTION; ANTIBODY; NANOPARTICLES; CLEARANCE; DELIVERY; VOLUME
AB Intravitreal injections are the standard procedure in the treatment of retinal pathologies, such as the administration of the anti-VEGF antibodies in age-related macular degeneration. The aim of this study is to evaluate the intraocular and blood pharmacokinetics after an intravitreal injection of Zr-89-labelled bevacizumab and Zr-89-labelled aflibercept in Sprague-Dawley rats using Positron Emission Tomography. First, both antibodies were radiolabelled to zirconium-89 with a maximum specific activity of 15 Mbq/mg for bevacizumab and 10 Mbq/mg for aflibercept. Four mu L containing 1-1.2 Mq of Zr-89-labelled compound were injected into the vitreous through a 35 G needle. A microPET acquisition was carried out immediately after the injection and at different time points through a 12-day study and blood samples were obtained through the tail vein. Radiolabelling was successfully performed with a radiochemical purity after ultrafiltration above 95% for both agents. Both antibodies ocular curves followed a two-compartment model in which an intraocular elimination half-life of 16.44 h was found for Zr-89-bevacizumab and 4.51 h for Zr-89-aflibercept, considering the alpha phase as the elimination phase. Regarding the beta phase, a half-life of 3.23 days for( 89)Zr-bevacizumab and 4.69 days for( 89)Zr-aflibercept were observed. With regards to blood concentration, Zr-89-bevacizumab showed a blood half-life of 7.08 days, whereas Zr-89-aflibercept's was 3.18 days, by a one-compartment model with first-order absorption kinetics. In conclusion, this study shows for the first time the ocular and blood pharmacokinetic analysis after intravitreal injection of aflibercept and bevacizumab in rats.
C1 [Luaces-Rodriguez, Andrea; Gonzalez-Barcia, Miguel; Otero-Espinar, Francisco J.] Univ Santiago de Compostela USC, Fac Pharm, Pharmacol Pharm & Pharmaceut Technol Dept, Santiago De Compostela, Spain.
   [Luaces-Rodriguez, Andrea; Mondelo-Garcia, Cristina; Gonzalez-Barcia, Miguel; Zarra-Ferro, Irene; Fernandez-Ferreiro, Anxo] Hlth Res Inst Santiago de Compostela IDIS, Pharmacol Grp, Santiago De Compostela, Spain.
   [del Amo, Eva M.] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Kuopio, Finland.
   [Mondelo-Garcia, Cristina; Gonzalez-Barcia, Miguel; Zarra-Ferro, Irene; Fernandez-Ferreiro, Anxo] Univ Clin Hosp Santiago de Compostela SERGAS, Pharm Dept, Santiago De Compostela, Spain.
   [Gomez-Lado, Noemi; Ruibal, Alvaro; Aguiar, Pablo] Univ Clin Hosp Santiago de Compostela SERGAS, Nucl Med Dept, Santiago De Compostela, Spain.
   [Gomez-Lado, Noemi; Ruibal, Alvaro; Aguiar, Pablo] Hlth Res Inst Santiago de Compostela IDIS, Mol Imaging Grp, Santiago De Compostela, Spain.
   [Gonzalez, Francisco] Univ Santiago de Compostela USC, Univ Clin Hosp Santiago de Compostela SERGAS, Hlth Res Inst Santiago de Compostela IDIS, Ophthalmol Dept,CIMUS, Santiago De Compostela, Spain.
C3 Universidade de Santiago de Compostela; Complexo Hospitalario
   Universitario de Santiago de Compostela; University of Eastern Finland;
   Complexo Hospitalario Universitario de Santiago de Compostela; Complexo
   Hospitalario Universitario de Santiago de Compostela; Complexo
   Hospitalario Universitario de Santiago de Compostela; Complexo
   Hospitalario Universitario de Santiago de Compostela; Universidade de
   Santiago de Compostela
RP Fernandez-Ferreiro, A (通讯作者)，Hlth Res Inst Santiago de Compostela IDIS, Pharmacol Grp, Santiago De Compostela, Spain.; Aguiar, P (通讯作者)，Univ Clin Hosp Santiago de Compostela SERGAS, Nucl Med Dept, Santiago De Compostela, Spain.
EM anxordes@gmail.com; pablo.aguiar.fernandez@sergas.es
RI Aguiar, Pablo/S-3371-2019; Fernández, Pablo Aguiar/ABD-9169-2022; del
   Amo, Eva María/AAX-1089-2020; Otero-Espinar, F. J./K-1337-2014;
   Gonzalez, Francisco/N-4135-2014; Gómez-Lado, Noemí/AAR-2538-2021
OI Aguiar, Pablo/0000-0002-7322-2195; del Amo, Eva
   María/0000-0002-5705-4515; Otero-Espinar, F. J./0000-0001-9030-2253;
   Gonzalez, Francisco/0000-0002-1461-5474; Gómez-Lado,
   Noemí/0000-0003-2362-3051; Mondelo-Garcia, Cristina/0000-0001-8555-1415;
   Zarra Ferro, Irene/0000-0003-0835-034X
FU ISCIII - FEDER [PI17/00940, RD16/0008/0003, RD12/0034/0017]; Spanish
   Ministry of Science, Innovation and Universities [RTI2018-099597-B-100]
FX This work was partially supported by ISCIII cofunded by FEDER
   (PI17/00940, RETICS Oftared, RD16/0008/0003 and RD12/0034/0017) and by
   the Spanish Ministry of Science, Innovation and Universities
   (RTI2018-099597-B-100).
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NR 50
TC 4
Z9 4
U1 1
U2 6
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29a, 1043 NX AMSTERDAM, NETHERLANDS
SN 0939-6411
EI 1873-3441
J9 EUR J PHARM BIOPHARM
JI Eur. J. Pharm. Biopharm.
PD SEP
PY 2020
VL 154
BP 330
EP 337
DI 10.1016/j.ejpb.2020.06.024
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA NK4OZ
UT WOS:000566712700011
PM 32659326
DA 2022-11-30
ER

PT J
AU Sommer, AC
   Blumenthal, EZ
AF Sommer, Adir C.
   Blumenthal, Eytan Z.
TI Telemedicine in ophthalmology in view of the emerging COVID-19 outbreak
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Telemedicine; Telehealth; Teleophthalmology; COVID-19; SARS-CoV-2;
   Remote care
ID NONMYDRIATIC FUNDUS CAMERA; ACUTE-PHASE RETINOPATHY;
   DIABETIC-RETINOPATHY; TELE-OPHTHALMOLOGY; TELEOPHTHALMOLOGY; DIAGNOSIS;
   ACCURACY; CARE
AB Purpose Technological advances in recent years have resulted in the development and implementation of various modalities and techniques enabling medical professionals to remotely diagnose and treat numerous medical conditions in diverse medical fields, including ophthalmology. Patients who require prolonged isolation until recovery, such as those who suffer from COVID-19, present multiple therapeutic dilemmas to their caregivers. Therefore, utilizing remote care in the daily workflow would be a valuable tool for the diagnosis and treatment of acute and chronic ocular conditions in this challenging clinical setting. Our aim is to review the latest technological and methodical advances in teleophthalmology and highlight their implementation in screening and managing various ocular conditions. We present them as well as potential diagnostic and treatment applications in view of the recent SARS-CoV-2 virus outbreak.
   Methods A computerized search from January 2017 up to March 2020 of the online electronic database PubMed was performed, using the following search strings: "telemedicine," "telehealth," and "ophthalmology." More generalized complementary contemporary research data regarding the COVID-19 pandemic was also obtained from the PubMed database.
   Results A total of 312 records, including COVID-19-focused studies, were initially identified. After exclusion of non-relevant, non-English, and duplicate studies, a total of 138 records were found eligible. Ninety records were included in the final qualitative analysis.
   Conclusion Teleophthalmology is an effective screening and management tool for a range of adult and pediatric acute and chronic ocular conditions. It is mostly utilized in screening of retinal conditions such as retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration; in diagnosing anterior segment condition; and in managing glaucoma. With improvements in image processing, and better integration of the patient's medical record, teleophthalmology should become a more accepted modality, all the more so in circumstances where social distancing is inflicted upon us.
C1 [Sommer, Adir C.; Blumenthal, Eytan Z.] Rambam Hlth Care Campus, Dept Ophthalmol, POB 9602, IL-31096 Haifa, Israel.
   [Blumenthal, Eytan Z.] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
C3 Rambam Health Care Campus; Technion Israel Institute of Technology;
   Rappaport Faculty of Medicine
RP Blumenthal, EZ (通讯作者)，Rambam Hlth Care Campus, Dept Ophthalmol, POB 9602, IL-31096 Haifa, Israel.; Blumenthal, EZ (通讯作者)，Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
EM e_blumenthal@rambam.health.gov.il
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NR 91
TC 44
Z9 45
U1 1
U2 13
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 NOV
PY 2020
VL 258
IS 11
BP 2341
EP 2352
DI 10.1007/s00417-020-04879-2
EA AUG 2020
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OH1OE
UT WOS:000560977200004
PM 32813110
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Mueller, B
   Ibraimova, S
   Mamutalieva, E
   Limburg, H
   Ibraimova, A
   Paduca, A
AF Mueller, Brigitte
   Ibraimova, Sabina
   Mamutalieva, Elzat
   Limburg, Hans
   Ibraimova, Aigul
   Paduca, Ala
TI Findings from a Rapid Assessment of Avoidable Blindness (RAAB) in the
   Southwest Region of Kyrgyzstan
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE RAAB; visual impairment; blindness; ageing
ID CATARACT BLINDNESS; DISTRICT; SURGERY
AB Purpose: Reliable data on eye care needs in Kyrgyzstan are not readily available. The purpose of this study was to determine the prevalence and causes of blindness and visual impairment in persons aged 50 and above in the southwest of Kyrgyzstan and to support the Ministry of Health (MoH) in the planning of eye care in the region. Methods: A population-based survey was conducted in three states (Oblast) in the southwest region of Kyrgyzstan. Sixty clusters of 50 people aged 50 years and older were selected by probability proportionate to size sampling. Ethical approval was obtained from the MoH, consent was obtained from each participant. Results: A total number of 3,000 persons aged 50 and older were sampled. Among these 2,897 (95.9%) were examined. The prevalence of bilateral blindness was 1.7% [95%CI: 1.1-2.4]. Cataract (43.3%) was the main cause of blindness, followed by glaucoma (30%), age-related macular degeneration (ARMD) (8.3%), other posterior segment diseases (6.7%) and non-trachomatous corneal opacities (5%). The prevalence of blindness and visual impairment increased strongly with age. The cataract surgical coverage in blind persons was 59%. Conclusion: Cataract and glaucoma were the major causes of blindness and visual impairment in persons 50 and above. The majority of the causes (85%) were avoidable, with 45% (cataract and uncorrected aphakia) treatable, 6.7% (corneal opacity and phthisis) preventable by primary health care/eye care services and 33.3% (cataract surgical complications, glaucoma) preventable by specialized ophthalmic services. The data suggest that an expansion of eye care services to reduce avoidable blindness is needed, as ageing will lead to an increase in older people at risk and a higher demand for eye care in the future.
C1 [Mueller, Brigitte; Mamutalieva, Elzat] Int Cooperat, Swiss Red Cross, Int Cooperat Dept, Werkstr 18, CH-3084 Wabern, Switzerland.
   [Ibraimova, Sabina] Red Crescent Soc Kyrgyzstan, Bishkek, Kyrgyzstan.
   [Limburg, Hans] Hlth Informat Serv, Grootebroek, Netherlands.
   [Ibraimova, Aigul] Bishkek Sci Res Ctr Traumatol & Orthoped, Bishkek, Kyrgyzstan.
   [Paduca, Ala] State Univ Med & Pharm Nicolae Testemitanu, Ophthalmol Dept, Kishinev, Moldova.
C3 Nicolae Testemitanu State University of Medicine & Pharmacy
RP Mueller, B (通讯作者)，Int Cooperat, Swiss Red Cross, Int Cooperat Dept, Werkstr 18, CH-3084 Wabern, Switzerland.
EM Brigitte.Mueller-Schmid@redcross.ch
FU Swiss Red Cross
FX Funding was provided by the Swiss Red Cross.
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NR 17
TC 1
Z9 1
U1 2
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD MAR 3
PY 2020
VL 27
IS 2
BP 141
EP 147
DI 10.1080/09286586.2019.1701040
EA DEC 2019
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KO4TY
UT WOS:000501395100001
PM 31813309
DA 2022-11-30
ER

PT J
AU Azuma, K
   Tan, X
   Asano, S
   Shimizu, K
   Ogawa, A
   Inoue, T
   Murata, H
   Asaoka, R
   Obata, R
AF Azuma, Keiko
   Tan, Xue
   Asano, Shotaro
   Shimizu, Kimiko
   Ogawa, Asako
   Inoue, Tatsuya
   Murata, Hiroshi
   Asaoka, Ryo
   Obata, Ryo
TI The association of choroidal structure and its response to anti-VEGF
   treatment with the short-time outcome in pachychoroid neovasculopathy
SO PLOS ONE
LA English
DT Article
ID EXTEND REGIMEN; MACULAR DEGENERATION; AFLIBERCEPT; NEOVASCULARIZATION;
   THERAPY; VASCULOPATHY; THICKNESS
AB Pachychoroid neovasculopathy (PNV) shares some anatomical features with other pachychoroid spectrum diseases, but little is known about the characteristics on the treatment with anti-vascular endothelial growth factor (VEGF). We investigated the effect of choroidal structure and responses to anti-VEGF on the prognosis of pachychoroid neovasculopathy (PNV) and other types of neovascular age-related macular degeneration (non-PNV). Twenty-one eyes with PNV and 34 eyes with non-PNV who had anti-VEGF treatment were retrospectively reviewed. Choroidal neovascularization (CNV) area at baseline was measured with fluorescein angiography (FAG). The luminal and stromal area in the choroid was measured by enhanced-depth-imaging (EDI) OCT at baseline and 1 month. The association between dry macula or LogMAR VA (visual acuity, VA) at 1 month and baseline values or changes in the luminal or stromal area at 1 month, baseline CNV area, or anti-VEGF drugs were analyzed in patients with or without PNV. In non-PNV, change of luminal area (coefficient = 7.0x10(-5), p = 0.0001), baseline CNV area (coefficient = 0.18, p = 0.033), and aflibercept vs. ranibizumab (coefficient = 0.29, p = 0.0048) were chosen as predictors for dry macula by the model selection. Similarly, in non-PNV, change of luminal area (coefficient = 6.1x10(-6), p = 0.033), baseline CNV area (coefficient = 0.034, p = 0.022), and aflibercept vs. ranibizumab (coefficient = 0.056, p = 0.0020) were chosen as predictors for greater VA improvement. In PNV, however, none of these factors was chosen as predictors for dry macula or VA improvement by the model selection. The result of the present study implied that structural response after anti-VEGF might be different between non-PNV and PNV in the treatment with anti-VEGF agents.
C1 [Azuma, Keiko; Tan, Xue; Asano, Shotaro; Shimizu, Kimiko; Ogawa, Asako; Inoue, Tatsuya; Murata, Hiroshi; Asaoka, Ryo; Obata, Ryo] Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
   [Azuma, Keiko; Tan, Xue; Asano, Shotaro; Shimizu, Kimiko; Ogawa, Asako; Inoue, Tatsuya; Murata, Hiroshi; Asaoka, Ryo; Obata, Ryo] Univ Tokyo, Fac Med, Tokyo, Japan.
   [Tan, Xue] Tokyo Shinjuku Med Ctr, Dept Ophthalmol, Tokyo, Japan.
C3 University of Tokyo; University of Tokyo
RP Obata, R (通讯作者)，Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.; Obata, R (通讯作者)，Univ Tokyo, Fac Med, Tokyo, Japan.
EM robata-tky@umin.ac.jp
FU JSPS KAKENHI [JP16K11260]
FX This study was done under JSPS KAKENHI grant number JP16K11260. The
   organization had no role in study design, in the collection, analysis,
   and interpretation of data, in the writing of the report, or in the
   decision to submit the article for publication.
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NR 29
TC 14
Z9 14
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 FEB 14
PY 2019
VL 14
IS 2
AR e0212055
DI 10.1371/journal.pone.0212055
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HL5JX
UT WOS:000458763900036
PM 30763369
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Weber, S
   Gelman, A
   Lee, D
   Betancourt, M
   Vehtari, A
   Racine-Poon, A
AF Weber, Sebastian
   Gelman, Andrew
   Lee, Daniel
   Betancourt, Michael
   Vehtari, Aki
   Racine-Poon, Amy
TI BAYESIAN AGGREGATION OF AVERAGE DATA: AN APPLICATION IN DRUG DEVELOPMENT
SO ANNALS OF APPLIED STATISTICS
LA English
DT Article
DE Meta-analysis; hierarchical modeling; Bayesian computation;
   pharmacometrics; Stan
ID MACULAR DEGENERATION; RANIBIZUMAB; TRIALS; METAANALYSIS; MECHANISMS; EYE
AB Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by extrapolation from the available evidence at the time. This includes collected trial data and relevant external data. However, relevant external data are typically available as averages only, for example, from trials on alternative treatments reported in the literature. Here we report on such an example from a drug development for wet age-related macular degeneration. This disease is the leading cause of severe vision loss in the elderly. While current treatment options are efficacious, they are also a substantial burden for the patient. Hence, new treatments are under development which need to be compared against existing treatments.
   The general statistical problem this leads to is meta-analysis, which addresses the question of how we can combine data sets collected under different conditions. Bayesian methods have long been used to achieve partial pooling. Here we consider the challenge when the model of interest is complex (hierarchical and nonlinear) and one data set is given as raw data while the second data set is given as averages only. In such a situation, common meta-analytic methods can only be applied when the model is sufficiently simple for analytic approaches. When the model is too complex, for example, nonlinear, an analytic approach is not possible. We provide a Bayesian solution by using simulation to approximately reconstruct the likelihood of the external summary and allowing the parameters in the model to vary under the different conditions. We first evaluate our approach using fake data simulations and then report results for the drug development program that motivated this research.
C1 [Weber, Sebastian; Racine-Poon, Amy] Novartis Pharma AG, CH-4002 Basel, Switzerland.
   [Gelman, Andrew; Betancourt, Michael] Columbia Univ, Dept Stat, New York, NY 10027 USA.
   [Lee, Daniel] Generable, Brooklyn, NY 11205 USA.
   [Vehtari, Aki] Aalto Univ, Dept Comp Sci, HIIT, FI-00076 Aalto, Finland.
C3 Novartis; Columbia University; Aalto University
RP Weber, S (通讯作者)，Novartis Pharma AG, CH-4002 Basel, Switzerland.
EM sebastian.weber@novartis.com; gelman@stat.columbia.edu;
   daniel@generable.com; betanalpha@gmail.com; Aki.Vehtari@aalto.fi;
   amy.racine@novartis.com
OI Vehtari, Aki/0000-0003-2164-9469
FU Institute for Education Sciences [R305D140059-16]; Office of Naval
   Research [N00014-15-1-2541, N00014-16-P-2039]; Sloan Foundation
   [G-2015-13987]; National Science Foundation [CNS-1205516]; Defense
   Advanced Research Projects Agency [DARPA BAA-16-32]; Academy of Finland
   [298742]
FX Supported by Institute for Education Sciences R305D140059-16, Office of
   Naval Research N00014-15-1-2541 & N00014-16-P-2039, Sloan Foundation
   G-2015-13987, National Science Foundation CNS-1205516, Defense Advanced
   Research Projects Agency DARPA BAA-16-32.; Supported by Academy of
   Finland Grant 298742.
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NR 27
TC 8
Z9 8
U1 0
U2 5
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 1932-6157
J9 ANN APPL STAT
JI Ann. Appl. Stat.
PD SEP
PY 2018
VL 12
IS 3
BP 1583
EP 1604
DI 10.1214/17-AOAS1122
PG 22
WC Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematics
GA GT1TR
UT WOS:000444259500009
OA Green Submitted, Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Fu, ZJ
   Lieg, R
   Wang, ZX
   Gong, Y
   Liu, CH
   Sun, Y
   Cakir, B
   Burnim, SB
   Meng, SS
   Lofqvist, C
   SanGiovanni, JP
   Hellstrom, A
   Smith, LEH
AF Fu, Zhongjie
   Lieg, Raffael
   Wang, Zhongxiao
   Gong, Yan
   Liu, Chi-Hsiu
   Sun, Ye
   Cakir, Bertan
   Burnim, Samuel B.
   Meng, Steven S.
   Lofqvist, Chatarina
   SanGiovanni, John Paul
   Hellstrom, Ann
   Smith, Lois E. H.
TI Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty
   Acid Protection Against Choroidal Neovascularization in Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; omega-3 long-chain polyunsaturated
   fatty acids; adiponectin neovascularization
ID ANTI-VEGF AGENTS; MACULAR DEGENERATION; MATRIX METALLOPROTEINASES; RISK;
   EXPRESSION; ADIPOR1; MMP-9; INHIBITORS; INCREASE; RECEPTOR
AB PURPOSE. Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (omega 3-LCPUFA) correlate with a decreased risk of AMD. Dietary omega 3-LCPUFA versus omega 6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated x omega 3-LCPUFA suppression of neovessels in AMD.
   METHODS. The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn(-/-) mice fed either otherwise matched diets with 2% x3 or 2% omega 6-LCPUFAs. Vldlr(-/-) mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPK alpha/AMPK alpha and qPCR for Apn, Mmps, and IL-10 were used to define mechanism.
   RESULTS. omega 3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. omega 3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPK alpha phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr(-/-) mice, omega 3-LCPUFA increased retinal AdipoR1 and inhibited NV. omega 3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr(-/-) retinas.
   CONCLUSIONS. APN in part mediated omega 3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a omega 3-LCPUFA-enriched-diet may augment the beneficial effects of omega 3-LCPUFA in AMD patients.
C1 [Fu, Zhongjie; Lieg, Raffael; Wang, Zhongxiao; Gong, Yan; Liu, Chi-Hsiu; Sun, Ye; Cakir, Bertan; Burnim, Samuel B.; Meng, Steven S.; Smith, Lois E. H.] Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA USA.
   [Lofqvist, Chatarina; Hellstrom, Ann] Univ Gothenburg, Sahlgrenska Acad, Dept Ophthalmol, Gothenburg, Sweden.
   [SanGiovanni, John Paul] NIAAA, NIH, Bethesda, MD USA.
   [SanGiovanni, John Paul] Georgetown Univ, Sch Med, Washington, DC USA.
C3 Harvard University; Boston Children's Hospital; Harvard Medical School;
   University of Gothenburg; National Institutes of Health (NIH) - USA; NIH
   National Institute on Alcohol Abuse & Alcoholism (NIAAA); Georgetown
   University
RP Smith, LEH (通讯作者)，Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
EM lois.smith@childrens.harvard.edu
RI SanGiovanni, John Paul/AAU-3895-2020
OI Sun, Ye/0000-0002-7674-9056; FU, ZHONGJIE/0000-0002-8182-2983; Gong,
   Yan/0000-0002-4805-0459
FU Lowy Medical Research Institute, European Commission FP7 project [305485
   PREVENT-ROP]; Swedish Research Council [2016-01131]; Gothenburg County
   Council [ALFGBG-507741]; De Blindas Vanner; Kronprinsessan Margaretas
   Arbetsnamnd for synskadade; European Commission FP7 project [305485
   PREVENT-ROP]; Knights Templar Eye Foundation; Blind Children's Center;
   Boston Children's Hospital OFD/BTREC/CTREC Faculty Career Development
   Grant; German Research Foundation (DFG) [Li2650/1-1];  [NIH EY024864]; 
   [EY017017];  [EY022275];  [P01 HD18655];  [1U54HD090255]; EUNICE KENNEDY
   SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
   [U54HD090255] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R24EY024864, R01EY017017] Funding Source: NIH RePORTER
FX Supported by Grants NIH EY024864, EY017017, EY022275, P01 HD18655, BCH
   IDDRC, 1U54HD090255; Lowy Medical Research Institute, European
   Commission FP7 project 305485 PREVENT-ROP (LEHS); The Swedish Research
   Council (DNR# 2016-01131), and Gothenburg County Council (ALFGBG-507741)
   long-term support by De Blindas Vanner and Kronprinsessan Margaretas
   Arbetsnamnd for synskadade, European Commission FP7 project 305485
   PREVENT-ROP (AH); European Commission FP7 Project 305485 PREVENT-ROP
   (CL); Knights Templar Eye Foundation and Blind Children's Center (ZF);
   Knights Templar Eye Foundation (CHL); Boston Children's Hospital
   OFD/BTREC/CTREC Faculty Career Development Grant (YS); The German
   Research Foundation (DFG), and Li2650/1-1 (RL).
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NR 69
TC 16
Z9 17
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 2017
VL 58
IS 10
BP 3862
EP 3870
DI 10.1167/iovs.17-21796
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FH2AG
UT WOS:000410940400004
PM 28763559
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Xu, XR
   Yu, HT
   Yang, Y
   Hang, L
   Yang, XW
   Ding, SH
AF Xu, Xin-Rong
   Yu, Hai-Tao
   Yang, Yan
   Hang, Li
   Yang, Xue-Wen
   Ding, Shu-Hua
TI Quercetin phospholipid complex significantly protects against oxidative
   injury in ARPE-19 cells associated with activation of Nrf2 pathway
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Age-related macular degeneration; Quercetin; Phospholipid complex;
   Oxidative stress; Nrf2
ID MACULAR DEGENERATION; STRESS
AB Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27 mu g/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400 mu M. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200 mu M. In addition, quercetin-PC at 200 mu M significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200 mu M failed to do so. Molecular examinations revealed that quercetin-PC at 200 mu M significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Xu, Xin-Rong; Yang, Yan; Hang, Li; Ding, Shu-Hua] Nanjing Univ Tradit Chinese Med, Affiliated Hosp, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China.
   [Yu, Hai-Tao] Nanjing Univ Tradit Chinese Med, Coll Pharm, Nanjing 210023, Jiangsu, Peoples R China.
   [Yang, Xue-Wen] Nanjing Univ Tradit Chinese Med, Affiliated Hosp, Dept Clin Lab, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese
   Medicine; Nanjing University of Chinese Medicine
RP Xu, XR (通讯作者)，Nanjing Univ Tradit Chinese Med, Affiliated Hosp, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China.
EM xinrong_xu@aliyun.com
RI Xu, Xinrong/AAX-3118-2021
FU Science and Technology Planning Project of Jiangsu Province, China
   [BK20151601]; Program for Leading Talents of Traditional Chinese
   Medicine of Jiangsu Province, China [LJ200911]
FX This work was supported by Science and Technology Planning Project of
   Jiangsu Province, China (Grant no. BK20151601) and Program for Leading
   Talents of Traditional Chinese Medicine of Jiangsu Province, China
   (Grant no. LJ200911)
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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 JAN 5
PY 2016
VL 770
BP 1
EP 8
DI 10.1016/j.ejphar.2015.11.050
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA CZ6SJ
UT WOS:000367230700001
PM 26643168
DA 2022-11-30
ER

PT J
AU Schmid, MK
   Reich, O
   Faes, L
   Boehni, SC
   Bittner, M
   Howell, JP
   Thiel, MA
   Signorell, A
   Bachmann, LM
AF Schmid, Martin K.
   Reich, Oliver
   Faes, Livia
   Boehni, Sophie C.
   Bittner, Mario
   Howell, Jeremy P.
   Thiel, Michael A.
   Signorell, Andri
   Bachmann, Lucas M.
TI Comparison of Outcomes and Costs of Ranibizumab and Aflibercept
   Treatment in Real-Life
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; BEVACIZUMAB; EFFICACY; SAFETY
AB Background
   Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine.
   Objective
   To compare treatment costs and clinical outcomes of the medications when adjusting for patients' characteristics and clinical status.
   Design
   Comparative study.
   Setting
   The largest public ophthalmologic clinic in Switzerland.
   Patients
   Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data.
   Measurements
   Patients' underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured.
   Results
   We included 315 patients (19595 claims) with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8) covering the years 2006-2014. Mean age was 78 years (SD 9.3) and 200 (63.5%) were female. At baseline, the mean number of letters was 55.6 (SD 16.3) and the central retinal thickness was 400.1 mu m (SD 110.1). Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85). Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95% CI: 1094.50-3255.27; p<0.001) for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73-1436.15; p = 0.627).
   Conclusions
   Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.
C1 [Schmid, Martin K.; Faes, Livia; Boehni, Sophie C.; Bittner, Mario; Howell, Jeremy P.; Thiel, Michael A.] Cantonal Hosp Lucerne, Eye Clin, Luzern, Switzerland.
   [Reich, Oliver; Signorell, Andri] Helsana Grp, Dept Hlth Sci, Zurich, Switzerland.
   [Bachmann, Lucas M.] Medignit Inc Res Consultants, Zurich, Switzerland.
C3 Lucerne Cantonal Hospital
RP Bachmann, LM (通讯作者)，Medignit Inc Res Consultants, Zurich, Switzerland.
EM bachmann@medignition.ch
OI , Lucas/0000-0002-9868-154X
FU Novartis Pharma Schweiz AG, Switzerland
FX An unrestricted educational grant was awarded to Oliver Reich (OR) and
   Andri Signorell (AS) by Novartis Pharma Schweiz AG, Switzerland. The
   funder had no role in study design; collection, analysis, and
   interpretation of data; writing of the paper; or in the decision to
   submit the paper for publication. Lucas Bachmann (LB) is an employee of
   medignition Inc. OR and AS are employees of the Helsana Health Insurance
   Company. These funders provided support in the form of salaries but did
   not have any additional role in the study design, data collection and
   analysis, decision to publish, or preparation of the manuscript. The
   specific roles of all authors are articulated in the 'author
   contributions' section.
CR Black N, 1996, BRIT MED J, V312, P1215
   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   Heier JS, 2012, OPHTHALMOLOGY, V119, P2537, DOI 10.1016/j.ophtha.2012.09.006
   Holz FG, 2011, OPHTHALMOLOGY, V118, P663, DOI 10.1016/j.ophtha.2010.12.019
   Institute of Medicine, 2001, CROSSING QUALITY CHA, DOI DOI 10.17226/10027
   Johnston SS, 2013, ADV THER, V30, P1111, DOI 10.1007/s12325-013-0078-4
   Mitchell P, 2011, CURR MED RES OPIN, V27, P1465, DOI 10.1185/03007995.2011.585394
   Raftery J, 2007, BRIT J OPHTHALMOL, V91, P1244, DOI 10.1136/bjo.2007.116616
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   Vedula SS, 2008, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD005139.pub2
NR 12
TC 15
Z9 15
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 4
PY 2015
VL 10
IS 8
AR e0135050
DI 10.1371/journal.pone.0135050
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CO1VB
UT WOS:000358942700091
PM 26241852
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Dobbelsteyn, D
   McKee, K
   Bearnes, RD
   Jayanetti, SN
   Persaud, DD
   Cruess, AF
AF Dobbelsteyn, David
   McKee, Katherine
   Bearnes, Reece D.
   Jayanetti, Sujani N.
   Persaud, David D.
   Cruess, Alan F.
TI What percentage of patients presenting for routine eye examinations
   require referral for secondary care? A study of referrals from
   optometrists to ophthalmologists
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE asymptomatic ocular diseases; integrated vision care; routine eye
   examinations
ID VISION
AB BackgroundThe aim was to investigate the percentage of asymptomatic patients presenting for routine optometric eye examinations that have pathology or pathology-related risk factors warranting referral for ophthalmological consultation.
   MethodsThis was a retrospective, cohort case study and the inclusion criteria for participants included: (i) the patient presented for routine optometric eye care during a specified period of time; (ii) the patient was found to have pathology (or showed enough risk of pathology) resulting in referral to an ophthalmologist; and (iii) a referral report was received from the consulting ophthalmologist stating the diagnosis and the treatment plan. The data set was further reviewed to indicate presenting symptoms and patient age. Adult patients, ages 20 to 64 years, were reviewed separately; this age group is not covered by provincial health services for routine eye care in Nova Scotia. Files were obtained from two clinics through an electronic charting program. A database was created that included date of referral, clinical reasons for the referral, diagnosis and treatment plan. Clinical reasons for referral were extracted from the referral letters and reports and sorted into six disease categories: age-related macular degeneration, cataract, glaucoma, diabetic retinopathy, retinopathy and other'.
   ResultsThe overall referral rate for the combined data set was nine per cent for all ages; 2.4 per cent of the overall patients were asymptomatic. There was a similar number of asymptomatic patients referred in the adult (20 to 64 years) age group compared to all ages (2.5 per cent).
   ConclusionA significant number of patients that present for routine eye examinations without any symptoms indicative of ocular disease are subsequently found to have a degree of pathology or risk thereof requiring referral for ophthalmological consultation. These referrals occur for adults under 64 years as much as for all patients of all ages.
C1 [Persaud, David D.; Cruess, Alan F.] Dalhousie Univ, Halifax, NS, Canada.
C3 Dalhousie University
FU Canadian Optometric Trust Fund
FX The authors acknowledge the financial support of the Canadian Optometric
   Trust Fund, a charitable organisation in the provision of data
   collection and manuscript preparation.
CR [Anonymous], 2010, POP PROJ CAN PROV TE
   Breslin CW, 2007, CAN J OPHTHALMOL, V42, P790, DOI 10.3129/i07-177
   Health Professions Regulatory Advisory Council (HPRAC), 2010, REP MIN HLTH LONG TE
   Muzychka M., 2009, ENV SCAN VISION HLTH
   National Coalition for Vision Health (NCVH), 2007, FDN CAN VIS HLTH STR
   Persaud DD, 2004, CAN J OPHTHALMOL, V39, P219, DOI 10.1016/S0008-4182(04)80117-0
NR 6
TC 11
Z9 12
U1 1
U2 4
PU WILEY-BLACKWELL
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 2015
VL 98
IS 3
BP 214
EP 217
DI 10.1111/cxo.12255
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CI0BK
UT WOS:000354400400004
PM 25756613
DA 2022-11-30
ER

PT J
AU Butt, T
   Lee, A
   Lee, C
   Tufail, A
AF Butt, Thomas
   Lee, Aaron
   Lee, Cecilia
   Tufail, Adnan
CA UK AMD EMR Study Grp
TI The cost-effectiveness of initiating ranibizumab therapy in eyes with
   neovascular AMD with good vision: an economic model using real-world
   outcomes
SO BMJ OPEN
LA English
DT Article
AB Objectives: To evaluate the cost-effectiveness of immediate treatment with ranibizumab in patients with neovascular age-related macular degeneration (nAMD) with good (better than 6/12) starting visual acuity compared with current UK clinical guidance of waiting until vision falls below 6/12 to begin treatment, using real-world outcomes data.
   Design: A patient-level health economic state transition model based on levels of visual acuity in the better seeing eye was constructed to simulate the costs and consequences of treating patients with nAMD with ranibizumab.
   Setting: The model took the perspective of the UK National Health Service (NHS).
   Participants: The model was populated with real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes.
   Interventions: Two treatment approaches were compared: immediate intervention with 0.5 mg ranibizumab pro re nata, PRN (on detection of nAMD) or delayed intervention (waiting until vision fell to 6/12 before beginning treatment).
   Main outcome measures: Quality-adjusted life years (QALYs) for health states and healthcare costs were accrued for each strategy, and an incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model.
   Results: Over a 2-year time horizon, based on 10 000 Monte Carlo simulations, the early treatment arm accumulated 1.59 QALYs and 8469.79 pound cost. The delayed treatment arm accumulated 1.35 QALYs and 7460.21 pound cost. The central ICER estimate was 4251.60 pound.
   Conclusions: A model based on real-world data is likely to be a realistic reflection of the health gains and resource use of ranibizumab for nAMD in the UK NHS. Initiating treatment immediately with ranibizumab PRN regimen is a cost-effective strategy compared with current guidance of initiating treatment at a level of 6/12 or worse vision.
C1 [Butt, Thomas; Tufail, Adnan] UCL, Inst Ophthalmol, London, England.
   [Lee, Aaron; Lee, Cecilia; Tufail, Adnan] Moorfields Eye Hosp, London, England.
   [Lee, Cecilia] Univ Washington, Seattle, WA 98195 USA.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of Washington; University of Washington Seattle
RP Tufail, A (通讯作者)，UCL, Inst Ophthalmol, Mortimer St, London, England.
EM Tufail@moorfields.nhs.uk
RI Butt, Thomas/AAH-7882-2019; Lee, Aaron/AAT-2839-2020
OI Butt, Thomas/0000-0002-0387-4550; Keane, Pearse/0000-0002-9239-745X;
   Tufail, Adnan/0000-0001-6131-7640; Chakravarthy,
   Usha/0000-0002-2606-3734; Bunce, Catey/0000-0002-0935-3713; Lee,
   Aaron/0000-0002-7452-1648
FU Novartis Pharmaceuticals; NOTAL Vision; Department of Health's NIHR
   Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital;
   UCL Institute of Ophthalmology; National Institute for Health Research
   [CS-2014-14-023, CL-2010-18-004] Funding Source: researchfish; NATIONAL
   EYE INSTITUTE [K23EY024921] Funding Source: NIH RePORTER
FX This work was supported in part by unrestricted research awards by
   Novartis Pharmaceuticals and NOTAL Vision. This research has received a
   proportion of its funding from the Department of Health's NIHR
   Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital
   and UCL Institute of Ophthalmology.
CR Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   Brown GC, 2000, ARCH OPHTHALMOL-CHIC, V118, P47
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NR 13
TC 16
Z9 17
U1 0
U2 4
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 2015
VL 5
IS 5
AR e006535
DI 10.1136/bmjopen-2014-006535
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA CI3LB
UT WOS:000354648100003
PM 25943370
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lam, JSH
   Tay, WT
   Aung, T
   Saw, SM
   Wong, TY
AF Lam, Janice S. H.
   Tay, Wan Ting
   Aung, Tin
   Saw, Seang Mei
   Wong, Tien Yin
TI Female Reproductive Factors and Major Eye Diseases in Asian Women -The
   Singapore Malay Eye Study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Age of menopause; age-related macular degeneration; cataract; diabetic
   retinopathy; glaucoma
ID OPEN-ANGLE GLAUCOMA; BLUE MOUNTAINS EYE; AGE-RELATED MACULOPATHY;
   GANGLION-CELL DEATH; MACULAR DEGENERATION; ESTROGEN-RECEPTOR;
   DIABETIC-RETINOPATHY; RISK-FACTORS; OPTIC-NERVE; PREVALENCE
AB Purpose: To examine the association of reproductive factors and major eye diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy and cataract, in Asian women.
   Methods: The Singapore Malay Eye Study is a population-based cross-sectional epidemiological study which examined 3280 persons (78.7% response) of Malay ethnicity aged 40-80 years; 1704 were female. Information on reproductive factors and use of hormone replacement therapy (HRT) was collected using an interviewer-administered questionnaire. Glaucoma was defined according to the International Society for Geographical and Epidemiological Ophthalmology criteria. Retinal photographs were graded for AMD following the Wisconsin grading system, and diabetic retinopathy according to the modified Airlie House classification system. Cataract was graded according to the Lens Opacity Classification System III.
   Results: A total of 1176 women reported having experienced menopause by the time of the study with 1073 (91%) having a natural menopause, 88 (7.5%) a hysterectomy and 9 (0.8%) due to other reasons; HRT was used by 70 (6%) women. Women whose age at menopause was <= 52 years were 3.5 times more likely to have glaucoma (95% confidence interval, CI, 1.23-9.98, p value = 0.02) than those whose age at menopause was >= 53 years. Age of menopause was not associated with AMD (age-adjusted odds ratio, OR, 1.22, 95% CI 0.65-2.31), diabetic retinopathy (age-adjusted OR 1.01, 95% CI 0.66-1.54) or cataract (age-adjusted OR 1.38, 95% CI 0.95-2.00). Use of HRT was not associated with any of these eye diseases.
   Conclusion: Women who had menopause at a younger age were more likely to have glaucoma. This association needs to be confirmed in other studies.
C1 [Lam, Janice S. H.; Tay, Wan Ting; Aung, Tin; Saw, Seang Mei; Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore.
   [Lam, Janice S. H.; Wong, Tien Yin] Natl Univ Hlth Syst, Dept Ophthalmol, Singapore, Singapore.
   [Aung, Tin; Saw, Seang Mei; Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
   [Saw, Seang Mei; Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Commun Occupat & Family Med, Singapore 117595, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore;
   National University of Singapore
RP Wong, TY (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM tien_yin_wong@nuhs.edu.sg
RI Wong, Tien Yin/AAC-9724-2020
OI Wong, Tien Yin/0000-0002-8448-1264
FU National Medical Research Council [0796/2003, 0863/2004, CSI/002/2005];
   Biomedical Research Council [501/1/25-5]; Ministry of Health, Singapore
FX This study was supported by the National Medical Research Council
   (0796/2003, 0863/2004 and CSI/002/2005) and the Biomedical Research
   Council (501/1/25-5). Additional support was provided by the Ministry of
   Health, Singapore. The sponsors had no role in the study design,
   acquisition of data, statistical analysis and interpretation, and the
   final presentation and publication of this study.
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NR 44
TC 12
Z9 13
U1 0
U2 5
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 2014
VL 21
IS 2
BP 92
EP 98
DI 10.3109/09286586.2014.884602
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AC9RM
UT WOS:000332872000005
PM 24527687
DA 2022-11-30
ER

PT J
AU Liegl, R
   Koenig, S
   Siedlecki, J
   Haritoglou, C
   Kampik, A
   Kernt, M
AF Liegl, Raffael
   Koenig, Susanna
   Siedlecki, Jakob
   Haritoglou, Christos
   Kampik, Anselm
   Kernt, Marcus
TI Temsirolimus Inhibits Proliferation and Migration in Retinal Pigment
   Epithelial and Endothelial Cells via mTOR Inhibition and Decreases VEGF
   and PDGF Expression
SO PLOS ONE
LA English
DT Article
ID DIABETIC MACULAR EDEMA; GROWTH-FACTOR; MAMMALIAN TARGET; HYPOXIC
   REGULATION; DEGENERATION; ANGIOGENESIS; RAPAMYCIN; EFFICACY;
   RANIBIZUMAB; SAFETY
AB Due to their high prevalence, retinal vascular diseases including age related macular degeneration (AMD), retinal vein occlusions (RVO), diabetic retinopathy (DR) and diabetic macular edema have been major therapeutic targets over the last years. The pathogenesis of these diseases is complex and yet not fully understood. However, increased proliferation, migration and angiogenesis are characteristic cellular features in almost every retinal vascular disease. The introduction of vascular endothelial growth factor (VEGF) binding intravitreal treatment strategies has led to great advances in the therapy of these diseases. While the predominant part of affected patients benefits from the specific binding of VEGF by administering an anti-VEGF antibody into the vitreous cavity, a small number of non-responders exist and alternative or additional therapeutic strategies should therefore be evaluated. The mammalian target of rapamycin (mTOR) is a central signaling pathway that eventually triggers up-regulation of cellular proliferation, migration and survival and has been identified to play a key role in angiogenesis. In the present study we were able to show that both retinal pigment epithelial (RPE) cells as wells as human umbilical vein endothelial cells (HUVEC) are inhibited in proliferating and migrating after treatment with temsirolimus in non-toxic concentrations. Previous studies suggest that the production of VEGF, platelet derived growth factor (PDGF) and other important cytokines is not only triggered by hypoxia but also by mTOR itself. Our results indicate that temsirolimus decreases VEGF and PDGF expression on RNA and protein levels significantly. We therefore believe that the mTOR inhibitor temsirolimus might be a promising drug in the future and it seems worthwhile to evaluate complementary therapeutic effects with anti-VEGF drugs for patients not profiting from mono anti-VEGF therapy alone.
C1 [Liegl, Raffael; Koenig, Susanna; Siedlecki, Jakob; Haritoglou, Christos; Kampik, Anselm; Kernt, Marcus] Univ Munich, Dept Ophthalmol, Munich, Germany.
C3 University of Munich
RP Liegl, R (通讯作者)，Univ Munich, Dept Ophthalmol, Munich, Germany.
EM Raffael.Liegl@med.uni-muenchen.de
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NR 67
TC 28
Z9 30
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 FEB 26
PY 2014
VL 9
IS 2
AR e88203
DI 10.1371/journal.pone.0088203
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AC3BC
UT WOS:000332389000009
PM 24586308
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Bandyopadhyay, M
   Rohrer, B
AF Bandyopadhyay, Mausumi
   Rohrer, Baerbel
TI Matrix Metalloproteinase Activity Creates Pro-Angiogenic Environment in
   Primary Human Retinal Pigment Epithelial Cells Exposed to Complement
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   BRUCHS MEMBRANE; ALTERNATIVE PATHWAY; TARGETED INHIBITOR; DRUSEN
   FORMATION; MOUSE MODEL; RPE; EXPRESSION
AB PURPOSE. Mechanistic studies have shown that inflammation, complement activation, extracellular matrix (ECM) turnover, growth factor imbalance, and oxidative stress are fundamental components of age-related macular degeneration (AMD). Matrix metalloproteinases (MMPs) mediate ECM turnover but also process various bioactive molecules. Here, we tested whether complement attack on RPE monolayers changes MMP secretion and activation, thereby altering the availability of growth factors in the extracellular space.
   METHODS. Human embryonic RPE monolayers with stable transepithelial resistance (TER) were established. Complement activation was induced with H2O2 and normal human serum. MMP-2/9, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) protein, and mRNA levels were analyzed by Western blotting, ELISA, and real-time PCR; activity of MMP-2/9 by gelatin zymography.
   RESULTS. Complement activation resulted in a loss of TER, which required transient membrane attack complex formation, activation of the alternative pathway, and VEGF secretion and signaling. Despite the generation of reactive oxygen species, cellular integrity or intracellular adenosine triphosphate (ATP) levels were unaffected. However, expression of MMP-2/9 and their protease activity was elevated. Inhibition of MMP-2/9 activity increased PEDF and decreased VEGF levels in the apical and basal supernatants but had no effect on their expression levels. VEGF levels in the supernatant correlated with the level TER reduction.
   CONCLUSIONS. These studies suggest that complement activation, by altering the expression and activation of MMPs, has the ability to generate a proangiogenic environment by altering the balance between VEGF and PEDF. Our findings link reported results that have been associated with AMD pathogenesis; oxidative stress; complement activation; VEGF/PEDF ratio; and MMP activity. (Invest Ophthalmol Vis Sci. 2012;53:1953-1961) DOI:10.1167/iovs.11-8638
C1 [Bandyopadhyay, Mausumi; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center
RP Rohrer, B (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, Storm Eye Inst, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU National Institutes of Health [R01EY019320, C06 RR015455]; Department of
   Veterans Affairs [I01 RX000444]; Foundation Fighting Blindness; Research
   to Prevent Blindness, New York, New York (RPB); 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 Supported in part by the National Institutes of Health Grant
   R01EY019320; Department of Veterans Affairs Grant I01 RX000444;
   Foundation Fighting Blindness; and an unrestricted grant to MUSC from
   Research to Prevent Blindness, New York, New York (RPB). BR is a
   Research to Prevent Blindness Olga Keith Wiess Scholar. Animal studies
   were conducted in a facility constructed with support from the National
   Institutes of Health Grant C06 RR015455.
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NR 71
TC 42
Z9 44
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 2012
VL 53
IS 4
BP 1953
EP 1961
DI 10.1167/iovs.11-8638
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937PC
UT WOS:000303669400032
PM 22408008
OA Green Published
DA 2022-11-30
ER

PT J
AU Sheffield, VC
   Stone, EM
AF Sheffield, Val C.
   Stone, Edwin M.
TI Genomics and the Eye
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID COMPLEMENT FACTOR-H; GENE-THERAPY; DISEASE; MUTATIONS; GENERATION;
   PHOTORECEPTORS; SUSCEPTIBILITY; POLYMORPHISM; CELLS; DIFFERENTIATION
AB THE EYE HAS HAD A PIVOTAL ROLE IN THE EVOLUTION OF HUMAN GENOMICS. At least 90% of the genes in the human genome are expressed in one or more of the eye's many tissues and cell types at some point during a person's life. Consistent with this impressive genomic footprint is the observation that about a third of entries in the Online Mendelian Inheritance in Man database for which a clinical synopsis is provided include a term that refers to the structure or function of the eye.(1) Moreover, the phenotypic effects of even small genetic variations are made readily apparent by the many layers of amplification in the human visual system. For example, a single-nucleotide change in PAX6 can cause an anatomic abnormality of the macula less than a millimeter in diameter that results in noticeably reduced visual acuity and nystagmus.(2)
   The heritable inability to correctly perceive the color green, known as Daltonism (after the English chemist John Dalton, who himself was affected), was the first human trait mapped to the X chromosome.(3) (See Fig. 1 for a timeline of historic discoveries.) The Coppock cataract was the first human trait mapped to an autosome,(4) and Leber's hereditary optic neuropathy was the first human disease shown to be caused by a mutation in mitochondrial DNA.(5) More recently, age-related macular degeneration (AMD) and glaucoma(6,7) - two common causes of human blindness - have been shown to be largely genetic, as has Fuchs' endothelial dystrophy,(8) the most common cause of corneal transplantation in developed countries. Here, we review discoveries in mendelian and complex ophthalmic disorders and their implications for genetic testing and therapeutic intervention.
C1 [Sheffield, Val C.] Univ Iowa, Carver Coll Med, Howard Hughes Med Inst, Dept Pediat, Iowa City, IA 52242 USA.
   [Sheffield, Val C.; Stone, Edwin M.] Univ Iowa, Carver Coll Med, Howard Hughes Med Inst, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
C3 Howard Hughes Medical Institute; University of Iowa; Howard Hughes
   Medical Institute; University of Iowa
RP Stone, EM (通讯作者)，Univ Iowa, Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
EM edwin-stone@uiowa.edu
OI Stone, Edwin M./0000-0003-3343-4414; Sheffield, Val/0000-0002-6282-0835
FU Howard Hughes Medical Institute Funding Source: Medline; NEI NIH HHS
   [R01 EY017168, R01 EY011298] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY017168, R01EY011298] Funding Source: NIH RePORTER
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NR 63
TC 55
Z9 59
U1 1
U2 56
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 19
PY 2011
VL 364
IS 20
BP 1932
EP 1942
DI 10.1056/NEJMra1012354
PG 11
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 765PJ
UT WOS:000290720700008
PM 21591945
DA 2022-11-30
ER

PT J
AU Barker, FM
AF Barker, Felix M., III
TI Dietary supplementation: effects on visual performance and occurrence of
   AMD and cataracts
SO CURRENT MEDICAL RESEARCH AND OPINION
LA English
DT Review
DE AMD; Cataract; Diet; Lutein; Vision; Zeaxanthin
ID PIGMENT OPTICAL-DENSITY; AGE-RELATED MACULOPATHY; LONG-TERM INCIDENCE;
   MACULAR PIGMENT; EYE DISEASE; SERUM CONCENTRATIONS; VITAMIN-C;
   CONSTITUENT CAROTENOIDS; ANTIOXIDANT VITAMINS; ALPHA-TOCOPHEROL
AB Objective:
   To evaluate results of studies that have provided information regarding the effects of dietary supplementation on visual performance, development and progression of age-related macular degeneration (AMD), and risk for cataracts.
   Research design and methods:
   Studies with information about the effects of dietary supplementation were identified via PubMed searches that combined (in separate searches) the terms 'supplement' OR 'supplementation' OR 'diet' AND 'cataract' or 'macular degeneration' or 'visual' OR 'vision'. Additional references concerned with biologic effects of specific agents, measurement of visual function, and the etiology and epidemiology of cataracts and AMD were identified on the basis of PubMed conventional literature searches.
   Results:
   Studies of the effects of dietary supplementation, primarily with preparations including lutein and zeaxanthin, have demonstrated improvements in contrast sensitivity and visual performance under glare conditions that, in some studies, have been correlated with effects of treatment on macular pigment optical density. Results from both observational and prospective interventional studies generally support the conclusion that dietary supplements including these xanthophylls significantly decrease the occurrence of AMD and the development of nuclear lens opacities. However, there is variability in results regarding effects of dietary supplementation that may be related to limitations of long-term observational or interventional studies and which cannot be easily controlled or which may also be related in some studies to other important, yet unrecorded, diet- and lifestyle-related factors that are capable of influencing the risks for AMD and/or cataracts.
   Conclusions:
   The multiple benefits of dietary supplementation support the development and use of these preparations to promote optimal visual function and decrease risk for AMD and cataracts. Increasing understanding of the optimal approach to supplementation will depend upon results from interventional studies that also carefully evaluate and analyze well-established factors for these two conditions.
C1 Salus Univ, Penn Coll Optometry, Elkins Pk, PA 19027 USA.
RP Barker, FM (通讯作者)，Salus Univ, Penn Coll Optometry, 8360 Old York Rd, Elkins Pk, PA 19027 USA.
EM Felix@salus.edu
FU Pfizer Consumer Healthcare
FX This paper was funded by Pfizer Consumer Healthcare.
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NR 92
TC 18
Z9 19
U1 1
U2 15
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0300-7995
EI 1473-4877
J9 CURR MED RES OPIN
JI Curr. Med. Res. Opin.
PD AUG
PY 2010
VL 26
IS 8
BP 2011
EP 2023
DI 10.1185/03007995.2010.494549
PG 13
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA 636PQ
UT WOS:000280751000024
PM 20590393
DA 2022-11-30
ER

PT J
AU Liao, WL
   Turko, IV
AF Liao, Wei-Li
   Turko, Illarion V.
TI Accumulation of Large Protein Fragments in Prematurely Senescent ARPE-19
   Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE;
   MACULAR DEGENERATION; GEL-ELECTROPHORESIS; MASS-SPECTROMETRY; OXIDATIVE
   STRESS; DYSFUNCTION; PROTEASOME; AUTOPHAGY; ENZYMES
AB PURPOSE. Senescence of retinal pigment epithelial (RPE) cells is a crucial event in the pathogenesis of age-related macular degeneration (AMD). This study was designed to improve the understanding of proteomic changes that underlie RPE senescence. Specifically, the levels of several protein fragments in prematurely senescent ARPE-19 cells were quantitatively compared with those in control cells.
   METHODS. Premature senescence of human ARPE-19 cells was induced by repeated treatments with 6 mM tert-butylhydroperoxide (tert-BHP). Whole senescent cells were then treated with deuterated D-3-acrylamide, and control cells were treated with normal D-0-acrylamide. The D-3 and D-0 samples were mixed at a 1:1 ratio, and the proteins were separated by FPLC (fast protein liquid chromatography) and 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis). After in-gel trypsinolysis, the relative quantification of selected proteins and fragments in the senescent cells versus control ARPE-19 cells was achieved by calculating the ratio of signal intensities for the deuterated and normal forms of cysteine-containing labeled peptides in MALDI-MS (matrix-assisted laser desorption/ionization mass spectrometry) spectra.
   RESULTS. Several large fragments of typical cytosolic proteins, such as GAPDH, triosephosphate isomerase, and M2-type pyruvate kinase increased approximately two-to threefold in the prematurely senescent ARPE-19 cells.
   CONCLUSIONS. This study is the first demonstration that large fragments of cytosolic proteins can be accumulated in prematurely senescent ARPE-19 cells, the in vitro model of AMD. These data suggest that protein degradation processes are impaired in these cells and point to a new type of "waste" material in post-mitotic cells that may contribute to the senescent phenotype. (Invest Ophthalmol Vis Sci. 2009; 50: 4992-4997) DOI: 10.1167/iovs.09-3671
C1 [Liao, Wei-Li; Turko, Illarion V.] Univ Maryland, Inst Biotechnol, Natl Inst Stand & Technol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University
   System of Maryland; University of Maryland Baltimore
RP Turko, IV (通讯作者)，Univ Maryland, Inst Biotechnol, Natl Inst Stand & Technol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM turko@umbi.umd.edu
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NR 26
TC 8
Z9 8
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 OCT
PY 2009
VL 50
IS 10
BP 4992
EP 4997
DI 10.1167/iovs.09-3671
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 497XE
UT WOS:000270097200061
PM 19458325
DA 2022-11-30
ER

PT J
AU Sharma, RK
   Netland, PA
   Kedrov, MA
   Johnson, DA
AF Sharma, Rajesh K.
   Netland, Peter A.
   Kedrov, Marina A.
   Johnson, Dianna A.
TI Preconditioning protects the retinal pigment epithelium cells from
   oxidative stress-induced cell death
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; cell attachment; cell migration;
   oxidative preconditioning; redox
ID HYDROGEN-PEROXIDE; MACULAR DEGENERATION; MAMMALIAN-CELLS; DNA-DAMAGE;
   CYTOTOXICITY; APOPTOSIS; DEGRADATION; ADAPTATION; MECHANISMS; EXPOSURE
AB The cytotoxic effects of oxidative stress, which play an important role in ocular diseases, are well known. In this study, we investigated the effect of non-lethal doses of oxidative stress on various cell functions, namely cell viability, cell attachment and cell migration in a widely used retinal pigment epithelium (RPE) cell line (ARPE-19).
   A single exposure to various concentrations of hydrogen peroxide (H2O2) was used to establish a dose response for H2O2-induced cell death. Other cellular responses, such as changes in cell attachment and migration, were monitored after exposure to increasing doses. Finally, the effects of preconditioning cells with increasing non-lethal doses of H2O2, with and without a subsequent exposure to lethal doses of H2O2, were determined.
   The optimum dose for inducing cell death in ARPE-19 cells was between 900 and 1000 mu m H2O2. Preconditioning the cells with 1, 10 and 50 mu m of H2O2 provided a dose-dependent protection against cell death induced by a lethal dose (900-1000 mu m) of H2O2. Preconditioning with higher doses caused cells to become more susceptible to the cytotoxic effects of the lethal dose. Although H2O2 increased cell attachment in lower doses, it induced a dose-dependent inhibition of cell attachment to the substrate in higher doses. H2O2 did not affect cell migration in sub-lethal doses.
   Preconditioning RPE cells with limited exposure to non-lethal oxidative stress confers significant protection against subsequent H2O2-induced cell death. It also affects cell attachment in a dose-specific manner. This finding may help in understanding the pathogenesis of diseases in which oxidative stress plays an important role and in determining the suitability of certain treatment strategies, in particular RPE transplantation in the treatment of age-related macular degeneration.
C1 Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA.
   Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, 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 Sharma, RK (通讯作者)，Univ Tennessee, Res Ctr, Hamilton Eye Inst, Dept Ophthalmol, 930 Madison Ave, Memphis, TN 38163 USA.
EM rajesh.sharma@jax.ufl.edu
FU Hyde Foundation; NEI [EY-13080]; NATIONAL EYE INSTITUTE [P30EY013080]
   Funding Source: NIH RePORTER
FX The authors wish to thank Dr Barrett Haik for support. This work was
   supported by a grant from Gail and Richard Siegal, The Hyde Foundation,
   NEI grant EY-13080, Gerwin Scholar Award, Lion's Club, and Research to
   Prevent Blindness.
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NR 28
TC 13
Z9 13
U1 0
U2 8
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 2009
VL 87
IS 1
BP 82
EP 88
DI 10.1111/j.1755-3768.2008.01170.x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 399UZ
UT WOS:000262826100013
PM 18494742
DA 2022-11-30
ER

PT J
AU Khachik, F
   de Moura, FF
   Chew, EY
   Douglass, LW
   Ferris, FL
   Kim, J
   Thompson, DJS
AF Khachik, Frederick
   de Moura, Fabiana F.
   Chew, Emily Y.
   Douglass, Larry W.
   Ferris, Frederick L., III
   Kim, Jonghyeon
   Thompson, Darby J. S.
TI The effect of lutein and zeaxanthin supplementation on metabolites of
   these carotenoids in the serum of persons aged 60 or older
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID STRUCTURAL ELUCIDATION; GEOMETRICAL-ISOMERS; OXIDATION-PRODUCTS; MACULAR
   PIGMENT; IDENTIFICATION; MACULOPATHY; EXTRACTS; TISSUES; PLASMA
AB PURPOSE. To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol.
   METHODS. Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-to-copherol were identified and quantified on a C-18 reversed phase HPLC column.
   RESULTS. After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-ss, epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'- hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon, epsilon-carotene- 3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation.
   CONCLUSIONS. The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects.
C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
   Univ Maryland, Dept Avian Sci, College Pk, MD 20742 USA.
   NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
   EMMES Corp, Rockville, MD USA.
C3 University System of Maryland; University of Maryland College Park; US
   Food & Drug Administration (FDA); University System of Maryland;
   University of Maryland College Park; National Institutes of Health (NIH)
   - USA; NIH National Eye Institute (NEI); Emmes Corporation
RP Khachik, F (通讯作者)，Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, Bldg 091, College Pk, MD 20742 USA.
EM khachik@umd.edu
RI Khachik, Frederick/C-5055-2009
OI Ferris, Frederick/0000-0002-4933-0639; De Moura, Fabiana
   F./0000-0001-8176-5352
FU Intramural NIH HHS [ZIA EY000485-01, Z99 EY999999] Funding Source:
   Medline
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NR 30
TC 49
Z9 58
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2006
VL 47
IS 12
BP 5234
EP 5242
DI 10.1167/iovs.06-0504
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 110TW
UT WOS:000242404900017
PM 17122108
DA 2022-11-30
ER

PT J
AU Pegaz, B
   Debefve, E
   Ballini, JP
   Konan-Kouakou, YN
   van den Bergh, H
AF Pegaz, Bernadette
   Debefve, Elodie
   Ballini, Jean-Pierre
   Konan-Kouakou, Yvette Niamien
   van den Bergh, Hubert
TI Effect of nanoparticle size on the extravasation and the photothrombic
   activity of meso(p-tetracarboxyphenyl)porphyrin
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE photodynamic therapy; photosensitizer;
   meso-tetra(carboxyphenyl)porphyrin; chicken embryo; nanoparticles;
   particle size
ID SALTING-OUT PROCESS; POLY(LACTIC ACID) NANOPARTICLES; SUB-200 NM
   NANOPARTICLES; PHOTODYNAMIC THERAPY; IN-VITRO; BIODEGRADABLE
   NANOPARTICLES; MACULAR DEGENERATION; PARTICLE-SIZE; PARAMETERS;
   NANODISPERSIONS
AB Particle size should be optimized to achieve targeted and extended drug delivery to the affected tissues. We describe here the effects of the mean particle size on the pharmacokinetics and photothrombic activity of meso-tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable nanoparticles based on poly(D,L-lactic acid). Four batches of nanoparticles with different mean sizes ranging from 121 to 343 nm, were prepared using the emulsification-diffusion technique. The extravasations of each TCPP-loaded nanoparticle formulation from blood vessels were measured, as well as the extent of photochemically induced vascular occlusion. These preclinical tests were carried out in the chorioallantoic membrane (CAM) of the chicken's embryo. Fluorescence microscopy showed that both the effective leakage of TCPP from the CAM blood vessels and its photothrombic efficiency were dependent on the size of the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the blood vessels and the surrounding tissue increased at the applied conditions, when the particle size decreased. This suggests that large nanoparticles are more rapidly eliminated from the bloodstream. In addition, after injection of a drug dose of 1 mg/kg body weight and a drug-light application interval of 1 min, irradiation with a fluence of 10 J/cm(2) showed that the extent of vascular damage gradually decreased when the particle size increased. The highest photothrombic efficiency was observed when using the TCPP-loaded nanoparticles batch with a mean diameter of 121 nm. Thus, in this range of applied conditions, for the treatment of for instance a disease like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments suggest that the smallest nanoparticles may be considered as the optimal formulation since they exhibited the greatest extent of vascular thrombosis as well as the lowest extravasation. (c) 2006 Elsevier B.V. All rights reserved.
C1 Ecole Polytech Fed Lausanne, Fac Sci Base, Lab Photomed, Stn 6, CH-1015 Lausanne, Switzerland.
C3 Ecole Polytechnique Federale de Lausanne
RP van den Bergh, H (通讯作者)，Ecole Polytech Fed Lausanne, Fac Sci Base, Lab Photomed, Stn 6, CH-1015 Lausanne, Switzerland.
EM hubert.vandenbergh@epfl.ch
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NR 31
TC 29
Z9 31
U1 0
U2 16
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 DEC 1
PY 2006
VL 85
IS 3
BP 216
EP 222
DI 10.1016/j.jphotobiol.2006.07.008
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 115KE
UT WOS:000242732400008
PM 16979346
DA 2022-11-30
ER

PT J
AU Benzie, IFF
   Chung, WY
   Wang, J
   Richelle, M
   Bucheli, P
AF Benzie, Iris F. F.
   Chung, Wai Y.
   Wang, Junkuan
   Richelle, Myriam
   Bucheli, Peter
TI Enhanced bioavailability of zeaxanthin in a milk-based formulation of
   wolfberry (Gou Qi Zi; Fructus barbarum L.)
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE wolfberry; Kei Tze; Gou Qi Zi; Chinese medicine; macular degeneration;
   zeaxanthin
ID GOU-QI-ZI; MACULAR PIGMENT; LIQUID-CHROMATOGRAPHY; PROTECTIVE ROLE;
   LUTEIN; PLASMA; CAROTENOIDS; CHOLESTEROL; SERUM; SUPPLEMENTATION
AB The carotenoid zeaxanthin is concentrated within the macula. Increased macular zeaxanthin is suggested to lower the risk of age-related macular degeneration. The small red berry, wolfberry (Fructus barbarum L.; Gou Qi Zi and Kei Tze), is one of the richest natural sources of zeaxanthin. However, carotenoid bioavailability is low, and food-based products with enhanced bioavailability are of interest. The present study investigated zeaxanthin bioavailability from three wolfberry formulations. Berries were homogenised in hot (80 degrees C) water, warm (40 degrees C) skimmed milk and hot (80 degrees C) skimmed milk, with freeze drying of each preparation into a powdered form. A zeaxanthin-standardised dose (15 mg) of each was consumed, in randomised order, together with a standardised breakfast by twelve healthy, consenting subjects in a cross-over trial, with a 3-5-week washout period between treatments. Blood samples were taken via a venous cannula immediately before (fasting) and 2, 4, 6, 7, 8 and 10 h post-ingestion. Zeaxanthin concentration in the triacylglycerol-rich lipoprotein fraction of plasma was measured by HPLC. Results showed that triacylglycerol-rich lipoprotein zeaxanthin peaked at 6 h post-ingestion for all formulations. Zeaxanthin bioavailability from the hot milk formulation was significantly higher (P < 0 center dot 001) than from the others. Mean area under the curve (n 12) results were 9 center dot 73 (sem 2 center dot 45), 3 center dot 24 (sem 0 center dot 72) and 3 center dot 14 (sem 1 center dot 09) nmolxh/l for the hot milk, warm milk and hot water formulations, respectively. Results showed clearly that homogenisation of wolfberry in hot skimmed milk results in a formulation that has a 3-fold enhanced bioavailability of zeaxanthin compared with both the 'classical' hot water and warm skimmed milk treatment of the berries.
C1 Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Kowloon, Hong Kong, Peoples R China.
   Nestle Res Ctr, CH-1000 Lausanne, Switzerland.
   Shanghai Ltd, Nestel R&D Ctr, Shanghai, Peoples R China.
C3 Hong Kong Polytechnic University; Nestle SA
RP Benzie, IFF (通讯作者)，Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Kowloon, Hong Kong, Peoples R China.
EM iris.benzie@inet.polyu.edu.hk
OI Benzie, Iris/0000-0002-2312-0318
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NR 49
TC 42
Z9 54
U1 0
U2 18
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUL
PY 2006
VL 96
IS 1
BP 154
EP 160
DI 10.1079/BJN20061796
PG 7
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 067ED
UT WOS:000239283600022
PM 16870004
OA Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Johnson, PT
   Brown, MN
   Pulliam, BC
   Anderson, DH
   Johnson, LV
AF Johnson, PT
   Brown, MN
   Pulliam, BC
   Anderson, DH
   Johnson, LV
TI Synaptic pathology, altered gene expression, and degeneration in
   photoreceptors impacted by drusen
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; APOLIPOPROTEIN-E; DARK-ADAPTATION;
   RISK-FACTORS; FELLOW EYE; ABNORMALITIES; SYNAPTOTAGMIN; ACTIVATION;
   SYNTAXIN; COMMON
AB PURPOSE. Drusen are risk factors for age-related macular degeneration and have been shown to negatively impact cells of the RPE and retina. In this study, the effects of drusen on the synaptic machinery of retinal photoreceptors are investigated.
   METHODS. Human donor eye tissue containing retina, RPE, and choroid was processed for confocal immunofluorescence microscopy, laser capture microdissection, and light and electron microscopy. Tissue sections were immunostained with a panel of antibodies to synapse-associated proteins. Populations of photoreceptors over drusen and normal populations of photoreceptors were microdissected from fresh frozen tissue, RNA was purified, and quantitative PCR was performed to compare relative levels of gene expression.
   RESULTS. The number of photoreceptor synaptic terminals is reduced in regions of the outer plexiform layer over drusen, synaptic proteins are mislocalized in photoreceptor cells, and synaptic terminals are often observed within the outer nuclear layer. Photoreceptors over drusen also increase expression of the stress response proteins apolipoprotein E and alpha B-crystallin. Abnormal immunolabeling patterns are not restricted to photoreceptors directly over drusen but are also observed in cells flanking drusen. Gene expression analysis confirms reductions in the expression of genes coding for synapse-associated proteins and signal transduction proteins and increases in the expression of apolipoprotein E and alpha B-crystallin gene transcripts. Ultrastructural analysis of photoreceptor synaptic terminals over drusen reveals significant abnormalities, and cell counts show a reduction in photoreceptor density directly over, and lateral to, drusen of all sizes.
   CONCLUSIONS. Photoreceptors overlying and flanking drusen exhibit morphologic and biochemical signs of degeneration. The expression of synapse-associated proteins decreases in photoreceptor synaptic terminals, whereas the expression of stress-response proteins increases. Reductions in photoreceptor cell densities over, and flanking, drusen suggest that these degenerative effects eventually result in the death of photoreceptors.
C1 Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Johnson, PT (通讯作者)，Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
EM p_johnso@lifesci.ucsb.edu
FU NATIONAL EYE INSTITUTE [R01EY011521, R01EY011527] Funding Source: NIH
   RePORTER; NEI NIH HHS [EY11527, EY11521] Funding Source: Medline
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NR 50
TC 88
Z9 91
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 DEC
PY 2005
VL 46
IS 12
BP 4788
EP 4795
DI 10.1167/iovs.05-0767
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 988FV
UT WOS:000233578600062
PM 16303980
DA 2022-11-30
ER

PT J
AU Kokkinou, D
   Kasper, HU
   Schwarz, T
   Bartz-Schmidt, KU
   Schraermeyer, U
AF Kokkinou, D
   Kasper, HU
   Schwarz, T
   Bartz-Schmidt, KU
   Schraermeyer, U
TI Zinc uptake and storage: the role of fundus pigmentation
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; choroid; pigmentation; zinc uptake;
   zinc storage
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; OCULAR MELANIN;
   RISK-FACTORS; IRIS COLOR; ORAL ZINC; EYE; EPITHELIUM; ANTIOXIDANTS;
   MELANOSOME
AB Background: Age-related macular degeneration (AMD) is associated with lower melanin pigmentation and is more prevalent among the elderly Caucasian population than among Africans. A correlation between light iris colour, fundus pigmentation and the incidence of AMD is reported. Moreover, melanin represents the main storage of zinc in the eye. Zinc enhances antioxidant capacity through its function as a cofactor of important enzymes or by influencing gene expression of regulatory elements in the eye. In this study, we investigated the uptake and storage of zinc in the human choroid/retinal pigment epithelium (RPE) complexes in dependence on the fundus pigmentation as judged by the iris colour. Material and methods: Choroid/RPE complexes of blue and brown human eyes were used. Tissues without any substitution served as controls. Specimens from choroid/RPE complexes were incubated with 100 mu M zinc chloride for 24 h. After incubation, pieces of the complexes were stored to investigate the uptake of zinc. The rest of the tissues were kept for 3 and 7 days in culture medium (DMEM) for storage examination. The concentration of zinc was measured by inductively coupled plasma mass spectrometry. Results: After 24 h of zinc treatment the concentration of zinc in the choroid/RPE complexes of blue eyes was not significantly increased. The concentration of zinc in highly pigmented tissues (brown eyes) was increased by the factor 5.1 after 24 h and remained at high levels after 3 days (factor 4.4) and 7 days (factor 2.8). Conclusions: Zinc uptake in the choroid/RPE complex correlates to the iris colour. Alterations of the degree of iris pigmentation result in differences of zinc uptake and storage in the choroids. A potential protective role of zinc may be more prominent in dark- than in light-coloured eyes.
C1 Univ Tubingen, Sect Expt Vitreoretinal Surg, D-72076 Tubingen, Germany.
   Univ Cologne, Geochem Lab, Dept Geol & Mineral, D-50674 Cologne, Germany.
   Univ Tubingen, Dept Ophthalmol 1, D-72076 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 58
TC 18
Z9 18
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2005
VL 243
IS 10
BP 1050
EP 1055
DI 10.1007/s00417-005-1197-7
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 976GR
UT WOS:000232721500014
PM 15906061
DA 2022-11-30
ER

PT J
AU Fawzi, AA
   Vo, B
   Kriwanek, R
   Ramkumar, HL
   Cha, C
   Carts, A
   Heckenlively, JR
   Foos, RY
   Glasgow, BJ
AF Fawzi, AA
   Vo, B
   Kriwanek, R
   Ramkumar, HL
   Cha, C
   Carts, A
   Heckenlively, JR
   Foos, RY
   Glasgow, BJ
TI Asteroid hyalosis in an autopsy population - The University of
   California at Los Angeles (UCLA) Experience
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID POSTERIOR VITREOUS DETACHMENT; DIABETES-MELLITUS; BODIES; HYALITIS;
   HYPERCHOLESTEROLEMIA; VITRECTOMY; PREVALENCE; EYE
AB Objectives: To study the prevalence and associations of asteroid hyalosis (AH) in a series of autopsy eyes.
   Methods: Retrospective review of the University of California at Los Angeles (UCLA) autopsy eye database from 1965 to 2000 yielded 10801 patients. The patients' medical histories were reviewed for evidence of diabetes mellitus, hypertension, hyperlipidemia, alcohol abuse, hypercalcemia, hypothyroidism, and chronic renal failure. Autopsy records were searched for evidence of optic atrophy, macular degeneration, posterior vitreous detachment, atherosclerosis, and chronic renal failure. Asteroid hyalosis was diagnosed by examination of the autopsy eyes. Univariate and multivariate statistical methods were used to analyze our data.
   Results: The prevalence of AH was 1.96% in this autopsy population. By chi(2) analysis, AH was significantly correlated with age (P < .001), male sex (P = .006), age-related macular degeneration (P =.02), hypertension (P = .03), atherosclerosis (P < .001), and posterior vitreous attachment (P < .001). After adjusting for age in a multivariate logistic regression analysis, statistical significance was found only for posterior vitreous attachment (P = .002) and male sex (P = .046). No statistically significant association was found with diabetes mellitus or alcohol abuse by univariate or multivariate analysis. Analysis of the odds ratio showed a strong age effect that increased from 5.0 (95% confidence interval, 2.2-11.3) in age group 41 to 50 years, compared with 25.4 (95% Wald confidence interval, 8.2-77.9) in the age group of patients older than 90 years.
   Conclusions: A unique epidemiological autopsy cohort study of AH and its systemic associations yielded a higher prevalence of AH than previous studies. Asteroid hyalosis was strongly correlated with age and inversely correlated with posterior vitreous detachment. Unlike some previous reports, we found no statistically significant correlation between AH and diabetes mellitus.
C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Glasgow, BJ (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 100 Stein Plaza,B-279, Los Angeles, CA 90095 USA.
EM bglasgow@mednet.ucla.edu
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558
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   PROFILES GEN DEMOGRA
NR 28
TC 37
Z9 40
U1 0
U2 3
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 APR
PY 2005
VL 123
IS 4
BP 486
EP 490
DI 10.1001/archopht.123.4.486
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 913FQ
UT WOS:000228137400007
PM 15824221
DA 2022-11-30
ER

PT J
AU Hartmann, D
   Thurmann, PA
   Spitzer, V
   Schalch, W
   Manner, B
   Cohn, W
AF Hartmann, D
   Thurmann, PA
   Spitzer, V
   Schalch, W
   Manner, B
   Cohn, W
TI Plasma kinetics of zeaxanthin and 3 '-dehydro-lutein after multiple oral
   doses of synthetic zeaxanthin
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE xanthophyll; carotenoids; zeaxanthin; multiple oral dose kinetics;
   beadlet formulation; all-E-3 '-dehydro-lutein; lutein
ID CAROTENOIDS; LUTEIN; BIOAVAILABILITY; VEGETABLES; FRUITS
AB Background: Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration; however, kinetic information is limited.
   Objectives: The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the possible influence of other carotenoids on plasma zeaxanthin concentrations.
   Design: After a run-in of 3 d, 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either I mg (1.76 mumol) or 10 mg (17.6 mumol) zeaxanthin for 42 d. Plasma concentration-time profiles on days I and 42, concentrations immediately before zeaxanthin intake during the dosing period, and concentrations after the last dose until day 76 were monitored.
   Results: al-E-Zeaxanthin concentrations increased from 0.048 +/- 0.026 mumol/L at baseline to 0.20 +/- 0.07 and 0.92 +/- 0.28 mumol/L with I and 10 mg zeaxanthin, respectively. The dose-normalized bioavailability of all-E-zeaxanthin after the 10-mg dose was 40% lower(P < 0.001) than after the 1-mg dose. Other kinetic parameters did not differ significantly between groups. After 17 d of dosing, > 90% of steady state concentrations were reached, which was compatible with an effective half-life for accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d (n = 20). The time course of plasma all-E-3'-dehydro-lutein concentrations resembled that of all-E-zeaxanthin. The data provided evidence that all-E-3'-dehydro-lutein was derived from all-E-zeaxanthin. Concentrations of other carotenoids were not affected. Zeaxanthin was well tolerated.
   Conclusion: Long-term oral intake of I and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximate to4- and 20-fold, respectively. Evidence that all-E-3'-dehydro-lutein is formed from zeaxanthin was strong.
C1 Roche Vitamins Ltd, Dept Human Nutr & Hlth, CH-4070 Basel, Switzerland.
   Univ Witten Herdecke, HELIOS Klinikum Wuppertal, Inst Clin Pharmacol, Wuppertal, Germany.
C3 Roche Holding; Helios Kliniken; Witten Herdecke University
RP Cohn, W (通讯作者)，Roche Vitamins Ltd, Dept Human Nutr & Hlth, Grenzacherstr 124, CH-4070 Basel, Switzerland.
EM willy.cohn@roche.com
OI Thurmann, Petra/0000-0001-9724-1422
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NR 25
TC 55
Z9 58
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2004
VL 79
IS 3
BP 410
EP 417
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 777RD
UT WOS:000189190600011
PM 14985215
DA 2022-11-30
ER

PT J
AU Lem, DW
   Gierhart, DL
   Davey, PG
AF Lem, Drake W.
   Gierhart, Dennis L.
   Davey, Pinakin Gunvant
TI A Systematic Review of Carotenoids in the Management of Diabetic
   Retinopathy
SO NUTRIENTS
LA English
DT Review
DE diabetic retinopathy; macular xanthophylls; carotenoids; macular
   pigment; macular pigment optical density; MPOD; lutein; zeaxanthin;
   meso-zeaxanthin; diabetes; diabetic retinopathy; retinal
   neurodegeneration; neuroprotection
ID PIGMENT OPTICAL-DENSITY; HETEROCHROMATIC FLICKER PHOTOMETRY;
   DUAL-WAVELENGTH AUTOFLUORESCENCE; RETINAL METABOLIC ABNORMALITIES;
   MACULAR PIGMENT; SERUM CONCENTRATIONS; OXIDATIVE STRESS; ZEAXANTHIN
   SUPPLEMENTATION; PLASMA CAROTENOIDS; MESO-ZEAXANTHIN
AB Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine andWeb of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.
C1 [Lem, Drake W.; Davey, Pinakin Gunvant] Western Univ Hlth Sci, Coll Optometry, 309 E Second St, Pomona, CA 91766 USA.
   [Gierhart, Dennis L.] ZeaVision LLC, Chesterfield, MO 63005 USA.
C3 Western University of Health Sciences
RP Davey, PG (通讯作者)，Western Univ Hlth Sci, Coll Optometry, 309 E Second St, Pomona, CA 91766 USA.
EM drake.lem@westernu.edu; dgierhart@zeavision.com;
   contact@pinakin-gunvant.com
OI Davey, Pinakin/0000-0002-6683-7052
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NR 223
TC 10
Z9 10
U1 3
U2 8
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD JUL
PY 2021
VL 13
IS 7
AR 2441
DI 10.3390/nu13072441
PG 23
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA TN8YU
UT WOS:000676514300001
PM 34371951
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Biarnes, M
   Mones, J
AF Biarnes, Marc
   Mones, Jordi
TI Regression to the Mean in Measurements of Growth Rates in Geographic
   Atrophy
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Regression to the mean; Age-related macular degeneration; Geographic
   atrophy; Growth; Progression
ID MACULAR DEGENERATION; PROGRESSION; SECONDARY
AB Introduction:Comparison of patients with extremely high and low values of a given characteristic is a common strategy to gain insights into disease mechanisms, but this approach is particularly susceptible to regression to the mean (RTM).Objective:The aim of this work was to determine RTM in growth rate measurements in patients with geographic atrophy (GA) secondary to age-related macular degeneration.Methods:We conducted a retrospective analysis of the GAIN (NCT01694095) and its extension study, in which individuals 50 years or older with pure GA were followed for a minimum of 6 months. Two repeated and masked measurements of area of atrophy, both at baseline and final visits, were made, and growth rates were calculated for each. RTM was determined graphically and statistically, and the percentage of eyes misclassified as having fast and slow progression rates due to RTM was determined for different definitions of "fast" and "slow" growth.Results:We included 112 eyes of 112 patients: 64.3% were females, the mean age was 78.1 (SD +/- 7.6) years, and the mean follow-up time was 3.2 (+/- 2.2) years. There was RTM, which decreased when the mean of two measurements was used. The magnitude of RTM in growth rates ranged from 2 to 11 mu m/year and led to misclassification of eyes considered to have fast and slow growth between 2.9 and 10.3% of the cases, depending on the definition of fast and slow growth.Conclusions:RTM was present in measurements of GA growth rate, but it had a modest impact on patient misclassification. Comparison of features between patients with extreme growth rates is a reasonable strategy, but RTM should be minimized by taking the mean of two measurements.
C1 [Biarnes, Marc; Mones, Jordi] Barcelona Macula Fdn, Horaci St 41-43,Esc B, ES-08022 Barcelona, Spain.
   [Biarnes, Marc; Mones, Jordi] Hosp Quiron Teknon, Inst Macula, Barcelona, Spain.
RP Biarnes, M (通讯作者)，Barcelona Macula Fdn, Horaci St 41-43,Esc B, ES-08022 Barcelona, Spain.
EM mbiarnes@barcelonamaculafound.org
RI mones, jordi/CAJ-2963-2022
OI mones, jordi/0000-0003-3685-2160
FU EYE-RISK Consortium; European Union's Horizon 2020 Research and
   Innovation Program [634479]
FX This study was partially supported by the EYE-RISK Consortium and
   received funding from the European Union's Horizon 2020 Research and
   Innovation Program under grant 634479. The funding organization had no
   role in the design or conduct of this research.
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NR 16
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 AUG
PY 2020
VL 63
IS 5
BP 460
EP 465
DI 10.1159/000505755
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ND5TM
UT WOS:000561962200003
PM 31905352
OA Bronze
DA 2022-11-30
ER

PT J
AU Karesvuo, P
   Hakkala, L
   Kaarniranta, K
   Uusitalo, H
   Ojamo, M
   Tuuminen, R
AF Karesvuo, Petteri
   Hakkala, Laura
   Kaarniranta, Kai
   Uusitalo, Hannu
   Ojamo, Matti
   Tuuminen, Raimo
TI Correlation between the rate of intravitreal injections, use of
   aflibercept as a second-line treatment and visual impairment for wet AMD
   in Finland
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE aflibercept; anti-vascular endothelial growth factor; treat-and-extend
   regimen; wet age-related macular degeneration; visual impairment
ID GROWTH-FACTOR TREATMENT; MACULAR DEGENERATION; COST-EFFECTIVENESS;
   VEGF-TRAP; FOLLOW-UP; RANIBIZUMAB; EXTEND; REGIMEN; BEVACIZUMAB;
   BLINDNESS
AB Purpose To correlate the rate of intravitreal anti-VEGF injections and the use of aflibercept as a second-line treatment with visual impairment throughout Finland.
   Methods Information related to anti-VEGF treatment, proportions of bevacizumab and aflibercept and new visual impairments due to wet age-related macular degeneration (AMD) was gathered from 5 university hospitals and 14 central hospital districts between 2015 and 2017 covering 232 568 injections and 1172 visual impairments.
   Results Between 2015 and 2017, the number of annual total anti-VEGF injections increased from 60 412 to 93 589 (+24.5% annual change) and of aflibercept injections from 8299 to 20 833 (+58.7% annual change). The 3-year average for total anti-VEGF injections ranged from 9.6 to 21.1 (median 13.3) per 1000 citizens between hospital districts and for aflibercept injections from 0.8 to 4.0 (median 1.9). According to the primary protocol for wet AMD, during 2015-2017, the number of total anti-VEGF injections increased from 10.9 to 15.2 per 1000 citizens with the pro re nata (PRN) protocol and from 11.3 to 18.9 with the treat-and-extend regimen (TER). The 3-year average of aflibercept injections as a second-line treatment, but not the total number of anti-VEGF or bevacizumab injections, inversely correlated with new onset visual impairments (R = -0.505, P = 0.027) in the hospital districts. The number of visual impairments did not differ between the hospital districts according to the PRN and TER protocols (1.23 +/- 0.41 and 1.14 +/- 0.67, respectively, per 1000 citizens aged >= 64 years, P = 0.713).
   Conclusion These results emphasize that the use of aflibercept injections as a second-line treatment may decrease new onset visual impairments.
C1 [Karesvuo, Petteri; Tuuminen, Raimo] Univ Helsinki, Helsinki Retina Res Grp, Helsinki, Finland.
   [Karesvuo, Petteri] Helsinki Univ Hosp, Dept Ophthalmol, Helsinki, Finland.
   [Hakkala, Laura] Turunmaa Reg Hosp, Dept Ophthalmol, Turku, Finland.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio, Finland.
   [Kaarniranta, Kai] Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
   [Uusitalo, Hannu] Tampere Univ, Dept Ophthalmol, SILK, Tampere, Finland.
   [Uusitalo, Hannu] Tays Eye Ctr, Tampere, Finland.
   [Uusitalo, Hannu; Ojamo, Matti] Finnish Register Visual Impairment, Helsinki, Finland.
   [Uusitalo, Hannu; Ojamo, Matti] Natl Inst Hlth & Welf, Helsinki, Finland.
   [Tuuminen, Raimo] Kymenlaakso Cent Hosp, Ctr Eye, Kotkantie 41, FI-48210 Kotka, Finland.
C3 University of Helsinki; University of Helsinki; Helsinki University
   Central Hospital; University of Eastern Finland; Kuopio University
   Hospital; Tampere University; Finland National Institute for Health &
   Welfare
RP Tuuminen, R (通讯作者)，Kymenlaakso Cent Hosp, Ctr Eye, Kotkantie 41, FI-48210 Kotka, Finland.
EM raimo.tuuminen@helsinki.fi
OI Tuuminen, Raimo/0000-0003-1550-8125
FU Finnish Eye Foundation; Finnish Medical Foundation; Finnish
   Ophthalmological Society; Evald and Hilda Nissi Foundation; Paulo
   Foundation; Waldemar von Frenckell Foundation; HUS Specific Catchment
   Area (ERVA) Clinical Research Grants
FX We thank Finland's chief physicians in ophthalmology for their valuable
   data. We are also grateful to the controllers and pharmacists of the
   university and central hospitals. The valuable help of Ms. Jutta
   Jarvelin, MD, PhD, Unit Head from the National Institute for Health and
   Welfare, is also acknowledged. The study was supported by grants from
   the Finnish Eye Foundation, Finnish Medical Foundation, Finnish
   Ophthalmological Society, Evald and Hilda Nissi Foundation, the Paulo
   Foundation, the Waldemar von Frenckell Foundation and the HUS Specific
   Catchment Area (ERVA) Clinical Research Grants.
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NR 38
TC 2
Z9 2
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 AUG
PY 2020
VL 98
IS 5
BP 472
EP 476
DI 10.1111/aos.14376
EA FEB 2020
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ML4LC
UT WOS:000515332300001
PM 32096347
DA 2022-11-30
ER

PT J
AU Zhou, YQ
   Zhou, LB
   Zhou, KW
   Zhang, JY
   Shang, F
   Zhang, XY
AF Zhou, Yeqi
   Zhou, Linbin
   Zhou, Kewen
   Zhang, Jingyue
   Shang, Fu
   Zhang, Xinyu
TI Celastrol Protects RPE Cells from Oxidative Stress-Induced Cell Death
   via Activation of Nrf2 Signaling Pathway
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Celastrol; retinal pigment epithelial cell; oxidative stress; Nrf2
   signaling; age-related macular degeneration; RPE cells
ID MACULAR DEGENERATION; ARPE-19 CELLS; ANTIOXIDANT; INHIBITION;
   MECHANISMS; EXPRESSION; ENZYMES; OBESITY; DAMAGE; MODEL
AB Purpose: Oxidative stress to retinal pigment epithelial (RPE) cells and inflammation are closely related to the pathogenesis of age-related macular degeneration (AMD). Celastrol is a natural compound isolated from the root of Tripterygium wilfordii. Celastrol has been shown to have potent anti-inflammatory and anti-tumor effects in multiple disease models. The objective of this study was to test the anti-oxidative effects of celastrol in RPE cells and to investigate the underlying mechanisms.
   Methods: ARPE-19 cells were treated with hydrogen peroxide (H2O2) and menadione alone or in combination with celastrol. Cell viability and apoptosis were examined by CCK-8 and TUNEL assay, respectively. The expression of Nrf2 and its target genes, such as GCLM and HO-1 was determined by Western blotting. The knockdown of Nrf2 was done by transfecting ARPE-19 cells with lentivirus encoding shRNA against Nrf2. The knockdown efficiency was determined by real-time quantitative PCR and Western blotting.
   Results: Treatment of ARPE-19 cells with celastrol significantly attenuated the toxic effects of both H2O2 and menadione. Treatment with celastrol enhanced the expression of transcription factor Nrf2 and its targets, GCLM and HO-1. Knockdown of Nrf2 expression by shRNA partially abolished the protective effects of celastrol. Chemical inhibition of glutathione synthesis by L-buthionine-S,R-sulfoximine (BSO) completely abolished the protective effects of celastrol against H2O2 and menadione-induced damage. However, chemical inhibition of HO-1 activity by ZnPPIX did not reduce the protective effects of celastrol.
   Conclusion: This study provides evidence that treatment of RPE cells with celastrol shows potent protective effects against oxidative insults via activation of Nrf2 signaling pathway and upregulation of GCLM expression. This finding suggests that celastrol might be used as a potential therapeutic agent for oxidative stress-related eyes diseases, such as AMD.
C1 [Zhou, Yeqi; Zhou, Linbin; Zhou, Kewen; Zhang, Jingyue; Shang, Fu; Zhang, Xinyu] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
   [Zhou, Kewen] Sun Yat Sen Univ, Dept Physiol, Zhongshan Sch Med, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China.
C3 Sun Yat Sen University; Sun Yat Sen University
RP Shang, F; Zhang, XY (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM Shangf3@mail.sysu.edu.cn; Zhangxy7@mail.sysu.edu.cn
FU National Natural Science Foundation of China [81200670, 81570826]
FX This study was partially funded by the National Natural Science
   Foundation of China (No. 81200670; No. 81570826).
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NR 44
TC 5
Z9 6
U1 1
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 1566-5240
EI 1875-5666
J9 CURR MOL MED
JI Curr. Mol. Med.
PY 2019
VL 19
IS 3
BP 172
EP 182
DI 10.2174/1566524019666190424131704
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA IC3IG
UT WOS:000470852800003
PM 31032752
DA 2022-11-30
ER

PT J
AU Pasha, SPBS
   Sishtla, K
   Sulaiman, RS
   Park, B
   Shetty, T
   Shah, F
   Fishel, ML
   Wikel, JH
   Kelley, MR
   Corson, TW
AF Pasha, Sheik Pran Babu Sardar
   Sishtla, Kamakshi
   Sulaiman, Rania S.
   Park, Bomina
   Shetty, Trupti
   Shah, Fenil
   Fishel, Melissa L.
   Wikel, James H.
   Kelley, Mark R.
   Corson, Timothy W.
TI Ref-1/APE1 Inhibition with Novel Small Molecules Blocks Ocular
   Neovascularization
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID APE1/REF-1 REDOX ACTIVITY; DNA-REPAIR; APURINIC/APYRIMIDINIC
   ENDONUCLEASE-1; CHOROIDAL NEOVASCULARIZATION; GROWTH; PROTEIN; HYPOXIA;
   CELLS; IDENTIFICATION; COMPLICATIONS
AB Ocular neovascular diseases like wet age-related macular degeneration are a major cause of blindness. Novel therapies are greatly needed for these diseases. One appealing antiangiogenic target is reduction-oxidation factor 1-apurinic/apyrinnidinic endonuclease 1 (Ref-1/APE1). This protein can act as a redox-sensitive transcriptional activator for nuclear factor (NF)-kappa B and other proangiogenic transcription factors. An existing inhibitor of Ref-1's function, APX3330, previously showed antiangiogenic effects. Here, we developed improved APX3330 derivatives and assessed their antiangiogenic activity. We synthesized APX2009 and APX2014 and demonstrated enhanced inhibition of Ref-1 function in a DNA-binding assay compared with APX3330. Both compounds were antiproliferative against human retinal microvascular endothelial cells (HRECs; GI(50) APX2009: 1.1 mu M, APX2014: 110 nM) and macaque choroidal endothelial cells (Rf/6a; GI(50) APX2009: 26 mu M, APX2014: 5.0 mu M). Both compounds significantly reduced the ability of HRECs and Rf/6a cells to form tubes at mid-nanomolar concentrations compared with control, and both significantly inhibited HREC and Rf/6a cell migration in a scratch wound assay, reducing NF-kappa B activation and downstream targets. Ex vivo, APX2009 and APX2014 inhibited choroidal sprouting at low micromolar and high nanomolar concentrations, respectively. In the laser induced choroidal neovascularization mouse model, intraperitoneal APX2009 treatment significantly decreased lesion volume by 4-fold compared with vehicle (P < 0.0001, ANOVA with Dunnett's post-hoc tests), without obvious intraocular or systemic toxicity. Thus, Ref-1 inhibition with APX2009 and APX2014 blocks ocular angiogenesis in vitro and ex vivo, and APX2009 is an effective systemic therapy for choroidal neovascularization in vivo, establishing Ref-1 inhibition as a promising therapeutic approach for ocular neovascularization.
C1 [Pasha, Sheik Pran Babu Sardar; Sishtla, Kamakshi; Sulaiman, Rania S.; Park, Bomina; Shetty, Trupti; Corson, Timothy W.] Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, 1160 West Michigan St, Indianapolis, IN 46202 USA.
   [Sulaiman, Rania S.; Park, Bomina; Fishel, Melissa L.; Kelley, Mark R.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
   [Kelley, Mark R.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
   [Shah, Fenil; Fishel, Melissa L.; Kelley, Mark R.] Indiana Univ Sch Med, Dept Pediat, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
   [Fishel, Melissa L.; Kelley, Mark R.; Corson, Timothy W.] Indiana Univ Sch Med, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
   [Wikel, James H.] Apexian Pharmaceut, Indianapolis, IN USA.
C3 Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington; Indiana University
   System; Indiana University Bloomington; Indiana University System;
   Indiana University Bloomington; Indiana University System; Indiana
   University Bloomington
RP Corson, TW (通讯作者)，Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, 1160 West Michigan St, Indianapolis, IN 46202 USA.
EM tcorson@iu.edu
RI Pasha, Pran Babu Sardar/AAH-8388-2019; PASHA, PRAN BABU
   SARDAR/AAS-7266-2020; Corson, Timothy W./B-6851-2009; Fishel, Melissa
   L./AAH-6608-2020
OI PASHA, PRAN BABU SARDAR/0000-0001-8974-7562; Corson, Timothy
   W./0000-0002-1402-7875; Fishel, Melissa L./0000-0002-9436-6382; Sishtla,
   Kamakshi/0000-0002-1525-0155; Kelley, Mark/0000-0001-9472-1826; Kelley,
   Mark/0000-0002-6120-9532; Park, Bomina/0000-0003-1440-7066
FU Retina Research Foundation; Bright-Focus Foundation; National Institutes
   of Health National Eye Institute [R01EY025641]; Research to Prevent
   Blindness, Inc.; National Cancer Institute [R01CA138798, R01CA167291,
   R01CA205166]; National Institute of Neurologic Disorders and Stroke
   [R21NS091667]; Pediatric Oncology Research; Jeff Gordon Children's
   Foundation; Riley Children's Foundation; Apexian Pharmaceuticals
   [APX3330, APX2009, APX2014]; NATIONAL CANCER INSTITUTE [R01CA205166,
   R01CA167291, R01CA138798] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY025641] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF NEUROLOGICAL DISORDERS AND STROKE [R21NS091667] Funding Source: NIH
   RePORTER
FX This work was supported by the Retina Research Foundation, the
   Bright-Focus Foundation, the National Institutes of Health National Eye
   Institute [Grant R01EY025641], and an unrestricted grant from Research
   to Prevent Blindness, Inc. to T.W.C. Additional financial support for
   this work was provided by the National Cancer Institute [Grants
   R01CA138798 (to M.L.F. and M.R.K.), R01CA167291 (M.R.K.), R01CA205166
   (M.R.K.)] and the National Institute of Neurologic Disorders and Stroke
   [Grant R21NS091667 (to M.R.K.)], as well as financial support provided
   by the Earl and Betty Herr Professor in Pediatric Oncology Research,
   Jeff Gordon Children's Foundation and the Riley Children's Foundation
   (M.R.K.). APX3330, APX2009, and APX2014 were provided at no cost by
   Apexian Pharmaceuticals.
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NR 47
TC 17
Z9 17
U1 1
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD OCT 1
PY 2018
VL 367
IS 1
BP 108
EP 118
DI 10.1124/jpet.118.248088
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GT0EF
UT WOS:000444100900012
PM 30076264
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Chen, Q
   Niu, SJ
   Fang, WY
   Shuai, YL
   Fan, W
   Yuan, ST
   Liu, QH
AF Chen, Qiang
   Niu, Sijie
   Fang, Wangyi
   Shuai, Yuanlu
   Fan, Wen
   Yuan, Songtao
   Liu, Qinghuai
TI Automated choroid segmentation of three-dimensional SD-OCT images by
   incorporating EDI-OCT images
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Choroid segmentation; SD-OCT; EDI-OCT; Image registration; 3D graph
   search
ID OPTICAL COHERENCE TOMOGRAPHY; THICKNESS; HEALTHY
AB Background and Objective: The measurement of choroidal volume is more related with eye diseases than choroidal thickness, because the choroidal volume can reflect the diseases comprehensively. The purpose is to automatically segment choroid for three-dimensional (3D) spectral domain optical coherence tomography (SD-OCT) images.
   Methods: We present a novel choroid segmentation strategy for SD-OCT images by incorporating the enhanced depth imaging OCT (EDI-OCT) images. The down boundary of the choroid, namely choroidsclera junction (CSJ), is almost invisible in SD-OCT images, while visible in EDI-OCT images. During the SD-OCT imaging, the EDI-OCT images can be generated for the same eye. Thus, we present an EDI-OCT-driven choroid segmentation method for SD-OCT images, where the choroid segmentation results of the EDI-OCT images are used to estimate the average choroidal thickness and to improve the construction of the CSJ feature space of the SD-OCT images. We also present a whole registration method between EDIOCT and SD-OCT images based on retinal thickness and Bruch's Membrane (BM) position. The CSJ surface is obtained with a 3D graph search in the CSJ feature space.
   Results: Experimental results with 768 images (6 cubes, 128 B-scan images for each cube) from 2 healthy persons, 2 age-related macular degeneration (AMD) and 2 diabetic retinopathy (DR) patients, and 210 B-scan images from other 8 healthy persons and 21 patients demonstrate that our method can achieve high segmentation accuracy. The mean choroid volume difference and overlap ratio for 6 cubes between our proposed method and outlines drawn by experts were -1.96 mu m(3) and 88.56%, respectively.
   Conclusions: Our method is effective for the 3D choroid segmentation of SD-OCT images because the segmentation accuracy and stability are compared with the manual segmentation. (C) 2017 Published by Elsevier Ireland Ltd.
C1 [Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing, Jiangsu, Peoples R China.
   [Niu, Sijie] Univ Jinan, Sch Informat Sci & Engn, Jinan 250022, Shandong, Peoples R China.
   [Fang, Wangyi; Shuai, Yuanlu; Fan, Wen; Yuan, Songtao; Liu, Qinghuai] Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China.
   [Chen, Qiang] Minjiang Univ, Fujian Prov Key Lab Informat Proc & Intelligent C, Fuzhou 350121, Fujian, Peoples R China.
C3 Nanjing University of Science & Technology; University of Jinan; Nanjing
   Medical University; Minjiang University
RP Liu, QH (通讯作者)，Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China.
EM liuqh@njmu.edu.cn
OI Chen, Qiang/0000-0002-6685-2447
FU National Science Foundation of China [61671242]; Fundamental Research
   Funds for the Minjiang University [30920140111004]; six talent peaks
   project in Jiangsu Province [2014-SWYY-024]; Fujian Provincial Key
   Laboratory of Information Processing and Intelligent Control (Central
   Universities) [MJUKF201706]
FX This work was supported by the National Science Foundation of China
   (61671242), a grant from the Fundamental Research Funds for the Minjiang
   University (30920140111004), and a six talent peaks project in Jiangsu
   Province (2014-SWYY-024), and the Open Fund Project of Fujian Provincial
   Key Laboratory of Information Processing and Intelligent Control
   (Central Universities) (No. MJUKF201706).
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NR 22
TC 5
Z9 5
U1 2
U2 16
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0169-2607
EI 1872-7565
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD MAY
PY 2018
VL 158
BP 161
EP 171
DI 10.1016/j.cmpb.2017.11.002
PG 11
WC Computer Science, Interdisciplinary Applications; Computer Science,
   Theory & Methods; Engineering, Biomedical; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Medical Informatics
GA FZ7MW
UT WOS:000427786400015
PM 29544782
DA 2022-11-30
ER

PT J
AU Fragiotta, S
   Carnevale, C
   Cutini, A
   Rigoni, E
   Grenga, PL
   Vingolo, EM
AF Fragiotta, Serena
   Carnevale, Carmela
   Cutini, Alessandro
   Rigoni, Erika
   Grenga, Pier Luigi
   Vingolo, Enzo Maria
TI Factors Influencing Fixation Stability Area: A Comparison of Two Methods
   of Recording
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
ID SCANNING LASER OPHTHALMOSCOPE; PREFERRED RETINAL LOCI; CENTRAL VISION
   LOSS; MACULAR DEGENERATION; READING SPEED; MAIA MICROPERIMETER; MP-1
   MICROPERIMETER; NIDEK MP-1; AGE; DISEASE
AB SIGNIFICANCE: The authors analyze factors influencing bivariate contour ellipse area (BCEA) in healthy and pathologic eyes and how such factors may affect isolated (static BCEA) or microperimetric fixation (dynamic BCEA). They conclude that aging increases both dynamic BCEA and examination time, whereas static BCEA offers less variance and the maximum distinction with pathologic eyes.
   PURPOSE: The aim of this study was to assess factors influencing BCEA and the recording method that offer less variability and thus maximum distinction between healthy and pathologic eyes.
   METHODS: A total of 136 eyes were retrospectively reviewed, 85 eyes without ophthalmic disorders (logMAR acuity <= 0.0) and 51 eyes with late age-related macular degeneration (AMD) were enrolled. All patients underwent two consecutive examinations, a 30-second isolated fixation (static BCEA) and a microperimetric test with continuous fixation recording (dynamic BCEA). All the examinations were carried out using MP1 microperimeter (NAVIS software version 1.7.6; Nidek Technologies, Padova, Italy).
   RESULTS: Dynamic BCEA was significantly correlated with age (r = 0.38, P < .001), total (r = 0.32, P = .03), and tracking time (r = 0.33, P = .02) in controls, whereas no significant relationships were found in the AMD group. The greatest difference between static and dynamic BCEA was observed in 70- to 79-year decade in healthy subjects (P < .01). Logistic regression analysis showed that late AMD status was significantly predicted by +/- 2 SD and +/- 3 SD static BCEA (both P = .03).
   CONCLUSIONS: Dynamic BCEA is influenced by a certain degree of variability in advanced-age healthy subjects. In such cases, the use of +/- 2 SD and +/- 3 SD static BCEAs seems to offer a more accurate detection of fixation stability changes in the AMD group with respect to normal subjects. Copyright (C) 2018 American Academy of Optometry
C1 [Fragiotta, Serena; Carnevale, Carmela; Cutini, Alessandro; Rigoni, Erika; Grenga, Pier Luigi; Vingolo, Enzo Maria] Sapienza Univ Rome, UOC Ophthalmol, Dept Med Surg Sci & Biotechnol, Terracina, Italy.
C3 Sapienza University Rome
RP Fragiotta, S (通讯作者)，Sapienza Univ Rome, UOC Ophthalmol, Dept Med Surg Sci & Biotechnol, Terracina, Italy.
EM serena.fragiotta@uniroma1.it
RI Vingolo, Enzo Maria/E-6674-2010; Fragiotta, Serena/I-5227-2016
OI Vingolo, Enzo Maria/0000-0002-8363-5866; Fragiotta,
   Serena/0000-0002-6214-6270
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NR 36
TC 9
Z9 9
U1 0
U2 5
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 APR
PY 2018
VL 95
IS 4
BP 384
EP 390
DI 10.1097/OPX.0000000000001201
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GE4JK
UT WOS:000431181500014
PM 29554006
DA 2022-11-30
ER

PT J
AU Lotery, A
   Griner, R
   Ferreira, A
   Milnes, F
   Dugel, P
AF Lotery, A.
   Griner, R.
   Ferreira, A.
   Milnes, F.
   Dugel, P.
TI Real-world visual acuity outcomes between ranibizumab and aflibercept in
   treatment of neovascular AMD in a large US data set
SO EYE
LA English
DT Article
ID PIGMENT EPITHELIAL DETACHMENT; OPTICAL COHERENCE TOMOGRAPHY; 2.0 MG
   RANIBIZUMAB; MACULAR DEGENERATION; GROWTH-FACTOR; CHOROIDAL
   NEOVASCULARIZATION; INTRAVITREAL RANIBIZUMAB; TREATMENT PATTERNS; VEGF
   TRAP; BEVACIZUMAB
AB Purpose To examine 12-month real-world visual acuity outcomes and treatment patterns in neovascular age-related macular degeneration (nAMD) eyes, including those with pigment epithelial detachment (PED), receiving ranibizumab or aflibercept.
   Patients and methods Electronic medical records were used to identify ranibizumab or aflibercept-treated nAMD eyes with 12 months follow-up from first prescription. The primary objective was to compare mean change in visual acuity (VA) between index and month 12, in eyes treated with ranibizumab and aflibercept to assess the non-inferiority of ranibizumab vs aflibercept using a -5 letter non-inferiority margin. The number of injections and non-injection visits during follow-up were key secondary objectives.
   Results A total of 3350 ranibizumab and 4300 aflibercept treatment-naive eyes were included. At month 12, mean change from index in VA letter score was -0.30 for ranibizumab and -0.19 for aflibercept (P = 0.81). The adjusted difference of mean change was -0.14 (-0.79 to 0.51) (P = 0.67) (generalized estimating equations method) confirming the non-inferiority of ranibizumab. Eyes received a similar number of injections during follow-up. The mean (+/- SD) number of ranibizumab and aflibercept injections were 6.70 (+/- 2.54) and 7.00 (+/- 2.40), respectively (P < 0.0001). In PED eyes, the mean (+/- SD) change between baseline to month 12 was 1.25 (+/- 11.3) for ranibizumab and -0.39 (+/- 13.3) for aflibercept (adjusted between-group difference 1.80 (-0.71 to 4.30; P = 0.16)) achieved with a mean (+/- SD) 7.85 (+/- 2.68) ranibizumab and 7.47 (+/- 2.45) aflibercept injections, (P = 0.11).
   Conclusions Ranibizumab and aflibercept treatment yielded comparable VA outcomes in nAMD eyes, including those with PED, with similar treatment patterns over 12 months in real-world clinical practice.
C1 [Lotery, A.] Univ Hosp Southampton NHS Fdn Trust, Eye Unit, Southampton, Hants, England.
   [Lotery, A.] Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England.
   [Griner, R.] QuintilesIMS, Cambridge, MA USA.
   [Ferreira, A.; Milnes, F.] Novartis Pharma AG, Basel, Switzerland.
   [Dugel, P.] Retinal Consultants Arizona LTD, Phoenix, AZ USA.
C3 University of Southampton; University Hospital Southampton NHS
   Foundation Trust; University of Southampton; IQVIA; Novartis
RP Lotery, A (通讯作者)，Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England.
EM a.j.lotery@soton.ac.uk
FU Novartis Pharma AG, Basel, Switzerland; Novartis; National Institute for
   Health Research [NF-SI-0515-10020] Funding Source: researchfish
FX Novartis Pharma AG, Basel, Switzerland funded this study. Medical
   writing support was provided by Jonathan Askham at Wellmera AG and was
   funded by Novartis.
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NR 35
TC 50
Z9 50
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 DEC
PY 2017
VL 31
IS 12
BP 1697
EP 1706
DI 10.1038/eye.2017.143
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FP7XL
UT WOS:000417853300011
PM 28731052
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Bae, JH
   Hwang, AR
   Kim, CY
   Yu, HG
   Koh, HJ
   Yang, WI
   Chang, HR
   Lee, SC
AF Bae, Jeong Hun
   Hwang, Ah Reum
   Kim, Chan Yun
   Yu, Hyeong Gon
   Koh, Hyoung Jun
   Yang, Woo Ick
   Chang, Hae Ran
   Lee, Sung Chul
TI Intravitreal itraconazole inhibits laser-induced choroidal
   neovascularization in rats
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; GROWTH; VEGF; ANTIFUNGAL; ANGIOGENESIS;
   EXPRESSION; CANCER; TRIAMCINOLONE; TRAFFICKING; ACTIVATION
AB Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p< 0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.
C1 [Bae, Jeong Hun; Chang, Hae Ran] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Med Res Inst,Dept Ophthalmol, Seoul, South Korea.
   [Bae, Jeong Hun; Hwang, Ah Reum; Kim, Chan Yun; Koh, Hyoung Jun; Lee, Sung Chul] Yonsei Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea.
   [Yu, Hyeong Gon] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea.
   [Yang, Woo Ick] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center; Yonsei
   University; Yonsei University Health System; Seoul National University
   (SNU); Yonsei University; Yonsei University Health System
RP Lee, SC (通讯作者)，Yonsei Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea.
EM sunglee@yuhs.ac
OI , Sung Chul/0000-0001-9438-2385; Koh, Hyoung Jun/0000-0002-5932-8516;
   Kim, Chan Yun/0000-0002-8373-9999
FU Medical Research Funds from Kangbuk Samsung Hospital; Samsung Biomedical
   Research Institute [SMX1132251]
FX This work was supported by Medical Research Funds from Kangbuk Samsung
   Hospital (https://www.kbsmc.co.kr/) and Samsung Biomedical Research
   Institute grant #SMX1132251 (http://www.smc.or.kr/). 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 40
TC 10
Z9 11
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 JUN 30
PY 2017
VL 12
IS 6
AR e0180482
DI 10.1371/journal.pone.0180482
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EZ3KB
UT WOS:000404608700011
PM 28666022
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Bisht, R
   Jaiswal, JK
   Rupenthal, ID
AF Bisht, Rohit
   Jaiswal, Jagdish K.
   Rupenthal, Ilva D.
TI Nanoparticle-loaded biodegradable light-responsive in situ forming
   injectable implants for effective peptide delivery to the posterior
   segment of the eye
SO MEDICAL HYPOTHESES
LA English
DT Article
DE Ocular drug delivery; Injectable implants; Light-responsive systems;
   Photocrosslinking; PLGA nanoparticles
ID DRUG-DELIVERY; GELLING SYSTEMS; HYDROGELS; CELL; POLYMERS; RELEASE;
   DEPOT
AB Diseases affecting the posterior segment the eye, such as age-related macular degeneration (AMD), are the leading cause of blindness worldwide. Conventional dosage forms, such as eye drops, have to surmount several elimination mechanisms and complex barriers to achieve therapeutic concentrations at the target site often resulting in low anterior segment bioavailability (ca. 2-5%) with generally none of the drug reaching posterior segment tissues. Thus, frequent intravitreal injections are currently required to treat retinal conditions which have been associated with poor patient compliance due to pain, risk of infection, hemorrhages, retinal detachment and high treatment related costs. To partially overcome these issues, ocular implants have been developed for some posterior segment indications; however, the majority require surgical implantation and removal at the end of the intended treatment period. The transparent nature of the cornea and lens render light-responsive systems an attractive strategy for the management of diseases affecting the back of the eye. Light -responsive in situ forming injectable implants (ISFIs) offer various benefits such as ease of application in a minimally invasive manner and more site specific control over drug release. Moreover, the biodegradable nature of such implants avoids the need for surgical removal after release of the payload. Incorporating drug-loaded polymeric nanoparticles (NPs) into these implants may reduce the high initial burst release from the polymeric matrix and further sustain drug release thus avoiding the need for frequent injections as well as minimizing associated side effects. However, light -responsive systems for ophthalmic application are still in their early stages of development with limited reports on their safety and effectiveness. We hypothesize that the innovative design and properties of NP-containing light-responsive ISFIs can serve as a platform for effective management of ocular diseases requiring long term treatment.(C) 2017 Elsevier Ltd. All rights reserved.
C1 [Rupenthal, Ilva D.] Univ Auckland, Fac Med & Hlth Sci, New Zealand Natl Eye Ctr, Buchanan Ocular Therapeut Unit,Dept Ophthalmol, Private Bag 92019, Auckland 1142, New Zealand.
   Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc, Res Ctr, Auckland 1142, New Zealand.
C3 University of Auckland; University of Auckland
RP Rupenthal, ID (通讯作者)，Univ Auckland, Fac Med & Hlth Sci, New Zealand Natl Eye Ctr, Buchanan Ocular Therapeut Unit,Dept Ophthalmol, Private Bag 92019, Auckland 1142, New Zealand.
EM i.rupenthal@auckland.ac.nz
RI Bisht, Rohit/AAY-7445-2020; Rupenthal, Ilva D/M-5340-2016
OI Rupenthal, Ilva D/0000-0001-5997-5994
FU Health Research Council of New Zealand [14/018]; University of Auckland
FX The proposed work was financially supported by the Health Research
   Council of New Zealand (14/018). The authors would also like to thank
   the University of Auckland for providing an International Doctoral
   Scholarship to Rohit Bisht.
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NR 48
TC 15
Z9 15
U1 0
U2 33
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
EI 1532-2777
J9 MED HYPOTHESES
JI Med. Hypotheses
PD JUN
PY 2017
VL 103
BP 5
EP 9
DI 10.1016/j.mehy.2017.03.033
PG 5
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EY1NC
UT WOS:000403731600002
PM 28571808
DA 2022-11-30
ER

PT J
AU Li, BX
   Vachali, PP
   Shen, ZQ
   Gorusupudi, A
   Nelson, K
   Besch, BM
   Bartschi, A
   Longo, S
   Mattinson, T
   Shihab, S
   Polyakov, NE
   Suntsova, LP
   Dushkin, AV
   Bernstein, PS
AF Li, Binxing
   Vachali, Preejith P.
   Shen, Zhengqing
   Gorusupudi, Aruna
   Nelson, Kelly
   Besch, Brian M.
   Bartschi, Alexis
   Longo, Simone
   Mattinson, Ty
   Shihab, Saeed
   Polyakov, Nikolay E.
   Suntsova, Lyubov P.
   Dushkin, Alexander V.
   Bernstein, Paul S.
TI Retinal accumulation of zeaxanthin, lutein, and beta-carotene in mice
   deficient in carotenoid cleavage enzymes
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Knockout mice; Carotenoid cleavage; Retina; HPLC; Carotenoid metabolism
ID AGE-RELATED MACULOPATHY; MACULAR PIGMENT; SUBSTRATE-SPECIFICITY;
   MESO-ZEAXANTHIN; OCULAR-TISSUES; ADIPOSE-TISSUE; COMPLEXES;
   OLIGOSACCHARIDES; TRANSFORMATIONS; SUPPLEMENTATION
AB Carotenoid supplementation can prevent and reduce the risk of age-related macular degeneration (AMD) and other ocular disease, but until now, there has been no validated and well-characterized mouse model which can be employed to investigate the protective mechanism and relevant metabolism of retinal carotenoids. beta-Carotene oxygenases 1 and 2 (BCO1 and BCO2) are the only two carotenoid cleavage enzymes found in animals. Mutations of the bco2 gene may cause accumulation of xanthophyll carotenoids in animal tissues, and BCO1 is involved in regulation of the intestinal absorption of carotenoids. To determine whether or not mice deficient in BCO1 and/or BCO2 can serve as a macular pigment mouse model, we investigated the retinal accumulation of carotenoids in these mice when fed with zeaxanthin, lutein, or beta-carotene using an optimized carotenoid feeding method. HPLC analysis revealed that all three carotenoids were detected in sera, livers, retinal pigment epithelium (RPE)/choroids, and retinas of all of the mice, except that no carotenoid was detectable in the retinas of wild type (WT) mice. Significantly higher amounts of zeaxanthin and lutein accumulated in the retinas of BCO2 knockout (bco2(-/-)) mice and BCO1/BCO2 double knockout (bco1(-/-)/bco2(-/-)) mice relative to BCO1 knockout (bco1(-/-)) mice, while bco1(-/-) mice preferred to take up beta-carotene. The levels of zeaxanthin and lutein were higher than beta-carotene levels in the bco1(-/-)/bco2(-/-) retina, consistent with preferential uptake of xanthophyll carotenoids by retina. Oxidative metabolites were detected in mice fed with lutein or zeaxanthin but not in mice fed with beta-carotene. These results indicate that bco2(-/-) and bco1(-/-)/bco2(-/-) mice could serve as reasonable non-primate models for macular pigment function in the vertebrate eye, while bco1(-/-) mice may be more useful for studies related to beta-carotene. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Li, Binxing; Vachali, Preejith P.; Shen, Zhengqing; Gorusupudi, Aruna; Nelson, Kelly; Besch, Brian M.; Bartschi, Alexis; Longo, Simone; Mattinson, Ty; Shihab, Saeed; Bernstein, Paul S.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
   [Polyakov, Nikolay E.] Inst Chem Kinet & Combust, Novosibirsk, Russia.
   [Suntsova, Lyubov P.; Dushkin, Alexander V.] Inst Solid State Chem & Mechanochem, Novosibirsk, Russia.
C3 Utah System of Higher Education; University of Utah; Voevodsky Institute
   of Chemical Kinetics & Combustion SB RAS; Institute of Solid State
   Chemistry & Mechanochemistry, Siberian Branch of the Russian Academy of
   Sciences
RP Bernstein, PS (通讯作者)，Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
RI Polyakov, Nikolay E/D-9364-2014; Valer'evitch, Alexandr/AAB-9444-2019;
   Li, Binxing/ABB-7775-2020
OI Polyakov, Nikolay E/0000-0002-3666-7750; Li, Binxing/0000-0002-0715-7495
FU U.S. Civilian Research & Development Foundation (CRDF Global)
   [RUC-7067-NO-12]; United States Department of State; NIH [EY-11600,
   EY-14800]; Research to Prevent Blindness; Russian Academy of Science
   [V.48.1.8]; NATIONAL EYE INSTITUTE [P30EY014800, R29EY011600,
   R01EY011600] Funding Source: NIH RePORTER
FX We would like to thank Dr. Johannes von Lintig from Case Western Reserve
   University for his generosity in providing the bco1<SUP>-/-</SUP> and
   bco2<SUP>-/-</SUP> founder mice. This work was supported by grant
   RUC-7067-NO-12 from the U.S. Civilian Research & Development Foundation
   (CRDF Global) with funding from the United States Department of State,
   by NIH grants EY-11600 and EY-14800, by unrestricted departmental funds
   from Research to Prevent Blindness, and by research project V.48.1.8 of
   the Russian Academy of Science.
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NR 46
TC 35
Z9 36
U1 4
U2 35
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2017
VL 159
BP 123
EP 131
DI 10.1016/j.exer.2017.02.016
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EW6AV
UT WOS:000402588500013
PM 28286282
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Guo, CX
   Nor, MNM
   Danesh-Meyer, HV
   Vessey, KA
   Fletcher, EL
   O'Carroll, SJ
   Acosta, ML
   Green, CR
AF Guo, Cindy X.
   Nor, Mohd N. Mat
   Danesh-Meyer, Helen V.
   Vessey, Kirstan A.
   Fletcher, Erica L.
   O'Carroll, Simon J.
   Acosta, Monica L.
   Green, Colin R.
TI Connexin43 Mimetic Peptide Improves Retinal Function and Reduces
   Inflammation in a Light-Damaged Albino Rat Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroid; retina; light damage; connexin43; inflammation;
   electroretinogram
ID GAP-JUNCTION CHANNELS; CELL-DEATH; CHOROIDAL CIRCULATION; MACULAR
   DEGENERATION; NITRIC-OXIDE; HEMICHANNELS; MICROGLIA; EXPOSURE; ROD;
   IMMUNOREACTIVITY
AB PURPOSE. Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury.
   METHODS. Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours. Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5, or sham were administered 2 hours after the onset and at the end of the light damage period. Retinal function was assessed by electroretinogram and inflammatory responses in the choroid and retina were assessed using immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1], leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]).
   RESULTS. Light-damaged rat eyes had (1) reduced neuronal responses in both the rod and cone pathways and (2) marked inflammatory responses in the choroid and retina. Peptide5 significantly preserved function of photoreceptoral and postphotoreceptoral neurons in these animals. This was evident 24 hours after injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when compared with sham-treated controls. Retinal thinning and inflammation were also significantly reduced in Peptide5-treated eyes when compared with sham-treated controls.
   CONCLUSIONS. Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration.
C1 [Guo, Cindy X.; Nor, Mohd N. Mat; Acosta, Monica L.] Univ Auckland, Sch Optometry & Vis Sci, Auckland, New Zealand.
   [Guo, Cindy X.; Nor, Mohd N. Mat; Danesh-Meyer, Helen V.; Acosta, Monica L.; Green, Colin R.] Univ Auckland, New Zealand Natl Eye Ctr, Auckland, New Zealand.
   [Danesh-Meyer, Helen V.; Green, Colin R.] Univ Auckland, Dept Ophthalmol, Auckland, New Zealand.
   [Vessey, Kirstan A.; Fletcher, Erica L.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic, Australia.
   [O'Carroll, Simon J.] Univ Auckland, Dept Anat & Med Imaging, Auckland, New Zealand.
C3 University of Auckland; University of Auckland; University of Auckland;
   University of Melbourne; University of Auckland
RP Acosta, ML (通讯作者)，Univ Auckland, Sch Optometry & Vis Sci, Auckland, New Zealand.
EM m.acosta@auckland.ac.nz
RI Acosta, Monica/H-2700-2019; Green, Colin R/B-5663-2012; Fletcher,
   Erica/E-6364-2012
OI Acosta, Monica/0000-0002-5018-339X; Green, Colin R/0000-0003-3459-6298;
   Mat Nor, Mohd Nasir/0000-0001-5654-5593; Mat Nor, Mohd
   Nasir/0000-0002-2652-7893; Vessey, Kirstan/0000-0003-1031-1964;
   Fletcher, Erica/0000-0001-9412-9523
FU Health Research Council of New Zealand; Auckland Medical Research
   Foundation; University of Auckland Faculty of Science Research and
   Development Fund; Ministry of Higher Education Malaysia
FX Supported by the Health Research Council of New Zealand, the Auckland
   Medical Research Foundation, University of Auckland Faculty of Science
   Research and Development Fund, and PhD scholarship from Ministry of
   Higher Education Malaysia (MNMN).
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NR 70
TC 38
Z9 41
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2016
VL 57
IS 10
BP 3961
EP 3973
DI 10.1167/iovs.15-16643
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DW9LR
UT WOS:000383981600003
PM 27490318
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Schutze, C
   Teleky, K
   Baumann, B
   Pircher, M
   Gotzinger, E
   Hitzenberger, CK
   Schmidt-Erfurth, U
AF Schuetze, Christopher
   Teleky, Katharina
   Baumann, Bernhard
   Pircher, Michael
   Goetzinger, Erich
   Hitzenberger, Christoph K.
   Schmidt-Erfurth, Ursula
TI Polarisation-sensitive OCT is useful for evaluating retinal pigment
   epithelial lesions in patients with neovascular AMD
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; GEOGRAPHIC ATROPHY; FUNDUS
   AUTOFLUORESCENCE; SEGMENTATION; IMAGES; EYE
AB Background/aims To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE.
   Methods Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed.
   Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Results Mean variability of all atrophy lesion dimensions was 0.10 mm (SD +/-= 0.06 mm). Coefficient of variation (SD +/-/mean) was 0.06 on average (SD +/-= 0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of similar to 90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01).
   Conclusions PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably.
C1 [Schuetze, Christopher; Teleky, Katharina; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
   [Baumann, Bernhard; Pircher, Michael; Goetzinger, Erich; Hitzenberger, Christoph K.] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Baumann, Bernhard/0000-0001-6419-1932; Hitzenberger,
   Christoph/0000-0002-6608-8821; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Michael, Pircher/0000-0001-9285-7527
FU FWF [P19624-B02]; European Union [201880]
FX This study was supported by an independent scientific grant (FWF grant
   P19624-B02, Austrian Science Fund) and the European Union (FP7 HEALTH
   programme grant 201880, FUN-OCT).
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NR 25
TC 6
Z9 6
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2016
VL 100
IS 3
BP 371
EP 377
DI 10.1136/bjophthalmol-2015-306607
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DE9SN
UT WOS:000370979300016
PM 26183936
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Liu, L
   Yu, HJ
   Huang, X
   Tan, HZ
   Li, S
   Luo, Y
   Zhang, L
   Jiang, SM
   Jia, HF
   Xiong, Y
   Zhang, RL
   Huang, Y
   Chu, CC
   Tian, WZ
AF Liu, Lily
   Yu, Haijia
   Huang, Xin
   Tan, Hongzhi
   Li, Song
   Luo, Yan
   Zhang, Li
   Jiang, Sumei
   Jia, Huifeng
   Xiong, Yao
   Zhang, Ruliang
   Huang, Yi
   Chu, Charles C.
   Tian, Wenzhi
TI A novel engineered VEGF blocker with an excellent pharmacokinetic
   profile and robust anti-tumor activity
SO BMC CANCER
LA English
DT Article
DE VEGF inhibitor; VEGFR1; Recombinant Fc-fusion protein; Anti-tumor
   therapy; Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; CELL
   LUNG-CANCER; OVARIAN-CANCER; SOLID TUMORS; CLINICAL-APPLICATIONS;
   MONOCLONAL-ANTIBODY; NEOPLASTIC TISSUES; 1ST-LINE TREATMENT;
   LIGAND-BINDING
AB Background: Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered.
   Methods: We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for its target-binding and target-blocking activities, pharmacokinetic profile, angiogenesis inhibition activity, and anti-tumor therapeutic efficacy.
   Results: HB-002.1 has a molecular weight of similar to 80 kDa, isoelectric point of similar to 6.7, and an optimal target binding affinity of < 1 nM. The pharmacokinetic profile was excellent with a half-life of 5 days, maximal concentration of 20.27 mu g/ml, and area under the curve of 81.46 mu g.days/ml. When tested in a transgenic zebrafish embryonic angiogenesis model, dramatic inhibition in angiogenesis was exhibited by a markedly reduced number of subintestinal vessels. When tested for anti-tumor efficacy, HB-002.1 was confirmed in two xenograft tumor models (A549 and Colo-205) to have a robust tumor killing activity, showing a percentage of inhibition over 90% at the dose of 20 mg/kg. Most promisingly, HB-002.1 showed a superior therapeutic efficacy compared to bevacizumab in the A549 xenograft model (tumor inhibition: 84.7% for HB-002.1 versus 67.6% for bevacizumab, P < 0.0001).
   Conclusions: HB-002.1 is a strong angiogenesis inhibitor that has the potential to be a novel promising drug for angiogenesis-related diseases such as tumor neoplasms and age-related macular degeneration.
C1 [Liu, Lily; Yu, Haijia; Luo, Yan; Tian, Wenzhi] Huabo Biopharm Co Ltd, Dept Cell Biol, Shanghai 201203, Peoples R China.
   [Huang, Xin; Li, Song] Huabo Biopharm Co Ltd, Dept Antibody Technol, Shanghai 201203, Peoples R China.
   [Tan, Hongzhi; Zhang, Li; Jiang, Sumei; Jia, Huifeng; Xiong, Yao; Huang, Yi] Huabo Biopharm Co Ltd, Dept Prot Sci, Shanghai 201203, Peoples R China.
   [Zhang, Ruliang] Huabo Biopharm Co Ltd, Dept Project Management, Shanghai 201203, Peoples R China.
   [Chu, Charles C.] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA.
   [Chu, Charles C.] Hofstra North Shore LIJ Sch Med, Dept Med, Hempstead, NY 11549 USA.
   [Chu, Charles C.] Hofstra North Shore LIJ Sch Med, Dept Mol Med, Hempstead, NY 11549 USA.
C3 Northwell Health; Hofstra University; Northwell Health; Hofstra
   University; Northwell Health
RP Tian, WZ (通讯作者)，Huabo Biopharm Co Ltd, Dept Cell Biol, Shanghai 201203, Peoples R China.
EM tian110602@huabobio.com
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NR 50
TC 16
Z9 20
U1 1
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAR 25
PY 2015
VL 15
AR 170
DI 10.1186/s12885-015-1140-1
PG 14
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA CN6RY
UT WOS:000358563100001
PM 25881012
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Munk, MR
   Kiss, C
   Huf, W
   Sulzbacher, F
   Roberts, P
   Mittermuller, TJ
   Sacu, S
   Simader, C
   Schmidt-Erfurth, U
AF Munk, Marion R.
   Kiss, Christopher
   Huf, Wolfgang
   Sulzbacher, Florian
   Roberts, Philipp
   Mittermueller, Tamara J.
   Sacu, Stefan
   Simader, Christian
   Schmidt-Erfurth, Ursula
TI One Year Follow-up of Functional Recovery in Neovascular AMD During
   Monthly Anti-VEGF Treatment
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; SCANNING LASER
   OPHTHALMOSCOPE; MACULAR DEGENERATION; CONTRAST SENSITIVITY; READING
   PERFORMANCE; VISUAL FUNCTION; RANIBIZUMAB TREATMENT; RETINAL MORPHOLOGY;
   MICROPERIMETRY
AB PURPOSE: To identify neurosensory recovery, testing different functional variables during monthly intravitreal standard anti vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD).
   DESIGN: Prospective interventional cohort study.
   METHODS: Sixty-four treatment-naive neovascular AMD patients with subfoveal lesions were treated and examined monthly for distance visual acuity, reading acuity, maximum reading speed, and contrast sensitivity and with microperimetry evaluating the percentage of absolute and relative scotoma and mean central retinal sensitivity weighted by area. Improvements in reading acuity, distance acuity, reading speed, contrast sensitivity, mean central retinal sensitivity, and scotoma area in dependence of age, lesion type, lesion size, and mean central retinal sensitivity were evaluated by a random-slope and random-intercept model. Recovery pattern of parameters was compared by correlating the individual slopes of each variable.
   RESULTS: Initially, a rapid short-term effect of anti-VEGF treatment was documented throughout all functional variables. Progressive functional gain over 1 year was observed for distance visual acuity (P = .011), contrast sensitivity (P <= .0001), and mean central retinal sensitivity (P <= .0001), but not for reading acuity (P = .31) and maximum reading speed (P = .94). Decrease of absolute scotoma area missed statistical significance over time (P = .053) and also fixation stability did not improve (P = .08). However, lesion size influenced the course of absolute scotoma area (P = .0015), while lesion type had no effect on any visual function variable evaluated. The individual slopes of reading acuity and distance visual acuity showed a moderate correlation; however, all other variables showed only a weak or no significant correlation among each other.
   CONCLUSION: Visual recovery in anti-VEGF therapy is reflected in a characteristic pattern of functional changes over time, whereas distance visual acuity does not seem to comprehensively reflect overall visual function gain. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Munk, Marion R.; Kiss, Christopher; Sulzbacher, Florian; Roberts, Philipp; Mittermueller, Tamara J.; Sacu, Stefan; Simader, Christian; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
   [Huf, Wolfgang] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Kiss, C (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM christopher.kiss@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Simader,
   Christian/0000-0002-1784-2883
FU Alcon Laboratory Inc; Bayer Health Care; Novartis
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF INTEREST. Ursula Schmidt-Erfurth receives
   consultancy and lecture fees and travel support from Alcon Laboratory
   Inc, Bayer Health Care, and Novartis. The authors indicate no funding or
   financial support. Contributions of authors: design and conduct of the
   study (M.M., C.K., W.H., C.S., U.S.E.), collection and management of the
   data (M.M., F.S., P.R., T.M., A.M., C.S., S.S.), analysis and
   interpretation of the data (M.M., W.H., T.M., S.S., C.S.), preparation
   of the manuscript (M.M.), and review of the manuscript (M.M, C.K, as,
   W.H., F.S., U.S.E).
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NR 46
TC 26
Z9 26
U1 0
U2 14
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 2013
VL 156
IS 4
BP 633
EP 643
DI 10.1016/j.ajo.2013.05.037
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 231VT
UT WOS:000325447200001
PM 23891335
DA 2022-11-30
ER

PT J
AU Rabin, DM
   Rabin, RL
   Blenkinsop, TA
   Temple, S
   Stern, JH
AF Rabin, David M.
   Rabin, Richard L.
   Blenkinsop, Timothy A.
   Temple, Sally
   Stern, Jeffrey H.
TI Chronic oxidative stress upregulates Drusen-related protein expression
   in adult human RPE stem cell-derived RPE cells: A novel culture model
   for dry AMD
SO AGING-US
LA English
DT Article
DE RPE; oxidative stress; AMD
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; MITOCHONDRIAL
   PERMEABILITY TRANSITION; CAUSE-SPECIFIC PREVALENCE; AGE-RELATED
   MACULOPATHY; ALPHA-B-CRYSTALLIN; FACTOR-KAPPA-B; MACULAR DEGENERATION;
   AMYLOID-BETA; GENE-EXPRESSION
AB Purpose: The goal of this study was to examine changes in the expression of transcripts and proteins associated with drusen in Age-related Macular Degeneration (AMD) after exposing human retinal pigment epithelium (hRPE) cells to chronic oxidative stress.
   Methods: Primary adult human RPE cells were isolated from cadaveric donor eyes. The subpopulation of RPE stem cells (RPESCs) was activated, expanded, and then differentiated into RPE progeny. Confluent cultures of RPESC-derived hRPE and ARPE-19 cells were exposed to a regimen of tert-butylhydroperoxide (TBHP) for 1-5 days. After treatment, gene expression was measured by quantitative PCR (qPCR), protein expression was assessed by immunocytochemistry and transepithelial resistance and cell toxicity were measured.
   Results: hRPE cells exposed to a regimen of TBHP for 5 days upregulate expression of several molecules identified in drusen, including molecular chaperones and pro-angiogenic factors. 5-day TBHP treatment was significantly more effective than 1-day treatment at eliciting these effects. The extent of hRPE response to 5-day treatment varied significantly between individual donors, nevertheless, 6 transcripts were reliably significantly upregulated. ARPE-19 cells treated with the same 5-day stress regime did not show the same pattern of response and did not upregulate this group of transcripts.
   Conclusions: RPESC-derived hRPE cells change significantly when exposed to repeated oxidative stress conditions, upregulating expression of several drusen-related proteins and transcripts. This is consistent with the hypothesis that hRPE cells are competent to be a source of proteins found in drusen deposits. Our results suggest that donor-specific genetic and environmental factors influence the RPE stress response. ARPE-19 cells appear to be less representative of AMD-like changes than RPESC-derived hRPE. This adult stem cell-based system using chronic TBHP treatment of hRPE represents a novel in vitro model useful for the study of drusen formation and dry AMD pathophysiology.
C1 [Rabin, David M.; Rabin, Richard L.] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA.
   [Rabin, David M.; Blenkinsop, Timothy A.; Temple, Sally; Stern, Jeffrey H.] Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
C3 Albany Medical College
RP Stern, JH (通讯作者)，Neural Stem Cell Inst, 1 Discovery Dr, Rensselaer, NY 12144 USA.
EM jeffstern@nynsci.org
OI Rabin, Richard/0000-0002-7372-2413
FU American Health Assistance Foundation [M2008-042]; NYS Department of
   health NYSTEM program [C024414]; Regenerative Research Foundation
FX This work was supported by funding from the American Health Assistance
   Foundation (grant M2008-042 to J.H.S.), the NYS Department of health
   NYSTEM program (grant C024414), the Regenerative Research Foundation and
   by a generous donation from Dr. Heinrich Medicus. We thank Enrique
   Salero for help in establishing the culture system, Nathan C. Boles for
   help with statistical analysis, Barbara Corneo for valuable discussion,
   and Carol Charniga and Patricia Lederman for technical assistance. We
   are grateful to the eye donors and their families whose generosity made
   this study possible.
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NR 78
TC 46
Z9 48
U1 0
U2 11
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JAN
PY 2013
VL 5
IS 1
BP 51
EP 66
PG 16
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 104HH
UT WOS:000315982300005
PM 23257616
DA 2022-11-30
ER

PT J
AU Yaacov-Pena, F
   Jure, D
   Ocampos, J
   Samudio, M
   Furtado, JM
   Carter, M
   Lansingh, V
AF Yaacov-Pena, Fernando
   Jure, David
   Ocampos, Jose
   Samudio, Margarita
   Furtado, Joao Marcello
   Carter, Marissa
   Lansingh, Van Charles
TI Prevalence and causes of blindness in an urban area of Paraguay
SO ARQUIVOS BRASILEIROS DE OFTALMOLOGIA
LA English
DT Article
DE Cataract/complications; Blindness/epidemiology; Blindness/etiology;
   Visual acuity; Epidemiologic studies; Paraguay
ID VISUAL IMPAIRMENT; CATARACT BLINDNESS
AB Purpose: To determine the prevalence and causes of blindness in Piribebuy, Paraguay.
   Methods: A population based study was conducted from September to November 2007 in Piribebuy, Paraguay. Based on the city map, seven clusters were randomly selected, containing 22 to 36 squares (423 to 578 houses) each, where all subjects >= 40 years old who agreed to participate were included in the study. Presenting vision acuity (VA) was obtained for each eye, with 'E' Snellen charts 6 meters far from the patient with appropriate light. Eyes with VA <= 20/60 were also tested with the pinhole. Objective and subjective refraction was performed, followed by examination of anterior segment under the slit-lamp, Goldmann applanation tonometry, and pupil dilatation with 0.5% tropicamide plus 0.5% phenylephrine, followed by evaluation of the posterior pole. Best corrected visual acuity was used to classify the patients as follows: blindness was defined as visual acuity of the better eye <20/400, low vision as 20/400 <= VA<20/60 and visual impairment as VA <= 20/60. Similar to the methodology followed by the Rapid Assessment of Avoidable Blindness studies, in patients presenting more than one eye disease equally contributing to visual loss, only the most treatable or avoidable cause was recorded.
   Results: 402 subjects received ophthalmological evaluation (92.2% of the original sample). Prevalence of blindness and low vision adjusted for gender and age was 1.0% (95% CI: 0.3-2.7) and 4.5% (95% CI: 2.8-7.1), respectively. Cataract was the only cause of blindness and the main cause of low vision (77.8% of the cases), followed by age-related macular degeneration (11.1%), pterygium (5.6%) and bilateral macular scar (5.6%).
   Conclusion: The prevalence of blindness in Piribebuy was 1% and the main cause was cataract.
C1 Fdn Vis, Asuncion, Paraguay.
RP Yaacov-Pena, F (通讯作者)，Calle 120 7-38, Bogota, Colombia.
EM ojosalud@yahoo.com
RI Samudio, M/AFR-4127-2022; Furtado, Joao/D-4436-2012; Furtado, Joao
   M./AAB-5356-2022; Lansingh, Van/C-8672-2018
OI Samudio, M/0000-0003-2813-218X; Furtado, Joao M./0000-0003-2490-5747;
   Lansingh, Van/0000-0002-0090-4195
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   World Health Organization, 2004, INT STAT CLASS DIS 1
NR 15
TC 3
Z9 5
U1 0
U2 3
PU CONSEL BRASIL OFTALMOLOGIA
PI SAO PAULO
PA ALAMEDA SANTOS 1343, 11 ANDAR CJ 1110, CERQUEIRA CESAR, SAO PAULO, SP
   00000, BRAZIL
SN 0004-2749
J9 ARQ BRAS OFTALMOL
JI Arq. Bras. Oftalmol.
PD SEP-OCT
PY 2012
VL 75
IS 5
BP 341
EP 343
DI 10.1590/S0004-27492012000500009
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 104AZ
UT WOS:000315962800009
PM 23471329
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Cao, GF
   Chen, MR
   Song, QL
   Liu, Y
   Xie, LP
   Han, Y
   Liu, Z
   Ji, Y
   Jiang, Q
AF Cao, Guofan
   Chen, Meirong
   Song, Qinglu
   Liu, Yuan
   Xie, Liping
   Han, Yi
   Liu, Zhen
   Ji, Yong
   Jiang, Qin
TI EGCG protects against UVB-induced apoptosis via oxidative stress and the
   JNK1/c-Jun pathway in ARPE19 cells
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE epigallocatechin gallate; ultraviolet B; mitogen-activated protein
   kinase; retinal pigment epithelial cells; cell apoptosis
ID LIGHT DAMAGE; ACTIVATION; JNK; MECHANISMS; DEATH
AB Ultraviolet B (UVB) radiation is part of the spectrum of light produced by the sun. This form of radiation has been implicated as one of the potential etiological factors causing age-related macular degeneration (AMD). Oxidative injury to the retinal pigment epithelium (RPE) has also been thought to play a key role in AMD. The aim of the present study was to determine the mechanism by which UVB causes damage to the RPE cells, whether it occurs through oxidative stress and the mitogen-activated protein kinase (MAPK) pathway and whether the green tea extract, (-)-epigallocatechin gallate (EGCG), has a protective role. Cell viability assays were used to determine the viability of the cells under different conditions. Cell death caused by apoptosis was determined using fluorescein isothiocyanate conjugated-annexin V/PI labeling, followed by flow cytometry. Intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Western blot analysis was used to detect UVB-induced MAPK signaling pathways. The findings showed that UVB induced apoptosis, which increased intracellular ROS in ARPE19 cells. Inhibition of c-Jun NH2-terminal kinase (JNK) with a specific inhibitor augmented this apoptosis, and anisomycin (an activator of JNK) attenuated this apoptosis. In addition, UVB decreased the phosphorylation of JNK I and c-Jun. Finally, EGCG reduced the ROS generation and apoptosis, and also partially blocked the decreased phosphorylation of JNK1 and c-Jun by UVB irradiation. The findings show that UVB irradiation is able to induce apoptosis in ARPE19 cells through oxidative stress, but EGCG treatment attenuates this damage. In this situation, the JNK pathway plays an anti-apoptotic role. The use of selective activators or antioxidants may be useful in reducing the oxidative damage occurring in AMD.
C1 [Cao, Guofan; Chen, Meirong; Liu, Yuan; Jiang, Qin] Nanjing Med Univ, Affiliated Ophthalm Hosp, Nanjing 210029, Jiangsu, Peoples R China.
   [Xie, Liping; Liu, Zhen; Ji, Yong] Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Jiangsu, Peoples R China.
   [Song, Qinglu] Nanjing Med Univ, Clin Med Coll 4, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Meirong] Jurong First Peoples Hosp, Nanjing 212400, Jiangsu, Peoples R China.
   [Han, Yi] Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Dept Geriatr, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing Medical University; Nanjing Medical University; Nanjing Medical
   University; Nanjing Medical University
RP Jiang, Q (通讯作者)，Nanjing Med Univ, Affiliated Ophthalm Hosp, Nanjing 210029, Jiangsu, Peoples R China.
EM yongji@njmu.edu.cn; jqin710@vip.sina.com
RI liu, yuan/L-9239-2018
OI liu, yuan/0000-0003-4887-907X
FU Nanjing Foundation for Development of Science and Technology, China
   [200801093]; Province Postdoctoral Science Foundation; Natural Science
   Foundation for Colleges and Universities in Jiangsu Province of China
FX This study was supported in part by a grant from the Nanjing Foundation
   for Development of Science and Technology, China (200801093, to Q.J.), a
   grant from the Province Postdoctoral Science Foundation (to Q.J.), and a
   grant from the Natural Science Foundation for Colleges and Universities
   in Jiangsu Province of China (to Q.J). The authors wish to thank Qi Chen
   for the guidance and help.
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NR 25
TC 47
Z9 54
U1 1
U2 14
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 JAN
PY 2012
VL 5
IS 1
BP 54
EP 59
DI 10.3892/mmr.2011.582
PG 6
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA 854HX
UT WOS:000297486700011
PM 21909619
OA Bronze
DA 2022-11-30
ER

PT J
AU An, L
   Shen, TT
   Wang, RKK
AF An, Lin
   Shen, Tueng T.
   Wang, Ruikang K.
TI Using ultrahigh sensitive optical microangiography to achieve
   comprehensive depth resolved microvasculature mapping for human retina
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE microvasculature imaging; retinal imaging; optical microangiography;
   spectral domain optical coherence tomography
ID COHERENCE TOMOGRAPHY; IN-VIVO; BLOOD-FLOW; DOPPLER TOMOGRAPHY;
   DIABETIC-RETINOPATHY; VASCULAR PERFUSION; MICRO-ANGIOGRAPHY; HUMAN SKIN;
   ACQUISITION; SPEED
AB This paper presents comprehensive and depth-resolved retinal microvasculature images within human retina achieved by a newly developed ultrahigh sensitive optical microangiography (UHS-OMAG) system. Due to its high flow sensitivity, UHS-OMAG is much more sensitive to tissue motion due to the involuntary movement of the human eye and head compared to the traditional OMAG system. To mitigate these motion artifacts on final imaging results, we propose a new phase compensation algorithm in which the traditional phase-compensation algorithm is repeatedly used to efficiently minimize the motion artifacts. Comparatively, this new algorithm demonstrates at least 8 to 25 times higher motion tolerability, critical for the UHS-OMAG system to achieve retinal microvasculature images with high quality. Furthermore, the new UHS-OMAG system employs a high speed line scan CMOS camera (240 kHz A-line scan rate) to capture 500 A-lines for one B-frame at a 400 Hz frame rate. With this system, we performed a series of in vivo experiments to visualize the retinal microvasculature in humans. Two featured imaging protocols are utilized. The first is of the low lateral resolution (16 mu m) and a wide field of view (4x3 mm(2) with single scan and 7x8 mm(2) for multiple scans), while the second is of the high lateral resolution (5 mu m) and a narrow field of view (1.5x1.2 mm(2) with single scan). The great imaging performance delivered by our system suggests that UHS-OMAG can be a promising noninvasive alternative to the current clinical retinal microvasculature imaging techniques for the diagnosis of eye diseases with significant vascular involvement, such as diabetic retinopathy and age-related macular degeneration. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3642638]
C1 [An, Lin; Shen, Tueng T.; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
   [Shen, Tueng T.; Wang, Ruikang K.] Univ Washington, Dept Ophthalmol, Seattle, WA 98104 USA.
C3 University of Washington; University of Washington Seattle; University
   of Washington; University of Washington Seattle
RP Wang, RKK (通讯作者)，Univ Washington, Dept Bioengn, 3720 15th Ave NE, Seattle, WA 98195 USA.
EM wangrk@uw.edu
RI An, Lin/E-6445-2013; An, Lin/C-9923-2016; Wang, Ruikang/L-3889-2019
OI Wang, Ruikang/0000-0001-5169-8822
FU National Heart, Lung, and Blood Institute [R01 HL093140]; National
   Institute of Biomedical Imaging and Bioengineering [R01 EB009682];
   American Heart Association [0855733G]; Research to Prevent Blindness;
   NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL093140] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND
   BIOENGINEERING [R01EB009682] Funding Source: NIH RePORTER
FX This work was supported in part by research grants from the National
   Heart, Lung, and Blood Institute (R01 HL093140), National Institute of
   Biomedical Imaging and Bioengineering (R01 EB009682), the American Heart
   Association (0855733G), and Research to Prevent Blindness.
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NR 33
TC 75
Z9 78
U1 0
U2 12
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD OCT
PY 2011
VL 16
IS 10
AR 106013
DI 10.1117/1.3642638
PG 9
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 853ZV
UT WOS:000297465200020
PM 22029360
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Zheng, YF
   Lavanya, R
   Wu, RY
   Wong, WL
   Wang, JJ
   Mitchell, P
   Cheung, N
   Cajucom-Uy, H
   Lamoureux, E
   Aung, T
   Saw, SM
   Wong, TY
AF Zheng, Yingfeng
   Lavanya, Raghavan
   Wu, Renyi
   Wong, Wan-Ling
   Wang, Jie Jin
   Mitchell, Paul
   Cheung, Ning
   Cajucom-Uy, Howard
   Lamoureux, Ecosse
   Aung, Tin
   Saw, Seang-Mei
   Wong, Tien Y.
TI Prevalence and Causes of Visual Impairment and Blindness in an Urban
   Indian Population: The Singapore Indian Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID CATARACT-SURGERY; OLDER-ADULTS; LOW-VISION; RISK-FACTORS; MALAY EYE;
   CHINESE; DISEASES; EPIDEMIOLOGY; METHODOLOGY; DISTRICT
AB Purpose: To describe the prevalence and causes of visual impairment and blindness in an urban Indian population.
   Design: Population-based study.
   Participants: Ethnic Indians aged more than 40 years living in Singapore.
   Methods: Participants underwent standardized ophthalmic assessments for visual impairment and blindness, defined using best-corrected visual acuity (BCVA) and presenting visual acuity (PVA), according to US and modified World Health Organization (WHO) definitions.
   Main Outcome Measures: Unilateral visual impairment or blindness was defined on the basis of the worse eye, and bilateral visual impairment or blindness was defined on the basis of the better eye. Primary causes of visual impairment were determined.
   Results: A total of 3400 eligible individuals (75.6% response rate) participated. On the basis of US definitions, the age-standardized prevalence was 0.4% for bilateral blindness (<= 20/200, better eye) and 3.4% for bilateral visual impairment (<20/40 to >20/200, better eye). Another 0.3% of bilateral blindness and 13.4% of bilateral visual impairment were correctable with refraction. Cataract was the principal cause of best-corrected bilateral blindness (60.0%) and bilateral visual impairment (65.7%). Other major causes of blindness and visual impairment included diabetic retinopathy, age-related macular degeneration, glaucoma, corneal opacity, and myopic maculopathy.
   Conclusions: The prevalence of bilateral blindness and visual impairment in Indians living in Singapore is lower than estimates from populations living in India, but similar to estimates obtained from Singapore Malay and Chinese populations. Cataract is the leading cause of blindness and visual impairment. One in 20 cases of bilateral blindness and 1 in 10 cases of bilateral visual impairment are attributable to diabetic retinopathy. These data may have relevance to many ethnic Indian persons living outside India.
C1 [Zheng, Yingfeng; Lavanya, Raghavan; Wu, Renyi; Wong, Wan-Ling; Cajucom-Uy, Howard; Lamoureux, Ecosse; Aung, Tin; Saw, Seang-Mei; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore.
   [Zheng, Yingfeng] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
   [Wang, Jie Jin; Cheung, Ning; Lamoureux, Ecosse; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
   [Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Aung, Tin; Saw, Seang-Mei; Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
   [Saw, Seang-Mei; Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore.
C3 National University of Singapore; Singapore National Eye Center; Sun Yat
   Sen University; Centre for Eye Research Australia; University of
   Melbourne; University of Sydney; National University of Singapore;
   National University of Singapore
RP Wong, TY (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 3rd Hosp Ave,05-00, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
RI Cheung, Ning Danny/F-2043-2013; Wang, Jie Jin/P-1499-2014; Mitchell,
   Paul/P-1498-2014; wang, jie/GRS-0942-2022; Lamoureux,
   Ecosse/Z-5482-2019; Zheng, Yingfeng/CAE-9225-2022; Wong, Tien
   Yin/AAC-9724-2020; Zheng, Yingfeng/AAE-2983-2022
OI Wang, Jie Jin/0000-0001-9491-4898; Zheng, Yingfeng/0000-0002-0914-7864;
   Wong, Tien Yin/0000-0002-8448-1264; 
FU Biomedical Research Council [08/1/35/19/550]; National Medical Research
   Council, Singapore [STaR/0003/2008]
FX This study was funded by the Biomedical Research Council
   (08/1/35/19/550) and the National Medical Research Council,
   STaR/0003/2008, Singapore.
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NR 45
TC 94
Z9 97
U1 0
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2011
VL 118
IS 9
BP 1798
EP 1804
DI 10.1016/j.ophtha.2011.02.014
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 814TD
UT WOS:000294479200016
PM 21621261
DA 2022-11-30
ER

PT J
AU Markovets, AM
   Fursova, AZ
   Kolosova, NG
AF Markovets, Anton M.
   Fursova, Anzhella Z.
   Kolosova, Natalia G.
TI Therapeutic Action of the Mitochondria-Targeted Antioxidant SkQ1 on
   Retinopathy in OXYS Rats Linked with Improvement of VEGF and PEDF Gene
   Expression
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; SENESCENCE; CATARACT; DYNAMICS; VISION; EYE
AB The incidence of age-related macular degeneration (AMD), the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1) is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF) and its antagonist pigment epithelium-derived factor (PEDF) genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg) prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months) caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. Conclusions: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.
C1 [Markovets, Anton M.; Fursova, Anzhella Z.; Kolosova, Natalia G.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, SB RAS, Novosibirsk 630090, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS
RP Markovets, AM (通讯作者)，Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, SB RAS, Novosibirsk 630090, Russia.
EM kolosova@bionet.nsc.ru
RI Kolosova, Nataliya G/AAR-7409-2020; Kolosova, Nataliya G/P-3178-2015;
   fursova, anzhella/AAE-1495-2022
OI Kolosova, Nataliya G/0000-0003-2398-8544; Kolosova, Nataliya
   G/0000-0003-2398-8544; fursova, anzhella/0000-0001-6311-5452
FU Russian Foundation for Basic Research RFBR [11-04-00666]; presidium of
   Russian Academy of Science (RAS) [5.11]; FASI [14.740.11.0758]
FX This work was supported by grants of Russian Foundation for Basic
   Research RFBR (11-04-00666), presidium of Russian Academy of Science
   (RAS) (5.11) and FASI state contract 14.740.11.0758. The funders had no
   role in study design, datacollection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 28
TC 42
Z9 47
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 5
PY 2011
VL 6
IS 7
AR e21682
DI 10.1371/journal.pone.0021682
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 789JO
UT WOS:000292512000019
PM 21750722
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Barnes, CS
   De l'Aune, W
   Schuchard, RA
AF Barnes, Claire S.
   De l'Aune, William
   Schuchard, Ronald A.
TI A Test of Face Discrimination Ability in Aging and Vision Loss
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE age-related macular degeneration; aging; contrast sensitivity; face
   perception; visual acuity
ID MACULAR DEGENERATION; OLDER-ADULTS; CONTRAST SENSITIVITY;
   AGE-DIFFERENCES; VISUAL-ACUITY; RECOGNITION; PERFORMANCE; ENHANCEMENT;
   IMPAIRMENT; PERCEPTION
AB Purpose. The ability to recognize faces is fundamental to social interactions but has not been studied extensively in visual disorders such as age-related macular degeneration (AMD). We report here the development of a face discrimination test, in which both response times (RTs) and accuracies are measured. Results are compared for young and older control subjects and older adults with AMD to determine the factors underlying performance on this test.
   Methods. Subjects were 14 older controls, 11 young adult controls, and 34 individuals with binocular AMD. In the face discrimination test, colored reference photographs of eight people were presented continuously (male faces in the first half of the test, female faces in the second). On each trial, subjects reported which reference face matched the test face (shown with different poses and/or expressions). In addition, the older controls then identified the expression on the test face.
   Results. The older controls showed generally small numbers of errors (0 to 9%) on the face identifications but more errors on expression identifications (up to 22%). They tended to show shorter RTs (but no changes in accuracy) with repeated presentations of the same face. The young controls responded more quickly, and they made almost no mistakes. Although performance varied, as a group, those with AMD were slower and showed more errors in identification than the older controls did. Across all subjects, both visual acuity and contrast sensitivity contributed significantly to the variances in RTs and accuracy.
   Conclusions. The group of older controls had poorer and more variable RTs and accuracies than the young controls. Difficulties in face matching, in terms of both accuracy and RT, were observed for subjects with AMD. Performance accuracy and RTs for this new test depended on both visual acuity and contrast sensitivity. (Optom Vis Sci 2011; 88:188-199)
C1 [Barnes, Claire S.; De l'Aune, William; Schuchard, Ronald A.] Atlanta Vet Affairs Med Ctr, Rehabil R&D Ctr Excellence, Decatur, GA USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Atlanta VA Health Care System
RP Barnes, CS (通讯作者)，Vet Affairs Palo Alto Hlth Care Syst 151A, 3801 Miranda Ave, Palo Alto, CA 94304 USA.
EM claire.barnes@va.gov
FU Department of Veterans Affairs Rehabilitation Research and Development
   Service
FX This work was supported by the Department of Veterans Affairs
   Rehabilitation Research and Development Service. The authors thank their
   research coordinators, Mary Margaret Ciavatta, Justin Hartley, Wendy
   LiKamWa, and Erica Watkins for their assistance with subject testing.
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NR 45
TC 31
Z9 32
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-5488
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD FEB
PY 2011
VL 88
IS 2
BP 188
EP 199
DI 10.1097/OPX.0b013e318205a17c
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 711IV
UT WOS:000286584900007
PM 21150678
DA 2022-11-30
ER

PT J
AU Hussain, AA
   Lee, YH
   Marshall, J
AF Hussain, Ali A.
   Lee, Yunhee
   Marshall, John
TI High Molecular-Weight Gelatinase Species of Human Bruch's Membrane:
   Compositional Analyses and Age-Related Changes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; SORSBYS FUNDUS DYSTROPHY; MATRIX
   METALLOPROTEINASES; TISSUE INHIBITOR; ACCUMULATION; ACTIVATION;
   EXPRESSION; TRANSPORT; DEPOSITS; DISEASE
AB PURPOSE. The structural and functional demise of aging Bruch's membrane is associated with a reduction in the activity of the matrix metalloproteinase (MMP) degradation system. The gelatinase component of the MMP system consists of MMP2 and MMP9 and two high molecular-weight (HMW1, HMW2) species that are yet to be characterized and whose roles in the aging process are yet to be elucidated. The purpose of this study was to determine the age-related changes in levels of expression and subunit characterization of the HMW gelatinase species of Bruch's membrane.
   METHODS. Gelatin zymography followed by densitometric scanning was used to quantify the level of the HMW species present. Gel-filtration chromatography allowed the fractionation of the gelatinases according to their molecular weight, and subsequent degradation of the HMW species with a minophenyl acetate activation, reduction, and alkylation produced subunit fragments for analysis.
   RESULTS. Most of the HMW1 and HMW2 pool (80% and 87%, respectively) were tightly bound to the matrix. Aging was associated with significant increases in the levels of HMW1 and HMW2 (P < 0.005 and P < 0.05 respectively). On gel filtration, a single large macromolecular complex (LMMC) was observed containing HMW1, HMW2, MMP9, and some MMP2. Activation-mediated fragmentation of HMW1 and HMW2 showed them to be composed of heteropolymers of MMP2 and MMP9.
   CONCLUSIONS. The age-related increase of HMW1 and HMW2, together with the formation of LMMC, resulted in the sequestration of MMP2 and MMP9, thereby reducing the free pool for activation. This is likely to contribute to reduced matrix degradation and turnover of Bruch's membrane in both normal aging and age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2010;51:2363-2371) DOI: 10.1167/iovs.09-4259
C1 [Hussain, Ali A.] St Thomas Hosp, Kings Coll London, Dept Ophthalmol, London SE1 7EH, England.
C3 Guy's & St Thomas' NHS Foundation Trust; University of London; King's
   College London
RP Hussain, AA (通讯作者)，St Thomas Hosp, Kings Coll London, Dept Ophthalmol, Lambeth Palace Rd, London SE1 7EH, England.
EM alyhussain@aol.com
FU Guide Dogs for the Blind Association (GDBA); Fight for Sight (UK)
FX Supported by The Guide Dogs for the Blind Association (GDBA) and Fight
   for Sight (UK).
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NR 27
TC 17
Z9 17
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2010
VL 51
IS 5
BP 2363
EP 2371
DI 10.1167/iovs.09-4259
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 589UU
UT WOS:000277180500012
PM 20007823
DA 2022-11-30
ER

PT J
AU Menghini, M
   Kurz-Levin, MM
   Amstutz, C
   Michels, S
   Windisch, R
   Barthelmes, D
   Sutter, FK
AF Menghini, M.
   Kurz-Levin, M. M.
   Amstutz, C.
   Michels, S.
   Windisch, R.
   Barthelmes, D.
   Sutter, F. Kp.
TI Response to Ranibizumab Therapy in Neovascular AMD - An Evaluation of
   Good and Bad Responders
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE AMD; Lucentis; treatment; response; MARINA
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   PHOTODYNAMIC THERAPY; VERTEPORFIN; CHARTS; TRIAL; TAP
AB Background: Treatment of neovascular age-related macular degeneration (AMD) with Lucentis (R) shows a broad spectrum regarding the course of visual acuity (VA). While some patients show a good response (increase in VA), others disclose much less promising results.
   Patients and Methods: A retrospective data analysis of all eyes treated for neovascular AMD at the University Hospital of Zurich, Switzerland for at least 12 months was carried out. The courses of VA between the 90th (good responders, GR) and the 10th (bad responders, BR) percentiles were compared at 3, 12 and 24 months from baseline. An analysis regarding demographic data, lesion type and size as well as injection frequency and visits was done and predictive factors for GR and BR were evaluated.
   Results: Marked differences in the course of VA between GR (n = 30) and BR (n = 30) are already observed 3 months from baseline. In GR the gains in VA after 3, 12 and 24 were 15.7 +/- 9 letters ETDRS, 25.3 +/- 7 and 14.0 +/- 14. BR showed a deterioration of 8.3 +/- 11 letters ETDRS after 3, 22.1 +/- 8 after 12 and 23.6 +/- 13 after 24 months. The gender distribution was equal with a higher percentage of female patients (64% in BR and 66% in GR). The baseline VA was statistically significantly lower in GR (45.7 +/- 10 vs. 55.4 +/- 11, p < 0.05) than in BR. No other significant differences in baseline data were found, and no predictor for group membership could be identified.
   Conclusions: Only the course of VA in the first three months seems to be of value for an estimation of the response to treatment. In the future the response to treatment in the early phase may influence the treatment algorithm and the injection frequency.
C1 [Menghini, M.; Kurz-Levin, M. M.; Amstutz, C.; Michels, S.; Windisch, R.; Barthelmes, D.; Sutter, F. Kp.] Univ Zurich Hosp, Dept Ophthalmol, CH-8091 Zurich, Switzerland.
C3 University of Zurich; University Zurich Hospital
RP Barthelmes, D (通讯作者)，Univ Zurich Hosp, Dept Ophthalmol, Frauenklin Str 24, CH-8091 Zurich, Switzerland.
EM daniel@barthelmes.ch
OI Menghini, Moreno/0000-0002-1432-2524
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   LUCENTIS ONE YEAR
NR 15
TC 22
Z9 24
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0023-2165
J9 KLIN MONATSBL AUGENH
JI Klinische Monatsblat. Augenheilkunde
PD APR
PY 2010
VL 227
IS 4
BP 244
EP 248
DI 10.1055/s-0029-1245203
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 585XH
UT WOS:000276863200003
PM 20408066
OA Green Accepted
DA 2022-11-30
ER

PT J
AU O'Brien, N
   Jones, ST
   Williams, DG
   Cunningham, HB
   Moreno, K
   Visentin, B
   Gentile, A
   Vekich, J
   Shestowsky, W
   Hiraiwa, M
   Matteo, R
   Cavalli, A
   Grotjahn, D
   Grant, M
   Hansen, G
   Campbell, MA
   Sabbadini, R
AF O'Brien, Nicole
   Jones, S. Tarran
   Williams, David G.
   Cunningham, H. Brad
   Moreno, Kelli
   Visentin, Barbara
   Gentile, Angela
   Vekich, John
   Shestowsky, William
   Hiraiwa, Masao
   Matteo, Rosalia
   Cavalli, Amy
   Grotjahn, Douglas
   Grant, Maria
   Hansen, Genevieve
   Campbell, Mary-Ann
   Sabbadini, Roger
TI Production and characterization of monoclonal
   anti-sphingosine-1-phosphate antibodies
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE sphingosine-1-phosphate; monoclonal antibodies; angiogenesis; cancer;
   bioactive lipids; humanization; age-related macular degeneration;
   choroidal neovascularization; complementarity determining region;
   lymphocyte trafficking
ID IMATINIB-INDUCED APOPTOSIS; LOW-DENSITY-LIPOPROTEIN; MYELOID-LEUKEMIA
   CELLS; SPHINGOSINE 1-PHOSPHATE; CHOROIDAL NEOVASCULARIZATION;
   MULTIPLE-SCLEROSIS; LYMPHOCYTE EGRESS; SPHINGOSINE-1-PHOSPHATE;
   KINASE-1; FTY720
AB Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid involved in multiple physiological processes. Importantly, dysregulated S1P levels are associated with several pathologies, including cardiovascular and inflammatory diseases and cancer. This report describes the successful production and characterization of a murine monoclonal antibody, LT1002, directed against S1P, using novel immunization and screening methods applied to bioactive lipids. We also report the successful generation of LT1009, the humanized variant of LT1002, for potential clinical use. Both LT1002 and LT1009 have high affinity and specificity for S1P and do not cross-react with structurally related lipids. Using an in vitro bioassay, LT1002 and LT1009 were effective in blocking S1P-mediated release of the pro-angiogenic and prometastatic cytokine, interleukin-8, from human ovarian carcinoma cells, showing that both antibodies can out-compete S1P receptors in binding to S1P. In vivo anti-angiogenic activity of all antibody variants was demonstrated using the murine choroidal neovascularization model. Importantly, intravenous administration of the antibodies showed a marked effect on lymphocyte trafficking. The resulting lead candidate, LT1009, has been formulated for Phase 1 clinical trials in cancer and age-related macular degeneration. The anti-S1P antibody shows promise as a novel, first-in-class therapeutic acting as a "molecular sponge" to selectively deplete S1P from blood and other compartments where pathological S1P levels have been implicated in disease progression or in disorders where immune modulation may be beneficial.-O'Brien, N., S. T. Jones, D. G. Williams, H. B. Cunningham, K. Moreno, B. Visentin, A. Gentile, J. Vekich, W. Shestowsky, M. Hiraiwa, R. Matteo, A. Cavalli, D. Grotjahn, M. Grant, G. Hansen, M- A. Campbell, and R. Sabbadini. Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies. J. Lipid Res. 2009. 50: 2245-2257.
C1 [O'Brien, Nicole; Cunningham, H. Brad; Moreno, Kelli; Visentin, Barbara; Gentile, Angela; Vekich, John; Shestowsky, William; Hiraiwa, Masao; Matteo, Rosalia; Cavalli, Amy; Hansen, Genevieve; Campbell, Mary-Ann; Sabbadini, Roger] Lpath Inc, San Diego, CA 92121 USA.
   [O'Brien, Nicole; Visentin, Barbara; Vekich, John; Sabbadini, Roger] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Grotjahn, Douglas] San Diego State Univ, Dept Chem & Biochem, San Diego, CA 92182 USA.
   [Jones, S. Tarran; Williams, David G.] MRC Technol, London NW7 1AD, England.
   [Grant, Maria] Univ Florida, Gainesville, FL USA.
C3 California State University System; San Diego State University;
   California State University System; San Diego State University; State
   University System of Florida; University of Florida
RP Sabbadini, R (通讯作者)，Lpath Inc, San Diego, CA 92121 USA.
EM rsabbadini@lpath.com
RI Grotjahn, Douglas/S-8792-2019
FU National Cancer Institute [R44CA110298-3]; NATIONAL CANCER INSTITUTE
   [R44CA110298] Funding Source: NIH RePORTER
FX This work was supported in part by a grant from the National Cancer
   Institute (R44CA110298-3). Its contents are solely the responsibility of
   the authors and do not necessarily represent the official views of the
   National Cancer Institute or the National Institutes of Health.
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NR 49
TC 88
Z9 92
U1 0
U2 10
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD NOV
PY 2009
VL 50
IS 11
BP 2245
EP 2257
DI 10.1194/jlr.M900048-JLR200
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 507NJ
UT WOS:000270860900013
PM 19509417
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Houle, JM
   Strong, A
AF Houle, JM
   Strong, A
TI Clinical pharmacokinetics of verteporfin
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
ID MOUSE-TUMOR MODEL; RING-A BPD; MACULAR DEGENERATION; PHOTODYNAMIC
   THERAPY; BENZOPORPHYRIN; NEOVASCULARIZATION; PHOTOSENSITIZER
AB Verteporfin, a benzoporphyrin derivative, is the first photosensitive (light-activated) drug to be proven effective in treating certain types of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The pharmacokinetics of light-activated drugs are central to their safety and efficacy. Forty healthy Caucasian volunteers, 24 healthy Japanese volunteers, 9 patients with mild hepatic dysfunction, 69 patients with CNV due to AMD, and 21 patients with skin cancer were infused with verteporfin 3 to 20 mg/m(2) of body surface area over 1.5 to 45 minutes. Verteporfin regioisomers and the metabolite benzoporphyrin derivative diacid (BPD-DA) were quantified by validated methods of liquid chromatography and capillary electrophoresis with laser-induced fluorescence. C-max of verteporfin occurred at the end of the infusion and was proportional to the dose and rate of infusion. The extent of formation of the metabolite BPD-DA was less than 10%, based on the AUC ratio. Renal elimination was minimal (< 0.01% of the dose). All groups studied had similar pharmacokinetics, which were biexponential with distribution in the first 1 to 3 hours and elimination t(1/2) of 5 to 6 hours. No significant differences were observed between Japanese and Caucasian volunteers or between men and women. Patients older than 65 years had a slightly higher average Cm than patients younger than 65 years (1.14 vs. 1.03 mug/ml, p = 0.066), but the ranges of the two age groups overlapped. Verteporfin has a short half-life and is rapidly eliminated in the bile, mainly as unchanged drug. Based on pharmacokinetic data, dose adjustments are not required for age, gender, race, or mild hepatic or renal impairment. The rapid elimination of verteporfin shows that the period of skin photosensitivity is unlikely to persist after 24 to 48 hours. (C) 2002 the American College of Clinical Pharmacology.
C1 QLT Inc, Vancouver, BC V5T 4T5, Canada.
RP Houle, JM (通讯作者)，QLT Inc, 887 Great No Way, Vancouver, BC V5T 4T5, Canada.
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   *VIP STUD GROUP, IN PRESS OPHTHALMOL
NR 19
TC 67
Z9 71
U1 1
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0091-2700
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD MAY
PY 2002
VL 42
IS 5
BP 547
EP 557
DI 10.1177/00912700222011607
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 544ZL
UT WOS:000175191700009
PM 12017349
DA 2022-11-30
ER

PT J
AU Mai, JL
   Riedl, S
   Reiter, GS
   Lachinov, D
   Vogl, WD
   Bogunovic, H
   Schmidt-Erfurth, U
AF Mai, Julia
   Riedl, Sophie
   Reiter, Gregor S.
   Lachinov, Dmitrii
   Vogl, Wolf -Dieter
   Bogunovic, Hrvoje
   Schmidt-Erfurth, Ursula
TI Comparison of Fundus Autofluorescence Versus Optical Coherence
   Tomography-based Evaluation of the Therapeutic Response to Pegcetacoplan
   in Geographic Atrophy br
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; RETINAL SENSITIVITY; END-POINTS; PROGRESSION;
   SECONDARY; MICROPERIMETRY; PREVALENCE; DISEASE
AB PURPOSE: To perform an optical coherence tomogra-phy (OCT)-based analysis of geographic atrophy (GA) progression in patients treated with pegcetacoplan. center dot DESIGN: Post hoc analysis of a phase 2 multicenter, randomized, sham-controlled trial.center dot METHODS: Manual annotation of retinal pigment ep-ithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss was performed on OCT volumes from baseline and month 12 from the phase 2 FILLY trial of intravitreal pegcetacoplan for the treatment of GA sec-ondary to age-related macular degeneration.center dot MAIN OUTCOME MEASURES: Correlation of GA areas measured on fundus autofluorescence and OCT. Differ-ence in square root transformed growth rates of RPE, EZ, and ELM loss between treatment groups (monthly injec-tion [AM], injection every other month [AEOM], and sham [SM]).center dot RESULTS: OCT volumes from 113 eyes of 113 pa-tients (38 AM, 36 AEOM, and 39 SM) were included, resulting in 11 074 B-scans. The median growth of RPE loss was significantly slower in the AM group (0.158 [0.057-0.296]) than the SM group (0.255 [0.188-0.359], P = .014). Importantly, the growth of EZ loss was also significantly slower in the AM group (0.127 [0.041-0.247]) than the SM group (0.232 [0.130-0.349], P = .017). There was no significant difference in the growth of ELM loss between the treatment groups ( P = .114).center dot CONCLUSIONS: OCT imaging provided consistent re-sults for GA growth compared with fundus autofluores-cence. In addition to slower RPE atrophy progression in patients treated with pegcetacoplan, a significant reduction in EZ impairment was also identified by OCT, suggesting the use of OCT as a potentially more sensi-tive monitoring tool in GA therapy. (Am J Ophthalmol 2022;244: 175-182. (c) 2022 Elsevier Inc. All rights re-served.)
C1 [Mai, Julia; Riedl, Sophie; Reiter, Gregor S.; Lachinov, Dmitrii; Vogl, Wolf -Dieter; Bogunovic, Hrvoje; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol & Optometry, OPTIMA Lab Ophthalm Image Anal, Vienna, Austria.
   [Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Ursula Schmidt Erfurth, Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Ursula Schmidt Erfurth, Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Riedl,
   Sophie/0000-0003-0003-0886; Reiter, Gregor/0000-0001-7661-4015
FU Apellis research grant
FX The FILLY phase 2 study was conducted by Apellis Pharmaceuticals, and
   our work was in part supported by an Apellis research grant. The
   organization had no role in the design and conduct of this research.
CR Apellis, 2021, RETINA SOC ANN M
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NR 36
TC 0
Z9 0
U1 0
U2 0
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 2022
VL 244
BP 175
EP 182
DI 10.1016/j.ajo.2022.06.023
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5G9PK
UT WOS:000867321700004
PM 35853489
DA 2022-11-30
ER

PT J
AU Nair, M
   Tagare, S
   Venkatesh, R
   Odayappan, A
AF Nair, Megha
   Tagare, Shivraj
   Venkatesh, Rengaraj
   Odayappan, Annamalai
TI Artificial intelligence in glaucoma
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE artificial intelligence; glaucoma; screening; machine learning; deep
   learning
AB Background: Artificial Intelligence (AI) is an area of computer science that encompasses the creation of intelligent machines that work and react like humans. It deals with the development algorithms that seek to simulate human brain and also mimic cognitive functions typically associated with the human mind such as learning and problem solving. Purpose: Do we need artificial intelligence in Glaucoma? Glaucoma is the second most common cause of blindness in the world. Its prevalence was over 60 million in 2010 and over 80 million by 2020. It is so common, yet so easily overlooked. More importantly, about 50% of patients in developed countries and 90% in developing countries are unaware of having glaucoma. Early detection can delay the progression of glaucoma. Hence the time is ripe to advovate glaucoma screening. Synopsis: The application of AI in ophthalmology mainly concentrates on the diseases with a high incidence, such as diabetic retinopathy, age-related macular degeneration, glaucoma, retinopathy of prematurity, age-related or congenital cataract etc AI involves mainly 1. machine learning that are algorithms with the ability to learn without being explicitly programmed and 2. deep learning in which artificial neural networks adapt and learn from vast amounts of data. But there are limitations to screening - such as disparity between ophthalmologist:patient ratio and also the availability of the specialty services. The large amount of data acquired from patients makes it nearly impossible for ophthalmologists to screen them with equal efficacy and consistency. Highlights: AI in glaucoma aims at including factors such as clinical data, genomic data, life style behaviors, risk factors, and medical history to predict the risk of developing glaucoma, help customise the most appropriate management protocol for a given patient, and estimate prognosis and surgical success. Video Link: https://youtu.be/IwYS7wDMhkY
C1 [Nair, Megha; Tagare, Shivraj; Venkatesh, Rengaraj; Odayappan, Annamalai] Aravind Eye Hosp, Pondicherry, India.
RP Nair, M (通讯作者)，Aravind Eye Hosp, Pondicherry, India.
EM megnair@gmail.com
NR 0
TC 0
Z9 0
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 MAY
PY 2022
VL 70
IS 5
BP 1868
EP 1869
DI 10.4103/ijo.IJO_1015_22
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2C1CH
UT WOS:000810614200113
PM 35502116
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Domagoj, I
   Anton, H
   Martin, W
   Gerald, S
   Christoph, MX
   Ewald, L
   Andreas, G
   Andreas, W
AF Domagoj, Ivastinovic
   Anton, Haas
   Martin, Weger
   Gerald, Seidel
   Christoph, Mayer-Xanthaki
   Ewald, Lindner
   Andreas, Guttmann
   Andreas, Wedrich
TI Vitrectomy for diabetic macular edema and the relevance of external
   limiting membrane
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Vitrectomy; Diabetic macular edema; Epiretinal membrane; External
   limiting membrane; Internal limiting membrane
ID OPTICAL COHERENCE TOMOGRAPHY; VITREORETINAL INTERFACE ABNORMALITIES;
   ENDOTHELIAL GROWTH-FACTOR; EPIRETINAL MEMBRANES; VISUAL-ACUITY;
   PREDICTOR; SURGERY; LAYERS; CELLS; EYES
AB Purpose To evaluate the relevance of external limiting membrane (ELM) on the visual and morphological results in eyes with diabetic macular edema (DME) that underwent pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling. Methods Medical records of patients with DME who underwent PPV at our unit between January 2017 and December 2019 were reviewed. We assessed preoperative and postoperative best-corrected visual acuity (BCVA), central macular thickness (CMT) using spectral domain OCT (optical coherence tomography). Exclusion criteria were previous PPV; incomplete data; concomitant diseases including retinal vein occlusion, age-related macular degeneration, uveitis; and a follow-up of less than 12 months. The surgeries were performed using 23- or 27-gauge vitrectomy. The ELM was graded depending on its configuration (grade 0 = intact, grade 1 to 3: disruption of varying extent). Results Ninety-nine eyes were enrolled. The postoperative follow up averaged 23.7 months. The preoperative and final BCVA averaged 0.71 +/- 0.28 and 0.52 +/- 0.3 logMAR, respectively (p = 0.002). The CMT averaged 515.2 +/- 209.1 mu m preoperatively and 327 +/- 66.1 mu m postoperatively (p = 0.001). Eyes with intact ELM (n = 8) had a significantly better BCVA compared to those with ELM disruption (0.28 +/- 0.14 vs. 0.7 +/- 0.25 logMAR, p = 0.01). The final CMT was similar among the groups (intact ELM: 317 +/- 54.6 mu m; ELM disruption: 334 +/- 75.2, p = 0.31). Conclusions PPV with ERM and ILM peeling is an effective treatment of DME. Eyes with intact ELM preoperatively had a significantly better final visual outcome. To maximize the benefit for patients with DME we recommend early PPV as long as ELM is intact.
C1 [Domagoj, Ivastinovic; Anton, Haas; Martin, Weger; Gerald, Seidel; Christoph, Mayer-Xanthaki; Ewald, Lindner; Andreas, Guttmann; Andreas, Wedrich] Med Univ Graz, Dept Ophthalmol, Auenbruggerpl 4, A-8036 Graz, Austria.
C3 Medical University of Graz
RP Domagoj, I (通讯作者)，Med Univ Graz, Dept Ophthalmol, Auenbruggerpl 4, A-8036 Graz, Austria.
EM domagoj.ivastinovic@medunigraz.at
RI Lindner, Ewald/AEM-1071-2022
OI Wedrich, Prof. Dr., Andreas/0000-0003-2533-7067
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NR 42
TC 1
Z9 1
U1 0
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD SEP 15
PY 2021
VL 21
IS 1
AR 334
DI 10.1186/s12886-021-02095-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UQ6ZV
UT WOS:000696211800002
PM 34525998
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Marchesi, N
   Fahmideh, F
   Boschi, F
   Pascale, A
   Barbieri, A
AF Marchesi, Nicoletta
   Fahmideh, Foroogh
   Boschi, Federica
   Pascale, Alessia
   Barbieri, Annalisa
TI Ocular Neurodegenerative Diseases: Interconnection between Retina and
   Cortical Areas
SO CELLS
LA English
DT Review
DE eye; SNC; retinal neurodegeneration; neurodegenerative diseases;
   age-related diseases
ID DIABETIC-RETINOPATHY; MULTIPLE-SCLEROSIS; GLAUCOMA; BRAIN; DEGENERATION;
   MANAGEMENT; DIAGNOSIS; DAMAGE; ORGANIZATION; DYSFUNCTION
AB The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that the eye is properly considered an extension of the brain. Both organs consist of neurons and derived from a neural tube. The visual process involves photoreceptors that receive light stimulus from the external environment and send it to retinal ganglionic cells (RGC), one of the cell types of which the retina is composed. The retina, the internal visual membrane of the eye, processes the visual stimuli in electric stimuli to transfer it to the brain, through the optic nerve. Retinal chronic progressive neurodegeneration, which may occur among the elderly, can lead to different disorders of the eye such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Mainly in the elderly population, but also among younger people, such ocular pathologies are the cause of irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases of the CSN are a group of pathologies with common characteristics and etiology not fully understood; some risk factors have been identified, but they are not enough to justify all the cases observed. Furthermore, several studies have shown that also ocular disorders present characteristics of neurodegenerative diseases and, on the other hand, CNS pathologies, i.e., Alzheimer disease (AD) and Parkinson disease (PD), which are causes of morbidity and mortality worldwide, show peculiar alterations at the ocular level. The knowledge of possible correlations could help to understand the mechanisms of onset. Moreover, the underlying mechanisms of these heterogeneous disorders are still debated. This review discusses the characteristics of the ocular illnesses, focusing on the relationship between the eye and the brain. A better comprehension could help in future new therapies, thus reducing or avoiding loss of vision and improve quality of life.
C1 [Marchesi, Nicoletta; Fahmideh, Foroogh; Boschi, Federica; Pascale, Alessia; Barbieri, Annalisa] Univ Pavia, Dept Drug Sci, Pharmacol Sect, Viale Taramelli 14, I-27100 Pavia, Italy.
C3 University of Pavia
RP Barbieri, A (通讯作者)，Univ Pavia, Dept Drug Sci, Pharmacol Sect, Viale Taramelli 14, I-27100 Pavia, Italy.
EM nicoletta.marchesi@unipv.it;
   foroogh.fahmidehtavako01@universitadipavia.it; federica.boschi@unipv.it;
   alessia.pascale@unipv.it; annalisa.barbieri@unipv.it
RI Barbieri, Annalisa/ABE-6328-2021; Marchesi, Nicoletta/GQZ-7428-2022
OI Barbieri, Annalisa/0000-0003-2947-0084; Marchesi,
   Nicoletta/0000-0001-6271-1420
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NR 117
TC 14
Z9 14
U1 2
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD SEP
PY 2021
VL 10
IS 9
AR 2394
DI 10.3390/cells10092394
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA UV3MO
UT WOS:000699387300001
PM 34572041
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Rossouw, P
   Guichard, MM
   Hatz, K
AF Rossouw, Petra
   Guichard, Maria M.
   Hatz, Katja
TI Contrast sensitivity and binocular reading speed best correlating with
   near distance vision-related quality of life in bilateral nAMD
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE age related macular degeneration; contrast sensitivity; ETDRS;
   NEI-VFQ25; quality of life; reading speed
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION PATIENTS;
   VISUAL FUNCTION; RANIBIZUMAB TREATMENT; FOLLOW-UP; BURDEN; EYE;
   AFLIBERCEPT; RELIABILITY; PERFORMANCE
AB Purpose Bilateral neovascular age-related macular degeneration (nAMD) causes difficulties in daily life, especially with regard to near-vision tasks, despite well preserved Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) at distance. Therefore, alternative visual function measures were evaluated in terms of their correlation with vision-related quality of life scores (QoL). Methods A prospective cross-sectional pilot study including patients with a diagnosis of bilateral nAMD having lesions within the central 1 mm ETDRS grid subfield. Standardised testing included a vision-related QoL assessment (NEI-VFQ25), best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), Radner maximum reading speed and Pelli-Robson contrast sensitivity (CS). Results N = 54. The mean better eye (range) BCVA was 79 (55-96) letters, median (range) LLVA 79.5 (58-97) letters and median (range) CS 1.35 (0-1.65) log units. Mean binocular maximum reading speed was 117.33 +/- 28.42 wpm. The best correlations with the near subscale score were found for CS followed by binocular maximum reading speed (r = 0.59,p = 0.0001;r = 0.36,p = 0.008, respectively). A weaker correlation was observed for the BCVA in the better eye (r = 0.33,p = 0.02). The correlation between the NEI-VFQ25 distance subscale and BCVA was weaker (r = 0.37,p = 0.005) than the correlations with CS (r = 0.67,p = 0.0001) and LLVA (r = 0.40,p = 0.003). Conclusions For patients with a bilateral centre-involving nAMD, the best correlation with near QoL was the better eye CS followed by maximum binocular reading speed. These measures could be valuable in quantifying vision-related QoL outcomes in AMD clinical trials.
C1 [Rossouw, Petra] Univ Aalen, Dept Vis Sci & Optometry, Aalen, Germany.
   [Rossouw, Petra; Guichard, Maria M.; Hatz, Katja] Vista Klin Binningen, Binningen, Switzerland.
   [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, Binningen, Switzerland.; Hatz, K (通讯作者)，Univ Basel, Fac Med, Basel, Switzerland.
EM katja.hatz@vista.ch
FU Retina Suisse Foundation; Retina Suisse
FX This project was supported by a grant from The Retina Suisse Foundation.
   No honoraria, grants or other forms of payment were paid to the authors
   for the writing of the manuscript. Retina Suisse had no role in the
   design or conduct of this research. The authors report no conflicts of
   interest and have no proprietary interest in any of the materials
   mentioned in this article. This study has been presented at EURETINA
   2019 annual meeting, Paris, France.
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NR 41
TC 6
Z9 7
U1 1
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD NOV
PY 2020
VL 40
IS 6
BP 760
EP 769
DI 10.1111/opo.12736
EA SEP 2020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OH4PT
UT WOS:000571511800001
PM 32959926
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Josifovska, N
   Albert, R
   Nagymihaly, R
   Lytvynchuk, L
   Moe, MC
   Kaarniranta, K
   Vereb, ZJ
   Petrovski, G
AF Josifovska, Natasha
   Albert, Reka
   Nagymihaly, Richard
   Lytvynchuk, Lyubomyr
   Moe, Morten C.
   Kaarniranta, Kai
   Vereb, Zoltan J.
   Petrovski, Goran
TI Resveratrol as Inducer of Autophagy, Pro-Survival, and Anti-Inflammatory
   Stimuli in Cultured Human RPE Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE resveratrol; retinal pigment epithelium; autophagy; proteasomal
   inhibition; survival; inflammation; protein array; age-related macular
   degeneration
ID EPITHELIAL-CELLS; EXPRESSION; APOPTOSIS; DEATH
AB Purpose: To investigate the mechanism by which resveratrol acts upon retinal pigment epithelial (RPE) cells and to characterize its effect upon autophagy, survival, and inflammation, with consequent implications to treatment for age-related macular degeneration (AMD). Methods: Cultured ARPE-19 cells were exposed to 10 and 50 mu Mresveratrol. Cell survival/death was determined by annexin-FITC/propidium iodide using flow cytometry, while autophagy was studied by detecting autophagic vacuoles formation (acridine orange and transmission electron microscopy), as well as LC3II/I ratio and p62 expression by Western blot. In addition, time-lapse confocal microscopy of a pDENDRA-LC3 expression vector was performed to detect autophagy in transfected ARPE-19 cells under the different treatment conditions. Inhibition of proteasomal and autophagy-lysosomal fusion was carried out by MG-132 and chloroquine, respectively, while induction of autophagy was achieved by rapamycin treatment. Detection of secreted cytokines by ARPE-19 cells using Human XL Cytokine Array was performed under oxidative stress (H2O2) and resveratrol treatments, respectively. Results: Resveratrol induced autophagy in ARPE-19 cells as determined by augmented presence of autophagic vacuoles, increased LC3II/I ratio and decreased p62 expression, as well as time-lapse confocal microscopy using pDENDRA-LC3 expression vector. Resveratrol acted similarly to proteasomal inhibition and downstream of mammalian target of rapamycin (mTOR), since upstream inhibition of autophagy by 3-methyladenine could not inhibit autophagy in ARPE-19 cells. Co-treatmeant by rapamycin and/or proteasome inhibition showed no additive effect upon autophagy induction. ARPE-19 cells treated by resveratrol showed lower cell death rate compared to untreated controls. Resveratrol induced a specific anti-inflammatory response in ARPE-19 cells. Conclusions: Resveratrol can induce autophagy, pro-survival, and anti-inflammatory stimuli in ARPE-19 cells, properties which could be plausible to formulate future treatment modalities for AMD.
C1 [Josifovska, Natasha; Nagymihaly, Richard; Moe, Morten C.; Petrovski, Goran] Oslo Univ Hosp, Dept Ophthalmol, Ctr Eye Res, N-0450 Oslo, Norway.
   [Josifovska, Natasha; Nagymihaly, Richard; Moe, Morten C.; Petrovski, Goran] Univ Oslo, N-0450 Oslo, Norway.
   [Albert, Reka; Nagymihaly, Richard; Lytvynchuk, Lyubomyr; Vereb, Zoltan J.; Petrovski, Goran] Univ Szeged, Dept Ophthalmol, Fac Med, H-6720 Szeged, Hungary.
   [Lytvynchuk, Lyubomyr] Justus Liebig Univ Giessen, Dept Ophthalmol, Eye Clin, Univ Hosp Giessen, D-35390 Giessen, Germany.
   [Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Inst Clin Med, Kuopio 70210, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Kuopio 70210, Finland.
C3 University of Oslo; University of Oslo; Szeged University; Justus Liebig
   University Giessen; University Hospital of Giessen & Marburg; University
   of Eastern Finland; Kuopio University Hospital; University of Eastern
   Finland
RP Petrovski, G (通讯作者)，Oslo Univ Hosp, Dept Ophthalmol, Ctr Eye Res, N-0450 Oslo, Norway.; Petrovski, G (通讯作者)，Univ Oslo, N-0450 Oslo, Norway.; Petrovski, G (通讯作者)，Univ Szeged, Dept Ophthalmol, Fac Med, H-6720 Szeged, Hungary.
EM natasa_josifovska@yahoo.com; albertreka86@gmail.com; enmihaly@gmail.com;
   Lyubomyr.Lytvynchuk@augen.med.uni-giessen.de; m.c.moe@medisin.uio.no;
   kai.kaarniranta@uef.fi; jzvereb@gmail.com;
   goran.petrovski@medisin.uio.no
RI Vereb, Zoltan/AAR-4092-2020
OI Josifovska, Natasha/0000-0002-3898-9729; Vereb,
   Zoltan/0000-0002-9518-2155
FU Norwegian Association of the Blind and Partially Sighted
FX The work was partially funded by grants from the Norwegian Association
   of the Blind and Partially Sighted.
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NR 35
TC 23
Z9 24
U1 2
U2 8
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD FEB
PY 2020
VL 21
IS 3
AR 813
DI 10.3390/ijms21030813
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KY4PQ
UT WOS:000522551602026
PM 32012692
OA Green Published, Green Accepted, gold
DA 2022-11-30
ER

PT J
AU Horton, C
   Davies, TJ
   Lahiri, P
   Sachamitr, P
   Fairchild, PJ
AF Horton, Christopher
   Davies, Timothy J.
   Lahiri, Priyoshi
   Sachamitr, Patty
   Fairchild, Paul J.
TI Developing a simple method to enhance the generation of cone and rod
   photoreceptors in pluripotent stem cell-derived retinal organoids
SO STEM CELLS
LA English
DT Article
DE retinal organoids; photoreceptors; pluripotent stem cells
ID ACID; DIFFERENTIATION; EXPRESSION; OPSIN
AB Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age-related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has shown that a simple three-dimensional culture system enables differentiation of human pluripotent stem cells to retinal organoids containing large numbers of photoreceptors developing alongside retinal neurons and Muller glia cells in a laminated structure that resembles the native retina. Despite these promising developments, current protocols show different efficiencies across pluripotent stem cells and result in retinal organoids with a mixture of photoreceptor cells at varying maturation states, along with nonphotoreceptor cell types. In this study, we investigated the impact of stage-specific addition of retinoic acid (RA), 9-cis-retinal, 11-cis-retinal, levodopa (l-DOPA), triiodothyronine (T3), and gamma-secretase inhibitor ((2S)-N-[(3,5-Difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine1,1-dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 120 of differentiation enhanced the generation of rod and S-cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 of differentiation led to enhanced generation of L/M-cones at the expense of rods. l-DOPA when added together with RA during days 90 to 120 of differentiation also promoted the emergence of S-cones at the expense of rod photoreceptors. Collectively, these data represent an advance in our ability to direct generation of rod and cone photoreceptors in vitro.
C1 [Horton, Christopher; Davies, Timothy J.; Lahiri, Priyoshi; Sachamitr, Patty; Fairchild, Paul J.] Univ Oxford, Sir William Dunn Sch Pathol, South Parks Rd, Oxford OX1 3RE, England.
   [Lahiri, Priyoshi] Univ Calgary, Fac Vet Med, Dept Prod Anim Hlth, TRW 2D09,2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.
   [Sachamitr, Patty] Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Toronto, ON, Canada.
C3 University of Oxford; University of Calgary; University of Toronto;
   University Toronto Affiliates; Hospital for Sick Children (SickKids)
RP Fairchild, PJ (通讯作者)，Univ Oxford, Sir William Dunn Sch Pathol, South Parks Rd, Oxford OX1 3RE, England.
EM paul.fairchild@path.ox.ac.uk
OI ZERTI, DARIN/0000-0003-0865-8088
FU MRC [MC_PC_16056, MC_PC_15029] Funding Source: UKRI
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NR 23
TC 8
Z9 8
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD JAN
PY 2020
VL 38
IS 1
BP 67
EP 79
DI 10.1002/stem.3095
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA KE1KH
UT WOS:000508318000008
PM 31621975
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Perin, C
   Vigano, B
   Piscitelli, D
   Matteo, BM
   Meroni, R
   Cerri, CG
AF Perin, Cecilia
   Vigano, Barbara
   Piscitelli, Daniele
   Matteo, Barbara Maria
   Meroni, Roberto
   Cerri, Cesare Giuseppe
TI Non-invasive current stimulation in vision recovery: a review of the
   literature
SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE
LA English
DT Review
DE Electrical stimulation; transcorneal electrical stimulation (tcES);
   repetitive transorbital alternating current stimulation (rtACS);
   high-frequency random noise stimulation (hf-RNS); transcranial direct
   current stimulation (tDCS); visual damage; hypovision
ID TRANSCORNEAL ELECTRICAL-STIMULATION; ALTERNATING-CURRENT STIMULATION;
   RANDOM NOISE STIMULATION; VISUAL FUNCTION; CONTRAST SENSITIVITY; OPTIC
   NEUROPATHY; RESTORATION; BRAIN; INDIVIDUALS; IMPROVEMENT
AB Background: Around 253 million people worldwide suffer from irreversible visual damage. Numerous studies have been carried out in order to unveil the effects of electrical stimulation (ES) as a useful tool for rehabilitation for different visual conditions and pathologies.
   Objective: This systematic review aimed to 1) examine the current evidence of ES efficacy for the treatment of visual pathologies and 2) define the corresponding degree of the recommendation of different ES techniques.
   Methods: A systematic review was conducted in MEDLINE and Cochrane Library database to collect documents published between 2000 and 2018. For each study, Level of Evidence of Effectiveness of ES as well as the Class of Quality for the treatment of different visual pathologies were determined.
   Results: Thirty-eight articles were included. Studies were grouped according to the pathology treated and the type of stimulation administered. The first group included studies treating pre-chiasmatic pathologies (age-related macular degeneration, macular dystrophy, retinal artery occlusion, retinitis pigmentosa, glaucoma, optic nerve damage, and optic neuropathy) using pre-chiasmatic stimulation; the second group included studies treating both pre-chiasmatic pathologies (amblyopia, myopia) and post-chiasmatic pathologies or brain conditions (hemianopsia, brain trauma) by means of post-chiasmatic stimulation. In the first group, repetitive transorbital alternating current stimulation (rtACS) reached level A recommendation, and transcorneal electrical stimulation (tcES) reached level B. In the second group, both high-frequency random noise stimulation (hf-RNS) and transcranial direct current stimulation (tDCS) reached level C recommendation.
   Conclusions: Study's findings suggest conclusive evidence for rtACS treatment. For other protocols results are promising but not conclusive since the examined studies assessed different stimulation parameters and endpoints. A comparison of the effects of different combinations of these variables still lacks in the literature. Further studies are needed to optimize existing protocols and determine if different protocols are needed for different diseases.
C1 [Perin, Cecilia; Piscitelli, Daniele; Matteo, Barbara Maria; Meroni, Roberto; Cerri, Cesare Giuseppe] Univ Milano Bicocca, Sch Med & Surg, Dipartimento Med & Chirurg, Via Cadore 48, I-20900 Milan, MB, Italy.
   [Perin, Cecilia; Meroni, Roberto; Cerri, Cesare Giuseppe] Univ Milano Bicocca, Milan Ctr Neurosci NeuroMI, Milan, Italy.
   [Vigano, Barbara] Ist Clin Zucchi, Carate Brianza, MB, Italy.
   [Piscitelli, Daniele] McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ, Canada.
   [Meroni, Roberto] LUNEX Int Univ Hlth Exercise & Sports, Dept Physiotherapy, Differdange, Luxembourg.
C3 University of Milano-Bicocca; University of Milano-Bicocca; McGill
   University
RP Perin, C (通讯作者)，Univ Milano Bicocca, Sch Med & Surg, Dipartimento Med & Chirurg, Via Cadore 48, I-20900 Milan, MB, Italy.
EM cecilia.perin@unimib.it
RI Meroni, Roberto/AGA-7143-2022; Piscitelli, Daniele/L-9387-2019
OI Meroni, Roberto/0000-0002-5717-1148; Piscitelli,
   Daniele/0000-0002-5240-3798
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NR 55
TC 10
Z9 10
U1 2
U2 10
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 0922-6028
EI 1878-3627
J9 RESTOR NEUROL NEUROS
JI Restor. Neurol. Neurosci.
PY 2020
VL 38
IS 3
BP 239
EP 250
DI 10.3233/RNN-190948
PG 12
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA NF7RV
UT WOS:000563492600004
PM 31884495
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Querques, L
   Parravano, M
   Borrelli, E
   Chiaravalloti, A
   Tedeschi, M
   Sacconi, R
   Zucchiatti, I
   Bandello, F
   Querques, G
AF Querques, Lea
   Parravano, Mariacristina
   Borrelli, Enrico
   Chiaravalloti, Adele
   Tedeschi, Massimiliano
   Sacconi, Riccardo
   Zucchiatti, Ilaria
   Bandello, Francesco
   Querques, Giuseppe
TI Anatomical and functional changes in neovascular AMD in remission:
   comparison of fibrocellular and fibrovascular phenotypes
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE neovascularisation; imaging; age-related macular degeneration
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; MACULAR DEGENERATION; MEMBRANES;
   FIBROSIS; CHORIOCAPILLARIS; MICROPERIMETRY
AB Purpose To investigate the anatomical changes and the macular function in neovascular age-related macular degeneration (AMD) eyes, according to the recognition of either fibrocellular or fibrovascular phenotype. Methods We enrolled eyes with previously treated neovascular AMD in remission (no subretinal haemorrhage, sign of fluid in or under the retina and no treatment for at least 6 months). Subjects underwent multimodal imaging assessment and were tested for macular sensitivity using microperimetry. The study cohort was divided according to the presence of fibrosis on multicolour (MC) images, yielding two distinct phenotypic subgroups: (1) fibrocellular group and (2) fibrovascular group. Results Nineteen eyes were classified as fibrocellular on MC images, while 22 eyes as fibrovascular. Mean +/- SD age was 73.9 +/- 11.0 years in the fibrocellular group and 75.9 +/- 7.1 years in the fibrovascular group (p=0.221). Best-corrected visual acuity was 0.7 +/- 0.5 logarithm of the minimum angle of resolution (LogMAR) in the fibrocellular group and 0.3 +/- 0.2 LogMAR in the fibrovascular group (p=0.003). On the optical coherence tomography and fundus autofluorescence evaluation, 17/19 eyes with the fibrocellular phenotype and 8/22 eyes with the fibrovascular phenotype displayed the presence of retinal pigment epithelium (RPE) atrophy (p=0.001). The perfusion density within the neovascular lesion was 28.9%+/- 9.9% in the fibrocellular group and 44.2%+/- 5.9 % in the fibrovascular group (p<0.0001). Conclusion Neovascular AMD eyes in remission and with evidence of fibrocellular scar are characterised by RPE atrophy and reduced perfusion, which are associated with a higher degree of functional impairment. These findings suggest that maturation of vessels in fibrosis might be a better target in neovascular AMD treatments rather than their abolishment.
C1 [Querques, Lea; Borrelli, Enrico; Sacconi, Riccardo; Zucchiatti, Ilaria; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, Hosp San Raffaele, Dept Ophthalmol, Milan, Italy.
   [Parravano, Mariacristina; Chiaravalloti, Adele; Tedeschi, Massimiliano] Fdn GB Bietti IRCCS, Dept Ophthalmol, Rome, Italy.
   [Borrelli, Enrico] Univ G DAnnunzio, Dept Ophthalmol, Chieti, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; IRCCS
   - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in Oftalmologia; G
   d'Annunzio University of Chieti-Pescara
RP Querques, G (通讯作者)，Osped San Raffaele, Ophthalmol, Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Zucchiatti, Ilaria/ABA-7083-2020; Borrelli, Enrico/AAR-3693-2020
OI Borrelli, Enrico/0000-0003-2815-5031; Sacconi,
   Riccardo/0000-0003-2891-2012; bandello, francesco/0000-0003-3238-9682;
   Querques, Giuseppe/0000-0002-3292-9581
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NR 33
TC 15
Z9 15
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JAN
PY 2020
VL 104
IS 1
BP 47
EP 52
DI 10.1136/bjophthalmol-2018-313685
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KA1YB
UT WOS:000505593600010
PM 31000509
DA 2022-11-30
ER

PT J
AU Barth, T
   Zeman, F
   Helbig, H
   Gamulescu, MA
AF Barth, T.
   Zeman, F.
   Helbig, H.
   Gamulescu, M. -A.
TI Intravitreal anti-VEGF treatment for choroidal neovascularization
   secondary to traumatic choroidal rupture
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Secondary choroidal neovascularization; Choroidal rupture; Intravitreal
   anti-VEGF (vascular endothelial growth factor) treatment
ID RANIBIZUMAB TREATMENT; MACULAR DEGENERATION; MEMBRANES; PATIENT
AB Background So far only single cases with short follow-up have been reported on the use of intravitreal anti-VEGF for traumatic choroidal neovascularizations (CNV). This paper reports a large case series of patients with CNV secondary to choroidal rupture after ocular trauma receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. Methods Fifty-four patients with unilateral choroidal rupture after ocular trauma diagnosed between 2000 and 2016 were retrospectively evaluated. Eleven patients with CNV secondary to choroidal rupture were identified. Five eyes with traumatic secondary CNV were treated with anti-VEGF and were systematically analysed. The other 4 patients with inactive CNV underwent watchful observation. Results Four men and one woman with a mean age of 29 years (SD 12.4; range 19-45) had intravitreal anti-VEGF therapy for traumatic CNV. Another 4 patients with a mean age of 37 years (SD 6.6; range 31-46) presented with inactive CNV and did not receive specific treatment. In all 9 cases the mean interval between the ocular trauma and the diagnosis of CNV was 5.7 months (SD 4.75; range 2-12). In the treatment group per eye 4.2 injections (SD 3.2; range 1-8) were given on average. Four eyes were treated with bevacizumab and one eye with ranibizumab. Regression of CNV was noted in all eyes. In 4 eyes visual acuity (VA) improved, one eye kept stable visual acuity. Conclusions Here, we present the up to now largest case series of traumatic CNV membranes treated with anti-VEGF injections with a mean follow-up period of 5 years. Intravitreal anti-VEGF therapy seems to be safe and effective for secondary CNV after choroidal rupture. Compared to exudative age-related macular degeneration fewer injections are needed to control the disease.
C1 [Barth, T.; Helbig, H.; Gamulescu, M. -A.] Univ Med Ctr Regensburg, Dept Ophthalmol, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
   [Zeman, F.] Univ Med Ctr Regensburg, Ctr Clin Studies ZKS, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
C3 University of Regensburg; University of Regensburg
RP Barth, T (通讯作者)，Univ Med Ctr Regensburg, Dept Ophthalmol, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
EM teresa.barth@ukr.de
RI Zeman, Florian/GNH-3239-2022
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NR 19
TC 3
Z9 3
U1 0
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD NOV 26
PY 2019
VL 19
IS 1
AR 239
DI 10.1186/s12886-019-1242-7
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JR1YG
UT WOS:000499428700001
PM 31771544
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Feng, QT
   Yang, WZ
   Gao, ZY
   Ruan, XC
   Zhang, YH
AF Feng, Qiting
   Yang, Weizhong
   Gao, Zongyin
   Ruan, Xiangcai
   Zhang, Yuehong
TI Up-regulation of P-gp via NF-kappa B activation confers protection
   against oxidative damage in the retinal pigment epithelium cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE P-glycoprotein; Oxidative stress; NF-kappa B; Retinal pigment epithelium
   cells
ID PROXIMAL TUBULE CELLS; MITOCHONDRIAL LOCALIZATION; GLYCOPROTEIN;
   EXPRESSION; RESISTANCE; STRESS; MDR1; TRANSPORTERS; MECHANISM; TOXICITY
AB Dysfunction of retinal pigment epithelial (RPE) cells has been associated with the pathogenesis of age-related macular degeneration in relation to increased oxidative stress, subsequent mitochondrial dysfunction and cell death. Permeability-glycoprotein (P-gp), encoded by the multidrug resistance 1 gene (MDR1), is an active efflux pump involved in cell homeostasis and nuclear factor kappa B (NF-kappa B) shows potential involvement in P-gp regulation due to its binding to the promoter domains of MDR1 gene. This study sought to determine the role of P-gp expression regulated by NF-kappa B in RPE cells during oxidative stress. The human RPE D407 cells were exposed to increasing concentrations of hydrogen peroxide (H2O2) for 24 h. The small-interfering RNA (siRNA) transfection was used to down-regulate P-gp and NF-kappa B, and the expressions of P-gp and NF-kappa B p65 were determined by quantitative real-time PCR, western blot and immunofluorescence. The activity of NF-kappa B was detected by luciferase reporter assay. Mitochondrial membrane potential and cell death rate were detected by flow cytometry. We found that H2O2 exposure caused increasing rate of cell death and induced an elevated expression of P-gp as well as NF-kappa B activation and nucleus translocation in D407 cells. Inhibiting or silencing NF-kappa B led to a decrease in the oxidative-induced expression of P-gp. Down-regulation of P-gp by siRNA transfection further impaired the mitochondrial membrane potential and cell death rate in oxidative cells. Moreover, inhibition/knockdown of NF-kappa B decreased the high rate of cell death caused by H2O2. In conclusion, P-gp can provide moderate cyto-protection for the human RPE cells by ameliorating the mitochondrial dysfunction and NF-kappa B activation may be a potential regulator of P-gp expression response to oxidative stress.
C1 [Feng, Qiting; Yang, Weizhong; Gao, Zongyin; Zhang, Yuehong] South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Ophthalmol,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.
   [Ruan, Xiangcai] South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Anesthesia,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.
   [Ruan, Xiangcai] South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Pain Med,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.
C3 Guangzhou Medical University; South China University of Technology;
   Guangzhou Medical University; South China University of Technology;
   Guangzhou Medical University; South China University of Technology
RP Zhang, YH (通讯作者)，South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Ophthalmol,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.; Ruan, XC (通讯作者)，South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Anesthesia,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.; Ruan, XC (通讯作者)，South China Univ Technol, Affiliated Hosp 2, Guangzhou Med Univ, Dept Pain Med,Guangzhou Peoples Hosp 1, Guangzhou 510080, Guangdong, Peoples R China.
EM xc_ruan@hotmail.com; carmenzhangyh@163.com
FU Natural Science Foundation of China [81200709, 81271196]; Guangzhou
   Commission on Technology and Innovation [201607010119]
FX This project was partially supported by the Natural Science Foundation
   of China (grants 81200709 and 81271196), and Guangzhou Commission on
   Technology and Innovation (grant 201607010119).
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NR 26
TC 10
Z9 10
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2019
VL 181
BP 367
EP 373
DI 10.1016/j.exer.2018.11.024
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HT5TJ
UT WOS:000464625900043
PM 30496729
DA 2022-11-30
ER

PT J
AU Abdianwall, MH
   Dogan, BG
AF Abdianwall, Mohammad Haris
   Dogan, Bahar Guciz
TI Prevalence of visual impairment and related factors in Nangarhar
   Province of Afghanistan: a cross sectional study
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE prevalence; visual impairment; blindness; Afghanistan
ID AGE-RELATED MACULOPATHY; ULTRAVIOLET-RADIATION; RISK-FACTORS; SYSTEMIC
   HYPERTENSION; EYE DISEASES; BLINDNESS; POPULATION; EXPOSURE; CHINESE;
   ADULTS
AB AIM: To determine the prevalence, main causes, and related factors of visual impairment (VI) among people aged 50y and over in Jalalabad City and four surrounding districts of Nangarhar Province of Afghanistan.
   METHODS: The data for the population based cross-sectional study was collected in 2015. The calculated sample size was 1353, allocated to urban-rural strata using probability proportion to size method. At the end of the study, 1281 people participated in to the study. VI was defined as presenting visual acuity (VA) of less than 6/18 and blindness as VA less than 3/60 in the better eye by using Snellen chart only. Data was analyzed using IBM SPSS 21.0 software.
   RESULTS: The prevalence of VI was 22.6% (95%Cl, 20%-25%) of which 13.9% (95%Cl, 12%-16%) was low vision and 8.7% (95%Cl, 7%-10%) was blindness. The most common causes of the VI were cataract (52.8%), followed by uncorrected refractive error (URE) (26.9%) and glaucoma (8.6%). Number one cause of the low vision was URE (42%), followed by cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), while for blindness they are cataract (72%), other posterior segment disorders, glaucoma, URE and AMD. Illiteracy, bad economic status, hypertension and overweight were factors independently associated with both VI and low vision, whereas, age, illiteracy, bad economic status, hypertension and using of sunglasses were independently associated with blindness.
   CONCLUSION: Cataract, URE, glaucoma, AMD and DR are the leading causes of VI and blindness in the study area. They are mostly avoidable. In order to decrease the burden of VI and blindness in the study area as well as the whole country, it is strongly recommended to apply the prevention policies of VI and blindness.
C1 [Abdianwall, Mohammad Haris] Nangarhar Univ, Dept Ophthalmol, Fac Med, GPO 2601, Jalalabad, Afghanistan.
   [Dogan, Bahar Guciz] Hacettepe Univ, Dept Publ Hlth, Fac Med, TR-06100 Ankara, Turkey.
C3 Hacettepe University
RP Abdianwall, MH (通讯作者)，Nangarhar Univ, Dept Ophthalmol, Fac Med, GPO 2601, Jalalabad, Afghanistan.
EM haris_abdianwall@yahoo.com.tr
RI Dogan, Bahar/ABC-2838-2020
OI Abdianwall, Mohammad Haris/0000-0002-1180-099X
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NR 63
TC 9
Z9 9
U1 0
U2 2
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD DEC 18
PY 2018
VL 11
IS 12
BP 1968
EP 1977
DI 10.18240/ijo.2018.12.16
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HD8SU
UT WOS:000452830000016
PM 30588432
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Smit-McBride, ZS
   Nguyen, J
   Elliott, GW
   Wang, Z
   McBride, RA
   Nguyen, AT
   Oltjen, SL
   Yin, G
   Thomasy, SM
   Pinkerton, KE
   Lee, ES
   Cunefare, D
   Farsiu, S
   Morse, LS
AF Smit-McBride, Zeljka
   Nguyen, Johnny
   Elliott, Garrett W.
   Wang, Zhe
   McBride, Ryan A.
   Nguyen, Anthony T.
   Oltjen, Sharon L.
   Yin, Glenn
   Thomasy, Sara M.
   Pinkerton, Kent E.
   Lee, Eugene S.
   Cunefare, David
   Farsiu, Sina
   Morse, Lawrence S.
TI Effects of aging and environmental tobacco smoke exposure on ocular and
   plasma circulatory microRNAs in the Rhesus macaque
SO MOLECULAR VISION
LA English
DT Article
ID NONHUMAN PRIMATE MODEL; NERVE-FIBER LAYER; CIGARETTE-SMOKING; POTENTIAL
   BIOMARKERS; MACULAR DEGENERATION; OXIDATIVE STRESS; IMMUNE-RESPONSE;
   CELLS; RISK; INTERLEUKIN-17A
AB Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD).
   Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA).
   Results: The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >+/- 1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages.
   Conclusions: ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.
C1 [Smit-McBride, Zeljka; Nguyen, Johnny; Elliott, Garrett W.; Nguyen, Anthony T.; Oltjen, Sharon L.; Yin, Glenn; Thomasy, Sara M.; Morse, Lawrence S.] Univ Calif Davis, Sch Med, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
   [Wang, Zhe] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA.
   [McBride, Ryan A.] Univ Calif Davis, Sch Med, Dept Cell Biol & Human Anat, Davis, CA 95616 USA.
   [Thomasy, Sara M.] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA.
   [Pinkerton, Kent E.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
   [Pinkerton, Kent E.] Univ Calif Davis, CHE, Davis, CA 95616 USA.
   [Lee, Eugene S.] Sacramento VA Med Ctr, Mather, CA USA.
   [Cunefare, David; Farsiu, Sina] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
   [Farsiu, Sina] Duke Univ, Dept Ophthalmol, Durham, NC USA.
C3 University of California System; University of California Davis;
   University of California System; University of California Davis;
   University of California System; University of California Davis;
   University of California System; University of California Davis;
   University of California System; University of California Davis;
   University of California System; University of California Davis; Duke
   University; Duke University
RP Smit-McBride, ZS (通讯作者)，Univ Calif Davis, Vitreoretinal Res Lab, Sch Med, Dept Ophthalmol & Vis Sci, One Shields Ave,Tupper Hall 2403, Davis, CA 95616 USA.
EM zsmcbride@ucdavis.edu
RI Lee, Eugene S/AAN-6188-2020
OI Lee, Eugene S/0000-0001-5153-1109; Yiu, Glenn/0000-0003-3061-3310
FU Barr Family Retina Research Foundation; Environmental Health Center
   National Institute of Environmental Health Sciences [P30ES023513]; NIH
   [P30EY005722]; NEI Eye Core grant [P30 EY012576]; CNPRC NIH
   [P51OD011107]; NATIONAL EYE INSTITUTE [P30EY005722, K08EY026101,
   P30EY012576] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   ENVIRONMENTAL HEALTH SCIENCES [P30ES023513] Funding Source: NIH
   RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
   [P51OD011107] Funding Source: NIH RePORTER
FX The authors are grateful to the CNPRC, the UC Davis Inhalation Exposure
   Core operators Louise Olsen, Chris Royer and Ross Allen, Dale Uyeminami
   from Environmental Health Center for nicotine exposure calculations,
   Kevin NH Nguyen for assisting with OCT scan readings, and Dr. Philip H.
   Kass, Professor Population Health & Reproduction, UC Davis, for
   mentoring ZW in statistical analysis. This project was funded by Barr
   Family Retina Research Foundation generous gift to the UC Davis
   Department of Ophthalmology (LSM, ZSM) and a pilot grant from the
   Environmental Health Center National Institute of Environmental Health
   Sciences P30ES023513 (ZSM) and NIH P30EY005722 (SF). The NEI Eye Core
   grant P30 EY012576 provided support for the tissue fixation, paraffin
   embedding and H&E staining. The CNPRC NIH P51OD011107 grant provided
   support for the colony and infrastructure, including the cores. The
   Affymetrix microRNA TitanChips 4.0 were processed through genomics
   services offered at the Institute for Human Genetics at UCSF.
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NR 51
TC 12
Z9 12
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD SEP 24
PY 2018
VL 24
BP 633
EP 646
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA GU7IB
UT WOS:000445493400002
PM 30294202
DA 2022-11-30
ER

PT J
AU Martin, DF
AF Martin, Daniel F.
TI Evolution of Intravitreal Therapy for Retinal Diseases-From CMV to CNV:
   The LXXIV Edward Jackson Memorial Lecture
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; IMMUNODEFICIENCY-VIRUS-INFECTION;
   FLUOCINOLONE ACETONIDE IMPLANT; VEGFR2 GENE POLYMORPHISMS; CD4 CELL
   COUNTS; MACULAR DEGENERATION; CYTOMEGALOVIRUS RETINITIS;
   SUSTAINED-RELEASE; CONTROLLED-TRIAL; INTRAOCULAR INJECTION
AB PURPOSE: To present the evolution of intravitreal therapy for retinal diseases and its impact on clinical practice.
   DESIGN: Retrospective literature review and personal perspective.
   METHODS: Retrospective literature review and personal perspective.
   RESULTS: Pharmacotherapeutic advances in retinal disease have been remarkable over the last 25 years. Almost all of the new drugs developed have required intravitreal administration to be highly effective, leading to an exponential increase in the annual number of intravitreal injections given. The use of intravitreal antibiotic injections to treat endophthalmitis, usually on a one-time basis, first familiarized ophthalmologists with this method of drug delivery. Ganciclovir was the first widely available, relatively inexpensive compounded drug that was used for repeat intravitreal injection to treat a chronic retinal disease, followed by triamcinolone for diabetic macular edema and bevacizumab for neovascular age-related macular degeneration. Ganciclovir was formulated for sustained-release drug delivery to avoid frequent intravitreal injections, a goal that has been more elusive for anti-VEGF drugs. Political obstacles encountered while conducting some of the trials to evaluate these treatments were substantial. Addressing the issues they raised led to important national policy changes that will impact the conduct of future clinical trials. The first comparative efficacy trial of intravitreal therapies was the Comparison of AMD Treatments Trials (CATT). The primary results from CATT and the many publications that followed continue to shape the use of intravitreal therapy today.
   CONCLUSION: Intravitreal therapy has proven highly effective for the treatment of many retinal diseases. The treatment burden for patients from numerous injections, the cost to health care systems, and the impact on work-flows in clinical practice have been substantial. Efforts to develop effective intravitreal therapies with reduced treatment burden and cost are ongoing. (C) 2018 Elsevier Inc. All rights reserved.
C1 [Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,Suite i30, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation
RP Martin, DF (通讯作者)，Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,Suite i30, Cleveland, OH 44195 USA.
EM martind5@ccf.org
FU National Eye Institute, National Institutes of Health, Department of
   Health and Human Services [U10EY017828, U10EY023530]; NATIONAL EYE
   INSTITUTE [U10EY023530, U10EY017828] Funding Source: NIH RePORTER
FX THIS WORK WAS SUPPORTED IN PART BY COOPERATIVE AGREEMENTS (U10EY017828
   AND U10EY023530) from the National Eye Institute, National Institutes of
   Health, Department of Health and Human Services.
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NR 114
TC 22
Z9 22
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 JUL
PY 2018
VL 191
BP XLI
EP LVIII
DI 10.1016/j.ajo.2017.12.019
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GL7MX
UT WOS:000437387100005
PM 29339063
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bourne, RRA
   Jonas, JB
   Bron, AM
   Cicinelli, MV
   Das, A
   Flaxman, SR
   Friedman, DS
   Keeffe, JE
   Kempen, JH
   Leasher, J
   Limburg, H
   Naidoo, K
   Pesudovs, K
   Peto, T
   Saadine, J
   Silvester, AJ
   Tahhan, N
   Taylor, HR
   Varma, R
   Wong, TY
   Resnikoff, S
AF Bourne, Rupert R. A.
   Jonas, Jost B.
   Bron, Alain M.
   Cicinelli, Maria Vittoria
   Das, Aditi
   Flaxman, Seth R.
   Friedman, David S.
   Keeffe, Jill E.
   Kempen, John H.
   Leasher, Janet
   Limburg, Hans
   Naidoo, Kovin
   Pesudovs, Konrad
   Peto, Tunde
   Saadine, Jinan
   Silvester, Alexander J.
   Tahhan, Nina
   Taylor, Hugh R.
   Varma, Rohit
   Wong, Tien Y.
   Resnikoff, Serge
CA Vision Loss Expert Grp Global Burd
TI Prevalence and causes of vision loss in high-income countries and in
   Eastern and Central Europe in 2015: magnitude, temporal trends and
   projections
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; VISUAL IMPAIRMENT; GLOBAL PREVALENCE; BLINDNESS;
   RANIBIZUMAB; DISTANCE; BURDEN
AB Background Within a surveillance of the prevalence and causes of vision impairment in high-income regions and Central/Eastern Europe, we update figures through 2015 and forecast expected values in 2020.
   Methods Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment and presbyopia was estimated for 1990, 2010, 2015, and 2020.
   Results Age-standardised prevalence of blindness and MSVI for all ages decreased from 1990 to 2015 from 0.26% (0.10-0.46) to 0.15% (0.06-0.26) and from 1.74% (0.76-2.94) to 1.27% (0.55-2.17), respectively. In 2015, the number of individuals affected by blindness, MSVI and mild vision impairment ranged from 70 000, 630 000 and 610 000, respectively, in Australasia to 980 000, 7.46 million and 7.25 million, respectively, in North America and 1.16 million, 9.61 million and 9.47 million, respectively, in Western Europe. In 2015, cataract was the most common cause for blindness, followed by age-related macular degeneration (AMD), glaucoma, uncorrected refractive error, diabetic retinopathy and cornea-related disorders, with declining burden from cataract and AMD over time. Uncorrected refractive error was the leading cause of MSVI.
   Conclusions While continuing to advance control of cataract and AMD as the leading causes of blindness remains a high priority, overcoming barriers to uptake of refractive error services would address approximately half of the MSVI burden. New data on burden of presbyopia identify this entity as an important public health problem in this population. Additional research on better treatments, better implementation with existing tools and ongoing surveillance of the problem is needed.
C1 [Bourne, Rupert R. A.] Anglia Ruskin Univ, Vis & Eye Res Unit, Cambridge, England.
   [Jonas, Jost B.] Univ Med, Dept Ophthalmol, Mannheim, Germany.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Mannheim, Germany.
   [Bron, Alain M.] Ctr Sci Gout & Alimentat, UMR1324, INRA, Dijon, France.
   [Bron, Alain M.] Ctr Sci Gout & Alimentat, UMR6265, CNRS, Dijon, France.
   [Bron, Alain M.] Univ Bourgogne Franche Comte, Ctr Sci Gout & Alimentat, Dijon, France.
   [Bron, Alain M.] Dijon Univ Hosp, Ophthalmol Dept, Dijon, France.
   [Cicinelli, Maria Vittoria] Ist Sci San Raffaele, Milan, Italy.
   [Das, Aditi] Hlth Educ Yorkshire & Humber, Leeds, W Yorkshire, England.
   [Flaxman, Seth R.] Imperial Coll London, Dept Math & Data Sci Inst, London, England.
   [Flaxman, Seth R.] Univ Oxford, Dept Stat, Oxford, England.
   [Friedman, David S.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21205 USA.
   [Keeffe, Jill E.] LV Prasad Eye Inst, Hyderabad, Andhra Prades, India.
   [Kempen, John H.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
   [Kempen, John H.] Discovery Eye Ctr, Addis Ababa, Ethiopia.
   [Kempen, John H.] Myungsung Christian Med Ctr & Med Sch, Addis Ababa, Ethiopia.
   [Leasher, Janet] Nova Southeastern Univ, Davie, FL USA.
   [Limburg, Hans] Hlth Informat Serv, Grootebroek, Netherlands.
   [Naidoo, Kovin] Univ Kwazulu Natal, African Visi Res Inst, Brien Holden Vis Inst, Durban, South Africa.
   [Pesudovs, Konrad] Flinders Univ S Australia, NHMRC Ctr Clin Eye Res, Adelaide, SA, Australia.
   [Peto, Tunde] Queens Univ Belfast, Sch Med, Dent & Biomed Sci, Belfast, Antrim, North Ireland.
   [Saadine, Jinan] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Silvester, Alexander J.] Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England.
   [Tahhan, Nina; Resnikoff, Serge] Brien Holden Vis Inst, Sydney, NSW, Australia.
   [Tahhan, Nina; Resnikoff, Serge] Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia.
   [Taylor, Hugh R.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia.
   [Varma, Rohit] Keck Sch Med USC, Dept Ophthalmol, Los Angeles, CA USA.
   [Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Duke NUS Grad Med Sch, Singapore, Singapore.
C3 Anglia Ruskin University; Ruprecht Karls University Heidelberg; Ruprecht
   Karls University Heidelberg; INRAE; Institut Agro; AgroSup Dijon; Centre
   National de la Recherche Scientifique (CNRS); Universite de Bourgogne;
   Centre National de la Recherche Scientifique (CNRS); CNRS - National
   Institute for Biology (INSB); Institut Agro; AgroSup Dijon; Universite
   de Bourgogne; Institut Agro; AgroSup Dijon; Centre National de la
   Recherche Scientifique (CNRS); Universite de Bourgogne; CHU Dijon
   Bourgogne; Vita-Salute San Raffaele University; IRCCS Ospedale San
   Raffaele; Imperial College London; University of Oxford; Johns Hopkins
   University; Johns Hopkins Medicine; L. V. Prasad Eye Institute; Harvard
   University; Massachusetts Eye & Ear Infirmary; Nova Southeastern
   University; University of Kwazulu Natal; Flinders University South
   Australia; Queens University Belfast; Centers for Disease Control &
   Prevention - USA; Royal Liverpool & Broadgreen University Hospitals NHS
   Trust; Royal Liverpool University Hospital; University of Liverpool;
   Brien Holden Vision Institute; University of New South Wales Sydney;
   University of Melbourne; National University of Singapore; Singapore
   National Eye Center
RP Bourne, RRA (通讯作者)，Anglia Ruskin Univ, Sch Med, Visi & Eye Res Unit, Cambridge CB1 1PT, England.
EM rb@rupertbourne.co.uk
RI Peto, Tunde/G-8812-2018; Resnikoff, Serge/N-2355-2019; Wong, Tien
   Yin/AAC-9724-2020; Naidoo, Kovin Shunmugam/AAF-5914-2020; cicinelli,
   maria vittoria/M-1611-2019; Bron, Alain/AAP-8010-2020; Pesudovs,
   Konrad/T-9403-2019; Tejedor, Jaime/G-7728-2015; Leasher,
   Janet/B-8889-2016
OI Peto, Tunde/0000-0001-6265-0381; Resnikoff, Serge/0000-0002-5866-4446;
   Wong, Tien Yin/0000-0002-8448-1264; cicinelli, maria
   vittoria/0000-0003-2938-0409; Bron, Alain/0000-0002-7265-931X; Pesudovs,
   Konrad/0000-0002-6322-9369; Leasher, Janet/0000-0002-8779-5162;
   Friedman, David/0000-0002-2055-5797; Tejedor Fraile,
   Jaime/0000-0001-5507-5622; Jonas, Jost/0000-0003-2972-5227; Battaglia
   Parodi, Maurizio/0000-0002-0385-7961; Kempen, John/0000-0002-2967-4792
FU Brien Holden Vision Institute
FX This study was funded by the Brien Holden Vision Institute. The results
   in this paper are prepared independently of the final estimates of the
   Global Burden of Diseases, Injuries and Risk Factors study.
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TC 148
Z9 148
U1 1
U2 22
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 2018
VL 102
IS 5
BP 575
EP 585
DI 10.1136/bjophthalmol-2017-311258
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GD3YN
UT WOS:000430439800001
PM 29545417
OA Green Published, Green Submitted, Green Accepted, hybrid
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Natoli, R
   Fernando, N
   Dahlenburg, T
   Jiao, HH
   Aggio-Bruce, R
   Barnett, NL
   de la Barca, JMC
   Tcherkez, G
   Reynier, P
   Fang, J
   Chu-Tan, JA
   Valter, K
   Provis, J
   Rutar, M
AF Natoli, Riccardo
   Fernando, Nilisha
   Dahlenburg, Tess
   Jiao, Haihan
   Aggio-Bruce, Riemke
   Barnett, Nigel L.
   de la Barca, Juan Manuel Chao
   Tcherkez, Guillaume
   Reynier, Pascal
   Fang, Johnny
   Chu-Tan, Joshua A.
   Valter, Krisztina
   Provis, Jan
   Rutar, Matt
TI Obesity-induced metabolic disturbance drives oxidative stress and
   complement activation in the retinal environment
SO MOLECULAR VISION
LA English
DT Article
ID AGE-RELATED MACULOPATHY; LEPTIN-DEFICIENT OB/OB; BODY-MASS INDEX;
   MACULAR DEGENERATION; PHOTORECEPTOR DEGENERATION; MICROGLIAL ACTIVATION;
   DIABETIC-NEUROPATHY; RISK-FACTORS; MICE; INFLAMMATION
AB Purpose: Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between obesity and retinal inflammation has yet to be assessed. We used the leptin-deficient (ob/ob) mouse to further our understanding of the contribution of obesity to retinal oxidative stress and inflammation.
   Methods: Retinas from ob/ob mice were compared to age-matched wild-type controls for retinal function (electroretinography) and gene expression analysis of retinal stress (Gfap), oxidative stress (Gpx3 and Hmox1), and complement activation (C3, C2, Cfb, and Cfh). Oxidative stress was further quantified using a reactive oxygen species and reactive nitrogen species (ROS and RNS) assay. Retinal microglia and macrophage migration to the outer retina and complement activation were determined using immunohistochemistry for IBA1 and C3, respectively. Retinas and sera were used for metabolomic analysis using QTRAP mass spectrometry.
   Results: Retinal function was reduced in ob/ob mice, which correlated to changes in markers of retinal stress, oxidative stress, and inflammation. An increase in C3-expressing microglia and macrophages was detected in the outer retinas of the ob/ob mice, while gene expression studies showed increases in the complement activators (C2 and Cfb) and a decrease in a complement regulator (Cfh). The expression of several metabolites were altered in the ob/ob mice compared to the controls, with changes in polyunsaturated fatty acids (PUFAs) and branched-chain amino acids (BCAAs) detected.
   Conclusions: The results of this study indicate that oxidative stress, inflammation, complement activation, and lipid metabolites in the retinal environment are linked with obesity in ob/ob animals. Understanding the interplay between these components in the retina in obesity will help inform risk factor analysis for acquired retinal degenerations, including AMD.
C1 [Natoli, Riccardo; Fernando, Nilisha; Dahlenburg, Tess; Jiao, Haihan; Aggio-Bruce, Riemke; de la Barca, Juan Manuel Chao; Chu-Tan, Joshua A.; Valter, Krisztina; Provis, Jan; Rutar, Matt] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.
   [Natoli, Riccardo; Fang, Johnny; Valter, Krisztina; Provis, Jan] Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
   [Barnett, Nigel L.] Queensland Eye Inst, South Brisbane, Qld, Australia.
   [Barnett, Nigel L.] Univ Queensland, UQ Ctr Clin Res, Herston, Qld, Australia.
   [Barnett, Nigel L.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia.
   [Tcherkez, Guillaume] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia.
   [Reynier, Pascal] Univ Angers, PREMMi Pole Rech Enseignement & Med Mitochondrial, INSERM, Inst MITOVASC,CNRS 6214,U1083, F-49933 Angers, France.
   [Reynier, Pascal] Ctr Hosp Univ, Dept Biochim & Genet, F-49933 Angers, France.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Queensland Eye Institute; University of
   Queensland; Queensland University of Technology (QUT); Australian
   National University; Centre National de la Recherche Scientifique
   (CNRS); Institut National de la Sante et de la Recherche Medicale
   (Inserm); Universite d'Angers; Universite d'Angers; Centre Hospitalier
   Universitaire d'Angers
RP Natoli, R (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.
EM riccardo.natoli@anu.edu.au
RI Tcherkez, Guillaume/L-1300-2015; Chu-Tan, Joshua A/A-9728-2019; Valter,
   Krisztina/L-3015-2016; Barnett, Nigel L/F-1226-2010; Aggio-Bruce,
   Riemke/AAX-4522-2020
OI Barnett, Nigel L/0000-0002-0704-2233; Aggio-Bruce,
   Riemke/0000-0003-3086-2739; Reynier, Pascal/0000-0003-0802-4608;
   Fernando, Nilisha/0000-0002-8488-1348; Chu-Tan,
   Joshua/0000-0001-7936-8972; Valter, Krisztina/0000-0002-2033-0408; Jiao,
   Haihan/0000-0002-5404-9307; Rutar, Matthew/0000-0002-8893-5120; Natoli,
   Riccardo/0000-0002-9350-0439
FU Australian Government Research Training Program (RTP) Scholarship
FX This study was supported by an Australian Government Research Training
   Program (RTP) Scholarship.
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NR 66
TC 14
Z9 14
U1 0
U2 7
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 7
PY 2018
VL 24
BP 201
EP 217
PG 17
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA FY7XU
UT WOS:000427077800001
PM 29527116
DA 2022-11-30
ER

PT J
AU Ragauskas, S
   Kielczewski, E
   Vance, J
   Kaja, S
   Kalesnykas, G
AF Ragauskas, Symantas
   Kielczewski, Eva
   Vance, Joseph
   Kaja, Simon
   Kalesnykas, Giedrius
TI In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal
   Neovascularization Model
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neurobiology; Issue 131; Laser-induced choroidal neovascularization;
   mouse CNV; age-related macular degeneration; angiogenesis; in vivo
   imaging; optical coherence tomography; SD-OCT
ID MICE
AB Laser-induced choroidal neovascularization (CNV) is a well-established model to mimic the wet form of age-related macular degeneration (AMD). In this protocol, we aim to guide the reader not simply through the technical considerations of generating laser-induced lesions to trigger neovascular processes, but rather focus on the powerful information that can be obtained from multimodal longitudinal in vivo imaging throughout the follow-up period.
   The laser-induced mouse CNV model was generated by a diode laser administration. Multimodal in vivo imaging techniques were used to monitor CNV induction, progression and regression. First, spectral domain optical coherence tomography (SD-OCT) was performed immediately after the lasering to verify a break of Bruch's membrane. Subsequent in vivo imaging using fluorescein angiography (FA) confirmed successful damage of Bruch's membrane from serial images acquired at the choroidal level. Longitudinal follow-up of CNV proliferation and regression on days 5, 10, and 14 after the lasering was performed using both SD-OCT and FA. Simple and reliable grading of leaky CNV leasions from FA images is presented. Automated segmentation for measurement of total retinal thickness, combined with manual caliber application for measurement of retinal thickness at CNV sites, allow unbiased evaluation of the presence of edema. Finally, histological verification of CNV is performed using isolectin GS-IB4 staining on choroidal flatmounts. The staining is thresholded, and the isolectin-positive area is calculated with ImageJ.
   This protocol is especially useful in therapeutics studies requiring high-throughput-like screening of CNV pathology as it allows fast, multimodal, and reliable classification of CNV pathology and retinal edema. In addition, high resolution SD-OCT enables the recording of other pathological hallmarks, such as the accumulation of subretinal or intraretinal fluid. However, this method does not provide a possibility to automate CNV volume analysis from SD-OCT images, which has to be performed manually.
C1 [Ragauskas, Symantas; Kaja, Simon; Kalesnykas, Giedrius] Experimentica Ltd, Kuopio, Finland.
   [Kielczewski, Eva; Vance, Joseph] Leica Microsyst, Wetzlar, Germany.
   [Vance, Joseph] Spective LLC, Durham, NC USA.
   [Kaja, Simon] Loyola Univ Chicago, Stritch Sch Med, Dept Ophthalmol, Chicago, IL USA.
C3 Loyola University Chicago
RP Kalesnykas, G (通讯作者)，Experimentica Ltd, Kuopio, Finland.
EM giedrius.kalesnykas@experimentica.com
RI Kalesnykas, Giedrius/AAG-4084-2021
FU Dr. John P. and Therese E. Mulcahy Endowed Professorship in
   Ophthalmology at Loyola University Chicago.
FX The authors would like to thank Yuliya Naumchuk (Loyola University
   Chicago) and Agne Ziniauskaite. (Experimentica Ltd.) for excellent
   technical and videographic support. Dr. Kaja's research program is
   supported by the Dr. John P. and Therese E. Mulcahy Endowed
   Professorship in Ophthalmology at Loyola University Chicago.
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NR 10
TC 0
Z9 0
U1 1
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 JAN
PY 2018
IS 131
AR e56173
DI 10.3791/56173
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FX5CM
UT WOS:000426095700019
PM 29443029
OA Green Published
DA 2022-11-30
ER

PT J
AU Nguyen, AM
   Arora, KS
   Swenor, BK
   Friedman, DS
   Ramulu, PY
AF Nguyen, Angeline M.
   Arora, Karun S.
   Swenor, Bonnielin K.
   Friedman, David S.
   Ramulu, Pradeep Y.
TI Physical activity restriction in age-related eye disease: a
   cross-sectional study exploring fear of falling as a potential mediator
SO BMC GERIATRICS
LA English
DT Article
DE Glaucoma; Age-related macular degeneration; Fear of falling; Physical
   activity
ID VISUAL-FIELD LOSS; DWELLING OLDER-ADULTS; UNITED-STATES; MACULAR
   DEGENERATION; MOBILITY PERFORMANCE; BALANCE CONFIDENCE; RISK-FACTORS;
   VISION LOSS; COMMUNITY; ACCELEROMETER
AB Background: Fear of falling (FoF) is predictive of decreased physical activity. This study sought to determine if FoF mediates the relationship between decreased vision and physical activity restriction in individuals with glaucoma and age-related macular degeneration (AMD).
   Methods: Accelerometers were used to measure physical activity over 1 week in 59 control, 83 glaucoma, and 58 AMD subjects. Subjects completed the University of Illinois at Chicago Fear of Falling Questionnaire, and the extent of FoF was estimated using Rasch analysis. In negative binomial models adjusting for demographic, health, and social factors, FoF was investigated as a potential mediator between the severity of visual field (VF) loss (in glaucoma patients) or the severity of contrast sensitivity (CS) loss (in AMD patients) and decreased engagement in physical activity, defined as minutes spent in moderate-to-vigorous physical activity (MVPA) per day.
   Results: In multivariate negative binomial regression models, 5-decibels worse VF mean deviation was associated with 26 % less engagement in MVPA [rate ratio (RR) = 0.74, p < 0.01] amongst glaucoma subjects. When FoF was added to the model, the RR increased from 0.74 to 0.78, and VF loss severity remained associated with less MVPA at a statistically significant level (p < 0.01). Likewise, 0.1 log units worse CS was associated with 11 % less daily MVPA (RR = 0.89, p < 0.01) amongst AMD subjects. When FoF was added to the model, the RR increased from 0.89 to 1.02, and CS loss was no longer associated with MVPA at a statistically significant level (p = 0.53).
   Conclusions: FoF may mediate the relationship between vision loss and physical activity restriction amongst patients with AMD. Future work should determine optimal strategies for reducing FoF in individuals with vision loss in order to prevent the deleterious effects of physical activity restriction.
C1 [Nguyen, Angeline M.; Arora, Karun S.; Swenor, Bonnielin K.; Friedman, David S.; Ramulu, Pradeep Y.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Swenor, Bonnielin K.; Friedman, David S.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Swenor, Bonnielin K.; Friedman, David S.; Ramulu, Pradeep Y.] Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins Bloomberg School of Public Health; Johns
   Hopkins University; Johns Hopkins Medicine
RP Ramulu, PY (通讯作者)，Johns Hopkins Univ, Wilmer Eye Inst, 600 North Wolfe St,Maumenee B-110, Baltimore, MD 21287 USA.
EM pramulu@jhmi.edu
RI Swenor, Bonnie/ABH-1542-2021
OI Swenor, Bonnie/0000-0002-6044-0951; Friedman, David/0000-0002-2055-5797
FU Dennis W. Jahnigen Memorial Award, NIH [EY018595, EY022976]; Research to
   Prevent Blindness Robert and Helen Schaub Special Scholar Award;
   NATIONAL EYE INSTITUTE [R01EY022976, K23EY018595] Funding Source: NIH
   RePORTER
FX This research was supported in part by the Dennis W. Jahnigen Memorial
   Award, NIH Grants EY018595 and EY022976, and the Research to Prevent
   Blindness Robert and Helen Schaub Special Scholar Award. All funding
   organizations had no role in the design or conduct of this research. 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 66
TC 31
Z9 31
U1 0
U2 10
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2318
J9 BMC GERIATR
JI BMC Geriatr.
PD JUN 12
PY 2015
VL 15
AR 64
DI 10.1186/s12877-015-0062-8
PG 10
WC Geriatrics & Gerontology; Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA CK0OT
UT WOS:000355905200001
PM 26062727
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kawada, H
   Blessing, K
   Kiyota, T
   Woolman, T
   Winchester, L
   Kador, PF
AF Kawada, Hiroyoshi
   Blessing, Karen
   Kiyota, Tomomi
   Woolman, Theodor
   Winchester, Lee
   Kador, Peter F.
TI Effects of Multifunctional Antioxidants on Mitochondrial Dysfunction and
   Amyloid-beta Metal Dyshomeostasis
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Age-related macular degeneration; Alzheimer's disease; amyloid-beta;
   clioquinol; JAX transgenic Alzheimer mouse; mitochondrial dysfunction;
   multifunctional antioxidants
ID TARGETING A-BETA; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MANGANESE
   NEUROTOXICITY; MODIFYING THERAPY; FLUORESCENT-PROBE; TRANSGENIC MICE;
   ZINC; PEPTIDE; DEGRADATION
AB Background: Redox-active metal dyshomeostasis and oxidative stress are associated with mitochondrial dysfunction and amyloid-beta (A beta) neurotoxicity that are linked to both the development of age-related macular degeneration (AMD) and Alzheimer's disease (AD). As potential therapeutic agents, orally active multifunctional antioxidants (MFAOs) possessing two independent functional groups capable of binding redox-active metals and scavenging free radicals have been synthesized.
   Objective: To determine whether MFAOs affect mitochondrial function and reduce the presence of A beta plaque formation.
   Methods: The MFAOs were evaluated in cultured SH-SY5Y cells and ARPE-19 cells. MFAO effects on mitochondrial function were investigated using rhodamine 123 staining after 2 hour exposure to MnCl2. MFAO effects on A beta : Zn complex formation were evaluated with Zinquin staining and the ability of the A beta : Zn complex to be degraded by matrix metalloproteinase-2 (MMP-2). The ability of MFAOs to reduce A beta plaque in the brain was determined by orally feeding MFAO for one year to B6; 129-Psen1tm1Mpm Tg(A beta PPSwe, tauP301L) 1Lfa/ Mmjax transgenic mice. A beta levels were determined by ELISA.
   Results: MFAOs neither adversely affected mitochondrial signaling nor labile cytoplasmic zinc levels. MFAOs protected cells against Mn2+-induced mitochondrial dysfunction. MFAOs also removed zinc from the A beta : Zn complex so that A beta plaque could be degraded by MMP-2. Zinquin staining indicated that the removed zinc was present in the cytoplasm as labile zinc. Orally administered MFAOs reduced the brain levels of both A beta(40) and A beta(42) isoforms of A beta.
   Conclusion: These studies demonstrate that these MFAOs have metal attenuating properties with therapeutic potential in the treatment of both AMD and AD.
C1 [Kawada, Hiroyoshi; Blessing, Karen; Woolman, Theodor; Winchester, Lee; Kador, Peter F.] Univ Nebraska Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE USA.
   [Kiyota, Tomomi] Univ Nebraska Med Ctr, Coll Med, Dept Pharmacol & Expt Neurosci, Omaha, NE USA.
   [Kador, Peter F.] Univ Nebraska Med Ctr, Coll Med, Dept Ophthalmol, Omaha, NE USA.
C3 University of Nebraska System; University of Nebraska Medical Center;
   University of Nebraska System; University of Nebraska Medical Center;
   University of Nebraska System; University of Nebraska Medical Center
RP Kador, PF (通讯作者)，Coll Pharm, 986025 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM pkador@unmc.edu
RI Winchester, Lee/AAH-3497-2020
FU Therapeutic Vision Inc.; Alzheimer's Drug Discovery Foundation
FX The synthesis of these MFAOs was supported by Therapeutic Vision Inc.
   while the present biological evaluation was supported by the Alzheimer's
   Drug Discovery Foundation.
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NR 49
TC 12
Z9 13
U1 3
U2 23
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 2015
VL 44
IS 1
BP 297
EP 307
DI 10.3233/JAD-132471
PG 11
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA AY3AQ
UT WOS:000347457400028
PM 25227315
DA 2022-11-30
ER

PT J
AU Aleman, TS
   Garrity, ST
   Brucker, AJ
AF Aleman, Tomas S.
   Garrity, Sean T.
   Brucker, Alexander J.
TI Retinal structure in vitamin A deficiency as explored with multimodal
   imaging
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Vitamin A; Optical coherence tomography; Photoreceptors; Rods; Retinoid
   cycle
ID SUBRETINAL DRUSENOID DEPOSITS; OUTER SEGMENT MATERIAL;
   FUNDUS-ALBIPUNCTATUS; MACULAR DEGENERATION; RHODOPSIN LEVELS; VISUAL
   FUNCTION; AUTOFLUORESCENCE; MUTATION; GENE; RDH5
AB To define the retinal structural abnormalities in a patient with vitamin A deficiency.
   The patient had a complete ophthalmic examination, electroretinography (ERG), short-wave fundus autofluorescence (SW-AF) and spectral domain optical coherence tomography (SD-OCT) imaging. Serum vitamin A levels were measured.
   A 63-year-old man with alcoholic cirrhosis, sclerosing cholangitis and chronic pancreatitis experienced blurred vision and nyctalopia for over a year. There was no family history of eye disorders or consanguinity. His best-corrected visual acuity was 20/20 in each eye; color vision as determined with Ishihara color plates was normal in each eye. Anterior segment examination was unremarkable. He was pseudophakic in both eyes. Standard ERGs showed non-detectable rod function, a cone-mediated dark-adapted response to the standard flash and borderline reduced cone function. Serum vitamin A levels were below 0.06 mg/L (normal 0.3-1.2 mg/L). Fundus examination revealed numerous round yellow-white lesions along the superior arcade and nasal to the optic nerve in both eyes. These lesions were hypoautofluorescent on SW-AF. SD-OCT cross sections demonstrated that they were focal disruptions distal to the ellipsoid band of the photoreceptors with hyperreflective images bulging up the ellipsoid and region. The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. The retinal lesions remained unchanged.
   Imaging of this patient with nyctalopia and severe rod dysfunction suggests that the retinal white lesions known to occur in vitamin A deficiency localize to the photoreceptor layer, particularly the outer segment. On OCT, they are reminiscent of lesions observed in genetic diseases with retinoid cycle dysfunction and of drusenoid subretinal deposits, an abnormality commonly associated with age-related macular degeneration.
C1 [Aleman, Tomas S.; Garrity, Sean T.; Brucker, Alexander J.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine
RP Aleman, TS (通讯作者)，Univ Penn, Scheie Eye Inst, Dept Ophthalmol, 51 N 39th St, Philadelphia, PA 19104 USA.
EM aleman@mail.med.upenn.edu
FU Hope for Vision
FX We thank Alejandro J. Roman and Beth A. Serpentine for critical help.
   This work was supported by a grant from Hope for Vision.
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NR 34
TC 38
Z9 39
U1 0
U2 29
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0012-4486
EI 1573-2622
J9 DOC OPHTHALMOL
JI Doc. Ophthalmol.
PD DEC
PY 2013
VL 127
IS 3
BP 239
EP 243
DI 10.1007/s10633-013-9403-0
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 244KW
UT WOS:000326388200006
PM 23900584
DA 2022-11-30
ER

PT J
AU Pilotto, E
   Benetti, E
   Convento, E
   Guidolin, F
   Longhin, E
   Parrozzani, R
   Midena, E
AF Pilotto, Elisabetta
   Benetti, Elisa
   Convento, Enrica
   Guidolin, Francesca
   Longhin, Evelyn
   Parrozzani, Raffaele
   Midena, Edoardo
TI Microperimetry, fundus autofluorescence, and retinal layer changes in
   progressing geographic atrophy
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO ASSESSMENT; MULTIPLE-SCLEROSIS;
   DEGENERATION; SECONDARY
AB Objective: To analyze correlation among microperimetry, inner and outer retinal layers, and fundus autofluorescence (FAF) changes in eyes with progressing geographic atrophy (GA) secondary to age-related macular degeneration.
   Methods: Microperimetry, spectral-domain optical coherence tomography (SD-OCT), standard short-wavelength FAF (SW-FAF), and near-infrared-wavelength FAF (NIR-FAF) were performed for all patients at both baseline and follow-up visits. FAF pattern, integrity of photoreceptor inner segment/outer segment (IS/OS) junction, total retinal thickness (RT), inner retinal layers (IRL), and outer retinal layers (ORL) thickness changes of every microperimetry extrafoveal tested point were analyzed.
   Results: A total of 366 microperimetry tested points were analyzed (6 patients, 7 eyes). Mean retinal sensitivity significantly decreased (p = 0.0149), and the percentage of dense scotomas significantly increased (p = 0.0125). Mean RT and mean ORL thickness significantly decreased (both p < 0.0001). Mean IRL thickness significantly increased (p = 0.0001). The decrease of ORL thickness was inversely correlated to the IRL thinning (rho = -0.710). FAF pattern at baseline was correlated to RT and ORL thickness (both p < 0.0001) and was significantly correlated to the risk to evolve to dense scotoma during follow-up (p 0.0001 at SW-FAF, p < 0.0001 at NIR-FAF). Tested points showing at baseline the loss of photoreceptor IS/OS junction had a greater risk for evolving to dense scotoma compared with those with intact photoreceptor IS/OS junction (odds ratio 3.56, 95% CI 2.41-5.27).
   Conclusions: Retinal sensitivity changes are correlated to IRL and ORL thickness changes, and to photoreceptor IS/OS junction integrity. FAF patterns remain a relevant factor in predicting GA evolution. Microperimetry, SW-FAF and NIR-FAF, and SD-OCT should be combined to obtain adequate morphologic and functional prospective information.
C1 [Pilotto, Elisabetta; Benetti, Elisa; Convento, Enrica; Guidolin, Francesca; Midena, Edoardo] Univ Padua, Dept Ophthalmol, I-35128 Padua, Italy.
   [Longhin, Evelyn; 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, Dept Ophthalmol, Via Giustiniani 2, I-35128 Padua, Italy.
EM edoardo.midena@unipd.it
RI parrozzani, raffaele/K-2034-2016; Parrozzani, Raffaele/W-3341-2017;
   Midena, Edoardo/AAB-6010-2020
OI parrozzani, raffaele/0000-0003-0216-727X; Parrozzani,
   Raffaele/0000-0003-0216-727X; 
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NR 36
TC 39
Z9 38
U1 0
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 386
EP 393
DI 10.1016/j.jcjo.2013.03.022
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AA5OM
UT WOS:000331149300023
PM 24093185
DA 2022-11-30
ER

PT J
AU Nakao, S
   Zandi, S
   Kohno, R
   Sun, DW
   Nakama, T
   Ishikawa, K
   Yoshida, S
   Enaida, H
   Ishibashi, T
   Hafezi-Moghadam, A
AF Nakao, Shintaro
   Zandi, Souska
   Kohno, Ri-ichiro
   Sun, Dawei
   Nakama, Takahito
   Ishikawa, Keijiro
   Yoshida, Shigeo
   Enaida, Hiroshi
   Ishibashi, Tatsuro
   Hafezi-Moghadam, Ali
TI Lack of Lymphatics and Lymph Node-Mediated Immunity in Choroidal
   Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE macrophage; LYVE-1; VEGFR-3; VEGF-C; AMD; uveitis
ID GROWTH-FACTOR-C; MACULAR DEGENERATION; TUMOR-GROWTH; LYMPHANGIOGENESIS;
   MACROPHAGES; ANGIOGENESIS; INFILTRATION; CAPILLARIES; CELLS
AB PURPOSE. Inflammation and immune cells regulate choroidal neovascularization (CNV) and could become therapeutic targets in age-related macular degeneration (AMD). Lymphangiogenesis is a key component of various inflammatory diseases. Whether lymphangiogenesis and lymph node-mediated immunity are involved in the pathogenesis of AMD is not understood.
   METHODS. To investigate lymphangiogenesis in CNV, we generated CNV in animals by laser and studied surgically removed CNV membranes from uveitis and AMD patients. Immunohistochemistry was performed with lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) and podoplanin antibodies. VEGF-C and VEGFR-3 expressions were examined with immunohistochemistry and Western blotting. To examine the role of lymph node in CNV, we lasered lymphotoxin alpha-deficient mice (LT alpha-/-) and measured the CNV volume.
   RESULTS. Immunohistochemistry showed that LYVE-1(+) macrophages infiltrated in acutely induced CNV, although lymphatic tubes did not form. CNV membranes from patients did not show LYVE-1(+)podoplanin(+) vessels, suggesting the lack of lymphangiogenesis in AMD and uveitis. Western blots and immunostaining revealed VEGF-C and VEGFR-3 expression in CNV lesions, mainly in macrophages and angiogenic endothelial cells. Using fluorescent microsphere tracers, we show a path for cellular migration from the eye to the cervical lymph nodes (LNs) during CNV. However, CNV injury did not cause LN swelling. CNV volume did not differ between wild-type and LN-deficient mice, suggesting that LN is not a key component of early CNV formation.
   CONCLUSIONS. Laser-induced CNV is not primarily dependent on acquired immunity, nor does the fundus injury affect peripheral LNs. Our results reveal a previously unknown cellular connection between the ocular fundus and the cervical LNs. This connection that in function resembles lymphatics is actively utilized in CNV.
C1 [Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hafezi-Moghadam, Ali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Excellence Funct & Mol Imaging, Boston, MA 02115 USA.
   [Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
   [Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA USA.
   [Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   [Nakao, Shintaro; Kohno, Ri-ichiro; Nakama, Takahito; Ishikawa, Keijiro; Yoshida, Shigeo; Enaida, Hiroshi; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan.
   [Zandi, Souska] Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland.
C3 Harvard University; Brigham & Women's Hospital; Harvard Medical School;
   Harvard University; Harvard Medical School; Harvard University; Harvard
   Medical School; Massachusetts Eye & Ear Infirmary; Harvard University;
   Harvard Medical School; Kyushu University; University of Geneva
RP Hafezi-Moghadam, A (通讯作者)，Brigham & Womens Hosp, 221 Longwood Ave,3rd Floor, Boston, MA 02115 USA.
EM ahm@bwh.harvard.edu
OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Nakama,
   Takahito/0000-0001-8999-3667; Zandi, Souska/0000-0001-9351-4278;
   Yoshida, Shigeo/0000-0003-1049-8909
FU NIH Grant [AI050775]; Bausch Lomb; Japan Eye Bank Association; Tear Film
   and Ocular Surface Society; Young Investigator Fellowship; NATIONAL
   INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI050775] Funding
   Source: NIH RePORTER
FX Supported by NIH Grant AI050775 (AH-M), an overseas Research Fellowship
   Award from Bausch & Lomb, a Fellowship Award from the Japan Eye Bank
   Association and Tear Film and Ocular Surface Society, and a Young
   Investigator Fellowship (to SN under the mentorship of AH-M).
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NR 30
TC 7
Z9 8
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2013
VL 54
IS 6
BP 3830
EP 3836
DI 10.1167/iovs.12-10341
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 173YW
UT WOS:000321120700002
PM 23580489
OA Green Published
DA 2022-11-30
ER

PT J
AU Gutfleisch, M
   Heimes, B
   Schumacher, M
   Dietzel, M
   Lommatzsch, A
   Bird, A
   Pauleikhoff, D
AF Gutfleisch, M.
   Heimes, B.
   Schumacher, M.
   Dietzel, M.
   Lommatzsch, A.
   Bird, A.
   Pauleikhoff, D.
TI Long-term visual outcome of pigment epithelial tears in association with
   anti-VEGF therapy of pigment epithelial detachment in AMD
SO EYE
LA English
DT Article
DE bevacizumab (Avastin); ranibizumab (Lucentis); pegaptanib (Macugen);
   age-related macular degeneration; retinal pigment epithelium detachment;
   retinal pigment epithelium tears
ID MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; CHOROIDAL
   NEOVASCULARIZATION; INTRAVITREAL BEVACIZUMAB; RANIBIZUMAB; INJECTION;
   PHOTOCOAGULATION; VERTEPORFIN; SECONDARY; RIP
AB Purpose Retinal pigment epithelium (RPE) tears may develop as a complication after anti-VEGF (vascular endothelial growth factor) treatment for pigment epithelial detachments (PEDs) in exudative age-related macular degeneration (AMD). This retrospective study analyses best-corrected visual acuity (BCVA) and foveal involvement after RPE tears that are associated with anti-VEGF therapy due to PED in exudative AMD.
   Methods A total of 37 patients with RPE tears during anti-VEGF therapy (bevacizumab 12, ranibizumab 21 and pegaptanib 4 eyes) for progressive PED in AMD (PED with occult choroidal neovascularization 25 eyes and PED with retinal angiomatous proliferation 12 eyes) were included in this study. We analyzed BCVA and different morphologic aspects by means of appearance on fluorescein angiography and optical coherence tomography. Mean follow-up was 88 weeks.
   Results RPE tears were diagnosed a mean of 56 days after the first injection. BCVA deteriorated after RPE tear and during follow-up significantly (P < 0.001), with 53.2% of eyes being legally blind (WHO, world health organization) at 12 months. RPE-free foveal area, foveal wrinkling of the RPE, and fibrotic scar development were significantly associated with worse visual acuity.
   Discussion RPE tears can be observed in 12-15% of treated eyes during anti-VEGF therapy for PED in exudative AMD. Owing to the close time relationship with the therapy, this complication must be taken into consideration. Visual prognosis is associated with a decrease in vision in the long term, often resulting in a severe visual disability. Relevant factors for a negative visual prognosis were the potential foveal involvement of the central RPE and morphologic fibrovascular transformation of the RPE tear. Eye (2011) 25, 1181-1186; doi:10.1038/eye.2011.146; published online 24 June 2011
C1 [Gutfleisch, M.; Heimes, B.; Schumacher, M.; Dietzel, M.; Lommatzsch, A.; Pauleikhoff, D.] St Franziskus Hosp, Dept Ophthalmol, D-48145 Munster, Germany.
   [Bird, A.] Moorfields Eye Hosp, London, England.
C3 St. Franziskus-Hospital; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust
RP Gutfleisch, M (通讯作者)，St Franziskus Hosp, Dept Ophthalmol, Hohenzollernring 74, D-48145 Munster, Germany.
EM matthiasgutfleisch@hotmail.com
OI Gutfleisch, Matthias/0000-0002-2001-5838; Heimes-Bussmann,
   Britta/0000-0003-3898-1679
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NR 32
TC 50
Z9 54
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 SEP
PY 2011
VL 25
IS 9
BP 1181
EP 1186
DI 10.1038/eye.2011.146
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 818NW
UT WOS:000294760300012
PM 21701525
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Nork, TM
   Dubielzig, RR
   Christian, BJ
   Miller, PE
   Miller, JM
   Cao, JT
   Zimmer, EP
   Wiegand, SJ
AF Nork, T. Michael
   Dubielzig, Richard R.
   Christian, Brian J.
   Miller, Paul E.
   Miller, Jacqueline M.
   Cao, Jingtai
   Zimmer, Edward P.
   Wiegand, Stanley J.
TI Prevention of Experimental Choroidal Neovascularization and Resolution
   of Active Lesions by VEGF Trap in Nonhuman Primates
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED CLINICAL-TRIALS; VERTEPORFIN
   PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; LASER PHOTOCOAGULATION;
   UNITED-STATES; RANIBIZUMAB; MODEL; BENZOPORPHYRIN; ANGIOGENESIS
AB Objective: To evaluate the efficacy of systemic and intravitreous administration of VEGF Trap (aflibercept) in a nonhuman primate model of choroidal neovascularization (CNV).
   Methods: VEGF Trap treatment on laser-induced CNV was evaluated in 48 adult cynomolgus monkeys. In the prevention arms of the study, VEGF Trap was administered by intravenous injection (3 or 10 mg/kg weekly) or intravitreous injection (50, 250, or 500 mu g/eye every 2 weeks) beginning before laser injury. In the treatment arm, a single intravitreous injection (500 mu g) was given 2 weeks following laser injury. Laser-induced lesions were scored from grade 1 (no hyperfluorescence) to grade 4 (clinically relevant leakage). Representative lesions were evaluated histologically.
   Results: Grade 4 leakage developed at 32.4% and 45.4% of the laser sites in animals receiving intravitreous or intravenous administration of placebo at 2 weeks following laser injury, respectively. In contrast, the development of grade 4 lesions was completely or nearly completely prevented in all groups receiving intravenous or intravitreous injections of VEGF Trap. A single intravitreous injection of VEGF Trap (500 mu g) administered following the development of CNV reduced the frequency of grade 4 lesions from 44.4% to 0% within 14 days of treatment. Intravitreous VEGF Trap was well tolerated with either no or only mild ocular inflammation. Histological evaluation showed decreased scores for morphologic features of tissue proliferation in the VEGF Trap prevention groups.
   Conclusions: VEGF Trap prevented the development of clinically relevant CNV leakage when administered at the lowest doses tested. Moreover, a single intravitreous injection induced inhibition of active CNV leakage.
   Clinical Relevance: The animal model used in this study has an established track record as a predictor of pharmacologic efficacy of antineovascular drugs in humans having the neovascular, or wet, form of age-related macular degeneration.
C1 [Nork, T. Michael; Dubielzig, Richard R.; Miller, Paul E.] Comparat Ophthalm Res Labs CORL, Madison, WI 53792 USA.
   [Christian, Brian J.; Miller, Jacqueline M.] Covance Labs Inc, Madison, WI USA.
   [Cao, Jingtai; Zimmer, Edward P.; Wiegand, Stanley J.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
C3 Covance; Regeneron
RP Nork, TM (通讯作者)，Comparat Ophthalm Res Labs CORL, 600 Highland Ave,F4-336, Madison, WI 53792 USA.
EM tmnork@wisc.edu
FU Regeneron Pharmaceuticals, Inc.
FX This study was funded by Regeneron Pharmaceuticals, Inc.
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   VASCULAR ENDOTHELIAL
NR 48
TC 37
Z9 44
U1 0
U2 4
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 2011
VL 129
IS 8
BP 1042
EP 1052
DI 10.1001/archophthalmol.2011.210
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 804IZ
UT WOS:000293648800010
PM 21825187
DA 2022-11-30
ER

PT J
AU Blaum, BS
   Deakin, JA
   Johansson, CM
   Herbert, AP
   Barlow, PN
   Lyon, M
   Uhrin, D
AF Blaum, Baerbel S.
   Deakin, Jon A.
   Johansson, Conny M.
   Herbert, Andrew P.
   Barlow, Paul N.
   Lyon, Malcolm
   Uhrin, Dusan
TI Lysine and Arginine Side Chains in Glycosaminoglycan-Protein Complexes
   Investigated by NMR, Cross-Linking, and Mass Spectrometry: A Case Study
   of the Factor H-Heparin Interaction
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; BINDING-PROPERTIES; SULFATE;
   GROWTH; SITE; ACID; SPECTROSCOPY; QUANTIFICATION; POLYMORPHISM
AB We have used the interaction between module 7 of complement factor H (CFH similar to 7) and a fully sulfated heparin tetrasaccharide to exemplify a new approach for studying contributions of basic side chains to the formation of glycosaminoglycan (GAG)-protein complexes. We first employed HISQC and H2CN NMR experiments to monitor the side-chain resonances of lysines and arginines in N-15, C-13-labeled protein during titrations with a fully sulfated heparin tetrasaccharide under physiological conditions. Under identical conditions and using N-15-labeled protein, we then cross-linked tetrasaccharide to CFH similar to 7 and confirmed the 1:1 stoichiometry by FT-ICR-MS. We subsequently characterized this covalent protein-GAG conjugate by NMR and further MS techniques. MALDI-TOF MS identified protein fragments obtained via trypsin digestion or chemical fragmentation, yielding information concerning the site of GAG attachment. Combining MS and NMR data allowed us to identify the side chain of K405 as the point of attachment of the crosslinked heparin oligosaccharide to CFH similar to 7. On the basis of the analysis of NMR and MS data of the noncovalent and cross-linked CFH similar to 7-tetrasaccharide complexes, we conclude that the K446 side chain is not essential for binding the tetrasaccharide, despite the large chemical shift perturbations of its backbone amide N-15 and H-1 resonances during titrations. We show that R444 provides the most important charge-charge interaction within a C-terminal heparin-binding subsite of CFH similar to 7 whereas side chains of R404, K405, and K388 are the predominant contributors to an N-terminal binding subsite located in the immediate vicinity of residue 402, which is implicated in age-related macular degeneration (AMD).
C1 [Blaum, Baerbel S.; Johansson, Conny M.; Herbert, Andrew P.; Barlow, Paul N.; Uhrin, Dusan] Univ Edinburgh, Edinburgh Biomol NMR Unit, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Blaum, Baerbel S.; Johansson, Conny M.; Herbert, Andrew P.; Barlow, Paul N.; Uhrin, Dusan] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Deakin, Jon A.; Lyon, Malcolm] Univ Manchester, Canc Res UK Glycooncol Grp, Sch Canc & Imaging Sci, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England.
C3 University of Edinburgh; University of Edinburgh; Paterson Institute for
   Cancer Research; University of Manchester
RP Uhrin, D (通讯作者)，Univ Edinburgh, Edinburgh Biomol NMR Unit, Sch Chem, W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM dusan.uhrin@ed.ac.uk
RI Herbert, Andrew P/C-4755-2008; Barlow, Paul N/G-2853-2011; Herbert, Andy
   P/F-6693-2010
OI Herbert, Andrew P/0000-0002-4549-6965; Herbert, Andy
   P/0000-0002-4549-6965; Blaum, Baerbel/0000-0003-4312-8912; Lyon,
   Malcolm/0000-0001-9575-6879
FU Wellcome Trust [078780/Z/05/Z]; CRUK Programme
FX This work was supported by the Wellcome Trust (078780/Z/05/Z to D.U.)
   and a CRUK Programme grant (M.L. and J.A.D.). We thank Stefan K. Weidt
   for acquiring the FT-ICR spectra.
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NR 60
TC 32
Z9 33
U1 1
U2 40
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
EI 1520-5126
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD MAY 12
PY 2010
VL 132
IS 18
BP 6374
EP 6381
DI 10.1021/ja1000517
PG 8
WC Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA 593IB
UT WOS:000277445400028
PM 20394361
OA Green Accepted
DA 2022-11-30
ER

PT J
AU van Rooijen, E
   Voest, EE
   Logister, I
   Bussmann, J
   Korving, J
   van Eeden, FJ
   Giles, RH
   Schulte-Merker, S
AF van Rooijen, Ellen
   Voest, Emile E.
   Logister, Ive
   Bussmann, Jeroen
   Korving, Jeroen
   van Eeden, Fredericus J.
   Giles, Rachel H.
   Schulte-Merker, Stefan
TI von Hippel-Lindau tumor suppressor mutants faithfully model pathological
   hypoxia-driven angiogenesis and vascular retinopathies in zebrafish
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; IN-VIVO; RETINAL
   VASCULATURE; INDUCIBLE FACTOR-1; CXCR4 EXPRESSION; MACULAR EDEMA;
   DANIO-RERIO; DISEASE; VEGF
AB Biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes human patients to the development of highly vascularized neoplasms in multiple organ systems. We show that zebrafish vhl mutants display a marked increase in blood vessel formation throughout the embryo, starting at 2 days post-fertilization. The most severe neovascularization is observed in distinct areas that overlap with high vegfa mRNA expression, including the vhl mutant brain and eye. Real-time quantitative PCR revealed increased expression of the duplicated VEGFA orthologs vegfaa and vegfab, and of vegfb and its receptors flt1, kdr and kdr-like, indicating increased vascular endothelial growth factor (Vegf) signaling in vhl mutants. Similar to VHL-associated retinal neoplasms, diabetic retinopathy and age-related macular degeneration, we show, by tetramethyl rhodamine-dextran angiography, that vascular abnormalities in the vhl(-/-) retina lead to vascular leakage, severe macular edema and retinal detachment. Significantly, vessels in the brain and eye express cxcr4a, a marker gene expressed by tumor and vascular cells in VHL-associated hemangioblastomas and renal cell carcinomas. VEGF receptor (VEGFR) tyrosine kinase inhibition (through exposure to sunitinib and 676475) blocked vhl(-/-)-induced angiogenesis in all affected tissues, demonstrating that Vegfaa, Vegfab and Vegfb are key effectors of the vhl(-/-) angiogenic phenotype through Flt1, Kdr and Kdr-like signaling. Since we show that the vhl(-/-) angiogenic phenotype shares distinct characteristics with VHL-associated vascular neoplasms, zebrafish vhl mutants provide a valuable in vivo vertebrate model to elucidate underlying mechanisms contributing to the development of these lesions. Furthermore, vhl mutant zebrafish embryos carrying blood vessel-specific transgenes represent a unique and clinically relevant model for tissue-specific, hypoxia-induced pathological angiogenesis and vascular retinopathies. Importantly, they will allow for a cost-effective, non-invasive and efficient way to screen for novel pharmacological agents and combinatorial treatments.
C1 [van Rooijen, Ellen; Logister, Ive; Bussmann, Jeroen; Korving, Jeroen; Schulte-Merker, Stefan] Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [van Rooijen, Ellen; Logister, Ive; Bussmann, Jeroen; Korving, Jeroen; Schulte-Merker, Stefan] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [van Rooijen, Ellen; Voest, Emile E.; Logister, Ive; Giles, Rachel H.] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CG Utrecht, Netherlands.
   [van Eeden, Fredericus J.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW);
   Utrecht University; Utrecht University Medical Center; Utrecht
   University; Utrecht University Medical Center; University of Sheffield
RP Schulte-Merker, S (通讯作者)，Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
EM s.schulte@hubrecht.eu
RI Van Eeden, Freek/E-6198-2010; Bussmann, Jeroen/D-8106-2011
OI Bussmann, Jeroen/0000-0003-2814-3305; Giles, Rachel/0000-0001-9133-2008
FU Dutch Cancer Society [UU-2006-3565]; NWO; Cancer Research UK
   [C23207/A8066]; Stichting Vrienden van het Hubrecht; Medical Research
   Council [G0700091B] Funding Source: researchfish
FX This project was funded by the Dutch Cancer Society (UU-2006-3565). R.
   H. G. is supported by a VIDI award (NWO). F.J.v.E. is supported by
   Cancer Research UK (C23207/A8066), and J.B. by the Stichting Vrienden
   van het Hubrecht. We gratefully acknowledge Bart Weijts (Veterinary
   Medicine, Utrecht University) for help with quantitative real-time PCR;
   Roel Goldschmeding and Kevin van de Ven (Department of Pathology, UMC
   Utrecht) for transmission electron microscopy; Henk Verheul and Kristy
   Gotink (Department of Medical Oncology, VUMC Amsterdam) for helpful
   discussions; and Lasse Dahl Jensen (Karolinska Institute, Sweden) for
   sharing information on sunitinib treatments in zebrafish.
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Z9 81
U1 2
U2 18
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD MAY-JUN
PY 2010
VL 3
IS 5-6
BP 343
EP 353
DI 10.1242/dmm.004036
PG 11
WC Cell Biology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Pathology
GA 622YA
UT WOS:000279701700018
PM 20335444
OA Green Published
DA 2022-11-30
ER

PT J
AU Krohne, TU
   Holz, FG
   Kopitz, J
AF Krohne, Tim U.
   Holz, Frank G.
   Kopitz, Juergen
TI Apical-to-Basolateral Transcytosis of Photoreceptor Outer Segments
   Induced by Lipid Peroxidation Products in Human Retinal Pigment
   Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; LOW-DENSITY LIPOPROTEINS; MACULAR DEGENERATION;
   COMPLEMENT ACTIVATION; PROTEIN MODIFICATIONS; DRUSEN FORMATION; BRUCHS
   MEMBRANE; RPE; PATHOGENESIS; INHIBITION
AB PURPOSE. Progressive accumulation of extracellular material at the basolateral side of the retinal pigment epithelium (RPE) is a key event in the pathogenesis of age-related macular degeneration (AMD). The authors previously demonstrated that modifications with lipid peroxidation products, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), stabilize photoreceptor outer segment (POS) proteins against lysosomal degradation. Herein, they tested RPE cells for the basolateral release of undegraded modified POS proteins.
   METHODS. Polarized cultures of the human RPE cell line ARPE-19 on permeable membranes were incubated with iodine-125-labeled POS on the apical side. After 24 hours, radioactivity was quantified in apical medium, cell lysates, and basolateral medium after separation of undegraded proteins by precipitation. Protein composition of basolaterally released POS material was analyzed by two-dimensional gel electrophoresis. C3a- and SC5b-9-specific enzyme-linked immunosorbent assays were used to assess complement activation by modified POS.
   RESULTS. The amount of phagocytic uptake was similar for native and modified POS. Unmodified POS proteins were almost completely (98.1%) degraded, whereas degradation of HNE- and MDA-modified POS proteins was significantly reduced (47.2%; 56.5%). Undegraded POS proteins accumulated intracellularly (14.2%; 12.1%) and were trafficked through the cells to be released into the basolateral medium (38.5%; 31.5%). Protein composition of basolaterally released material matched the original POS preparations. Protein modifications did not confer increased complement-activating capacity to POS material.
   CONCLUSIONS. Inhibition of lysosomal degradation by lipid peroxidation-related protein modifications induces apical-to-basolateral transcytosis of undegraded POS proteins by human RPE cells in vitro. This mechanism may contribute to sub-RPE de-posit formation and drusen biogenesis in AMD. (Invest Ophthalmol Vis Sci. 2010;51:553-560) DOI:10.1167/iovs.09-3755
C1 [Krohne, Tim U.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Kopitz, Juergen] Univ Heidelberg, Dept Mol Pathol, Heidelberg, Germany.
C3 University of Bonn; Ruprecht Karls University Heidelberg
RP Krohne, TU (通讯作者)，Univ 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
OI Krohne, Tim/0000-0003-2280-925X
FU German Research Foundation (DFG) [KR 2863/6-1, HO 1926/2-1]; University
   of Bonn; German Ophthalmological Society; Dr. Eberhard und Hilde Rudiger
   Foundation
FX Supported by the German Research Foundation (DFG) Grant KR 2863/6-1
   (TUK); DFG Priority Program "Age-related macular degeneration" (SPP
   1088) Grant HO 1926/2-1 (JK, FGH); the University of Bonn BONFOR Program
   Gerok Fellowship (TUK); the German Ophthalmological Society Alcon Retina
   Scholarship (TUK); and the Dr. Eberhard und Hilde Rudiger Foundation
   (TUK).
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NR 53
TC 34
Z9 34
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JAN
PY 2010
VL 51
IS 1
BP 553
EP 560
DI 10.1167/iovs.09-3755
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 539OI
UT WOS:000273264200073
PM 19696182
DA 2022-11-30
ER

PT J
AU Magotti, P
   Ricklin, D
   Qu, HC
   Wu, YQ
   Kaznessis, YN
   Lambris, JD
AF Magotti, Paola
   Ricklin, Daniel
   Qu, Hongchang
   Wu, You-Qiang
   Kaznessis, Yiannis N.
   Lambris, John D.
TI Structure-kinetic relationship analysis of the therapeutic complement
   inhibitor compstatin
SO JOURNAL OF MOLECULAR RECOGNITION
LA English
DT Article
DE complement; compstatin; C3; surface plasmon resonance; isothermal
   titration calorimetry; kinetics
ID AMINO-ACIDS; BINDING; ANALOGS; ACTIVATION; ENERGETICS; COMPONENT;
   STRATEGY; SURVIVAL; DESIGN; TARGET
AB Compstatin is a 13-residue peptide that inhibits activation of the complement system by binding to the central component C3 and its fragments C3b and C3c. A combination of theoretical and experimental approaches has previously allowed us to develop analogs of the original compstatin peptide with up to 264-fold higher activity, one of these analogs is now in clinical trials for the treatment of age-related macular degeneration (AMD). Here we used functional assays, surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) to assess the effect of modifications at three key residues (Trp-4, Asp-6, Ala-9) on the affinity and activity of compstatin and its analogs, and we correlated our findings to the recently reported co-crystal structure of compstatin and C3c. The K-D values for the panel of tested analogs ranged from 10(-6) to 10(-8) M. These differences in binding affinity could be attributed mainly to differences in dissociation rather than association rates, with a >4-fold range in k(on) values (2-10 X 10(5) M-1 s(-1)) and a k(off) variation of >35-fold (1-37 X 10(-2) s(-1)) being observed. The stability of the C3b-compstatin complex seemed to be highly dependent on hydrophobic effects at position 4, and even small changes at position 6 resulted in a loss of complex formation. Induction of a beta-turn shift by an A9P modification resulted in a more favorable entropy but a loss of binding specificity and stability. The results obtained by the three methods utilized here were highly correlated with regard to the activity/affinity of the analogs. Thus, our analyses have identified essential structural features of compstatin and provided important information to support the development of analogs with improved efficacy. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Magotti, Paola; Ricklin, Daniel; Qu, Hongchang; Wu, You-Qiang; Lambris, John D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Kaznessis, Yiannis N.] Univ Minnesota, Dept Chem Engn & Mat Sci, Minneapolis, MN 55455 USA.
C3 University of Pennsylvania; University of Minnesota System; University
   of Minnesota Twin Cities
RP Lambris, JD (通讯作者)，Univ Penn, Dept Pathol & Lab Med, 401 Stellar Chance,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM lambris@upenn.edu
RI Lambris, John/Q-5633-2018; Kaznessis, Yiannis N/H-1795-2015; Magotti,
   Paola/A-2903-2012; Ricklin, Daniel/F-5104-2011
OI Lambris, John/0000-0002-9370-5776; Ricklin, Daniel/0000-0001-6140-0233;
   Kaznessis, Yiannis/0000-0002-5088-1104
FU National Institutes of Health [A1068730, GM062134, GM069736, EB003968];
   NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI068730]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING
   AND BIOENGINEERING [R01EB003968] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM062134, R24GM069736] Funding
   Source: NIH RePORTER
FX This study was supported by the National Institutes of Health grants
   A1068730, GM062134, GM069736, and EB003968. The authors gratefully
   acknowledge Dr Serapion Pyrpassopoulos for his help with the initial ITC
   experiments and Dr Georgia Sfyroera for providing biotinylated C3b. They
   also thank Dr Deborah McClellan for editorial assistance.
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NR 38
TC 38
Z9 40
U1 0
U2 8
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3499
EI 1099-1352
J9 J MOL RECOGNIT
JI J. Mol. Recognit.
PD NOV-DEC
PY 2009
VL 22
IS 6
BP 495
EP 505
DI 10.1002/jmr.972
PG 11
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 513SF
UT WOS:000271342800009
PM 19658192
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sun, K
   Cai, H
   Tezel, TH
   Paik, D
   Gaillard, ER
   Del Priore, LV
AF Sun, Kai
   Cai, Hui
   Tezel, Tongalp H.
   Paik, David
   Gaillard, Elizabeth R.
   Del Priore, Lucian V.
TI Bruch's membrane aging decreases phagocytosis of outer segments by
   retinal pigment epithelium
SO MOLECULAR VISION
LA English
DT Article
ID RCS RAT MODEL; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX;
   RETINITIS-PIGMENTOSA; DYSTROPHY PHENOTYPE; GENE-TRANSFER; CROSS-LINK;
   AGE; CELLS; MERTK
AB Purpose: We have shown previously that aging of human Bruch's membrane affects the attachment, survival and gene expression profile of the overlying retinal pigment epithelium (RPE). Herein we determine the effects of Bruch's membrane aging on RPE phagocytosis of rod outer segments.
   Methods: Explants of human Bruch's membrane were prepared from cadaver donor eyes (aged 9-81 years) within 48 h of death, and 6 mm punches were embedded with the basal lamina in a 96-well plate. Approximately 50,000 ARPE-19 cells per well were seeded onto the explant surface and cultured for two weeks until they reached confluence. In addition, ARPE-19 were also seeded onto RPE-derived extracellular matrix (RPE-ECM) that was unmodified or modified by nonenzymatic nitration. Bovine rod outer segments were purified by sucrose gradient centrifugation, labeled with 10 ug/ml fluorescein isothiocyanate, and added to ARPE-19 cultured on Bruch's membrane or RPE-ECM for 24 h. Phagocytic activity was quantified by flow cytometry of harvested cells.
   Results: The ability of RPE to phagocytose rod outer segments decreased as a function of aging of Bruch's membrane; mean phagocytotic activity of ARPE-19 on younger Bruch's membrane was significantly higher than on older Bruch's membrane (129.7 +/- 34.8 versus 67.4 +/- 4.2 arbitrary units, respectively; p < 0.01). Nitrite treatment of RPE-ECM decreased rod outer segment phagocytosis compared to untreated RPE-ECM and mimicked the effects of aging of human Bruch's membrane.
   Conclusions: Aging of human Bruch's membrane decreases rod outer segment phagocytosis by ARPE-19. This effect can be mimicked by nonenzymatic nitration of extracellular matrix in vitro. Our observations may have implications for understanding the role of aging changes within Bruch's membrane on pathogenesis of age-related macular degeneration and other disorders.
C1 [Sun, Kai; Cai, Hui; Paik, David; Del Priore, Lucian V.] Columbia Univ, Harkness Eye Inst, Dept Ophthalmol, New York, NY 10032 USA.
   [Tezel, Tongalp H.] Univ Louisville, Sch Med, Kentucky Lions Eye Res Inst, Louisville, KY 40292 USA.
   [Gaillard, Elizabeth R.] No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
C3 Columbia University; University of Louisville; Northern Illinois
   University
RP Del Priore, LV (通讯作者)，Columbia Univ, Harkness Eye Inst, Dept Ophthalmol, 635 W 165th St, New York, NY 10032 USA.
EM ldelpriore@yahoo.com
RI Gaillard, Elizabeth/M-2627-2019
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NR 56
TC 45
Z9 47
U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 21
PY 2007
VL 13
IS 261-65
BP 2310
EP 2319
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 310RM
UT WOS:000256547800001
PM 18199972
DA 2022-11-30
ER

PT J
AU Justilien, V
   Pang, JJ
   Renganathan, K
   Zhan, X
   Crabb, JW
   Kim, SR
   Sparrow, JR
   Hauswirth, WW
   Lewin, AS
AF Justilien, Verline
   Pang, Ji-Jing
   Renganathan, Kutralanathan
   Zhan, Xianquan
   Crabb, John W.
   Kim, So Ra
   Sparrow, Janet R.
   Hauswirth, William W.
   Lewin, Alfred S.
TI SOD2 knockdown mouse model of early AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; RETINAL-PIGMENT
   EPITHELIUM; BEAVER DAM EYE; MITOCHONDRIAL SUPEROXIDE-DISMUTASE;
   LIGHT-INDUCED DAMAGE; BLUE-MOUNTAINS EYE; MACULAR DEGENERATION;
   CHOROIDAL-NEOVASCULARIZATION; INDUCED APOPTOSIS
AB PURPOSE. To test the hypothesis that oxidative injury to the retinal pigment epithelium (RPE) may lead to retinal damage similar to that associated with the early stages of age-related macular degeneration (AMD).
   METHODS. A ribozyme that targets the protective enzyme manganese superoxide dismutase ( MnSOD) was expressed in RPE-J cells, and adeno-associated virus (AAV) expressing the ribozyme gene was injected beneath the retinas of adult C57BL/6 mice. The RPE/choroid complex was examined for SOD2 protein levels and protein markers of oxidative damage using immunoblot analysis and LC MS/MS-identification of proteins and nitration sites. Lipids were extracted from retinal tissue and analyzed for the bis-retinoid compounds A2E and iso-A2E. The mice were analyzed by full-field electroretinography ( ERG) for light response. Light and electron microscopy were used to measure cytological changes in the retinas.
   RESULTS. The treatment of RPE-J cells with Rz432 resulted in decreased MnSOD mRNA and protein as well as increased levels of superoxide anion and apoptotic cell death. When delivered by AAV, Rz432 reduced MnSOD protein and increased markers of oxidative damage, including nitrated and carboxyethylpyrrole-modified proteins in the RPE-choroid of mice. Ribozyme delivery caused a progressive loss of electroretinograph response, vacuolization, degeneration of the RPE, thickening of Bruch's membrane, and shortening and disorganization of the photoreceptor outer and inner segments. Progressive thinning of the photoreceptor outer nuclear layer resulted from apoptotic cell death. Similar to the eyes of patients with AMD, ribozyme-treated eyes exhibited increased autofluorescence and elevated levels of A2E and iso-A2E, major bis-retinoid pigments of lipofuscin.
   CONCLUSIONS. These results support the hypothesis that oxidative damage to the RPE may play a role in some of the key features of AMD.
C1 Univ Florida, Coll Med, Dept Mol Genet, Gainesville, FL 32610 USA.
   Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
   Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
   Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA.
   Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida; Cleveland Clinic
   Foundation; Cleveland Clinic Foundation; Columbia University
RP Lewin, AS (通讯作者)，Univ Florida, Coll Med, Dept Mol Genet, Box 100266, Gainesville, FL 32610 USA.
EM lewin@ufl.edu
RI renganathan, Kutralanathan/F-8580-2010
OI renganathan, Kutralanathan/0000-0001-9001-2934; Lewin,
   Alfred/0000-0002-4192-9727
FU NEI NIH HHS [EY11123, EY13729, R01 EY020825, R01 EY012951, EY15638, R01
   EY016073, EY12951, U10 EY013729, EY08571, R01 EY014239, EY14239, R01
   EY011123, EY016073, P30 EY008571, R01 EY012951-10] Funding Source:
   Medline; NINDS NIH HHS [NS36302, P01 NS036302] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [P30EY008571, R01EY012951, U10EY013729,
   R01EY020825, R01EY014239, R01EY011123, R24EY015638, R01EY016073] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND
   STROKE [P01NS036302] Funding Source: NIH RePORTER
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NR 67
TC 170
Z9 177
U1 2
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 OCT
PY 2007
VL 48
IS 10
BP 4407
EP 4420
DI 10.1167/iovs.07-0432
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 214SE
UT WOS:000249757600006
PM 17898259
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Adegbehingbe, BO
   Malengbasan, TO
AF Adegbehingbe, Bernice O.
   Malengbasan, Timothy O.
TI Ocular health status of rural dwellers in south-western Nigeria
SO AUSTRALIAN JOURNAL OF RURAL HEALTH
LA English
DT Article
DE blindness aetiology; eye diseases epidemiology; rural health
ID BLINDNESS
AB Objective: To determine the prevalence and causes of ocular morbidity, visual impairment and blindness, and suggest strategies for blindness prevention in a rural population.
   Design: A population-based cross-sectional study.
   Setting: Imesi-Ile, in Obokun local government area of Osun State, Nigeria.
   Methods: All participants had preliminary interview and screening consisting of vision assessment using an illiterate E-chart and anterior segment hand light examination at their houses. Those who had signs and symptoms Of ocular disease were offered comprehensive eye examination at the base hospital, including visual acuity using illiterate E-chart and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry and dilated fundus examination as necessary.
   Results: Of the 2201. patients examined, 298 (13.5%) bad signs and symptoms of ocular disease. This consisted of 153 male (51.3%) and 145 (48.7%) female patients. Their ages ranged between 8 and 92 years, with a peak age range of 41-70 years (45.6%). Most of them had never seen an eye care specialist for appropriate ophthalmic care. The common eye problems encountered were cataract (48.0%), glaucoma (21.1%), allergic conjunctivitis (16.4%), refractive errors (12.4%), age-related macular degeneration (0.7%) and corneal opacities (0.7%). Thirty-two eyes of 27 persons (1.2%) (22 monocular and 5 binocular) were blind by the World Health Organisation definition. Cataract was the leading cause of blindness (44.4%), followed by glaucoma (33.3%), macular degeneration (7.4%), corneal opacity (7.4%), optic atrophy (3.7%) and phthisis bulbi (3.7%).
   Conclusion: A significant proportion (13.5%) of people in this community bad ocular diseases which require treatment. The role of primary eye care health workers in a rural community as Imesi-Ile cannot be overemphasised.
C1 [Adegbehingbe, Bernice O.; Malengbasan, Timothy O.] Obafemi Awolowo Univ, Coll Hlth Sci, Dept Surg, Ophthalmol Unit, Ife 220005, Nigeria.
C3 Obafemi Awolowo University
RP Adegbehingbe, BO (通讯作者)，Obafemi Awolowo Univ, Coll Hlth Sci, Dept Surg, Ophthalmol Unit, Ife 220005, Nigeria.
EM berniceola2003@yahoo.co.uk
OI Adegbehingbe, Bernice/0000-0002-3817-583X
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NR 11
TC 22
Z9 22
U1 0
U2 3
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1038-5282
J9 AUST J RURAL HEALTH
JI Aust. J. Rural Health
PD AUG
PY 2007
VL 15
IS 4
BP 269
EP 272
DI 10.1111/j.1440-1584.2007.00906.x
PG 4
WC Public, Environmental & Occupational Health; Nursing
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health; Nursing
GA 273AL
UT WOS:000253902700009
PM 17617092
DA 2022-11-30
ER

PT J
AU Bunce, C
   Wormald, R
AF Bunce, C
   Wormald, R
TI Leading causes of certification for blindness and partial sight in
   England & Wales
SO BMC PUBLIC HEALTH
LA English
DT Article
ID MACULAR DEGENERATION; VISUAL IMPAIRMENT
AB Background: Prevention of visual impairment is an international priority agreed at the World Health Assembly of 2002- yet many countries lack contemporary data about incidence and causes from which priorities for prevention, treatment and management can be identified.
   Methods: Registration as blind or partially-sighted in England and Wales is voluntary and is initiated by certification by a consultant ophthalmologist. From all certificates completed during the year April 1999 to March 2000, the main cause of visual loss was ascertained where possible and here we present information on the leading causes observed and comment on changes in the three leading causes since the last analysis conducted for 1990 - 1991 data.
   Results: 13788 people were certified as blind, 19107 were certified as partially sighted. The majority of certifications were in the older age groups. The most commonly recorded main cause of certifications for both blindness (57.2 %) and partial sight ( 56 %) was degeneration of the macula and posterior pole which largely comprises age-related macular degeneration. Glaucoma and diabetic retinopathy were the next most commonly recorded main causes. Overall, the age specific incidence of all three leading causes has increased since 1990 - 1991 - with changes in diabetic retinopathy being the most marked - particularly in the over 65' s where figures have more than doubled.
   Conclusion: The numbers of individuals per 100,000 population being certified blind or partially sighted due to the three leading causes - AMD, diabetic retinopathy and glaucoma have increased since 1990. This may to some extent be explained by improved ascertainment. The process of registration for severe visual impairment in England and Wales is currently undergoing review. Efforts must be made to ensure that routine collection of data on causes of severe visual impairment is continued, particularly in this age of improved technology, to allow such trends to be monitored and changes in policy to be informed.
C1 Moorfields Eye Hosp, London, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust
RP Bunce, C (通讯作者)，Moorfields Eye Hosp, City Rd, London, England.
EM c.bunce@ucl.ac.uk; r.wormald@ucl.ac.uk
OI Bunce, Catey/0000-0002-0935-3713
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NR 18
TC 191
Z9 200
U1 0
U2 27
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD MAR 8
PY 2006
VL 6
AR 58
DI 10.1186/1471-2458-6-58
PG 7
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health
GA 026ZV
UT WOS:000236383100001
PM 16524463
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Magnusson, KP
   Duan, S
   Sigurdsson, H
   Petursson, H
   Yang, ZL
   Zhao, Y
   Bernstein, PS
   Ge, J
   Jonasson, F
   Stefansson, E
   Helgadottir, G
   Zabriskie, NA
   Jonsson, T
   Bjornsson, A
   Thorlacius, T
   Jonsson, PV
   Thorleifsson, G
   Kong, A
   Stefansson, H
   Zhang, K
   Stefansson, K
   Gulcher, JR
AF Magnusson, KP
   Duan, S
   Sigurdsson, H
   Petursson, H
   Yang, ZL
   Zhao, Y
   Bernstein, PS
   Ge, J
   Jonasson, F
   Stefansson, E
   Helgadottir, G
   Zabriskie, NA
   Jonsson, T
   Bjornsson, A
   Thorlacius, T
   Jonsson, PV
   Thorleifsson, G
   Kong, A
   Stefansson, H
   Zhang, K
   Stefansson, K
   Gulcher, JR
TI CFH Y402H confers similar risk of soft drusen and both forms of advanced
   AMD
SO PLOS MEDICINE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   SUSCEPTIBILITY LOCI; EXTENDED FAMILIES; GENOMEWIDE-SCAN; REYKJAVIK EYE;
   LINKAGE; PREVALENCE; HAPLOTYPE
AB Background Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD-or the relationship between them-is unclear.
   Methods and Findings We genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen). A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 X 10(-12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 X 10(-9)) with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD).
   Conclusion Soft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.
C1 DeCODE Genet, Reykjavik, Iceland.
   Univ Utah, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   Univ Utah, Eccles Inst Human Genet, Program Human Mol Biol & Genet, Salt Lake City, UT USA.
   Natl Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guang Zhou, Peoples R China.
   Natl Univ Hosp Reykjavik, Dept Ophthalmol, Reykjavik, Iceland.
   Univ Iceland, Fac Med, Reykjavik, Iceland.
   Sichuan Acad Med Sci, Chengdu, Peoples R China.
   Sichuan Provincial Peoples Hosp, Chengdu, Peoples R China.
   Natl Univ Hosp Reykjavik, Dept Geriatr, Reykjavik, Iceland.
C3 Utah System of Higher Education; University of Utah; Utah System of
   Higher Education; University of Utah; Sun Yat Sen University;
   Landspitali National University Hospital; University of Iceland; Sichuan
   Provincial People's Hospital; Sichuan Provincial People's Hospital;
   Landspitali National University Hospital
RP Magnusson, KP (通讯作者)，DeCODE Genet, Reykjavik, Iceland.
EM kristinn.p.magnusson@decode.is; kang.zhang@hmbg.utah.edu;
   jeffery.gulcher@decode.is
RI Jonasson, Fridbert/ABA-9889-2021; Zhang, Kang/Y-2740-2019; Stefansson,
   Kari/AAE-7187-2019; Magnusson, Kristinn/A-6479-2011; Magnusson, Kristinn
   P Pétur/X-4907-2019
OI Zhang, Kang/0000-0002-4549-1697; Magnusson,
   Kristinn/0000-0003-4528-6826; Magnusson, Kristinn P
   Pétur/0000-0003-4528-6826; Kong, Augustine/0000-0001-8193-5438;
   Stefansson, Hreinn/0000-0002-9331-6666
FU NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000064] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY014448, R01EY014428, P30EY014800]
   Funding Source: NIH RePORTER; NCRR NIH HHS [M01-RR00064, M01 RR000064]
   Funding Source: Medline; NEI NIH HHS [R01EY14428, P30EY014800,
   R01EY14448, R01 EY014448, R01 EY014428, P30 EY014800] Funding Source:
   Medline
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NR 37
TC 177
Z9 194
U1 1
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD JAN
PY 2006
VL 3
IS 1
BP 109
EP 114
AR e5
DI 10.1371/journal.pmed.0030005
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 026MJ
UT WOS:000236342700019
PM 16300415
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Yatsenko, AN
   Shroyer, NF
   Lewis, RA
   Lupski, JR
AF Yatsenko, AN
   Shroyer, NF
   Lewis, RA
   Lupski, JR
TI An ABCA4 genomic deletion in patients with Stargardt Disease
SO HUMAN MUTATION
LA English
DT Article
DE ABCA4; photoreceptor; mutation screening; genomic rearrangement; genomic
   deletion; Stargardt disease; STGD1
ID CASSETTE TRANSPORTER GENE; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA;
   BIOCHEMICAL DEFECTS; MISSENSE MUTATIONS; RIM PROTEIN; PHOTORECEPTORS;
   REARRANGEMENTS; PHENOTYPE; POLYMER
AB Stargardt disease (STGD1) segregates with mutations in the ABCA4 (ABCR) locus. However, mutations of the ABCA4 coding region detected by sequencing account for only 66-80% of disease chromosomes. We hypothesized a potential contribution of otherwise undetected genomic rearrangements of the ABCA4 region. To investigate this hypothesis, we performed genomic Southern analysis on samples from 96 STGD families in which we had identified either one or no ABCA4 mutations by conventional methods. Among 192 chromosomes evaluated, we found one deletion (0.52%), IVS17-905-IVS18+35del, that spans 1,030 bp and eliminates exon 18 of ABCA4. By conceptual translation, this alteration creates an in-frame deletion of 30 amino acids, G885-H915del, and cosegregates with the disease in this family, implying a disease-associated allele. STGD subjects with this deletion were found to have a second mutant ABCA4 allele, 2588G > C. DNA sequence analysis of the deletion junction revealed consensus DNA topoisomerase I sites at both breakpoints that may predispose to nonhomologous recombination. Using deletion-specific PCR, we found the same allele in 2 of 308 STGD subjects (0.32%), in 1 of 96 age related macular degeneration (AMD) subjects (0.52%), and in 2 of 480 (0.2%) individuals with no known eye diseases, but it was absent in a control group consisting of 96 individuals over age 60 and with normal eye examinations. In vitro biochemical studies of the cloned G885-H915del mutation revealed diminished expression, suggesting that partial deletion of the putative nucleotide-binding domain I leads to either misfolding or defective membrane interactions and eventually reduces the protein function in the retinopathy-affected subjects. Our experiments suggest that genomic alterations contribute to only a small fraction of retinopathy-associated alleles. (C) 2003 Wiley-Liss, Inc.
C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College
   of Medicine; Baylor College of Medicine
RP Lupski, JR (通讯作者)，Baylor Coll Med, Dept Mol & Human Genet, Room 604B,1 Baylor Plaza, Houston, TX 77030 USA.
EM jlupski@bcm.tmc.edu
OI Shroyer, Noah/0000-0002-5934-2852; Yatsenko,
   Alexander/0000-0002-1690-0172
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NR 41
TC 28
Z9 28
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD JUN
PY 2003
VL 21
IS 6
BP 636
EP 644
DI 10.1002/humu.10219
PG 9
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 687UN
UT WOS:000183395500012
PM 12754711
DA 2022-11-30
ER

PT J
AU Tuo, SH
   Li, C
   Liu, F
   Zhu, YL
   Chen, TR
   Feng, ZY
   Liu, HY
   Li, AM
AF Tuo, Shouheng
   Li, Chao
   Liu, Fan
   Zhu, YanLing
   Chen, TianRui
   Feng, ZengYu
   Liu, Haiyan
   Li, Aimin
TI A Novel Multitasking Ant Colony Optimization Method for Detecting
   Multiorder SNP Interactions
SO INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES
LA English
DT Article
DE Multitasking; Ant colony optimization algorithm; Single-nucleotide
   polymorphisms; SNP interaction
ID EVOLUTIONARY MULTITASKING; EPISTATIC INTERACTIONS; BTNL2 GENE; GENOME;
   SUSCEPTIBILITY; ASSOCIATION; LOCUS; POLYMORPHISM; SARCOIDOSIS
AB Motivation Linear or nonlinear interactions of multiple single-nucleotide polymorphisms (SNPs) play an important role in understanding the genetic basis of complex human diseases. However, combinatorial analytics in high-dimensional space makes it extremely challenging to detect multiorder SNP interactions. Most classic approaches can only perform one task (for detecting k-order SNP interactions) in each run. Since prior knowledge of a complex disease is usually not available, it is difficult to determine the value of k for detecting k-order SNP interactions.
   Methods A novel multitasking ant colony optimization algorithm (named MTACO-DMSI) is proposed to detect multiorder SNP interactions, and it is divided into two stages: searching and testing. In the searching stage, multiple multiorder SNP interaction detection tasks (from 2nd-order to kth-order) are executed in parallel, and two subpopulations that separately adopt the Bayesian network-based K2-score and Jensen-Shannon divergence (JS-score) as evaluation criteria are generated for each task to improve the global search capability and the discrimination ability for various disease models. In the testing stage, the G test statistical test is adopted to further verify the authenticity of candidate solutions to reduce the error rate.
   Result Three multiorder simulated disease models with different interaction effects and three real age-related macular degeneration (AMD), rheumatoid arthritis (RA) and type 1 diabetes (T1D) datasets were used to investigate the performance of the proposed MTACO-DMSI. The experimental results show that the MTACO-DMSI has a faster search speed and higher discriminatory power for diverse simulation disease models than traditional single-task algorithms. The results on real AMD data and RA and T1D datasets indicate that MTACO-DMSI has the ability to detect multiorder SNP interactions at a genome-wide scale.
   [GRAPHICS]
   .
C1 [Tuo, Shouheng; Li, Chao; Liu, Fan; Zhu, YanLing; Chen, TianRui; Feng, ZengYu; Liu, Haiyan] Xian Univ Posts & Telecommun, Sch Comp Sci & Technol, Xian 710121, Shaanxi, Peoples R China.
   [Tuo, Shouheng; Li, Chao; Liu, Fan; Zhu, YanLing; Chen, TianRui; Feng, ZengYu; Liu, Haiyan] Shaanxi Key Lab Network Data Anal & Intelligent P, Xian 710121, Shaanxi, Peoples R China.
   [Tuo, Shouheng; Li, Chao; Liu, Fan; Zhu, YanLing; Chen, TianRui; Feng, ZengYu; Liu, Haiyan] Xian Key Lab Big Data & Intelligent Comp, Xian 710121, Shaanxi, Peoples R China.
   [Li, Aimin] Xian Univ Technol, Sch Comp Sci & Engn, Xian 710048, Shaanxi, Peoples R China.
C3 Xi'an University of Posts & Telecommunications; Xi'an University of
   Technology
RP Tuo, SH (通讯作者)，Xian Univ Posts & Telecommun, Sch Comp Sci & Technol, Xian 710121, Shaanxi, Peoples R China.; Tuo, SH (通讯作者)，Shaanxi Key Lab Network Data Anal & Intelligent P, Xian 710121, Shaanxi, Peoples R China.; Tuo, SH (通讯作者)，Xian Key Lab Big Data & Intelligent Comp, Xian 710121, Shaanxi, Peoples R China.
EM tuo_sh@126.com
OI Li, Aimin/0000-0002-6983-2310
FU Natural Science Foundation of Shaanxi Provincial Education Department
   [18JK0165]; Natural Science Foundation of China [62002289]
FX This work was supported in part by the Natural Science Foundation of
   Shaanxi Provincial Education Department (Grant No. 18JK0165) and Natural
   Science Foundation of China under Grant No. 62002289.
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NR 70
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1913-2751
EI 1867-1462
J9 INTERDISCIP SCI
JI Interdiscip. Sci.
PD DEC
PY 2022
VL 14
IS 4
BP 814
EP 832
DI 10.1007/s12539-022-00530-2
EA JUL 2022
PG 19
WC Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology
GA 5L3ET
UT WOS:000821447800001
PM 35788965
DA 2022-11-30
ER

PT J
AU Luo, JY
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   Luo, RJ
   Long, CD
AF Luo, Jing-Yi
   Yu, Shi-Tong
   Xu, Xiao-Yu
   Lin, Xian-Xuan
   Luo, Rong-Jiang
   Long, Chong-De
TI Primary Vitreoretinal Lymphoma: A Retrospective Study of 20 Eyes
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PRIMARY INTRAOCULAR LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA;
   CLINICAL-FEATURES; DIAGNOSIS; PATIENT
AB Purpose. This study aimed to describe and analyze the clinical features of 20 eyes of 15 primary vitreoretinal lymphoma (PVRL) patients. Methods. This was a retrospective case series and a review of the literature. Fifteen PVRL patients (20 affected eyes) referred between February 2011 and December 2019 were recruited, and their medical records were retrospectively reviewed. Results. Among these 15 PVRL patients, seven were men (46.67%), and five had bilateral PVRL (33.33%). The median onset age was 66 +/- 9.26 years and six (40%) patients had central nervous system (CNS) involvement, and two of them died of CNS-related complications. The ocular symptoms varied from decreased vision to binocular diplopia. The ocular manifestations were diverse and involved both the anterior and posterior segments, including the vitreous cells, subretinal white-yellow lesions, cotton-wool spots, and ophthalmoplegia. The rate of misdiagnosis and failure to diagnose was 100%, and 30% of them were misdiagnosed as uveitis. We found five cases revealing rare characteristics of this malignancy. Among them, there were two cases with mild hypertensive retinopathy exhibiting cotton-wool spots, one case mimicking age-related macular degeneration (AMD), one case with systemic lupus erythematosus (SLE), and one patient had extraocular muscle involvement. To the best of our knowledge, we reported PVRL exhibiting cotton-wool spots as the main manifestation and coexisting with extraocular myopathy for the first time. Conclusions. PVRL is a rare intraocular malignancy that commonly masquerades as uveitis. As the clinical signs and symptoms are atypical, ophthalmologists must carefully examine patients to avoid misdiagnosis or a failure to diagnose. Cotton-wool spots and extraocular myopathy might be the dominant initial symptoms in PVRL patients, and AMD should be considered a differential diagnosis of PVRL. SLE patients under immunosuppressive treatment could have spontaneous PVRL.
C1 [Luo, Jing-Yi; Xu, Xiao-Yu; Long, Chong-De] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangdong Prov Clin Res Ctr Ocular Dis, State Key Lab Ophthalmol,Guangdong Prov Key Lab Op, Guangzhou 510060, Guangdong, Peoples R China.
   [Luo, Jing-Yi; Lin, Xian-Xuan; Luo, Rong-Jiang] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China.
   [Yu, Shi-Tong] Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Dept Gen Surg, Guangzhou 510150, Guangdong, Peoples R China.
   [Yu, Shi-Tong] Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Guangdong Prov Key Lab Precis Med Gastrointestinal, Guangzhou 510150, Guangdong, Peoples R China.
   [Luo, Rong-Jiang] C MER Guangzhou Dennis Lam Eye Hosp, Guangzhou 510030, Guangdong, Peoples R China.
C3 Sun Yat Sen University; Sun Yat Sen University; Southern Medical
   University - China; Southern Medical University - China
RP Long, CD (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangdong Prov Clin Res Ctr Ocular Dis, State Key Lab Ophthalmol,Guangdong Prov Key Lab Op, Guangzhou 510060, Guangdong, Peoples R China.; Luo, RJ (通讯作者)，Sun Yat Sen Univ, Affiliated Hosp 1, Dept Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China.; Luo, RJ (通讯作者)，C MER Guangzhou Dennis Lam Eye Hosp, Guangzhou 510030, Guangdong, Peoples R China.
EM camel043@126.com; 258417083@qq.com; fishemily@163.com;
   13662373156@163.com; lr047@163.com; longchd@mail.sysu.edu.cn
RI Yu, Shi-Tong/H-3747-2018
OI Yu, Shi-Tong/0000-0001-5443-2886
FU National Natural Science Foundation of China [81800879]; Guangdong
   Provincial Key Laboratory of Precision Medicine for Gastrointestinal
   Cancer [2020B121201004]; Guangdong Basic and Applied Basic Research
   Foundation [2020A1515110925, 2021A1515011653, 2021A1515010513];
   Guangzhou Basic and Applied Basic Research Foundation [202102020180];
   President Funding of Nanfang Hospital [2018C024]; Fundamental Research
   Funds for the Central Universities; Sun Yat-Sen University [22qntd3902];
   Thyroid Research Program of Young and Middle-aged Physicians of China
   Health Promotion Foundation
FX This work was supported by grants from the National Natural Science
   Foundation of China (81800879), Guangdong Provincial Key Laboratory of
   Precision Medicine for Gastrointestinal Cancer (2020B121201004),
   Guangdong Basic and Applied Basic Research Foundation (2020A1515110925,
   2021A1515011653, and 2021A1515010513), Guangzhou Basic and Applied Basic
   Research Foundation (202102020180), President Funding of Nanfang
   Hospital (2018C024), the Fundamental Research Funds for the Central
   Universities, Sun Yat-Sen University (22qntd3902), and Thyroid Research
   Program of Young and Middle-aged Physicians of China Health Promotion
   Foundation.
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NR 39
TC 0
Z9 0
U1 1
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD JUL 1
PY 2022
VL 2022
AR 4522974
DI 10.1155/2022/4522974
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2X9HW
UT WOS:000825508900001
PM 35814482
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU McLenachan, S
   Balaratnasingam, C
   Jeffery, RCH
   Chen, SC
   Zhang, D
   Chan, GF
   Dolz-Marco, R
   Bacci, T
   Lo, JHY
   Wiffen, SA
   Yannuzzi, LK
   Chen, FD
AF McLenachan, Samuel
   Balaratnasingam, Chandrakumar
   Jeffery, Rachael C. Heath
   Chen, Shang-Chih
   Zhang, Dan
   Chan, Geoffrey
   Dolz-Marco, Rosa
   Bacci, Tommaso
   Lo, Johnny
   Wiffen, Steven A.
   Yannuzzi, Lawrence K.
   Chen, Fred
TI Anti-retinal IgG antibodies in patients with early and advanced type 2
   macular telangiectasia
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Macular telangiectasia; MacTel-2; Anti-retinal antibodies; Retinal
   degeneration; Autoantibodies; Age-related macular degeneration; AMD;
   Western blot
ID ANTIRETINAL ANTIBODIES; AUTOANTIBODY; DEGENERATION; AUTOIMMUNITY;
   IDENTIFICATION; RETINOPATHY
AB Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti retinal antibodies in MacTel-2 patients are a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration (AMD), inherited retinal diseases (IRDs) or no retinal disease (healthy controls) were recruited as controls. Blood serum samples were screened for immunoglobulin G anti-retinal antibodies by western blotting, followed by densitometry analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and p < 0.05 considered statistically significant. Overall, anti-retinal antibody-positive cases were older (64 & nbsp;+/- 15 vs 53 & nbsp;+/- 17 years, p < 0.001) and females were more likely to develop anti-retinal antibodies (OR: 2.41, CI: 1.12-5.18). The frequency of anti-retinal antibody detection in MacTel-2 patients (n = 42, 36%) was not significantly different from healthy controls (n = 52, 25%) or IRD patients (n = 18, 25%) and the majority of MacTel-2 patients had no anti-retinal antibodies. In contrast, the frequency of anti-retinal antibody detection was significantly higher in patients with AMD (n = 15, 73%, p < 0.001). The lack of a greater anti-retinal antibody frequency or specificity in the MacTel-2 cohort suggests that antibody mediated immunological mechanisms may play a less significant role in MacTel-2 disease pathogenesis.
C1 [McLenachan, Samuel; Balaratnasingam, Chandrakumar; Jeffery, Rachael C. Heath; Chan, Geoffrey; Chen, Fred] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia.
   [McLenachan, Samuel; Balaratnasingam, Chandrakumar; Jeffery, Rachael C. Heath; Chen, Shang-Chih; Zhang, Dan; Chan, Geoffrey; Wiffen, Steven A.; Chen, Fred] L Eye Inst, Nedlands, WA, Australia.
   [Balaratnasingam, Chandrakumar] Sir Charles Gairdner Hosp, Dept Ophthalmol, Nedlands, WA, Australia.
   [Jeffery, Rachael C. Heath; Chen, Fred] Royal Perth Hosp, Dept Ophthalmol, Perth, WA, Australia.
   [Chan, Geoffrey; Dolz-Marco, Rosa; Bacci, Tommaso; Yannuzzi, Lawrence K.] Manhattan Eye Ear & Throat Hosp, Vitreous Retina Macular Consultants New York, LuEster T Mertz Retinal Res Ctr, New York, NY USA.
   [Lo, Johnny] Edith Cowan Univ, Sch Sci, Perth, WA, Australia.
   [Wiffen, Steven A.; Yannuzzi, Lawrence K.] Fremantle Hosp, Dept Ophthalmol, Fremantle, WA, Australia.
   [Chen, Fred] Univ Melbourne, Dept Surg, Ophthalmol, East Melbourne, Vic, Australia.
   [Chen, Fred] L Eye Inst, WA, 2 Verdun St, Nedlands, WA 6009, Australia.
C3 University of Western Australia; University of Western Australia; Royal
   Perth Hospital; University of Western Australia; Manhattan Eye Ear &
   Throat Hospital; Vitreous Retina Macula Consultants of New York; Edith
   Cowan University; University of Western Australia; University of
   Melbourne
RP Yannuzzi, LK (通讯作者)，Manhattan Eye Ear & Throat Hosp, Vitreous Retina Macular Consultants New York, LuEster T Mertz Retinal Res Ctr, New York, NY USA.; Yannuzzi, LK (通讯作者)，Fremantle Hosp, Dept Ophthalmol, Fremantle, WA, Australia.; Chen, FD (通讯作者)，L Eye Inst, WA, 2 Verdun St, Nedlands, WA 6009, Australia.
EM fredchen@lei.org.au
RI Bacci, Tommaso/GQA-8840-2022
OI Bacci, Tommaso/0000-0001-7477-2263; Chen, Fred/0000-0003-2809-9930;
   Wiffen, Steven/0000-0002-1077-8321; McLenachan,
   Samuel/0000-0001-5732-7387
FU Australian National Health and Medical Research Council [GNT1116360,
   GNT1188694, GNT1054712, MRF1142962]; McCusker Charitable Foundation;
   Macula Foundation; Miocevich Retina Fellowship
FX This research was supported by the Australian National Health and
   Medical Research Council under GNT1116360 (FKC), GNT1188694 (FKC),
   GNT1054712 (FKC), MRF1142962 (FKC), McCusker Charitable Foundation
   (FKC); Miocevich Retina Fellowship (RHJ); and The Macula Foundation
   (LAY). The sponsor or funding organization had no role in the design or
   conduct of this research.
CR Adamus G, 2015, INVEST OPHTH VIS SCI, V56, P1680, DOI 10.1167/iovs.14-15739
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NR 29
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAY
PY 2022
VL 218
AR 109024
DI 10.1016/j.exer.2022.109024
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0Y7ZO
UT WOS:000790605100002
PM 35271830
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Liisborg, C
   Skov, V
   Kjaer, L
   Hasselbalch, HC
   Sorensen, TL
AF Liisborg, Charlotte
   Skov, Vibe
   Kjaer, Lasse
   Hasselbalch, Hans Carl
   Sorensen, Torben Lykke
TI Patients with MPNs and retinal drusen show signs of complement system
   dysregulation and a high degree of chronic low-grade inflammation
SO ECLINICALMEDICINE
LA English
DT Article
DE Myeloproliferative neoplasms; "Human inflammation model"; Biological
   continuum; Age-related macular degeneration; Chronic low-grade
   inflammation; Complement dysregulation; Drusen; Complement regulatory
   proteins; Cytokines; Growth factors; Anaphylatoxins
ID MEMBRANE ATTACK COMPLEX; FACTOR-H POLYMORPHISM; MACULAR-DEGENERATION;
   IMMUNE-COMPLEXES; ESSENTIAL THROMBOCYTHEMIA; CIRCULATING MONOCYTES;
   POLYCYTHEMIA-VERA; CODING VARIANT; COMPONENT 3; ACTIVATION
AB Background The hematopoietic stem cell disorders, myeloproliferative neoplasms (MPNs), are characterised by chronic low-grade inflammation (CLI). Recently, we showed that patients with MPNs have an increased prevalence of drusen and age-related macular degeneration (AMD), and drusen prevalence seemed associated with higher CLI. Studying MPNs may reveal more about drusen pathophysiology. This study investigated CLI further by measuring cytokine levels and complement system markers, comparing these between patients with MPNs and AMD.
   Methods This cross-sectional study, between July 2018 and November 2020 conducted at Zealand University Hospital (ZUH) - Roskilde, Denmark, included 29 patients with neovascular AMD (nAMD), 28 with intermediate-stage AMD (iAMD), 62 with MPNs (35 with drusen - MPNd and 27 with healthy retinas - MPNn). With flow cytometry, we measured complement-regulatory-proteins (Cregs). With immunoassays, we investigated cytokine levels combined into a summary-inflammation-score (SIS).
   Findings The MPNd and nAMD groups had similar SIS, significantly higher than the MPNn and iAMD groups. Additionally, we found SIS to increase over the MPN biological continuum from early cancer stage, essential thrombocytaemia (ET), over polycythaemia vera (PV) to the late-stage primary myelofibrosis (PMF). MPNs showed signs of complement dysregulation, with Cregs expression lower in PV than ET and PMF and even lower in PV patients with drusen.
   Interpretation This study suggests that MPNd have a higher CLI than MPNn and may indicate systemic CLI to play a greater part in, and even initiate drusen formation. We suggest using MPNs as a "Human Inflammation Model" of drusen development. The CLI in MPNs elicits drusen formation, triggering more CLI creating a vicious cycle, increasing the risk of developing AMD. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
C1 [Liisborg, Charlotte; Sorensen, Torben Lykke] Zealand Univ Hosp, Dept Ophthalmol, Vestermarksvej 23, DK-4000 Roskilde, Denmark.
   [Liisborg, Charlotte; Hasselbalch, Hans Carl; Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth & Med Sci, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
   [Skov, Vibe; Kjaer, Lasse; Hasselbalch, Hans Carl] Zealand Univ Hosp, Dept Haematol, Vestermarksvej 15-17, DK-4000 Roskilde, Denmark.
C3 University of Copenhagen
RP Liisborg, C (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, Vestermarksvej 23, DK-4000 Roskilde, Denmark.; Liisborg, C (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
EM Liisborg@c.dk
OI Liisborg, Charlotte/0000-0002-6353-6027
FU Fight for Sight, Denmark; Region Zealand's research promotion fund
FX Fight for Sight, Denmark, and Region Zealand's research promotion fund.
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NR 87
TC 2
Z9 2
U1 2
U2 2
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 2589-5370
J9 ECLINICALMEDICINE
JI EClinicalMedicine
PD JAN
PY 2022
VL 43
AR 101248
DI 10.1016/j.eclinm.2021.101248
EA DEC 2021
PG 15
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA YO3NT
UT WOS:000747850800016
PM 35128362
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, YH
   Huang, C
   Tseng, YL
   Zhong, J
   Li, XM
AF Wang, Yin-hao
   Huang, Chen
   Tseng, Yu-lin
   Zhong, Jing
   Li, Xue-min
TI Refractive Error and Eye Health: An Umbrella Review of Meta-Analyses
SO FRONTIERS IN MEDICINE
LA English
DT Review
DE refractive error; umbrella review; eye health; glaucoma; cataract;
   age-related macular degeneration (AMD); diabetic retinopathy; strabismus
ID SILICONE OIL REMOVAL; OPEN-ANGLE GLAUCOMA; BLOOD-FLOW CHANGES;
   DIABETIC-RETINOPATHY; AXIAL LENGTH; RISK-FACTORS; RETINAL-DETACHMENT;
   MYOPIC RETINOPATHY; SYSTEMATIC REVIEWS; SCLERAL RIGIDITY
AB Purpose: To explore the associations between refractive errors and multiple eye health outcomes.
   Methods: This is an umbrella review based on systematic reviews with-meta-analyses. In our study, refractive errors included myopia, hyperopia, astigmatism, and anisometropia. We reconducted the meta-analyses whose primary data were available in sufficient detail by random effect model. Heterogeneity was assessed by I-2. The main outcomes included myopic macular degeneration (MMD), retinal detachment (RD), cataract, open-angle glaucoma (OAG), strabismus, age-related macular degeneration (AMD), and diabetic retinopathy (DR).
   Results: Myopia was associated with increased risk of MMD (relative risk = 102.11, 95% CI 52.6-198.22), RD (3.45, 1.08-11.00), nuclear cataract (2.15, 1.53-3.03), posterior subcapsular (PSC) cataract (1.74, 1.41-2.15), OAG (1.95, 1.74-2.19), exotropia (5.23, 2.26-12.09), but decreased risk of DR (0.83, 0.66-1.04), and early AMD (0.80, 0.67-0.94). From mild-to-high myopia, the association strengthened for MMD, RD, nuclear cataract, PSC cataract, OAG, and DR. Hyperopia was associated with an increased risk of early AMD (1.09, 1.01-1.18) and esotropia (22.94, 10.20-51.62). Astigmatism and anisometropia were associated with increased risk of both exotropia and esotropia.
   Conclusions: Myopia, especially high myopia, demonstrated the highest risk for eye health outcomes, such as MMD, RD, OAG, nuclear and PSC cataracts, and exotropia. However, myopia was associated with a lower risk of early AMD and DR. Individuals with hyperopia are more likely to suffer early AMD and esotropia. Astigmatism and anisometropia predispose to strabismus. A lot of research studies on the mechanism of the associations are needed.
C1 [Wang, Yin-hao; Huang, Chen; Tseng, Yu-lin; Zhong, Jing; Li, Xue-min] Peking Univ Third Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Wang, Yin-hao; Tseng, Yu-lin; Zhong, Jing; Li, Xue-min] Peking Univ Third Hosp, Beijing Key Lab Restorat Damaged Ocular Nerve, Beijing, Peoples R China.
   [Huang, Chen] Peking Univ Third Hosp, Ctr Basic Med Res, Beijing, Peoples R China.
C3 Peking University
RP Li, XM (通讯作者)，Peking Univ Third Hosp, Dept Ophthalmol, Beijing, Peoples R China.; Li, XM (通讯作者)，Peking Univ Third Hosp, Beijing Key Lab Restorat Damaged Ocular Nerve, Beijing, Peoples R China.
EM lxmlxm66@sina.com
FU National Science Foundation of Beijing Municipality [7202229]
FX This study was supported by the National Science Foundation of Beijing
   Municipality [grant number: 7202229].
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NR 81
TC 1
Z9 1
U1 5
U2 8
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 NOV 4
PY 2021
VL 8
AR 759767
DI 10.3389/fmed.2021.759767
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA ZO9GH
UT WOS:000766035000001
PM 34805225
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Swampillai, AJ
   Kaabneh, AK
   Habib, NE
   Hamer, C
   Buckhurst, PJ
AF Swampillai, Andrew J.
   Kaabneh, Ali Khanan
   Habib, Nabil E.
   Hamer, Catriona
   Buckhurst, Phillip J.
TI Efficacy of toric intraocular lens implantation with high corneal
   astigmatism within the United Kingdom's National Health Service
SO EYE
LA English
DT Article
ID CATARACT-SURGERY; INCISIONS
AB Objectives To determine the efficacy of toric intraocular lens (TIOL) implantation in cataract surgery patients with high levels of pre-operative corneal astigmatism and ocular co-morbidities in a state funded, National Health Service (NHS) hospital. Methods Retrospective cohort study involving consecutive cases of TIOL implantation in cataract surgery with over 3.00DC of pre-operative corneal astigmatism. Subjects were implanted with the Tecnis TIOL (Abbot Medical Optics) with capsular tension ring stabilisation using the Callisto system (Carl Zeiss Meditec). Visual acuity and refraction were assessed at 4-6 weeks post-operatively. Vector analysis was used to calculate the intended refractive correction, surgically induced refractive correction (SIRC), correction ratio (CR), error of magnitude (EM) and error vector (EV). Results Sixty-six eyes of forty-seven subjects aged 73.8 +/- 11.9 were included. Eyes with ocular co-morbidities included dry age-related macular degeneration (n = 13), amblyopia (n = 7), high myopia (n = 7), glaucoma (n = 6), previous corneal transplantation (n = 2), nanophthalmos (n = 2) and corneal scarring (n = 1). Pre-operative corneal astigmatism was 4.25 +/- 1.69DC (range 3.00-12.00), post-operative refractive astigmatism was 1.31 +/- 1.05DC (range 0.00-6.50DC) and post-operative unaided visual acuity was 0.25 +/- 0.19 LogMAR. Vector analysis demonstrated an SIRC of 4.08 +/- 1.39DC, CR = 1.1 +/- 0.3, EM -0.4 +/- 1.0 and EV of 1.23 +/- 0.72. Conclusions The results demonstrate the efficacy of TIOL implantation in patients with high corneal astigmatism and provide strong evidence advocating their use in cataract surgery within a state funded hospital eye service. Refractive astigmatism was significantly lower than the pre-operative corneal astigmatism and a low error vector was achieved relative to the magnitude of correction.
C1 [Swampillai, Andrew J.; Kaabneh, Ali Khanan; Habib, Nabil E.] Univ Hosp Plymouth NHS Trust, Royal Eye Infirm, Plymouth, Devon, England.
   [Hamer, Catriona; Buckhurst, Phillip J.] Plymouth Univ, Sch Hlth Profess, Plymouth, Devon, England.
C3 University of Plymouth
RP Buckhurst, PJ (通讯作者)，Plymouth Univ, Sch Hlth Profess, Plymouth, Devon, England.
EM phillip.buckhurst@plymouth.ac.uk
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NR 29
TC 4
Z9 4
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 JUN
PY 2020
VL 34
IS 6
BP 1142
EP 1148
DI 10.1038/s41433-019-0744-0
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LR9NJ
UT WOS:000536021600025
PM 31844167
OA Bronze, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Majithia, S
   Tham, YC
   Chee, ML
   Teo, CL
   Chee, ML
   Dai, W
   Kumari, N
   Lamoureux, EL
   Sabanayagam, C
   Wong, TY
   Cheng, CY
AF Majithia, Shivani
   Tham, Yih Chung
   Chee, Miao Li
   Teo, Cong Ling
   Chee, Miao-Ling
   Dai, Wei
   Kumari, Neelam
   Lamoureux, Ecosse Luc
   Sabanayagam, Charumathi
   Wong, Tien Yin
   Cheng, Ching-Yu
TI Singapore Chinese Eye Study: key findings from baseline examination and
   the rationale, methodology of the 6-year follow-up series
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE epidemiology; eye (globe); vision
ID VISUAL IMPAIRMENT; MACULAR DEGENERATION; RISK-FACTORS;
   DIABETIC-RETINOPATHY; ADULT-POPULATION; RURAL-COMMUNITY; PREVALENCE;
   GLAUCOMA; DISEASES; URBAN
AB Background/aims
   In order to address the eye care needs of the increasing numbers of elderly Chinese globally, there is a need for comprehensive understanding on the longitudinal trends of age-related eye diseases among Chinese. We herein report the key findings from the baseline Singapore Chinese Eye Study (SCES-1), and describe the rationale and methodology of the 6-year follow-up study (SCES-2).
   Methods
   3353 Chinese adults who participated in the baseline SCES-1 (2009-2011) were invited for the 6-year follow-up SCES-2 (2015-2017). Examination procedures for SCES-2 included standardised ocular, systemic examinations and questionnaires identical to SCES-1. SCES-2 further included new examinations such as optical coherence tomography angiography, and questionnaires to evaluate health impact and economic burden of eye diseases.
   Results
   In SCES-1, the age-adjusted prevalence of best-corrected low vision (VA<6/12, better-seeing eye) and blindness (VA<6/60, better-seeing eye) were 3.4% and 0.2%, respectively. The prevalence rates for glaucoma, age related macular degeneration, and diabetic retinopathy (among diabetics) were 3.2%, 6.8%, 26.2%, respectively. Of the 3033 eligible individuals from SCES-1, 2661 participated in SCES-2 (response rate=87.7%). Comparing with those who did not attend SCES-2, those attended were younger, had higher SES (all p<0.001), but less likely to be a current smoker, to have diabetes, hypertension, hyperlipidaemia (all p <= 0.025).
   Conclusions
   Building on SCES-1, SCES-2 will be one of the few longitudinal population-based eye studies to report incidence, progression, and risk factors of major age-related eye diseases. Findings from this cohort may offer new insights, and provide useful reference information for other Chinese populations elsewhere.
C1 [Majithia, Shivani; Tham, Yih Chung; Chee, Miao Li; Teo, Cong Ling; Chee, Miao-Ling; Dai, Wei; Kumari, Neelam; Lamoureux, Ecosse Luc; Sabanayagam, Charumathi; Wong, Tien Yin; Cheng, Ching-Yu] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Ocular Epidemiol, Singapore, Singapore.
   [Tham, Yih Chung; Lamoureux, Ecosse Luc; Sabanayagam, Charumathi; Wong, Tien Yin; Cheng, Ching-Yu] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
   [Kumari, Neelam] Singapore Khoo Teck Puat Hosp, Ophthalmol, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore
RP Cheng, CY (通讯作者)，Singapore Eye Res Inst, Ocular Epidemiol Res Grp, Singapore 169856, Singapore.
EM chingyu.cheng@duke-nus.edu.sg
RI Cheng, Ching-Yu/Y-2229-2019; Chung, Yih/AIF-2414-2022; Sabanayagam,
   Charumathi/C-1294-2011; Wong, Tien Yin/AAC-9724-2020
OI Cheng, Ching-Yu/0000-0003-0655-885X; Chung, Yih/0000-0002-6752-797X;
   Sabanayagam, Charumathi/0000-0002-4042-4719; Wong, Tien
   Yin/0000-0002-8448-1264
FU National Medical Research Council [NMRC/CIRG/1417/2015]
FX The study is funded by the National Medical Research Council
   (NMRC/CIRG/1417/2015).
CR Ansah JP, 2018, ANN ACAD MED SINGAP, V47, P13
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NR 32
TC 16
Z9 16
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 2020
VL 104
IS 5
BP 610
EP 615
DI 10.1136/bjophthalmol-2019-314760
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LL2KF
UT WOS:000531384100004
PM 31401553
DA 2022-11-30
ER

PT J
AU Grau, E
   Horn, F
   Nixdorff, U
   Michelson, G
AF Grau, Elisabeth
   Horn, F.
   Nixdorff, U.
   Michelson, G.
TI OCT and IOP findings in a healthy worker cohort: results from a
   teleophthalmic study in occupational medicine
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Teleophthalmology; Occupational medicine; OCT scan; IOP; RNFL
ID NERVE-FIBER LAYER; OPEN-ANGLE GLAUCOMA; OPTICAL COHERENCE TOMOGRAPHY;
   INTRAOCULAR-PRESSURE; EPIRETINAL MEMBRANES; RISK-FACTORS; HYPERTENSIVE
   RETINOPATHY; MACULAR DEGENERATION; GLOBAL PREVALENCE; THICKNESS
AB Purpose To avoid significant loss of vision in employees, the working population could be examined with ophthalmic methods as OCT and IOP measurement for detection of serious eye diseases. The value of "virtual eye clinics" in occupational preventive medicine has been previously shown. We used a telemedical approach to gather epidemiological information about prevalence of eye diseases such as glaucoma, ocular hypertension, hypertensive retinopathy, diabetic retinopathy, epiretinal membrane, AMD, adult vitelliform maculopathy, cystoid maculopathy, choroidal nevi, and macular drusen. Methods The study included 931 people ranging from age 39 to 65 years. Using a telemedical approach, all medical examinations and the ophthalmic examination were performed by a technician using an optical coherence tomography (SD-OCT) and a pulse air tonometer. The data were saved in the web-based patient chart MedStage (R) of the Talkingeyes (R) Collaboration Network. Results We found a high prevalence of eye diseases in a group representative for the working-age population by telemedical examination. 13.47% of the workers examined showed ocular findings necessitating treatment or control by an ophthalmologist, including ocular hypertension (5.7%), hypertensive retinopathy with loss of temporal retinal nerve fiber thickness (2.3%), epiretinal membrane (1.07%), glaucoma (0.97%), age-related macular degeneration and adult vitelliform maculopathy (0.53%), and diabetic retinopathy (0.2%). Two of the examined persons presented ocular findings requiring urgent treatment to prevent serious vision loss. Conclusion Using a telemedical approach, we collected epidemiological information about prevalence of eye diseases in the working-age population. Virtual eye clinics in occupational preventive medicine are a useful method to improve sight and reduce vision loss of workers by reducing travel time and inconvenience associated with an in-person appointment with an ophthalmologist.
C1 [Grau, Elisabeth; Horn, F.; Michelson, G.] Friedrich Alexander Univ, Interdisciplinary Ctr Prevent Med, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany.
   [Nixdorff, U.] European Prevent Ctr, Luise Rainer Str 6-10, D-40235 Dusseldorf, Germany.
   [Michelson, G.] Talkingeyes&More GmbH, Henkestr 91, D-91052 Erlangen, Germany.
C3 University of Erlangen Nuremberg
RP Grau, E (通讯作者)，Friedrich Alexander Univ, Interdisciplinary Ctr Prevent Med, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany.
EM Elisabeth.Grau@gmx.net
RI Nixdorff, Uwe/ABC-3298-2020
OI Grau, Elisabeth/0000-0002-1707-7763
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NR 52
TC 5
Z9 6
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD NOV
PY 2019
VL 257
IS 11
BP 2571
EP 2578
DI 10.1007/s00417-019-04457-1
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JI6YO
UT WOS:000493612800023
PM 31489489
DA 2022-11-30
ER

PT J
AU Al-Hity, A
   Steel, DH
   Yorston, D
   Gilmour, D
   Koshy, Z
   Young, D
   Hillenkamp, J
   McGowan, G
AF Al-Hity, Aws
   Steel, David H.
   Yorston, David
   Gilmour, David
   Koshy, Zachariah
   Young, David
   Hillenkamp, Jost
   McGowan, Gerard
TI Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish
   Ophthalmic Surveillance Unit (SOSU) study
SO EYE
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; CHOROIDAL NEOVASCULAR LESIONS; ENDOTHELIAL
   GROWTH-FACTOR; MACULAR DEGENERATION; INTRAVITREAL; RANIBIZUMAB;
   SECONDARY; ENDOPHTHALMITIS; EPIDEMIOLOGY; VITRECTOMY
AB Purpose Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD.
   Methods A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded.
   Results Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days.
   Conclusions The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented.
C1 [Al-Hity, Aws; Steel, David H.; Gilmour, David; McGowan, Gerard] Gartnavel Royal Hosp, Tennent Inst Ophthalmol, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
   [Yorston, David] Sunderland Eye Infirm, Sunderland, England.
   [Yorston, David] Newcastle Univ, Inst Genet Med, Newcastle, NSW, Australia.
   [Koshy, Zachariah] Univ Hosp Ayr, Ayr, Scotland.
   [Young, David] Univ Strathclyde, Dept Math & Stat, Glasgow, Lanark, Scotland.
   [Hillenkamp, Jost] Univ Kiel, Kiel, Germany.
C3 Gartnavel Royal Hospital; University of Newcastle; University of
   Strathclyde; University of Kiel
RP Al-Hity, A (通讯作者)，Gartnavel Royal Hosp, Tennent Inst Ophthalmol, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
EM alhitya@gmail.com
RI ; Steel, David/I-8053-2015
OI Young, David/0000-0002-3652-0513; Steel, David/0000-0001-8734-3089
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NR 26
TC 6
Z9 6
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 MAR
PY 2019
VL 33
IS 3
BP 486
EP 491
DI 10.1038/s41433-018-0239-4
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN9UD
UT WOS:000460544800023
PM 30374150
OA Green Accepted, Green Published, Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Nayak, K
   Misra, M
AF Nayak, Kritika
   Misra, Manju
TI A review on recent drug delivery systems for posterior segment of eye
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Review
DE Trans-scleral; Drug delivery system; Nano-formulations; Posterior
   segment of eye
ID DEXAMETHASONE IMPLANT OZURDEX(R); SUPRACHOROIDAL SPACE; OCULAR DELIVERY;
   IN-VIVO; TRIAMCINOLONE ACETONIDE; INTRAVITREAL INJECTION;
   SUSTAINED-RELEASE; RETINAL DISEASES; CLINICAL-TRIAL; GENE DELIVERY
AB Eye is the unique sense organ with complex and sophisticated anatomy and physiology. Being most instrumental for vision, it is secured by varied protective barriers; ranging from static (membranous) to dynamic (vascular) barrier. Although these barriers are very efficient to protect eye from exogenous substances and external stress, it is caught by various irreversible vision impairing ailments like cataract, conjunctivitis, glaucoma, uveitis, diabetic retinopathy (DR), diabetic macular edema (DME), age related macular degeneration (AMD), cytomegalovirus (CMV) retinitis, retinitis pigmentosa (RP), retinal vein occlusion (RVO), endophthalmitis affecting both anterior and posterior segment of eye. The treatment needed to reach the site of action is restricted by its characteristic barriers. The protective mechanism turns into hurdles when it comes to drug delivery especially in case of posterior segment of eye. Most common and preferable routes for ocular drug delivery are topical and systemic routes owing to their compliance and non-invasive nature, however they turned inefficient in delivering drugs to posterior segment. Currently, other local routes like intraocular and periocular (subconjunctival, sub-tenon, posterior juxtascleral, retrobulbar, peribulbar) are being explored and are showing positive outcomes in terms of symptomatic relief for a certain time period. But as these are invasive techniques, they also have some hidden long-term drawbacks on other side. Various advancements have been achieved till date in delivery of drug to posterior segment of eye, however despite these advancements; there is need of non-invasive or preferably less invasive technique considering prolonged treatments for such ailments. At times, dependency on invasive techniques may cause problems like patient incompliance, inflammation, contact cataract, retinal detachment, endophthalmitis etc. Here, in this review, barriers in ocular delivery, routes and recent advances in drug delivery to eye including patented commercial formulations with emphasis on posterior segment will be discussed.
C1 [Nayak, Kritika; Misra, Manju] NIPER, Dept Pharmaceut, Opposite AirForce Stn,Palaj Basan Rd, Gandhinagar 382355, Gujarat, India.
C3 National Institute of Pharmaceutical Education & Research (NIPER)
RP Misra, M (通讯作者)，NIPER, Dept Pharmaceut, Opposite AirForce Stn,Palaj Basan Rd, Gandhinagar 382355, Gujarat, India.
EM manju@niperahm.ac.in
RI Misra, Manju/AAQ-2964-2021; Nayak, Kritika/B-1696-2017; Misra,
   Manju/GRO-1395-2022
OI Misra, Manju/0000-0002-5907-4659; Nayak, Kritika/0000-0002-7332-1716;
   Misra, Manju/0000-0002-5907-4659
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NR 139
TC 89
Z9 92
U1 9
U2 87
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 NOV
PY 2018
VL 107
BP 1564
EP 1582
DI 10.1016/j.biopha.2018.08.138
PG 19
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA GU1PC
UT WOS:000445036200173
PM 30257375
DA 2022-11-30
ER

PT J
AU Barthelmes, D
   Nguyen, V
   Walton, R
   Gillies, MC
   Daien, V
AF Barthelmes, Daniel
   Vuong Nguyen
   Walton, Richard
   Gillies, Mark C.
   Daien, Vincent
CA Fight Retinal Blindness Study Grp
TI A pharmacoepidemiologic study of ranibizumab and aflibercept use
   2013-2016. The Fight Retinal Blindness! Project
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Ranibizumab; Aflibercept; Neovascular age-related macular degeneration;
   Pharmacoepidemiology
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; VEGF-TRAP; INHIBITORS;
   BEVACIZUMAB; INJECTION; OUTCOMES; BINDING
AB To report 12-month pharmacoepidemiologic data on aflibercept and ranibizumab use in treatment-na < ve eyes with neovascular age-related macular degeneration (nAMD).
   Participants were treatment-na < ve eyes with nAMD tracked by the Fight Retinal Blindness! registry starting therapy with aflibercept or ranibizumab treatment between January 1st, 2013 and 31st December, 2016. Demographic and clinical characteristics were compared between treatment groups.
   During the study period, 689 eyes initiated treatment with ranibizumab compared to 568 with aflibercept. We found a similar rate of use of both drugs. Ranibizumab-treated patients were older than aflibercept-treated patients (overall mean [SD] 82.0 [8.4] vs. 78.6 [8.1], P < 0.001). Median (Q1, Q3) lesion size was significantly larger in aflibercept-treated patients (2450 mu m [1242, 3000]) compared with ranibizumab patients (2000 mu m [1148, 2890], P = 0.008). Eyes treated with ranibizumab and aflibercept received a similar mean number of injections in the first 3 months (3.1 [0.7] vs. 3.0 [0.6]; P = 0.233) and at 12 months (7.3 [2.4] vs. 7.2 [2.2]; P = 0.139). The 12-month switching rates from 2013 onwards for eyes completing 12 months of follow-up were much higher for switching from ranibizumab to aflibercept (19.2%) compared with switching from aflibercept to ranibizumab (5.4%). The proportion of eyes that did not complete 12 months of treatment was 23.2% for ranibizumab and 22.2% for aflibercept-treated groups.
   A similar rate of use for ranibizumab and aflibercept among Australian practitioners was observed between 2013 and 2016. Ranibizumab was used more often in older patients while aflibercept tended to be used more often in eyes with larger lesions.
C1 [Barthelmes, Daniel] Univ Zurich, Univ Zurich Hosp, Dept Ophthalmol, Zurich, Switzerland.
   [Barthelmes, Daniel; Vuong Nguyen; Walton, Richard; Gillies, Mark C.; Daien, Vincent] Univ Sydney, Save Sight Inst, Sydney Med Sch, Sydney, NSW, Australia.
   [Daien, Vincent] Montpellier Univ Hosp, Dept Ophthalmol, Montpellier, France.
   [Daien, Vincent] Natl Inst Hlth & Med Res, INSERM, Unit 1061, Villejuif, France.
C3 University of Zurich; University Zurich Hospital; University of Sydney;
   Universite de Montpellier; CHU de Montpellier; Institut National de la
   Sante et de la Recherche Medicale (Inserm)
RP Daien, V (通讯作者)，Univ Sydney, Save Sight Inst, Sydney Med Sch, Sydney, NSW, Australia.; Daien, V (通讯作者)，Montpellier Univ Hosp, Dept Ophthalmol, Montpellier, France.; Daien, V (通讯作者)，Natl Inst Hlth & Med Res, INSERM, Unit 1061, Villejuif, France.
EM vincent.daien@sydney.edu.au
RI DAIEN, Vincent/Z-5516-2019
OI DAIEN, Vincent/0000-0001-5675-0861; Nguyen, Vuong/0000-0001-9070-9803
FU Royal Australian NZ College of Ophthalmologists Eye Foundation; National
   Health and Medical Research Council, Australia (NHMRC 2010-2012);
   Macular Disease Foundation, Australia; Novartis; Bayer
FX This study was 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 Macular Disease Foundation, Australia.
   Funding was also provided by Novartis and Bayer. These sponsors had no
   role in the design or conduct of this research.
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NR 27
TC 10
Z9 10
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2018
VL 256
IS 10
BP 1839
EP 1846
DI 10.1007/s00417-018-4061-2
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GT7XF
UT WOS:000444744500007
PM 30051312
DA 2022-11-30
ER

PT J
AU Li, Y
   Busoy, JM
   Zaman, BA
   Tan, QSW
   Tan, GSW
   Barathi, VA
   Cheung, N
   Wei, JJY
   Hunziker, W
   Hong, WJ
   Wong, TY
   Cheung, CMG
AF Li, Yong
   Busoy, Joanna Marie
   Zaman, Ben Alfyan Achirn
   Tan, Queenie Shu Woon
   Tan, Gavin Siew Wei
   Barathi, Veluchamy Amutha
   Cheung, Ning
   Wei, Jay Ji-Ye
   Hunziker, Walter
   Hong, Wanjin
   Wong, Tien Yin
   Cheung, Chui Ming Gemmy
TI A novel model of persistent retinal neovascularization for the
   development of sustained anti-VEGF therapies
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal neovascularization; Anti-VEGF therapy; DL-Alpha-aminoadipic
   acid; Muller cells; Persistence of leakage; Rabbit model
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; DIABETIC-RETINOPATHY; CONE
   PHOTORECEPTORS; GLOBAL PREVALENCE; RABBIT RETINA; CELLS; PERMEABILITY;
   PATHOLOGIES; RANIBIZUMAB; COMBINATION
AB Anti-vascular endothelial growth factor (VEGF) therapies lead to a major breakthrough in treatment of neovascular retinal diseases such as age-related macular degeneration or diabetic retinopathy. Current management of these conditions require regular and frequent intravitreal injections to prevent disease recurrence once the effect of the injected drug wears off. This has led to a pressing clinical need of developing sustained release formulations or therapies with longer duration. A major drawback in developing such therapies is that the currently available animal models show spontaneous regression of vascular leakage. They therefore not only fail to recapitulate retinal vascular disease in humans, but also prevent to discern if regression is due to prolonged therapeutic effect or simply reflects spontaneous healing.
   Here, we described the development of a novel rabbit model of persistent retinal neovascularization (PRNV). Retinal Muller glial are essential for maintaining the integrity of the blood-retinal barrier. Intravitreal injection of DL-alpha-aminoadipic acid (DL-AAA), a selective retinal glial (Miiller) cell toxin, results in persistent vascular leakage for up to 48 weeks. We demonstrated that VEGF concentrations were significantly increased in vitreous suggesting VEGF plays a significant role in mediating the leakage observed. Intravitreal administration of anti-VEGF drugs (e.g. bevacizumab, ranibizumab and aflibercept) suppresses vascular leakage for 8-10 weeks, before recurrence of leakage to pre-treatment levels. All three anti-VEGF drugs are very effective in re-ducing angiographic leakage in PRNV model, and aflibercept demonstrated a longer duration of action compared with the others, reminiscent of what is observed with these drugs in human in the clinical setting. Therefore, this model provides a unique tool to evaluate novel anti-VEGF formulations and therapies with respect to their duration of action in comparison to the currently used drugs.
C1 [Li, Yong; Zaman, Ben Alfyan Achirn; Tan, Queenie Shu Woon; Wei, Jay Ji-Ye; Hunziker, Walter; Hong, Wanjin] ASTAR, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore.
   [Li, Yong; Busoy, Joanna Marie; Tan, Gavin Siew Wei; Barathi, Veluchamy Amutha; Cheung, Ning; Wei, Jay Ji-Ye; Wong, Tien Yin; Cheung, Chui Ming Gemmy] Singapore Eye Res Inst, Academia, 20 Coll Rd,Level 6,Discovery Tower, Singapore 169856, Singapore.
   [Li, Yong; Busoy, Joanna Marie; Tan, Gavin Siew Wei; Barathi, Veluchamy Amutha; Cheung, Ning; Wei, Jay Ji-Ye; Wong, Tien Yin; Cheung, Chui Ming Gemmy] Singapore Natl Eye Ctr, 11 Third Hosp Ave,SNEC Bldg, Singapore 168751, Singapore.
   [Wong, Tien Yin] Duke NUS Med Sch, 8 Coll Rd, Singapore 169857, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of
   Molecular & Cell Biology (IMCB); National University of Singapore;
   Singapore National Eye Center; Singapore National Eye Center; National
   University of Singapore
RP Li, Y (通讯作者)，ASTAR, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore.; Li, Y (通讯作者)，Singapore Eye Res Inst, Academia, 20 Coll Rd,Level 6,Discovery Tower, Singapore 169856, Singapore.
EM lyong@imcb.a-star.edu.sg
RI Hunziker, Walter/B-3140-2010; Wong, Tien Yin/AAC-9724-2020; Hunziker,
   Walter/GSM-8190-2022
OI Hunziker, Walter/0000-0002-5265-4933; Wong, Tien
   Yin/0000-0002-8448-1264; Cheung, Chui Ming Gemmy/0000-0003-3358-3516
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NR 41
TC 22
Z9 21
U1 1
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 SEP
PY 2018
VL 174
BP 98
EP 106
DI 10.1016/j.exer.2018.05.027
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GU0HT
UT WOS:000444931100010
PM 29852133
DA 2022-11-30
ER

PT J
AU Nuzzi, R
   Scalabrin, S
   Becco, A
   Panzica, G
AF Nuzzi, Raffaele
   Scalabrin, Simona
   Becco, Alice
   Panzica, Giancarlo
TI Gonadal Hormones and Retinal Disorders: A Review
SO FRONTIERS IN ENDOCRINOLOGY
LA English
DT Review
DE gonadal hormones; estrogens; hormone therapy; eye disorders;
   retinopathies; optic nerve; age-related macular degeneration;
   sex-related differences
ID AGE-RELATED MACULOPATHY; OPEN-ANGLE GLAUCOMA; OCULAR BLOOD-FLOW; CENTRAL
   SEROUS CHORIORETINOPATHY; FEMALE REPRODUCTIVE FACTORS; LONG-TERM
   INCIDENCE; CONE CELL-DEATH; MACULAR DEGENERATION; RISK-FACTORS;
   REPLACEMENT THERAPY
AB Aim: Gonadal hormones are essential for reproductive function, but can act on neural and other organ systems, and are probably the cause of the large majority of known sex differences in function and disease. The aim of this review is to provide evidence for this hypothesis in relation to eye disorders and to retinopathies in particular.
   Methods: Epidemiological studies and research articles were reviewed.
   Results: Analysis of the biological basis for a relationship between eye diseases and hormones showed that estrogen, androgen, and progesterone receptors are present throughout the eye and that these steroids are locally produced in ocular tissues. Sex hormones can have a neuroprotective action on the retina and modulate ocular blood flow. There are differences between the male and the female retina; moreover, sex hormones can influence the development (or not) of certain disorders. For example, exposure to endogenous estrogens, depending on age at menarche and menopause and number of pregnancies, and exposure to exogenous estrogens, as in hormone replacement therapy and use of oral contraceptives, appear to protect against age-related macular degeneration (both drusenoid and neurovascular types), whereas exogenous testosterone therapy is a risk factor for central serous chorioretinopathy. Macular hole is more common among women than men, particularly in postmenopausal women probably owing to the sudden drop in estrogen production in later middle age. Progestin therapy appears to ameliorate the course of retinitis pigmentosa. Diabetic retinopathy, a complication of diabetes, may be more common among men than women.
   Conclusion: We observed a correlation between many retinopathies and sex, probably as a result of the protective effect some gonadal hormones may exert against the development of certain disorders. This may have ramifications for the use of hormone therapy in the treatment of eye disease and of retinal disorders in particular.
C1 [Nuzzi, Raffaele; Scalabrin, Simona; Becco, Alice] Univ Turin, Dept Surg Sci, Eye Clin, Turin, Italy.
   [Panzica, Giancarlo] Univ Turin, Dept Neurosci Rita Levi Montalcini, Lab Neuroendocrinol, Turin, Italy.
   [Panzica, Giancarlo] NICO, Orbassano, Italy.
C3 University of Turin; University of Turin
RP Nuzzi, R (通讯作者)，Univ Turin, Dept Surg Sci, Eye Clin, Turin, Italy.
EM raffaele.nuzzi@unito.it
RI Panzica, Giancarlo/C-2685-2008; Panzica, GianCarlo/I-1257-2019
OI Panzica, Giancarlo/0000-0002-9302-4647; Panzica,
   GianCarlo/0000-0002-9302-4647
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NR 166
TC 47
Z9 48
U1 0
U2 17
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-2392
J9 FRONT ENDOCRINOL
JI Front. Endocrinol.
PD MAR 2
PY 2018
VL 9
AR 66
DI 10.3389/fendo.2018.00066
PG 15
WC Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism
GA FY0SK
UT WOS:000426521800001
PM 29551993
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Balaratnasingam, C
   Yannuzzi, LA
   Curcio, CA
   Morgan, WH
   Querques, G
   Capuano, V
   Souied, E
   Jung, J
   Freund, KB
AF Balaratnasingam, Chandrakumar
   Yannuzzi, Lawrence A.
   Curcio, Christine A.
   Morgan, William H.
   Querques, Giuseppe
   Capuano, Vittorio
   Souied, Eric
   Jung, Jesse
   Freund, K. Bailey
TI Associations Between Retinal Pigment Epithelium and Drusen Volume
   Changes During the Lifecycle of Large Drusenoid Pigment Epithelial
   Detachments
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; drusen; geographic atrophy; pigment epithelial detachment; retinal
   pigment epithelium
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY;
   HYPERREFLECTIVE FOCI; GRADING SYSTEM; EYES; EXPRESSION; LESION; DRY
AB PURPOSE. Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT).
   METHODS. Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectraldomain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE_basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity.
   RESULTS. Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6-6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm(3)/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm(3)/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE_basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001).
   CONCLUSIONS. Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.
C1 [Balaratnasingam, Chandrakumar; Yannuzzi, Lawrence A.; Jung, Jesse; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA.
   [Balaratnasingam, Chandrakumar; Yannuzzi, Lawrence A.; Jung, Jesse; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, Pk Ave,5th Floor, New York, NY 10022 USA.
   [Balaratnasingam, Chandrakumar; Morgan, William H.; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA.
   [Balaratnasingam, Chandrakumar] Univ Western Australia, Dept Physiol & Pharmacol, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA, Australia.
   [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
   [Querques, Giuseppe; Capuano, Vittorio; Souied, Eric] Univ Paris Est Creteil, Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Querques, Giuseppe; Souied, Eric] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, IRCCS, Dept Ophthalmol, Milan, Italy.
   [Jung, Jesse] East Bay Retina Consultants Inc, Oakland, CA USA.
C3 Manhattan Eye Ear & Throat Hospital; Vitreous Retina Macula Consultants
   of New York; New York University; Lions Eye Institute; University of
   Western Australia; University of Alabama System; University of Alabama
   Birmingham; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI
   Creteil; Vita-Salute San Raffaele University; IRCCS Ospedale San
   Raffaele
RP Freund, KB (通讯作者)，Vitreous Retina Macula Consultants New York, Pk Ave,5th Floor, New York, NY 10022 USA.
EM kbfnyf@aol.com
RI ; Freund, K. Bailey/V-7488-2018
OI Querques, Giuseppe/0000-0002-3292-9581; Freund, K.
   Bailey/0000-0002-7888-9773
FU LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat
   Hospital (New York, NY, USA); Macula Foundation, Inc., (New York, NY,
   USA); National Eye Institute (Bethesda, MD, USA) [EY06109]; EyeSight
   Foundation of Alabama (Birmingham, AL, USA); RANZCO Eye Foundation (New
   South Wales, Australia); Research to Prevent Blindness, Inc. (New York,
   NY, USA); NATIONAL EYE INSTITUTE [R01EY006109] Funding Source: NIH
   RePORTER
FX Supported by grants from the LuEsther T. Mertz Retinal Research Center,
   Manhattan Eye, Ear and Throat Hospital (New York, NY, USA), The Macula
   Foundation, Inc., (New York, NY, USA), the National Eye Institute
   (EY06109; Bethesda, MD, USA) Research to Prevent Blindness, Inc. (New
   York, NY, USA), EyeSight Foundation of Alabama (Birmingham, AL, USA),
   and The RANZCO Eye Foundation (New South Wales, Australia).
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NR 45
TC 68
Z9 69
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 2016
VL 57
IS 13
BP 5479
EP 5489
DI 10.1167/iovs.16-19816
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EI4ND
UT WOS:000392469600055
PM 27760262
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Eramudugolla, R
   Wood, J
   Anstey, KJ
AF Eramudugolla, Ranmalee
   Wood, Joanne
   Anstey, Kaarin J.
TI Co-morbidity of depression and anxiety in common age-related eye
   diseases: a population-based study of 662 adults
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE aging; vision disorders; sensory impairment; depression; anxiety;
   epidemiology
ID MACULAR DEGENERATION; VISUAL IMPAIRMENT; CATARACT-SURGERY; PSYCHOLOGICAL
   DISTRESS; COGNITIVE IMPAIRMENT; OLDER-PEOPLE; RISK-FACTORS; VISION;
   SYMPTOMS; DISABILITY
AB This study examined the prevalence of co-morbid age-related eye disease and symptoms of depression and anxiety in late life, and the relative roles of visual function and disease in explaining symptoms of depression and anxiety. A community-based sample of 662 individuals aged over 70 years was recruited through the electoral roll. Vision was measured using a battery of tests including high and low contrast visual acuity, contrast sensitivity, motion sensitivity, stereoacuity, Useful Field of View, and visual fields. Depression and anxiety symptoms were measured using the Goldberg scales. The prevalence of self-reported eye disease [cataract, glaucoma, or age-related macular degeneration (AMD)] in the sample was 43.4%, with 7.7% reporting more than one form of ocular pathology. Of those with no eye disease, 3.7% had clinically significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3% among those with glaucoma, and 10.5% for AMD. Generalized linear models adjusting for demographics, general health, treatment, and disability examined self-reported eye disease and visual function as correlates of depression and anxiety. Depressive symptoms were associated with cataract only, AMD, comorbid eye diseases and reduced low contrast visual acuity. Anxiety was significantly associated with self-reported cataract, and reduced low contrast visual acuity, motion sensitivity and contrast sensitivity. We found no evidence for elevated rates of depressive or anxiety symptoms associated with self-reported glaucoma. The results support previous findings of high rates of depression and anxiety in cataract and AMD, and in addition show that mood and anxiety are associated with objective measures of visual function independently of self-reported eye disease. The findings have implications for the assessment and treatment of mental health in the context of late-life visual impairment.
C1 [Eramudugolla, Ranmalee; Anstey, Kaarin J.] Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT 0200, Australia.
   [Wood, Joanne] Queensland Univ Technol, Fac Hlth, Sch Optometry & Vis Sci, Brisbane, Qld 4001, Australia.
C3 Australian National University; Queensland University of Technology
   (QUT)
RP Eramudugolla, R (通讯作者)，Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, ANU Coll Med Biol & Environm, Bldg 62A,Eggleston Rd, Canberra, ACT 0200, Australia.
EM ranmalee.eramudugolla@anu.edu.au
RI Anstey, Kaarin/A-3852-2008; Eramudugolla, Ranmalee/AAL-7661-2021
OI Anstey, Kaarin/0000-0002-9706-9316; , Joanne/0000-0002-0776-7736;
   Eramudugolla, Ranmalee/0000-0001-5097-8267
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   World Health Organization (WHO), 2012, GLOBAL DATA VISUAL I
NR 52
TC 62
Z9 62
U1 0
U2 30
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD OCT 2
PY 2013
VL 5
AR 56
DI 10.3389/fnagi.2013.00056
PG 9
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 227TG
UT WOS:000325136900001
PM 24106477
OA Green Accepted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Sobaci, G
   Gungor, R
   Ozge, G
AF Sobaci, Gungor
   Gungor, Riza
   Ozge, Gokhan
TI Effects of multiple intravitreal anti-VEGF injections on retinal nerve
   fiber layer and intraocular pressure: a comparative clinical study
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE anti-VEGF; bevacizumab; ranibizumab; retinal nerve fiber layer;
   intraocular pressure; adverse effect
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; BEVACIZUMAB AVASTIN;
   RANIBIZUMAB; SAFETY; NEUROPATHY; PEGAPTANIB; AGENTS; CELLS
AB AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD).
   METHODS: This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus (TM)); IOP measurements were taken 30 minutes and 24 hours after each injection.
   RESULTS: The mean ages were 68.0 +/- 7.5 and 69.1 +/- 7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3 +/- 1.9) and (5.1 +/- 1.3) injections (P=0.07) over (13.6 +/- 2.1) and (14.05 +/- 2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3 +/- 6.9 mu m and 74.4 +/- 11.2 mu m) were not different from those in untreated eyes in the IVR group (104.6 +/- 8.4 mu m and 75.1 +/- 12.6 mu m) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8 +/- 8.1 mu m and 74.5 +/- 11.8 mu m) were not different from those in untreated eyes in the IVB group (104.6 +/- 8 mu m and 74.8 +/- 12.9 mu m) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P =0.16) were comparable between groups.
   CONCLUSION: Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.
C1 [Sobaci, Gungor; Gungor, Riza; Ozge, Gokhan] GATA Med Sch, Dept Ophthalmol, Ankara, Turkey.
C3 Gulhane Military Medical Academy
RP Sobaci, G (通讯作者)，GATA Med Sch, Dept Ophthalmol, Ankara, Turkey.
EM gsobaci@hotmail.com
RI Sobaci, Gungor/H-6080-2015
OI Sobaci, Gungor/0000-0002-3533-0224; Ozge, Gokhan/0000-0003-0943-8917
CR Adelman RA, 2010, J OCUL PHARMACOL TH, V26, P105, DOI 10.1089/jop.2009.0076
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NR 28
TC 25
Z9 29
U1 0
U2 5
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 APR 18
PY 2013
VL 6
IS 2
BP 211
EP 215
DI 10.3980/j.issn.2222-3959.2013.02.20
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 129VY
UT WOS:000317873300020
PM 23638426
DA 2022-11-30
ER

PT J
AU Kim, JH
   Im, GH
   Yoon, J
   Yang, J
   Chung, JJ
   Cha, JH
   Kim, SI
   Ham, DI
   Lee, JH
AF Kim, Jae-Hun
   Im, Geun Ho
   Yoon, Jaemoon
   Yang, Jehoon
   Chung, Julius Juhyun
   Cha, Ji Hoon
   Kim, Sun I.
   Ham, Don-il
   Lee, Jung Hee
TI Dynamic Contrast-Enhanced MRI for Assessing Therapeutic Response of
   Choroidal Neovascularization in a Rat Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BLOOD-RETINAL BARRIER; ANTIANGIOGENIC AGENT KR-31831; MACULAR
   DEGENERATION; PARAMETERS; PERMEABILITY; BEVACIZUMAB; DTPA
AB PURPOSE. We evaluated the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a noninvasive biomarker of choroidal neovascularization (CNV) and its utility as a tool for monitoring therapeutic response in laser-induced rat CNV models.
   METHODS. CNV was induced in the right eyes of 14 rats using a laser. Rats (n = 7) were treated daily for 14 days with a candidate drug (KR-31831, 50 mg/kg of body weight) having antiangiogenic effects, whereas control rats (n - 7) were treated with the vehicle alone (10% cremophor, 10% absolute ethyl alcohol, and 80% saline). DCE-MRI examinations were performed on the day before surgery (D - 1), and 3, 7, and 14 days after surgery (D + 3, D + 7, and D + 14), from which pharmacokinetic parameters (K-trans, v(e), v(p)) were calculated. Angiography was performed to visualize CNV using FITC-labeled high molecular weight dextran after MRI on D + 14. The paired Wilcoxon test and Mann-Whitney U test were performed for statistical analysis.
   RESULTS. The K-trans and v(e) values of the CNV-induced right eyes were significantly higher than those of the intact eyes in control rats at D+14 (P < 0.05). In the CNV-induced eyes, the relative K-trans and v(e) values of the KR-31831-treated group were significantly lower than those of the nontreated group at D + 14 (P < 0.05). The angiography showed that decreased CNV was observed in rats treated with KR-31831.
   CONCLUSIONS. Quantitative DCE-MRI produces noninvasive biomarker of CNV, thus allowing monitoring of therapeutic response of antiangiogenic drugs in neovascular age-related macular degeneration (AMD). (Invest Ophthalmol Vis Sci. 2012;53:7693-7700) DOI:10.1167/iovs.12-9805
C1 [Kim, Jae-Hun; Cha, Ji Hoon; Lee, Jung Hee] Sungkyunkwan Univ, Sch Med, Dept Radiol, Samsung Med Ctr,Samsung Biomed Res Inst, Seoul 135710, South Korea.
   [Yoon, Jaemoon; Ham, Don-il] Sungkyunkwan Univ, Sch Med, Dept Ophthalmol, Samsung Med Ctr,Samsung Biomed Res, Seoul 135710, South Korea.
   [Im, Geun Ho; Yang, Jehoon; Lee, Jung Hee] Samsung Biomed Res Inst, Ctr Mol & Cellular Imaging, Seoul, South Korea.
   [Im, Geun Ho; Kim, Sun I.] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea.
   [Chung, Julius Juhyun; Lee, Jung Hee] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Seoul 135710, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center; Samsung;
   Sungkyunkwan University (SKKU); Samsung Medical Center; Sungkyunkwan
   University (SKKU); Samsung Medical Center; Hanyang University;
   Sungkyunkwan University (SKKU); Samsung Medical Center
RP Lee, JH (通讯作者)，Sungkyunkwan Univ, Sch Med, Dept Radiol, Samsung Med Ctr,Samsung Biomed Res Inst, 50 Ilwon Dong, Seoul 135710, South Korea.
EM di.ham@samsung.com; hijunghee@skku.edu
RI lee, jung hee/H-8107-2018; lee, junghee/D-6130-2017
OI Chung, Julius/0000-0002-1513-5181
FU Basic Science Research Program through the National Research Foundation
   of Korea (NRF); Ministry of Education, Science, and Technology
   [2011-0031520, 2010-0023606]
FX Supported by the Basic Science Research Program through the National
   Research Foundation of Korea (NRF) funded by the Ministry of Education,
   Science, and Technology (2011-0031520 and 2010-0023606).
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NR 32
TC 3
Z9 3
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 NOV
PY 2012
VL 53
IS 12
BP 7693
EP 7700
DI 10.1167/iovs.12-9805
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EE
UT WOS:000313053500037
PM 23111615
DA 2022-11-30
ER

PT J
AU Seiler, MJ
   Aramant, RB
AF Seiler, Magdalene J.
   Aramant, Robert B.
TI Cell replacement and visual restoration by retinal sheet transplants
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Retinal degeneration; Retinal transplantation; Retinal progenitor
   sheets; Electrophysiology; Superior colliculus; Trans-synaptic tracing;
   Electron microscopy
ID PIGMENT EPITHELIAL-CELL; EMBRYONIC STEM-CELLS; ADULT-RAT RETINA; OPTICAL
   COHERENCE TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; FULL-THICKNESS RETINA;
   FETAL NEURAL RETINA; DYSTROPHIC RCS RAT; LONG-TERM SAFETY; MACULAR
   DEGENERATION
AB Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a 'nursing' role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance - they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity.
   In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Seiler, Magdalene J.; Aramant, Robert B.] Univ Calif Irvine, Dept Anat & Neurobiol, Reeve Irvine Res Ctr, Sue & Bill Gross Stem Cell Res Ctr, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine
RP Seiler, MJ (通讯作者)，Univ Calif Irvine, Dept Anat & Neurobiol, Reeve Irvine Res Ctr, Sue & Bill Gross Stem Cell Res Ctr, 1101 Gross Hall,845 Hlth Sci Rd, Irvine, CA 92697 USA.
EM mseiler@uci.edu
RI Seiler, Magdalene J./I-2942-2019
OI Seiler, Magdalene J./0000-0002-0869-9923
FU Lincy Foundation; International Stem Cell Corporation; Beckman
   Initiative for Macular Research; NEI SBIR [1 R44 EY015584,
   1R43EY020787]; Doheny Eye Institute: Foundation Fighting Blindness;
   Foundation for Retinal Research; Michael Panitch Fund for Retinal
   Research; NIH [EY03040, EY054375, EY08519]; Foundation Fighting
   Blindness; NATIONAL CANCER INSTITUTE [P30CA014089] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY008519, R44EY015584, R43EY015584,
   P30EY003040, R43EY020787] Funding Source: NIH RePORTER
FX This work was supported recently by the Lincy Foundation, the
   International Stem Cell Corporation, and the Beckman Initiative for
   Macular Research. RBA has been supported by NEI SBIR grants 1 R44
   EY015584, and 1R43EY020787. MJS and RBA have proprietary interests in
   the transplantation instrument and procedure (Ocular Transplantation
   LLC).; Part of the work described here was performed at the Doheny Eye
   Institute, University of Southern California, Dept. of Ophthalmology
   (2002-2006), and at the University of Louisville, Departments of
   Ophthalmology & Visual Sciences, Anatomical Sciences & Neurobiology
   (1993-2002). Previous support: at Doheny Eye Institute: Foundation
   Fighting Blindness, Foundation for Retinal Research, Michael Panitch
   Fund for Retinal Research, NIH EY03040, NIH EY054375; at University of
   Louisville: NIH EY08519 (RBA), Foundation Fighting Blindness, private
   funds.
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NR 272
TC 104
Z9 109
U1 0
U2 52
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 661
EP 687
DI 10.1016/j.preteyeres.2012.06.003
PG 27
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 035IV
UT WOS:000310940900006
PM 22771454
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Folgar, FA
   Chow, JH
   Farsiu, S
   Wong, WT
   Schuman, SG
   O'Connell, RV
   Winter, KP
   Chew, EY
   Hwang, TS
   Srivastava, SK
   Harrington, MW
   Clemons, TE
   Toth, CA
AF Folgar, Francisco A.
   Chow, Jessica H.
   Farsiu, Sina
   Wong, Wai T.
   Schuman, Stefanie G.
   O'Connell, Rachelle V.
   Winter, Katrina P.
   Chew, Emily Y.
   Hwang, Thomas S.
   Srivastava, Sunil K.
   Harrington, Molly W.
   Clemons, Traci E.
   Toth, Cynthia A.
TI Spatial Correlation between Hyperpigmentary Changes on Color Fundus
   Photography and Hyperreflective Foci on SDOCT in Intermediate AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; MACULAR
   DEGENERATION; GEOGRAPHIC ATROPHY; AUTOMATIC SEGMENTATION; SEVERITY
   SCALE; SD-OCT; PREVALENCE; DRUSEN; MIGRATION
AB PURPOSE. Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD.
   METHODS. A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators.
   RESULTS. Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001).
   CONCLUSIONS. A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.) (Invest Ophthalmol Vis Sci. 2012; 53:4626-4633) DOI: 10.1167/iovs.12-9813
C1 [Folgar, Francisco A.; Chow, Jessica H.; Farsiu, Sina; Schuman, Stefanie G.; O'Connell, Rachelle V.; Winter, Katrina P.; Toth, Cynthia A.] Duke Univ, Ctr Eye, Durham, NC 27710 USA.
   [Farsiu, Sina; Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA.
   [Wong, Wai T.; Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
   [Srivastava, Sunil K.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
   [Hwang, Thomas S.] Devers Eye Inst, Portland, OR USA.
   [Harrington, Molly W.; Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
C3 Duke University; Duke University; National Institutes of Health (NIH) -
   USA; NIH National Eye Institute (NEI); Cleveland Clinic Foundation;
   Devers Eye Institute; Emmes Corporation
RP Toth, CA (通讯作者)，Duke Univ, Ctr Eye, DUMC 3802, Durham, NC 27710 USA.
EM cynthia.toth@duke.edu
RI Hwang, Thomas/AAV-5146-2020; Hwang, Thomas S./AAW-6618-2020; toth,
   cynthia a/F-5614-2011; Wong, Wai/B-6118-2017; Toth, Cynthia/L-5534-2019
OI Hwang, Thomas S./0000-0002-0535-4823; Wong, Wai/0000-0003-0681-4016;
   Toth, Cynthia/0000-0002-2324-0854; Farsiu, Sina/0000-0003-4872-2902
FU AREDS2 Ancillary SDOCT Study; American Health Assistance Foundation;
   Research to Prevent Blindness; Genentech [IST-4400S]; Alcon Laboratories
FX Supported by the AREDS2 Ancillary SDOCT Study (ClinicalTrials.gov
   identifier: NCT00734487), the American Health Assistance Foundation
   (SF), and Research to Prevent Blindness (SF). The AREDS2 Grant is
   supported in part by Bioptigen (equipment), Genentech (IST-4400S grant),
   and Alcon Laboratories (unrestricted grant).
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NR 32
TC 55
Z9 56
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2012
VL 53
IS 8
BP 4626
EP 4633
DI 10.1167/iovs.12-9813
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400036
PM 22589439
DA 2022-11-30
ER

PT J
AU Nangia, V
   Jonas, JB
   Gupta, R
   Khare, A
   Sinha, A
AF Nangia, Vinay
   Jonas, Jost B.
   Gupta, Rajesh
   Khare, Anshu
   Sinha, Ajit
TI Prevalence of cataract surgery and postoperative visual outcome in rural
   central India Central India Eye and Medical Study
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID ARAVIND COMPREHENSIVE EYE; TANJONG-PAGAR SURVEY; BLUE MOUNTAINS EYE;
   RISK-FACTORS; LENS OPACITIES; ANDHRA-PRADESH; OLDER ADULTS; VISION
   IMPAIRMENT; SERVICES SCOUTS; SOUTHERN INDIA
AB PURPOSE: To determine the prevalence of cataract surgery and the postoperative visual outcomes in rural central India.
   SETTING: Villages in rural central India.
   DESIGN: Cohort study.
   METHODS: The population-based Central India Eye and Medical Study examined the prevalence of surgical pseudophakia/aphakia, the postoperative visual acuity, and the reasons for decreased postoperative vision in subjects aged 30+ in rural central India. Visual impairment was defined as (1) presenting visual acuity worse than 6/18 or (2) corrected distance visual acuity (CDVA) worse than 6/18.
   RESULTS: Of the 9392 eyes (99.7%) of 4711 subjects with available data on the lens status, 318 eyes (3.4%) (234 patients, 129 women) had had cataract surgery (5.0% +/- 0.3%). Cataract surgery was significantly associated with age (P<.001), female sex (P=.008), shorter axial length (P<.001), and diabetes mellitus (P<.001). The prevalence of postoperative presenting visual impairment was 63% (201/318 eyes) and of postoperative CDVA impairment, 36% (117/318 eyes). The major cause of the former was incorrect intraocular lens (IOL) power (42%); the major causes of the latter were posterior capsule opacification (24%), surgical complications (21%), age-related macular degeneration (10.3%), other macular disorders (4.3%), corneal opacities (3.4%), and glaucoma (2.0%). Surgical complications were significantly more common in the aphakic group than in the pseudophakic group (46.4% versus 2.0%; P<.001).
   CONCLUSIONS: Approximately 5% of the central India population aged 30 years or older had had cataract surgery. Postoperative visual impairment was present in 2 of 3 eyes. The major reasons were incorrect IOL power and surgical complications. Improved IOL power calculations and improved surgical techniques may markedly improve postoperative outcome.
C1 [Nangia, Vinay; Jonas, Jost B.; Gupta, Rajesh; Khare, Anshu; Sinha, Ajit] Suraj Eye Inst, Nagpur 440001, Maharashtra, India.
   [Jonas, Jost B.] Univ Heidelberg, Dept Ophthalmol, Med Fac Mannheim, D-6800 Mannheim, Germany.
C3 Suraj Eye Institute; Ruprecht Karls University Heidelberg
RP Nangia, V (通讯作者)，Suraj Eye Inst, Plot 559 New Colony, Nagpur 440001, Maharashtra, India.
EM nagpursuraj@gmail.com
FU Om Drishti Trust, Nagpur, India; Rotary Sight Saver, The Netherlands;
   Heidelberg Engineering Co., Heidelberg, Germany; ORBIS International;
   Carl Zeiss Meditec Ag, Jena, Germany
FX Supported by an unrestricted grant from Om Drishti Trust, Nagpur, India;
   Rotary Sight Saver, The Netherlands; Heidelberg Engineering Co.,
   Heidelberg, Germany; ORBIS International; and Carl Zeiss Meditec Ag,
   Jena, Germany.
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NR 43
TC 13
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD NOV
PY 2011
VL 37
IS 11
BP 1932
EP 1938
DI 10.1016/j.jcrs.2011.08.020
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 843NJ
UT WOS:000296678400004
PM 21908172
DA 2022-11-30
ER

PT J
AU Collier, RJ
   Patel, Y
   Martin, EA
   Dembinska, O
   Hellberg, M
   Krueger, DS
   Kapin, MA
   Romano, C
AF Collier, Robert J.
   Patel, Yamini
   Martin, Elizabeth A.
   Dembinska, Olga
   Hellberg, Mark
   Krueger, D. Scott
   Kapin, Michael A.
   Romano, Carmelo
TI Agonists at the Serotonin Receptor (5-HT1A) Protect the Retina from
   Severe Photo-Oxidative Stress
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BAY X 3702; GLOBAL CEREBRAL-ISCHEMIA; FIBROBLAST-GROWTH-FACTOR;
   SIGNAL-REGULATED KINASE; LIGHT-INDUCED APOPTOSIS; IN-VIVO; INDUCED
   DAMAGE; PHOTIC INJURY; CAUSES SUPPRESSION; SERUM DEPRIVATION
AB PURPOSE. 5-HT1A agonists are neuroprotective in CNS injury models. The authors evaluated the efficacy of 5-HT1A agonists to protect the retina from severe blue light-induced photooxidative damage.
   METHODS. Albino rats were dosed (subcutaneously) with AL8309A, 8-OH DPAT, or buspirone once or three times before 6-hour exposure to blue light. Electroretinograms (ERGs) were measured to assess retinal function, and retinal damage was evaluated by light microscopy. Topical ocular dosing with 1.75% AL-8309B was also evaluated. Rats were dosed with WAY-100635, a 5-HT1A antagonist, to determine whether protection required activation of the 5-HT1A receptor.
   RESULTS. ERG response amplitudes were significantly (P < 0.05) depressed more than 66% in vehicle-dosed rats after light exposure. ERGs were significantly higher in rats treated with AL-8309A (0.1-30 mg/kg), 8-OH DPAT (0.1-1 mg/kg), buspirone (5-20 mg/kg) or topical ocular with 1.75% AL-8309B. Retinas from AL-8309A and 8-OH DPAT-treated rats were devoid of histologic lesions. Significant protection was measured in rats dosed once 0, 24, or 48 hours before light exposure. Protection provided by dosing with AL-8309B or 8-OH DPAT was inhibited in rats predosed with WAY-100635.
   CONCLUSIONS. 5-HT1A agonists provided potent and complete functional and structural protection. Protection was inhibited by treatment with WAY-100635, confirming the requirement for activating the 5-HT1A receptor in initiating this survival pathway. Single-dose experiments with AL-8309A suggest that the mechanism of protection is rapidly activated and protection persists for 48 hours. AL-8309B (1.75%) was effective after topical ocular dosing. AL-8309B is under evaluation in the clinic and may be useful in treating age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2011;52:2118-2126) DOI:10.1167/iovs.106304
C1 [Collier, Robert J.; Patel, Yamini; Martin, Elizabeth A.; Dembinska, Olga; Hellberg, Mark; Krueger, D. Scott; Kapin, Michael A.; Romano, Carmelo] Alcon Res Ltd, Ft Worth, TX 76134 USA.
C3 Novartis; Alcon
RP Collier, RJ (通讯作者)，Alcon Res Ltd, 6201 S Freeway, Ft Worth, TX 76134 USA.
EM robert.collier@alconlabs.com
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NR 88
TC 41
Z9 43
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 APR
PY 2011
VL 52
IS 5
BP 2118
EP 2126
DI 10.1167/iovs.10-6304
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 746XK
UT WOS:000289282600005
PM 21087971
DA 2022-11-30
ER

PT J
AU Olivarius, ND
   Siersma, V
   Almind, GJ
   Nielsen, NV
AF Olivarius, Niels de Fine
   Siersma, Volkert
   Almind, Gitte Juul
   Nielsen, Niels Vesti
TI Prevalence and progression of visual impairment in patients newly
   diagnosed with clinical type 2 diabetes: a 6-year follow up study
SO BMC PUBLIC HEALTH
LA English
DT Article
ID RISK-FACTORS; EYE DISEASE; VISION LOSS; REGISTERED BLINDNESS;
   RETINOPATHY; ACUITY; POPULATION; MELLITUS; AUSTRALIA; SURVIVAL
AB Background: Many diabetic patients fear visual loss as the worst consequence of diabetes. In most studies the main eye pathology is assigned as the cause of visual impairment. This study analysed a broad range of possible ocular and non-ocular predictors of visual impairment prospectively in patients newly diagnosed with clinical type 2 diabetes.
   Methods: Data were from a population-based cohort of 1,241 persons newly diagnosed with clinical, often symptomatic type 2 diabetes aged >= 40 years. After 6 years, 807 patients were followed up. Standard eye examinations were done by practising ophthalmologists.
   Results: At diabetes diagnosis median age was 65.5 years. Over 6 years, the prevalence of blindness (visual acuity of best seeing eye <= 0.1) rose from 0.9% (11/1,241) to 2.4% (19/807) and the prevalence of moderate visual impairment (> 0.1; < 0.5) rose from 5.4% (67/1,241) to 6.7% (54/807). The incidence (95% confidence interval) of blindness was 40.2 (25.3-63.8) per 10,000 patient-years. Baseline predictors of level of visual acuity (age, age-related macular degeneration (AMD), cataract, living alone, low self-rated health, and sedentary life-style) and speed of continued visual loss (age, AMD, diabetic retinopathy (DR), cataract, living alone, and high fasting triglycerides) were identified.
   Conclusions: In a comprehensive assessment of predictors of visual impairment, even in a health care system allowing self-referral to free eye examinations, treatable eye pathologies such as DR and cataract emerge together with age as the most notable predictors of continued visual loss after diabetes diagnosis. Our results underline the importance of eliminating barriers to efficient eye care by increasing patients' and primary care practitioners' awareness of the necessity of regular eye examinations and timely surgical treatment.
C1 [Olivarius, Niels de Fine; Siersma, Volkert; Almind, Gitte Juul] Univ Copenhagen, Res Unit Gen Practice, Dept Publ Hlth, Copenhagen, Denmark.
   [Olivarius, Niels de Fine; Siersma, Volkert; Almind, Gitte Juul] Univ Copenhagen, Sect Gen Practice, Dept Publ Hlth, Copenhagen, Denmark.
   [Nielsen, Niels Vesti] Rigshosp, Univ Eye Clin, DK-2100 Copenhagen, Denmark.
C3 University of Copenhagen; University of Copenhagen; Rigshospitalet;
   University of Copenhagen
RP Olivarius, ND (通讯作者)，Univ Copenhagen, Res Unit Gen Practice, Dept Publ Hlth, Copenhagen, Denmark.
EM olivarius@sund.ku.dk
RI Siersma, Volkert D/G-6867-2016; de Fine Olivarius, Niels/K-6832-2015
OI Siersma, Volkert D/0000-0003-1941-2681; de Fine Olivarius,
   Niels/0000-0001-6465-3615
FU Danish Medical Research Council; Danish Research Foundation for General
   Practice; Health Insurance Foundation; Danish Ministry of Health; Novo
   Nordisk Farmaka Denmark Ltd.; Pharmacy Foundation
FX We are grateful to the patients, ophthalmologists and general
   practitioners who participated in the study and to Lise Bergsoe for her
   expert technical assistance. Major funding for this study was received
   from The Danish Medical Research Council, The Danish Research Foundation
   for General Practice, The Health Insurance Foundation, The Danish
   Ministry of Health, Novo Nordisk Farmaka Denmark Ltd., and The Pharmacy
   Foundation.
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NR 49
TC 23
Z9 23
U1 0
U2 4
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD FEB 4
PY 2011
VL 11
AR 80
DI 10.1186/1471-2458-11-80
PG 13
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health
GA 727QT
UT WOS:000287817000001
PM 21294871
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, YW
   Tao, W
   Luo, LY
   Huang, DQ
   Kauper, K
   Stabila, P
   LaVail, MM
   Laties, AM
   Wen, R
AF Li, Yiwen
   Tao, Weng
   Luo, Lingyu
   Huang, Deqiang
   Kauper, Konrad
   Stabila, Paul
   LaVail, Matthew M.
   Laties, Alan M.
   Wen, Rong
TI CNTF Induces Regeneration of Cone Outer Segments in a Rat Model of
   Retinal Degeneration
SO PLOS ONE
LA English
DT Article
ID CILIARY NEUROTROPHIC FACTOR; ROD PHOTORECEPTORS; GANGLION-CELLS;
   PHOTOTRANSDUCTION MACHINERY; AXONAL REGENERATION; ANIMAL-MODELS;
   GENE-TRANSFER; SURVIVAL; DEATH; DIFFERENTIATION
AB Background: Cone photoreceptors are responsible for color and central vision. In the late stage of retinitis pigmentosa and in geographic atrophy associated with age-related macular degeneration, cone degeneration eventually causes loss of central vision. In the present work, we investigated cone degeneration secondary to rod loss in the S334ter-3 transgenic rats carrying the rhodopsin mutation S334ter.
   Methodology/Principal Findings: Recombinant human ciliary neurotrophic factor (CNTF) was delivered by intravitreal injection to the left eye of an animal, and vehicle to the right eye. Eyes were harvested 10 days after injection. Cone outer segments (COS), and cell bodies were identified by staining with peanut agglutinin and cone arrestin antibodies in whole-mount retinas. For long-term treatment with CNTF, CNTF secreting microdevices were implanted into the left eyes at postnatal day (PD) 20 and control devices into the right eyes. Cone ERG was recorded at PD 160 from implanted animals. Our results demonstrate that an early sign of cone degeneration is the loss of COS, which concentrated in many small areas throughout the retina and is progressive with age. Treatment with CNTF induces regeneration of COS and thus reverses the degeneration process in early stages of cone degeneration. Sustained delivery of CNTF prevents cones from degeneration and helps them to maintain COS and light-sensing function.
   Conclusions/Significance: Loss of COS is an early sign of secondary cone degeneration whereas cell death occurs much later. At early stages, degenerating cones are capable of regenerating outer segments, indicating the reversal of the degenerative process. Sustained delivery of CNTF preserves cone cells and their function. Long-term treatment with CNTF starting at early stages of degeneration could be a viable strategy for preservation of central vision for patients with retinal degenerations.
C1 [Li, Yiwen; Luo, Lingyu; Huang, Deqiang; Wen, Rong] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [LaVail, Matthew M.] Univ Calif San Francisco, Beckman Vis Ctr, San Francisco, CA 94143 USA.
   [Tao, Weng; Kauper, Konrad; Stabila, Paul] Neurotech USA, Lincoln, RI USA.
   [Laties, Alan M.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
C3 Bascom Palmer Eye Institute; University of Miami; University of
   California System; University of California San Francisco; University of
   Pennsylvania
RP Li, YW (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
EM rwen@med.miami.edu
FU National Institutes of Health (NIH) [R01EY015289, R01EY018586,
   R01EY001919, R01EY006842, P30EY14801, P30EY002162]; James and Esther
   King Biomedical Research Program of the State of Florida; Department of
   Defense [08192003]; Foundation Fighting Blindness; Research to Prevent
   Blindness Inc.; NATIONAL EYE INSTITUTE [R01EY001919, R01EY006842,
   R01EY018586, P30EY014801, R01EY015289, P30EY002162] Funding Source: NIH
   RePORTER
FX This work was supported by National Institutes of Health (NIH) grants
   R01EY015289 (RW), R01EY018586 (RW), R01EY001919 (MML), R01EY006842
   (MML), Hope for Vision (RW), a grant from the James and Esther King
   Biomedical Research Program of the State of Florida (YL) and a grant
   from the Department of Defense (USAMRMC NO: 08192003, RW). It was also
   supported by NIH Core Grants P30EY14801 and P30EY002162, the Foundation
   Fighting Blindness (MML), and unrestricted grants from Research to
   Prevent Blindness Inc. to Bascom Palmer Eye Institute and Beckman Vision
   Center. The above funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
   Neurotech USA supplied the CNTF intraocular implants for this study.
   Neurotech USA is developing CNTF intraocular implants. As some of the
   authors are employed by Neurotech USA, this company had a role in the
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 46
TC 92
Z9 96
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 MAR 2
PY 2010
VL 5
IS 3
AR e9495
DI 10.1371/journal.pone.0009495
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 562OY
UT WOS:000275063300011
PM 20209167
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Fleckenstein, M
   Adrion, C
   Schmitz-Valckenberg, S
   Gobel, AP
   Bindewald-Wittich, A
   Scholl, HPN
   Mansmann, U
   Holz, FG
AF Fleckenstein, Monika
   Adrion, Christine
   Schmitz-Valckenberg, Steffen
   Goebel, Arno P.
   Bindewald-Wittich, Almut
   Scholl, Hendrik P. N.
   Mansmann, Ulrich
   Holz, Frank G.
CA Grp, FS
TI Concordance of Disease Progression in Bilateral Geographic Atrophy Due
   to AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; FUNDUS AUTOFLUORESCENCE PATTERNS; INDOCYANINE
   GREEN ANGIOGRAPHY; SCANNING LASER OPHTHALMOSCOPY; RETINAL-PIGMENT
   EPITHELIUM; MACULAR DEGENERATION; NATURAL-HISTORY; JUNCTIONAL ZONE;
   CLINICAL-TRIALS; VISUAL-ACUITY
AB PURPOSE. To determine the degree of concordance for progression rate, size of atrophy, and visual acuity in patients with bilateral geographic atrophy (GA) due to age-related macular degeneration (AMD).
   METHODS. Analysis was performed in 156 eyes of 78 patients with bilateral GA. Best corrected visual acuity was determined with ETDRS charts. GA was quantified in digital fundus autofluorescence images (excitation, 488 nm; emission, >500 nm) by semiautomated imaging analysis. A linear, two-level, random-effects model was used to assess the natural course of disease. The concordance correlation coefficient (CCC) was calculated to assess the degree of agreement between disease characteristics of the left and right eyes. Bland-Altman plots were applied to compare measurements in the eyes.
   RESULTS. CCC between the eyes was 0.310 (95% CI, 0.097-0.495) for visual acuity, 0.706 (95% CI, 0.575-0.801) for GA size, and 0.756 (95% CI, 0.644-0.837) for GA progression rate. Although Bland-Altman plots revealed high concordance for the progression rate, there was considerable discrepancy between both eyes for GA.
   CONCLUSIONS. GA progression in bilateral atrophic AMD is a symmetrical process; however, GA size may differ substantially between the eyes. High concordance in intraindividual disease progression in the presence of a high degree of interindividual variability indicates an influence by genetic and/or environmental factors rather than nonspecific ageing changes. The relatively small concordance of GA size in this cohort may indicate asymmetric evolution of the disease in affected individuals. The results may be useful in the design of future clinical trials designed to slow the rate of GA progression (Clinical Trials. gov number, NCT00393692). (Invest Ophthalmol Vis Sci. 2010; 51: 637-642) DOI: 10.1167/iovs.09-3547
C1 [Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Goebel, Arno P.; Bindewald-Wittich, Almut; Scholl, Hendrik P. N.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Adrion, Christine; Mansmann, Ulrich] Univ Munich, Dept Med Informat Biometry & Epidemiol, Munich, Germany.
C3 University of Bonn; University of Munich
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
OI Bindewald-Wittich, Almut/0000-0002-8151-3953; Adrion,
   Christine/0000-0003-2408-2533; Fleckenstein, Monika/0000-0001-8321-8037
FU DFG (German Research Council) [SPP 1088, Ho 1926/1-3]; EU [FP6];
   Integrated Project EVI-GENORET [LSHG-CT-2005-512036]; DOG (German
   Society of Ophthalmology); BON-FOR Program Grant [O-137-0012]
FX Supported by DFG (German Research Council) Research Priority Program
   Age-Related Macular Degeneration Grant SPP 1088, Ho 1926/1-3; EU FP6;
   Integrated Project EVI-GENORET (LSHG-CT-2005-512036); a DOG (German
   Society of Ophthalmology) research grant; and BON-FOR Program Grant
   O-137-0012 to the Faculty of Medicine, University of Bonn.
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NR 45
TC 36
Z9 36
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2010
VL 51
IS 2
BP 637
EP 642
DI 10.1167/iovs.09-3547
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 545AS
UT WOS:000273704700002
PM 19797219
DA 2022-11-30
ER

PT J
AU Murray-Rust, TA
   Kerr, FK
   Thomas, AR
   Wu, TN
   Yongqing, T
   Ong, PC
   Quinsey, NS
   Whisstock, JC
   Wagenaar-Bos, IC
   Freeman, C
   Pike, RN
AF Murray-Rust, Thomas A.
   Kerr, Felicity K.
   Thomas, Adele R.
   Wu, Tina
   Yongqing, Tang
   Ong, Poh Chee
   Quinsey, Noelene S.
   Whisstock, James C.
   Wagenaar-Bos, Ineke C.
   Freeman, Craig
   Pike, Robert N.
TI Modulation of the proteolytic activity of the complement protease C1s by
   polyanions: implications for polyanion-mediated acceleration of
   interaction between C1s and SERPING1
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE C1 inhibitor; complement; glycosaminoglycan (GAG); protease; SERPING1
ID 4TH C4 COMPONENT; C1-ESTERASE INHIBITOR; DIMETHYL-SULFOXIDE; HUMAN
   C1-INHIBITOR; CRYSTAL-STRUCTURE; ANTITHROMBIN-III; SUB-COMPONENTS; 1ST
   COMPONENT; 2ND C2; HEPARIN
AB The complement system plays crucial roles in the immune system, but incorrect regulation causes inflammation and targeting of self-tissue, leading to diseases such as systemic lupus erythematosus, rheumatoid arthritis and age-related macular degeneration. In vivo, the initiating complexes of the classical complement and lectin pathways are controlled by SERPING1 [(C1 inhibitor) serpin peptidase inhibitor, clade G, member 1], which inactivates the components C1s and MASP-2 (mannan-binding lectin serine peptidase 2). GAGs (glycosaminoglycan) and DXS (dextran sulfate) are able to significantly accelerate SERPING1-mediated inactivation of C1s, the key effector enzyme of the classical Cl complex, although the mechanism is poorly understood. In the present study we have shown that C Is can bind to DXS and heparin and that these polyanions enhanced C Is proteolytic activity at low concentrations and inhibited it at higher concentrations. The recent determination of the crystal structure of SERPING1 has given rise to the hypothesis that both the serpin (serine protease inhibitor)-polyanion and protease-polyanion interactions might be required to accelerate the association rate of SERPING1 and C Is. To determine what proportion of the acceleration was due to protease-polyanion interactions, a chimareric mutant of alpha(1)-anti-trypsin containing the P-4-P-1 residues from the SERPING1 RCL (reactive-centre loop) was produced. Like SERPING1, this molecule is able to effectively inhibit C Is, but is unable to bind polyanions. DXS exerted a biphasic effect on the association rate of C Is which correlated strongly with the effect of DXS on C Is proteolytic activity. Thus, whereas polyanions are able to bind C1s and modulate its activity, polyanion interactions with SERPING1 must also play a vital role in the mechanism by which these cofactors accelerate the C1s-SERPING1 reaction.
C1 [Murray-Rust, Thomas A.; Kerr, Felicity K.; Thomas, Adele R.; Wu, Tina; Yongqing, Tang; Ong, Poh Chee; Quinsey, Noelene S.; Whisstock, James C.; Pike, Robert N.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Whisstock, James C.] ARC Ctr Excellence Struct & Funct Microbial Genom, Canberra, ACT 2601, Australia.
   [Wagenaar-Bos, Ineke C.] Sanquin Res CLB, Dept Immunopathol, NL-1066 CX Amsterdam, Netherlands.
   [Wagenaar-Bos, Ineke C.] Univ Amsterdam, Acad Med Ctr, Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands.
   [Freeman, Craig] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
C3 Monash University; University of Amsterdam; Academic Medical Center
   Amsterdam; Australian National University; John Curtin School of Medical
   Research
RP Pike, RN (通讯作者)，Monash Univ, Dept Biochem & Mol Biol, Wellington Rd, Clayton, Vic 3800, Australia.
EM rob.pike@med.monash.edu.au
OI Whisstock, James/0000-0003-4200-5611; Pike, Robert/0000-0002-2083-0269
FU National Health and Medical Research Council [490900, 455395];
   Australian Research Council Federation Fellow
FX This work was supported by National Health and Medical Research Council
   [program grant numbers 490900 and 455395]. J.C.W. is an Australian
   Research Council Federation Fellow.
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NR 50
TC 14
Z9 15
U1 1
U2 5
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD SEP 1
PY 2009
VL 422
BP 295
EP 303
DI 10.1042/BJ20090198
PN 2
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 489OM
UT WOS:000269429900011
PM 19522701
DA 2022-11-30
ER

PT J
AU Ireson, CR
   Kelland, LR
AF Ireson, Christopher R.
   Kelland, Lloyd R.
TI Discovery and development of anticancer aptamers
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; SURFACE-EXPRESSED NUCLEOLIN; CELL-SURFACE;
   ANTIPROLIFERATIVE ACTIVITY; SYSTEMATIC EVOLUTION; BINDING PROTEIN;
   APOPTOSIS; OLIGONUCLEOTIDES; LIGANDS
AB Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation. The first aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib) that is administered locally (intravitreally) to treat age-related macular degeneration by targeting vascular endothelial growth factor. The most advanced aptamer in the cancer setting is AS 1411, formerly known as AGRO 100, which is being administered systemically in clinical trials. AS1411 is a 26-mer unmodified guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has shown activity against human tumor xenografts in vivo. The mechanism underlying its antiproliferative effects in cancer cells seems to involve initial binding to cell surface nucleolin and internalization, leading to an inhibition of DNA replication. In contrast to other unmodified oligonucleotides, AS 1411 is relatively stable in serum-containing medium, probably as a result of the formation of dimers and a quartet structure. In a dose escalation phase I study in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or seven continuous infusion regime) have been studied. Promising signs of activity have been reported (multiple cases of stable disease and one near complete response in a patient with renal cancer) in the absence of any significant adverse effects. Further trials are ongoing in renal and non-small cell lung cancers. In preclinical studies, additional aptamers have been described against several cancer targets, such as tenascin-C, the transcription factor signal transducer and activator of transcription 3, and antiapoptotic and Ku proteins.
C1 Antisoma Res Labs, London, England.
RP Kelland, LR (通讯作者)，UCL, Wolfson Inst Biomed Res, Cruciform Bldg,Gower St, London WC1E 6BT, England.
EM lkelland@cancertechnology.com
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NR 30
TC 375
Z9 415
U1 1
U2 226
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD DEC
PY 2006
VL 5
IS 12
BP 2957
EP 2962
DI 10.1158/1535-7163.MCT-06-0172
PG 6
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 122UO
UT WOS:000243252800001
PM 17172400
DA 2022-11-30
ER

PT J
AU Davies, NP
   Morland, AB
AF Davies, NP
   Morland, AB
TI Macular pigments: their characteristics and putative role
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
ID AGE-RELATED MACULOPATHY; OPTICAL-DENSITY; LUTEIN SUPPLEMENTATION;
   SPECTRAL SENSITIVITY; SPATIAL-DISTRIBUTION; IN-VIVO; SERUM
   CONCENTRATIONS; RAMAN MEASUREMENT; CRYSTALLINE LENS; CAROTENOIDS
AB The macular pigments (MP) absorb light in the blue-green region of the visible spectrum and comprise two carotenoids, lutein and zeaxanthin. In humans the concentration of MP varies widely across the normal population. There are two (not mutually exclusive) proposed roles for MP: to improve visual function and to act as an antioxidant and protect the macula from damage by oxidative stress. In this article we review the origin, spectral characteristics and ocular distribution of MP and also discuss the effect MP has on central visual function and the techniques available for measurement of MP optical density in vivo. Finally, we review the evidence for both proposed physiological roles of MP. Considering the first of these, we conclude that although MP might improve visual function in theory, to date there is no firm evidence that higher levels of MP are correlated with enhanced measures of visual performance. There is a growing body of evidence that has highlighted associations between macular disease and low levels of MP, most particularly with age-related macular degeneration (AMD) and with risk factors for AMD. However, all findings to date are associative only and there is no direct evidence for high MP levels conferring a protective effect. Increased dietary intake of MP gives rise to increased levels of serum and retinal MP. This, taken together with the associative evidence of low MP levels in disease, indicates that a potential, and perhaps serendipitous, therapeutic strategy for macular disease exists. We conclude, however, that the potential protective properties of MP will only be fully evaluated by undertaking longitudinal studies that follow initially healthy participants through to the development of macular disease. (C) 2004 Elsevier Ltd. All rights reserved.
C1 Univ London Royal Holloway & Bedford New Coll, Dept Psychol, Egham TW20 0EX, Surrey, England.
   Chelsea & Westminster Hosp, Dept Ophthalmol, London SW10 9NH, England.
C3 University of London; Royal Holloway University London; Imperial College
   London
RP Morland, AB (通讯作者)，Univ London Royal Holloway & Bedford New Coll, Dept Psychol, Egham TW20 0EX, Surrey, England.
EM a.morland@rhbnc.ac.uk
OI Morland, Antony/0000-0002-6754-5545
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NR 116
TC 74
Z9 78
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD SEP
PY 2004
VL 23
IS 5
BP 533
EP 559
DI 10.1016/j.preteyeres.2004.05.004
PG 27
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 850XC
UT WOS:000223646700004
PM 15302350
DA 2022-11-30
ER

PT J
AU Nusinovici, S
   Zhang, L
   Chai, XR
   Zhou, L
   Tham, YC
   Vasseneix, C
   Majithia, S
   Sabanayagam, C
   Wong, TY
   Cheng, CY
AF Nusinovici, Simon
   Zhang, Liang
   Chai, Xiaoran
   Zhou, Lei
   Tham, Yih Chung
   Vasseneix, Caroline
   Majithia, Shivani
   Sabanayagam, Charumathi
   Wong, Tien Yin
   Cheng, Ching Yu
TI Machine learning to determine relative contribution of modifiable and
   non-modifiable risk factors of major eye diseases
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID HYPEROPIC REFRACTIVE ERROR; RETINAL VASCULAR CALIBER; FACTOR-H
   POLYMORPHISM; SINGAPORE MALAY EYE; MACULAR-DEGENERATION; GLOBAL
   PREVALENCE; DIABETIC-RETINOPATHY; AXIAL LENGTH; SOCIOECONOMIC-STATUS;
   LENS OPACITY
AB Aims To use machine learning (ML) to determine the relative contributions of modifiable and non-modifiable clinical, metabolic, genetic, lifestyle and socioeconomic factors on the risk of major eye diseases.
   Methods We conducted analyses in a cross-sectional multi-ethnic population-based study (n=10 033 participants) and determined a range of modifiable and non-modifiable risk factors of common eye diseases, including diabetic retinopathy (DR), non-diabetic-related retinopathy (NDR); early and late age-related macular degeneration (AMD); nuclear, cortical and posterior subcapsular (PSC) cataract; and primary open-angle (POAG) and primary angle-closure glaucoma (PACG). Risk factors included individual characteristics, metabolic profiles, genetic background, lifestyle patterns and socioeconomic status (n similar to 100 risk factors). We used gradient boosting machine to estimate the relative influence (RI) of each risk factor.
   Results Among the range of risk factors studied, the highest contributions were duration of diabetes for DR (RI=22.1%), and alcohol consumption for NDR (RI=6.4%). For early and late AMD, genetic background (RI similar to 20%) and age (RI similar to 15%) contributed the most. Axial length was the main risk factor of PSC (RI=30.8%). For PACG, socioeconomic factor (mainly educational level) had the highest influence (20%). POAG was the disease with the highest contribution of modifiable risk factors (cumulative RI similar to 35%), followed by PACG (cumulative RI similar to 30%), retinopathy (cumulative RI between 20% and 30%) and late AMD (cumulative RI similar to 20%).
   Conclusion This study illustrates the utility of ML in identifying factors with the highest contributions. Risk factors possibly amenable to interventions were intraocular pressure (IOP) and Body Mass Index (BMI) for glaucoma, alcohol consumption for NDR and levels of HbA1c for DR.
C1 [Nusinovici, Simon; Zhang, Liang; Chai, Xiaoran; Zhou, Lei; Tham, Yih Chung; Vasseneix, Caroline; Majithia, Shivani; Sabanayagam, Charumathi; Wong, Tien Yin; Cheng, Ching Yu] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Zhou, Lei; Wong, Tien Yin; Cheng, Ching Yu] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Tham, Yih Chung; Sabanayagam, Charumathi; Wong, Tien Yin; Cheng, Ching Yu] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore
RP Cheng, CY (通讯作者)，Singapore Eye Res Inst, 20 Coll Rd,Level 6, Singapore 169856, Singapore.
EM cheng.ching.yu@seri.com.sg
RI Chung, Yih/AIF-2414-2022; Cheng, Ching-Yu/Y-2229-2019; Wong, Tien
   Y/AAC-9724-2020
OI Chung, Yih/0000-0002-6752-797X; Cheng, Ching-Yu/0000-0003-0655-885X;
   Sabanayagam, Charumathi/0000-0002-4042-4719; Wong, Tien
   Y/0000-0002-8448-1264
FU  [NMRC/CIRG/1488/2018];  [NMRC/OFLCG/004a/2018]
FX NMRC/CIRG/1488/2018 and NMRC/OFLCG/004a/2018.
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NR 59
TC 2
Z9 2
U1 2
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 FEB
PY 2022
VL 106
IS 2
BP 267
EP 274
DI 10.1136/bjophthalmol-2020-317454
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YN6FH
UT WOS:000747351900021
PM 33208351
DA 2022-11-30
ER

PT J
AU Michl, M
   Fabianska, M
   Seebock, P
   Sadeghipour, A
   Najeeb, BH
   Bogunovic, H
   Schmidt-Erfurth, UM
   Gerendas, BS
AF Michl, Martin
   Fabianska, Maria
   Seebock, Philipp
   Sadeghipour, Amir
   Najeeb, Bilal Haj
   Bogunovic, Hrvoje
   Schmidt-Erfurth, Ursula Margarethe
   Gerendas, Bianca S.
TI Automated quantification of macular fluid in retinal diseases and their
   response to anti-VEGF therapy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Retina; Imaging; Macula; Treatment Medical
ID SUBRETINAL FLUID; FUNDUS CHANGES; VISUAL-ACUITY; RANIBIZUMAB; EDEMA;
   ANGIOGRAPHY; DETACHMENT; RELEVANT; OUTCOMES; REGIMEN
AB Aim To objectively assess disease activity and treatment response in patients with retinal vein occlusion (RVO), neovascular age-related macular degeneration (nAMD) and centre-involved diabetic macular oedema (DME), using artificial intelligence-based fluid quantification. Methods Posthoc analysis of 2311 patients (11 151 spectral-domain optical coherence tomography volumes) from five clinical, multicentre trials, who received a flexible antivascular endothelial growth factor (anti-VEGF) therapy over a 12-month period. Fluid volumes were measured with a deep learning algorithm at baseline/months 1, 2, 3 and 12, for three concentric circles with diameters of 1, 3 and 6 mm (fovea, paracentral ring and pericentral ring), as well as four sectors surrounding the fovea (superior, nasal, inferior and temporal). Results In each disease, at every timepoint, most intraretinal fluid (IRF) per square millimetre was present at the fovea, followed by the paracentral ring and pericentral ring (p<0.0001). While this was also the case for subretinal fluid (SRF) in RVO/DME (p<0.0001), patients with nAMD showed more SRF in the paracentral ring than at the fovea up to month 3 (p<0.0001). Between sectors, patients with RVO/DME showed the highest IRF volumes temporally (p<0.001/p<0.0001). In each disease, more SRF was consistently found inferiorly than superiorly (p<0.02). At month 1/12, we measured the following median reductions of initial fluid volumes. For IRF: RVO, 95.9%/97.7%; nAMD, 91.3%/92.8%; DME, 37.3%/69.9%. For SRF: RVO, 94.7%/97.5%; nAMD, 98.4%/99.8%; DME, 86.3%/97.5%. Conclusion Fully automated localisation and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. There is a specific anatomical response of IRF/SRF to anti-VEGF therapy in all diseases studied.
C1 [Michl, Martin; Fabianska, Maria; Seebock, Philipp; Sadeghipour, Amir; Najeeb, Bilal Haj; Bogunovic, Hrvoje; Schmidt-Erfurth, Ursula Margarethe; Gerendas, Bianca S.] Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Gerendas, BS (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM bianca.gerendas@meduniwien.ac.at
OI Haj Najeeb, Bilal/0000-0002-8147-1415; Gerendas, Bianca
   S./0000-0001-8940-8130; Schmidt-Erfurth, Ursula/0000-0002-7788-7311
CR Ahn SE, 2013, INVEST OPHTH VIS SCI, V54, P5944, DOI 10.1167/iovs.13-12279
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NR 35
TC 14
Z9 14
U1 3
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 JAN
PY 2022
VL 106
IS 1
BP 113
EP 120
DI 10.1136/bjophthalmol-2020-317416
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XR0XT
UT WOS:000731963800019
PM 33087314
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Zanon-Moreno, V
   Pedrol, JCD
   Sanz-Gonzalez, SM
   Raga-Cervera, J
   Salazar-Corral, J
   Pinazo-Duran, MD
AF Zanon-Moreno, Vicente
   Domingo Pedrol, Joan C.
   Sanz-Gonzalez, Silvia M.
   Raga-Cervera, Jorge
   Salazar-Corral, Juan
   Dolores Pinazo-Duran, Maria
TI Feasibility Study of a Docosahexaenoic Acid-Optimized Nutraceutical
   Formulation on the Macular Levels of Lutein in a Healthy Mediterranean
   Population
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Macular pigment optical density; Lutein; Docosahexaenoic acid; Ocular
   health
ID OPTICAL-DENSITY; PIGMENT DENSITY; EYE DISEASE; FATTY-ACIDS; AGE;
   SUPPLEMENTATION; ZEAXANTHIN; DEGENERATION; OMEGA-3-FATTY-ACIDS;
   CAROTENOIDS
AB Introduction: Macular pigment optical density (MPOD) plays a pivotal role in maintaining macular structure and functioning. Research shows that daily consumption of lutein reduces the risk of eye diseases such as age-related macular degeneration. Objective: This study analyzes the influence of a supplementation containing lutein and antioxidant vitamins either with or without docosahexaenoic acid (DHA), with the main objective of identifying MPOD changes in both eyes at the end of the follow-up using the Visucam (R) retinograph. The secondary end point was to determine variation in the lutein and DHA levels in plasma and red blood cell membranes (RBCMs), respectively. Methods: One hundred healthy participants (200 eyes) aged 40-70 years (mean age 49.3 years, SEM = 13.7) were randomized in a 1:1 ratio to receive daily one of the following supplements for 3 months: lutein group (LT-G, n = 49) and lutein plus DHA group (LT/DHA-G, n = 51). The MPOD was measured at baseline and end of the follow-up by retinography (Visucam (R) retinograph). Lutein in plasma was determined by HPLC, and DHA in RBC membranes was analyzed by gas chromatograph/mass spectrometer. Results: From baseline, MPOD showed significantly higher values in the LT/DHA-G than in the LT-G at the end of the study (p < 0.0001). Significantly higher lutein in plasma (p < 0.0001) and DHA (p < 0.0001) levels in the RBC membrane were seen in the LT/DHA-G than in the LT-G at the 3-month follow-up. Conclusion: Lutein supplementation improves MPOD in healthy subjects from a Mediterranean population being significantly increased in the presence of DHA. Therefore, our findings highlight the relevance of the adjunctive role of DHA for better lutein availability. (c) 2020 The Author(s). Published by S. Karger AG, Basel
C1 [Zanon-Moreno, Vicente; Sanz-Gonzalez, Silvia M.; Raga-Cervera, Jorge; Dolores Pinazo-Duran, Maria] Univ Valencia, Ophthalm Res Unit Santiago Grisolia FISABIO, Valencia, Spain.
   [Zanon-Moreno, Vicente; Sanz-Gonzalez, Silvia M.; Raga-Cervera, Jorge; Dolores Pinazo-Duran, Maria] Univ Valencia, Cellular & Mol Ophthalmobiol Grp, Dept Surg, Valencia, Spain.
   [Zanon-Moreno, Vicente; Sanz-Gonzalez, Silvia M.; Salazar-Corral, Juan; Dolores Pinazo-Duran, Maria] Minist Sci Innovat & Univ, Carlos III Hlth Inst, Spanish Network Cooperat Res Ophthalmol OFTARED, Madrid, Spain.
   [Zanon-Moreno, Vicente] Valencian Int Univ, Fac Hlth Sci, Valencia, Spain.
   [Domingo Pedrol, Joan C.] Univ Barcelona, Dept Biochem & Mol Biomed, Fac Biol, Barcelona, Spain.
   [Raga-Cervera, Jorge] Hosp Manises, Dept Ophthalmol, Manises, Spain.
   [Salazar-Corral, Juan] Complutensis Univ Madrid, Inst Ophthalm Res Ramon Castroviejo, Madrid, Spain.
C3 University of Valencia; University of Valencia; Universidad
   Internacional de Valencia VIU; University of Barcelona; Complutense
   University of Madrid
RP Pinazo-Duran, MD (通讯作者)，Univ Valencia, Ophthalm Res Unit Santiago Grisolia FISABIO, Valencia, Spain.; Pinazo-Duran, MD (通讯作者)，Univ Valencia, Cellular & Mol Ophthalmobiol Grp, Dept Surg, Valencia, Spain.; Pinazo-Duran, MD (通讯作者)，Minist Sci Innovat & Univ, Carlos III Hlth Inst, Spanish Network Cooperat Res Ophthalmol OFTARED, Madrid, Spain.
EM dolores.pinazo@uv.es
RI Zanon-Moreno, Vicente/B-8348-2009; Zanon-Moreno, Vicente/ABB-7328-2021
OI Zanon-Moreno, Vicente/0000-0003-1179-1592; 
FU RETICs (OFTARED) from the Institute of Health Carlos III (Spanish
   Government); Brudylab(R) (Barcelona, Spain)
FX This work was partially funded by RETICs (OFTARED) from the Institute of
   Health Carlos III (Spanish Government) and by a grant from Brudylab (R)
   (Barcelona, Spain).
CR [Anonymous], 2014, USE DHA TREATING PAT
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NR 44
TC 4
Z9 4
U1 3
U2 9
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD DEC
PY 2021
VL 64
IS 6
BP 1068
EP 1076
DI 10.1159/000509439
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZC4VR
UT WOS:000757520400020
PM 32544914
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Grant, A
   Leung, G
   Aubin, MJ
   Kergoat, MJ
   Li, G
   Freeman, EE
AF Grant, Alyssa
   Leung, Gareth
   Aubin, Marie-Josee
   Kergoat, Marie-Jeanne
   Li, Gisele
   Freeman, Ellen E.
TI Fine Particulate Matter and Age-Related Eye Disease: The Canadian
   Longitudinal Study on Aging
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE fine particulate matter; air pollution; glaucoma; eye disease;
   intraocular pressure; CLSA
ID AIR-POLLUTION; RISK; ASSOCIATION; MORTALITY; PRESSURE; GLAUCOMA;
   EXPOSURE; SMOKING; PM2.5
AB PURPOSE. To determine the relationship between fine particulate matter (PM2.5) and ocular outcomes such as visual impairment and age-related eye disease.
   METHODS. Baseline data were used from the Canadian Longitudinal Study on Aging. The Comprehensive Cohort consisted of 30,097 adults ages 45 to 85 years. Annual mean PM2.5 levels (mu g/m(3)) for each participant's postal code were estimated from satellite data. Ozone, sulfur dioxide, and nitrogen dioxide levels were also estimated. Binocular presenting visual acuity was measured using a visual acuity chart. Intraocular pressure (IOP) was measured in millimeters of mercury using the Reichart Ocular Response Analyzer. Participants were asked about a diagnosis of glaucoma, macular degeneration, or cataract. Logistic and linear regression models were used.
   RESULTS. The overall mean PM2.5 level was 6.5 mu g/m(3) (SD = 1.8). In the single pollutant models, increased PM2.5 levels (per interquartile range) were associated with visual impairment (odds ratio [OR] = 1.12; 95% confidence interval [CI], 1.02-1.24), glaucoma (OR = 1.14; 95% CI, 1.01-1.29), and visually impairing age-related macular degeneration (OR = 1.52; 95% CI, 1.10-2.09) after adjustment for sociodemographics and disease. PM2.5 had a borderline adjusted association with cataract (OR = 1.06; 95% CI, 0.99-1.14). In the multi-pollutant models, increased PM2.5 was associated with glaucoma and IOP only after adjustment for sociodemographics and disease (OR = 1.24; 95% CI, 1.05-1.46 and beta = 0.24; 95% CI, 0.12-0.37).
   CONCLUSIONS. Increased PM2.5 is associated with glaucoma and IOP. These associations should be confirmed using longitudinal data and potential mechanisms should be explored. If confirmed, this work may have relevance for revision of World Health Organization thresholds to protect human health.
C1 [Grant, Alyssa; Leung, Gareth; Freeman, Ellen E.] Univ Ottawa, Sch Epidemiol & Publ Hlth, 600 Peter Morand Crescent,Off 301H, Ottawa, ON, Canada.
   [Aubin, Marie-Josee; Li, Gisele] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Aubin, Marie-Josee; Li, Gisele] Ctr Univ Ophtalmol Hop Maisonneuve Rosemont, Montreal, PQ, Canada.
   [Aubin, Marie-Josee] Univ Montreal, Dept Social & Prevent Med, ESPUM, Montreal, PQ, Canada.
   [Kergoat, Marie-Jeanne] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Kergoat, Marie-Jeanne] Univ Montreal, Dept Med, Montreal, PQ, Canada.
   [Freeman, Ellen E.] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
C3 University of Ottawa; Universite de Montreal; Universite de Montreal;
   Universite de Montreal; Universite de Montreal; University of Ottawa;
   Ottawa Hospital Research Institute
RP Freeman, EE (通讯作者)，Univ Ottawa, Sch Epidemiol & Publ Hlth, 600 Peter Morand Crescent,Off 301H, Ottawa, ON, Canada.
OI Leung, Gareth/0000-0002-2299-5673
FU Government of Canada through the Canadian Institutes of Health Research
   (CIHR) [LSA 94473]; Canada Foundation for Innovation; CIHR [ACD-170303]
FX Funding for the CLSA is provided by the Government of Canada through the
   Canadian Institutes of Health Research (CIHR) under grant reference LSA
   94473 and the Canada Foundation for Innovation. The research by E.E.F.
   was funded by an operating grant from the CIHR (ACD-170303). The funders
   had no role in the design, analysis, or the interpretation of results.
   The opinions expressed in this manuscript are the authors' own and do
   not reflect the views of the CLSA. Calculated air pollution metrics
   indexed to DMTI Spatial Inc. postal codes were provided by the Canadian
   Urban Environmental Health Research Consortium.
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NR 38
TC 7
Z9 7
U1 5
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 AUG
PY 2021
VL 62
IS 10
AR 7
DI 10.1167/iovs.62.10.7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UP2QS
UT WOS:000695230000007
PM 34369984
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Bazan, NG
AF Bazan, Nicolas G.
TI Overview of how N32 and N34 elovanoids sustain sight by protecting
   retinal pigment epithelial cells and photoreceptors
SO JOURNAL OF LIPID RESEARCH
LA English
DT Review
DE adiponectin receptor 1; age-related macular degeneration; Clq tumor
   necrosis factor-related protein-5; elovanoids; MALDI IMS; membrane-type
   frizzled-related protein; neuroprotectin D1; interphotoreceptor matrix;
   very long-chain polyunsaturated fatty acids; Senescence gene programming
ID POLYENOIC FATTY-ACIDS; FRIZZLED-RELATED PROTEIN; LONG-CHAIN PUFAS;
   DOCOSAHEXAENOIC ACID; DIPOLYUNSATURATED PHOSPHATIDYLCHOLINES;
   MITOCHONDRIAL SIRTUINS; MACULAR DEGENERATION; ELOVL4; ADIPOR1; MFRP
AB The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRCs), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine, amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (n-3, >= 28 carbons) are at the sn-1 of this phosphatidylcholine molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes. Here, we review the structures and stereochemistry of novel elovanoid (ELV)-N32 and ELV-N34 to be ELV-N32: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydro xydo-triaconta-14,17,21,23,25,29-hexaenoic acid; ELV-N34: (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydrox ytetra-triaconta-16,19,23,25,27,31-hexaenoic acid. ELVs are low-abundance, high-potency, protective mediators. Their bioactivity includes enhancing of antiapoptotic and prosurvival protein expression with concomitant downregulation of proapoptotic proteins when RPE is confronted with uncompensated oxidative stress. ELVs also target PRC/RPE senescence gene programming, the senescence secretory phenotype in the interphotoreceptor matrix, as well as inflammaging (chronic, sterile, low-grade inflammation). An important lesson on neuroprotection is highlighted by the ELV mediators that target the terminally differentiated PRC and RPE, sustaining a beautifully synchronized renewal process. The role of ELVs in PRC and RPE viability and function uncovers insights on disease mechanisms and the development of therapeutics for age-related macular degeneration, Alzheimer's disease, and other pathologies.
C1 [Bazan, Nicolas G.] Louisiana State Univ, Neurosci Ctr Excellence, Sch Med, Hlth Sci Ctr, New Orleans, LA 70803 USA.
C3 Louisiana State University System; Louisiana State University Health
   Sciences Center New Orleans
RP Bazan, NG (通讯作者)，Louisiana State Univ, Neurosci Ctr Excellence, Sch Med, Hlth Sci Ctr, New Orleans, LA 70803 USA.
EM nbazan@lsuhsc.edu
OI Bazan, Nicolas/0000-0002-9243-5444
FU National Institutes of Health (NIH) (National Eye Institute) [R01
   EY005121]; Ernest C. and Ivette C. Villere Chair for Retinal
   Degeneration; Eye, Ear, Nose & Throat Foundation of New Orleans
FX This work was supported by National Institutes of Health (NIH) grant R01
   EY005121 (National Eye Institute; to N. G. B.), the Ernest C. and Ivette
   C. Villere Chair for Retinal Degeneration, and the Eye, Ear, Nose &
   Throat Foundation of New Orleans. The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the National Institutes of Health.
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NR 72
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PY 2021
VL 62
AR 100058
DI 10.1194/jlr.TR120001137
EA APR 2021
PG 16
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA SD5RN
UT WOS:000651432700001
PM 33662383
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Liu, CH
   Kang, EYC
   Lin, YH
   Wu, WC
   Liu, ZH
   Kuo, CF
   Lai, CC
   Hwang, YS
AF Liu, Chun-Hao
   Kang, Eugene Yu-Chuan
   Lin, Yu-Hsiang
   Wu, Wei-Chi
   Liu, Zhuo-Hao
   Kuo, Chang-Fu
   Lai, Chi-Chun
   Hwang, Yih-Shiou
TI Association of ocular diseases with schizophrenia, bipolar disorder, and
   major depressive disorder: a retrospective case-control,
   population-based study
SO BMC PSYCHIATRY
LA English
DT Article
DE Glaucoma; Ocular neurovascular diseases; Psychiatric disorders; Mental
   disorders
ID GLAUCOMA; PREVALENCE; ANXIETY; BLINDNESS; BURDEN
AB Background Psychiatric disorders and ocular neurovascular diseases may share a similar pathophysiological route of vascular structures or neurological changes. The aim of this study is to investigate the association between ocular neurovascular diseases and the risk of major psychiatric disorders. Methods This was a retrospective case-control, population-based study including patients aged >= 20 and were diagnosed between 1997 and 2013. Ocular neurovascular diseases diagnosed between 1997 and 2006 and newly diagnosed psychiatric disorders including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia between 2007 and 2013 were registered. Patients were propensity-score matched with control groups without psychiatric disorders in each cohort based on selected covariates. Results A total of one million sampled patients in the database were categorized based on their diagnoses; 2243 (37.4% men) were categorized into the BD group, 10,110 (35.2% men) into the MDD group, and 1623 (43.1% men) into the schizophrenia group. In the BD group, all glaucoma (OR 1.49, [1.18-1.89]), open-angle glaucoma (OR 2.08, [1.34-3.24]), and closed-angle glaucoma (OR 2.12, [1.36-3.33]) showed statistical significance of risk. In the MDD group, age-related macular degeneration (OR 1.33, [1.13-1.57]), all glaucoma (OR 1.24, [1.11-1.37]), open-angle glaucoma (OR 1.47, [1.21-1.80]), and dry eye syndrome (OR 1.22, [1.13-1.31]) were associated with a significantly higher risk. In the schizophrenia group, only all glaucoma (OR 1.47, [1.02-2.11]), glaucoma suspect (OR 1.88, [1.01-3.49]), and open-angle glaucoma (OR 2.19, [1.13-4.26]) showed statistical significance. Conclusions In this population-based study, ocular neurovascular diseases, especially glaucoma, were associated with increased risks of BD, MDD, and schizophrenia.
C1 [Liu, Chun-Hao] Chang Gung Mem Hosp, Dept Psychiat, Linkou Med Ctr, Taoyuan, Taiwan.
   [Liu, Chun-Hao] New Taipei Municipal Tu Cheng Hosp, Dept Psychiat, New Taipei, Taiwan.
   [Liu, Chun-Hao; Kang, Eugene Yu-Chuan; Lin, Yu-Hsiang; Wu, Wei-Chi; Liu, Zhuo-Hao; Kuo, Chang-Fu; Lai, Chi-Chun; Hwang, Yih-Shiou] Chang Gung Univ, Coll Med, Taoyuan, Taiwan.
   [Liu, Chun-Hao] Natl Dong Hwa Univ, Dept Sinophone Literatures, Hualien, Taiwan.
   [Kang, Eugene Yu-Chuan; Wu, Wei-Chi; Lai, Chi-Chun; Hwang, Yih-Shiou] Chang Gung Mem Hosp, Dept Ophthalmol, Linkou Med Ctr, Taoyuan, Taiwan.
   [Lin, Yu-Hsiang] Chang Gung Mem Hosp, Dept Urol, Linkou Med Ctr, Taoyuan, Taiwan.
   [Lin, Yu-Hsiang] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan, Taiwan.
   [Liu, Zhuo-Hao] Chang Gung Mem Hosp, Dept Neurosurg, Linkou Med Ctr, Taoyuan, Taiwan.
   [Kuo, Chang-Fu] Chang Gung Mem Hosp, Dept Rheumatol, Linkou Med Ctr, Taoyuan, Taiwan.
C3 Chang Gung Memorial Hospital; Chang Gung University; National Dong Hwa
   University; Chang Gung Memorial Hospital; Chang Gung Memorial Hospital;
   Chang Gung University; Chang Gung Memorial Hospital; Chang Gung Memorial
   Hospital
RP Hwang, YS (通讯作者)，Chang Gung Univ, Coll Med, Taoyuan, Taiwan.; Hwang, YS (通讯作者)，Chang Gung Mem Hosp, Dept Ophthalmol, Linkou Med Ctr, Taoyuan, Taiwan.
EM yihshiou.hwang@gmail.com
RI Liu, Chun-Hao/K-3602-2019
OI Liu, Chun-Hao/0000-0002-2368-6266; Lai, Chi-Chun/0000-0001-9547-7212;
   Liu, Zhuo-Hao/0000-0003-4079-8697
FU Chang Gung Memorial Hospital, Taoyuan, Taiwan [CMRPG3C0171, CMRPG3B0441,
   CORPG3C0081]; National Science Council Research Grants, Taipei, Taiwan
   [MOST 105-2314-B-182A-076, MOST 106-2314-B-182A-045 -MY3]
FX The study was supported by Chang Gung Memorial Hospital, Taoyuan, Taiwan
   (CMRPG3C0171, CMRPG3B0441, CORPG3C0081) and National Science Council
   Research Grants, Taipei, Taiwan (MOST 105-2314-B-182A-076, MOST
   106-2314-B-182A-045 -MY3). The funding organization had no role in the
   design and conduct of this study, including data collection, analysis,
   interpretation of the data, approval of the manuscript, or decision to
   submit the work for publication.
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   [No title captured]
NR 41
TC 3
Z9 3
U1 0
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-244X
J9 BMC PSYCHIATRY
JI BMC Psychiatry
PD OCT 2
PY 2020
VL 20
IS 1
AR 486
DI 10.1186/s12888-020-02881-w
PG 9
WC Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Psychiatry
GA NZ2XO
UT WOS:000576961900003
PM 33008365
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Zhang, YZ
   Yang, Y
   Yu, HT
   Li, M
   Li Hang
   Xu, XR
AF Zhang, Yuanzhong
   Yang, Yan
   Yu, Haitao
   Li, Min
   Li Hang
   Xu, Xinrong
TI Apigenin Protects Mouse Retina against Oxidative Damage by Regulating
   the Nrf2 Pathway and Autophagy
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; STRESS; CELLS; DEGENERATION; KEAP1-NRF2;
   MEMBRANES; DEATH; EYES
AB Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.
C1 [Zhang, Yuanzhong; Li Hang; Xu, Xinrong] Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Ophthalmol, Nanjing 210029, Peoples R China.
   [Yang, Yan] Nanjing Univ Chinese Med, Affiliated Hosp 2, Dept Ophthalmol, Nanjing 210017, Peoples R China.
   [Yu, Haitao] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China.
   [Li, Min] Jiangsu Prov Hosp Chinese Med, Liyang Branch, Dept Ophthalmol, Liyang 213300, Peoples R China.
C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese
   Medicine; Nanjing University of Chinese Medicine
RP Xu, XR (通讯作者)，Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Ophthalmol, Nanjing 210029, Peoples R China.
EM 13851641312@qq.com
RI Xu, Xinrong/AAX-3118-2021
OI xu, xinrong/0000-0003-2047-7298
FU Jiangsu Provincial Key Research and Development Program [BE2018757]
FX The work was supported by the Jiangsu Provincial Key Research and
   Development Program (Grant No. BE2018757).
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NR 53
TC 16
Z9 18
U1 0
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 MAY 14
PY 2020
VL 2020
AR 9420704
DI 10.1155/2020/9420704
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA LT5TC
UT WOS:000537132400001
PM 32509154
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, X
   Xia, HY
   Qin, HY
   Kang, XP
   Hu, HY
   Zheng, J
   Jiang, JY
   Yao, LA
   Xu, YW
   Zhang, T
   Zhang, XL
AF Wang, Xue
   Xia, Hua-Ying
   Qin, Hong-You
   Kang, Xiang-Ping
   Hu, Hai-Yan
   Zheng, Jing
   Jiang, Jia-Ye
   Yao, Ling-Ai
   Xu, Yan-Wu
   Zhang, Tong
   Zhang, Xue-Li
TI 20(S)-protopanaxadiol induces apoptosis in human umbilical vein
   endothelial cells by activating the PERK-eIF2alpha-ATF4 signaling
   pathway
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE apoptosis; ATF4; endoplasmic reticulum stress (ER stress); human
   umbilical vein endothelial cells (HUVECs); protein kinase R-like
   endoplasmic reticulum kinase (PERK); protopanaxadiol (PPD); small
   interfering RNA (siRNA)
ID ENDOPLASMIC-RETICULUM STRESS; ATHEROSCLEROTIC LESIONS; INDUCED
   CYTOTOXICITY; BCL-2 FAMILY; ER STRESS; GINSENG; ANGIOGENESIS;
   NEOVASCULARIZATION; GINSENOSIDES; METABOLITE
AB 20(S)-protopanaxadiol (PPD)-type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti-cancer activity. Anti-angiogenesis is a promising therapeutic approach for controlling angiogenesis-related diseases such as malignant tumors, age-related macular degeneration, and atherosclerosis. Studies showed that 20(S)-PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)-PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)-PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)-PPD induces apoptosis in HUVECs for the first time. We found that caspase-9 and its downstream caspase, caspase-3, were cleaved into their active forms after 20(S)-PPD treatment. Treatment with 20(S)-PPD decreased the level of Bcl-2 expression but did not change the level of Bax expression. 20(S)-PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R-like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP-homologous protein (CHOP) expression increased after treatment with 20(S)-PPD. Furthermore, siRNA-mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)-PPD-induced apoptosis. Collectively, our findings show that 20(S)-PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK-eIF2 alpha signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)-PPD could be used to treat angiogenesis-related diseases.
C1 [Wang, Xue; Xia, Hua-Ying; Kang, Xiang-Ping; Hu, Hai-Yan; Zheng, Jing; Yao, Ling-Ai; Xu, Yan-Wu; Zhang, Xue-Li] Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China.
   [Qin, Hong-You] Shanghai Shenyou Biol Technol Co, Shanghai, Peoples R China.
   [Jiang, Jia-Ye; Zhang, Tong] Shanghai Univ Tradit Chinese Med, Expt Ctr Teaching & Learning, Shanghai 201203, Peoples R China.
C3 Shanghai University of Traditional Chinese Medicine; Shanghai University
   of Traditional Chinese Medicine
RP Zhang, XL (通讯作者)，Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China.; Zhang, T (通讯作者)，Shanghai Univ Tradit Chinese Med, Expt Ctr Teaching & Learning, Shanghai 201203, Peoples R China.
EM zhangtdmj@hotmail.com; zhangxueli8403@163.com
RI Xu, Yanwu/AAK-6357-2020
OI Xu, Yanwu/0000-0002-9253-7790
FU Shanghai Municipal Education Commission Research Program [2016YSN05];
   Foundation of the Ministry of Education of China [NCET-10-0944];
   National Natural Science Foundation of China [81173561]
FX Shanghai Municipal Education Commission Research Program, Grant/Award
   Number: 2016YSN05; Foundation of the Ministry of Education of China,
   Grant/Award Number: NCET-10-0944; National Natural Science Foundation of
   China, Grant/Award Number: 81173561
CR Bae EA, 2004, ARCH PHARM RES, V27, P61, DOI 10.1007/BF02980048
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NR 36
TC 8
Z9 9
U1 0
U2 16
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD APR
PY 2019
VL 120
IS 4
BP 5085
EP 5096
DI 10.1002/jcb.27785
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA HL8RK
UT WOS:000459010100037
PM 30259568
DA 2022-11-30
ER

PT J
AU Wu, MF
   Feng, ZQ
   Deng, YP
   Zhong, C
   Liu, YJ
   Liu, JY
   Zhao, XH
   Fu, YJ
AF Wu, Mingfang
   Feng, Ziqi
   Deng, Yiping
   Zhong, Chen
   Liu, Yanjie
   Liu, Jiaying
   Zhao, Xiuhua
   Fu, Yujie
TI Liquid antisolvent precipitation: an effective method for ocular
   targeting of lutein esters
SO INTERNATIONAL JOURNAL OF NANOMEDICINE
LA English
DT Article
DE solubility; nanotechnology; drug delivery system; bioavailability;
   ocular pharmacokinetics
ID SOLUBLE DRUGS; NANOPARTICLES; BIOAVAILABILITY; TECHNOLOGY; ABSORPTION;
   ENCAPSULATION; ENHANCEMENT; DISSOLUTION; SOLUBILITY; DELIVERY
AB Background: Lutein ester (LE) is an important carotenoid fatty acid ester. It is a form in which lutein is present in nature and is produced by free non-esterification and fatty acid esterification. LE is one of the safe sources of lutein. Increasing lutein intake can prevent and treat age-related macular degeneration. In addition, it can effectively inhibit gastric cancer, breast cancer, and esophageal cancer. However, the poor aqueous solubility of LE has impeded its clinical applications.
   Objective: The objective of this study was to prepare lutein ester nanoparticles (LE-NPs) by liquid antisolvent precipitation techniques to improve the bioavailability of LE in vivo and improve eye delivery efficiency.
   Materials and methods: The physical characterization of LE-NPs was performed, and their in vitro dissolution rate, in vitro antioxidant capacity, in vivo bioavailability, tissue distribution, and ocular pharmacokinetics were studied and evaluated.
   Results: The LE freeze-dried powder obtained under the optimal conditions possessed a particle size of similar to 164.1 +/- 4.3 nm. The physical characterization analysis indicated the amorphous form of LE-NPs. In addition, the solubility and dissolution rate of LE-NPs in artificial gastric juice were 12.75 and 9.65 times that of the raw LE, respectively. The bioavailability of LE-NPs increased by 1.41 times compared with that of the raw LE. The antioxidant capacity of LE-NPs was also superior to the raw LE. The concentration of lutein in the main organs of rats treated with the LE-NPs was higher than that in rats treated with the raw LE. The bioavailability of LE-NPs in rat eyeballs was found to be 2.34 times that of the original drug.
   Conclusion: LE-NPs have potential application as a new oral pharmaceutical formulation and could be a promising eye-targeted drug delivery system.
C1 [Wu, Mingfang; Feng, Ziqi; Deng, Yiping; Liu, Yanjie; Liu, Jiaying; Zhao, Xiuhua; Fu, Yujie] Northeast Forestry Univ, Minist Educ, Key Lab Forest Plant Ecol, 26 Hexing Rd, Harbin 150040, Heilongjiang, Peoples R China.
   [Zhong, Chen] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
C3 Northeast Forestry University - China; Fudan University
RP Zhao, XH; Fu, YJ (通讯作者)，Northeast Forestry Univ, Minist Educ, Key Lab Forest Plant Ecol, 26 Hexing Rd, Harbin 150040, Heilongjiang, Peoples R China.
EM xiuhuazhao@nefu.edu.cn; yujie_fu@163.com
OI Zhao, Xiuhua/0000-0003-4602-1934
FU National Key Research and Development Program [2017YFD060070601]
FX The authors are grateful for the precious comments and careful
   corrections made by the anonymous reviewers. They would also like to
   acknowledge the financial support from the National Key Research and
   Development Program (2017YFD060070601).
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   2015, SEP PURIF TECHNOL, V148, P49, DOI DOI 10.1016/J.SEPPUR.2015.04.037
NR 49
TC 15
Z9 15
U1 3
U2 28
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1178-2013
J9 INT J NANOMED
JI Int. J. Nanomed.
PY 2019
VL 14
BP 2667
EP 2681
DI 10.2147/IJN.S194068
PG 15
WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Pharmacology & Pharmacy
GA HU8UE
UT WOS:000465565500001
PM 31043780
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Klee, S
   Link, D
   Sinzinger, S
   Haueisen, J
AF Klee, Sascha
   Link, Dietmar
   Sinzinger, Stefan
   Haueisen, Jens
TI Scotoma Simulation in Healthy Subjects
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
ID VISION REHABILITATION; MACULAR DEGENERATION; VISUAL IMPAIRMENT;
   REORGANIZATION; SPECTACLES; PUPIL
AB SIGNIFICANCE This article shows a successful concept for simulating central scotoma, which is associated with age-related macular degeneration (AMD), in healthy subjects by an induced dark spot at the retina using occlusive contact lenses. The new concept includes a control mechanism to adjust the scotoma size through controlling pupil size without medication. Therefore, a miniaturized full-field adaptation device was used. PURPOSE The aim of this study was to design a novel concept to simulate AMD scotoma in healthy subjects using occlusive contact lenses. METHODS To define an optimal set of lens parameters, we constructed an optical model and considered both the anatomical pupil diameter and the opaque central zone diameter of the contact lens. To adjust the scotoma size, we built a miniaturized full-field adaptation device. We demonstrate the validity of this novel concept by functional measurements of visual fields using automated threshold perimetry. Finally, we conducted a perception study including two tasks, consisting of pictograms and letters. The stimuli were presented at different eccentricities and magnifications. RESULTS The visual fields of all 10 volunteers exhibited absolute scotomas. The loss of contrast sensitivity ranged within 27 and 36 dB (P < .05), and the scotoma localizations were nearly centered to the macula (mean variation, 2.0 +/- 4.8 degrees horizontally; 3.5 +/- 4.7 degrees vertically). The eccentric perception of letters showed the largest numbers of correctly identified stimuli. The perception of pictograms showed significantly reduced numbers (P < .0001) and revealed a dependency on magnification. The results suggest that best perception is possible for magnified stimuli near the scotoma. Conclusions We demonstrated that the creation of an absolute simulated AMD scotoma is possible using occlusive contact lenses combined with a miniaturized full-field adaptation device.
C1 [Klee, Sascha; Link, Dietmar] Tech Univ Ilmenau, Dept Optoelectrophysiol Engn, Ilmenau, Germany.
   [Sinzinger, Stefan] Tech Univ Ilmenau, Dept Mech Engn, Ilmenau, Germany.
   [Haueisen, Jens] Friedrich Schiller Univ Jena, Dept Neurol, Jena, Germany.
   [Haueisen, Jens] Tech Univ Ilmenau, Inst Biomed Engn & Informat, Ilmenau, Germany.
C3 Technische Universitat Ilmenau; Technische Universitat Ilmenau;
   Friedrich Schiller University of Jena; Technische Universitat Ilmenau
RP Klee, S (通讯作者)，Tech Univ Ilmenau, Dept Optoelectrophysiol Engn, Ilmenau, Germany.
EM sascha.klee@tu-ilmenau.de
RI ; Haueisen, Jens/B-7183-2011
OI Klee, Sascha/0000-0002-0321-1255; Haueisen, Jens/0000-0003-3871-2890;
   Sinzinger, Stefan/0000-0001-8031-4787
FU Thuringian Ministry for Industry and Science [2012FGR0014]
FX Thuringian Ministry for Industry and Science (2012FGR0014; to SK).
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NR 31
TC 1
Z9 2
U1 0
U2 3
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 DEC
PY 2018
VL 95
IS 12
BP 1120
EP 1128
DI 10.1097/OPX.0000000000001310
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HC5TS
UT WOS:000451865900006
PM 30451808
OA Green Published, Green Submitted, hybrid
DA 2022-11-30
ER

PT J
AU Kerr, H
   Wong, E
   Makou, E
   Yang, Y
   Marchbank, K
   Kavanagh, D
   Richards, A
   Herbert, AP
   Barlow, PN
AF Kerr, Heather
   Wong, Edwin
   Makou, Elisavet
   Yang, Yi
   Marchbank, Kevin
   Kavanagh, David
   Richards, Anna
   Herbert, Andrew P.
   Barlow, Paul N.
TI Disease-linked mutations in factor H reveal pivotal role of cofactor
   activity in self-surface-selective regulation of complement activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; TRANSLATIONAL MINIREVIEW SERIES; ALTERNATIVE
   PATHWAY; FUNCTIONAL-CHARACTERIZATION; DECAY ACCELERATION; STRUCTURAL
   BASIS; BINDING-SITES; C-TERMINUS; PROTEIN; RISK
AB Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1-20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris. We found that recombinant I62-CFH (protective against age-related macular degeneration) and V62-CFH functioned equivalently, matching or outperforming plasma-derived CFH, whereas R53H-CFH, linked to atypical hemolytic uremic syndrome (aHUS), was defective in C3bBb decay-accelerating activity (DAA) and factor I cofactor activity (CA). The aHUS-linked CCP 19 mutant D1119G-CFH had virtually no CA on (self-like) sheep erythrocytes (E-S) but retained DAA. The aHUS-linked CCP 20 mutant S1191L/V1197A-CFH (LA-CFH) had dramatically reduced CA on ES but was less compromised in DAA. D1119G-CFH and LA-CFH both performed poorly at preventing complement-mediated hemolysis of ES. PspCN, a CFH-binding Streptococcus pneumoniae protein domain, binds CFH tightly and increases accessibility of CCPs 19 and 20. PspCN did not improve the DAA of any CFH variant on ES. Conversely, PspCN boosted the CA, on ES, of I62-CFH, R53H-CFH, and LA-CFH and also enhanced hemolysis protection by I62-CFH and LA-CFH. We conclude that CCPs 19 and 20 are critical for efficient CA on self-surfaces but less important for DAA. Exposing CCPs 19 and 20 with PspCN and thus enhancing CA on self-surfaces may reverse deficiencies of some CFH variants.
C1 [Barlow, Paul N.] Univ Edinburgh, Sch Chem, Joseph Black Bldg,David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland.
   Univ Edinburgh, Sch Biol Sci, Joseph Black Bldg,David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland.
C3 University of Edinburgh; University of Edinburgh
RP Barlow, PN (通讯作者)，Univ Edinburgh, Sch Chem, Joseph Black Bldg,David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland.
EM Paul.Barlow@ed.ac.uk
RI Herbert, Andrew P/C-4755-2008
OI Herbert, Andrew P/0000-0002-4549-6965; marchbank, kevin
   james/0000-0003-1312-5411; Wong, Edwin/0000-0003-4867-6117
FU Leverhulme Trust [RPG-2015-109]; Biotechnology and Biological Sciences
   Research Council [BB/024403/1]; Biotechnology and Biological Sciences
   Research Council [BB/L024403/1] Funding Source: researchfish; Kidney
   Research UK [JF1/2011, RP7/2015, ST5/2009] Funding Source: researchfish;
   Medical Research Council [G1001971, MR/K023519/1] Funding Source:
   researchfish; National Institute for Health Research [CL-2016-01-005]
   Funding Source: researchfish; BBSRC [BB/L024403/1] Funding Source: UKRI;
   MRC [G1001971, MR/K023519/1] Funding Source: UKRI
FX This work was supported in part by the Leverhulme Trust (RPG-2015-109)
   and by Biotechnology and Biological Sciences Research Council Grant
   BB/024403/1. A.P.H. and P.N.B. are consultants for, and scientific
   founders of, Gemini Therapeutics.
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NR 65
TC 20
Z9 21
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 AUG 11
PY 2017
VL 292
IS 32
BP 13345
EP 13360
DI 10.1074/jbc.M117.795088
PG 16
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA FD3XI
UT WOS:000407465300021
PM 28637873
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Cao, SJ
   Wang, JCC
   Gao, JY
   Wong, M
   To, E
   White, VA
   Cui, JZ
   Matsubara, JA
AF Cao, Sijia
   Wang, Jay Ching Chieh
   Gao, Jiangyuan
   Wong, Matthew
   To, Elliott
   White, Valerie A.
   Cui, Jing Z.
   Matsubara, Joanne A.
TI CFH Y402H polymorphism and the complement activation product C5a:
   effects on NF-kappa B activation and inflammasome gene regulation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; FACTOR-H; MACULAR DEGENERATION; NLRP3
   INFLAMMASOME; EXPRESSION; SECRETION; INDIVIDUALS; STIMULATION;
   PROGRESSION; VARIANT
AB Background/aims The Y402H polymorphism in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). Complement activation products and proinflammatory cytokines are associated with this polymorphism at the systemic level, but less is known of the associations in the outer retina of the genotyped eye. Here we investigate complement activation products and their role in nuclear factor (NF)-kappa B activation and gene expression of the NLRP3 inflammasome pathway.
   Methods Postmortem donor eyes were genotyped for the CFH Y402H polymorphism and assessed for complement C3a, C5a, interleukin (IL)-18 and tumour necrosis factor (TNF)-alpha. ARPE19 cells were stimulated basolaterally with C5a or TNF-alpha in polarised cultures. NF-kappa B activation was assessed with a reporter cell line. Gene expression of inflammasome-related (NLRP3, caspase-1, IL-1 beta and IL-18) and classic inflammatory (IL-6 and IL-8) genes was studied. The distribution of inflammasome products, IL-1 beta and IL-18, was studied in postmortem donor eyes with AMD pathologies.
   Results Eyes with the homozygous at-risk variant demonstrated higher levels of C5a, IL-18 and TNF-alpha in Bruch's membrane and choroid. C5a promoted NF-kappa B activation and upregulation of IL-18 in polarised ARPE19. TNF-alpha promoted NF-kappa B activation and gene expression of caspase-1, IL-1 beta, IL-18, IL-6 and IL-8, but downregulated NLRP3. In eyes with geographic atrophy, strong immunoreactivity was observed for inflammasome products IL-1 beta and IL-18 compared with age-matched controls.
   Conclusion The at-risk polymorphism of the CFH Y402H may contribute to AMD disease process through increased complement and NF-kappa B activation, and the upregulation of IL-18, a product of inflammasome activation.
C1 [Cao, Sijia; Wang, Jay Ching Chieh; Gao, Jiangyuan; Wong, Matthew; To, Elliott; White, Valerie A.; Cui, Jing Z.; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
   [White, Valerie A.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
C3 University of British Columbia; University of British Columbia
RP Matsubara, JA (通讯作者)，Eye Care Ctr, Dept Ophthalmol & Visual Sci, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
FU Canadian Institute of Health Research (CIHR) [MOP-97806, MOP-126195]
FX This study was supported by Canadian Institute of Health Research (CIHR)
   grant number MOP-97806 and MOP-126195 to JAM.
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NR 25
TC 30
Z9 34
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 2016
VL 100
IS 5
BP 713
EP 718
DI 10.1136/bjophthalmol-2015-307213
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL0OT
UT WOS:000375333000026
PM 26746578
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Jiao, HH
   Natoll, R
   Valter, K
   Provis, JM
   Rutar, M
AF Jiao, Haihan
   Natoll, Riccardo
   Valter, Krisztina
   Provis, Jan M.
   Rutar, Matt
TI Spatiotemporal Cadence of Macrophage Polarisation in a Model of
   Light-Induced Retinal Degeneration
SO PLOS ONE
LA English
DT Article
ID BONE-MARROW; PHOTORECEPTOR DEGENERATION; MICROGLIAL ACTIVATION;
   CASPASE-3 ACTIVATION; MACULAR DEGENERATION; MOUSE MODEL; CELLS;
   INFLAMMATION; RECRUITMENT; EXPRESSION
AB Background
   The recruitment of macrophages accompanies almost every pathogenic state of the retina, and their excessive activation in the subretinal space is thought to contribute to the progression of diseases including age-related macular degeneration. Previously, we have shown that macrophages aggregate in the outer retina following damage elicited by photo-oxidative stress, and that inhibition of their recruitment reduces photoreceptor death. Here, we look for functional insight into macrophage activity in this model through the spatiotemporal interplay of macrophage polarisation over the course of degeneration.
   Methods
   Rats were exposed to 1000 lux light damage (LD) for 24hrs, with some left to recover for 3 and 7 days post-exposure. Expression and localisation of M1-and M2-macrophage markers was investigated in light-damaged retinas using qPCR, ELISA, flow cytometry, and immunohistochemistry.
   Results
   Expression of M1- (Ccl3, Il-6, Il-12, Il-1 beta, TNF alpha) and M2- (CD206, Arg1, Igf1, Lyve1, Clec7a) related markers followed discrete profiles following light damage; up-regulation of M1 genes peaked at the early phase of cell death, while M2 genes generally exhibited more prolonged increases during the chronic phase. Moreover, Il-1 beta and CD206 labelled accumulations of microglia/macrophages which differed in their morphological, temporal, and spatial characteristics following light damage.
   Conclusions
   The data illustrate a dynamic shift in macrophage polarisation following light damage through a broad swathe of M1 and M2 markers. Pro-inflammatory M1 activation appears to dominate the early phase of degeneration while M2 responses appear to more heavily mark the chronic post-exposure period. While M1/M2 polarisation represents two extremes amongst a spectrum of macrophage activity, knowledge of their predominance offers insight into functional consequences of macrophage activity over the course of damage, which may inform the spatiotemporal employment of therapeutics in retinal disease.
C1 [Jiao, Haihan; Natoll, Riccardo; Valter, Krisztina; Provis, Jan M.; Rutar, Matt] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
   [Natoll, Riccardo; Valter, Krisztina; Provis, Jan M.] Australian Natl Univ, ANU Med Sch, Canberra, ACT 2601, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
EM matt.rutar@anu.edu.au
RI Valter, Krisztina/L-3015-2016; Provis, Jan/C-9529-2009
OI Rutar, Matthew/0000-0002-8893-5120; Provis, Jan/0000-0002-6405-2868;
   Natoli, Riccardo/0000-0002-9350-0439; Valter,
   Krisztina/0000-0002-2033-0408; Jiao, Haihan/0000-0002-5404-9307
FU National Health and Medical Research Council (NHMRC) Project Grant;
   Ophthalmic Research Institute of Australia (ORIA)
FX This work was supported by National Health and Medical Research Council
   (NHMRC) Project Grant, Chief Investigators: Dr. Krisztina Valter and
   Prof. Jan Provis, and the Ophthalmic Research Institute of Australia
   (ORIA), Chief Investigators: Dr. Matt Rutar.
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NR 51
TC 30
Z9 30
U1 0
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2015
VL 10
IS 12
AR e0143952
DI 10.1371/journal.pone.0143952
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CX8BI
UT WOS:000365926300129
PM 26630454
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Biswal, MR
   Ahmed, CM
   Ildefonso, CJ
   Han, PY
   Li, H
   Jivanji, H
   Mao, HY
   Lewin, AS
AF Biswal, Manas R.
   Ahmed, Chulbul M.
   Ildefonso, Cristhian J.
   Han, Pingyang
   Li, Hong
   Jivanji, Hiral
   Mao, Haoyu
   Lewin, Alfred S.
TI Systemic treatment with a 5HT1a agonist induces anti-oxidant protection
   and preserves the retina from mitochondrial oxidative stress
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age related macular degeneration; Oxidative stress; Mitochondria;
   Retinal pigment epithelium; 5-hydroxy-tryptamine 1a receptor; Drug
   therapy; Mouse model; Superoxide dismutase
ID ACTIVATED PROTEIN-KINASE; PIGMENT EPITHELIUM; 5-HT1A RECEPTOR; DAMAGE;
   MODEL; MICE; CONSEQUENCES; INHIBITION; RESISTANCE; NEURONS
AB Chronic oxidative stress contributes to age related diseases including age related macular degeneration (AMD). Earlier work showed that the 5-hydroxy-tryptamine 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide treatment and mouse retinas from oxidative insults including light injury. In our current experiments, RPE derived cells subjected to mitochondrial oxidative stress were protected from cell death by the up-regulation of anti-oxidant enzymes and of the metal ion chaperone metallothionein. Differentiated RPE cells were resistant to oxidative stress, and the expression of genes for protective proteins was highly increased by oxidative stress plus drug treatment. In mice treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced in the neural retina, but the drug did not affect the expression of Sod2, the gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2 in the RPE to accelerate age-related oxidative stress in the retina and to test the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in these mice. Treatment of mice with daily injections of the drug led to increased electroretinogram (ERG) amplitudes in dark-adapted mice and to a slight improvement in visual acuity. Most strikingly, in mice treated with a high dose of the drug (5 mg/kg) the structure of the RPE and Bruch's membrane and the normal architecture of photoreceptor outer segments were preserved. These results suggest that systemic treatment with this class of drugs may be useful in preventing geographic atrophy, the advanced form of dry AMD, which is characterized by RPE degeneration. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Biswal, Manas R.; Ahmed, Chulbul M.; Ildefonso, Cristhian J.; Han, Pingyang; Li, Hong; Jivanji, Hiral; Mao, Haoyu; Lewin, Alfred S.] Univ Florida, Dept Mol Genet & Microbiol, Coll Med, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida
RP Lewin, AS (通讯作者)，Univ Florida, Dept Mol Genet & Microbiol, Coll Med, Box 100266, Gainesville, FL 32610 USA.
EM lewin@ufl.edu
RI Ildefonso, Cristhian/AAC-3576-2021
OI Lewin, Alfred/0000-0002-4192-9727; Ildefonso,
   Cristhian/0000-0001-6179-720X; Biswal, Manas/0000-0002-9685-2923
FU BrightFocus Foundation [M2012029]; Alcon Laboratories, Inc.; Shaler
   Richardson Professorship endowment; NEI core grant [P30 EY02172];
   NATIONAL EYE INSTITUTE [P30EY021721] Funding Source: NIH RePORTER
FX This work was supported by grants from the BrightFocus Foundation
   (M2012029) and from Alcon Laboratories, Inc. Additional support was
   provided by the Shaler Richardson Professorship endowment and by the NEI
   core grant to the University of Florida (P30 EY02172). We thank Dr.
   Eduardo Candelario-Jalil for allowing us to use his voltohmmeter to
   measure transepithelial resistance and to Dr. Changjun Yang for teaching
   us how to use it.
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NR 43
TC 23
Z9 23
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2015
VL 140
BP 94
EP 105
DI 10.1016/j.exer.2015.07.022
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CV4TP
UT WOS:000364259700011
PM 26315784
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Campochiaro, PA
AF Campochiaro, Peter A.
TI Molecular pathogenesis of retinal and choroidal vascular diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Angiogenesis; Age-related macular degeneration; Diabetic retinopathy;
   Hypoxia-inducible factor-1; Vascular endothelial growth factor; Vascular
   endothelial-protein tyrosine phosphatase; TIE2; Angiopoietins;
   Platelet-derived growth factor
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; DIABETIC MACULAR
   EDEMA; OCCLUSION 12-MONTH OUTCOMES; FACTOR VEGF; IN-VIVO; OCULAR
   NEOVASCULARIZATION; PROLIFERATIVE RETINOPATHY; SOLUBLE VEGF; PDGF-B
AB There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch's membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch's membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for VEGF antagonists a priority. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   [Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 815,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
FU National Eye Institute [EY012609]; NATIONAL EYE INSTITUTE [R01EY012609]
   Funding Source: NIH RePORTER
FX Supported by EY012609 from the National Eye Institute.
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NR 121
TC 282
Z9 292
U1 7
U2 78
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 2015
VL 49
BP 67
EP 81
DI 10.1016/j.preteyeres.2015.06.002
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CY0DH
UT WOS:000366076000004
PM 26113211
OA Green Accepted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Iloki-Assanga, SB
   Lewis-Lujan, LM
   Fernandez-Angulo, D
   Gil-Salido, AA
   Lara-Espinoza, CL
   Rubio-Pino, JL
AF Bernard Iloki-Assanga, Simon
   Maria Lewis-Lujan, Lidianys
   Fernandez-Angulo, Daniela
   Andrea Gil-Salido, Armida
   Lizeth Lara-Espinoza, Claudia
   Luis Rubio-Pino, Jose
TI Retino-protective effect of Bucida buceras against oxidative stress
   induced by H2O2 in human retinal pigment epithelial cells line
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
DE Bucida buceras L; Retinal pigment epithelial cells; Oxidative stress;
   Hydrogen peroxide; Cellular redox status; Free radicals
ID HYDROGEN-PEROXIDE; ANTITUMOR AGENTS; GENE-EXPRESSION; APOPTOSIS;
   SURVIVAL; DAMAGE; GLUTATHIONE; ACTIVATION; INDUCTION; CULTURES
AB Background: Reactive Oxygen Species (ROS) impair the physiological functions of Retinal Pigment Epithelial (RPE) cells, which are known as one major cause of age-related macular degeneration and retinopathy diseases. The purpose of this study is to explore the cytoprotective effects of the antioxidant Bucida buceras extract in co-treatment with hydrogen peroxide (H2O2) delivery as a single addition or with continuous generation using glucose oxidase (GOx) in ARPE-19 cell cultures. The mechanism of Bucida buceras extract is believed to be associated with their antioxidant capacity to protect cells against oxidative stress.
   Methods: A comparative oxidative stress H2O2-induced was performed by addition and enzymatic generation using glucose oxidase on human retinal pigment epithelial cells line. H2O2-induced injury was measured by toxic effects (cell death and apoptotic pathway) and intracellular redox status: glutathione (GSH), antioxidant enzymes (catalase and glutathione peroxidase) and reducing power (FRAP). The retino-protective effect of co-treatment with Bucida buceras extract on H2O2-induced human RPE cell injury was investigated by cell death (MTT assay) and oxidative stress biomarkers (H2O2, GSH, CAT, GPx and FRAP).
   Results: Bucida buceras L. extract is believed to be associated with the ability to prevent cellular oxidative stress. When added as a pulse, H2O2 is rapidly depleted and the cytotoxicity analyses show that cells can tolerate short exposure to high peroxide doses delivered as a pulse but are susceptible to lower chronic doses. Co-treatment with Bucida buceras was able to protect the cells against H2O2-induced injury. In addition to preventing cell death treatment with antioxidant plant could also reverse the significant decrease in GSH level, catalase activity and reducing power caused by H2O2.
   Conclusion: These findings suggest that Bucida buceras could protect RPE against ocular pathogenesis associated with oxidative stress induced by H2O2-delivered by addition and enzymatic generation.
C1 [Bernard Iloki-Assanga, Simon; Maria Lewis-Lujan, Lidianys; Andrea Gil-Salido, Armida; Lizeth Lara-Espinoza, Claudia; Luis Rubio-Pino, Jose] Rubio Pharma & Asociados SA CV, LIBAF, Hermosillo 83210, Sonora, Mexico.
   [Fernandez-Angulo, Daniela] Univ Sonora UNISON Hermosillo, Hermosillo 83210, Sonora, Mexico.
RP Lewis-Lujan, LM (通讯作者)，Rubio Pharma & Asociados SA CV, LIBAF, Blvd Garcia Morales Km 6-5 330 El Llano, Hermosillo 83210, Sonora, Mexico.
EM lidianyslewis@rubiopharma.com
RI Iloki Assanga, Simon Bernard/GNP-3218-2022
OI Iloki Assanga, Simon Bernard/0000-0002-2058-5881
FU National Council of Science and Technology of Mexico (CONACYT)
FX This work was partly supported by funds from the National Council of
   Science and Technology of Mexico (CONACYT). In addition, we are very
   grateful to Dr. Horacio Rilo (Arizona, University, USA) who kindly
   gifted ARPE-19 cell line, to the botanist Dr. Jose Cosme Guerrero Ruiz
   for the botanical identification of the plant specimen and Dr. Aaron for
   helping graphical assistance and revision of the manuscript. The authors
   are sincerely grateful to Mark F. McCarty Ph.D, president of NUTRI
   GUARD, San Diego, California, USA for his hard work for refining the
   text so as to improve its clarity formatting, and editing this article.
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NR 59
TC 25
Z9 25
U1 0
U2 17
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD JUL 29
PY 2015
VL 15
AR 254
DI 10.1186/s12906-015-0765-6
PG 22
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA CN8SB
UT WOS:000358711600001
PM 26219933
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Neto, CAM
   Moreira, CA
   Moreira, ATR
AF Moreira Neto, Carlos Augusto
   Moreira Junior, Carlos Augusto
   Ramos Moreira, Ana Tereza
TI Optical coherence tomography in patients undergoing cataract surgery
SO ARQUIVOS BRASILEIROS DE OFTALMOLOGIA
LA English
DT Article
DE Cataract extraction; Fovea centralis; Diabetes mellitus; Tomography,
   optical coherence; Visual acuity
ID CYSTOID MACULAR EDEMA; UNCOMPLICATED PHACOEMULSIFICATION SURGERY;
   DIABETIC-RETINOPATHY; INTRAOCULAR-LENS; IOL IMPLANTATION;
   NATURAL-HISTORY; HEALTHY EYES; THICKNESS; EXTRACTION
AB Purpose: To assess the ability of spectral domain optical coherence tomography (SD-OCT) to diagnose macular changes pre- and post-cataract surgery and to identify changes in central foveal thickness (CFT) relative to age, sex, and presence of concomitant ophthalmic pathologies, for a period of 6 months post-surgery.
   Methods: A prospective study of patients evaluated by SD-OCT within 5 h before surgery at 7, 30, 60, 90, and 180 days post-op, with respect to CFT and presence of maculopathy.
   Results: Ninety-eight eyes of 98 patients were evaluated, with the following mean results: age = 71.4 years, pre-op VA = 0.27 logMAR, and final VA = 0.73 logMAR. There were 21 eyes in patients with diabetes mellitus (DM) and 10 eyes with age-related macular degeneration (AMD), three with epiretinal membrane, and four with glaucoma. Sixty eyes had no other ophthalmic-related pathologies (NOO), and had a mean pre-op CFT of 222 mu m, which progressively increased up to the 60th day post-op, reaching a mean of 227.2 mu m. No pseudophakic cystoid macular edema was observed. The mean CFT was statistically significantly different (p<0.001) between NOO and diabetic patients from 30 days post-op. Four eyes presented with preoperative diagnosis of AMD as measured by ophthalmoscopy. After completion of the OCT, which was performed within 5 h before surgery, six additional patients were found to have AMD. Of the 98 total eyes, 10 were diagnosed with maculopathy only by OCT exam. Binocular indirect ophthalmoscopy (BIO) was unable to detect such changes.
   Conclusion: OCT diagnosed preoperative maculopathies in 21.4% of the patients, and was more effective than BIO (11.2%). OCT showed a progressive increase in CFT in diabetics up to 180 days post-operatively, as well as greater CFT in male patients and patients older than 70 years.
C1 [Moreira Neto, Carlos Augusto] Hosp Olhos Parana, Curitiba, Parana, Brazil.
   [Moreira Junior, Carlos Augusto; Ramos Moreira, Ana Tereza] Univ Fed Parana UFPR, Dept Ophthalmol, Curitiba, Parana, Brazil.
C3 Universidade Federal do Parana
RP Neto, CAM (通讯作者)，Rua Fernando Simas 1-010, BR-80710660 Curitiba, Parana, Brazil.
EM moreiraguto@hotmail.com
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NR 26
TC 18
Z9 18
U1 0
U2 6
PU CONSEL BRASIL OFTALMOLOGIA
PI SAO PAULO
PA ALAMEDA SANTOS 1343, 11 ANDAR CJ 1110, CERQUEIRA CESAR, SAO PAULO, SP
   00000, BRAZIL
SN 0004-2749
EI 1678-2925
J9 ARQ BRAS OFTALMOL
JI Arq. Bras. Oftalmol.
PD JUL-AUG
PY 2015
VL 78
IS 4
BP 241
EP 245
DI 10.5935/0004-2749.20150062
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CR7QV
UT WOS:000361546500010
PM 26375340
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Gounarides, J
   Cobb, JS
   Zhou, J
   Cook, F
   Yang, XM
   Yin, H
   Meredith, E
   Rao, C
   Huang, Q
   Xu, YY
   Anderson, K
   De Erkenez, A
   Liao, SM
   Crowley, M
   Buchanan, N
   Poor, S
   Qiu, YB
   Fassbender, E
   Shen, SY
   Woolfenden, A
   Jensen, A
   Cepeda, R
   Etemad-Gilbertson, B
   Giza, S
   Mogi, M
   Jaffee, B
   Azarian, S
AF Gounarides, John
   Cobb, Jennifer S.
   Zhou, Jing
   Cook, Frank
   Yang, Xuemei
   Yin, Hong
   Meredith, Erik
   Rao, Chang
   Huang, Qian
   Xu, YongYao
   Anderson, Karen
   De Erkenez, Andrea
   Liao, Sha-Mei
   Crowley, Maura
   Buchanan, Natasha
   Poor, Stephen
   Qiu, Yubin
   Fassbender, Elizabeth
   Shen, Siyuan
   Woolfenden, Amber
   Jensen, Amy
   Cepeda, Rosemarie
   Etemad-Gilbertson, Bijan
   Giza, Shelby
   Mogi, Muneto
   Jaffee, Bruce
   Azarian, Sassan
TI Lack of Involvement of CEP Adducts in TLR Activation and in Angiogenesis
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; NEOVASCULARIZATION; INFLAMMATION; BIOMARKERS;
   COMPLEX; DAMAGE; CRB1
AB Proteins that are post-translationally adducted with 2-(omega-carboxyethyl) pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others.
C1 [Gounarides, John; Cobb, Jennifer S.; Zhou, Jing; Cook, Frank; Yang, Xuemei; Yin, Hong; Meredith, Erik; Rao, Chang; Huang, Qian; Xu, YongYao; Anderson, Karen; De Erkenez, Andrea; Liao, Sha-Mei; Crowley, Maura; Buchanan, Natasha; Poor, Stephen; Qiu, Yubin; Fassbender, Elizabeth; Shen, Siyuan; Woolfenden, Amber; Jensen, Amy; Cepeda, Rosemarie; Etemad-Gilbertson, Bijan; Giza, Shelby; Mogi, Muneto; Jaffee, Bruce; Azarian, Sassan] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
C3 Novartis
RP Azarian, S (通讯作者)，Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
EM Sassan.Azarian@novartis.com
OI Giza, Shelby/0000-0002-0772-8200
FU Novartis Institutes for Biomedical Research
FX This study was funded by the Novartis Institutes for Biomedical
   Research. The funder provided support in the form of salaries for all
   authors, but did not have any additional role in the study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript. The specific roles of these authors are articulated in the
   'author contributions' section.
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NR 22
TC 6
Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2014
VL 9
IS 10
AR e111472
DI 10.1371/journal.pone.0111472
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AS0BL
UT WOS:000343943500102
PM 25343517
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Flynn-Evans, EE
   Tabandeh, H
   Skene, DJ
   Lockley, SW
AF Flynn-Evans, Erin E.
   Tabandeh, Homayoun
   Skene, Debra J.
   Lockley, Steven W.
TI Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women
   with and without Light Perception
SO JOURNAL OF BIOLOGICAL RHYTHMS
LA English
DT Article
DE melatonin; blindness; 6-sulfatoxymelatonin; circadian rhythms; sleep;
   melanopsin; ipRGCs; nonentrained; circadian rhythm disorder
ID RETINAL GANGLION-CELLS; BREAST-CANCER; SLEEP; MELANOPSIN; PUPILLARY;
   PERIOD; ENTRAINMENT; SECRETION; EXPOSURE; NEURONS
AB Light is the major environmental time cue that synchronizes the endogenous central circadian pacemaker, located in the suprachiasmatic nuclei of the hypothalamus, and is detected exclusively by the eyes primarily via specialized non-rod, non-cone ganglion cell photoreceptors. Consequently, most blind people with no perception of light (NPL) have either nonentrained or abnormally phased circadian rhythms due to this inability to detect light. Conversely, most visually impaired participants with some degree of light perception (LP) exhibit normal entrainment, emphasizing the functional separation of visual and "nonvisual" photoreception. The aims of the study were to identify the prevalence of circadian disorders in blind women, with the further aim of examining how eye disease may relate to the type of circadian disorder. Participants (n = 127, age 50.8 +/- 13.4 years) completed an 8-week field study including daily sleep diaries and sequential 4 to 8 hourly urine collections over 48 h on 2 to 3 occasions separated by at least 2 weeks. Circadian type was determined from the timing and time course of the melatonin rhythm measured by cosinor-derived urinary 6-sulfatoxymelatonin rhythm peak. Of the participants with NPL (n = 41), the majority were abnormally phased (24%) or nonentrained (39%), with 37% classified as normally entrained. Of the participants with LP (n = 86), the majority were normally entrained (69%). Eighteen LP participants (21%) were abnormally phased (8 advanced, 10 delayed). Nine LP participants (10%) were nonentrained. The eye conditions most associated with abnormal phase and/or nonentrained circadian rhythms were bilateral enucleation (67%) and retinopathy of prematurity (57%). By contrast, 84% of participants with retinitis pigmentosa and 83% of those with age-related macular degeneration were normally entrained. These findings suggest that the etiology of blindness in addition to LP status is related to an individual's ability to process the circadian light signal.
C1 [Flynn-Evans, Erin E.; Lockley, Steven W.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Dept Med, Boston, MA 02115 USA.
   [Flynn-Evans, Erin E.; Lockley, Steven W.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Dept Neurol, Boston, MA 02115 USA.
   [Flynn-Evans, Erin E.; Lockley, Steven W.] Harvard Univ, Sch Med, Dept Med, Div Sleep Med, Boston, MA USA.
   [Flynn-Evans, Erin E.; Skene, Debra J.] Univ Surrey, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England.
   [Tabandeh, Homayoun] Retina Vitreous Associates, Beverly Hills, CA USA.
C3 Harvard University; Brigham & Women's Hospital; Harvard University;
   Brigham & Women's Hospital; Harvard University; Harvard Medical School;
   University of Surrey; Retina Vitreous Associates Medical Group
RP Lockley, SW (通讯作者)，Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 221 Longwood Ave,BLI 438, Boston, MA 02115 USA.
EM steven_lockley@hms.harvard.edu
OI Skene, Debra/0000-0001-8202-6180; Lockley, Steven/0000-0001-5209-2881
FU US Department of Defense Breast Cancer Research Program Idea Award
   [BC030928, W81XWH-04-1-0553]; Harvard Medical School Division of Sleep
   Medicine Training Program in Sleep, Circadian and Respiratory
   Neurobiology [HL07901-11]
FX The authors thank Dr. Elizabeth B. Klerman, Dr. Benita Middleton,
   Emeritus Professor Josephine Arendt, Dr. Richard G. Stevens, Dr. Eva S.
   Schernhammer, Eve Silver, Amy Ruell, and Dr. Joseph T. Hull for
   assistance with this project. The authors also wish to thank the
   students who assisted with data collection, including Kathleen Maguire,
   Emily McCoy, Rebecca Steinberg, Jennifer Markham, Kai Romero, Yunxue Xu,
   Michael Steinhaus, Ines Pacheco, Grace Kim, Folasade Odenyi, Naila
   Ramji, Anna Rosenblum, Emma Prokic, Erica Bloom, Natasha Makengo, Ashley
   Pawlisz, Nicholas Moser, Alana Vivolo, Jessica Giordano, Marissa
   Sheldon, Tomoko Okada, Liwei Fan, Kristoff Nelson, Kevin Sun, and Jane
   Flynn. The authors also wish to thank several organizations that donated
   time and effort to assist with this project, including the American
   Council of the Blind, the Bay State Council for the Blind, the
   Massachusetts Commission for the Blind, the Canadian National Institute
   of the Blind, the National Braille Press, the National Federation of the
   Blind, the Perkins Braille and Talking Book Library, radio reading
   services nationwide, and Ripco. Finally, the authors would like to thank
   Velir Studios for development of the study website. This work was
   supported by a US Department of Defense Breast Cancer Research Program
   Idea Award (BC030928, #W81XWH-04-1-0553 to SWL) and a predoctoral
   fellowship from the Harvard Medical School Division of Sleep Medicine
   Training Program in Sleep, Circadian and Respiratory Neurobiology
   (HL07901-11 to EEE).
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NR 43
TC 59
Z9 60
U1 0
U2 35
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0748-7304
EI 1552-4531
J9 J BIOL RHYTHM
JI J. Biol. Rhythms
PD JUN
PY 2014
VL 29
IS 3
BP 215
EP 224
DI 10.1177/0748730414536852
PG 10
WC Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Physiology
GA AJ3KZ
UT WOS:000337566500006
PM 24916394
DA 2022-11-30
ER

PT J
AU Blackmore-Wright, S
   Georgeson, MA
   Anderson, SJ
AF Blackmore-Wright, Sally
   Georgeson, Mark A.
   Anderson, Stephen J.
TI Enhanced Text Spacing Improves Reading Performance in Individuals with
   Macular Disease
SO PLOS ONE
LA English
DT Article
ID PREFERRED RETINAL LOCUS; EYE-MOVEMENTS; LETTER-RECOGNITION; PERCEPTUAL
   SPAN; SPEED; PSYCHOPHYSICS; FONT; SCOTOMAS; LINE; IDENTIFICATION
AB The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that 'visual crowding' may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency.
C1 [Blackmore-Wright, Sally; Georgeson, Mark A.; Anderson, Stephen J.] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
C3 Aston University
RP Anderson, SJ (通讯作者)，Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
EM s.j.anderson@aston.ac.uk
OI Georgeson, Mark/0000-0002-8173-9522
FU Macular Disease Society, UK
FX Funded by The Macular Disease Society, UK. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 64
TC 15
Z9 15
U1 0
U2 25
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 11
PY 2013
VL 8
IS 11
AR e80325
DI 10.1371/journal.pone.0080325
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Science & Technology - Other Topics
GA 255EG
UT WOS:000327221600203
PM 24244676
OA Green Published, Green Submitted, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Kloeckener-Gruissem, B
   Barthelmes, D
   Labs, S
   Schindler, C
   Kurz-Levin, M
   Michels, S
   Fleischhauer, J
   Berger, W
   Sutter, F
   Menghini, M
AF Kloeckener-Gruissem, Barbara
   Barthelmes, Daniel
   Labs, Stephan
   Schindler, Christian
   Kurz-Levin, Malaika
   Michels, Stephan
   Fleischhauer, Johannes
   Berger, Wolfgang
   Sutter, Florian
   Menghini, Moreno
TI Genetic Association with Response to Intravitreal Ranibizumab in
   Patients with Neovascular AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION;
   FACTOR-B; POLYMORPHISMS; HTRA1; LOC387715; CFH; VARIANT; RISK
AB PURPOSE. Neovascular age-related macular degeneration (AMD) resulting in decreased central vision severely impairs affected individuals. Current standard treatment is an intravitreal anti-VEGF therapy (ranibizumab), but responses to treatment show large variability. Genetic factors that influence AMD and that affect the outcome of ranibizumab treatment were sought within a sample of Swiss patients.
   METHODS. Changes in visual acuity (VA) after initiation of anti-VEGF treatment were observed during 12 months, and percentiles of VA were calculated. Genotypes of polymorphisms in known AMD susceptibility loci (CFH, CFB, HTRA1, AMRS2, and VEGFA) as well as not yet reported AMD-associated genes (KDR, LRP5, and FZD4) were determined, and their frequencies were compared.
   RESULTS. Of the 309 eyes included in the study, 243 completed VA assessment. On average, 3.9 +/- 2.6 ranibizumab injections were administered. Based on the change in visual acuity, two responder groups were established: 63 eyes were assigned to the poor responders (<= 25th percentile) and 63 eyes to the good responders (>= 75th percentile). Individuals with genotype CC of p. Y402H in CFH had a decreased chance of positive treatment outcome compared with those with the CT and TT genotypes (P = 0.005 and P = 0.006). In this study, the genotype combination of AG at CFH with CT at FZD4 (SNP rs10898563) promised an increased chance of positive treatment outcome (P = 0.004). Furthermore, the association with the known genetic susceptibility loci CFH, HTRA1, and AMRS2 were confirmed, and a risk-conferring polymorphism in one new locus, LRP5, was identified.
   CONCLUSIONS. Genetic predisposition may account for the variability in response to anti-VEGF treatment. (Invest Ophthalmol Vis Sci. 2011;52:4694-4702) DOI:10.1167/iovs.10-6080
C1 [Kloeckener-Gruissem, Barbara; Labs, Stephan; Berger, Wolfgang] Univ Zurich, Inst Med Mol Genet, CH-8603 Schwerzenbach, Switzerland.
   [Kloeckener-Gruissem, Barbara] ETHZ, Dept Biol, Zurich, Switzerland.
   [Barthelmes, Daniel; Kurz-Levin, Malaika; Michels, Stephan; Fleischhauer, Johannes; Sutter, Florian; Menghini, Moreno] Univ Zurich Hosp, Dept Ophthalmol, CH-8091 Zurich, Switzerland.
   [Barthelmes, Daniel] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
   [Schindler, Christian] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
   [Michels, Stephan] Stadtspital Triemli, Augenklin, Zurich, Switzerland.
C3 University of Zurich; Swiss Federal Institutes of Technology Domain; ETH
   Zurich; University of Zurich; University Zurich Hospital; University of
   Sydney; University of Basel; Swiss Tropical & Public Health Institute;
   Triemli Hospital
RP Kloeckener-Gruissem, B (通讯作者)，Univ Zurich, Inst Med Mol Genet, CH-8603 Schwerzenbach, Switzerland.
EM kloeckener@medgen.uzh.ch; florian@sutter-adler.ch
RI Schindler, Christian/D-3472-2015
OI Menghini, Moreno/0000-0002-1432-2524
FU Novartis Pharma Schweiz, AG; Swiss National Foundation; Walter and
   Gertrud Siegenthaler Foundation, Zurich, Switzerland
FX Supported by an unrestricted research grant from Novartis Pharma
   Schweiz, AG; the Swiss National Foundation (DB); and the Walter and
   Gertrud Siegenthaler Foundation, Zurich, Switzerland (DB).
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NR 59
TC 102
Z9 113
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 JUN
PY 2011
VL 52
IS 7
BP 4694
EP 4702
DI 10.1167/iovs.10-6080
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800BP
UT WOS:000293332500102
PM 21282580
DA 2022-11-30
ER

PT J
AU Liu, BY
   Faia, L
   Hu, MJ
   Nussenblatt, RB
AF Liu, Baoying
   Faia, Lisa
   Hu, Mengjun
   Nussenblatt, Robert B.
TI Pro-angiogenic effect of IFN gamma is dependent on the
   PI3K/mTOR/translational pathway in human retinal pigmented epithelial
   cells
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; INTERFERON-GAMMA;
   TNF-ALPHA; GENE-EXPRESSION; TRANSGENIC MICE; TRANSCRIPTIONAL
   SUPPRESSION; PROINFLAMMATORY CYTOKINES; TUMOR ANGIOGENESIS; IN-VITRO
AB Purpose: To investigate the molecular signaling pathway of Interferon gamma (IFN gamma) contributing to angiogenesis in retinal pigmented epithelial (RPE) cells and the role of Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) in this process.
   Methods: Human adult and fetal RPE cells were used in this study. Real-time polymerase chain reaction was used to detect human vascular endothelial growth factor (VEGF) mRNA expression. Thiazolyl blue tetrazolium bromide (MTT) assay was used to detect cell viability. VEGF expression from cell supernatant was measured using enzyme-linked immunosorbent assay (ELISA). Small interfering RNA (SiRNA) of signal transducers and activators of transcription 1 (stat1) and protein kinases B (akt) were transfected into ARPE-19 cells to directly study the roles of these molecules in VEGF expression. Sodium dodecyl sulfate PAGE (SDS-PAGE) and western blot analysis were used to detect the expression of signaling molecules.
   Results: IFN gamma promoted human VEGF expression in both adult and fetal RPE cells. The PI-3K/Akt/mTOR/p70 S6 kinase pathway is required for IFN gamma-induced VEGF expression in retinal cells. The mTOR inhibitor, rapamycin, along with the SiRNA targeted to akt and the PI3K inhibitor, LY294002, decreased hVEGF secretion from RPE cells. Moreover, IFN gamma-induced hVEGF expression was not affected by SiRNA targeted to Stat1, implying that the classic Jak-Stat1 pathway of IFN gamma may not be involved in this process.
   Conclusions: We provide evidence that IFN gamma induces VEGF expression in human retinal pigment epithelial cells. Our work emphasizes that the activation of the PI-3K/mTOR/translational pathway is important for IFN gamma-mediated VEGF expression in RPE cells. By elucidating molecular signaling involved in this process, our findings provide further mechanistic insight into the successful clinical application of rapamycin therapy for choroidal neovascularization in age-related macular degeneration (AMD) and uveitis.
C1 [Liu, Baoying; Faia, Lisa; Hu, Mengjun; Nussenblatt, Robert B.] NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Nussenblatt, RB (通讯作者)，NEI, NIH, Immunol Lab, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU NIH; National Eye Institute
FX We thank Drs. Arvydas Maminishkis and Sheldon Miller for providing fetal
   RPE cells and Shayma Jawad for her critics of the manuscript. This
   research was supported by the Intramural Research Program of NIH,
   National Eye Institute.
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NR 56
TC 32
Z9 33
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 FEB 10
PY 2010
VL 16
IS 22-26
BP 184
EP 193
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 570ZG
UT WOS:000275716800002
PM 20157617
DA 2022-11-30
ER

PT J
AU Ng, KP
   Gugiu, BD
   Renganathan, K
   Davies, MW
   Gu, XR
   Crabb, JS
   Kim, SR
   Rozanowska, MB
   Bonilha, VL
   Rayborn, ME
   Salomon, RG
   Sparrow, JR
   Boulton, ME
   Hollyfield, JG
   Crabb, JW
AF Ng, Kwok-Peng
   Gugiu, Bogdan
   Renganathan, Kutralanathan
   Davies, Matthew W.
   Gu, Xiaorong
   Crabb, John S.
   Kim, So Ra
   Rozanowska, Malgorzata B.
   Bonilha, Vera L.
   Rayborn, Mary E.
   Salomon, Robert G.
   Sparrow, Janet R.
   Boulton, Michael E.
   Hollyfield, Joe G.
   Crabb, John W.
TI Retinal pigment epithelium lipofuscin proteomics
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID PROTEIN ADDUCTS; AGE PIGMENT; VISUAL CYCLE; ACCUMULATION; DAMAGE; A2E;
   FLUOROPHORES; PRODUCTS; CELLS; RPE
AB Lipofuscin accumulates with age in the retinal pigment epithelium (RPE) in discrete granular organelles and may contribute to age-related macular degeneration. Because previous studies suggest that lipofuscin contains protein that may impact pathogenic mechanisms, we pursued proteomics analysis of lipofuscin. The composition of RPE lipofuscin and its mechanisms of pathogenesis are poorly understood in part because of the heterogeneity of isolated preparations. We purified RPE lipofuscin granules by treatment with proteinase K or SDS and showed by light, confocal, and transmission electron microscopy that the purified granules are free of extragranular material and associated membranes. Crude and purified lipofuscin preparations were quantitatively compared by (i) LC MS/MS proteomics analyses, (ii) immunoanalyses of oxidative protein modifications, (iii) amino acid analysis, (iv) HPLC of bisretinoids, and (v) assaying phototoxicity to RPE cells. From crude lipofuscin preparations 186 proteins were identified, many of which appeared to be modified. In contrast, very little protein (similar to 2% (w/w) by amino acid analysis) and no identifiable protein were found in the purified granules, which retained full phototoxicity to cultured RPE cells. Our analyses showed that granules in purified and crude lipofuscin preparations exhibit no statistically significant differences in diameter or circularity or in the content of the bisretinoids A2E, isoA2E, and all-trans-retinal dimer-phosphatidylethanolamine. The finding that the purified granules contain minimal protein yet retain phototoxic activity suggests that RPE lipofuscin pathogenesis is largely independent of associated protein. The purified granules also exhibited oxidative protein modifications, including nitrotyrosine generated from reactive nitrogen oxide species and carboxyethylpyrrole and iso[4] levuglandin E-2 adducts generated from reactive lipid fragments. This finding is consistent with previous studies demonstrating RPE lipofuscin to be a potent generator of reactive oxygen species and supports the hypothesis that such species, including reactive fragments from lipids and retinoids, contribute to the mechanisms of RPE lipofuscin pathogenesis.
C1 [Ng, Kwok-Peng; Gugiu, Bogdan; Renganathan, Kutralanathan; Gu, Xiaorong; Crabb, John S.; Bonilha, Vera L.; Rayborn, Mary E.; Hollyfield, Joe G.; Crabb, John W.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
   [Ng, Kwok-Peng; Gugiu, Bogdan; Renganathan, Kutralanathan; Gu, Xiaorong; Crabb, John S.; Bonilha, Vera L.; Rayborn, Mary E.; Hollyfield, Joe G.; Crabb, John W.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Renganathan, Kutralanathan; Salomon, Robert G.; Crabb, John W.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44195 USA.
   [Davies, Matthew W.; Rozanowska, Malgorzata B.; Boulton, Michael E.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF10 3XQ, S Glam, Wales.
   [Kim, So Ra; Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Boulton, Michael E.] Univ Texas Galveston, Med Branch, Galveston, TX 77555 USA.
   [Hollyfield, Joe G.; Crabb, John W.] Case Western Reserve Univ, Dept Ophthalmol, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Case Western
   Reserve University; Cardiff University; Columbia University; University
   of Texas System; University of Texas Medical Branch Galveston; Case
   Western Reserve University; Cleveland Clinic Foundation
RP Crabb, JW (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM crabbj@ccf.org
RI Bonilha, Vera/AAS-8566-2020; Salomon, Robert G/C-3463-2008; renganathan,
   Kutralanathan/F-8580-2010; Rozanowska, Malgorzata B/B-7860-2014;
   Rozanowska, Malgorzata/AAD-4806-2021
OI Bonilha, Vera/0000-0002-6166-5124; renganathan,
   Kutralanathan/0000-0001-9001-2934; Rozanowska, Malgorzata
   B/0000-0003-2913-8954; Rozanowska, Malgorzata/0000-0003-2913-8954;
   Salomon, Robert/0000-0001-9456-3557
FU NATIONAL EYE INSTITUTE [R21EY017153, R01EY014240, R01EY016813,
   R01EY012951, R56EY014240, R01EY014239, R24EY015638] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM021249]
   Funding Source: NIH RePORTER
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NR 48
TC 126
Z9 128
U1 0
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD JUL
PY 2008
VL 7
IS 7
BP 1397
EP 1405
DI 10.1074/mcp.M700525-MCP200
PG 9
WC Biochemical Research Methods
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 323QR
UT WOS:000257463000016
PM 18436525
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Tatar, O
   Yoeruek, E
   Szurman, P
   Bartz-Schmidt, KU
   Adam, A
   Shinoda, K
   Eckardt, C
   Boeyden, V
   Claes, C
   Pertile, G
   Scharioth, GB
   Grisanti, S
AF Tatar, Olcay
   Yoeruek, Efdal
   Szurman, Peter
   Bartz-Schmidt, Karl Ulrich
   Adam, Annemarie
   Shinoda, Kei
   Eckardt, Claus
   Boeyden, Vicky
   Claes, Carl
   Pertile, Grazia
   Scharioth, Gabor B.
   Grisanti, Salvatore
CA Tubingen Bevacizumab Study Grp
TI Effect of bevacizumab on inflammation and proliferation in human
   choroidal neovascularization
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1;
   RETINAL-PIGMENT EPITHELIUM; INTRAVITREAL BEVACIZUMAB; MACULAR
   DEGENERATION; 360-DEGREES RETINOTOMY; PHOTODYNAMIC THERAPY; FACTOR
   EXPRESSION; FACTOR VEGF; MACROPHAGES
AB Objective: To evaluate the effect of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California) on inflammation and proliferation in human choroidal neovascularization (CNV) secondary to age-related macular degeneration.
   Methods: Retrospective review of interventional series of 38 patients who underwent choroidal neaovascular membrane (CNVM) extraction. Twenty-four patients received intravitreal bevacizumab 1 to 154 days preoperatively (bevacizumab CNV group). Fourteen patients received no preoperative therapy (control CNV group). The CNVM were stained for cytokeratin 18, CD68, CD45, intercellular adhesion molecule (ICAM)-1, E-selectin, Ki-67, Thy-1, and endostatin.
   Results: No significant difference was detected in ICAM-1 and E-selectin expression between groups. The density of leukocytes in the bevacizumab CNV group(median, 271.61 cells/mm(2)) was higher than in the control CNV group (median, 116.87 cells/mm(2); P=.07), but without significance. Density of macrophages (median, 4661.95 cells/mm(2)), proliferative activity (median, 160.19 cells/mm(2)), and percentage of Thy-1-expressing vessels (median, 100%) were significantly higher in the bevacizumab CNV group than in the control CNV group(median, 882.66 cells/mm(2), P<.001; median, 34.34 cells/mm(2), P<.001; and median, 80%, P<.001, respectively). Endostatin immunoreactivity was considerably stronger in the retina pigment epithelium (RPE)-Bruch membrane complex (median, 3; range, 2-3; P<.001), and stroma (median, 3; range, 1-3; P<.001) of the bevacizumab CNV group than control CNV group (median, 1.5; range, 0-3 and median, 1; range, 0-3, respectively).
   Conclusions: Unexpectedly, CNVM from patients treated by bevacizumab are characterized by significantly high inflammatory and proliferative activity and enhanced endostatin expression. These characteristics need to be considered when protocols for combination therapies are established.
C1 [Tatar, Olcay; Yoeruek, Efdal; Szurman, Peter; Bartz-Schmidt, Karl Ulrich; Grisanti, Salvatore] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany.
   [Adam, Annemarie] Univ Tubingen, Dept Pathol, D-72074 Tubingen, Germany.
   [Eckardt, Claus] Augenklin Staedt Kliniken, Frankfurt, Germany.
   [Scharioth, Gabor B.] Augenzentrum Recklinghausen, Recklinghausen, Germany.
   [Shinoda, Kei] Natl Inst Sensory Organs, Lab Visual Physiol, Tokyo, Japan.
   [Boeyden, Vicky; Claes, Carl] Algemeen Ziekenhuis Sint Augustinus Hosp, Dept Achtersegment, Antwerp, Belgium.
   [Pertile, Grazia] Sacro Cuore Hosp, Dept Ophthalmol, Negrar, Italy.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen; Eberhard Karls
   University Hospital; IRCCS Sacro Cuore Don Calabria
RP Grisanti, S (通讯作者)，Med Univ Lubeck, Dept Ophthalmol, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM Salvatore.Grisanti@uk-sh.de
RI Shinoda, Kei/ABC-7993-2020; Pertile, Grazia/AAC-4956-2022
OI Shinoda, Kei/0000-0002-1543-9345; 
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NR 83
TC 32
Z9 33
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 JUN
PY 2008
VL 126
IS 6
BP 782
EP 790
DI 10.1001/archopht.126.6.782
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 310RX
UT WOS:000256548900003
PM 18541840
OA Bronze
DA 2022-11-30
ER

PT J
AU Hahn, P
   Dentchev, T
   Qian, Y
   Rouault, T
   Harris, ZL
   Dunaief, JL
AF Hahn, P
   Dentchev, T
   Qian, Y
   Rouault, T
   Harris, ZL
   Dunaief, JL
TI Immunolocalization and regulation of iron handling proteins ferritin and
   ferroportin in the retina
SO MOLECULAR VISION
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; MITOCHONDRIAL FERRITIN;
   NEURODEGENERATIVE DISORDERS; MACULAR DEGENERATION; PIGMENT EPITHELIUM;
   METABOLISM; CERULOPLASMIN; TRANSFERRIN; CELLS
AB Purpose: CNS iron accumulation is associated with several neurodegenerative diseases, including age-related macular degeneration. Intracellular overload of free iron is prevented, in part, by the iron export protein, ferroportin, and the iron storage protein, ferritin. The purpose of this study was to assess retinal localization and regulation of ferroportin and ferritin.
   Methods: Normal murine retinas were analyzed by immunohistochemistry to localize ferroportin, cytosolic ferritin, and mitochondrial ferritin, with double-labeling using cell-specific markers to identify cell types. Retinas deficient in the ferroxidases, ceruloplasmin and hephaestin, accumulate iron in their retinas and RPE, while retinas deficient in iron regulatory proteins (IRPs) lack the ability to regulate several proteins involved in iron metabolism; retinas from these knockout mice along with their age matched wild type littermates were also examined to study regulation of ferritin and ferroportin. To enable visualization of label in the retinal pigment epithelial cells, sections from pigmented mice were bleached with H2O2 prior to IHC, a novel use of this technique for study of the RPE.
   Results: In normal retinas, cytosolic ferritins were found predominantly in rod bipolar cells and photoreceptors. Ferroportin was found in RPE and MUller cells. Iron accumulation in mice deficient in ceruloplasmin and hephaestin was associated with upregulation of ferritin and ferroportin. Mice deficient in IRPs showed upregulation of ferritin and ferroportin, likely because of their inability to repress translation.
   Conclusions: Normal retinas contain ferritin and ferroportin, whose levels are regulated by iron-responsive, iron regulatory proteins. Ferroportin colocalizes with ceruloplasmin and hephaestin to RPE and MUller cells, supporting a potential cooperation between these ferroxidases and the iron exporter. Cytosolic ferritin accumulates in rod bipolar synaptic terminals, suggesting that ferritin may be involved in axonal iron transport. Mitochondrial ferritin increases with iron accumulation, suggesting a role in iron storage.
C1 Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA USA.
   NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Div Pediat Anesthesiol & Crit Care Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; National Institutes
   of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of
   Child Health & Human Development (NICHD); Johns Hopkins University
RP Dunaief, JL (通讯作者)，Stellar Chance Labs 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
OI Hahn, Paul/0000-0002-6574-388X; Harris, Zena Leah/0000-0003-0110-8438
FU NEI NIH HHS [R01EY015240, K08EY00417] Funding Source: Medline; NIDDK NIH
   HHS [DK02464, DK58086] Funding Source: Medline; NIGMS NIH HHS
   [T32GM7170] Funding Source: Medline; EUNICE KENNEDY SHRIVER NATIONAL
   INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [ZIAHD001602] Funding
   Source: NIH RePORTER; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD
   HEALTH &HUMAN DEVELOPMENT [Z01HD001602] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY015240, K08EY000417] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [R01DK058086, K08DK002464] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007170] Funding
   Source: NIH RePORTER
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NR 43
TC 58
Z9 61
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 AUG 26
PY 2004
VL 10
IS 72
BP 598
EP 607
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 852EG
UT WOS:000223737400001
PM 15354085
DA 2022-11-30
ER

PT J
AU Liu, Y
   Lee, RK
AF Liu, Yuan
   Lee, Richard K.
TI Cell transplantation to replace retinal ganglion cells faces challenges
   - the Switchboard Dilemma
SO NEURAL REGENERATION RESEARCH
LA English
DT Review
DE cell transplantation; optic nerve regeneration; photoreceptors; retina
   degeneration; retinal ganglion cells; stem cells
ID PLURIPOTENT STEM-CELLS; AXON REGENERATION; OPTIC-NERVE; PHOTORECEPTORS
   RESTORES; MULLER GLIA; IN-VITRO; MOUSE; GENERATION; DIFFERENTIATION;
   EXPRESSION
AB The mammalian retina displays incomplete intrinsic regenerative capacities; therefore, retina degeneration is a major cause of irreversible blindness such as glaucoma, age-related macular degeneration and diabetic retinopathy. These diseases lead to the loss of retinal cells and serious vision loss in the late stage. Stem cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative neurotherapy. Several suitable stem cell sources for transplantation including human embryonic stem cells, induced pluripotent stem cells and adult stem cells have been identified as promising target populations. However, the retina is an elegant neuronal complex composed of various types of cells with different functions. The replacement of these different types of cells by transplantation should be addressed separately. So far, retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials, while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal models. In this review, we opine on the key problems that need to be addressed before stem cells transplantation, especially for replacing injured retinal ganglion cells, may be used practically for treatment. A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell replacement. We use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual signaling. Retinal ganglion cell transplantation is confronted by significant hurdles, because retinal ganglion cells receive signals from different interneurons, integrate and send signals to the correct targets of the visual system, which functions similar to the switchboard in a telephone network - therefore the Switchboard Dilemma.
C1 [Liu, Yuan; Lee, Richard K.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami
RP Lee, RK (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
EM rlee@med.miami.edu
FU NIH Center Core Grant [P30EY014801]; Research to Prevent Blindness;
   Walter G. Ross Foundation
FX This work was supported by the NIH Center Core Grant, No. P30EY014801
   (to Bascom Palmer Eye Institute) and a Research to Prevent Blindness
   Unrestricted Grant (to Bascom Palmer Eye Institute); the Walter G. Ross
   Foundation (to RKL).
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NR 48
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U2 46
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 1673-5374
EI 1876-7958
J9 NEURAL REGEN RES
JI Neural Regen. Res.
PD JUN
PY 2021
VL 16
IS 6
BP 1138
EP 1143
DI 10.4103/1673-5374.300329
PG 6
WC Cell Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Neurosciences & Neurology
GA PE8PL
UT WOS:000598623300020
PM 33269762
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Alagorie, AR
   Verma, A
   Nassisi, M
   Nittala, M
   Velaga, S
   Tiosano, L
   Sadda, SR
AF Alagorie, Ahmed Roshdy
   Verma, Aditya
   Nassisi, Marco
   Nittala, Muneeswar
   Velaga, Swetha
   Tiosano, Liran
   Sadda, Srinivas R.
TI QUANTITATIVE ASSESSMENT OF CHORIOCAPILLARIS FLOW DEFICITS SURROUNDING
   CHOROIDAL NEOVASCULAR MEMBRANES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal neovascular membrane; choriocapillaris; optical coherence
   tomography angiography
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SWEPT-SOURCE OCT; MACULAR
   DEGENERATION; SPECTRAL-DOMAIN; IMAGE
AB Purpose: To quantify the regional variation in choriocapillaris (CC) flow deficits percentage (FD%) surrounding treatment-naive Type 1 choroidal neovascularization (CNV) associated with age-related macular degeneration. Methods: Patients were imaged with swept-source optical coherence tomography angiography system (Carl Zeiss PLEX Elite 9000; Carl Zeiss Meditec AG, Jena, Germany). Two 6 x 6-mm volume scans were acquired. Boundary-specific segmentation was used to isolate the Type 1 CNV. For CC assessment, both structural and optical coherence tomography angiography CC slabs (10-mu m thick, starting 21 mu m below the retinal pigment epithelium fit reference) were exported for signal compensation and averaging using ImageJ. The resultant CC image was binarized to calculate the FD%, for para-CNV and peri-CNV rings (each 500-mu m wide). In a subgroup of 20 eyes, the FD% was compared with similar regions of age-matched controls. The FD% was also analyzed in small 500 x 500-mu m squares equidistant from the fovea to compensate for regional variation of CC FD% as a potential confounding factor. Results: Thirty-two eyes from 27 subjects were enrolled in this study. The CC FD% in the para-CNV ring was 26.58 +/- 7.36, which was significantly higher than the peri-CNV ring (21.94 +/- 6.31); P < 0.001. The FD% in para-CNV and peri-CNV rings was significantly greater than that of healthy controls (15.82 +/- 1.29% and 15.53 +/- 1.32%, respectively); P < 0.001. The FD% computed in the 500-mu m squares equidistant from the fovea was also greater in the para-CNV ring (26.14 +/- 7.11) than that in the peri-CNV ring (22.31 +/- 6.21); P < 0.001. Conclusion: Choriocapillaris FD% is the highest in the region immediately surrounding the CNV.
C1 [Alagorie, Ahmed Roshdy; Verma, Aditya; Nassisi, Marco; Nittala, Muneeswar; Velaga, Swetha; Tiosano, Liran; Sadda, Srinivas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Alagorie, Ahmed Roshdy; Verma, Aditya; Nassisi, Marco; Nittala, Muneeswar; Velaga, Swetha; Tiosano, Liran; Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Alagorie, Ahmed Roshdy] Tanta Univ, Fac Med, Dept Ophthalmol, Tanta, Egypt.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; Egyptian Knowledge Bank
   (EKB); Tanta University
RP Sadda, SR (通讯作者)，1355 San Pablo St,Suite 211, Los Angeles, CA 90033 USA.
EM SSadda@doheny.org
RI Verma, Aditya/AGK-6502-2022; Nassisi, Marco/P-9939-2019; Alagorie,
   Ahmed/AAW-5304-2020
OI Nassisi, Marco/0000-0002-9354-9005; Alagorie, Ahmed/0000-0001-5489-0617
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NR 35
TC 12
Z9 13
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 NOV
PY 2020
VL 40
IS 11
BP 2106
EP 2112
DI 10.1097/IAE.0000000000002878
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OP0WT
UT WOS:000587803100010
PM 32658166
DA 2022-11-30
ER

PT J
AU Koh, BMQR
   Banu, R
   Sabanayagam, C
AF Koh, Barry Moses Quan Ren
   Banu, Riswana
   Sabanayagam, Charumathi
TI The 100 Most Cited Articles in Ophthalmology in Asia
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE 100 most cited; Asia; bibliometric analysis; ophthalmology; review
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; ANGLE-CLOSURE GLAUCOMA;
   DIABETIC-RETINOPATHY; JAPANESE POPULATION; MACULAR DEGENERATION; GLOBAL
   PREVALENCE; REFRACTIVE ERRORS; SELF-CITATION; EYE DISEASES; RISK-FACTORS
AB Purpose: The aim of this study was to review the top 100 most-cited articles in ophthalmology in Asia since 1970.
   Methods: The Scopus database was used to identify the top 100 most-cited ophthalmology articles published in ophthalmology (T100-Eye) and nonophthalmology (T100-General) journals.
   Results: The T100-Eye articles were published between 1982 and 2015, and T100-General from 1982 to 2017. T100-Eye had higher citations [median (range) = 317 (249 1326)] than T100-General [158 (105 2628)], but T100-General were published in journals with higher impact factor (IF) than T100-Eye (median IF 5.5 vs 4.4) and produced more landmark papers (3 vs 1 articles that were cited >1000 times). Fifty-five % of T100-Eye were published in 3 journals: Ophthalmology (n = 22), Investigative Ophthalmology and Visual Science (n = 17), and American Journal of Ophthalmology (n= 16). T100-Eye had 88 original research articles and 12 reviews, whereas T100-General had 84 original research and 16 reviews. The most-frequent studied disease categories were myopia (n = 16) and age-related macular degeneration (n = 15) in T100-Eye and diabetic retinopathy (n = 24) and glaucoma (n = 16) in T100-General. Japan and Singapore contributed most to T100-Eye (n = 42, n =17) and T100-General (n = 36, n = 26) articles. More than 80% and 95% of first and last authors were male in both lists. Emerging research topics were optical coherence tomography in T100-Eye and artificial intelligence in T100-General.
   Conclusions: Our citation analysis reveals differences in the focus of research topics of top-cited ophthalmology articles published in ophthalmology and nonophthalmology journals in Asia. It highlights that certain eye diseases are studied more in Asia and shows the contribution of specific countries to highly cited publications in ophthalmology research in Asia.
C1 [Koh, Barry Moses Quan Ren; Banu, Riswana; Sabanayagam, Charumathi] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.
   [Koh, Barry Moses Quan Ren] Duke NUS Med Sch, Singapore, Singapore.
   [Sabanayagam, Charumathi] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore
RP Sabanayagam, C (通讯作者)，Singapore Eye Res Inst, 20 Coll Rd,Discovery Tower Level 6, Singapore 169856, Singapore.
EM charumathi.sabanayagam@seri.com.sg
RI Sabanayagam, Charumathi/C-1294-2011
OI Sabanayagam, Charumathi/0000-0002-4042-4719
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NR 78
TC 5
Z9 5
U1 2
U2 8
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 SEP-OCT
PY 2020
VL 9
IS 5
BP 379
EP 397
DI 10.1097/APO.0000000000000325
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OA2CF
UT WOS:000577599600002
PM 32956190
OA gold
DA 2022-11-30
ER

PT J
AU Zernii, EY
   Nazipova, AA
   Nemashkalova, EL
   Kazakov, AS
   Gancharova, OS
   Serebryakova, MV
   Tikhomirova, NK
   Baksheeva, VE
   Vladimirov, VI
   Zinchenko, DV
   Philippov, PP
   Senin, II
   Permyakov, SE
AF Zernii, Evgeni Yu.
   Nazipova, Aliya A.
   Nemashkalova, Ekaterina L.
   Kazakov, Alexey S.
   Gancharova, Olga S.
   Serebryakova, Marina V.
   Tikhomirova, Natalya K.
   Baksheeva, Viktoriia E.
   Vladimirov, Vasiliy I.
   Zinchenko, Dmitry V.
   Philippov, Pavel P.
   Senin, Ivan I.
   Permyakov, Sergei E.
TI Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin
   Desensitization
SO FRONTIERS IN MOLECULAR NEUROSCIENCE
LA English
DT Article
DE light-induced retinal damage; photoreceptor; apoptosis; neuronal calcium
   sensor; recoverin; thiol oxidation; disulfide dimerization; GRK1
ID CANCER-ASSOCIATED RETINOPATHY; CALCIUM SENSOR PROTEINS; NITRIC-OXIDE
   SYNTHASE; PHOTOCHEMICAL DAMAGE; RETINAL DEGENERATION; MACULAR
   DEGENERATION; MOUSE MODEL; C-JUN; BINDING; DIMERIZATION
AB The excessive light illumination of mammalian retina is known to induce oxidative stress and photoreceptor cell death linked to progression of age-related macular degeneration. The photochemical damage of photoreceptors is suggested to occur via two apoptotic pathways that involve either excessive rhodopsin activation or constitutive phototransduction, depending on the light intensity. Both pathways are dramatically activated in the absence of rhodopsin desensitization by GRK1. Previously, we have shown that moderate illumination (halogen lamp, 1,500 lx, 1-5 h) of mammalian eyes provokes disulfide dimerization of recoverin, a calcium-dependent regulator of GRK1. Here, we demonstrate under in vivo conditions that both moderate long-term (metal halide lamp, 2,500 lx, 14 h, rat model) and intense short-term (halogen lamp, 30,000 lx for 3 h, rabbit model) illumination of the mammalian retina are accompanied by accumulation of disulfide dimer of recoverin. Furthermore, in the second case we reveal alternatively oxidized derivatives of the protein, apparently including its monomer with sulfinic group. Histological data indicate that thiol oxidation of recoverin precedes apoptosis of photoreceptors. Both disulfide dimer and oxidized monomer (or oxidation mimicking C39D mutant) of recoverin exhibit lowered a-helical content and thermal stability of their apo-forms, as well as increased Ca2+ affinity. Meanwhile, the oxidized monomer and C39D mutant of recoverin demonstrate impaired ability to bind photoreceptor membranes and regulate GRK1, whereas disulfide dimer exhibits notably improved membrane binding and GRK1 inhibition in absence of Ca2+. The latter effect is expected to slow down rhodopsin desensitization in the light, thereby favoring support of the light-induced oxidative stress, ultimately leading to photoreceptor apoptosis. Overall, the intensity and duration of illumination of the retina affect thiol oxidation of recoverin likely contributing to propagation of the oxidative stress and photoreceptor damage.
C1 [Zernii, Evgeni Yu.; Gancharova, Olga S.; Serebryakova, Marina V.; Tikhomirova, Natalya K.; Baksheeva, Viktoriia E.; Philippov, Pavel P.; Senin, Ivan I.] Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia.
   [Zernii, Evgeni Yu.] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow, Russia.
   [Nazipova, Aliya A.; Nemashkalova, Ekaterina L.; Kazakov, Alexey S.; Permyakov, Sergei E.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino, Russia.
   [Gancharova, Olga S.] Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia.
   [Vladimirov, Vasiliy I.; Zinchenko, Dmitry V.] Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Pushchino, Russia.
C3 Lomonosov Moscow State University; Sechenov First Moscow State Medical
   University; Russian Academy of Sciences; Sechenov First Moscow State
   Medical University; 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 Permyakov, SE (通讯作者)，Russian Acad Sci, Inst Biol Instrumentat, Pushchino, Russia.
EM permyakov.s@gmail.com
RI Kazakov, Alexey S./M-9129-2014; Viktoriia, Baksheeva E/Q-8035-2018;
   Zinchenko, Dmitry/C-8000-2014; Serebryakova, Marina/E-2986-2012;
   Baksheeva, Viktoriia/AAO-3153-2020; Permyakov, Sergei E./B-8156-2011;
   Vladimirov, Vasiliy I/T-8132-2017; Zernii, Evgeni Yu./D-9446-2012;
   Gancharova, Olga S/M-9980-2014
OI Kazakov, Alexey S./0000-0002-1586-7649; Zinchenko,
   Dmitry/0000-0001-7181-6283; Serebryakova, Marina/0000-0002-5402-8215;
   Baksheeva, Viktoriia/0000-0002-0445-2667; Permyakov, Sergei
   E./0000-0003-4086-3137; Vladimirov, Vasiliy I/0000-0002-0723-2758;
   Zernii, Evgeni Yu./0000-0002-3013-7863; Gancharova, Olga
   S/0000-0001-7441-1062
FU Russian Science Foundation [16-15-00255]; Russian Foundation for Basic
   Research [18-04-01250]
FX The development of rabbit models of iatrogenic light-induced retinal
   damage, histological characterization of pathomorphological changes in
   the retina as well as immunochemical and mass-spectrometric
   identification of alterations in redox state of recoverin were performed
   with support of the Russian Science Foundation (Grant No. 16-15-00255).
   The structural and functional in vitro studies of oxidized forms of
   recoverin were supported by the Russian Foundation for Basic Research
   (Grant No. 18-04-01250).
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NR 75
TC 9
Z9 9
U1 0
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1662-5099
J9 FRONT MOL NEUROSCI
JI Front. Molec. Neurosci.
PD JAN 7
PY 2019
VL 11
AR 474
DI 10.3389/fnmol.2018.00474
PG 19
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA HG5RF
UT WOS:000455035900001
PM 30666186
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wong, MYH
   Tan, NYQ
   Sabanayagam, C
AF Wong, Matthew Yu Heng
   Tan, Nicholas Y. Q.
   Sabanayagam, Charumathi
TI Time trends, disease patterns and gender imbalance in the top 100 most
   cited articles in ophthalmology
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID INTRAVITREAL BEVACIZUMAB AVASTIN; AGE-RELATED MACULOPATHY; FACTOR-H
   POLYMORPHISM; INTERNATIONAL CLASSIFICATION; CHOROIDAL
   NEOVASCULARIZATION; DIABETIC-RETINOPATHY; CITATION-CLASSICS;
   SELF-CITATION; RANIBIZUMAB; EYE
AB We analysed the 100 top cited articles in ophthalmology to identify and characterise the most influential articles of the past four decades. Two independent investigators searched the Scopus database to determine the 100 most frequently cited articles in ophthalmology (T100-Eye) and general non-ophthalmology journals (T100-Gen) published from 1975 to December 2017. The T100-Eye list consisted of 83 original articles and 17 reviews, and the number of citations ranged from 582 to 2833. Seventy-eight of these articles were published in three journals alone (impact factor (IF): 5.05-8.2), led by the Archives of Ophthalmology. The T100-Gen list consisted of 84 original articles and 16 reviews and the number of citations ranged from 358 to 3272. Forty-five of these articles were published in four journals alone (IF: 9.66-72.41). In both lists, majority of the first authors were from the USA (T100-Eye, n=80; T100-Gen, n=66), and were men (n=76 in T100-Eye; n=72 in T100-Gen). With regard to the article type, in the T100-Eye, among the 83 original research articles, most were randomised controlled trials (n=26) or clinical observational studies related to description of a new condition or new management (n=26). In the T100-Gen, of the 84 original research articles, many were clinical observational studies (n=27) or basic science research (n=26). In both lists, the most frequently examined diseases were age-related macular degeneration, diabetic retinopathy and glaucoma. Our analysis reveals landmark articles, trends and medical advancements in ophthalmology over the past four decades. It also highlights gender disparity and influence of the USA in seminal ophthalmic research.
C1 [Wong, Matthew Yu Heng; Tan, Nicholas Y. Q.; Sabanayagam, Charumathi] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.
   [Wong, Matthew Yu Heng] Anglo Chinese Sch Independent, Singapore, Singapore.
   [Sabanayagam, Charumathi] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 169856, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore
RP Sabanayagam, C (通讯作者)，Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 169856, Singapore.
EM charumathi.sabanayagam@seri.com.sg
RI Sabanayagam, Charumathi/C-1294-2011
OI Sabanayagam, Charumathi/0000-0002-4042-4719
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NR 62
TC 13
Z9 13
U1 0
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 JAN
PY 2019
VL 103
IS 1
BP 18
EP 25
DI 10.1136/bjophthalmol-2018-312388
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IC9BI
UT WOS:000471275800004
PM 30002071
DA 2022-11-30
ER

PT J
AU Minnelli, C
   Moretti, P
   Fulgenzi, G
   Mariani, P
   Laudadio, E
   Armeni, T
   Galeazzi, R
   Mobbili, G
AF Minnelli, Cristina
   Moretti, Paolo
   Fulgenzi, Gianluca
   Mariani, Paolo
   Laudadio, Emiliano
   Armeni, Tatiana
   Galeazzi, Roberta
   Mobbili, Giovanna
TI A Poloxamer-407 modified liposome encapsulating
   epigallocatechin-3-gallate in the presence of magnesium:
   Characterization and protective effect against oxidative damage
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Liposomes; Oxidative damage; Epigallocatechin-3-gallate; Poloxamer-407;
   Drug delivery; X-ray diffraction
ID GREEN TEA POLYPHENOLS; STRESS; ANTIOXIDANT; CATECHINS; PROLIFERATION;
   FLAVANOLS; HYDRATION; RADICALS; VESICLES; DELIVERY
AB Epigallocatechin-3-gallate (EGCG) is a polyphenolic catechin from green tea, well known for being bioactive in age-associated pathologies where oxidative stress plays a preeminent role. The activity of this molecule is however contrasted by its high chemical and metabolic instability that determines a poor concentration of the antioxidant within the biological system after administration. In order to protect the molecule and increase its delivery efficiency, we have encapsulated EGCG inside anionic liposomes made of 1-palmitoy1-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesteryl hemisuccinate. To maximize EGCG internalization, magnesium salt was added in the preparation. However stable nanodispersions suitable for drug delivery were obtained only after treatment with Poloxamer-407, a polyethylene-propylene glycol copolymer. The structural and morphological properties of the produced dispersion were studied by X-ray diffraction, which showed a multilamellar structure even after EGCG addition and an ordering effect of Poloxamer-407; Dynamic Light Scattering demonstrated serum stability of the liposomes. The characterization was completed by evaluating both encapsulation efficiency (100%, in the final formulation) and in vitro EGCG release. Since oxidative stress is involved in numerous retinal degenerative diseases, such as age-related macular degeneration, the ability of these liposomes to contrast H2O2-induced cell death was assessed in human retinal cells. Morphological changes at the subcellular level were analyzed by Transmission Electron Microscopy, which showed that mitochondria were better preserved in cells treated with liposomes then those treated with free EGCG. In conclusion, the results demonstrated that the produced formulation enhances the efficacy of EGCG under stress conditions, thus representing a potential formulation for the intracellular delivery of EGCG in diseases caused by oxidative damage.
C1 [Minnelli, Cristina; Moretti, Paolo; Mariani, Paolo; Laudadio, Emiliano; Galeazzi, Roberta; Mobbili, Giovanna] Univ Politecn Marche, Dipartimento Sci Vita & Ambiente DISVA, Via Brecce Bianche, I-60131 Ancona, Italy.
   [Fulgenzi, Gianluca] Univ Politecn Marche, Dipartimento Sci Clin & Mol, Via Conca, I-60131 Ancona, Italy.
   [Armeni, Tatiana] Univ Politecn Marche, Dipartimento Sci Clin Specialist & Odontostomatol, Via Brecce Bianche, I-60131 Ancona, Italy.
C3 Marche Polytechnic University; Marche Polytechnic University; Marche
   Polytechnic University
RP Mobbili, G (通讯作者)，Univ Politecn Marche, Dipartimento Sci Vita & Ambiente DISVA, Via Brecce Bianche, I-60131 Ancona, Italy.
EM g.mobbili@staff.univpm.it
RI Mariani, Paolo/R-2210-2019; Minnelli, Cristina CM/O-4986-2018; Armeni,
   Tatiana/J-8228-2013; Moretti, Paolo/AAC-1301-2020; Fulgenzi,
   Gianluca/AAL-4552-2020; Laudadio, Emiliano/AAS-7515-2021; Galeazzi,
   Roberta/D-2555-2009; Minnelli, Cristina/AAA-5305-2020
OI Mariani, Paolo/0000-0003-4293-1009; Armeni, Tatiana/0000-0003-0931-1342;
   Moretti, Paolo/0000-0002-1904-0251; Laudadio,
   Emiliano/0000-0002-8053-6539; Galeazzi, Roberta/0000-0003-1792-654X;
   Minnelli, Cristina/0000-0001-8034-8557
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NR 50
TC 25
Z9 26
U1 5
U2 32
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD DEC 1
PY 2018
VL 552
IS 1-2
BP 225
EP 234
DI 10.1016/j.ijpharm.2018.10.004
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GX7VB
UT WOS:000447985800025
PM 30291957
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Ober, MD
   Fine, HF
   Saraf, SS
AF Ober, Michael D.
   Fine, Howard F.
   Saraf, Steven S.
TI Cataract Surgery in Patients With Wet Macular Degeneration
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; BLUE MOUNTAINS EYE;
   INTRAVITREAL BEVACIZUMAB; THICKNESS CHANGES; BEAVER DAM;
   PHACOEMULSIFICATION; EXTRACTION; DISEASE; RISK
AB Cataract surgery has been controversial in the setting of age-related macular degeneration (AMD) for decades. The question of whether surgical intervention leads to progression of AMD is at the heart of this issue. AMD is currently the leading cause of blindness in the developed world for those older than 60 years of age and is projected to affect 196 million people globally by 2020.1 Given its occurrence in an age group with a high incidence of cataract development, the clinical situation is common and likely to become more frequent. Several large population-based studies and randomized, controlled trials like the Age Related Eye Disease Studies, have focused attention on the progression of dry AMD following cataract extraction with mixed conclusions. The clinical dilemma of patients in need of cataract surgery who are already receiving treatment for wet AMD has received much less attention.
   There is a plausible concern that cataract surgery may exacerbate wet AMD, manifesting as increased subretinal fluid, intraretinal cystoid changes, macular hemorrhage, progression of geographic atrophy, and/or increased anti-vascular endothelial growth factor (VEGF) treatment demands. Proposed mechanisms include the release of inflammatory mediators from the surgery itself, such as VEGF, as well as increased light exposure both during surgery and afterward due to removal of media opacity. Despite these theoretical possibilities, there is growing evidence regarding the efficacy of cataract surgery in patients receiving anti-VEGF treatments for wet AMD.
   To address this question, we conducted a retrospective cohort analysis of 40 eyes (39 patients) with wet AMD who were receiving anti-VEGF therapy and underwent cataract surgery between January 2008 and May 2013. We specifically compared the visual acuity, number of anti-VEGF injections, and optical coherence tomography (OCT) features such as retinal thickness, subretinal fluid, and intraretinal cystoid changes in the 6 months prior to and following cataract surgery.
C1 [Ober, Michael D.] Retina Consultants Michigan, 29201 Telegraph Rd,Suite 606, Southfield, MI 48034 USA.
   [Fine, Howard F.] Univ Med & Dent New Jersey, NJ Retina, Dept Ophthalmol, 10 Plum St,Suite 600, New Brunswick, NJ 08901 USA.
   [Saraf, Steven S.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center; Bascom Palmer Eye Institute; University of Miami
RP Ober, MD (通讯作者)，Retina Consultants Michigan, 29201 Telegraph Rd,Suite 606, Southfield, MI 48034 USA.
EM obermike@gmail.com; hfine@njretina.com; stevesaraf@gmail.com
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NR 21
TC 1
Z9 1
U1 0
U2 2
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD SEP
PY 2017
VL 48
IS 9
BP 700
EP 704
DI 10.3928/23258160-20170829-03
PG 5
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA FN5TY
UT WOS:000416072300002
PM 28902329
DA 2022-11-30
ER

PT J
AU Zhou, YL
   Chen, CL
   Wang, YX
   Tong, Y
   Fang, XL
   Li, L
   Wang, ZY
AF Zhou, Ya-li
   Chen, Chun-li
   Wang, Yi-xiao
   Tong, Yao
   Fang, Xiao-ling
   Li, Lin
   Wang, Zhao-yang
TI Association between polymorphism rs11200638 in the HTRA1 gene and the
   response to anti-VEGF treatment of exudative AMD: a meta-analysis
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF; Exudative AMD; HTRA1 gene; Treatment response
ID GROWTH-FACTOR TREATMENT; MACULAR DEGENERATION; INTRAVITREAL RANIBIZUMAB;
   NEOVASCULAR AMD; PROMOTER POLYMORPHISM; THERAPY; RISK; SUSCEPTIBILITY;
   DISEASE; PHARMACOGENETICS
AB Background: Anti-angiogenesis treatments are the most commonly used treatments for the vision loss caused by exudative age-related macular degeneration (AMD), in which the anti-vascular endothelial growth factor (VEGF) drugs with ranibizumab and bevacizumab are current standard treatments. However, the outcome of anti-VEGF therapeutics is not uniform in all patients.
   Methods: We performed a literature-based meta-analysis including, five published studies relevant to HTRA1 and response to anti-VEGF treatment (bevacizumab or ranibizumab). Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-and random-effects models. Sensitivity analysis and meta-regression were also performed. Q-statistic test and Egger's test was used to evaluate heterogeneity and publication bias respectively.
   Results: Overall, no association between the rs11200638 polymorphism in HTRA1 gene and the anti-VEGF treatment response was found in the genotype GG versus AA (OR = 1.06; 95% CI: 0.77 to 1.48; P = 0.98), genotype GA versus AA (OR = 1.11; 95% CI: 0.83 to 1.47; P = 0.93), genotype GG + GA versus AA (OR = 1.22; 95% CI: 0.94 to 1.57; P = 0.09), and allele G versus A (OR = 0.92; 95% CI: 0.78 to 1.08; P = 0.14). In the subgroup analysis by ethnicity Caucasian population, and a significant association was still not observed in all genetic models. Sensitivity analysis indicated the robustness of our findings, and no publication bias was observed in our meta-analysis.
   Conclusions: This study shows that there was no association between the polymorphism rs11200638 in HTRA1 gene and response to anti-VEGF treatment of exudative AMD. However, more studies are needed to further prove the conclusion of present study, especially well-designed and high quality randomised controlled trials or intervention studies.
C1 [Zhou, Ya-li; Wang, Yi-xiao; Li, Lin; Wang, Zhao-yang] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Ophthalmol, Sch Med, Shanghai 200011, Peoples R China.
   [Tong, Yao] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Ophthalmol, Sch Med, Shanghai, Peoples R China.
   [Chen, Chun-li] Shengli Oilfield Cent Hosp, Dept Ophthalmol, Dongying, Shandong, Peoples R China.
   [Fang, Xiao-ling] Shanghai Eye Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University
RP Li, L; Wang, ZY (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Ophthalmol, Sch Med, Shanghai 200011, Peoples R China.
EM Jannetlee1300@163.com; zhaokekewzy@hotmail.com
FU Project of the National Natural Science Funds of China [81371040];
   Shanghai Pujiang Program [15PJD028]
FX This study was partly supported by the Project of the National Natural
   Science Funds of China (No. 81371040), and the Shanghai Pujiang Program
   (No. 15PJD028).
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NR 40
TC 13
Z9 15
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUN 21
PY 2017
VL 17
AR 97
DI 10.1186/s12886-017-0487-2
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EY6BT
UT WOS:000404068200001
PM 28637435
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Izawa, H
   Shimazawa, M
   Inoue, Y
   Uchida, S
   Moroe, H
   Tsuruma, K
   Hara, H
AF Izawa, Hiroshi
   Shimazawa, Masamitsu
   Inoue, Yuki
   Uchida, Seiichi
   Moroe, Hiroko
   Tsuruma, Kazuhiro
   Hara, Hideaki
TI Protective effects of NSP-116, a novel imidazolyl aniline derivative,
   against light-induced retinal damage in vitro and in vivo
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE NSP-116; Free radical scavenger; Light, photoreceptor degeneration;
   Retina; AMD
ID FREE-RADICAL SCAVENGER; MACULAR DEGENERATION; LIPID-PEROXIDATION;
   OXIDATIVE STRESS; BLUE-LIGHT; PARKINSONS-DISEASE; TRANSGENIC MICE;
   NITRIC-OXIDE; DNA-DAMAGE; CELL-LINE
AB In this study, we investigated the protective effects of NSP-116 [4-(4-acetylpiperazin-1-yl)-2-(1H-imidazol-1-yl) aniline], a novel imidazolyl aniline derivative, against light-induced photoreceptor cell damage. In an in vitro experiment, murine photoreceptor (661 W) cells were damaged by exposure to light for 24 h. Viability of 661 W cells after light exposure was assessed by Hoechst 33342/Propidium iodide nuclear staining and a tetrazolium salt (WST-8) assay. Intracellular radical production in 661 W cells was evaluated using the reactive oxygen species (ROS) sensitive probe 5-(and 6)-chloromethyl-2, 7-di-chlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA). NSP-116 significantly suppressed light induced cell death and ROS production in 661 W cells. In an in vivo mouse experiment, retinal damage was induced by exposure to white light at 8000 lx for 3 h after dark adaptation. Retinal damage was evaluated by recording the electroretinogram and measuring the outer nuclear layer (ONL) thickness at 5 days after light exposure. Single oral administration of NSP-116 before light exposure protected retinal function and ONL thinning after light exposure. Furthermore, the effect of NSP-116 on lipid peroxidation was evaluated using thiobarbituric acid reactive substance (TBARS) assay in porcine retina, and was found to decrease the production of TBARS. Electron spin resonance (ESR) measurements showed that NSP-116 exhibited radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (center dot O-2(-)), and hydroxyl radical (center dot OH). These findings suggest that NSP-116 has protective effects against light-induced photoreceptor degeneration in vitro and in vivo as a free radical scavenger, and it may be a novel therapeutic agent for retinal degenerative disorders, such as dry age related macular degeneration (AMD). (C) 2016 Elsevier Inc. All rights reserved.
C1 [Izawa, Hiroshi; Shimazawa, Masamitsu; Inoue, Yuki; Tsuruma, Kazuhiro; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
   [Uchida, Seiichi; Moroe, Hiroko] Nippon Soda Co Ltd, Odawara Res Ctr, Tokyo, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
EM hidehara@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
FU Nippon Soda Co., Ltd (Tokyo, Japan)
FX We received financial support from Nippon Soda Co., Ltd (Tokyo, Japan)
   as a collaborative research. We thank Nippon Soda Co., Ltd for gifting
   NSP-116 and Mr. Tomohiro Otsuka and Ms. Emi Ooe (Molecular Pharmacology,
   Department of Biofunctional Evaluation, Gifu Pharmaceutical University,
   Gifu, Japan) for technical support. We also thank Dr. Shin-ichi Kondo
   (Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical
   University, Gifu, Japan) for technical advice.
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NR 48
TC 14
Z9 14
U1 3
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2016
VL 96
BP 304
EP 312
DI 10.1016/j.freeradbiomed.2016.03.036
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DO2OO
UT WOS:000377619600027
PM 27151507
DA 2022-11-30
ER

PT J
AU Ma, J
   Sun, Y
   Lopez, FJ
   Adamson, P
   Kurali, E
   Lashkari, K
AF Ma, Jie
   Sun, Yu
   Lopez, Francisco J.
   Adamson, Peter
   Kurali, Edit
   Lashkari, Kameran
TI Blockage of PI3K/mTOR Pathways Inhibits Laser-Induced Choroidal
   Neovascularization and Improves Outcomes Relative to VEGF-A Suppression
   Alone
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE GSK2126458; aflibercept; age-related macular degeneration; intravitreal
   injection; choroidal neovascularization; vascular leakage
ID MACULAR DEGENERATION; VASCULAR-PERMEABILITY; ANGIOGENESIS; ACTIVATION;
   PI3K; HYPERGLYCEMIA; GSK2126458; ANESTHESIA; THERAPIES; REQUIRES
AB PURPOSE. Choroidal neovascularization (CNV) is a major cause of visual loss with age-related macular degeneration (AMD). We evaluated whether blockade of phosphatidyl-inositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), by impairing VEGF-A and other growth factor receptors like platelet-derived growth factor (PDGF), would reduce laser-induced CNV in mice.
   METHODS. Choroidal neovascularization lesions were induced in C57BL/6 mice. Two groups of mice received oral GSK2126458 (3 mg/kg) or vehicle for 14 days following laser, whereas three groups were treated with GSK2126458 (6 mu g/eye), aflibercept (2 mu L/eye), or vehicle intravitrealy on days 0 and 7 after laser. Vascular leakage was measured by fluorescein angiography (FA) on day 14. Choroidal neovascularization membranes were evaluated on choroidal flat mounts following FITC-dextran perfusion, as well as EDI and isolectin B4 (IB4) immunohistochemistry.
   RESULTS. Oral and intravitreal (IVT) GSK2126458 reduced leakage and area of CNV lesions. Greater probability of leaking lesions (similar to 60%; P < 0.05) was observed in both vehicle groups. Fluorescein isothiocyanate-dextran-labeled total CNV burden area (total lesion area/eye) was reduced similar to 67% (P < 0.05) and 35% (P = 0.0528) after oral and WT GSK2126458 administration. GSK2126458 treatment reduced lesion size by similar to 80% (P < 0.05) and 50% (P < 0.05) for oral and VT control groups. Aflibercept did not alter lesion size (similar to 27% reduction).
   CONCLUSIONS. Phosphatidyl-inositol-3-kinase/mTOR is involved in laser-induced CNV angiogenic processes. GSK2126458 effectively reduces CNV size and leakage. Choroidal neovascularization size following IVT GSK2126458 was smaller than after oral administration. Therefore, inhibition of PI3K/mTOR pathways may be more effective due to blockade of action of multiple growth factors.
C1 [Ma, Jie; Sun, Yu; Lashkari, Kameran] Harvard Med Sch, Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
   [Lopez, Francisco J.] GlaxoSmithKline, Ophthalmol Discovery Performance Unit, King Of Prussia, PA USA.
   [Adamson, Peter] GlaxoSmithKline, Ophthalmol Discovery Performance Unit, Stevenage, Herts, England.
   [Adamson, Peter] UCL Inst Ophthalmol, Ocular Biol & Therapeut, London, England.
   [Kurali, Edit] GlaxoSmithKline, RD Alternat Discovery & Dev, Quantitat Sci, King Of Prussia, PA USA.
   [Lopez, Francisco J.] Allergan Plc, Irvine, CA USA.
   [Adamson, Peter] ProQR Therapeut, Leiden, Netherlands.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Schepens Eye Research Institute; GlaxoSmithKline;
   GlaxoSmithKline; University of London; University College London;
   GlaxoSmithKline; AbbVie; Allergan
RP Lashkari, K (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM kameran_lashkari@meei.harvard.edu
OI Lashkari, Kameran/0000-0003-3855-0246
FU GlaxoSmithKline; Massachusetts Eye and Ear (Boston, MA, USA)
FX Supported by GlaxoSmithKline through an academic collaboration grant to
   Schepens Eye Research Institute, Massachusetts Eye and Ear (Boston, MA,
   USA).
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NR 33
TC 12
Z9 12
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2016
VL 57
IS 7
BP 3138
EP 3144
DI 10.1167/iovs.15-18795
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DT8GA
UT WOS:000381726600028
PM 27304845
OA gold
DA 2022-11-30
ER

PT J
AU Rezzola, S
   Belleri, M
   Gariano, G
   Ribatti, D
   Costagliola, C
   Semeraro, F
   Presta, M
AF Rezzola, Sara
   Belleri, Mirella
   Gariano, Giuseppina
   Ribatti, Domenico
   Costagliola, Ciro
   Semeraro, Francesco
   Presta, Marco
TI In vitro and ex vivo retina angiogenesis assays
SO ANGIOGENESIS
LA English
DT Review
DE Angiogenesis; Endothelium; Retina; VEGF; Zebrafish
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; GLOBOID-CELL
   LEUKODYSTROPHY; VEGF TRAP-EYE; FAMILIAL EXUDATIVE VITREORETINOPATHY;
   VEIN OCCLUSION; OCULAR ANGIOGENESIS; ANTI-VEGF; VERTEBRATE DEVELOPMENT;
   VASCULAR-PERMEABILITY
AB Pathological angiogenesis of the retina is a key component of irreversible causes of blindness, as observed in proliferative diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. Seminal studies in the early 1980 s about the angiogenic activity exerted by mammalian retinal tissue extracts on the chick embryo chorioallantoic membrane and the later discovery of vascular endothelial growth factor (VEGF) accumulation in eyes of patients with diabetic retinopathy paved the way for the development of anti-angiogenic VEGF blockers for the treatment of retinal neovascularization. Since then, numerous preclinical and clinical studies about diabetic retinopathy and other retinal disorders have opened new lines of angiogenesis inquiry, indicating that limitations to anti-VEGF therapies may exist. Moreover, the production of growth factors other than VEGF may affect the response to anti-VEGF approaches. Thus, experimental models of retinal angiogenesis remain crucial for investigating novel anti-angiogenic therapies and bringing them to patients. To this aim, in vitro and ex vivo angiogenesis assays may be suitable for a rapid screening of potential anti-angiogenic molecules before in vivo validation of the putative lead compounds. This review focuses on the different in vitro and ex vivo angiogenesis assays that have been developed over the years based on the isolation of endothelial cells from the retina of various animal species and ex vivo cultures of neonatal and adult retina explants. Also, recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryos, an in vivo animal platform experimentally analogous to in vitro/ex vivo models, may represent a novel target for the identification of angiogenesis inhibitors. When compared to in vivo assays, in vitro and ex vivo models of retina neovascularization, including zebrafish embryo, may represent cost-effective and rapid tools for the screening of novel anti-angiogenic therapeutics.
C1 [Rezzola, Sara; Belleri, Mirella; Gariano, Giuseppina; Presta, Marco] Univ Brescia, Dept Mol & Translat Med, I-25123 Brescia, Italy.
   [Rezzola, Sara; Semeraro, Francesco] Univ Brescia, Spedali Civili, Dept Ophthalmol, I-25123 Brescia, Italy.
   [Ribatti, Domenico] Univ Bari, Dept Basic Biomed Sci Neurosci & Sensory Organs, Unit Human Anat & Histol, Bari, Italy.
   [Ribatti, Domenico] Natl Canc Inst, Bari, Italy.
   [Costagliola, Ciro] Univ Molise, Dept Med & Hlth Sci, Campobasso, Italy.
C3 University of Brescia; Hospital Spedali Civili Brescia; University of
   Brescia; Universita degli Studi di Bari Aldo Moro; IRCCS Istituto Tumori
   Bari Giovanni Paolo II; University of Molise
RP Presta, M (通讯作者)，Univ Brescia, Dept Mol & Translat Med, Viale Europa 11, I-25123 Brescia, Italy.
EM semeraro@med.unibs.it; presta@med.unibs.it
RI Costagliola, Ciro/G-5707-2012; Rezzola, Sara/AAE-8980-2020; Rezzola,
   Sara/AAA-2745-2019; Semeraro, Francesco fs/K-8667-2016
OI Costagliola, Ciro/0000-0001-8477-6188; Rezzola,
   Sara/0000-0003-1193-8929; Semeraro, Francesco fs/0000-0002-2275-4917;
   PRESTA, Marco/0000-0002-4398-8376; RIBATTI, Domenico/0000-0003-4768-8431
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NR 161
TC 56
Z9 59
U1 7
U2 45
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JUL
PY 2014
VL 17
IS 3
BP 429
EP 442
DI 10.1007/s10456-013-9398-x
PG 14
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA AK1XU
UT WOS:000338213400001
PM 24121991
DA 2022-11-30
ER

PT J
AU Zhang, QR
   Long, Q
   Ott, J
AF Zhang, Qingrun
   Long, Quan
   Ott, Jurg
TI AprioriGWAS, a New Pattern Mining Strategy for Detecting Genetic
   Variants Associated with Disease through Interaction Effects
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION;
   MISSING HERITABILITY; BIPOLAR DISORDER; EPISTASIS; RECOGNITION;
   RECEPTORS; PROTEIN; GLYCOSAMINOGLYCAN
AB Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the 2 x f contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple evidences.
C1 [Zhang, Qingrun; Long, Quan] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
   [Ott, Jurg] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China.
   [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA.
C3 Icahn School of Medicine at Mount Sinai; Chinese Academy of Sciences;
   Institute of Psychology, CAS; Rockefeller University
RP Zhang, QR (通讯作者)，Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
EM zhangqr@gmail.com; quan.long@mssm.edu
FU National Natural Science Foundation of China (NSFC);  [30730057]; 
   [30700442]
FX This work was supported by National Natural Science Foundation of China
   (NSFC). http://www.nsfc.gov.cn/e_nsfc/desktop/zn/0104.htm Project number
   30730057 (JO) and 30700442 (QZ). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 69
TC 16
Z9 16
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD JUN
PY 2014
VL 10
IS 6
AR e1003627
DI 10.1371/journal.pcbi.1003627
PG 14
WC Biochemical Research Methods; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA AL0WP
UT WOS:000338848100007
PM 24901472
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Hanus, J
   Zhang, H
   Wang, Z
   Liu, Q
   Zhou, Q
   Wang, S
AF Hanus, J.
   Zhang, H.
   Wang, Z.
   Liu, Q.
   Zhou, Q.
   Wang, S.
TI Induction of necrotic cell death by oxidative stress in retinal pigment
   epithelial cells
SO CELL DEATH & DISEASE
LA English
DT Article
DE cell death; RIPK3; RPE cell; oxidative stress; AMD
ID MACULAR DEGENERATION; PROGRAMMED NECROSIS; NECROPTOSIS INHIBITOR;
   INDUCED APOPTOSIS; PATHWAYS; DOWNSTREAM; ACTIVATION; KINASES; INJURY;
   RIP3
AB Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in the elderly. Retinal pigment epithelial (RPE) cell death and the resultant photoreceptor apoptosis are characteristic of late-stage dry AMD, especially geographic atrophy (GA). Although oxidative stress and inflammation have been associated with GA, the nature and underlying mechanism for RPE cell death remains controversial, which hinders the development of targeted therapy for dry AMD. The purpose of this study is to systematically dissect the mechanism of RPE cell death induced by oxidative stress. Our results show that characteristic features of apoptosis, including DNA fragmentation, caspase 3 activation, chromatin condensation and apoptotic body formation, were not observed during RPE cell death induced by either hydrogen peroxide or tert-Butyl hydroperoxide. Instead, this kind of cell death can be prevented by RIP kinase inhibitors necrostatins but not caspase inhibitor z-VAD, suggesting necrotic feature of RPE cell death. Moreover, ATP depletion, receptor interacting protein kinase 3 (RIPK3) aggregation, nuclear and plasma membrane leakage and breakdown, which are the cardinal features of necrosis, were observed in RPE cells upon oxidative stress. Silencing of RIPK3, a key protein in necrosis, largely prevented oxidative stressinduced RPE death. The necrotic nature of RPE death is consistent with the release of nuclear protein high mobility group protein B1 into the cytoplasm and cell medium, which induces the expression of inflammatory gene TNFa in healthy RPE and THP-1 cells. Interestingly, features of pyroptosis or autophagy were not observed in oxidative stress-treated RPE cells. Our results unequivocally show that necrosis, but not apoptosis, is a major type of cell death in RPE cells in response to oxidative stress. This suggests that preventing oxidative stress-induced necrotic RPE death may be a viable approach for late-stage dry AMD.
C1 [Hanus, J.; Zhou, Q.; Wang, S.] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
   [Zhang, H.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
   [Wang, Z.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Liu, Q.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Wang, S.] Tulane Univ, Dept Ophthalmol, New Orleans, LA 70118 USA.
C3 Tulane University; 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;
   Tulane University
RP Wang, S (通讯作者)，Tulane Univ, Dept Cell & Mol Biol & Ophthalmol, 2000 Percival Stern Hall,6400 Freret St, New Orleans, LA 70118 USA.
EM swang1@tulane.edu
FU Tulane University; UT Southwestern Medical Center; NIH [EY021862];
   Research to Prevent Blindness foundation; Bright Focus Foundation Award
   in Age-related Macular Degeneration; NATIONAL EYE INSTITUTE
   [R01EY021862] Funding Source: NIH RePORTER
FX SW was supported by a Startup fund from Tulane University, President's
   Research Council New Investigator Award from UT Southwestern Medical
   Center, NIH Grant EY021862, a career development award from the Research
   to Prevent Blindness foundation, and a Bright Focus Foundation Award in
   Age-related Macular Degeneration.
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NR 44
TC 107
Z9 111
U1 1
U2 21
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 DEC
PY 2013
VL 4
AR e965
DI 10.1038/cddis.2013.478
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 282HM
UT WOS:000329161300026
PM 24336085
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schneider, RM
   Thurtell, MJ
   Eisele, S
   Lincoff, N
   Bala, E
   Leigh, RJ
AF Schneider, Rosalyn M.
   Thurtell, Matthew J.
   Eisele, Sylvia
   Lincoff, Norah
   Bala, Elisa
   Leigh, R. John
TI Neurological Basis for Eye Movements of the Blind
SO PLOS ONE
LA English
DT Article
ID HEIMANN-BIELSCHOWSKY PHENOMENON; OCULOMOTOR BURST GENERATOR; MONOCULAR
   VISUAL-LOSS; NEURAL-NETWORK MODEL; VESTIBULOOCULAR REFLEX; OCULAR
   OSCILLATIONS; VERTICAL NYSTAGMUS; ON-DIRECTIONS; NEURONS; VISION
AB When normal subjects fix their eyes upon a stationary target, their gaze is not perfectly still, due to small movements that prevent visual fading. Visual loss is known to cause greater instability of gaze, but reported comparisons with normal subjects using reliable measurement techniques are few. We measured binocular gaze using the magnetic search coil technique during attempted fixation (monocular or binocular viewing) of 4 individuals with childhood-onset of monocular visual loss, 2 individuals with late-onset monocular visual loss due to age-related macular degeneration, 2 individuals with bilateral visual loss, and 20 healthy control subjects. We also measured saccades to visual or somatosensory cues. We tested the hypothesis that gaze instability following visual impairment is caused by loss of inputs that normally optimize the performance of the neural network (integrator), which ensures both monocular and conjugate gaze stability. During binocular viewing, patients with early-onset monocular loss of vision showed greater instability of vertical gaze in the eye with visual loss and, to a lesser extent, in the normal eye, compared with control subjects. These vertical eye drifts were much more disjunctive than upward saccades. In individuals with late monocular visual loss, gaze stability was more similar to control subjects. Bilateral visual loss caused eye drifts that were larger than following monocular visual loss or in control subjects. Accurate saccades could be made to somatosensory cues by an individual with acquired blindness, but voluntary saccades were absent in an individual with congenital blindness. We conclude that the neural gaze-stabilizing network, which contains neurons with both binocular and monocular discharge preferences, is under adaptive visual control. Whereas monocular visual loss causes disjunctive gaze instability, binocular blindness causes both disjunctive and conjugate gaze instability (drifts and nystagmus). Inputs that bypass this neural network, such as projections to motoneurons for upward saccades, remain conjugate.
C1 [Schneider, Rosalyn M.; Eisele, Sylvia; Leigh, R. John] Case Western Reserve Univ, Vet Affairs Med Ctr, Cleveland, OH 44106 USA.
   [Thurtell, Matthew J.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Thurtell, Matthew J.] Vet Affairs Med Ctr, Neurol Serv, Iowa City, IA 52242 USA.
   [Thurtell, Matthew J.] Vet Affairs Med Ctr, Ctr Prevent & Treatment Visual Loss, Iowa City, IA 52242 USA.
   [Lincoff, Norah] SUNY Buffalo, Jacobs Neurol Inst, Buffalo, NY 14260 USA.
   [Bala, Elisa] Cleveland Clin Fdn, Dept Ophthalmol, Cleveland, OH 44195 USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Case Western Reserve University; Louis Stokes Cleveland Veterans Affairs
   Medical Center; University of Iowa; US Department of Veterans Affairs;
   Veterans Health Administration (VHA); Iowa City VA Health Care System;
   US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Iowa City VA Health Care System; State University of New York (SUNY)
   System; State University of New York (SUNY) Buffalo; Cleveland Clinic
   Foundation
RP Leigh, RJ (通讯作者)，Case Western Reserve Univ, Vet Affairs Med Ctr, Cleveland, OH 44106 USA.
EM rjl4@case.edu
OI Thurtell, Matthew/0000-0002-1546-5463
FU National Institutes of Health [NIH R01 EY06717]; Department of Veterans
   Affairs; Evenor Armington Fund of Case Medical Center; NATIONAL EYE
   INSTITUTE [R01EY006717] Funding Source: NIH RePORTER
FX This study was supported by the National Institutes of Health (NIH R01
   EY06717), the Department of Veterans Affairs, and the Evenor Armington
   Fund of Case Medical Center. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 50
TC 32
Z9 32
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 18
PY 2013
VL 8
IS 2
AR e56556
DI 10.1371/journal.pone.0056556
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 092YP
UT WOS:000315159200060
PM 23441203
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Crewe, JM
   Morgan, WH
   Morlet, N
   Spilsbury, K
   Mukhtar, A
   Clark, A
   Ng, JQ
   Crowley, M
   Semmens, JB
AF Crewe, Julie M.
   Morgan, William H.
   Morlet, Nigel
   Spilsbury, Katrina
   Mukhtar, Aqif
   Clark, Antony
   Ng, Jonathon Q.
   Crowley, Margaret
   Semmens, James B.
TI Assessing the diagnostic validity of a blind register
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE blindness; blind register; positive predictive value; validation
ID UNREGISTERED VISUAL IMPAIRMENT; WESTERN-AUSTRALIA; REGISTRATION
AB Background: To validate the accuracy of clinical ophthalmic information held on the West Australian blind register.
   Design: Community-based cross-sectional study.
   Participants: Legally blind or severely vision-impaired people were selected randomly from the Association for the Blind of Western Australia register.
   Methods: Individuals were reviewed by one of two consultant ophthalmologists.
   Main Outcome Measures: The positive predictive value (ppv), sensitivity and specificity for legal blindness status and diagnostic causes of vision loss were calculated using data extracted from the Association for the Blind of Western Australia blind register.
   Results: 273 blind or near blind people were reviewed from the register total of 4271 individuals. There were more women (57%) than men, median age 81 years. For legal blindness status the ppv was 0.88 (95% confidence interval [CI] 0.82-0.92), sensitivity 0.75 (95% CI 0.74-0.84) and specificity 0.6 (95% CI 0.46-0.73). The ppv for the diagnostic causes of blindness were: age-related macular degeneration = 0.95 (95% CI 0.91-0.97), retinitis pigmentosa ppv = 1 (95% CI 0.81-1.0), diabetic retinopathy ppv = 0.9 (95% CI 0.57-0.99), optic neuropathies ppv = 0.77 (95% CI 0.51-0.92) and glaucoma ppv = 0.87 (95% Cl 0.7-0.96). Forty individuals (15%) had treatable conditions contributing to their vision loss.
   Conclusions: The blind register diagnoses and legal blindness status are of high accuracy. This information allows useful linkages to other databases for studies of blindness interactions. A regular updating mechanism would improve the future accuracy of this valuable regional asset. The presence of untreated cataract suggests that regular follow up and appropriate treatment may help optimize vision in blind patients.
C1 [Crewe, Julie M.; Morlet, Nigel; Spilsbury, Katrina; Mukhtar, Aqif; Clark, Antony; Ng, Jonathon Q.; Semmens, James B.] Curtin Univ, Ctr Populat Hlth Res, Curtin Hlth Innovat Res Inst, Perth, WA 6845, Australia.
   [Morgan, William H.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
   [Crowley, Margaret] Assoc Blind Western Australia, Perth, WA, Australia.
C3 Curtin University; Lions Eye Institute; University of Western Australia
RP Crewe, JM (通讯作者)，Curtin Univ, Ctr Populat Hlth Res, Curtin Hlth Innovat Res Inst, GPO Box U1987, Perth, WA 6845, Australia.
EM j.crewe@curtin.edu.au
RI Clark, Antony/A-2641-2009; Clark, Antony/K-7419-2014; Spilsbury,
   Katrina/B-5646-2016; Mukhtar, Syed Aqif/L-2349-2015
OI Clark, Antony/0000-0001-8393-9870; Clark, Antony/0000-0001-8393-9870;
   Spilsbury, Katrina/0000-0002-7434-2957; Mukhtar, Syed
   Aqif/0000-0001-5228-244X; Ng, Jonathon/0000-0002-4731-6673
FU Eye Surgery Foundation, Perth, Western Australia
FX This study was supported by the Eye Surgery Foundation, Perth, Western
   Australia. We thank all the clients and staff of the ABWA who
   contributed their time to this study.
CR *AUSTR BUR STAT, 2010, 32380 AUSTR BUR STAT
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NR 10
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1442-6404
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD AUG
PY 2011
VL 39
IS 6
BP 494
EP 500
DI 10.1111/j.1442-9071.2011.02509.x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 810BG
UT WOS:000294099800004
PM 21819503
DA 2022-11-30
ER

PT J
AU Norkus, EP
   Norkus, KL
   Dharmarajan, TS
   Schierle, J
   Schalch, W
AF Norkus, Edward P.
   Norkus, Katherine L.
   Dharmarajan, T. S.
   Schierle, Joseph
   Schalch, Wolfgang
TI Serum Lutein Response Is Greater from Free Lutein Than from Esterified
   Lutein during 4 Weeks of Supplementation in Healthy Adults
SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
LA English
DT Article
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; BETA-CAROTENE; MACULAR PIGMENT;
   CATARACT-EXTRACTION; NATIONAL-HEALTH; ALPHA-CAROTENE; HUMAN PLASMA;
   ZEAXANTHIN; BIOAVAILABILITY; ANTIOXIDANT
AB Background: Current data suggest great variability in serum response following lutein ingestion from various sources.
   Objective: To compare the relative serum response during supplementation with free lutein (fL) and lutein esters (Le).
   Methods: 72 volunteers (23-52 years; body mass index [BMI] >20 and <30 kg/m(2); baseline serum lutein <20 mu g/dL [<352 nmol/L]) were identified. Subjects, matched for gender, age, and BMI, were randomly assigned to the fL or Le group. fL and Le capsules contained 12.2 mg of free lutein or 27 mg of lutein ester (equivalent to 13.5 mg free lutein), respectively. Fasting blood was obtained at baseline and after 7, 14, 21, and 28 days of supplementation. Supplements were consumed with standard portions of dry, ready-to-eat cereal and 2% cow's milk.
   Results: Absolute changes in serum lutein, per mg daily dose, were significantly greater in fL vs. Le after 21 days (p = 0.0012) and remained so after 28 days (p = 0.0011) of supplementation. Serum lutein Area Under the Curve [AUC((day 0-28))] response was 17% greater for fL vs. Le (p = 0.0187). Regression models were used and determined that (I) baseline serum lutein levels and (2) the form of lutein ingested (fL > Le) influence the serum lutein response during supplementation, while subject age, gender, BMI, and serum lipids do not affect serum response.
   Conclusions: These results suggest that the relative serum lutein response will be significantly greater from supplements containing free lutein than from supplements containing lutein esters. These findings should be useful for future clinical trials exploring the effectiveness of lutein supplementation in the prevention of or protection against age-related macular degeneration and/or cataracts.
C1 [Norkus, Edward P.] Montefiore Med Ctr, North Div, Dept Med Res, Bronx, NY 10466 USA.
   [Dharmarajan, T. S.] Montefiore Med Ctr, North Div, Dept Med, Bronx, NY 10466 USA.
   [Norkus, Katherine L.] Vassar Coll, Poughkeepsie, NY 12601 USA.
   [Schierle, Joseph; Schalch, Wolfgang] DSM Nutr Prod Ltd, Wurmisweg, Kaiseraugst, Switzerland.
C3 Montefiore Medical Center; Yeshiva University; Albert Einstein College
   of Medicine; Montefiore Medical Center; Yeshiva University; Albert
   Einstein College of Medicine; Vassar College; DSM NV
RP Norkus, EP (通讯作者)，Montefiore Med Ctr, North Div, Dept Med Res, 600 E 233rd St, Bronx, NY 10466 USA.
EM enorkus@montefiore.org
FU DSM Nutritional Products, Inc.
FX Study funding was provided by DSM Nutritional Products, Inc.
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NR 51
TC 28
Z9 30
U1 3
U2 24
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0731-5724
EI 1541-1087
J9 J AM COLL NUTR
JI J. Am. Coll. Nutr.
PD DEC
PY 2010
VL 29
IS 6
BP 575
EP 585
DI 10.1080/07315724.2010.10719896
PG 11
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 776XO
UT WOS:000291574300006
PM 21677121
DA 2022-11-30
ER

PT J
AU Wu, Y
   Fishkin, NE
   Pande, A
   Pande, J
   Sparrow, JR
AF Wu, Yalin
   Fishkin, Nathan E.
   Pande, Ajay
   Pande, Jayanti
   Sparrow, Janet R.
TI Novel Lipofuscin Bisretinoids Prominent in Human Retina and in a Model
   of Recessive Stargardt Disease
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AGE PIGMENT A2-E; MACULAR DEGENERATION; MOUSE MODEL; EPITHELIAL-CELLS;
   RPE LIPOFUSCIN; OUTER SEGMENTS; VISUAL CYCLE; A2E; FLUOROPHORE; ABCR
AB Bisretinoid adducts accumulate as lipofuscin in retinal pigment epithelial (RPE) cells of the eye and are implicated in the pathology of inherited and age-related macular degeneration. Characterization of the bisretinoids A2E and the all-trans-retinal dimer series has shown that these pigments form from reactions in photoreceptor cell outer segments that involve all-trans-retinal, the product of photoisomerization of the visual chromophore 11-cis-retinal. Here we have identified two related but previously unknown RPE lipofuscin compounds. By high performance liquid chromatography-electrospray ionization-tandem mass spectrometry, we determined that the first of these compounds is a phosphatidyl-dihydropyridine bisretinoid; to indicate this structure and its formation from two vitamin A-aldehyde (A2), we will refer to it as A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE). The second pigment, A2-dihydropyridine-ethanolamine, forms from phosphate hydrolysis of A2-DHP-PE. The structure of A2-DHP-PE was corroborated by Fourier transform infrared spectroscopy, and density functional theory confirmed the presence of a dihydropyridine ring. This lipofuscin pigment is a fluorescent compound with absorbance maxima at similar to 490 and 330 nm, and it was identified in human, mouse, and bovine eyes. We found that A2-DHP-PE forms in reaction mixtures of all-trans-retinal and phosphatidylethanolamine, and in mouse eyecups we observed an age-related accumulation. As compared with wild-type mice, A2-DHP-PE is more abundant in mice with a null mutation in Abca4 (ATP-binding cassette transporter 4), the gene causative for recessive Stargardt macular degeneration. Efforts to clarify the composition of RPE lipofuscin are important because these compounds are targets of gene-based and drug therapies that aim to alleviate ABCA4-related retinal disease.
C1 [Wu, Yalin; Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Sparrow, Janet R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Fishkin, Nathan E.] ImmunoGen Inc, Waltham, MA 02451 USA.
   [Pande, Ajay; Pande, Jayanti] SUNY Albany, Dept Chem, Albany, NY 12222 USA.
C3 Columbia University; Columbia University; ImmunoGen, Inc.; State
   University of New York (SUNY) System; State University of New York
   (SUNY) Albany
RP Sparrow, JR (通讯作者)，630 W 168th St, New York, NY 10032 USA.
EM jrs88@columbia.edu
FU National Institutes of Health [EY 12951, EY 10535]; Kaplen Foundation;
   Department of Ophthalmology, Columbia University; NATIONAL EYE INSTITUTE
   [R01EY012951, R01EY010535] Funding Source: NIH RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY 12951 (to J. R. S.) and EY 10535 (to J. P.). This work
   was also supported by funds from the Kaplen Foundation (to J. R. S.) and
   unrestricted funds from Research to Prevent Blindness (to the Department
   of Ophthalmology, Columbia University).
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U2 10
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
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PD JUL 24
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VL 284
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EP 20166
DI 10.1074/jbc.M109.021345
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 471ZO
UT WOS:000268097400043
PM 19478335
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Yang, P
   Tyrrell, J
   Han, I
   Jaffe, GJ
AF Yang, Ping
   Tyrrell, Jillian
   Han, Ian
   Jaffe, Glenn J.
TI Expression and Modulation of RPE Cell Membrane Complement Regulatory
   Proteins
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID DECAY-ACCELERATING FACTOR; VASCULAR ENDOTHELIAL-CELLS; PIGMENT
   EPITHELIAL-CELLS; COFACTOR PROTEIN; MACULAR DEGENERATION; OXIDATIVE
   STRESS; BOUND REGULATORS; CULTURED HUMAN; UP-REGULATION; IN-VITRO
AB PURPOSE. Complement, inflammation, and oxidant injury contribute to age-related macular degeneration (AMD). Membrane complement regulatory proteins (mCRPs) such as CD46, CD55, and CD59, protect host cells from complement attack. The factors that regulate RPE mCRP expression are not well understood. In this study, the authors sought to determine whether cytokines and hydroquinone (HQ) affect mCRP expression in cultured human RPE (hRPE) and cultured mouse RPE (mRPE) cells.
   METHODS. Cultured hRPE and mRPE cells were stimulated with cytokines for various times or with HQ for multiple 6-hour periods. mRNA and protein expression of mCRPs in cultured hRPE cells from 10 donors, native hRPE, and mouse eyecups and native mRPE cells were evaluated by real-time RT-PCR, Western blot analysis, and flow cytometry, respectively.
   RESULTS. Three mCRPs were expressed in cultured hRPE cells (CD59>CD46>CD55). CD46 and CD59 protein were detected in native hRPE cells. CD59 protein levels in cultured hRPE cells were higher than in native hRPE cells. CD46 protein polymorphisms were observed in cultured hRPE cells. Cultured hRPE cell mCRP expression was upregulated by TNF-alpha, IL-1 beta, and a repetitive nonlethal dose of HQ. CD59a levels were higher in mouse eyecups than in nonocular tissues. Mouse mCRP mRNA and protein were detected in native mRPE cells. Responsiveness to cytokines in cultured mRPE cells differed from that in cultured hRPE cells.
   CONCLUSIONS. Human and mouse RPE cell mCRPs are upregulated by inflammatory cytokines and repetitive nonlethal oxidant exposure in a species-specific manner. Increased cell mCRPs may help to protect RPE cells from complement- and oxidant-mediated injury in diseases such as AMD. (Invest Ophthalmol Vis Sci. 2009; 50: 3473-3481) DOI: 10.1167/iovs.08-3202
C1 [Yang, Ping; Tyrrell, Jillian; Han, Ian; Jaffe, Glenn J.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
C3 Duke University
RP Jaffe, GJ (通讯作者)，Duke Eye Ctr, Dept Ophthalmol, 2351 Erwin Rd, Durham, NC 27710 USA.
EM jaffe001@mc.duke.edu
OI Han, Ian/0000-0002-2371-727X
FU National Eye Institute Core [930EY05722]; NATIONAL EYE INSTITUTE
   [P30EY005722] Funding Source: NIH RePORTER
FX Supported by National Eye Institute Core Grant 930EY05722.
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NR 50
TC 63
Z9 64
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2009
VL 50
IS 7
BP 3473
EP 3481
DI 10.1167/iovs.08-3202
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 461SP
UT WOS:000267292100057
PM 19168900
DA 2022-11-30
ER

PT J
AU Zhou, J
   Kim, SR
   Westlund, BS
   Sparrow, JR
AF Zhou, Jilin
   Kim, So Ra
   Westlund, Barbro S.
   Sparrow, Janet R.
TI Complement Activation by Bisretinoid Constituents of RPE Lipofuscin
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID C-REACTIVE PROTEIN; RETINAL-PIGMENT EPITHELIUM; FACTOR-H POLYMORPHISM;
   AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; PHOTOOXIDATION PRODUCTS; Y402H VARIANT; VITAMIN-E;
   RISK
AB PURPOSE. Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). Questions pertain to the trigger(s) responsible for the complement-associated events. The authors previously reported that photooxidation products of A2E can activate complement. Here they have further explored these events.
   METHODS. In vitro assays using human serum as a source of complement were used, and the C3 split product iC3b was measured by enzyme immunoassay. Serum was placed in contact with ARPE-19 cells and polarized human fetal retinal pigment epithelium that had accumulated A2E and were irradiated (430 nm). Serum was also incubated in wells precoated with bisretinoid pigments of lipofuscin and their oxidized forms. iC3b generation in normal human serum (NHS) was compared with that in factor B-depleted and C1q-depleted human serum.
   RESULTS. iC3b levels were elevated in NHS placed in contact with A2E-laden retinal pigment epithelium that were irradiated to generate A2E photooxidation products. iC3b was also increased in serum incubated in wells precoated with peroxy-A2E, the lipofuscin pigment all-trans-retinal dimer, and oxidized forms of all-trans-retinal dimer. Substitution of NHS with factor B-depleted sera abrogated these increases in iC3b. Complement activation was also suppressed by the addition of C-reactive protein and by a C3 cleavage inhibitor.
   CONCLUSIONS. The authors suggest that bisretinoid pigments of retinal pigment epithelial lipofuscin, subsequent to photoactivation and cleavage, serve to activate complement. Complement activation by this mechanism is dependent on the alternative pathway and can be modulated by an inhibitor of C3 cleavage. These events in the setting of complement dysregulation could contribute to the chronic inflammation that underlies AMD pathogenesis. (Invest Ophthalmol Vis Sci. 2009; 50: 1392-1399) DOI: 10.1167/iovs.08-2868
C1 [Zhou, Jilin; Kim, So Ra; Westlund, Barbro S.; Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Sparrow, Janet R.] Columbia Univ, 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, 630 W 168th St, New York, NY 10032 USA.
EM jrs88@columbia.edu
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768
FU National Institutes of Health Grant [EY12951]; NATIONAL EYE INSTITUTE
   [R01EY012951] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grant EY12951 (JRS), a gift
   from Gertrude Neumark Rothschild, and a grant from Research to Prevent
   Blindness to the Department of Ophthalmology. JRS is the recipient of a
   Research to Prevent Blindness Senior Investigator Award.
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NR 61
TC 107
Z9 116
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 2009
VL 50
IS 3
BP 1392
EP 1399
DI 10.1167/iovs.08-2868
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 411QO
UT WOS:000263665000055
PM 19029031
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wang, YS
   Friedrichs, U
   Eichler, W
   Hoffmann, S
   Wiedemann, P
AF Wang, Yu-Sheng
   Friedrichs, Ulrike
   Eichler, Wolfram
   Hoffmann, Stephan
   Wiedemann, Peter
TI Advanced glycation endproducts enhance proliferation, but not tube
   formation in choroidal microvascular endothelial cells
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE advanced glycation endproducts; angiogenesis; choroidal microvascular
   endothelial cells; proliferation; tube formation; age-related macular
   degeneration
AB AIM: To investigate the role of advanced glycation end-products (AGES) in the pathogenesis of age-related macular degeneration (AMD).
   METHODS: Bovine choroidal endothelial cells (CEC) were isolated by the modified protocol using lycopersicon esculentum agglutinin coated Dynabeads, and identified by immunocytochemical staining with anti-Factor VIII antibody and uptaking of dil-acetylated low-density lipoprotein (dil-ac-LDL). AGEs were prepared by incubating 50g/L bovine serum albumin and 150g/L glucose at 37 degrees C for 6 weeks, which were characterized by dot blot assay with anti-AGEs antibody. CEC proliferation was evaluated by 3, (4,5-dimethylthiazol-2-y1)-2,5- diphenyl tetrazolium bromide (MTT) assay, and tube formation in CEC was determined by a Vitrogen system.
   RESULTS: More than 90% of the cultured cells were positive to Factor VIII immunostaining and had the ability to uptake dil-ac-LDL, which were the features of endothelial cells. 219AGEs we prepared were affinitive to anti-AGEs antibody. After treatment with AGEs for a time course of 3 days, CEC proliferation was significantly increased in a dose-dependent manner by AGEs at concentrations between 62.5mg/L and 500mg/L. The cytokine, basic fibroblast growth factor (bFGF), enhanced strongly tube-like structure formation in CEC to 124%(P<0.05) above that of untreated controls. In this condition, AGEs at the concentrations of 500mg/L and 50mg/L showed no effect on CEC tube formation (P>0.05).
   CONCLUSION: The present study demonstrated that CEC proliferation was increased by AGEs. However, there was no statistical effect on CEC tube formation. These findings confirm and extend that AGEs could be a potential initiator in the pathogenesis of choroidal neovascularization in exudative AMD, at least in part, through enhancement of CEC proliferation.
C1 [Wang, Yu-Sheng; Friedrichs, Ulrike; Eichler, Wolfram; Hoffmann, Stephan; Wiedemann, Peter] Univ Leipzig, Dept Ophthalmol, Fac Med, D-04103 Leipzig, Germany.
   [Wang, Yu-Sheng] Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Shaanxi Prov, Peoples R China.
C3 Leipzig University; Air Force Military Medical University
RP Wiedemann, P (通讯作者)，Univ Leipzig, Dept Ophthalmol, Fac Med, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM wiedeman@medizin.uni-leipzig.de
FU German Research Community (Deutsche Forschungsgemeinschaft, DFG) [WI
   880/9-1]; Alexander von Humboldt Foundation (Die Alexander von
   Humboldt-Stiftung) of Germany
FX Foundation item: Supported by German Research Community (Deutsche
   Forschungsgemeinschaft, DFG) Grant WI 880/9-1 to Prof. P Wiedemann;
   Alexander von Humboldt Foundation (Die Alexander von Humboldt-Stiftung)
   of Germany is acknowledged for its scholarship to YS Wang. We thank Dr.
   HP Hammes, Giessen, Germany for his geneous gifts of anti-CML monoclonal
   antibody and AGEs as positive control, Dr. Volker Enzmann and Mr. Dirk
   Scharf for their kind help in the image analysis of tube formation
   assay, and Ms. Ute Weinbrecht for her technical assistance. This work
   was supported by German Research Community (Deutsche
   Forschungsgemeinschaft, DFG) grant WI 880/9-1 to Prof. P Wiedemann.
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NR 36
TC 0
Z9 0
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 SEP 18
PY 2008
VL 1
IS 3
BP 212
EP 218
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V13QY
UT WOS:000207682500006
DA 2022-11-30
ER

PT J
AU Rogers, AH
   Martidis, A
   Greenberg, PB
   Puliafito, CA
AF Rogers, AH
   Martidis, A
   Greenberg, PB
   Puliafito, CA
TI Optical coherence tomography findings following photodynamic therapy of
   choroidal neovascularization
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID TUMOR
AB PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age,related macular degeneration (AMD).
   DESIGN: Retrospective interventional case series.
   METHODS: Ninety eyes (88 patients) with AMD and predominantly classic subfoveal CNV treated with PDT using verteporfin were identified by a laser log and retrospectively reviewed. Optical coherence tomography and fluorescein angiography (FA) were performed before treatment and at subsequent follow-up examinations in all eyes. Optical coherence tomography findings were evaluated and compared with corresponding FA.
   RESULTS: A five-stage OCT classification of eyes treated with PDT was created from the evaluation of 79 total eyes (77 patients). Stage I (two eyes) is recognized within the first week of treatment and demonstrates an acute inflammatory response with increased subretinal fluid. Stage 11 (28 eyes) represents the restoration of a near-normal fovea contour with diminished subretinal fluid occurring 1 to 4 weeks after treatment. Stage III (79 eyes) occurs between 4 to 12 weeks following treatment and is subdivided into two categories based on the amount of subretinal fibrosis and fluid present. Stage IIIa (15 eyes) contains a greater subretinal fluid to fibrosis ratio indicating an active CNV process. Lesions in stage IIIb (64 eyes) less actively leak and have more prominent fibrosis with minimal intraretinal fluid. Cystoid macular edema defines a stage IV lesion (11 eyes). In stage V lesions (19 eyes) the subretinal fluid resolves with thinning of the retina as well as fibrosis merging with the retinal pigment epithelial layer (RPE).
   CONCLUSION: Optical coherence tomography appears to be useful in monitoring the retinal changes that occur following PDT of CNV and may assist in understanding the changes observed on angiography. (C) 2002 by Elsevier Science Inc. All rights reserved.
C1 Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA USA.
   Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Tufts University;
   Jefferson University
RP Puliafito, CA (通讯作者)，Univ Miami, Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
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NR 14
TC 127
Z9 143
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 OCT
PY 2002
VL 134
IS 4
BP 566
EP 576
AR PII S0002-9394(02)01566-0
DI 10.1016/S0002-9394(02)01566-0
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 601KY
UT WOS:000178446100010
PM 12383814
DA 2022-11-30
ER

PT J
AU Lee, JS
   Lin, KK
   Hou, CH
   Li, PR
   See, LC
AF Lee, Jiahn-Shing
   Lin, Ken-Kuo
   Hou, Chiun-Ho
   Li, Pei-Ru
   See, Lai-Chu
TI Chinese Version of the Vision-Related Quality of Life (NEI-VFQ-25) among
   Patients with Various Ocular Disorders: A Pilot Study
SO MEDICINA-LITHUANIA
LA English
DT Article
DE vision-related quality of life; refractive error; keratoconus; senile
   cataract; age-related macular degeneration
ID VISUAL-FIELD LOSS; EYE DISEASE; MACULAR DEGENERATION; CATARACT-SURGERY;
   RISK-FACTORS; IMPAIRMENT; IMPACT; POPULATION; PREVALENCE; TAIWAN
AB Background and Objectives: Subjective visual function is currently becoming an increasing appreciation in assessing the health-related quality of life. This study aimed to assess the vision-related quality of life (VRQOL) among patients with refractive errors, keratoconus, senile cataract, and age-related macular degeneration (AMD) using the Chinese version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Materials and Methods: The questionnaire of NEI-VFQ-25 was filled out in a clinical setting or by telephone/mail. Univariate and multivariate analyses were used to determine which factors are associated with the NEI-VFQ-25. Results: From June 2018 to January 2019, 28 patients with refractive error, 20 patients with keratoconus, 61 with senile cataracts, and 17 with AMD completed the questionnaire NEI-VFQ-25. There were significant differences in the NEI-VFQ-25 subscale of general vision (p = 0.0017), ocular pain (p = 0.0156), near activities (p = 0.0002), vision-specific social functioning (p = 0.007), vision-specific mental health (p = 0.0083), vision-specific dependency (p = 0.0049), color vision (p < 0.0001), peripheral vision (p = 0.0065), and total score (p < 0.0001) among four disease groups, respectively. The multiple linear regression revealed that the best-corrected visual acuity (BCVA) and disease group were important factors of the total NEI-VFQ-25. After adjusting for BCVA, patients with AMD had a worse total NEI-VFQ-25 score than patients with refractive error, keratoconus, or senile cataracts. Conclusions: Among the patients with four ocular disorders and a broad vision spectrum from normal, partial sight, low vision to legal blindness, the BCVA of their better eye was the most important factor in the VRQOL.
C1 [Lee, Jiahn-Shing; Lin, Ken-Kuo; Hou, Chiun-Ho] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Dept Ophthalmol, Taoyuan 333, Taiwan.
   [Li, Pei-Ru; See, Lai-Chu] Chang Gung Univ, Coll Med, Dept Publ Hlth, Taoyuan 333, Taiwan.
   [See, Lai-Chu] Chang Gung Univ, Mol Med Res Ctr, Biostat Core Lab, Taoyuan 333, Taiwan.
   [See, Lai-Chu] Chang Gung Mem Hosp Linkou, Div Rheumatol Allergy & Immunol, Taoyuan 333, Taiwan.
C3 Chang Gung Memorial Hospital; Chang Gung University; Chang Gung
   University; Chang Gung University; Chang Gung Memorial Hospital
RP See, LC (通讯作者)，Chang Gung Univ, Coll Med, Dept Publ Hlth, Taoyuan 333, Taiwan.; See, LC (通讯作者)，Chang Gung Univ, Mol Med Res Ctr, Biostat Core Lab, Taoyuan 333, Taiwan.; See, LC (通讯作者)，Chang Gung Mem Hosp Linkou, Div Rheumatol Allergy & Immunol, Taoyuan 333, Taiwan.
EM leejsh@cgmh.org.tw; d12093@cgmh.org.tw; chiunho@cgmh.org.tw;
   peili0506@cgmh.org.tw; lichu@mail.cgu.edu.tw
OI See, Lai-Chu/0000-0002-1379-8969
FU Chang Gung Memorial Hospital, Linkou, Taiwan [CMRPG1H0011, CMRPD1H0151]
FX This study was supported by grants CMRPG1H0011 and CMRPD1H0151 from
   Chang Gung Memorial Hospital, Linkou, Taiwan.
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NR 49
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1010-660X
EI 1648-9144
J9 MEDICINA-LITHUANIA
JI Med. Lith.
PD MAY
PY 2022
VL 58
IS 5
AR 602
DI 10.3390/medicina58050602
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 1R6EB
UT WOS:000803460100001
PM 35630019
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Enoch, J
   Ghulakhszian, A
   Crabb, DP
   Dinah, C
   Taylor, DJ
AF Enoch, Jamie
   Ghulakhszian, Arevik
   Crabb, David P.
   Dinah, Christiana
   Taylor, Deanna J.
TI Acceptability of intravitreal injections in geographic atrophy: protocol
   for a mixed-methods pilot study
SO BMJ OPEN
LA English
DT Article
DE qualitative research; medical retina; health services administration
   &amp; management
ID DISCRETE-CHOICE EXPERIMENT; MACULAR DEGENERATION; RANIBIZUMAB TREATMENT;
   QUALITATIVE RESEARCH; PATIENT PREFERENCES; DISEASE BURDEN; EXPERIENCES;
   UNCERTAINTY; MANAGEMENT; ADHERENCE
AB Introduction Age-related macular degeneration (AMD) is a common cause of visual impairment, affecting central vision. Geographic atrophy (GA) is an advanced form of the non-neovascular (dry) type of AMD. Late-stage clinical trials suggest that intravitreal injections of novel therapeutics may slow down the rate of GA progression by up to 30% in 1 year, thus allowing people with GA to preserve central vision for a longer period. While intravitreal injections have become an established treatment modality for neovascular (wet) AMD, it is unknown whether patients with (more gradually progressing) GA would accept regular injections that slow down, but do not stop or reverse, vision loss. Therefore, this mixed-methods pilot study will aim to explore whether regular intravitreal injections will be acceptable as treatment for patients with GA, and the factors that may affect treatment acceptability. Methods and analysis A mixed-methods survey has been designed in collaboration with a GA patient advisory group. The survey comprises of structured questionnaires, semi-structured interview questions regarding patients' perceptions of intravitreal injections and the burden of treatment, and a task eliciting preferences between different potential treatments. Due to COVID-19 restrictions, this study will be conducted remotely by telephone. Thirty individuals will be recruited from NHS Medical Retina clinics at Central Middlesex Hospital, London. Half of the participants will be naive to intravitreal injections, while half will have previous experience of intravitreal injections for neovascular (wet) AMD. Qualitative data analysis will be conducted using the Framework Method of analysis to identify key themes from participants' accounts. Ethics and dissemination The study received Health Research Authority approval on 23 March 2021 (IRAS Project ID: 287824). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.
C1 [Enoch, Jamie; Crabb, David P.; Taylor, Deanna J.] City Univ London, Optometry & Visual Sci, London, England.
   [Ghulakhszian, Arevik; Dinah, Christiana] London North West Univ Healthcare NHS Trust, Cent Middlesex Hosp, Ophthalmol Dept, London, England.
C3 City University London; Imperial College London
RP Taylor, DJ (通讯作者)，City Univ London, Optometry & Visual Sci, London, England.
EM Deanna.Taylor.2@city.ac.uk
OI Ghulakhszian, Arevik/0000-0002-5503-3892; Taylor,
   Deanna/0000-0001-8261-5225; Crabb, David/0000-0001-8754-3902; Dinah,
   Christiana/0000-0002-0815-4771; Enoch, Jamie/0000-0002-4614-6676
FU National Institute for Health Research (NIHR) Enabling Involvement Fund
   (EIF) [397]; City, University of London School of Health Sciences Higher
   Education Innovation Fund (HEIF)
FX This work has been supported by the National Institute for Health
   Research (NIHR) Enabling Involvement Fund (EIF) (Grant number EIFApp ID:
   397) and the City, University of London School of Health Sciences Higher
   Education Innovation Fund (HEIF).
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD APR
PY 2021
VL 11
IS 4
AR e049495
DI 10.1136/bmjopen-2021-049495
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC General & Internal Medicine
GA ZM0LD
UT WOS:000764057400010
PM 33895721
OA Green Accepted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Di Marco, S
   Carnicelli, V
   Franceschini, N
   Di Paolo, M
   Piccardi, M
   Bisti, S
   Falsini, B
AF Di Marco, Stefano
   Carnicelli, Veronica
   Franceschini, Nicola
   Di Paolo, Mattia
   Piccardi, Marco
   Bisti, Silvia
   Falsini, Benedetto
TI Saffron: A Multitask Neuroprotective Agent for Retinal Degenerative
   Diseases
SO ANTIOXIDANTS
LA English
DT Article
DE oxidative stress; age related macular degeneration; light induced
   damage; matrix metalloproteinases; saffron
ID DAMAGING LIGHT; EYE DISEASE; LUTEIN/ZEAXANTHIN; EXPOSURE
AB Both age related macular degeneration (AMD) and light induced retinal damage share the common major role played by oxidative stress in the induction/progression of degenerative events. Light damaged (LD) rats have been widely used as a convenient model to gain insight into the mechanisms of degenerative disease, to enucleate relevant steps and to test neuroprotectants. Among them, saffron has been shown to ameliorate degenerative processes and to regulate many genes and protective pathways. Saffron has been also tested in AMD patients. We extended our analysis to a possible additional effect regulated by saffron and compared in AMD patients a pure antioxidant treatment (Lutein/zeaxanthin) with saffron treatment. Methods: Animal model. Sprague-Dawley (SD) adult rats, raised at 5 lux, were exposed to 1000 lux for 24 h and then either immediately sacrificed or placed back at 5 lux for 7 days recovery period. A group of animals was treated with saffron. We performed in the animal model: (1) SDS-PAGE analysis; (2) Western Blotting (3) Enzyme activity assay (4) Immunolabelling; in AMD patients: a longitudinal open-label study 29 (+/- 5) months in two groups of patients: lutein/zeaxanthin (19) and saffron (23) treated. Visual function was tested every 8 months by ERG recordings in addition to clinical examination. Results: Enzymatic activity of MMP-3 is reduced in LD saffron treated retinas and is comparable to control as it is MMP-3 expression. LD treated retinas do not present "rosettes" and microglia activation and migration is highly reduced. Visual function remains stable in saffron treated AMD patients while deteriorates in the lutein/zeaxanthin group. Conclusion: Our results provide evidence of an additional way of action of saffron treatment confirming the complex nature of neuroprotective activities of its chemical components. Accordingly, long term follow-up in AMD patients reveals an added value of saffron supplementation treatment compared to classical antioxidant protocol.
C1 [Di Marco, Stefano; Carnicelli, Veronica; Franceschini, Nicola; Di Paolo, Mattia; Bisti, Silvia] Univ Aquila, Dept Appl Clin Sci & Biotechnol, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.
   [Di Marco, Stefano; Bisti, Silvia] INBB, Via Medaglie DOro 305, I-00136 Rome, Italy.
   [Piccardi, Marco; Falsini, Benedetto] Univ Cattol S Cuore, Fdn Policlin A Gemelli, Fac Med & Chirurg, I-00136 Rome, Italy.
C3 University of L'Aquila; Catholic University of the Sacred Heart; IRCCS
   Policlinico Gemelli
RP Di Marco, S; Bisti, S (通讯作者)，Univ Aquila, Dept Appl Clin Sci & Biotechnol, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.; Di Marco, S; Bisti, S (通讯作者)，INBB, Via Medaglie DOro 305, I-00136 Rome, Italy.
EM stefano.dimarco@univaq.it; silvia.bisti@univaq.it
RI Piccardi, Marco/AAA-7849-2019; Di Marco, Stefano/AAO-8073-2020;
   Di+Paolo, Mattia/AAX-3592-2021; Falsini, Benedetto/AAC-5907-2022
OI Di Marco, Stefano/0000-0003-4847-6270; CARNICELLI,
   Veronica/0000-0003-3375-4637
FU Fondi di Ateneo, Linea D3 "Nutrition and Ageing" of Universita'
   Cattolica del S. Cuore, Rome, Italy; Essse Caffe srl
FX BF is supported by the grant: Fondi di Ateneo, Linea D3 "Nutrition and
   Ageing" of Universita' Cattolica del S. Cuore, Rome, Italy. SDM position
   is supported by Essse Caffe srl. The grant providers (Hortus Novus srl,
   Universita' Cattolica del S. Cuore, Essse Caffe srl) had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 36
TC 22
Z9 22
U1 0
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUL
PY 2019
VL 8
IS 7
AR 224
DI 10.3390/antiox8070224
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 IN3XB
UT WOS:000478608600033
PM 31319529
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Posarelli, C
   Salvetti, G
   Piaggi, P
   Guido, F
   Ceccarini, G
   Santini, F
   Figus, M
AF Posarelli, Chiara
   Salvetti, Guido
   Piaggi, Paolo
   Guido, Francesca
   Ceccarini, Giovanni
   Santini, Ferruccio
   Figus, Michele
TI Ophthalmologic evaluation of severely obese patients undergoing
   bariatric surgery: A pilot, monocentric, prospective, open-label study
SO PLOS ONE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; NERVE-FIBER LAYER; BODY-MASS INDEX;
   INTRAOCULAR-PRESSURE; BLOOD-PRESSURE; RISK-FACTORS; MACULAR
   DEGENERATION; EYE; THICKNESS; ASSOCIATION
AB Purpose
   The aim of this study was to investigate the pathogenic role of obesity on blinding eye diseases in a population of severely obese patients with no history of eye diseases, and to verify whether weight loss induced by bariatric surgery may have a protective effect.
   Methods
   This was a pilot, monocentric, prospective, and open label study conducted at the University Hospital of Pisa. Fifty-seven severely obese patients with a mean body mass index value of 44.1 +/- 6 kg/m(2) were consecutively recruited and received a complete ophthalmological evaluation and optical coherence tomography. Twenty-nine patients who underwent gastric bypass were evaluated also 3 months, and 1 year after surgery.
   Results
   At baseline, blood pressure value were directly and significantly related to intraocular pressure values (p<0.05, R = 0.35). Blood pressure values were also significantly and inversely related to retinal nerve fiber layer thickness, particularly in the temporal sector (RE p<0.05 r-0.30; LE p<0.01, R = -0.43). Moreover, minimum foveal thickness values were significantly and inversely associated with body mass index (RE p<0.02, R = -0.40; LE p<0.02, R = -0.30). A significant reduction of body mass index (p<0.05) and a significant (p<0.05) improvement of blood pressure was observed three months and one year after gastric bypass, which were significantly associated with an increase in retinal nerve fiber layer thickness and minimum foveal thickness values in both eyes (p<0.05).
   Conclusions
   The results of this study suggest that obese patients may have a greater susceptibility to develop glaucomatous optic nerve head damage and age-related macular degeneration. Moreover, weight reduction and improvement of comorbidities obtained by bariatric surgery may be effective in preventing eye disease development by improving retinal nerve fiber layer and foveal thickness.
C1 [Posarelli, Chiara; Guido, Francesca; Figus, Michele] Univ Hosp Pisa, Ophthalmol, Dept Surg, Med Mol Pathol & Crit Area, Pisa, Italy.
   [Salvetti, Guido; Piaggi, Paolo; Ceccarini, Giovanni; Santini, Ferruccio] Univ Hosp Pisa, Obes Ctr, Endocrine Unit, Pisa, Italy.
   [Piaggi, Paolo] NIDDK, NIH, Phoenix, AZ USA.
C3 University of Pisa; Azienda Ospedaliero Universitaria Pisana; University
   of Pisa; Azienda Ospedaliero Universitaria Pisana; National Institutes
   of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive &
   Kidney Diseases (NIDDK)
RP Posarelli, C (通讯作者)，Univ Hosp Pisa, Ophthalmol, Dept Surg, Med Mol Pathol & Crit Area, Pisa, Italy.
EM chiara.posarelli@med.unipi.it
RI Santini, Ferruccio/J-9272-2018; CECCARINI, GIOVANNI/S-3871-2019; Figus,
   Michele/AAD-6850-2020; Posarelli, Chiara/AAA-8278-2019; Piaggi,
   Paolo/E-2539-2011; Posarelli, Chiara/AAW-9528-2020; Figus,
   Michele/AAA-9808-2019
OI Santini, Ferruccio/0000-0002-1706-0822; CECCARINI,
   GIOVANNI/0000-0003-0701-642X; Posarelli, Chiara/0000-0003-0222-5177;
   Piaggi, Paolo/0000-0003-2774-9161; Figus, Michele/0000-0003-2243-9033
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NR 38
TC 6
Z9 6
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 MAY 16
PY 2019
VL 14
IS 5
AR e0216351
DI 10.1371/journal.pone.0216351
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HY3MG
UT WOS:000468030100022
PM 31095581
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Tiwari, A
   Talwekar, RH
AF Tiwari, Ashish
   Talwekar, R. H.
TI Journey of Visual Prosthesis with Progressive Development of Electrode
   Design Techniques and Experience with CMOS Image Sensors: A Review
SO IETE JOURNAL OF RESEARCH
LA English
DT Review
DE AMD; Biocompatibility; CCD; CMOS-APS; Feasibility; High dynamic range;
   Photoreceptor; RP
ID HIGH-DYNAMIC-RANGE; ELECTRICALLY-EVOKED RESPONSE;
   SUPRACHOROIDAL-TRANSRETINAL STIMULATION; POLYIMIDE FILM ELECTRODES;
   RETINAL PROSTHESES; INTRACORTICAL MICROSTIMULATION; MICROELECTRODE
   ARRAY; SUBRETINAL IMPLANTS; NEURAL STIMULATION; ARTIFICIAL VISION
AB The objective of visual prosthesis is to develop techniques which can functionally replace the degenerated photoreceptors either by inserting the clinical aid inside the eye or by providing external means. Except AIDS and Cancer, there is hardly any disease than blindness which creates more fear in human's mind. Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) were found to be main cause of vision loss followed by cataract and glaucoma. This paper addresses the journey of visual prosthesis by first highlighting the initial challenges and technical advancement later. We have tactically analyzed the conception of visualization, phosphenes detection and modeling of retina through electrodes which had been the focus of researchers before 1990s. Afterwards with the technological improvement, techniques which could enhance the safety, longevity, biocompatibility, resolution and feasibility were targeted. Categorically visual prosthesis is divided into visual cortex, optic nerve and retinal implantation techniques for restoration of vision in blinds. After analyzing the advantages and shortcomings of all these techniques it is concluded that, retinal implants have been the popular method and adopted as potential way for yielding the artificial vision. Key areas of safety standards, use of new biomaterials for improved resolution and durability, power requirements, image processing techniques, new stimulation methods such as biphasic stimulation, and impact of stimulation current/heat on retinal nerves behavior are also addressed in this paper. With low-cost, lower power consumption and integration technology of CMOS devices, nowadays the CMOS active pixel sensor (CMOS-APS) is the new hope for researchers and clinicians. Analysis of electrode design techniques with microphotodiodes, CCD and now with CMOS-APS suggests that the focus of future research will be in developing the high dynamic range (HDR) pixel that can be directly attached to retina for greater efficiency and resolution.
C1 [Tiwari, Ashish] Shri Shankaracharya Grp Inst, Dept Elect & Telecommun, Bhilai, Chhattisgarh, India.
   [Talwekar, R. H.] Govt Engn Coll, Dept Elect & Telecommun, Raipur, Chhattisgarh, India.
C3 Shri Shankaracharya Group Of Institutions
RP Tiwari, A (通讯作者)，Shri Shankaracharya Grp Inst, Dept Elect & Telecommun, Bhilai, Chhattisgarh, India.
EM tiwari.ashish99@gmail.com; ursk.talwekar@gmail.com
OI TIWARI, Dr. ASHISH/0000-0002-1441-1797
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NR 163
TC 5
Z9 5
U1 2
U2 39
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0377-2063
EI 0974-780X
J9 IETE J RES
JI IETE J. Res.
PD MAR 4
PY 2019
VL 65
IS 2
BP 172
EP 200
DI 10.1080/03772063.2017.1417750
PG 29
WC Engineering, Electrical & Electronic; Telecommunications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Telecommunications
GA HW0IY
UT WOS:000466365300006
DA 2022-11-30
ER

PT J
AU Imamura, T
   Tsuruma, K
   Inoue, Y
   Otsuka, T
   Ohno, Y
   Ogami, S
   Yamane, S
   Shimazawa, M
   Hara, H
AF Imamura, Tomoyo
   Tsuruma, Kazuhiro
   Inoue, Yuki
   Otsuka, Tomohiro
   Ohno, Yuta
   Ogami, Shiho
   Yamane, Shinsaku
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Involvement of cannabinoid receptor type 2 in light-induced degeneration
   of cells from mouse retinal cell line in vitro and mouse photoreceptors
   in vivo
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Cannabinoid type 2 receptor; Light-induced retinal degeneration; Retinal
   cell death
ID PIGMENT EPITHELIAL-CELLS; ADULT-RAT RETINA; CB2 RECEPTOR; OXIDATIVE
   STRESS; EXPRESSION; IDENTIFICATION; MIGRATION; AGONIST; DISEASE; CLONING
AB Earlier studies showed that the expressions of the agonists of the cannabinoid receptors are reduced in the vitreous humor of patients with age-related macular degeneration (AMD), and the cannabinoid type 2 receptor is present in the retinas of rats and monkeys. The purpose of this study was to determine whether the cannabinoid type 2 receptor is involved in the light-induced death of cultured 661W cells, an immortalized murine retinal cell line, and in the light-induced retinal degeneration in mice. Time-dependent changes in the expression and location of retinal cannabinoid type 2 receptor were determined by Western blot and immunostaining. The cannabinoid type 2 receptor was down-regulated in murine retinae and cone cells. In the in vitro studies, HU-308, a cannabinoid type 2 receptor agonist, had a protective effect on the light-induced death of 661W cells, and this effect was attenuated by SR144528, a cannabinoid type 2 receptor antagonist. Because the cannabinoid type 2 receptor is a G-protein coupled receptor and is coupled with Go, protein, we investigated the effects of the cAMP-dependent protein kinase (PICA). HU-308 and 1189, a PICA inhibitor, deactivated PICA in retinal cone cells, and H89 also suppressed light-induced cell death. For the in vivo studies, a cannabinoid type 2 receptor agonist, HU-308, or an antagonist, SR144528, was injected intravitreally into mouse eyes before the light exposure. Electroretinography was used to determine the physiological status of the retinas. Injection of HU-308 improved the a- and b-waves of the ERGs and also the thickness of the outer nuclear layer of the murine retina after light exposure. These findings indicate that the cannabinoid type 2 receptor is involved in the light-induced retinal damage through PKA signaling. Thus, activation of cannabinoid type 2 receptor may be a therapeutic approach for light-associated retinal diseases.
C1 [Imamura, Tomoyo; Tsuruma, Kazuhiro; Inoue, Yuki; Otsuka, Tomohiro; Ohno, Yuta; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
   [Ogami, Shiho; Yamane, Shinsaku] Ono Pharmaceut Co Ltd, Discovery Res Labs 3, Osaka, Japan.
C3 Gifu Pharmaceutical University; Ono Pharmaceutical Co Ltd
RP Tsuruma, K (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM tsuruma@gifu-pu.ac.jp
RI Ohno, Yuta/AIE-4047-2022
OI Ohno, Yuta/0000-0002-8182-3150; Hara, Hideaki/0000-0003-2046-9001
FU Ono Pharmaceutical Co., Ltd. (Osaka, Japan)
FX This study was supported by Ono Pharmaceutical Co., Ltd. (Osaka, Japan).
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NR 28
TC 6
Z9 6
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2018
VL 167
BP 44
EP 50
DI 10.1016/j.exer.2017.11.003
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FX8FC
UT WOS:000426325800006
PM 29133122
DA 2022-11-30
ER

PT J
AU Roddy, GW
   Yasumura, D
   Matthes, MT
   Alavi, MV
   Boye, SL
   Rosa, RH
   Fautsch, MP
   Hauswirth, WW
   LaVail, MM
AF Roddy, Gavin W.
   Yasumura, Douglas
   Matthes, Michael T.
   Alavi, Marcel V.
   Boye, Sanford L.
   Rosa, Robert H., Jr.
   Fautsch, Michael P.
   Hauswirth, William W.
   LaVail, Matthew M.
TI Long-term photoreceptor rescue in two rodent models of retinitis
   pigmentosa by adeno-associated virus delivery of Stanniocalcin-1
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retinal degeneration; Neuroprotection; Stanniocalcin-1; P23H; S334ter;
   Rhodopsin
ID RENAL ISCHEMIA/REPERFUSION INJURY; TRANSGENIC RAT MODEL; APOPTOTIC
   PHOTORECEPTORS; OXIDATIVE STRESS; EXPRESSION; DEGENERATION; CELLS;
   MECHANISMS; PROTECTION; TARGET
AB Retinal degenerations, including age-related macular degeneration and the retinitis pigmentosa family of diseases, are among the leading causes of legal blindness in the United States. We previously found that Stanniocalcin-1 (STC-1) reduced photoreceptor loss in the S334ter-3 and Royal College of Surgeons rat models of retinal degeneration. The results were attributed in part to a reduction in oxidative stress. Herein, we tested the hypothesis that long-term delivery of STC-1 would provide therapeutic rescue in more chronic models of retinal degeneration. To achieve sustained delivery, we produced an adenoassociated virus (AAV) construct to express STC-1 (AAV-STC-1) under the control of a retinal ganglion cell targeting promoter human synapsin 1 (hSYN1). AAV-STC-1 was injected intravitreally into the P23H1 and S334ter-4 rhodopsin transgenic rats at postnatal day 10. Tissues were collected at postnatal day 120 for confirmation of STC-1 overexpression and histologic and molecular analysis. Electroretinography (ERG) was performed in a cohort of animals at that time. Overexpression of STC-1 resulted in a significant preservation of photoreceptors as assessed by outer nuclear thickness in the P23H-1 (P < 0.05) and the S334ter-4 (P < 0.005) models compared to controls. Additionally, retinal function was significantly improved in the P23H-1 model with overexpressed STC-1 as assessed by ERG analysis (scotopic b-wave P < 0.005 and photopic b-wave P < 0.05). Microarray analysis identified common downstream gene expression changes that occurred in both models. Genes of interest based on their function were selected for validation by quantitative real-time PCR and were significantly increased in the S334ter-4 model. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Roddy, Gavin W.; Fautsch, Michael P.] Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
   [Yasumura, Douglas; Matthes, Michael T.; Alavi, Marcel V.; LaVail, Matthew M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Boye, Sanford L.; Hauswirth, William W.] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Rosa, Robert H., Jr.] Scott & White Med Ctr, Dept Ophthalmol, Temple, TX 76508 USA.
C3 Mayo Clinic; University of California System; University of California
   San Francisco; State University System of Florida; University of
   Florida; Scott & White Medical Center
RP LaVail, MM (通讯作者)，Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
EM Roddy.Gavin@mayo.edu; michael.matthes@sbcglobal.net;
   marcel.alavi@gmail.com; sboye@UFL.EDU; Robert.Rosa@BSWHealth.org;
   Fautsch.Michael@mayo.edu; hauswrth@ufl.edu; mmlv@sonic.net
OI Alavi, Marcel/0000-0002-1319-3062; hauswirth,
   william/0000-0002-3244-4947
FU NIH [EY001919, EY006842, P30EY002162, P30EY021721, EY021727]; Research
   to Prevent Blindness; University of Florida; Mayo Clinic; Foundation
   Fighting Blindness; That Man May See, Inc.; Mayo Foundation; NATIONAL
   EYE INSTITUTE [R01EY006842, F32EY006842, R01EY001919, R01EY021727,
   P30EY002162, P30EY021721] Funding Source: NIH RePORTER
FX This work was funded in part by NIH research grants EY001919, EY006842,
   P30EY002162 (MML), P30EY021721 (WWH) and EY021727 (MPF); Unrestricted
   Awards from Research to Prevent Blindness to UCSF, University of
   Florida, and Mayo Clinic; the Foundation Fighting Blindness (MML, WWH),
   That Man May See, Inc. (MML) and the Mayo Foundation (GWR). WWH and the
   University of Florida have a financial interest in the use of AAV
   therapies, WWH owns equity in and is a consultant for AGTC and has a
   conflict of interest to the extent that this work potentially increases
   their financial interests. The other authors declare that no conflict of
   interest exists.
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NR 51
TC 10
Z9 10
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 2017
VL 165
BP 175
EP 181
DI 10.1016/j.exer.2017.09.011
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FQ4GL
UT WOS:000418315600020
PM 28974356
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sun, JR
   Huang, PR
   Liang, J
   Li, J
   Shen, MX
   She, XJ
   Feng, YJ
   Luo, XT
   Liu, T
   Sun, XD
AF Sun, Junran
   Huang, Peirong
   Liang, Jian
   Li, Jie
   Shen, Mengxi
   She, Xiangjun
   Feng, Yiji
   Luo, Xueting
   Liu, Te
   Sun, Xiaodong
TI Cooperation of Rel family members in regulating A beta(1-40)-mediated
   pro-inflammatory cytokine secretion by retinal pigment epithelial cells
SO CELL DEATH & DISEASE
LA English
DT Article
ID NF-KAPPA-B; MACULAR DEGENERATION; AMYLOID-BETA; NLRP3 INFLAMMASOME;
   C-REL; CHOROIDAL NEOVASCULARIZATION; ACTIVATION; EXPRESSION; DEPOSITS;
   MICE
AB Amyloid-beta (A beta) is a hallmark component of age-related macular degeneration (AMD), which induces secretion of proinflammatory cytokines from retinal pigment epithelium (RPE). Previous studies have shown that p50/RelA (p65), a member of NF-kappa B family, is an essential pro-inflammatory transcription factor responding to A beta(1-40) stimulation, but few focused on the other two Rel transcription factor members - RelB and c-Rel - and their role in A beta(1-40)-mediated inflammation. It was reported that RelA, RelB and c-Rel are also implicated in various NF-kappa B-mediated inflammatory diseases. Therefore, we infer that A beta(1-40)-mediated inflammation targets not only the classical inflammation regulator, RelA, but also RelB and c-Rel. In this study, we demonstrate that intravitreally injected A beta(1-40) mice develop AMD-like pathologic changes, coupled with Rel protein (RelA, RelB and c-Rel) synthesis and nuclear translocation. To focus on the interaction mechanism of Rel proteins, we found that RelB and c-Rel formed a heterodimer with RelA in mice model. We also found that c-Rel silencing decreased the levels of A beta(1-40)-dependent RelA expression, indicating that RelB and c-Rel may interact with RelA as coactivator and c-Rel is required to activate the expression of RelA. Moreover, Rel protein silencing decreased the expression of distinct pro-inflammatory cytokines. Together, we demonstrate that besides RelA, RelB and c-Rel can also be activated by A beta(1-40), all of which mediate pro-inflammatory cytokine transcription and RPE damage. Our findings imply that RPE-mediated inflammation under the stimulation of A beta(1-40) is multi-targeted and RelA, RelB and c-Rel proteins may be the new targets of anti-inflammatory agents.
C1 [Sun, Junran; Huang, Peirong; Shen, Mengxi; She, Xiangjun; Feng, Yiji; Sun, Xiaodong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol,Shanghai Gen Hosp, Shanghai, Peoples R China.
   [Sun, Junran; Huang, Peirong; Shen, Mengxi; She, Xiangjun; Feng, Yiji; Sun, Xiaodong] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai 200080, Peoples R China.
   [Liang, Jian; Luo, Xueting; Sun, Xiaodong] Shanghai Key Lab Fundus Dis, Shanghai, Peoples R China.
   [Li, Jie] Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Dept Ophthalmol, Shanghai, Peoples R China.
   [Liu, Te] Yale Univ, Sch Med, Dept Pathol, 10 Amistad St, New Haven, CT 06520 USA.
   [Liu, Te] Shanghai Univ Tradit Chinese Med, Shanghai Geriatr Inst Chinese Med, Longhua Hosp, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai University of Traditional
   Chinese Medicine; Yale University; Shanghai University of Traditional
   Chinese Medicine
RP Liu, T (通讯作者)，Yale Univ, Sch Med, Dept Pathol, 10 Amistad St, New Haven, CT 06520 USA.; Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Dept Ophthalmol, Shanghai Gen Hosp,Shanghai Engn Ctr Visual Sci &, Shanghai Peoples Hosp 1,Sch Med,Shanghai Key Lab, 100 Hai Ning Rd, Shanghai 200080, Peoples R China.
EM te.liu@yale.edu; xdsun@sjtu.edu.cn
RI Shen, Mengxi/ABC-6941-2021; she, xiangjun/AAH-5955-2019
OI Shen, Mengxi/0000-0002-1336-1695
FU National Science Fund for Distinguished Young Scholars [81425006];
   Translational Medicine Innovation Fund of Shanghai Jiao Tong University
   School of Medicine [15ZH4005]; Science and Technology Commission of
   Shanghai Municipality [16dz2251500, 16140900800]; Program for Eastern
   Young Scholar at Shanghai Institutions of Higher Learning [QD2016003]
FX The study was supported by the National Science Fund for Distinguished
   Young Scholars (81425006), Translational Medicine Innovation Fund of
   Shanghai Jiao Tong University School of Medicine (15ZH4005), Science and
   Technology Commission of Shanghai Municipality (16dz2251500 and
   16140900800) and Program for Eastern Young Scholar at Shanghai
   Institutions of Higher Learning (QD2016003).
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NR 39
TC 20
Z9 20
U1 0
U2 10
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 OCT
PY 2017
VL 8
AR e3115
DI 10.1038/cddis.2017.502
PG 9
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FL2CV
UT WOS:000414022900044
PM 29022897
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, W
   Lee, SH
   Kim, SH
   Lee, JC
   Moon, SW
   Yu, JS
   Choi, S
AF Kim, Wansun
   Lee, Soo Hyun
   Kim, Sang Hun
   Lee, Jae-Chul
   Moon, Sang Woong
   Yu, Jae Su
   Choi, Samjin
TI Highly Reproducible Au-Decorated ZnO Nanorod Array on a Graphite Sensor
   for Classification of Human Aqueous Humors
SO ACS APPLIED MATERIALS & INTERFACES
LA English
DT Article
DE ZnO nanorod; graphite sheet; surface-enhanced Raman scattering (SERS);
   finite element method (FEM) computation; aqueous humor
ID ENHANCED RAMAN-SCATTERING; IONIC LAYER ABSORPTION; PAPER PLATFORM;
   ZINC-OXIDE; LOW-COST; SERS; GROWTH; NANOPARTICLES; SPECTROSCOPY;
   FABRICATION
AB Gold-decorated, vertically grown ZnO nanorods (NRs) on a flexible graphite sheet (Au/ZnONRs/G) were developed for surface-enhanced Raman scattering (SERS)-based biosensing to identify trace amounts of human aqueous humors. This Au/ZnONRs/G SERS-functionalized sensor was fabricated via two steps: hydrothermal synthesis-induced growth of ZnO NRs on graphite sheets for nanostructure fabrication, followed by e-beam evaporator-induced gold metallization on ZnONRs/G for SERS functionalization. The thickness of the Au layer and the height of the ZnO NRs for enhancing SERS performance were adjusted to maximize Raman intensity, and the optimized Au/ZnONRs/G nanostructures were verified by the electric finite element computational models to maximize the electric fields. The proposed Au/ZnONRs/G SERS sensor showed an enhancement factor of 2.3x10(6) via rhodamine 6G Raman probe and excellent reproducibility (relative standard deviation of <10%) via Raman mapping of a SERS active area with a square of 100 x 100 mu m(2). To evaluate the actual bioapplicability of point-of-care-testing (POCT) analysis in clinics, SERS data acquisition was performed with an integration time of 1 s from a 1 mu L analytic droplet of the sample. The performance of this Au/ZnONRs/G sensor was evaluated using human aqueous humors with cataract and two oxidative stress-induced eye diseases, age-related macular degeneration, and diabetic macular edema. These three eye diseases could be identified without any labeling or modification using the Au/ZnONRs/G SERS sensor and the computational algorithm incorporating a support vector machine and multivariate statistical prediction. Therefore, these findings indicate that our label-free, highly reproducible and flexible Au/ZnONRs/G SERS-functionalized sensor supported by a multivariate statistics-derived bioclassification method has great potential in POCT applications for identifying eye diseases.
C1 [Kim, Wansun; Choi, Samjin] Kyung Hee Univ, Grad Sch, Dept Med Engn, Seoul 02447, South Korea.
   [Lee, Soo Hyun; Kim, Sang Hun; Yu, Jae Su] Kyung Hee Univ, Dept Elect & Radio Engn, Yongin 17104, Gyeonggi Do, South Korea.
   [Lee, Jae-Chul; Choi, Samjin] Kyung Hee Univ, Dept Biomed Engn, Coll Med, Seoul 02447, South Korea.
   [Moon, Sang Woong] Kyung Hee Univ, Coll Med, Dept Ophthalmol, Seoul 05278, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University; Kyung
   Hee University
RP Choi, S (通讯作者)，Kyung Hee Univ, Grad Sch, Dept Med Engn, Seoul 02447, South Korea.; Yu, JS (通讯作者)，Kyung Hee Univ, Dept Elect & Radio Engn, Yongin 17104, Gyeonggi Do, South Korea.; Choi, S (通讯作者)，Kyung Hee Univ, Dept Biomed Engn, Coll Med, Seoul 02447, South Korea.; Moon, SW (通讯作者)，Kyung Hee Univ, Coll Med, Dept Ophthalmol, Seoul 05278, South Korea.
EM ophmoon@gmail.com; jsyu@khu.ac.kr; medchoi@khu.ac.kr
RI Yu, Jae Su/ABF-4158-2020
OI Yu, Jae Su/0000-0003-0258-7936; KIM, Wansun/0000-0001-9186-6448; Choi,
   Samjin/0000-0003-3498-0652; Lee, Soo Hyun/0000-0002-6690-741X
FU National Research Foundation of Korea (NRF) - Korean Ministry of
   Science, ICT and Future Planning [2015R1A5A1037656]; Korean Health
   Technology Research & Development Project by the Ministry of Health &
   Welfare, Republic of Korea [HI14C2241]
FX This research was supported by the Basic Science Research Program
   through the National Research Foundation of Korea (NRF) funded by the
   Korean Ministry of Science, ICT and Future Planning (2015R1A5A1037656),
   and by a grant from the Korean Health Technology Research & Development
   Project, by the Ministry of Health & Welfare, Republic of Korea
   (HI14C2241).
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NR 46
TC 40
Z9 40
U1 7
U2 146
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1944-8244
EI 1944-8252
J9 ACS APPL MATER INTER
JI ACS Appl. Mater. Interfaces
PD FEB 22
PY 2017
VL 9
IS 7
BP 5891
EP 5899
DI 10.1021/acsami.6b16130
PG 9
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science
GA EL7VQ
UT WOS:000394829800026
PM 28156092
DA 2022-11-30
ER

PT J
AU Choi, MH
   Ahn, J
   Park, DJ
   Lee, SM
   Kim, K
   Cho, DID
   Senok, SS
   Koo, KI
   Goo, YS
AF Choi, Myoung-Hwan
   Ahn, Jungryul
   Park, Dae Jin
   Lee, Sang Min
   Kim, Kwangsoo
   Cho, Dong-il Dan
   Senok, Solomon S.
   Koo, Kyo-in
   Goo, Yong Sook
TI Topographic prominence discriminator for the detection of short-latency
   spikes of retinal ganglion cells
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE short-latency spike; retinal ganglion cell; artifact subtraction
   algorithm; subtraction of artifacts by local polynomial approximation
   (SALPA); topographic prominence discrimination
ID STIMULUS ARTIFACT REMOVAL; MORPHOMETRIC ANALYSIS; RESPONSES;
   STIMULATION; ACTIVATION; PULSE
AB Objective. Direct stimulation of retinal ganglion cells in degenerate retinas by implanting epi-retinal prostheses is a recognized strategy for restoration of visual perception in patients with retinitis pigmentosa or age-related macular degeneration. Elucidating the best stimulusresponse paradigms in the laboratory using multielectrode arrays (MEA) is complicated by the fact that the short-latency spikes (within 10 ms) elicited by direct retinal ganglion cell (RGC) stimulation are obscured by the stimulus artifact which is generated by the electrical stimulator. Approach. We developed an artifact subtraction algorithm based on topographic prominence discrimination, wherein the duration of prominences within the stimulus artifact is used as a strategy for identifying the artifact for subtraction and clarifying the obfuscated spikes which are then quantified using standard thresholding. Main results. We found that the prominence discrimination based filters perform creditably in simulation conditions by successfully isolating randomly inserted spikes in the presence of simple and even complex residual artifacts. We also show that the algorithm successfully isolated short-latency spikes in an MEA-based recording from degenerate mouse retinas, where the amplitude and frequency characteristics of the stimulus artifact vary according to the distance of the recording electrode from the stimulating electrode. By ROC analysis of false positive and false negative first spike detection rates in a dataset of one hundred and eight RGCs from four retinal patches, we found that the performance of our algorithm is comparable to that of a generally- used artifact subtraction filter algorithm which uses a strategy of local polynomial approximation (SALPA). Significance. We conclude that the application of topographic prominence discrimination is a valid and useful method for subtraction of stimulation artifacts with variable amplitudes and shapes. We propose that our algorithm may be used as stand-alone or supplementary to other artifact subtraction algorithms like SALPA.
C1 [Choi, Myoung-Hwan; Koo, Kyo-in] Univ Ulsan, Dept Biomed Engn, Ulsan, South Korea.
   [Ahn, Jungryul; Park, Dae Jin; Goo, Yong Sook] Chungbuk Natl Univ, Dept Physiol, Sch Med, Cheongju, South Korea.
   [Lee, Sang Min] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea.
   [Kim, Kwangsoo] Hanbat Natl Univ, Dept Elect & Control Engn, Daejeon, South Korea.
   [Cho, Dong-il Dan] Seoul Natl Univ, Dept Elect & Comp Engn, Seoul, South Korea.
   [Senok, Solomon S.] Alfaisal Univ, Coll Med, Dept Physiol Sci, Riyadh, Saudi Arabia.
C3 University of Ulsan; Chungbuk National University; Kyung Hee University;
   Hanbat National University; Seoul National University (SNU); Alfaisal
   University
RP Koo, KI (通讯作者)，Univ Ulsan, Dept Biomed Engn, Ulsan, South Korea.; Goo, YS (通讯作者)，Chungbuk Natl Univ, Dept Physiol, Sch Med, Cheongju, South Korea.
EM kikoo@ulsan.ac.kr; ysgoo@chungbuk.ac.kr
RI Koo, Kyo-in/E-4611-2017
OI Koo, Kyo-in/0000-0003-4173-9218; Lee, Sangmin/0000-0002-4396-6118;
   Senok, Solomon/0000-0002-9041-5845; Cho, Dong-il/0000-0002-8040-5803
FU Korea government (Ministry of Education, Science and Technology, ICT &
   Future Planning) through National Research Foundation (NRF)
   [NRF-2013R1A1A3009574, 2015R1D1A1A01056903, NRF-2014R1A1A1038335];
   University accounting research fund of the Hanbat National University
FX This work was supported by the Korea government (Ministry of Education,
   Science and Technology, ICT & Future Planning) through National Research
   Foundation (NRF) grants (NRF-2013R1A1A3009574 and 2015R1D1A1A01056903 to
   YSG and NRF-2014R1A1A1038335 to KIK) and also partially supported by the
   University accounting research fund of the Hanbat National University to
   KSK.
CR Ahn KN, 2015, KOREAN J PHYSIOL PHA, V19, P167, DOI 10.4196/kjpp.2015.19.2.167
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   Davidson MA, 2011, COAST ENG, V58, P802, DOI 10.1016/j.coastaleng.2011.03.007
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NR 35
TC 6
Z9 6
U1 0
U2 3
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 FEB
PY 2017
VL 14
IS 1
AR 016017
DI 10.1088/1741-2552/aa5646
PG 11
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA EK5KT
UT WOS:000393966000001
PM 28045002
DA 2022-11-30
ER

PT J
AU Kwon, HJ
   Lee, SM
   Pak, KY
   Park, SW
   Lee, JE
   Byon, IS
AF Kwon, Han Jo
   Lee, Seung Min
   Pak, Kang Yeun
   Park, Sung Who
   Lee, Ji Eun
   Byon, Ik Soo
TI Gender Differences in the Relationship between Sex Hormone Deficiency
   and Soft Drusen
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; menopause; partial androgen deficiency
   of the aging male; sex hormone deficiency; soft drusen
ID AGE-RELATED MACULOPATHY; BLUE-MOUNTAINS-EYE; CARDIOVASCULAR
   RISK-FACTORS; LONG-TERM INCIDENCE; VITAMIN-D LEVELS; BEAVER DAM EYE;
   MACULAR DEGENERATION; POSTMENOPAUSAL WOMEN; LIPID-METABOLISM; PREVALENCE
AB Purpose: To investigate the association between sex hormone deficiency and soft drusen in women and men.Materials and Methods: We retrospectively reviewed the medical records and fundus photographs of subjects who underwent a health screening for additional examination of climacterium and age-related changes including sex hormone status. In women, sex hormone deficiency was defined as cessation of menstruation that had lasted for at least 12 months and follicular stimulating hormone (FSH) levels 25 mIU/mL; in men, it was defined as testosterone levels 3.5 ng/mL. The subjects were divided into two groupsthe soft drusen and control groupsbased on the presence of soft drusen in the fundus photographs. The total drusen area was measured using ImageJ software.Results: Of total 2036 subjects, 638 (271 women; 367 men) were included. Two hundred thirteen subjects (33.4%) had soft drusen (97/271 women, 116/367 men). In women, sex hormone deficiency was more common in the soft drusen group than in the control group (P < 0.001); this was not the case in men. Multivariate logistic regression analysis revealed that sex hormone deficiency was an independent risk factor for soft drusen in women (P < 0.001; odds ratio [OR] = 3.494), as was age (P < 0.001; OR = 1.092). A long post-menopausal period was a risk factor for large soft drusen ( 125 m). (P < 0.001; OR = 1.220). Age was significantly associated with total drusen area in both women (P = 0.022; = 0.406) and men (P = 0.015; = 0.246).Conclusions: Sex hormone deficiency and its duration were significantly associated with the development and progression of soft drusen in women but not in men. It may be necessary to assess and manage the sex hormone deficiency in women with age-related macular degeneration.
C1 [Kwon, Han Jo; Park, Sung Who; Lee, Ji Eun] Pusan Natl Univ Hosp, Dept Ophthalmol, Med Res Inst, Busan, South Korea.
   [Lee, Seung Min; Byon, Ik Soo] Pusan Natl Univ, Dept Ophthalmol, Res Inst Convergence Biomed Sci & Technol, Yangsan Hosp, Yangsan, South Korea.
   [Park, Sung Who; Lee, Ji Eun; Byon, Ik Soo] Pusan Natl Univ, Coll Med, Busan, South Korea.
   [Pak, Kang Yeun] Inje Univ, Dept Ophthalmol, Haeundae Paik Hosp, Busan, South Korea.
C3 Pusan National University; Pusan National University Hospital; Pusan
   National University; Pusan National University Hospital; Pusan National
   University; Inje University
RP Byon, IS (通讯作者)，Pusan Natl Univ, Yangsan Hosp, 20,Geumo Ro, Yangsan, South Korea.
EM isbyon@naver.com
OI Byon, Iksoo/0000-0002-2638-8192; Han Jo, Kwon/0000-0003-2973-9725
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NR 58
TC 3
Z9 3
U1 2
U2 26
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2017
VL 42
IS 11
BP 1527
EP 1536
DI 10.1080/02713683.2017.1337155
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FN3NV
UT WOS:000415906800017
PM 28910205
DA 2022-11-30
ER

PT J
AU Galvin, O
   Srivastava, A
   Carroll, O
   Kulkarni, R
   Dykes, S
   Vickers, S
   Dickinson, K
   Reynolds, AL
   Kilty, C
   Redmond, G
   Jones, R
   Cheetham, S
   Pandit, A
   Kennedy, BN
AF Galvin, Orla
   Srivastava, Akshay
   Carroll, Oliver
   Kulkarni, Rajiv
   Dykes, Steve
   Vickers, Steven
   Dickinson, Keith
   Reynolds, Alison L.
   Kilty, Claire
   Redmond, Gareth
   Jones, Rob
   Cheetham, Sharon
   Pandit, Abhay
   Kennedy, Breandan N.
TI A sustained release formulation of novel quininib-hyaluronan
   microneedles inhibits angiogenesis and retinal vascular permeability in
   vivo
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Blindness; Angiogenesis; Vascular permeability; Novel drug therapy
ID OXYGEN-INDUCED RETINOPATHY; MACULAR DEGENERATION; DIABETIC-RETINOPATHY;
   DRUG-DELIVERY; SUPRAMOLECULAR ORGANIZATION; CYSTEINYL LEUKOTRIENES;
   BARRIER BREAKDOWN; MOUSE MODEL; NANOPARTICLES; MICROSPHERES
AB Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5 mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4 months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4 months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (p < 0.0001) inhibited ocular developmental angiogenesis compared to control. Sustained amelioration of retinal vascular permeability (RVP) was demonstrated using a bespoke cysteinyl leukotriene induced rodent model. Quininib-HA microparticles significantly inhibited RVP in Brown Norway rats one month after administration compared to neat quininib control (p = 0.0071). In summary, quininib-HA microneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Galvin, Orla; Reynolds, Alison L.; Kilty, Claire; Kennedy, Breandan N.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland.
   [Srivastava, Akshay; Carroll, Oliver; Pandit, Abhay] Natl Univ Ireland Galway, Ctr Res Med Devices CURAM, Galway, Ireland.
   [Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Jones, Rob; Cheetham, Sharon] RenaSci Ltd, BioCity, Pennyfoot St, Nottingham NG1 1GF, England.
   [Redmond, Gareth] Univ Coll Dublin, UCD Sch Chem, Dublin 4, Ireland.
C3 University College Dublin; Ollscoil na Gaillimhe-University of Galway;
   Renasci Ltd; University College Dublin
RP Kennedy, BN (通讯作者)，Univ Coll Dublin, UCD Conway Inst F062, Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland.
EM brendan.kennedy@ucd.ie
RI kennedy, Breandan/H-5643-2019; Pandit, Abhay/B-6187-2008
OI kennedy, Breandan/0000-0001-7991-4689; Pandit,
   Abhay/0000-0002-6292-4933; Reynolds, Alison/0000-0002-3147-0094;
   Srivastava, Akshay/0000-0001-5048-9420
FU Science Foundation Ireland and Technology Innovation and Development
   Award [13/TIDA/B2678]; European Regional Development Fund [13/RC/2073];
   Marie Curie Industry-Academia Partnerships and Pathways (IAPP) grant
   [612218/3D-NET]
FX This work was supported by a Science Foundation Ireland and Technology
   Innovation and Development Award [Project Number: 13/TIDA/B2678], a
   European Regional Development Fund under Grant Number 13/RC/2073, and a
   Marie Curie Industry-Academia Partnerships and Pathways (IAPP) grant
   [Project Number: 612218/3D-NET].
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NR 75
TC 19
Z9 19
U1 3
U2 64
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD JUL 10
PY 2016
VL 233
BP 198
EP 207
DI 10.1016/j.jconrel.2016.04.004
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA DO8TJ
UT WOS:000378056400021
PM 27086168
DA 2022-11-30
ER

PT J
AU Al Gwairi, O
   Osman, N
   Getachew, R
   Zheng, WH
   Liang, XL
   Kamato, D
   Thach, L
   Little, PJ
AF Al Gwairi, Othman
   Osman, Narin
   Getachew, Robel
   Zheng, Wenhua
   Liang, X-L.
   Kamato, Danielle
   Thach, Lyna
   Little, Peter J.
TI Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan
   Hyperelongation in Retinal Choroidal Endothelial Cells
SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
LA English
DT Article
DE Age related macular degeneration; proteoglycans; growth factors; Bruch's
   membrane; VEGF; xyloside
ID VASCULAR SMOOTH-MUSCLE; LINKER REGION PHOSPHORYLATION; KINASE RECEPTOR
   TRANSACTIVATION; MEDIATED PROTEOGLYCAN SYNTHESIS; REDUCES LIPOPROTEIN
   BINDING; MACULAR DEGENERATION; THERAPEUTIC TARGETS; AKT PHOSPHORYLATION;
   BIGLYCAN SYNTHESIS; CHAIN ELONGATION
AB A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGF beta, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGF beta, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD.
C1 [Al Gwairi, Othman; Osman, Narin; Kamato, Danielle; Little, Peter J.] RMIT Univ, Sch Hlth & Biomed Sci, Bundoora, Vic 3083, Australia.
   [Osman, Narin] Monash Univ, Dept Immunol, Melbourne, Vic 3004, Australia.
   [Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Taipa, Macau, Peoples R China.
   [Zheng, Wenhua; Liang, X-L.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510006, Guangdong, Peoples R China.
   [Thach, Lyna; Little, Peter J.] Univ Queensland, Sch Pharm, Woolloongabba, Qld 4102, Australia.
C3 Royal Melbourne Institute of Technology (RMIT); Monash University;
   University of Macau; Sun Yat Sen University; University of Queensland
RP Little, PJ (通讯作者)，Univ Queensland, Pharm Australia Ctr Excellence, Sch Pharm, 20 Cornwall St, Woolloongabba, Qld 4102, Australia.
EM p.little@uq.edu.au
RI Kamato, Danielle/B-5894-2018; Little, Peter J./F-9865-2015
OI Kamato, Danielle/0000-0002-1089-2829; Little, Peter
   J./0000-0002-0335-3835
FU Saudi Arabia Ministry of Higher Education; Ministry of Foreign Experts
   of the Government of the People's Republic of China
FX OA was supported by the Saudi Arabia Ministry of Higher Education. We
   thank the Ministry of Foreign Experts of the Government of the People's
   Republic of China for support of PJL by way of a High End Professor
   (Education) Award through Zhongshan (Sun Yat-sen) University to Prof.
   Zheng.
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NR 56
TC 4
Z9 4
U1 0
U2 3
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1449-2288
J9 INT J BIOL SCI
JI Int. J. Biol. Sci.
PY 2016
VL 12
IS 9
BP 1041
EP 1051
DI 10.7150/ijbs.16134
PG 11
WC Biochemistry & Molecular Biology; Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics
GA DW7WA
UT WOS:000383862300001
PM 27570478
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Gamal, W
   Borooah, S
   Smith, S
   Underwood, I
   Srsen, V
   Chandran, S
   Bagnaninchi, PO
   Dhillon, B
AF Gamal, W.
   Borooah, S.
   Smith, S.
   Underwood, I.
   Srsen, V.
   Chandran, S.
   Bagnaninchi, P. O.
   Dhillon, B.
TI Real-time quantitative monitoring of hiPSC-based model of macular
   degeneration on Electric Cell-substrate Impedance Sensing
   microelectrodes
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Tissue-on-a-chip; Impedance sensing; Wound healing; Human induced
   pluripotent stem cells; Macular degeneration; Disease model
ID PLURIPOTENT STEM-CELLS; RETINAL DEGENERATION; GENE-EXPRESSION;
   MIGRATION; ASSAY; ADHESION; MUTATION; PROTEIN; RPE; DYNAMICS
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD.
   In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell-substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences (P < 0.01) in migration rates were found between case (8.6 +/- 0.46 mu m/h) and control cell lines (10.69 +/- 0.21 mu m/h). Quantitative data analysis suggested this was achieved due to lower cell-substrate adhesion in the control cell line. The ECIS cell-substrate adhesion parameter (alpha) was found to be 7.8 +/- 0.28 Omega(1/2) cm for the case cell line and 6.5 +/- 0.15 Omega(1/2) cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies. (C) 2015 The Authors. Published by Elsevier B.V.
C1 [Borooah, S.; Chandran, S.; Bagnaninchi, P. O.] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland.
   [Gamal, W.; Smith, S.; Srsen, V.] Univ Edinburgh, Inst Bioengn, Sch Engn, Edinburgh EH9 3DW, Midlothian, Scotland.
   [Underwood, I.] Univ Edinburgh, Sch Engn, Inst Integrated Micro & Nano Syst, Edinburgh EH9 3JF, Midlothian, Scotland.
   [Borooah, S.; Chandran, S.; Dhillon, B.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Borooah, S.; Chandran, S.] Univ Edinburgh, Euan MacDonald Ctr MND Res, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Borooah, S.; Chandran, S.] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Borooah, S.; Chandran, S.; Dhillon, B.] Univ Edinburgh, Anne Rowling Regenerat Neurol Clin, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Dhillon, B.] Univ Edinburgh, Sch Clin Sci, Edinburgh EH16 4SB, Midlothian, Scotland.
C3 University of Edinburgh; University of Edinburgh; University of
   Edinburgh; University of Edinburgh; University of Edinburgh; University
   of Edinburgh; University of Edinburgh; University of Edinburgh
RP Bagnaninchi, PO (通讯作者)，Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland.
EM Pierre.Bagnaninchi@ed.ac.uk
RI Smith, Stewart/C-1178-2008; Borooah, Shyamanga/AAM-6581-2021; UNDERWOOD,
   IAN/AAM-5039-2020
OI Smith, Stewart/0000-0002-7004-9219; Chandran,
   Siddharthan/0000-0001-6827-1593; bagnaninchi, pierre/0000-0001-5433-9630
FU College of Science and Engineering; University of Edinburgh; Eye
   Research Fund Edinburgh; Royal College of Surgeons of Edinburgh; Eyecare
   charity; Wellcome Trust STMTI scheme [R42141]; RCUK; Lothian Health
   Foundation
FX We thank Karen Burr and David Story for assistance with hiPSCs culture,
   Nina Rzechorzek and Elaine Cleary for technical assistance, Dr. Colin
   Campbell for providing immortalized RPE cell lines. We would also like
   to particularly express our gratitude to Dr. Ludovic Vallier and Dr.
   David Gamm for their guidance and advices. We would like to acknowledge
   financial support from the College of Science and Engineering, The
   University of Edinburgh, the Eye Research Fund Edinburgh and Lothian
   Health Foundation. Shyamanga Borooah acknowledges support from the Royal
   College of Surgeons of Edinburgh, Eyecare charity, Wellcome Trust STMTI
   scheme (grant number R42141). Pierre Bagnaninchi and Stewart Smith
   acknowledge support from RCUK fellowships.
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NR 50
TC 34
Z9 36
U1 0
U2 70
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
   OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD SEP 15
PY 2015
VL 71
BP 445
EP 455
DI 10.1016/j.bios.2015.04.079
PG 11
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
   Electrochemistry; Nanoscience & Nanotechnology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
   Electrochemistry; Science & Technology - Other Topics
GA CL0PZ
UT WOS:000356646000065
PM 25950942
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Brandstetter, C
   Mohr, LKM
   Latz, E
   Holz, FG
   Krohne, TU
AF Brandstetter, Carolina
   Mohr, Lena K. M.
   Latz, Eicke
   Holz, Frank G.
   Krohne, Tim U.
TI Light induces NLRP3 inflammasome activation in retinal pigment
   epithelial cells via lipofuscin-mediated photooxidative damage
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium;
   Interleukin-1 beta; Lysosomal membrane permeabilization; Lipid
   peroxidation
ID MACULAR DEGENERATION; SUNLIGHT EXPOSURE; ARPE-19 CELLS; RPE CELLS;
   DEATH; EYE; DESTABILIZATION; ACCUMULATION; MACROPHAGES; DRUSEN
AB Photooxidative damage and chronic innate immune activation have been implicated in retinal pigment epithelium (RPE) dysfunction, a process that underlies blinding diseases such as age-related macular degeneration (AMD). To identify a potential molecular link between these mechanisms, we investigated whether lipofuscin-mediated phototoxicity activates the NLRP3 inflammasome in RPE cells in vitro. We found that blue light irradiation (dominant wavelength 448 nm, irradiance 0.8 mW/cm(2), duration 6 h) of lipofuscin-loaded primary human RPE cells and ARPE-19 cells induced photooxidative damage, lysosomal membrane permeabilization (79.5 % of cells vs. 3.8 % in nonirradiated controls), and cytosolic leakage of lysosomal enzymes. This resulted in activation of the inflammasome with activation of caspase-1 and secretion of interleukin-1 beta (14.6 vs. 0.9 pg/ml in nonirradiated controls) and interleukin-18 (87.7 vs. 0.2 pg/ml in nonirradiated controls). Interleukin secretion was dependent on the activity of NLRP3, caspase-1, and lysosomal proteases cathepsin B and L. These results demonstrate that accumulation of lipofuscin-like material in vitro renders RPE cells susceptible to phototoxic destabilization of lysosomes, resulting in NLRP3 inflammasome activation and secretion of inflammatory cytokines. This new mechanism of inflammasome activation links photooxidative damage and innate immune activation in RPE pathology and may provide novel targets for therapeutic intervention in retinal diseases such as AMD.
   aEuro cent Visible light irradiation of lipofuscin-loaded RPE cells activates inflammasome.
   aEuro cent Inflammasome activation results from lysosomal permeabilization and enzyme leakage.
   aEuro cent Inflammasome activation induces secretion of inflammatory cytokines by RPE cells.
   aEuro cent Photooxidative damage by visible light as new mechanism of inflammasome activation.
   aEuro cent Novel link between hallmark pathogenetic features of retinal degenerative diseases.
C1 [Brandstetter, Carolina; Mohr, Lena K. M.; Holz, Frank G.; Krohne, Tim U.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Latz, Eicke] Univ Bonn, Inst Innate Immun, D-53127 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/D-1497-2013; Krohne, Tim/AAG-4412-2020; Latz,
   Eicke/H-3951-2014
OI Krohne, Tim/0000-0003-2280-925X; Latz, Eicke/0000-0003-1488-5666
FU German Research Foundation (DFG) [KR 2863/7-1]; Pro Retina Foundation;
   University of Bonn BONFOR Program; University of Bonn SciMed Program;
   Dr. Eberhard and Hilde Rudiger Foundation
FX The authors thank Claudine Strack, BTA, for the expert technical
   assistance. This study was supported by German Research Foundation (DFG)
   grant KR 2863/7-1, Pro Retina Foundation, University of Bonn BONFOR and
   SciMed Programs, and Dr. Eberhard and Hilde Rudiger Foundation (all to
   TUK). The paper was presented at the 2012 annual meeting of the
   Association of Research in Vision and Ophthalmology (ARVO) in Ft.
   Lauderdale, FL (Brandstetter C, Kopitz J, Latz E, Holz FG, Krohne TU.
   Effects of lipofuscin photoreactivity on RPE lysosomal membrane
   stability and activation of the NALP3 inflammasome. Invest Ophthalmol
   Vis Sci 2012; 53: E-Abstract 1673.).
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NR 33
TC 57
Z9 59
U1 3
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD AUG
PY 2015
VL 93
IS 8
BP 905
EP 916
DI 10.1007/s00109-015-1275-1
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA CN3LA
UT WOS:000358326500009
PM 25783493
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Aredo, B
   Li, T
   Chen, X
   Zhang, KY
   Wang, CXZ
   Gou, D
   Zhao, B
   He, YG
   Ufret-Vincenty, RL
AF Aredo, Bogale
   Li, Tao
   Chen, Xiao
   Zhang, Kaiyan
   Wang, Cynthia Xin-Zhao
   Gou, Darlene
   Zhao, Biren
   He, Yuguang
   Ufret-Vincenty, Rafael L.
TI A Chimeric Cfh Transgene Leads to Increased Retinal Oxidative Stress,
   Inflammation, and Accumulation of Activated Subretinal Microglia in Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE CFH; AMD; MDA; malondialdehyde; CD16; hydroquinone; oxidative stress;
   402H; inflammation; gene expression; microglia; macrophages; MG/M Phi;
   basal laminar deposits
ID SUB-RPE DEPOSITS; PIGMENTED EPITHELIAL-CELLS; FACTOR-H POLYMORPHISM;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; NLRP3 INFLAMMASOME;
   LIPID-PEROXIDATION; CHOROIDAL NEOVASCULARIZATION; PHOTORECEPTOR
   DEGENERATION; COMPLEMENT ACTIVATION
AB PURPOSE. Variants of complement factor H (Cfh) affecting short consensus repeats (SCRs) 6 to 8 increase the risk of age-related macular degeneration. Our aim was to explore the effect of expressing a Cfh variant on the in vivo susceptibility of the retina and RPE to oxidative stress and inflammation, using chimeric Cfh transgenic mice (chCfhTg).
   METHODS. The chCfhTg and age-matched C57BL/6J (B6) mice were subjected to oxidative stress by either normal aging, or by exposure to a combination of oral hydroquinone (0.8% HQ) and increased light. Eyes were collected for immunohistochemistry of RPE-choroid flat mounts and of retinal sections, ELISA, electron microscopy, and RPE/microglia gene expression analysis.
   RESULTS. Aging mice to 2 years led to an increased accumulation of basal laminar deposits, subretinal microglia/macrophages (MG/MU) staining for CD16 and for malondialdehyde (MDA), and MDA-modified proteins in the retina in chCfhTg compared to B6 mice. The chCfhTg mice maintained on HQ diet and increased light showed greater deposition of basal laminar deposits, more accumulation of fundus spots suggestive of MG/MU, and increased deposition of C3d in the sub-RPE space, compared to controls. In addition, chCfhTg mice demonstrated upregulation of NLRP3, IP-10, CD68, and TREM-2 in the RNA isolates from RPE/MG/MU.
   CONCLUSIONS. Expression of a Cfh transgene introducing a variant in SCRs 6 to 8 was sufficient to lead to increased retinal/RPE susceptibility to oxidative stress, a proinflammatory MG/MU phenotype, and a proinflammatory RPE/MG/MU gene expression profile in a transgenic mouse model. Our data suggest that altered interactions of Cfh with MDA-modified proteins may be relevant in explaining the effects of the Cfh variant.
C1 [Aredo, Bogale; Li, Tao; Chen, Xiao; Zhang, Kaiyan; Wang, Cynthia Xin-Zhao; Gou, Darlene; Zhao, Biren; He, Yuguang; Ufret-Vincenty, Rafael L.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
   [Li, Tao] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Ophthalmol, Wuhan 430074, Peoples R China.
C3 University of Texas System; University of Texas Southwestern Medical
   Center Dallas; Huazhong University of Science & Technology
RP Ufret-Vincenty, RL (通讯作者)，Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Rafael.Ufret-Vincenty@UTSouthwestern.edu
FU National Institutes of Health [1R01EY022652]; Visual Science Core Grant
   [EY020799]; UT Southwestern Medical Center; Research to Prevent
   Blindness; Hainan Provincial Social Development Special Fund for Science
   and Technology; David M. Crowley Foundation; NATIONAL EYE INSTITUTE
   [R01EY022652, P30EY020799] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grant 1R01EY022652, Visual
   Science Core Grant EY020799, a Disease Oriented Clinical Scholars grant
   from UT Southwestern Medical Center, an unrestricted grant from Research
   to Prevent Blindness, a grant from the Hainan Provincial Social
   Development Special Fund for Science and Technology, and a grant from
   the David M. Crowley Foundation.
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NR 134
TC 21
Z9 24
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2015
VL 56
IS 6
BP 3427
EP 3440
DI 10.1167/iovs.14-16089
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CM5PJ
UT WOS:000357740200001
PM 26030099
OA Green Published
DA 2022-11-30
ER

PT J
AU Coscas, F
   Coscas, G
   Lupidi, M
   Dirani, A
   Srour, M
   Semoun, O
   Francais, C
   Souied, EH
AF Coscas, Florence
   Coscas, Gabriel
   Lupidi, Marco
   Dirani, Ali
   Srour, Mayer
   Semoun, Oudy
   Francais, Catherine
   Souied, Eric H.
TI Restoration of Outer Retinal Layers After Aflibercept Therapy in
   Exudative AMD: Prognostic Value
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aflibercept; age-related macular degeneration (AMD); anti-VEGF
   treatment; choroidal neovascularization (CNV); ellipsoid zone swelling;
   external limiting membrane (ELM); optical coherence tomography (OCT);
   pigmented epithelial detachment (PED); subretinal hyper-reflective
   exudation (SHE)
ID OPTICAL COHERENCE TOMOGRAPHY; EXTERNAL LIMITING MEMBRANE; VISUAL-ACUITY;
   FOVEAL MICROSTRUCTURE; MACULAR DEGENERATION; RANIBIZUMAB; ASSOCIATION;
   INJECTION
AB PURPOSE. To evaluate the outer retinal layer (ellipsoid zone [EZ] and external limiting membrane [ELM]) changes following intravitreal aflibercept injections in eyes with treatment-naive exudative age-related macular degeneration (eAMD) and to correlate these changes with fluid response and visual improvement.
   METHODS. A retrospective case series of 50 treatment-naive eAMD eyes followed-up for 18 months. All patients underwent regular comprehensive ophthalmic examinations. The presence of EZ disruption, ELM disruption, EZ swelling, subretinal hyper-reflective exudation (SHE), central macular thickness (CMT), cystoid spaces, subretinal fluid, and pigmented epithelium detachment were evaluated by two different retinal specialists at baseline and final visits, and correlated with best corrected visual acuity (BCVA) improvement.
   RESULTS. At 18 months, BCVA, EZ disruption, ELM disruption, EZ swelling and SHE improved significantly (P = 0.001) at 18 months. Improvement of BCVA showed a statistically significant correlation with ELM restoration (P = 0.018), but not with EZ restoration (P = 0.581). Swelling of the EZ decreased from 72% of the cases at baseline to 30% in 18 months while SHE decreased from 52% to 6% in 18 months (P = 0.001). We observed a statistically significant (P = 0.001) reduction between the baseline and final value of CMT.
   CONCLUSIONS. Aflibercept is safe and effective in treating exudative AMD with the restoration of the outer retinal layers. Restoration of the EZ is not statistically correlated with the final BCVA, even though persistent EZ changes could be associated with irreversible decrease in vision. On the contrary, the final status of the ELM is directly correlated with final BCVA. Also, baseline changes in outer retinal layers, especially the ELM, appear to predict photoreceptor restoration and final BCVA, and must be comprehensively analyzed to enable and determine a future prognosis.
C1 [Coscas, Florence; Coscas, Gabriel; Lupidi, Marco; Srour, Mayer; Semoun, Oudy; Souied, Eric H.] Univ Paris Est, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Coscas, Florence; Coscas, Gabriel; Francais, Catherine] Ctr Odeon, Paris, France.
   [Lupidi, Marco] Univ Perugia, S Maria della Misericordia Hosp, Sect Ophthalmol, Dept Biomed & Surg Sci, Perugia, Italy.
   [Dirani, Ali] St Josephs Univ, Fac Med, Beirut, Lebanon.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; Hospital
   Santa Maria della Misericordia; University of Perugia; Saint Joseph
   University Beirut
RP Coscas, F (通讯作者)，Ctr Hosp Intercommunal Creteil, 40 Ave Verdun, F-94000 Creteil, France.
EM gabriel.coscas@gmail.com
OI Lupidi, Marco/0000-0002-6817-2488
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NR 36
TC 27
Z9 28
U1 1
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2015
VL 56
IS 6
BP 4129
EP 4134
DI 10.1167/iovs.15-16735
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CM5PJ
UT WOS:000357740200080
PM 26114491
DA 2022-11-30
ER

PT J
AU Jindal, V
AF Jindal, Vishal
TI Interconnection Between Brain and Retinal Neurodegenerations
SO MOLECULAR NEUROBIOLOGY
LA English
DT Review
DE Age-related macular degeneration; Glaucoma; Alzheimer's disease; Amyloid
ID LATERAL GENICULATE-NUCLEUS; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E
   GENE; ALZHEIMERS-DISEASE; MACULAR DEGENERATION; COMPLEMENT ACTIVATION;
   PARVOCELLULAR LAYERS; PUPILLARY RESPONSE; VISUAL DYSFUNCTION; JAPANESE
   PATIENTS
AB The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of A beta-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.
C1 GMCH, Chandigarh, India.
RP Jindal, V (通讯作者)，GMCH, Chandigarh, India.
EM vishaljindal87@gmail.com
RI Jindal, Vishal/AAG-7529-2021
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TC 14
Z9 14
U1 0
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD JUN
PY 2015
VL 51
IS 3
BP 885
EP 892
DI 10.1007/s12035-014-8733-6
PG 8
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA CI3CM
UT WOS:000354625100005
PM 24826919
DA 2022-11-30
ER

PT J
AU Cantley, JL
   Hanlon, J
   Chell, E
   Lee, C
   Smith, WC
   Bolch, WE
AF Cantley, Justin L.
   Hanlon, Justin
   Chell, Erik
   Lee, Choonsik
   Smith, W. Clay
   Bolch, Wesley E.
TI Influence of eye size and beam entry angle on dose to non-targeted
   tissues of the eye during stereotactic x-ray radiosurgery of AMD
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; PLAQUE RADIATION-THERAPY;
   MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION; RADIOTHERAPY;
   BRACHYTHERAPY; BEVACIZUMAB; SAFETY; RANIBIZUMAB; IRRADIATION
AB Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay (R) Radiotherapy System, developed by Oraya (R) Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye-total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body-all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18 degrees to 34 degrees in 2 degrees increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26 degrees or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.
C1 [Cantley, Justin L.; Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
   [Hanlon, Justin; Chell, Erik] Oraya Therapeut Inc, Newark, CA 94560 USA.
   [Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Smith, W. Clay] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida; National
   Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI);
   State University System of Florida; University of Florida
RP Bolch, WE (通讯作者)，Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
EM jlcantley@gmail.com; wbolch@ufl.edu
RI Lee, Choonsik/C-9023-2015; Smith, W. Clay/AAQ-1589-2021
OI Lee, Choonsik/0000-0003-4289-9870; 
FU Oraya Therapeutics, Inc. [Oraya-002-2010]; NATIONAL CANCER INSTITUTE
   [ZIACP010222] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [P30EY021721, R01EY014864] Funding Source: NIH RePORTER
FX This work was supported by grant Oraya-002-2010 from Oraya Therapeutics,
   Inc. to the University of Florida.
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NR 32
TC 9
Z9 11
U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD OCT 7
PY 2013
VL 58
IS 19
BP 6887
EP 6896
DI 10.1088/0031-9155/58/19/6887
PG 10
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 220HN
UT WOS:000324573600017
PM 24025704
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Longhin, E
   Convento, E
   Pilotto, E
   Bonin, G
   Vujosevic, S
   Kotsafti, O
   Midena, E
AF Longhin, Evelyn
   Convento, Enrica
   Pilotto, Elisabetta
   Bonin, Giorgia
   Vujosevic, Stela
   Kotsafti, Olympia
   Midena, Edoardo
TI Static and dynamic retinal fixation stability in microperimetry
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID DIABETIC MACULAR EDEMA; SCANNING LASER OPHTHALMOSCOPE; OPTICAL COHERENCE
   TOMOGRAPHY; LOW-VISION REHABILITATION; TERM-FOLLOW-UP; FUNDUS
   AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; VISUAL-ACUITY; AGE; DEGENERATION
AB Objective: To compare static (during a pure fixation task) versus dynamic (during microperimetry) quantification of fixation stability using microperimetry in normal and pathologic eyes, by means of 2 available (clinical and bivariate contour ellipse area [BCEA]) classification methods.
   Design: Prospective comparative observational study.
   Participants: One hundred and forty-nine eyes (110 patients) with different macular diseases and 171 normal eyes (109 subjects).
   Methods: In all eyes studied, fixation stability was acquired during an isolated fixation task (static fixation) and during microperimetry (dynamic fixation). All fixation data were analyzed and compared by means of a clinical classification and by means of BCEA quantification.
   Results: Pathologic eyes were classified as follows: 41 eyes with diabetic macular edema (DME group), 13 eyes with vitreoretinal interface disease, 60 eyes with age-related macular degeneration (AMD group), and 35 eyes with primary open-angle glaucoma. Fixation stability was not uniform among groups according to clinical classification in both static and dynamic modalities (p < 0.0001). AMD group showed larger BCEA areas compared with all other groups (p < 0.0001). All pathologic groups showed more unstable fixation in dynamic fashion according to both clinical and BCEA methods (p < 0.0001). The variation of fixation stability of control group in dynamic task was highlighted only by BCEA analysis (p < 0.0001). A deterioration of retinal fixation according to clinical method matches a significant increase in BCEA areas (p < 0.0001).
   Conclusions: The detection of clinical fixation stability changes improves when acquired in the dynamic modality. BCEA analysis provides more accurate evaluation of fixation stability and may detect minimal quantitative changes of the fixation area. However, a standard clinical classification can also detect changes in fixation stability in pathologic eyes. Both methods are useful tools in the evaluation of fixation stability.
C1 [Longhin, Evelyn; Vujosevic, Stela; Kotsafti, Olympia; Midena, Edoardo] IRCCS, GB Bietti Fdn, Rome, Italy.
   [Convento, Enrica; Pilotto, Elisabetta; Bonin, Giorgia; Midena, Edoardo] Univ Padua, Dept Ophthalmol, I-35128 Padua, Italy.
C3 IRCCS - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in
   Oftalmologia; University of Padua
RP Midena, E (通讯作者)，Univ Padua, Dept Ophthalmol, Via Giustiniani 2, I-35128 Padua, Italy.
EM edoardo.midena@unipd.it
RI Vujosevic, Stela/AAI-4874-2020; Midena, Edoardo/AAB-6010-2020
OI Vujosevic, Stela/0000-0001-6773-9967
CR Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
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   Midena E, 2012, INT OPHTHALMOL
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   Reinhard J, 2007, VISION RES, V47, P2076, DOI 10.1016/j.visres.2007.04.012
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NR 37
TC 31
Z9 31
U1 0
U2 6
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 375
EP 380
DI 10.1016/j.jcjo.2013.05.021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AA5OM
UT WOS:000331149300021
PM 24093183
DA 2022-11-30
ER

PT J
AU Kwon, OW
   Lee, FL
   Chung, H
   Lai, CC
   Sheu, SJ
   Yoon, YH
AF Kwon, Oh-Woong
   Lee, Fenq Lih
   Chung, Hum
   Lai, Chi-Chun
   Sheu, Shwu-Jiuan
   Yoon, Young-Hee
CA EXTEND III Study Grp
TI EXTEND III: Efficacy and safety of ranibizumab in South Korean and
   Taiwanese patients with subfoveal CNV secondary to AMD
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Choroidal neovascularization; Age-related macular degeneration;
   Best-corrected visual acuity; Intravitreal ranibizumab; Fluorescein
   leakage
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; MACULAR DEGENERATION;
   VERTEPORFIN; THERAPY; EYE; POPULATION; FRAGMENT; ANCHOR
AB The purpose of this study was to investigate the efficacy and safety of intravitreal ranibizumab 0.5 mg in South Korean and Taiwanese patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
   This was a 12-month, open-label, single-arm, multi-center, phase III study. Ninety-five patients (Taiwanese: 51; South Korean: 44) were included in the study. Key outcome measures assessed included: mean change in best-corrected visual acuity (BCVA) from baseline to months 4 (primary endpoint) and 12 (secondary endpoint); other secondary endpoints comprising categorized mean change in BCVA from baseline at month 4 and month 12, mean change in BCVA from baseline at month 4 and month 12 per baseline characteristics; and incidence of ocular and non-ocular adverse events and serious adverse events (SAEs) at month 12.
   The mean BCVA change improved significantly (p < 0.0001) from baseline to both month 4 (+9.3 letters) and month 12 (+10.1 letters). At month 12, the proportion of patients who gained a parts per thousand yen5, 10, or 15 letters from baseline was 75.8%, 54.7%, and 32.6% respectively. Total and CNV lesion area significantly decreased from baseline (p < 0.0001). About 57% of patients showed complete absence of fluorescein leakage at month 12. Mean change from baseline visual acuity scores also increased significantly over time for all subgroups. At month 12, ocular SAEs occurred in 2.1% of patients (out of which one patient [1.1%] experienced endophthalmitis) and 16.8% of patients experienced non-ocular SAEs. There were no deaths reported during the study.
   Consistent with previous studies in Caucasian and Japanese populations, EXTEND III confirms that monthly intravitreal injections of ranibizumab 0.5 mg administered over 12 months is effective and well-tolerated in South Korean and Taiwanese patients with subfoveal CNV secondary to AMD.
C1 [Lee, Fenq Lih] Taipei Vet Gen Hosp 201, Taipei 112, Taiwan.
   [Kwon, Oh-Woong] Nune Eye Hosp, Retina Ctr, Seoul, South Korea.
   [Chung, Hum] Seoul Natl Univ Hosp, Dept Ophthalmol, Seoul 110744, South Korea.
   [Lai, Chi-Chun] Chang Gung Mem Hosp, Lin Ko, Taiwan.
   [Sheu, Shwu-Jiuan] Natl Yang Ming Univ, Taipei 112, Taiwan.
   [Sheu, Shwu-Jiuan] Kaohsiung Vet Gen Hosp, Kaohsiung, Taiwan.
   [Yoon, Young-Hee] Univ Ulsan, Dept Ophthalmol, Asan Med Ctr, Coll Med, Seoul, South Korea.
C3 Taipei Veterans General Hospital; Seoul National University (SNU); Seoul
   National University Hospital; Chang Gung Memorial Hospital; National
   Yang Ming Chiao Tung University; Kaohsiung Veterans General Hospital;
   University of Ulsan; Asan Medical Center
RP Lee, FL (通讯作者)，Taipei Vet Gen Hosp 201, Sect 2,Shih Pai Rd, Taipei 112, Taiwan.
EM fllee@vghtpe.gov.tw
RI Chung, Hum/J-5657-2012
OI Lai, Chi-Chun/0000-0001-9547-7212; YANG, CHUNG-MAY/0000-0003-4082-420X
FU Novartis Pharma AG, Switzerland
FX Novartis Pharma AG, Switzerland sponsored the study and was involved in
   the study conception and design, protocol writing, study drug provision,
   study coordination, data collection, data analysis, and interpretation.
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   World Health Organization (WHO), 2011, MAGN CAUS VIS IMP FA
NR 17
TC 9
Z9 10
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2012
VL 250
IS 10
BP 1467
EP 1476
DI 10.1007/s00417-012-1970-3
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 013ZR
UT WOS:000309345300009
PM 22382503
DA 2022-11-30
ER

PT J
AU Olusanya, B
   Onoja, G
   Ibraheem, W
   Bekibele, C
AF Olusanya, Bolutife
   Onoja, Godfrey
   Ibraheem, Waheed
   Bekibele, Charles
TI Profile of patients presenting at a low vision clinic in a developing
   country
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Low vision; Patient characteristics; Developing countries
ID FUNCTIONAL LOW-VISION; NATIONAL BLINDNESS; VISUAL IMPAIRMENT;
   RISK-FACTORS; HAND MOTION; PREVALENCE; SERVICES; NIGERIA; FINGERS
AB Background: Low vision is an important public health problem; however, very few low vision clinics are available to address the needs of low vision patients in most developing countries. The purpose of this study was to describe the characteristics of patients attending the low vision clinic of a Nigerian tertiary hospital.
   Methods: This was a prospective cross sectional study of all new patients seen at the low vision clinic over a 36 month period. Patients were administered with a structured questionnaire, and were examined and tested with low vision devices by the attending low vision specialist. Information on the demographic and clinical characteristics of the patients was recorded.
   Results: A total of 193 new patients seen during the period were studied. The mean age was 41.4 years, and their ages ranged between 6 and 90 years with a male to female ratio of 1.9:1. Majority (58%) were aged below 50 years, 23.3% were children (<= 15 years), while 21.8% were elderly patients (>= 65 years). The commonest cause of low vision was retinitis pigmentosa (16.6%); 14.5% had age related macular degeneration (ARMD); 9.8% had albinism; while only 1% had diabetic retinopathy. ARMD (45.2%) was the commonest cause in the elderly patients, while albinism (24.4%) and optic atrophy (24.4%) were the commonest in children.
   Conclusion: The demographic and clinical characteristics of low vision patients seen in this clinic are similar to that of patients in other developing countries, but different from those in developed countries. Elderly patients and females may be under-utilising low vision services. There is a need for further research into the determinants of low vision service utilisation in developing countries. This would further aid the planning and delivery of services to low vision patients in these countries.
C1 [Olusanya, Bolutife; Onoja, Godfrey; Ibraheem, Waheed; Bekibele, Charles] Univ Coll Hosp, Dept Ophthalmol, Ibadan, Nigeria.
C3 University of Ibadan; University College Hospital, Ibadan
RP Olusanya, B (通讯作者)，Univ Coll Hosp, Dept Ophthalmol, Ibadan, Nigeria.
EM bolutifeo@yahoo.com
RI Olusanya, Bolutife/AHD-3340-2022; Bekibele, Charles/AAF-3012-2020;
   Bekibele, Charles/W-1177-2019
OI Olusanya, Bolutife/0000-0002-8027-2844; Ibraheem,
   Waheed/0000-0001-8780-1748
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NR 24
TC 28
Z9 30
U1 0
U2 1
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUL 30
PY 2012
VL 12
AR 31
DI 10.1186/1471-2415-12-31
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 018UE
UT WOS:000309687900001
PM 22846399
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zeimer, M
   Dietzel, M
   Hense, HW
   Heimes, B
   Austermann, U
   Pauleikhoff, D
AF Zeimer, Meike
   Dietzel, Martha
   Hense, Hans Werner
   Heimes, Britta
   Austermann, Ulrike
   Pauleikhoff, Daniel
TI Profiles of Macular Pigment Optical Density and Their Changes Following
   Supplemental Lutein and Zeaxanthin: New Results from the LUNA Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; HUMAN RETINA; SPATIAL-DISTRIBUTION; RAMAN
   MEASUREMENT; PRIMATE RETINAS; IN-VIVO; CAROTENOIDS; AUTOFLUORESCENCE;
   DEGENERATION; POPULATION
AB PURPOSE. Based on latest analyses disclosing an inverse association between ring-like structures in macular pigment (MP) spatial profile and age-related macular degeneration, we performed additional analyses of MP measurements obtained in participants of our earlier lutein nutrition effects measured by autoflourescence (LUNA) study to disclose if oral lutein (L) and zeaxanthin (Z) can attenuate, amplify, or generate a ring structure.
   METHODS. A total of 97 subjects attended the last follow-up visit 3 months after discontinuation of a 6-month trial of 12 mg L and 1 mg Z supplementation. Of the subjects, 11 eyes had a secondary peak (ring-like structure) and 8 had an implied pericentral plateau/shoulder on the slope of MP density profile (intermediate distribution).
   RESULTS. L and Z intake led to a general shift toward higher MP values in eyes without ring structure. The difference between mean optical density of retinal MP (Diff MPOD) at last follow-up and baseline was +0.16 density units (D. U.) at 0 degrees eccentricity. Increments at 0.25 degrees, 0.5 degrees, 1 degrees, and 2 degrees (all P < 0.0001) decayed exponentially with higher eccentricity. MPOD showed comparatively slight central changes in eyes with ring and intermediate distribution (diff_MPOD at 0 degrees +0.03 and +0.09), and increased at minimum (+0.06, P = 0.01) and maximum (+0.07, P=0.02) of the ring, and at inner (+0.07, P=0.04) and outer (+0.09, P=0.01) radius of the pericentral "shoulder.''
   CONCLUSIONS. Ring structures were neither attenuated nor generated de novo following supplementation. Individuals with second peak/implied plateau in the slope of the profile appear to have the most effective retinal stabilization of L and Z located at a pericentral rather than the central location. (Invest Ophthalmol Vis Sci. 2012;53:4852-4859) DOI:10.1167/iovs.12-9713
C1 [Zeimer, Meike; Dietzel, Martha; Heimes, Britta; Austermann, Ulrike; Pauleikhoff, Daniel] St Franziskus Hosp, Inst Ophthalmol, Munster, Germany.
   [Hense, Hans Werner] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
C3 St. Franziskus-Hospital; University of Munster
RP Zeimer, M (通讯作者)，Hohenzollernring 74, D-48145 Munster, Germany.
EM meiketri@aol.com
OI Heimes-Bussmann, Britta/0000-0003-3898-1679
FU Bausch and Lomb
FX Supported by Bausch and Lomb.
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NR 37
TC 20
Z9 22
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2012
VL 53
IS 8
BP 4852
EP 4859
DI 10.1167/iovs.12-9713
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400062
PM 22743321
DA 2022-11-30
ER

PT J
AU Mujat, M
   Ferguson, RD
   Patel, AH
   Iftimia, N
   Lue, N
   Hammer, DX
AF Mujat, Mircea
   Ferguson, R. Daniel
   Patel, Ankit H.
   Iftimia, Nicusor
   Lue, Niyom
   Hammer, Daniel X.
TI High resolution multimodal clinical ophthalmic imaging system
SO OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SCANNING LASER OPHTHALMOSCOPE;
   ADAPTIVE-OPTICS; CONE PHOTORECEPTORS; HUMAN RETINA; 1050 NM; PENETRATION
AB We developed a multimodal adaptive optics (AO) retinal imager which is the first to combine high performance AO-corrected scanning laser ophthalmoscopy (SLO) and swept source Fourier domain optical coherence tomography (SSOCT) imaging modes in a single compact clinical prototype platform. Such systems are becoming ever more essential to vision research and are expected to prove their clinical value for diagnosis of retinal diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinitis pigmentosa. The SSOCT channel operates at a wavelength of 1 mu m for increased penetration and visualization of the choriocapillaris and choroid, sites of major disease activity for DR and wet AMD. This AO system is designed for use in clinical populations; a dual deformable mirror (DM) configuration allows simultaneous low-and high-order aberration correction over a large range of refractions and ocular media quality. The system also includes a wide field (33 deg.) line scanning ophthalmoscope (LSO) for initial screening, target identification, and global orientation, an integrated retinal tracker (RT) to stabilize the SLO, OCT, and LSO imaging fields in the presence of lateral eye motion, and a high-resolution LCD-based fixation target for presentation of visual cues. The system was tested in human subjects without retinal disease for performance optimization and validation. We were able to resolve and quantify cone photoreceptors across the macula to within similar to 0.5 deg (similar to 100-150 mu m) of the fovea, image and delineate ten retinal layers, and penetrate to resolve features deep into the choroid. The prototype presented here is the first of a new class of powerful flexible imaging platforms that will provide clinicians and researchers with high-resolution, high performance adaptive optics imaging to help guide therapies, develop new drugs, and improve patient outcomes. (C) 2010 Optical Society of America
C1 [Mujat, Mircea; Ferguson, R. Daniel; Patel, Ankit H.; Iftimia, Nicusor; Lue, Niyom; Hammer, Daniel X.] Phys Sci Inc, Andover, MA 01810 USA.
C3 Physical Sciences Inc.
RP Mujat, M (通讯作者)，Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA.
EM mujat@psicorp.com
RI Mujat, Mircea/AAY-7608-2020
FU NIH [EY018986]; NATIONAL EYE INSTITUTE [R43EY018986, R44EY018986]
   Funding Source: NIH RePORTER
FX This work was supported by NIH grant EY018986. We thank Stephen Burns,
   James Fujimoto, Joel Schuman, Gadi Wollstein, and Larry Kagemann for
   advice and assistance.
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NR 38
TC 51
Z9 57
U1 0
U2 11
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD MAY 24
PY 2010
VL 18
IS 11
BP 11607
EP 11621
DI 10.1364/OE.18.011607
PG 15
WC Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Optics
GA 607OB
UT WOS:000278512300075
PM 20589021
OA Green Accepted, Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Lamartina, S
   Cimino, M
   Roscilli, G
   Dammassa, E
   Lazzaro, D
   Rota, R
   Ciliberto, G
   Toniatti, C
AF Lamartina, Stefania
   Cimino, Monica
   Roscilli, Giuseppe
   Dammassa, Ernesta
   Lazzaro, Domenico
   Rota, Rossella
   Ciliberto, Gennaro
   Toniatti, Carlo
TI Helper-dependent adenovirus for the gene therapy of proliferative
   retinopathies: stable gene transfer, regulated gene expression and
   therapeutic efficacy
SO JOURNAL OF GENE MEDICINE
LA English
DT Article
DE helper-dependent adenovirus; retinopathy; sFlt-1; transcriptional
   regulation
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; TERM TRANSGENE
   EXPRESSION; OCULAR NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION;
   IMMUNE-RESPONSE; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   NEUROTROPHIC FACTOR; NONHUMAN-PRIMATES
AB Background: Ocular neovascular disorders, such as diabetic retinopathy and age-related macular degeneration, are the principal causes of blindness in developed countries. Current treatments are of limited efficacy, whereas a therapy based on intraocular gene transfer of angiostatic factors represents a promising alternative. For the first time we have explored the potential of helper-dependent adenovirus (HD-Ad), the last generation of Ad vectors, in the therapy of retinal neovascularization.
   Methods: We first analyzed efficiency and stability of intraretinal gene transfer following intravitreous injection in mice. A HD-Ad vector expressing green fluorescent protein (GFP) under the control of the cytomegalovirus (CMV) promoter (HD-Ad/GFP) was compared with a first-generation (EI/E3-deleted) Ad vector carrying an identical GFP expression cassette (FG-Ad/GFP). We also constructed HD-Ad vectors expressing a soluble form of the VEGF receptor (sFlt-1) in a constitutive (HD-Ad/sFlt-1) or doxycycline (dox)inducible (HD-Ad/S-M2/sFlt-I) manner and tested their therapeutic efficacy upon intravitreous delivery in a rat model of oxygen-induced retinopathy (0111).
   Results: HD-Ad/GFP promoted long-lasting (up to I year) transgene expression in retinal Milller cells, in marked contrast with the short-term expression observed with FG-Ad/GFP. Intravitreous injection of HD-Ad vectors expressing sFlt-1 resulted in detectable levels of sFlt-1 and inhibited retinal neovascularization by more than 60% in a rat model of OIR. Notably, the therapeutic efficacy of the inducible vector HD-Ad/S-M2/sFlt-1 was strictly dox-dependent.
   Conclusions: HD-Ad vectors enable stable gene transfer and regulated expression of angiostatic factors following intravitreous injection and thus are attractive vehicles for the gene therapy of neovascular diseases of the retina. Copyright (C) 2007 John Wiley & Sons, Ltd.
C1 IRBM, Ist Ric Biol Mol P Angeletti, I-00040 Pomezia, Italy.
   CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
   Childrens Hosp Bambino Gesu, Lab Endothelial Cells, I-00165 Rome, Italy.
C3 Merck & Company; CEINGE Biotecnologie Avanzate; IRCCS Bambino Gesu
RP Toniatti, C (通讯作者)，IRBM, Ist Ric Biol Mol P Angeletti, Via Pontina Km 30600, I-00040 Pomezia, Italy.
EM carlo_toniatti@merck.com
RI Ciliberto, Gennaro/J-4131-2017; Rota, Rossella/AAB-2497-2019
OI Ciliberto, Gennaro/0000-0003-2851-8605; Rota,
   Rossella/0000-0002-9408-7711; Toniatti, Carlo/0000-0001-9493-344X
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NR 71
TC 39
Z9 41
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1099-498X
EI 1521-2254
J9 J GENE MED
JI J. Gene. Med.
PD OCT
PY 2007
VL 9
IS 10
BP 862
EP 874
DI 10.1002/jgm.1083
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 224NC
UT WOS:000250452700004
PM 17685494
DA 2022-11-30
ER

PT J
AU Bora, PS
   Kaliappan, S
   Xu, Q
   Kumar, S
   Wang, YL
   Kaplan, HJ
   Bora, NS
AF Bora, PS
   Kaliappan, S
   Xu, Q
   Kumar, S
   Wang, YL
   Kaplan, HJ
   Bora, NS
TI Alcohol linked to enhanced angiogenesis in rat model of choroidal
   neovascularization
SO FEBS JOURNAL
LA English
DT Article
DE adiponectin; angiogenesis; choroids; macular degeneration;
   neovascularization
ID ACID ETHYL-ESTER; HEPATOCYTE GROWTH-FACTOR; AGE-RELATED MACULOPATHY;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; PURIFICATION; EXPRESSION;
   DEHYDROGENASE; MACROPHAGES; METABOLISM
AB One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.
C1 Univ Arkansas Med Sci, Jones Eye Inst, Dept Ophthalmol, Little Rock, AR 72205 USA.
   Univ Arkansas Med Sci, Jones Eye Inst, Dept Ophthalmol & Visual Sci, Little Rock, AR 72205 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences;
   University of Arkansas System; University of Arkansas Medical Sciences
RP Bora, PS (通讯作者)，Univ Arkansas Med Sci, Jones Eye Inst, Dept Ophthalmol, 4301 W Markham 523, Little Rock, AR 72205 USA.
EM pbora@uams.edu
OI Bora, Puran/0000-0003-4781-1217
FU NEI NIH HHS [1R24EY015636-01] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R24EY015636] Funding Source: NIH RePORTER
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NR 52
TC 33
Z9 37
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD APR
PY 2006
VL 273
IS 7
BP 1403
EP 1414
DI 10.1111/j.1742-4658.2006.05163.x
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 040CU
UT WOS:000237357400006
PM 16689928
DA 2022-11-30
ER

PT J
AU Flieger, J
   Sniegocki, T
   Dolar-Szczasny, J
   Zaluska, W
   Rejdak, R
AF Flieger, Jolanta
   Sniegocki, Tomasz
   Dolar-Szczasny, Joanna
   Zaluska, Wojciech
   Rejdak, Robert
TI The First Evidence on the Occurrence of Bisphenol Analogues in the
   Aqueous Humor of Patients Undergoing Cataract Surgery
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE bisphenols; bisphenol A; bisphenol F; bisphenol A isomers; aqueous
   humor; ultrahigh-pressure liquid chromatography (UHPLC)
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; HUMAN
   BLOOD-SERUM; SOFT DRINKS; HUMAN URINE; A EXPOSURE; ENVIRONMENTAL
   PHENOLS; PREFRONTAL CORTEX; TRACE LEVELS; BREAST-MILK
AB Human exposure to BPs is inevitable mostly due to contaminated food. In this preliminary study, for the first time, the presence of bisphenols (BPs) in aqueous humor (AH) collected from 44 patients undergoing cataract surgery was investigated. The measurements were performed using a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was achieved using a reverse-phase column and a gradient elution mode. Multiple reaction monitoring (MRM) was used. The method was validated for bisphenol A (BPA) and bisphenol F (BPF). The limits of quantification (LOQs) of both investigated analytes were 0.25 ng mL(-1). The method was linear in the range of 0.25-20.0 ng mL(-1) with correlation coefficients (R-2) higher than 0.98. Recovery of analytes was in the range of 99.9 to 104.3% and intra-assay and inter-assay precision expressed by relative standard deviations (RSD%) were less than 5%. BPA was detected in 12 AH samples with mean concentrations of 1.41 ng mL(-1). BPF was not detected at all. Furthermore, two structural isomers termed BPA-1, and BPA-2 were identified, for the first time, in 40.9% of the AH samples, with almost twice higher mean concentrations of 2.15 ng mL(-1), and 2.25 ng mL(-1), respectively. The total content of BPs were higher in patients with coexisting ocular pathologies such as glaucoma, age-related macular degeneration (AMD), and diabetes in comparison to cataracts alone. However, the difference between these groups did not reach statistical significance (p > 0.05). Performed investigations indicate the need for further research on a larger population with the aim of knowing the consequences of BPs' accumulation in AH for visual function.
C1 [Flieger, Jolanta] Med Univ Lublin, Dept Analyt Chem, Chodzki 4A, PL-20093 Lublin, Poland.
   [Sniegocki, Tomasz] Natl Vet Res Inst, Dept Pharmacol & Toxicol, PL-24100 Pulawy, Poland.
   [Dolar-Szczasny, Joanna; Rejdak, Robert] Med Univ Lublin, Dept Gen & Pediat Ophthalmol, Chmielna 1, PL-20079 Lublin, Poland.
   [Zaluska, Wojciech] Med Univ Lublin, Dept Nephrol, Jaczewskiego 8, PL-20090 Lublin, Poland.
C3 Medical University of Lublin; National Veterinary Institute - National
   Research Institute; Medical University of Lublin; Medical University of
   Lublin
RP Flieger, J (通讯作者)，Med Univ Lublin, Dept Analyt Chem, Chodzki 4A, PL-20093 Lublin, Poland.
EM j.flieger@umlub.pl
OI SNIEGOCKI, Tomasz/0000-0003-3564-3279; Flieger,
   Jolanta/0000-0001-6881-3161
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NR 100
TC 0
Z9 0
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 NOV
PY 2022
VL 11
IS 21
AR 6402
DI 10.3390/jcm11216402
PG 18
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 6F6AU
UT WOS:000884141900001
PM 36362630
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Patikulsila, D
   Winaikosol, P
   Choovuthayakorn, J
   Watanachai, N
   Chaikitmongkol, V
   Kunavisarut, P
AF Patikulsila, Direk
   Winaikosol, Pawara
   Choovuthayakorn, Janejit
   Watanachai, Nawat
   Chaikitmongkol, Voraporn
   Kunavisarut, Paradee
TI Pars plana vitrectomy and subretinal tissue plasminogen activator for
   large exudative submacular hemorrhage: a case series
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Large submacular hemorrhage; Pars plana vitrectomy; Tissue plasminogen
   activator; Exudative macular degeneration
ID MACULAR DEGENERATION; PNEUMATIC DISPLACEMENT; SURGICAL OUTCOMES;
   ASSISTED REMOVAL; INJECTION; MANAGEMENT; SECONDARY; GAS; RANIBIZUMAB;
   EXPERIENCE
AB Background To evaluate anatomical and functional outcomes of patients with large submacular hemorrhage (SMH) who treated by pars plana vitrectomy (PPV) in combination with subretinal tissue plasminogen activator (TPA) injection, intraocular gas tamponade, and with additional post-operative interventions. Methods Medical records of 9 patients who presented with large SMH secondary to age-related macular degeneration (AMD) and underwent PPV, subretinal TPA injection, and gas tamponade at Chiang Mai university hospital between January 2012 and January 2020 were reviewed. Collected data included preoperative visual acuity (VA), SMH extent and duration, intraoperation and post-operation complications, post-operative anatomical and VA responses, and the need for administer post-operation additional treatments. Results Overall, five patients were male and four patients were female with a mean (SD) age of 66.9 (7.7) years and a mean (SD) follow-up of 21.1 (16.1) months. A mean (SD) duration of SMH was 15.1 (10.9) days with a mean (SD) extent of SMH was 6.2 (3.4) disc diameters. At 1-month post-operation, complete SMH displacement was noted in eight (88.9%) patients. The mean (SD) VA significantly improved from LogMAR 1.9 (0.4) to 1.1 (0.4), (P = 0.004). During follow-up, eight patients (88.9%) were given additional therapy (anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy, or in combination). At final follow-up, a mean (SD) LogMAR VA of 0.9 (0.4) was significantly improved compared to baseline (P = 0.004). For intra- and post-operation complications, none developed intraoperative retinal break and retinal detachment. Conclusions Vitrectomy with subretinal TPA injection, intraocular gas tamponade, and additional post-operation treatments provide benefit for anatomical and visual outcomes for patients with large SMH. It may consider as one of effective treatment in this group of patients.
C1 [Patikulsila, Direk; Winaikosol, Pawara; Choovuthayakorn, Janejit; Watanachai, Nawat; Chaikitmongkol, Voraporn; Kunavisarut, Paradee] Chiang Mai Univ, Fac Med, Dept Ophthalmol, 110 Intavaroros Rd, Chiang Mai 50200, Thailand.
C3 Chiang Mai University
RP Choovuthayakorn, J (通讯作者)，Chiang Mai Univ, Fac Med, Dept Ophthalmol, 110 Intavaroros Rd, Chiang Mai 50200, Thailand.
EM janejit.c@cmu.ac.th
FU Faculty of Medicine Endowment Fund, Chiang Mai University, Thailand
FX This study received funding support from the Faculty of Medicine
   Endowment Fund, Chiang Mai University, Thailand. The authors have no
   commercial interest in any materials discussed in this article.
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NR 39
TC 0
Z9 0
U1 0
U2 0
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD OCT 27
PY 2022
VL 22
IS 1
AR 411
DI 10.1186/s12886-022-02639-w
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5S0UF
UT WOS:000874915600001
PM 36303103
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Bhattarai, N
   Hytti, M
   Reinisalo, M
   Kaarniranta, K
   Mysore, Y
   Kauppinen, A
AF Bhattarai, Niina
   Hytti, Maria
   Reinisalo, Mika
   Kaarniranta, Kai
   Mysore, Yashavanthi
   Kauppinen, Anu
TI Hydroquinone predisposes for retinal pigment epithelial (RPE) cell
   degeneration in inflammatory conditions
SO IMMUNOLOGIC RESEARCH
LA English
DT Article
DE Antioxidants; ARPE-19; Hydroquinone; IL-1 alpha; PEDF; ROS; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; OXIDATIVE STRESS;
   OXIDANT INJURY; GEOGRAPHIC ATROPHY; CIGARETTE-SMOKING; IN-VITRO; VEGF;
   EXPRESSION; APOPTOSIS
AB In addition to hypoxia, inflammation is capable of inducing vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. Excessive levels of VEGF promote choroidal neovascularization and thereby contribute to the pathogenesis of wet age-related macular degeneration (AMD). Intravitreal anti-VEGF injections ameliorate pathological vessel neoformation in wet AMD but excessive dampening of VEGF can result in a degeneration of the RPE. In the present study, we induced VEGF production by exposing human ARPE-19 cells to the pro-inflammatory IL-1 alpha and subsequently to hydroquinone, a component of tobacco smoke that is a major environmental risk factor for AMD. Effects were monitored by measuring the levels of VEGF and anti-angiogenic pigment epithelium-derived factor (PEDF) using an enzyme-linked immunosorbent assay (ELISA) technique. In addition, we measured the production of reactive oxygen species (ROS) using the 2',7'-dichlorofluorescin diacetate (H2DCFDA) probe and studied the effects of two anti-oxidants, ammonium pyrrolidinedithiocarbamate (APDC) and N-acetyl-cysteine (NAC), on VEGF production. Cellular and secreted VEGF as well as secreted PEDF levels were reduced at all tested hydroquinone concentrations (10, 50, or 200 mu M); these effects were evident prior to any reduction of cell viability evoked by hydroquinone. Cell viability was carefully explored in our previous study and verified by microscoping in the present study. APDC further reduced the VEGF levels, whereas NAC increased them. The 50 mu M concentration of hydroquinone increased ROS production in ARPE-19 cells primed with IL-1 alpha. Hydroquinone disturbs the regulatory balance of VEGF and PEDF in inflammatory conditions. These data support the idea that hydroquinone mediates RPE degeneration by reducing VEGF levels and may predispose to dry AMD since VEGF is as well important for retinal integrity.
C1 [Bhattarai, Niina; Hytti, Maria; Reinisalo, Mika; Mysore, Yashavanthi; Kauppinen, Anu] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Kuopio 70210, Finland.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio 70210, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70210, Finland.
C3 University of Eastern Finland; University of Eastern Finland; Kuopio
   University Hospital; University of Eastern Finland
RP Bhattarai, N; Kauppinen, A (通讯作者)，Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Kuopio 70210, Finland.
EM niina.bhattarai@uef.fi; anu.kauppinen@uef.fi
OI Harju (ex-Bhattarai), Niina/0000-0001-9031-5353
FU University of Eastern Finland (UEF); Academy of Finland [297267, 307341,
   328443, 296840, 333302]; Emil Aaltonen Foundation; Kuopio University
   Hospital VTR grant [5503770]; Sigrid Juselius Foundation; Paivikki and
   Sakari Sohlberg Foundation; University of Eastern Finland; Finnish Eye
   Foundation; Finnish Pharmaceutical Society; Sokeain Ystavat ry; Silma-ja
   kudospankkisaatio; Kuopio University Hospital
FX Open access funding provided by University of Eastern Finland (UEF)
   including Kuopio University Hospital. This study was funded by the
   Academy of Finland (297267, 307341, 328443, 296840, 333302), the Emil
   Aaltonen Foundation, the Kuopio University Hospital VTR grant (5503770),
   the Sigrid Juselius Foundation, the Paivikki and Sakari Sohlberg
   Foundation, the University of Eastern Finland strategical support, the
   Finnish Eye Foundation, Finnish Pharmaceutical Society, Sokeain Ystavat
   ry, and Silma-ja kudospankkisaatio.
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NR 57
TC 1
Z9 1
U1 2
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0257-277X
EI 1559-0755
J9 IMMUNOL RES
JI Immunol. Res.
PD OCT
PY 2022
VL 70
IS 5
BP 678
EP 687
DI 10.1007/s12026-022-09300-0
EA JUN 2022
PG 10
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 4U7QI
UT WOS:000805914900001
PM 35661979
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Bae, SS
   Sodhi, M
   Maberley, D
   Kezouh, A
   Etminan, M
AF Bae, Steven S.
   Sodhi, Mohit
   Maberley, David
   Kezouh, Abbas
   Etminan, Mahyar
TI Risk of maculopathy with pentosan polysulfate sodium use
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE drug toxicity; epidemiology; interstitial cystitis; maculopathy;
   pentosan polysulfate sodium
ID CAUSAL DIAGRAMS; PREVALENCE; NUMBER; BIAS
AB Aims Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use. Methods We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders. Results The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250. Conclusions The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.
C1 [Bae, Steven S.; Maberley, David; Etminan, Mahyar] Univ British Columbia, Fac Med, Dept Ophthalmol & Visual Sci, Collaborat Epidemiol Ocular Dis CEPOD, Vancouver, BC, Canada.
   [Sodhi, Mohit; Etminan, Mahyar] Univ British Columbia, Fac Med, Dept Pharmacol & Therapeut, Vancouver, BC, Canada.
   [Sodhi, Mohit] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
   [Maberley, David] Univ Ottawa, Fac Med, Dept Ophthalmol, Ottawa, ON, Canada.
   [Kezouh, Abbas] McGill Univ, Dept Biostat Epidemiol & Occupat Hlth, Montreal, PQ, Canada.
C3 University of British Columbia; University of British Columbia;
   University of British Columbia; University of Ottawa; McGill University
RP Etminan, M (通讯作者)，Univ British Columbia, Fac Med, Eye Care Ctr, Ophthalmol & Visual Sci, Room 323-2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM etminanm@mail.ubc.ca
OI Etminan, Mahyar/0000-0003-4628-6270
FU Department of Ophthalmology and Visual Sciences, University of British
   Columbia [GR007435]
FX The study was funded by the Department of Ophthalmology and Visual
   Sciences, University of British Columbia (GR007435).
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NR 25
TC 0
Z9 0
U1 0
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
EI 1365-2125
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD JUL
PY 2022
VL 88
IS 7
BP 3428
EP 3433
DI 10.1111/bcp.15303
EA MAR 2022
PG 6
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 2B7WY
UT WOS:000771979300001
PM 35277990
DA 2022-11-30
ER

PT J
AU Abbas, Q
   Qureshi, I
   Yan, JH
   Shaheed, K
AF Abbas, Qaisar
   Qureshi, Imran
   Yan, Junhua
   Shaheed, Kashif
TI Machine Learning Methods for Diagnosis of Eye-Related Diseases: A
   Systematic Review Study Based on Ophthalmic Imaging Modalities
SO ARCHIVES OF COMPUTATIONAL METHODS IN ENGINEERING
LA English
DT Review
ID DETECTING DIABETIC-RETINOPATHY; COHERENCE TOMOGRAPHY IMAGES; NERVE-FIBER
   LAYER; MACULAR DEGENERATION; FUNDUS IMAGES; AUTOMATED DETECTION; RETINAL
   IMAGES; ARTIFICIAL-INTELLIGENCE; GLAUCOMA DIAGNOSIS; OCT IMAGES
AB Glaucoma, diabetic retinopathy, diabetic hypertension (DHR), Cataract, and age-related macular degeneration are some of the most common and important retinal diseases. A permanent vision loss occurs if these diseases are not discovered at an early stage. It is illustrated by numerous abnormalities in the retina such as microaneurysms (MA), hard exudates, soft exudates, or cotton wool spots, hemorrhages (HEM), neovascularization (NV), and macular edema (DME). An analysis of Ophthalmic imaging modalities is used as computerized tools by ophthalmologists for faster screening and diagnosis of these diseases. Compared to traditional-machine learning, multilayer deep learning (MDL), speeds up diagnosis and improves precision and accuracy. As a result, this survey offers a thorough overview of the new technologies used in each phase of the retinal diagnosis process concerning various image modalities. Among different imaging modalities, this paper is primarily focused on the retinal fundus photograph and optical coherence tomography images. This review aims to provide a more in-depth survey of the most significant components, types, and network architectures of MDL algorithms. This paper also describes the advantage of using other different MDL algorithms that are not being used in the past. To assist the researcher, the challenges and potential developments of current traditional and deep learning methods are described in depth. At last, the challenges and recommended solutions are also presented to support scientists in terms of research gaps. We have measured the influence of benchmarks (GPU, and CPU) on MDL algorithms in this paper. Moreover, the limitations and future direction are also mentioned to assist other experts. The comparative results and discussion section of this article suggest that a rigorous MDL model is still required compared to traditional machine-learning to effectively diagnose eye-related diseases in several modalities.
C1 [Abbas, Qaisar] Imam Mohammad Ibn Saud Islamic Univ IMSIU, Coll Comp & Informat Sci, POB 5701, Riyadh 11432, Saudi Arabia.
   [Qureshi, Imran; Yan, Junhua] Nanjing Univ Aeronaut & Astronaut, Minist Ind & Informat Technol, Key Lab Space Photoelect Detect & Percept, Nanjing 211106, Jiangsu, Peoples R China.
   [Qureshi, Imran; Yan, Junhua] Nanjing Univ Aeronaut & Astronaut, Coll Astronaut, Nanjing 211106, Jiangsu, Peoples R China.
   [Shaheed, Kashif] South China Univ Technol, Sch Comp Sci & Engn, Guangzhou 510006, Peoples R China.
C3 Imam Mohammad Ibn Saud Islamic University (IMSIU); Nanjing University of
   Aeronautics & Astronautics; Nanjing University of Aeronautics &
   Astronautics; South China University of Technology
RP Abbas, Q (通讯作者)，Imam Mohammad Ibn Saud Islamic Univ IMSIU, Coll Comp & Informat Sci, POB 5701, Riyadh 11432, Saudi Arabia.
EM qaabbas@imamu.edu.sa; imarwat11@gmail.com; yjh9758@126.com;
   Kashifshaheed1@gmail.com
OI Abbas, Qaisar/0000-0002-0361-1363
FU Deanship of Scientific Research, Imam Mohammad Ibn Saud Islamic
   University (IMSIU), Saudi Arabia [20-13-09-002]
FX This research was supported by the Deanship of Scientific Research, Imam
   Mohammad Ibn Saud Islamic University (IMSIU), Saudi Arabia, Grant No.
   (20-13-09-002).
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NR 265
TC 0
Z9 0
U1 3
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1134-3060
EI 1886-1784
J9 ARCH COMPUT METHOD E
JI Arch. Comput. Method Eng.
PD OCT
PY 2022
VL 29
IS 6
BP 3861
EP 3918
DI 10.1007/s11831-022-09720-z
EA FEB 2022
PG 58
WC Computer Science, Interdisciplinary Applications; Engineering,
   Multidisciplinary; Mathematics, Interdisciplinary Applications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Mathematics
GA 6I6HP
UT WOS:000757763700001
DA 2022-11-30
ER

PT J
AU Seah, I
   Liu, ZP
   Wong, DSL
   Wong, W
   Holder, GE
   Barathi, VA
   Lingam, G
   Su, XY
   Stanzel, BV
AF Seah, Ivan
   Liu, Zengping
   Wong, Daniel Soo Lin
   Wong, Wendy
   Holder, Graham E.
   Barathi, Veluchamy Amutha
   Lingam, Gopal
   Su, Xinyi
   Stanzel, Boris, V
TI Retinal Pigment Epithelium Transplantation in a Non-human Primate Model
   for Degenerative Retinal Diseases
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
ID STEM-CELLS; OCRIPLASMIN; EFFICACY; DELIVERY; SAFETY
AB Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These conditions include retinitis pigmentosa (RP) and advanced forms of age-related macular degeneration (AMD), such as geographic atrophy (GA). Together, these disorders represent a significant proportion of currently untreatable blindness globally. These unmet medical needs have generated heightened academic interest in developing methods of RPE replacement. Among the animal models commonly utilized for preclinical testing of therapeutics, the non-human primate (NHP) is the only animal model that has a macula. As it shares this anatomical similarity with the human eye, the NHP eye is an important and appropriate preclinical animal model for the development of advanced therapy medicinal products (ATMPs) such as RPE cell therapy.
   This manuscript describes a method for the submacular transplantation of an RPE monolayer, cultured on a polyethylene terephthalate (PET) cell carrier, underneath the macula onto a surgically created RPE wound in immunosuppressed NHPs. The fovea-the central avascular portion of the macula-is the site of the greatest mechanical weakness during the transplantation. Foveal trauma will occur if the initial subretinal fluid injection generates an excessive force on the retina. Hence, slow injection under perfluorocarbon liquid (PFCL) vitreous tamponade is recommended with a dual-bore subretinal injection cannula at low intraocular pressure (IOP) settings to create a retinal bleb.
   Pretreatment with an intravitreal plasminogen injection to release parafoveal RPEphotoreceptor adhesions is also advised. These combined strategies can reduce the likelihood of foveal tears when compared to conventional techniques. The NHP is a key animal model in the preclinical phase of RPE cell therapy development. This protocol addresses the technical challenges associated with the delivery of RPE cellular therapy in the NHP eye.
C1 [Seah, Ivan; Wong, Wendy; Holder, Graham E.; Lingam, Gopal; Su, Xinyi; Stanzel, Boris, V] Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.
   [Liu, Zengping; Su, Xinyi] ASTAR, Inst Mol & Cell Biol IMCB, Singapore, Singapore.
   [Liu, Zengping; Wong, Daniel Soo Lin; Holder, Graham E.; Barathi, Veluchamy Amutha; Lingam, Gopal; Su, Xinyi] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Liu, Zengping; Barathi, Veluchamy Amutha; Lingam, Gopal; Su, Xinyi] Singapore Eye Res Inst SERI, Singapore, Singapore.
   [Holder, Graham E.] UCL Inst Ophthalmol, London, England.
   [Barathi, Veluchamy Amutha] Duke NUS Med Sch, Acad Clin Program Ophthalmol, Singapore, Singapore.
   [Stanzel, Boris, V] Knappschaft Hosp Saar, Macula Ctr Saar, Eye Clin Sulzbach, Sulzbach, Germany.
   [Stanzel, Boris, V] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
C3 National University of Singapore; Agency for Science Technology &
   Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology
   (IMCB); National University of Singapore; University of London;
   University College London; National University of Singapore; University
   of Bonn
RP Su, XY; Stanzel, BV (通讯作者)，Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.; Su, XY (通讯作者)，ASTAR, Inst Mol & Cell Biol IMCB, Singapore, Singapore.; Su, XY (通讯作者)，Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.; Su, XY (通讯作者)，Singapore Eye Res Inst SERI, Singapore, Singapore.; Stanzel, BV (通讯作者)，Knappschaft Hosp Saar, Macula Ctr Saar, Eye Clin Sulzbach, Sulzbach, Germany.; Stanzel, BV (通讯作者)，Univ Bonn, Dept Ophthalmol, Bonn, Germany.
EM xinyi_su@nuhs.edu.sg; boris.stanzel@kksaar.de
RI Liu, Zengping/GQO-9030-2022; Seah, Ivan/AAK-6341-2020; Stanzel,
   Boris/AAG-7010-2022; Stanzel, Boris/ADP-9221-2022
OI Seah, Ivan/0000-0001-7843-1917; Stanzel, Boris/0000-0002-4316-1539;
   Stanzel, Boris/0000-0002-4316-1539; Liu, Zengping/0000-0002-2578-293X;
   WONG, WENDY/0000-0002-4514-250X
FU IAF-PP (HMBS Domain) (OrBID): OculaR BIomaterials and Device, A*STAR,
   Singapore [H17/01/a0/013]; NUS Start-up grant [NUHSRO/2016/100/SU/01];
   NUHS Clinical Scientist Program (NCSP); National Research Foundation
   Competitive Research Programme, Singapore [NRF-CRP21-2018-0008]; Hong
   Leong Endowed Professorship funds; veterinary team at the Translational
   Pre-Clinical Model Platform (Singapore Eye Research Institute,
   Singapore)
FX This study was supported by IAF-PP (HMBS Domain) (OrBID): OculaR
   BIomaterials and Device, A*STAR, Singapore (H17/01/a0/013), the NUS
   Start-up grant NUHSRO/2016/100/SU/01, NUHS Clinical Scientist Program
   (NCSP) grant and National Research Foundation Competitive Research
   Programme, Singapore (NRF-CRP21-2018-0008) to X.S., Hong Leong Endowed
   Professorship funds to G.E.H. and B.V.S. We would like to acknowledge
   the veterinary team at the Translational Pre-Clinical Model Platform
   (Singapore Eye Research Institute, Singapore) for providing support in
   NHP surgery preparation and animal follow-up. We would like to extend
   our appreciation to Jill Teo and colleagues from C. Zeiss Meditec
   Singapore for technical support for the OPMILumera 700 with integrated
   intraoperative OCT device.
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NR 50
TC 1
Z9 1
U1 1
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 JUN
PY 2021
IS 172
AR e62638
DI 10.3791/62638
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA TX1AE
UT WOS:000682821800052
PM 34180899
DA 2022-11-30
ER

PT J
AU Colombo, L
   Caretti, A
   Dei Cas, M
   Luciano, F
   Romano, D
   Paroni, R
   Patelli, F
   Ghidoni, R
   Rossetti, L
AF Colombo, Leonardo
   Caretti, Anna
   Dei Cas, Michele
   Luciano, Francesco
   Romano, Dario
   Paroni, Rita
   Patelli, Fabio
   Ghidoni, Riccardo
   Rossetti, Luca
TI Vitreous composition modification after transpalpebral electrical
   stimulation of the eye: Biochemical analysis
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Electrical stimulation; Inflammation; Vitreous fluid; Lipids;
   Lysophosphatidylcholine; Cytokines
ID FATTY-ACID-COMPOSITION; RETINITIS-PIGMENTOSA; RETINAL FUNCTION;
   IN-VITRO; LYSOPHOSPHATIDYLCHOLINE; PHOTORECEPTORS; PROMOTES; SURVIVAL;
   LIPIDS; CELLS
AB Electrical stimulation (ES) of the eye represents a therapeutic approach in various clinical applications ranging from retinal dystrophies, age-related macular degeneration, retinal artery occlusion and nonarteritic ischemic optic neuropathy. In clinical practice, ES of the eye is mainly performed with a transcorneal or transpalpebral approach. These procedures are non-invasive and well-tolerated by the patients, reporting only minimal and transient adverse events, while serious adverse effects were not observed. Despite the growing literature on animal models, only clinical parameters have been investigated in humans and few data are available about biochemical changes induced by ES of the eye. The purpose of this study is to investigate the possible mechanism that regulates the beneficial effects of ES on retinal cells function and survival in humans. 28 patients undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (iERM) were randomly divided in two groups: 13 patients were treated with transpalpebral ES before surgery and 15 underwent surgery with no prior treatment. Vitreous samples were collected for biochemical analysis during PPV. ES treatment leads to a reduction in the vitreous expression of both proinflammatory cytokines, namely IL-6 and IL-8, and proinflammatory lipid mediators, such as lysophosphatidylcholine. Indeed, we observed a 70% decrease of lysophosphatidylcholine 18:0, which has been proven to exert the greatest proinflammatory activities among the lysophosphatidylcholine class. The content of triglycerides is also affected and significantly decreased following ES application. The vitreous composition of patients undergoing PPV for iERM displays significant changes following ES treatment. Proinflammatory cytokines and bioactive lipid mediators expression decreases, suggesting an overall antiinflammatory potential of ES. The investigation of the mechanism by which this treatment alters the retinal neurons leading to good outcomes is essential for supporting ES therapeutic application in various types of retinal diseases.
C1 [Colombo, Leonardo; Romano, Dario; Patelli, Fabio; Rossetti, Luca] Univ Milan, ASST Santi Paolo & Carlo Hosp, Eye Clin, Milan, Italy.
   [Caretti, Anna; Luciano, Francesco; Ghidoni, Riccardo] Univ Milan, Dept Hlth Sci, Biochem & Mol Biol Lab, Milan, Italy.
   [Dei Cas, Michele; Paroni, Rita] Univ Milan, Dept Hlth Sci, Clin Biochem & Mass Spectrometry Lab, Via Rudini 8, I-20142 Milan, Italy.
C3 University of Milan; University of Milan; University of Milan
RP Dei Cas, M (通讯作者)，Univ Milan, Dept Hlth Sci, Clin Biochem & Mass Spectrometry Lab, Via Rudini 8, I-20142 Milan, Italy.
EM michele.deicas@unimi.it
RI Dei Cas, Michele/AAO-2132-2020; Luciano, Francesco/GSJ-3066-2022;
   Luciano, Francesco/ABB-4284-2021; PARONI, RITA/C-2955-2012; CARETTI,
   ANNA/O-8958-2017
OI Dei Cas, Michele/0000-0001-7359-8558; Luciano,
   Francesco/0000-0002-1179-8578; PARONI, RITA/0000-0002-3186-8860; Romano,
   Dario/0000-0002-5045-8787; CARETTI, ANNA/0000-0001-6140-6969; Colombo,
   Leonardo/0000-0002-9556-994X
FU Universita degli Studi di Milano, Milan, Italy
FX Michele Dei Cas was supported by the PhD programme in Molecular and
   Translational Medicine of the Universita degli Studi di Milano, Milan,
   Italy. Part of this work was carried out in OMICs, an advanced mass
   spectrometry platform established by the Universita degli Studi di
   Milano. We thank Dr Tommaso Nuzzo (Eye Clinic, ASST Santi Paolo e Carlo
   Hospital, Universita degli Studi di Milano, Milan, Italy) for surgical
   management of the patients and Dr Paolo Ferri (Eye Clinic, ASST Santi
   Paolo e Carlo Hospital, Universit`a degli Studi di Milano, Milan, Italy)
   for ES treatment of the patients.
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NR 43
TC 0
Z9 0
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2021
VL 207
AR 108601
DI 10.1016/j.exer.2021.108601
EA MAY 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SQ8CL
UT WOS:000660577600003
PM 33910035
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Chen, YY
   Lai, YJ
   Yen, YF
   Chou, P
AF Chen, Yu-Yen
   Lai, Yun-Ju
   Yen, Yung-Feng
   Chou, Pesus
TI Increased mortality after intravitreal injections of anti-VEGF for
   neovascular AMD among patients with prior stroke or acute myocardial
   infarction
SO EYE
LA English
DT Article
AB Objectives To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality. Methods From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined as the IVI group. The mortality of the IVI group during the study period was compared to that of the non-IVI group, which consisted of nAMD patients who had prior stroke/AMI but were never exposed to anti-VEGF. The IVI group and the non-IVI group were 1-4 matched according to propensity score (PS), which was derived from age, sex, date of stroke/AMI and comorbidities. PS-adjusted Cox regression analyses were used to estimate the hazard ratio (HR) for mortality associated with IVI of anti-VEGF. Subgroup analyses were also performed according to the interval between stroke/AMI and IVI (<= 6 months, 6 months to 1 year, 1-2 years, >2 years). Results There were 3384 individuals in the IVI group and 13,536 individuals in the non-IVI group. The IVI group had a significantly higher mortality risk (adjusted HR = 2.37; 95% confidence interval (CI), 2.14-2.62) than the non-IVI group. Subgroup analyses revealed that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke/AMI. Conclusions We found an increased mortality risk associated with IVI of anti-VEGF in nAMD patients with prior stroke/AMI compared to the mortality risk of nAMD patients with prior stroke/AMD but without exposure to anti-VEGF.
C1 [Chen, Yu-Yen] Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung 407, Taiwan.
   [Chen, Yu-Yen; Lai, Yun-Ju; Yen, Yung-Feng; Chou, Pesus] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
   [Chen, Yu-Yen; Lai, Yun-Ju; Yen, Yung-Feng; Chou, Pesus] Natl Yang Ming Univ, Community Med Res Ctr, Taipei 112, Taiwan.
   [Chen, Yu-Yen; Yen, Yung-Feng; Chou, Pesus] Natl Yang Ming Univ, Inst Publ Hlth, Taipei 112, Taiwan.
   [Chen, Yu-Yen] Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan.
   [Lai, Yun-Ju] Taichung Vet Gen Hosp, Div Endocrinol & Metab, Dept Internal Med, Puli Branch, Nantou 545, Taiwan.
   [Lai, Yun-Ju] Natl Taiwan Univ Sport, Dept Exercise Hlth Sci, Taichung 404, Taiwan.
   [Yen, Yung-Feng] Taipei City Hosp, Sect Infect Dis, Taipei 103, Taiwan.
   [Yen, Yung-Feng] Natl Taipei Univ Nursing & Hlth Sci, Dept Hlth Care Management, Taipei 112, Taiwan.
C3 Taichung Veterans General Hospital; National Yang Ming Chiao Tung
   University; National Yang Ming Chiao Tung University; National Yang Ming
   Chiao Tung University; Chung Shan Medical University; Taichung Veterans
   General Hospital; National Taiwan University of Sport; Taipei City
   Hospital; National Taipei University of Nursing & Health Science
   (NTUNHS)
RP Chen, YY (通讯作者)，Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung 407, Taiwan.; Chen, YY (通讯作者)，Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.; Chen, YY (通讯作者)，Natl Yang Ming Univ, Community Med Res Ctr, Taipei 112, Taiwan.; Chen, YY (通讯作者)，Natl Yang Ming Univ, Inst Publ Hlth, Taipei 112, Taiwan.; Chen, YY (通讯作者)，Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan.
EM yuyenchen.phd@gmail.com
OI Chen, Yu-Yen/0000-0003-0891-3819
FU Taichung Veterans General Hospital [TCVGH-1106901B]
FX This work was supported by the Taichung Veterans General Hospital (Grant
   number TCVGH-1106901B).
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NR 28
TC 1
Z9 1
U1 0
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2022
VL 36
IS 1
BP 153
EP 159
DI 10.1038/s41433-021-01416-1
EA MAR 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YA9VP
UT WOS:000624380000005
PM 33654317
DA 2022-11-30
ER

PT J
AU Naravane, AV
   Mundae, R
   Zhou, YJ
   Santilli, C
   van Kuijk, FJGM
   Nazari, H
   Yamanuha, J
   Emerson, GG
   Koozekanani, DD
   Montezuma, SR
AF Naravane, Ameay, V
   Mundae, Rusdeep
   Zhou, Yujia
   Santilli, Christopher
   van Kuijk, Frederik J. G. M.
   Nazari, Hossein
   Yamanuha, Justin
   Emerson, Geoffrey G.
   Koozekanani, Dara D.
   Montezuma, Sandra R.
TI Short term visual and structural outcomes of anti-vascular endothelial
   growth factor (anti-VEGF) treatment delay during the first COVID-19
   wave: A pilot study
SO PLOS ONE
LA English
DT Article
AB Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The 'COVID-19 lockdown' was defined as the period after March, 28(th), 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.
C1 [Naravane, Ameay, V; Mundae, Rusdeep; Zhou, Yujia; van Kuijk, Frederik J. G. M.; Nazari, Hossein; Yamanuha, Justin; Koozekanani, Dara D.; Montezuma, Sandra R.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
   [Santilli, Christopher] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
   [Emerson, Geoffrey G.] Retina Ctr, Minneapolis, MN USA.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of Minnesota System; University of Minnesota Twin Cities
RP Montezuma, SR (通讯作者)，Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
EM smontezu@umn.edu
RI Nazari, Hossein/GOK-8161-2022
OI Nazari, Hossein/0000-0002-8945-9680; Naravane, Ameay/0000-0003-2570-7857
FU Minnesota Lions Foundation; Knobloch Chair Professorship; VitreoRetinal
   Surgery 2020 Research Award
FX Funding was provided by the Minnesota Lions Foundation, the Knobloch
   Chair Professorship (SRM), and VitreoRetinal Surgery 2020 Research Award
   (AN). The funding organizations had no role in the design or conduct of
   this research.
CR Agarwal D, 2020, INDIAN J OPHTHALMOL, V68, P1216, DOI 10.4103/ijo.IJO_1391_20
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NR 26
TC 18
Z9 18
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 17
PY 2021
VL 16
IS 2
AR e0247161
DI 10.1371/journal.pone.0247161
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA QK8ME
UT WOS:000620633200052
PM 33596257
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Weill, Y
   Hanhart, J
   Zadok, D
   Smadja, D
   Gelman, E
   Abulafia, A
AF Weill, Yishay
   Hanhart, Joel
   Zadok, David
   Smadja, David
   Gelman, Evgeny
   Abulafia, Adi
TI Patient management modifications in cataract surgery candidates
   following incorporation of routine preoperative macular optical
   coherence tomography
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
AB Purpose: To assess the clinical relevance of routine preoperative spectral-domain optical coherence tomography (SD-OCT) for identifying macular pathologies in patients scheduled for cataract surgery.
   Setting: Shaare-Zedek Medical Center, Jerusalem, Israel.
   Design: Retrospective case series.
   Methods: Consecutive patients, 50 years of age and older, scheduled for standard cataract extraction surgery were enrolled from November 2017 to January 2018. All study patients underwent routine SD-OCT scanning before cataract surgery. The scans were reviewed by a retinal specialist for macular pathology and compared with preoperative fundus biomicroscopic examination findings. The incidence of macular pathologies and changes in patient management as a result of the macular SD-OCT findings were assessed.
   Results: Four hundred fifty-three eyes of 453 patients were enrolled in the study; 42 eyes (9.2%) were excluded because of noninterpretable SD-OCT scans attributable to advanced cataract, leaving scans of 411 eyes of 411 patients for study inclusion. Macular pathologies were detected by SD-OCT in 167 eyes (40.6%), including age-related macular degeneration (50%), epiretinal membrane (28.3%), and cystoid macular edema (12.8%). Overall, the management of 107 patients (26.0%) was modified because of macular SD-OCT findings, which were either missed (22.8%) or underestimated (3.2%) by the fundus biomicroscopic examination. Changes in preoperative patient management included altering patient consultation regarding presbyopia correction solutions (73 eyes [17.8%]) and referral to a retinal specialist for consultation (34 eyes [8.3%]).
   Conclusions: Routine macular SD-OCT scans for cataract surgery candidates helped to identify macular pathologies that might be missed or underestimated by standard fundus bio-microscopic examination. The added information could improve patient management. Copyright (C) 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS
C1 [Weill, Yishay] Shaare Zedek Med Ctr, Dept Ophthalmol, Shmuel Bait St 12, IL-9103102 Jerusalem, Israel.
   Hebrew Univ Jerusalem, Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Shaare Zedek Medical Center; Hebrew
   University of Jerusalem
RP Weill, Y (通讯作者)，Shaare Zedek Med Ctr, Dept Ophthalmol, Shmuel Bait St 12, IL-9103102 Jerusalem, Israel.
EM Yishayweill@gmail.com
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NR 20
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0886-3350
EI 1873-4502
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD JAN
PY 2021
VL 47
IS 1
BP 78
EP 82
DI 10.1097/j.jcrs.0000000000000389
PG 5
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA PR5UJ
UT WOS:000607301100011
PM 32815862
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Corbelli, E
   Carnevali, A
   Querques, L
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Corbelli, Eleonora
   Carnevali, Adriano
   Querques, Lea
   Bandello, Francesco
   Querques, Giuseppe
TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN GEOGRAPHIC ATROPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE dry age-related macular degeneration; geographic atrophy; optical
   coherence tomography angiography; multimodal imaging; vessel density
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; FUNDUS AUTOFLUORESCENCE;
   CHORIOCAPILLARIS; EYES; PROGRESSION; DRUSEN; RPE
AB Purpose: To analyze choriocapillaris (CC) vessel density (VD) around geographic atrophy (GA) secondary to non-neovascular dry age-related macular degeneration using optical coherence tomography angiography.
   Methods: We compared CC VD surrounding GA margin (500 mm radius) with control CC (outside GA margin) in a consecutive series of GA patients presenting between August 2016 and February 2017 at the Medical Retina and Imaging Unit of University Vita-Salute, IRCCS Ospedale San Raffaele in Milan. Images were obtained through thresholding and binarization. We also compared the CC VD in a sample area of 500 mu m x 500 mu m surrounding GA margin rated as hyperautofluorescent on fundus autofluorescence to a similar area rated as isoautofluorescent.
   Results: Fifty eyes of 29 patients (19 women and 10 men; mean age 77 +/- 6 years) with mean GA area of 9.43 +/- 5.08 mm(2) and mean subfoveal choroidal thickness of 164 +/- 73 mm were included. Choriocapillaris VD surrounding GA margin as detected by optical coherence tomography angiography revealed a significant impairment compared with control CC outside GA margin (0.317 +/- 0.083 vs. 0.461 +/- 0.054, P < 0.001), which was even greater in patients with foveal involvement (P = 0.013). Furthermore, mean VD in hyperautofluorescent areas was significantly lower compared with isoautofluorescent areas (0.242 +/- 0.112 vs. 0.327 +/- 0.130, P = 0.001). A positive correlation was disclosed between VD surrounding GA margin and subfoveal choroidal thickness (r = 0.332, P = 0.019).
   Conclusion: Optical coherence tomography angiography discloses CC impairment surrounding GA margin. Such CC impairment at GA margin seems to precede retinal pigment epithelium alterations at fundus autofluorescence. Optical coherence tomography angiography could be a new valuable tool for detecting CC alterations and to evaluate potential therapeutic responses in clinical studies.
C1 [Sacconi, Riccardo; Corbelli, Eleonora; Carnevali, Adriano; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute, IRCCS San Raffaele Hosp, Dept Ophthalmol, Via Olgettina 60, I-20132 Milan, Italy.
   [Sacconi, Riccardo] Univ Verona, 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; Magna Graecia University of Catanzaro
RP Querques, G (通讯作者)，Univ Vita Salute, IRCCS San Raffaele Hosp, Dept Ophthalmol, Via Olgettina 60, I-20132 Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Corbelli, Eleonora/AAA-3186-2019; bandello, francesco/AAH-2405-2019
OI Corbelli, Eleonora/0000-0003-1658-1922; bandello,
   francesco/0000-0003-3238-9682; Querques, Giuseppe/0000-0002-3292-9581;
   Sacconi, Riccardo/0000-0003-2891-2012
CR Bhutto I, 2012, MOL ASPECTS MED, V33, P295, DOI 10.1016/j.mam.2012.04.005
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NR 28
TC 53
Z9 53
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 DEC
PY 2018
VL 38
IS 12
BP 2350
EP 2355
DI 10.1097/IAE.0000000000001873
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HF1WG
UT WOS:000454008700015
PM 29016457
DA 2022-11-30
ER

PT J
AU Kumar, P
   Nag, TC
   Jha, KA
   Dey, SK
   Kathpalia, P
   Maurya, M
   Gupta, CL
   Bhatia, J
   Roy, TS
   Wadhwa, S
AF Kumar, Pankaj
   Nag, Tapas Chandra
   Jha, Kumar Abhiram
   Dey, Sanjay Kumar
   Kathpalia, Poorti
   Maurya, Meenakshi
   Gupta, Chandan Lal
   Bhatia, Jagriti
   Roy, Tara Sankar
   Wadhwa, Shashi
TI Experimental oral iron administration: Histological investigations and
   expressions of iron handling proteins in rat retina with aging
SO TOXICOLOGY
LA English
DT Article
DE Iron homeostasis; Choriocapillaris; Retina; Photoreceptors;
   Histopathology
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; OXIDATIVE DAMAGE; AGE; FERRITIN;
   CHORIOCAPILLARIS; ACCUMULATION; FERROPORTIN; TOXICITY; OVERLOAD
AB Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500 mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressiAs of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging ( > 14 months). The serum and retinal TSARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL + cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD.
C1 [Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Roy, Tara Sankar; Wadhwa, Shashi] All India Inst Med Sci, Dept Anat, New Delhi 110029, India.
   [Dey, Sanjay Kumar] Delhi Univ, Dept Biochem, South Campus, New Delhi 110021, India.
   [Bhatia, Jagriti] All India Inst Med Sci, Dept Pharmacol, New Delhi 110029, India.
   [Jha, Kumar Abhiram] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN 38163 USA.
   [Wadhwa, Shashi] North Delhi Municipal Corp, Dept Anat, Med Coll, Delhi 110007, India.
   [Wadhwa, Shashi] Hindu Rao Hosp, Delhi 110007, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; University of
   Delhi; All India Institute of Medical Sciences (AIIMS) New Delhi;
   University of Tennessee System; University of Tennessee Health Science
   Center
RP Nag, TC (通讯作者)，All India Inst Med Sci, Dept Anat, New Delhi 110029, India.
EM pankajkumar4020@gmail.com; tapas_nag@yahoo.com; jha9a@yahoo.co.in;
   sanjaydey@south.du.ac.in; poorti88@gmail.com; mmnnkshi@gmail.com;
   clgtheboss@gmail.com; jagriti2012@gmail.com; tarasankar@hotmail.com;
   shashiwadhwa@hotmail.com
RI NAG, TAPAS CHANDRA/R-6285-2019; Dey, Sanjay Kumar/W-5646-2018; ROY, TARA
   SANKAR/J-3264-2019
OI NAG, TAPAS CHANDRA/0000-0002-6962-0844; Dey, Sanjay
   Kumar/0000-0001-7062-9574; ROY, TARA SANKAR/0000-0002-9852-2952
FU Council of Scientific and Industrial Research (CSIR), New Delhi, India
   [37/1593/13/EMR-II]; Indian Council of Medical Research, New Delhi
   [IR-480]
FX This study was supported by research grant from Council of Scientific
   and Industrial Research (CSIR), New Delhi, India (No. 37/1593/13/EMR-II)
   to TCN, and Senior Research Fellowship from Indian Council of Medical
   Research, New Delhi to PK (No. IR-480).
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NR 36
TC 7
Z9 7
U1 0
U2 2
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 DEC 1
PY 2017
VL 392
BP 22
EP 31
DI 10.1016/j.tox.2017.10.005
PG 10
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA FP6ZY
UT WOS:000417777300003
PM 28993186
DA 2022-11-30
ER

PT J
AU Thapa, R
   Bajimaya, S
   Bouman, R
   Paudyal, G
   Khanal, S
   Tan, S
   Thapa, SS
   van Rens, G
AF Thapa, Raba
   Bajimaya, Sanyam
   Bouman, Renske
   Paudyal, Govinda
   Khanal, Shankar
   Tan, Stevie
   Thapa, Suman S.
   van Rens, Ger
TI Intra- and inter-rater agreement between an ophthalmologist and
   mid-level ophthalmic personnel to diagnose retinal diseases based on
   fundus photographs at a primary eye center in Nepal: the Bhaktapur
   Retina Study
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Fundus photograph grading; Retinal pathology; Ophthalmologist; Mid-level
   ophthalmic personnel
ID GRADING DIABETIC-RETINOPATHY; MACULAR DEGENERATION; POPULATION;
   PREVALENCE; EPIDEMIOLOGY; SPECIFICITY; SENSITIVITY; IMAGES; CAMERA
AB Background: Early detection can reduce irreversible blindness from retinal diseases. This study aims to assess the intra- and inter-rater agreement of retinal pathologies observed on fundus photographs between an ophthalmologist and two-mid level ophthalmic personnel (MLOPs).
   Method: A population-based, cross-sectional study was conducted among subjects 60 years and above in the Bhaktapur district of Nepal. Fundus photographs of 500 eyes of 500 subjects were assessed. The macula-centered 45-degree photographs were graded twice by one ophthalmologist and two MLOPs. Intra-rater and inter-rater agreements were assessed for the ophthalmologist and the MLOPs.
   Result: Mean age was 70.22 years +/- 6.94 (SD). Retinal pathologies were observed in 55.6 % of photographs (age-related macular degeneration: 34.2 %; diabetic retinopathy: 4.2 %; retinal vein occlusion: 3.8 %). Twelve (2.4 %) fundus pictures were non-gradable. The intra-rater agreement for overall retinal pathologies, retinal hemorrhage, and maculopathy were substantial both for the ophthalmologist as well as for the MLOPs. There was moderate inter-rater agreement between the ophthalmologist and the first MLOP on second rating for overall retinal pathologies, [kappa (k); 95 % CI = 0.59 (0.51-0.66)], retinal hemorrhage [k; 95% CI = 0.60 (0.41-0. 78)], and maculopathy [k; 95% CI = 0.52 (0.43-0.60)]. Inter-rater agreement between the ophthalmologist and the second MLOP for second rating was moderate for overall retinal pathologies [k; 95 % CI = 0.52 (0.44-0.60)], substantial agreement for retinal hemorrhage [k; 95 % CI= 0. 68 (0.52-0.84)], moderate agreement for maculopathy [k; 95 % CI= 0.59 (0.50-0.67)].
   Conclusion: There is moderate agreement between the MLOPs and the ophthalmologist in grading fundus photographs for retinal hemorrhages and maculopathy.
C1 [Thapa, Suman S.] Tilganga Inst Ophthalmol, Kathmandu, Nepal.
   [Bouman, Renske; Tan, Stevie; van Rens, Ger] Vrije Univ, Med Ctr, Amsterdam, Netherlands.
   [Khanal, Shankar] Tribhuvan Univ, Cent Dept Stat, Kirtipur, Nepal.
   [Thapa, Raba; Bajimaya, Sanyam; Paudyal, Govinda] Tilganga Inst Ophthalmol, Vitreoretina Serv, POB 561, Kathmandu, Nepal.
C3 Vrije Universiteit Amsterdam; Tribhuvan University
RP Thapa, R (通讯作者)，Tilganga Inst Ophthalmol, Vitreoretina Serv, POB 561, Kathmandu, Nepal.
EM rabathapa@live.com
RI van Rens, Ger/I-6247-2018
OI Tan, H. Stevie/0000-0001-8368-1048
FU Vrije University Medical Center, Amsterdam, The Netherlands; Tilganga
   Institute of Ophthalmology, Kathmandu, Nepal
FX The study was funded by the Vrije University Medical Center, Amsterdam,
   The Netherlands and Tilganga Institute of Ophthalmology, Kathmandu,
   Nepal.
CR [Anonymous], 2005, REPORT WHO CONSULTAT
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NR 32
TC 9
Z9 9
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD JUL 18
PY 2016
VL 16
AR 112
DI 10.1186/s12886-016-0295-0
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DR9RJ
UT WOS:000380233500003
PM 27430579
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yilmaz, T
   Karci, AA
   Yilmaz, I
   Yilmaz, A
   Yildirim, Y
   Sakalar, YB
AF Yilmaz, Tolga
   Karci, Ayse Aslihan
   Yilmaz, Ihsan
   Yilmaz, Ahu
   Yildirim, Yusuf
   Sakalar, Yildirim Bayezit
TI Long-Term Changes in Subfoveal Choroidal Thickness After Cataract
   Surgery
SO MEDICAL SCIENCE MONITOR
LA English
DT Article
DE Cataract Extraction; Choroidal Neovascularization; Macular Degeneration;
   Tomography, Optical Coherence
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; VISUAL-ACUITY;
   MACULAR EDEMA
AB Background: Cataract surgery is associated with the development of late-onset age-related macular degeneration (AMD). The pathogenic mechanism is still not fully established. The purpose of this study was to evaluate the possible changes in central macula thickness (CMT) and subfoveal choroid thickness (SCT) after uneventful cataract surgery.
   Material/Methods: A total of 65 eyes of 65 patients who underwent phacoemulsification and intracapsular lens implantation were included in this prospective study. Patients had not undergone previous ocular surgery and had no other ocular abnormality. CMT and SCT were measured at baseline and postoperatively at week 1 and months 1, 3, 6 and 12 via spectral domain optical cohorence tomography (SD-OCT).
   Results: CMT was 252.4 +/- 27.6 mu m (mean +/- SD) preoperatively, then 253.5 +/- 29.8, 256.1 +/- 28.7, 257.4 +/- 27.2, 253.18 +/- 23.7, and 252.8 +/- 21.7 mu m at postoperative week 1 and postoperative months 1, 3, 6, and 12, respectively. There were insignificant changes in CMT, and it returned to baseline at six months after surgery (all p>0.05). SCT was 237.4 +/- 21.6 mu m preoperatively, and 240.5 +/- 24.8, 241.2 +/- 25.7, 242.7 +/- 26.3, 243.1 +/- 24.2, and 244.2 +/- 21.4 mu m at postoperative week 1 and postoperative months 1, 3, 6, and 12, respectively. Although there was an increase in SCT during follow-up, the difference between preoperative and postoperative values was not significant (p>0.05).
   Conclusions: Uncomplicated phacoemulsification induces subclinical changes in CMT, probably due to the inflammatory insult of surgery, and CMT returns to baseline value. There were slight, insignificant increases in choroid thickness during follow-up, and this did not return to baseline during follow-up. Changes in the choroid after cataract surgery may provide clues to the development of late-onset AMD.
C1 [Yilmaz, Tolga; Yilmaz, Ihsan; Yildirim, Yusuf] Beyoglu Eye Training & Res Hosp, Dept Ophthalmol, Istanbul, Turkey.
   [Karci, Ayse Aslihan; Sakalar, Yildirim Bayezit] Derince Training & Res Hosp, Dept Ophthalmol, Kocaeli, Turkey.
   [Yilmaz, Ahu] Bagcilar Training & Res Hosp, Dept Ophthalmol, Istanbul, Turkey.
C3 Istanbul Prof Dr N Resat Belger Beyoglu Eye Training & Research
   Hospital; Kocaeli Derince Training & Research Hospital; Istanbul
   Bagcilar Training & Research Hospital
RP Yilmaz, T (通讯作者)，Beyoglu Eye Training & Res Hosp, Dept Ophthalmol, Istanbul, Turkey.
EM dr.tolgayilmaz@hotmail.com
RI Yildirim, Yusuf/AAD-7381-2020
OI Yildirim, Yusuf/0000-0002-4161-0919
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NR 28
TC 21
Z9 22
U1 0
U2 0
PU INT SCIENTIFIC INFORMATION, INC
PI MELVILLE
PA 150 BROADHOLLOW RD, STE 114, MELVILLE, NY 11747 USA
SN 1643-3750
J9 MED SCI MONITOR
JI Med. Sci. Monitor
PD MAY 9
PY 2016
VL 22
BP 1566
EP 1570
PG 5
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA DL2GQ
UT WOS:000375452000002
PM 27158971
DA 2022-11-30
ER

PT J
AU Shah, RS
   Soetikno, BT
   Lajko, M
   Fawzi, AA
AF Shah, Ronil S.
   Soetikno, Brian T.
   Lajko, Michelle
   Fawzi, Amani A.
TI A Mouse Model for Laser-induced Choroidal Neovascularization
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 106; Laser-induced choroidal neovascularization;
   experimental CNV; age-related macular degeneration; neovascular
   age-related macular degeneration; wet AMD
ID ANIMAL-MODELS; AGE; SEVERITY; VEGF
AB The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch's membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD.
   First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects.
   The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD.
   Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.
C1 [Shah, Ronil S.; Soetikno, Brian T.; Lajko, Michelle; Fawzi, Amani A.] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Evanston, IL 60208 USA.
C3 Northwestern University; Feinberg School of Medicine
RP Fawzi, AA (通讯作者)，Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Evanston, IL 60208 USA.
EM amani.fawzi@northwestern.edu
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558; Soetikno, Brian/0000-0003-4530-4959
FU Macula Society Research Grant; Research to Prevent Blindness, Inc., New
   York, NY, USA;  [NIH-EY019951]; NATIONAL EYE INSTITUTE [R01EY019951]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [DP3DK108248] Funding Source: NIH RePORTER
FX The authors would like to acknowledge Jonathan Chou, MD for his
   assistance on preparation and editing of the final manuscript and
   Wenzhong Liu for the OCT data. We would also like to acknowledge support
   from the Macula Society Research Grant (AAF), support from an
   unrestricted grant to Northwestern University from Research to Prevent
   Blindness, Inc., New York, NY, USA, and support from NIH-EY019951.
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NR 25
TC 40
Z9 40
U1 0
U2 6
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 DEC
PY 2015
IS 106
AR e53502
DI 10.3791/53502
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DB5SR
UT WOS:000368574400069
PM 26779879
OA Green Published
DA 2022-11-30
ER

PT J
AU Fangueiro, JF
   Andreani, T
   Fernandes, L
   Garcia, ML
   Egea, MA
   Silva, AM
   Souto, EB
AF Fangueiro, Joana F.
   Andreani, Tatiana
   Fernandes, Lisete
   Garcia, Maria L.
   Egea, Maria A.
   Silva, Amelia M.
   Souto, Eliana B.
TI Physicochemical characterization of epigallocatechin gallate lipid
   nanoparticles (EGCG-LNs) for ocular instillation
SO COLLOIDS AND SURFACES B-BIOINTERFACES
LA English
DT Article
DE Catechins; Cationic lipid; Epigallocatechin gallate; Lipid
   nanoparticles; Ocular delivery; Multiple emulsion
ID GREEN TEA; IN-VITRO; ANTIOXIDANT; DELIVERY; DERIVATIVES;
   (-)-EPIGALLOCATECHIN-3-GALLATE; ACTIVATION; STABILITY; ARTHRITIS; LIGHT
AB The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Fangueiro, Joana F.; Souto, Eliana B.] Fernando Pessoa Univ, UFP FCS, Res Ctr Biomed, CEBIMED, P-4249004 Oporto, Portugal.
   [Fangueiro, Joana F.; Andreani, Tatiana] Fernando Pessoa Univ, UFP FCS, Fac Hlth Sci, P-4200150 Oporto, Portugal.
   [Andreani, Tatiana; Silva, Amelia M.] Univ Tras Os Montes & Alto Douro, CITAB, Ctr Res & Technol Agroenvironm & Biol Sci, UTAD, P-5000801 Vila Real, Portugal.
   [Andreani, Tatiana; Silva, Amelia M.] Univ Tras Os Montes & Alto Douro, Dept Biol & Environm, UTAD, P-5000801 Vila Real, Portugal.
   [Fernandes, Lisete] Univ Tras Os Montes & Alto Douro, Electron Microscopy Unit, UTAD, P-5000801 Vila Real, Portugal.
   [Garcia, Maria L.; Egea, Maria A.] Univ Barcelona, Fac Pharm, Dept Phys Chem, E-08028 Barcelona, Spain.
   [Garcia, Maria L.; Egea, Maria A.] Univ Barcelona, Inst Nanosci & Nanotechnol, E-08028 Barcelona, Spain.
   [Souto, Eliana B.] Univ Coimbra FFUC, Fac Pharm, P-3000548 Coimbra, Portugal.
C3 Universidade Fernando Pessoa; Universidade Fernando Pessoa; University
   of Tras-os-Montes & Alto Douro; University of Tras-os-Montes & Alto
   Douro; University of Tras-os-Montes & Alto Douro; University of
   Barcelona; University of Barcelona; Universidade de Coimbra
RP Souto, EB (通讯作者)，Univ Coimbra FFUC, Fac Pharm, P-3000548 Coimbra, Portugal.
EM ebsouto@ff.uc.pt
RI Souto, Eliana/T-1645-2019; Souto, Eliana/GQZ-3071-2022; Fernandes,
   Lisete Sofia Gomes/GZK-4443-2022; Fangueiro, Joana/AAB-5102-2020;
   Andreani, Tatiana/ADJ-2242-2022; Silva, Amélia M/J-7128-2013; Garcia, M.
   Luisa/O-6020-2014
OI Souto, Eliana/0000-0002-9737-6017; Fernandes, Lisete Sofia
   Gomes/0000-0002-2986-7818; Fangueiro, Joana/0000-0001-6544-3943;
   Andreani, Tatiana/0000-0002-3794-8159; Silva, Amélia
   M/0000-0002-7524-9914; Garcia, M. Luisa/0000-0002-4526-3344
FU European Funds (FEDER) [PTDC/SAU-FAR/113100/2009,
   FCOMP-01-0124-FEDER-022696 (PEst-C/AGR/UI403312011)]; European Funds
   (COMPETE) [PTDC/SAU-FAR/113100/2009, FCOMP-01-0124-FEDER-022696
   (PEst-C/AGR/UI403312011)]
FX Ms. Joana Fangueiro and Ms. Tatiana Andreani wish to acknowledge
   Fundacao para a Ciencia e Tecnologia do Ministerio da Ciencia e
   Tecnologia (FCT, Portugal) under the references SFRH/BD/80335/2011 and
   SFRH/BD/60640/2009, respectively. FCT and European Funds (FEDER and
   COMPETE) are also acknowledged under the research project
   PTDC/SAU-FAR/113100/2009 and FCOMP-01-0124-FEDER-022696
   (PEst-C/AGR/UI403312011). The Subprograma de Proyectos de Investigacion
   Fundamental no Orientada del Ministerio de Ciencia e Innovacion is also
   acknowledged under the reference MAT2011-26994.
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NR 62
TC 75
Z9 76
U1 2
U2 53
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0927-7765
EI 1873-4367
J9 COLLOID SURFACE B
JI Colloid Surf. B-Biointerfaces
PD NOV 1
PY 2014
VL 123
BP 452
EP 460
DI 10.1016/j.colsurfb.2014.09.042
PG 9
WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biophysics; Chemistry; Materials Science
GA AY4YI
UT WOS:000347580500055
PM 25303852
DA 2022-11-30
ER

PT J
AU Katoh, M
AF Katoh, Masaru
TI Therapeutics targeting angiogenesis: Genetics and epigenetics,
   extracellular miRNAs and signaling networks
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Review
DE bevacizumab; sunitinib; sorafenib; dovitinib; ponatinib; AZD4547; breast
   cancer; lung cancer; colorectal cancer; gastric cancer; field
   cancerization; poly(lactic-co-glycolic acid); chitosan; vascular
   medicine
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR DEVELOPMENT; OVARIAN-CANCER;
   BREAST-CANCER; ANTI-VEGF; THERAPY; CELLS; DELIVERY; DISEASE; BEVACIZUMAB
AB Angiogenesis is a process of neovascular formation from pre-existing blood vessels, which consists of sequential steps for vascular destabilization, angiogenic sprouting, lumen formation and vascular stabilization. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiopoietin, Notch, transforming growth factor-beta (TGF-beta), Hedgehog and WNT signaling cascades orchestrate angiogenesis through the direct or indirect regulation of quiescence, migration and the proliferation of endothelial cells. Small-molecule compounds and human/humanized monoclonal antibodies interrupting VEGF signaling have been developed as anti-angiogenic therapeutics for cancer and neovascular age-related macular degeneration (AMD). Gene or protein therapy delivering VEGF, FGF2 or FGF4, as well as cell therapy using endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been developed as pro-angiogenic therapeutics for ischemic heart disease and peripheral vascular disease. Anti-angiogenic therapy for cancer and neovascular AMD is more successful than pro-angiogenic therapy for cardiovascular diseases, as VEGF-signal interruption is technically feasible compared with vascular re-construction. Common and rare genetic variants are detected using array-based technology and personal genome sequencing, respectively. Drug and dosage should be determined based on personal genotypes of VEGF and other genes involved in angiogenesis. As epigenetic alterations give rise to human diseases, polymer-based hydrogel film may be utilized for the delivery of drugs targeting epigenetic processes and angiogenesis as treatment modalities for cardiovascular diseases. Circulating microRNAs (miRNAs) in exosomes and microvesicles are applied as functional biomarkers for diagnostics and prognostics, while synthetic miRNAs in polymer-based nanoparticles are applicable for therapeutics. A more profound understanding of the spatio-temporal interactions of regulatory signaling cascades and advances in personal genotyping and miRNA profiling are required for the optimization of targeted therapy.
C1 [Katoh, Masaru] Natl Canc Ctr, Div Integrat Omics & Bioinformat, Tokyo 1040045, Japan.
C3 National Cancer Center - Japan
RP Katoh, M (通讯作者)，Natl Canc Ctr, Chuo Ward, 5-1-1 Tsukiji, Tokyo 1040045, Japan.
EM mkatoh-kkr@umin.ac.jp
FU National Cancer Center Research and Development Fund
FX The present study was supported in part by the National Cancer Center
   Research and Development Fund.
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NR 56
TC 108
Z9 111
U1 2
U2 138
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 OCT
PY 2013
VL 32
IS 4
BP 763
EP 767
DI 10.3892/ijmm.2013.1444
PG 5
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 209AL
UT WOS:000323725200003
PM 23863927
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Pechtl, IC
   Kavanagh, D
   Mcintosh, N
   Harris, CL
   Barlow, PN
AF Pechtl, Isabell C.
   Kavanagh, David
   Mcintosh, Nicola
   Harris, Claire L.
   Barlow, Paul N.
TI Disease-associated N-terminal Complement Factor H Mutations Perturb
   Cofactor and Decay-accelerating Activities
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; TRANSLATIONAL
   MINIREVIEW SERIES; MACULAR DEGENERATION; MEMBRANOPROLIFERATIVE
   GLOMERULONEPHRITIS; ALTERNATIVE PATHWAY; REGULATORY DOMAINS;
   ENDOTHELIAL-CELLS; BINDING-AFFINITY; PROTEIN CD46
AB Many mutations associated with atypical hemolytic uremic syndrome (aHUS) lie within complement control protein modules 19-20 at the C terminus of the complement regulator factor H (FH). This region mediates preferential action of FH on self, as opposed to foreign, membranes and surfaces. Hence, speculation on disease mechanisms has focused on deficiencies in regulation of complement activation on glomerular capillary beds. Here, we investigate the consequences of aHUS-linked mutations (R53H and R78G) within the FH N-terminal complement control protein module that also carries the I62V variation linked to dense-deposit disease and age-related macular degeneration. This module contributes to a four-module C3b-binding site (FH1-4) needed for complement regulation and sufficient for fluid-phase regulatory activity. Recombinant FH1-4(V62) and FH1-4(I62) bind immobilized C3b with similar affinities (K-D = 10-14 mu M), whereas FH1-4(I62) is slightly more effective than FH1-4(V62) as cofactor for factor I-mediated cleavage of C3b. The mutant (R53H) FH1-4(V62) binds to C3b with comparable affinity (K-D similar to 12 mu M) yet has decreased cofactor activities both in fluid phase and on surface-bound C3b, and exhibits only weak decay-accelerating activity for C3 convertase (C3bBb). The other mutant, (R78G) FH1-4(V62), binds poorly to immobilized C3b (K-D > 35 mu M) and is severely functionally compromised, having decreased cofactor and decay-accelerating activities. Our data support causal links between these mutations and disease; they demonstrate that mutations affecting the N-terminal activities of FH, not just those in the C terminus, can predispose to aHUS. These observations reinforce the notion that deficiency in any one of several FH functional properties can contribute to the pathogenesis of this disease.
C1 [Pechtl, Isabell C.; Mcintosh, Nicola; Barlow, Paul N.] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Pechtl, Isabell C.; Mcintosh, Nicola; Barlow, Paul N.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JJ, Midlothian, Scotland.
   [Kavanagh, David] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Harris, Claire L.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales.
C3 University of Edinburgh; University of Edinburgh; Newcastle University -
   UK; Cardiff University
RP Barlow, PN (通讯作者)，Univ Edinburgh, Sch Chem, Joseph Black Chem Bldg,Kings Bldg,W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland.
EM Paul.Barlow@ed.ac.uk
RI Barlow, Paul N/G-2853-2011; Kavanagh, David/E-8498-2011
OI Kavanagh, David/0000-0003-4718-0072
FU Medical Research Council United Kingdom [G0701298]; Wellcome Trust
   [081179]; Kidney Research United Kingdom; Academy of Medical Sciences;
   MRC [G0701298] Funding Source: UKRI; Medical Research Council [G0701298]
   Funding Source: researchfish
FX This work was supported by Medical Research Council United Kingdom Grant
   G0701298 (to C. L. H.), Wellcome Trust Grant 081179 (to P. N. B.), and
   the Kidney Research United Kingdom and the Academy of Medical Sciences
   (D. K.).
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NR 64
TC 64
Z9 65
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 1
PY 2011
VL 286
IS 13
BP 11082
EP 11090
DI 10.1074/jbc.M110.211839
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 740LW
UT WOS:000288797100019
PM 21270465
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Gayton, JL
   Seabolt, RA
AF Gayton, Johnny L.
   Seabolt, ReBecca A.
TI Clinical Outcomes of Complex and Uncomplicated Cataractous Eyes After
   Lens Replacement With the AcrySof Toric IOL
SO JOURNAL OF REFRACTIVE SURGERY
LA English
DT Article
ID INTRAOCULAR LENSES; ROTATIONAL STABILITY; ASTIGMATISM; PIECE; SURGERY
AB PURPOSE: To compare outcomes for uncomplicated versus complex eyes after implantation of AcrySof toric intraocular lenses (IOLs) (Alcon Laboratories Inc) in a retrospective series of cataractous astigmatic eyes.
   METHODS: Toric IOLs were implanted in 230 eyes of 162 adult patients. Approximately half (52%, n = 120) the eyes had no complications (uncomplicated group). The other 110 (48%) eyes (complex group) had a variety of complexities, including retinal or macular problems (eg, age-related macular degeneration), angle or pressure problems (eg, glaucoma), or high astigmatism that required adjunctive limbal relaxing incisions (LRIs). Outcomes were retrospectively assessed approximately 6 weeks after surgery.
   RESULTS: Preoperative corneal astigmatism was 1.60 +/- 1.20 diopters (D) overall (1.40 +/- 0.70 D in the uncomplicated group and 1.90 +/- 1.60 D in the complex group). Residual cylinder was 0.40 +/- 0.60 D overall (P < .01 compared to baseline) and was significantly lower (P < .01) for the uncomplicated group (0.30 +/- 0.40 D) than for the complex group (0.50 +/- 0.80 D), which contained the adjunctive LRI subgroup (residual cylinder 0.80 +/- 0.70 D). A larger percentage of uncomplicated eyes (26%) than complex eyes (16%) had at least 20/20 uncorrected distance visual acuity (UDVA) (P = .05). Excluding eyes with intentionally targeted myopic postoperative spherical equivalent, no eyes lost Snellen lines of UDVA, and the average improvement in UDVA was 0.8 +/- 0.6 logMAR. Corrected distance visual acuity of the retinal/macular subgroup was poorer than the uncomplicated group pre- and postoperatively but was significantly improved by the surgery (P < .001; average improvement similar to 3 Snellen lines).
   CONCLUSIONS: AcrySof toric IOLs reduced cylinder and improved UDVA in both complex and uncomplicated eyes with cataractous astigmatism. [J Refract Surg. 2011;27(1):56-62.] doi:10.3928/1081597X-20100325-01
C1 [Gayton, Johnny L.; Seabolt, ReBecca A.] Eyesight Associates, Warner Robins, GA 31088 USA.
RP Gayton, JL (通讯作者)，Eyesight Associates, 216 Corder Rd, Warner Robins, GA 31088 USA.
EM JLGayton@aol.com
CR [Anonymous], 2005, ACRYSOF TOR SINGL PI
   Bauer NJC, 2008, J CATARACT REFR SURG, V34, P1483, DOI 10.1016/j.jcrs.2008.05.031
   BETHKE W, 2009, REV OPHTHALMOL, V16, P43
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NR 14
TC 13
Z9 13
U1 0
U2 6
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1081-597X
J9 J REFRACT SURG
JI J. Refractive Surg.
PD JAN
PY 2011
VL 27
IS 1
BP 56
EP 62
DI 10.3928/1081597X-20100325-01
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 720BM
UT WOS:000287255200009
PM 20415287
DA 2022-11-30
ER

PT J
AU Sheridan, CM
   Pate, S
   Hiscott, P
   Wong, D
   Pattwell, DM
   Kent, D
AF Sheridan, Carl M.
   Pate, Stephanie
   Hiscott, Paul
   Wong, David
   Pattwell, David M.
   Kent, David
TI Expression of hypoxia-inducible factor-1 alpha and-2 alpha in human
   choroidal neovascular membranes
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE RPE; Hypoxia; Choroidal neovascular membranes; Cytokine expression
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; GENE-EXPRESSION;
   HIF-1; HIF-2-ALPHA; HIF-1-ALPHA; PEGAPTANIB
AB Up-regulation of pro-angiogenic cytokine expression occurring secondary to hypoxia in physiologic and pathophysiologic conditions is mediated by the family of transcription regulators know as hypoxia inducible factors (HIF). The present study was undertaken to investigate the expression of HIF occurring in human choroidal neovascularization (CNV) and the posterior segment of young and old eyes.
   Surgically excised CNV from patients with either age-related macular degeneration (AMD; n = 9), punctuate inner choroidopathy (PIC; n = 3) and young normal eyes were immunohistochemically probed with monoclonal antibodies against HIF-1 alpha and -2 alpha and compared to that for cell markers specific for vascular endothelial cells (CD34), macrophages (CD68), retinal pigment epithelial cells (RPE; panel cytokeratins/CK18) and VEGF. Following secondary antibody amplification, reactions were visualized with fast red chromogen.
   Cellular immunoreactivity of membranes for HIF-2 alpha was strong in eight out of nine AMD specimens but it was only weakly positive for HIF-1 alpha in five specimens. In contrast, two out of three PIC specimens were weakly positive for HIF-1 alpha but demonstrated no staining for HIF-2 alpha. Immunohistochemical analysis revealed areas within the CNV membranes that were predominantly immunopositive for CD68 and cytokeratin indicating the presence of RPE and/or macrophages and that these cells strongly co-localized with the presence of HIF and VEGF. No immunochemical co-localization was observed with HIF and the endothelial cell marker CD34 in any membranes studied. Normal globes also demonstrated HIF-2 positivity to be predominantly localized to the central RPE rather than peripheral RPE irrespective of age of donor.
   The localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process.
C1 [Sheridan, Carl M.; Pate, Stephanie; Hiscott, Paul; Wong, David; Pattwell, David M.; Kent, David] Univ Liverpool, Unit Ophthalmol, Sch Clin Sci, Liverpool L69 3GA, Merseyside, England.
   [Wong, David] Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England.
   [Kent, David] Aut Even Hosp, Eye Serv, Kilkenny, Ireland.
C3 University of Liverpool; Royal Liverpool & Broadgreen University
   Hospitals NHS Trust; Royal Liverpool University Hospital; University of
   Liverpool
RP Sheridan, CM (通讯作者)，Univ Liverpool, Unit Ophthalmol, Sch Clin Sci, Daulby St, Liverpool L69 3GA, Merseyside, England.
EM c.sheridan@liverpool.ac.uk
RI Wong, Sai Hung David/D-8482-2015; Sheridan, Carl/AAH-3607-2021
OI Sheridan, Carl/0000-0003-0100-9587
CR Albina JE, 2001, AM J PHYSIOL-CELL PH, V281, pC1971, DOI 10.1152/ajpcell.2001.281.6.C1971
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NR 31
TC 64
Z9 64
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2009
VL 247
IS 10
BP 1361
EP 1367
DI 10.1007/s00417-009-1133-3
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 488AD
UT WOS:000269320000008
PM 19590888
DA 2022-11-30
ER

PT J
AU Wakamatsu, K
   Hu, DN
   McCormick, SA
   Ito, S
AF Wakamatsu, Kazumasa
   Hu, Dan-Ning
   McCormick, Steven A.
   Ito, Shosuke
TI Characterization of melanin in human iridal and choroidal melanocytes
   from eyes with various colored irides
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE melanin; eumelanin; pheomelanin; uveal melanocytes; iridal melanocytes;
   choroidal melanocytes; uveal melanoma; age-related macular degeneration
AB Variance in iris color is related to the incidence of several important ocular diseases, including uveal melanoma and age-related macular degeneration. The purposes of this study were to determine the quantity and the types of melanin in cultured human uveal melanocytes in relation to the iris color. Sixty-one cell cultures of pure uveal melanocytes were isolated from donor eyes with various iris colors. The amount of eumelanin (EM) and pheomelanin (PM) of these cells was measured by chemical degradation and microanalytical high-performance liquid chromatography (HPLC) methods. The total amount of melanin was measured by both microanalytical methods and spectrophotometry. Total melanin content, measured by HPLC and spectrophotometry, correlated well with r = 0.872 (P < 0.0001). The quantity and type of melanin in iridal and choroidal melanocytes showed no significant difference (P > 0.05). When cells became senescent, the levels of EM, PM and total melanin were significantly increased. In both growing and senescent melanocytes, the quantity and type of melanin were closely correlated to the iris color. In cells from eyes with dark-colored irides (dark brown and brown), the amount of EM, the ratio of EM/PM and total melanin were significantly greater than that from eyes with light-colored irides (hazel, green, yellow-brown and blue) (P < 0.0001). The quantity of PM in uveal melanocytes from eyes with light-colored irides was slightly greater than that from dark-colored irides, although not statistically significant (P > 0.05). The present study shows that iris color is determined by both the quantity and the type of melanin in uveal melanocytes. These results suggest a possibility that uveal melanin in eyes with dark-colored irides is eumelanic at the surface and acts as an antioxidant while that in eyes with light-colored irides exposes pheomelanic core and behaves as a pro-oxidant.
C1 Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi, Japan.
   New York Med Coll, New York Eye & Ear Infirm, Dept Pathol, Tissue Culture Ctr, New York, NY USA.
   New York Med Coll, New York Eye & Ear Infirm, Dept Ophthalmol, Tissue Culture Ctr, New York, NY USA.
C3 Fujita Health University; New York Eye & Ear Infirmary of Mount Sinai;
   New York Medical College; New York Eye & Ear Infirmary of Mount Sinai;
   New York Medical College
RP Ito, S (通讯作者)，Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi, Japan.
EM sito@fujita-hu.ac.jp
RI Wakamatsu, Kazumasa/AAZ-5877-2020
OI Wakamatsu, Kazumasa/0000-0003-1748-9001; Ito,
   Shosuke/0000-0001-9182-5144
NR 0
TC 88
Z9 90
U1 0
U2 13
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD FEB
PY 2008
VL 21
IS 1
BP 97
EP 105
DI 10.1111/j.1755-148X.2007.00415.x
PG 9
WC Oncology; Cell Biology; Dermatology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology; Dermatology
GA 258PN
UT WOS:000252879900014
PM 18353148
DA 2022-11-30
ER

PT J
AU Arias, L
   Garcia-Arumi, J
   Ramon, JM
   Badia, M
   Rubio, M
   Pujol, O
AF Arias, Luis
   Garcia-Arumi, J.
   Ramon, J. M.
   Badia, M.
   Rubio, M.
   Pujol, O.
TI Photodynamic therapy with intravitreal triamcinolone in predominantly
   classic choroidal neovascularization - One-year results of a randomized
   study
SO OPHTHALMOLOGY
LA English
DT Article
ID ACETONIDE; ENDOPHTHALMITIS; VERTEPORFIN; INJECTION; CATARACT
AB Purpose: To determine whether intravitreal triamcinolone acetonide (IVTA) improves the efficacy of photodynamic therapy (PDT) with verteporfin in predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
   Design: Prospective randomized study.
   Participants: Sixty-one patients with predominantly classic subfoveal CNV secondary to AMD.
   Methods: Patients were randomized to receive PDT (n = 30) or PDT followed by approximately 11 mg IVTA (n = 31), with retreatment every 3 months when leakage was documented by fluorescein angiography. At baseline and each follow-up visit, best-corrected visual acuity (VA) was measured with Early Treatment Diabetic Retinopathy Study charts by a certified examiner masked to the patient's treatment, lesion size on fluorescein angiography, and foveal thickness on optical coherence tomography.
   Main Outcome Measures: Mean change in VA (logarithm of the minimum angle of resolution [logMAR]) from baseline, percentage of patients losing fewer than 15 letters (3 lines) of VA, mean change in lesion size, mean change in foveal thickness, and retreatment rate.
   Results: At the 12-month follow-up, VA (mean logMAR change from baseline) was significantly better (P = 0.001) in the group of patients who received combined therapy. Seventy-four percent of patients treated with combined therapy compared with 61% treated with verteporfin alone lost fewer than 15 letters of VA (P = 0.78). Reduction in lesion size (P = 0.001) and in foveal thickness (P = 0.03) was significantly greater with combined therapy than with verteporfin. Retreatment rate was significantly lower (P = 0.04) in the combined therapy group. Triamcinolone-related adverse events included glaucoma (25.8%) and cataract progression (32%).
   Conclusions: Combined PDT and IVTA therapy seemed to be more effective than PDT alone for managing predominantly classic subfoveal lesions secondary to AMD. The triamcinolone-related adverse events included glaucoma and cataract progression.
C1 Bellvitge Univ Hosp, Dept Ophthalmol, Hosp Llobregat, Barcelona 08907, Spain.
   Univ Autonoma Barcelona, E-08193 Barcelona, Spain.
   Univ Autonoma Barcelona, Dept Ophthalmol, Hosp Gen Valle Hebron, E-08193 Barcelona, Spain.
   Inst Microcirugia Ocular, Barcelona, Spain.
   Bellvitge Univ Hosp, Dept Prevent Med, Barcelona, Spain.
   Bellvitge Univ Hosp, Dept Pharm, Barcelona, Spain.
C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge
   University Hospital; Autonomous University of Barcelona; Autonomous
   University of Barcelona; Hospital Universitari Vall d'Hebron; Institut
   d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge University
   Hospital; University of Barcelona; Institut d'Investigacio Biomedica de
   Bellvitge (IDIBELL); Bellvitge University Hospital; University of
   Barcelona
RP Arias, L (通讯作者)，Bellvitge Univ Hosp, Dept Ophthalmol, Hosp Llobregat, C Feixa Llarga S-N, Barcelona 08907, Spain.
EM luisarias@telefonica.net
RI Rubio Caso, Marcos Javier/L-6866-2013
OI Rubio Caso, Marcos Javier/0000-0002-7072-9855; Garcia-Arumi,
   Jose/0000-0001-8827-1160; ARIAS, LUIS/0000-0001-7041-5576
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   Schmidt-Erfurth U, 2003, INVEST OPHTH VIS SCI, V44, P4473, DOI 10.1167/iovs.02-1115
   Singh IP, 2004, AM J OPHTHALMOL, V138, P286, DOI 10.1016/j.ajo.2004.03.001
   Smithen LM, 2004, AM J OPHTHALMOL, V138, P740, DOI 10.1016/j.ajo.2004.06.067
   Spaide RF, 2005, OPHTHALMOLOGY, V112, P301, DOI 10.1016/j.ophtha.2004.08.012
   Spaide RF, 2003, OPHTHALMOLOGY, V110, P1517, DOI 10.1016/S0161-6420(03)00544-X
   Spandau UHM, 2005, AM J OPHTHALMOL, V139, P712, DOI 10.1016/j.ajo.2004.09.059
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NR 26
TC 46
Z9 51
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2006
VL 113
IS 12
BP 2243
EP 2250
DI 10.1016/j.ophtha.2006.04.039
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 114KH
UT WOS:000242664600018
PM 16996600
DA 2022-11-30
ER

PT J
AU Mennel, S
   Peter, S
   Meyer, CH
   Thumann, G
AF Mennel, Stefan
   Peter, Silvia
   Meyer, Carsten H.
   Thumann, Gabriele
TI Effect of photodynamic therapy on the function of the outer
   blood-retinal barrier in an in vitro model
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE photodynamic therapy; PDT; blood retinal barrier; BRB; verteporfin;
   retinal pigment epithelium; RPE
ID PIGMENT EPITHELIAL TEAR; CHOROIDAL NEOVASCULARIZATION SECONDARY;
   INDOCYANINE GREEN ANGIOGRAPHY; VERTEPORFIN; DETACHMENT; FLUID
AB Background: Photodynamic therapy (PDT) is a well established clinical treatment for age-related macular degeneration (AMD), and comprises intravenous injection of verteporfin and subsequent application of a non-thermal laser beam to the area of AMD to induce selective vascular occlusion. Since there is evidence that PDT may cause outer blood-retinal barrier (BRB) breakdown and possibly RPE cell alteration, we investigated the effect of PDT on the BRB function of the RPE in an in vitro model. Methods: Twenty-one monolayers of human RPE cells were cultured on semipermeable membranes until a stable barrier function was achieved as determined by transepithelial electrical resistance (TER) and sodium fluorescein permeability. To test the effect of PDT on the outer BRB function, non-thermal laser (692 nm), verteporfin or a combination of both were applied. TER assessment prior to and after PDT was utilized to identify changes in barrier function of the RPE in this in vitro model. Finally, monolayers of RPE cells were evaluated by transmission electron microscopy (TEM). Results: No significant TER decrease was observed after application of non-thermal laser alone or after administration of verteporfin in therapeutic concentrations, but combination of these modalities resulted in significantly decreased TER within 4 h. Except for intercellular blisters, no damage to the RPE was evident in TEM. Verteporfin added at concentrations higher than therapeutic doses (2 mg/ml) resulted in an immediate decrease in TER and damage to the RPE cells. Conclusion: The combination of a therapeutic concentration of verteporfin and application of non-thermal laser resulted in a morphologically and functionally detectable breakdown of the outer BRB function of the RPE without any damage to the RPE cells themselves in vitro. However, increasing the concentration of verteporfin can result in RPE cell damage.
C1 Univ Marburg, Dept Ophthalmol, D-35037 Marburg, Germany.
   Acad Hosp Feldkirch, Dept Ophthalmol, Feldkirch, Austria.
   Univ Cologne, Dept Ophthalmol, Cologne, Germany.
C3 Philipps University Marburg; University of Cologne
RP Mennel, S (通讯作者)，Univ Marburg, Dept Ophthalmol, Robert Koch Str 4, D-35037 Marburg, Germany.
EM stefan.mennel@lycos.com
RI Meyer, Carsten/A-3981-2017
OI Meyer, Carsten/0000-0002-0530-5298
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NR 39
TC 12
Z9 13
U1 1
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 AUG
PY 2006
VL 244
IS 8
BP 1015
EP 1021
DI 10.1007/s00417-005-0237-7
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 070XE
UT WOS:000239559000017
PM 16421742
DA 2022-11-30
ER

PT J
AU Smith, RT
   Chan, JK
   Nagasaki, T
   Ahmad, UF
   Barbazetto, I
   Sparrow, J
   Figueroa, M
   Merriam, J
AF Smith, RT
   Chan, JK
   Nagasaki, T
   Ahmad, UF
   Barbazetto, I
   Sparrow, J
   Figueroa, M
   Merriam, J
TI Automated detection of macular drusen using geometric background
   leveling and threshold selection
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; IMAGE-ANALYSIS; FUNDUS PHOTOGRAPHS; GRADING
   SYSTEM; DEGENERATION; PROGNOSIS; CLASSIFICATION; ABNORMALITIES;
   SEGMENTATION
AB Background: Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD.
   Objectives: To segment and quantify drusen found in patients with ARMD using image analysis and to compare the efficacy of image analysis segmentation with that of stereoscopic manual grading of drusen.
   Design: Retrospective study.
   Setting: University referral center.
   Patients: Photographs were randomly selected from an available database of patients with known ARMD in the ongoing Columbia University Macular Genetics Study. All patients were white and older than 60 years.
   Interventions: Twenty images from 17 patients were selected as representative of common manifestations of drusen. Image preprocessing included automated color balancing and, where necessary, manual segmentation of confounding lesions such as geographic atrophy (3 images). The operator then chose among 3 automated processing options suggested by predominant drusen type. Automated processing consisted of elimination of background variability by a mathematical model and subsequent histogram-based threshold selection. A retinal specialist using a graphic tablet while viewing stereo pairs constructed digital drusen drawings for each image.
   Main Outcome Measures: The sensitivity and specificity of drusen segmentation using the automated method with respect to manual stereoscopic drusen drawings were calculated on a rigorous pixel-by-pixel basis.
   Results: The median sensitivity and specificity of automated segmentation were 70% and 81%, respectively. After preprocessing and option choice, reproducibility of automated drusen segmentation was necessarily 100%.
   Conclusions: Automated drusen segmentation can be reliably performed on digital fundus photographs and result in successful quantification of drusen in a more precise manner than is traditionally possible with manual stereoscopic grading of drusen. With only minor preprocessing requirements, this automated detection technique may dramatically improve our ability to monitor drusen in ARMD.
C1 New York Presbyterian Med Ctr, Edward S Harkness Eye Inst, New York, NY 10032 USA.
   Hosp Ramon y Cajal, Dept Ophthalmol, E-28034 Madrid, Spain.
C3 Hospital Universitario Ramon y Cajal
RP Smith, RT (通讯作者)，New York Presbyterian Med Ctr, Edward S Harkness Eye Inst, Suite 314,635 W 165th St, New York, NY 10032 USA.
EM rts1@columbia.edu
OI smith, theodore/0000-0002-1693-943X
FU NATIONAL EYE INSTITUTE [R01EY015520] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY015520-01A2, R01 EY015520-03, R01 EY015520-04, R01
   EY015520, R01 EY015520-02, R01 EY015520-05] Funding Source: Medline
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NR 26
TC 62
Z9 63
U1 1
U2 5
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 FEB
PY 2005
VL 123
IS 2
BP 200
EP 206
DI 10.1001/archopht.123.2.200
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 893XS
UT WOS:000226755000008
PM 15710816
OA Green Submitted, Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Markert, EK
   Klein, H
   Viollet, C
   Rust, W
   Strobel, B
   Kauschke, SG
   Makovoz, B
   Neubauer, H
   Bakker, RA
   Blenkinsop, TA
AF Markert, Elke K.
   Klein, Holger
   Viollet, Coralie
   Rust, Werner
   Strobel, Benjamin
   Kauschke, Stefan G.
   Makovoz, Bar
   Neubauer, Heike
   Bakker, Remko A.
   Blenkinsop, Timothy A.
TI Transcriptional comparison of adult human primary Retinal Pigment
   Epithelium, human pluripotent stem cell-derived Retinal Pigment
   Epithelium, and ARPE19 cells
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE retinal pigment epithelium; iPSC-RPE; ARPE-19; epithelial to mesenchymal
   transition; age-related macular degeneration; proliferative
   vitreoretinopathy; RNA-sequencing; transplantation
ID MACULAR DEGENERATION; MOLECULAR SIGNATURE; RPE; DISEASE; TISSUE
AB The therapeutic potential of pluripotent stem cells is great as they promise to usher in a new era of medicine where cells or organs may be prescribed to replace dysfunctional tissue. At the forefront are efforts in the eye to develop this technology as it lends itself to in vivo monitoring and sophisticated non-invasive imaging modalities. In the retina, retinal pigment epithelium (RPE) is the most promising replacement cell as it has a single layer, is relatively simple to transplant, and is associated with several eye diseases. However, after transplantation, the cells may transform and cause complications. This transformation may be partially due to incomplete maturation. With the goal of learning how to mature RPE, we compared induced pluripotent stem cell-derived RPE (iPSC-RPE) cells with adult human primary RPE (ahRPE) cells and the immortalized human ARPE-19 line. We cultured ARPE-19, iPSC-RPE, and ahRPE cells for one month, and evaluated morphology, RPE marker staining, and transepithelial electrical resistance (TEER) as quality control indicators. We then isolated RNA for bulk RNA-sequencing and DNA for genotyping. We genotyped ahRPE lines for the top age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR) risk allele polymorphisms. Transcriptome data verified that both adult and iPSC-RPE exhibit similar RPE gene expression signatures, significantly higher than ARPE-19. In addition, in iPSC-RPE, genes relating to stem cell maintenance, retina development, and muscle contraction were significantly upregulated compared to ahRPE. We compared ahRPE to iPSC-RPE in a model of epithelial-mesenchymal transition (EMT) and observed an increased sensitivity of iPSC-RPE to producing contractile aggregates in vitro which resembles incident reports upon transplantation. P38 inhibition was capable of inhibiting iPSC-RPE-derived aggregates. In summary, we find that the transcriptomic signature of iPSC-RPE conveys an immature RPE state which may be ameliorated by targeting "immature " gene regulatory networks.
C1 [Markert, Elke K.; Klein, Holger; Viollet, Coralie; Rust, Werner] Boehringer Ingelheim Pharm GmbH, Global Computat Biol & Digital Sci, Biberach, Germany.
   [Strobel, Benjamin] Boehringer Ingelheim Pharm GmbH, Translat Med & Clin Pharmacol, Biberach, Germany.
   [Kauschke, Stefan G.; Neubauer, Heike; Bakker, Remko A.] Boehringer Ingelheim Pharm GmbH, Cardiometab Dis Res, Biberach, Germany.
   [Makovoz, Bar; Blenkinsop, Timothy A.] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Ophthalmol Cell Dev & Regenerat Biol, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai
RP Blenkinsop, TA (通讯作者)，Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Ophthalmol Cell Dev & Regenerat Biol, New York, NY 10029 USA.
EM timothy.blenkinsop@mssm.edu
FU Boehringer Ingelheim; National Eye Institute (NEI) [1R21EY030215-01,
   1R01EY029736-01A1]; Icahn School of Medicine at Mount Sinai; Research to
   Prevent Blindness
FX We would like to thank the donors for their sacrifice and generosity as
   well as the Eye Bank for Sight Restoration, New York, NY, United States.
   We would also like to thank Boehringer Ingelheim for funding this
   research. Within Boehringer Ingelheim, we thank CardioMetabolic Diseases
   Research members involved in scientific discussions during the
   collaboration. We would like to thank the Challenge Grant award from
   Research to Prevent Blindness, the National Eye Institute (NEI)
   extramural grants 1R21EY030215-01, 1R01EY029736-01A1, and Icahn School
   of Medicine at Mount Sinai for supporting this work.
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NR 30
TC 1
Z9 1
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-634X
J9 FRONT CELL DEV BIOL
JI Front. Cell. Dev. Biol.
PD AUG 26
PY 2022
VL 10
AR 832952
DI 10.3389/fcell.2022.910040
PG 14
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA 5R5OM
UT WOS:000874559800001
PM 36092714
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Paques, M
   Norberg, N
   Chaumette, C
   Sennlaub, F
   Rossi, E
   Borella, Y
   Grieve, K
AF Paques, Michel
   Norberg, Nathaniel
   Chaumette, Celine
   Sennlaub, Florian
   Rossi, Ethan
   Borella, Yse
   Grieve, Kate
TI Long Term Time-Lapse Imaging of Geographic Atrophy: A Pilot Study
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; scanning laser
   ophthalmoscopy; optical coherence tomography; time-lapse imaging
ID RETINAL-PIGMENT EPITHELIUM; OPTICAL COHERENCE TOMOGRAPHY; NEAR-INFRARED
   AUTOFLUORESCENCE; MACULAR DEGENERATION; SUBRETINAL INFLAMMATION; EYES;
   DRY; PREDICTION; CELLS
AB Geographic atrophy (GA), the late stage of age-related macular degeneration, is a major cause of visual disability whose pathophysiology remains largely unknown. Modern fundus imaging and histology revealed the complexity of the cellular changes that accompanies atrophy. Documenting the activity of the disease in the margins of atrophy, where the transition from health to disease occurs, would contribute to a better understanding of the progression of GA. Time-lapse imaging facilitates the identification of structural continuities in changing environments. In this retrospective pilot study, we documented the long-term changes in atrophy margins by time-lapse imaging of infrared scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) images in 6 cases of GA covering a mean period of 32.8 months (range, 18-72). The mean interval between imaging sessions was 2.4 months (range, 1.4-3.8). By viewing time-lapse sequences we observed extensive changes in the pattern of marginal hyperreflective spots, which associated fragmentation, increase and/or disappearance. Over the entire span of the follow-up, the most striking changes were those affecting hyperreflective spots closest to margins of atrophy, on the non-atrophic side of the retina; a continuum between the successive positions of some of the hyperreflective spots was detected, both by SLO and OCT. This continuum in their successive positions resulted in a subjective impression of a centrifugal motion of hyperreflective spots ahead of atrophy progression. Such mobilization of hyperreflective spots was detected up to several hundred microns away from atrophic borders. Such process is likely to reflect the inflammatory and degenerative process underlying GA progression and hence deserves further investigations. These results highlight the interest of multimodal time-lapse imaging to document cell-scale dynamics during progression of GA.
C1 [Paques, Michel; Norberg, Nathaniel; Chaumette, Celine; Borella, Yse; Grieve, Kate] Sorbonne Univ, Quinze Vingts Hosp, Clin Invest Ctr 1423, Paris Eye Imaging Grp,INSERM DHOS, Paris, France.
   [Paques, Michel; Sennlaub, Florian; Borella, Yse; Grieve, Kate] Inst Vis, Paris, France.
   [Rossi, Ethan] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA USA.
C3 CHNO des Quinze-Vingts; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; UDICE-French Research Universities; Sorbonne Universite;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh
RP Paques, M (通讯作者)，Sorbonne Univ, Quinze Vingts Hosp, Clin Invest Ctr 1423, Paris Eye Imaging Grp,INSERM DHOS, Paris, France.; Paques, M (通讯作者)，Inst Vis, Paris, France.
EM mpaques@15-20.fr
FU Region Ile-de-France [EX047007 - SESAME 2019]; LabEx LifeSenses
   [ANR-10-LABX-65]; Institut Hospitalo-Universitaire ForeSIGHT
   [ANR-18-IAHU-01]; Edward N. & Della L. Thome Memorial Foundation
FX This study was funded by the Region Ile-de-France (EX047007 - SESAME
   2019), the LabEx LifeSenses (ANR-10-LABX-65), the Institut
   Hospitalo-Universitaire ForeSIGHT (ANR-18-IAHU-01) and the Edward N. &
   Della L. Thome Memorial Foundation. The funding organizations had no
   role in the design or conduct of this research.
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NR 29
TC 0
Z9 0
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD JUN 22
PY 2022
VL 9
AR 868163
DI 10.3389/fmed.2022.868163
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 2T8BR
UT WOS:000822693800001
PM 35814763
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Anton, N
   Ciuntu, RE
   Chiselita, D
   Danielescu, C
   Alexa, AI
   Cantemir, A
   Bogdanici, CM
   Branisteanu, DC
   Doroftei, B
AF Anton, Nicoleta
   Ciuntu, Roxana Elena
   Chiselita, Dorin
   Danielescu, Ciprian
   Alexa, Anisia Iuliana
   Cantemir, Alina
   Bogdanici, Camelia Margareta
   Branisteanu, Daniel Constantin
   Doroftei, Bogdan
TI Ocular Implications in Patients with Sleep Apnea
SO APPLIED SCIENCES-BASEL
LA English
DT Review
DE eye diseases; dry eye syndrome; obstructive sleep apnea; glaucoma;
   ischemic optic neuropathy; diabetic retinopathy; continuous positive
   airway pressure
ID ISCHEMIC OPTIC NEUROPATHY; RETINAL VEIN OCCLUSION; ASSOCIATION;
   GLAUCOMA; MANIFESTATIONS; DISEASES
AB Sleep apnea syndrome (SAS) is a condition characterized by recurrent episodes of total or partial collapse of the upper respiratory tract associated with daytime drowsiness that cannot be explained by other factors. SAS is a pathology that can cause ophthalmological damage both directly through the pathophysiological mechanism characteristic of the disease on the ocular system, and indirectly by promoting the development of other pathologies (cardiovascular, metabolic), which are a risk factor for ocular morbidity in the absence of sleep apnea syndrome. The aim of this paper is to highlight the ocular symptoms determined by sleep apnea syndrome (SAS), by analyzing literature over the past 20 years. Method: A mini-review that collected data from Pub Med Central, ResearchGate, GoogleScholar, DovePress, ScienceDirect, Elsevier, related to the ocular implications given by sleep apnea syndrome, with or without continuous positive airway pressure (CPAP) treatment. The study included articles that identified a number of eye conditions associated with sleep apnea, such as: dry eye syndrome and impaired ocular surface, glaucoma, non-arteritic anterior ischemic optic neuropathy, floppy eyelid syndrome, keratoconus, central serous chorioretinopathy, central vein occlusion, corneal neovascularization, and age-related macular degeneration. Sleep apnea syndrome is a pathology that can cause the onset or worsening of varying degrees of severity eye diseases by its pathophysiological mechanism, with a different impact on the quality of the individual's life. On one hand, the purpose of this review is to identify studies in literature that associate sleep apnea syndrome with eye alterations; on the other hand, to inform the Romanian medical staff in different fields of the patients' guidance diagnosed with SAS to an ophthalmology clinic since early and mild symptoms, so that these patients benefit from an ophthalmological approach and monitoring, in an attempt to diagnose and treat eye diseases in time and prevent their worsening.
C1 [Anton, Nicoleta; Ciuntu, Roxana Elena; Danielescu, Ciprian; Alexa, Anisia Iuliana; Bogdanici, Camelia Margareta; Branisteanu, Daniel Constantin] Grigore T Popa Univ Med & Pharm, Dept Ophthalmol, Iasi 700115, Romania.
   [Chiselita, Dorin; Cantemir, Alina] Oftaprof Ophthalmol Clin, Iasi 700327, Romania.
   [Doroftei, Bogdan] Grigore T Popa Univ Med & Pharm, Fac Med, Mother & Child Med Dept, 16 Univ St, Iasi 700115, Romania.
C3 Grigore T Popa University of Medicine & Pharmacy; Grigore T Popa
   University of Medicine & Pharmacy
RP Ciuntu, RE; Bogdanici, CM; Branisteanu, DC (通讯作者)，Grigore T Popa Univ Med & Pharm, Dept Ophthalmol, Iasi 700115, Romania.
EM roxana-elena.ciuntu@umfiasi.ro; ciprian.danielescu@umfiasi.ro;
   alina.cantemir@gmail.com; camelia.bogdanici@umfiasi.ro;
   daniel.branisteanu@umfiasi.ro; bogdandoroftei@gmail.com
RI Branisteanu, Daniel Constantin/AGZ-3495-2022; Bogdanici,
   Camelia/AAA-7575-2022; Danielescu, Ciprian/GWC-1642-2022; Doroftei,
   Bogdan/K-9442-2014
OI Danielescu, Ciprian/0000-0002-1639-2921; Anton,
   Nicoleta/0000-0002-4987-5049; Doroftei, Bogdan/0000-0002-6618-141X
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NR 47
TC 0
Z9 0
U1 3
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3417
J9 APPL SCI-BASEL
JI Appl. Sci.-Basel
PD NOV
PY 2021
VL 11
IS 21
AR 10086
DI 10.3390/app112110086
PG 10
WC Chemistry, Multidisciplinary; Engineering, Multidisciplinary; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering; Materials Science; Physics
GA WX3ZP
UT WOS:000718538300001
OA gold
DA 2022-11-30
ER

PT J
AU Burri, C
   Al-Nawaiseh, S
   Wakili, P
   Salzmann, S
   Krotz, C
   Povazay, B
   Meier, C
   Frenz, M
   Szurman, P
   Schulz, A
   Stanzel, B
AF Burri, Christian
   Al-Nawaiseh, Sami
   Wakili, Philip
   Salzmann, Simon
   Kroetz, Christina
   Povazay, Boris
   Meier, Christoph
   Frenz, Martin
   Szurman, Peter
   Schulz, Andre
   Stanzel, Boris
TI Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond
   Laser in Preparation for Cell Therapy
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE cell therapy; RPE removal; RPE transplantation; selective retina
   therapy; laser microsurgery
ID ROD-SIGNAL INTERNEURONS; MACULAR DEGENERATION; RABBIT RETINA; RPE;
   TRANSPLANTATION; DAMAGE; THRESHOLD
AB Purpose: Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases such as age-related macular degeneration. Herein, selective microsecond laser irradiation targeting RPE cells was used for minimally invasive, large-area RPE removal in preparation for delivery of retinal cell therapeutics.
   Methods: Ten rabbit eyes were exposed to laser pulses 8, 12, 16, and 20 mu s in duration (wavelength, 532 nm; top-hat beam profile, 223 x 223 mu m(2)). Post-irradiation retinal changes were assessed with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). RPE viability was evaluated with an angiographic probit model. Following vitrectomy, a subretinal injection of balanced salt solution was performed over a lasered (maximum 13.6 mm(2)) and untreated control area. Bleb retinal detachment (bRD) morphology was then evaluated by intraoperative OCT.
   Results: Within 1 hour after irradiation, laser lesions showed FA and ICGA leakage. OCT revealed that large-area laser damage was limited to the RPE. The angiographic median effective dose irradiation thresholds (ED50) were 45 mu J (90 mJ/cm(2)) at 8 mu s, 52 mu J (104 mJ/cm(2)) at 12 mu s, 59 mu J (118 mJ/cm(2)) at 16 mu s, and 71 mu J (142 mJ/cm(2)) at 20 mu s. Subretinal injection over the lasered area resulted in a controlled, shallow bRD rise, whereas control blebs were convex in shape, with less predictable spread.
   Conclusions: Large-area, laser-based removal of host RPE without visible photoreceptor damage is possible and facilitates surgical retinal detachment.
   Translational Relevance: Selective microsecond laser-based, large-area RPE removal prior to retinal cell therapy may reduce iatrogenic trauma.
C1 [Burri, Christian; Salzmann, Simon; Povazay, Boris; Meier, Christoph] Bern Univ Appl Sci, Inst Human Ctr Engn HuCE OptoLab, Biel, Switzerland.
   [Burri, Christian; Frenz, Martin] Univ Bern, Inst Appl Phys, Biomed Photon Grp, Bern, Switzerland.
   [Al-Nawaiseh, Sami; Wakili, Philip; Szurman, Peter; Schulz, Andre; Stanzel, Boris] Knappschaft Hosp Saar, Eye Clin Sulzbach, Klin 10, D-66280 Sulzbach, Saar, Germany.
   [Al-Nawaiseh, Sami] Univ Munster, Dept Ophthalmol, Munster, Germany.
   [Kroetz, Christina] Fraunhofer Inst Biomed Engn, Sulzbach, Saar, Germany.
   [Szurman, Peter; Schulz, Andre; Stanzel, Boris] Klaus Heimann Eye Res Inst, Sulzbach, Saar, Germany.
C3 University of Bern; University of Munster; Fraunhofer Gesellschaft
RP Stanzel, B (通讯作者)，Knappschaft Hosp Saar, Eye Clin Sulzbach, Klin 10, D-66280 Sulzbach, Saar, Germany.
EM boris.stanzel@kksaar.de
RI Stanzel, Boris/AAG-7010-2022; Stanzel, Boris/ADP-9221-2022
OI Stanzel, Boris/0000-0002-4316-1539; Stanzel, Boris/0000-0002-4316-1539;
   Burri, Christian/0000-0003-2690-7527; Salzmann,
   Simon/0000-0001-5453-8808
FU Swiss National Science Foundation [325230-141189, 323523163306]; Swiss
   Innovation Agency [KTI 25030.1 PFLS-LS, BMBF 01EK1613A, DFG STA
   1135/2-1]
FX Supported by grants from the Swiss National Science Foundation
   (325230-141189 and 323523163306) and from the Swiss Innovation Agency
   (KTI 25030.1 PFLS-LS: ReSight Consortium BMBF 01EK1613A to BVS; DFG STA
   1135/2-1 to BVS).
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NR 55
TC 0
Z9 0
U1 1
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD AUG
PY 2021
VL 10
IS 10
SI SI
BP 1
EP 15
AR 17
DI 10.1167/tvst.10.10.17
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YH2BT
UT WOS:000742978300001
PM 34842907
OA gold, Green Published
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: Receiver-Operating Characteristic (ROC)
   Analysis for Correlated Eye Data
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Ocular test; area under ROC curve; ROC analysis; cluster bootstrap;
   correlated eye data
ID MACULAR DEGENERATION; CHARACTERISTIC CURVE; SEVERITY SCALE; BOOTSTRAP;
   RETINOPATHY; AREA
AB Purpose: To demonstrate methods for receiver-operating characteristic (ROC) analysis of correlated eye data. Methods: We applied the Obuchowski's nonparametric approach and cluster bootstrap for estimating and comparing the area under ROC curve (AUC) between different sets of predictors to three datasets with varying inter-eye correlation. Results: In an optic neuritis (ON) study of 152 eyes (80 patients), the AUC of optical coherence tomography retinal nerve fiber layer thickness for diagnosing ON (inter-eye kappa = 0.13) was 0.71 [95% confidence interval (95% CI): 0.622, 0.792] from the naive approach without accounting for inter-eye correlation was narrower than from nonparametric (95% CI: 0.613, 0.801) or cluster bootstrap (95% CI: 0.614, 0.797) approaches. In an analysis of 198 eyes (135 patients), the baseline Age-related Eye disease Study scale predicted 5-year incidence of advanced age-related macular degeneration (inter-eye kappa = 0.23) with AUC of 0.72. The 95% CI from the naive approach was slightly narrower (0.645, 0.794) than from the nonparametric (0.641, 0.797) or cluster bootstrap (0.641, 0.793) approaches. In an analysis of 1542 eyes (771 infants), birthweight and gestational age predicted treatment-requiring retinopathy of prematurity (inter-eye kappa = 0.98) with AUC of 0.80. Furthermore, the 95% CI from the naive approach was narrower (0.769, 0.835) than from the nonparametric (0.755, 0.848) or cluster bootstrap (0.755, 0.845) approaches. 95% CIs for AUC differences between different models were narrower in the naive approach than the nonparametric or cluster bootstrap approaches. Conclusion: In ROC analysis of correlated eye data, ignoring inter-eye correlation leads to narrower 95% CI with underestimation dependent on magnitude of inter-eye correlation. Nonparametric and cluster bootstrap approaches properly account for inter-eye correlation.
C1 [Ying, Gui-Shuang; Maguire, Maureen G.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Ctr Prevent Ophthalmol & Biostat, 3711 Market St,Suite 801, 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, 75 Francis St, Boston, MA 02115 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, 3711 Market St,Suite 801, 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 27
TC 1
Z9 1
U1 0
U2 4
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 2022
VL 29
IS 2
BP 117
EP 127
DI 10.1080/09286586.2021.1921226
EA MAY 2021
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0U4EZ
UT WOS:000649628400001
PM 33977829
DA 2022-11-30
ER

PT J
AU Chen, X
   Zuo, J
   Hu, TM
   Shi, XQ
   Zhu, YJ
   Wu, H
   Xia, Y
   Shi, W
   Wei, W
AF Chen, Xi
   Zuo, Jing
   Hu, Tianming
   Shi, Xiaoqing
   Zhu, Yujie
   Wu, Hao
   Xia, Ying
   Shi, Wei
   Wei, Wei
TI Exploration of the Effect and Mechanism of Fructus Lycii, Rehmanniae
   Radix Praeparata, and Paeonia lactiflora in the Treatment of AMD Based
   on Network Pharmacology and in vitro Experimental Verification
SO DRUG DESIGN DEVELOPMENT AND THERAPY
LA English
DT Article
DE age-related macular degeneration; Fructus Lycii; Rehmanniae Radix
   Praeparata; Paeonia lactiflora; network pharmacology; oxidative stress
ID OXIDATIVE STRESS; PREDICTION; APOPTOSIS
AB Purpose: The aim of this study was to observe the mechanism of Fructus Lycii (FL), Rehmanniae Radix Praeparata (RRP) and Paeonia lactiflora (PL) in treating age-related macular degeneration (AMD) based on network pharmacology and biological experiments.
   Methods: Bioactive compounds, potential targets of FL, RRP and PL, and genes related to AMD, were acquired from public databases. Functional and pathway enrichment analyses of the core targets were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the finding was further verified with cell experiments. The MTT assay and flow cytometric analysis were used to assess cell viability and apoptosis. The production of reactive oxygen species (ROS) was analyzed by DCFH-DA staining; the activity of antioxidant enzymes was chemically measured with assay kits. The expression of key proteins was evaluated by Western blot analysis.
   Results: Fifty-nine active compounds, 182 potential targets, and 2536 AMD-related human genes were identified. A total of 103 key targets of the three herbs on AMD were identified by protein-protein interaction (PPI) analysis. The abovementioned targets were correlated with nuclear receptor activity, oxidative stress, and apoptosis pathways according to the GO and KEGG analyses. MTT assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with the three herbs significantly increased cell viability and decreased apoptosis induced by H2O2. The three herbs might reduce the intracellular ROS levels and increase the SOD and CAT activities after H2O2. Furthermore, the three herbs significantly inhibited oxidative stress via increasing the expression of Nrf2, HO-1 and NQO1.
   Conclusion: The combined results of network pharmacology and validation experiments showed that FL, RRP and PL reduce oxidative stress and apoptosis in RPE cells to exert its effect in the treatment of AMD.
C1 [Chen, Xi; Shi, Xiaoqing; Zhu, Yujie; Wei, Wei] Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Xi; Zuo, Jing; Hu, Tianming; Shi, Xiaoqing; Zhu, Yujie; Wu, Hao; Xia, Ying; Shi, Wei; Wei, Wei] Nanjing Univ Chinese Med, Affiliated Hosp, Dept Ophthalmol, 155 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
   [Chen, Xi; Shi, Xiaoqing; Zhu, Yujie] 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 Shi, W; Wei, W (通讯作者)，Nanjing Univ Chinese Med, Affiliated Hosp, Dept Ophthalmol, 155 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
EM Shiwei-1218@163.com; 13951776603@163.com
FU National Natural Science Foundation of China [81774370]
FX The current work was supported by the National Natural Science
   Foundation of China (No. 81774370).
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NR 44
TC 2
Z9 3
U1 10
U2 18
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 2021
VL 15
BP 2831
EP 2842
DI 10.2147/DDDT.S310481
PG 12
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA TB1UC
UT WOS:000667729200001
PM 34234414
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nguyen, AAK
   Turner, A
AF Nguyen, Andrew Anh Kiet
   Turner, Angus
TI Follow-up rates for patients needing regular intravitreal therapy in
   rural north-western Western Australia
SO RURAL AND REMOTE HEALTH
LA English
DT Article
DE diabetic macula oedema; intravitreal injection; ophthalmology; Western
   Australia
AB Introduction: Regular intravitreal injections are an important treatment for significant vision impairment caused by diabetic macular oedema. Barriers to intravitreal treatment for rural Australian patients include travel time to appointments, especially as patients face a high volume of other medical appointments for their diabetes and related co-morbidities. This audit addresses intravitreal injection compliance by identifying patients lost to follow up in north-western Western Australia.
   Methods: A retrospective audit of all injections was performed in the Pilbara and Kimberley between January and December 2018. Outcome measures included total injections, number of injection patients, rates of patients lost to follow-up by region, Aboriginal and Torres Strait Islander status and diagnosis. The audit was extended to include the first 6 months of 2019 to ensure further treatment plan timeframes had lapsed.
   Results: A total of 140 patients received injections, resulting in 346 injections. Ten patients were excluded due to relocation to another region and three patients were deceased. Seventeen patients were lost to follow-up (12.1%). Of those lost to follow-up, 14.3% were in the Pilbara region and 10% in the Kimberley region. Similar rates with respect to Indigenous status with 12.6% identifying as Aboriginal and 11.4% not. 15.8% were treated for diabetic macular oedema and 3.8% for age-related macular degeneration.
   Conclusion: The logistics of providing appropriate intravitreal therapy, including scheduling timely visits and working in hospital and community-controlled settings, requires a specific focus on those needing intravitreal treatment. The study highlights the importance of coordination and systems to enable patients to receive injections in remote settings. Further analysis of optimal patient management plans for appropriate frequency and treatment outcomes is required.
C1 [Nguyen, Andrew Anh Kiet; Turner, Angus] Lions Eye Inst, Lions Outback Vis, Nedlands, WA 6009, Australia.
C3 Lions Eye Institute; University of Western Australia
RP Nguyen, AAK (通讯作者)，Lions Eye Inst, Lions Outback Vis, Nedlands, WA 6009, Australia.
EM nguyenaak@gmail.com
CR Copeland S, 2017, AUST J RURAL HEALTH, V25, P268, DOI 10.1111/ajr.12348
   Insight, LACK FUND NONCL SUPP
   Schnabel R, 2016, VALUE HEALTH, V19, pA844, DOI 10.1016/j.jval.2016.08.508
   Yashadhana A, 2020, MED J AUSTRALIA, V212, P222, DOI 10.5694/mja2.50480
NR 4
TC 0
Z9 0
U1 0
U2 0
PU COLL MEDICINE & DENTISTRY JAMES COOK UNIV TOWNSVILLE
PI DOUGLAS
PA 1 JAMES COOK DR, DOUGLAS, QUEENSLAND, AUSTRALIA
SN 1445-6354
J9 RURAL REMOTE HEALTH
JI Rural Remote Health
PY 2021
VL 21
IS 3
AR 6001
DI 10.22605/RRH6001
PG 3
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA XD2SC
UT WOS:000722558700021
PM 34376054
OA gold
DA 2022-11-30
ER

PT J
AU Bae, K
   Cho, K
   Kang, SW
   Kim, SJ
   Kim, JM
AF Bae, Kunho
   Cho, Kyuyeon
   Kang, Se Woong
   Kim, Sang Jin
   Kim, Jong Min
TI Peripheral Reticular Pigmentary Degeneration and Choroidal Vascular
   Insufficiency, Studied by Ultra Wide-Field Fluorescein Angiography
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; FUNDUS APPEARANCE; CIRCULATION; EPITHELIUM;
   DYSTROPHY; DRUSEN
AB Purpose
   To explore the pathogenesis of peripheral reticular pigmentary degeneration (PRPD) and its clinical significance.
   Methods
   This cross-sectional, observational study (conducted between January 2010 and May 2015) enrolled 441 eyes of 229 subjects, including 35 eyes with PRPD and 406 eyes without PRPD, which was identified by ultra-wide-field fluorescein angiography (UWFA). The distribution and angiographic circulation time of PRPD were assessed by UWFA. The frequencies of systemic and ophthalmologic comorbidities were compared between groups. Univariate and multivariate generalized estimation equation methods were used to determine the risk factors for PRPD.
   Results
   The patients with PRPD had a mean age of 75.7 +/- 8.5 years (range, 59-93 years), whereas the patients without PRPD had a mean age of 60.1 +/- 14.9 years (range, 9-92 years). All eyes with PRPD manifested the lesion in the superior nasal periphery with or without circumferential extension. Among those, only 16 eyes (45.7%) in the PRPD group showed distinctive features in the same location on fundus photographs. There was significant choroidal filling delay in the PRPD group when compared with the control group (1.42 +/- 1.22 vs.-0.02 +/- 1.05 seconds, P < 0.001). Multivariate regression analysis revealed that older age (P < 0.001), stroke (P= 0.018), ischemic optic neuropathy (P < 0.001), and age-related macular degeneration (P = 0.022) were significantly associated with PRPD.
   Conclusions
   UWFA may enhance the diagnostic sensitivity of PRPD. Choroidal vascular insufficiency with compromised systemic circulation in the elderly was related to the manifestation of PRPD. These results help to better understand the pathophysiology of PRPD. Co-existence of systemic and ophthalmic circulatory disorders should be considered in patients with PRPD.
C1 [Bae, Kunho; Cho, Kyuyeon; Kang, Se Woong; Kim, Sang Jin; Kim, Jong Min] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center
RP Kang, SW (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea.
EM swkang@skku.edu
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NR 30
TC 10
Z9 10
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 23
PY 2017
VL 12
IS 1
AR e0170526
DI 10.1371/journal.pone.0170526
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EN6QR
UT WOS:000396129000063
PM 28114409
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Yang, PM
   Wu, ZZ
   Zhang, YQ
   Wung, BS
AF Yang, Po-Min
   Wu, Zhi-Zhen
   Zhang, Yu-Qi
   Wung, Being-Sun
TI Lycopene inhibits ICAM-1 expression and NF-kappa B activation by
   Nrf2-regulated cell redox state in human retinal pigment epithelial
   cells
SO LIFE SCIENCES
LA English
DT Article
DE Lycopene; Intercellular adhesion molecule-1; Nuclear factor-kappa B;
   Nrf2; Retinal pigment epithelial cell
ID MACULAR DEGENERATION; HEME OXYGENASE-1; INFLAMMATORY CYTOKINES;
   ANTIOXIDANT RESPONSE; TRANSCRIPTION FACTOR; ADHESION MOLECULES;
   ENDOTHELIAL-CELLS; OXIDATIVE STRESS; NRF2; CAROTENOIDS
AB Aims: Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells.
   Main methods: We exposed ARPE-19 cells to TNF alpha after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-kappa B nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA.
   Key findings: Lycopene could reduce TNF-alpha-induced monocyte adhesion and H2O2-induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-kappa B activation for up to 12 h in TNF alpha-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-alpha-induced ICAM-1 expression and NF-kappa B activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-alpha-induced ROS production was abolished.
   Significance: The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-kappa B activation in lycopene-treated ARPE-19 cells. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Yang, Po-Min] Chiayi Christian Hosp, Dept Ophthalmol, Chiayi, Taiwan.
   [Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun] Natl Chiayi Univ, Dept Microbiol Immunol & Biopharmaceut, Chiayi 60004, Taiwan.
C3 Chia-Yi Christian Hospital; National Chiayi University
RP Wung, BS (通讯作者)，Natl Chiayi Univ, Dept Microbiol Immunol & Biopharmaceut, Chiayi 60004, Taiwan.
EM bswung@mail.ncyu.edu.tw
FU National Science Council of Taiwan [102-2320-B-415-002-MY3]; Chiayi
   Christian Hospital [R103-10]
FX This work was supported by grants from the National Science Council of
   Taiwan (102-2320-B-415-002-MY3) and from Chiayi Christian Hospital
   (R103-10).
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NR 35
TC 25
Z9 27
U1 1
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
EI 1879-0631
J9 LIFE SCI
JI Life Sci.
PD JUN 15
PY 2016
VL 155
BP 94
EP 101
DI 10.1016/j.lfs.2016.05.006
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DO1LW
UT WOS:000377540700013
PM 27155396
DA 2022-11-30
ER

PT J
AU Novais, EA
   Adhi, M
   Moult, EM
   Louzada, RN
   Cole, ED
   Husvogt, L
   Lee, B
   Dang, S
   Regatieri, CVS
   Witkin, AJ
   Baumal, CR
   Hornegger, J
   Jayaraman, V
   Fujimoto, JG
   Duker, JS
   Waheed, NK
AF Novais, Eduardo A.
   Adhi, Mehreen
   Moult, Eric M.
   Louzada, Ricardo N.
   Cole, Emily D.
   Husvogt, Lennart
   Lee, Byungkun
   Dang, Sabin
   Regatieri, Caio V. S.
   Witkin, Andre J.
   Baumal, Caroline R.
   Hornegger, Joachim
   Jayaraman, Vijaysekhar
   Fujimoto, James G.
   Duker, Jay S.
   Waheed, Nadia K.
TI Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source
   Optical Coherence Tomography Angiography Compared to Spectral-Domain
   Optical Coherence Tomography Angiography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AMPLITUDE-DECORRELATION ANGIOGRAPHY; INDOCYANINE GREEN ANGIOGRAPHY;
   MACULAR DEGENERATION; SOURCE OCT; FLUORESCEIN ANGIOGRAPHY; MOTION
   CORRECTION; NORMAL EYES; VASCULOPATHY; THICKNESS; NM
AB PURPOSE: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMID) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device.
   DESIGN: Comparative analysis of diagnostic instruments.
   METHODS: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at 840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long wavelength prototype that operates at 1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant.
   RESULTS: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm x 3 mm OCTA were 0.949 +/- 1.168 mm(2) and 0.340 +/- 0.301 mm(2), respectively (P = .001). For the 6 mm x 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 +/- 1.284 mm(2) and 0.604 +/- 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively).
   CONCLUSION: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature. (C) 2016 by Elsevier Inc. All rights reserved.
C1 [Novais, Eduardo A.; Adhi, Mehreen; Louzada, Ricardo N.; Cole, Emily D.; Dang, Sabin; Regatieri, Caio V. S.; Witkin, Andre J.; Baumal, Caroline R.; Duker, Jay S.; Waheed, Nadia K.] Tufts Med Ctr, New England Eye Ctr, 260 Tremont St,Biewend Bldg,9-11th Floor, Boston, MA 02116 USA.
   [Novais, Eduardo A.; Regatieri, Caio V. S.] Univ Fed Sao Paulo, Sch Med, Sao Paulo, Brazil.
   [Adhi, Mehreen; Moult, Eric M.; Cole, Emily D.; Husvogt, Lennart; Lee, Byungkun; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA.
   [Louzada, Ricardo N.] Univ Fed Goias, Goiania, Go, Brazil.
   [Husvogt, Lennart; Hornegger, Joachim] Univ Erlangen Nurnberg, Pattern Recognit Lab, D-91054 Erlangen, Germany.
   [Hornegger, Joachim] Erlangen Grad Sch Adv Opt Technol SAOT, Erlangen, Germany.
   [Jayaraman, Vijaysekhar] Praevium Res Inc, Santa Barbara, CA USA.
C3 Tufts Medical Center; Universidade Federal de Sao Paulo (UNIFESP);
   Massachusetts Institute of Technology (MIT); Universidade Federal de
   Goias; University of Erlangen Nuremberg; University of Erlangen
   Nuremberg
RP Waheed, NK (通讯作者)，Tufts Med Ctr, New England Eye Ctr, 260 Tremont St,Biewend Bldg,9-11th Floor, Boston, MA 02116 USA.
EM nadiakwaheed@gmail.com
RI Moult, Eric/G-1099-2017; Regatieri, Caio/G-8152-2014; Adhi,
   Mehreen/AAS-9733-2021; Hornegger, Joachim/H-2465-2017; Jayaraman,
   Vijaysekhar/GLR-7595-2022
OI Moult, Eric/0000-0003-3859-3094; Regatieri, Caio/0000-0003-1511-8696;
   Hornegger, Joachim/0000-0002-1834-8844; 
FU MACULA VISION RESEARCH FOUNDATION, New York; National Institutes of
   Health [NIH R01-EY011289-28, R44-EY022864-03, R01-CA075289-17]; Air
   Force Office of Scientific Research [AFOSR FA9550-10-1-0551,
   FA9550-12-1-0499]; Thorlabs matching funds to Praevium Research Inc;
   MVRF grant to study wet AMD; Massachusetts Lions Clubs; Samsung
   Scholarship; Natural Sciences and Engineering Research Council of Canada
   Scholarship; CAPES Foundation, Ministry of Education of Brazil,
   Brasilia, DF, Brazil; NATIONAL CANCER INSTITUTE [R01CA075289] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [R01EY011289, R44EY022864]
   Funding Source: NIH RePORTER
FX THIS WORK WAS SUPPORTED IN PART BY A GRANT FROM THE MACULA VISION
   RESEARCH FOUNDATION, New York; National Institutes of Health (NIH
   R01-EY011289-28, R44-EY022864-03, R01-CA075289-17); Air Force Office of
   Scientific Research (AFOSR FA9550-10-1-0551 and FA9550-12-1-0499);
   Thorlabs matching funds to Praevium Research Inc; and an MVRF grant to
   study wet AMD. Additional support was received from the Massachusetts
   Lions Clubs, a Samsung Scholarship, and a Natural Sciences and
   Engineering Research Council of Canada Scholarship. Eduardo A. Novais
   and Ricardo N. Louzada are researchers supported by CAPES Foundation,
   Ministry of Education of Brazil, Brasilia, DF, Brazil.
CR Adhi M, 2014, AM J OPHTHALMOL, V157, P1272, DOI 10.1016/j.ajo.2014.02.034
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NR 33
TC 117
Z9 119
U1 0
U2 13
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 APR
PY 2016
VL 164
BP 80
EP 88
DI 10.1016/j.ajo.2016.01.011
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DI7CS
UT WOS:000373657300011
PM 26851725
OA Green Accepted, Green Published, Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Khanna, RC
   Murthy, GVS
   Marmamula, S
   Mettla, AL
   Giridhar, P
   Banerjee, S
   Shekhar, K
   Chakrabarti, S
   Gilbert, C
   Rao, GN
AF Khanna, Rohit C.
   Murthy, Gudlavalleti V. S.
   Marmamula, Srinivas
   Mettla, Asha Latha
   Giridhar, Pyda
   Banerjee, Seema
   Shekhar, Konegari
   Chakrabarti, Subhabrata
   Gilbert, Clare
   Rao, Gullapalli N.
CA Andhra Pradesh Eye Dis Study Grp
TI Longitudinal Andhra Pradesh Eye Disease Study: rationale, study design
   and research methodology
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Andhra Pradesh Eye Disease Study; cohort; incidence; progression; risk
   factors
ID BEAVER-DAM EYE; VISUAL IMPAIRMENT SURVEY; AGE-RELATED MACULOPATHY;
   ANGLE-CLOSURE GLAUCOMA; NATIONAL BLINDNESS; SOUTHERN INDIA;
   RISK-FACTORS; MACULAR DEGENERATION; URBAN-POPULATION; 4-YEAR INCIDENCE
AB BackgroundThe rationale, objectives, study design and procedures for the longitudinal Andhra Pradesh Eye Disease Study are described.
   DesignA longitudinal cohort study was carried out.
   ParticipantsParticipants include surviving cohort from the rural component of Andhra Pradesh Eye Disease Study.
   MethodsDuring 1996-2000, Andhra Pradesh Eye Disease Survey was conducted in three rural (n=7771) and one urban (n=2522) areas (now called Andhra Pradesh Eye Disease Study 1). In 2009-2010, a feasibility exercise (Andhra Pradesh Eye Disease Study 2) for a longitudinal study (Andhra Pradesh Eye Disease Study 3) was undertaken in the rural clusters only, as urban clusters no longer existed. In Andhra Pradesh Eye Disease Study 3, a detailed interview will be carried out to collect data on sociodemographic factors, ocular and systemic history, risk factors, visual function, knowledge of eye diseases and barriers to accessing services. All participants will also undergo a comprehensive eye examination including photography of lens, optic disc and retina, Optic Coherence Tomography of the posterior segment, anthropometry, blood pressure and frailty measures.
   Main Outcome MeasuresMeasures include estimates of the incidence of visual impairment and age-related eye disease (lens opacities, glaucoma and age-related macular degeneration) and the progression of eye disease (lens opacities and myopia) and associated risk factors.
   ResultsOf the 7771 respondents examined in rural areas in Andhra Pradesh Eye Disease Study 1, 5447 (70.1%) participants were traced in Andhra Pradesh Eye Disease Study 2. These participants will be re-examined.
   ConclusionsAndhra Pradesh Eye Disease Study 3 will provide data on the incidence and progression of visual impairment and major eye diseases and their associated risk factors in India. The study will provide further evidence to aid planning eye care services.
C1 [Khanna, Rohit C.; Marmamula, Srinivas; Mettla, Asha Latha; Giridhar, Pyda; Banerjee, Seema; Shekhar, Konegari; Rao, Gullapalli N.] LV Prasad Eye Inst, Gullapalli Pratibha Rao Int Ctr Adv Rural Eye Car, Allen Foster Community Eye Hlth Res Ctr, Hyderabad 500034, Andhra Pradesh, India.
   [Khanna, Rohit C.; Marmamula, Srinivas; Mettla, Asha Latha; Giridhar, Pyda; Banerjee, Seema; Shekhar, Konegari; Chakrabarti, Subhabrata; Rao, Gullapalli N.] LV Prasad Eye Inst, Brien Holden Eye Res Ctr, Banjara Hills, Hyderabad 500034, Andhra Pradesh, India.
   [Khanna, Rohit C.; Murthy, Gudlavalleti V. S.] Indian Inst Publ Hlth, Hyderabad, Andhra Pradesh, India.
   [Murthy, Gudlavalleti V. S.; Gilbert, Clare] London Sch Hyg & Trop Med, Dept Clin Res, Int Ctr Eye Hlth, London WC1, England.
C3 L. V. Prasad Eye Institute; L. V. Prasad Eye Institute; University of
   London; London School of Hygiene & Tropical Medicine
RP Khanna, RC (通讯作者)，LV Prasad Eye Inst, Kallam Anji Reddy Campus,Rd 2,Banjara Hills, Hyderabad 500034, Andhra Pradesh, India.
EM rohit@lvpei.org
RI Chakrabarti, Subhabrata/F-2468-2015; Banerjee, Seema/AAF-3540-2022;
   Banerjee, Seema/AFH-9772-2022
OI Chakrabarti, Subhabrata/0000-0003-3717-4963; Banerjee,
   Seema/0000-0002-5158-7062; Banerjee, Seema/0000-0002-5158-7062
FU Hyderabad Eye Research Foundation, India; Lions Clubs International
   Foundation; SightFirst Research grant, USA; Department of Biotechnology,
   Centre of Excellence (CoE) grant, India
FX Financial support for this study is provided by Hyderabad Eye Research
   Foundation, India, Lions Clubs International Foundation, SightFirst
   Research grant, USA, and Department of Biotechnology, Centre of
   Excellence (CoE) grant, India.
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NR 42
TC 12
Z9 12
U1 0
U2 1
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 MAR
PY 2016
VL 44
IS 2
BP 95
EP 105
DI 10.1111/ceo.12633
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DH6OA
UT WOS:000372908900004
PM 26283446
DA 2022-11-30
ER

PT J
AU Takahashi, H
   Nomura, Y
   Nishida, J
   Fujino, Y
   Yanagi, Y
   Kawashima, H
AF Takahashi, Hidenori
   Nomura, Yoko
   Nishida, Junko
   Fujino, Yujiro
   Yanagi, Yasuo
   Kawashima, Hidetoshi
TI Vascular Endothelial Growth Factor (VEGF) Concentration Is
   Underestimated by Enzyme-Linked Immunosorbent Assay in the Presence of
   Anti-VEGF Drugs
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE measurement error; enzyme-linked immunosorbent assay; vascular
   endothelial growth factor; antivascular endothelial growth factor drug
ID INTRAVITREAL INJECTION; MACULAR DEGENERATION; IN-VITRO; RANIBIZUMAB;
   BEVACIZUMAB; PHARMACOKINETICS; PEGAPTANIB; BINDING; TRAP
AB PURPOSE. Commercially available enzyme-linked immunosorbent assay (ELISA) kits are often used to monitor vascular endothelial growth factor (VEGF) levels in exudative age-related macular degeneration. To test their accuracy, this study performed measurements using the ELISA kits in the presence of anti-VEGF drugs.
   METHODS. The concentrations of bevacizumab, pegaptanib, or ranibizumab at 28 days and aflibercept at 28 and 56 days after an injection were estimated based on previous pharmacokinetic studies. Vascular endothelial growth factor concentrations were measured with two widely used VEGF ELISA kits in the presence of anti-VEGF drugs or control mouse immunoglobulin G (IgG). The monocyte chemotactic protein-1 (MCP-1) ELISA kit was used as a non-VEGF ELISA control kit.
   RESULTS. The concentrations of aflibercept, bevacizumab, pegaptanib, and ranibizumab were estimated at 0.14 to 7.2, 4.9, 8.6, and 0.11 to 1.1 mu g/mL, respectively. ELISA underestimated the VEGF concentration 2- to 100-fold lower in the presence of an anti-VEGF drug, except for pegaptanib, at all VEGF concentrations tested (7.8-1500 pg/mL). Vascular endothelial growth factor at 1000 pg/mL was measured as 92, 150, and 170 pg/mL in the presence of aflibercept (7.2 mu g/mL), bevacizumab (4.9 mu g/mL), and ranibizumab (1.1 mu g/mL), respectively (all P < 0.0001), and the measured VEGF concentration decreased proportionately by 90% to 92% with aflibercept, 85% to 94% with bevacizumab, and 83% to 99% with ranibizumab. The control mouse IgG did not interfere with the measurement of VEGF. Ranibizumab did not affect the measurements with MCP-1 ELISA.
   CONCLUSIONS. Investigators should exercise caution when interpreting measurements of VEGF ELISA in patients being treated with an anti-VEGF drug.
C1 [Takahashi, Hidenori; Kawashima, Hidetoshi] Jichi Med Univ, Dept Ophthalmol, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290431, Japan.
   [Takahashi, Hidenori; Nomura, Yoko; Nishida, Junko; Fujino, Yujiro] Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
   [Takahashi, Hidenori; Nomura, Yoko; Nishida, Junko; Fujino, Yujiro] Univ Tokyo, Fac Med, Tokyo 113, Japan.
   [Takahashi, Hidenori; Fujino, Yujiro] Tokyo Shinjuku Med Ctr, Japan Community Healthcare Org, Tokyo, Japan.
   [Yanagi, Yasuo] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
C3 Jichi Medical University; University of Tokyo; University of Tokyo;
   National University of Singapore; Singapore National Eye Center
RP Takahashi, H (通讯作者)，Jichi Med Univ, Dept Ophthalmol, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290431, Japan.
EM takahah-tky@umin.ac.jp
RI Takahashi, Hidenori/H-2945-2019; Yanagi, Yasuo/AAA-5441-2022; Yanagi,
   Yasuo/AAF-2670-2020
OI Takahashi, Hidenori/0000-0001-5331-4730; Yanagi,
   Yasuo/0000-0002-0362-7285
FU Japan Society for the Promotion of Science (JSPS) [15K10899];
   Grants-in-Aid for Scientific Research [15K10899] Funding Source: KAKEN
FX Supported by the Japan Society for the Promotion of Science (JSPS)
   Grants-in-Aid for Scientific Research KAKENHI, Grant 15K10899.
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NR 16
TC 23
Z9 23
U1 1
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2016
VL 57
IS 2
BP 462
EP 466
DI 10.1167/iovs.15-18245
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DI6EF
UT WOS:000373591300019
PM 26868748
OA gold
DA 2022-11-30
ER

PT J
AU Kim, CS
   Park, S
   Chun, Y
   Song, W
   Kim, HJ
   Kim, J
AF Kim, Chan-Sik
   Park, Sok
   Chun, Yoonseok
   Song, Wook
   Kim, Hee-Jae
   Kim, Junghyun
TI Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged
   Mice: An Immunohistochemical Study
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE aging; exercise; oxidative stress; retina; treadmill
ID NITRIC-OXIDE SYNTHASE; APOPTOTIC CELL-DEATH; PIGMENT EPITHELIUM;
   MODERATE EXERCISE; AEROBIC EXERCISE; ANTIOXIDANT; EXPRESSION; INCREASE;
   NEURONS; MODEL
AB In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control). Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks). The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML), 8-hydroxy-2-deoxyguanosine (8-OHdG) and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress.
C1 [Kim, Chan-Sik; Kim, Junghyun] Korea Inst Oriental Med, Korean Med Convergence Res Div, Taejon 34054, South Korea.
   [Park, Sok] Mokwon Univ, Dept Sports & Hlth Management, Taejon 35349, South Korea.
   [Chun, Yoonseok] Yong In Univ, Sports Wellness Ctr, Gyeonggi Do 17092, South Korea.
   [Song, Wook; Kim, Hee-Jae] Seoul Natl Univ, Hlth & Exercise Sci Lab, Seoul 08826, South Korea.
C3 Korea Institute of Oriental Medicine (KIOM); Mokwon University; Seoul
   National University (SNU)
RP Kim, J (通讯作者)，Korea Inst Oriental Med, Korean Med Convergence Res Div, Taejon 34054, South Korea.
EM chskim@kiom.re.kr; sok@ajou.ac.kr; chjordan@naver.com; songw3@snu.ac.kr;
   skim82@snu.ac.kr; dvmhyun@kiom.re.kr
RI Song, Wook/AAV-4940-2020
OI Song, Wook/0000-0002-8825-6259
FU Korea Institute of Oriental Medicine [C15040]; National Research
   Foundation of Korea grant - Korean Government [NRF-2014S1A5A8018765];
   Ministry of Science, ICT & Future Planning [MEST2011-0030135]
FX This research was supported by the Korea Institute of Oriental Medicine
   (C15040). Part of this work was also supported by a National Research
   Foundation of Korea grant funded by the Korean Government
   (NRF-2014S1A5A8018765) and the Ministry of Science, ICT & Future
   Planning (MEST2011-0030135).
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NR 42
TC 17
Z9 18
U1 0
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD SEP
PY 2015
VL 16
IS 9
BP 21008
EP 21020
DI 10.3390/ijms160921008
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA CV8MD
UT WOS:000364541000049
PM 26404251
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Gao, GH
   Ouyang, CH
   Dai, JH
   Xue, F
   Wang, XY
   Zou, LL
   Chen, MJ
   Ma, F
   Yu, MR
AF Gao, Guohong
   Ouyang, Chaohu
   Dai, Jinhui
   Xue, Feng
   Wang, Xiaoying
   Zou, Leilei
   Chen, Minjie
   Ma, Fei
   Yu, Manrong
TI Baseline traits of patients presenting at a low vision clinic in
   Shanghai, China
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Low vision clinic; Visual impairment; Patient characteristics; Low
   vision aids; Rehabilitation
ID QUALITY-OF-LIFE; VISUAL IMPAIRMENT; MACULAR DEGENERATION; UNITED-STATES;
   REHABILITATION; SERVICES; IMPACT; BARRIERS
AB Background: Low vision, along with cataract, trachoma, onchocerciasis, childhood blindness and refractive error, is one of the priorities in the global initiative, VISION 2020 - The Right to Sight. The purpose of this study was to characterize the traits of patients presenting at a low vision clinic in China.
   Methods: A retrospective study was conducted of the records of 299 patients who visited the Low Vision Clinic of Eye and ENT Hospital Affiliated to Fudan University from January 2009 to May 2014. Reviewed parameters included age, gender, education, occupation, cause of visual impairment and types of low vision aids (LVAs) dispensed.
   Results: Of all the patients (193 male; aged from 3 to 96 years, with a mean of 29.74 +/- 25.23 years), 43.48% experienced moderate visual impairment, 25.42% had severe visual impairment and 21.07% were blind. The four major causes of visual impairment were congenital cataract (14.38%), degenerative myopia (13.71%), juvenile macular degeneration (9.36%) and retinitis pigmentosa (9.36%). The most common causes of visual impairment were congenital cataract (22.67%) in 0-19-year-olds, retinitis pigmentosa (20.62%) in 20-59-year-olds, and age-related macular degeneration (36.54%) in the 60+ group. With the help of LVAs, a significant improvement of distance and/ or near vision or visual field was observed in 243 patients, of whom 185 accepted LVAs and 58 patients refused due to high price, inconvenience, young age (<= 6 y), clumsy appearance and ignorance. The most commonly dispensed LVAs were stand magnifiers (21.57%) followed by spectacle-type LVAs (19.21%).
   Conclusions: The majority of the patients in our low vision clinic were young, the main causes of visual impairment were congenital and hereditary diseases. Stand magnifiers were the most commonly dispensed LVAs. High price was the major reason for refusing LVAs.
C1 [Gao, Guohong; Dai, Jinhui; Xue, Feng; Wang, Xiaoying; Zou, Leilei; Chen, Minjie; Ma, Fei; Yu, Manrong] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
   [Gao, Guohong; Dai, Jinhui; Xue, Feng; Wang, Xiaoying; Zou, Leilei; Chen, Minjie; Ma, Fei; Yu, Manrong] Minist Hlth PR China, Key Lab Myopia, Shanghai, Peoples R China.
   [Ouyang, Chaohu] Shanghai Peace Eye Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
C3 Fudan University
RP Dai, JH (通讯作者)，Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
EM daijinhui8@126.com
FU National Natural Science Foundation of China [81070750, 81271040];
   Ministry of Health of China [201302015]
FX This paper was funded by the National Natural Science Foundation of
   China (No. 81070750 and 81271040) and the Ministry of Health of China
   (No. 201302015).
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NR 34
TC 10
Z9 13
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD MAR 13
PY 2015
VL 15
AR 16
DI 10.1186/s12886-015-0013-3
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CD2ML
UT WOS:000350912400001
PM 25884841
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Andreatta, W
   Nessim, M
   Nightingale, P
   Shah, P
AF Andreatta, Walter
   Nessim, Maged
   Nightingale, Peter
   Shah, Peter
TI ReGAE 10: Long-term Visual Acuity Outcomes After Acute Primary Angle
   Closure
SO JOURNAL OF GLAUCOMA
LA English
DT Article
DE visual acuity; primary acute angle closure; primary angle closure
   glaucoma
ID GLAUCOMA; OPHTHALMOLOGISTS; AGREEMENT
AB Purpose:
   The aim of this study was to identify the long-term visual acuity (VA) outcomes of eyes following an attack of acute primary angle closure in an urban UK population.
   Patients and Methods:
   This was a retrospective observational case series of 134 consecutive eyes of 123 subjects presenting with acute primary angle closure to a supraregional tertiary referral unit in the United Kingdom over a period of 60 months. The VA in the affected eye was recorded at presentation 6 months after the acute event and at the final follow-up. In addition, causes of poor vision were documented as sociodemographic variables and surgical interventions. The main outcome measure was severe visual impairment (SVI). SVI was classified as VA < 6/60 in the affected eye.
   Results:
   A total of 134 eyes of 123 subjects were assessed, 89 (72%) female and 34 (28%) male patients. The majority of the individuals were White Caucasians (78%), followed by Indian and Pakistani (14%), African Caribbean (4%), and Chinese (2.4%). The mean age was 67.3 +/- 11.9 years.
   During the period of follow-up, 44 (33%) eyes needed a cataract surgery, whereas 13 (10%) eyes underwent filtration surgery. Eight (6%) eyes had combined cataract and filtration surgery. The mean final follow-up period was 31.4 +/- 18.1 months. At this stage, 16 (12%) of the affected eyes had SVI. Glaucomatous optic neuropathy was responsible for SVI in 5/16 eyes, 1 eye had corneal decompensation, whereas 2/16 eyes were affected by central retinal vein occlusion. Other SVI causes were age-related macular degeneration (5/16) and cataract (3/16).
   Conclusions:
   Sixteen (12%) eyes had SVI at the final follow-up. One third of SVI was secondary to GON.
C1 [Andreatta, Walter; Nessim, Maged; Shah, Peter] Sandwell & West Birmingham Hosp NHS Trust, Birmingham & Midland Eye Ctr, Birmingham, W Midlands, England.
   [Nightingale, Peter] Univ Birmingham, Wellcome Trust Clin Res Facil, Birmingham, W Midlands, England.
   [Shah, Peter] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England.
   [Shah, Peter] Wolverhampton Univ, Ctr Hlth & Social Care Improvement, Wolverhampton WV1 1DJ, W Midlands, England.
   [Shah, Peter] Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, England.
   [Shah, Peter] UCL Inst Ophthalmol, London, England.
C3 University of Birmingham; University of Birmingham; University of
   Wolverhampton; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of London;
   University College London
RP Andreatta, W (通讯作者)，Birmingham & Midland Eye Ctr, Dudley Rd, Birmingham B18 7QH, W Midlands, England.
EM andreattawalter@hotmail.com
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NR 19
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-0829
EI 1536-481X
J9 J GLAUCOMA
JI J. Glaucoma
PD APR-MAY
PY 2014
VL 23
IS 4
BP 206
EP 210
DI 10.1097/IJG.0000000000000042
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AE8JG
UT WOS:000334245600004
PM 24522106
DA 2022-11-30
ER

PT J
AU Singh, AK
   Srivastava, GK
   Martin, L
   Alonso, M
   Pastor, JC
AF Singh, Amar K.
   Srivastava, Girish K.
   Martin, Laura
   Alonso, Matilde
   Carlos Pastor, J.
TI Bioactive substrates for human retinal pigment epithelial cell growth
   from elastin-like recombinamers
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE biomaterial; elastin-like recombinamers; hRPE cells
ID MACULAR DEGENERATION; VISUAL FUNCTION; RODENT MODEL; RPE CELLS; RCS
   RATS; TRANSPLANTATION; CULTURE; EXPRESSION; RESCUE; REPAIR
AB The aim of this study was to investigate the use of bioactive RGD-containing elastin-like recombinamers (ELR-RGDs) as a substrate that can maintain human retinal pigment epithelial cell (hRPE) phenotype and growth pattern. Results obtained are compared with previously published behavior of ARPE19 cells. The extension of these results to hRPE is required because ARPE19 cells cannot be used clinically to treat age-related macular degeneration. hRPE cells were isolated, cultured, seeded, and grown on surface of glass, treated polystyrene (TCP), and solvent-cast ELR-RGD and ELR-IK film with no specific sequence. Cells were analyzed to study cell adhesion, proliferation, morphology, and RPE65 protein expression by staining with diamidino-2-phenylindole, Rhodamine-Phalloidin, and anti-RPE65 antibody at 12, 24, 72, 120, 168, and 360 h. hRPE cells always grew better on ELR-RGD than on glass and ELR-IK but not on TCP. The kinetic hRPE growth curves confirmed that growth differences started to appear at 24 h for these surfaces in ascending order of cell growths, namely glass, ELR-IK, ELR-RGD, and TCP. There was a clear difference at 360 h. ELR-RGD maintained hRPE cells stable morphology and RPE65 protein expression. ELR-RGD seems to be a good substrate for growing hRPE cells with stable morphology and RPE65 protein expression. As such, this work confirms our hypothesis regarding ELR-RGD substrates viability, which can be used as a Bruch's membrane prosthesis for further studies in animals. However, these results must subsequently be extrapolated to use of hRPE cells in animals to evaluate them as a transplantation vehicle in human. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 639-646, 2014.
C1 [Singh, Amar K.; Srivastava, Girish K.; Carlos Pastor, J.] Univ Valladolid, IOBA Eye Inst, Valladolid, Spain.
   [Srivastava, Girish K.] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Valladolid, Spain.
   [Srivastava, Girish K.; Carlos Pastor, J.] Regenerat Med & Cell Therapy Networking Ctr Casti, Madrid, Spain.
   [Martin, Laura; Alonso, Matilde] Univ Valladolid, BIOFORGE Grp, 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, IOBA Eye Inst, Valladolid, Spain.
EM girish@ioba.med.uva.es
RI SINGH, AMAR/H-6569-2016; ALONSO, MATILDE/G-6719-2017; Srivastava, Girish
   K/L-7608-2014; Jimeno, J Carlos Pastor/AAP-1156-2020; Martin,
   Laura/J-9291-2017
OI SINGH, AMAR/0000-0002-1767-5907; ALONSO, MATILDE/0000-0002-6853-8427;
   Srivastava, Girish K/0000-0002-9791-4057; Jimeno, J Carlos
   Pastor/0000-0001-5934-7306; Martin, Laura/0000-0002-6583-8731
CR Al-Hussaini H, 2008, MOL VIS, V14, P1784
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NR 39
TC 12
Z9 12
U1 0
U2 22
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 MAR
PY 2014
VL 102
IS 3
BP 639
EP 646
DI 10.1002/jbm.a.34726
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 289JS
UT WOS:000329679100004
PM 23554132
DA 2022-11-30
ER

PT J
AU Peng, Y
   Tao, QS
   Liang, YB
   Friedman, DS
   Yang, XH
   Jhanji, V
   Duan, XR
   Sun, LP
   Wang, NL
AF Peng, Yi
   Tao, Qiu Shan
   Liang, Yuan Bo
   Friedman, David S.
   Yang, Xiao Hui
   Jhanji, Vishal
   Duan, Xin Rong
   Sun, Lan Ping
   Wang, Ning Li
TI Eye Care Use Among Rural Adults in China: The Handan Eye Study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Eye care; eye care use; Handan Eye Study; Northern China
ID CATARACT-SURGERY; DIABETIC-PATIENTS; SERVICES; POPULATION; OLDER;
   BARRIERS; VISION; URBAN; AUSTRALIANS; PREVALENCE
AB Purpose: To assess the use of eye care services in a rural population in North China and to analyze the factors associated with underuse of these services.
   Methods: In a cross-sectional population-based study, demographic, health and vision-related information including use of eye care services were determined during a face-to-face interview. A single visit to an eye care provider qualified as "use" of eye care services.
   Results: Of 6612 participants, 754 (11.4%, 95% confidence interval, CI, 8.7-14.1%) had used eye care services. The most common reason cited for not seeing an eye care provider was "no need" (n = 5754). Of the 5754 who thought that there was no need to see an ophthalmologist, 3458 (60.1%) were found to have one or more type of eye disease, including glaucoma (56, 1.0%), cataract (1056, 18.4%), age-related macular degeneration (AMD; 164, 2.9%) and refractive error (3048, 53.0%). Also, 74 (1.3%) and 409 (7.1%) of the 5754 participants had visual impairment (<20/60) according to best-corrected visual acuity and presenting visual acuity, respectively. In a multiple regression model, participants who had glaucoma (adjusted odds ratio, OR, 4.0, 95% CI 3.0-5.4), AMD (adjusted OR 1.6, 95% CI 1.2-2.3) or refractive error (adjusted OR 1.4, 95% CI 1.1-1.8), were more likely to visit an eye care provider.
   Conclusion: A high proportion of the Chinese rural population had never used eye care services although three fifths had eye diseases. Further efforts towards better education of the general population about common eye problems as well as increasing the number of ocular health providers would be necessary in future.
C1 [Peng, Yi; Liang, Yuan Bo; Yang, Xiao Hui; Duan, Xin Rong; Wang, Ning Li] Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China.
   [Peng, Yi; Liang, Yuan Bo; Jhanji, Vishal] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
   [Tao, Qiu Shan] Peking Univ, Sch Publ Hlth, Beijing 100871, Peoples R China.
   [Friedman, David S.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
   [Friedman, David S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
   [Jhanji, Vishal] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
   [Sun, Lan Ping] Handan Eye Hosp, Handan, Hebei Province, Peoples R China.
C3 Capital Medical University; Chinese University of Hong Kong; Peking
   University; Johns Hopkins University; Johns Hopkins Medicine; Johns
   Hopkins University; Johns Hopkins Bloomberg School of Public Health;
   Centre for Eye Research Australia; University of Melbourne
RP Liang, YB (通讯作者)，Capital Med Univ, Tongren Hosp, Beijing Tongren Eye Ctr, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.
EM yuanboliang@gmail.com
RI Jhanji, Vishal/I-5676-2014
OI liang, Yuanbo/0000-0001-9685-7356; Friedman, David/0000-0002-2055-5797
FU program of Health Policy for Blindness Prevention from the Ministry of
   Health, the People's Republic of China; Key Technologies RD Program;
   Bureau of Science and Technology of Handan city, Hebei Province, China
   [2006-10903]; Beijing Tongren Hospital
FX This study was supported by the program of Health Policy for Blindness
   Prevention from the Ministry of Health, the People's Republic of China;
   and partially funded by the Key Technologies R&D Program. It was also
   supported by Grant no. 2006-10903 from the Bureau of Science and
   Technology of Handan city, Hebei Province, China, and received
   additional support from Beijing Tongren Hospital and the key discipline
   fund of Bureau of Health, Handan city, Hebei Province, China.
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NR 33
TC 7
Z9 9
U1 0
U2 9
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0928-6586
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD OCT
PY 2013
VL 20
IS 5
BP 274
EP 280
DI 10.3109/09286586.2013.823216
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 226BC
UT WOS:000325008200005
PM 23988218
DA 2022-11-30
ER

PT J
AU Biasutto, L
   Chiechi, A
   Couch, R
   Liotta, LA
   Espina, V
AF Biasutto, Lucia
   Chiechi, Antonella
   Couch, Robin
   Liotta, Lance A.
   Espina, Virginia
TI Retinal pigment epithelium (RPE) exosomes contain signaling
   phosphoproteins affected by oxidative stress
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE ARPE-19 cells; Exosomes; Reverse phase protein arrays; Age related
   macular degeneration; Oxidative stress
ID PHASE PROTEIN MICROARRAYS; MACULAR DEGENERATION; HYDROGEN-PEROXIDE;
   CELL-SURVIVAL; HUMAN SALIVA; PHAGOCYTOSIS; ACTIVATION; LIPOFUSCIN;
   BIOGENESIS; MECHANISMS
AB Age-related macular degeneration (AMD) is a leading cause of vision loss and blindness among the elderly population in the industrialized world. One of the typical features of this pathology is the gradual death of retinal pigment epithelial (RPE) cells, which are essential for maintaining photoreceptor functions and survival. The etiology is multifactorial, and oxidative stress is clearly one of the key factors involved in disease pathogenesis (Plafker, Adv. Exp. Med. Biol. 664 (2010) 447-56; Qin, Drug Dev. Res. 68 (2007) 213-225).
   Recent work has revealed the presence of phosphorylated signaling proteins in the vitreous humour of patients affected by AMD or other retinal diseases. While the location of these signaling proteins is typically the cell membrane or intracellular compartments, vitreous samples were proven to be cell-free (Davuluri et al., Arch. Ophthalmol. 127 (2009) 613-21).
   To gain a better understanding of how these proteins can be shed into the vitreous, we used reverse phase protein arrays (RPMA) to analyze the protein and phosphoprotein content of exosomes shed by cultured ARPE-19 cells under oxidative stress conditions.
   Seventy two proteins were shown to be released by ARPE-19 cells and compartmentalized within exosomes. Forty one of them were selectively detected in their post-translationally modified form (i.e., phosphorylated or cleaved) for the first time in exosomes. Sets of these proteins were linked together reflecting activation of pathway units within exosomes. A subset of (phospho)proteins were altered in exosomes secreted by ARPE-19 cells subjected to oxidative stress, compared to that secreted by control/non stressed cells. Stress-altered exosome proteins were found to be involved in pathways regulating apoptosis/survival (i.e, Bak, Smac/Diablo, PDK1 (S241), Akt (T308), Src (Y416), Elk1 (S383), ERK 1/2 (T202/Y204)) and cell metabolism (i.e., AMPK alpha 1 (S485), acetyl-CoA carboxylase (S79), LDHA).
C1 [Biasutto, Lucia] CNR Inst Neurosci, I-35121 Padua, Italy.
   [Biasutto, Lucia] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
   [Chiechi, Antonella; Liotta, Lance A.; Espina, Virginia] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA.
   [Couch, Robin] George Mason Univ, Dept Chem & Biochem, Manassas, VA 20110 USA.
C3 Consiglio Nazionale delle Ricerche (CNR); Istituto di Neuroscienze
   (IN-CNR); University of Padua; George Mason University; George Mason
   University
RP Biasutto, L (通讯作者)，CNR Inst Neurosci, Dept Biomed Sci, Viale G Colombo 3, I-35121 Padua, Italy.
EM lucia.biasutto@cnr.it; vespina@gmu.edu
RI Biasutto, Lucia/GLR-4808-2022
OI Biasutto, Lucia/0000-0002-7638-6865; Espina,
   Virginia/0000-0001-5080-5972; Chiechi, Antonella/0000-0003-2075-6254
FU University of Padova; George Mason University; NIH/NEI
   [1R21EY018942-01]; NATIONAL EYE INSTITUTE [R21EY018942] Funding Source:
   NIH RePORTER
FX This work was funded by the University of Padova, George Mason
   University and the grant 1R21EY018942-01 to LAL from NIH/NEI. We thank
   Prof. S. Garbisa and Dr. M. Zoratti for their support and interest and
   for useful discussions.
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NR 69
TC 81
Z9 89
U1 1
U2 46
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD AUG 1
PY 2013
VL 319
IS 13
BP 2113
EP 2123
DI 10.1016/j.yexcr.2013.05.005
PG 11
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA 186PE
UT WOS:000322055800019
PM 23669273
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lyall, DAM
   Tey, A
   Foot, B
   Roxburgh, STD
   Virdi, M
   Robertson, C
   MacEwen, CJ
AF Lyall, D. A. M.
   Tey, A.
   Foot, B.
   Roxburgh, S. T. D.
   Virdi, M.
   Robertson, C.
   MacEwen, C. J.
TI Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom:
   incidence, features, risk factors, and outcomes
SO EYE
LA English
DT Article
DE endophthalmitis; intravitreal injections; wet macular degeneration
ID AGE-RELATED MACULOPATHY; CATARACT-SURGERY; ANTERIOR-CHAMBER;
   POSTOPERATIVE ENDOPHTHALMITIS; INFECTIOUS ENDOPHTHALMITIS; MACULAR
   DEGENERATION; TREATMENT STRATEGIES; INJECTION; PREVALENCE; MANAGEMENT
AB Purpose To describe the incidence, features, management, and risk factors of post-intravitreal anti-VEGF endophthalmitis (PIAE) in patients undergoing treatment for exudative age-related macular degeneration in the United Kingdom.
   Methods Prospective observational case control study. Forty-seven cases of PIAE were identified through the British Ophthalmological Surveillance Unit from January 2009 to March 2010. Data collected at diagnosis and at 6 months follow-up included patient demographics, intravitreal injection details, pre- and post-injection management, visual acuity, clinical features and management of PIAE, causative organisms, and clinical outcomes. Details were compared with 200 control cases from 10 control centres to identify potential risk factors.
   Results Estimated PIAE was 0.025%. Culture-positive PIAE incidence was 0.015%. Mean age of presentation was 78 years. Mean number of intravitreal injections before PIAE was 5. Mean days to presentation was 5 (range 1-39). Positive microbiology culture was found in 59.6%. The majority of causative organisms were Gram positive (92.8%). Significant risk factors were failure to administer topical antibiotics immediately after the injection (P = 0.001), blepharitis (P = 0.006), subconjunctival anaesthesia (P = 0.021), patient squeezing during the injection (P 0.021), and failure to administer topical antibiotics before anti-VEGF injection (P = 0.05).
   Discussion The incidence of PIAE in the United Kingdom is comparable to other studies at a rate of 0.025%. The most common causative organisms were Gram positive. Measures to minimise the risk of PIAE include treatment of blepharitis before injection, avoidance of subconjunctival anaesthesia, topical antibiotic administration immediately after injection with consideration to administering topical antibiotics before injection. Eye (2012) 26, 1517-1526; doi: 10.1038/eye.2012.199; published online 12 October 2012
C1 [Lyall, D. A. M.] Gartnavel Royal Hosp, Tennent Inst Ophthalmol, Glasgow G12 0YN, Lanark, Scotland.
   [Tey, A.; Roxburgh, S. T. D.; MacEwen, C. J.] Univ Dundee, Ninewells Hosp & Med Sch, Dept Ophthalmol, Dundee DD1 9SY, Scotland.
   [Foot, B.] Royal Coll Ophthalmologists, British Ophthalmol Surveillance Unit, London, England.
   [Virdi, M.] Hairmyres Hosp, Dept Ophthalmol, E Kilbride, Lanark, Scotland.
   [Robertson, C.] Univ Strathclyde, Dept Math & Stat, Glasgow, Lanark, Scotland.
C3 Gartnavel Royal Hospital; University of Dundee; University Hospital
   Hairmyres; University of Strathclyde
RP Lyall, DAM (通讯作者)，Gartnavel Royal Hosp, Tennent Inst Ophthalmol, Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
EM douglas_am_lyall@hotmail.com
FU Fight for Sight; Fight for Sight Research Bursary through the BOSU
FX We would like to thank the BOSU for the opportunity to perform this
   study. We are grateful to Fight for Sight for their funding support.
   Fight for Sight Research Bursary was awarded to perform this study
   through the BOSU. We thank Dr Kimia Ziahosseini for advice on analysis
   of incident data and the following consultants who reported incident
   cases of PIAE to BOSU and assisted with data collection: Dr A Armbrecht,
   Mr S Armstrong, Mr N Beare, Mr A Browning, Mr RL Burton, Professor U
   Chakravarthy, Mr HC Chen, Mrs JK Chinna, Miss H Cook, Mr M Costen, Mr J
   Deane, Mrs S Dhar-munshi, Miss SM Downes, Mr R Gupta, Dr HM Hammer, Mrs
   BA Harney, Mr E Hughes, Mr N Islam, Mr J Keenan, Mr A King, Mr GR Kirby,
   Mr JNP Kirkpatrick, Mr S Mahmood, Mr J Mathews, Mr T McMullan, Mr R
   McPherson, Mr KB Mills, Mr DA Mulholland, Dr A Purdie, Mr RJ
   Pushpanathan, Mr P Rao, Mr M Saeed, Mr RAH Scott, Ms G Silvestri, Mr K
   Sim, Mr A Sinha, Miss S Sivaprasad, Mr YC Yang, and Mr N Zaman. We would
   also like to thank the following clinicians who assisted in data
   collection of control cases at their centres: Mr N Beare (Royal
   Liverpool University Hospital), Mr C Blyth and Dr M Popiela (University
   Hospital of Wales), Dr P Cackett (Princess Alexandra Eye Pavillion), Dr
   M Gavin (Gartnavel General Hospital), Mr N Lee (Hillingdon Hospital), Mr
   M Majid (Bristol Eye Hospital), Mr M McKibbin (St James's University
   Hospital), Miss J Silvestri and Dr S Twaij (Royal Victoria Hospital), Mr
   J Talks (Royal Victoria Infirmary), and Mr A Tufail (Moorfields Eye
   Hospital).
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NR 49
TC 89
Z9 92
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD DEC
PY 2012
VL 26
IS 12
BP 1517
EP 1526
DI 10.1038/eye.2012.199
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 055WB
UT WOS:000312447400003
PM 23060022
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Wang, JY
   Ohno-Matsui, K
   Morita, I
AF Wang, Jiying
   Ohno-Matsui, Kyoko
   Morita, Ikuo
TI Cholesterol enhances amyloid beta deposition in mouse retina by
   modulating the activities of A beta-regulating enzymes in retinal
   pigment epithelial cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Amyloid beta; Retinal pigment epithelium; Age-related macular
   degeneration; Cholesterol; Neprilysin; alpha-Secretase
ID GAMMA-SECRETASE ACTIVITY; HIGH-FAT DIET; LIPID RAFTS; MACULAR
   DEGENERATION; NEUTRAL ENDOPEPTIDASE-24.11; ALZHEIMERS-DISEASE; PRECURSOR
   PROTEIN; APOLIPOPROTEIN-E; PATHOLOGY; MEMBRANE
AB Subretinally-deposited amyloid beta (A beta) is a main contributor of developing age-related macular degeneration (AMD). However, the mechanism causing A beta deposition in AMD eyes is unknown. Hypercholesterolemia is a significant risk for developing AMD. Thus, we investigated the effects of cholesterol on A beta production in retinal pigment epithelial (RPE) cells in vitro and in the mouse retina in vivo. RPE cells isolated from senescent (12-month-old) C57BL/6 mice were treated with 10 mu g/ml cholesterol for 48 h. A beta amounts in culture supernatants were measured by ELISA. Activity and expression of enzymes and proteins that regulate A beta production were examined by activity assay and real time PCR. The retina of mice fed cholesterol-enriched diet was examined by transmission electron microscopy. Cholesterol significantly increased A beta production in cultured RPE cells. Activities of A beta degradation enzyme; neprilysin (NEP) and anti-amyloidogenic secretase; alpha-secretase were significantly decreased in cell lysates of cholesterol-treated RPE cells compared to non-treated cells, but there was no change in the activities of beta- or gamma-secretase. mRNA levels of NEP and alpha-secretase (ADAM 10 and ADAM17) were significantly lower in cholesterol-treated RPE cells than non-treated cells. Senescent (12-month-old) mice fed cholesterol-enriched chow developed subRPE deposits containing A beta, whereas age-matched mice fed standard rodent chow diet did not. Activities and mRNA levels of NEP and alpha-secretase were significantly lower in native RPE cells freshly isolated from cholesterol-enriched chow fed mice compared to standard rodent chow fed mice. These findings suggest that cholesterol enhances subretinal A beta accumulation by modulating the activities of enzymes degrading and processing A beta in RPE cells in senescent subjects. Crown Copyright (c) 2012 Published by Elsevier Inc. All rights reserved.
C1 [Wang, Jiying; Ohno-Matsui, Kyoko] Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Bunkyo Ku, Tokyo 1138519, Japan.
   [Morita, Ikuo] Tokyo Med & Dent Univ, Sect Cellular Physiol Chem, Bunkyo Ku, Tokyo 1138519, Japan.
C3 Tokyo Medical & Dental University (TMDU); Tokyo Medical & Dental
   University (TMDU)
RP Ohno-Matsui, K (通讯作者)，Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan.
EM k.ohno.oph@tmd.ac.jp
FU Japanese Society of Promotion of Science [23659808, 22390322]
FX The authors thank Prof. Duco Hamasaki for his critical discussion and
   final manuscript revision. Contact Grant sponsor: 23659808 and 22390322
   from Japanese Society of Promotion of Science
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NR 50
TC 18
Z9 20
U1 0
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 10
PY 2012
VL 424
IS 4
BP 704
EP 709
DI 10.1016/j.bbrc.2012.07.014
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 993NB
UT WOS:000307865300011
PM 22796523
DA 2022-11-30
ER

PT J
AU Krebs, I
   Krepler, K
   Stolba, U
   Goll, A
   Binder, S
AF Krebs, Ilse
   Krepler, Katharina
   Stolba, Ulrike
   Goll, Alexandra
   Binder, Susanne
TI Retinal angiomatous proliferation: combined therapy of intravitreal
   triamcinolone acetonide and PDT versus PDT alone
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE triamcinolone acetonide; photodynamic therapy; choroidal
   neovascularisation; retinal angiomatous proliferation
ID OCCULT CHOROIDAL NEOVASCULARIZATION; PIGMENT EPITHELIAL TEARS;
   PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; CHORIORETINAL ANASTOMOSES;
   VERTEPORFIN THERAPY; INJECTION; VITREORETINOPATHY; DETACHMENTS; LESIONS
AB Background The objective of the study was to investigate whether combined treatment with photodynamic therapy (PDT) and triamcinolone acetonide intravitreally applied is superior to PDT alone in eyes with retinal angiomatous proliferation (RAP).
   Methods Between July 2004 and June 2005 eyes with RAP in age-related macular degeneration were included in a prospective study and were treated with 4 mg of triamcinolone acetonide followed by PDT (group 1). Eyes with RAP treated with PDT alone before June 2004 were retrospectively reviewed (group 2). Distance visual acuity (VA) with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, greatest diameter of the lesion (measured by fluorescein angiography), and retinal thickness (measured by optical coherence tomography) were performed at baseline and at 6 weeks, 3 months, 6 months and 12 months thereafter.
   Results Fifty-eight eyes in 58 patients were included: 27 eyes in the combined treatment group and 31 eyes in the PDT monotherapy group. The groups were comparable with regard to age, gender and RAP stage. VA decreased from 65.6 to 52.0 and from 60.7 to 44.0 letters, and lesion size increased from 3.2 mm to 3.5 mm and from 3.3 mm to 3.5 mm in the combined and monotherapy groups respectively. There was a trend towards a better outcome in the combined group. Significantly (p=0.01) fewer complications occurred in the combined group (22.2%) than in the monotherapy group (54.8%).
   Conclusion No significant differences could be found in the time course of distance VA, retinal thickness, and lesion size between the PDT monotherapy group and the combined PDT and IVTA group. However, significantly fewer complications occurred in the combined treatment group. New therapeutic strategies might be required in RAP lesions, probably including therapy with anti-angiogenic agents.
C1 [Krebs, Ilse; Krepler, Katharina; Stolba, Ulrike; Binder, Susanne] Rudolf Fdn Clin, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Dept Ophthalmol, A-1030 Vienna, Austria.
   [Goll, Alexandra] Inst Med Stat, Vienna, Austria.
C3 Ludwig Boltzmann Institute
RP Krebs, I (通讯作者)，Rudolf Fdn Clin, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
EM Ilse.Krebs@wienkav.at
OI Graf, Alexandra/0000-0003-0035-2658
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NR 32
TC 26
Z9 27
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD FEB
PY 2008
VL 246
IS 2
BP 237
EP 243
DI 10.1007/s00417-007-0651-0
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 252SU
UT WOS:000252467700012
PM 17674018
DA 2022-11-30
ER

PT J
AU Bourre, JM
AF Bourre, Jean-Marie
TI Dietary omega-3 fatty acids for women
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Review
DE omega-3 fatty acids; polyunsaturated fatty acids; woman; pregnancy;
   lactation; cancer; infant; ALA; DHA
ID POLYUNSATURATED FATTY-ACIDS; CORONARY-HEART-DISEASE; ALPHA-LINOLENIC
   ACID; BREAST-CANCER RISK; COD-LIVER OIL; HUMAN-MILK; ADIPOSE-TISSUE;
   DOCOSAHEXAENOIC ACID; FISH CONSUMPTION; POSTPARTUM DEPRESSION
AB This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood.
   ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes.
   The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. (c) 2007 Elsevier Masson SAS. All rights reserved.
C1 Univ Paris 07, CNRS, UMR 7157, INSERM U705, F-75745 Paris 10, France.
   Univ Paris 05, Hop Fernand Widal, F-75745 Paris 10, France.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Universite Paris Cite; Assistance Publique Hopitaux Paris
   (APHP); Hopital Universitaire Lariboisiere-Fernand-Widal - APHP;
   UDICE-French Research Universities; Universite Paris Cite
RP Bourre, JM (通讯作者)，Univ Paris 07, CNRS, UMR 7157, INSERM U705, 200 Rue Faubourg St Denis, F-75745 Paris 10, France.
EM jean-marie.bourre@fwidal.inserm.fr
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NR 103
TC 69
Z9 83
U1 2
U2 61
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 FEB-APR
PY 2007
VL 61
IS 2-3
BP 105
EP 112
DI 10.1016/j.biopha.2006.09.015
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 169QJ
UT WOS:000246606400001
PM 17254747
DA 2022-11-30
ER

PT J
AU Fraunfelder, FW
AF Fraunfelder, FW
TI Pegaptanib for wet macular degeneration
SO DRUGS OF TODAY
LA English
DT Article
ID PHASE-II; TRIAL; FLUOROURACIL; LEUCOVORIN; THERAPY; PROMISES
AB Pegaptanib sodium injection (Macugen(R), Eyetech Pharmaceuticals, Pfizer, New York, NY, USA) is a relatively new medication intended to treat the so-called wet (neovascular) form of age-related macular degeneration (AMD). This form of AMD is characterized by the growth of unwanted new blood vessels into the macula (angiogenesis). The aqueous solution containing pegaptanib is injected into the vitreous of the eye, where it binds to the 165 amino acid isoform of vascular endothelial growth factor (VEGF), a secreted protein that is thought to play a major role in the pathologic angiogenesis that occurs in wet AMD. Neovascular AMD is the leading cause of severe vision loss in people over age 60 in the United States and other industrialized countries (1).
   Pegaptanib acts as a selective VEGF antagonist through its molecular structure as an aptamer, a pegylated modified oligonucleotide that adopts a three-dimensional configuration, enabling it to bind to extracellular VEGF (Fig. 1). Aptamers are macromolecules composed of chemically synthesized single-stranded nucleic acids (either RNA or DNA) that bind with a high degree of selectivity and affinity when exposed to target proteins. Pegaptanib binds VEGF(165), and bound VEGF(165) is not able to bind to the VEGF receptor, thereby negating its ability to cause angiogenesis and vascular permeability.
   Other aptamers exist, as do other forms of treatment for AMD. To date, however, no treatment for AMD has allowed for better vision after treatment, with most surgical treatments leading to almost immediate loss of some vision in the expectation of preventing more severe loss. Research in the field of macular degeneration is advancing rapidly, and treatment with an aptamer such as pegaptanib is a viable option despite the possibility of adverse events. (C) 2005 Prous Science. All rights reserved.
C1 Oregon Hlth & Sci Univ, Natl Registry Drug Induced Iclular Side Effects, Casey Eye Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University
RP Fraunfelder, FW (通讯作者)，Oregon Hlth & Sci Univ, Natl Registry Drug Induced Iclular Side Effects, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM fraunfer@ohsu.edu
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NR 31
TC 23
Z9 23
U1 1
U2 10
PU PROUS SCIENCE, SAU-THOMSON REUTERS
PI BARCELONA
PA 398 PROVENCA, 08025 BARCELONA, SPAIN
SN 1699-3993
EI 1699-4019
J9 DRUG TODAY
JI Drugs Today
PD NOV
PY 2005
VL 41
IS 11
BP 703
EP 709
DI 10.1358/dot.2005.41.11.917340
PG 7
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 014BK
UT WOS:000235453500002
PM 16395411
DA 2022-11-30
ER

PT J
AU James, G
   Bohannan, W
   Adewunmi, E
   Schmidt, K
   Park, HG
   Shchepinov, MS
   Agbaga, MP
   Brenna, JT
AF James, Genevieve
   Bohannan, Whitney
   Adewunmi, Eniola
   Schmidt, Karsten
   Park, Hui Gyu
   Shchepinov, Mikhail S.
   Agbaga, Martin -Paul
   Brenna, J. Thomas
TI Pharmacokinetics and metabolism in mouse retina of bis-allylic
   deuterated docosahexaenoic acid (D-DHA), a new dry AMD drug candidate
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; LONG-CHAIN; MACULAR DYSTROPHY; ELOVL4;
   ACCRETION; BRAIN; MODEL
AB Docosahexaenoic acid (DHA; 22:6n-3) rich photoreceptors function in a highly oxidizing microenvironment. Lipid peroxidation and inflammation contribute to initiation and progression of eye diseases including age-related macular degeneration (AMD). Deuteration of DHA at the bis-allylic positions (D-DHA) increases its resilience to oxidative damage in vitro. We studied the pharmacokinetics of dietary D-DHA as a therapy for replacing natural retinal DHA in vivo. Mice were fed 0.5% D-DHA for 77 days then switched to natural DHA (H-DHA) for 74 days. Tissue were harvested for analyses at various time points. D-DHA substitution levels were 75%-80% in the CNS and above 90% in all other tissues by day 77. D-DHA accretion was rapid in plasma and liver (t1/2a-2.8 d), followed by heart and red blood cells (t1/2a-8.5 d), then ocular tissues (choroid-RPE, neural retina, and optic nerve with t1/2a of 10.1, 23.4, and 26.3 days, respectively), while CNS accretion was slowest (t1/2a of 29.0-44.3 days). D-DHA elimination rates were comparable to, or slower than, accretion rates except for optic nerve. Retina had very long chain D-PUFA (D-VLC-PUFA) with 5 and 6 double bonds up to C36, as well as D-EPA and D-DPA derived metabolically from D-DHA. The neural retina and optic nerve reached the therapeutic target window (20%-50%) in 2-4 weeks. Biosynthesis of D-VLC-PUFA is consistent with normal metabolism. D-DHA crosses the blood-retina -barrier, enters visually active tissues, and is metabolized as its natural DHA parent where, as shown previously (Liu et al., 2022), it protects against lipid peroxidation.
C1 [James, Genevieve; Park, Hui Gyu; Brenna, J. Thomas] Univ Texas Austin, Dell Pediat Res Inst, Austin, TX 78712 USA.
   [Bohannan, Whitney; Adewunmi, Eniola; Agbaga, Martin -Paul] Dept Cell Biol, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
   [Bohannan, Whitney; Adewunmi, Eniola; Agbaga, Martin -Paul] Dept Ophthalmol, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
   [Bohannan, Whitney; Adewunmi, Eniola; Agbaga, Martin -Paul] Dean McGee Eye Inst, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
   [Bohannan, Whitney; Adewunmi, Eniola; Agbaga, Martin -Paul] Univ Oklahoma Hlth Sci Ctr, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
   [Schmidt, Karsten; Shchepinov, Mikhail S.] Retrotope Inc, 4300 El Camino Real Suite 201, Los Altos, CA 94022 USA.
C3 University of Texas System; University of Texas Austin; University of
   Oklahoma System; University of Oklahoma Health Sciences Center
RP Park, HG; Brenna, JT (通讯作者)，Univ Texas Austin, Dell Pediat Res Inst, Austin, TX 78712 USA.; Agbaga, MP (通讯作者)，Dept Cell Biol, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.; Agbaga, MP (通讯作者)，Univ Oklahoma Hlth Sci Ctr, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.; Schmidt, K; Shchepinov, MS (通讯作者)，Retrotope Inc, 4300 El Camino Real Suite 201, Los Altos, CA 94022 USA.
EM gejames@utexas.edu; Whitney-Bohannan@ouhsc.edu;
   Eniola-Adewunmi@ouhsc.edu; Karsten.schmidt@retrotope.com;
   hi.park@austin.utexas.edu; misha@retrotope.com;
   martin-paul-agbaga@ouhsc.edu; tbrenna@austin.utexas.edu
OI Park, Hui Gyu/0000-0002-0510-2095; Agbaga,
   Martin-Paul/0000-0002-1920-915X; Brenna, James
   Thomas/0000-0001-9494-4245; James, Genevieve/0000-0002-7275-7227
FU NIH [R01 EY030513, R21 AR076035, P30 EY021725]; Research to Prevent
   Blindness; Retrotope, Inc
FX Funding was provided by Retrotope, Inc., NIH grants R01 EY030513 and R21
   AR076035 (MPA) , P30 EY021725 to the Dean McGee Eye Institute, and an
   unrestricted grant from Research to Prevent Blindness.
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NR 35
TC 0
Z9 0
U1 2
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2022
VL 222
AR 109193
DI 10.1016/j.exer.2022.109193
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3V1OG
UT WOS:000841430200001
PM 35870486
DA 2022-11-30
ER

PT J
AU Marginean, BA
   Groza, A
   Muntean, G
   Nicoara, SD
AF Marginean, Beatrice-Andreea
   Groza, Adrian
   Muntean, George
   Nicoara, Simona Delia
TI Predicting Visual Acuity in Patients Treated for AMD
SO DIAGNOSTICS
LA English
DT Article
DE diagnosis of retinal conditions; OCT; predicting visual acuity; machine
   learning
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; RANIBIZUMAB; OCT
AB The leading diagnostic tool in modern ophthalmology, Optical Coherence Tomography (OCT), is not yet able to establish the evolution of retinal diseases. Our task is to forecast the progression of retinal diseases by means of machine learning technologies. The aim is to help the ophthalmologist to determine when early treatment is needed in order to prevent severe vision impairment or even blindness. The acquired data are made up of sequences of visits from multiple patients with age-related macular degeneration (AMD), which, if not treated at the appropriate time, may result in irreversible blindness. The dataset contains 94 patients with AMD and there are 161 eyes included with more than one medical examination. We used various techniques from machine learning (linear regression, gradient boosting, random forest and extremely randomised trees, bidirectional recurrent neural network, LSTM network, GRU network) to handle technical challenges such as how to learn from small-sized time series, how to handle different time intervals between visits, and how to learn from different numbers of visits for each patient (1-5 visits). For predicting the visual acuity, we performed several experiments with different features. First, by considering only previous measured visual acuity, the best accuracy of 0.96 was obtained based on a linear regression. Second, by considering numerical OCT features such as previous thickness and volume values in all retinal zones, the LSTM network reached the highest score (R2=0.99). Third, by considering the fundus scan images represented as embeddings obtained from the convolutional autoencoder, the accuracy was increased for all algorithms. The best forecasting results for visual acuity depend on the number of visits and features used for predictions, i.e., 0.99 for LSTM based on three visits (monthly resampled series) based on numerical OCT values, fundus images, and previous visual acuities.
C1 [Marginean, Beatrice-Andreea; Groza, Adrian] Tech Univ Cluj Napoca, Dept Comp Sci, Cluj Napoca 400114, Romania.
   [Muntean, George; Nicoara, Simona Delia] Iuliu Hatieganu Univ Med & Pharm, Dept Ophthalmol, Cluj Napoca 400012, Romania.
   [Muntean, George; Nicoara, Simona Delia] Emergency Cty Hosp, Cluj Napoca 400347, Romania.
C3 Technical University of Cluj Napoca; Iuliu Hatieganu University of
   Medicine & Pharmacy
RP Groza, A (通讯作者)，Tech Univ Cluj Napoca, Dept Comp Sci, Cluj Napoca 400114, Romania.
EM andreea.beatrice2@yahoo.com; adrian.Groza@cs.utcluj.ro;
   georgemuntean99@gmail.com; simonanicoara1@gmail.com
RI Groza, Adrian/D-6401-2011; Muntean, George Adrian/GSE-1383-2022;
   Nicoara, Simona Delia/D-3353-2016
OI Groza, Adrian/0000-0003-0143-5631; Nicoara, Simona
   Delia/0000-0002-7886-2044
CR Banerjee I., 2019, ARXIV
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NR 33
TC 0
Z9 0
U1 1
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-4418
J9 DIAGNOSTICS
JI Diagnostics
PD JUN
PY 2022
VL 12
IS 6
AR 1504
DI 10.3390/diagnostics12061504
PG 23
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 2M0YH
UT WOS:000817435800001
PM 35741314
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wolf, J
   Boneva, S
   Rosmus, DD
   Agostini, H
   Schlunck, G
   Wieghofer, P
   Schlecht, A
   Lange, C
AF Wolf, Julian
   Boneva, Stefaniya
   Rosmus, Dennis-Dominik
   Agostini, Hansjuergen
   Schlunck, Guenther
   Wieghofer, Peter
   Schlecht, Anja
   Lange, Clemens
TI In-Depth Molecular Profiling Specifies Human Retinal Microglia Identity
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE retinal microglia; brain microglia; human; mouse; monocytes; RNA
   sequencing; age-related macular degeneration (AMD); diabetic retinopathy
   (DR)
ID ANALYSIS REVEALS; MACROPHAGES; MONOCYTES; FATE; RNA
AB Microglia are the tissue-resident macrophages of the retina and brain, being critically involved in organ development, tissue homeostasis, and response to cellular damage. Until now, little is known about the molecular signature of human retinal microglia and how it differs from the one of brain microglia and peripheral monocytes. In addition, it is not yet clear to what extent murine retinal microglia resemble those of humans, which represents an important prerequisite for translational research. The present study applies fluorescence-activated cell sorting to isolate human retinal microglia from enucleated eyes and compares their transcriptional profile with the one of whole retinal tissue, human brain microglia as well as classical, intermediate and non-classical monocytes. Finally, human retinal microglia are compared to murine retinal microglia, isolated from Cx3cr1(GFP/+) mice. Whereas human retinal microglia exhibited a high grade of similarity in comparison to their counterparts in the brain, several enriched genes were identified in retinal microglia when compared to whole retinal tissue, as well as classical, intermediate, and non-classical monocytes. In relation to whole retina sequencing, several risk genes associated with age-related macular degeneration (AMD) and diabetic retinopathy (DR) were preferentially expressed in retinal microglia, indicating their potential pathophysiological involvement. Although a high degree of similarity was observed between human and murine retinal microglia, several species-specific genes were identified, which should be kept in mind when employing mouse models to investigate retinal microglia biology. In summary, this study provides detailed insights into the molecular profile of human retinal microglia, identifies a plethora of tissue-specific and species-specific genes in comparison to human brain microglia and murine retinal microglia, and thus highlights the significance of retinal microglia in human retinal diseases and for translational research approaches.
C1 [Wolf, Julian; Boneva, Stefaniya; Agostini, Hansjuergen; Schlunck, Guenther; Schlecht, Anja; Lange, Clemens] Univ Freiburg, Fac Med, Eye Ctr, Med Ctr, Freiburg, Germany.
   [Rosmus, Dennis-Dominik; Wieghofer, Peter] Univ Leipzig, Inst Anat, Leipzig, Germany.
   [Wieghofer, Peter] Univ Augsburg, Inst Theoret Med, Med Fac, Cellular Neuroanat, Augsburg, Germany.
   [Schlecht, Anja] Julius Maximilians Univ Wuerzburg, Inst Anat & Cell Biol, Wurzburg, Germany.
   [Lange, Clemens] St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, Munster, Germany.
C3 University of Freiburg; Leipzig University; University of Augsburg;
   University of Wurzburg; St. Franziskus-Hospital
RP Lange, C (通讯作者)，Univ Freiburg, Fac Med, Eye Ctr, Med Ctr, Freiburg, Germany.; Lange, C (通讯作者)，St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, Munster, Germany.
EM clemens.lange@augen-franziskus.de
RI Wieghofer, Peter/AAV-9572-2020
OI Boneva, Stefaniya/0000-0002-9811-2160; Wolf, Julian/0000-0002-3470-9697
FU Open Access Publication Fund of the University of Freiburg
FX The authors thank Gabriele Prinz for excellent technical assistance, M.
   Follo and team at Lighthouse Fluorescence Technologies Core Facility,
   University Medical Center, Freiburg for cell sorting, and KFB, Center of
   Excellence for Fluorescent Bioanalytics, Regensburg for RNA sequencing.
   We acknowledge support by the Open Access Publication Fund of the
   University of Freiburg.
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NR 55
TC 2
Z9 2
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD MAR 18
PY 2022
VL 13
AR 863158
DI 10.3389/fimmu.2022.863158
PG 13
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 0I0SB
UT WOS:000779136800001
PM 35371110
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Pfau, M
   von der Emde, L
   Dysli, C
   Moller, PT
   Thiele, S
   Lindner, M
   Schmid, M
   Rubin, DL
   Fleckenstein, M
   Holz, FG
   Schmitz-Valckenberg, S
AF Pfau, Maximilian
   von der Emde, Leon
   Dysli, Chantal
   Moeller, Philipp T.
   Thiele, Sarah
   Lindner, Moritz
   Schmid, Matthias
   Rubin, Daniel L.
   Fleckenstein, Monika
   Holz, Frank G.
   Schmitz-Valckenberg, Steffen
TI Determinants of Cone and Rod Functions in Geographic Atrophy: AI-Based
   Structure-Function Correlation
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PROGRESSION; PERIMETRY; EYES
AB PURPOSE: To investigate the association between retinal microstructure and cone and rod function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) by using artificial intelligence (AI) algorithms.
   DESIGN: Prospective, observational case series.
   METHODS: A total of 41 eyes of 41 patients (75.8 +/- 8.4 years old; 22 females) from a tertiary referral hospital were included. Mesopic, dark-adapted (DA) cyan and red sensitivities were assessed by using fundus-controlled perimetry ("microperimetry''); and retinal microstructure was assessed by using spectral-domain optical-coherence-tomography (SD-OCT), fundus autofluorescence (FAF), and near-infrared-reflectance (IR) imaging. Layer thicknesses and intensities and FAF and IR intensities were extracted for each test point. The cross-validated mean absolute error (MAE) was evaluated for random forest-based predictions of retinal sensitivity with and without patient-specific training data and percentage of increased mean-squared error (%IncMSE) as measurement of feature importance.
   RESULTS: Retinal sensitivity was predicted with a MAE of 4.64 dB for mesopic, 4.89 dB for DA cyan, and 4.40 dB for DA red testing in the absence of patient-specific data. Partial addition of patient-specific sensitivity data to the training sets decreased the MAE to 2.89 dB, 2.86 dB, and 2.77 dB. For all 3 types of testing, the outer nuclear layer thickness constituted the most important predictive feature (35.0, 42.22, and 53.74 %IncMSE). Spatially resolved mapping of "inferred sensitivity'' revealed regions with differential degrees of mesopic and DA cyan sensitivity loss outside of the GA lesions.
   CONCLUSIONS: "Inferred sensitivity'' accurately reflected retinal function in patients with GA. Mapping of "inferred sensitivity'' could facilitate monitoring of disease progression and serve as "quasi functional'' surrogate outcome in clinical trials, especially in consideration of retinal regions beyond areas of GA. ((C) 2020 Elsevier Inc. All rights reserved.)
C1 [Pfau, Maximilian; von der Emde, Leon; Dysli, Chantal; Moeller, Philipp T.; Thiele, Sarah; Lindner, Moritz; Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
   [Pfau, Maximilian; Moeller, Philipp T.; Thiele, Sarah; Fleckenstein, Monika; Holz, Frank G.; Schmitz-Valckenberg, Steffen] GRADE Reading Ctr, Bonn, Germany.
   [Pfau, Maximilian; Rubin, Daniel L.] Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA.
   [Dysli, Chantal] Bern Univ Hosp, Inselspital, Dept Ophthalmol, Bern, Switzerland.
   [Dysli, Chantal] Bern Univ Hosp, Inselspital, Dept Clin Res, Bern, Switzerland.
   [Dysli, Chantal] Univ Bern, Bern, Switzerland.
   [Lindner, Moritz] Univ Oxford, Nuffield Dept Clin Neurosci, Sleep & Circadian Neurosci Inst, Nuffield Lab Ophthalmol, Oxford, England.
   [Lindner, Moritz] Philipps Univ, Inst Physiol & Pathophysiol, Dept Neurophysiol, Marburg, Germany.
   [Schmid, Matthias] Univ Bonn, Fac Med, Inst Med Biometry Informat & Epidemiol, Bonn, Germany.
   [Fleckenstein, Monika; Schmitz-Valckenberg, Steffen] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA.
C3 University of Bonn; Stanford University; University of Bern; University
   Hospital of Bern; University of Bern; University Hospital of Bern;
   University of Bern; University of Oxford; Philipps University Marburg;
   University of Bonn; Utah System of Higher Education; University of Utah
RP Schmitz-Valckenberg, S (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM Steffen.schmitz-valckenberg@ukbonn.de
RI Lindner, Moritz/AAC-8639-2021
OI Lindner, Moritz/0000-0002-4416-3421; Pfau,
   Maximilian/0000-0001-9761-9640; Schmid, Matthias/0000-0002-0788-0317
FU German Research Foundation [PF 950/1-1, 658/4-1, 658/4-2, 2846/1-1];
   BONFOR GEROK Program of the Faculty of Medicine, University of Bonn
   [O-137.0022, O-137.0025]; Research to Prevent Blindness (New York, NY)
FX This work was supported by German Research Foundation grants PF 950/1-1
   (to M.P.), 658/4-1 and 658/4-2 (to M.F.), and 2846/1-1 (to M.L.), and by
   BONFOR GEROK Program of the Faculty of Medicine, University of Bonn
   grants O-137.0022 and O-137.0025 (to M.P.), and by an unrestricted grant
   from Research to Prevent Blindness (New York, NY) to the Department of
   Ophthalmology and Visual Sciences, University of Utah. CenterVue SpA,
   Padova, Italy, provided research material (Scotopic Macular Integrity
   Assessment, CenterVue, Padua, Italy) for the conduct of this study.
   CenterVue had no role in the design or conduct of the experiments.
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NR 36
TC 17
Z9 17
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2020
VL 217
BP 162
EP 173
DI 10.1016/j.ajo.2020.04.003
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NW3NW
UT WOS:000574918000018
PM 32289293
DA 2022-11-30
ER

PT J
AU Stumpf, C
   Wimmer, T
   Lorenz, B
   Stieger, K
AF Stumpf, Constanze
   Wimmer, Tobias
   Lorenz, Birgit
   Stieger, Knut
TI Creation of different bioluminescence resonance energy transfer based
   biosensors with high affinity to VEGF
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TRANSFER BRET; FLUORESCENT PROTEIN;
   REAL-TIME; RECEPTOR; BINDING; CELLS; QUANTIFICATION; LUCIFERASE;
   DISTANCE
AB In age-related macular degeneration (AMD) or diabetic retinopathy (DR), hypoxia and inflammatory processes lead to an upregulation of the vascular endothelial growth factor (VEGF) expression and thereby to pathological neovascularisation with incorrectly formed vessels prone to damage, thus increasing the vascular permeability and the risk of bleeding and oedema in the retina. State of the art treatment is the repeated intraocular injection of anti-VEGF molecules. For developing improved individualized treatment approaches, a minimally invasive, repeatable method for in vivo quantification of VEGF in the eye is necessary. Therefore, we designed single molecule eBRET2 VEGF biosensors by directly fusing a Renilla luciferase mutant (Rluc8) N-terminal and a green fluorescent protein (GFP2) C-terminal to a VEGF binding domain. In total, 10 different VEGF biosensors (Re01- Re10) were generated based on either single domains or full length of VEGF receptor 1 or 2 extracellular regions as VEGF binding domains. Full length expression of the biosensors in HEK293-T cells was verified via Western Blot employing an anti-Rluc8-IgG. Expression of alternative splice variants was eliminated through the deletion of the donor splice site by introduction of a silent point mutation. In all ten biosensors the energy transfer from the Rluc8 to the GFP2 occurs and generates a measurable eBRET2 ratio. Four biosensors show a relevant change of the BRET ratio (Delta BR) after VEGF binding. Furthermore, each biosensor shows a unique detection range for VEGF quantification and especially Re06 and Re07 have a high sensitivity in the range of in vivo VEGF concentrations in the eye, previously measured by invasive methods. In conclusion, we generated several eBRET2 biosensors that are suitable for VEGF quantification in vitro and could identify two eBRET2 biosensors, which may be suitable for non-invasive in vivo VEGF quantification with an implantable device.
C1 [Stumpf, Constanze; Wimmer, Tobias; Lorenz, Birgit; Stieger, Knut] Justus Liebig Univ Giessen, Dept Ophthalmol, Giessen, Germany.
C3 Justus Liebig University Giessen
RP Wimmer, T (通讯作者)，Justus Liebig Univ Giessen, Dept Ophthalmol, Giessen, Germany.
EM Tobias.Wimmer@augen.med.uni-giessen.de
OI Wimmer, Tobias/0000-0001-8176-4747
FU Justus-Liebig-University Giessen
FX This study was funded in part by a graduate scholarship from the
   Justus-Liebig-University Giessen awarded to CS. No additional external
   funding was received for this study.
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NR 43
TC 3
Z9 3
U1 3
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2020
VL 15
IS 3
AR e0230344
DI 10.1371/journal.pone.0230344
PG 16
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA LR8GI
UT WOS:000535934200025
PM 32214330
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, LM
   Xia, QQ
   Zhou, YY
   Li, J
AF Zhang, Lingmin
   Xia, Qingqing
   Zhou, Yingying
   Li, Jie
TI Endoplasmic reticulum stress and autophagy contribute to cadmium-induced
   cytotoxicity in retinal pigment epithelial cells
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Cadmium; Retinal pigment epithelial cell; Reactive oxygen species;
   ER-stress; Autophagy
ID MACULAR DEGENERATION; INDUCED APOPTOSIS; AGE; PROTECTS; EXPRESSION;
   INVOLVEMENT; ACTIVATION; MECHANISMS; KEAP1-NRF2; SYSTEM
AB Excessive accumulation of cadmium (Cd) in retina plays an important role in tobacco smoking-associated age-related macular degeneration (AMD). Plenty of evidence has revealed that the retinal pigment epithelium (RPE) is the primary site of pathology in AMD. Our current study demonstrated that Cd induced apoptosis in a human RPE cell line ARPE-19 cells, as it dose-dependently caused cell viability loss and activated caspase-3. The reactive oxygen species (ROS) were confirmed to be important mediators for Cd-triggered cell death in ARPE-19 cells. We found that endoplasmic reticulum (ER) stress was activated as its marker BiP was remarkably upregulated by Cd-exposure. Whereas the antioxidants N-acetylcysteine (NAC) and Tempol significantly suppressed the expression of BiP and CHOP, suggesting that ROS generation is an early trigger of Cd-activated ER stress. Furthermore, we found that Cd-induced oxidative stress significantly increased autophagic flux and p62 expression. A temporal impact of Cd exposure is possibly existed in p62 expression in ARPE-19 cells. Moreover, an ER stress inhibitor salubrinal diminished Cd-induced LC3BII expression and attenuated cytotoxicity, indicating that ER stress mediates autophagy and was implicated in apoptosis of Cd-exposed ARPE-19 cells. However, CHOP expression may not exert impact on the regulation of Cd-caused autophagy. Additionally, inhibition of autophagy with si-Beclin 1 and 3-Methyladenine significantly ameliorated Cd-induced CHOP expression and cytotoxicity, indicating that autophagy was detrimental in Cd-accumulated ARPE-19 cells, and a positive feedback regulation mechanism may exist between Cd-triggered ER stress and autophagy. Taken together, these results suggest that Cd-caused ER stress and autophagy are implicated in RPE cell death associated retinopathies especially related to smoking.
C1 [Zhang, Lingmin; Xia, Qingqing; Zhou, Yingying; Li, Jie] Wenzhou Med Univ, Taizhou Peoples Hosp 1, Huangyan Hosp, Cent Lab, Taizhou 318020, Zhejiang, Peoples R China.
C3 Wenzhou Medical University
RP Li, J (通讯作者)，Wenzhou Med Univ, Taizhou Peoples Hosp 1, Huangyan Hosp, Cent Lab, Taizhou 318020, Zhejiang, Peoples R China.
EM liyijie12580@126.com
OI Li, Jie/0000-0001-5463-3995
FU Medical Science and Technology Program of Zhejiang Province [2016KYA195,
   2017KY714]; Zhejiang Provincial Natural Science Foundation of China
   [LQ17H120001]; National Natural Science Foundation of China [81801424];
   211 talents training program of Taizhou
FX The present study was supported by the Medical Science and Technology
   Program of Zhejiang Province (2016KYA195 and 2017KY714); Zhejiang
   Provincial Natural Science Foundation of China (LQ17H120001); the
   National Natural Science Foundation of China (81801424); and the 211
   talents training program of Taizhou (Jie Li).
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0378-4274
EI 1879-3169
J9 TOXICOL LETT
JI Toxicol. Lett.
PD SEP 1
PY 2019
VL 311
BP 105
EP 113
DI 10.1016/j.toxlet.2019.05.001
PG 9
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA HZ1QJ
UT WOS:000468622000012
PM 31054874
DA 2022-11-30
ER

PT J
AU Invernizzi, A
   Nguyen, V
   Teo, K
   Barthelmes, D
   Fung, A
   Vincent, A
   Gimes, M
AF Invernizzi, Alessandro
   Vuong Nguyen
   Teo, Kelvin
   Barthelmes, Daniel
   Fung, Adrian
   Vincent, Andrea
   Gimes, Mark
TI Five-Year Real-World Outcomes of Occult and Classic Choroidal
   Neovascularization: Data From the Fight Retinal Blindness! Project
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID BASE-LINE PREDICTORS; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; VISUAL
   OUTCOMES; VERTEPORFIN; RANIBIZUMAB; TRIALS; VEGF; BEVACIZUMAB; TAP
AB PURPOSE: To compare 5-year real-world outcomes of eyes with classic and occult choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (anti-VEGF) injections.
   DESIGN: Retrospective analysis from a prospectively designed observational database.
   METHODS: Treatment-naive eyes diagnosed with occult or minimally or predominantly classic CNV that commenced anti-VEGF treatment between January 2007 and December 2012 were identified from a registry of neovascular age-related macular degeneration (nAMD) treatment outcomes. Baseline characteristics, visual acuity (VA) at 5 years, change in VA, time to first inactivation, number of injections, and proportion of visits graded with active nAMD over the 5 years were compared between the 3 groups.
   RESULTS: A total of 1929 eyes from 1730 subjects (1196 occult, 289 minimally classic, and 444 predominantly classic CNV) were analyzed. Baseline VA (mean [standard deviation]) was higher in occult CNVs (56.9 [17.4] letters) than in minimally (52.9 [19.7] letters) and predominantly (49.1 [19.9] letters) classic CNVs (P =.003 and P <.0001, respectively). VA change was similar across the groups. At 5 years eyes with occult CNVs still had better VA than other CNVs. Age, lesion size, and baseline VA, but not CNV type, significantly affected final VA in the multivariate model. Predominantly classic CNVs became inactive sooner and were overall less active than other CNV types. The number of injections received was similar across the groups.
   CONCLUSIONS: Eyes with occult CNVs had overall a better VA than other CNVs. The difference in final VA was not significant after adjusting for baseline VA. Five-year outcomes and treatment patterns were not affected by the lesion type. (Am J Ophthalmol 2019;204:105-112. (C) 2019 Elsevier Inc. All rights reserved.)
C1 [Invernizzi, Alessandro] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
   [Invernizzi, Alessandro; Vuong Nguyen; Teo, Kelvin; Barthelmes, Daniel; Fung, Adrian; Gimes, Mark] Univ Sydney, Save Sight Inst, Discipline Ophthalmol, Sydney Med Sch, Sydney, NSW, Australia.
   [Teo, Kelvin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Barthelmes, Daniel] Univ Hosp Zurich, Zurich, Switzerland.
   [Barthelmes, Daniel] Univ Zurich, Zurich, Switzerland.
   [Fung, Adrian] Westmead Hosp, Sydney, NSW, Australia.
   [Fung, Adrian] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia.
   [Vincent, Andrea] Univ Auckland, Fac Med & Hlth Sci, New Zealand Natl Eye Ctr, Dept Ophthalmol, Auckland, New Zealand.
C3 University of Milan; Luigi Sacco Hospital; University of Sydney;
   National University of Singapore; Singapore National Eye Center;
   University of Zurich; University Zurich Hospital; University of Zurich;
   University of Sydney; Macquarie University; University of Auckland
RP Invernizzi, A (通讯作者)，Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
EM alessandro.invernizzi@gmail.com
OI Teo, Kelvin/0000-0002-7458-7081
FU MACULAR DISEASE Foundation Australia; Bayer; Novartis
FX THE FIGHT RETINAL BLINDNESS! PROJECT IS SUPPORTED BY A GRANT FROM THE
   MACULAR DISEASE Foundation Australia and unrestricted educational grants
   from Bayer and Novartis.
CR [Anonymous], 1991, Arch Ophthalmol, V109, P1220
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NR 35
TC 13
Z9 14
U1 1
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 AUG
PY 2019
VL 204
BP 105
EP 112
DI 10.1016/j.ajo.2019.03.001
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IN7KD
UT WOS:000478859400013
PM 30862501
DA 2022-11-30
ER

PT J
AU Uchida, A
   Hu, M
   Babiuch, A
   Srivastava, SK
   Singh, RP
   Kaiser, PK
   Talcott, K
   Rachitskaya, A
   Ehlers, JP
AF Uchida, Atsuro
   Hu, Ming
   Babiuch, Amy
   Srivastava, Sunil K.
   Singh, Rishi P.
   Kaiser, Peter K.
   Talcott, Katherine
   Rachitskaya, Aleksandra
   Ehlers, Justis P.
TI Optical coherence tomography angiography characteristics of choroidal
   neovascularization requiring varied dosing frequencies in
   treat-and-extend management: An analysis of the AVATAR study
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; OCT ANGIOGRAPHY;
   RANIBIZUMAB; TACHYPHYLAXIS; THERAPY
AB Purpose
   To evaluate optical coherence tomography angiography (OCTA) characteristics of choroidal neovascularization (CNV) in eyes requiring different treatment frequency of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD).
   Design
   Prospective observational case series.
   Methods
   Subjects who had undergone anti-VEGF treatment for NVAMD in the AVATAR study were subdivided into 3 groups depending on required anti-VEGF dosing: (i) treat-and-extend requiring every 4-6 weeks dosing (TEq4-6w), (ii) treat-and-extend requiring every 7-12 weeks dosing (TEq7-12w), (iii) eyes not requiring injection within last 12 months (PRN > 12mo). OCTA images were evaluated for the morphological characteristics of CNV and the choriocapillaris flow void.
   Results
   Study consisted 40 eyes of 31 patients with a mean age of 79.9 +/- 6.2 years. CNV morphology analysis on OCTA was feasible in 29 (73%) eyes. Ninety percent of CNVs in TEq7-12w group were irregular in shape involving foveal center, while 67% of CNVs in PRN> 12mo group were circular in shape sparing foveal center. Among three groups, statistical difference was found in CNV shape (P =.012) and CNV location (P =.003), while no statistical difference was found in the CNV area (P =.14), vessel density (P =.19), presence of core vessels (P =.23), the presence of small margin loops (P =.20), large margin loops (P =.14), CNV maturity (P =.40), or the mean percentage of choriocapillaris area with flow void (P =.66).
   Conclusion
   The combination of CNV sparing the foveal center with higher circularity may suggest a clinically inactive CNV following initial anti-VEGF therapy. We found minimal distinguishing OCTA characteristics between those eyes that required ongoing therapy with the treat-andextend regimen. More research is needed to identify specific CNV characteristics on OCTA that may become a useful tool for the management of NVAMD and timing of treatment.
C1 [Uchida, Atsuro; Hu, Ming; Babiuch, Amy; Srivastava, Sunil K.; Talcott, Katherine; Ehlers, Justis P.] Cleveland Clin, Cole Eye Inst, Tony & Leona Campane Ctr Excellence Image Guided, Cleveland, OH 44106 USA.
   [Hu, Ming] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
   [Babiuch, Amy; Srivastava, Sunil K.; Singh, Rishi P.; Kaiser, Peter K.; Talcott, Katherine; Rachitskaya, Aleksandra; Ehlers, Justis P.] Cleveland Clin, Cole Eye Inst, Retina Serv, Cleveland, OH 44106 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation
RP Ehlers, JP (通讯作者)，Cleveland Clin, Cole Eye Inst, Tony & Leona Campane Ctr Excellence Image Guided, Cleveland, OH 44106 USA.; Ehlers, JP (通讯作者)，Cleveland Clin, Cole Eye Inst, Retina Serv, Cleveland, OH 44106 USA.
EM ehlersj@ccf.org
RI Uchida, Atsuro/GVT-8593-2022
OI Uchida, Atsuro/0000-0002-1378-7151; Ehlers, Justis/0000-0001-6763-7768
FU Alcon Novartis Hida Memorial Award 2015 - Alcon Japan Ltd; Betty J.
   Powers Retina Research Fellowship; NIH/NEI [K23-EY022947-01A1]; Research
   to Prevent Blindness; NATIONAL EYE INSTITUTE [K23EY022947] Funding
   Source: NIH RePORTER
FX Unrestricted travel grant from Alcon Novartis Hida Memorial Award 2015
   funded by Alcon Japan Ltd (AU); The Betty J. Powers Retina Research
   Fellowship (AU); NIH/NEI K23-EY022947-01A1 (JPE); Research to Prevent
   Blindness (Cole Eye Institutional Grant). The funders had no role in the
   design and conduct of the study, in the collection, analysis and
   interpretation of the data, and in the preparation, review or approval
   of the manuscript. Justis P. Ehlers, M. D. has 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 44
TC 13
Z9 13
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 25
PY 2019
VL 14
IS 6
AR e0218889
DI 10.1371/journal.pone.0218889
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IW3BT
UT WOS:000484856000047
PM 31237929
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Wang, YX
   Wei, WB
   Xu, L
   Jonas, JB
AF Wang, Ya Xing
   Wei, Wen Bin
   Xu, Liang
   Jonas, Jost B.
TI Physical activity and eye diseases. The Beijing Eye Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; Beijing Eye Study; diabetes mellitus;
   diabetic retinopathy; glaucoma; physical activity
ID MACULAR DEGENERATION; INTRAOCULAR-PRESSURE; EXERCISE; ASSOCIATION;
   MORTALITY; GLAUCOMA; CHINA
AB Purpose To assess associations between the amount of physical activity and the prevalence of ocular diseases. Methods The participants of the population-based Beijing Eye Study underwent a detailed ophthalmological examination and an interview. Physical activity was assessed in a standardized questionnaire. Results Out of 3468 study participants, information on their physical activity was available for 3031 (87.4%) individuals (age: 64.6 +/- 9.7 years; range: 50-93 years). In multivariate analysis (regression coefficient r: 0.41), higher physical activity was associated with a lower prevalence of diabetic retinopathy [p = 0.009; standardized regression coefficient beta: -0.05; non-standardized regression coefficient B: -15.7; 95% confidence interval (CI): -27.6, -3.90] after adjusting for younger age, rural region of habitation, lower level of education, lower blood concentrations of triglycerides and low-density lipoproteins and higher blood concentrations of high-density lipoproteins, higher systolic blood pressure, lower body mass index and lower depression score. Other major ocular diseases such as open-angle glaucoma (p = 0.25), angle-closure glaucoma (p = 0.59), nuclear cataract (p = 0.78), cortical cataract (p = 0.54), posterior subcapsular cataract (p = 0.96), retinal vein occlusions (p = 0.93) and central serous choroidopathy (p = 0.39) were not statistically associated with physical activity in that model. The association between higher physical activity and prevalence of age-related macular degeneration (p = 0.04; beta: 0.04; B: 4.87; 95% CI: 0.25, 9.50) was marginally significant. Conclusions Higher physical activity and less sedentary lifestyle were associated with a lower prevalence of diabetic retinopathy, while the occurrence of other major ocular diseases such as any type of cataract and of glaucoma, retinal vein occlusions and central serous choroidopathy was statistically independent of physical activity or a more sedentary lifestyle.
C1 [Wang, Ya Xing; Xu, Liang; Jonas, Jost B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol, Beijing, Peoples R China.
   [Wang, Ya Xing; Xu, Liang; Jonas, Jost B.] Beijing Key Lab Ophthalmol & Visual Sci, Beijing, Peoples R China.
   [Wei, Wen Bin] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannhe, Dept Ophthalmol, Mannheim, Germany.
C3 Capital Medical University; Capital Medical University; Ruprecht Karls
   University Heidelberg
RP Wei, WB (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.; Wei, WB (通讯作者)，Beijing Ophthalmol & Visual Sci Key Lab, Beijing Key Lab Intraocular Tumor Diag & Treatmen, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.
EM tr_weiwenbin@163.com
RI wang, YA XING/K-9671-2016
OI wang, YA XING/0000-0003-2749-7793; Jonas, Jost/0000-0003-2972-5227
FU State Natural Sciences Fund [81041018]; Natural Sciences Fund of Beijing
   government [7092021, 7112031]
FX Supported by State Natural Sciences Fund (81041018) and the Natural
   Sciences Fund of Beijing government (7092021; 7112031).
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NR 29
TC 14
Z9 15
U1 0
U2 6
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 2019
VL 97
IS 3
BP 325
EP 331
DI 10.1111/aos.13962
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HU2IS
UT WOS:000465095200015
PM 30338672
DA 2022-11-30
ER

PT J
AU Grieve, K
   Gofas-Salas, E
   Ferguson, RD
   Sahel, JA
   Paques, M
   Rossi, EA
AF Grieve, Kate
   Gofas-Salas, Elena
   Ferguson, R. Daniel
   Sahel, Jose Alain
   Paques, Michel
   Rossi, Ethan A.
TI In vivo near-infrared autofluorescence imaging of retinal pigment
   epithelial cells with 757 nm excitation
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID FUNDUS AUTOFLUORESCENCE; LIGHT; RESOLUTION; LIPOFUSCIN; RPE;
   PHOTORECEPTORS
AB We demonstrate near-infrared autofluorescence (NIRAF) imaging of retinal pigment epithelial (RPE) cells in vivo in healthy volunteers and patients using a 757 nm excitation source in adaptive optics scanning laser ophthalmoscopy (AOSLO). NIRAF excited at 757 nm and collected in an emission band from 778 to 810 nm produced a robust NIRAF signal, presumably arising from melanin, and revealed the typical hexagonal mosaic of RPE cells at most eccentricities imaged within the macula of normal eyes. Several patterns of altered NIRAF structure were seen in patients, including disruption of the NIRAF over a drusen, diffuse hyper NIRAF signal with loss of individual cell delineation in a case of non-neovascular age-related macular degeneration (AMD), and increased visibility of the RPE mosaic under an area showing loss of photoreceptors. In some participants, a superposed cone mosaic was clearly visible in the fluorescence channel at eccentricities between 2 and 6 degrees from the fovea. This was reproducible in these participants and existed despite the use of emission filters with an optical attenuation density of 12 at the excitation wavelength, minimizing the possibility that this was due to bleed through of the excitation light. This cone signal may be a consequence of cone waveguiding on either the ingoing excitation light and/or the outgoing NIRAF emitted by fluorophores within the RPE and/or choroid and warrants further investigation. NIRAF imaging at 757 nm offers efficient signal excitation and detection, revealing structural alterations in retinal disease with good contrast and shows promise as a tool for monitoring future therapies at the level of single RPE cells. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Grieve, Kate; Gofas-Salas, Elena; Sahel, Jose Alain; Paques, Michel] Vis Inst, 28 Rue Charenton, F-75712 Paris, France.
   [Grieve, Kate; Gofas-Salas, Elena; Sahel, Jose Alain; Paques, Michel] Quinze Vingts Natl Ophthalmol Hosp, PARIS Grp, 28 Rue Charenton, F-75712 Paris, France.
   [Gofas-Salas, Elena] Univ Paris Saclay, ONERA, DOTA, F-91123 Palaisea, France.
   [Ferguson, R. Daniel] Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA.
   [Sahel, Jose Alain; Rossi, Ethan A.] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
   [Rossi, Ethan A.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15213 USA.
C3 UDICE-French Research Universities; Sorbonne Universite; CHNO des
   Quinze-Vingts; UDICE-French Research Universities; Sorbonne Universite;
   National Office for Aerospace Studies & Research (ONERA); UDICE-French
   Research Universities; Universite Paris Saclay; Physical Sciences Inc.;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh
RP Rossi, EA (通讯作者)，Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.; Rossi, EA (通讯作者)，Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15213 USA.
EM rossiea@pitt.edu
RI Sahel, Jose-Alain/F-3172-2017; Rossi, Ethan/AAC-6204-2019
OI Sahel, Jose-Alain/0000-0002-4831-1153; Rossi, Ethan/0000-0003-3210-0551;
   Gofas Salas, Elena/0000-0003-1975-0373; Grieve, Kate/0000-0002-2937-6285
FU European Research Council SYNERGY Grant scheme (HELMHOLTZ, ERC Grant)
   [610110]; Edward N. & Della L. Thome Memorial Foundation; University of
   Pittsburgh; NIH CORE Grant [P30 EY08098]; Eye and Ear Foundation of
   Pittsburgh; Research to Prevent Blindness, New York, N.Y., USA
FX European Research Council SYNERGY Grant scheme (HELMHOLTZ, ERC Grant
   Agreement #610110), a grant from the Edward N. & Della L. Thome Memorial
   Foundation to Jose Alain Sahel and by departmental startup funds from
   the University of Pittsburgh to Ethan A. Rossi. This work was also
   supported by NIH CORE Grant P30 EY08098 to the University of Pittsburgh
   Department of Ophthalmology, the Eye and Ear Foundation of Pittsburgh,
   and from an unrestricted grant from Research to Prevent Blindness, New
   York, N.Y., USA.
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   Zhang Q. X., SCI REP, V3, P2644
NR 43
TC 16
Z9 16
U1 0
U2 5
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 DEC 1
PY 2018
VL 9
IS 12
BP 5946
EP 5961
DI 10.1364/BOE.9.005946
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 HC5PQ
UT WOS:000451855300007
PM 31065405
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rishi, P
   Rishi, E
   Maitray, A
   Agarwal, A
   Nair, S
   Gopalakrishnan, S
AF Rishi, Pukhraj
   Rishi, Ekta
   Maitray, Aditya
   Agarwal, Ashutosh
   Nair, Sridevi
   Gopalakrishnan, Sarika
TI Hospital anxiety and depression scale assessment of 100 patients before
   and after using low vision care: A prospective study in a tertiary
   eye-care setting
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anxiety; depression; eye; hospital anxiety and depression scale; low
   vision care; low vision devices; visual impairment
ID QUALITY-OF-LIFE; MACULAR DEGENERATION; REHABILITATION SERVICES
AB Purpose: Assessment of anxiety and depression in patients attending low vision care (LVC) using Hospital Anxiety and Depression Scale (HADS). Methods: In this prospective, observational study, 100 patients with best-corrected visual acuity (BCVA) worse than 6/18 in the better eye or limitation of field of vision to <10 degrees from center of fixation were assessed on the depression and anxiety subscales of HADS questionnaire before and after LVC. HADS is a 14-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression. Results: Mean age at presentation was 38.2 years. Mean duration of symptoms was 9.6 years. Underlying etiology of visual impairment included retinal dystrophy/degeneration (n = 35), disorders of the optic nerve (n = 17), glaucoma (n = 10), diabetic retinopathy (n = 9), age-related macular degeneration (n = 5), uncorrected refractive errors (n = 5), and miscellaneous diseases (n = 19). Mean presenting BCVA in the better eye was 0.83 (+/- 0.64) which improved significantly to 0.78 (+/- 0.63) after LVC (P < 0.001). The HADS-Depression subscale score was comparable for severity of visual impairment for both distance (P = 0.57) and near vision (P = 0.61). Similarly, HADS-Anxiety scores were also comparable for severity of distance (P = 0.34) and near-visual impairment (NVI; P = 0.50). At baseline, mean HADS-Depression and HADS-Anxiety scores were 8.4 (+/- 3.7) and 9.6 (+/- 4.3) points, which improved significantly to 6.0 (+/- 3.4) and 6.7 (+/- 3.7), respectively, after low-vision correction (P < 0.001). Conclusion: Low vision correction can significantly improve anxiety and depression indicators in visually impaired patients.
C1 [Rishi, Pukhraj; Rishi, Ekta; Maitray, Aditya; Agarwal, Ashutosh; Nair, Sridevi] Shri Bhagwan Mahavir Vitreoretinal Serv, Madras, Tamil Nadu, India.
   [Gopalakrishnan, Sarika] Low Vis Care Clin, Madras, Tamil Nadu, India.
RP Rishi, P (通讯作者)，Sankara Nethralaya, Shri Bhagwan Mahavir Vitreoretinal Serv, 18 Coll Rd, Madras 600006, Tamil Nadu, India.
EM docrishi@yahoo.co.in
RI Rishi, Pukhraj/AAZ-5296-2020; Maitray, Aditya/AAX-4540-2020
OI Maitray, Aditya/0000-0002-7569-687X
CR [Anonymous], 2017, AG REL MAC DEG PPP U
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NR 12
TC 21
Z9 21
U1 0
U2 4
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD NOV
PY 2017
VL 65
IS 11
BP 1203
EP 1208
DI 10.4103/ijo.IJO_436_17
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FM7HP
UT WOS:000415246000027
PM 29133652
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wilde, C
   Poostchi, A
   Mehta, RL
   MacNab, HK
   Hillman, JG
   Vernon, SA
   Amoaku, WM
AF Wilde, C.
   Poostchi, A.
   Mehta, R. L.
   MacNab, H. K.
   Hillman, J. G.
   Vernon, S. A.
   Amoaku, W. M.
TI Prevalence of agerelated macular degeneration in an elderly UK Caucasian
   population-The Bridlington Eye Assessment Project: a cross-sectional
   study
SO EYE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; VISUAL IMPAIRMENT; UNITED-KINGDOM; FOLLOW-UP;
   ROTTERDAM; DISEASE; OLDER; CERTIFICATIONS; MANAGEMENT; COMMUNITY
AB Importance There is paucity of data on prevalence and disease asymmetry of agerelated macular degeneration (AMD), particularly the earlier stages, in the UK population.
   Objective and Purpose To determine the prevalence of age-related macular degeneration in an elderly Caucasian UK population. Design Cross-sectional population study, 2002-2006.
   Participants Residents in the study area of Bridlington aged 65 years and older.
   Methods Full-ophthalmic examination was undertaken in 3549 participants, of eligible 6319 Caucasian population (response rate of 56%). Non-stereoscopic Colour fundus photographs (30(circle)) were graded masked using a modified Rotterdam Classification for 3475 (98%) participants with gradable images. Prevalence for different AMD grades were calculated. Demographic details were analysed then integrated with the AMD gradings for full analysis. Prevalence rates for the different AMD Grades were calculated, as well as the age-specific prevalences.
   Results AMD prevalence in the worst eye were 38.5% grade 0, 41.4% grade 1, 12.8% grade 2, 2.8% grade 3, and 4.6% grade 4. Geographic atrophy (grade 4a) occurred in 2.5%, and neovascular AMD (grade 4b) in 1.8%. Prevalence increased with age such that grade 4 (advanced) AMD was 2.2% in the 65-69 years group, 15.8% for the 85-90, and 21.2% for over 90 years. There was significant asymmetry between the two eyes of individuals with advanced AMD (P<0.001), such that vision loss was unilateral. Persons with more advanced AMD grades were more likely to be dissatisfied with their vision.
   Conclusions Advanced AMD occurs more commonly in the UK Caucasian population than previously reported. Significant asymmetry between the two eyes occurs in individuals with unilateral advanced AMD so that visual impairment statistics do not represent true prevalence of advanced AMD. Persons with more advanced AMD were more likely to be dissatisfied with their vision.
C1 [Wilde, C.; Poostchi, A.; Amoaku, W. M.] Univ Nottingham, Queens Med Ctr, EENT Ctr, Ophthalmol & Vis Sci,Div Clin Neurosci, B Floor, Nottingham NG7 2UH, England.
   [Mehta, R. L.] Univ Nottingham, Sch Med, Nottingham Hlth Sci Partners, Res Design Serv,East Midlands RDS EM, Nottingham, England.
   [MacNab, H. K.; Hillman, J. G.] Med Ctr, Stn Ave, Bridlington, England.
   [Vernon, S. A.] Univ Hosp, Queens Med Ctr, Nottingham, England.
   [Vernon, S. A.] Univ Nottingham, Ophthalmol, Nottingham, England.
   [Vernon, S. A.] Pk Hosp, Nottingham, England.
C3 University of Nottingham; University of Nottingham; Nottingham
   University Hospital NHS Trust; University of Nottingham; University of
   Nottingham
RP Amoaku, WM (通讯作者)，Univ Nottingham, Queens Med Ctr, EENT Ctr, Ophthalmol & Vis Sci,Div Clin Neurosci, B Floor, Nottingham NG7 2UH, England.
EM wma@nottingham.ac.uk
OI Mehta, Rajnikant/0000-0002-5341-5598; Amoaku,
   Winfried/0000-0001-5028-7984
FU Macular Society UK, Andover, Hants, UK; Pfizer; Pharmacia, Yorkshire
   Wolds and Coast Primary Care Trust; Lords Feoffees of Bridlington,
   Bridlington Hospital League of Friends; Hull and East Riding Charitable
   Trust; National Eye Research Centre (Yorkshire); Rotary Club of
   Bridlington; Alexander Pigott Wernher Memorial Trust, Bridlington Lions
   Club; Inner Wheel Club of Bridlington, Soroptimist International of
   Bridlington; Patricia and Donald Shepherd Charitable Trust
FX This research was funded in part by a Research Grant from the Macular
   Society UK, Andover, Hants, UK. The Bridlington Eye Assessment Project
   was funded by an unrestricted grant from Pfizer. We would also like to
   thank the following organisations for financial support of the Project:
   Pharmacia, Yorkshire Wolds and Coast Primary Care Trust, The Lords
   Feoffees of Bridlington, Bridlington Hospital League of Friends, The
   Hull and East Riding Charitable Trust, The National Eye Research Centre
   (Yorkshire), The Rotary Club of Bridlington, The Alexander Pigott
   Wernher Memorial Trust, Bridlington Lions Club, The Inner Wheel Club of
   Bridlington, Soroptimist International of Bridlington, and The Patricia
   and Donald Shepherd Charitable Trust. We would also like to thank Sheila
   MacNab (Project Manager), and Stephen Brown, Janet Button, Graham
   Langton, and Mark Kunz (Optometrists) for their work with the Project;
   John Bapty, Nigel Connell, Peter Jay, and Gillian Poole for their work
   as the charity trustees of the Bridlington Eye Assessment Project.
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NR 43
TC 32
Z9 32
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 JUL
PY 2017
VL 31
IS 7
BP 1042
EP 1050
DI 10.1038/eye.2017.30
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FA4YA
UT WOS:000405448600008
PM 28282062
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Fenwick, EK
   Ong, PG
   Man, REK
   Sabanayagam, C
   Cheng, CY
   Wong, TY
   Lamoureux, EL
AF Fenwick, Eva K.
   Ong, Peng Guan
   Man, Ryan E. K.
   Sabanayagam, Charumathi
   Cheng, Ching-Yu
   Wong, Tien Y.
   Lamoureux, Ecosse L.
TI Vision impairment and major eye diseases reduce vision-specific
   emotional well-being in a Chinese population
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; DEPRESSIVE SYMPTOMS; VISUAL IMPAIRMENT; IMPACT;
   SUPPRESSION; PREVALENCE; DISTRESS; GLAUCOMA; PEOPLE
AB Aims To assess the relationship between vision impairment (VI) and major eye diseases, with vision-specific emotional well-being in a Chinese population.
   Methods In this population-based cross-sectional study, 3353 Chinese participants aged 40-80 years answered the emotional well-being scale of the Impact of Vision Impairment questionnaire, validated using Rasch analysis. Participants underwent visual acuity testing and collection of sociodemographic and medical data from standardised questionnaires. The relationships between presenting bilateral VI, presence of major eye diseases (cataract, undercorrected refractive error, glaucoma, age-related macular degeneration and diabetic retinopathy) and emotional well-being were assessed using linear regression models. Stratified analyses for age, gender, education and immigration status were conducted to determine if change in beta coefficients differed within each stratum.
   Results Approximately half of patients (n=1805) had normal vision, and 43% (n=1534) and 3.4% (n=114) had moderate and severe bilateral VI, respectively. Vision-specific emotional well-being systematically worsened as severity of bilateral VI increased (p<0.001). Compared with no VI and no eye diseases, respectively, severe bilateral VI (23%; beta -1.84; 95% CI -2.23 to -1.43) and glaucoma (beta -1.88; 95% CI -3.00 to -0.76) were associated with a clinically meaningful reduction in emotional well-being. The reduction in vision-related emotional well-being was substantially and significantly greater in men compared with women (p<0.05).
   Conclusions Severe VI and glaucoma are associated with substantial decrements in vision-specific emotional well-being, highlighting the importance of preventing progression of vision loss. Evidence-based interventions to improve vision-related coping skills and emotional management for patients with severe VI and glaucoma are warranted.
C1 [Fenwick, Eva K.; Ong, Peng Guan; Man, Ryan E. K.; Sabanayagam, Charumathi; Cheng, Ching-Yu; Wong, Tien Y.; Lamoureux, Ecosse L.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Fenwick, Eva K.; Lamoureux, Ecosse L.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
   [Fenwick, Eva K.; Sabanayagam, Charumathi; Cheng, Ching-Yu; Wong, Tien Y.; Lamoureux, Ecosse L.] Duke NUS Med Sch, Singapore, Singapore.
   [Cheng, Ching-Yu; Wong, Tien Y.; Lamoureux, Ecosse L.] Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore.
   [Cheng, Ching-Yu; Wong, Tien Y.; Lamoureux, Ecosse L.] Natl Univ Hlth Syst, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center; Centre
   for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; National University of Singapore; National
   University of Singapore; National University of Singapore
RP Lamoureux, EL (通讯作者)，Duke NUS Med Sch Singapore, Off Clin Sci, 20 Coll Rd Level 6, Singapore 169856, Singapore.
EM ecosse.lamoureux@duke-nus.edu.sg
RI Lamoureux, Ecosse/Z-5482-2019; Wong, Tien Yin/AAC-9724-2020;
   Sabanayagam, Charumathi/C-1294-2011; Cheng, Ching-Yu/Y-2229-2019
OI Wong, Tien Yin/0000-0002-8448-1264; Sabanayagam,
   Charumathi/0000-0002-4042-4719; Cheng, Ching-Yu/0000-0003-0655-885X;
   Man, Ryan/0000-0001-5028-605X
FU National Medical Research Council [STaR/0003/2008, CIRG/1417/2015];
   Singapore Bio Imaging Consortium [C-011/2006]; Biomedical Research
   Council [08/1/35/19/550]; Australian National Health and Medical
   Research Council Early Career Fellowship [1072987]
FX This study was supported by grants from the National Medical Research
   Council (STaR/0003/2008 and CIRG/1417/2015), the Singapore Bio Imaging
   Consortium (C-011/2006) and the Biomedical Research Council
   (08/1/35/19/550). EKF is funded by the Australian National Health and
   Medical Research Council Early Career Fellowship (# 1072987). The Centre
   for Eye Research Australia receives Operational Infrastructure Support
   from the Victorian Government.
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NR 27
TC 19
Z9 19
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 MAY
PY 2017
VL 101
IS 5
BP 686
EP 690
DI 10.1136/bjophthalmol-2016-308701
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA EW2MQ
UT WOS:000402331100026
PM 27565988
DA 2022-11-30
ER

PT J
AU Maniglia, M
   Cottereau, BR
   Soler, V
   Trotter, Y
AF Maniglia, Marcello
   Cottereau, Benoit R.
   Soler, Vincent
   Trotter, Yves
TI Rehabilitation Approaches in Macular Degeneration Patients
SO FRONTIERS IN SYSTEMS NEUROSCIENCE
LA English
DT Review
DE AMD; perceptual learning; peripheral vision; cortical plasticity; brain
   stimulation
ID RANDOM NOISE STIMULATION; IDENTIFY CROWDED LETTERS; VISUAL-CORTEX;
   CORTICAL REORGANIZATION; CONTRAST SENSITIVITY; LATERAL INTERACTIONS;
   LETTER-RECOGNITION; SPATIAL-FREQUENCY; IMPROVING VISION; ADULT AMBLYOPIA
AB Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patients quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patients visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients.
C1 [Maniglia, Marcello; Cottereau, Benoit R.; Trotter, Yves] Univ Toulouse UPS, Ctr Rech Cerveau & Cognit, Toulouse, France.
   [Maniglia, Marcello; Cottereau, Benoit R.; Trotter, Yves] Ctr Natl Rech Sci, Toulouse, France.
   [Maniglia, Marcello] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA.
   [Soler, Vincent] Hop CHU Purpan, Dept Ophthalmol, Toulouse, France.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre
   National de la Recherche Scientifique (CNRS); Universite Federale
   Toulouse Midi-Pyrenees (ComUE); Centre National de la Recherche
   Scientifique (CNRS); University of California System; University of
   California Riverside
RP Maniglia, M; Trotter, Y (通讯作者)，Univ Toulouse UPS, Ctr Rech Cerveau & Cognit, Toulouse, France.; Maniglia, M; Trotter, Y (通讯作者)，Ctr Natl Rech Sci, Toulouse, France.; Maniglia, M (通讯作者)，Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA.
EM marcello.maniglia@gmail.com; yves.trotter@cnrs.fr
RI Cottereau, Benoit R/AAU-4741-2020; Maniglia, Marcello/J-7245-2019
OI Cottereau, Benoit R/0000-0002-2624-7680; Maniglia,
   Marcello/0000-0002-2053-0071; SOLER, Vincent/0000-0002-3837-0619
FU Fondation de France (Fouassier) [2013 00039351, 2014 00048124];
   Fondation de l'Avenir [AP-RMA-2015-003]
FX MM was supported by the "Fondation de France (Fouassier; 2013 00039351
   and 2014 00048124)'' and "Fondation de l'Avenir (AP-RMA-2015-003)''.
   Authors would like to thank Russell Cohen Hoffing for english
   proofreading.
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NR 120
TC 14
Z9 14
U1 0
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-5137
J9 FRONT SYST NEUROSCI
JI Front. Syst. Neurosci.
PD DEC 27
PY 2016
VL 10
AR 107
DI 10.3389/fnsys.2016.00107
PG 11
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA EF9MH
UT WOS:000390653800002
PM 28082876
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Shen, XF
   Huang, P
   Fox, DA
   Lin, Y
   Zhao, ZH
   Wang, W
   Wang, JY
   Liu, XQ
   Chen, JY
   Luo, WJ
AF Shen, Xue-Feng
   Huang, Ping
   Fox, Donald A.
   Lin, Yan
   Zhao, Zai-Hua
   Wang, Wen
   Wang, Ji-Ye
   Liu, Xin-Qin
   Chen, Jing-Yuan
   Luo, Wen-Jing
TI Adult lead exposure increases blood-retinal permeability: A risk factor
   for retinal vascular disease
SO NEUROTOXICOLOGY
LA English
DT Article
DE Lead; Neurotoxicity; Blood-retinal-barrier; Tight junctions; Vascular
   permeability; PI3K-Akt
ID BRAIN-BARRIER; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED RETINOPATHY;
   ENDOTHELIAL-CELLS; TIGHT JUNCTIONS; HUMAN EYES; IN-VITRO; OCCLUDIN;
   PHOSPHORYLATION; RATS
AB Low-to-moderate level developmental and adult lead exposure produces retinal dysfunction and/or degeneration in humans and experimental animals. Although high level in vivo or in vitro lead disrupts blood-brain-barrier tight junctions and increases its permeability, the blood-retinal-barrier (BRB) has not been examined. There were four overall goals. First, generate environmentally relevant dose-response models of short-term lead exposure in adult rats. Second, assess retinal histology and functional integrity of the BRB. Third, investigate the transmembrane proteins occludin and claudin-5 as targets mediating the increased BRB permeability. Fourth, examine the contribution of the PI3K-Akt signaling pathway as a mechanism underlying increased BRB permeability. Young adult rats were given water, 0.01% or 0.02% lead drinking solutions for six weeks. In control, 0.01% and 0.02% groups the six week mean blood [Pb] were 1, 12.5 and 19 mu g/dl, respectively. We employed histology, stereology, quantitative image analysis, immunoblots and densitometry, and pharmacology techniques. Major findings were that adult lead exposure produced dose-dependent 1) decreases in outer and inner nuclear layer thickness, 2) increases in BRB permeability, 3) decreases in occludin and claudin-5 expression, 4) increases in pAkt (Ser473), but not pAkt (Thr308), expression, and 5) wortmannin partially or completely blocked the increased BRB permeability and changes in protein expression. These results indicate that lead-induced increases in PI3K-Akt signaling partially underlie the increased BRB permeability and advance our knowledge about lead-induced retinotoxicity. Furthermore, they suggest that environmental and occupational lead exposures are risk factors for increased BRB permeability in diseases such as age-related macular degeneration, diabetes and stroke. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Shen, Xue-Feng; Huang, Ping; Zhao, Zai-Hua; Wang, Ji-Ye; Liu, Xin-Qin; Chen, Jing-Yuan; Luo, Wen-Jing] Fourth Mil Med Univ, Dept Occupat & Environm Hlth, Xian, Shanxi Province, Peoples R China.
   [Shen, Xue-Feng; Huang, Ping; Zhao, Zai-Hua; Wang, Ji-Ye; Liu, Xin-Qin; Chen, Jing-Yuan; Luo, Wen-Jing] Fourth Mil Med Univ, Minist Educ, Key Lab Hazard Assessment & Control Special Opera, Xian, Shanxi Province, Peoples R China.
   [Fox, Donald A.] Univ Houston, Coll Optometry, Dept Biol & Biochem, Houston, TX USA.
   [Fox, Donald A.] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA.
   [Lin, Yan] Fourth Mil Med Univ, PLA, Inst Eye, Dept Ophthalmol,Xijing Hosp, Xian, Shanxi Province, Peoples R China.
   [Wang, Wen] Fourth Mil Med Univ, Tangdu Hosp, Dept Radiol, Xian, Shanxi Province, Peoples R China.
C3 Air Force Military Medical University; Air Force Military Medical
   University; University of Houston System; University of Houston;
   University of Houston System; University of Houston; Air Force Military
   Medical University; Air Force Military Medical University
RP Luo, WJ (通讯作者)，Fourth Mil Med Univ, Dept Occupat & Environm Hlth, Sch Publ Hlth, Xian 710032, Peoples R China.; Luo, WJ (通讯作者)，Fourth Mil Med Univ, Minist Educ, Sch Publ Hlth, Key Lab Hazard Assessment & Control Special Opera, Xian 710032, Peoples R China.
EM luowenj@fmmu.edu.cn
FU National Basic Research Program of China [2012CD525002]; National
   Natural Scientific Foundation of China [81273101, 81230063, 81273100,
   30830087]; Program for Changjiang Scholars and Innovative Research Team
   in University (PCSIRT); Program for New Century Excellent Talents in
   University; Shaanxi science and technology coordinating innovative
   project [2011KTCL03-19, 2016KTCQ03-01]
FX This work was supported by the National Basic Research Program of China
   (2012CD525002), the National Natural Scientific Foundation of China
   Grant (Nos. 81273101,81230063, 81273100 and 30830087), Program for
   Changjiang Scholars and Innovative Research Team in University (PCSIRT),
   Program for New Century Excellent Talents in University, Shaanxi science
   and technology coordinating innovative project (2011KTCL03-19,
   2016KTCQ03-01).
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NR 61
TC 6
Z9 7
U1 1
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD DEC
PY 2016
VL 57
BP 145
EP 152
DI 10.1016/j.neuro.2016.09.013
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA EE3NT
UT WOS:000389497000018
PM 27663850
DA 2022-11-30
ER

PT J
AU Brue, C
   Pazzaglia, A
   Mariotti, C
   Reibaldi, M
   Giovannini, A
AF Brue, C.
   Pazzaglia, A.
   Mariotti, C.
   Reibaldi, M.
   Giovannini, A.
TI Aflibercept as primary treatment for myopic choroidal
   neovascularisation: a retrospective study
SO EYE
LA English
DT Article
ID INTRAVITREAL ANTI-VEGF; PATHOLOGICAL MYOPIA; MACULAR DEGENERATION;
   PHOTODYNAMIC THERAPY; PROGNOSTIC-FACTORS; FOLLOW-UP; TRAP-EYE;
   RANIBIZUMAB; BEVACIZUMAB; VERTEPORFIN
AB Aim The aim of this study is to evaluate long-term efficacy of intravitreal injections of aflibercept as primary treatment for subfoveal/juxtafoveal myopic choroidal neovascularisation (CNV).
   Methods Thirty-eight treatment-naive eyes of thirty-eight patients with subfoveal/juxtafoveal myopic CNV received initial intravitreal aflibercept injections and were followed for at least 18 months. Aflibercept was applied again for persistent or recurrent CNV, as required. Statistical analysis was carried out using SPSS.
   Results Mean patient age was 45.8 years, and mean eye refractive error was -7.79 D. For the total patient group (n = 38 eyes), mean logMAR best-corrected visual acuity (BCVA) significantly improved from 0.69 at baseline to 0.15 at 18 months (P < 0.01). Over half of the treated eyes obtained resolution with one aflibercept injection. Patients were also grouped according to age, as <50 years (n = 20 eyes) and >= 50 years (n = 18 eyes). Mean BCVA improvement was significantly greater in eyes of the younger myopic CNV group, compared with those of >= 50 years (0.21 vs 0.35; P < 0.05). The mean number of aflibercept injections was 1.8 for the <50 years myopic CNV group, and 3.6 for the >= 50 years myopic CNV group (P < 0.001). Correlation between spherical equivalent refraction and final visual acuity reached statistical significance only for the <50 years myopic CNV group (P < 0.001; Levene's correlation).
   Conclusions Intravitreal aflibercept provides long-term visual acuity improvement in myopic CNV. The <50 years old myopic CNV group had significantly fewer injections, with greater visual acuity improvement. Intravitreal aflibercept in myopic CNV does not require the three-injection loading phase used for aflibercept treatment of neovascular age-related macular degeneration.
C1 [Brue, C.; Mariotti, C.; Giovannini, A.] Polytech Univ Marche, Ophthalmol, Dept Neurosci, Ancona, Italy.
   [Brue, C.] Macerata Hosp, Ophthalmol, Macerata, Italy.
   [Pazzaglia, A.] St Orsola Hosp, Ophthalmol, Malpighi, Italy.
   [Reibaldi, M.] G Rodolico Vittorio Emanuele Hosp, Ophthalmol, Catania, Italy.
C3 Marche Polytechnic University; Azienda Ospedaliera Universitaria
   Policlinico Vittorio Emanuele Presidio Ferraotto
RP Brue, C (通讯作者)，Polytech Univ Ancona, Ophthalmol, Dept Neurosci, Via Brecce Bianca, I-60020 Ancona, Italy.
EM claudia.brue@gmail.com
RI Reibaldi, Michele/AAL-1113-2021
CR Baba T, 2010, BRIT J OPHTHALMOL, V94, P864, DOI 10.1136/bjo.2009.166025
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NR 35
TC 19
Z9 20
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2016
VL 30
IS 1
BP 139
EP 145
DI 10.1038/eye.2015.199
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DA5PW
UT WOS:000367856000021
PM 26514244
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Fuma, S
   Murase, H
   Kuse, Y
   Tsuruma, K
   Shimazawa, M
   Hara, H
AF Fuma, Shinichiro
   Murase, Hiromi
   Kuse, Yoshiki
   Tsuruma, Kazuhiro
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Photobiomodulation with 670 nm light increased phagocytosis in human
   retinal pigment epithelial cells
SO MOLECULAR VISION
LA English
DT Article
ID PHOTORECEPTOR OUTER SEGMENTS; EMITTING DIODE IRRADIATION; OXIDATIVE
   STRESS; PROMOTES PHAGOCYTOSIS; MERTK; DAMAGE; DYSFUNCTION; INHIBITION;
   MECHANISMS; MUTATIONS
AB Purpose: Photobiomodulation is the treatment with light in the far-red to near-infrared region of the spectrum and has been reported to have beneficial effects in various animal models of disease, including an age-related macular degeneration (AMD) mouse model. Previous reports have suggested that phagocytosis is reduced by age-related increased oxidative stress in AMD. Therefore, we investigated whether photobiomodulation improves phagocytosis caused by oxidative stress in the human retinal pigment epithelial (ARPE-19) cell line.
   Methods: ARPE-19 cells and human primary retinal pigment epithelium (hRPE) cells were incubated and irradiated with near-infrared light (670 nm LED light, 2,500 lx, twice a day, 250 s/per time) for 4 d. Next, hydrogen peroxide (H2O2) and photoreceptor outer segments (POS) labeled using a pH-sensitive fluorescent dye were added to the cell culture, and phagocytosis was evaluated by measuring the fluorescence intensity. Furthermore, cell death was observed by double staining with Hoechst33342 and propidium iodide after photobiomodulation. CM-H(2)DCFDA, JC-1 dye, and CCK-8 were added to the cell culture to investigate the reactive oxygen species (ROS) production, mitochondrial membrane potential, and cell viability, respectively. We also investigated the expression of phagocytosis-related proteins, such as focal adhesion kinase (FAK) and Mer tyrosine kinase (MerTK).
   Results: Oxidative stress inhibited phagocytosis, and photobiomodulation increased the oxidative stress-induced hypoactivity of phagocytosis in ARPE-19 cells and hRPE cells. Furthermore, H2O2 and photobiomodulation did not affect cell death in this experimental condition. Photobiomodulation reduced ROS production but did not affect cell viability or mitochondrial membrane potential. The expression of phosphorylated MerTK increased, but phosphorylated FAK was not affected by photobiomodulation.
   Conclusions:
   These findings indicate that near-infrared light photobiomodulation (670 nm) may be a noninvasive, inexpensive, and easy adjunctive therapy to help inhibit the development of ocular diseases induced by the activation of phagocytosis.
C1 [Fuma, Shinichiro; Murase, Hiromi; Kuse, Yoshiki; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
RI Kuse, Yoshiki/AAB-7445-2021
OI Hara, Hideaki/0000-0003-2046-9001
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NR 31
TC 19
Z9 23
U1 2
U2 19
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 21
PY 2015
VL 21
BP 883
EP 892
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA CP8QC
UT WOS:000360158100001
PM 26321863
DA 2022-11-30
ER

PT J
AU Qiu, YT
   Yuan, Y
   Wei, Z
   Qing, G
   Wu, XW
   Qiu, QH
   Yin, LL
AF Qiu Yating
   Yuan, Yao
   Wei, Zhang
   Qing, Gu
   Wu Xingwei
   Qiu, Qinhua
   Yin Lili
TI Oxidized LDL Induces Apoptosis of Human Retinal Pigment Epithelium
   Through Activation of ERK-Bax/Bcl-2 Signaling Pathways
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age related macular degeneration; apoptosis; Oxidized LDL; retinal
   pigment epithelium
ID LOW-DENSITY LIPOPROTEINS; AGE-RELATED MACULOPATHY; HUMAN RPE CELLS;
   OXIDATIVE STRESS; BRUCHS MEMBRANE; VISUAL IMPAIRMENT; BASAL DEPOSITS;
   ARPE-19 CELLS; IN-VITRO; CHOLESTEROL
AB Purpose: Retinal pigment epithelium (RPE) cell dysfunction and death play a vital role in the pathogenesis of age-related macular degeneration (AMD). We previously reported that oxidized low-density lipoprotein (OX-LDL) induces retinal degeneration in vivo. In this study, we investigated the role of the ERK-Bax/Bcl-2 signaling pathways in OX-LDL-induced apoptosis in human RPE.
   Methods: ARPE-19 cells were incubated with 10-100mg/mL n-LDL or OX-LDL for 24 h. Cell viability was assessed using the Cell Titer 96 Aqueous One Solution cell proliferation assay. RPE apoptosis was measured with a flow cytometer. Reverse transcription polymerase chain reaction was used to detect Bcl-2 and Bax mRNA levels in RPE cells. Bcl-2 and Bax protein expression was measured by western blotting. Activation of extracellular signal-regulated kinase (ERK) protein was evaluated by western blot analysis. One-way analysis of variance was used to compare differences.
   Results: OX-LDL treatment decreased ARPE-19 cell viability in a dose-dependent manner, whereas n-LDL had no effect. Compared with the control group, OX-LDL significantly increased the apoptosis of RPE, 10 mg/mL, 50 mg/mL, 100mg/mL apoptosis rate was 6.43 +/- 0.19%, 5.12 +/- 0.27%, 5.53 +/- 0.35%, respectively. OX-LDL also increased Bcl-2 expression and decreased Bax expression significantly. The Bcl-2 to Bax ratio was elevated after OX-LDL treatment. Inhibition of ERK downregulated Bax and was associated with RPE apoptosis.
   Conclusions: Our data suggest that apoptosis induced by OX-LDL in RPE partly depends on Erk-Bax/Bcl-2 signaling pathway activation. These results may provide further information regarding the effects of OX-LDL in human RPE and their potential role in AMD pathogenesis.
C1 [Qiu Yating; Yuan, Yao; Wei, Zhang; Qing, Gu; Wu Xingwei; Qiu, Qinhua; Yin Lili] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
C3 Shanghai Jiao Tong University
RP Qiu, QH (通讯作者)，Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China.
EM 1519234030@qq.com; yll144@aliyun.com
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NR 27
TC 22
Z9 23
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD APR
PY 2015
VL 40
IS 4
BP 415
EP 422
DI 10.3109/02713683.2014.927507
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CD9XU
UT WOS:000351454800007
PM 24956392
DA 2022-11-30
ER

PT J
AU Coffey, EE
   Beckel, JM
   Laties, AM
   Mitchell, CH
AF Coffey, E. E.
   Beckel, J. M.
   Laties, A. M.
   Mitchell, C. H.
TI LYSOSOMAL ALKALIZATION AND DYSFUNCTION IN HUMAN FIBROBLASTS WITH THE
   ALZHEIMER'S DISEASE-LINKED PRESENILIN 1 A246E MUTATION CAN BE REVERSED
   WITH CAMP
SO NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease; presenilin 1; autophagy; lysosomal pH; age-related
   macular degeneration (AMD); cathepsin D
ID VACUOLAR H+-ATPASE; SYNTHASE KINASE 3; CATHEPSIN-D; MACULAR
   DEGENERATION; DIFFERENTIAL EXPRESSION; PARKINSONS-DISEASE;
   PROTEIN-KINASE; CULTURED HUMAN; C DISEASE; RPE CELLS
AB Mutation in presenilin 1 (PS1) is one of the leading causes of familial Alzheimer's disease (fAD). PS1 mutation exacerbates the autophagic and lysosomal pathology in AD patients, leading to accumulation of partially degraded material in bloated lysosomes and autophagosomes - a pathology that bears some resemblance to other diseases characterized by elevated lysosomal pH, like age-related macular degeneration. In this study, we examined the effect of the PS1-fAD mutation A246E on lysosomal pH and lysosomal function, and asked whether restoration of lysosomal pH could reverse some of these changes. Lysosomal pH was elevated by 0.2-0.3 pH units in human fibroblasts with the PS1-fAD mutation. The lysosomal alkalization in PS1-fAD fibroblasts was supported by a reduction in the pH-dependent cleavage of cathepsin D and by a reduction in binding of boron-dipyrromethene (BODIPY) FL-pepstatin A to the cathepsin D active site. PS1-fAD cells had increased LC3B-II/-I ratios and p62 levels, consistent with impaired lysosomal degradation and analogous to changes induced by lysosomal alkalinization with chloroquine. PS1-fAD fibroblasts had increased expression of ATP6V1B2, ATG5, BECN1 TFEB mRNA, and of ATP6V1B2, ATG5 and beclin at the protein level, consistent with chronic impairment of autophagic and lysosomal functions in the mutant cells. Critically, cyclic adenosine monophosphate (cAMP) treatment reacidified lysosomal pH in mutant PS1-fAD; cAMP also increased the availability of active cathepsin D and lowered the LC3B-II/-I ratio. These results confirm a small elevation in the lysosomal pH of human PS1-fAD fibroblasts, demonstrate that this lysosomal alkalization is associated with chronic changes in autophagy and degradation, and suggest that treatment to reacidify the lysosomes with cAMP can reverse these changes. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Coffey, E. E.; Beckel, J. M.; Mitchell, C. H.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
   [Laties, A. M.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Mitchell, C. H.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of
   Pennsylvania
RP Mitchell, CH (通讯作者)，Univ Penn, Dept Anat & Cell Biol, 440 Levy Bldg,240 S 40th St, Philadelphia, PA 19104 USA.
EM chm@exchange.upenn.edu
RI Beckel, Jonathan/A-6758-2008
OI Beckel, Jonathan/0000-0003-1390-2292
FU Hearst Foundation Fellowship (EEC); National Institutes of Health
   [EY013434, EY015537]; Vision Research Core Grant [EY001583]; Research to
   Prevent Blindness; Foundation Fighting Blindness; NATIONAL EYE INSTITUTE
   [P30EY001583, R01EY015537, R01EY013434] Funding Source: NIH RePORTER
FX We thank Wennan Lu, Jason Lim, Ann O'Brien Jenkins and Gabriel Baltazar
   for training and support, and Kathleen Boesze-Battaglia for help with
   the cathepsin D immunoblots. These experiments were supported by the
   Hearst Foundation Fellowship (EEC), National Institutes of Health
   through grants EY013434, EY015537, Vision Research Core Grant EY001583
   (C. H. M., A. M. L.), Research to Prevent Blindness (A. M. L.), and the
   Foundation Fighting Blindness (A. M. L.). This work has been previously
   presented in abstract form (Coffey et al., 2013).
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NR 74
TC 121
Z9 124
U1 2
U2 27
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD MAR 28
PY 2014
VL 263
BP 111
EP 124
DI 10.1016/j.neuroscience.2014.01.001
PG 14
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA AC3GF
UT WOS:000332403400011
PM 24418614
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chou, CF
   Cotch, MF
   Vitale, S
   Zhang, XZ
   Klein, R
   Friedman, DS
   Klein, BEK
   Saaddine, JB
AF Chou, Chiu-Fang
   Cotch, Mary Frances
   Vitale, Susan
   Zhang, Xinzhi
   Klein, Ronald
   Friedman, David S.
   Klein, Barbara E. K.
   Saaddine, Jinan B.
TI Age-Related Eye Diseases and Visual Impairment Among U.S. Adults
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID ANGELES LATINO EYE; BLUE MOUNTAINS EYE; QUALITY-OF-LIFE; UNDERCORRECTED
   REFRACTIVE ERRORS; UNITED-STATES; MACULAR DEGENERATION;
   SOCIOECONOMIC-FACTORS; VISION IMPAIRMENT; OLDER POPULATION; RISK
   INDICATORS
AB Background: Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported.
   Purpose: To examine common eye conditions and other correlates associated with visual impairment in the U.S.
   Methods: Data from the 2005-2008 National Health and Nutrition Examination Survey of 5222 Americans aged >= 40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement.
   Results: Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55).
   Conclusions: Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases.
C1 [Chou, Chiu-Fang; Zhang, Xinzhi; Saaddine, Jinan B.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA.
   [Cotch, Mary Frances; Vitale, Susan] NIH, NEI, Div Epidemiol & Clin Applicat, Bethesda, MD USA.
   [Friedman, David S.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
   [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
C3 Centers for Disease Control & Prevention - USA; National Institutes of
   Health (NIH) - USA; NIH National Eye Institute (NEI); Johns Hopkins
   University; Johns Hopkins Medicine; University of Wisconsin System;
   University of Wisconsin Madison
RP Chou, CF (通讯作者)，CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, 4770 Buford Hwy,NE K-10, Atlanta, GA 30341 USA.
EM CChou@cdc.gov
OI Friedman, David/0000-0002-2055-5797; Klein, Ronald/0000-0002-4428-6237;
   vitale, susan/0000-0002-5972-6848; Cotch, Mary
   Frances/0000-0002-2046-4350
FU National Center for Health Statistics (NCHS), CDC; Division of Diabetes
   Translation, CDC [05FED47304]; National Eye Institute, NIH
   [ZIAEY000402]; NATIONAL EYE INSTITUTE [ZIAEY000402] Funding Source: NIH
   RePORTER
FX This study was supported by the National Center for Health Statistics
   (NCHS), CDC. Funding for the National Health and Nutrition Examination
   Survey (NHANES) retinal and frequency-doubling technology component was
   provided by the Intra Agency Agreement 05FED47304 from the Division of
   Diabetes Translation, CDC. Funding for the vision component was provided
   by the National Eye Institute, NIH, Intramural Research Program award
   ZIAEY000402.
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NR 39
TC 60
Z9 61
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2013
VL 45
IS 1
BP 29
EP 35
DI 10.1016/j.amepre.2013.02.018
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 170CO
UT WOS:000320827500004
PM 23790986
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Shirasawa, M
   Sonoda, S
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   Yamashita, T
   Uchino, E
   Hisatomi, T
   Ishibashi, T
   Sakamoto, T
AF Shirasawa, Makoto
   Sonoda, Shozo
   Terasaki, Hiroto
   Arimura, Noboru
   Otsuka, Hiroki
   Yamashita, Takehiro
   Uchino, Eisuke
   Hisatomi, Toshio
   Ishibashi, Tatsuro
   Sakamoto, Taiji
TI TNF-alpha disrupts morphologic and functional barrier properties of
   polarized retinal pigment epithelium
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE porcine RPE; membrane polarity; barrier function; TNF-alpha
ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; ENDOTHELIAL-CELL PERMEABILITY;
   GROWTH-FACTOR SECRETION; MACULAR DEGENERATION; TIGHT JUNCTIONS;
   SIGNAL-TRANSDUCTION; EXPRESSION; NEOVASCULARIZATION; INFLAMMATION
AB Retinal pigment epithelial (RPE) cells form a blood ocular barrier, and their polarized property is crucial for maintaining the barrier functions. Tumor necrosis factor alpha (TNF-alpha), a major pleotropic inflammatory cytokine that disrupts the barrier function and eventual angiogenesis, is expressed in the choroidal neovascularizations of age-related macular degeneration eyes. Thus, it most likely plays an important role in the progression of the disease. The purpose of this study was to compare the effects of TNF-alpha on the barrier function of polarized RPE cells. Non-polarized RPE cells were used as negative controls. Isolated porcine RPE cells were seeded on Transwell (TM) membranes. The polarization of the RPE cells was determined by their high transepithelial electrical resistance (TER > 150 Omega cm(2)) and by their differential secretion of vascular endothelial growth factor (lower layer/upper layer >2.5X). Polarized RPE cells were incubated with 10 ng/ml of TNF-alpha and the TER was measured. TNF-alpha significantly decreased the TER of polarized RPE cells by 17.6 +/- 2.7% (P < 0.001) of the control at 24 h and that of non-polarized RPE cells by 5.4 +/- 6.5% (P = 0.401). The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked the effects of TNF-alpha of decreasing the TER. Cell junction-related molecules, e.g., ZO-1, located between cells in control RPE cells, were disassembled by TNF-alpha, and this breakdown was suppressed by SB203580 in polarized RPEs. These results indicate that the breakdown of the RPE barrier function was caused exclusively by TNF-alpha in polarized RPEs, and TNF-alpha was acting through the p38 MAPK pathways. Investigations of polarized RPE cells should be more suitable for in vitro studies of the pathophysiology of retinochoroidal diseases. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Shirasawa, Makoto; Sonoda, Shozo; Terasaki, Hiroto; Arimura, Noboru; Otsuka, Hiroki; Yamashita, Takehiro; Uchino, Eisuke; Sakamoto, Taiji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Kagoshima 8908520, Japan.
   [Hisatomi, Toshio; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan.
C3 Kagoshima University; Kyushu University
RP Sakamoto, T (通讯作者)，Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, 8-35-1 Sakuragaoka Kagoshima, Kagoshima 8908520, Japan.
EM tsakamot@m3.kufm.kagoshima-u.ac.jp
OI Hisatomi, Toshio/0000-0003-2552-9595
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 [20390450]
FX This research was supported in part by a Grant from the Research
   Committee on Chorioretinal Degeneration and Optic Atrophy, Ministry of
   Health, Labor, and Welfare (T. Sakamoto), and by a Grant-in-Aid for
   Scientific Research (No 20390450) from the Ministry of Education,
   Science, and Culture of the Japanese Government.
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NR 46
TC 39
Z9 42
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAY
PY 2013
VL 110
BP 59
EP 69
DI 10.1016/j.exer.2013.02.012
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 135YR
UT WOS:000318327100009
PM 23454586
DA 2022-11-30
ER

PT J
AU Rutar, M
   Natoli, R
   Albarracin, R
   Valter, K
   Provis, J
AF Rutar, Matt
   Natoli, Riccardo
   Albarracin, Rizalyn
   Valter, Krisztina
   Provis, Jan
TI 670-nm light treatment reduces complement propagation following retinal
   degeneration
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EMITTING DIODE TREATMENT; FACTOR-H
   POLYMORPHISM; NEAR-INFRARED LIGHT; MACULAR DEGENERATION; OXIDATIVE
   STRESS; AREA CENTRALIS; PHOTORECEPTOR; INFLAMMATION; DAMAGE
AB Aim: Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD.
   Methods: Sprague-Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE).
   Results: Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment.
   Conclusions: Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy.
C1 [Rutar, Matt; Natoli, Riccardo; Albarracin, Rizalyn; Valter, Krisztina; Provis, Jan] Australian Natl Univ, John Curtin Sch Med Res, Coll Med Biol & Environm, Canberra, ACT 2601, Australia.
   [Rutar, Matt; Natoli, Riccardo; Albarracin, Rizalyn; Valter, Krisztina; Provis, Jan] Australian Natl Univ, ARC Ctr Excellence Vis Sci, Canberra, ACT 2601, Australia.
   [Natoli, Riccardo; Valter, Krisztina; Provis, Jan] Australian Natl Univ, ANU Med Sch, Canberra, ACT 2601, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Coll Med Biol & Environm, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
EM matt.rutar@anu.edu.au
RI Provis, Jan/C-9529-2009; Valter, Krisztina/L-3015-2016
OI Provis, Jan/0000-0002-6405-2868; Valter, Krisztina/0000-0002-2033-0408;
   Rutar, Matthew/0000-0002-8893-5120; Natoli, Riccardo/0000-0002-9350-0439
FU Australian Research Council Centres of Excellence Program Grant
   [CE0561903]
FX This work was funded by the Australian Research Council Centres of
   Excellence Program Grant (CE0561903).
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NR 76
TC 43
Z9 44
U1 0
U2 8
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD NOV 26
PY 2012
VL 9
AR 257
DI 10.1186/1742-2094-9-257
PG 10
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 049PL
UT WOS:000311995600001
PM 23181358
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Pacella, E
   Pacella, F
   Mazzeo, F
   Turchetti, P
   Carlesimo, SC
   Cerutti, F
   Lenzi, T
   De Paolis, G
   Giorgi, D
AF Pacella, E.
   Pacella, F.
   Mazzeo, F.
   Turchetti, P.
   Carlesimo, S. C.
   Cerutti, F.
   Lenzi, T.
   De Paolis, G.
   Giorgi, D.
TI Effectiveness of vision rehabilitation treatment through MP-1
   microperimeter in patients with visual loss due to macular disease
SO CLINICA TERAPEUTICA
LA English
DT Article
DE biofeedback; rehabilitation; stimulation; microperimetry; MP-1; macular
   degeneration; central scotoma
ID SCANNING LASER OPHTHALMOSCOPE; DEGENERATION; FIXATION;
   NEOVASCULARIZATION; SCOTOMA
AB Purpose. To evaluate the effectiveness of biofeedback treatment for low-vision rehabilitation in patients affected by macular disease.
   Materials and Methods. 171 eyes of 99 patients (42 female and 57 male) between 50 to 75 years old (mean age: 64.6) were included in this study. All patients were suffering from age-related macular degeneration (AMD) (122 eyes) or macular myopic degeneration (MMD) (49 eyes). All patients underwent an assessment of examinations including visual acuity, reading speed test, slit lamp examination and tonometry, ophthalmoscopic fundus examination, microperimetry, fixation test, retinal sensitivity, fluorangiography (FAG), optical coherence tomography (OCT). The treatment was divided in 16 sessions, the patients underwent other examination assessment at 6 and 12 months, except for FAG and OCT. Statistical analysis was performed using Student's t-test, and p-value <= 0.05 was considered statistically significant.
   Results. After training 130 eyes of 171 in the study group (76.02%) had a statistically significant improvement of the distant visual acuity (p<0.01): 38 eyes suffering from MMD and 92 eyes suffering from AMD. After 12 months of follow-up a group of 25 eyes of 130 (19.23%) had a loss of benefits that were observed at the end of the treatment sessions: 16 eyes and 9 eyes were suffering from MMD and AMD respectively. Examination assessment during follow-up showed that 4 eyes and 2 eyes of the group that lost benefits had a worsening of MMD and AMD primary disease respectively.
   Conclusions. It is not yet understood how biofeedback produces amelioration of visual function. According to the "Eccentric fixation" theory, with biofeedback rehabilitation patients are trained to use the non-damaged retina areas to develop a new preferred retinal locus. In our study group we found a significant improvement in both visual acuity and fixation. Clin Ter 2012; 163(6):e423-428
C1 [Pacella, E.; Pacella, F.; Mazzeo, F.; Carlesimo, S. C.; Cerutti, F.; Lenzi, T.; De Paolis, G.; Giorgi, D.] Univ Roma La Sapienza, Fac Med & Dent, Dept Sense Organs, I-00161 Rome, Italy.
   [Turchetti, P.] Natl Inst Hlth Migrat & Poverty INMP NIHMP, Rome, Italy.
C3 Sapienza University Rome
RP Pacella, E (通讯作者)，Univ Roma La Sapienza, Fac Med & Dent, Dept Sense Organs, Viale Policlin, I-00161 Rome, Italy.
EM elena.pacella@uniroma1.it
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NR 19
TC 17
Z9 18
U1 0
U2 17
PU SOC EDITRICE UNIV
PI ROME
PA VIA G B MORGAGNI 1, ROME, 10061, ITALY
SN 0009-9074
EI 1972-6007
J9 CLIN TER
JI Clin. Ter.
PD NOV-DEC
PY 2012
VL 163
IS 6
SU S
BP E423
EP E428
PG 6
WC Medicine, General & Internal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Pharmacology & Pharmacy
GA 143WI
UT WOS:000318899100010
PM 23306757
DA 2022-11-30
ER

PT J
AU Kelly, SP
   Barua, A
AF Kelly, S. P.
   Barua, A.
TI A review of safety incidents in England and Wales for vascular
   endothelial growth factor inhibitor medications
SO EYE
LA English
DT Review
DE vascular endothelial growth factor; macular; retina; patient safety
   incident; endophthalmitis; organization
ID MACULAR DEGENERATION; INTRAVITREAL INJECTION; PATIENT SAFETY;
   RANIBIZUMAB; ENDOPHTHALMITIS; BEVACIZUMAB; VERTEPORFIN; BARRIERS; SYSTEM
AB Purpose To learn from patient safety incidents (PSIs) following recent introduction of vascular endothelial growth factor inhibitor medications (anti-VEGF) in ophthalmic care, as reported via a national incident reporting database.
   Methods Thematic retrospective review of anti-VEGF medications PSIs as reported via clinical incident reporting methods in NHS care in England and Wales from 2003 to 2010, ascertained from database mining at the National Patient Safety Agency (NPSA).
   Results In all, 166 relevant anti-VEGF incidents were reported. Reports have increased year on year from 2006. Incident severity as reported: 10 were reported as 'severe harm' and 23 as 'moderate harm'. The remainder were 'low' or 'no harm' events. The incident themes and/or causes found and by order of severity included: intra-ocular inflammation/endophthalmitis (n = 16); treatment or follow-up delays (n = 45); wrong medication (n = 26); wrong eye/patient injection (n = 17); missing records (n 12). Other problems included medication availability and refrigeration failures. We reflect on potential solutions for addressing the matters found. Systemic safety matters, stroke, subdural hemorrhage, and myocardial infarction (total n 3) followed anti-VEGF treatments.
   Conclusion Although infrequent, anti-VEGF medication PSIs or errors do occur and are thus a threat to quality. This review also provides supporting evidence to existing concerns and challenges surrounding age-related macular degeneration service pressures and provision. Lessons for improvement of care from a national incident reporting database for a frequently undertaken and recently introduced ophthalmic procedure were found. Suggestions are proposed for improving quality by reducing such problems based on analysis of such reports. Endophthalmitis reports following intra-vitreal injections suggest rigorous infection control measures are required. Eye (2011) 25, 710-716; doi:10.1038/eye.2011.89; published online 29 April 2011
C1 [Kelly, S. P.; Barua, A.] Royal Bolton Hosp NHS Fdn Trust, Bolton BL4 OJR, Lancs, England.
C3 Royal Bolton Hospital
RP Kelly, SP (通讯作者)，Royal Bolton Hosp NHS Fdn Trust, Minerva Rd, Bolton BL4 OJR, Lancs, England.
FU Novartis; Allergan; Pfizer
FX SP Kelly is Chairman of Quality and Safety Sub-Committee at the Royal
   College of Ophthalmologists. This is an unpaid position. He has declared
   received consulting fees for attending advisory board meetings and
   travel support from Novartis, Allergan and Pfizer.
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NR 40
TC 25
Z9 27
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 JUN
PY 2011
VL 25
IS 6
BP 710
EP 716
DI 10.1038/eye.2011.89
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 775BA
UT WOS:000291430100006
PM 21527957
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Murdaugh, LS
   Avalle, LB
   Mandal, S
   Dill, AE
   Dillon, J
   Simon, JD
   Gaillard, ER
AF Murdaugh, L. S.
   Avalle, L. B.
   Mandal, S.
   Dill, A. E.
   Dillon, J.
   Simon, J. D.
   Gaillard, E. R.
TI Compositional studies of human RPE lipofuscin
SO JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE lipofuscin; A2E; blue light damage; oxidative stress; age-related
   macular degeneration
ID PIGMENT EPITHELIAL-CELLS; POLYUNSATURATED FATTY-ACIDS; HUMAN RETINAL
   LIPOFUSCIN; AGE PIGMENT; A2E; ACCUMULATION; COMPONENT; FLUOROPHORE;
   OXIDATION; DAMAGE
AB Age-related macular degeneration (AMD) is an ocular disease that causes visual loss and legal blindness in the elderly population. The etiology of AMD is complex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. The accumulation of lipofuscin has been shown to precede the death of photoreceptor cells and the deterioration of the RPE. As a result, the determination of the photosensitive components of lipofuscin has been of major interest. One of these components, previously identified as a bis-retinoid pyridinium compound, is referred to as A2E. A2E has been characterized by mass spectrometry and is known to have a mass of 592 Da. Most remaining chromophores in RPE lipofuscin are structurally related to A2E as determined by their fragmentation pattern with losses of M +/- 190, 174 and/or 150 Da. Analysis of lipofuscin from various donors indicated that the extracts consist of as many as 15 of these hydrophobic components, which are also observed to form spontaneously in vitro over extended periods of time. These consist of ca 90% of the A2E-like components in RPE lipofuscin and correspond to derivatized A2E with discrete molecular weights of 800-900 m/z, 970-1080 m/z and above 1200 m/z regions. It was determined that these species are formed from self-reaction of A2E oxidation products or their reaction with A2E itself to form higher molecular weight products. The majority of modifications are much more hydrophobic than A2E and exhibit increasingly higher values of log P. This acts as a driving force for the sequestering of A2E into granules resulting in a concomitant diminution of its reactivity in vivo. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Murdaugh, L. S.; Mandal, S.; Dill, A. E.; Gaillard, E. R.] No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   [Avalle, L. B.] Natl Univ Cordoba, IFFaMAF, Electrochem Grp, Cordoba, Argentina.
   [Dillon, J.; Gaillard, E. R.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   [Simon, J. D.] Duke Univ, Dept Chem, Durham, NC 27706 USA.
C3 Northern Illinois University; National University of Cordoba; Columbia
   University; Duke University
RP Gaillard, ER (通讯作者)，No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
EM Gaillard@niu.edu
RI Gaillard, Elizabeth/M-2627-2019
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NR 53
TC 31
Z9 31
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1076-5174
EI 1096-9888
J9 J MASS SPECTROM
JI J. Mass Spectrom.
PD OCT
PY 2010
VL 45
IS 10
BP 1139
EP 1147
DI 10.1002/jms.1795
PG 9
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 672TQ
UT WOS:000283610200007
PM 20860013
DA 2022-11-30
ER

PT J
AU Szabo, SM
   Janssen, PA
   Khan, K
   Lord, SR
   Potter, MJ
AF Szabo, S. M.
   Janssen, P. A.
   Khan, K.
   Lord, S. R.
   Potter, M. J.
TI Neovascular AMD: an overlooked risk factor for injurious falls
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Age-related macular degeneration (AMD); Elderly; Falls; Prevention
ID MACULAR DEGENERATION; VISUAL FUNCTION; OLDER-PEOPLE; PREVENTING FALLS;
   AGE; COMMUNITY; ADULTS; POPULATION; IMPAIRMENT; FRACTURES
AB While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls.
   Impaired vision, particularly peripheral visual function, is a key risk factor for injurious falls. NV-AMD is a leading cause of severely impaired vision among older adults but is associated with a profound central, rather than peripheral, deficit. The objective was to determine whether older women with NV-AMD are at an increased risk of falls or injurious falls.
   We conducted a 12-month prospective cohort study of community-dwelling older (a parts per thousand yen70 years) women, enrolling 114 with NV-AMD and 132 without from a retinal clinic in Vancouver, Canada. Fall incidence was determined through monthly telephone follow-up, with fall severity classified by a blinded reviewer. We compared mean injurious falls per person-year between groups using negative binomial regression.
   A mean of 0.37 injurious falls per person-year were experienced among NV-AMD participants, compared to 0.16 injurious falls per person-year among non-NV-AMD participants (p = 0.006). The age-adjusted incidence rate ratio for injurious falls, for an individual with NV-AMD compared to without, was 1.77 (1.07-3.02).
   Older women with NV-AMD are at almost twice the risk of injurious falls compared to those without. Clinicians caring for older adults should recognise NV-AMD as an important risk factor for injurious falls.
C1 [Szabo, S. M.] Willow Chest Ctr, Ctr Hip Hlth & Mobil, Vancouver, BC V5Z 1M9, Canada.
   [Lord, S. R.] UNSW, Prince Wales Med Res Inst, Sydney, NSW, Australia.
   [Szabo, S. M.; Janssen, P. A.; Khan, K.] Vancouver Coastal Hlth Res Inst, Ctr Hip Hlth & Mobil, Vancouver, BC, Canada.
   [Szabo, S. M.; Potter, M. J.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
   [Szabo, S. M.; Janssen, P. A.] Univ British Columbia, Sch Populat & Publ Hlth & Epidemiol, Vancouver, BC V5Z 1M9, Canada.
C3 Prince Wales Medical Research Institute; University of New South Wales
   Sydney; Vancouver Coastal Health Research Institute; University of
   British Columbia; University of British Columbia
RP Szabo, SM (通讯作者)，Willow Chest Ctr, Ctr Hip Hlth & Mobil, 3-F,2647 Willow St, Vancouver, BC V5Z 1M9, Canada.
EM shelagh.szabo@oxfordoutcomes.com
RI Lord, Stephen R/C-9612-2011; Janssen, Patricia/B-1036-2018
OI Janssen, Patricia/0000-0002-4178-1195; Lord, Stephen
   R/0000-0002-7111-8802
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NR 42
TC 21
Z9 21
U1 0
U2 7
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAY
PY 2010
VL 21
IS 5
BP 855
EP 862
DI 10.1007/s00198-009-1025-8
PG 8
WC Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Endocrinology & Metabolism
GA 575OB
UT WOS:000276075600019
PM 19629614
DA 2022-11-30
ER

PT J
AU Yildiz, EH
   Cohen, EJ
   Virdi, AS
   Hammersmith, KM
   Laibson, PR
   Rapuano, CJ
AF Yildiz, Elvin H.
   Cohen, Elisabeth J.
   Virdi, Ajoy S.
   Hammersmith, Kristin M.
   Laibson, Peter R.
   Rapuano, Christopher J.
TI Quality of Life in Keratoconus Patients After Penetrating Keratoplasty
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VISUAL FUNCTION QUESTIONNAIRE; PEOPLE
AB PURPOSE: To determine vision-related quality of life (QoL) measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in keratoconus (KCN) patients who have undergone penetrating keratoplasty (PK) in I or both eyes and to compare the results of our study to those of historical controls.
   DESIGN: Clinical-based, cross-sectional study.
   METHODS: SETTING: Wills Eye Institute, Cornea Service, Thomas Jefferson University, Philadelphia, Pennsylvania.
   STUDY POPULATION: This study included 149 consecutive patients who had undergone PK for KCN.
   INTERVENTION: Between June 1, 2008 and December 31, 2008, the NEI-VFQ was administered to 149 patients. The relationship between demographic and clinical factors and NEI-VFQ subscale scores was evaluated.
   MAIN OUTCOME MEASURE: Vision-related quality of life.
   RESULTS: Eighty-three of 149 patients (55.7%) were male. Approximately half of the patients (76/149; 51.0%) had PK in both eyes. Visual acuity with current correction in the better eye was better than 20/40 in 80% of patients (119/149). Our sample had significantly lower (worse) NEI-VFQ scores compared to Collaborative Longitudinal Evaluation of Keratoconus (CLEK) historical control group for the subscales of role difficulties, dependency, driving, and peripheral vision. In general, scores of our sample were between scores of patients with age-related macular degeneration (AMD) category 3 and 4. Patients with visual acuity better than 20/40 (in the better eye) showed significantly higher scores in all subscales except color vision. There was a significant relationship between minimum time since the graft of 5 years or greater and NEI-VFQ overall score better than AMD category 3 (P = .004).
   CONCLUSION: Despite satisfactory results on visual outcome measures obtained after PK, vision-related QoL in KCN patients remains impaired. (Am J Ophthalmol 2010;149:416-422. (C) 2010 by Elsevier Inc. All rights reserved.)
C1 [Yildiz, Elvin H.; Cohen, Elisabeth J.; Virdi, Ajoy S.; Hammersmith, Kristin M.; Laibson, Peter R.; Rapuano, Christopher J.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Inst, Cornea Serv, Philadelphia, PA 19107 USA.
   [Yildiz, Elvin H.] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Ophthalmol, Ankara, Turkey.
C3 Jefferson University; Ankara Numune Training & Research Hospital;
   Ministry of Health - Turkey
RP Cohen, EJ (通讯作者)，Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Inst, Cornea Serv, 840 Walnut St,Suite 920, Philadelphia, PA 19107 USA.
EM ecohen@willseye.org
CR Brierly SC, 2000, CORNEA, V19, P329, DOI 10.1097/00003226-200005000-00014
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NR 20
TC 26
Z9 27
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAR
PY 2010
VL 149
IS 3
BP 416
EP 422
DI 10.1016/j.ajo.2009.10.005
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 565MD
UT WOS:000275296400010
PM 20172068
DA 2022-11-30
ER

PT J
AU Pitha-Rowe, I
   Liby, K
   Royce, D
   Sporn, M
AF Pitha-Rowe, Ian
   Liby, Karen
   Royce, Darlene
   Sporn, Michael
TI Synthetic Triterpenoids Attenuate Cytotoxic Retinal Injury: Cross-talk
   between Nrf2 and PI3K/AKT Signaling through Inhibition of the Lipid
   Phosphatase PTEN
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY;
   ANTIOXIDANT-RESPONSIVE ELEMENT; HEME OXYGENASE-1 GENE; TUMOR-SUPPRESSOR
   PTEN; NF-KAPPA-B; MACULAR DEGENERATION; CDDO-IMIDAZOLIDE; PHOTOOXIDATIVE
   DAMAGE; OXIDATIVE DAMAGE
AB PURPOSE. Evidence implicating oxidative stress in the pathogenesis of age-related macular degeneration suggests that antioxidant therapy could play a role in preventing its progression. The aim of this study was to determine whether derivatives of the triterpenoid (TP) 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO; CDDO-imidazolide [-Im], CDDO-ethylamide [-EA], and CDDO-trifluoroethylamide [-TFEA]) confer cytoprotection from oxidative-and photooxidative-induced cellular damage and to explore the molecular mechanisms of this cytoprotection.
   METHODS. Retinal pigment epithelial and retinal photoreceptor cell lines were treated with TP derivatives. Induction of Nrf2 signaling was measured by reporter assay. Cytoprotection was quantified by MTT assay. To determine whether TPs confer in vivo cytoprotection, BALB/c mice were pretreated with CDDO-TFEA, and retinal degeneration was induced by light exposure. To explore the association of TPs with PTEN, a biotinylated derivative of CDDO (CDDO-Bt) was used.
   RESULTS. Treatment with CDDO-Im-, -TFEA-, or -EA-induced Nrf2 signaling and TP pretreatment protected retinal cell lines from oxidant-induced cell death. The antioxidant and cytoprotective potential of these compounds was then examined in vivo. Treatment of BALB/c mice with CDDO-TFEA induced the Nrf2-regulated transcripts glcl and trx1 in retinal tissue and was protective from photooxidative retinal damage. Treatment with CDDO-Im leads to phosphorylation of AKT. CDDO-Bt directly binds cysteine 124 within PTEN's active site and inhibits PTEN's lipid phosphatase activity in vitro. Thus the stimulation of AKT activity is mediated by TP inhibition of PTEN activity.
   CONCLUSIONS. These studies highlight the potential of TPs in retinal cytoprotection and implicate PTEN inhibition as a target in cytoprotection. (Invest Ophthalmol Vis Sci. 2009;50:5339-5347) DOI:10.1167/iovs.09-3648
C1 [Pitha-Rowe, Ian; Liby, Karen; Royce, Darlene; Sporn, Michael] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA.
C3 Dartmouth College
RP Pitha-Rowe, I (通讯作者)，Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Box 8096,660 S Euclid Ave, St Louis, MO 63110 USA.
EM ipremail@gmail.com
OI Liby, Karen/0000-0003-3317-3437
FU Reata Pharmaceuticals; National Institutes of Health [CA-78814];
   NATIONAL CANCER INSTITUTE [R01CA078814] Funding Source: NIH RePORTER
FX Supported by grants from Reata Pharmaceuticals and the National
   Institutes of Health (Grant CA-78814).
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   2001, ARCH OPHTHALMOL, V119, P1417
NR 47
TC 67
Z9 71
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2009
VL 50
IS 11
BP 5339
EP 5347
DI 10.1167/iovs.09-3648
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 514XH
UT WOS:000271429200044
PM 19494206
DA 2022-11-30
ER

PT J
AU Chung, STL
   Jarvis, SH
   Woo, SY
   Hanson, K
   Jose, RT
AF Chung, Susana T. L.
   Jarvis, Samuel H.
   Woo, Stanley Y.
   Hanson, Kara
   Jose, Randall T.
TI Reading speed does not benefit from increased line spacing in AMD
   patients
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
ID FOVEAL; AGE
AB Purpose. Crowding, the adverse spatial interaction due to the proximity of adjacent targets, has been suggested as an explanation for slow reading in peripheral vision. Previously, we showed that increased line spacing, which presumably reduces crowding between adjacent lines of text, improved reading speed in the normal periphery (Chung, Optom Vis Sci 2004;81:525-35). The purpose of this study was to examine whether or not individuals with age-related macular degeneration (AMD) would benefit from increased line spacing for reading.
   Methods. Experiment 1: Eight subjects with AMD read aloud 100-word passages rendered at five line spacings: the standard single spacing, 1.5X, 2X, 3X, and 4X the standard spacing. Print sizes were 1X and 2X of the critical print size. Reading time and number of reading errors for each passage were measured to compute the reading speed. Experiment 2: Four subjects with AMD read aloud sequences of six 4-letter words, presented on a computer monitor using the rapid serial visual presentation (RSVP) paradigm. Target words were presented singly, or flanked above and below by two other words that changed in synchrony with the target word, at various vertical word separations. Print size was 2X the critical print size. Reading speed was calculated based on the RSVP exposure duration that yielded 80% of the words read correctly.
   Results. Averaged across subjects, reading speeds for passages were virtually constant for the range of line spacings tested. For sequences of unrelated words, reading speeds were also virtually constant for the range of vertical word separations tested, except at the smallest (standard) separation at which reading speed was lower.
   Conclusions Contrary to the previous finding that reading speed improved in normal peripheral vision, increased line spacing in passages, or increased vertical separation between words in RSVP, did not lead to improved reading speed in people with AMD.
C1 [Chung, Susana T. L.; Jarvis, Samuel H.; Woo, Stanley Y.; Hanson, Kara; Jose, Randall T.] Univ Houston, Coll Optometry, Houston, TX USA.
C3 University of Houston System; University of Houston
RP Chung, STL (通讯作者)，Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
EM s.chung@berkeley.edu
OI Chung, Susana/0000-0003-2729-1808; Woo, Stanley/0000-0002-9011-6749
FU National Eye Institute [R01-EY12810, T35-EY07088, P30-EY07551]; NATIONAL
   EYE INSTITUTE [P30EY007551, R01EY012810, T35EY007088] Funding Source:
   NIH RePORTER
FX This work was supported by Research Grant R01-EY12810 (STLC), Training
   Grant T35-EY07088 (SHJ) and Core Grant P30-EY07551 (UHCO) from the
   National Eye Institute.
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NR 22
TC 23
Z9 23
U1 0
U2 10
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 SEP
PY 2008
VL 85
IS 9
BP 827
EP 833
DI 10.1097/OPX.0b013e31818527ea
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 347YW
UT WOS:000259178800007
PM 18772718
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Baath, J
   Ells, AL
   Crichton, A
   Kherani, A
   Williams, RG
AF Baath, J.
   Ells, A. L.
   Crichton, A.
   Kherani, A.
   Williams, R. G.
TI Safety profile of intravitreal triamcinolone acetonide
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID DIABETIC MACULAR EDEMA; OPTICAL COHERENCE TOMOGRAPHY; RETINAL VEIN
   OCCLUSION; INTRAOCULAR-PRESSURE; INJECTION; DEGENERATION;
   PHOTOCOAGULATION; COMPLICATIONS; CATARACT
AB Background: There is currently a widespread use of intravitreal triamcinolone acetonide (IVTA) for age-related macular degeneration, diabetic macular edema, cystoid macular edema secondary to retinal vein occlusions, and uveitis. The aim of this investigation was to assess the rates of various complications associated with this treatment and to determine which factors are associated with the development of these complications. Methods: A retrospective interventional case series of all patients from one retina specialist undergoing IVTA was conducted in a clinical setting from 2002 to 2005. All disease entities were included. Patients were followed for a mean of 9.5 months after receiving 4 mg (0.1 mL) of nonfiltered triamcinolone acetonide (TA). All complications associated with the injection procedure or with the TA were noted. Results: Two hundred and twenty-three (223) eyes of 192 patients received a total of 336 IVTA injections between 2002 and 2005. The mean age was 73.3 years and mean follow-up was 9.5 months. A single injection was performed in 144 eyes (64.6%); 2 IVTAs in 55 eyes (24.7%); 3 IVTAs in 16 eyes (7.2%), and 3.6% of eyes had more than 3 injections at a minimal interval of 3 months. The only immediate complication was a single injection (0.3%) associated with a temporary occlusion of the central retinal artery, which opened immediately following anterior paracentesis. Late complications included endophthalmitis in 1 of 336 (0.3%) injections and a steroid response requiring glaucoma medication in 60 of 192 patients (31.3%). In patients with preexisting glaucoma, 58.8% required additional glaucoma medication. Glaucoma-filtering surgery was required in 2 of 192 patients (1.0%). Conclusions: In the study center, the IVTA is extremely safe in patients without a history of glaucoma. However, patients with preexisting glaucoma with progressive optic neuropathy must be treated with great caution.
C1 Calgary Retina Consultants, Calgary, AB T3E 7M8, Canada.
   Univ Toronto, Toronto, ON, Canada.
   Univ Calgary, Fac Med Ophthalmol, Calgary, AB, Canada.
C3 University of Toronto; University of Calgary
RP Ells, AL (通讯作者)，Calgary Retina Consultants, 103 49 Richard Way SW, Calgary, AB T3E 7M8, Canada.
EM anna.ells@calgaryhealthregion.ca
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NR 25
TC 40
Z9 41
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN
PY 2007
VL 23
IS 3
BP 304
EP 310
DI 10.1089/jop.2006.125
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 181RS
UT WOS:000247454400013
PM 17593015
DA 2022-11-30
ER

PT J
AU Glotin, AL
   Calipel, A
   Brossas, JY
   Faussat, AM
   Treton, J
   Mascarelli, F
AF Glotin, Anne-Lise
   Calipel, Armelle
   Brossas, Jean-Yves
   Faussat, Anne-Marie
   Treton, Jacques
   Mascarelli, Frederic
TI Sustained versus transient ERK1/2 signaling underlies the anti- and
   proapoptotic effects of oxidative stress in human RPE cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; PIGMENTED EPITHELIAL-CELLS; FOCAL
   CEREBRAL-ISCHEMIA; MACULAR DEGENERATION; INHIBITION; PATHWAYS; NEURONS;
   ARPE-19; DAMAGE; DEATH
AB PURPOSE. Oxidative stress is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which involves retinal pigmented epithelial (RPE) cell death. However, signaling pathways involved in the oxidative-stress-induced RPE cell death are poorly understood. This study was conducted to investigate the involvement of the MAP kinase pathways during the induction of RPE cell death by oxidative stress.
   METHODS. ARPE-19 cells were exposed to the oxidant tert-butyl hydroperoxide (t-BHP). Cell viability was assessed by cell counting and MTT-staining, and apoptosis was quantified by TUNEL and flow cytometry. Activation of JNK1/3, p38 alpha beta MAPKs and ERK1/2 and their potential targets was detected by Western blot analysis and immunochemistry with specific antiphospho protein antibodies. Specific pharmacologic inhibitors directed against the MAPKs were used to analyze the signaling involved in cell death of RPE cells exposed to t-BHP.
   RESULTS. Exposure of RPE cells to t-BHP, associated with increase in reactive oxygen species and intracellular glutathione depletion, induced time-and concentration-dependent apoptosis, which was associated with the accumulation of inactive ERK1/2 in cell nuclei and a transient and weak ERK1/2 activation. This activation was accompanied by a deactivation of P90RSK, the major target of ERK1/2 and consequently by the delayed activation of its transcription factor CREB. MEK1/2 inhibition completely suppressed the transient activation of ERK1/2 and completely blocked apoptosis, demonstrating the role of the MEK-ERK module in mediating oxidative-stress induced RPE cell death. In contrast, neither JNKs nor p38 alpha beta MAPKs were involved in mediating t-BHP-induced apoptotic signaling in RPE cells.
   CONCLUSIONS. The results suggest that inhibiting the MEK-ERK module may allow the development of selective methods for treating oxidative-stress-induced RPE degeneration, such as AMD.
C1 INSERM, Inst Biomed Cordeliers, U598, F-75006 Paris, France.
   IFR58, Inst Biomed Cordeliers, Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; UDICE-French Research Universities; Sorbonne Universite;
   Universite Paris Cite
RP Mascarelli, F (通讯作者)，INSERM, Inst Biomed Cordeliers, U598, 15 Rue Ecole Med, F-75006 Paris, France.
EM mascarelli@idf.inserm.fr
RI Mascarelli, Frederic/L-8916-2018
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NR 39
TC 79
Z9 84
U1 1
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2006
VL 47
IS 10
BP 4614
EP 4623
DI 10.1167/iovs.06-0297
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 088AU
UT WOS:000240784700056
PM 17003459
DA 2022-11-30
ER

PT J
AU Dwinger, MC
   Pieper-Bodeewes, I
   Eter, N
   Holz, FG
AF Dwinger, MC
   Pieper-Bodeewes, I
   Eter, N
   Holz, FG
TI Variations in intraocular pressure (IOP) and necessity for paracentesis
   following intravitreal triamcinolone injection
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE intravitreal injection; triamcinolone acetonide; intraocular pressure;
   paracentesis; macular edema; age-related macular degeneration; glaucoma
ID DIABETIC MACULAR EDEMA; ANTERIOR-CHAMBER PARACENTESIS; RANDOMIZED
   CLINICAL-TRIAL; ACETONIDE INJECTION; NONINFECTIOUS ENDOPHTHALMITIS;
   DEGENERATION
AB Background: Intravitreal triamcinolone injection (IVT) has become a treatment option for macular edema of heterogeneous etiology and neovascular retinal diseases including AMD. Besides the risk for a steroid-induced secondary open-angle glaucoma, the acute rise in intravitreal volume induces IOP elevations immediately after injection. To decrease the intravitreal volume a paracentesis is advocated by many surgeons. The aim of this study was to determine variations in IOP at different time points immediately after IVT in order to assess the necessity for routine paracentesis. Methods: The IOP was recorded by Goldmann applanation tonometry preoperatively, 10 minutes, 1, 3 and 24 hours after intravitreal injection of 0.1 mL (4 mg) triamcinolone. A consecutive series of 32 eyes of 32 patients with diabetic macular edema, diffuse edema after central vein occlusion or occult subfoveal choroidal neovascularization due to age-related macular degeneration was included. Statistical analysis was performed with ANOVA test and Bonferroni correction. Results: Compared to baseline (15.24 +/- 0.52 mm Hg) IOP was significantly elevated 10 min postoperatively (22.28 +/- 1.4 mmHg; p < 0.05). One hour after injection IOP decreased to 15.58 +/- 0.69 mmHg (p < 0.05). Three and 24 h after injection mean IOP was not significantly different from preoperative baseline levels. Immediately after IVT light perception was tested and retinal perfusion was evaluated by indirect ophthalmoscopy. In none of the patients was a paracentesis necessary. Conclusion: Intravitreal injection of 0.1 mL triamcinolone led to a moderate transient rise in IOP. Based on these results, a routinely performed paracentesis immediately before or after IVT is not required. As paracentesis bears an additional risk including endophthalmitis it should only be considered if functional testing following injection indicates a relevant impairment of retinal perfusion.
C1 Univ Bonn, Augenklin, D-53127 Bonn, Germany.
C3 University of Bonn; University of Hamburg; University Medical Center
   Hamburg-Eppendorf
RP Holz, FG (通讯作者)，Univ Bonn, Augenklin, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM frank.holz@ukb.uni-bonn.de
CR AIELLO LP, 2004, RETINA, P3
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NR 25
TC 28
Z9 29
U1 0
U2 0
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 AUG
PY 2005
VL 222
IS 8
BP 638
EP 642
DI 10.1055/s-2005-858459
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 961DL
UT WOS:000231642000006
PM 16118744
DA 2022-11-30
ER

PT J
AU Zhang, CY
   Qin, SY
   Xie, H
   Qiu, QY
   Wang, HY
   Zhang, JT
   Luo, DW
   Zhang, JF
AF Zhang, Chaoyang
   Qin, Shiyue
   Xie, Hai
   Qiu, Qinghua
   Wang, Haiyan
   Zhang, Jingting
   Luo, Dawei
   Zhang, Jingfa
TI RO4929097, a Selective.-Secretase Inhibitor, Inhibits Subretinal
   Fibrosis Via Suppressing Notch and ERK1/2 Signaling in Laser-Induced
   Mouse Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE neovascular age-related macular degeneration (nAMD); choroidal
   neovascularization (CNV); subretinal fibrosis; Notch; transforming
   growth factor beta; retinal pigment epithelium (RPE)
ID INDUCED CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   GROWTH-FACTOR; TGF-BETA/SMAD; AGE; PATHWAY; RANIBIZUMAB; PF-03084014;
   MACROPHAGES; CARCINOMA
AB PURPOSE. This study aimed to explore whether RO4929097 (RO), a specific gamma-secretase inhibitor, could inhibit the subretinal fibrosis in laser-induced mouse model and the relevant molecular mechanisms.
   METHODS. Male C57BL/6J mice were used to produce choroidal neovascularization (CNV) and subretinal fibrosis by laser photocoagulation, and RO was administered intravitreally 1 day after laser induction. The sizes of CNV and subretinal fibrosis were measured and quantified in both 2D and 3D constructions. The ARPE-19 cell line and primary human RPE (phRPE) cells were treated with TGF beta 1, in combination with or without RO, to examine Notch related molecules, epithelial mesenchymal transition (EMT), cell viability, migration, and contractile function, as well as the crosstalk between Notch and other EMT relevant signaling pathways.
   RESULTS. Intravitreal injection of RO reduced the sizes of both CNV and subretinal fibrosis in laser-induced young and old mice at day 7 and day 14 after laser induction. Moreover, EMT and Notch activation in RPE-choroid complexes from laser-induced mice were significantly attenuated by RO. In vitro, TGF beta 1 activated Notch signaling and induced EMT in ARPE-19 cells, accompanied by enhanced EMT-related function, which were inhibited by RO. The inhibition of RO on EMT was further confirmed in TGF beta 1-treated phRPE cells. Blockage of Notch signaling by RO could inhibit ERK1/2 signaling; whereas ERK1/2 inhibition had no effect on Notch. The action of RO was independent of Smad2/3 or p38, and co-inhibition of Notch and Smad2/3 showed synergistic effect on EMT inhibition.
   CONCLUSIONS. RO exerts its antifibrotic effect by directly inhibiting Notch signaling and indirectly suppressing ERK1/2 signaling. Targeting Notch signaling might provide a therapeutic strategy in prevention and treatment of subretinal fibrosis in neovascular age-related macular degeneration (nAMD).
C1 [Zhang, Chaoyang; Xie, Hai; Qiu, Qinghua; Wang, Haiyan; Zhang, Jingting; Luo, Dawei; Zhang, Jingfa] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp,Sch Med, Dept Ophthalmol, Shanghai, Peoples R China.
   [Zhang, Chaoyang; Xie, Hai; Qiu, Qinghua; Wang, Haiyan; Zhang, Jingting; Luo, Dawei; Zhang, Jingfa] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai Engn Ctr Visual Sci & Photomed, Natl Clin Res Ctr Eye Dis, Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Qin, Shiyue] Soochow Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou, Peoples R China.
   [Qiu, Qinghua] Shigatse Peoples Hosp, Dept Ophthalmol, Xizang, Peoples R China.
C3 Shanghai Jiao Tong University; Soochow University - China
RP Luo, DW; Zhang, JF (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp,Sch Med, Dept Ophthalmol, 100 Haining Rd, Shanghai 200080, Peoples R China.
EM dr-davie@yeah.net; 13917311571@139.com
FU National Natural Science Foundation of China [82171062, 81970810];
   Domestic Science and Technology Cooperation Project of Shanghai
   Municipal Science and Technology Commission [21015800700]
FX Supported by the National Natural Science Foundation of China (82171062
   and, 81970810) and Domestic Science and Technology Cooperation Project
   of Shanghai Municipal Science and Technology Commission (21015800700).
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NR 66
TC 0
Z9 0
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2022
VL 63
IS 10
AR 14
DI 10.1167/iovs.63.10.14
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5U9FW
UT WOS:000876846600006
PM 36155746
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Maurya, M
   Nag, TC
   Kumar, P
   Roy, TS
AF Maurya, Meenakshi
   Nag, Tapas C.
   Kumar, Pankaj
   Roy, Tara Sankar
TI Expression patterns of iron regulatory proteins after intense light
   exposure in a cone-dominated retina
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Retina; Light damage; Iron; Lipid peroxidation; Iron regulatory proteins
ID HANDLING PROTEINS; GENE-EXPRESSION; OIL DROPLETS; CERULOPLASMIN; DAMAGE;
   DEGENERATION; ILLUMINATION; TRANSFERRIN; FERRITIN; CELLS
AB Iron is implicated in ocular diseases such as in age-related macular degeneration. Light is also considered as a pathological factor in this disease. Earlier, two studies reported the influence of constant light environment on the pattern of expressions of iron-handling proteins. Here, we aimed to see the influence of light in 12-h light-12-h dark (12L:12D) cycles on the expression of iron-handling proteins in chick retina. Chicks were exposed to 400 lx (control) and 5000 lx (experimental) light at 12L:12D cycles and sacrificed at variable timepoints. Retinal ferrous ion (Fe2+) level, ultrastructural changes, lipid peroxidation level, immunolocalization and expression patterns of iron-handling proteins were analysed after light exposure. Both total Fe2+ level (p = 0.0004) and lipid peroxidation (p = 0.002) significantly increased at 12-, 48- and 168-h timepoint (for Fe2+) and 48- and 168-h timepoint (for lipid peroxidation), and there were degenerative retinal changes after 168 h of light exposure. Intense light exposure led to an increase in the levels of transferrin and transferrin receptor-1 (at 168-h) and ferroportin-1, whereas the levels of ferritins, hephaestin, (at 24-, 48- and 168-h timepoint) and ceruloplasmin (at 168-h timepoint) were decreased. These changes in iron-handling proteins after light exposure are likely due to a disturbance in the iron storage pool evident from decreased ferritin levels, which would result in increased intracellular Fe2+ levels. To counteract this, Fe2+ is released into the extracellular space, an observation supported by increased expression of ferroportin-1. Ceruloplasmin was able to convert Fe2+ into Fe3+ until 48 h of light exposure, but its decreased expression with time (at 168-h timepoint) resulted in increased extracellular Fe2+ that might have caused oxidative stress and retinal cell damage.
C1 [Maurya, Meenakshi; Nag, Tapas C.; Kumar, Pankaj; Roy, Tara Sankar] All India Inst Med Sci, Dept Anat, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi
RP Nag, TC (通讯作者)，All India Inst Med Sci, Dept Anat, New Delhi 110029, India.
EM tapas_nag@yahoo.com
OI NAG, TAPAS/0000-0002-6962-0844
FU Science and Engineering Board, New Delhi [SERB/AS-027-2012]
FX The study was supported by research grants from Science and Engineering
   Board (SERB/AS-027-2012), New Delhi, to TCN. The TEM work was carried
   out at Sophisticated Analytical Instrumentation Facility (DST), AIIMS,
   New Delhi.
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NR 63
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
EI 1573-4919
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD SEP
PY 2021
VL 476
IS 9
BP 3483
EP 3495
DI 10.1007/s11010-021-04175-5
EA MAY 2021
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA TV5NI
UT WOS:000650177700002
PM 33983563
DA 2022-11-30
ER

PT J
AU Yamamoto, T
   Kanda, A
   Kase, S
   Ishida, S
AF Yamamoto, Taku
   Kanda, Atsuhiro
   Kase, Satoru
   Ishida, Susumu
TI Hypoxia Induces Galectin-1 Expression Via Autoinduction of Placental
   Growth Factor in Retinal Pigment Epithelium Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; galectin-1; hypoxia-inducible factor-1
   alpha; placental growth factor; retinal pigment epithelium
ID VEGF-TRAP; MACULAR DEGENERATION; MEDIATES EXPRESSION; BLOOD-FLOW;
   FACTOR-I; AUTOCRINE; AP-1; MECHANISMS; INDUCTION; DISEASE
AB PURPOSE. Galectin-1/LGALS1, a beta-galactoside-binding protein, contributes to angiogenesis and fibrosis in various ocular diseases. Hypoxia-dependent and -independent pathways upregulate galectin-1/LGALS1 expression in Muller glial cells. Here, we present novel findings on the galectin-1/LGALS1 regulatory system in human retinal pigment epithelium (RPE) cells, the major cellular participant in the pathogenesis of neovascular age-related macular degeneration (nAMD).
   METHODS. Human RPE cells were used to evaluate changes in gene and protein expression with real-time quantitative PCR and immunoblot analyses, respectively. The promoter and enhancer regions of LGALS1 were analyzed by reporter assay and chromatin immunoprecipitation. Immunofluorescence analysis of nAMD patient specimens was used to confirm the in vitro findings.
   RESULTS. Hypoxia induced galectin-1/LGALS1 expression via binding of hypoxia-inducible factor 1 alpha (HIF-1 alpha) to hypoxia-responsive elements in the LGALS1 promoter region. Blockade of vascular endothelial growth factor receptor 1 (VEGFR1) partially decreased hypoxia-induced galectin-1/LGALS1 expression. Among several VEGFR1 ligands induced by hypoxia, placental growth factor (PlGF)/PGF alone upregulated galectin-1/LGALS1 expression via phosphorylation of activator protein 1 (AP-1) subunits following AKT and p38 mitogen-activated protein kinase (MAPK) activation. An AP-1 site in the LGALS1 enhancer region was required for PlGF-induced galectin-1/LGALS1 expression in RPE cells. PlGF application upregulated PGF expression via extracellular signal-regulated kinase 1 and 2, AKT, and p38 MAPK pathways. nAMD patient specimens demonstrated co-localization of galectin-1 with HIF-1 alpha, PlGF, and VEGFR1 in RPE cells.
   CONCLUSIONS. Our present findings implicate the significance of hypoxia as a key inducer of galectin-1/LGALS1 in RPE cells and the autoinduction of hypoxia-induced PlGF as a vicious cycle amplifying the pathogenesis of nAMD.
C1 Hokkaido Univ, Fac Med, Dept Ophthalmol, Lab Ocular Cell Biol & Visual Sci, Sapporo, Hokkaido, Japan.
   Hokkaido Univ, Sch Med, Sapporo, Hokkaido, Japan.
C3 Hokkaido University; Hokkaido University
RP Kanda, A (通讯作者)，Hokkaido Univ, Fac Med, Dept Ophthalmol, Kita Ku, N-15,W-7, Sapporo, Hokkaido 0608638, Japan.; Kanda, A (通讯作者)，Hokkaido Univ, Grad Sch Med, Kita Ku, N-15,W-7, Sapporo, Hokkaido 0608638, Japan.
EM kanda@med.hokudai.ac.jp
OI Yamamoto, Taku/0000-0001-7375-8021
FU Bayer Yakuhin, Ltd.;  [MEXT KAKENHI 19K09944]
FX Supported in part by Bayer Yakuhin, Ltd., and by a Grant-in-Aid for
   Scientific Research on Innovative Areas (MEXT KAKENHI 19K09944 to AK).
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NR 49
TC 1
Z9 1
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2021
VL 62
IS 2
AR 22
DI 10.1167/iovs.62.2.22
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QQ5MM
UT WOS:000624567800022
PM 33599733
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Varin, M
   Kergoat, MJ
   Belleville, S
   Li, G
   Rousseau, J
   Roy-Gagnon, MH
   Moghadaszadeh, S
   Freeman, EE
AF Varin, Melanie
   Kergoat, Mark-Jeanne
   Belleville, Sylvie
   Li, Gisele
   Rousseau, Jacqueline
   Roy-Gagnon, Marie-Helene
   Moghadaszadeh, Solmaz
   Freeman, Ellen E.
TI Age-Related Eye Disease and Cognitive Function The Search for Mediators
SO OPHTHALMOLOGY
LA English
DT Review
ID MACULAR DEGENERATION; SENSORY IMPAIRMENTS; OLDER-ADULTS; DEMENTIA;
   DECLINE; RISK; CONNECTIVITY; GLAUCOMA; MOBILITY; BRAIN
AB Purpose: Age-related eye disease may be associated with cognitive decline, but the scientific literature has not been consistent. Furthermore, no studies have been able to explain the relationship. Our objective was to assess whether older adults with age-related macular degeneration (AMD) or glaucoma performed worse on 6 cognitive tests compared with older adults with normal vision and, if so, to understand why.
   Design: Cross-sectional analysis of hospital-based study (Maisonneuve-Rosemont Hospital Ophthalmology Clinics, Montreal, Canada).
   Participants: Three hundred thirty-six adults 65 years of age or older with either AMD, glaucoma, or normal vision.
   Methods: Cognition was measured with 6 cognitive tests administered orally. Activity levels were measured using the Victoria Longitudinal Study Activity Lifestyle Questionnaire. Visual acuity and visual field were measured. Multiple linear regression was used. Mediation was assessed using structural equation modeling.
   Main Outcome Measures: Results of the verbal fluency test (animal and letter versions), the digit span test (forward and backward versions), and the logical memory test (immediate and delayed recall).
   Results: People with glaucoma showed lower scores on 3 cognitive tests than the group with normal vision: the digit span forward and backward tests (beta = -0.8 [95% confidence interval (CI), -1.5 to -0.2] and beta = -0.7 [95% CI, -1.3 to -0.1], respectively) and the logical memory test with immediate recall (beta = -1.3 [95% CI, -2.4 to -0.2]). Activity levels statistically significantly mediated the relationship between glaucoma and the digit span forward test (P = 0.043; percentage of the total effect mediated, 17%).
   Conclusions: People with glaucoma showed lower scores on cognitive tests that may depend on verbal working memory and encoding. If confirmed in longitudinal studies, interventions should be developed that are appropriate for a visually impaired population to slow this cognitive decline. (C) 2019 by the American Academy of Ophthalmology.
C1 [Varin, Melanie; Roy-Gagnon, Marie-Helene; Freeman, Ellen E.] Univ Ottawa, Sch Epidemiol & Publ Hlth, 600 Peter Morand Crescent, Ottawa, ON K1G 5Z3, Canada.
   [Kergoat, Mark-Jeanne; Belleville, Sylvie; Rousseau, Jacqueline] Inst Univ Geriatr Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Li, Gisele; Moghadaszadeh, Solmaz; Freeman, Ellen E.] Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ, Canada.
   [Li, Gisele; Freeman, Ellen E.] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Rousseau, Jacqueline] Univ Montreal, Sch Rehabil, Montreal, PQ, Canada.
   [Freeman, Ellen E.] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
C3 University of Ottawa; Universite de Montreal; Universite de Montreal;
   Universite de Montreal; Universite de Montreal; University of Ottawa;
   Ottawa Hospital Research Institute
RP Freeman, EE (通讯作者)，Univ Ottawa, Sch Epidemiol & Publ Hlth, 600 Peter Morand Crescent, Ottawa, ON K1G 5Z3, Canada.
EM eefreeman@gmail.com
OI Roy-Gagnon, Marie-Helene/0000-0001-8747-0846
FU Canadian Institutes of Health Research [MOP 133560]
FX Supported by the Canadian Institutes of Health Research (grant no.: MOP
   133560).
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NR 46
TC 18
Z9 18
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2020
VL 127
IS 5
BP 660
EP 666
DI 10.1016/j.ophtha.2019.10.004
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA LE7XR
UT WOS:000526937900023
PM 31727427
OA hybrid
DA 2022-11-30
ER

PT J
AU Scheers, D
   Van Os, L
   Dhubhghaill, SN
   Wouters, K
   Tassignon, MJ
AF Scheers, Dorothee
   Van Os, Luc
   Dhubhghaill, Sorcha Ni
   Wouters, Kristien
   Tassignon, Marie-Jose
TI Clinically significant pseudophakic cystoid macular edema after
   bag-in-the-lens implantation
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID POSTERIOR CAPSULE OPACIFICATION; CATARACT-SURGERY; RISK-FACTORS;
   CAPSULORHEXIS; EYES
AB Purpose: To determine the incidence of clinically significant pseudophakic cystoid macular edema (CSPME) after phacoemulsification using the bag-in-the-lens intraocular lens (BIL IOL) implantation technique and to examine the influence of associated risk factors, both ocular and systemic.
   Setting: Monocentric, Antwerp University Hospital, Belgium.
   Design: Retrospective.
   Methods: This study included 1 077 first-operated eyes of 1 077 adults who underwent phaco-emulsification cataract surgery using the BIL IOL implantation technique between January 2013 and December 2015.
   Results: The 3-month incidence of CSPME in the subgroup without risk factors was 0% (95% CI, 0.0-0.0). The 3-month incidence of CSPME in the subgroup with risk factors was 2.8% (95% CI, 1.3-4.3). The 3-month incidence of CSPME in the total group of 1077 patients was 1.4% (95% CI, 0.6-2.1). The risk factors most significantly associated with CSPME included diabetes (hazard ratio [HR]: 5.37; 95% CI, 1.5-19.3; P = .019), exudative age-related macular degeneration (HR: 121; 95% CI, 36.1-409; P < .001), and macular traction (HR: 6.47; 95% CI, 1.9-22.1; P < .009).
   Conclusions: The incidence of CSPME was zero in eyes without risk factors. The incidence was consistent with previous reports in the literature regarding the lens-in-the-bag IOL implantation technique in eyes with risk factors. This indicates that the BIL IOL implantation technique is a safe procedure and does not confer a higher risk for developing cystoid macular edema after cataract surgery compared with the lens-in-the-bag IOL implantation technique, despite the requirement of a primary posterior continuous curvilinear capsulorhexis. Copyright (C) 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS
C1 [Scheers, Dorothee; Van Os, Luc; Dhubhghaill, Sorcha Ni; Tassignon, Marie-Jose] Antwerp Univ Hosp, Dept Ophthalmol, Edegem, Belgium.
   [Scheers, Dorothee; Van Os, Luc; Dhubhghaill, Sorcha Ni; Tassignon, Marie-Jose] Univ Antwerp, Fac Med & Hlth Sci, Dept Ophthalmol Visual Opt & Visual Rehabil, Edegem, Belgium.
   [Wouters, Kristien] Univ Antwerp, Antwerp Univ Hosp, Clin Trial Ctr, CRC Antwerp, Edegem, Belgium.
C3 University of Antwerp; University of Antwerp; University of Antwerp
RP Scheers, D (通讯作者)，Univ Antwerp, Antwerp Univ Hosp, Wilrijkstr 10, B-2650 Edegem, Belgium.
EM dorothee.scheers@gmail.com
RI Ní Dhubhghaill, Sorcha/D-4278-2015; Wouters, Kristien/ADM-4146-2022
OI Ní Dhubhghaill, Sorcha/0000-0002-1115-7834; 
CR Belair ML, 2009, AM J OPHTHALMOL, V148, P128, DOI 10.1016/j.ajo.2009.02.029
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NR 25
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0886-3350
EI 1873-4502
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD APR
PY 2020
VL 46
IS 4
BP 606
EP 611
DI 10.1097/j.jcrs.0000000000000102
PG 6
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA OD0IN
UT WOS:000579538200017
PM 32271297
DA 2022-11-30
ER

PT J
AU Jadeja, RN
   Jones, MA
   Abdelrahman, AA
   Powell, FL
   Thounaojam, MC
   Gutsaeva, D
   Bartoli, M
   Martin, PM
AF Jadeja, Ravirajsinh N.
   Jones, Malita A.
   Abdelrahman, Ammar A.
   Powell, Folami L.
   Thounaojam, Menaka C.
   Gutsaeva, Diana
   Bartoli, Manuela
   Martin, Pamela M.
TI Inhibiting microRNA-144 potentiates Nrf2-dependent antioxidant signaling
   in RPE and protects against oxidative stress-induced outer retinal
   degeneration
SO REDOX BIOLOGY
LA English
DT Article
DE Nrf2; Oxidative stress; microRNA; miR-144; Retinal pigment epithelium;
   RPE
ID SODIUM IODATE; MACULAR DEGENERATION; PIGMENT EPITHELIUM; NRF2; CELLS;
   GLUTATHIONE; MECHANISMS; HEALTH; DAMAGE; EYE
AB The retinal pigment epithelium (RPE) is consistently exposed to high levels of pro-oxidant and inflammatory stimuli. As such, under normal conditions the antioxidant machinery in the RPE cell is one of the most efficient in the entire body. However, antioxidant defense mechanisms are often impacted negatively by the process of aging and/or degenerative disease leaving RPE susceptible to damage which contributes to retinal dysfunction. Thus, understanding better the mechanisms governing antioxidant responses in RPE is critically important. Here, we evaluated the role of the redox sensitive microRNA miR-144 in regulation of antioxidant signaling in human and mouse RPE. In cultured human RPE, miR-144-3p and miR-144-5p expression was upregulated in response to pro-oxidant stimuli. Likewise, overexpression of miR-144-3p and -5p using targeted miR mimics was associated with reduced expression of Nrf2 and downstream antioxidant target genes (NQO1 and GCLC), reduced levels of glutathione and increased RPE cell death. Alternately, some protection was conferred against the above when miR-144-3p and miR-144-5p expression was suppressed using antagomirs. Expression analyses revealed a higher conservation of miR-144-3p expression across species and additionally, the presence of two potential Nrf2 binding sites in the 3p sequence compared to only one in the 5p sequence. Thus, we evaluated the impact of miR-144-3p expression in the retinas of mice in which a robust pro-oxidant environment was generated using sodium iodate (SI). Subretinal injection of miR-144-3p antagomir in SI mice preserved retinal integrity and function, decreased oxidative stress, limited apoptosis and enhanced antioxidant gene expression. Collectively, the present work establishes miR-144 as a potential target for preventing and treating degenerative retinal diseases in which oxidative stress is paramount and RPE is prominently affected (e.g., age-related macular degeneration and diabetic retinopathy).
C1 [Jadeja, Ravirajsinh N.; Jones, Malita A.; Abdelrahman, Ammar A.; Powell, Folami L.; Martin, Pamela M.] Augusta Univ, Med Coll Georgia, Dept Biochem, Augusta, GA 30912 USA.
   [Jadeja, Ravirajsinh N.; Jones, Malita A.; Abdelrahman, Ammar A.; Powell, Folami L.; Martin, Pamela M.] Augusta Univ, Med Coll Georgia, Dept Mol Biol, Augusta, GA 30912 USA.
   [Abdelrahman, Ammar A.] Cairo Univ, Fac Pharm, Dept Clin Pharm, Cairo 11562, Egypt.
   [Thounaojam, Menaka C.; Gutsaeva, Diana; Bartoli, Manuela; Martin, Pamela M.] Augusta Univ, Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA.
   [Bartoli, Manuela; Martin, Pamela M.] Augusta Univ, Discovery Inst, Dept Culver Vis, Augusta, GA 30912 USA.
   [Bartoli, Manuela; Martin, Pamela M.] Augusta Univ, Med Coll Georgia, Augusta, GA 30912 USA.
   [Martin, Pamela M.] Augusta Univ, Med Coll Georgia, Georgia Canc Ctr, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; Egyptian Knowledge Bank (EKB); Cairo
   University; University System of Georgia; Augusta University; University
   System of Georgia; Augusta University; University System of Georgia;
   Augusta University; University System of Georgia; Augusta University
RP Jadeja, RN; Martin, PM (通讯作者)，Augusta Univ, Med Coll Georgia, Dept Biochem, Augusta, GA 30912 USA.; Jadeja, RN; Martin, PM (通讯作者)，Augusta Univ, Med Coll Georgia, Dept Mol Biol, Augusta, GA 30912 USA.
EM rjadeja@augusta.edu; pmmartin@augusta.edu
RI Thounaojam, Menaka/AAO-5842-2020; ABDELRAHMAN, Ammar/AAQ-6231-2021
OI ABDELRAHMAN, Ammar/0000-0002-6120-1231
FU National Eye Institute [EY022704, EY029113, EY022416]; Augusta
   University Research Institute [IGPB00002]
FX We would like to thank Jianghe Yuan for assistance with animal studies.
   We would additionally like to acknowledge funding support for these
   studies from National Eye Institute grants EY022704 and EY029113 to
   Pamela Martin and grant EY022416 to Manuela Bartoli and, Augusta
   University Research Institute grant IGPB00002 to Pamela Martin.
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NR 54
TC 37
Z9 39
U1 1
U2 10
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD JAN
PY 2020
VL 28
AR 101336
DI 10.1016/j.redox.2019.101336
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA JU2FG
UT WOS:000501490700041
PM 31590045
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Yang, Y
   Wu, ZZ
   Cheng, YL
   Lin, W
   Qu, C
AF Yang, Y.
   Wu, Z-Z
   Cheng, Y-L
   Lin, W.
   Qu, C.
TI Resveratrol protects against oxidative damage of retinal pigment
   epithelium cells by modulating SOD/MDA activity and activating Bcl-2
   expression
SO EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
LA English
DT Article
DE Resveratrol; Age-related macular degeneration; Oxidative damage; Retinal
   pigment epithelium; Oxidant
ID VITAMIN-C; INHIBITS PROLIFERATION; DIABETIC-NEPHROPATHY; MACULAR
   DEGENERATION; SIGNALING PATHWAY; APOPTOSIS; STRESS; INJURY; UV
AB OBJECTIVE: Age-related macular degeneration (AMD) is mainly characterized by dysfunction of retinal pigment epithelium (RPE) cells. This study aimed to investigate the protective effects of resveratrol on oxidative damaged RPE cells.
   MATERIALS AND METHODS: Human D407 cells were divided into normal control (NC), H2O2 treated (H2O2, treating with H2O2 at a final concentration of 200 mol/l) and resveratrol treatment groups (treating with resveratrol at a concentration of 12.5, 25, 50 and 100 mg/l). Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were examined using enzyme-linked immunosorbent assay (ELISA). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and cell count kit-8 (CCK-8) were used to examine cell viability. Cell cycle phase distribution and apoptosis of D407 cells were evaluated using flow cytometry assay. B-cell lymphoma-2 (Bcl-2) and cleaved caspase 3 expression were detected using quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively.
   RESULTS: Resveratrol significantly decreased inhibitive ratios of D407 cell growth compared to that of H2O2 group (p<0.05). Resveratrol significantly increased SOD activity compared to that of H2O2 group (p<0.05). Resveratrol significantly reduced MDA activity compared to that of H2O2 group (p<0.05). Resveratrol affected cell cycle phase distribution of D407 cells compared to that of H2O2 group (p<0.05). Resveratrol significantly decreased the early stage and late stage apoptosis rates compared to that of H2O2 group (p<0.05). Resveratrol significantly enhanced Bcl-2 levels and decreased cleaved caspase 3 levels compared to that of H2O2 group (p<0.05).
   CONCLUSIONS: Resveratrol protected against the oxidative damage of RPE cells by modulating SOD/MDA activity and activating Bcl-2 expression.
C1 [Lin, W.] Sichuan Acad Med Sci, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China.
   [Lin, W.] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China.
C3 Sichuan Provincial People's Hospital; Sichuan Provincial People's
   Hospital
RP Lin, W (通讯作者)，Sichuan Acad Med Sci, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China.; Lin, W (通讯作者)，Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China.
EM linweidoc@outlook.com
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NR 36
TC 17
Z9 20
U1 1
U2 5
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 JAN
PY 2019
VL 23
IS 1
BP 378
EP 388
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HI3WI
UT WOS:000456381800045
PM 30657580
DA 2022-11-30
ER

PT J
AU Robbie, SJ
   Tabernero, J
   Artal, P
   Qureshi, MA
AF Robbie, Scott J.
   Tabernero, Juan
   Artal, Pablo
   Qureshi, Muhammad A.
TI Initial Clinical Results With a Novel Monofocal-Type Intraocular Lens
   for Extended Macular Vision in Patients With Macular Degeneration
SO JOURNAL OF REFRACTIVE SURGERY
LA English
DT Article
ID IMPLANTABLE MINIATURE TELESCOPE; PREFERRED RETINAL LOCUS;
   CATARACT-SURGERY; AGE; ACUITY; QUALITY
AB PURPOSE: To determine the feasibility of a novel intraocular lens (IOL) designed to improve retinal image quality at up to 10 degrees of retinal eccentricity and optionally provide retinal magnification in patients with macular disease.
   METHODS: In this prospective, interventional pilot study, 8 eyes of 7 patients with bilateral dry age-related macular degeneration and 1+ or less cataract underwent phacoemulsification and capsular bag implantation of a single, injectable, hydrophobic acrylic IOL. Safety and efficacy were assessed by monitoring IogMAR corrected distance and near visual acuity, intraocular Ares- sure, specular microscopy, 80-point visual field testing, and anterior segment and macular optical coherence tomography at baseline and 1 week, 1 month, and 2 months postoperatively. Microperimetry was undertaken at baseline and 1 and/or 2 months postoperatively. Reading performance was assessed at baseline and 1 month postoperatively using the Minnesota low vision reading chart (MNREAD; Precision Vision, LaSalle, IL).
   RESULTS: Safety outcomes were equivalent to standard monofocal IOLs. Visual acuities improved in all patients. Mean corrected distance visual acuity improved from 0.93 +/- 0.22 preoperatively to 0.59 +/- 0.25 at 2 months postoperatively. Mean reading speed increased from 28 +/- 19 to 44 +/- 31 words per minute. Mean mi- croperimetry threshold sensitivities increased from 8.2 +/- 4.6 to 12 +/- 5.6 dB. Mean percentage of fixation points within a 4 degrees circle increased from 77% +/- 17% to 91% +/- 11% with evidence for progressive movement of preferred retinal loci away from areas of geographic atrophy.
   CONCLUSIONS: Initial results indicate this novel IOL has a safety profile comparable with standard IOLs. Visual benefits may exceed those obtained with existing technologies in patients with macular disease. Further work is required to determine the full potential of extended macular vision technology.
C1 [Robbie, Scott J.; Qureshi, Muhammad A.] London Eye Hosp, 4 Harley St, London W1G 9PB, England.
   [Tabernero, Juan] Anglia Ruskin Univ, Vis & Eye Res Unit, Cambridge, England.
   [Tabernero, Juan; Artal, Pablo] Univ Murcia, Lab Opt, Murcia, Spain.
C3 Anglia Ruskin University; University of Murcia
RP Robbie, SJ (通讯作者)，London Eye Hosp, 4 Harley St, London W1G 9PB, England.
EM srobbie1@hotmail.com
RI Artal, Pablo/AGV-7547-2022; Artal, Pablo/AAG-4485-2020; Tabernero,
   Juan/AAO-9855-2020
OI Artal, Pablo/0000-0003-1284-6591; Artal, Pablo/0000-0003-1284-6591; 
CR Abdelnour O, 2001, OPTOMETRY VISION SCI, V78, P914, DOI 10.1097/00006324-200112000-00014
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NR 26
TC 4
Z9 4
U1 0
U2 10
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1081-597X
EI 1938-2391
J9 J REFRACT SURG
JI J. Refractive Surg.
PD NOV
PY 2018
VL 34
IS 11
BP 718
EP +
DI 10.3928/1081597X-20180831-01
PG 16
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA HB6RL
UT WOS:000451199200001
PM 30428091
DA 2022-11-30
ER

PT J
AU Osada, H
   Okamoto, T
   Kawashima, H
   Toda, E
   Miyake, S
   Nagai, N
   Kobayashi, S
   Tsubota, K
   Ozawa, Y
AF Osada, Hideto
   Okamoto, Tomohiro
   Kawashima, Hirohiko
   Toda, Eriko
   Miyake, Seiji
   Nagai, Norihiro
   Kobayashi, Saori
   Tsubota, Kazuo
   Ozawa, Yoko
TI Neuroprotective effect of bilberry extract in a murine model of
   photo-stressed retina
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; PIGMENT EPITHELIUM; CELL-DEATH; LIGHT;
   DEGENERATION; DAMAGE; ANTHOCYANIN; EXPRESSION; BLUE; ACTIVATION
AB Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight). Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS), oxidative and endoplasmic reticulum (ER) stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Muller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo-stress and contribute to developing a new, potentially useful therapeutic approach using bilberry extract for preventing retinal photo-damage.
C1 [Osada, Hideto; Okamoto, Tomohiro; Kawashima, Hirohiko; Toda, Eriko; Miyake, Seiji; Nagai, Norihiro; Ozawa, Yoko] Keio Univ, Dept Ophthalmol, Lab Retinal Cell Biol, Sch Med, Tokyo, Japan.
   [Okamoto, Tomohiro; Kawashima, Hirohiko; Nagai, Norihiro; Tsubota, Kazuo; Ozawa, Yoko] Keio Univ, Dept Ophthalmol, Sch Med, Tokyo, Japan.
   [Miyake, Seiji; Kobayashi, Saori] Wakasa Seikatsu Co Ltd, Kyoto, Japan.
C3 Keio University; Keio University
RP Ozawa, Y (通讯作者)，Keio Univ, Dept Ophthalmol, Lab Retinal Cell Biol, Sch Med, Tokyo, Japan.; Ozawa, Y (通讯作者)，Keio Univ, Dept Ophthalmol, Sch Med, Tokyo, Japan.
EM ozawa@a5.keio.jp
RI Kobayashi, Saori/GXV-3835-2022; Ozawa, Yoko/AAH-9888-2020; Tsubota,
   Kazuo/M-1915-2013
OI Osada, Hideto/0000-0001-9971-8992; Tsubota, Kazuo/0000-0002-8874-7111
FU Wakasa Seikatsu Co., Ltd
FX The study was supported by Wakasa Seikatsu Co., Ltd. SK is an employee
   of Wakasa Seikatsu Co., Ltd. and provided a resource. The funder had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript. The funder provided support in the
   form of salary to HO and in the grant to YO, but did not have any
   additional role in the study design, data collection and analysis,
   decision to publish, or preparation of the manuscript. The specific
   roles of these authors were articulated in the 'author contributions'
   section.
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NR 55
TC 32
Z9 33
U1 1
U2 15
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 1
PY 2017
VL 12
IS 6
AR e0178627
DI 10.1371/journal.pone.0178627
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EW6HZ
UT WOS:000402611800090
PM 28570634
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Rayess, N
   Rahimy, E
   Shah, CP
   Wolfe, JD
   Chen, E
   DeCroos, FC
   Storey, P
   Garg, SJ
   Hsu, J
AF Rayess, Nadim
   Rahimy, Ehsan
   Shah, Chirag P.
   Wolfe, Jeremy D.
   Chen, Eric
   DeCroos, Francis C.
   Storey, Philip
   Garg, Sunir J.
   Hsu, Jason
TI Incidence and clinical features of post-injection endophthalmitis
   according to diagnosis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ANTIBIOTIC-RESISTANCE PATTERNS; GROWTH-FACTOR AGENTS; INTRAVITREAL
   INJECTION; CONJUNCTIVAL FLORA; CATARACT-SURGERY; RISK-FACTORS; TOPICAL
   ANTIBIOTICS; IMMUNE DYSFUNCTION; DIABETES-MELLITUS; PROPHYLAXIS
AB Purpose To compare the incidence and clinical features of endophthalmitis after intravitreal antivascular endothelial growth factor (VEGF) therapy for diabetic eye disease, neovascular age-related macular degeneration (AMD) and retinal vein occlusion (RVO).
   Methods Multicentre, retrospective, consecutive case-control study. All patients treated with intravitreal bevacizumab, ranibizumab or aflibercept for diabetic eye disease, neovascular AMD or RVO between 1 January 2009 and 30 September 2013 at three retina practices were included in this study. The total number of anti-VEGF injections administered for the three indications was calculated using billing records. Endophthalmitis cases were identified using both endophthalmitis log sheets and billing records. Patient charts were reviewed to confirm that endophthalmitis was directly related to anti-VEGF injection and to record clinical features and culture results.
   Results During the study period, a total of 353 978 intravitreal anti-VEGF injections were performed. Presumed infectious endophthalmitis occurred in 119 of 296 017 injections performed for neovascular AMD (1/2487, 0.040%), 12 of 24 541 for diabetic eye disease (1/2045, 0.049%) and 4 of 32 418 for RVO (1/8104, 0.012%) chi(2) analysis found endophthalmitis rates to be higher in diabetic eye disease compared with RVO (p=0.010) and higher in neovascular AMD compared with RVO (p=0.014), while diabetic eye disease and neovascular AMD (p=0.517) had similar rates. The average age of the overall neovascular AMD patient population (81.9 years) was significantly older than the diabetic eye disease (64.7 years, p<0.001) and RVO (73.4 years, p<0.001) populations.
   Conclusions Endophthalmitis rates appear to be lower in eyes with RVO compared with diabetic eye disease and neovascular AMD, possibly due to impaired immunity in diabetics and waning immunity in the generally older AMD population.
C1 [Rayess, Nadim; Rahimy, Ehsan; Storey, Philip; Garg, Sunir J.; Hsu, Jason] Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA USA.
   [Shah, Chirag P.] Ophthalm Consultants Boston, Boston, MA USA.
   [Wolfe, Jeremy D.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
   [Chen, Eric] Retina Consultants Houston, Houston, TX USA.
   [DeCroos, Francis C.] Southeastern Retina Associates, Chattanooga, TN USA.
C3 Jefferson University; Ophthalmic Consultants of Boston; Beaumont Health
RP Hsu, J (通讯作者)，Thomas Jefferson Univ, Wills Eye Hosp, Retina Serv, Mid Atlantic Retina,Dept Ophthalmol, Philadelphia, PA 19107 USA.
EM jhsu@midatlanticretina.com
OI Rahimy, Ehsan/0000-0001-8446-7078; Wolfe, Jeremy/0000-0003-2781-7152
FU J. Arch McNamara Memorial Fund for Retina Research through Wills Eye
   Hospital
FX J. Arch McNamara Memorial Fund for Retina Research through Wills Eye
   Hospital was used to fund the central IRB. The sponsor or funding
   organisation had no role in the design or conduct of this research.
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NR 21
TC 37
Z9 37
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2016
VL 100
IS 8
BP 1058
EP 1061
DI 10.1136/bjophthalmol-2015-307707
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DS4JR
UT WOS:000380747900008
PM 26584579
DA 2022-11-30
ER

PT J
AU Sobolewska, B
   Utebey, E
   Bartz-Schmidt, KU
   Tatar, O
AF Sobolewska, Bianka
   Utebey, Eray
   Bartz-Schmidt, Karl Ulrich
   Tatar, Olcay
TI Long-Term Visual Outcome and Its Predictive Factors Following Treatment
   of Acute Submacular Hemorrhage with Intravitreous Injection of Tissue
   Plasminogen Factor and Gas
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID EXPERIMENTAL SUBRETINAL HEMORRHAGE; MACULAR DEGENERATION; PNEUMATIC
   DISPLACEMENT; ACTIVATOR TREATMENT; NATURAL-HISTORY; MANAGEMENT;
   TRANSLOCATION
AB Purpose: To investigate the long-term functional outcome and its predictive factors of treatment of acute submacular hemorrhage secondary to age-related macular degeneration with intravitreal application of recombinant tissue plasminogen activator (rt-PA) and gas.
   Methods: Twenty-six patients were enrolled in the retrospective case series. A complete history and ocular examination, including fluorescein angiography, were performed. The best-corrected visual acuity was measured with a Snellen chart. Patients were followed up for 12 to 131 months (mean: 49 months). All patients underwent intravitreal injection of rt-PA (50 mu g) and expansile gas. Primary outcome measures were best postoperative and final visual acuity and degree of blood displacement.
   Results: The size of the subretinal hemorrhage ranged from 0.5 to 28 disc diameters, and the degree of blood displacement was defined as complete (1 disc area from the center of the fovea), partial, or no displacement. Twenty-one (81%) patients showed partial or complete displacement of hemorrhage. Due to lack of displacement of hemorrhage in 5 patients (19%), submacular surgery was performed. In 13 of 21 (62%; P = 0.0001) patients with displacement of hemorrhage, the best postoperative visual acuity improved >= 2 lines. The final visual acuity improved >= 2 lines in 42.9% (9 of 21), was stable in 23.8% (5 of 21), and worse >= 2 lines in 33.3% (7 of 21) of patients. The short duration of hemorrhage (<= 4 days) and complete displacement of blood, independent of the hemorrhage size, were significantly associated with better postoperative visual acuity (P = 0.0001, P = 0.0001, respectively).
   Conclusion: Intravitreal injection of rt-PA and gas seem to be more effective when applied within the first 4 days of acute submacular hemorrhage. Preoperative visual acuity as well as displacement of hemorrhage might be useful to predict final visual acuity.
C1 [Sobolewska, Bianka; Bartz-Schmidt, Karl Ulrich; Tatar, Olcay] Univ Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   [Utebey, Eray] Ankara Univ, Fac Med, TR-06100 Ankara, Turkey.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Ankara University
RP Sobolewska, B (通讯作者)，Univ Tubingen, Ctr Ophthalmol, Schleichstr 12, D-72076 Tubingen, Germany.
EM bianka.sob@gmx.de
RI Sobolewska, Bianka/A-8492-2015
CR Aisenbrey S, 2007, ARCH OPHTHALMOL-CHIC, V125, P1367, DOI 10.1001/archopht.125.10.1367
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NR 21
TC 9
Z9 9
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD SEP
PY 2014
VL 30
IS 7
BP 567
EP 572
DI 10.1089/jop.2013.0135
PG 6
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA AP0FR
UT WOS:000341737200008
PM 24821566
DA 2022-11-30
ER

PT J
AU Forte, R
   Cennamo, G
   de Crecchio, G
   Cennamo, G
AF Forte, Raimondo
   Cennamo, Gilda
   de Crecchio, Giuseppe
   Cennamo, Giovanni
TI Microperimetry of Subretinal Drusenoid Deposits
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Reticular pseudodrusen; Optical coherence tomography; Retinal
   sensitivity; Choroidal thickness
ID RETICULAR PSEUDODRUSEN; MACULAR DEGENERATION; MULTIFOCAL
   ELECTRORETINOGRAPHY; MACULOPATHY; PREVALENCE
AB Purpose: To investigate light sensitivity in eyes presenting with subretinal drusenoid deposits (SDD). Methods: All consecutive patients with SDD only seen between January 2012 and July 2012 were included. A control group of consecutive age- and sex-matched control subjects presenting at least one eye with early age-related macular degeneration was considered. In all cases best-corrected visual acuity (BCVA), color fundus photography, fundus autofluorescence imaging and spectral-domain-optical coherence tomography with integrated microperimetry were performed. Results: Twenty-one eyes (21 patients, 9 females, 12 males, mean age 69.2 +/- 5.3 years, mean BCVA 0.18 +/- 0.14 LogMAR) were included in the SDD group. Twenty eyes of 20 patients (13 females, 7 males, mean age 69.1 +/- 3.9 years, mean BCVA 0.16 +/- 0.15 LogMAR) were included in the control group. In eyes with SDD the choroid was thinner at the subfoveal location, and at 1,500 mu m superior, inferior, temporal and nasal to the fovea (p < 0.05). In eyes with SDD, the overall mean light sensitivity in the central macula (4.21 +/- 2.46 dB) was significantly reduced when compared to the control group (6.81 +/- 2.12 dB, p = 0.001), while stable fixation was present in both groups. Correlation between BCVA and mean light sensitivity in the central 7 x 7 mm square was low in the SDD group (Pearson's rho = 0.4, p = 0.01), while it was good in the control group (Pearson's rho = 0.7, p = 0.001). Conclusions: Eyes with SDD showed reduced sensitivity despite preserved BCVA. Reduced choroidal thickness could be involved in reduction of light sensitivity. (C) 2013 S. Karger AG, Basel
C1 [Forte, Raimondo; Cennamo, Gilda; de Crecchio, Giuseppe; Cennamo, Giovanni] Univ Naples Federico II, Eye Dept, IT-80131 Naples, Italy.
   [Forte, Raimondo] Univ Salerno, Pediat Eye Dept, Fisciano Salerno, Italy.
C3 University of Naples Federico II; University of Salerno
RP Forte, R (通讯作者)，Univ Naples Federico II, Dept Ophthalmol, Via Pansini 5, IT-80131 Naples, Italy.
EM raifor@hotmail.com
OI CENNAMO, Giovanni/0000-0002-3013-2528; DE CRECCHIO,
   Giuseppe/0000-0002-1916-3112
FU Research Projects of Relevant National Interest (PRIN)
FX This study was funded by Research Projects of Relevant National Interest
   (PRIN).
CR Alten F, 2012, INVEST OPHTH VIS SCI, V53, P6263, DOI 10.1167/iovs.12-10094
   ARNOLD JJ, 1995, RETINA-J RET VIT DIS, V15, P183, DOI 10.1097/00006982-199515030-00001
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NR 18
TC 16
Z9 16
U1 0
U2 8
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2014
VL 51
IS 1
BP 32
EP 36
DI 10.1159/000354117
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 265AS
UT WOS:000327922700004
PM 24158037
DA 2022-11-30
ER

PT J
AU Liu, YY
   Ishikawa, H
   Chen, M
   Wollstein, G
   Duker, JS
   Fujimoto, JG
   Schuman, JS
   Rehg, JM
AF Liu, Yu-Ying
   Ishikawa, Hiroshi
   Chen, Mei
   Wollstein, Gadi
   Duker, Jay S.
   Fujimoto, James G.
   Schuman, Joel S.
   Rehg, James M.
TI Computerized Macular Pathology Diagnosis in Spectral Domain Optical
   Coherence Tomography Scans Based on Multiscale Texture and Shape
   Features
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
AB PURPOSE. To develop an automated method to identify the normal macula and three macular pathologies (macular hole [MH], macular edema [ME], and age-related macular degeneration [AMD]) from the fovea-centered cross sections in threedimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images.
   METHODS. A sample of SD-OCT macular scans (macular cube 200 x 200 or 512 x 128 scan protocol; Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) was obtained from healthy subjects and subjects with MH, ME, and/or AMD (dataset for development: 326 scans from 136 subjects [193 eyes], and dataset for testing: 131 scans from 37 subjects [58 eyes]). A fovea-centered cross-sectional slice for each of the SD-OCT images was encoded using spatially distributed multiscale texture and shape features. Three ophthalmologists labeled each fovea-centered slice independently, and the majority opinion for each pathology was used as the ground truth. Machine learning algorithms were used to identify the discriminative features automatically. Two-class support vector machine classifiers were trained to identify the presence of normal macula and each of the three pathologies separately. The area under the receiver operating characteristic curve (AUC) was calculated to assess the performance.
   RESULTS. The cross-validation AUC result on the development dataset was 0.976, 0.931, 0939, and 0.938, and the AUC result on the holdout testing set was 0.978, 0.969, 0.941, and 0.975, for identifying normal macula, MH, ME, and AMD, respectively.
   CONCLUSIONS. The proposed automated data-driven method successfully identified various macular pathologies (all AUC > 0.94). This method may effectively identify the discriminative features without relying on a potentially error-prone segmentation module. (Invest Ophthalmol Vis Sci. 2011;52:8316-8322) DOI: 10.1167/iovs.10-7012
C1 [Ishikawa, Hiroshi; Wollstein, Gadi; Schuman, Joel S.] Univ Pittsburgh, Sch Med, Inst Eye & Ear, Ophthalmol & Visual Sci Res Ctr,Dept Ophthalmol,U, Pittsburgh, PA 15213 USA.
   [Liu, Yu-Ying; Rehg, James M.] Georgia Inst Technol, Sch Interact Comp, Atlanta, GA 30332 USA.
   [Ishikawa, Hiroshi; Schuman, Joel S.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15213 USA.
   [Chen, Mei] Carnegie Mellon Univ, Intel Sci & Technol Ctr, Pittsburgh, PA 15213 USA.
   [Duker, Jay S.] Tufts Univ, Sch Med, Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA.
   [Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; University System of Georgia; Georgia Institute of
   Technology; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Carnegie Mellon University; Intel
   Corporation; Tufts Medical Center; Tufts University; Massachusetts
   Institute of Technology (MIT); Massachusetts Institute of Technology
   (MIT)
RP Ishikawa, H (通讯作者)，Univ Pittsburgh, Sch Med, Inst Eye & Ear, Ophthalmol & Visual Sci Res Ctr,Dept Ophthalmol,U, 203 Lothrop St,Room 835-2, Pittsburgh, PA 15213 USA.
EM ishikawah@upmc.edu
RI Ishikawa, Hiroshi/D-6370-2014; Schuman, Joel S/K-7304-2012; Rehg,
   James/AAM-6888-2020; Ishikawa, Hiroshi/ABC-6293-2020; Schuman, Joel
   S/M-2389-2019
OI Ishikawa, Hiroshi/0000-0001-6310-5748; Schuman, Joel
   S/0000-0002-8885-3766; Rehg, James/0000-0003-1793-5462; Ishikawa,
   Hiroshi/0000-0001-6310-5748; Schuman, Joel S/0000-0002-8885-3766
FU National Institutes of Health (Bethesda, MD) [NIH R01-EY013178,
   R01-EY011289, P30-EY008098]; Eye and Ear Foundation (Pittsburgh, PA);
   Research to Prevent Blindness, Inc. (New York, NY); Intel Labs, Intel
   Corporation (Mountain View CA); NATIONAL EYE INSTITUTE [R01EY011289,
   P30EY008098, R01EY013178] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grants NIH R01-EY013178,
   R01-EY011289, and P30-EY008098 (Bethesda, MD); The Eye and Ear
   Foundation (Pittsburgh, PA); Research to Prevent Blindness, Inc. (New
   York, NY); and Intel Labs, Intel Corporation (Mountain View CA).
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NR 8
TC 33
Z9 35
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2011
VL 52
IS 11
BP 8316
EP 8322
DI 10.1167/iovs.10-7012
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 846MN
UT WOS:000296907700011
PM 21911579
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Jo, N
   Ju, MH
   Nishijima, K
   Robinson, GS
   Adamis, AP
   Shima, DT
   Mailhos, C
AF Jo, Nobuo
   Ju, Meihua
   Nishijima, Kazuaki
   Robinson, Gregory S.
   Adamis, Anthony P.
   Shima, David T.
   Mailhos, Carolina
TI Inhibitory effect of an antibody to cryptic collagen type IV epitopes on
   choroidal neovascularization
SO MOLECULAR VISION
LA English
DT Article
ID MATRIX METALLOPROTEINASES; MACULAR DEGENERATION; BASEMENT-MEMBRANES;
   CELL-MIGRATION; ANGIOGENESIS; THERAPY; GROWTH; GENE; ORGANIZATION;
   BIOCHEMISTRY
AB Purpose: The wet form of age-related macular degeneration (AMD) occurs as a consequence of abnormal blood vessel growth from the choroid into the retina. Pathological angiogenesis during tumor growth and ocular disease has been associated with specific exposure of cryptic extracellular matrix epitopes. We investigated the presence of cryptic collagen IV epitopes in a murine model of choroidal neovascularization (CNV), and tested the effect on blood vessel growth of H8, a humanized antibody directed against a cryptic collagen type IV epitope.
   Methods: To induce experimental CNV in adult C57BL/6 mice, Bruch's membrane was ruptured using a diode laser. Subsequently, mice were treated with daily intraperitoneal (i.p.) injections of either H8 (10 mg/kg or 30 mg/kg) or an isotype-matched antibody control. Two weeks postinjection, choroidal flat mounts were immunostained with the blood vessel marker platelet/endothelial cell adhesion molecule-1 (PECAM-1) and H8. CNV was visualized using fluorescence microscopy and the CNV lesion area measured using Open Lab software.
   Results: Collagen type IV and the cryptic epitope were observed at the site of laser-induced lesions. Staining with H8 was first observed three days post injury, two days after MMP2 expression in CNV lesions, becoming most intense five days following laser injury and extending beyond the area of neovascularization. At 14 days post injury, H8 staining was reduced in intensity, colocalized with the area of CNV, and was nearly absent from the underlying choroidal vessels. In addition, mice treated with H8 had a significant dose-dependant decrease in the area of CNV as compared to isotype-matched antibody controls.
   Conclusions: Results suggest that exposure of cryptic collagen type IV epitopes is associated with the incidence of CNV and that the humanized antibody H8 may provide a new treatment for CNV.
C1 OSI Eyetech, Eyetech Res Ctr, Lexington, MA 02421 USA.
RP Mailhos, C (通讯作者)，OSI Eyetech, Eyetech Res Ctr, 35 Hartwell Ave, Lexington, MA 02421 USA.
EM carolinamailhos@hotmail.co.uk
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NR 37
TC 12
Z9 15
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 26
PY 2006
VL 12
IS 139-47
BP 1243
EP 1249
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 105NG
UT WOS:000242036400003
PM 17110907
DA 2022-11-30
ER

PT J
AU Kikuchi, Y
   Odashima, Y
   Yoshikawa, K
   Oda, T
   Tanaka, F
   Oikawa, H
   Ishigaki, Y
   Asahi, K
AF Kikuchi, Yawara
   Odashima, Yoshimi
   Yoshikawa, Kazuhiro
   Oda, Tomoyasu
   Tanaka, Fumitaka
   Oikawa, Hiroki
   Ishigaki, Yasushi
   Asahi, Koichi
TI Renal thrombotic microangiopathy and nephrotic proteinuria induced by
   intravitreal injection of aflibercept for diabetic macular edema
SO BMC NEPHROLOGY
LA English
DT Article
DE Intravitreal injections; Thrombotic microangiopathy; Vascular
   endothelial growth factor inhibitor; Aflibercept; Diabetic macular
   edema; Diabetic nephropathy
ID GROWTH-FACTOR INHIBITORS; PRESSURE CHANGES; BLOOD-PRESSURE; FACTOR
   THERAPY; BEVACIZUMAB; TOXICITY; INJURY
AB Background Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. Case presentation A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. Conclusions This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.
C1 [Kikuchi, Yawara; Yoshikawa, Kazuhiro; Tanaka, Fumitaka; Asahi, Koichi] Iwate Med Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Morioka, Iwate, Japan.
   [Odashima, Yoshimi; Oda, Tomoyasu; Ishigaki, Yasushi] Iwate Med Univ, Sch Med, Dept Internal Med, Div Diabet Metab & Endocrinol, Morioka, Iwate, Japan.
   [Oikawa, Hiroki] Morioka Tsunagi Onsen Hosp, Dept Internal Med, Morioka, Iwate, Japan.
C3 Iwate Medical University; Iwate Medical University
RP Yoshikawa, K (通讯作者)，Iwate Med Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Morioka, Iwate, Japan.
EM yoshikaw@iwate-med.ac.jp
CR Amoaku WM, 2020, EYE, V34, P1, DOI 10.1038/s41433-020-0961-6
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NR 40
TC 0
Z9 0
U1 0
U2 0
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD OCT 29
PY 2022
VL 23
IS 1
AR 348
DI 10.1186/s12882-022-02986-2
PG 6
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA 5U5EE
UT WOS:000876569200001
PM 36309669
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Stattin, M
   Haas, AM
   Ahmed, D
   Graf, A
   Krepler, K
   Ansari-Shahrezaei, S
AF Stattin, Martin
   Haas, Anna-Maria
   Ahmed, Daniel
   Graf, Alexandra
   Krepler, Katharina
   Ansari-Shahrezaei, Siamak
TI Evaluation of a calculation model to estimate the impact of the COVID-19
   pandemic lockdown on visual acuity in neovascular AMD
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anti-vascular endothelial growth factor; calculation model; coronavirus
   disease 2019; exudative neovascular age-related macular degeneration;
   intravitreal injection; visual acuity
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   RANIBIZUMAB; VERTEPORFIN
AB Purpose A model was calculated during the first Austrian coronavirus disease-2019 (COVID-19) pandemic lockdown to estimate the effect of a short-term treatment interruption due to healthcare restrictions on visual acuity (VA) in neovascular age-related macular degeneration (nAMD). The model was compared to the real-life outcomes before treatment re-started. Methods Retrospective data-collection of 142 eyes in 142 patients receiving repeated intravitreal injections with anti-VEGF at a retina unit in Vienna in a personalized pro-re-nata regimen prior to the COVID-19 associated lockdown, when treatment was deferred between March 16 and May 4, 2020. During the lockdown, the preliminary data was integrated into pre-existing formulae based on the natural course of the disease in untreated eyes in the long term. Patients were re-scheduled and treated after gradually opening operating rooms. The calculation model was compared to the effective VA change. Results The model calculated an overall VA loss of 3.5 +/- 0.8 letters early treatment diabetes retinopathy study (ETDRS) (p < 0.001 [95% CI:3.3;3.6]) on average compared to 2.5 +/- 6 letters ETDRS (p < 0.001 [95% CI:1.5;3.5]) as measured with a mean treatment delay of 61 +/- 14 days after previously scheduled appointments. The total difference between the model exercise and the real-life outcomes accounted for 1 +/- 5.9 letters ETDRS (p = 0.051 [95% CI: 0.1;1.9]). Conclusion The herein presented calculation model might not be suitable to estimate the effective VA loss correctly over time, although untreated eyes and eyes under therapy show similarities after short-term treatment interruption. However, this study demonstrated the potentially negative impact of the COVID-19 pandemic lockdown on patients compromised by nAMD.
C1 [Stattin, Martin; Haas, Anna-Maria; Ahmed, Daniel; Krepler, Katharina; Ansari-Shahrezaei, Siamak] Karl Landsteiner Inst Retinal Res & Imaging, Vienna, Austria.
   [Stattin, Martin; Haas, Anna-Maria; Ahmed, Daniel; Krepler, Katharina; Ansari-Shahrezaei, Siamak] Rudolf Fdn Hosp, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
   [Stattin, Martin] Med Univ Innsbruck, Dept Ophthalmol & Optometry, Innsbruck, Austria.
   [Graf, Alexandra] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria.
   [Ansari-Shahrezaei, Siamak] Sigmund Freud Univ Vienna, Med Sch, Vienna, Austria.
   [Ansari-Shahrezaei, Siamak] Med Univ Graz, Dept Ophthalmol, Graz, Austria.
C3 Medical University of Innsbruck; Medical University of Vienna; Medical
   University of Graz
RP Ansari-Shahrezaei, S (通讯作者)，Rudolf Fdn Hosp, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
EM siamak.ansari-shahrezaei@wienkay.at
OI Ansari Shahrezaei, Siamak/0000-0001-8032-4686; Graf,
   Alexandra/0000-0003-0035-2658
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NR 34
TC 1
Z9 1
U1 0
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JUL
PY 2022
VL 32
IS 4
BP 2312
EP 2318
AR 11206721211052389
DI 10.1177/11206721211052389
EA NOV 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3B9CF
UT WOS:000715683800001
PM 34726553
OA Green Published
DA 2022-11-30
ER

PT J
AU Hervella, AS
   Rouco, J
   Novo, J
   Ortega, M
AF Hervella, Alvaro S.
   Rouco, Jose
   Novo, Jorge
   Ortega, Marcos
TI Self-supervised multimodal reconstruction pre-training for retinal
   computer-aided diagnosis
SO EXPERT SYSTEMS WITH APPLICATIONS
LA English
DT Article
DE Deep learning; Medical imaging; Self-supervised learning; Eye fundus;
   Transfer learning; Computer-aided diagnosis
ID DIABETIC-RETINOPATHY; IMAGE; MACULOPATHY
AB Computer-aided diagnosis using retinal fundus images is crucial for the early detection of many ocular and systemic diseases. Nowadays, deep learning-based approaches are commonly used for this purpose. However, training deep neural networks usually requires a large amount of annotated data, which is not always available. In practice, this issue is commonly mitigated with different techniques, such as data augmentation or transfer learning. Nevertheless, the latter is typically faced using networks that were pre-trained on additional annotated data. An emerging alternative to the traditional transfer learning source tasks is the use of self-supervised tasks that do not require manually annotated data for training. In that regard, we propose a novel self-supervised visual learning strategy for improving the retinal computer-aided diagnosis systems using unlabeled multimodal data. In particular, we explore the use of a multimodal reconstruction task between complementary retinal imaging modalities. This allows to take advantage of existent unlabeled multimodal data in the medical domain, improving the diagnosis of different ocular diseases with additional domain-specific knowledge that does not rely on manual annotation. To validate and analyze the proposed approach, we performed several experiments aiming at the diagnosis of different diseases, including two of the most prevalent impairing ocular disorders: glaucoma and age-related macular degeneration. Additionally, the advantages of the proposed approach are clearly demonstrated in the comparisons that we perform against both the common fully-supervised approaches in the literature as well as current self-supervised alternatives for retinal computer-aided diagnosis. In general, the results show a satisfactory performance of our proposal, which improves existing alternatives by leveraging the unlabeled multimodal visual data that is commonly available in the medical field.
C1 [Hervella, Alvaro S.] Univ A Coruna, Ctr Invest CITIC, La Coruna, Spain.
   Univ A Coruna, Inst Invest Biomed A Coruna INIBIC, VARPA Res Grp, La Coruna, Spain.
C3 Universidade da Coruna; Universidade da Coruna; Instituto de
   Investigacion Biomedica de A Coruna (INIBIC)
RP Hervella, AS (通讯作者)，Univ A Coruna, Ctr Invest CITIC, La Coruna, Spain.
EM a.suarezh@udc.es; jrouco@udc.es; jnovo@udc.es; mortega@udc.es
RI Hortas, Marcos Ortega/A-5955-2011; Buján, Jorge Novo/N-3366-2014; Rouco,
   J./A-7255-2011
OI Hortas, Marcos Ortega/0000-0002-2798-0788; Buján, Jorge
   Novo/0000-0002-0125-3064; Rouco, J./0000-0003-4407-9091; Suarez
   Hervella, Alvaro/0000-0002-9080-9836
FU Instituto de Salud Carlos III, Government of Spain [DTS18/00136];
   European Regional Development Fund (ERDF) of the European Union (EU)
   [DTS18/00136]; Ministerio de Ciencia e Innovacion, Government of Spain
   [RTI2018-095894-B-I00, PID2019-108435RB-I00]; Xunta de Galicia
   [ED481A-2017/328]; European Social Fund (ESF) of the EU
   [ED481A-2017/328]; Conselleria de Cultura, Educacion e Universidade,
   Xunta de Galicia, through Grupos de Referencia Competitiva [ED431C
   2020/24]; Conselleria de Educacion, Universidade e Formacion Profesional
   [ED431G 2019/01]; Xunta de Galicia, through the ERDF; Secretaria Xeral
   de Universidades
FX This work is supported by Instituto de Salud Carlos III, Government of
   Spain, and the European Regional Development Fund (ERDF) of the European
   Union (EU) through the DTS18/00136 research project; Ministerio de
   Ciencia e Innovacion, Government of Spain, through the
   RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Xunta
   de Galicia and the European Social Fund (ESF) of the EU through the
   predoctoral grant contract ref. ED481A-2017/328; Conselleria de Cultura,
   Educacion e Universidade, Xunta de Galicia, through Grupos de Referencia
   Competitiva, grant ref. ED431C 2020/24. CITIC, Centro de Investigacion
   de Galicia ref. ED431G 2019/01, receives financial support from
   Conselleria de Educacion, Universidade e Formacion Pro-fesional, Xunta
   de Galicia, through the ERDF (80%) and Secretaria Xeral de Universidades
   (20%).
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NR 40
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 0957-4174
EI 1873-6793
J9 EXPERT SYST APPL
JI Expert Syst. Appl.
PD DEC 15
PY 2021
VL 185
AR 115598
DI 10.1016/j.eswa.2021.115598
EA JUL 2021
PG 10
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
   Electronic; Operations Research & Management Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Operations Research & Management Science
GA UZ1EF
UT WOS:000701954400007
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Johari, YB
   Mercer, AC
   Liu, Y
   Brown, AJ
   James, DC
AF Johari, Yusuf B.
   Mercer, Andrew C.
   Liu, Ye
   Brown, Adam J.
   James, David C.
TI Design of synthetic promoters for controlled expression of therapeutic
   genes in retinal pigment epithelial cells
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE cell&#8208; specific expression; gene therapy; RPE cells; synthetic
   biology; synthetic promoter; transcriptomics
AB Age-related macular degeneration (AMD) associated with dysfunction of retinal pigment epithelial (RPE) cells is the most common cause of untreatable blindness. To advance gene therapy as a viable treatment for AMD there is a need for technologies that enable controlled, RPE-specific expression of therapeutic genes. Here we describe design, construction and testing of compact synthetic promoters with a pre-defined transcriptional activity and RPE cell specificity. Initial comparative informatic analyses of RPE and photoreceptor (PR) cell transcriptomic data identified conserved and overrepresented transcription factor regulatory elements (TFREs, 8-19 bp) specifically associated with transcriptionally active RPE genes. Both RPE-specific TFREs and those derived from the generically active cytomegalovirus-immediate early (CMV-IE) promoter were then screened in vitro to identify sequence elements able to control recombinant gene transcription in model induced pluripotent stem (iPS)-derived and primary human RPE cells. Two libraries of heterotypic synthetic promoters varying in predicted RPE specificity and transcriptional activity were designed de novo using combinations of up to 20 discrete TFREs in series (323-602 bp) and their transcriptional activity in model RPE cells was compared to that of the endogenous BEST1 promoter (661 bp, plus an engineered derivative) and the highly active generic CMV-IE promoter (650 bp). Synthetic promoters with a highpredicted specificity, comprised predominantly of endogenous TFREs exhibited a range of activities up to 8-fold that of the RPE-specific BEST1 gene promoter. Moreover, albeit at a lower predicted specificity, synthetic promoter transcriptional activity in model RPE cells was enhanced beyond that of the CMV-IE promoter when viral elements were utilized in combination with endogenous RPE-specific TFREs, with a reduction in promoter size of 15%. Taken together, while our data reveal an inverse relationship between synthetic promoter activity and cell-type specificity, cell context-specific control of recombinant gene transcriptional activity may be achievable.
C1 [Johari, Yusuf B.; Brown, Adam J.; James, David C.] Univ Sheffield, Dept Chem & Biol Engn, Mappin St, Sheffield S1 3JD, S Yorkshire, England.
   [Mercer, Andrew C.; Liu, Ye] REGENXBIO Inc, Res & Early Dev, Rockville, MD USA.
C3 University of Sheffield
RP James, DC (通讯作者)，Univ Sheffield, Dept Chem & Biol Engn, Mappin St, Sheffield S1 3JD, S Yorkshire, England.
EM d.c.james@sheffield.ac.uk
FU REGENXBIO
FX REGENXBIO
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NR 49
TC 5
Z9 5
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
EI 1097-0290
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD MAY
PY 2021
VL 118
IS 5
BP 2001
EP 2015
DI 10.1002/bit.27713
EA MAR 2021
PG 15
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA RM8KP
UT WOS:000624463400001
PM 33580508
OA hybrid, Green Accepted
DA 2022-11-30
ER

PT J
AU Chaqour, B
   Karrasch, C
AF Chaqour, Brahim
   Karrasch, Charles
TI Eyeing the Extracellular Matrix in Vascular Development and
   Microvascular Diseases and Bridging the Divide between Vascular
   Mechanics and Function
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE retina; angiogenesis; extracellular matrix; growth factor; ischemia;
   ischemic retinopathy; diabetic retinopathy; neovascularization; CCN2;
   CTGF; basement membrane; stiffness
ID TISSUE-GROWTH-FACTOR; MATRICELLULAR PROTEIN CCN1; BASEMENT-MEMBRANE;
   FACTOR CTGF; FACTOR EXPRESSION; GENE-EXPRESSION; OXIDATIVE STRESS;
   CELLS; ANGIOGENESIS; FAMILY
AB The extracellular matrix (ECM) is critical in all aspects of vascular development and health: supporting cell anchorage, providing structure, organization and mechanical stability, and serving as a sink for growth factors and sustained survival signals. Abnormal changes in ECM protein expression, organization, and/or properties, and the ensuing changes in vascular compliance affect vasodilator responses, microvascular pressure transmission, and collateral perfusion. The changes in microvascular compliance are independent factors initiating, driving, and/or exacerbating a plethora of microvascular diseases of the eye including diabetic retinopathy (DR) and vitreoretinopathy, retinopathy of prematurity (ROP), wet age-related macular degeneration (AMD), and neovascular glaucoma. Congruently, one of the major challenges with most vascular regenerative therapies utilizing localized growth factor, endothelial progenitor, or genetically engineered cell delivery, is the regeneration of blood vessels with physiological compliance properties. Interestingly, vascular cells sense physical forces, including the stiffness of their ECM, through mechanosensitive integrins, their associated proteins and the actomyosin cytoskeleton, which generates biochemical signals that culminate in a rapid expression of matricellular proteins such as cellular communication network 1 (CCN1) and CCN2 (aka connective tissue growth factor or CTGF). Loss or gain of function of these proteins alters genetic programs of cell growth, ECM biosynthesis, and intercellular signaling, that culminate in changes in cell behavior, polarization, and barrier function. In particular, the function of the matricellular protein CCN2/CTGF is critical during retinal vessel development and regeneration wherein new blood vessels form and invest a preformed avascular neural retina following putative gradients of matrix stiffness. These observations underscore the need for further in-depth characterization of the ECM-derived cues that dictate structural and functional properties of the microvasculature, along with the development of new therapeutic strategies addressing the ECM-dependent regulation of pathophysiological stiffening of blood vessels in ischemic retinopathies.
C1 [Chaqour, Brahim; Karrasch, Charles] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
   [Chaqour, Brahim] Suny Downstate Med Ctr, Dept Ophthalmol, Brooklyn, NY 11203 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Downstate Medical Center; State University of New York (SUNY)
   System; State University of New York (SUNY) Downstate Medical Center
RP Chaqour, B (通讯作者)，Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.; Chaqour, B (通讯作者)，Suny Downstate Med Ctr, Dept Ophthalmol, 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 [EY024998,
   EY022091]
FX This work was supported by grants EY024998 and EY022091 from the
   National Eye Institute of the National Institutes of Health to B.C.
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NR 169
TC 8
Z9 8
U1 2
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAY
PY 2020
VL 21
IS 10
DI 10.3390/ijms21103487
PG 22
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LW7GO
UT WOS:000539312100083
PM 32429045
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Farjood, F
   Ahmadpour, A
   Ostvar, S
   Vargis, E
AF Farjood, Farhad
   Ahmadpour, Amir
   Ostvar, Sassan
   Vargis, Elizabeth
TI Acute mechanical stress in primary porcine RPE cells induces angiogenic
   factor expression and in vitro angiogenesis
SO JOURNAL OF BIOLOGICAL ENGINEERING
LA English
DT Article
DE Mechanical stress; Angiogenesis; RPE; AMD; EMT; CNV; VEGF; IL-6; IL-8;
   ANG2
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MESENCHYMAL
   TRANSITION; MACULAR DEGENERATION; VEGF EXPRESSION; INDUCTION;
   ACTIVATION; IL-8
AB Background Choroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration. CNV is characterized by new blood vessel growth and subretinal fluid accumulation, which results in mechanical pressure on retinal pigment epithelial (RPE) cells. The overexpression of RPE-derived angiogenic factors plays an important role in inducing CNV. In this work, we investigated the effect of mechanical stress on the expression of angiogenic factors in porcine RPE cells and determined the impact of conditioned medium on in-vitro angiogenesis. Results The goal of this study was to determine whether low levels of acute mechanical stress during early CNV can induce the expression of angiogenic factors in RPE cells and accelerate angiogenesis. Using a novel device, acute mechanical stress was applied to primary porcine RPE cells and the resulting changes in the expression of major angiogenic factors, VEGF, ANG2, HIF-1 alpha, IL6, IL8 and TNF-alpha, were examined using immunocytochemistry, qRT-PCR, and ELISA. An in vitro tube formation assay was used to determine the effect of secreted angiogenic proteins due to mechanical stress on endothelial tube formation by human umbilical vein endothelial cells (HUVECs). Our results showed an increase in the expression of VEGF, ANG2, IL-6 and IL-8 in response to mechanical stress, resulting in increased in vitro angiogenesis. Abnormal epithelial-mesenchymal transition (EMT) in RPE cells is also associated with CNV and further retinal degeneration. Our qRT-PCR results verified an increase in the expression of EMT genes, CDH2, VIM and FN1, in RPE cells. Conclusions In conclusion, we showed that acute mechanical stress induces the expression of major angiogenic and EMT factors and promotes in vitro angiogenesis, suggesting that mechanical stress plays a role in promoting aberrant angiogenesis in AMD.
C1 [Farjood, Farhad; Ahmadpour, Amir; Vargis, Elizabeth] Utah State Univ, Dept Biol Engn, 4105 Old Main Hill, Logan, UT 84322 USA.
   [Farjood, Farhad] Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
   [Ahmadpour, Amir] Univ Yasuj, Dept Anim Sci, Yasuj 7591874934, Iran.
   [Ostvar, Sassan] Columbia Univ, Med Ctr, Div Gen Med, New York, NY 10032 USA.
C3 Utah System of Higher Education; Utah State University; Yasouj
   University; Columbia University
RP Vargis, E (通讯作者)，Utah State Univ, Dept Biol Engn, 4105 Old Main Hill, Logan, UT 84322 USA.
EM vargis@usu.edu
RI Ahmadpour, Amir/ABG-9744-2020
FU National Eye Institute of the National Institutes of Health
   [R15EY028732]; Knights Templar Eye Foundation; Ralph E. Powe Junior
   Faculty Award from the Oak Ridge Associated Universities (ORAU); Utah
   State University's Office of Graduate Studies; Utah State University's
   College of Engineering
FX This work was supported by a National Eye Institute of the National
   Institutes of Health Grant R15EY028732, a Career Starter Grant from the
   Knights Templar Eye Foundation, a Ralph E. Powe Junior Faculty Award
   from the Oak Ridge Associated Universities (ORAU), Utah State
   University's Office of Graduate Studies, and Utah State University's
   College of Engineering.
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NR 44
TC 2
Z9 2
U1 0
U2 7
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-1611
J9 J BIOL ENG
JI J. Biol. Eng.
PD APR 25
PY 2020
VL 14
IS 1
AR 13
DI 10.1186/s13036-020-00235-4
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA LJ7KK
UT WOS:000530339500001
PM 32355505
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Barone, F
   Muscatello, LV
   Ventrella, D
   Elmi, A
   Romagnoli, N
   Mandrioli, L
   Maya-Vetencourt, JF
   Bombardi, C
   Mete, M
   Sarli, G
   Benfenati, F
   Pertile, G
   Bacci, ML
AF Barone, Francesca
   Muscatello, Luisa Vera
   Ventrella, Domenico
   Elmi, Alberto
   Romagnoli, Noemi
   Mandrioli, Luciana
   Maya-Vetencourt, Jose Fernando
   Bombardi, Cristiano
   Mete, Maurizio
   Sarli, Giuseppe
   Benfenati, Fabio
   Pertile, Grazia
   Bacci, Maria Laura
TI The porcine iodoacetic acid model of retinal degeneration:
   Morpho-functional characterization of the visual system
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Porcine model; Photoreceptor degeneration; Iodoacetic acid; Visual
   system; Electrophysiology; Histology
ID LARGE ANIMAL-MODEL; ISCEV STANDARD; PROSTHESIS; VISION; ROD
AB Porcine models of ophthalmological diseases are often used in pre-clinical translational studies due to pigs similarities to humans. In particular, the iodoacetic acid (IAA) model of photoreceptor degeneration seems to mimic well the endstage phenotype of human pathologies as retinitis pigmentosa and age-related macular degeneration, with high potential for prosthesis/retinal devices testing. IAA is capable of inducing photoreceptor death by blockage of glycolysis, and its effects on the retina have been described. Nonetheless, up to date, literature lacks of a comprehensive morpho-functional characterization of the entire visual system of this model. This gap is particularly critical for prosthesis testing as inner retinal structures and optic pathways must be preserved to elicit cortical responses and restore vision. In this study, we investigated the functional and anatomical features of the visual system of IAA-treated pigs and compared them to control animals. IAA was administered intravenously at 12 mg/kg; control animals received saline solution (NaCl 0.9% w/v). Electrophysiological analyses included full-field (ffERGs) and pattern (PERGs) electroretinograms and flash visually evoked potentials (fVEPs). Histological evaluations were performed on the retina and the optic pathways and included thickness of the different retinal layers, ganglion cells count, and immunohistochemistry for microglial cells, macroglial cells, and oligodendrocytes. The histological results indicate that IAA treatment does not affect the morphology of the inner retina and optic pathways. Electrophysiology confirms the selective rod and partial cone degeneration, but is ambiguous as to the functionality of the optic pathways, seemingly preserved as indicated by the still detectable fVEPs. Overall, the work ameliorates the characterization of such rapid and cost-effective model, providing more strength and reliability for future pre-clinical translational trials.
C1 [Barone, Francesca] NEI, NIH, 10 Ctr Dr, Bethesda, MD 20814 USA.
   [Barone, Francesca; Mete, Maurizio; Pertile, Grazia] Sacro Cuore Hosp Don Calabria, Ophthalmol Dept, Via Don A Sempreboni 5, I-37024 Negrar, VR, Italy.
   [Muscatello, Luisa Vera; Ventrella, Domenico; Elmi, Alberto; Romagnoli, Noemi; Mandrioli, Luciana; Bombardi, Cristiano; Sarli, Giuseppe; Bacci, Maria Laura] Univ Bologna, Alma Mater Studiorum, Dept Vet Med Sci, Via Tolara di Sopra 50, I-40064 Ozzano Dellemilia, BO, Italy.
   [Maya-Vetencourt, Jose Fernando; Benfenati, Fabio] Italian Inst Technol, Ctr Synapt Neurosci & Technol, Via Morego 30, I-16163 Genoa, GE, Italy.
   [Maya-Vetencourt, Jose Fernando] Univ Pisa, Dept Biol, Via Alessandro Volta 4Bis, I-56126 Pisa, PI, Italy.
   [Benfenati, Fabio] Univ Genoa, Dept Expt Med, Via Leon Battista Alberti 2, I-16132 Genoa, GE, Italy.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); IRCCS Sacro Cuore Don Calabria; University of Bologna; Istituto
   Italiano di Tecnologia - IIT; University of Pisa; University of Genoa
RP Ventrella, D (通讯作者)，Univ Bologna, Alma Mater Studiorum, Dept Vet Med Sci, Via Tolara di Sopra 50, I-40064 Ozzano Dellemilia, BO, Italy.
EM domenico.ventrella2@unibo.it
RI Elmi, Alberto/U-2252-2019; Pertile, Grazia/AAC-4956-2022;
   Maya-Vetencourt, JF/AAT-5130-2020; Mete, Maurizio/C-2149-2018;
   Mandrioli, Luciana/AAB-2587-2021
OI Elmi, Alberto/0000-0002-7827-5034; Mandrioli,
   Luciana/0000-0002-0579-9136; Ventrella, Domenico/0000-0002-9330-979X;
   Maya-Vetencourt, Jose Fernando/0000-0003-3808-8944
FU UNIBO [RFO]; Telethon-Italy [GGP14022]; Italian Ministry of Health
   [RE-2013-02358313]
FX This work was supported by UNIBO [RFO ex 60% to M.L.B.]; Telethon-Italy
   [GGP14022 to G.P. and F.Be.]; and the Italian Ministry of Health
   [RE-2013-02358313 to G.P.].
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NR 41
TC 3
Z9 3
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2020
VL 193
AR 107979
DI 10.1016/j.exer.2020.107979
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KZ8MD
UT WOS:000523511400018
PM 32087230
DA 2022-11-30
ER

PT J
AU Lian, CP
   Lou, H
   Zhang, JF
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AF Lian, Chunpin
   Lou, Hui
   Zhang, Jingfa
   Tian, Haibin
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   Xu, Jing-Ying
   Jin, Caixia
   Gao, Furong
   Zhang, Jieping
   Wang, Juan
   Li, Weiye
   Xu, Guoxu
   Lu, Lixia
   Xu, Guo-Tong
TI MicroRNA-24 protects retina from degeneration in rats by down-regulating
   chitinase-3-like protein 1
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE MicroRNA-24; Chitinase-3-like protein 1; Retinal degeneration;
   Autophagy; RPE
ID MACULAR DEGENERATION; PIGMENT EPITHELIUM; ROYAL-COLLEGE; AUTOPHAGY;
   YKL-40; KINASE; GENE; INFLAMMATION; PATHWAYS; CELLS
AB MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-kappa B was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-kappa B signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERIC pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD.
C1 [Lian, Chunpin; Zhang, Jingfa; Tian, Haibin; Ou, Qingjian; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Zhang, Jieping; Wang, Juan; Li, Weiye; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Dept Ophthalmol, Tongji Eye Inst, Shanghai Peoples Hosp 10,Sch Med, Shanghai 200092, Peoples R China.
   [Lian, Chunpin; Tian, Haibin; Ou, Qingjian; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Zhang, Jieping; Wang, Juan; Li, Weiye; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Dept Regenerat Med, Lab Clin Visual Sci, Shanghai 200092, Peoples R China.
   [Lian, Chunpin; Tian, Haibin; Ou, Qingjian; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Zhang, Jieping; Wang, Juan; Li, Weiye; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Stem Cell Res Ctr, Shanghai 200092, Peoples R China.
   [Lian, Chunpin; Tian, Haibin; Ou, Qingjian; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Zhang, Jieping; Wang, Juan; Li, Weiye; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Dept Pharmacol, Shanghai 200092, Peoples R China.
   [Lou, Hui; Xu, Guoxu] Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou 215004, Peoples R China.
   [Zhang, Jingfa] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Ophthalmol,Shanghai Peoples Hosp 1, Shanghai, Peoples R China.
   [Li, Weiye] Drexel Univ, Dept Ophthalmol, Coll Med, Philadelphia, PA 19129 USA.
   [Xu, Guo-Tong] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200092, Peoples R China.
C3 Tongji University; Tongji University; Tongji University; Tongji
   University; Soochow University - China; Shanghai Jiao Tong University;
   Drexel University; Tongji University
RP Xu, GX (通讯作者)，Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou 215004, Peoples R China.; Xu, GT (通讯作者)，Tongji Univ, Sch Med, Tongji Eye Inst, Dept Ophthalmol,Shanghai Hosp 10, Shanghai 200072, Peoples R China.; Lu, LX (通讯作者)，Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R China.; Lu, LX; Xu, GT (通讯作者)，Tongji Univ, Sch Med, Tongji Eye Inst, Shanghai 200092, Peoples R China.
EM phacoxu@aliyun.com; lulixia@tongji.edu.cn; gtxu@tongji.edu.cn
RI Ou, Qingjian/GON-9963-2022
OI Ou, Qingjian/0000-0002-6881-8680
FU Ministry of Science and Technology of China [2016YFA0101302,
   2015CB964601, 2017YFA0104100]; National Natural Science Foundation of
   China [81670867, 81770942, 81570852]; Shanghai Municipal Commission of
   Health and Family Planning [201640229]; Shanghai Science and Technology
   Committee Grant [17ZR1431300]; Shanghai East Hospital [ZJ2014-ZD-002]
FX This work was supported by grants from the Ministry of Science and
   Technology of China (2016YFA0101302, 2015CB964601, 2017YFA0104100),
   National Natural Science Foundation of China (81670867, 81770942,
   81570852), Shanghai Municipal Commission of Health and Family Planning
   (201640229), Shanghai Science and Technology Committee Grant
   (17ZR1431300) and the grant from Shanghai East Hospital (ZJ2014-ZD-002).
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NR 52
TC 9
Z9 9
U1 2
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 2019
VL 188
AR 107791
DI 10.1016/j.exer.2019.107791
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JJ9XC
UT WOS:000494503700023
PM 31491426
DA 2022-11-30
ER

PT J
AU Zhang, W
   Ma, YX
   Zhang, Y
   Yang, J
   He, GH
   Chen, S
AF Zhang, Wei
   Ma, Yingxue
   Zhang, Yue
   Yang, Jing
   He, Guanghui
   Chen, Song
TI Photo-Oxidative Blue-Light Stimulation in Retinal Pigment Epithelium
   Cells Promotes Exosome Secretion and Increases the Activity of the NLRP3
   Inflammasome
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Retinal pigment epithelium cells; exosomes; NLRP3 inflammasome;
   photooxidative; oxidative stress
ID OXIDATIVE STRESS; MACULAR DEGENERATION; EXTRACELLULAR VESICLES;
   INVOLVEMENT; DYSFUNCTION; EXPRESSION; BIOMARKERS; RELEASE
AB Purpose: Age-related macular degeneration (AMD) is a major cause of blindness in the elderly, and the activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome is involved in AMD pathogenesis. We investigated whether photooxidative blue-light stimulation in retinal pigment epithelium (RPE) cells promotes exosome secretion and modulates the activity of the NLRP3 inflammasome in vitro. Methods: Exosomes were isolated from ARPE-19 cultures stimulated or not with blue-light photostimulation (488 nm). Isolated exosomes were characterized by transmission electron microscope and Western blot analyses. The contents of the NLRP3 inflammasome (IL-1 beta, IL-18, and caspase-1 as markers of the inflammasome) in exosomes were analyzed by Western blotting. After culture, IL-1 beta, IL-18, and caspase-1 in RPE cells were analyzed by both immunofluorescence and Western blotting. RT-PCR and Western blotting were conducted to assess the contents of NLRP3 in RPE cells. Results: Exosomes exhibited a typical characteristic morphology (cup-shaped) and size (diameter between 50 and 150 nm) in both groups. The exosome markers CD9, CD63, and CD81 were strongly present. After blue-light photostimulation, ARPE-19 cells were noted to release exosomes with higher levels of IL-1 beta, IL-18, and caspase-1 than those in the control group. The levels of IL-1 beta, IL-18, and caspase-1 in ARPE-19 cells were signi?cantly enhanced when treated with stressed RPE exosomes. Additionally, the NLRP3 mRNA and protein levels were found to be markedly higher in the treated group than in the control group. Conclusions: Under photooxidative blue-light stimulation, RPE-derived exosomes may aggravate a potentially harmful oxidative response through the upregulation of the NLRP3 inflammasome.
C1 [Zhang, Wei; Ma, Yingxue; Zhang, Yue; Yang, Jing; He, Guanghui; Chen, Song] Tianjin Med Univ, Clin Coll Ophthalmol, Tianjin Eye Hosp,Tianjin Eye Inst, Tianjin Key Lab Ophthalmol & Visual Sci,Eye Hosp, 4 Gansu Rd, Tianjin 300020, Peoples R China.
C3 Tianjin Medical University
RP Chen, S (通讯作者)，Tianjin Med Univ, Clin Coll Ophthalmol, Tianjin Eye Hosp,Tianjin Eye Inst, Tianjin Key Lab Ophthalmol & Visual Sci,Eye Hosp, 4 Gansu Rd, Tianjin 300020, Peoples R China.
EM chensong20@hotmail.com
FU Tianjin Science and Technology Project of China [14JCYBJC27400];
   National Natural Science Foundation of China [81700846]
FX This work was supported by Tianjin Science and Technology Project of
   China (No. 14JCYBJC27400) and the National Natural Science Foundation of
   China (No. 81700846).
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NR 34
TC 18
Z9 19
U1 1
U2 16
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 67
EP 75
DI 10.1080/02713683.2018.1518458
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HG4NL
UT WOS:000454952100010
PM 30198786
DA 2022-11-30
ER

PT J
AU Patel, R
   Wang, J
   Campbell, JP
   Kiang, L
   Lauer, A
   Flaxel, C
   Hwang, T
   Lujan, B
   Huang, D
   Bailey, ST
   Jia, YL
AF Patel, Rachel
   Wang, Jie
   Campbell, J. Peter
   Kiang, Lee
   Lauer, Andreas
   Flaxel, Christina
   Hwang, Thomas
   Lujan, Brandon
   Huang, David
   Bailey, Steven T.
   Jia, Yali
TI Classification of Choroidal Neovascularization Using Projection-Resolved
   Optical Coherence Tomographic Angiography
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE projection-resolved optical coherence tomographic angiography; OCTA;
   choroidal neovascularization; age-related macular degeneration
ID AMPLITUDE-DECORRELATION ANGIOGRAPHY; MACULAR DEGENERATION; RANIBIZUMAB;
   ALGORITHM
AB PURPOSE. To evaluate if projection-resolved optical coherence tomographic angiography (PR-OCTA) reduces projection artifact with less attenuation of choroidal neovascularization (CNV) flow signal compared to conventional OCTA with slab subtraction.
   METHODS. In this retrospective cross-sectional study, participants with subfoveal treatment-naive CNV secondary to age-related macular degeneration underwent OCTA. Scans were exported for custom processing including manual segmentation as necessary, application of slab subtraction and PR-OCTA algorithm, and calculation of CNV vascular area and connectivity. CNV was classified as type 1, minimally type 2, or predominantly type 2 based on fluorescein angiography (FA) and OCT. Two masked retina specialists independently classified CNV using cross-sectional conventional OCTA and PR-OCTA.
   RESULTS. A total of 17 eyes were enrolled in this study. Mean CNV vessel area (mm 2) was 0.67 +/- 0.51 for PR-OCTA and 0.53 +/- 0.41 for slab subtraction (P = 0.018). Mean vascular connectivity was 96.80 +/- 1.28 for PR-OCTA and 90.90 +/- 4.42 (P = 0.018) for slab subtraction. Within-visit repeatability (coefficient of variation) of PR-OCTA was 0.044 for CNV vessel area and 0.012 for vascular connectivity, compared to 0.093 and 0.028 by slab subtraction. PR-OCTA classification agreement with FA/OCT was 88.2% and 76.5% for the two graders, while conventional OCTA agreement was 58.8% and 70.6% (grader 1, P = 0.025; grader 2, P = 0.56). Moreover, PR-OCTA enabled the individual quantification of type 1 and type 2 components of a CNV.
   CONCLUSIONS. PR-OCTA had greater CNV vessel area and vascular connectivity, as well as better repeatability, compared to slab subtraction, suggesting PR-OCTA is a superior technique for imaging CNV. Furthermore, PR-OCTA removes projection artifact on cross-sectional OCTA, improving the ability to classify and quantify CNV components.
C1 [Patel, Rachel; Wang, Jie; Campbell, J. Peter; Kiang, Lee; Lauer, Andreas; Flaxel, Christina; Hwang, Thomas; Lujan, Brandon; Huang, David; Bailey, Steven T.; Jia, Yali] Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
   [Patel, Rachel] Univ Utah Hlth, John A Moran Eye Ctr, Salt Lake City, UT USA.
C3 Oregon Health & Science University; Utah System of Higher Education;
   University of Utah
RP Jia, YL (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM jiaya@ohsu.edu
RI Hwang, Thomas S./AAW-6618-2020; Hwang, Thomas/AAV-5146-2020
OI Hwang, Thomas S./0000-0002-0535-4823; Bailey,
   Steven/0000-0003-4949-1464; Jia, Yali/0000-0002-2784-1905
FU National Institutes of Health (Bethesda, MD, USA) [R01 EY024544, R01
   EY027833, P30 EY010572]; William & Mary Greve Special Scholar Award from
   Research to Prevent Blindness (New York, NY, USA); Alpha Omega Alpha
   Carolyn L. Kuckein Student Research Fellowship; NATIONAL EYE INSTITUTE
   [P30EY010572, R01EY027833, R01EY024544, K12EY027720] Funding Source: NIH
   RePORTER
FX Supported by National Institutes of Health (Bethesda, MD, USA) Grants
   R01 EY024544, R01 EY027833, and P30 EY010572; unrestricted departmental
   funding; the William & Mary Greve Special Scholar Award from Research to
   Prevent Blindness (New York, NY, USA); and the Alpha Omega Alpha Carolyn
   L. Kuckein Student Research Fellowship. The authors alone are
   responsible for the content and writing of the paper.
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NR 23
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Z9 16
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2018
VL 59
IS 10
BP 4285
EP 4291
DI 10.1167/iovs.18-24624
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GR7EB
UT WOS:000442849800018
PM 30372757
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sun, Q
   Qing, W
   Qi, R
   Zou, M
   Gong, L
   Liu, Y
   Li, DWC
AF Sun, Q.
   Qing, W.
   Qi, R.
   Zou, M.
   Gong, L.
   Liu, Y.
   Li, D. W. -C.
TI Inhibition of Sumoylation Alleviates Oxidative Stress-induced Retinal
   Pigment Epithelial Cell Senescence and Represses Proinflammatory Gene
   Expression
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Protein sumoylation; RPE senescence; oxidative stress; AMD
ID MACULAR DEGENERATION; DISEASE; SUMO; PREVALENCE; MECHANISMS; PROTEIN;
   TARGET
AB Purpose: Advanced age is the largest risk factor for age-related macular degeneration (AMD). Sumoylation is a reversible post-translational modification that conjugates small peptide, small ubiquitin-like modifier (SUMO), to a target protein. Dysregulation of sumoylation is recently found to be critically involved in several age-related disorders. However, the effects of sumoylation during retina senescence and aging remains elusive. This study is aimed to investigate the function and regulation of sumoylation pathway in the aging retina and premature senescent retinal pigment epithelial (RPE) cells.
   Methods: 1.5- and 10-month C57/B6 mice were used for comparative aging study. Both ARPE primary cultures and ARPE-19 cells were used for assay systems. The qRT-PCR was used for analysis of mRNA expression. Western blot and immunofluorescence were used to analyze the protein expression. Cell flow cytometry was used for cell cycle progression analysis. RPE barrier function and senescent-associated beta-galactosidase (SA beta-gal) activity were analyzed to measure cellular senescence.
   Results: We show that the expression of SUMO enzymes and global protein sumoylation were downregulated in the aging mouse retina, and in the oxidative stress (OS) -induced premature senescent RPE cells. Dramatical altered distribution of SUMO E1, E2 and E3 enzymes were observed during RPE senescence. Inhibition of sumoylation alleviated OS-induced cell senescence in RPE cells, as indicated by decreased p21 and p53 expression and decreased percentage of cell cycle arrest at G(0)/G(1 )phase. Intriguingly, inhibition of SUMO E1 repressed the expression of proinflammatory cytokine and chemokine in the premature senescent RPE cells. However, inhibition of sumoylation did not prevent DNA damage during the OS-induced RPE senescence process.
   Conclusions: Our data indicate sumoylation critically regulates retina and RPE aging and that targeting sumoylation process may provide potential therapeutic strategy for AMD treatment.
C1 [Sun, Q.; Qi, R.; Zou, M.; Gong, L.; Liu, Y.; Li, D. W. -C.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [Qing, W.; Li, D. W. -C.] Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, Changsha, Hunan, Peoples R China.
C3 Sun Yat Sen University; Hunan Normal University
RP Li, DWC (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 7 Jinsui Rd,Res Bldg,Room 602-5, Guangzhou 510230, Guangdong, Peoples R China.; Gong, L (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 7 Jinsui Rd,Res Bldg,Room 602-7, Guangzhou 510230, Guangdong, Peoples R China.; Liu, Y (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 7 Jinsui Rd,Res Bldg,Room 602-2, Guangzhou 510230, Guangdong, Peoples R China.
EM gonglili978@163.com; liuyizhi@gzzoc.com; liwancheng@gzzoc.com
RI Li, David/AAN-9205-2021
FU National Natural Science Foundation of China [81500738, 81570824,
   81770910]; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic
   Center, Sun Yat-Sen University
FX This work was supported by the grants from National Natural Science
   Foundation of China (81500738, 81570824 and 81770910), and the
   foundation funds of State Key Laboratory of Ophthalmology, Zhongshan
   Ophthalmic Center, Sun Yat-Sen University.
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NR 34
TC 6
Z9 6
U1 0
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1566-5240
EI 1875-5666
J9 CURR MOL MED
JI Curr. Mol. Med.
PY 2018
VL 18
IS 9
BP 575
EP 583
DI 10.2174/1566524019666190107154250
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA HL7BM
UT WOS:000458892000001
PM 30621561
DA 2022-11-30
ER

PT J
AU Reitmeir, P
   Linkohr, B
   Heier, M
   Molnos, S
   Strobl, R
   Schulz, H
   Breier, M
   Faus, T
   Kuster, DM
   Wulff, A
   Grallert, H
   Grill, E
   Peters, A
   Graw, J
AF Reitmeir, Peter
   Linkohr, Birgit
   Heier, Margit
   Molnos, Sophie
   Strobl, Ralf
   Schulz, Holger
   Breier, Michaela
   Faus, Theresa
   Kuester, Dorothea M.
   Wulff, Andrea
   Grallert, Harald
   Grill, Eva
   Peters, Annette
   Graw, Jochen
TI Common eye diseases in older adults of southern Germany: results from
   the KORA-Age study
SO AGE AND AGEING
LA English
DT Article
DE older people; population study; ageing; cataract; AMD; glaucoma
ID VISUAL IMPAIRMENT; MACULAR DEGENERATION; POPULATION; EPIDEMIOLOGY; RISK;
   PREVENTION; PREVALENCE; BLINDNESS; CATARACT; EUROPE
AB Purpose: a population-based study in the region of Augsburg (Germany, KORA) was used to identify the prevalence of eye diseases and their risk factors in a sample of aged individuals.
   data originated from the KORA-Age study collected in 2012 and 822 participants (49.6% women, 50.4% men, aged 68-96 years) were asked standardised questions about eye diseases. Positive answers were validated and specified by treating ophthalmologists. Additional information came from laboratory data. Polymorphic markers were tested for candidate genes.
   we received validations and specifications for 339 participants. The most frequent eye diseases were cataracts (299 cases, 36%), dry eyes (120 cases, 15%), glaucoma (72 cases, 9%) and age-related macular degeneration (AMD) (68 cases, 8%). Almost all participants suffering from glaucoma or from AMD also had cataracts. Cataract surgery was associated with diabetes (in men; OR = 2.24; 95% confidence interval [CI] 1.11-4.53; P = 0.025) and smoking (in women; OR = 6.77; CI 1.62-28.35; P = 0.009). In men, treatments in airway diseases was associated with cataracts (glucocorticoids: OR = 5.29, CI 1.20-23.37; P = 0.028; sympathomimetics: OR = 4.57, CI 1.39-15.00; P = 0.012). Polymorphisms in two genes were associated with AMD (ARMS2: OR = 2.28, CI 1.48-3.51; P = 0.005; CFH: OR = 2.03, CI 1.35-3.06; P = 0.010).
   combinations of eye diseases were frequent at old age. The importance of classical risk factors like diabetes, hypertension and airway diseases decreased either due to a survivor bias leaving healthier survivors in the older age group, or due to an increased influence of other up to now unknown risk factors.
C1 [Reitmeir, Peter; Wulff, Andrea] Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Hlth Econ & Hlth Care Management, Neuherberg, Germany.
   [Linkohr, Birgit; Heier, Margit; Molnos, Sophie; Breier, Michaela; Kuester, Dorothea M.; Grallert, Harald; Peters, Annette] Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Epidemiol 2, Neuherberg, Germany.
   [Molnos, Sophie; Breier, Michaela; Grallert, Harald] Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Res Unit Mol Epidemiol, Neuherberg, Germany.
   [Strobl, Ralf; Grill, Eva] Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany.
   [Strobl, Ralf; Grill, Eva] Ludwig Maximilians Univ Munchen, German Ctr Vertigo & Balance Disorders, Munich, Germany.
   [Schulz, Holger] Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Epidemiol 1, Neuherberg, Germany.
   [Faus, Theresa; Graw, Jochen] Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Dev Genet, Neuherberg, Germany.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center
   for Environmental Health; Helmholtz Association; Helmholtz-Center Munich
   - German Research Center for Environmental Health; Helmholtz
   Association; Helmholtz-Center Munich - German Research Center for
   Environmental Health; University of Munich; University of Munich;
   Helmholtz Association; Helmholtz-Center Munich - German Research Center
   for Environmental Health; Helmholtz Association; Helmholtz-Center Munich
   - German Research Center for Environmental Health
RP Graw, J (通讯作者)，Helmholtz Zentrum Munchen, Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Dev Genet, Neuherberg, Germany.
EM graw@helmholtz-muenchen.de
RI Grallert, Harald/B-3424-2013; Grill, Eva/AAF-8104-2020; Schulz,
   Holger/J-5643-2015; Heier, Margit/AAT-5280-2020; Peters,
   Annette/A-6117-2011
OI Grill, Eva/0000-0002-0273-7984; Schulz, Holger/0000-0002-1157-200X;
   Peters, Annette/0000-0001-6645-0985; Graw, Jochen/0000-0003-0298-9660
FU Helmholtz Zentrum Munchen - German Research Center for Environmental
   Health - German Federal Ministry of Education and Research; State of
   Bavaria; German Federal Ministry of Education and Research (BMBF) [FKZ
   01ET0713, 01ET1003A, 01ET1003C]
FX The KORA research platform (KORA, Cooperative Research in the Region of
   Augsburg) was initiated and financed by the Helmholtz Zentrum Munchen -
   German Research Center for Environmental Health, which is funded by the
   German Federal Ministry of Education and Research and by the State of
   Bavaria. The KORA-Age project was financed at least in part by the
   German Federal Ministry of Education and Research (BMBF FKZ 01ET0713,
   01ET1003A and 01ET1003C) as part of the 'Health in old age' programme.
   The sponsors hat no influence on the design, execution, analysis and
   interpretation of the data or in writing the study. Annette Peters and
   Eva Grill applied for funding of those parts of KORA-Age2, which are
   reported here.
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NR 27
TC 12
Z9 12
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD MAY
PY 2017
VL 46
IS 3
BP 481
EP 486
DI 10.1093/ageing/afw234
PG 6
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA EU3AU
UT WOS:000400901800025
PM 27974306
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Burlina, P
   Pacheco, KD
   Joshi, N
   Freund, DE
   Bressler, NM
AF Burlina, Philippe
   Pacheco, Katia D.
   Joshi, Neil
   Freund, David E.
   Bressler, Neil M.
TI Comparing humans and deep learning performance for grading AMD: A study
   in using universal deep features and transfer learning for automated AMD
   analysis
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Deep learning; Deep Convolutional Neural Networks, (DCNNs); Universal
   features; Retinal image analysis; Age -related macular degeneration,
   (AMD); Transfer learning
AB Background: When left untreated, age-related macular degeneration (AMD) is the leading cause of vision loss in people over fifty in the US. Currently it is estimated that about eight million US individuals have the intermediate stage of AMD that is often asymptomatic with regard to visual deficit. These individuals are at high risk for progressing to the advanced stage where the often treatable choroidal neovascular form of AMD can occur. Careful monitoring to detect the onset and prompt treatment of the neovascular form as well as dietary supplementation can reduce the risk of vision loss from AMD, therefore, preferred practice patterns recommend identifying individuals with the intermediate stage in a timely manner.
   Methods: Past automated retinal image analysis (ARIA) methods applied on fundus imagery have relied on engineered and hand-designed visual features. We instead detail the novel application of a machine learning approach using deep learning for the problem of ARIA and AMD analysis. We use transfer learning and universal features derived from deep convolutional neural networks (DCNN). We address clinically relevant 4 class, 3-class, and 2-class AMD severity classification problems.
   Results: Using 5664 color fundus images from the NIH AREDS dataset and DCNN universal features, we obtain values for accuracy for the (4-, 3-, 2-) class classification problem of (79.4%, 81.5%, 93.4%) for machine vs. (75.8%, 85.0%, 95.2%) for physician grading.
   Discussion: This study demonstrates the efficacy of machine grading based on deep universal features/transfer learning when applied to ARIA and is a promising step in providing a pre-screener to identify individuals with intermediate AMD and also as a tool that can facilitate identifying such individuals for clinical studies aimed at developing improved therapies. It also demonstrates comparable performance between computer and physician grading.
C1 [Burlina, Philippe; Joshi, Neil; Freund, David E.] Johns Hopkins Univ, Appl Phys Lab, Baltimore, MD 21218 USA.
   [Burlina, Philippe; Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Retina Div, Baltimore, MD 21218 USA.
   [Burlina, Philippe] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
   [Pacheco, Katia D.] Vis Eye Hosp, Brazilian Ctr, Retina Div, Brasilia, DF, Brazil.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics
   Laboratory; Johns Hopkins University; Johns Hopkins Medicine; Johns
   Hopkins University
RP Freund, DE (通讯作者)，Johns Hopkins Univ, Appl Phys Lab, Baltimore, MD 21218 USA.
EM David.Freund@jhuapl.edu
RI Freund, D.E./AAW-9401-2020
FU National Eye Institute of the National Institutes of Health
   [R21EY024310]; JHU Whiting School of Engineering SPUR Program; Retina
   Division Research Fund of the Brazilian Center of Vision Eye Hospital;
   NATIONAL EYE INSTITUTE [R21EY024310] Funding Source: NIH RePORTER
FX Research reported in this publication was supported primarily 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 James P. Gills
   Professorship and unrestricted research funds to the Retina Division for
   Macular Degeneration and Related Diseases Research. Additional support
   from JHU Whiting School of Engineering SPUR Program and the Retina
   Division Research Fund of the Brazilian Center of Vision Eye Hospital is
   acknowledged.
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NR 36
TC 115
Z9 120
U1 1
U2 42
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 MAR 1
PY 2017
VL 82
BP 80
EP 86
DI 10.1016/j.compbiomed.2017.01.018
PG 7
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 EN2MI
UT WOS:000395844200010
PM 28167406
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zaheer, K
AF Zaheer, K.
TI Hen egg carotenoids (lutein and zeaxanthin) and nutritional impacts on
   human health: a review
SO CYTA-JOURNAL OF FOOD
LA English
DT Review
DE Egg yolk; nutrients; carotenoid analysis; feeding systems;
   bioavailability; macular degeneration; cardiovascular; oxidative stress;
   Alzheimer's; cancer; human health; Yema de huevo; nutrientes; analisis
   de carotenoides; sistemas de alimentacion; biodisponibilidad;
   degeneracion macular; cardiovascular; estres oxidativo; Alzheimer;
   cancer; salud humana
ID BREAST-CANCER RISK; PIGMENT OPTICAL-DENSITY; MACULAR DEGENERATION;
   VITAMIN-C; DIETARY CAROTENOIDS; PLASMA CAROTENOIDS; OXIDATION-PRODUCTS;
   SERUM CONCENTRATIONS; ALZHEIMERS-DISEASE; PRODUCTION SYSTEM
AB Hen egg is a unique and important carrier of lipid soluble bioactive carotenoids - lutein and zeaxanthin. Egg yolk carotenoid profile is largely dependent on hen's feed composition. Naturally, lutein and zeaxanthin are polar carotenoids primarily deposited in human retina and provide several protective functions, i.e. protect the macula from damage by blue light, improve visual acuity, and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration and cataracts, cardiovascular diseases, Alzheimer's, and possibly different cancers. This review summarizes the latest data on content and composition of hen egg carotenoids, effect of processing, feeding systems, feed additives, bioavailability, and physiological effect of egg carotenoids on human health issues. RESUMENLa yema de huevo es un importante y unico portador de carotenoides bioactivos liposolubles: luteina y zeaxantina. El perfil de carotenoides de la yema de huevo depende notablemente de la composicion alimentaria de la gallina. La luteina y la zeaxantina son carotenoides polares naturales depositados principalmente en la retina humana y que aportan diversas funciones protectoras, como por ejemplo la proteccion de la macula del dano provocado por la luz azulada, la mejora de la agudeza visual y expulsan las especies daninas reactivas al oxigeno. Estos tambien estan relacionados con reducir el riesgo de degeneracion macular producido por la edad y las cataratas, enfermedades cardiovasculares, Alzheimer, ademas de la posibilidad de diferentes tipos de cancer. Este estudio resume los datos mas recientes acerca del contenido y la composicion de los carotenoides de la yema de huevo de gallina, el efecto del procesamiento, los sistemas de alimentacion, los aditivos alimentarios, la biodisponibilidad y el efecto psicologico de los carotenoides del huevo en los problemas de salud de las personas.
EM kzaheer2000@gmail.com
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NR 162
TC 36
Z9 38
U1 6
U2 55
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1947-6337
EI 1947-6345
J9 CYTA-J FOOD
JI CyTA-J. Food
PY 2017
VL 15
IS 3
BP 474
EP 487
DI 10.1080/19476337.2016.1266033
PG 14
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA EW6ID
UT WOS:000402612300020
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, H
   Linetsky, M
   Guo, JH
   Yu, AO
   Salomon, RG
AF Wang, Hua
   Linetsky, Mikhail
   Guo, Junhong
   Yu, Annabelle O.
   Salomon, Robert G.
TI Metabolism of 4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone by Retinal
   Pigmented, Epithelial Cells
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID PHOSPHOLIPIDS; GENERATION
AB 4-Hydroxy-7-oxo-S-heptenic acid (HOHA)-lactone is a biologically active oxidative truncation product released (t(1/2) = 30 min at 37 degrees C) by nonenzymatic transesterification/deacylation from docosahexaenoate lipids. We now report that HOHA-lactone readily diffuses into retinal pigmented epithelial (RPE) cells where it is metabolized. A reduced glutathione (GSH) Michael adduct of HOHA-lactone is the most prominent metabolite detected by LC-MS in both the extracellular medium and cell lysates. This molecule appeared inside of ARPE-19 cells within seconds after exposure to HOHA-lactone. The intracellular level reached a maximum concentration at 30 min and then decreased with concomitant increases in its level in the extracellular medium, thus revealing a unidirectional export of the reduced GSH-HOHA-lactone adduct from the cytosol to extracellular medium. This metabolism is likely to modulate the involvement of HOHA-lactone in the pathogenesis of human diseases. HOHA-lactone is biologically active, e.g., low concentrations (0.1-1 mu M) induce secretion of vascular endothelial growth factor (VEGF) from ARPE-19 cells. HOHA-lactone is also a precursor of 2-(co-carboxyethyl)pyrrole (CEP) derivatives of primary amino groups in proteins and ethanolamine phospholipids that have significant pathological and physiological relevance to age-related macular degeneration (AMD), cancer, and wound healing. Both HOHA-lactone and the derived CEP can contribute to the angiogenesis that defines the neovascular "wet" form of Alvin and that promotes the growth of tumors. While GSH depletion can increase the lethality of radiotherapy, because it will impair the metabolism of HOHA-lactone, the present study suggests that GSH depletion will also increase levels of HOHA-lactone and CEP that may promote recurrence of tumor growth.
C1 [Wang, Hua; Linetsky, Mikhail; Guo, Junhong; Yu, Annabelle O.; Salomon, Robert G.] 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@case.edu
RI Guo, Junhong/O-6316-2017
OI Guo, Junhong/0000-0003-0005-4837; Salomon, Robert/0000-0001-9456-3557
FU NIH [EY016813, GM021249]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported by NIH Grants EY016813 and GM021249.
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BP 1198
EP 1210
DI 10.1021/acs.chemrestox.6b00153
PG 13
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA DR8XQ
UT WOS:000380182100013
PM 27355557
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Teoli, DA
   Smith, MD
   Leys, MJ
   Jain, P
   Odom, JV
AF Teoli, Dac A.
   Smith, Merideth D.
   Leys, Monique J.
   Jain, Priyanka
   Odom, J. Vernon
TI Visual function affects prosocial behaviors in older adults
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Low vision; Prosocial behaviors; Adults; Visual acuity; Age related
ID QUALITY-OF-LIFE; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; DISABLEMENT
   PROCESS; PHYSICAL DISEASE; CARE RECIPIENTS; IMPAIRMENT; PEOPLE;
   DISABILITY; HEALTH
AB Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged a parts per thousand yen60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.
C1 [Teoli, Dac A.] Univ Pittsburgh, Sch Med, 3550 Terrace St, Pittsburgh, PA 15261 USA.
   [Smith, Merideth D.] PsiMed Inc, POB 9569, S Charleston, WV 25309 USA.
   [Leys, Monique J.; Jain, Priyanka; Odom, J. Vernon] W Virginia Univ, 1 Statium Dr,POB 9193, Morgantown, WV 26505 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; West Virginia University
RP Teoli, DA (通讯作者)，Univ Pittsburgh, Sch Med, 3550 Terrace St, Pittsburgh, PA 15261 USA.
EM dat88@pitt.edu
RI Odom, J Vernon/ABA-8150-2021; Odom, James V/A-1344-2013
OI Odom, James V/0000-0001-5874-1707
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NR 61
TC 3
Z9 3
U1 0
U2 11
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 FEB
PY 2016
VL 36
IS 1
BP 45
EP 54
DI 10.1007/s10792-015-0080-8
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA DC1YC
UT WOS:000369013200007
PM 25939988
DA 2022-11-30
ER

PT J
AU Gong, J
   Fields, MA
   Moreira, EF
   Bowrey, HE
   Gooz, M
   Ablonczy, Z
   Del Priore, LV
AF Gong, Jie
   Fields, Mark A.
   Moreira, Ernesto F.
   Bowrey, Hannah E.
   Gooz, Monika
   Ablonczy, Zsolt
   Del Priore, Lucian V.
TI Differentiation of Human Protein-Induced Pluripotent Stem Cells toward a
   Retinal Pigment Epithelial Cell Fate
SO PLOS ONE
LA English
DT Article
ID OUTER SEGMENT MEMBRANES; MACULAR DEGENERATION; ROD; PHAGOCYTOSIS;
   GENERATION; HTRA1; ISOMEROHYDROLASE; STABILITY; INTEGRIN; BINDING
AB Compared with many induced pluripotent stem cell (iPSC) lines generated using retrovirus and other non-integrating methods, the utilization of human protein-induced iPSC (piPSC) lines may provide a safer alternative for the generation of retinal pigment epithelial (RPE) cells for transplantation in retinal degenerative diseases. Here we assess the ability of piPSCs to differentiate into RPE cells, and to perform native RPE cell behavior. piPSCs were seeded in 6-well low-attachment plates to allow embryoid body formation, and then analyzed for pluripotent stem cell markers NANOG, SSEA4 and TRA-1-60 by immunofluorescence. Following colony formation, piPSCs were assessed for confirmation of RPE cell differentiation by staining for zonula occludens (ZO-1), bestrophin, microphthalmia-associated transcription factor (MITF) and retinal pigment epithelium specific protein-65 (RPE65). To evaluate piPSC-RPE cell phagocytic ability, adult bovine photoreceptor rod outer segments (ROS) were fed to piPSC-RPE cells, which were analyzed by fluorescent microscopy and flow cytometry. Undifferentiated piPSCs expressed all pluripotent markers assessed and formed embryoid body aggregates after 7 days. Differentiated piPSC-RPE cells expressed ZO-1, bestrophin, MITF and RPE65, typical RPE cell markers. Flow cytometry revealed robust ingestion of fluorescently-labeled ROS by piPSC-RPE cells, which was over four-times greater than that of undifferentiated piPSCs and comparable to that of an immortalized RPE cell line. Phagocytosis activity by piPSC-RPE cells was significantly reduced after the addition of anti-integrin alpha V beta 5. In conclusion, piPSCs can be differentiated toward an RPE cell fate, expressing RPE cell markers and resembling native RPE cells in behavior. These results demonstrate that piPSCs can be differentiated into RPE-like cells using a method that has an increased safety profile, a critical consideration for the development of better treatments for retinal degenerative diseases such as age-related macular degeneration (AMD).
C1 [Gong, Jie; Fields, Mark A.; Moreira, Ernesto F.; Bowrey, Hannah E.; Ablonczy, Zsolt; Del Priore, Lucian V.] Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Fields, Mark A.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
   [Gooz, Monika] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; Medical University of South Carolina
RP Del Priore, LV (通讯作者)，Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
EM delprior@musc.edu
OI Bowrey, Hannah/0000-0002-3774-4201
FU Research to Prevent Blindness (RPB); Department of Ophthalmology,
   Medical University of South Carolina; Foundation Fighting Blindness
   (FFB) [C-RM-0710-0542-MUSC-03]; NATIONAL CANCER INSTITUTE [P30CA138313]
   Funding Source: NIH RePORTER
FX This work was funded by Research to Prevent Blindness (RPB), Department
   of Ophthalmology, Medical University of South Carolina (to LDP), and
   Foundation Fighting Blindness (FFB) C-RM-0710-0542-MUSC-03 (to LDP). 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 48
TC 17
Z9 17
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 25
PY 2015
VL 10
IS 11
AR e0143272
DI 10.1371/journal.pone.0143272
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CX7ES
UT WOS:000365865300050
PM 26606685
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Feng, ZL
   Li, RS
   Shi, HQ
   Bi, WJ
   Hou, WW
   Zhang, XM
AF Feng, Zhuolei
   Li, Ruishu
   Shi, Huanqi
   Bi, Wenjiao
   Hou, Wenwen
   Zhang, Xiaomei
TI Combined silencing of TGF-beta 2 and Snail genes inhibit
   epithelial-mesenchymal transition of retinal pigment epithelial cells
   under hypoxia
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Epithelial-mesenchymal transition; Retinal pigment epithelial cell;
   Transforming growth factor-beta(2); Snail; Hypoxia; Age-related macular
   degeneration; Multi-gene silencing
ID E-CADHERIN; TGF-BETA; UP-REGULATION; EXPRESSION; PHENOTYPE; FIBROSIS;
   SLUG; RPE
AB The formation of scar-like fibrous tissue in age-related macular degeneration (AMD) is associated with hypoxia. Under hypoxia, retinal pigment epithelial (RPE) cells can secret more transforming growth factor-beta(2) (TGF-beta(2)), which is determined to induce epithelial-mesenchymal transition (EMT) at certain concentrations. Whether hypoxia can induce EMT by stimulating RPE cell line secrets TGF-beta(2) or not remains unknown. To gain a better understanding of the signaling mechanisms of fibrosis in AMD under hypoxic conditions, we investigated EMT in retinal pigment epithelial (RPE) cells and the effect of TGF-beta(2) and Snail in this process.
   Human RPE cell line (ARPE-19) was incubated with 5 % O-2 for different periods of time. The expression of N-cadherin, alpha-smooth muscle actin (alpha-SMA), TGF-beta(2) , and Snail were determined by Western blot and real-time PCR. Cell proliferation was assessed by CCK8 kit. RNA interference was used for multi-gene silencing of TGF-beta(2) and Snail genes.
   N-cadherin was decreased and mesenchymal cell marker alpha-SMA was increased after the ARPE-19 cell line was incubated with 5 % O-2. Meanwhile, the proliferation capability of the cell line was increased. TGF-beta(2) and Snail expression were increased in a time-dependent manner under hypoxia. After multi-silencing TGF-beta(2) and Snail genes, N-cadherin was increased and alpha-SMA was reduced. Meanwhile, the proliferation of the cell line was suppressed.
   Under hypoxic conditions, RPE cells undergo EMT. Endogenic TGF-beta(2) and Snail are involved in this process. Furthermore, knockdown of both TGF-beta(2) and Snail inhibited EMT to a greater extent than knockdown of either gene individually.
C1 [Feng, Zhuolei; Li, Ruishu; Shi, Huanqi; Bi, Wenjiao; Hou, Wenwen; Zhang, Xiaomei] Harbin Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Harbin 150001, Heilongjiang, Peoples R China.
C3 Harbin Medical University
RP Zhang, XM (通讯作者)，Harbin Med Univ, Affiliated Hosp 1, Dept Ophthalmol, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China.
EM zhangxm667@163.com
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NR 44
TC 10
Z9 11
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2015
VL 253
IS 6
BP 875
EP 884
DI 10.1007/s00417-014-2922-x
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CJ1AM
UT WOS:000355213500007
PM 25875044
DA 2022-11-30
ER

PT J
AU Yi, ZHZ
   Chen, CZ
   Su, Y
   Li, L
   Zhou, YY
AF Yi, Zuohuizi
   Chen, Changzheng
   Su, Yu
   Li, Lu
   Zhou, Yunyun
TI Changes in Clotting Time, Plasma Fibrinogen Levels, and Blood Viscosity
   After Administration of Ranibizumab for Treatment of Choroidal
   Neovascularization
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; anti-VEGF; choroidal
   neovascularization; ranibizumab; safety
ID ENDOTHELIAL GROWTH-FACTOR; MYOCARDIAL-INFARCTION; MACULAR DEGENERATION;
   RISK; MORTALITY; EVENTS; HEMATOCRIT; INHIBITORS; THERAPY; DISEASE
AB Purpose: To observe changes in clotting time, plasma fibrinogen levels, and blood viscosity after intravitreal ranibizumab (IVR) injection in patients with macular choroidal neovascularization (CNV).
   Methods: A total of 77 patients were enrolled in the study. Patients were divided into a study group (n = 42 CNV patients) and a control group (n = 35 age-and gender-matched healthy subjects). Study group patients received IVR injections; control group patients received none. Clotting times, plasma fibrinogen levels and blood viscosity were evaluated before, and 1 week and 1 month after the first IVR injection, and again 1 month after the second injection in the study group, but only once in the control group. A paired-sample t-test was used to analyze data at four time points in the study group. Study group patients were further categorized as those with neovascular age-related macular degeneration (AMD subgroup) or CNV secondary to pathological myopia (PM subgroup). Indicators were also analyzed for each subgroup.
   Results: There were no significant differences between study and control group patients in baseline values. Results showed that 1 week after the first IVR injection, the mean activated partial thromboplastin time (APTT) of study group patients was significantly reduced compared with baseline values (27.88 +/- 4.00 versus 30.70 +/- 5.56 s), respectively. Low-, median- and high-shear viscosity rates were increased significantly compared with baseline values. No statistically significant changes in tested indicators were found at other time points. In AMD subgroup patients, changes in all indicators were similar to those found overall. In contrast, only changes in median-and high-shear viscosity rates were statistically significant in PM subgroup patients.
   Conclusion: IVR injection may cause short-term fluctuations in APTT and blood viscosity in AMD patients. Further studies are needed to establish the long-term safety of IVR treatment.
C1 [Yi, Zuohuizi; Chen, Changzheng; Su, Yu; Li, Lu; Zhou, Yunyun] Wuhan Univ, Ctr Eye, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei Province, Peoples R China.
C3 Wuhan University
RP Chen, CZ (通讯作者)，Wuhan Univ, Ctr Eye, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei Province, Peoples R China.
EM whuchenchzh@163.com
RI Yi, Zuohuizi/HDN-1699-2022
OI Chen, Changzheng/0000-0002-7281-552X
FU National Natural Science Foundation of China [81271023]
FX This research was supported by the National Natural Science Foundation
   of China (81271023).
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NR 34
TC 7
Z9 7
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 2015
VL 40
IS 11
BP 1166
EP 1171
DI 10.3109/02713683.2014.990638
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DD4KM
UT WOS:000369891500011
PM 25495575
DA 2022-11-30
ER

PT J
AU Zhang, Y
   Yao, ZL
   Kaila, N
   Kuebler, P
   Visich, J
   Maia, M
   Tuomi, L
   Ehrlich, JS
   Rubio, RG
   Campochiaro, PA
AF Zhang, Yi
   Yao, Zhenling
   Kaila, Nitin
   Kuebler, Peter
   Visich, Jennifer
   Maia, Mauricio
   Tuomi, Lisa
   Ehrlich, Jason S.
   Rubio, Roman G.
   Campochiaro, Peter A.
TI Pharmacokinetics of Ranibizumab after Intravitreal Administration in
   Patients with Retinal Vein Occlusion or Diabetic Macular Edema
SO OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; SUSTAINED BENEFITS; 12-MONTH OUTCOMES;
   PHASE-III; IN-VITRO; VEGF; DEGENERATION; NEOVASCULARIZATION;
   BEVACIZUMAB; INHIBITION
AB Objective: To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME).
   Design: A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration.
   Participants: Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration.
   Methods: A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check.
   Main Outcome Measures: Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients.
   Results: The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis.
   Conclusions: The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure. (C) 2014 by the American Academy of Ophthalmology.
C1 [Zhang, Yi; Yao, Zhenling; Kuebler, Peter; Visich, Jennifer; Maia, Mauricio; Tuomi, Lisa; Ehrlich, Jason S.; Rubio, Roman G.] Genentech Inc, South San Francisco, CA USA.
   [Kaila, Nitin] Quantitat Solut, Menlo Pk, CA USA.
   [Campochiaro, Peter A.] Johns Hopkins Univ Hosp, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
C3 Roche Holding; Genentech; Johns Hopkins University; Johns Hopkins
   Medicine
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ Hosp, Sch Med, Wilmer Eye Inst, 719 Maumenee,600 North Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
RI Maia, Mauricio/I-5892-2015; Yao, Zhenling/AAJ-5968-2020
OI Maia, Mauricio/0000-0002-7034-8091; 
FU Genentech; GlaxoSmithKline; Genzyme; Oxford BioMedica; Genentech, Inc.,
   South San Francisco, California
FX Peter A. Campochiaro: Consultant - Genentech, Inc. (South San Francisco,
   California), GlaxoSmithKline, Regeneron, Aerpio Therapeutics (employer,
   Johns Hopkins University, receives compensation), and Elan, Gene Signal,
   Norvorx (receives personal compensation); Data and Safety Monitoring
   Committee - Advanced Cell Technology, Regeneron; Financial support -
   Genentech, GlaxoSmithKline, Genzyme, Oxford BioMedica; Equity owner -
   Graybug, Inc.; Genentech, Inc., South San Francisco, California,
   provided support for the study; participated in study design and conduct
   of the study; provided data collection, management, and interpretation;
   as well as reviewed and approved the manuscript.
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NR 28
TC 24
Z9 25
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2014
VL 121
IS 11
BP 2237
EP 2246
DI 10.1016/j.ophtha.2014.05.012
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AS8DM
UT WOS:000344480400030
PM 25001159
DA 2022-11-30
ER

PT J
AU Peng, SM
   Gan, GL
   Rao, VS
   Adelman, RA
   Rizzolo, LJ
AF Peng, Shaomin
   Gan, Geliang
   Rao, Veena S.
   Adelman, Ron A.
   Rizzolo, Lawrence J.
TI Effects of Proinflammatory Cytokines on the Claudin-19 Rich Tight
   Junctions of Human Retinal Pigment Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; BARRIER FUNCTION; INTERFERON-GAMMA; TNF-ALPHA;
   CELL-LINE; FLUID TRANSPORT; IFN-GAMMA; RPE CELLS; EXPRESSION;
   PERMEABILITY
AB PURPOSE. Chronic, subclinical inflammation contributes to the pathogenesis of several ocular diseases, including age-related macular degeneration. Proinflammatory cytokines affect tight junctions in epithelia that lack claudin-19, but in the retinal pigment epithelium claudin-19 predominates. We examined the effects of cytokines on the tight junctions of human fetal RPE(hfRPE).
   METHODS. hfRPE was incubated with interleukin 1-beta (IL-1 beta), interferon-gamma (IFN gamma), or tumor necrosis factor-alpha (TNF alpha), alone or in combination. Permeability and selectivity of the tight junctions were assessed using nonionic tracers and electrophysiology. Claudins, occludin, and ZO-1 were examined using PCR, immunoblotting, and confocal immunofluorescence microscopy.
   RESULTS. Only TNF alpha consistently reduced transepithelial electrical resistance (TER) >80%. A serum-free medium revealed two effects of TNF alpha: (1) decreased TER was observed only when TNFa was added to the apical side of the monolayer, and (2) expression of TNF alpha receptors and inhibitors of apoptosis were induced from either side of the monolayer. In untreated cultures, tight junctions were slightly cation selective, and this was affected minimally by TNF alpha. The results were unexplained by effects on claudin-2, claudin-3, claudin-19, occludin, and ZO-1, but changes in the morphology of the junctions and actin cytoskeleton may have a role.
   CONCLUSIONS. Claudin-19-rich tight junctions have low permeability for ionic and nonionic solutes, and are slightly cation-selective. Claudin-19 is not a direct target of TNF alpha. TNF alpha may protect RPE from apoptosis, but makes the monolayer leaky when it is presented to the apical side of the monolayer. Unlike other epithelia, IFN gamma failed to augment the effect of TNF alpha on tight junctions. (Invest Opthalmol Vis Sci. 2012;53:5016-5028) DOI:10.1167/iovs.11-8311.
C1 [Peng, Shaomin; Gan, Geliang; Rizzolo, Lawrence J.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA.
   [Peng, Shaomin] Harbin Univ, Affiliated Hosp 2, Dept Ophthalmol, Harbin, Peoples R China.
   [Peng, Shaomin; Gan, Geliang; Rao, Veena S.; Adelman, Ron A.; Rizzolo, Lawrence J.] Yale Univ, Sch Med, Dept Ophthalmol, New Haven, CT 06520 USA.
C3 Yale University; Harbin University; Yale University
RP Rizzolo, LJ (通讯作者)，Yale Univ, Sch Med, Dept Surg, POB 208062, New Haven, CT 06520 USA.
EM lawrence.rizzolo@yale.edu
OI Rizzolo, Lawrence/0000-0002-2393-8419; Rao, Veena/0000-0002-7602-6309
FU National Eye Institute vision core Grant [EY000785]; Research to Prevent
   Blindness (Yale Department of Ophthalmology); International Retinal
   Research Foundation; Connecticut Innovations [10SBC02]; Leir Foundation;
   Newman's Own Foundation; National Natural Science Foundation of China
   [30772381]; Yale Endowed Student Research Fellowship; NATIONAL EYE
   INSTITUTE [P30EY000785] Funding Source: NIH RePORTER
FX Supported by the National Eye Institute vision core Grant EY000785 (Yale
   University), Research to Prevent Blindness (Yale Department of
   Ophthalmology), the International Retinal Research Foundation (LJR),
   Connecticut Innovations 10SBC02 (LJR), the Leir Foundation (RAA), the
   Newman's Own Foundation (RAA), the National Natural Science Foundation
   of China No. 30772381 (SP), and the Yale Endowed Student Research
   Fellowship (VSR).
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NR 60
TC 38
Z9 39
U1 0
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2012
VL 53
IS 8
BP 5016
EP 5028
DI 10.1167/iovs.11-8311
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400085
PM 22761260
OA Green Published
DA 2022-11-30
ER

PT J
AU Kim, JE
   Leite, JO
   deOgburn, R
   Smyth, JA
   Clark, RM
   Fernandez, ML
AF Kim, Jung Eun
   Leite, Jose O.
   deOgburn, Ryan
   Smyth, Joan A.
   Clark, Richard M.
   Fernandez, Maria Luz
TI A Lutein-Enriched Diet Prevents Cholesterol Accumulation and Decreases
   Oxidized LDL and Inflammatory Cytokines in the Aorta of Guinea Pigs
SO JOURNAL OF NUTRITION
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; LOS-ANGELES-ATHEROSCLEROSIS;
   CORONARY-HEART-DISEASE; BETA-CAROTENE; MACULAR DEGENERATION;
   CARBOHYDRATE; ZEAXANTHIN; PROGRESSION; PREVALENCE; METABOLISM
AB Lutein has been shown to be protective against age-related macular degeneration; however, the antiinflammatory and antioxidant effects of this carotenoid in aortas are less known. Guinea pigs were fed a hypercholesterolemic diet (0.25 g cholesterol/100 g) and randomly allocated to a control group (n = 9) or a lutein group In = 10) (0.1 g/100 g lutein) and fed the experimental diets for 12 wk. Plasma LDL cholesterol and TG did not differ between groups; however, the lutein group had lower concentrations of medium size LDL (P < 0.05). As expected, guinea pigs from the lutein group had higher concentrations of plasma and liver lutein than those from the control group (P < 0.0001). Aortic cholesterol and malondialdehyde concentrations were lower in the lutein group (9.6 +/- 2.8 mmol/g and 1.69 +/- 1.35 nmol/mg protein) compared to the control group 115.5 +/- 2.3 mmol/g and 2.98 +/- 1.45 nmol/mg protein) (P < 0.05). Hematoxilin and eosin staining indicated that aortas from the control group presented focal intimal thickening, whereas either less thickness or no visible thickness was present in aortas from the lutein group. Oxidized LDL (oxLDL) was lower both in plasma and aorta in the lutein group compared to the control group (P < 0.0011. Aortic cytokines were also lower in the lutein group (P < 0.05). Plasma lutein and oxLDL (r = 0.79; P < 0.0001) and plasma lutein and aortic oxLDL (r = 0.64; P < 0.0001) were negatively correlated. These data suggest that lutein exerts potent antioxidant and antiinflammatory effects in aortic tissue that may protect against development of atherosclerosis in guinea pigs. J. Nutr. 141: 1458-1463, 2011.
C1 [Kim, Jung Eun; Leite, Jose O.; deOgburn, Ryan; Clark, Richard M.; Fernandez, Maria Luz] Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
   [Smyth, Joan A.] Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA.
C3 University of Connecticut; University of Connecticut
RP Fernandez, ML (通讯作者)，Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
EM maria-luz.fernandez@uconn.edu
OI Smyth, Joan/0000-0002-8879-6474
FU University of Connecticut Research Foundation
FX Supported by a University of Connecticut Research Foundation grant to
   M.L.F.
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NR 44
TC 70
Z9 71
U1 1
U2 8
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 AUG
PY 2011
VL 141
IS 8
BP 1458
EP 1463
DI 10.3945/jn.111.141630
PG 6
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 796KE
UT WOS:000293049400007
PM 21697302
OA Bronze
DA 2022-11-30
ER

PT J
AU Peyman, G
   Tsipursky, M
   Gohel, P
   Conway, M
AF Peyman, Gholam
   Tsipursky, Michael
   Gohel, Parin
   Conway, Mandi
TI Regression of peripapillary choroidal neovascularization after
   oscillatory transpupillary thermotherapy and anti-VEGF pharmacotherapy
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Peripapillary choroidal
   neovascularization; Photodynamic therapy
ID HEAT-SHOCK PROTEINS; DIODE-LASER PHOTOCOAGULATION; PHOTODYNAMIC THERAPY;
   MACULAR DEGENERATION; INDOCYANINE GREEN; SUBRETINAL NEOVASCULARIZATION;
   INTRAVITREAL BEVACIZUMAB; THRESHOLD PARAMETERS; VERTEPORFIN THERAPY;
   VASCULOPATHY
AB PURPOSE. We prospectively evaluated a new treatment for recalcitrant choroidal neovascularization (CNV) in 4 patients. We used an infrared laser (810 nm) in oscillatory thermotherapy (OTT) mode combined with indocyanine green (ICG) dye, utilizing the beneficial effect of both thermotherapy and photodynamic therapy. We describe preliminary experiences with ICG-assisted OTT (I-OTT) combined with intravitreal bevacizumab/dexamethasone for refractory peripapillary CNV resistant to standard therapy.
   METHODS. Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography were performed at baseline and postoperatively. Infrared laser spot size was approximately one-half the lesion size (oscillation 2-3 Hz). Intravitreal injections of bevacizumab (1.25 mg) and dexamethasone (1000 mu g) were done during the same visit.
   RESULTS. Mean follow-up was 12.5 months (range 5-17). Mean energy level was 325 mW (range 200-500) in oscillatory mode (2-3 Hz/sec) pre- and post-ICG infusion. Indocyanine green dose was approximately 1 mg/kg (75 mg/patient). All patients had a single treatment. Mean visual acuity improved in 1 patient from 20/60 to 20/30 and remained the same in the other 3 (20/20, 20/40, and 20/400). At final examination, there was no evidence of clinical or angiographic activity of CNV.
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C1 [Peyman, Gholam; Conway, Mandi] Tulane Univ, Dept Ophthalmol, New Orleans, LA 70118 USA.
   [Peyman, Gholam; Tsipursky, Michael; Gohel, Parin; Conway, Mandi] Univ Arizona Biomed Sci, Phoenix, AZ USA.
C3 Tulane University; University of Arizona
RP Peyman, G (通讯作者)，10650 W Tropicana Circle, Sun City, AZ 85351 USA.
EM gpeyman1@yahoo.com
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NR 52
TC 4
Z9 4
U1 0
U2 5
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD MAR-APR
PY 2011
VL 21
IS 2
BP 162
EP 172
DI 10.5301/EJO.2010.3272
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 760TR
UT WOS:000290347300007
PM 20623469
DA 2022-11-30
ER

PT J
AU Hirano, Y
   Ito, T
   Nozaki, M
   Yasukawa, T
   Sakurai, E
   Yoshida, M
   Ogura, Y
AF Hirano, Yoshio
   Ito, Takeshi
   Nozaki, Miho
   Yasukawa, Tsutomu
   Sakurai, Eiji
   Yoshida, Munenori
   Ogura, Yuichiro
TI Intraocular pressure elevation following triamcinolone acetonide
   administration as related to administration routes
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE intraocular pressure elevation; risk factor; steroid glaucoma;
   triamcinolone acetonide
ID RETINAL VEIN OCCLUSION; CYSTOID MACULAR EDEMA; INTRAVITREAL
   TRIAMCINOLONE; RISK-FACTORS; INJECTION; UVEITIS
AB To evaluate the incidence and risk factors of intraocular pressure (IOP) elevation following triamcinolone acetonide (TA) administration.
   In this retrospective observational case series, patients (224 eyes of 202 patients) with diffuse diabetic macular edema (66 eyes), branch retinal vein occlusion (39 eyes), central retinal vein occlusion (25 eyes), exudative age-related macular degeneration (49 eyes), myopic choroidal neovascularization (10 eyes), uveitis (30 eyes), or other conditions (5 eyes) were administered an intravitreal or posterior sub-Tenon capsule injection, or both, of TA. Sub-Tenon capsule injection was performed on 106 eyes (STTA group). Intravitreal injection was performed on 118 eyes (IVTA group), of which 85 eyes underwent simultaneous intravitreal and sub-Tenon capsule injections. Mean follow-up after TA administration was 15.9 +/- 10.4 (range, 3-39) months. The sub-Tenon capsule injection and intravitreal injection of TA were compared with respect to the frequency of IOP elevation and the time between TA administration and the initial IOP elevation, and the possible risk factors responsible for IOP elevation were identified.
   There was no significant difference in frequency of IOP > 21 mmHg between the STTA group and the IVTA group (P = 0.0588). There was, however, a significant difference in the frequency of IOP > 30 mmHg between the two groups (P = 0.0004). In the IVTA group, more patients needed antiglaucoma medication than in the STTA group (P = 0.0052). The incidence rate of IOP elevation within 1 week after TA administration in the IVTA group was significantly higher than in the STTA group (P = 0.0154). Risk factors for IOP elevation included higher baseline IOP (P < 0.0001), younger patients (P = 0.0095), and simultaneous administration of sub-Tenon capsule and intravitreal injections (P = 0.0228).
   Careful follow-up of IOP is required after TA injections.
C1 [Hirano, Yoshio] Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
C3 Nagoya City University
RP Hirano, Y (通讯作者)，Nagoya City Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
EM yossyeye@med.nagoya-cu.ac.jp
OI Hirano, Yoshio/0000-0002-9173-0839
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   Singh IP, 2004, AM J OPHTHALMOL, V138, P286, DOI 10.1016/j.ajo.2004.03.001
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NR 25
TC 28
Z9 29
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD SEP
PY 2009
VL 53
IS 5
BP 519
EP 522
DI 10.1007/s10384-009-0692-5
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 509OF
UT WOS:000271026600015
PM 19847609
DA 2022-11-30
ER

PT J
AU Kaemmerer, E
   Schutt, F
   Krohne, TU
   Holz, FG
   Kopitz, J
AF Kaemmerer, Elke
   Schutt, Florian
   Krohne, Tim U.
   Holz, Frank G.
   Kopitz, Jurgen
TI Effects of lipid peroxidation-related protein modifications on RPE
   lysosomal functions and POS phagocytosis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; FUNDUS
   AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; OXIDATIVE STRESS; OUTER SEGMENTS;
   AGE PIGMENT; RAT RETINA; LIPOFUSCIN; CELLS
AB PURPOSE. Lipofuscin accumulation in the RPE is a common downstream pathogenic pathway in various monogenic and complex retinal diseases including age-related macular degeneration (AMD). Lipid peroxidation-induced modification of proteins is thought to play a role in lipofuscinogenesis and may contribute to RPE dysfunction. A prior study demonstrated that a variety of lipofuscin-associated proteins are damaged by aberrant covalent modifications of malondialdehyde (MDA) and 4-hydroxynonenal (HNE). The present study was conducted to test the hypothesis that these damaged proteins are more resistant to proteolytic attack and act as protease inhibitors.
   METHODS. Isolated photoreceptor outer segments (POS) were radioactively labeled and in vitro modified with MDA and HNE. Pure lysosomal fractions isolated from human RPE were tested for their proteolytic activities toward modified and unmodified POS proteins. In parallel, modified and radiolabeled POS were fed to RPE cell cultures for phagocytosis and their lysosomal degradation as well as intracellular accumulation was compared with unmodified POS.
   RESULTS. Both experimental approaches revealed that MDA or FINE modifications strikingly increase the resistance of POS proteins to the attack by lysosomal proteases. When cultured RPE cells were fed with modified or unmodified POS the amount of degraded POS proteins was reduced by approximately 60% to 70% for the modified POS compared with those in normal control subjects. Some of the modified proteins remained undegraded in the lysosomal compartment of cultured RPE cells and were still detectable 3 weeks after feeding, whereas unmodified POS were completely degraded within.1 week after feeding. Moreover, modified proteins had the potential to impair degradation of unmodified proteins, indicating their efficacy as proteolytic antagonists.
   CONCLUSIONS. The results indicate that lipid peroxidation-derived protein modifications are involved in lipofuscinogenesis and may contribute to cell damaging effects of lipofuscin in retinal diseases such as AMD.
C1 Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   Heidelberg Univ, Dept Pathol, D-6900 Heidelberg, Germany.
   Heidelberg Univ, Dept Ophthalmol, D-6900 Heidelberg, Germany.
C3 University of Bonn; Ruprecht Karls University Heidelberg; Ruprecht Karls
   University Heidelberg
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 Krohne, Tim/D-1497-2013; Krohne, Tim/AAG-4412-2020
OI Krohne, Tim/0000-0003-2280-925X; 
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NR 38
TC 94
Z9 122
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2007
VL 48
IS 3
BP 1342
EP 1347
DI 10.1167/iovs.06-0549
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 142YF
UT WOS:000244686500052
PM 17325182
DA 2022-11-30
ER

PT J
AU Takeda, A
   Hata, Y
   Shiose, S
   Sassa, Y
   Honda, M
   Fujisawa, K
   Sakamoto, T
   Ishibashi, T
AF Takeda, A
   Hata, Y
   Shiose, S
   Sassa, Y
   Honda, M
   Fujisawa, K
   Sakamoto, T
   Ishibashi, T
TI Suppression of experimental choroidal neovascularization utilizing KDR
   selective receptor tyrosine kinase inhibitor
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; EXPRESSION; CELLS;
   VEGF; MEMBRANES; ANGIOGENESIS; PROMOTES; PATHWAYS; MITOGEN
AB Background. We investigated the role of the VEGF-VEGF receptor 2 (KDR) system in the development of choroidal neovascularization (CNV) and its possibility as a therapeutic target utilizing KDR selective receptor tyrosine kinase (RTK) inhibitor (SU5416) both in vitro and in an experimental CNV model. Methods. VEGF-induced phosphorylation of KDR and p44/p42 MAPK in cultured bovine choroidal endothelial cells (BCECs) was determined by Western blot analysis. The proliferation and in vitro tube formation were analyzed by [H-3]thymidine uptake and three-dimensional collagen gel model. For experimental CNV model, intense fundus laser photocoagulation was performed on pigmented rats. The anti-angiogenic efficacy of intraperitoneally injected SU5416 on experimental CNV was evaluated by fluorescein angiography and histology. The extent of fluorescein leakage on late-phase angiograms was scored, and the thickness of CNV membrane was histologically measured under a light microscope. Results. VEGF-induced KDR phosphorylation in cultured BCECs was inhibited by SU5416 in a dose-dependent manner (0-3 muM) with IC50 of 0.29+/-0.071 muM. SU5416 treatment also resulted in a dose-dependent prohibition of VEGF-induced p44/p42 MAPK phosphorylation, [H-3]thymidine uptake and in vitro tube formation with corresponding concentrations that inhibited KDR phosphorylation. The leakage score on fluorescein angiography for experimental CNV was significantly lower in the SU5416-treated group than in the control group (P<0.01). Histologically, the CNV membranes in the SU5416-treated group were 31.6% thinner than those in the control group (P<0.01). Conclusion. These results strengthen the evidence for a critical role of the VEGF-KDR system in the development of CNV, indicating that KDR selective inhibitor might be beneficial for the treatment of intraocular angiogenic diseases, including age-related macular degeneration.
C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan.
C3 Kyushu University
RP Ishibashi, T (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
RI Sassa, Yukio/H-6339-2012
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NR 24
TC 24
Z9 27
U1 0
U2 1
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 SEP
PY 2003
VL 241
IS 9
BP 765
EP 772
DI 10.1007/s00417-003-0688-7
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 734CF
UT WOS:000186037100013
PM 12937991
DA 2022-11-30
ER

PT J
AU Wang, H
   Ninomiya, Y
   Sugino, IK
   Zarbin, MA
AF Wang, H
   Ninomiya, Y
   Sugino, IK
   Zarbin, MA
TI Retinal pigment epithelium wound healing in human Bruch's membrane
   explants
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; SUBFOVEAL NEOVASCULAR MEMBRANES; SURGICAL
   REMOVAL; CLINICOPATHOLOGICAL CORRELATION; MACULAR DEGENERATION;
   EXTRACELLULAR-MATRIX; CHOROIDAL NEOVASCULARIZATION; SUBMACULAR
   MEMBRANECTOMY; CELL-MIGRATION; IN-VITRO
AB PURPOSE. To compare retinal pigment epithelium (RPE) resurfacing on the RPE basement membrane and inner collagenous layer (ICL) in human submacular Bruch's membrane explants.
   METHODS. Debridements were created in RPE-choroid-sclera explants (mean donor age 71.91 +/- 7.76 years) to create defects exposing the RPE basement membrane (RPEbm(+) defects), the ICL immediately below the RPE basement membrane (superficial ICL, [SICL]) or deeper layers of the ICL (DICL). Eleven pairs of eyes-four pairs with one eye having an RPEbm(+) defect and the fellow eye having an SICL defect and seven pairs with corresponding RPEbm(+) and DICL defects-were observed for 10 days by visualizing RPE ingrowth with 4',6'-diamino-2-phenylindole (DAPI) filters. At day 10, specimens were processed for scanning electron microscopy.
   RESULTS. Resurfacing of localized RPE defects occurred to some degree in all 11 pairs of eyes. No significant difference in the percentage of resurfacing of RPEbm(+) defects (67-35% +/- 18.82%) and SICL defects (64.26% +/- 16.07%) was observed although healing of the SICL showed more variability in the morphology of RPE cells migrating into the defect. Significant differences in healing were observed between pairs with RPEbm(+) defects versus DICL defects (84.07% +/- 15.35% and 54.00% +/- 14.54% resurfacing, respectively). RPE ingrowth into DICL defects exhibited the greatest morphologic variability.
   CONCLUSIONS. RPE basement membrane supports RPE resurfacing of localized RPE defects. The deeper portion of the ICL of aged submacular human Bruch's membrane does not support RPE resurfacing to the same extent as does the RPE basement membrane. The poor RPE resurfacing observed in DICL defects mimics the histopathological findings in patients with age-related macular degeneration after excision of choroidal new vessels.
C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Inst Ophthalmol & Visual Sci, Newark, NJ 07103 USA.
   Osaka Univ, Sch Med, Osaka, Japan.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center; Osaka University
RP Zarbin, MA (通讯作者)，Univ Med & Dent New Jersey, New Jersey Med Sch, Inst Ophthalmol & Visual Sci, 90 Bergen St,6th Floor, Newark, NJ 07103 USA.
EM zarbin@umdnj.edu
OI Zarbin, Marco/0000-0002-7811-7132
FU NEI NIH HHS [EY09750] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY009750] Funding Source: NIH RePORTER
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NR 81
TC 40
Z9 42
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2003
VL 44
IS 5
BP 2199
EP 2210
DI 10.1167/iovs.02-0435
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 672CQ
UT WOS:000182503700057
PM 12714662
DA 2022-11-30
ER

PT J
AU Rudeen, KM
   Liu, WQ
   Mieler, WF
   Kang-Mieler, JJ
AF Rudeen, Kayla M.
   Liu, Wenqiang
   Mieler, William F.
   Kang-Mieler, Jennifer J.
TI Simultaneous Release of Aflibercept and Dexamethasone from an Ocular
   Drug Delivery System
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Controlled release; anti-VEGF; corticosteroid; drug delivery system;
   neovascularization
ID ANTI-VEGF; MACULAR DEGENERATION; PROTEIN INSTABILITY; INTRAVITREAL
   INJECTION; RETINAL DISEASES; GLUCOCORTICOIDS; MICROSPHERES; BEVACIZUMAB;
   EXPRESSION; STABILITY
AB Purpose Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. Methods Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. Results The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. Conclusions The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.
C1 [Rudeen, Kayla M.; Liu, Wenqiang; Kang-Mieler, Jennifer J.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
   [Mieler, William F.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA.
C3 Illinois Institute of Technology; University of Illinois System;
   University of Illinois Chicago; University of Illinois Chicago Hospital
RP Kang-Mieler, JJ (通讯作者)，3255 S Dearborn St,Wishnick Hall 314, Chicago, IL 60616 USA.
EM Kang-mieler@iit.edu
RI Liu, Wenqiang/ABE-8502-2020
OI Liu, Wenqiang/0000-0002-1752-9838
FU NIH [EY029298]
FX This work was supported by the NIH under Grant EY029298.
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NR 53
TC 1
Z9 1
U1 4
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD JUL 3
PY 2022
VL 47
IS 7
BP 1034
EP 1042
DI 10.1080/02713683.2022.2053166
EA FEB 2022
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2T6WG
UT WOS:000773971300001
PM 35343355
OA hybrid
DA 2022-11-30
ER

PT J
AU Sacconi, R
   Corbelli, E
   Borrelli, E
   Capone, L
   Carnevali, A
   Gelormini, F
   Querques, L
   Bandello, F
   Querques, G
AF Sacconi, Riccardo
   Corbelli, Eleonora
   Borrelli, Enrico
   Capone, Luigi
   Carnevali, Adriano
   Gelormini, Francesco
   Querques, Lea
   Bandello, Francesco
   Querques, Giuseppe
TI Choriocapillaris flow impairment could predict the enlargement of
   geographic atrophy lesion
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE macula; retina; imaging
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SWEPT-SOURCE; MACULAR DEGENERATION;
   DRUSEN; RATES; EYES
AB Aim To analyse the choriocapillaris (CC) flow status in the area that subsequently showed geographic atrophy (GA) expansion secondary to age-related macular degeneration (AMD) during 1-year follow-up, matching optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF).
   Methods In this prospective longitudinal observational study, 30 eyes of 20 consecutive patients with GA secondary to AMD (mean age 75.5 +/- 7.4 years) were included. All patients underwent OCT-A and FAF at baseline and 1-year follow-up. Main outcome measures included analysis of perfusion density (PD) in the 'area surrounding GA margin' (between the GA border and 500 mu m distance) in comparison with the 'control area' (area outside the 500 mu m line), and of the 'expansion area' (area that subsequently developed GA expansion during 1-year follow-up).
   Results During the 1-year follow-up, visual acuity significantly decreased from 0.34 +/- 0.38 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.39 +/- 0.40 LogMAR (p<0.001), and mean GA area increased from 6.82 +/- 5.47 mm(2) to 8.76 +/- 6.28 mm(2) (p<0.001). CC PD of the area surrounding the GA margin revealed a significant flow impairment compared with control area (PD 0.679 +/- 0.076 and 0.734 +/- 0.057, respectively (p<0.001)). Furthermore, the PD of the expansion area showed a greater CC flow impairment in comparison to the remaining area surrounding GA margin (p<0.001).
   Conclusions We reported a greater CC impairment in the area that subsequently developed GA expansion, suggesting that the CC flow impairment could predict the enlargement of GA lesion. The CC impairment could be considered as a new a risk factor for GA progression and a biomarker to be measured to determine efficacy of new interventions aiming to slow progression of GA.
C1 [Sacconi, Riccardo; Corbelli, Eleonora; Borrelli, Enrico; Capone, Luigi; Gelormini, Francesco; Bandello, Francesco; Querques, Giuseppe] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
   [Sacconi, Riccardo; Corbelli, Eleonora; Borrelli, Enrico; Capone, Luigi; Carnevali, Adriano; Gelormini, Francesco; Querques, Lea; Bandello, Francesco; Querques, Giuseppe] IRCCS San Raffaele Sci Inst, Div Head & Neck, Ophthalmol Unit, Milan, Italy.
   [Carnevali, Adriano] Univ Hosp Magna Graecia, Dept Ophthalmol, Catanzaro, Italy.
C3 Vita-Salute San Raffaele University; Vita-Salute San Raffaele
   University; IRCCS Ospedale San Raffaele; Magna Graecia University of
   Catanzaro
RP Querques, G (通讯作者)，Univ Vita Salute San Raffaele, Ophthalmol, Milan, Lombardia, Italy.
EM giuseppe.querques@hotmail.it
RI Borrelli, Enrico/AAR-3693-2020
OI Borrelli, Enrico/0000-0003-2815-5031; bandello,
   francesco/0000-0003-3238-9682; Querques, Giuseppe/0000-0002-3292-9581;
   Sacconi, Riccardo/0000-0003-2891-2012
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NR 30
TC 17
Z9 17
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JAN
PY 2021
VL 105
IS 1
BP 97
EP 102
DI 10.1136/bjophthalmol-2019-315800
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PR6JI
UT WOS:000607340000018
PM 32201374
DA 2022-11-30
ER

PT J
AU Bolla, PK
   Gote, V
   Singh, M
   Patel, M
   Clark, BA
   Renukuntla, J
AF Bolla, Pradeep Kumar
   Gote, Vrinda
   Singh, Mahima
   Patel, Manan
   Clark, Bradley A.
   Renukuntla, Jwala
TI Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein
   Uptake in Retinal Cells
SO PHARMACEUTICS
LA English
DT Article
DE lutein; PLGA; PLGA-PEG-biotin; ARPE-19; retina; macular edema;
   age-related macular degeneration; biotin-decorated nanoparticles;
   polymeric nanoparticles; targeted therapy
ID POSTERIOR SEGMENT; DRUG-DELIVERY; RELEASE; FORMULATION; MECHANISMS;
   ZEAXANTHIN; SYSTEMS; PIGMENT
AB Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood-retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA-PEG-biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA-PEG-biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was approximate to 56% and approximate to 75% for lutein-loaded PLGA and PLGA-PEG-biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA-PEG-biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA-PEG-biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.
C1 [Bolla, Pradeep Kumar; Clark, Bradley A.; Renukuntla, Jwala] High Point Univ, Fred Wilson Sch Pharm, Dept Basic Pharmaceut Sci, High Point, NC 27262 USA.
   [Gote, Vrinda] Univ Missouri, Sch Pharm, Div Pharmacol & Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
   [Singh, Mahima; Patel, Manan] Univ Sci Philadelphia, Dept Pharmaceut Sci, Philadelphia, PA 19104 USA.
C3 University of Missouri System; University of Missouri Kansas City
RP Renukuntla, J (通讯作者)，High Point Univ, Fred Wilson Sch Pharm, Dept Basic Pharmaceut Sci, High Point, NC 27262 USA.
EM bollaniper@gmail.com; vrindagote@mail.umkc.edu;
   msingh@mail.usciences.edu; mpatel@biolinkonline.com;
   bclark@highpoint.edu; jrenukun@highpoint.edu
RI Bolla, Pradeep/L-2559-2019
OI Bolla, Pradeep/0000-0001-5049-3550; Gote, Vrinda/0000-0002-8967-601X;
   Singh, Mahima/0000-0003-2505-6994
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NR 59
TC 12
Z9 12
U1 8
U2 34
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD SEP
PY 2020
VL 12
IS 9
AR 798
DI 10.3390/pharmaceutics12090798
PG 17
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA OE7WX
UT WOS:000580737400001
PM 32847030
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dervenis, N
   Harris, A
   Coleman, AL
   Wilson, MR
   Founti, P
   Yu, F
   Siesky, B
   Anastasopoulos, E
   Pappas, T
   Koskosas, A
   Kilintzis, V
   Topouzis, F
AF Dervenis, Nikolaos
   Harris, Alon
   Coleman, Anne L.
   Wilson, M. Roy
   Founti, Panayiota
   Yu, Fei
   Siesky, Brent
   Anastasopoulos, Eleftherios
   Pappas, Theofanis
   Koskosas, Archimidis
   Kilintzis, Vassilis
   Topouzis, Fotis
TI Factors associated with non-active retinal capillary density as measured
   with Confocal Scanning Laser Doppler Flowmetry in an elderly population:
   the Thessaloniki Eye Study (TES)
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTIC-NERVE HEAD; OPEN-ANGLE GLAUCOMA; BLOOD-FLOW MEASUREMENTS; MACULAR
   DEGENERATION; RISK-FACTORS; AGE; REPRODUCIBILITY; MIGRAINE; PREVALENCE;
   NUMBER
AB Purpose To identify factors associated with retinal capillary density as measured with Confocal Scanning Laser Doppler Flowmetry (Heidelberg retina flowmeter (HRF)) in the Thessaloniki Eye Study (TES).
   Methods Participants of the TES (age >= 60 years, cross-sectional population-based study) were assessed for active capillary density in the superior and inferior peripapillary retina using the HRF. Pixel-by-pixel analysis was performed to quantify the percentage of zero flow pixels (ZFPs; surrogate for % retinal area with non-active capillaries). Multivariable regression analyses were performed to assess the association of non-active vascular density with ophthalmic and systemic variables. Glaucoma, late age-related macular degeneration and diabetic retinopathy subjects were excluded.
   Results 1189 subjects were included in the analysis. Older age (per year) was associated with higher percentage of ZFP in both the superior (slope estimate (SE)=0.0020) and the inferior (SE=0.0019) peripapillary retina (p<0.0001). History of migraine was associated with lower percentage of ZFP (SE=-0.0166) compared with no history of migraine in the superior peripapillary retina only (p<0.05). Higher intraocular pressure ((IOP) per mm Hg) and height (per cm) were associated with higher percentage of ZFP in the inferior peripapillary retina only (SE=0.0012, p<0.05 and SE=0.0005, p<0.05, respectively). The group consuming vegetables one to three times per week compared with the group consuming vegetables at least once a day had higher percentage of ZFP only in the inferior peripapillary retina (SE=0.0080, p<0.05).
   Conclusion At a population level, our study revealed associations of older age, higher IOP and taller height with lower active retinal capillary density and of migraine with higher capillary density. Looking further into these associations may provide insight into disease mechanisms.
C1 [Dervenis, Nikolaos; Founti, Panayiota; Anastasopoulos, Eleftherios; Pappas, Theofanis; Koskosas, Archimidis; Kilintzis, Vassilis; Topouzis, Fotis] Aristotle Univ Thessaloniki, Dept Ophthalmol, Thessaloniki 54636, Greece.
   [Harris, Alon; Siesky, Brent] Mt Sinai Hosp, Dept Ophthalmol, Icahn Sch Med, New York, NY USA.
   [Coleman, Anne L.] Jules Stein Eye Inst, Ophthalmol, Los Angeles, CA 90024 USA.
   [Wilson, M. Roy] Wayne State Univ, Detroit, MI USA.
   [Founti, Panayiota] Moorfields Eye Hosp, Glaucoma Serv, London, England.
   [Yu, Fei] Univ Calif Los Angeles, Biostat, Los Angeles, CA USA.
C3 Aristotle University of Thessaloniki; Icahn School of Medicine at Mount
   Sinai; Wayne State University; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust; University of
   California System; University of California Los Angeles
RP Topouzis, F (通讯作者)，Aristotle Univ Thessaloniki, Dept Ophthalmol, Thessaloniki 54636, Greece.
EM ftopouzis@otenet.gr
RI Dervenis, Nikolaos/AAK-2376-2020
OI Dervenis, Nikolaos/0000-0002-7269-2785; Topouzis,
   Fotis/0000-0002-8966-537X; Kilintzis, Vassilis/0000-0002-9783-6757;
   Harris, Alon/0000-0001-8770-3726
FU Center for Eye Epidemiology, UCLA, California, USA; Health Future
   Foundation, Creighton University, Omaha, Nebraska, USA; International
   Glaucoma Association, UK; Texas Tech University, Texas, USA; Pfizer, New
   York, USA; Merck and Co, New Jersey, USA; Pharmacia Hellas, Athens,
   Greece; Novartis Hellas, Athens, Greece
FX Grants from Center for Eye Epidemiology, UCLA, California, USA, grants
   from Health Future Foundation, Creighton University, Omaha, Nebraska,
   USA, grants from International Glaucoma Association, UK, grants from
   Texas Tech University, Texas, USA, grants from Pfizer, New York, USA,
   grants from Merck and Co, New Jersey, USA, grants from Pharmacia Hellas,
   Athens, Greece, grants from Novartis Hellas, Athens, Greece, during the
   conduct of this study.
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NR 35
TC 3
Z9 3
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2020
VL 104
IS 9
BP 1246
EP 1253
DI 10.1136/bjophthalmol-2019-315212
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI3IA
UT WOS:000600986900012
PM 31784501
DA 2022-11-30
ER

PT J
AU Yuan, ZL
   Du, WW
   He, XD
   Zhang, DL
   He, W
AF Yuan, Zhenli
   Du, Weiwei
   He, Xiangdong
   Zhang, Donglei
   He, Wei
TI Tribulus terrestris Ameliorates Oxidative Stress-Induced ARPE-19 Cell
   Injury through the PI3K/Akt-Nrf2 Signaling Pathway
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MITOCHONDRIAL DYSFUNCTION; RPE CELLS; NRF2
AB Oxidative stress on retinal pigment epithelial (RPE) cells has been confirmed to play a crucial role in the development and progression of age-related macular degeneration (AMD) or other retinal degenerative diseases. Tribulus terrestris (TT) is a Chinese traditional herb medicine, which has been used for the treatment of ocular diseases for many centuries. In this study, we investigated the underlying mechanisms of TT and examined its ability to protect and restore the human retinal pigment epithelial cells (ARPE-19) against H2O2-induced oxidative stress. Our data show that 200 mu g/mL of ethanol extract of Tribulus terrestris (EE-TT) significantly increased the cell viability and prevented the apoptosis of H2O2-treated ARPE-19 cells through the regulation of Bcl2, Bax, cleaved caspase-3, and caspase-9. Treatment with EE-TT also significantly decreased the upregulated reactive oxygen species (ROS) activities and increased the downregulated superoxide dismutase (SOD) activities induced by H(2)O(2)in ARPE-19 cells. Additionally, H(2)O(2)at 1 mM significantly decreased the mRNA expression levels of Nrf2, CAT, SOD1, SOD2, HO-1, GST-pi, NQO1, and GLCM in ARPE-19 cells; however, treatment with EE-TT reversed the downregulated mRNA expression levels of all these genes induced by H2O2. Furthermore, treatment with 200 mu g/mL EE-TT alone for 24 h significantly increased Nrf2, HO-1, NQO1, and GCLM mRNA expressions in ARPE-19 cells when compared with untreated control cells. Pretreatment with the inhibitor of PI3K/Akt signaling (LY294002) completely blocked these EE-TT-upregulated mRNA expressions and abolished the improvement of cell viability in H2O2-treated ARPE-19 cells. These findings all suggest that Tribulus terrestris has significant antioxidant effects on oxidative stressed ARPE-19 cells through regulating PI3K/Akt-Nrf2 signaling pathway.
C1 [Yuan, Zhenli; Du, Weiwei; He, Xiangdong; Zhang, Donglei; He, Wei] He Univ, Sch Pharm, Shenyang 110163, Peoples R China.
   [He, Wei] Shenyang Ind Technol Inst Ophthalmol, Shenyang 110163, Peoples R China.
RP Zhang, DL; He, W (通讯作者)，He Univ, Sch Pharm, Shenyang 110163, Peoples R China.; He, W (通讯作者)，Shenyang Ind Technol Inst Ophthalmol, Shenyang 110163, Peoples R China.
EM yuanzhenli@huh.edu.cn; duweiwei@huh.edu.cn; hexiangdong@huh.edu.cn;
   zhangdonglei@huh.edu.cn; hewei@huh.edu.cn
OI Zhang, Donglei/0000-0003-1962-5257; Yuan, Zhen Li/0000-0001-8890-9689
FU Natural Science Foundation of Technology Department of Liaoning Province
   of China [20180550378]; Science and Technology Program of Liaoning
   [2019JH2/10300011]
FX We are grateful to Professor Zhan-Lin Li of the School of Traditional
   Chinese Meteria Medica, Shenyang Pharmaceutical University, for
   assisting the EE-TT preparation. Dr. Donglei Zhang and Dr. Wei He are
   the cocorresponding authors. This work was partially supported by grants
   from the Natural Science Foundation of Technology Department of Liaoning
   Province of China (20180550378) and the Science and Technology Program
   of Liaoning (grant numbers 2019JH2/10300011).
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NR 64
TC 10
Z9 11
U1 1
U2 12
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 28
PY 2020
VL 2020
AR 7962393
DI 10.1155/2020/7962393
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA NC7GG
UT WOS:000561383100005
PM 32774685
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Fiess, A
   Nickels, S
   Urschitz, MS
   Munzel, T
   Wild, PS
   Beutel, ME
   Lackner, KJ
   Hoffmann, EM
   Pfeiffer, N
   Schuster, AK
AF Fiess, Achim
   Nickels, Stefan
   Urschitz, Michael S.
   Muenzel, Thomas
   Wild, Philipp S.
   Beutel, Manfred E.
   Lackner, Karl J.
   Hoffmann, Esther M.
   Pfeiffer, Norbert
   Schuster, Alexander K.
TI Association of Birth Weight with Peripapillary Retinal Nerve Fiber Layer
   Thickness in Adulthood-Results from a Population-Based Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE birth weight; peripapillary retinal nerve fiber layer; optic nerve;
   anatomy; epidemiology
ID CHILDREN BORN; TERM INFANTS; PRETERM; AGE; PREVALENCE; PREGNANCY
AB PURPOSE. Low birth weight is associated with altered retinal development in childhood, including reduced peripapillary retinal nerve fiber layer (pRNFL) thickness. However, to the best of our knowledge, no population-based study has analyzed the relationship of low birth weight to pRNFL thickness in adulthood. The purpose of this study was to investigate whether birth weight has a long-term effect on pRNFL thickness in adulthood.
   METHODS. In the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography using a peripapillary scan and automated measurement of pRNFL thickness as a global parameter and in six sectors. The association between self-reported birth weight and the different pRNFL sectors were analyzed with multivariable linear regression, adjusted for potential confounders including sex, age, axial length, self-reported age-related macular degeneration, and glaucoma.
   RESULTS. In 3,028 participants, self-reported birth weight was documented and pRNFL measurements were successfully performed (1632 females, ages 54.9 +/- 10.0 years). After adjustment for several confounders in the multivariable model, a positive association was observed between birth weight and pRNFL thickness in the global sector (beta = 0.13 mu m/100 g; 95% CI, 0.08-0.18; P < 0.001; R-2 = 0.007) and especially in the inferotemporal sector (beta = 0.22 mu m/100 g; 95% CI, 0.15-0.29; P < 0.001; R-2 = 0.008) and inferonasal sector (beta = 0.28 mu m/100 g; 95% CI, 0.17-0.39; P < 0.001; R-2 = 0.005).
   CONCLUSIONS. Our data show that there is a weak relationship between birth weight and pRNFL thickness in adulthood. This weak association is particularly present in the inferior part of the optic nerve head. Therefore, low birth weight may have an impact on optic nerve head development and potentially on ocular disease development.
C1 [Fiess, Achim; Nickels, Stefan; Hoffmann, Esther M.; Pfeiffer, Norbert; Schuster, Alexander K.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany.
   [Urschitz, Michael S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat, Div Pediat Epidemiol, Mainz, Germany.
   [Muenzel, Thomas] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol Cardiol 1, Mainz, Germany.
   [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Prevent Cardiol & Prevent Med, Ctr Cardiol, Mainz, Germany.
   [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, Mainz, Germany.
   [Wild, Philipp S.] partner site Rhine Main, German Ctr Cardiovasc Res DZHK, Mainz, Germany.
   [Beutel, Manfred E.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Psychosomat Med & Psychotherapy, Mainz, Germany.
   [Lackner, Karl J.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Clin Chem & Lab Med, Mainz, Germany.
C3 Johannes Gutenberg University of Mainz; Johannes Gutenberg University of
   Mainz; Johannes Gutenberg University of Mainz; Johannes Gutenberg
   University of Mainz; Johannes Gutenberg University of Mainz; German
   Centre for Cardiovascular Research; 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 Munzel, Thomas/A-2912-2014; Hoffmann, Esther/AAO-5968-2021; Hoffmann,
   Esther/AAY-3575-2020
OI Munzel, Thomas/0000-0001-5503-4150; Hoffmann,
   Esther/0000-0002-0949-4268; Wild, Philipp/0000-0003-4413-9752
FU government of Rhineland-Palatinate (Stiftung Rheinland-Pfalz fur
   Innovation) [AZ 961-386261/733]; research program Wissen schafft
   Zukunft; research program Center for Translational Vascular Biology of
   the Johannes Gutenberg University of Mainz; Philips Medical Systems;
   Boehringer Ingelheim
FX The Gutenberg Health Study is funded by the government of
   Rhineland-Palatinate (Stiftung Rheinland-Pfalz fur Innovation, contract
   AZ 961-386261/733); by the research programs Wissen schafft Zukunft and
   Center for Translational Vascular Biology of the Johannes Gutenberg
   University of Mainz; and by a contract with Boehringer Ingelheim and
   Philips Medical Systems, including an unrestricted grant for the
   Gutenberg Health Study.
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NR 40
TC 9
Z9 9
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 4
DI 10.1167/iovs.61.8.4
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MS8BL
UT WOS:000554499000005
PM 35917383
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lee, D
   Chan, CK
   Abraham, P
   Sarraf, D
AF Lee, Daniel
   Chan, Clement K.
   Abraham, Prema
   Sarraf, David
TI Post-hoc analysis of single nucleotide polymorphism profile for eyes
   with vascularized pigment epithelial detachment due to ARMD
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration (RETINA); genetics (GENETICS);
   molecular (GENETICS); retina-medical therapies (RETINA); retinal
   pathology; research (RETINA)
ID FACTOR-H POLYMORPHISMS; MACULAR DEGENERATION; APOLIPOPROTEIN-E; VEGF;
   THERAPY; RANIBIZUMAB; ASSOCIATION; DISEASE
AB Introduction: This post-hoc case-control study compares single nucleotide polymorphism (SNP) profile of eyes with vascularized pigment epithelial detachment (vPED) due to age-related macular degeneration (ARMD) with: (1) Control-1 eyes (no ARMD and AREDS Severity Scale 0); and (2) Control-2 eyes (drusen or AREDS Severity Scale 2). SNP profile of High Responders (HR) was also compared with Low Responders (LR) to ranibizumab. Methods: Blood samples from 40 patients with vPED treated with ranibizumab were sent for SNP-specific genotype analysis for comparison of variant allele frequencies of 23 SNPs associated with ARMD (VAF) to VAF in 184 Control-1 eyes, and VAF in 85 Control-2 eyes. VAF of HR-50 (> 50% decrease in PED height) and VAF of HR-75 (> 75% decrease in PED height) were also compared with VAF of LR. Results: These SNPs were more frequent in vPED than Control-1 eyes: APOE rs4420638 (A/G), HTRA1 rs104904924 (G/T), VEGF rs943080 (T/C), CFH rs1061170 (T/C), CFH rs2274700 (C/T), CFH rs10737680 (A/C), CFH rs10801555 (G/A). These SNPs were more frequent in vPED than Control-2 eyes: APOE rs4420638 (A/G), CFI rs4698775 (G/T), COL15A1/TGFBR1 rs334353 (T/G). FRK rs3812111 (T/A) was more frequent in HR-50 and HR-75 eyes compared with LR. Conclusion: Seven SNPs were more frequent in vPED eyes than non-ARMD eyes, and three SNPs were more frequent in vPED eyes than drusen eyes. Adjusting for multiplicity, only CFH rs2274700 (C/T) was significant for first comparison, and only COL15A1/TGFBR1 rs334353 (T/G) was significant for second comparison. APOE rs4420638 (A/G) was the single SNP more frequently linked to vPED eyes for both comparisons. FRK rs3812111 (T/A) was consistently associated with high responders.
C1 [Lee, Daniel] Loma Linda Univ, Sch Med, Loma Linda, CA USA.
   [Chan, Clement K.] Southern Calif Desert Retina Consultants, Palm Desert, CA USA.
   [Chan, Clement K.] Loma Linda Univ, Dept Ophthalmol, Loma Linda, CA 92350 USA.
   [Abraham, Prema] Black Hills Reg Eye Inst, Retina Sect, Rapid City, SD USA.
   [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA.
C3 Loma Linda University; Loma Linda University; University of California
   System; University of California Los Angeles
RP Chan, CK (通讯作者)，Southern Calif Desert Retina Consultants, POB 2467, Palm Springs, CA 92263 USA.
EM CChan@desertretina.com
FU Roche-Genentech [FVF4332s]
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This
   investigator-initiated study was supported by a grant (FVF4332s) from
   Roche-Genentech.
CR Amoaku WM, 2015, EYE, V29, P721, DOI 10.1038/eye.2015.48
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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 2021
VL 31
IS 3
BP 1281
EP 1290
AR 1120672120932829
DI 10.1177/1120672120932829
EA JUN 2020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TZ2CF
UT WOS:000543216400001
PM 32578437
DA 2022-11-30
ER

PT J
AU Liu, J
   Ma, ZZ
   Ran, ZL
AF Liu, Jiong
   Ma, Zhizhong
   Ran, Zhenlong
TI MiR-21-3p modulates lipopolysaccharide-induced inflammation and
   apoptosis via targeting TGS4 in retinal pigment epithelial cells
SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
LA English
DT Article
DE apoptosis; inflammation; MiR-21-3p; RGS4
AB Age-related macular degeneration (AMD) is a major reason of blindness in the elderly. MicroRNAs are implicated in various pathological processes, including inflammation and apoptosis. In this study, we aim to investigate the biological functions of miR-21-3p in inflammation and apoptosis caused by lipopolysaccharide (LPS) in human retinal pigment epithelial (ARPE-19) cells. The miR-21-3p inhibitor and mimic were transfected into ARPE-19 cells for 48 hours, followed by exposed to LPS (10 mu g/mL) for 24 hours. The mRNA and protein expression of IL-6 and MCP-1 were measured using real-time PCR (RT-PCR) and enzyme-linked immunosorbent assays. Cell viability, apoptosis, caspase 3 activity, cleaved caspase-3 and cleaved-PARP protein levels were detected to evaluate the effects of miR-21-3p on apoptosis. Additionally, the target relationship between miR-21-3p and regulator of G-protein signalling 4 (RGS4) was verified by dual luciferase reporter assay. RT-PCR analysis demonstrated that LPS induced miR-21-3p expression. Inhibition of miR-21-3p reduced the mRNA and protein levels of IL-6 and MCP-1. Apoptosis, caspase-3 activity, and cleaved-caspase 3 and cleaved PARP protein levels were repressed by the miR-21-3p inhibitor. However, overexpression of miR-21-3p showed the opposite results. Furthermore, we identified that miR-21-3p directly targeted the 3 ' untranslated region of RGS4. MiR-21-3p negatively regulated the expression of RGS4 both in mRNA and protein levels. Silencing RGS4 reduced the anti-inflammatory and anti-apoptotic effects of miR-21-3p inhibitor. Our results revealed that miR-21-3p inhibition targeted RGS4 to attenuate inflammatory responses and apoptosis caused by LPS in ARPE-19 cells.
C1 [Liu, Jiong] Beijing Jishuitan Hosp, Dept Ophthalmol, Beijing, Peoples R China.
   [Ma, Zhizhong] Peking Univ, Hosp 3, Dept Ophthalmol, Beijing, Peoples R China.
   [Ran, Zhenlong] Boding First Cent Hosp, Dept Ophthalmol 2, 443 Wusi East Rd, Baoding 071000, Hebei, Peoples R China.
C3 Peking University
RP Ran, ZL (通讯作者)，Boding First Cent Hosp, Dept Ophthalmol 2, 443 Wusi East Rd, Baoding 071000, Hebei, Peoples R China.
EM zhenlongranbd@163.com
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NR 22
TC 4
Z9 6
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0305-1870
EI 1440-1681
J9 CLIN EXP PHARMACOL P
JI Clin. Exp. Pharmacol. Physiol.
PD OCT
PY 2019
VL 46
IS 10
BP 883
EP 889
DI 10.1111/1440-1681.13142
PG 7
WC Pharmacology & Pharmacy; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Physiology
GA IY2GM
UT WOS:000486208400002
PM 31330059
DA 2022-11-30
ER

PT J
AU Soheilian, M
   Karimi, S
   Montahae, T
   Nikkhah, H
   Mosavi, SA
AF Soheilian, Masoud
   Karimi, Saeed
   Montahae, Talieh
   Nikkhah, Homayoun
   Mosavi, Seyed Aliasghar
TI Effects of intravitreal injection of bevacizumab with or without
   anterior chamber paracentesis on intraocular pressure and peripapillary
   retinal nerve fiber layer thickness: a prospective study
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Peripapillary retinal nerve fiber layer thickness; Intravitreal
   injection; Intraocular pressure; Bevacizumab; Paracentesis
ID ENDOTHELIAL GROWTH-FACTOR; OPTIC-NERVE; MACULAR DEGENERATION;
   AXOPLASMIC-TRANSPORT; SUSTAINED ELEVATION; GLAUCOMA; RANIBIZUMAB;
   PEGAPTANIB; TRIAMCINOLONE; REPRODUCIBILITY
AB To investigate the effects of intravitreal injection of bevacizumab (IVB) with or without anterior chamber paracentesis on intraocular pressure (IOP) and peripapillary retinal nerve fiber layer (PRNFL) thickness.
   In this prospective randomized clinical trial, 90 eyes with center involving diabetic macular edema or wet type age-related macular degeneration (AMD) were randomly assigned to receive IVB either without (group A) or with (group B) anterior chamber paracentesis. IOP was measured before and within 2 min, 30 min, 24 hours and 3 months after injections. Peripapillary spectral-domain optical coherence tomography (SD-OCT) was performed before and 3 months after injections.
   Mean IOP changes 2 minutes, 30 minutes, 24 hours, and 3 months after injections were 26.4 +/- 5.7 mmHg (P < 0.001), 6.5 +/- 6.3 mmHg (P < 0.001), 0.2 +/- 2.9 mmHg (P > 0.99) and 0.5 +/- 2.4 mmHg (P > 0.99) in group A and -1.3 +/- 2.4 mmHg (P < 0.001), -3.2 +/- 1.8 mmHg (P < 0.001), -3.1 +/- 1.8 mmHg (P < 0.001) and -1.8 +/- 2.2 mmHg (P < 0.001) in group B, respectively Mean baseline average PRNFL thickness was 85.3 +/- 5.6 mu m and 85.6 +/- 5 mu m in groups A and B respectively. Mean PRNFL thickness changes after 3 month was -2 +/- 2 mu m (P < 0.001) in group A and 0 +/- 2 mu m (P = 0.101) in group B. Mean PRNFL thickness in group A decreased more than group B (P < 0.001).
   Conventional method of IVB injection was associated with acute IOP rise and significant PRNFL loss 3 months after injection. Anterior chamber paracentesis prevents acute IOP rise and PRNFL loss.
C1 [Soheilian, Masoud; Montahae, Talieh; Mosavi, Seyed Aliasghar] Shahid Beheshti Univ Med Sci, Ophthtalm Res Ctr, Labbafinejad Med Ctr, Tehran, Iran.
   [Karimi, Saeed; Nikkhah, Homayoun] Shahid Beheshti Univ Med Sci, Torfeh Eye Hosp, Ophthalm Res Ctr, Tehran, Iran.
C3 Shahid Beheshti University Medical Sciences; Shahid Beheshti University
   Medical Sciences
RP Karimi, S (通讯作者)，Shahid Beheshti Univ Med Sci, Torfeh Eye Hosp, Ophthalm Res Ctr, Tehran, Iran.
EM dr.saeedkarimi@gmail.com
RI Karimi, Saeed/AAW-4905-2020; Soheilian, Masoud/AAW-4743-2020; Nikkhah,
   Homayoun/AAW-4663-2020
OI Nikkhah, Homayoun/0000-0002-2414-4661; Soheilian,
   Masoud/0000-0001-7508-426X
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NR 37
TC 20
Z9 20
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 SEP
PY 2017
VL 255
IS 9
BP 1705
EP 1712
DI 10.1007/s00417-017-3702-1
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FD5RN
UT WOS:000407587600003
PM 28616715
DA 2022-11-30
ER

PT J
AU Hark, LA
   Leiby, BE
   Waisbourd, M
   Myers, JS
   Fudemberg, SJ
   Mantravadi, AV
   Dai, Y
   Gilligan, JP
   Resende, AF
   Katz, LJ
AF Hark, Lisa A.
   Leiby, Benjamin E.
   Waisbourd, Michael
   Myers, Jonathan S.
   Fudemberg, Scott J.
   Mantravadi, Anand V.
   Dai, Yang
   Gilligan, John P.
   Resende, Arthur F.
   Katz, L. Jay
TI Adherence to Follow-up Recommendations Among Individuals in the
   Philadelphia Glaucoma Detection and Treatment Project
SO JOURNAL OF GLAUCOMA
LA English
DT Article
DE glaucoma; Philadelphia Glaucoma Detection and Treatment Project;
   follow-up adherence; community-based
ID OPEN-ANGLE GLAUCOMA; VISUAL-FIELD; RISK-FACTORS; EYE; NONCOMPLIANCE;
   PREVALENCE; OUTCOMES; CARE
AB Purpose:To evaluate rates of adherence to free follow-up eye exam appointments among participants in the Philadelphia Glaucoma Detection and Treatment Project.Patients and Methods:Ophthalmologists and testing equipment were brought directly to participants at risk for glaucoma at 43 community sites in Philadelphia. Those diagnosed with glaucoma-related pathology were recommended to return for follow-up to be reexamined on site. Rates of adherence and clinical and demographic risk factors for adherence were evaluated.Results:Five hundred thirty-one participants were diagnosed with glaucoma-related conditions and recommended to attend community-based follow-up exams. Follow-up adherence rate was 61.2% (n=325/531). Significant factors associated with greater eye exam appointment adherence, based on our univariable analysis, included final diagnosis of glaucoma (risk ratio [RR]=1.33; 95% confidence interval [CI], 1.13-1.57), male sex (RR=1.19; 95% CI, 1.04-1.36), white race (RR=1.26; 95% CI, 1.08-1.48), age (RR=1.17; 95% CI, 1.00-1.37) recommendation for glaucoma medication (RR=1.52; 95% CI, 1.35-1.71), recommendation for laser peripheral iridotomy (RR=1.18; 95% CI, 1.02-1.35), diagnosis of age-related macular degeneration (RR=1.42; 95% CI, 1.13-1.77) and an increased intraocular pressure (>22 mm Hg in the worse eye) (RR=1.23; 95% CI, 1.06-1.42). On the basis of our multivariable model, diagnosis, sex, and recommended glaucoma medications were significantly associated with follow-up adherence.Conclusions:This study demonstrates that individuals living in underserved urban communities would take advantage of free eye exams in community sites and return for follow-up eye exams in these same settings. Future studies could investigate interventions to improve eye exam appointment adherence in community-based settings to detect glaucoma-eye conditions.
C1 [Hark, Lisa A.; Waisbourd, Michael; Myers, Jonathan S.; Fudemberg, Scott J.; Mantravadi, Anand V.; Dai, Yang; Gilligan, John P.; Resende, Arthur F.; Katz, L. Jay] Wills Eye Hosp & Res Inst, Glaucoma Res Ctr, 840 Walnut St, Philadelphia, PA 19107 USA.
   [Hark, Lisa A.; Leiby, Benjamin E.; Myers, Jonathan S.; Fudemberg, Scott J.; Mantravadi, Anand V.; Katz, L. Jay] Sidney Kimmel Med Coll, Philadelphia, PA USA.
   [Leiby, Benjamin E.] Thomas Jefferson Univ, Div Biostat, Philadelphia, PA 19107 USA.
C3 Jefferson University; Jefferson University; Jefferson University
RP Hark, LA (通讯作者)，Wills Eye Hosp & Res Inst, Glaucoma Res Ctr, 840 Walnut St, Philadelphia, PA 19107 USA.
EM lhark@willseye.org
OI Myers, Jonathan/0000-0002-8251-6750
FU United States Centers for Disease Control and Prevention [1U58DP004060]
FX Supported by United States Centers for Disease Control and Prevention
   (Grant number 1U58DP004060). Lumenis (San Jose) donated the Selecta Duet
   laser platform used in this project.
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NR 25
TC 8
Z9 9
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-0829
EI 1536-481X
J9 J GLAUCOMA
JI J. Glaucoma
PD AUG
PY 2017
VL 26
IS 8
BP 697
EP 701
DI 10.1097/IJG.0000000000000716
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FC8RJ
UT WOS:000407108300003
PM 28671920
DA 2022-11-30
ER

PT J
AU Huang, PR
   Sun, JR
   Wang, FH
   Luo, XT
   Feng, JY
   Gu, Q
   Liu, T
   Sun, XD
AF Huang, Peirong
   Sun, Junran
   Wang, Fenghua
   Luo, Xueting
   Feng, Jingyang
   Gu, Qing
   Liu, Te
   Sun, Xiaodong
TI MicroRNA Expression Patterns Involved in Amyloid Beta-Induced Retinal
   Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE amyloid beta; retina; microRNA; age-related macular degeneration
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; IN-VIVO; CHOROIDAL
   NEOVASCULARIZATION; SALMONELLA INFECTION; MICROARRAY ANALYSIS; OXIDATIVE
   STRESS; TIGHT JUNCTION; BREAST-CANCER; INFLAMMATION
AB PURPOSE. Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (A beta) is speculated to be one of the key pathologic factors. While the detrimental effects of A beta on retinas have been widely explored, A beta-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an A beta-induced mouse model of retinal degeneration.
   METHODS. C57BL/6 mice were intravitreally injected with A beta(1-40) or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling. After filtering, 10 miRNAs and their target genes were chosen for quantitative RT-PCR (qRT-PCR) confirmations. Pathway analyses were employed for further bioinformatic analyses.
   RESULTS. Hematoxylin and eosin-stained sections of retinal pigment epithelium (RPE)/neural retina tissue demonstrated degenerative alterations, and immunofluorescence testing revealed apoptosis within the retina after A beta treatments. MicroRNA profiling revealed 61 miRNAs that were differentially expressed between the model and the control group. Among these, 38 miRNAs were upregulated (fold change > 1.5, P < 0.05) and 23 miRNAs were downregulated (fold change < 0.667, P < 0.05). Five of the 10 selected miRNAs (miR-142, miR-216, miR-155, miR-223, and miR-433) as well as several key target genes (CFH, IGF-1R, c-MET, and ABCA1) were confirmed by qRT-PCR analyses.
   CONCLUSIONS. Our study is the first to profile the miRNA expression patterns and suggests that A beta accumulation could lead to relevant biochemical alternations such as complement activation, barrier impairment, apoptosis, and positive feedback of A beta production.
C1 [Huang, Peirong; Sun, Junran; Wang, Fenghua; Feng, Jingyang; Sun, Xiaodong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai, Peoples R China.
   [Huang, Peirong; Sun, Junran; Wang, Fenghua; Feng, Jingyang; Gu, Qing; Sun, Xiaodong] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
   [Luo, Xueting; Sun, Xiaodong] Shanghai Key Lab Fundus Dis, Shanghai, Peoples R China.
   [Liu, Te] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai Geriatr Inst Chinese Med, Bldg C,365 Xiangyang Rd, Shanghai 200031, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai University of Traditional
   Chinese Medicine
RP Liu, T (通讯作者)，Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai Geriatr Inst Chinese Med, Bldg C,365 Xiangyang Rd, Shanghai 200031, Peoples R China.; Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1,Shanghai Engn Ctr Visual, Dept Ophthalmol,Shanghai Key Lab Fundus Dis, 100 Hai Ning Rd, Shanghai 200080, Peoples R China.
EM liute1979@126.com; xdsun@sjtu.edu.cn
OI Feng, Jingyang/0000-0001-6031-7980
FU National Natural Science Foundation of China [81425006]; Shanghai
   Creative Key Medical Research Grant [1341195400]; Translational Medicine
   Grant of Shanghai Jiao Tong University, School of Medicine [5ZH4005];
   Shanghai Engineering Center for Visual Science and Photomedicine Science
   [16dz2251500]; Technology Commission of Shanghai Municipality
   [16140900800]
FX Supported by the National Natural Science Foundation of China (Grant
   81425006), Shanghai Creative Key Medical Research Grant (1341195400),
   Translational Medicine Grant of Shanghai Jiao Tong University, School of
   Medicine (5ZH4005), Shanghai Engineering Center for Visual Science and
   Photomedicine Science (16dz2251500), and Technology Commission of
   Shanghai Municipality (16140900800).
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NR 64
TC 18
Z9 19
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 MAR
PY 2017
VL 58
IS 3
BP 1726
EP 1735
DI 10.1167/iovs.16-20043
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EQ4ZA
UT WOS:000398089000046
PM 28324113
OA gold
DA 2022-11-30
ER

PT J
AU Yan, GG
   Jiang, SM
   Yu, LZ
   Liu, SJ
AF Yan, Guigang
   Jiang, Songmei
   Yu, Lianzhi
   Liu, Shujun
TI Oxidized low density lipoprotein (oxLDL) promotes mitochondrial
   dysfunction and induces apoptosis in retinal pigmented epithelium cells
SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
LA English
DT Article
DE Oxidized low density lipoprotein (oxLDL); apoptosis; toll-like
   receptor-4 (TLR-4); ARPE-19 cells
ID TOLL-LIKE RECEPTORS; MACULAR DEGENERATION; PATHOGENESIS; INNATE; DEATH
AB Oxidized low density lipoprotein (oxLDL) may contribute to the capillary injury in diabetic retinopathy. In particular, sustained high oxLDL is closely associated with the dysfunction and death of retinal pigment epithelium (RPE) cells, as may play a vital role in the pathogenesis of age-related macular degeneration (AMD). In the current study, we determined the promotion by oxLDL to the apoptosis in retinal pigmented epithelium ARPE-19 cells, and investigated whether the oxLDL-induced apoptosis depended on the activation of toll-like receptor-4 (TLR-4) signaling pathway. ARPE-19 cells were cultivated with and without oxLDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess TLR-4 expression on both protein and mRNA expressions. The RNAi technology was also utilized to examine the dependence of TLR-4 in the oxLDL-induced apoptosis in ARPE-19 cells. Results demonstrated that the incubation of ARPE-19 cells with ox-LDL (more than 50 mu g/mL) for 24 hours increased the apoptosis of ARPE-19 cells and promoted the cleaved levels of caspase-3 and 9, which are the active forms of both caspases. The lyzed level of Poly (ADP-ribose) polymerase (PARP), which is mainly lyzed by active caspase 3, was also significantly upregulated by the oxLDL. Moreover, it was demonstrated that TLR-4 expression was also significantly upregulated by the oxLDL treatment with more than 50 mu g/mL. However, the RNAi-mediated knockdown of TLR-4 markedly reduced the oxLDL-induced apoptosis in ARPE-19 cells. In conclusion, our findings indicate that the apoptosis was induced by oxLDL in cultured retinal pigmented epithelium ARPE-19 cells at least in part by modulating the TLR-4 signaling pathway. TLR-4 might be a valuable target for the AMD prevention.
C1 [Yan, Guigang; Liu, Shujun] Qingdao Univ, Dept Ophthalmol, Coll Med, Affiliated Yantai Yuhuangding Hosp, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China.
   [Jiang, Songmei] Laiyang Cent Hosp, Dept Ophthalmol, Yantai, Shandong, Peoples R China.
   [Yu, Lianzhi] Qingdao Univ, Dept Oncol, Affiliated Yantai Yuhuangding Hosp, Coll Med, Yantai 264000, Shandong, Peoples R China.
C3 Qingdao University; Qingdao University
RP Liu, SJ (通讯作者)，Qingdao Univ, Dept Ophthalmol, Coll Med, Affiliated Yantai Yuhuangding Hosp, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China.; Yu, LZ (通讯作者)，Qingdao Univ, Dept Oncol, Affiliated Yantai Yuhuangding Hosp, Coll Med, Yantai 264000, Shandong, Peoples R China.
EM lianzhiyu_yhd@sohu.com; shujunliuyantai@sina.com
FU Yantai Science and Technology Development Plan [2010307]
FX The present study was supported by the grant from Yantai Science and
   Technology Development Plan (2010307).
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NR 20
TC 3
Z9 3
U1 0
U2 1
PU E-CENTURY PUBLISHING CORP
PI MADISON
PA 40 WHITE OAKS LN, MADISON, WI 53711 USA
SN 1936-2625
J9 INT J CLIN EXP PATHO
JI Int. J. Clin. Exp. Pathol.
PY 2017
VL 10
IS 2
BP 1619
EP 1626
PG 8
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA EN0ZC
UT WOS:000395739000081
DA 2022-11-30
ER

PT J
AU Islam, KMS
   Khalil, M
   Manner, K
   Raila, J
   Rawel, H
   Zentek, J
   Schweigert, FJ
AF Islam, K. M. S.
   Khalil, M.
   Manner, K.
   Raila, J.
   Rawel, H.
   Zentek, J.
   Schweigert, F. J.
TI Effect of dietary alpha-tocopherol on the bioavailability of lutein in
   laying hen
SO JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
LA English
DT Article
DE carotenoids; tocopherol; egg yolk; bioavailability; HPLC; iCheck
ID VITAMIN-E; BETA-CAROTENE; ESTERIFIED LUTEIN; EGG COMPOSITION; PLASMA;
   SUPPLEMENTATION; RETINOL; QUANTIFICATION; PERFORMANCE; ENRICHMENT
AB Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as -tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without -tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21days, laying hens (n=42) were equally divided into three groups and fed the following diets for 21days: control (basal diet), a LE group (40mg LE/kg feed) and LE+T group (40mg LE plus 100mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and -tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck(())). Lutein, zeaxanthin, -tocopherol and total carotenoids in egg yolk were highest after 14days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE+T group contained higher amount of lutein (13.72), zeaxanthin (0.65), -tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0mg/kg, respectively, p<0.05). Blood plasma values of LE+T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90mg/l, respectively, p<0.05). In conclusion, dietary -tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of -tocopherol as an antioxidant.
C1 [Islam, K. M. S.] Bangladesh Agr Univ, Dept Anim Nutr, Mymensingh 2202, Bangladesh.
   [Islam, K. M. S.; Khalil, M.; Raila, J.; Rawel, H.; Schweigert, F. J.] Univ Potsdam, Inst Nutr Sci, Nuthetal, Germany.
   [Manner, K.; Zentek, J.] Freie Univ, Inst Anim Nutr, Berlin, Germany.
C3 Bangladesh Agricultural University (BAU); University of Potsdam; Free
   University of Berlin
RP Islam, KMS (通讯作者)，Bangladesh Agr Univ, Dept Anim Nutr, Mymensingh 2202, Bangladesh.
EM kmsislam1@yahoo.com
RI Rawel, Harshadrai/AFL-5307-2022
OI Rawel, Harshadrai/0000-0003-2768-1531; Zentek,
   Jurgen/0000-0003-2864-9250; Schweigert, Florian/0000-0001-7103-2438
FU Alexander von Humboldt Foundation, Germany
FX Author deeply acknowledges the financial support provided by the
   Alexander von Humboldt Foundation, Germany. Authors are also grateful to
   the Institute of Animal Nutrition, Nutritional Diseases and Dietetics,
   University of Leipzig, Germany, for technical support in conducting the
   research.
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NR 35
TC 4
Z9 4
U1 3
U2 18
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0931-2439
EI 1439-0396
J9 J ANIM PHYSIOL AN N
JI J. Anim. Physiol. Anim. Nutr.
PD OCT
PY 2016
VL 100
IS 5
BP 868
EP 875
DI 10.1111/jpn.12464
PG 8
WC Agriculture, Dairy & Animal Science; Veterinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Veterinary Sciences
GA DX1CY
UT WOS:000384104400010
PM 27080067
DA 2022-11-30
ER

PT J
AU Rudnisky, CJ
   Belin, MW
   Guo, R
   Ciolino, JB
AF Rudnisky, Christopher J.
   Belin, Michael W.
   Guo, Rong
   Ciolino, Joseph B.
CA Boston Type 1 Keratoprosthesis
TI Visual Acuity Outcomes of the Boston Keratoprosthesis Type 1:
   Multicenter Study Results
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COUNTING FINGERS; HAND MOTION; GLAUCOMA; ENDOPHTHALMITIS; COMPLICATIONS;
   CATEGORIES; VISION
AB PURPOSE: To report logarithm of the minimal angle of resolution (logMAR) visual outcomes of the Boston keratoprosthesis type 1.
   DESIGN: Prospective cohort study.
   METHODS: Preoperative, intraoperative, and postoperative parameters of 300 eyes of 300 patients who underwent implantation of a Boston keratoprosthesis type 1 device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers were collected.
   RESULTS: After an average of 17.1 +/- 14.8 months, visual acuity improved significantly (P < .0001) to a mean final value of 0.89 +/- 0.64 (20/150). There were also significantly fewer eyes with light perception (6.7%; n = 19; P < .0001), although 3.1% (n = 9) progressed to no light perception. There was no association between age (P = .08), sex (P = .959), operative side (P = .167), or failure (P = .494) and final visual acuity. The median time to achieve 20/200 visual acuity was 1 month (95% confidence interval 1.0-6.0) and it was retained for an average of 47.8 months. Multivariate analysis, controlling for preoperative visual acuity, demonstrated 2 factors associated with final visual outcome: chemical injury was associated with better final vision (P = .007), whereas age-related macular degeneration was associated with poorer vision (P < .0001).
   CONCLUSIONS: The Boston keratoprosthesis type 1 is an effective device for rehabilitation in advanced ocular surface disease, resulting in a significant improvement in visual acuity. Eyes achieved a mean value of 20/150 (0.89 0.64 IogMAR units) after 6 months and this was relatively stable thereafter. The best visual prognosis is observed in chemical injury eyes, whereas the worst prognosis is in aniridia, although the latter has limited visual potential. (C) 2016 by Elsevier Inc. All rights reserved.
C1 [Rudnisky, Christopher J.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada.
   [Belin, Michael W.] Univ Arizona, Dept Ophthalmol & Vis Sci, Tucson, AZ USA.
   [Guo, Rong; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
C3 University of Alberta; University of Arizona; Harvard University;
   Harvard Medical School; Massachusetts Eye & Ear Infirmary
RP Ciolino, JB (通讯作者)，Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Joseph_Ciolino@meei.harvard.edu
OI Abad, Juan Carlos/0000-0002-4570-8964; Ciolino,
   Joseph/0000-0002-6223-3091
FU NEI, BETHESDA, MARYLAND, USA [1K08EY019686-01]; Research to Prevent
   Blindness, Inc, New York, New York; Alcon, Fort Worth, Texas, USA;
   Bausch & Lomb, Rochester, New York, USA; Glaucoma Research Society of
   Canada, East York, Ontario, Canada; National Institutes of Health,
   Bethesda, Maryland, USA; Research to Prevent Blindness, New York, New
   York, USA; NATIONAL EYE INSTITUTE [K08EY019686] Funding Source: NIH
   RePORTER
FX THIS RESEARCH WAS FUNDED BY NEI 1K08EY019686-01, BETHESDA, MARYLAND, USA
   (J.B.C.) AND A Career Development Award from Research to Prevent
   Blindness, Inc, New York, New York (J.B.C.). Financial disclosures:
   Chris J. Rudnisky: Alcon, Fort Worth, Texas, USA (speaking fees); Bausch
   & Lomb, Rochester, New York, USA (speaking fees); Glaucoma Research
   Society of Canada, East York, Ontario, Canada (grant); Novartis, Basel,
   Switzerland (stock).; Merck, Kenilworth, New Jersey, USA (stock).
   Michael W. Belin: Oculus, Wetzlar, Germany (consultancy); Joseph B.
   Ciolino: ORA, Andover, Massachusetts, USA (consultancy); Massachusetts
   Eye and Ear Infirmary, Boston, Massachusetts, USA (employment); National
   Institutes of Health, Bethesda, Maryland, USA (grant support); Research
   to Prevent Blindness, New York, New York, USA (grant support). The
   following author has no financial disclosures: Rong Guo. All authors
   attest that they meet the current ICMJE criteria for authorship.
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NR 25
TC 34
Z9 33
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 FEB
PY 2016
VL 162
BP 89
EP 98
DI 10.1016/j.ajo.2015.10.023
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DC8JU
UT WOS:000369466500012
PM 26550696
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Ramchani-Ben Othman, K
   Cercy, C
   Amri, M
   Doly, M
   Ranchon-Cole, I
AF Ramchani-Ben Othman, Khaoula
   Cercy, Christine
   Amri, Mohamed
   Doly, Michel
   Ranchon-Cole, Isabelle
TI Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from
   Progressive Light-Induced Retinal Degeneration
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; MACULAR DEGENERATION; ANIMAL-CELLS; DAMAGE;
   PLASMALOGENS; SUSCEPTIBILITY; RHODOPSIN; LIPIDS; MODEL; DHA
AB In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.
C1 [Ramchani-Ben Othman, Khaoula; Cercy, Christine; Doly, Michel; Ranchon-Cole, Isabelle] Univ Auvergne, UFR Pharm, Inserm UMR 1107, Lab Biophys Neurosensorielle, Clermont Ferrand, France.
   [Ramchani-Ben Othman, Khaoula; Amri, Mohamed] Tunis El Manar Univ, Dept Biol Sci, Lab Funct Neurophysiol & Pathol, Tunis 1, Tunisia.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite Clermont Auvergne (UCA); Universite de Tunis-El-Manar
RP Ranchon-Cole, I (通讯作者)，Univ Auvergne, UFR Pharm, Inserm UMR 1107, Lab Biophys Neurosensorielle, Clermont Ferrand, France.
EM isabelle.ranchon-cole@udamail.fr
OI Amri, Mohamed/0000-0001-5309-7633; Ranchon-Cole,
   Isabelle/0000-0002-7092-6744
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NR 63
TC 9
Z9 9
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 4
PY 2015
VL 10
IS 6
AR e0128395
DI 10.1371/journal.pone.0128395
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CJ7TC
UT WOS:000355701600047
PM 26042773
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Koinzer, S
   Reinecke, K
   Herdegen, T
   Roider, J
   Klettner, A
AF Koinzer, Stefan
   Reinecke, Kirstin
   Herdegen, Thomas
   Roider, Johann
   Klettner, Alexa
TI Oxidative Stress Induces Biphasic ERK1/2 Activation in the RPE with
   Distinct Effects on Cell Survival at Early and Late Activation
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Cell death; ERK1/2; Nrf2; oxidative stress; retinal pigment epithelium
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; PATHWAY; INDUCTION;
   NRF2; GENES; PATHOGENESIS; TOXICITY; KINASES; DAMAGE
AB Purpose: Oxidative stress is considered a major factor in the deterioration of retinal pigment epithelium (RPE) cells in dry age-related macular degeneration (AMD). The MAPK ERK1/2 can be activated by oxidative stress, may exert both pro-and anti-apoptotic functions, and has recently been proposed as a major factor in RPE degeneration in atrophic changes. Nrf2 is a master regulator of oxidative stress defense and ERK1/2 is an upstream activator of Nrf2. In this study, we investigate the participation of ERK1/2 in oxidative stress pathways in connection with Nrf2.
   Methods: Nrf2 knock-out and wild-type primary RPE cells were prepared from mouse eyes. Oxidative stress was induced by different concentrations of t-butylhydroperoxide. Mitogen-activated protein kinases (MAPKs) were blocked by commercially available inhibitors (SB203580, U0126, SP600125). Cell viability was determined by MTT assay. ERK1/2 expression and activation were assessed by Western blotting.
   Results: Oxidative stress induced concentration dependent cell death, which occurred at lower concentrations in Nrf2 knock-out RPE. Western blot analysis displayed a biphasic activation of ERK1/2 in murine wild-type RPE and the inhibition of late, but not early activation of ERK1/2 exerted protection in wild-type murine RPE cells. The biphasic activation of ERK1/2 is lost in Nrf2 knock-out mice, and inhibition of ERK1/2 was generally protective. The inhibition of MAPK JNK or p38 exerted no protection, irrespective of Nrf2.
   Conclusion: RPE cells display a biphasic activation of ERK1/2 after oxidative insult, of which the late activation is pro-apoptotic. The biphasic activation is lost in Nrf2 knock-outs, suggesting that early ERK1/2 activation may be connected to Nrf2 signaling. In addition, ERK1/2 activation in Nrf2 knock-outs mediates oxidative stress-induced cell death.
C1 [Koinzer, Stefan; Roider, Johann; Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, D-24105 Kiel, Germany.
   [Reinecke, Kirstin; Herdegen, Thomas] Univ Kiel, Univ Med Ctr, Dept Pharmacol, D-24105 Kiel, Germany.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Kiel; Schleswig Holstein University Hospital
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 Klettner, Alexa Karina/M-8344-2018
OI Klettner, Alexa/0000-0002-2709-1059
FU CAU Medical Faculty intramural research grant
FX The work was financially supported by a CAU Medical Faculty intramural
   research grant.
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NR 25
TC 26
Z9 27
U1 1
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2015
VL 40
IS 8
BP 853
EP 857
DI 10.3109/02713683.2014.961613
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CR4RX
UT WOS:000361326700013
PM 25251900
DA 2022-11-30
ER

PT J
AU Rahimy, E
   Rayess, N
   Maguire, JI
   Hsu, J
AF Rahimy, Ehsan
   Rayess, Nadim
   Maguire, Joseph I.
   Hsu, Jason
TI Radial Versus Raster Spectral-Domain Optical Coherence Tomography Scan
   Patterns for Detection of Macular Pathology
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GROWTH-FACTOR THERAPY; DEGENERATION; DENSITY; TREAT; REGIMEN; IMPACT;
   EDEMA
AB PURPOSE: To compare the 6-line radial vs the 25-line raster spectral-domain optical coherence tomography (SD OCT) acquisition patterns at detecting intraretinal fluid, subretinal fluid, vitreomacular traction, and full-thickness macular hole (MH).
   DESIGN: Retrospective cross-sectional analysis.
   METHODS: Series of 365 eyes with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), central and branch retinal vein occlusion (CRVO/BRVO), central serous chorioretinopathy, vitreomacular traction, and full-thickness MH. Sequential 6-line radial and 25-line raster scans were evaluated for intraretinal/subretinal fluid and, when applicable, vitreomacular traction and MH.
   RESULTS: For neovascular AMD (133 scans), 7 25-line raster scans confirmed subretinal/intraretinal fluid not identified by the 6-line radial (P = .02). For DME (140 scans) and central serous chorioretinopathy (91 scans), 25-line raster confirmed fluid in 4 scans (P = .13) and 1 scan (P = .32), respectively, that was not observed with the 6-line radial. For CRVO (123 scans) and BRVO (126 scans), 25-line raster confirmed fluid on 2 (P = .25) and 4 scans (P = .13), respectively, that was not detected by the 6-line radial. Conversely, for focal vitreomacular traction (70 scans) and full-thickness MH (82 scans), 25-line raster missed focal traction (< 1500 mu m) and MH in 5 scans (P = .07) and 7 scans (P = .02), respectively, that were identified using the 6-line radial.
   CONCLUSIONS: The 6-line radial scan is statistically comparable to the 25-line raster at detecting fluid in DME, BRVO/CRVO, and central serous chorioretinopathy, but not neovascular AMD. Furthermore, it is superior to the 25-line raster pattern at detecting early MH formation, while demonstrating a positive trend in identifying focal vitreomacular traction. ((C) 2014 by Elsevier Inc. All rights reserved.)
C1 [Rahimy, Ehsan; Rayess, Nadim; Maguire, Joseph I.; Hsu, Jason] Thomas Jefferson Univ, Wills Eye Hosp, Retina Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Hsu, J (通讯作者)，Thomas Jefferson Univ, Wills Eye Hosp, Retina Serv, Philadelphia, PA 19107 USA.
EM jhsu@midatlanticretina.com
OI Rahimy, Ehsan/0000-0001-8446-7078
FU Santen; Ophthotech
FX J.M. is a speaker for Genentech and Regeneron and serves on an advisory
   board for Genentech. J.H. receives grant support from Santen and
   Ophthotech and has served as a consultant for Xoma. The authors indicate
   no funding support.
CR Baranano AE, 2012, ACTA OPHTHALMOL, V90, pE274, DOI 10.1111/j.1755-3768.2012.02398.x
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NR 19
TC 16
Z9 16
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 345
EP 353
DI 10.1016/j.ajo.2014.05.013
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN6EB
UT WOS:000340686600019
PM 24857688
DA 2022-11-30
ER

PT J
AU Ersoy, L
   Ristau, T
   Kirchhof, B
   Liakopoulos, S
AF Ersoy, Lebriz
   Ristau, Tina
   Kirchhof, Bernd
   Liakopoulos, Sandra
TI Response to anti-VEGF therapy in patients with subretinal fluid and
   pigment epithelial detachment on spectral-domain optical coherence
   tomography
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Neovascular age-related macular degeneration (nvAMD); Optical coherence
   tomography (OCT); Pigment epithelial detachment (PED); Subretinal fluid
   (SRF)
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; MACULAR DEGENERATION;
   INTRAVITREAL RANIBIZUMAB; VISUAL-ACUITY; PHOTODYNAMIC THERAPY; SUBGROUP
   ANALYSIS; BEVACIZUMAB; EYES; TACHYPHYLAXIS; AFLIBERCEPT
AB Purpose To analyse the long-term functional and morphological response of a specific choroidal neovascular membrane (CNV) phenotype to anti-vascular endothelial growth factor (VEGF) therapy.
   Methods Data from 30 eyes of 30 consecutive patients with subretinal fluid (SRF) and fibrovascular pigment epithelial detachment (PED) due to CNV on spectral-domain optical coherence tomography (SDOCT) with a follow-up of at least 20 months were retrospectively collected. Main outcome measures included change in visual acuity, quantitative and qualitative parameters on SDOCT [photoreceptor layer, outer nuclear layer (ONL), choroid, PED, SRF] and on fluorescein angiography (CNV activity). Subjects were divided into responders and non-responders based on morphological and functional aspects.
   Results An average number of 20.23 +/- 9.9 anti-VEGF injections were administered during a mean follow-up of 40.25 +/- 13.5 months. Fourteen eyes were categorized as morphological non-responders, 12 as functional non-responders and eight as complete non-responders. Complete non-responders were significantly younger than complete responders (68.5+4.5 vs 74.3+6.8 years; p < 0.05) and presented thinner baseline ONL values (68.43+15.2 vs103.5+32.8 mu m; p < 0.05). Intermediate or large drusen as typical features for age-related macular degeneration (AMD) were less frequently present in complete non-responders; however, this was not statistically significant (62.5 % vs 91.7 %; p = 0.25).
   Conclusions Our preliminary findings indicate that eyes with the specific SDOCT phenotype with isolated fibrovascular PED and SRF frequently demonstrate non-response to anti-VEGF therapy, and the underlying disease mechanism may be different from AMD. Larger prospective trials are required to validate those results, and to develop strategies to improve the morphological as well as functional outcome.
C1 [Ersoy, Lebriz; Ristau, Tina; Kirchhof, Bernd; Liakopoulos, Sandra] Univ Hosp Cologne, Dept Ophthalmol, Cologne Image Reading Ctr, D-50924 Cologne, Germany.
C3 University of Cologne
RP Ersoy, L (通讯作者)，Univ Hosp Cologne, Dept Ophthalmol, Cologne Image Reading Ctr, Kerpener Str 92, D-50924 Cologne, Germany.
EM lebriz.ersoy@uk-koeln.de
FU Ilse Palm-Foundation, Germany
FX Supported in part by Ilse Palm-Foundation, Germany
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NR 51
TC 13
Z9 14
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2014
VL 252
IS 6
BP 889
EP 897
DI 10.1007/s00417-013-2519-9
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AK5UN
UT WOS:000338492000004
PM 24271025
DA 2022-11-30
ER

PT J
AU Guo, X
   Meng, Y
   Yu, N
   Pan, Y
AF Guo, Xuan
   Meng, Yu
   Yu, Ning
   Pan, Yi
TI Cloud computing for detecting high-order genome-wide epistatic
   interaction via dynamic clustering
SO BMC BIOINFORMATICS
LA English
DT Article
DE Cloud computing; Genome-wide association studies; Dynamic clustering
ID MULTIFACTOR-DIMENSIONALITY REDUCTION; GENE-GENE INTERACTIONS;
   ASSOCIATION; INFERENCE; PRIORITIZATION; DISEASES
AB Backgroud: Taking the advan tage of high-throughput single nucleotide polymorphism (SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unravelling complex relationships between genotype and phenotype. At present, traditional single-locus-based methods are insufficient to detect interactions consisting of multiple-locus, which are broadly existing in complex traits. In addition, statistic tests for high order epistatic interactions with more than 2 SNPs propose computational and analytical challenges because the computation increases exponentially as the cardinality of SNPs combinations gets larger.
   Results: In this paper, we provide a simple, fast and powerful method using dynamic clustering and cloud computing to detect genome-wide multi-locus epistatic interactions. We have constructed systematic experiments to compare powers performance against some recently proposed algorithms, including TEAM, SNPRuler, EDCF and BOOST. Furthermore, we have applied our method on two real GWAS datasets, Age-related macular degeneration (AMD) and Rheumatoid arthritis (RA) datasets, where we find some novel potential disease-related genetic factors which are not shown up in detections of 2-loci epistatic interactions.
   Conclusions: Experimental results on simulated data demonstrate that our method is more powerful than some recently proposed methods on both two-and three- locus disease models. Our method has discovered many novel high-order associations that are significantly enriched in cases from two real GWAS datasets. Moreover, the running time of the cloud implementation for our method on AMD dataset and RA dataset are roughly 2 hours and 50 hours on a cluster with forty small virtual machines for detecting two-locus interactions, respectively. Therefore, we believe that our method is suitable and effective for the full-scale analysis of multiple-locus epistatic interactions in GWAS.
C1 [Guo, Xuan; Meng, Yu; Yu, Ning; Pan, Yi] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
C3 University System of Georgia; Georgia State University
RP Pan, Y (通讯作者)，Georgia State Univ, Dept Comp Sci, 34 Peachtree St, Atlanta, GA 30303 USA.
EM yipan@gsu.edu
RI Pan, Yi/AAJ-2341-2021
OI Pan, Yi/0000-0002-2766-3096
FU Molecular Basis of Disease (MBD) program at Georgia State University;
   NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
   [R01AR044422, N01AR022263] Funding Source: NIH RePORTER
FX The National Institutes of Health (NO1-AR-2-2263 and RO1-AR-44422), and
   the National Arthritis Foundation provided the RA dataset. This study is
   supported by the Molecular Basis of Disease (MBD) program at Georgia
   State University.
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NR 36
TC 64
Z9 64
U1 2
U2 25
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD APR 10
PY 2014
VL 15
AR 102
DI 10.1186/1471-2105-15-102
PG 16
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA AG3WA
UT WOS:000335349400002
PM 24717145
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, Y
   Liu, X
   Zhou, T
   Kelley, MR
   Edwards, P
   Gao, H
   Qiao, X
AF Li, Y.
   Liu, X.
   Zhou, T.
   Kelley, M. R.
   Edwards, P.
   Gao, H.
   Qiao, X.
TI Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment
   epithelial cells from oxidative stress and reduces choroidal
   neovascularization
SO REDOX BIOLOGY
LA English
DT Article
DE APE1/Ref-1redox function; E3330; Oxidative stress; Retinal pigment
   epithelial cell; Transcription factor; Age-related macular degeneration
ID DNA-REPAIR ENZYME; MACULAR DEGENERATION; APOLIPOPROTEIN-E;
   GENE-EXPRESSION; CANCER CELL; PROTEIN; PATHOGENESIS; ACTIVATION; REF-1;
   RPE
AB The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal closes of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor kappa B (NF-kappa B) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-kappa B, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser induced damages to RPE-Bruch's membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. (C) 2014 The Authors. Published by Elsevier B.V.
C1 [Li, Y.; Liu, X.; Zhou, T.; Edwards, P.; Gao, H.; Qiao, X.] Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI 48202 USA.
   [Li, Y.] Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Shanxi, Peoples R China.
   [Kelley, M. R.] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
C3 Henry Ford Health System; Henry Ford Hospital; Air Force Military
   Medical University; Indiana University System; Indiana University
   Bloomington
RP Qiao, X (通讯作者)，Henry Ford Hlth Syst, Dept Ophthalmol, 1 Ford Pl 5D, Detroit, MI 48202 USA.
EM xqiao1@hfhs.org
OI Kelley, Mark/0000-0002-6120-9532
FU International Retinal Research Foundation; Midwest Eye Bank; Reeves
   Foundation; Alliance for Vision Research; Henry Ford Research
   Foundation; National Institutes of Health [CA121168, CA167291]; Riley
   Children's Foundation; National Natural Science Foundation of China
   [81000390]; NATIONAL CANCER INSTITUTE [R01CA121168, R01CA167291] Funding
   Source: NIH RePORTER
FX This work was supported by Grants from the International Retinal
   Research Foundation, Midwest Eye Bank, Reeves Foundation, Alliance for
   Vision Research, and Henry Ford Research Foundation to X.Q., Grants from
   the National Institutes of Health CA121168 and CA167291 and the Riley
   Children's Foundation to M.R.K and by Grants from the National Natural
   Science Foundation of China (Grant no. 81000390), Alliance for Vision
   Research to Y.L.
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NR 80
TC 37
Z9 37
U1 2
U2 15
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PY 2014
VL 2
BP 485
EP 494
DI 10.1016/j.redox.2014.01.023
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CD0MY
UT WOS:000350769600058
PM 24624338
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rutar, M
   Natoli, R
   Provis, JM
AF Rutar, Matt
   Natoli, Riccardo
   Provis, Jan M.
TI Small interfering RNA-mediated suppression of Ccl2 in Muller cells
   attenuates microglial recruitment and photoreceptor death following
   retinal degeneration
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS-FACTOR-ALPHA; EXPERIMENTAL
   CHOROIDAL NEOVASCULARIZATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
   MULTIPLE-SCLEROSIS LESIONS; MARROW-DERIVED MICROGLIA; ANTIGEN-PRESENTING
   CELLS; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; MACULAR
   DEGENERATION
AB Background: The recruitment and activation of inflammatory cells is thought to exacerbate photoreceptor death in retinal degenerative conditions such as age-related macular degeneration (AMD). We investigated the role of Muller cell-derived chemokine (C-C motif) ligand (Ccl)2 expression on monocyte/microglia infiltration and photoreceptor death in light-mediated retinal degeneration, using targeted small interfering (si)RNA.
   Methods: Adult Sprague-Dawley rats were injected intravitreally with 1 mu g of either Ccl2 siRNA or scrambled siRNA, and were then exposed to 1000 lux of light for a period of 24 hours. The mice were given an overdose of barbiturate, and the retinas harvested and evaluated for the effects of bright-light exposure. Ccl2 expression was assessed by quantitative PCR, immunohistochemistry, and in situ hybridization. Monocytes/microglia were counted on retinal cryostat sections immunolabeled with the markers ED1 and ionized calcium binding adaptor (IBA)1, and photoreceptor apoptosis was assessed using terminal dUTP nick end labeling.
   Results: Intravitreal injection of Ccl2 siRNA significantly reduced the expression of Ccl2 following light damage to 29% compared with controls. In retinas injected with Ccl2 siRNA, in situ hybridization and immunohistochemistry on retinal cryostat sections showed a substantial decrease in Ccl2 within Muller cells. Cell counts showed significantly fewer ED1-positive and IBA1-positive cells in the retinal vasculature and outer nuclear layer of Ccl2 siRNA-injected retinas, compared with controls. Moreover, there was significantly less photoreceptor apoptosis in Ccl2 siRNA-injected retinas compared with controls.
   Conclusions: Our data indicate that Ccl2 expression by Muller cells promotes the infiltration of monocytes/microglia, thereby contributing to the neuroinflammatory response and photoreceptor death following retinal injury. Modulation of exaggerated chemokine responses using siRNA may have value in reducing inflammation-mediated cell death in retinal degenerative disease such as AMD.
C1 [Rutar, Matt; Natoli, Riccardo; Provis, Jan M.] Australian Natl Univ, Coll Med Biol & Environm, John Curtin Sch Med Res, Canberra, ACT 0200, Australia.
   [Rutar, Matt; Provis, Jan M.] Australian Natl Univ, ARC Ctr Excellence Vis Sci, Canberra, ACT 0200, Australia.
   [Natoli, Riccardo; Provis, Jan M.] Australian Natl Univ, ANU Med Sch, Canberra, ACT 0200, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, Coll Med Biol & Environm, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 0200, Australia.
EM matt.rutar@anu.edu.au
RI Provis, Jan/C-9529-2009
OI Provis, Jan/0000-0002-6405-2868; Natoli, Riccardo/0000-0002-9350-0439;
   Rutar, Matthew/0000-0002-8893-5120
FU Australian Research Council Centres of Excellence Program Grant
   [CF0561903]
FX This study was supported by an Australian Research Council Centres of
   Excellence Program Grant (CF0561903),
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NR 107
TC 86
Z9 93
U1 0
U2 11
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD SEP 19
PY 2012
VL 9
AR 221
DI 10.1186/1742-2094-9-221
PG 15
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA 087GQ
UT WOS:000314749900001
PM 22992301
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dutt, K
   Cao, Y
   Ezeonu, I
AF Dutt, Kamla
   Cao, Yang
   Ezeonu, Ifeoma
TI Ciliary neurotrophic factor: a survival and differentiation inducer in
   human retinal progenitors
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Article
DE Ciliary neurotrophic factor; Survival factor; Human retinal progenitors;
   Differentiation
ID INTRACELLULAR SIGNALING PATHWAYS; CHICK PHOTORECEPTOR DEVELOPMENT;
   INTRAOCULAR GENE-TRANSFER; FIBROBLAST GROWTH-FACTOR; DEVELOPING RAT
   RETINA; GANGLION-CELLS; IN-VITRO; NEURONAL DIFFERENTIATION; ROD
   PHOTORECEPTORS; RECEPTOR COMPLEX
AB Retinitis pigmentosa, age-related macular degeneration, and Parkinson's disease remain major problems in the field of medicine. Some of the strategies being explored for treatment include replacement of damaged tissue by transplantation of healthy tissues or progenitor cells and delivery of neurotrophins to rescue degenerating tissue. One of the neurotrophins with promise is the ciliary neurotrophic factor (CNTF). In this study, we report the role played by CNTF in retinal cell differentiation and survival in retinal progenitors. We found that CNTF is a survival factor for multipotential human retinal cells and increased cell survival by 50%, over a 7-d period, under serum-free conditions, as determined by apoptotic assays (immunohistochemistry and flow cytometry). This effect is dose dependent with a maximum survival at a CNTF concentration of 20 ng/ml. We also report that CNTF might be a cell commitment factor, directing the differentiation mainly toward large multipolar cells with ganglionic and amacrine phenotype. These cells express tyrosine hydroxylase (amacrine cells) as well as, thy 1.1 and neuron-specific enolase (ganglionic cells). Additionally, there was also an increase in protein kinase C alpha, a protein expressed in rod and cone bipolars as well as cone photoreceptors and calbindin, a protein expressed in cone photoreceptors and horizontal cells. In our studies, CNTF doubled the number of cells with ganglionic phenotypes, and basic fibroblast growth factor doubled the number of cells with photoreceptor phenotype. Additionally, CNTF induced a subset of progenitors to undergo multiple rounds of cell division before acquiring the large multipolar ganglionic phenotype. Our conclusion is that CNTF could be an agent that has therapeutic potential and possibly induces differentiation of large multipolar ganglionic phenotype in a subset of progenitors.
C1 [Dutt, Kamla; Cao, Yang; Ezeonu, Ifeoma] Morehouse Sch Med, Dept Pathol, Atlanta, GA 30310 USA.
C3 Morehouse School of Medicine
RP Dutt, K (通讯作者)，Morehouse Sch Med, Dept Pathol, 720 Westview Dr SW, Atlanta, GA 30310 USA.
EM kdutt@msm.edu
OI Ezeonu, Ifeoma/0000-0001-6758-2066
FU RCMI [5 G12RR03034]; NASA [NCC-11-112]; NATIONAL CENTER FOR RESEARCH
   RESOURCES [G12RR003034] Funding Source: NIH RePORTER
FX The authors thank Renarder Pressley for the excellent secretarial
   assistance, Mr. Patrick Abramson for the graphics, and Ms. Suzanne
   Alexander for the critical reading of the manuscript (Morehouse School
   of Medicine). We thank Ms. Darlene Kelley, information specialist
   (Morehouse School of Medicine). We also thank Dr. Myrtle Thierry-Palmer,
   Dr. Sandra Harris-Hooker, and Dr. Marjorie Smith for their friendship
   and support. The work was supported by RCMI Grant 5 G12RR03034 (K. D.)
   NASA NCC-11-112 (K. D.).
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NR 63
TC 5
Z9 6
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD JUL
PY 2010
VL 46
IS 7
BP 635
EP 646
DI 10.1007/s11626-010-9319-x
PG 12
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA 622JB
UT WOS:000279657100011
PM 20428961
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Luhmann, UFO
   Robbie, S
   Munro, PMG
   Barker, SE
   Duran, Y
   Luong, V
   Fitzke, FW
   Bainbridge, JWB
   Ali, RR
   MacLaren, RE
AF Luhmann, Ulrich F. O.
   Robbie, Scott
   Munro, Peter M. G.
   Barker, Susie E.
   Duran, Yanai
   Luong, Vy
   Fitzke, Frederick W.
   Bainbridge, James W. B.
   Ali, Robin R.
   MacLaren, Robert E.
TI The Drusenlike Phenotype in Aging Ccl2-Knockout Mice Is Caused by an
   Accelerated Accumulation of Swollen Autofluorescent Subretinal
   Macrophages
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CHEMOKINE RECEPTOR 2; MACULAR DEGENERATION; MONOCYTE RECRUITMENT;
   MICROGLIAL CELLS; ATHEROSCLEROSIS; ABNORMALITIES; ANGIOGENESIS;
   EXPRESSION; ENDOSTATIN; ETIOLOGY
AB PURPOSE. Drusen, which are defined clinically as yellowish white spots in the outer retina, are cardinal features of age-related macular degeneration (AMD). Ccl2-knockout (Ccl2(-/-)) mice have been reported to develop drusen and phenotypic features similar to AMD, including an increased susceptibility to choroidal neovascularization (CNV). This study was conducted to investigate the nature of the drusenlike lesions in vivo and further evaluate the Ccl2(-/-) mouse as a model of AMD.
   METHODS. The eyes of 2- to 25-month-old Ccl2(-/-) and C57Bl/6 mice were examined in vivo by autofluorescence scanning laser ophthalmoscopy (AF-SLO) and electroretinography, and the extent of laser-induced CNV was measured by fluorescein fundus angiography. The retinal morphology was also assessed by immunohistochemistry and quantitative histologic and ultrastructural morphometry.
   RESULTS. The drusenlike lesions of Ccl2(-/-) mice comprised accelerated accumulation of swollen CD68(+), F4/80(+) macrophages in the subretinal space that were apparent as autofluorescent foci on AF-SLO. These macrophages contained pigment granules and phagosomes with outer segment and lipofuscin inclusions that may account for their autofluorescence. Only age-related retinal pigment epithelium (RPE) damage, photoreceptor loss, and sub-RPE deposits were observed but, despite the accelerated accumulation of macrophages, we identified no spontaneous development of CNV in the senescent mice and found a reduced susceptibility to laser-induced CNV in the Ccl2(-/-) mice.
   CONCLUSIONS. These findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury. Other, previously described features of Ccl2(-/-) mice that are similar to AMD may be the result of aging alone. (Invest Ophthalmol Vis Sci. 2009;50:5934-5943) DOI:10.1167/iovs.09-3462
C1 [Luhmann, Ulrich F. O.; Robbie, Scott; Barker, Susie E.; Duran, Yanai; Bainbridge, James W. B.; Ali, Robin R.; MacLaren, Robert E.] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Munro, Peter M. G.] UCL Inst Ophthalmol, Imaging Unit, London EC1V 9EL, England.
   [Luong, Vy; Fitzke, Frederick W.] UCL Inst Ophthalmol, Dept Visual Sci, London EC1V 9EL, England.
   [MacLaren, Robert E.] Moorfields Eye Hosp, Vitreoretinal Serv, London, England.
C3 University of London; University College London; University of London;
   University College London; University of London; University College
   London; University of London; University College London; Moorfields Eye
   Hospital NHS Foundation Trust
RP Luhmann, UFO (通讯作者)，UCL Inst Ophthalmol, Dept Genet, 11-43 Bath St, London EC1V 9EL, England.
EM u.luhmann@ucl.ac.uk
RI Luhmann, Ulrich/D-8905-2012
OI Ali, Robin/0000-0003-3126-6517; Bainbridge, James/0000-0003-1318-8201;
   MacLaren, Robert/0000-0002-3096-4682
FU Moorfields Eye Hospital/Institute of Ophthalmology NIHR BMRC; The Royal
   College of Surgeons of Edinburgh; The Health Foundation; Royal Blind and
   the Scottish National Institution for the War Blinded; MRC [G0601588,
   G0801004] Funding Source: UKRI; Medical Research Council [G0801004,
   G0601588] Funding Source: researchfish; National Institute for Health
   Research [NF-SI-0508-10130] Funding Source: researchfish
FX Supported by Moorfields Eye Hospital/Institute of Ophthalmology NIHR
   BMRC; The Royal College of Surgeons of Edinburgh; The Health Foundation;
   Royal Blind and the Scottish National Institution for the War Blinded.
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NR 28
TC 163
Z9 173
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 DEC
PY 2009
VL 50
IS 12
BP 5934
EP 5943
DI 10.1167/iovs.09-3462
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 527GS
UT WOS:000272355900059
PM 19578022
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Li, Y
   Wang, YS
   Shen, XF
   Hui, YN
   Han, J
   Zhao, W
   Zhu, J
AF Li, Yue
   Wang, Yu-Sheng
   Shen, Xue-Feng
   Hui, Yan-Nian
   Han, Jing
   Zhao, Wei
   Zhu, Jie
TI Alterations of activity and intracellular distribution of the 20S
   proteasome in ageing retinal pigment epithelial cells
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Proteasome; Ageing; Redistribution; Retinal pigment epithelial cells;
   Age-related macular degeneration
ID CHYMOTRYPSIN-LIKE ACTIVITY; SENESCENCE-LIKE PHENOTYPE;
   PROTEIN-DEGRADATION; OXIDIZED PROTEINS; OXIDATIVE STRESS; IN-VITRO;
   HUMAN FIBROBLASTS; INHIBITION; OVEREXPRESSION; SUBUNITS
AB Age-related macular degeneration (AMD) remains high incidence and accounts for a main cause of blindness in ageing people, but its mechanism is still poorly understood. Ageing and associated dysfunction of retinal pigment epithelial (RPE) cells were believed to be the pathological onset of AMD. 20S proteasome has been tightly correlated with cell ageing due to its fundamental role in maintaining cellular homeostasis, but its implication in the ageing process of human RPE cells was seldom concerned. This study aimed to demonstrate the interconnections between 20S proteasome and ageing RPE cells by characterizing age-dependent alterations of the 20S proteasome in primarily cultured human RPE cells. For this purpose, a replicative ageing RPE cell model was established and validated through testing the cell viability, P-galactosidase activity and cellular autofluorescence. Decline in chymotrypsin-like, peptidylglutamyl-peptide hydrolase and trypsin-like activities of the 20S proteasome was detected in aged RPE cells through degradation of fluorogenic substrates. Immunofluorescence assay revealed that the 20S proteasome was concentrated in RPE nucleus, and redistributed partly to the peri-nuclear regions in old RPE passages. These age-dependent changes of the 20S complex were accompanied with a significantly increased fluorescent intensity of intracellular oxidized proteins. Further analysis of the proteasome-to-oxidized protein ratio indicated a preferred protection of the RPE nuclear proteins by the 20S proteasome, which also subsided remarkably as a function of the cell ageing. In conclusion, we demonstrated functional impairment and redistribution of the 20S proteasome with age in human RPE cells and supposed these alterations impactful on the process of RPE cell ageing and furthermore on the pathogenesis of AMD. Future researches on the mechanism of these alterations and the pathways to manipulate their effects are still strongly recommended. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Li, Yue; Wang, Yu-Sheng; Hui, Yan-Nian; Han, Jing; Zhao, Wei; Zhu, Jie] Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Xian 710032, Shaanxi, Peoples R China.
   [Li, Yue; Wang, Yu-Sheng; Hui, Yan-Nian; Han, Jing; Zhao, Wei; Zhu, Jie] Eye Inst PLA, Xian 710032, Shaanxi, Peoples R China.
   [Shen, Xue-Feng] Fourth Mil Med Univ, Inst Neurosci, Xian 710032, Shaanxi, Peoples R China.
C3 Air Force Military Medical University; Air Force Military Medical
   University
RP Hui, YN (通讯作者)，Fourth Mil Med Univ, Xijing Hosp, Dept Ophthalmol, Chang Le Rd 17, Xian 710032, Shaanxi, Peoples R China.
EM fmmuhyn@fmmu.edu.cn
RI Zhu, Jie/AAD-1330-2022
OI Zhu, Jie/0000-0001-6862-9022
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NR 58
TC 34
Z9 35
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
EI 1873-6815
J9 EXP GERONTOL
JI Exp. Gerontol.
PD DEC
PY 2008
VL 43
IS 12
BP 1114
EP 1122
DI 10.1016/j.exger.2008.08.052
PG 9
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA 386BY
UT WOS:000261858500012
PM 18817863
DA 2022-11-30
ER

PT J
AU Moan, J
   Peng, Q
AF Moan, J
   Peng, Q
TI An outline of the hundred-year history of PDT
SO ANTICANCER RESEARCH
LA English
DT Review
DE photodynamic therapy; history; review
ID SULFONATED ALUMINUM PHTHALOCYANINES; CHINESE-HAMSTER CELLS; PHOTODYNAMIC
   THERAPY; INTRACELLULAR-LOCALIZATION; MESO-TETRAPHENYLPORPHINES;
   ATHEROMATOUS PLAQUES; ENDOSCOPIC DETECTION; MALIGNANT DISEASE;
   CELLULAR-UPTAKE; SKIN TUMORS
AB Photosensitizing drugs have been known and applied in medicine for several thousand years. However, the scientific basis for such use was vague or non-existent before about 1900. Photodynamic therapy, PDT, has now become an established treatment modality for several medical indications. Notably, in the cases of skin actinic keratosis, several forms of cancer and blindness due to age-related macular degeneration, PDT has been successful. PDT is the combined application of a lesion-localizing photosensitizer and light. PDT with porphyrin derivatives as photosensitizing drugs was developed from about 1960. The basic, underlying mechanisms for tumour localization of photosensitizers and processes explaining the effect of PDT on tumours were elucidated from about that time. It has become clear that PDT is efficient only in the presence of oxygen, and that the oxygen dependency of PDT is similar to that of X-rays. Singlet oxygen, O-1(2), a short-lived product of the reaction between an excited sensitizer molecule and oxygen, plays a key role. In contrast to radiation therapy and chemotherapy, PDT has a low mutagenic potential and, except for skin phototoxicity, few adverse effects. Approvals for clinical use of PDT now exist in many countries. The annual number of scientific articles on PDT, clinical as well as basic, steadily increases and new aspects and applications of it continue to be discovered. Many of the new investigators are obviously not aware of the early work in the field and repeat many of the experiments that had been reported before the Internet and modem data bases were established. Therefore, in the present historical review, the early work is weighted more heavily than recent work that is more easily accessible to the readers.
C1 Univ Oslo, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway.
   Univ Oslo, Norwegian Radium Hosp, Dept Biophys, Inst Canc Res, N-0310 Oslo, Norway.
   Fudan Univ, State Key Lab Adv Photon Mat & Devices, Shanghai 200433, Peoples R China.
C3 University of Oslo; University of Oslo; Fudan University
RP Peng, Q (通讯作者)，Univ Oslo, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway.
EM qian.peng@labmed.uio.no
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NR 104
TC 291
Z9 313
U1 6
U2 135
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
   ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD SEP-OCT
PY 2003
VL 23
IS 5A
BP 3591
EP 3600
PG 10
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 748VE
UT WOS:000186881100003
PM 14666654
DA 2022-11-30
ER

PT J
AU Danciger, M
   Lyon, J
   Worrill, D
   LaVail, MM
   Yang, HD
AF Danciger, M
   Lyon, J
   Worrill, D
   LaVail, MM
   Yang, HD
TI A strong and highly significant QTL on chromosome 6 that protects the
   mouse from age-related retinal degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RECESSIVE RETINITIS-PIGMENTOSA; STARGARDT-DISEASE GENE; NUCLEAR RECEPTOR
   GENE; MACULAR DEGENERATION; APOLIPOPROTEIN-E; ABCR GENE; MONOZYGOTIC
   TWINS; VISUAL IMPAIRMENT; ALLELIC VARIATION; BETA-SUBUNIT
AB Purpose. BALB/cByJ (C) albino mice have significantly more retinal degeneration as they age than C577BL/6J-c(2J) (136) albinos. To discover the genetic loci that influence age-related retinal degeneration (ARD), a quantitative genetics study was performed with 8-month-old progeny from an intercross between these two strains.
   Methods. The thickness of the outer nuclear layer of the retina was used as the quantitative trait. A genome-wide scan was performed with 86 genetic markers at an average distance of 15.7 cM. Map Manager QTX was used to analyze the data.
   Results. Three highly significant quantitative trait loci (QTLs) were detected on mouse chromosomes (Chrs) 6, 10, and 16. The B6 alleles were protective against ARD in the first two, and the C allele was protective in the third. Several suggestive, weak QTLs were also found, along with a gender-related effect. The strongest and most highly significant QTL on Chr 6 accounted for 30% of the total genetic effect with a LOD score of 13.5. The RPE65/MET450 variant of major influence on constant light-induced retinal degeneration (LRD) in a previous study of these same two mouse strains had no influence on ARD, and only some of the weak, suggestive QTLs influencing ARD were also observed in LRD.
   Conclusions. Because none of the ARD QTLs was homologous to human chromosomal loci so far implicated in age-related macular degeneration, each represents a new candidate gene for potential study. The gene represented by the Chr 6 QTL is of particular interest because it has broad influence, very high significance, and a B6 allele that protects against ARD. (Invest Ophthalmol Vis Sci. 2003;44:2442-2449) DOI: 10.1167/iovs.02-1252.
C1 Loyola Marymount Univ, Dept Biol, Los Angeles, CA 90045 USA.
   Univ Calif San Francisco, Sch Med, Beckman Vis Ctr, San Francisco, CA USA.
C3 Loyola Marymount University; University of California System; University
   of California San Francisco
RP Danciger, M (通讯作者)，Loyola Marymount Univ, Dept Biol, Los Angeles, CA 90045 USA.
EM mdancige@lmu.edu
FU NATIONAL EYE INSTITUTE [R01EY001919, R37EY001919, R01EY013280] Funding
   Source: NIH RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTE
   [N01HG065403] Funding Source: NIH RePORTER; NEI NIH HHS [EY13280,
   EY01919] Funding Source: Medline; NHGRI NIH HHS [N01-HG-65403] Funding
   Source: Medline
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NR 53
TC 20
Z9 20
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 2003
VL 44
IS 6
BP 2442
EP 2449
DI 10.1167/iovs.02-1252
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 682FU
UT WOS:000183081700011
PM 12766041
DA 2022-11-30
ER

PT J
AU Erdem, B
   Kapti, HB
AF Erdem, B.
   Kapti, H. B.
TI The effect of two different intravitreal injection techniques on
   frequency of vitreous reflux and on treatment response in neovascular
   AMD patients
SO JOURNAL FRANCAIS D OPHTALMOLOGIE
LA English
DT Article
DE Age-related macular degeneration; Intravitreal injection; Macular
   thickness; Treatment response; Vitreous reflux
ID DRUG
AB Purpose. - To determine the effect of two distinct intravitreal injection (IVI) techniques on the frequency of vitreous reflux (VR) and on treatment response at cumulative dosages in neovascular age-related macular degeneration (nAMD) patients.
   Patients and methods. - Ninety-three eyes of 93 nAMD patients were included in the study. IVI was performed in 47 eyes using the straight technique (ST) and 46 eyes with the tunneled technique (TT). Patients received three loading doses of intravitreal bevacizumab, and substantial VR was noted for each IVI. Central (CMT), 1 mm (MT1), and 3 mm (MT3) macular thicknesses were measured before and after treatment. VR frequency and treatment response were compared in both groups, and correlation analysis was performed.
   Results. - Post-treatment VR was seen in 91 of 141 IVI with the ST and 33 of 138 IVI with the TT. The decrease in CMT, MT1, and MT3 after treatment with the ST was 121.4 +/- 92.5 mu m, 65.3 +/- 50.6 mu m, 28.8 +/- 30.8 mu m, respectively, and with the TT was 114.0 +/- 97.5 mu m, 67.8 +/- 72.6 mu m, and 27.1 +/- 31.4 mu m, respectively. The ST substantially increased the rate of VR compared to the TT (P < 0.001), whereas the decrease in CMT, MT1, and MT3 did not vary significantly (P > 0.05). There was no correlation between VR rate and decreases in CMT, MT1, or MT3 (P > 0.05).
   Conclusions. - According to our findings, the ST resulted in a higher frequency of VR than the TT, but VR did not affect the treatment response, despite multiple doses. Complication rates were negligible with both approaches. As a result, it appears that practitioners may use either IVI approach. (C) 2022 Elsevier Masson SAS. All rights reserved.
C1 [Erdem, B.; Kapti, H. B.] Ordu Univ, Fac Med, Dept Ophthalmol, TR-52200 Ordu, Turkey.
C3 Ordu University
RP Erdem, B (通讯作者)，Ordu Univ, Res & Training Hosp, Minist Hlth, TR-52200 Ordu, Turkey.
EM burakerdem89@gmail.com
RI Kaptı, Hasan Burhanettin/AAD-6423-2022
OI KAPTI, HASAN BURHANETTIN/0000-0002-3960-654X; Erdem,
   Burak/0000-0002-8889-6096
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NR 16
TC 0
Z9 0
U1 0
U2 0
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 0181-5512
EI 1773-0597
J9 J FR OPHTALMOL
JI J. Fr. Ophthamol.
PD APR
PY 2022
VL 45
IS 4
BP 405
EP 412
DI 10.1016/j.jfo.2021.10.005
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1C5NA
UT WOS:000793164500007
PM 35093263
DA 2022-11-30
ER

PT J
AU Chauhan, A
   Khan, T
AF Chauhan, Akshita
   Khan, Tabassum
TI Prodrugs-Current development and applications in ocular drug delivery
SO JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
LA English
DT Article
DE Lipid based prodrugs; Ocular delivery; Transporter targeting; Polymer
   prodrugs; Ocular bioavailability
ID MONOESTER GANCICLOVIR PRODRUGS; PHYSICOCHEMICAL PROPERTIES;
   P-GLYCOPROTEIN; IN-VITRO; PEPTIDE TRANSPORTERS; PILOCARPINE PRODRUGS;
   CORNEAL ABSORPTION; TOPICAL DELIVERY; MEDIATED EFFLUX; ESTER PRODRUGS
AB The clinical therapeutic regimen for disease treatment of the anterior portion of an eye involves the use of eye drops with mediocre success due to rapid eye drainage and poor bioavailability. These conventional delivery mechanisms do not penetrate the posterior portion of the eye and are ineffective in treating posterior segment diseases like, retinitis pigmentosa, age related macular degeneration, diabetic retinopathies, and glaucoma. This has led to augmented research in development of drug delivery alternatives for subconjunctival and periocular administration, drug that targets bloodstream to the retinal pigment epithelium or choroidal vasculature, and prodrugs. Ocular pharmacokinetics is a highly studied area to develop strategies that circumvent the associated barriers in ocular drug delivery and achieve better clinical outcomes. The viable strategies for enhancing ocular bioavailability involves physical methods like formulating drugs as solutions, suspensions, gels and chemical methods like development of prodrugs and soft drugs. The application of prodrug design offers the advantages of higher ocular tissue permeability, superior bioavailability, transporter targeting, site specificity and enhanced aqueous solubility with minimal disruption of the barriers to ocular diffusion. This review focuses mainly on recent progress in prodrug strategies like lipid-based prodrugs, transporter targeted prodrugs, hydrophilic and polymeric prodrugs developed to improve delivery to the otherwise resilient eye. The success of conventional and emerging prodrug design strategies depends on many factors like chemical structure of the drug, ease of prodrug synthesis, capacity of targeted transporters and in vivo metabolic activation attributes. Inspite of the associated challenges, prodrugs have witnessed reasonable market success and the new prodrug design strategies are envisaged to enable delivery of conventional drugs, antibodies, oligonucleotides, genes, and growth factors to the eye offering patient compliant, safer and superior treatment of posterior segment diseases.
C1 [Chauhan, Akshita] SVKMs Dr Bhanuben Nanavati Coll Pharm, Dept Qual Assurance, Mumbai, Maharashtra, India.
   [Khan, Tabassum] SVKMs Dr Bhanuben Nanavati Coll Pharm, Dept Pharmaceut Chem & Qual Assurance, Mumbai, Maharashtra, India.
RP Khan, T (通讯作者)，SVKMs Dr Bhanuben Nanavati Coll Pharm, Dept Pharmaceut Chem & Qual Assurance, Mumbai, Maharashtra, India.
EM tabassum.khan@bncp.ac.in
OI Khan, Tabassum Asif/0000-0002-3723-0833
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NR 67
TC 2
Z9 2
U1 5
U2 21
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1773-2247
EI 2588-8943
J9 J DRUG DELIV SCI TEC
JI J. Drug Deliv. Sci. Technol.
PD DEC
PY 2021
VL 66
AR 102836
DI 10.1016/j.jddst.2021.102836
EA SEP 2021
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA WB6PW
UT WOS:000703693500002
DA 2022-11-30
ER

PT J
AU Baraas, RC
   Horjen, A
   Gilson, SJ
   Pedersen, HR
AF Baraas, Rigmor C.
   Horjen, Ashild
   Gilson, Stuart J.
   Pedersen, Hilde R.
TI The Relationship Between Perifoveal L-Cone Isolating Visual Acuity and
   Cone Photoreceptor Spacing-Understanding the Transition Between Healthy
   Aging and Early AMD
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE age-related macular degeneration; isolated L-cone acuity; cone density;
   aging; outer segment length; inner segment length; cone spacing
ID MACULAR DEGENERATION; PACKING DENSITY; OPTICS; DRUSEN; VARIABILITY;
   SENSITIVITY; TOPOGRAPHY; DEPOSITS; SLOPE
AB Background: Age-related macular degeneration (AMD) is a multifactorial degenerative disorder that can lead to irreversible loss of visual function, with aging being the prime risk factor. However, knowledge about the transition between healthy aging and early AMD is limited. We aimed to examine the relationship between psychophysical measures of perifoveal L-cone acuity and cone photoreceptor structure in healthy aging and early AMD.
   Methods and Results: Thirty-nine healthy participants, 10 with early AMD and 29 healthy controls were included in the study. Multimodal high-resolution retinal images were obtained with adaptive-optics scanning-light ophthalmoscopy (AOSLO), optical-coherence tomography (OCT), and color fundus photographs. At 5 degrees retinal eccentricity, perifoveal L-cone isolating letter acuity was measured with psychophysics, cone inner segment and outer segment lengths were measured using OCT, while cone density, spacing, and mosaic regularity were measured using AOSLO. The Nyquist sampling limit of cone mosaic (Nc) was calculated for each participant. Both L-cone acuity and photoreceptor inner segment length declined with age, but there was no association between cone density nor outer segment length and age. A multiple regression showed that 56% of the variation in log L-cone acuity was accounted for by Nc when age was taken into account. Six AMD participants with low risk of progression were well within confidence limits, while two with medium-to-severe risk of progression were outliers. The observable difference in cone structure between healthy aging and early AMD was a significant shortening of cone outer segments.
   Conclusion: The results underscore the resilience of cone structure with age, with perifoveal functional changes preceding detectable changes in the cone photoreceptor mosaic. L-cone acuity is a sensitive measure for assessing age-related decline in this region. The transition between healthy aging of cone structures and changes in cone structures secondary to early AMD relates to outer segment shortening.
C1 [Baraas, Rigmor C.; Horjen, Ashild; Gilson, Stuart J.; Pedersen, Hilde R.] Univ South Eastern Norway, Fac Hlth & Social Sci, Natl Ctr Opt Vis & Eye Care, Kongsberg, Norway.
C3 University College of Southeast Norway
RP Baraas, RC (通讯作者)，Univ South Eastern Norway, Fac Hlth & Social Sci, Natl Ctr Opt Vis & Eye Care, Kongsberg, Norway.
EM rigmor.baraas@usn.no
RI Baraas, Rigmor/H-9137-2016
OI Baraas, Rigmor/0000-0003-3259-7617
FU University of South-Eastern Norway; Norwegian Research Council Regional
   Research Funds: the Oslofjord Fund [268696]
FX The study was funded by the University of South-Eastern Norway and
   Norwegian Research Council Regional Research Funds: the Oslofjord Fund
   Grant No. 268696.
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NR 49
TC 1
Z9 1
U1 0
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD SEP 9
PY 2021
VL 13
AR 732287
DI 10.3389/fnagi.2021.732287
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA UN1ID
UT WOS:000693774900001
PM 34566629
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ofoedu, CE
   Iwouno, JO
   Ofoedu, EO
   Ogueke, CC
   Igwe, VS
   Agunwah, IM
   Ofoedum, AF
   Chacha, JS
   Muobike, OP
   Agunbiade, AO
   Njoku, NE
   Nwakaudu, AA
   Odimegwu, NE
   Ndukauba, OE
   Ogbonna, CU
   Naibaho, J
   Korus, M
   Okpala, COR
AF Ofoedu, Chigozie E.
   Iwouno, Jude O.
   Ofoedu, Ebelechukwu O.
   Ogueke, Chika C.
   Igwe, Victory S.
   Agunwah, Ijeoma M.
   Ofoedum, Arinze F.
   Chacha, James S.
   Muobike, Onyinye P.
   Agunbiade, Adedoyin O.
   Njoku, Njideka E.
   Nwakaudu, Angela A.
   Odimegwu, Nkiru E.
   Ndukauba, Onyekachi E.
   Ogbonna, Chukwuka U.
   Naibaho, Joncer
   Korus, Maciej
   Okpala, Charles Odilichukwu R.
TI Revisiting food-sourced vitamins for consumer diet and health needs: a
   perspective review, from vitamin classification, metabolic functions,
   absorption, utilization, to balancing nutritional requirements
SO PEERJ
LA English
DT Review
DE Vitamin absorption; Vitamin transport; Micronutrient; Physiological
   function; Animal-based; Plant-based
ID INTESTINAL-ABSORPTION; SOLUBLE VITAMINS; FAT; FOLATE; BIOAVAILABILITY;
   RIBOFLAVIN; PREVALENCE; ACID; MICRONUTRIENTS; COMPLICATIONS
AB The significant attention gained by food-sourced vitamins has provided insights into numerous current researches; for instance, the potential reversal of epigenetic age using a diet and lifestyle intervention, the balance between food and dietary supplements in the general population, the role of diet and food intake in age-related macular degeneration, and the association of dietary supplement use, nutrient intake and mortality among adults. As relevant literature about food-sourced vitamin increases, continuous synthesis is warranted. To supplement existing information, this perspective review discussed food-sourced vitamins for consumer diet and health needs, scoping from vitamin absorption, metabolic functions, utilization, to balancing nutritional requirements. Relevant literatures were identified through a search of databases like Google Scholar, Web of Science, the Interscience Online Library, ScienceDirect, and PubMed. We demonstrated that vitamins whether from plant- and animal-based sources are prerequisites for the metabolic functions of the human body. The fat- and water-soluble classification of vitamins remains consistent with their respective absorption and dissolution potentials, underpinned by numerous physiological functions. Vitamins, largely absorbed in the small intestine, have their bioavailability dependent on the food composition, its associated interactions, as well as alignment with their metabolic functions, which involves antioxidants, coenzymes, electron acceptor/donor, and hormones. Moreover, vitamin deficiencies, in every form, pose a serious threat to human health. Vitamin toxicities remain rare, but can still occur mainly from supplementation, although it appears much less in water-soluble vitamins of which some excesses get readily removed by the human body, different from the fat-soluble ones that are stored in tissues and organs. Besides discussions of absorption, transport, and cellular uptake of vitamins, this perspective review also included approaches to meeting vitamin requirements and therapeutic strategies against micronutrient deficiency and COVID-19. We have also attempted on how to strike the balance between food-sourced vitamins and dietary supplements.
C1 [Ofoedu, Chigozie E.; Igwe, Victory S.; Chacha, James S.; Agunbiade, Adedoyin O.] South China Univ Technol, Dept Food Sci & Engn, Guangzhou, Guangdong, Peoples R China.
   [Ofoedu, Chigozie E.; Iwouno, Jude O.; Ofoedu, Ebelechukwu O.; Ogueke, Chika C.; Igwe, Victory S.; Agunwah, Ijeoma M.; Ofoedum, Arinze F.; Muobike, Onyinye P.; Njoku, Njideka E.; Nwakaudu, Angela A.; Odimegwu, Nkiru E.; Ndukauba, Onyekachi E.] Fed Univ Technol Owerri, Dept Food Sci & Technol, Owerri, Imo State, Nigeria.
   [Chacha, James S.] Sokoine Univ Agr, Dept Food Technol Nutr & Consumer Sci, Morogoro, Tanzania.
   [Agunbiade, Adedoyin O.] Univ Ibadan, Dept Food Sci, Ibadan, Nigeria.
   [Ogbonna, Chukwuka U.] Fed Univ Agr, Dept Biochem, Abeokuta, Ogun, Nigeria.
   [Naibaho, Joncer; Korus, Maciej; Okpala, Charles Odilichukwu R.] Wroclaw Univ Environm & Life Sci, Fac Biotechnol & Food Sci, Wroclaw, Poland.
C3 South China University of Technology; Sokoine University of Agriculture;
   University of Ibadan; University of Agriculture, Abeokuta; Wroclaw
   University of Environmental & Life Sciences
RP Ofoedu, CE (通讯作者)，South China Univ Technol, Dept Food Sci & Engn, Guangzhou, Guangdong, Peoples R China.; Ofoedu, CE (通讯作者)，Fed Univ Technol Owerri, Dept Food Sci & Technol, Owerri, Imo State, Nigeria.; Naibaho, J (通讯作者)，Wroclaw Univ Environm & Life Sci, Fac Biotechnol & Food Sci, Wroclaw, Poland.
EM chigozie.ofoedu@futo.edu.ng; joncer.naibaho@upwr.edu.pl
RI Ofoedu, Chigozie Emmanuel/AAG-2581-2021; Naibaho, Joncer/ABC-6508-2021;
   Okpala, Charles/GQI-4266-2022; Ogueke, Chika/CAF-8124-2022
OI Ofoedu, Chigozie Emmanuel/0000-0002-0835-5872; Naibaho,
   Joncer/0000-0001-9273-0366; Okpala, Charles Odilichukwu
   R./0000-0003-4475-8887
FU Chinese Scholarship Council (CSC); South China University of Technology,
   Guangzhou, Guangdong, China; Wroclaw University of Environmental and
   Life Sciences, Wroclaw, Poland; project UPWR 2.0: international and
   interdisciplinary programme of development of Wroclaw University of
   Environmental and Life Sciences; European Social Fund under the
   Operational Program Knowledge Education Development
   [POWR.03.05.00-00-Z062/18]
FX Chigozie E. Ofoedu, Victory S. Igwe, James S. Chacha, and Adedoyin O.
   Agunbiade received financial support from the Chinese Scholarship
   Council (CSC) and South China University of Technology, Guangzhou,
   Guangdong, China. Maciej Korus, Joncer Naibaho, and Charles Odilichukwu
   R. Okpala received financial support from the Wroclaw University of
   Environmental and Life Sciences, Wroclaw, Poland. This publication was
   financed by the project UPWR 2.0: international and interdisciplinary
   programme of development of Wroclaw University of Environmental and Life
   Sciences, co-financed by the European Social Fund under the Operational
   Program Knowledge Education Development, under contract No.
   POWR.03.05.00-00-Z062/18 of June 4, 2019. There was no additional
   funding received for this study. 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 179
TC 7
Z9 7
U1 4
U2 15
PU PEERJ INC
PI LONDON
PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND
SN 2167-8359
J9 PEERJ
JI PeerJ
PD SEP 1
PY 2021
VL 9
AR e11940
DI 10.7717/peerj.11940
PG 45
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA UR9LR
UT WOS:000697061800005
PM 34557342
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Runhart, EH
   Dhooge, P
   Meester-Smoor, M
   Pas, J
   Pott, JWR
   van Leeuwen, R
   Kroes, HY
   Bergen, AA
   De Jong-Hesse, Y
   Thiadens, AA
   van Schooneveld, MJ
   van Genderen, M
   Boon, C
   Klaver, C
   van den Born, LI
   Cremers, FPM
   Hoyng, CB
AF Runhart, Esmee H.
   Dhooge, Patty
   Meester-Smoor, Magda
   Pas, Jeroen
   Pott, Jan Willem R.
   van Leeuwen, Redmer
   Kroes, Hester Y.
   Bergen, Arthur A.
   De Jong-Hesse, Yvonne
   Thiadens, Alberta A.
   van Schooneveld, Mary J.
   van Genderen, Maria
   Boon, Camiel
   Klaver, Caroline
   van den Born, L. Ingeborg
   Cremers, Frans P. M.
   Hoyng, Carel B.
TI Stargardt disease: monitoring incidence and diagnostic trends in the
   Netherlands using a nationwide disease registry
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE ABCA4; incidence; prevalence; Stargardt Disease; STGD1
ID ABCA4 DISEASE; VARIANTS; GENE; PREVALENCE; DYSTROPHY; ALLELES
AB Purpose To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases. Methods For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry. Results A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (>= 45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (>= 2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1. Conclusion The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention.
C1 [Runhart, Esmee H.; Dhooge, Patty; Pas, Jeroen; Klaver, Caroline; Hoyng, Carel B.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Nijmegen, Netherlands.
   [Runhart, Esmee H.; Dhooge, Patty; Cremers, Frans P. M.; Hoyng, Carel B.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
   [Meester-Smoor, Magda; Thiadens, Alberta A.; Klaver, Caroline] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [Pott, Jan Willem R.] Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, Groningen, Netherlands.
   [van Leeuwen, Redmer; van Genderen, Maria] Univ Med Ctr Utrecht, Dept Ophthalmol, Utrecht, Netherlands.
   [Kroes, Hester Y.] Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands.
   [Bergen, Arthur A.] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
   [Bergen, Arthur A.] Netherlands Inst Neurosci NIN KNAW, Amsterdam, Netherlands.
   [De Jong-Hesse, Yvonne; van Schooneveld, Mary J.; Boon, Camiel] Amsterdam Univ Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands.
   [van Schooneveld, Mary J.; van Genderen, Maria] Bartimeus Diagnost Ctr Complex Visual Disorders, Zeist, Netherlands.
   [Boon, Camiel] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands.
   [Klaver, Caroline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
   [van den Born, L. Ingeborg] Rotterdam Eye Hosp, Rotterdam, Netherlands.
   [van den Born, L. Ingeborg] Rotterdam Ophthalm Inst, Rotterdam, Netherlands.
   [Cremers, Frans P. M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Erasmus
   University Rotterdam; Erasmus MC; University of Groningen; Utrecht
   University; Utrecht University Medical Center; Utrecht University;
   Utrecht University Medical Center; University of Amsterdam; Academic
   Medical Center Amsterdam; Royal Netherlands Academy of Arts & Sciences;
   Netherlands Institute for Neuroscience (NIN-KNAW); Leiden University;
   Leiden University Medical Center (LUMC); Leiden University - Excl LUMC;
   Erasmus University Rotterdam; Erasmus MC; Rotterdam Eye Hospital;
   Radboud University Nijmegen
RP Hoyng, CB (通讯作者)，Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands.
EM carel.hoyng@radboudumc.nl
RI Pas, Jeroen/ABC-2460-2021; Runhart, Esmee/H-6271-2017
OI Pas, Jeroen/0000-0002-0302-6690; Runhart, Esmee/0000-0003-2343-4699
FU Foundation Fighting Blindness USA [PPA-0517-0717-RAD]; Oogfonds;
   Retinafonds; Bartimeus Fonds; ODAS [2015-30]
FX This work was supported by the Foundation Fighting Blindness USA, grant
   no. PPA-0517-0717-RAD (to FPMC and CBH). The study was also supported by
   the Oogfonds, Retinafonds, Bartimeus Fonds and ODAS that contributed
   through UitZicht (2015-30). The funding organizations had no role in the
   design or conduct of this research.
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NR 33
TC 1
Z9 1
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD JUN
PY 2022
VL 100
IS 4
BP 395
EP 402
DI 10.1111/aos.14996
EA AUG 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 1A9ZF
UT WOS:000688099300001
PM 34431609
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Ho, E
   Lei, X
   Flores, T
   Lorach, H
   Huang, T
   Galambos, L
   Kamins, T
   Harris, J
   Mathieson, K
   Palanker, D
AF Ho, Elton
   Lei, Xin
   Flores, Thomas
   Lorach, Henri
   Huang, Tiffany
   Galambos, Ludwig
   Kamins, Theodore
   Harris, James
   Mathieson, Keith
   Palanker, Daniel
TI Characteristics of prosthetic vision in rats with subretinal flat and
   pillar electrode arrays
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; photovoltaics; restoration of sight; retinal
   degeneration
ID RETINAL GANGLION-CELLS; VISUAL-ACUITY; MORPHOMETRIC-ANALYSIS; BIPOLAR
   CELLS; FREQUENCY; DESIGN; TRIAL; EYES
AB Objective. Retinal prostheses aim to restore sight by electrically stimulating the surviving retinal neurons. In clinical trials of the current retinal implants, prosthetic visual acuity does not exceed 20/550. However, to provide meaningful restoration of central vision in patients blinded by age-related macular degeneration (AMD), prosthetic acuity should be at least 20/200, necessitating a pixel pitch of about 50 mu m or lower. With such small pixels, stimulation thresholds are high due to limited penetration of electric field into tissue. Here, we address this challenge with our latest photovoltaic arrays and evaluate their performance in vivo. Approach. We fabricated photovoltaic arrays with 55 and 40 mu m pixels (a) in flat geometry, and (b) with active electrodes on 10 mu m tall pillars. The arrays were implanted subretinally into rats with degenerate retina. Stimulation thresholds and grating acuity were evaluated using measurements of the visually evoked potentials (VEP). Main results. With 55 mu m pixels, we measured grating acuity of 48 +/- 11 mu m, which matches the linear pixel pitch of the hexagonal array. This geometrically corresponds to a visual acuity of 20/192 in a human eye, matching the threshold of legal blindness in the US (20/200). With pillar electrodes, the irradiance threshold was nearly halved, and duration threshold reduced by more than three-fold, compared to flat pixels. With 40 mu m pixels, VEP was too low for reliable measurements of the grating acuity, even with pillar electrodes. Significance. While being helpful for treating a complete loss of sight, current prosthetic technologies are insufficient for addressing the leading cause of untreatable visual impairment-AMD. Subretinal photovoltaic arrays may provide sufficient visual acuity for restoration of central vision in patients blinded by AMD.
C1 [Ho, Elton] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Ho, Elton; Flores, Thomas; Lorach, Henri; Galambos, Ludwig; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Lei, Xin; Huang, Tiffany; Kamins, Theodore; Harris, James] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Flores, Thomas] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Mathieson, Keith] Univ Strathclyde, Inst Photon, Glasgow, Lanark, Scotland.
   [Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford
   University; University of Strathclyde; Stanford University
RP Ho, E (通讯作者)，Stanford Univ, Dept Phys, Stanford, CA 94305 USA.; Ho, E (通讯作者)，Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
EM eltonho@stanford.edu
RI ; Mathieson, Keith/G-6308-2011
OI Palanker, Daniel/0000-0002-0480-3025; LORACH, HENRI/0000-0003-4337-2798;
   Mathieson, Keith/0000-0002-9517-8076
FU National Institutes of Health [R01-EY-018608, R01-EY-027786]; Department
   of Defense [W81XWH-15-1-0009]; Stanford Institute of Neuroscience;
   Research to Prevent Blindness; National Science Foundation
   [ECCS-1542152]; NATIONAL EYE INSTITUTE [R01EY027786] Funding Source: NIH
   RePORTER
FX Supported by the National Institutes of Health (Grants R01-EY-018608,
   R01-EY-027786), the Department of Defense (Grant W81XWH-15-1-0009),
   Stanford Institute of Neuroscience, and Research to Prevent Blindness.
   Photovoltaic arrays were fabricated in the Nano@Stanford labs, which are
   supported by the National Science Foundation under award ECCS-1542152.
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NR 46
TC 26
Z9 26
U1 0
U2 6
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 DEC
PY 2019
VL 16
IS 6
AR 066027
DI 10.1088/1741-2552/ab34b3
PG 10
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA JX5SY
UT WOS:000503795700001
PM 31341094
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Dalvi, S
   Galloway, CA
   Winschel, L
   Hashim, A
   Soto, C
   Tang, C
   MacDonald, LA
   Singh, R
AF Dalvi, Sonal
   Galloway, Chad A.
   Winschel, Lauren
   Hashim, Ali
   Soto, Celia
   Tang, Cynthia
   MacDonald, Leslie A.
   Singh, Ruchira
TI Environmental stress impairs photoreceptor outer segment (POS)
   phagocytosis and degradation and induces autofluorescent material
   accumulation in hiPSC-RPE cells
SO CELL DEATH DISCOVERY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; ARYL-HYDROCARBON RECEPTOR; VESICLE-LIKE
   STRUCTURES; MACULAR DEGENERATION; CIGARETTE-SMOKE; IRON OVERLOAD; FUNDUS
   AUTOFLUORESCENCE; OXIDATIVE STRESS; BRUCHS MEMBRANE; AGE
AB Retinal pigment epithelium (RPE) cell dysfunction is central to the pathogenesis of age-related macular degeneration (AMD), a leading cause of adult blindness. Aging, the single biggest risk factor for AMD development, favors increase in RPE autofluorescent material due to accumulation of POS-digestion by-products through lysosomal dysfunction and impaired POS degradation. Apart from aging, environmental agents affect lysosomal function in multiple model systems and are implicated in AMD. Iron (Fe) overload and cigarette smoke exposure are the two environmental factors that are known to affect the lysosomal pathway and impact RPE cell health. However, the impact of Fe and cigarette smoke, on POS processing and its consequence for autofluorescent material accumulation in human RPE cells are yet to be established. Human induced pluripotent stem cell (hiPSC)-derived RPE, which phagocytoses and degrades POS in culture and can be derived from control individuals (no history/susceptibility for retinal disease), provides a model system to investigate the singular effect of excess Fe and/or cigarette smoke on POS processing by RPE cells. Using at least three distinct control hiPSC lines, we show that, compared to untreated hiPSC-RPE cells, POS uptake is reduced in both Fe (ferric ammonium citrate or FAC) and FAC + CSE (cigarette smoke extract)-treated hiPSC-RPE cells. Furthermore, exposure of hiPSC-RPE cultures to FAC + CSE leads to reduced levels of active cathepsin-D (CTSD), a lysosomal enzyme involved in POS processing, and causes delayed degradation of POS. Notably, delayed degradation of POS over time (2 weeks) in hiPSC-RPE cells exposed to Fe and CSE was sufficient to increase autofluorescent material build-up in these cells. Given that inefficient POS processing-mediated autofluorescent material accumulation in RPE cells has already been linked to AMD development, our results implicate a causative role of environmental agents, like Fe and cigarette smoke, in AMD.
C1 [Dalvi, Sonal; Galloway, Chad A.; Winschel, Lauren; Hashim, Ali; Soto, Celia; Tang, Cynthia; MacDonald, Leslie A.; Singh, Ruchira] Univ Rochester, Dept Ophthalmol, Flaum Eye Inst, Rochester, NY 14627 USA.
   [Dalvi, Sonal; Galloway, Chad A.; Winschel, Lauren; Hashim, Ali; Soto, Celia; Tang, Cynthia; MacDonald, Leslie A.; Singh, Ruchira] Univ Rochester, Dept Biomed Genet, Rochester, NY 14627 USA.
   [Singh, Ruchira] UR Stem Cell & Regenerat Med Inst, Rochester, NY 14627 USA.
   [Singh, Ruchira] Univ Rochester, Ctr Visual Sci, Rochester, NY 14627 USA.
   [Galloway, Chad A.] Univ Rochester, Dept Pathol & Lab Med, Rochester, NY 14627 USA.
C3 University of Rochester; University of Rochester; University of
   Rochester; University of Rochester
RP Singh, R (通讯作者)，Univ Rochester, Dept Ophthalmol, Flaum Eye Inst, Rochester, NY 14627 USA.; Singh, R (通讯作者)，Univ Rochester, Dept Biomed Genet, Rochester, NY 14627 USA.; Singh, R (通讯作者)，UR Stem Cell & Regenerat Med Inst, Rochester, NY 14627 USA.; Singh, R (通讯作者)，Univ Rochester, Ctr Visual Sci, Rochester, NY 14627 USA.
EM ruchira_Singh@urmc.rochester.edu
RI Dalvi, Sonal/AAC-6768-2019; Dalvi, Sonal/GSD-5839-2022
OI Soto, Celia/0000-0003-1787-3249; Galloway, Chad/0000-0002-1978-7339
FU BrightFocus Foundation Macular Degeneration Grant; David Bryant Trust;
   Foundation of Fighting Blindness Individual Investigator Award; National
   Institute of Health [NIH-1R01EY028167]; Retina Research Foundation;
   Research to Prevent Blindness, RPB's Career Development Award; NATIONAL
   EYE INSTITUTE [R01EY028167] Funding Source: NIH RePORTER
FX The authors would like to acknowledge the access to Inhalation Core
   Facility at the University of Rochester to prepare CSE, and Susan
   Messing and Bokai Wang from the Department of Biostatistics and
   Computational Biology at University of Rochester for their consulting
   services in statistical analyses. Electron microscopy was completed at
   the University of Rochester Medical Center Electron Microscope Shared
   Resource Laboratory. This work was supported by the BrightFocus
   Foundation Macular Degeneration Grant (to R.S.), David Bryant Trust (to
   R.S.), Foundation of Fighting Blindness Individual Investigator Award
   (to R.S.), National Institute of Health, NIH-1R01EY028167 (to R.S.),
   Retina Research Foundation and Research to Prevent Blindness, RPB's
   Career Development Award (to R.S.), Unrestricted Challenge Grant to
   Department of Ophthalmology at University of Rochester.
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NR 73
TC 10
Z9 10
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 2058-7716
J9 CELL DEATH DISCOV
JI Cell Death Discov.
PD MAY 16
PY 2019
VL 5
AR 96
DI 10.1038/s41420-019-0171-9
PG 16
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA IC5PU
UT WOS:000471021100001
PM 31123602
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sasajima, H
   Tsuboi, K
   Murotani, K
   Kamei, M
AF Sasajima, Hirofumi
   Tsuboi, Kotaro
   Murotani, Kenta
   Kamei, Motohiro
TI Efficacy and safety of intravitreal drug injections using a short
   34-gauge needle
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Intraocular pressure; Intravitreal injection; Short 34-gauge needle;
   Vascular endothelial growth factor
ID INTRAOCULAR-PRESSURE; MACULAR DEGENERATION; RANIBIZUMAB;
   ENDOPHTHALMITIS; BEVACIZUMAB; EDEMA; SECONDARY; OUTCOMES; AGENTS; TRIAL
AB Purpose To evaluate the efficacy and safety of intravitreal drug injections using a short 34-gauge needle.
   Study design Retrospective study.
   Methods This study included patients with age-related macular degeneration, diabetic macular edema, or macular edema associated with retinal vein occlusion. We reviewed the medical records of consecutive patients with one of those three diseases treated with antivascular endothelial growth factor (VEGF) agents using an 8-mm-long 34-gauge needle. Sustained intraocular pressure (IOP) elevations were defined as IOP exceeding 21 mmHg or 6-mmHg or higher increases from baseline on 2 consecutive visits at least 1 month apart. The main outcome measures were improved best-corrected visual acuity (BCVA), central retinal thickness (CRT), IOP changes, and incidence of complications related to the 34-gauge needle.
   Results Six hundred ninety-eight injections were administered to 243 consecutive patients (mean age, 74.0 years) and reviewed. The mean follow-up time was 30.2 +/- 15.9 weeks. The mean number of intravitreal injections/eye was 2.7 +/- 1.8 (range, 1-9). The mean BCVA improved significantly (P < .0001), from 0.43 +/- 0.4 logarithm of the minimum angle of resolution (logMAR) units at baseline to 0.36 +/- 0.41 logMAR units at the last visit. The mean CRT decreased significantly (P < .0001), from 426.9 +/- 168.5 microns at baseline to 297.6 +/- 121.1 microns at the last visit. The mean IOP decreased significantly (P < .0001), from 13.6 +/- 3.0 mmHg at baseline to 12.9 +/- 3.1 mmHg at the visit after the first injection. A retinal tear occurred in 0.14%/injection (1/698). A sustained IOP elevation occurred in 1.29%/injection (9/698).
   Conclusion Despite a few complications, the short 34-gauge needle was efficacious and safe for anti-VEGF intravitreal injections.
C1 [Sasajima, Hirofumi; Tsuboi, Kotaro; Kamei, Motohiro] Aichi Med Univ, Dept Ophthalmol, 1-1 Yazako Karimata, Nagakute, Aichi 4801195, Japan.
   [Murotani, Kenta] Kurume Univ, Grad Sch Med, Biostat Ctr, Fukuoka, Fukuoka, Japan.
C3 Aichi Medical University; Kurume University
RP Tsuboi, K (通讯作者)，Aichi Med Univ, Dept Ophthalmol, 1-1 Yazako Karimata, Nagakute, Aichi 4801195, Japan.
EM tsuboi.koutarou.230@mail.aichi-med-u.ac.jp
RI Sasajima, Hirofumi/AID-4292-2022
OI Sasajima, Hirofumi/0000-0002-2256-8217; tsuboi,
   kotaro/0000-0001-5119-8414
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NR 31
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAY
PY 2019
VL 63
IS 3
BP 269
EP 275
DI 10.1007/s10384-019-00663-w
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HV9ZP
UT WOS:000466341000006
PM 30955120
DA 2022-11-30
ER

PT J
AU Endersid, C
   Lang, GE
   Dreyhaupt, J
   Loidl, M
   Lang, GK
   Werner, JU
AF Enders, Christian
   Lang, Gabriele E.
   Dreyhaupt, Jens
   Loidl, Max
   Lang, Gerhard K.
   Werner, Jens U.
TI Quantity and quality of image artifacts in optical coherence tomography
   angiography
SO PLOS ONE
LA English
DT Article
AB Objective
   To analyze quality and frequency of OCTA artifacts and to evaluate their impact on the interpretability of OCTA images.
   Design
   75 patients with diabetic retinopathy (DR), retinal artery occlusion (RAO), retinal vein occlusion (RVO), or neovascular age-related macular degeneration (nAMD) and healthy controls were enrolled in this cross-sectional study in the outpatient department of a tertiary eye care center.
   Methods
   All participants underwent an OCTA examination (spectral domain OCT Cirrus 5000 equipped with the AngioPlex module). OCTA scans were analyzed independently by two experienced ophthalmologists. Frequency of various artifacts for the entire OCTA scan and for different segmentation layers and the grading of OCTA interpretability were investigated.
   Results
   The analysis of 75 eyes of 38 women and 37 men between 24 and 94 years were included. Six eyes had no retinal disease, 19 eyes had nAMD, 16 had DR, 19 eyes had RVO, and 15 eyes showed RAO. A macular edema (ME) was present in 40 of the diseased eyes. Projection artifacts occurred in all eyes in any structure below the superficial retinal vessel layer, segmentation and motion artifacts were found in 55% (41/75) and 49% (37/75) of eyes, respectively. Other artifacts occurred less frequently. Segmentation artifacts were significantly more frequent in diseased than in healthy eyes (p< 0.01). Qualitative assessment of OCTA images was graded as excellent in 65% and sufficient in 25% of cases, adding up to 91% images deemed acceptable for examination. Presence of ME was associated with a significantly poorer interpretability (p< 0.01).
   Conclusion and relevance
   Various artifacts appear at different frequencies in OCTA images. Nevertheless, a qualitative assessment of the OCTA images is almost always possible. Good knowledge of possible artifacts and critical analysis of the complete OCTA dataset are essential for correct clinical interpretation and determining a precise clinical diagnosis.
C1 [Enders, Christian; Lang, Gabriele E.; Loidl, Max; Lang, Gerhard K.; Werner, Jens U.] Ulm Univ, Dept Ophthalmol, Ulm, Germany.
   [Dreyhaupt, Jens] Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany.
C3 Ulm University; Ulm University
RP Endersid, C (通讯作者)，Ulm Univ, Dept Ophthalmol, Ulm, Germany.
EM christian.enders@uniklinik-ulm.de
OI Enders, Christian/0000-0003-3922-3765
FU Carl Zeiss Meditec AG, Jena, Germany
FX The authors CE, GEL, ML, GKL and JUW received financial support from
   Carl Zeiss Meditec AG, Jena, Germany. 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 11
TC 38
Z9 39
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 25
PY 2019
VL 14
IS 1
AR e0210505
DI 10.1371/journal.pone.0210505
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HJ2YV
UT WOS:000457037500041
PM 30682050
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Batabyal, S
   Gajjeraman, S
   Bhattacharya, S
   Wright, W
   Mohanty, S
AF Batabyal, Subrata
   Gajjeraman, Sivakumar
   Bhattacharya, Sulagna
   Wright, Weldon
   Mohanty, Samarendra
TI Nano-enhanced Optical Gene Delivery to Retinal Degenerated Mice
SO CURRENT GENE THERAPY
LA English
DT Article
DE Ocular gene therapy; optical delivery; optogenetics; dry-AMD; macular
   degeneration; NOD method
ID ADENOVIRUS-MEDIATED TRANSFER; RESTORES VISUAL RESPONSES; GEOGRAPHIC
   ATROPHY; IN-VIVO; COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; ECTOPIC
   EXPRESSION; GOLD NANOCAGES; PHASE; NANOPARTICLES
AB Background: The efficient and targeted delivery of genes and other impermeable therapeutic molecules into retinal cells is of immense importance for the therapy of various visual disorders. Traditional methods for gene delivery require viral transfection, or chemical methods that suffer from one or many drawbacks, such as low efficiency, lack of spatially targeted delivery, and can generally have deleterious effects, such as unexpected inflammatory responses and immunological reactions.
   Methods: We aim to develop a continuous wave near-infrared laser-based Nano-enhanced Optical Delivery (NOD) method for spatially controlled delivery of ambient-light-activatable Muti-Characteristic opsin-encoding genes into retina in vivo and ex vivo. In this method, the optical field enhancement by gold nanorods is utilized to transiently permeabilize cell membrane, enabling delivery of exogenous impermeable molecules to nanorod-binding cells in laser-irradiated regions.
   Results and Discussion: With viral or other non-viral (e.g. electroporation, lipofection) methods, gene is delivered everywhere, causing uncontrolled expression over the whole retina. This will cause complications in the functioning of non-degenerated areas of the retina. In the NOD method, the contrast in temperature rise in laser-irradiated nanorod-attached cells at nano-hotspots is significant enough to allow site-specific delivery of large genes. The in vitro and in vivo results using NOD, clearly demonstrate in vivo gene delivery and functional cellular expression in targeted retinal regions without compromising the structural integrity of the eye or causing immune response.
   Conclusion: The successful delivery and expression of MCO in the targeted retina after in vivo NOD in the mice models of retinal degeneration opens a new vista for re-photosensitizing retina with geographic atrophies, such as in dry age-related macular degeneration.
C1 [Batabyal, Subrata; Gajjeraman, Sivakumar; Bhattacharya, Sulagna; Wright, Weldon; Mohanty, Samarendra] Nanoscope Technol LLC, 1312 Brown Trail, Bedford, TX 76022 USA.
RP Mohanty, S (通讯作者)，Nanoscope Technol LLC, 1312 Brown Trail, Bedford, TX 76022 USA.
EM smohanty@nanoscopetech.com
OI BATABYAL, SUBRATA/0000-0002-0859-6641; Mohanty,
   Samarendra/0000-0002-6533-383X
FU National Eye Institute; National Institute of Health [1R01EY025717-01A1,
   1R43EY026483-01, 1R43EY025905-01, 1R01 EY028216-01A1,
   2R44EY025905-02A1]; NATIONAL EYE INSTITUTE [R43EY026483, R43EY025905,
   R01EY025717, R01EY028216, R44EY025905] Funding Source: NIH RePORTER
FX The study is funded by National Eye Institute and National Institute of
   Health (1R01EY025717-01A1, 1R43EY026483-01, 1R43EY025905-01, 1R01
   EY028216-01A1, 2R44EY025905-02A1).
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NR 65
TC 5
Z9 5
U1 3
U2 11
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1566-5232
EI 1875-5631
J9 CURR GENE THER
JI Curr. Gene Ther.
PY 2019
VL 19
IS 5
BP 318
EP 329
DI 10.2174/1566523219666191017114044
PG 12
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA JZ0DH
UT WOS:000504774400004
PM 31625475
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Biswal, MR
   Prentice, HM
   Smith, GW
   Zhu, P
   Tong, Y
   Dorey, CK
   Lewin, AS
   Blanks, JC
AF Biswal, Manas R.
   Prentice, Howard M.
   Smith, George W.
   Zhu, Ping
   Tong, Yao
   Dorey, C. Kathleen
   Lewin, Alfred S.
   Blanks, Janet C.
TI Cell-specific gene therapy driven by an optimized hypoxia-regulated
   vector reduces choroidal neovascularization
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Choroidal neovascularization; Retinal pigment epithelium; Hypoxia
   responsive element; Endostatin; Adeno-associated virus; Gene therapy;
   Age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; MITOCHONDRIAL OXIDATIVE STRESS; INDUCIBLE
   FACTOR-I; MACULAR DEGENERATION; MEDIATED DELIVERY; OCULAR
   NEOVASCULARIZATION; TRANSGENE EXPRESSION; VMD2 PROMOTER; ENDOSTATIN;
   DISEASE
AB Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization. An adeno-associated virus (AAV2) vector comprising a RPE-specific promoter and HIF-1 response elements (HRE) was designed to regulate production of human endostatin (a powerful angiostatic protein) in RPE. The vector was tested in a mouse model of laser-induced CNV using subretinal delivery. Spectral domain optical coherence tomography (SD-OCT) images from live mice and confocal images from lectin stained RPE flat mount sections demonstrated reduction in CNV areas by 80% compared to untreated eyes. Quantitative real-time polymerase chain reaction (qPCR) confirmed exogenous endostatin mRNA expression from the regulated vector that was significantly elevated 3, 7, and 14days following laser treatment, but its expression was completely shut off after 45days. Thus, RPE-specific, hypoxia-regulated delivery of anti-angiogenic proteins could be a valuable therapeutic approach to treat neovascular AMD at the time and in the ocular space where it arises.Key pointsAn optimized gene therapy vector targeting hypoxia and tissue-specific expression has been designed.The inhibitory role of gene therapy vector was tested in a mouse model of laser-induced CNV.An 80% reduction in choroidal neovascularization was achieved by the optimized vector.The expression of endostatin was limited to retinal pigment epithelium and regulated by hypoxia.
C1 [Biswal, Manas R.; Smith, George W.; Blanks, Janet C.] Florida Atlantic Univ, Dept Biol, Integrat Biol Program, Boca Raton, FL 33431 USA.
   [Biswal, Manas R.; Tong, Yao; Lewin, Alfred S.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA.
   [Prentice, Howard M.] Florida Atlantic Univ, Charles E Schmidt Coll Med, 777 Glades Rd, Boca Raton, FL 33431 USA.
   [Prentice, Howard M.; Blanks, Janet C.] Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA.
   [Zhu, Ping] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Dorey, C. Kathleen] Virginia Tech Caril Sch Med, Roanoke, VA USA.
C3 State University System of Florida; Florida Atlantic University; State
   University System of Florida; University of Florida; State University
   System of Florida; Florida Atlantic University; State University System
   of Florida; Florida Atlantic University; State University System of
   Florida; University of Florida
RP Prentice, HM (通讯作者)，Florida Atlantic Univ, Charles E Schmidt Coll Med, 777 Glades Rd, Boca Raton, FL 33431 USA.; Prentice, HM (通讯作者)，Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA.
EM hprentic@health.fau.edu
RI Core, Vector/CAF-4832-2022
OI Biswal, Manas/0000-0002-9685-2923; Lewin, Alfred/0000-0002-4192-9727
FU NIH [EYO16119, 1K99EY027013]; NIH Core grant [P30EY014801]; Research
   Priority grant from FAU; Davimos Family Endowment for Excellence in
   Science; American Heart Association grant [0815022E]
FX This research was supported by NIH grant EYO16119 (JCB), NIH Core grant
   P30EY014801 (ASL), Research Priority grant from FAU (JCB), Davimos
   Family Endowment for Excellence in Science (JCB), American Heart
   Association grant 0815022E (MRB), and NIH grant 1K99EY027013 [MRB].
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NR 61
TC 10
Z9 10
U1 0
U2 10
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD OCT
PY 2018
VL 96
IS 10
BP 1107
EP 1118
DI 10.1007/s00109-018-1683-0
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Research & Experimental Medicine
GA GT3LL
UT WOS:000444404400009
PM 30105447
DA 2022-11-30
ER

PT J
AU Fernando, N
   Natoli, R
   Racic, T
   Wooff, Y
   Provis, J
   Valter, K
AF Fernando, Nilisha
   Natoli, Riccardo
   Racic, Tanja
   Wooff, Yvette
   Provis, Jan
   Valter, Krisztina
TI The use of the vaccinia virus complement control protein (VCP) in the
   rat retina
SO PLOS ONE
LA English
DT Article
ID SENILE MACULAR DEGENERATION; FACTOR-H POLYMORPHISM; PHOTORECEPTOR
   DEGENERATION; BRUCHS MEMBRANE; 2 PARTS; ACTIVATION; MICROGLIA; DRUSEN;
   SYSTEM; INFLAMMATION
AB The complement system is highly implicated in both the prevalence and progression of Age Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. We aimed to investigate the potential of VCP as a therapeutic molecule for retinal degenerations. In this study, we investigated the effect, localisation and delivery of VCP to the rodent retina. Complement inhibition activity of VCP was tested using a hemolytic assay. Photoreceptor cell death, inflammation and retinal stress were assayed to determine if any retinal toxicity was induced by an intravitreal injection of VCP. The effect of VCP was investigated in a model of photo-oxidative retinal degeneration. Localisation of VCP after injection was determined using a fluorescein-tagged form of VCP, as well as immunohistochemistry. Finally, a copolymer resin (Elvax) was trialled for the slow-release delivery of VCP to the retina. We found that a dose equivalent to 20 mu g VCP when intravitreally injected into the rat eye did not cause any photoreceptor cell death or immune cell recruitment, but led to an increase in GFAP. In photo-oxidative damaged retinas, there were no differences in photoreceptor loss, retinal stress (Gfap) and inflammation (Ccl2 and C3) between VCP and saline-injected groups; however, Jun expression was reduced in VCP-treated retinas. After VCP was injected into the eye, it was taken up in all layers of the retina but was cleared within 1-3 hours of delivery. This study indicates that a method to sustain the delivery of VCP to the retina is necessary to further investigate the effect of VCP as a complement inhibitor for retinal degenerations.
C1 [Fernando, Nilisha; Natoli, Riccardo; Racic, Tanja; Wooff, Yvette; Provis, Jan; Valter, Krisztina] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.
   [Natoli, Riccardo; Wooff, Yvette; Provis, Jan; Valter, Krisztina] Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University
RP Valter, K (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia.; Valter, K (通讯作者)，Australian Natl Univ, ANU Med Sch, Canberra, ACT, Australia.
EM krisztina.valter-kocsi@anu.edu.au
RI Wooff, Yvette/AAS-4835-2020; Valter, Krisztina/L-3015-2016
OI Natoli, Riccardo/0000-0002-9350-0439; Fernando,
   Nilisha/0000-0002-8488-1348; Valter, Krisztina/0000-0002-2033-0408
FU National Health and Medical Research Council (NHMRC) [APP1049990]; ARC
   CoE program [CE0561903]; Australian Government Research Training Program
FX This study was supported by the National Health and Medical Research
   Council (NHMRC, APP1049990), the ARC CoE program (CE0561903) and the
   Australian Government Research Training Program. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; This study was supported by the National
   Health and Medical Research Council (NHMRC, APP1049990), the ARC CoE
   program (CE0561903) and the Australian Government Research Training
   Program. The authors thank Girish Kotwal for his guidance at the early
   stages of this research, and Kathy Liszewski, Paula Bertram and John
   Atkinson (Washington University School of Medicine) for kindly providing
   the VCP antibodies.
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NR 62
TC 3
Z9 3
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 13
PY 2018
VL 13
IS 3
AR e0193740
DI 10.1371/journal.pone.0193740
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FZ0JA
UT WOS:000427253500011
PM 29534078
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Ayaz, L
   Dinc, E
AF Ayaz, Lokman
   Dinc, Erdem
TI Evaluation of microRNA responses in ARPE-19 cells against the oxidative
   stress
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Oxidative stress; miRNA; microRNA; ARPE-19 cells; age-related macular
   degeneration; AMD
ID DIABETIC-RETINOPATHY; EXPRESSION; INFLAMMATION
AB Purpose: This study aimed to determine microRNA (miRNA) expression profile of human retinal pigment epithelium cell (ARPE-19) against the oxidative stress induced by hydrogen peroxide (H2O2).Methods: ARPE-19 cells were incubated with different concentrations of H2O2 (200, 600 and 800M) for 18h, and then cell viability, vascular endothelial growth factor levels and total oxidant status were evaluated. Expressions of 1152 miRNA were determined by quantitative real-time PCR in each group.Results: Expressions of 90 miRNA were significantly changed in the ARPE-19 cells incubated with H2O2 compared to control group. However, miR-143-3p was only found to be expressed in groups incubated with H2O2. While 24 miRNA (hsa-miR-200c-3p, miR-192-5p, miR-194-5p, miR-141-3p, miR-658, miR-18b-5p, miR-486-5p, miR-525-3p, miR-493-3p, miR-518d-3p, miR-29b-1-5p, miR-675-3p, miR-1238-3p, miR-195-3p, miR-1539, miR-490-5p, miR-3200-5p, miR-1273d, miR-130a-5p, miR-30b-5p, miR-1247-5p, miR-1910-5p, miR27a-5p and miR-200b-3p) upregulated due to the increased dose of H2O2, nine miRNA (hsa-miR-96-5p, miR-33a-5p, miR-345-5p, miR-106b-3p, miR-1285-3p, miR-23b-5p, miR-27b-5p, miR-103a-3p and miR-4289) were also found to be downregulated.Conclusion: This study suggests that oxidative stress may be an important factor on expression of miRNAs in ARPE-19 cells. These miRNAs may have a role in the pathogenesis of age-related macular degeneration related to oxidative stress. However, this relationship needs to be examined in new studies by evaluation of pathways and target genes.
C1 [Ayaz, Lokman] Trakya Univ, Sch Pharm, Dept Biochem, TR-22030 Edirne, Turkey.
   [Dinc, Erdem] Mersin Univ, Sch Med, Dept Ophthalmol, Mersin, Turkey.
C3 Trakya University; Mersin University
RP Ayaz, L (通讯作者)，Trakya Univ, Sch Pharm, Dept Biochem, TR-22030 Edirne, Turkey.
EM lokmanayaz@yahoo.com
FU Scientific and Technological Research Council of Turkey (TUBITAK)
   [114S790]
FX This study was supported by The Scientific and Technological Research
   Council of Turkey (TUBITAK) [Grant No. 114S790].
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NR 25
TC 36
Z9 39
U1 1
U2 17
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1556-9527
EI 1556-9535
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PY 2018
VL 37
IS 2
BP 121
EP 126
DI 10.1080/15569527.2017.1355314
PG 6
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA GB7SW
UT WOS:000429276400003
PM 28707489
DA 2022-11-30
ER

PT J
AU Leyk, J
   Daly, C
   Janssen-Bienhold, U
   Kennedy, BN
   Richter-Landsberg, C
AF Leyk, Janina
   Daly, Conor
   Janssen-Bienhold, Ulrike
   Kennedy, Breandan N.
   Richter-Landsberg, Christiane
TI HDAC6 inhibition by tubastatin A is protective against oxidative stress
   in a photoreceptor cell line and restores visual function in a zebrafish
   model of inherited blindness
SO CELL DEATH & DISEASE
LA English
DT Article
ID CONE PHOTORECEPTORS; THERAPEUTIC TARGET; MOUSE MODEL; DEACETYLASE;
   HSP90; PEROXIREDOXINS; EXPRESSION; NEUROPROTECTION; PROLIFERATION;
   DEGENERATION
AB Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular degeneration, are characterized by the progressive loss of photoreceptors. Histone deacetylase 6 (HDAC6) is considered as a stress surveillance factor and a potential target for neuroprotection and regeneration. Overexpression of HDAC6 has been connected to neurodegenerative disorders, and its suppression may provide protection. Here we show that HDAC6 is constitutively present in the mouse retina, and in the cone-like mouse cell line 661W. In 661W cells HDAC6 inhibition by the specific inhibitor tubastatin A (TST) led to the acetylation of a-tubulin, which is a major substrate for HDAC6. After oxidative stress, exerted by hydrogen peroxide, TST promoted cell survival and the upregulation of heat-shock proteins HSP70 and HSP25 by activation of heat-shock transcription factor 1. Furthermore, in response to oxidative stress the redox regulatory protein peroxiredoxin 1 (Prx1) was modulated in 661W cells by HDAC6 inhibition. The peroxide reducing activity of Prx1 is dependent on its acetylation, which is mediated by HDAC6. Pre-incubation with TST prevented the inactivation of Prx1 and its preserved activity may exert protective effects in photoreceptor cells. To determine whether TST treatment has a therapeutic effect on visual function, the dye(ucd6) zebrafish model of inherited sight loss was utilized. Zebrafish have developed as a suitable model system for pharmacological testing. In vivo application of TST caused the hyperacetylation of alpha-tubulin, indicating that HDAC6 is active in this model. Furthermore, TST was sufficient to rescue visual function and retinal morphology. Hence, HDAC6 inhibition and the regulation of peroxiredoxin activity may play a significant role in protecting retinal cells and in particular photoreceptors, which are exposed to high levels of reactive oxygen species derived from oxidative stress-induced injuries.
C1 [Leyk, Janina; Richter-Landsberg, Christiane] Carl von Ossietzky Univ Oldenburg, Dept Neurosci, Mol Neurobiol, POB 2503, D-26111 Oldenburg, Germany.
   [Daly, Conor; Kennedy, Breandan N.] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin D04 V1W8, Ireland.
   [Janssen-Bienhold, Ulrike] Carl von Ossietzky Univ Oldenburg, Dept Neurosci, Visual Neurosci, D-26111 Oldenburg, Germany.
C3 Carl von Ossietzky Universitat Oldenburg; University College Dublin;
   Carl von Ossietzky Universitat Oldenburg
RP Richter-Landsberg, C (通讯作者)，Carl von Ossietzky Univ Oldenburg, Dept Neurosci, Mol Neurobiol, POB 2503, D-26111 Oldenburg, Germany.
EM Christiane.Richter.Landsberg@Uni-Oldenburg.de
RI Leyk, Janina/N-7182-2017; kennedy, Breandan/H-5643-2019
OI Leyk, Janina/0000-0001-5230-9382; kennedy, Breandan/0000-0001-7991-4689
FU DFG [GRK 1885/1]; Fighting Blindness; Health Research Board in Ireland
   [MRCG/2014/3]
FX This work was supported by the DFG grant GRK 1885/1. This publication is
   independent research partly funded by Fighting Blindness and the Health
   Research Board in Ireland under Grant No: MRCG/2014/3. Any opinions,
   findings, conclusions or recommendations expressed are those of the
   author(s) and not necessarily those of Fighting Blindness or the HRB.
   CRL and JL thank Angelika Spanjer, Irina Fomins and Bettina Kewitz for
   excellent technical assistance and Dr. Olaf Goldbaum for helpful
   discussions. BK and CD thank Ms. Julie Slade for assistance with
   zebrafish visual function assays. UCD Conway Institute Imaging Core for
   zebrafish histology preparation and imaging.
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NR 60
TC 30
Z9 31
U1 0
U2 15
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 AUG
PY 2017
VL 8
AR e3028
DI 10.1038/cddis.2017.415
PG 9
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FG1JB
UT WOS:000409550500066
PM 29048427
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Toledano, S
   Lu, HY
   Palacio, A
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   Kessler, O
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   Barak, Y
AF Toledano, Shire
   Lu, Huayi
   Palacio, Agustina
   Ziv, Keren
   Kessler, Ofra
   Schaal, Shlomit
   Neufeld, Gera
   Barak, Yoreh
TI A Sema3C Mutant Resistant to Cleavage by Furin (FR-Sema3C) Inhibits
   Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; BIPOLAR CELLS;
   SEMAPHORIN 3E; MOUSE MODEL; RECEPTOR; NEUROPILIN-1; VEGF; EXPRESSION;
   ANGIOGENESIS
AB In age-related macular degeneration (AMD), abnormal sub retinal choroidal neovascularization (CNV) is a major cause of blindness. FR-sema3C is a point mutated form of semaphorin-3C that is resistant to cleavage by furin like pro-protein convertases (FPPC). We have found in previous work that FR-sema3C functions as an anti-angiogenic factor. In this study we investigated the possible use of FR-sema3C as an inhibitor of CNV. FR-sema3C inhibits VEGF as well as PDGF-BB signal transduction in endothelial cells and to less extent bFGF induced signal transduction using a mechanism that does not depend upon the binding of VEGF like the drugs that are currently the mainstay treatment for AMD. CNV was induced in eyes of C57 black mice by laser photocoagulation. Intravitreal injection of FR-Sema3C or aflibercept (VEGF-trap) was then used to inhibit CNV formation. Invading choroidal vessels were visualized a week later by injection of FITC-dextran into the circulation, followed by the measurement of the area of the invading blood vessels. Injection of 0.1 mu g FR-Sema3C inhibited CNV by 55% (P<0.01) and was as effective as 5 mu g aflibercept. FR-sema3C did not display any adverse effects on retinal function following its injection into eyes of healthy mice as assessed by optokinetic reflex (OKR) and Electro-retinogram (ERG) criteria. Furthermore, FR-sema3C did not induce apoptosis in the retina as determined by TUNEL nor was there any discernable structural damage to the retina as assessed by several immuno-histochemical criteria. Our results suggest that FR-sema3C could perhaps be used for the treatment of AMD, and that it may perhaps be of benefit to patients that do not respond well to current treatments relying on VEGF sequestering agents.
C1 [Toledano, Shire; Ziv, Keren; Kessler, Ofra; Neufeld, Gera] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Canc Res & Vasc Biol Ctr, Haifa, Israel.
   [Lu, Huayi] Jilin Univ, Hosp 2, Changchun, Jilin Province, Peoples R China.
   [Lu, Huayi; Palacio, Agustina; Schaal, Shlomit] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
   [Schaal, Shlomit] Univ Massachusetts, Dept Ophthalmol & Visual Sci, Sch Med, Amherst, MA 01003 USA.
   [Barak, Yoreh] Rambam Med Ctr, Dept Ophthalmol, Haifa, Israel.
C3 Technion Israel Institute of Technology; Rappaport Faculty of Medicine;
   Jilin University; University of Louisville; University of Massachusetts
   System; University of Massachusetts Amherst; Rambam Health Care Campus;
   Technion Israel Institute of Technology
RP Neufeld, G (通讯作者)，Technion Israel Inst Technol, Bruce Rappaport Fac Med, Canc Res & Vasc Biol Ctr, Haifa, Israel.; Schaal, S (通讯作者)，Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.; Schaal, S (通讯作者)，Univ Massachusetts, Dept Ophthalmol & Visual Sci, Sch Med, Amherst, MA 01003 USA.; Barak, Y (通讯作者)，Rambam Med Ctr, Dept Ophthalmol, Haifa, Israel.
EM s.schaal@umassmed.edu; gera@tx.technion.ac.il; yorehb@gmail.com
RI Neufeld, Gera/F-1524-2019; Palacio, Agustina/ABD-7463-2021
OI Barak, Yoreh/0000-0002-6941-862X; Toledano, Shira/0000-0002-2590-6066
FU ISF [940/11]; BSF [2013213]; Rappaport family grant
FX This work was supported by ISF grant 940/11 to GN
   (http://www.isf.org.il/#/), BSF grant to YB and SS GRANT# 2013213,
   (http://www.bsf.org.il/BSFPublic/DefaultPage1.aspx?PageId=22&innerTextID
   =22), and Rappaport family grant to GN (http://www.rappaport.org.il/).
   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 60
TC 5
Z9 6
U1 1
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 30
PY 2016
VL 11
IS 12
AR e0168122
DI 10.1371/journal.pone.0168122
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EG7LN
UT WOS:000391229300012
PM 28036336
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Nariani, A
   Williams, B
   Hariprasad, SM
AF Nariani, Ashiyana
   Williams, Blake
   Hariprasad, Seenu M.
TI Long-term effect of anti-vascular endothelial growth factor injections
   on intraocular pressure
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; diabetic macular edema; intraocular
   pressure; intravitreal anti-vascular endothelial growth factor
   injections
ID INTRAVITREAL INJECTION; SUSTAINED ELEVATION; BEVACIZUMAB; RANIBIZUMAB;
   EYES; PREDICTORS
AB Objective: There is a substantial debate in the ophthalmology community about whether anti-vascular endothelial growth factor (VEGF) injections result in a long-term increase in intraocular pressure (IOP). Design: We performed a retrospective study to investigate how the number and timing of intravitreal injections in patients with age-related macular degeneration (AMD) and diabetic macular edema (DME) affect IOP over time. Methods: We collected long-term IOP data on patients receiving anti-VEGF injections at our institution. Patients over the age of 40 years who received injections for AMD (n = 76) or DME (n = 55) were included. Patients were grouped according to indication as well as number of injections received (1-3, 4-6, 7-9, or 10+ injections). IOP measurements were then placed into time points (0-6, 6-12, 12-18, 18-24, or 24+ months) and compared to the preinjection average IOP. Results: For patients with DME, average preinjection IOP was 15.7 mmHg. At 24+ months after injection, the average IOP was 15.2 (P = 0.68) for patients receiving 1-3 injections, 16.8 (P = 0.23) for 4-6 injections, and 14.4 (P = 0.66) for 7-9 injections. For patients with AMD, average initial IOP was 15.6 mmHg. At 24+ months after injection, the average IOP was 12.6 (P = 0.97) for 1-3 injections, 14.9 (P = 0.96) for 4-6 injections, 14.8 (P = 0.84) for 7-9 injections, and 15.7 (P = 0.56) for 10+ injections. Conclusions: There was no increase in IOP over time for AMD or DME patients, regardless of how many injections they received. For patients receiving unilateral injections, there was no increase in IOP in the injected eye when compared to the noninjected eye.
C1 [Nariani, Ashiyana; Williams, Blake; Hariprasad, Seenu M.] Univ Chicago, Pritzker Sch Med, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA.
C3 University of Chicago
RP Hariprasad, SM (通讯作者)，Univ Chicago, Dept Ophthalmol & Visual Sci, 5841 South Maryland,MC 2114, Chicago, IL 60637 USA.
EM retina@uchicago.edu
CR Abedi G, 2013, SEMIN OPHTHALMOL, V28, P126, DOI 10.3109/08820538.2013.771195
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NR 27
TC 5
Z9 6
U1 0
U2 0
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 SEP
PY 2016
VL 64
IS 9
BP 643
EP 647
DI 10.4103/0301-4738.194329
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EE0ZR
UT WOS:000389310100006
PM 27853011
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Calzia, D
   Panfoli, I
   Heinig, N
   Schumann, U
   Ader, M
   Traverso, CE
   Funk, RHW
   Roehlecke, C
AF Calzia, Daniela
   Panfoli, Isabella
   Heinig, Nora
   Schumann, Ulrike
   Ader, Marius
   Traverso, Carlo Enrico
   Funk, Richard H. W.
   Roehlecke, Cora
TI Impairment of extramitochondrial oxidative phosphorylation in mouse rod
   outer segments by blue light irradiation
SO BIOCHIMIE
LA English
DT Article
DE ATP synthase; Blue light; Electron transport chain; Reactive oxidative
   phosphorylation oxygen intermediates
ID MITOCHONDRIAL COMPLEX-I; MACULAR DEGENERATION; SUPERCOMPLEX
   ORGANIZATION; FUNCTIONAL EXPRESSION; VERTEBRATE RETINA; METABOLISM;
   PHOTORECEPTORS; RETINOPATHIES; DEACTIVATION; LIPOFUSCIN
AB Exposure to short wavelength light causes increased reactive oxygen intermediates production in the outer retina, particularly in the rod Outer Segments (OS). Consistently, the OS were shown to conduct aerobic ATP production through the ectopic expression of the electron transfer chain complexes I-IV and F1Fo-ATP synthase. These facts prompted us to verify if the oxidative phosphorylation in the OS is implied in the oxidative damage of the blue-light (BL) treated OS, in an organotypic model of mouse retina.
   Whole mouse eyeball cultures were treated with short wavelength BL (peak at 405 nm, output power 1 mW/cm(2)) for 6 h. Immunogold transmission electron microscopy confirmed the expression of Complex I and F1Fo-ATP synthase in the OS. In situ histochemical assays on unfixed sections showed impairment of respiratory Complexes I and II after BL exposure, both in the OS and IS, utilized as a control. Basal 02 consumption and ATP synthesis were impaired in the OS purified from blue-light irradiated eyeball cultures. Electron transfer capacity between Complex I and II as well as activity of Complexes I and II was decreased in blue-light irradiated purified OS.
   The severe malfunctioning of the OS aerobic respiratory capacity after 6 h BL treatment may be the consequence of a self-induced damage. BL exposure would cause an initial over-functioning of both the phototransduction and respiratory chain, with reactive oxygen species production. In a self-renewal vicious cycle, membrane and protein oxidative damage, proton leakage and uncoupling, would impair redox chains, perpetuating the damage and causing hypo-metabolism with eventual apoptosis of the rod. Data may shed new light on the rod-driven retinopathies such as Age Related Macular Degeneration, of which blue-light irradiated retina represents a model. (C) 2016 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
C1 [Calzia, Daniela; Panfoli, Isabella] Univ Genoa, Biochem & Physiol Lab, Dept Pharm DIFAR, Vle Benedetto 15 3, I-16132 Genoa, Italy.
   [Heinig, Nora; Schumann, Ulrike; Funk, Richard H. W.; Roehlecke, Cora] Tech Univ TU Dresden, Dept Anat, Dresden, Germany.
   [Ader, Marius] CRTD, Dresden, Germany.
   [Traverso, Carlo Enrico] Univ Genoa, IRCCS Azienda Osped Univ San Martino IST, Clin Oculist, DiNOGMI, Vle Benedetto 15 6, I-16132 Genoa, Italy.
C3 University of Genoa; Technische Universitat Dresden; Technische
   Universitat Dresden; University of Genoa; IRCCS AOU San Martino IST
RP Panfoli, I (通讯作者)，Univ Genoa, Sch Med & Pharmaceut Sci, DIFAR Dept Pharm, Biochem Lab, Vle Benedetto 15 3, I-16132 Genoa, Italy.
RI Ader, Marius/E-7535-2010; Panfoli, Isabella/X-1247-2019
OI Ader, Marius/0000-0001-9467-7677; Panfoli, Isabella/0000-0002-6261-1128;
   Schumann, Ulrike/0000-0003-3406-4849
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NR 36
TC 16
Z9 16
U1 0
U2 4
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
EI 1638-6183
J9 BIOCHIMIE
JI Biochimie
PD JUN
PY 2016
VL 125
BP 171
EP 178
DI 10.1016/j.biochi.2016.03.016
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DN1FJ
UT WOS:000376811400019
PM 27059514
DA 2022-11-30
ER

PT J
AU Foss, AJE
   Childs, M
   Reeves, BC
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   Tesha, P
   Dhar-Munshi, S
   Mughal, S
   Culliford, L
   Rogers, CA
   Tan, W
   Montgomery, A
AF Foss, Alexander J. E.
   Childs, Margaret
   Reeves, Barnaby C.
   Empeslidis, Theo
   Tesha, Paul
   Dhar-Munshi, Sushma
   Mughal, Samah
   Culliford, Lucy
   Rogers, Chris A.
   Tan, Wei
   Montgomery, Alan
TI Comparing different dosing regimens of bevacizumab in the treatment of
   neovascular macular degeneration: study protocol for a randomised
   controlled trial
SO TRIALS
LA English
DT Article
DE Age-related macular degeneration; Avastin (R); Bevacizumab; Trial
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL RANIBIZUMAB
   LUCENTIS; 2.0 MG RANIBIZUMAB; VEGF TRAP; AGE; PHARMACOKINETICS;
   EFFICACY; RECEPTOR; SAFETY; FCRN
AB Background: Bevacizumab (Avastin (R)) is as effective as ranibizumab (Lucentis (R)) in the treatment of neovascular age-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active sites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly longer half-life. These agents have been associated with systemic complications including strokes, so it is desirable to use the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which present a significant challenge both to the hospital services and to the patients (who are elderly).
   Methods/Design: Patients >= 50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received treatment to either eye for the previous six months. We have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention, with patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review. The aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year period. The primary endpoint is time to treatment failure to be analysed using Cox regression.
   Discussion: This randomised control trial will show if half dose and two monthly as required is as effective as full dose and monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost and the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the safety profile of this treatment regime.
C1 [Foss, Alexander J. E.] Queens Med Ctr, Dept Ophthalmol, Nottingham NG7 2UH, England.
   [Childs, Margaret; Mughal, Samah; Tan, Wei; Montgomery, Alan] Queens Med Ctr, Nottingham Clin Trials Unit, Nottingham NG7 2UH, England.
   [Reeves, Barnaby C.; Culliford, Lucy; Rogers, Chris A.] Univ Bristol, Bristol Royal Infirm, Clin Trials & Evaluat Unit, Bristol BS2 8HW, England.
   [Empeslidis, Theo] Leicester Royal Infirm, Leicester LE1 5WW, Leics, England.
   [Tesha, Paul] Lincoln Cty Hosp, Lincoln LN2 5QY, England.
   [Dhar-Munshi, Sushma] Kings Mill Hosp, Dept Ophthalmol, Sutton In Ashfield NG17 4JL, England.
C3 University of Nottingham; University of Nottingham; Bristol Royal
   Infirmary; University of Bristol; University of Leicester
RP Foss, AJE (通讯作者)，Queens Med Ctr, Dept Ophthalmol, Middleton Blvd, Nottingham NG7 2UH, England.
EM Alexander.Foss@nottingham.ac.uk
OI Reeves, Barnaby/0000-0002-5101-9487; Foss,
   Alexander/0000-0001-9649-0072; Montgomery, Alan/0000-0003-0450-1606
FU MRC [MR/K025643/1] Funding Source: UKRI; National Institute for Health
   Research [NF-SI-0514-10114] Funding Source: researchfish; Medical
   Research Council [MR/K025643/1] Funding Source: Medline
CR Arevalo JF, 2008, RETINA-J RET VIT DIS, V28, P1387, DOI 10.1097/IAE.0b013e3181884ff4
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NR 32
TC 6
Z9 6
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD MAR 10
PY 2015
VL 16
AR 85
DI 10.1186/s13063-015-0608-2
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA CE4SW
UT WOS:000351821400001
PM 25873213
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Pinheiro-Costa, J
   Costa, JM
   Beato, JN
   Freitas-da-Costa, P
   Brandao, E
   Falcao, MS
   Falcao-Reis, F
   Carneiro, AM
AF Pinheiro-Costa, Joao
   Costa, Jose M.
   Beato, Joao N.
   Freitas-da-Costa, Paulo
   Brandao, Elisete
   Falcao, Manuel S.
   Falcao-Reis, Fernando
   Carneiro, Angela M.
TI Switch to Aflibercept in the Treatment of Neovascular AMD: One-Year
   Results in Clinical Practice
SO OPHTHALMOLOGICA
LA English
DT Article
DE Aflibercept; Bevacizumab; Choroidal neovascularization; Ranibizumab;
   Switch; Wet age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; ANTI-VEGF THERAPY; MACULAR DEGENERATION;
   INTRAVITREAL BEVACIZUMAB; PHOTODYNAMIC THERAPY; ANATOMICAL OUTCOMES;
   TRAP-EYE; RANIBIZUMAB; TACHYPHYLAXIS; DISEASE
AB Purpose: To report the clinical outcomes of intravitreal aflibercept therapy in eyes with refractory and recurrent neovascular age-related macular degeneration (AMD) switched from intravitreal bevacizumab or ranibizunnab. Methods: This is a retrospective review of eyes with neovascular AMD switched to intravitreal aflibercept with at least 1 year of follow-up after the switch. All patients had had a minimum of 3 injections of bevacizumab or ranibizumab before the switch. Aflibercept was used in patients considered refractory to bevacizumab (group 1) and in recurrent patients on therapy with ranibizumab due to an institutional policy decision (group 2). Changes in best-corrected visual acuity, fluid on optical coherence tomography (OCT), central retinal thickness (CRT) and the frequency of injections were compared. Results: Eighty-five eyes of 69 patients were analyzed, 39 eyes in group 1 and 46 in group 2. The mean follow-up time was 31.6 months prior to the switch and 14.7 months on treatment with aflibercept. One year after the switch, there was a nonsignificant mean decrease of 2 letters in visual acuity in both groups (group 1: from 58.2 to 55.8 letters, p = 0.086; group 2: from 56.4 to 54.5 letters, p = 0.168), but the mean number of injections per month was significantly lower (from 0.76 to 0.57, p<0.001). With the switch, 90.6% of the patients showed anatomic improvement with a reduction of fluid on OCT, and both groups presented significant improvement in CRT (group 1: 65.3 mu m, p = 0.051; group 2: 91.0 mu m, p < 0.001). Conclusion: Aflibercept appears to be a valuable tool for the management of patients with poor responses to other anti-vascular endothelial growth factor drugs. These patients could have anatomic improvement, and the injection intervals could be extended. (C) 2015 S. Karger AG, Basel
C1 [Pinheiro-Costa, Joao; Beato, Joao N.; Freitas-da-Costa, Paulo; Brandao, Elisete; Falcao, Manuel S.; Falcao-Reis, Fernando; Carneiro, Angela M.] Univ Porto, Fac Med, Hosp Sao Joao, Dept Ophthalmol, P-4200319 Oporto, Portugal.
   [Costa, Jose M.] Univ Porto, Fac Med, P-4200319 Oporto, Portugal.
   [Pinheiro-Costa, Joao; Freitas-da-Costa, Paulo] Univ Porto, Fac Med, Dept Anat, P-4200319 Oporto, Portugal.
   [Falcao, Manuel S.; Falcao-Reis, Fernando; Carneiro, Angela M.] Univ Porto, Fac Med, Dept Sense Organs, P-4200319 Oporto, Portugal.
C3 Sao Joao Hospital; Universidade do Porto; Universidade do Porto;
   Universidade do Porto; Universidade do Porto
RP Pinheiro-Costa, J (通讯作者)，Univ Porto, Fac Med, Hosp Sao Joao, Dept Ophthalmol, P-4200319 Oporto, Portugal.
EM joaopinh@hotmail.com
RI Falcao/AAQ-8509-2020; Carneiro, Angela/N-9680-2013
OI Falcao/0000-0003-4718-0910; Carneiro, Angela/0000-0002-3370-7243; Beato,
   Joao/0000-0003-3820-4597; Freitas-da-Costa, Paulo/0000-0002-9567-4467;
   Falcao-Reis, Fernando/0000-0002-5995-9430
CR Adamis AP, 2005, RETINA-J RET VIT DIS, V25, P111, DOI 10.1097/00006982-200502000-00001
   Andreoli CM, 2007, CURR OPIN OPHTHALMOL, V18, P502, DOI 10.1097/ICU.0b013e3282f0ca54
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   Bashshur ZF, 2008, AM J OPHTHALMOL, V145, P249, DOI 10.1016/j.ajo.2007.09.031
   Binder S, 2012, BRIT J OPHTHALMOL, V96, P1, DOI 10.1136/bjophthalmol-2011-301236
   Bressler NM, 2003, ARCH OPHTHALMOL-CHIC, V121, P1621
   Brown DM, 2009, OPHTHALMOLOGY, V116, P57, DOI 10.1016/j.ophtha.2008.10.018
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   Carneiro AM, 2010, RETINA-J RET VIT DIS, V30, P85, DOI 10.1097/IAE.0b013e3181c700a9
   Chakravarthy U, 2012, OPHTHALMOLOGY, V119, DOI 10.1016/j.ophtha.2012.04.015
   Chang AA, 2014, OPHTHALMOLOGY, V121, P188, DOI 10.1016/j.ophtha.2013.08.035
   Cho H, 2013, BRIT J OPHTHALMOL, V97, P1032, DOI 10.1136/bjophthalmol-2013-303344
   Eghoj MS, 2012, BRIT J OPHTHALMOL, V96, P21, DOI 10.1136/bjo.2011.203893
   Fassnacht-Riederle H, 2014, GRAEF ARCH CLIN EXP, V252, P1705, DOI 10.1007/s00417-014-2589-3
   Forooghian F, 2009, RETINA-J RET VIT DIS, V29, P723, DOI 10.1097/IAE.0b013e3181a2c1c3
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   Martin DF, 2012, OPHTHALMOLOGY, V119, DOI 10.1016/j.ophtha.2012.03.053
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   Messenger WB, 2014, BRIT J OPHTHALMOL, V98, P1205, DOI 10.1136/bjophthalmol-2013-304829
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   Papadopoulos N, 2012, ANGIOGENESIS, V15, P171, DOI 10.1007/s10456-011-9249-6
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   Schaal S, 2008, OPHTHALMOLOGY, V115, P2199, DOI 10.1016/j.ophtha.2008.07.007
   Semeraro F, 2013, DRUG DES DEV THER, V7, P711, DOI 10.2147/DDDT.S40215
   Stewart MW, 2008, BRIT J OPHTHALMOL, V92, P667, DOI 10.1136/bjo.2007.134874
   Stewart MW, 2012, CLIN OPHTHALMOL, V6, P1175, DOI 10.2147/OPTH.S33372
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NR 37
TC 38
Z9 40
U1 0
U2 7
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2015
VL 233
IS 3-4
BP 155
EP 161
DI 10.1159/000381221
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CK3LO
UT WOS:000356117800005
PM 25896317
DA 2022-11-30
ER

PT J
AU Warrian, KJ
   Katz, LJ
   Myers, JS
   Moster, MR
   Pro, MJ
   Wizov, SS
   Spaeth, GL
AF Warrian, Kevin J.
   Katz, L. Jay
   Myers, Jonathan S.
   Moster, Marlene R.
   Pro, Michael J.
   Wizov, Sheryl S.
   Spaeth, George L.
TI A comparison of methods used to evaluate mobility performance in the
   visually impaired
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; WALKING SPEED; MACULAR DEGENERATION; ABILITY; TESTS;
   TASKS
AB Purpose To compare three different approaches to measuring mobility performance when evaluating the visually impaired.
   Methods 488 participants, including 192 glaucoma, 112 age-related macular degeneration, 91 diabetic retinopathy and 93 healthy volunteers, completed the Assessment of Disability Related to Vision (ADREV) mobility course. The performance of participants on the mobility course was evaluated by noting errors made and time required for completion. Errors noted and time taken were compared using multivariate logistic regression to determine which measurement better differentiated patients with visual disease from healthy volunteers. Multivariate logistic regression was also used to evaluate the combined metric of ADREV errors divided by time to determine its ability to discriminate participants with visual disease from healthy volunteers.
   Results Errors noted and time taken while ambulating through the standardised mobility course shared a weak but statistically significant association (Pearson's r=0.36, p<0.05). After controlling for demographic and medical comorbidities, logistic regression analysis revealed that errors noted were better at discriminating individuals with visual disease from healthy volunteers (OR 2.8-4.9, 95% CI 1.5 to 10.3) compared with the time taken for mobility course completion (OR 1.1, 95% CI 1.0 to 1.2). These findings were consistent across all comparisons between healthy volunteers and participants with each type of visual impairment. Finally, the combined metric of ADREV errors divided by time was far more predictive of visual disease compared with either time taken or errors noted during mobility testing (OR 11.0-17.7, 95% CI 3.6 to 77.1).
   Conclusions A validated scoring system based on errors is more effective when assessing visual disability during mobility testing than recording the time taken for course completion. The combined metric of ADREV errors noted divided by time taken was most predictive of all the methods used to evaluate visual disability during mobility testing.
C1 [Warrian, Kevin J.; Katz, L. Jay; Myers, Jonathan S.; Moster, Marlene R.; Pro, Michael J.; Wizov, Sheryl S.; Spaeth, George L.] Thomas Jefferson Univ, Wills Eye Hosp, Glaucoma Res Ctr, William & Anna Goldberg Glaucoma Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Warrian, KJ (通讯作者)，Elbow Retina Ctr, 7808 Elbow Dr SW, Calgary, AB T2V 1K4, Canada.
EM kevinjwarrian@gmail.com
FU Pfizer; Perelman Fund through Wills Eye Institute of Jefferson Medical
   College; Pearle Vision Foundation; Glaucoma Service Foundation to
   Prevent Blindness
FX Financial support provided by Pfizer, The Perelman Fund through Wills
   Eye Institute of Jefferson Medical College, The Pearle Vision Foundation
   and The Glaucoma Service Foundation to Prevent Blindness.
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NR 31
TC 9
Z9 9
U1 0
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 JAN
PY 2015
VL 99
IS 1
BP 113
EP 118
DI 10.1136/bjophthalmol-2014-305324
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AW6CW
UT WOS:000346358000023
PM 25138757
DA 2022-11-30
ER

PT J
AU Yu, J
   Johnson, EJ
   Shang, F
   Lim, A
   Zhou, HY
   Cui, L
   Xu, J
   Snellingen, T
   Liu, XP
   Wang, NL
   Liu, NP
AF Yu, Jie
   Johnson, Elizabeth J.
   Shang, Fu
   Lim, Apiradee
   Zhou, Haiying
   Cui, Lei
   Xu, Jun
   Snellingen, Torkel
   Liu, Xipu
   Wang, Ningli
   Liu, Ningpu
TI Measurement of Macular Pigment Optical Density in a Healthy Chinese
   Population Sample
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; HETEROCHROMATIC FLICKER PHOTOMETRY; RESONANCE
   RAMAN MEASUREMENT; SPATIAL-DISTRIBUTION; GEOGRAPHIC REGION; EYE DISEASE;
   VITAMIN-A; CAROTENOIDS; DEGENERATION; PREVALENCE
AB PURPOSE. Macular pigment may protect against age-related macular degeneration (AMD) by its capacity to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasian populations. The purpose of this study was to assess macular pigment density and its determinant factors in a Chinese population sample.
   METHODS. Macular pigment optical density (MPOD) was measured in a healthy Chinese population using heterochromatic flicker photometry (HFP). Participants received a standard ophthalmic examination, and only subjects who were confirmed not to have any eye diseases except mild age-related cataract were included in the study. Demographic and lifestyle data and general health status were recorded by questionnaire.
   RESULTS. A total of 281 unrelated healthy Chinese individuals, including 96 males and 185 females, with ages ranging from 17 to 85 years, participated in the study. The mean and standard deviation of MPOD levels were 0.56 +/- 0.19, 0.49 +/- 0.18, 0.36 +/- 0.15, and 0.19 +/- 0.12, respectively, at 0.25 degrees, 0.5 degrees, 1.0 degrees, and 1.75 degrees eccentricity points. A significant age-related decline in MPOD was observed at 0.25 degrees (P = 0.014). Females tended to have relatively lower levels of MPOD than males at 0.25 degrees (P = 0.21), 0.5 degrees (P = 0.025), and 1.0 degrees (P = 0.16). No statistically significant association of MPOD was observed with body mass index or smoking status.
   CONCLUSIONS. Macular pigment density measured by HFP tended to decline with aging in this healthy Chinese population sample. Females may have lower levels of MPOD than males. (Invest Ophthalmol Vis Sci. 2012;53:2106-2111) DOI:10.1167/iovs.11-8518
C1 [Yu, Jie; Zhou, Haiying; Cui, Lei; Xu, Jun; Wang, Ningli; Liu, Ningpu] Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China.
   [Johnson, Elizabeth J.; Shang, Fu] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Lim, Apiradee] Prince Songkla Univ, Fac Sci & Technol, Dept Math & Comp Sci, Muang Pattani, Thailand.
   [Snellingen, Torkel; Liu, Xipu] Sekwa Eye Hosp, Beijing, Peoples R China.
C3 Capital Medical University; Tufts University; United States Department
   of Agriculture (USDA); Prince of Songkla University
RP Liu, NP (通讯作者)，Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, 1 Dong Jiao Min Xiang, Beijing 100730, Peoples R China.
EM nliu001@gmail.com
FU National Basic Research Program of China (973 Program) [2007CB512201];
   Beijing Municipal Health Bureau [2009208]; National Natural Science
   Foundation of China [81070734]; Kemin Japan
FX Supported in part by the National Basic Research Program of China (973
   Program) Grant 2007CB512201, the Beijing Municipal Health Bureau Grant
   2009208, the National Natural Science Foundation of China Grant
   81070734, and an unrestricted research fund from Kemin Japan. Kemin
   Health USA kindly provided the heterochromatic flicker photometer for
   the study.
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NR 53
TC 22
Z9 23
U1 0
U2 14
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2012
VL 53
IS 4
BP 2106
EP 2111
DI 10.1167/iovs.11-8518
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 937PC
UT WOS:000303669400047
PM 22427543
DA 2022-11-30
ER

PT J
AU Cloutier, F
   Lawrence, M
   Goody, R
   Lamoureux, S
   Al-Mahmood, S
   Colin, S
   Ferry, A
   Conduzorgues, JP
   Hadri, A
   Cursiefen, C
   Udaondo, P
   Viaud, E
   Thorin, E
   Chemtob, S
AF Cloutier, Frank
   Lawrence, Matthew
   Goody, Robin
   Lamoureux, Stephanie
   Al-Mahmood, Salman
   Colin, Sylvie
   Ferry, Antoine
   Conduzorgues, Jean-Pascal
   Hadri, Amel
   Cursiefen, Claus
   Udaondo, Patricia
   Viaud, Eric
   Thorin, Eric
   Chemtob, Sylvain
TI Antiangiogenic Activity of Aganirsen in Nonhuman Primate and Rodent
   Models of Retinal Neovascular Disease after Topical Administration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL CORNEAL NEOVASCULARIZATION;
   INSULIN-RECEPTOR SUBSTRATE-1; CHOROIDAL NEOVASCULARIZATION; ANTISENSE
   OLIGONUCLEOTIDE; MACULAR DEGENERATION; RAT MODEL; BEVACIZUMAB; VEGF;
   RETINOPATHY
AB PURPOSE. Aganirsen, an antisense oligonucleotide inhibiting insulin receptor substrate (IRS)-1 expression, has been shown to promote the regression of pathologic corneal neovascularization in patients. In this study, the authors aimed to demonstrate the antiangiogenic activity of aganirsen in animal models of retinal neovascularization.
   METHODS. Eyedrops of aganirsen were applied daily in nonhuman primates after laser-induced choroidal neovascularization (CNV; model of wet age-related macular degeneration [AMD]) and in newborn rats after oxygen-induced retinopathy (OIR; model of ischemic retinopathy). Retinal aganirsen concentrations were assessed in rabbits and monkeys after topical delivery (21.5, 43, or 86 mu g). Clinical significance was further evaluated by determination of IRS-1 expression in monkey and human retinal biopsy specimens.
   RESULTS. Topical corneal application of aganirsen attenuated neovascular lesion development dose dependently in African green monkeys. The incidence of high-grade CNV lesions (grade IV) decreased from 20.5% in vehicle-treated animals to 1.7% (P < 0.05) at the 86-mu g dose. Topical aganirsen inhibited retinal neovascularization after OIR in rats (P < 0.05); furthermore, a single intravitreal injection of aganirsen reduced OIR as effectively as ranibizumab, and their effects were additive. Significantly, topical applications of aganirsen did not interfere with physiological retinal vessel development in newborn rats. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD.
   CONCLUSIONS. Topical application of aganirsen offers a safe and effective therapy for both choroidal and retinal neovascularization without preventing its normal vascularization. Together, these findings support the clinical testing of aganirsen for human retinal neovascular diseases. (Invest Ophthalmol Vis Sci. 2012;53:1195-1203) DOI:10.1167/iovs.11-9064
C1 [Thorin, Eric] Univ Montreal, Montreal Heart Inst, Dept Surg, Montreal, PQ H1T 1C8, Canada.
   [Cloutier, Frank; Lamoureux, Stephanie; Chemtob, Sylvain] Univ Montreal, Hop Ste Justine, Dept Pediat, Montreal, PQ H1T 1C8, Canada.
   [Lawrence, Matthew; Goody, Robin] RxGen Inc, Hamden, CT USA.
   [Al-Mahmood, Salman; Colin, Sylvie; Ferry, Antoine; Viaud, Eric; Thorin, Eric] Genopole Ind, Gene Signal Lab, Evry, France.
   [Conduzorgues, Jean-Pascal; Hadri, Amel] CRID Pharma, St Gely Du Fesc, France.
   [Cursiefen, Claus] Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany.
   [Udaondo, Patricia] Univ Cardenal Herrera Oria, CEU, Nuevo Hosp Univ & Politecn La Fe, Valencia, Spain.
C3 Universite de Montreal; Universite de Montreal; University of Cologne;
   Hospital Universitari i Politecnic La Fe; Universidad CEU Cardenal
   Herrera
RP Thorin, E (通讯作者)，Univ Montreal, Montreal Heart Inst, Dept Surg, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada.
EM eric.thorin@umontreal.ca
RI Thorin, Eric/K-3978-2013; Cursiefen, Claus/ABE-5284-2020
OI Thorin, Eric/0000-0001-5827-8935; cursiefen, claus/0000-0002-1958-411X;
   Udaondo, Patricia/0000-0002-5241-0066
FU Gene Signal Laboratories; University of Montreal, CRID Pharma (Amatsi);
   Rx-Gen, Inc
FX Supported by an unrestricted educational grant from Gene Signal
   Laboratories and performed in collaboration among the University of
   Montreal, CRID Pharma (Amatsi), and Rx-Gen, Inc.
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NR 35
TC 34
Z9 36
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1195
EP 1203
DI 10.1167/iovs.11-9064
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 925VT
UT WOS:000302790700017
PM 22323484
DA 2022-11-30
ER

PT J
AU Boutin, T
   Kergoat, MJ
   Latour, J
   Massoud, F
   Kergoat, H
AF Boutin, Tanguy
   Kergoat, Marie-Jeanne
   Latour, Judith
   Massoud, Fadi
   Kergoat, Helene
TI Vision in the Global Evaluation of Older Individuals Hospitalized
   Following a Fall
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Older adults; fall; Geriatric Assessment Unit; vision
ID EYE CATARACT-SURGERY; ELDERLY-PATIENTS; HEALTH-STATUS; RISK-FACTORS;
   PEOPLE; PREVENTION; PREVALENCE; MEDICATION; STATE; CARE
AB Introduction: The objective of this study was to verify if vision is appropriately evaluated in older individuals admitted to a Geriatric Assessment Unit following a fall.
   Methods: A retrospective clinical chart review of 158 patients from 3 university-based Geriatric Assessment Units is presented. The clinical charts of patients admitted following a fall in the Geriatric Assessment Units of 3 Montreal hospitals, between April 2006 and 2008, were reviewed. Clinical charts from age-and sex-matched controls hospitalized in the Geriatric Assessment Units during the same period but without a history of fall or fracture, were also reviewed. Pertinent sociodemographic, medical, and visual characteristics were extracted from the charts and entered into a database for analysis.
   Results: The mean age +/- standard deviation for the cases (n = 79) and controls (n = 79) were 82.3 +/- 6.2 years and 81.7 +/- 6.4 years, respectively. Most falls were not a result of accidents, but rather were more often related to underlying medical problems that were multifactorial in origin. More cases than controls were taking antiarrhythmic and antidepressant medications, whereas more controls were taking calcium channel blockers. Cases were more likely to have cataracts, age-related macular degeneration, and decreased visual acuity. Although cases were referred more often than controls for an eye examination, they were not referred in a systematic fashion.
   Discussion: Our results indicate that more visual problems are identified in persons who fall and, even if they are referred more often than controls for an eye examination, their vision is not evaluated systematically by an eye care specialist despite current clinical recommendations.
   Conclusion: These data indicate that eye care professionals should work more closely with the medical team to improve the overall clinical care of older individuals with a history of falls. Copyright (C) 2012 - American Medical Directors Association, Inc.
C1 [Kergoat, Helene] Univ Montreal, Sch Optometry, Inst Univ Geriatrie Montreal, Montreal, PQ H3C 3J7, Canada.
   [Boutin, Tanguy] Univ Montreal, Sch Optometry, Fac Med, Montreal, PQ H3C 3J7, Canada.
   [Kergoat, Marie-Jeanne] Univ Montreal, Fac Med, Inst Univ Geriatrie Montreal, Montreal, PQ H3C 3J7, Canada.
   [Latour, Judith; Massoud, Fadi] Univ Montreal, Fac Med, Inst Univ Geriatrie Montreal, Ctr Hosp Univ Montreal, Montreal, PQ H3C 3J7, Canada.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal;
   Universite de Montreal
RP Kergoat, H (通讯作者)，Univ Montreal, Sch Optometry, Inst Univ Geriatrie Montreal, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM helene.kergoat@umontreal.ca
FU Institut Universitaire de Geriatrie de Montreal-Comite Aviseur pour la
   Recherche Clinique; Canadian Institutes of Health Research
FX This work was supported by a grant from the Institut Universitaire de
   Geriatrie de Montreal-Comite Aviseur pour la Recherche Clinique and a
   bursary (T.B.) from the Canadian Institutes of Health Research.
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NR 34
TC 11
Z9 11
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 1525-8610
EI 1538-9375
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD FEB
PY 2012
VL 13
IS 2
AR 187.e15
DI 10.1016/j.jamda.2011.04.003
PG 5
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology
GA 898HX
UT WOS:000300733600020
PM 21621474
DA 2022-11-30
ER

PT J
AU Ford, KM
   Saint-Geniez, M
   Walshe, T
   Zahr, A
   D'Amore, PA
AF Ford, Knatokie M.
   Saint-Geniez, Magali
   Walshe, Tony
   Zahr, Alisar
   D'Amore, Patricia A.
TI Expression and Role of VEGF in the Adult Retinal Pigment Epithelium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB; MACULAR
   DEGENERATION; TUMOR ANGIOGENESIS; OXIDATIVE STRESS; VISUAL FUNCTION;
   SURVIVAL FACTOR; CELLS; MAINTENANCE; MICROVILLI
AB PURPOSE. Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE.
   METHODS. VEGF and VEGFR2 expression in the murine retina were assessed during development. Bevacizumab was used to neutralize VEGF in ARPE-19 cells, and the effects on cell survival and apical microvill were assessed by TUNEL and SEM, respectively. VEGF was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). Changes in gene expression were evaluated by quantitative real-time PCR.
   RESULTS. VEGF expression was detected in the developing RPE as early as embryonic day (E) 9.5, whereas VEGFR2 expression by RPE began nonuniformly between postnatal (P) day 6.5 and P8.5. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. Systemic VEGF neutralization led to transient degenerative changes; RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. VEGF levels were elevated in RPE of Ad-sFlt1 mice at day 4 postinfection, and there was increased expression of the neurotrophic factor CD59a at day 14.
   CONCLUSIONS. These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents. (Invest Ophthalmol Vis Sci. 2011;52:9478-9487) DOI:10.1167/iovs.11-8353
C1 [Ford, Knatokie M.; Saint-Geniez, Magali; Walshe, Tony; Zahr, Alisar; D'Amore, Patricia A.] Harvard Univ, Sch Med, Schepens Eye Res Inst Massachusetts Eye & Ear, Boston, MA 02114 USA.
   [Ford, Knatokie M.; D'Amore, Patricia A.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02114 USA.
   [Saint-Geniez, Magali; D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard
   Medical School; Harvard University; Harvard Medical School; Harvard
   University; Harvard Medical School
RP D'Amore, PA (通讯作者)，Harvard Univ, Sch Med, Schepens Eye Res Inst Massachusetts Eye & Ear, 20 Staniford St, Boston, MA 02114 USA.
EM patricia.damore@schepens.harvard.edu
RI SAINT-GENIEZ, MAGALI/P-3509-2019; Walshe, Tony/AAJ-8833-2020; D'Amore,
   Patricia A/G-5660-2017
OI SAINT-GENIEZ, MAGALI/0000-0001-9897-138X; D'Amore, Patricia
   A/0000-0001-9652-8974
FU National Institutes of Health [EY015435]; NATIONAL EYE INSTITUTE
   [R01EY015435] Funding Source: NIH RePORTER
FX Supported by the National Institutes of Health Grant EY015435 (PAD).
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NR 43
TC 126
Z9 127
U1 0
U2 13
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2011
VL 52
IS 13
BP 9478
EP 9487
DI 10.1167/iovs.11-8353
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 869WC
UT WOS:000298628200028
PM 22058334
OA Green Published
DA 2022-11-30
ER

PT J
AU Berdeaux, G
   Mesbah, M
   Bradley, C
AF Berdeaux, Gilles
   Mesbah, Mounir
   Bradley, Clare
TI Metric properties of the MacDQoL, individualized
   macular-disease-specific quality of life instrument, and newly
   identified subscales in French, German, Italian, and American
   populations
SO VALUE IN HEALTH
LA English
DT Article
DE Age-related macular degeneration; Quality of life; Cross-cultural
   validity; External validity; Internal validity
ID AGE-RELATED MACULOPATHY; BLUE MOUNTAINS EYE; BEAVER DAM EYE; VISUAL
   IMPAIRMENT; 5-YEAR INCIDENCE; NONMEDICAL COSTS; LOW-VISION;
   DEGENERATION; PREVALENCE; BLINDNESS
AB Objectives: The aims of this analysis were to confirm the UK results in other countries and to explore the possibility of subscales of the 25-Item Macular disease Dependent Quality of Life (MacDQoL) questionnaire.
   Methods: Two clinical studies were pooled. Principal components analyses (Varimax) were conducted on baseline data from each country and from all combined. Factorial structures were compared between countries, and Cronbach alpha values were used to identify item clusters. Four groups of patients were created according to visual acuity (VA) in the best eye (BE < 10/20; BE >= 10/20) and worst eye (WE < 10/100; WE >= 10/100). These groups were used to investigate (analysis of variance) the sensitivity of MacDQoL to VA impairment and to compare it with the NEI-VFQ-25 generic visual function questionnaire.
   Results: A total of 797 patients (mean age 76.8 years; 55.8% women) had wet age-related macular degeneration (AMD). Strong correlations between the MacDQoL items (r > 0.48) and factor loadings > 0.49 on a forced one-factor analysis supported the use of an average weighted impact score. Four constructs (Cronbach alpha > 0.8) were derived, represented by the labels: Essential tasks, Family/social life, Activities/capabilities, and Embarrassment. The structure did not differ among the four countries involved, except one item (Finance), which has been excluded. Patients with BE VA < 10/20 and WE VA < 10/100 produced significantly worse overall scores than those with BE VA > 10/20 and WE VA > 10/100 (MacDQoL P > 0.0001; NEI-VFQ-25 P < 0.0001).
   Conclusions: The analysis confirmed the metric properties of the MacDQoL. The MacDQoL offers a broad individualized measure of the impact of MD on quality of life. Copyright (C) 2011, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.
C1 [Berdeaux, Gilles] Alcon France, F-92563 Rueil Malmaison, France.
   [Berdeaux, Gilles] Conservatoire Natl Arts & Metiers, Paris, France.
   [Mesbah, Mounir] Univ Paris 06, Paris, France.
   [Bradley, Clare] Univ London, Egham, Surrey, England.
C3 Novartis; Alcon; heSam Universite; Conservatoire National Arts & Metiers
   (CNAM); UDICE-French Research Universities; Sorbonne Universite;
   University of London; Royal Holloway University London
RP Berdeaux, G (通讯作者)，Alcon France, 4 Rue Henri St Claire Deville, F-92563 Rueil Malmaison, France.
EM gilles.berdeaux@alconlabs.com
OI Bradley, Clare/0000-0002-4079-0364
FU Alcon France; Alcon
FX Gilles Berdeaux, MD, is employed by Alcon France. Mounir Mesbah, PhD,
   received research grants from Alcon France to perform the statistical
   analyses. Clare Bradley, PhD, is director and majority shareholder of
   Health Psychology Research (HPR Ltd), which licenses the MacDQoL and
   other questionnaires developed by Clare Bradley and her research team to
   other researchers and clinicians. Alcon provided consultancy and
   research grants to Royal Holloway, University of London, for development
   of the MacDQoL and linguistic validation work by Clare Bradley and
   members of her research team.
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NR 54
TC 4
Z9 7
U1 0
U2 9
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 JAN-FEB
PY 2011
VL 14
IS 1
BP 110
EP 120
DI 10.1016/j.jval.2010.10.027
PG 11
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 875OD
UT WOS:000299039700014
PM 21211493
OA Bronze
DA 2022-11-30
ER

PT J
AU Forte, R
   Cennamo, G
   Finelli, M
   Cesarano, I
   D'Amico, G
   de Crecchio, G
   Cennamo, G
AF Forte, Raimondo
   Cennamo, Gilda
   Finelli, Marialuisa
   Cesarano, Ida
   D'Amico, Giuseppe
   de Crecchio, Giuseppe
   Cennamo, Giovanni
TI Intravitreal triamcinolone, bevacizumab and pegaptanib for occult
   choroidal neovascularization
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; anti-VEGF; as needed treatment
ID RANDOMIZED CLINICAL-TRIAL; PIGMENT EPITHELIAL TEARS; DIABETIC MACULAR
   EDEMA; VISUAL-ACUITY; DEGENERATION; ACETONIDE; INJECTION; AVASTIN;
   THERAPY; SAFETY
AB Purpose:
   To evaluate best-corrected visual acuity (BCVA) and foveal thickness (FT) changes in occult subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD) after intravitreal bevacizumab (IVB, 1.25 mg/0.05 ml), pegaptanib (IVP, 0.3 mg/0.09 ml) and triamcinolone acetonide (IVTA, 4 mg/0.1 ml) injected on an as needed basis.
   Methods:
   Retrospective, interventional, comparative study. BCVA (Early Treatment Diabetic Retinopathy Study LogMAR) and FT by optical coherence tomography (OCT) were evaluated during 12 months from first treatment. Patients were retreated if signs of neovascular activity were still present on angiography or OCT.
   Results:
   Forty-eight eyes received IVB, 43 eyes received IVP, 52 eyes received IVTA. BCVA and FT at baseline were 1.22 +/- 0.49 LogMAR and 410.2 +/- 41.83 mu m in the IVB group, 1.25 +/- 0.43 LogMAR and 452.3 +/- 44.83 mu m in the IVP group and 1.31 +/- 0.4 LogMAR and 456.6 +/- 48.27 mu m in the IVTA group. BCVA and FT improved in the three groups during follow-up. A significantly greater improvement of BCVA was present at month-3, month-6 and at month-12 in the IVB and IVP groups (p = 0.01). Improvement of FT was greater in the IVTA group at month-3 (p = 0.02), while it was greater in the anti-Vascular Endothelial Growth Factor (VEGF) groups at month-6 and month-12 (p = 0.01). A postoperative increase of intraocular pressure was detected in 9/52 (17.3%) eyes treated with IVTA, and in two cases it was resistant to topical therapy.
   Conclusion:
   Intravitreal injection of anti-VEGF drugs administered on an as needed basis for AMD-related occult CNVs provided functional and anatomic improvement during 12 months of follow-up.
C1 [Forte, Raimondo; Cennamo, Gilda; Finelli, Marialuisa; Cesarano, Ida; D'Amico, Giuseppe; de Crecchio, Giuseppe; Cennamo, Giovanni] Univ Naples Federico 2, Eye Dept, I-80131 Naples, Italy.
C3 University of Naples Federico II
RP Forte, R (通讯作者)，Univ Naples Federico 2, Dipartimento Sci Oftalmol, Via Pansini 5, I-80131 Naples, Italy.
EM raifor@hotmail.com
RI CLIHON, Residencia Medica/K-4896-2013; Ricci, Giuseppe
   D'Amico/O-6051-2019
OI CLIHON, Residencia Medica/0000-0001-6734-2513; Ricci, Giuseppe
   D'Amico/0000-0002-9022-4790; DE CRECCHIO, Giuseppe/0000-0002-1916-3112
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NR 43
TC 9
Z9 9
U1 0
U2 7
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD DEC
PY 2010
VL 88
IS 8
BP e305
EP e310
DI 10.1111/j.1755-3768.2010.02021.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 686LZ
UT WOS:000284699100002
PM 20946332
OA Bronze
DA 2022-11-30
ER

PT J
AU Schlanitz, FG
   Ahlers, C
   Sacu, S
   Schutze, C
   Rodriguez, M
   Schriefl, S
   Golbaz, I
   Spalek, T
   Stock, G
   Schmidt-Erfurth, U
AF Schlanitz, Ferdinand G.
   Ahlers, Christian
   Sacu, Stefan
   Schuetze, Christopher
   Rodriguez, Marcos
   Schriefl, Sabine
   Golbaz, Isabelle
   Spalek, Tobias
   Stock, Geraldine
   Schmidt-Erfurth, Ursula
TI Performance of Drusen Detection by Spectral-Domain Optical Coherence
   Tomography
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; VISUAL IMPAIRMENT;
   PREVALENCE; SEGMENTATION; FEATURES; DISEASE
AB PURPOSE. To evaluate the performance of automated analyses integrated in three spectral-domain optical coherence tomography (SD-OCT) devices to identify drusen in eyes with early (i.e., nonatrophic and nonneovascular) age-related macular degeneration (AMD).
   METHODS. Twelve eyes of 12 AMD patients, classified as AREDS 2 and 3 and having a mean count of 113 drusen were examined with three clinical SD-OCT devices (Cirrus [Carl Zeiss Meditec, Dublin CA], 3DOCT-1000 [Topcon, Tokyo, Japan], and Spectralis [Heidelberg Engineering, GmbH, Heidelberg, Germany]) and five different scan patterns. After standard automated segmentation of the RPE was performed, every druse in each B-scan was identified and graded by two independent expert graders. Errors in the segmentation performance were classified as negligible, moderate, or severe. Correlations were based on the diameter and height of the druse and its automated segmentation. The overall drusen pattern identified by experts' detailed delineation was plotted with a custom-made computer program to compare automated to manual identification outcomes.
   RESULTS. A total of 1356 drusen were analyzed. The automated segmentation of the retinal pigment epithelium (RPE) by Cirrus made significantly fewer errors in detecting drusen than did the 3DOCT-1000 (P < 0.001). The Cirrus 200 X 200 scan pattern detected 30% of the drusen with negligible errors. Spectralis did not offer a true RPE segmentation. The drusen counts by expert graders were significantly higher in the scans than in the standard fundus photographs (P < 0.05).
   CONCLUSIONS. SD-OCT imaging proved an excellent performance in visualizing drusen-related RPE disease. However, the available automated segmentation algorithms showed distinct limitations to reliable identification of the amount of drusen, particularly smaller drusen, and the actual size. (Invest Ophthalmol Vis Sci. 2010;51:6715-6721) DOI:10.1167/iovs.105288
C1 [Schlanitz, Ferdinand G.; Ahlers, Christian; Sacu, Stefan; Schuetze, Christopher; Schriefl, Sabine; Golbaz, Isabelle; Spalek, Tobias; Stock, Geraldine; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Vienna, Austria.
   [Rodriguez, Marcos] Vienna Univ Technol, Dept Mech Engn, A-1060 Vienna, Austria.
C3 Medical University of Vienna; Technische Universitat Wien
RP Schmidt-Erfurth, U (通讯作者)，Gen Hosp Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311
CR Abdelsalam A, 1999, SURV OPHTHALMOL, V44, P1, DOI 10.1016/S0039-6257(99)00072-7
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NR 31
TC 31
Z9 31
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2010
VL 51
IS 12
BP 6715
EP 6721
DI 10.1167/iovs.10-5288
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 688GJ
UT WOS:000284837500081
PM 21123769
DA 2022-11-30
ER

PT J
AU Kurji, KH
   Cui, JZ
   Lin, T
   Harriman, D
   Prasad, SS
   Kojic, L
   Matsubara, JA
AF Kurji, Khaliq H.
   Cui, Jing Z.
   Lin, Tony
   Harriman, David
   Prasad, Shiv S.
   Kojic, Ljuba
   Matsubara, Joanne A.
TI Microarray Analysis Identifies Changes in Inflammatory Gene Expression
   in Response to Amyloid-beta Stimulation of Cultured Human Retinal
   Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; PHOTORECEPTOR OUTER SEGMENTS; MACULAR DEGENERATION;
   FACTOR-I; CYTOKINE EXPRESSION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS;
   IL-8 EXPRESSION; BRUCHS MEMBRANE; UP-REGULATION
AB PURPOSE. Age-related macular degeneration (AMD) is a common cause of irreversible vision loss in the elderly. The hypothesis was that in vitro stimulation of RPE cells with A beta(1-40), a constituent of drusen, promotes changes in gene expression and cellular pathways associated with the pathogenesis of AMD, including oxidative stress, inflammation, and angiogenesis.
   METHODS. Confluent human RPE cells were stimulated with A beta(1-40), or the reverse peptide A beta(1-40), and genome wide changes in gene expression were studied with gene microarrays. Selected genes were verified by qRT-PCR and ELISA. Pathway analysis with gene set enrichment analysis (GSEA) and ingenuity revealed top functional pathways in RPE after A beta(1-40) stimulation.
   RESULTS. RPE cells stimulated with A beta(1-40) (0.3 mu M) for 24 hours resulted in 63 upregulated and 22 downregulated previously known genes. The upregulated genes were predominantly in inflammatory and immune response categories, but other categories were also represented, including apoptosis, cell signaling, cell proliferation, and signal transduction. Categories of downregulated genes included immune response, transporters, metabolic functions and transcription factors. ELISA confirmed that secreted levels of IL-8 were two times higher than control levels. GSEA and ingenuity analysis confirmed that the top affected pathways in RPE cells after A beta(1-40) stimulation were inflammation and immune response related. Surprisingly, few angiogenic pathways were activated at the doses and exposure times studied.
   CONCLUSIONS. A beta(1-40) promotes RPE gene expression changes in pathways associated with immune response, inflammation, and cytokine and interferon signaling pathways. Results may relate to in vivo mechanisms associated with the pathogenesis of AMD. (Invest Ophthalmol Vis Sci. 2010;51:1151-1163) DOI:10.1167/iovs.09-3622
C1 [Kurji, Khaliq H.; Cui, Jing Z.; Lin, Tony; Harriman, David; Kojic, Ljuba; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
   [Kurji, Khaliq H.; Cui, Jing Z.; Kojic, Ljuba; Matsubara, Joanne A.] Univ British Columbia, Brain Res Ctr, Vancouver, BC V5Z 3N9, Canada.
   [Prasad, Shiv S.] Hlth Canada, Biol Res Ctr, Biol & Genet Therapies Directorate, Ottawa, ON K1A 0L2, Canada.
C3 University of British Columbia; University of British Columbia; Health
   Canada
RP Matsubara, JA (通讯作者)，Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
EM jms@interchange.ubc.ca
FU Canadian Institute of Health Research (CIHR) [MOP-97806, MOP-77736]
FX Supported by Canadian Institute of Health Research (CIHR) Grant
   MOP-97806 (JM) and MOP-77736.
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NR 87
TC 67
Z9 72
U1 0
U2 11
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2010
VL 51
IS 2
BP 1151
EP 1163
DI 10.1167/iovs.09-3622
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 545AS
UT WOS:000273704700073
PM 19797223
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Glenn, JV
   Mahaffy, H
   Wu, KQ
   Smith, G
   Nagai, R
   Simpson, DAC
   Boulton, ME
   Stitt, AW
AF Glenn, Josephine V.
   Mahaffy, Helen
   Wu, Keqiang
   Smith, Gill
   Nagai, Ryoji
   Simpson, David A. C.
   Boulton, Michael E.
   Stitt, Alan W.
TI Advanced Glycation End Product (AGE) Accumulation on Bruch's Membrane:
   Links to Age-Related RPE Dysfunction
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; GENE-EXPRESSION PROFILE; ROD OUTER SEGMENTS;
   MACULAR DEGENERATION; OXIDATIVE STRESS; CATHEPSIN-D;
   EXTRACELLULAR-MATRIX; ARPE-19 CELLS; GROWTH-FACTOR; PROTEINS
AB PURPOSE. Advanced glycation end products (AGEs) accumulate during aging and have been observed in postmortem eyes within the retinal pigment epithelium (RPE), Bruch's membrane, and subcellular deposits ( drusen). AGEs have been associated with age-related dysfunction of the RPE-in particular with development and progression to age-related macular degeneration (AMD). In the present study the impact of AGEs at the RPE-Bruch's membrane interface was evaluated, to establish how these modifications may contribute to age-related disease.
   METHODS. AGEs on Bruch's membrane were evaluated using immunohistochemistry. A clinically relevant in vitro model of substrate AGE accumulation was established to mimic Bruch's membrane ageing. Responses of ARPE-19 growing on AGE-modified basement membrane (AGE-BM) for 1 month were investigated by using a microarray approach and validated by quantitative (q)RT-PCR. In addition to identified AGE-related mRNA alterations, lysosomal enzyme activity and lipofuscin accumulation were also studied in ARPE-19 grown on AGE-BM.
   RESULTS. Autofluorescent and glycolaldehyde-derived AGEs were observed in clinical specimens on Bruch's membrane and choroidal extracellular matrix. In vitro analysis identified a range of dysregulated mRNAs in ARPE-19 exposed to AGE-BM. Altered ARPE-19 degradative enzyme mRNA expression was observed on exposure to AGE-BM. AGE- BM caused a significant reduction in cathepsin-D activity in ARPE-19 (P < 0.05) and an increase in lipofuscin accumulation (P < 0.01).
   CONCLUSIONS. AGEs influence ARPE-19 mRNA expression profiles and may contribute to reduced lysosomal enzyme degradative capacity and enhanced accumulation of lipofuscin. Formation of AGEs on Bruch's membrane may have important consequences for age-related outer retinal disease. (Invest Ophthalmol Vis Sci. 2009; 50: 441-451) DOI:10.1167/iovs.08-1724
C1 [Glenn, Josephine V.; Mahaffy, Helen; Simpson, David A. C.; Stitt, Alan W.] Queens Univ Belfast, Sch Med Dent & BioMed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Wu, Keqiang; Smith, Gill; Boulton, Michael E.] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL USA.
   [Nagai, Ryoji] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Biochem Med, Kumamoto, Japan.
   [Boulton, Michael E.] Cardiff Univ, Sch Optometry & Visual Sci, Cardiff, S Glam, Wales.
C3 Queens University Belfast; State University System of Florida;
   University of Florida; Kumamoto University; Cardiff University
RP Stitt, AW (通讯作者)，Queens Univ Belfast, Royal Victoria Hosp, Sch Med Dent & BioMed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM a.stitt@qub.ac.uk
RI Wu, Keqiang/C-9743-2013; Stitt, Alan/A-9842-2009
OI Wu, Keqiang/0000-0002-5791-3594; Stitt, Alan/0000-0002-8647-9918;
   Simpson, David/0000-0003-0157-1211
FU Wellcome Trust [066193/A/01/Z]
FX Supported by Wellcome Trust Grant 066193/A/01/Z, Action Medical
   Research, the Medical Research Council (MRC), and a Department for
   Employment and Learning-Northern Ireland (DEL-NI) PhD studentship.
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NR 67
TC 63
Z9 74
U1 2
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 JAN
PY 2009
VL 50
IS 1
BP 441
EP 451
DI 10.1167/iovs.08-1724
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 390YP
UT WOS:000262199900057
PM 18676633
DA 2022-11-30
ER

PT J
AU Wang, AL
   Lukas, TJ
   Yuan, M
   Neufeld, AH
AF Wang, Ai Ling
   Lukas, Thomas J.
   Yuan, Ming
   Neufeld, Arthur H.
TI Increased mitochondrial DNA damage and down-regulation of DNA repair
   enzymes in aged rodent retinal pigment epithelium and choroid
SO MOLECULAR VISION
LA English
DT Article
ID BASE EXCISION-REPAIR; OXIDATIVE DAMAGE; HUMAN BRAIN; DISEASE; CELLS
AB Purpose: In the central nervous system (CNS), increased mitochondrial DNA (mtDNA) damage is associated with aging and may underlie, contribute to, or increase the susceptibility to neurodegenerative diseases. Because of the focus on the retinal pigment epithelium (RPE) and choroid as tissue relevant to age-related macular degeneration (AMD), we examined young and aged RPE and choroid, harvested from rodent eyes, for DNA damage and for changes in selected DNA repair enzymes.
   Methods: Immunohistochemical labeling and quantitative ELISA for the oxidative DNA damage marker, 8-hydroxy-2'deoxy- guanosine (8-OHdG), were measured in young and aged rodent RPE and choroid. mtDNA and nuclear DNA (nDNA) damage was determined by quantitative polymerase chain reaction (PCR) by comparing the relative amplification of small and large DNA fragments. Expression of several DNA repair enzymes was measured using real-time quantitative reverse transcription-PCR (qRT-PCR) and immunoblot.
   Results: Immunohistochemical labeling for 8-OHdG increased in aged rodent RPE and choroid. Quantitative ELISA confirmed increased levels of 8-OHdG. Measurements of nDNA and mtDNA lesions indicated that DNA damage is primarily in mtDNA in aged RPE and choroid. Using qRT-PCR, we found that gene expression of DNA repair enzymes, 8-oxoguanine-DNA glycosylase 1 (OGG1), mutY homolog (MYH), and thymine DNA glycosylase were decreased in an age-dependent pattern in RPE and choroid. However, endonuclease III homolog 1 was not significantly changed in aged RPE and choroid. Using immunoblots, we found that protein levels of OGG1 and MYH were decreased in aged RPE and choroid.
   Conclusions: Our results show that there is increased mtDNA damage in aged RPE and choroid, which is likely due to decreased DNA repair capability. mtDNA damage in the RPE and choroid may be a susceptibility factor that underlies the development of AMD.
C1 [Wang, Ai Ling; Lukas, Thomas J.; Yuan, Ming; Neufeld, Arthur H.] Northwestern Univ, Sch Med, Dept Ophthalmol, Forsythe Lab Investigat Aging Retina, Chicago, IL 60611 USA.
C3 Northwestern University
RP Wang, AL (通讯作者)，Northwestern Univ, Sch Med, Dept Ophthalmol, Forsythe Lab Investigat Aging Retina, Tarry 13-762,303 E Chicago Ave, Chicago, IL 60611 USA.
EM a-wang@northwestern.edu
FU NATIONAL EYE INSTITUTE [R01EY012017] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY12017, R01 EY012017] Funding Source: Medline
CR Ayala-Torres S, 2000, METHODS, V22, P135, DOI 10.1006/meth.2000.1054
   Barron MJ, 2001, INVEST OPHTH VIS SCI, V42, P3016
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NR 20
TC 87
Z9 91
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 25
PY 2008
VL 14
IS 77
BP 644
EP 651
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 312IU
UT WOS:000256663800001
PM 18392142
DA 2022-11-30
ER

PT J
AU Parodi, MB
   Iacono, P
   Spasse, S
   Ravalico, G
AF Parodi, MB
   Iacono, P
   Spasse, S
   Ravalico, G
TI Photodynamic therapy for juxtafoveal choroidal neovascularization
   associated with multifocal choroiditis
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VERTEPORFIN; PANUVEITIS
AB PURPOSE: Evaluation of visual acuity outcome of photodynamic therapy (PDT) with verteporfin for juxtafoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MC).
   DESIGN: Open-label, prospective, interventional case series.
   METHODS: Seven patients (seven eyes) diagnosed with juxtafoveal CNV associated with MC at the Eye Clinic of Trieste were considered. Inclusion criteria were the presence of juxtafoveal CNV no larger than 5400 mu m in greatest linear dimension and best-corrected visual acuity (BCVA) (Snellen equivalent) of approximately 20/200 or better. PDT was performed according to the Treatment of Age-Related Macular Degeneration with Photo dynamic Therapy (TAP) study. The primary outcome was the variation in Early Treatment Diabetic Retinopathy Study (ETDRS) charts visual acuity. In particular, the study considered changes of at least eight letters (approximately < 1.5 lines of visual acuity loss) at the 12- and 24 month examinations compared with the baseline examination. Secondary outcomes included fluorescein angiographic features such as progression and area of CNV. 0
   RESULTS: At both the 12- and 24,month examinations, three patients (43%) gained at least 1.5 lines of visual acuity, three patients (43%) did not show changes in either direction, whereas visual acuity decreased by 1.5 or more lines from baseline in one patient (14%). The median CNV area was 0.3 mm(2) at baseline and 0.24 mm(2) at the 12, and 24,month controls, respectively.
   CONCLUSIONS: The positive results of the present study and the absence of treatment, related side effects suggest that PDT may be considered a safe and viable therapeutic option for juxtafoveal CNV for a 24,month period. Further studies including a greater number of patients are needed to confirm these preliminary results.
C1 Univ Trieste, Osped Maggiore, Eye Clin, Azienda Osped, I-34129 Trieste, Italy.
C3 University of Trieste
RP Parodi, MB (通讯作者)，Univ Trieste, Osped Maggiore, Eye Clin, Azienda Osped, I-34129 Trieste, Italy.
EM maubp@yahoo.it
RI Iacono, Pierluigi/AAD-3158-2020; Parodi, Maurizio Battaglia/K-7876-2016
OI Battaglia Parodi, Maurizio/0000-0002-0385-7961
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NR 20
TC 20
Z9 24
U1 0
U2 0
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 JAN
PY 2006
VL 141
IS 1
BP 123
EP 128
DI 10.1016/j.ajo.2005.07.045
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 000FQ
UT WOS:000234446700017
PM 16386985
DA 2022-11-30
ER

PT J
AU Postelmans, L
   Pasteels, B
   Coquelet, P
   El Ouardighi, H
   Verougstraete, C
   Schmidt-Erfurth, U
AF Postelmans, L
   Pasteels, B
   Coquelet, P
   El Ouardighi, H
   Verougstraete, C
   Schmidt-Erfurth, U
TI Severe pigment epithelial alterations in the treatment area following
   photodynamic therapy for classic choroidal neovascularization in young
   females
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; OCULAR HISTOPLASMOSIS SYNDROME;
   RANDOMIZED CLINICAL-TRIAL; PROSPECTIVE CASE SERIES; MACULAR
   DEGENERATION; PATHOLOGICAL MYOPIA; NORMAL RETINA; VERTEPORFIN;
   SECONDARY; TEAR
AB PURPOSE: Although photodynamic therapy (PDT) is an established treatment for choroidal neovascularization (CNV), the mechanisms are still not completely eluci- dated. Damage to the retinal pigment epithelium (RPE) was observed following uncomplicated PDT in young patients.
   DESIGN: Observational case series.
   METHODS: Four female patients between the age of 26 and 39 years presented with visual loss because of classic CNV. In two 39 years old females the CNV originated secondary to a small chorioretinal scar, in a 26 and a 36-year-old-woman the CNV was of idiopathic cause. All patients received standard PDT according to the Treatment of Age-Related Macular Degeneration with Photo, dynamic Therapy (TAP) Study protocol.
   RESULTS: One to three months after an uncomplicated PDT with verteporfin, severe pigment epithelial alterations in the treatment area were observed. The neovascular membranes responded favorably to the treatment and demonstrated fibrosis and resolution of leakage. Oplathalmoscopically and angiographically, atrophy of the retinal pigment epithelium was seen precisely delineating the size of the treatment spot used. Vision declined in two patients from 0.3 to 0.1 and 0.15 to 0.1. The two other patients demonstrated an increase of visual acuity from 0.7 to 0.9 and from 0.4 to 0.9. The retinal pigment epithelium alterations did not resolve during follow-up, but remained unchanged in area and intensity.
   CONCLUSIONS: Characteristic retinal pigment epithelium alterations were observed in young female patients with small classic CNV following PDT. Unusual retinal pigment epithelium damage in young female patients without any associated disease might be related to a possible inherent defect in the RPE or to the hormonal status of this specific patient population. (C) 2004 by Elsevier Inc. All rights reserved.
C1 CHU Brugmann, Dept Ophthalmol, B-1020 Brussels, Belgium.
   Free Univ Brussels, Brussels, Belgium.
   Med Univ Vienna, Klin Augenheilkunde & Optometrie, Vienna, Austria.
C3 Universite Libre de Bruxelles; Vrije Universiteit Brussel; Medical
   University of Vienna
RP Postelmans, L (通讯作者)，CHU Brugmann, Dept Ophthalmol, Pl Van Gehuchten,4, B-1020 Brussels, Belgium.
EM Laurence.postelmans@chu-brugmann.be
CR Arnold J, 2001, OPHTHALMOLOGY, V108, P841
   Arnold J, 2001, AM J OPHTHALMOL, V131, P541
   Blumenkranz MS, 2001, ARCH OPHTHALMOL-CHIC, V119, P198
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NR 16
TC 69
Z9 81
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 NOV
PY 2004
VL 138
IS 5
BP 803
EP 808
DI 10.1016/j.ajo.2004.06.033
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 870UF
UT WOS:000225083100014
PM 15531316
DA 2022-11-30
ER

PT J
AU Alves-Rodrigues, A
   Shao, A
AF Alves-Rodrigues, A
   Shao, A
TI The science behind lutein
SO TOXICOLOGY LETTERS
LA English
DT Review
DE lutein; supplementation; age-related macular degeneration; cataract;
   chronic disease; bioavailability; toxicity
ID BETA-CAROTENE SUPPLEMENTS; MACULAR PIGMENT DENSITY; AGE-RELATED
   MACULOPATHY; CORONARY HEART-DISEASE; VITAMIN-A; ALPHA-TOCOPHEROL;
   LUNG-CANCER; SERUM CONCENTRATIONS; CATARACT-EXTRACTION; NATIONAL-HEALTH
AB In humans, as in plants, the xanthophyll lutein is believed to function in two important ways: first as a filter of high energy blue light, and second as an antioxidant that quenches and scavenges photo induced reactive oxygen species (ROS). Evidence suggests that Intent consumption is inversely related to eye diseases such as age-related macular degeneration (AMD) and cataracts. This is supported by the finding that lutein (and a stereo isomer, zeaxanthin) are deposited in the lens and the macula lutea, an area of the retina responsible for central and high acuity vision. Human intervention studies show that lutein supplementation results in increased macular pigment and improved vision in patients with AMD and other ocular diseases. Lutein may also serve to protect skin from UV-induced damage and may help reduce the risk of cardiovascular disease. Crystalline lutein is readily absorbed from foods and from dietary supplements whereas, to enter the bloodstream, lutein esters require prior de-esterification by intestinal enzymes. Unlike the hydrocarbon carotenoids which are mainly found in the LDL fraction, xanthophylls like lutein and zeaxanthin are incorporated into both HDL and LDL. Today, lutein can be obtained from the diet in several different ways, including via supplements, and most recently in functional foods. Animal toxicology studies have been performed to established lutein's safety as a nutrient. These studies have contributed to the classification of purified crystalline lutein as generally recognized as safe (GRAS). The achievement of GRAS status for purified crystalline lutein allows for the addition of this form into several food and beverage applications. This achievement speaks directly to the quality and safety of purified lutein. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
C1 Kemin Foods Europe, Dept Res & Dev, P-1050242 Lisbon, Portugal.
   Gen Nutr Corp, Pittsburgh, PA 15222 USA.
RP Alves-Rodrigues, A (通讯作者)，Kemin Foods Europe, Dept Res & Dev, Ave Visconde Valmor 66,5 Andar, P-1050242 Lisbon, Portugal.
EM arodrigues@keminfoods.com
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   [No title captured]
   2002, MOL ASPECTS MED, V23, P41
NR 174
TC 273
Z9 309
U1 9
U2 96
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0378-4274
EI 1879-3169
J9 TOXICOL LETT
JI Toxicol. Lett.
PD APR 15
PY 2004
VL 150
IS 1
BP 57
EP 83
DI 10.1016/j.toxlet.2003.10.031
PG 27
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA 815NV
UT WOS:000221049900007
PM 15068825
DA 2022-11-30
ER

PT J
AU Lamoureux, EL
   Hassell, JB
   Keeffe, JE
AF Lamoureux, EL
   Hassell, JB
   Keeffe, JE
TI The determinants of participation in activities of daily living in
   people with impaired vision
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DISABILITY; ASSOCIATION; DEPRESSION; PROJECT; IMPACT; AGE
AB PURPOSE: To investigate the determinants of participation in daily activities in people with impaired vision using the Impact of Vision Impairment (IVI) instrument.
   DESIGN: Cross-sectional study.
   METHODS: We recruited 319 participants with no vision rehabilitation history, distance visual acuity (VA) <6/12 (better eye), the ability to converse in English, and 18 years or older. Participants completed the 32-item IVI questionnaire and provided demographic, personal, Cultural, and environmental details on vision-related functioning. Visual acuity data were either abstracted from the participants' files or assessed by qualified personnel. Participants also completed the SF-12 to evaluate physical (PCS-12) and mental health (MCS-12).
   RESULTS: The areas of greatest restriction of participation were associated with reading, outdoor mobility, participation in leisure activities, and shopping. In step, wise linear regression presenting VA, the PCS-12 and MCS-12 explained the variance in leisure and work (60 participants or 19%), consumer and social interaction (92 participants or 30%), household and personal care (76 participants or 24%), mobility (92 participants or 30%), emotional reaction to visual loss and (106 partic- ipants or 33%), and total IVI score (114 participants or 36%). Having age,related macular degeneration contributed marginally to the IVI domains and total score (P <.05-.01), except for the emotional domain. Belonging to a social group explained 3% and 2% of the variance in the consumer and social interaction and emotional domains, respectively (P <.05).
   CONCLUSIONS: Distance VA and physical and mental health explained more than a third of the variance of the total score, suggesting that an intervention aimed at improving quality of life may include strategies to improve not only vision-related rehabilitation but also mental and physical health. (C) 2004 by Elsevier Inc. All rights reserved.
C1 Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Melbourne, Vic, Australia.
C3 Centre for Eye Research Australia; University of Melbourne
RP Lamoureux, EL (通讯作者)，Ctr Eye Res Australia, Locked Bag 8, Melbourne, Vic 8002, Australia.
EM ecosse@unimelb.edu.au
RI Lamoureux, Ecosse/Z-5482-2019
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   *WHO, 2001, GLOB TUB CONTR REP 2, P18
NR 19
TC 154
Z9 157
U1 0
U2 19
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 FEB
PY 2004
VL 137
IS 2
BP 265
EP 270
DI 10.1016/j.ajo.2003.08.003
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 776ZB
UT WOS:000189148300007
PM 14962415
DA 2022-11-30
ER

PT J
AU Foran, S
   Wang, JJ
   Mitchell, P
AF Foran, S
   Wang, JJ
   Mitchell, P
TI Causes of visual impairment in two older population cross-sections: The
   Blue Mountains Eye Study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE visual impairment; visual acuity; population-based cohort; Blue
   Mountains Eye Study; blindness; age-related macular degeneration;
   cataract; glaucoma
ID COMMUNITY SUPPORT SERVICES; CAUSE-SPECIFIC PREVALENCE; AGE-SPECIFIC
   PREVALENCE; PARTIAL SIGHT; AUSTRALIA; BLINDNESS; VISION; ACUITY;
   REGISTRATION; MACULOPATHY
AB Alms To describe the causes of bilateral and unilateral blindness and visual impairment in two cross-sections of an older Australian population 6 years apart. METHODS The Blue Mountains Eye Study examined 3654 persons aged 49-97 years during 1992-1994 (population cross-section I). Cohort survivors (2335) and 1174 persons who moved to the area or reached an eligible age were examined during 1997-2000, a total of 3509 persons (population cross-section 2). LogMAR visual acuity was measured after standardized refraction. Blindness and visual impairment were respectively defined by visual acuity <6/6o and <6/I2. Causes were determined for the two temporal cross-sections.
   RESULTS Age-related macular degeneration (AMD) was the principal cause of bilateral and unilateral non-correctable blindness in both cross-sections. AMD caused 77% of bilateral blindness in Cross-section 1 and 50% in Cross-section 2. Cataract, glaucoma, corneal and neurological disease were next equally frequent causes (6% each) of bilateral blindness in Cross-section 1. In Cross-section 2, cataract ranked as the third most frequent principal cause (10%) after other retinal diseases (40%). The proportion of unilateral blindness with AMD as principal cause was very similar (around one-third of cases) in the two cross-sections; while in Cross-section 2 blindness was less frequently caused by cataract (19% vs. 13%). Cataract was the principal cause of both bilateral and unilateral visual impairment, responsible for 50% of bilateral (better eye) and 35-40% of unilateral (worse eye) impairment, with slightly lower rates found in Cross-section 2 than in Cross-section 1. AMD was consistently the second most frequent cause, causing one-third of bilateral and one-fifth of unilateral visual impairment.
   CONCLUSIONS These data indicate a relative stable pattern of causes for blindness and visual impairment, with AMD and cataract, respectively, dominating these two levels.
C1 Univ Sydney, Westmead Hosp, Dept Ophthalmol, Westmead, NSW 2145, Australia.
   Westmead Millennium, Sydney, NSW, Australia.
   Save Sight Inst, Sydney, NSW, Australia.
C3 University of Sydney; University of Sydney
RP Mitchell, P (通讯作者)，Univ Sydney, Dept Ophthalmol, Hawkesbury Rd, Westmead, NSW 2145, Australia.
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NR 25
TC 72
Z9 74
U1 0
U2 3
PU SWETS ZEITLINGER PUBLISHERS
PI LISSE
PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS
SN 0928-6586
J9 OPHTHALMIC EPIDEMIOL
JI Ophthalmic Epidemiol.
PD OCT
PY 2003
VL 10
IS 4
BP 215
EP 225
DI 10.1076/opep.10.4.215.15906
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 714WW
UT WOS:000184937300001
PM 14628964
DA 2022-11-30
ER

PT J
AU Glynn, RJ
   Rosner, B
AF Glynn, RJ
   Rosner, B
TI Multiple imputation to estimate the association between eyes in disease
   progression with interval-censored data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE multiple imputation; interval-censored data; survival analysis; frailty
   models; clustered data; ophthalmologic data
ID PROPORTIONAL HAZARDS MODEL; REGRESSION; FRAILTY
AB In many ophthalmologic studies, progression of diseases such as diabetic retinopathy, age-related maculopathy, cataract, and glaucoma is only noted when each eye is examined at intervals that commonly vary between subjects. Such data are often analysed using continuous time survival methods with observed progression assumed to occur at the end of the interval. Tied times of progression can lead to substantial bias in estimation of the association between progression in right and left eyes. We describe a multiple imputation strategy to create multiple data sets without ties, based on drawing interval-censored progression times from a parametric gamma frailty model that accounts for continuous and discrete covariates. We illustrate the method with data from 478 patients with insulin-dependent diabetes mellitus who were followed for progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution of tied failure times allows for valid estimation of the hazard of progression in one eye given the progression status of the other eye. A simulation study suggests that the method performs well. Results highlight the advantage of multiple imputation that data imputed under one model can be analysed tinder several alternative models. Copyright (C) 2004 John Wiley Sons, Ltd.
C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
   Harvard Univ, Cambridge, MA 02138 USA.
   Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA.
C3 Harvard University; Brigham & Women's Hospital; Harvard University;
   Harvard University; Brigham & Women's Hospital; Harvard University;
   Harvard T.H. Chan School of Public Health
RP Glynn, RJ (通讯作者)，Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02215 USA.
EM rglynn@rics.bwh.harvard.edu
FU NEI NIH HHS [EY012269] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY012269] Funding Source: NIH RePORTER
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NR 38
TC 6
Z9 6
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD NOV 15
PY 2004
VL 23
IS 21
BP 3307
EP 3318
DI 10.1002/sim.1770
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA 867UO
UT WOS:000224868200005
PM 15493063
DA 2022-11-30
ER

PT J
AU Subash, M
   Rotsos, T
   Wright, GA
   Devery, S
   Holder, GE
   Robson, AG
   Pal, B
   Tufail, A
   Webster, AR
   Moore, AT
   Michaelides, M
AF Subash, Mala
   Rotsos, Tryfonas
   Wright, Genevieve A.
   Devery, Sophie
   Holder, Graham E.
   Robson, Anthony G.
   Pal, Bishwanath
   Tufail, Adnan
   Webster, Andrew R.
   Moore, Anthony T.
   Michaelides, Michel
TI Unilateral vitelliform maculopathy: a comprehensive phenotype study with
   molecular screening of BEST1 and PRPH2
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DYSTROPHY; ISCEV STANDARD; ELECTRORETINOGRAPHY; RETINOPATHY;
   MUTATIONS
AB Aim To describe the clinical features of a case series of patients with unilateral vitelliform maculopathy and the results of screening BEST1 and PRPH2 for diseasecausing mutations.
   Design/Methods This was a retrospective case series study of six patients ascertained over a 2-year period. Ophthalmological examination, fundus photography, autofluorescence imaging, optical coherence tomography and detailed electrophysiological assessment were undertaken. Blood samples were taken for DNA extraction and mutation screening of BEST1 and PRPH2 was performed.
   Results Six patients (3 men and 3 women) with unilateral vitelliform maculopathy were identified, ranging in age from 30 to 68 years. Vision in the affected eye ranged from 20/10 to 20/100. There was no clinical, retinal imaging or electrophysiological evidence of fellow eye involvement. Direct sequencing of BEST1 and PRPH2 did not reveal any disease-causing variants.
   Conclusions A case series of patients is reported with an unusual unilateral vitelliform phenotype, often associated with good visual function. The patients do not have the typical characteristics associated with age-related maculopathy or any inherited macular disorders, such as Best vitelliform macular dystrophy. Molecular screening of the candidate genes BEST1 and PRPH2 revealed no mutations.
C1 [Holder, Graham E.; Robson, Anthony G.; Pal, Bishwanath; Tufail, Adnan; Webster, Andrew R.; Moore, Anthony T.; Michaelides, Michel] UCL, UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Subash, Mala; Rotsos, Tryfonas; Wright, Genevieve A.; Devery, Sophie; Holder, Graham E.; Robson, Anthony G.; Pal, Bishwanath; Tufail, Adnan; Webster, Andrew R.; Moore, Anthony T.; Michaelides, Michel] Moorfields Eye Hosp, Med Retina Serv, London, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust
RP Michaelides, M (通讯作者)，UCL, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM michel.michaelides@ucl.ac.uk
OI Robson, Anthony/0000-0002-8391-6123; Tufail, Adnan/0000-0001-6131-7640
FU Foundation Fighting Blindness (USA); Fight for Sight; Moorfields Special
   Trustees; National Institute for Health Research, UK; Foundation
   Fighting Blindness Career Development
FX The work was supported by grants from the Foundation Fighting Blindness
   (USA); Fight for Sight; Moorfields Special Trustees; and the National
   Institute for Health Research, UK, to the Biomedical Research Centre for
   Ophthalmology based at Moorfields Eye Hospital NHS Foundation Trust and
   UCL Institute of Ophthalmology. MM is supported by a Foundation Fighting
   Blindness Career Development Award.
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NR 19
TC 1
Z9 1
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAY
PY 2012
VL 96
IS 5
BP 719
EP 722
DI 10.1136/bjophthalmol-2011-300964
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 927UX
UT WOS:000302936900023
PM 22174098
DA 2022-11-30
ER

PT J
AU Rudolf, M
   Malek, G
   Messinger, JD
   Clark, ME
   Wang, L
   Curcio, CA
AF Rudolf, Martin
   Malek, Goldis
   Messinger, Jeffrey D.
   Clark, Mark E.
   Wang, Lan
   Curcio, Christine A.
TI Sub-retinal drusenoid deposits in human retina: Organization and
   composition
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE drusen; age-related maculopathy; membranous debris; sub-retinal space;
   imaging; complement factor H; apolipoprotein E; cholesterol
ID AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; MACULAR
   DEGENERATION; PIGMENT EPITHELIUM; BASAL DEPOSITS; UNESTERIFIED
   CHOLESTEROL; EYES; GENE; ATHEROSCLEROSIS; LOCALIZATION
AB We demonstrate histologically sub-retinal drusenoid debris in three aged human eyes, two of them affected by age-related maculopathy. By postmortem fund us examination, the lesions were drusen-like, i.e., they were pale spots apparently at the level of the retinal pigment epithelium (RPE). Light and electron microscopy revealed aggregations of membranous debris, the principal constituent of soft drusen, in the sub-retinal space. Immunohistochemistry and confocal microscopy confirmed the presence of molecules typically associated with drusen (positive for unesterified cholesterol, apoE, complement factor H, and vitronectin) without evidence for molecules associated with photoreceptors (lectin-binding disaccharide bridges and opsins), Muller cells (glial fibrillary acid protein and cellular retinal binding protein, CRALPB), or RPE (CRALPB). The fact that a drusenoid material, sharing some markers with conventional drusen, can occur on opposite faces of the RPE, suggests deranged polarity of normally highly vectorial processes for basolateral secretion from RPE, and that overproduction of secreted materials and direction of secretion are independently specified processes. In the future, drusenoid sub-retinal debris might be more frequently revealed by emerging high-resolution imaging techniques. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Rudolf, Martin; Messinger, Jeffrey D.; Clark, Mark E.; Wang, Lan; Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Callahan Eye Fdn Hosp, Birmingham, AL 35294 USA.
   [Rudolf, Martin] Univ Klinikum Schleswig Holstein, Univ Eye Hosp Lubeck, D-23538 Lubeck, Germany.
   [Malek, Goldis] Duke Univ, Dept Ophthalmol & Pathol, Durham, NC USA.
C3 University of Alabama System; University of Alabama Birmingham;
   University of Kiel; Schleswig Holstein University Hospital; Duke
   University
RP Curcio, CA (通讯作者)，Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Callahan Eye Fdn Hosp, 700 S 18th St Room H020, Birmingham, AL 35294 USA.
EM curcio@uab.edu
OI Malek, Goldis/0000-0003-0026-2388
FU NIH [EY06109]; Deutsche Forschungsgemeinschaft [13942]; International
   Retinal Research Foundation; Department of Ophthalmology from Research
   to Prevent Blindness, Inc.; EyeSight Foundation of Alabama; NATIONAL EYE
   INSTITUTE [R01EY006109] Funding Source: NIH RePORTER
FX We thank the Alabama Eye Bank for retrieval of donor eyes, James A.
   Kimble, M.D. and Scott Cousins, M.D., for helpful discussions, and
   Melissa F. Chimento and J. Brett Presley for technical assistance. We
   thank John C. Saari (University of Washington), Jeremy Nathans (Johns
   Hopkins University), and Robert Molday (University of British Columbia)
   for antibodies. This work was supported by NIH grant EY06109, Deutsche
   Forschungsgemeinschaft (13942), International Retinal Research
   Foundation, unrestricted funds to the Department of Ophthalmology from
   Research to Prevent Blindness, Inc., and EyeSight Foundation of Alabama.
   CAC received a Lew R. Wasserman Merit Award from Research to Prevent
   Blindness, Inc. and the 2002 Roger Johnson Prize in Macular Degeneration
   Research.
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NR 32
TC 140
Z9 144
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2008
VL 87
IS 5
BP 402
EP 408
DI 10.1016/j.exer.2008.07.010
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 374CT
UT WOS:000261020700002
PM 18721807
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Corvi, F
   Cozzi, M
   Corradetti, G
   Staurenghi, G
   Sarraf, D
   Sadda, SR
AF Corvi, Federico
   Cozzi, Mariano
   Corradetti, Giulia
   Staurenghi, Giovanni
   Sarraf, David
   Sadda, SriniVas R.
TI Quantitative assessment of choriocapillaris flow deficits in eyes with
   macular neovascularization
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Choriocapillaris; Macular
   neovascularization; Optical coherence tomography angiography; Type 1
   macular neovascularization; Type 2 macular neovascularization; Type 3
   macular neovascularization
ID RETINAL ANGIOMATOUS PROLIFERATION; OPTICAL COHERENCE TOMOGRAPHY;
   SUBFOVEAL CHOROIDAL THICKNESS; SPECTRAL-DOMAIN; TYPE-3
   NEOVASCULARIZATION; RETICULAR PSEUDODRUSEN; GEOGRAPHIC ATROPHY; SURGICAL
   EXCISION; BLOOD-FLOW; DEGENERATION
AB Purpose To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a group of eyes with Type 1 and/or 2 MNV versus healthy eyes. Methods In this cross-sectional, retrospective, multicenter, observational study, consecutive patients with Type 3 MNV, Type 1 and/or 2 MNV, and age-matched controls were included. PLEX Elite optical coherence tomography angiography was performed with a 6 x 6 mm scan pattern centered on the fovea. The CC FD was computed in 4 peripheral 1 x 1 mm squares to allow comparison between equidistant regions unaffected by MNV. Results Twenty Type 3, 20 Type 1 and/or 2 MNV [13 (65%) Type 1 MNV, 1 (5%) Type 2 MNV, and 6 (30%) mixed Type 1 and 2 MNV], and 20 age-matched controls were included. The mean impairment in the CC in the 4 peripheral squares was 16.07 +/- 7.27% in Type 3 MNV eyes, 11.48 +/- 5.59% in Type 1/2 MNV eyes, and 9.64 +/- 3.59% in controls. Type 3 MNV displayed a statistically significantly higher CC FD compared with both Type 1/2 MNV (P = 0.031) and controls (P < 0.0001). No significant differences were observed between Type 1/2 MNV and controls (P = 0.223). Conclusions CC FD was significantly greater in the peripheral macular regions of eyes with Type 3 MNV compared to eyes with Type 1/2 MNV and normal control eyes. Pathogenic choroidal mechanisms may differ in eyes with different MNV subtypes. Whereas focal CC impairment may drive the development of Type 1/2 MNV, diffuse CC disruption may be more important in eyes with Type 3 MNV.
C1 [Corvi, Federico; Corradetti, Giulia; Sadda, SriniVas R.] Doheny Eye Inst, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Corvi, Federico; Corradetti, Giulia; Sarraf, David; Sadda, SriniVas R.] UCLA, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Corvi, Federico; Cozzi, Mariano; Staurenghi, Giovanni] Univ Milan, Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Milan, Italy.
   [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; University of Milan;
   Luigi Sacco Hospital; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); VA Greater Los Angeles Healthcare System
RP Sadda, SR (通讯作者)，Doheny Eye Inst, 1355 San Pablo St, Los Angeles, CA 90033 USA.; Sadda, SR (通讯作者)，UCLA, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
EM ssadda@doheny.org
RI Corradetti, Giulia/Q-5400-2019; Corvi, Federico/AAD-7691-2021
OI Corradetti, Giulia/0000-0001-9213-5575; Corvi,
   Federico/0000-0002-2661-5500; Cozzi, Mariano/0000-0001-7777-2461
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NR 46
TC 5
Z9 5
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 2021
VL 259
IS 7
BP 1811
EP 1819
DI 10.1007/s00417-020-05056-1
EA JAN 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TI3LH
UT WOS:000606211000007
PM 33417089
DA 2022-11-30
ER

PT J
AU Alizadeh, Y
   Dourandeesh, M
   Akbari, M
AF Alizadeh, Yousef
   Dourandeesh, Maryam
   Akbari, Mitra
TI Laser-induced macular neovascularization following accidental exposure
   to Alexandrite laser and excellent response to anti-VEGF: A case report
SO JOURNAL OF COSMETIC DERMATOLOGY
LA English
DT Article
DE 750-nm Alexandrite laser; anti-VEGF; choroidal neovascularization;
   laser; macular laser injury
AB Objectives This study aimed to report a case of laser-induced macular neovascularization (MVN) following accidental exposure to Alexandrite laser. Methods A young female presented with a painless visual blurring of the right eye 25 days after direct inadvertent exposure to a single discharge from a 750-nm Alexandrite hair removal procedure. The best-corrected visual acuity (BCVA) of the right eye was finger count 3 m (M). Ophthalmoscopic findings, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, and optical coherence tomography angiography were evaluated. Results Fundus examination of the right eye revealed intraretinal hemorrhage and a round yellow-grayish subretinal lesion just beneath the fovea. SD-OCT of the right eye showed retinal thickening, subretinal hyperreflective lesion, subretinal and mild intraretinal fluid, and a small retinal pigment epithelium defect beneath the fovea. Optical coherence tomography angiography demonstrated MNV type 2. After the administration of intravitreal injection of three monthly anti-vascular endothelial growth factor, BCVA improved to 20/20.
C1 [Alizadeh, Yousef; Dourandeesh, Maryam; Akbari, Mitra] Guilan Univ Med Sci, Amiralmomenin Hosp, Eye Res Ctr, Dept Eye,Sch Med, Rasht, Iran.
RP Dourandeesh, M (通讯作者)，Guilan Univ Med Sci, Amiralmomenin Hosp, Eye Res Ctr, Dept Eye,Sch Med, Rasht, Iran.
EM Maryam.dourandeesh.di@gmail.com
CR Asiri MS, 2017, CAN J OPHTHALMOL, V52, pE71, DOI 10.1016/j.jcjo.2016.09.013
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   Huang Amy, 2018, J Clin Aesthet Dermatol, V11, P15
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   Youssef PN, 2011, EYE, V25, P1, DOI 10.1038/eye.2010.149
NR 10
TC 0
Z9 0
U1 1
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1473-2130
EI 1473-2165
J9 J COSMET DERMATOL-US
JI J. Cosmet. Dermatol.
PD JUN
PY 2022
VL 21
IS 6
BP 2445
EP 2448
DI 10.1111/jocd.14412
EA AUG 2021
PG 4
WC Dermatology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Dermatology
GA 2I1AR
UT WOS:000690658400001
PM 34449962
DA 2022-11-30
ER

PT J
AU Avila, MP
   Farah, ME
   Santos, A
   Duprat, JP
   Woodward, BW
   Nau, J
AF Avila, M. P.
   Farah, M. E.
   Santos, A.
   Duprat, J. P.
   Woodward, B. W.
   Nau, J.
TI Twelve-month short-term safety and visual-acuity results from a
   multicentre prospective study of epiretinal strontium-90 brachytherapy
   with bevacizumab for the treatment of subfoveal choroidal
   neovascularisation secondary to age-related macular degeneration
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PLAQUE RADIOTHERAPY; RADIATION-THERAPY; RANIBIZUMAB; MEMBRANES;
   IRRADIATION; VERTEPORFIN
AB Background/aims: This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned.
   Methods: In this prospective, non-randomised, multicentre study, 34 treatment-naive patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts.
   Results: Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >= 3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters.
   Conclusion: The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.
C1 [Avila, M. P.] Univ Fed Goias, Ctr Referencia Oftalmol, Goiania, Go, Brazil.
   [Farah, M. E.; Duprat, J. P.] Univ Fed Sao Paulo, Dept Oftalmol, Sao Paulo, Brazil.
   [Santos, A.] Ctr Med Puerta Hierro, Ctr Retina Med & Quirurg SC, Guadalajara, Jalisco, Mexico.
   [Woodward, B. W.; Nau, J.] NeoVista, Fremont, CA USA.
C3 Universidade Federal de Goias; Universidade Federal de Sao Paulo
   (UNIFESP); Centro Medico Puerta de Hierro
RP Avila, MP (通讯作者)，Ctr Brasileiro Cirurgia Olhos, BR-74210010 Goiania, Go, Brazil.
EM retina@cbco.com.br
RI Farah, Michel Eid E/F-3285-2012
OI Farah, Michel Eid E/0000-0001-5951-0193
CR AVILA MP, RETINA IN PRESS
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NR 24
TC 61
Z9 63
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2009
VL 93
IS 3
BP 305
EP 309
DI 10.1136/bjo.2008.145912
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 411NH
UT WOS:000263655800009
PM 19019935
DA 2022-11-30
ER

PT J
AU Buch, H
AF Buch, H
TI 14-year incidence of age-related maculopathy and cause-specific
   prevalence of visual impairment and blindness in a Caucasian population:
   the Copenhagen City Eye Study
SO ACTA OPHTHALMOLOGICA SCANDINAVICA
LA English
DT Article
ID STUDY/
C1 Natl Univ Hosp, Rigshosp, Dept Ophthalmol, DK-2100 Copenhagen, Denmark.
C3 Rigshospitalet; University of Copenhagen
RP Buch, H (通讯作者)，Natl Univ Hosp, Rigshosp, Dept Ophthalmol, E2061,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
EM hbh@dadlnet.dk
RI Hesgaard, Helena Buch/E-8226-2011
OI Hesgaard, Helena Buch/0000-0002-2097-0202
CR Buch H, 2005, OPHTHALMOLOGY, V112, P305, DOI 10.1016/j.ophtha.2004.08.025
   Buch H, 2004, OPHTHALMOLOGY, V111, P53, DOI 10.1016/j.ophtha.2003.05.010
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   Buch H, 2001, OPHTHALMOLOGY, V108, P2347, DOI 10.1016/S0161-6420(01)00823-5
   BUCH H, 2005, IN PRESS OPHTHALMOLO, V112
   BUCH H, 2005, IN PRESS ACTA OPHTHA, V83
NR 6
TC 26
Z9 26
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1395-3907
J9 ACTA OPHTHALMOL SCAN
JI Acta Ophthalmol. Scand.
PD JUN
PY 2005
VL 83
IS 3
BP 400
EP 401
DI 10.1111/j.1600-0420.2005.00474.x
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 930AV
UT WOS:000229389100028
PM 15857061
OA Bronze
DA 2022-11-30
ER

PT J
AU Mastropasqua, R
   Evangelista, F
   Amodei, F
   D'Aloisio, R
   Pinto, F
   Doronzo, E
   Viggiano, P
   Porreca, A
   Di Nicola, M
   Parravano, M
   Toto, L
AF Mastropasqua, Rodolfo
   Evangelista, Federica
   Amodei, Francesco
   D'Aloisio, Rossella
   Pinto, Filomena
   Doronzo, Emanuele
   Viggiano, Pasquale
   Porreca, Annamaria
   Di Nicola, Marta
   Parravano, Mariacristina
   Toto, Lisa
TI Optical Coherence Tomography Angiography in Macular Neovascularization:
   A Comparison Between Different OCTA Devices
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE macular neovascularization; optical coherence tomography; swept source
   OCTA
ID INDOCYANINE GREEN ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION;
   SPECTRAL-DOMAIN; TYPE-1
AB Purpose: The purpose of this study is to compare the ability of 3 optical coherence tomography angiography (OCTA) devices to measure lesion area in patients with macular neovascularization (MNV) with type 1, 2 and mixed neovascularization (NV).
   Methods: OCTA, fluorescein angiography (FA), indocyanine green angiography (ICGA), and structural optical coherence tomography (OCT) were performed. NV lesion area measurements were performed by two graders.
   Results: Twenty-eight eyes were included: 20 with NV were classified as type 1,6 as type 2, and 2 as mixed type. AngioVue and Spectralis detected the NV in 26 out of 28 eyes (92.8%). The intraclass correlation coefficient (ICC) between readers for the three different OCTA with the different slabs was high. The NV area was larger in the outer retina to choriocapillaris (ORCC) and choriocapillaris (CC) images for the AngioVue device and the PLEX Elite device compared to avascular images (P < 0.05). The mean values of the NV area were not significantly different among the three instruments (Friedman test, P > 0.05) for the avascular zone (AV), ORCC, and CC images. Median (interquartile range [IQR]) NV were significantly different among avascular images, ORCC images, and CC images of the AngioVue device (P = 0.046), of the Spectralis device (P = 0.015), and the PLEX Elite device (P < 0.001).
   Conclusions: The ORCC slabs showed the highest detection rate for NV detection independently to the device used, and swept source (SS)-OCTA measurements of ORCC slabs showed the highest detection rate of NVs compared to the spectral domain (SD)-OCTA.
   Translational Relevance: It is pivotal to realize how much we can rely on OCTA to make a diagnosis of NV.
C1 [Mastropasqua, Rodolfo] Univ Modena & Reggio Emilia, Inst Ophthalmol, Modena, Italy.
   [Evangelista, Federica; Amodei, Francesco; D'Aloisio, Rossella; Pinto, Filomena; Doronzo, Emanuele; Viggiano, Pasquale; Toto, Lisa] Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalm Clin, Via Vestini 31, I-66100 Chieti, Italy.
   [Porreca, Annamaria; Di Nicola, Marta] Univ G dAnnunzio, Dept Econ Studies, Chieti, Italy.
   [Parravano, Mariacristina] IRCCS Fdn Bietti, Rome, Italy.
C3 Universita di Modena e Reggio Emilia; G d'Annunzio University of
   Chieti-Pescara; G d'Annunzio University of Chieti-Pescara; IRCCS -
   Fondazione "G.B. Bietti" per lo Studio e la Ricerca in Oftalmologia
RP Evangelista, F (通讯作者)，Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalm Clin, Via Vestini 31, I-66100 Chieti, Italy.
EM federica.evan@hotmail.com
RI PORRECA, ANNAMARIA/O-3418-2018; DAloisio, Rossella/L-2251-2019; Toto,
   Lisa/K-3473-2018; Mastropasqua, Rodolfo/AAC-6453-2022
OI PORRECA, ANNAMARIA/0000-0003-3278-1561; Toto, Lisa/0000-0001-5311-5184;
   Viggiano, Pasquale/0000-0002-0323-967X
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NR 18
TC 3
Z9 3
U1 1
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD OCT
PY 2020
VL 9
IS 11
AR 6
DI 10.1167/tvst.9.11.6
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OO8KU
UT WOS:000587624500029
PM 33101783
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Trivizki, O
   Moult, EM
   Wang, L
   Iyer, P
   Shi, YY
   Gregori, G
   Feuer, W
   Fujimoto, JG
   Rosenfeld, PJ
AF Trivizki, Omer
   Moult, Eric M.
   Wang, Liang
   Iyer, Prashanth
   Shi, Yingying
   Gregori, Giovanni
   Feuer, William
   Fujimoto, James G.
   Rosenfeld, Philip J.
TI Local Geographic Atrophy Growth Rates Not Influenced by Close Proximity
   to Non-Exudative Type 1 Macular Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE geographic atrophy (GA); optical coherence tomography angiography
   (OCTA); non-exudative type 1; macular neovascularization (MNV); growth
   rate
ID NATURAL-HISTORY; DEGENERATION; ANGIOGRAPHY; PROGRESSION; TOPOGRAPHY;
   MORPHOLOGY
AB PURPOSE. The local growth rates of geographic atrophy (GA) adjacent to non-exudative type 1 macular neovascularization (MNV) were investigated to determine if MNV influ-enced GA growth.
   METHODS. Eyes with GA and non-exudative type 1 MNV were followed for at least 1 year. Both GA and the MNV were imaged and measured using swept-source optical coher-ence tomography angiography (SS-OCTA) scans. Pearson correlations were computed between local growth rates of GA, which were estimated using a biophysical GA growth model, and local distances-to-MNV. Corresponding P values for the null hypothesis of no Pearson correlation were computed using a Monte Carlo approach that adjusts for spatial autocorrelations.
   RESULTS. Nine eyes were included in this study. There were positive correlations (Pearson's r > 0) between distance-to-MNV and local GA growth in eight (89%) of the eyes; however, in all but one eye (11%), correlations were relatively weak and statistically nonsignificant after Bonferroni correction (corrected P > 0.05).
   CONCLUSIONS. SS-OCTA imaging combined with GA growth modeling and spatial statistical analysis enabled quantitative assessment of correlations between local GA growth rates and local distances-to-MNV. Our results are not consistent with non-exudative type 1 MNV having a strong inhibitory effect on local GA growth rates.
C1 [Trivizki, Omer; Wang, Liang; Iyer, Prashanth; Shi, Yingying; Gregori, Giovanni; Feuer, William; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Moult, Eric M.; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, Cambridge, MA 02139 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Massachusetts
   Institute of Technology (MIT)
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@miami.edu
FU Salah Foundation; Research to Prevent Blindness, Inc. (New York, NY);
   National Eye Institute Center Core Grant [P30EY014801]
FX Supported by grants from 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 the
   present research.
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NR 33
TC 1
Z9 1
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JAN
PY 2022
VL 63
IS 1
AR 20
DI 10.1167/iovs.63.1.20
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZP3ZK
UT WOS:000766363400001
PM 35029635
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Amoroso, F
   Mrejen, S
   Pedinielli, A
   Tabary, S
   Souied, EH
   Gaudric, A
   Cohen, SY
AF Amoroso, Francesca
   Mrejen, Sarah
   Pedinielli, Alexandre
   Tabary, Sandrine
   Souied, Eric H.
   Gaudric, Alain
   Cohen, Salomon Y.
TI INTRARETINAL HYPERREFLECTIVE LINES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE optical coherence tomography; hyperreflective foci; hyperreflective
   line; adult vitelliform macular dystrophy; pattern dystrophy;
   pachychoroid; epiretinal membrane; macular microhole; MEWDS
AB Purpose: To report intraretinal hyperreflective lines related to various macular conditions. Methods: All cases were imaged with color photographs, autofluorescence images, and spectral-domain optical coherence tomography, some with fluorescein and/or indocyanine green angiography. Demographic data, imaging, course and outcome were retrospectively analyzed. Results: Forty-nine eyes of 43 patients (16 men and 27 women) were included. Hyperreflective vertical lines (38 eyes) or curvilinear lines along the Henle fiber layer (11 eyes) were present in association with various macular conditions: adult vitelliform dystrophy or pattern dystrophy (24 eyes) frequently associated with an epiretinal membrane (six eyes) and/or thick choroid (nine eyes), age-related maculopathy or macular degeneration (nine eyes), partial resorption of subretinal or intraretinal hemorrhages (five eyes), idiopathic macular microhole (two eyes), vitreomacular traction (three eyes), multiple evanescent white dot syndrome (three eyes), fundus flavimaculatus (two eyes), and pachychoroid pigment epitheliopathy (one eye). The lines fully vanished in cases of hemorrhages, multiple evanescent white dot syndrome or resolution of vitreomacular traction, but usually persisted with gradual thinning in the other conditions. Conclusion: The present series showed that intraretinal hyperreflective lines could occur in various inflammatory, degenerative, or tractional conditions. They could reflect a previously unrecognized reaction to various photoreceptor, Muller cell, and/or retinal pigment epithelium damage.
C1 [Amoroso, Francesca; Pedinielli, Alexandre; Souied, Eric H.; Cohen, Salomon Y.] Univ Paris Est, Dept Ophthalmol, Creteil, France.
   [Mrejen, Sarah; Tabary, Sandrine; Gaudric, Alain; Cohen, Salomon Y.] Ophthalmol Ctr Imaging & Laser, Paris, France.
   [Gaudric, Alain] Univ Paris, Dept Ophthalmol, Hop Lariboisiere, AP HP, Paris, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Assistance Publique
   Hopitaux Paris (APHP); Hopital Universitaire Lariboisiere-Fernand-Widal
   - APHP; UDICE-French Research Universities; Universite Paris Cite
RP Cohen, SY (通讯作者)，Ctr Ophtalmol Imagerie & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
EM sycsyc75@gmail.com
OI Fontanel, Liviana/0000-0002-1032-8929
FU CIL-ASSOC (Paris, France)
FX Supported by an unrestricted grant from CIL-ASSOC (Paris, France), an
   association for research and education.
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NR 33
TC 5
Z9 5
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 JAN
PY 2021
VL 41
IS 1
BP 82
EP 92
DI 10.1097/IAE.0000000000002806
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PR6YJ
UT WOS:000607379100013
PM 32251237
DA 2022-11-30
ER

PT J
AU Kiraly, P
   Zupan, A
   Matjasic, A
   Mekjavic, PJ
AF Kiraly, Peter
   Zupan, Andrej
   Matjasic, Alenka
   Mekjavic, Polona Jaki
TI Associations of Single-Nucleotide Polymorphisms in Slovenian Patients
   with Acute Central Serous Chorioretinopathy
SO GENES
LA English
DT Article
DE central serous chorioretinopathy; CSC; genotype-phenotype correlation;
   collagen; CFH; rs1329428; TNFRSF10A; CDH5
ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   MINERALOCORTICOID RECEPTOR; SUSCEPTIBILITY; GENE; ADRENOMEDULLIN;
   VARIANTS; LOCI; RARE
AB Central serous chorioretinopathy (CSC) is a chorioretinal disease that usually affects the middle-aged population and is characterised by a thickened choroid, retinal pigment epithelium detachment, and subretinal fluid with a tendency towards spontaneous resolution. We investigated 13 single-nucleotide polymorphisms (SNPs) in 50 Slovenian acute CSC patients and 71 healthy controls in Complement Factor H (CFH), Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2), Cadherin 5 (CDH5) Age-Related Maculopathy Susceptibility 2 (ARMS2), TNF Receptor Superfamily Member 10a (TNFRSF10A), collagen IV alpha 3 (COL4A3) and collagen IV alpha 4 (COL4A4) genes using high-resolution melt analysis. Statistical calculations revealed significant differences in genotype frequencies for CFH rs1329428 (p = 0.042) between investigated groups and an increased risk for CSC in patients with TC (p = 0.040) and TT (p = 0.034) genotype. Genotype-phenotype correlation analysis revealed that CSC patients with CC genotype in CFH rs3753394 showed a higher tendency for spontaneous CSC episode resolution at 3 months from the disease onset (p = 0.0078), which could indicate clinical significance of SNP testing in CSC patients. Bioinformatics analysis of the non-coding polymorphisms showed alterations in transcription factor binding motifs for CFH rs3753394, CDH5 rs7499886 and TNFRSF10A rs13278062. No association of collagen IV polymorphisms with CSC was found in this study.
C1 [Kiraly, Peter; Mekjavic, Polona Jaki] Univ Med Ctr Ljubljana, Eye Hosp, Ljubljana 1000, Slovenia.
   [Kiraly, Peter] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford OX3 9DU, England.
   [Zupan, Andrej; Matjasic, Alenka] Univ Ljubljana, Inst Pathol, Fac Med, Ljubljana 1000, Slovenia.
   [Mekjavic, Polona Jaki] Univ Ljubljana, Fac Med, Ljubljana 1000, Slovenia.
   [Mekjavic, Polona Jaki] Inst Jozef Stefan, Ljubljana 1000, Slovenia.
C3 University Medical Centre Ljubljana; Oxford University Hospitals NHS
   Foundation Trust; University of Ljubljana; University of Ljubljana;
   Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute
RP Zupan, A (通讯作者)，Univ Ljubljana, Inst Pathol, Fac Med, Ljubljana 1000, Slovenia.
EM peter.kiraly20@gmail.com; andrej.zupan@mf.uni-lj.si;
   alenka.matjasic@mf.uni-lj.si; polona.jaki@guest.arnes.si
OI Jaki Mekjavic, Polona/0000-0003-1949-4525; Zupan,
   Andrej/0000-0003-3394-7690
FU Slovenian Research Agency (ARRS) [P3-0054, P3-0333]
FX FundingThe authors acknowledge financial support from the Slovenian
   Research Agency (ARRS) (research programs P3-0054 and P3-0333).
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NR 42
TC 0
Z9 0
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4425
J9 GENES-BASEL
JI Genes
PD JAN
PY 2022
VL 13
IS 1
AR 55
DI 10.3390/genes13010055
PG 14
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA YN9NW
UT WOS:000747578200001
PM 35052395
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Borooah, S
   Sim, PY
   Phatak, S
   Moraes, G
   Wu, CY
   Cheung, CMG
   Pal, B
   Bujarborua, D
AF Borooah, Shyamanga
   Sim, Peng Yong
   Phatak, Sumita
   Moraes, Gabriella
   Wu, Chris Yang
   Cheung, Chui Ming Gemmy
   Pal, Bishwanath
   Bujarborua, Dhiren
TI Pachychoroid spectrum disease
SO ACTA OPHTHALMOLOGICA
LA English
DT Review
DE central serous chorioretinopathy; polypoidal choroidal vasculopathy;
   aneurysmal type 1 neovascularization; pachychoroid; pachychoroid
   neovasculopathy; peripapillary pachychoroid disease; focal choroid
   excavation; pachychoroid pigment epitheliopathy
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; CENTRAL
   SEROUS CHORIORETINOPATHY; VERTEPORFIN PHOTODYNAMIC THERAPY; ENDOTHELIAL
   GROWTH-FACTOR; INDOCYANINE-GREEN VIDEOANGIOGRAPHY; PIGMENT EPITHELIAL
   DETACHMENTS; ONE-YEAR OUTCOMES; TERM-FOLLOW-UP; MACULAR DEGENERATION
AB Recent improvements in ophthalmic imaging have led to the identification of a thickened choroid or pachychoroid to be associated with a number of retinal diseases. The number of conditions linked to this phenotype has continued to widen with specific endophenotypes found within the pachychoroid spectrum. The spectrum includes choroidal features such as focal or diffuse choroidal thickening and thinning of the overlying inner choroid, and choroidal hyperpermeability as demonstrated by indocyanine green angiography. In addition, these diseases are associated with overlying retinal pigmentary changes and retinal pigment epithelial dysfunction and may also be associated with choroidal neovascularization. This article provides a comprehensive review of the literature looking at diseases currently described within the pachychoroid spectrum including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, peripapillary pachychoroid disease and focal choroidal excavation. We particularly focus on clinical imaging, genetics and pathological findings in these conditions with the aim of updating evidence suggesting a common aetiology between diseases within the pachychoroid spectrum.
C1 [Borooah, Shyamanga; Wu, Chris Yang] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA.
   [Borooah, Shyamanga; Sim, Peng Yong; Phatak, Sumita; Moraes, Gabriella; Pal, Bishwanath] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Borooah, Shyamanga] Univ Edinburgh, Sch Clin Sci, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
   [Sim, Peng Yong] Royal Free Hosp, London, England.
   [Cheung, Chui Ming Gemmy] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Bujarborua, Dhiren] Pragjyoti Eye Care & Amp Res Ctr, Gauhati, India.
C3 University of California System; University of California San Diego;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of Edinburgh; University of London;
   University College London; Royal Free London NHS Foundation Trust; UCL
   Medical School; Singapore National Eye Center
RP Borooah, S (通讯作者)，Univ Calif San Diego, Jacobs Retina Ctr, Shiley Eye Inst, 9415 Campus Point Dr, La Jolla, CA 92093 USA.
EM sborooah@ucsd.edu
RI Borooah, Shyamanga/AAM-6581-2021
OI Sim, Peng Yong/0000-0001-5500-2634
FU Bayer Funding Source: Medline; Foundation Fighting Blindness Funding
   Source: Medline; Fulbright Association Funding Source: Medline
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NR 210
TC 25
Z9 25
U1 3
U2 11
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD SEP
PY 2021
VL 99
IS 6
BP E806
EP E822
DI 10.1111/aos.14683
EA NOV 2020
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UO6TY
UT WOS:000595197600001
PM 33258304
DA 2022-11-30
ER

PT J
AU Pai, SA
   Shetty, R
AF Pai, Sivakami A.
   Shetty, Rohit
TI Sequential therapy with intravitreal bevacizumab and photodynamic
   therapy for idiopathic polypoidal choroidal vasculopathy
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
ID PIGMENT-EPITHELIUM DETACHMENT; MACULAR DEGENERATION; NEOVASCULARIZATION
C1 [Pai, Sivakami A.] Super Special Eye Hosp, Dept Vitreoretinal Surg, Bangalore 560010, Karnataka, India.
   Postgraduate Teaching Inst, Bangalore 560010, Karnataka, India.
RP Pai, SA (通讯作者)，Super Special Eye Hosp, Dept Vitreoretinal Surg, 121-C Chord Rd,Rajajinagar 1st R Block, Bangalore 560010, Karnataka, India.
EM sudhirshiv@yahoo.com
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NR 5
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 NOV
PY 2009
VL 87
IS 7
BP 806
EP 807
DI 10.1111/j.1755-3768.2008.01330.x
PG 2
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 509FF
UT WOS:000270999300022
PM 18721250
DA 2022-11-30
ER

PT J
AU Chao, WWJ
   Chen, YK
   Chao, HWH
   Pan, WHT
   Chao, HM
AF Chao, Windsor Wen-Jin
   Chen, Yu-Kuang
   Chao, Howard Wen-Haur
   Pan, Wynn Hwai-Tzong
   Chao, Hsiao-Ming
TI Fortified S-Allyl L-Cysteine: Animal Safety, Effect on Retinal Ischemia,
   and Role of Wnt in the Underlying Therapeutic Mechanism
SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID NORRIE-DISEASE; VASCULAR DEVELOPMENT; PROTECTS; CELLS; PATHWAY; CATENIN
AB Purpose. Retinal ischemia is a medical condition associated with numerous retinal vascular disorders, such as age-related macular degeneration, glaucoma, and diabetic retinopathy. This in vitro cell and in vivo animal study investigated not only the protective effect of S-allyl L-cysteine (SAC, an active component of garlic) against retinal ischemia but also its associated protective mechanisms.Methods. Retinal ischemia was mimicked by raising the intraocular pressure to 120 mmHg for 1 hour in one eye. The effects of pre-/postischemic administration of vehicle vs. SAC 0.18 mg vs. SAC 0.018 mg vs. SAC 0.0018 mg treatments on retina cells were evaluated through cellular viability (MTT assay), flash electroretinograms (ERGs), and fluorogold retrograde labelling (retinal ganglion cell (RGC) counting). Also, protein immunoblot was utilized to assess the role of Wnt, hypoxia inducible factor (HIF)-1 alpha, and vascular endothelium factor (VEGF) in the proposed anti-ischemic mechanism. Lastly, the safety of drug consumption was investigated for changes in the animal's body weight, ERG waves, and blood biochemical parameters (e.g., glucose levels).Results. The characteristic ischemic changes including significant reduction in ERG b-wave ratio and RGC number were significantly counteracted by pre- and postischemic low dose of SAC. Additionally, ischemia-induced overexpression of Wnt/HIF-1 alpha/VEGF protein was ameliorated significantly by preischemic low dose of SAC. In terms of the animal safety, no significant body weight and electrophysiological differences were observed among defined different concentrations of SAC without following ischemia. In low SAC dosage and vehicle groups, various blood biochemical parameters were normal; however, high and medium concentrations of SAC significantly lowered the levels of uric acid, Hb, and MCHC.Conclusion. This study shows that preischemic administration of low SAC dosage has been proved to be safe and most effective against rat retinal ischemia electrophysiologically and/or histopathologically. Moreover, counteracting the ischemia-induced overexpression of Wnt/HIF-1 alpha/VEGF might presently explain SAC's anti-ischemic mechanism.
C1 [Chao, Windsor Wen-Jin; Chen, Yu-Kuang; Chao, Howard Wen-Haur; Chao, Hsiao-Ming] Cheng Hsin Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Pan, Wynn Hwai-Tzong; Chao, Hsiao-Ming] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei, Taiwan.
   [Chao, Hsiao-Ming] China Med Univ, Sch Chinese Med, Dept Chinese Med, Taichung, Taiwan.
C3 Cheng Hsin General Hospital; National Yang Ming Chiao Tung University;
   China Medical University Taiwan
RP Chao, HM (通讯作者)，Cheng Hsin Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.; Chao, HM (通讯作者)，Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei, Taiwan.; Chao, HM (通讯作者)，China Med Univ, Sch Chinese Med, Dept Chinese Med, Taichung, Taiwan.
EM windsor.chao123@gmail.com; brady801227@gmail.com;
   wenhaur.chao@gmail.com; wynn@ym.edu.tw; hsiaoming.chao@gmail.com
FU APTORUM, Hong Kong
FX The authors convey their sincere grateful thanks to Ms. Yu-Chun Wang and
   Huei-Wen Shiu, for their skillful technical help with the animal
   experiments and molecular biological assays as well as Professor Ralph
   Kirby for his expertise in correcting the manuscript. They also convey
   the gratefulness to the APTORUM, Hong Kong, for the financial support to
   carry out the animal safety study, the anti-ischemic effects, and the
   therapeutic mechanisms of fortified doses of SAC.
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NR 33
TC 1
Z9 1
U1 1
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1741-427X
EI 1741-4288
J9 EVID-BASED COMPL ALT
JI Evid.-based Complement Altern. Med.
PD OCT 5
PY 2020
VL 2020
AR 3025946
DI 10.1155/2020/3025946
PG 12
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA OI4HY
UT WOS:000583243000002
PM 33082821
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sun, YK
   Zhang, HR
   Yao, XL
AF Sun, Yankui
   Zhang, Haoran
   Yao, Xianlin
TI Automatic diagnosis of macular diseases from OCT volume based on its
   two-dimensional feature map and convolutional neural network with
   attention mechanism
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE optical coherence tomography; convolutional neural network; transfer
   learning; image classification; attention mechanism
ID OPTICAL COHERENCE TOMOGRAPHY; DEGENERATION
AB Significance: Automatic and accurate classification of three-dimensional (3-D) retinal optical coherence tomography (OCT) images is essential for assisting ophthalmologist in the diagnosis and grading of macular diseases. Therefore, more effective OCT volume classification for automatic recognition of macular diseases is needed.
   Aim: For OCT volumes in which only OCT volume-level labels are known, OCT volume classifiers based on its global feature and deep learning are designed, validated, and compared with other methods.
   Approach: We present a general framework to classify OCT volume for automatic recognizing macular diseases. The architecture of the framework consists of three modules: B-scan feature extractor, two-dimensional (2-D) feature map generation, and volume-level classifier. Our architecture could address OCT volume classification using two 2-D image machine learning classification algorithms. Specifically, a convolutional neural network (CNN) model is trained and used as a B-scan feature extractor to construct a 2-D feature map of an OCT volume and volume-level classifiers such as support vector machine and CNN with/without attention mechanism for 2-D feature maps are described.
   Results: Our proposed methods are validated on the publicly available Duke dataset, which consists of 269 intermediate age-related macular degeneration (AMD) volumes and 115 normal volumes. Fivefold cross-validation was done, and average accuracy, sensitivity, and specificity of 98.17%, 99.26%, and 95.65%, respectively, are achieved. The experiments show that our methods outperform the state-of-the-art methods. Our methods are also validated on our private clinical OCT volume dataset, consisting of 448 AMD volumes and 462 diabetic macular edema volumes.
   Conclusions: We present a general framework of OCT volume classification based on its 2-D feature map and CNN with attention mechanism and describe its implementation schemes. Our proposed methods could classify OCT volumes automatically and effectively with high accuracy, and they are a potential practical tool for screening of ophthalmic diseases from OCT volume. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
C1 [Sun, Yankui; Zhang, Haoran; Yao, Xianlin] Tsinghua Univ, Dept Comp Sci & Technol, Beijing, Peoples R China.
C3 Tsinghua University
RP Sun, YK (通讯作者)，Tsinghua Univ, Dept Comp Sci & Technol, Beijing, Peoples R China.
EM syk@mail.tsinghua.edu.cn
FU National Natural Science Foundation of China [61671272]; Key Research
   and Development Project in Guangdong Province [2019B010153002]
FX This work was supported by the National Natural Science Foundation of
   China under Grant No. 61671272 and Key Research and Development Project
   in Guangdong Province under Grant No. 2019B010153002.
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NR 38
TC 5
Z9 5
U1 1
U2 14
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 SEP
PY 2020
VL 25
IS 9
AR 096004
DI 10.1117/1.JBO.25.9.096004
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 OS4OR
UT WOS:000590144100011
PM 32940026
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ozal, SA
   Turkekul, K
   Gurlu, V
   Guclu, H
   Erdogan, S
AF Ozal, S. Altan
   Turkekul, Kader
   Gurlu, Vuslat
   Guclu, Hande
   Erdogan, Suat
TI Esculetin Protects Human Retinal Pigment Epithelial Cells from
   Lipopolysaccharide-induced Inflammation and Cell Death
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Esculetin; ARPE-19 cells; age-related macular degeneration;
   inflammation; lipopolysaccharide
ID MACULAR DEGENERATION; OXIDATIVE STRESS; HYDROGEN-PEROXIDE;
   DIABETIC-RATS; EXPRESSION; ACTIVATION; PATHWAY; INDUCTION; CYTOKINES;
   VEGF
AB Purpose: Age-related macular degeneration (AMD) is the most common cause of visual loss. The dry AMD is characterized by retinal pigment epithelium (RPE) death and changes in AMD lead to severe loss of vision. Coumarin-derived esculetin has a number of therapeutic and pharmacological effects such as anti-inflammatory and antioxidant with various mechanisms. The purpose of this study was to investigate the effects of esculetin treatment on lipopolysaccharide (LPS)-induced inflammation, oxidative stress, and cell survival.Material and methods: Human RPE cells (ARPE-19) were incubated for 24-72h with 5g/ml LPS to induce inflammation and oxidative stress. Esculetin (5 M) was used to protect the cells from LPS-induced damage. The cell viability was evaluated by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Interleukin 6 (IL-6), IL-12, and vascular endothelial growth factor (VEGF) levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1, tumor necrosis factor receptor (TNFR), TNF-related apoptosis-inducing ligand (TRAIL), catalase, glutathione peroxidase (GPx), superoxide dismutase 1 (CuZnSOD) and SOD2 (MnSOD) mRNA expressions were analyzed by RT-quantitative polymerase chain reaction. Apoptosis was monitored by cell-based cytometer. NF-kappa B (NF-B) p65/RelA levels were determined by ELISA, and NF-B protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were evaluated by Western blot analysis.Results: Esculetin treatment significantly suppressed LPS-induced cell death mediated by apoptosis and necrosis in a concentration-dependent manner. While LPS caused significant inflammation with cytokine increase in cells, esculetin reduced the expression of LPS-induced cytokines, VEGF, TNFR, and TRAIL. Furthermore, exposure to LPS increased the expression of GPx and mitochondrial MnSOD, leading to oxidative stress in the cells. Esculetin treatment attenuated phosphorylation of ERK1/2 and NF-B expression mediated by LPS.Conclusions: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.
C1 [Turkekul, Kader; Erdogan, Suat] Trakya Univ, Sch Med, Dept Med Biol, Balkan Campus, TR-22030 Edirne, Turkey.
   [Ozal, S. Altan; Gurlu, Vuslat; Guclu, Hande] Trakya Univ, Sch Med, Dept Ophthalmol, Edirne, Turkey.
C3 Trakya University; Trakya University
RP Erdogan, S (通讯作者)，Trakya Univ, Sch Med, Dept Med Biol, Balkan Campus, TR-22030 Edirne, Turkey.
EM suaterdogan@trakya.edu.tr
RI Ozal, Sadık Altan/B-5123-2019; Güçlü, Hande/AAW-9756-2020
OI Ozal, Sadık Altan/0000-0003-0078-1049; Güçlü, Hande/0000-0002-3021-0493;
   ERDOGAN, SUAT/0000-0002-6823-6293
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NR 40
TC 17
Z9 19
U1 0
U2 22
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 9
BP 1169
EP 1176
DI 10.1080/02713683.2018.1481517
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GQ8IG
UT WOS:000441995900013
PM 29806490
DA 2022-11-30
ER

PT J
AU Giocanti-Auregan, A
   Tadayoni, R
   Fajnkuchen, F
   Dourmad, P
   Magazzeni, S
   Cohen, SY
AF Giocanti-Auregan, Audrey
   Tadayoni, Ramin
   Fajnkuchen, Franck
   Dourmad, Pauline
   Magazzeni, Stephanie
   Cohen, Salomon Y.
TI Predictive Value of Outer Retina En Face OCT Imaging for Geographic
   Atrophy Progression
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; en face optical coherence tomography;
   geographic atrophy
ID LUMINANCE VISUAL-ACUITY; MACULAR DEGENERATION; MICROPERIMETRY; AMD
AB PURPOSE. We determined if the ellipsoid zone (EZ) disruption pattern could be predictive of the geographic atrophy (GA) pattern at 1 year in dry age-related macular degeneration (AMD).
   METHODS. A retrospective study was done of dry eyes in patients with AMD and GA from July to November 2013. Eyes with previous choroidal neovascularization were excluded. Based on spectral domain optical coherence tomography (SD-OCT), the GA was assessed at each timepoint, using a sub-RPE slab derived from the Cirrus Advanced RPE Analysis software encompassing the RPE (sub-RPE slab). Disruption of the EZ also was assessed at baseline, using en face extraction of a 20-mu m-thick slab, 20 mu m above the RPE (EZ slab) encompassing the EZ band using two different algorithms (RPE and RPE-fit). The EZ disruption area surrounding GA at baseline was quantified using ImageJ software. Primary endpoint was to identify en face pattern similarities between the baseline EZ disruption and the 1-year GA. Secondary endpoint was to correlate the baseline EZ disruption area surrounding GA with the GA enlargement over 1 year. Statistical analysis was performed using a correlation test (Pearson) and a t-test.
   RESULTS. We included 37 eyes of 31 patients with dry AMD. En face EZ disruption pattern correlated in two-thirds of cases with the 1-year GA pattern using both algorithms. The EZ disruption area surrounding GA at baseline and GA enlargement over 1 year were poorly correlated when RPE-fit algorithm (R = 0.17) was used. The correlation was still poor using an RPE algorithm (R = 0.38), but increased after selection of eyes without reticular pseudodrusen (R = 0.79).
   CONCLUSIONS. The EZ disruption pattern could be an indicator for GA pattern progression, but is not a good quantitative tool to predict the size of GA in the overall population over a 1-year period except for patients without reticular pseudodrusen. The results in this specific population must be confirmed by further studies.
C1 [Giocanti-Auregan, Audrey; Fajnkuchen, Franck] Hop Avicenne, AP HP, Dept Ophthalmol, F-93009 Bobigny, France.
   [Giocanti-Auregan, Audrey; Fajnkuchen, Franck] Univ Paris 13, Bobigny, France.
   [Giocanti-Auregan, Audrey; Tadayoni, Ramin; Fajnkuchen, Franck] Dept Hosp Univ Vis & Handicaps, Paris, France.
   [Tadayoni, Ramin] Hop Lariboisiere, AP HP, Dept Ophthalmol, F-75475 Paris, France.
   [Tadayoni, Ramin] Univ Paris 07, Paris, France.
   [Fajnkuchen, Franck; Dourmad, Pauline; Cohen, Salomon Y.] Ctr Ophtalmol Imagerie & Laser, Paris, France.
   [Magazzeni, Stephanie] Carl Zeiss Meditec, Marly Le Roi, France.
   [Cohen, Salomon Y.] Hop Intercommunal Creteil, Dept Ophthalmol, Creteil, France.
   [Cohen, Salomon Y.] Univ Paris Est Creteil, Creteil, France.
C3 Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Avicenne - APHP; Universite Paris 13; Universite Paris 13; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire
   Lariboisiere-Fernand-Widal - APHP; UDICE-French Research Universities;
   Universite Paris Cite; UDICE-French Research Universities; Universite
   Paris Cite; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI
   Creteil; Universite Paris-Est-Creteil-Val-de-Marne (UPEC)
RP Cohen, SY (通讯作者)，CIL Ctr Ophtalmol Imagerie & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
EM sycsyc75@gmail.com
FU CIL-Assoc, Association for Research and Education, Paris, France
FX Supported in part by CIL-Assoc, Association for Research and Education,
   Paris, France.
CR Bhutto I, 2012, MOL ASPECTS MED, V33, P295, DOI 10.1016/j.mam.2012.04.005
   Holz FG, 2014, OPHTHALMOLOGY, V121, P1079, DOI 10.1016/j.ophtha.2013.11.023
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NR 11
TC 10
Z9 10
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2015
VL 56
IS 13
BP 8325
EP 8330
DI 10.1167/iovs.14-15480
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DB1BU
UT WOS:000368243800087
PM 26747761
DA 2022-11-30
ER

PT J
AU Uro, M
   Beauchet, O
   Cherif, M
   Graffe, A
   Milea, D
   Annweiler, C
AF Uro, Mathieu
   Beauchet, Olivier
   Cherif, Mehdi
   Graffe, Alix
   Milea, Dan
   Annweiler, Cedric
TI Age-Related Vitamin D Deficiency Is Associated with Reduced Macular
   Ganglion Cell Complex: A Cross-Sectional High-Definition Optical
   Coherence Tomography Study
SO PLOS ONE
LA English
DT Article
ID ALZHEIMERS-DISEASE; HYPOVITAMINOSIS D; DEGENERATION; IMPAIRMENT;
   THICKNESS; D-3
AB Background
   Vitamin D deficiency is associated with smaller volume of optic chiasm in older adults, indicating a possible loss of the visual axons and their cellular bodies. Our objective was to determine whether vitamin D deficiency in older adults is associated with reduced thickness of the ganglion cell complex(GCC) and of the retinal nerve fibre layer(RNFL), as measured with high-definition optical coherence tomography(HD-OCT).
   Methods
   Eighty-five French older community-dwellers without open-angle glaucoma and patent age-related macular degeneration(mean, 71.1 +/- 4.7years; 45.9% female) from the GAIT study were separated into 2 groups according to serum 25OHD level(i.e., deficient <= 25nmol/L or sufficient>25nmol/L). Measurements of GCC and RNFL thickness were performed using HD-OCT. Age, gender, body mass index, number of comorbidities, dementia, functional autonomy, intracranial volume, visual acuity, serum calcium concentration and season of testing were considered as potential confounders.
   Results
   Mean serum 25OHD concentration was 58.4 +/- 26.8nmol/L. Mean logMAR visual acuity was 0.03 +/- 0.06. Mean visual field mean deviation was -1.25 +/- 2.29dB. Patients with vitamin D deficiency(n=11) had a reduced mean GCC thickness compared to those without vitamin D deficiency(72.1 +/- 7.4 mu m versus 77.5 +/- 7.5 mu m, P=0.028). There was no difference of the mean RNFL thickness in these two groups(P=0.133). After adjustment for potential confounders, vitamin D deficiency was associated with reduced GCC thickness(beta=-5.12, P=0.048) but not RNFL thickness(beta=-9.98, P=0.061). Specifically, vitamin D deficiency correlated with the superior medial GCC area(P=0.017) and superior temporal GCC area(P=0.010).
   Conclusions
   Vitamin D deficiency in older patients is associated with reduced mean GCC thickness, which can represent an early stage of optic nerve damage, prior to RNFL loss.
C1 [Uro, Mathieu; Cherif, Mehdi; Graffe, Alix; Milea, Dan] Angers Univ Hosp, Dept Ophthalmol, Angers, France.
   [Beauchet, Olivier; Annweiler, Cedric] Univ Angers, UNAM, Angers Univ Hosp,UPRES EA 4638, Dept Neurosci,Div Geriatr Med,Univ Memory Clin An, Angers, France.
   [Milea, Dan] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Milea, Dan] Singapore Eye Res Inst, Singapore, Singapore.
   [Milea, Dan] Duke NUS, Neurosci & Behav Dis, Singapore, Singapore.
   [Annweiler, Cedric] Univ Western Ontario, Schulich Sch Med & Dent, Dept Med Biophys, Robarts Res Inst, London, ON, Canada.
C3 Universite d'Angers; Centre Hospitalier Universitaire d'Angers;
   Universite d'Angers; Centre Hospitalier Universitaire d'Angers;
   Singapore National Eye Center; National University of Singapore;
   Singapore National Eye Center; National University of Singapore; Western
   University (University of Western Ontario)
RP Annweiler, C (通讯作者)，Univ Angers, UNAM, Angers Univ Hosp,UPRES EA 4638, Dept Neurosci,Div Geriatr Med,Univ Memory Clin An, Angers, France.
EM CeAnnweiler@chu-angers.fr
RI Milea, Dan/AAT-8661-2021; Beauchet, Olivier/AAP-8108-2020
OI Annweiler, Cedric/0000-0002-7199-8109
FU French Ministry of Health (Projet Hospitalier de Recherche Clinique
   national) [2009-A00533-54]
FX The study was financially supported by the French Ministry of Health
   (Projet Hospitalier de Recherche Clinique national no 2009-A00533-54).
   The funder had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
CR Annweiler C, 2015, J INTERN MED, V277, P45, DOI 10.1111/joim.12279
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NR 43
TC 19
Z9 19
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 19
PY 2015
VL 10
IS 6
AR e0130879
DI 10.1371/journal.pone.0130879
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CL3FE
UT WOS:000356835000154
PM 26090872
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Kim, NK
   Kim, CY
   Choi, MJ
   Park, SR
   Choi, BH
AF Kim, Na Kyeong
   Kim, Chan Yun
   Choi, Min Joo
   Park, So Ra
   Choi, Byung Hyune
TI EFFECTS OF LOW-INTENSITY ULTRASOUND ON OXIDATIVE DAMAGE IN RETINAL
   PIGMENT EPITHELIAL CELLS IN VITRO
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Retinal pigment epithelium; Low-intensity ultrasound; Oxidative stress;
   Mitochondria; Cytoprotection
ID PULSED ULTRASOUND; MOLECULAR-MECHANISMS; APOPTOSIS; STRESS;
   OSTEOARTHRITIS; MITOCHONDRIA; STIMULATION; INDUCTION; THERAPY; CULTURE
AB Oxidative stress in retinal pigment epithelium (RPE) is one of the key causative factors of RPE injury in age-related macular degeneration (AMD). Low-intensity ultrasound (LIUS) less than 1 W/cm(2) in intensity has been found to have cytoprotective and anti-inflammatory effects in many cell types and diseases. In this study, we investigated for the first time the feasibility of using LIUS to protect RPE cells from oxidative damage. ARPE-19 cells were treated with H2O2 (an exogenous source of reactive oxygen species) or L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthase inhibitor, and exposed immediately to LIUS at intensities of 50, 100 and 200 mW/cm(2) and a frequency of 1 MHz for 20 min. Both H2O2 and BSO increased the percentage of cells positive for mitochondrial reactive oxygen species at 1 h, but not at 24 h. Co-treatment with LIUS clearly repressed these cells similarly at all intensities by approximately 34%-43% for H2O2 and 24%-25% for BSO (p < 0.05). The percentage of cells with mitochondrial membrane depolarization also increased with H2O2 and BSO treatment, particularly at 1 h, and decreased by approximately 60% with LIUS at 100 mW/cm(2) (p < 0.05). The amount of intracellular calcium ion ([Ca2+](i)) was elevated only by BSO at 24 h and was also significantly diminished, by approximately 45%, by LIUS at 100 mW/cm(2) (p < 0.05). Both H2O2 and BSO significantly hampered cell viability at 24 h, but LIUS at 100 mW/cm(2) restored only BSO-induced cell viability by approximately 2.7-fold (p < 0.05). This study illustrated that LIUS has a protective effect on RPE cells against oxidative damage caused by BSO, an endogenous mitochondrial reactive oxygen species generator. We speculate that LIUS has the potential to treat oxidative damage and related pathologic changes in RPE. (C) 2015 World Federation for Ultrasound in Medicine & Biology.
C1 [Kim, Na Kyeong; Park, So Ra] Inha Univ, Coll Med, Dept Physiol, Inchon, South Korea.
   [Kim, Chan Yun] Yonsei Univ, Coll Med, Dept Ophthalmol, Inst Vis Res, Seoul 120749, South Korea.
   [Choi, Min Joo] Jeju Natl Univ, Coll Med, Dept Med, Cheju, South Korea.
   [Choi, Byung Hyune] Inha Univ, Dept Biomath Sci, Coll Med, Inchon, South Korea.
C3 Inha University; Yonsei University; Yonsei University Health System;
   Jeju National University; Inha University
RP Choi, BH (通讯作者)，Inha Univ, Coll Med, Dept Biomed Sci & So Ra Pk, Dept Physiol, B-3 Jeongsuk Bldg,Sinheungdong 3 Ga, Inchon, South Korea.
EM srpark@inha.ac.kr; bryan@inha.ac.kr
OI Kim, Chan Yun/0000-0002-8373-9999
FU Inha University; Korea Health Technology R&D Project, Ministry of Health
   & Welfare, Republic of Korea [A101727]
FX This study was supported by an Inha University grant and a grant from
   the Korea Health Technology R&D Project, Ministry of Health & Welfare,
   Republic of Korea (A101727).
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   Zorov DB, 2000, J EXP MED, V192, P1001, DOI 10.1084/jem.192.7.1001
NR 39
TC 8
Z9 10
U1 2
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0301-5629
EI 1879-291X
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD MAY
PY 2015
VL 41
IS 5
BP 1363
EP 1371
DI 10.1016/j.ultrasmedbio.2014.12.665
PG 9
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA CF8JD
UT WOS:000352803100023
PM 25722027
DA 2022-11-30
ER

PT J
AU Nangia, V
   Jonas, JB
   Gupta, R
   Khare, A
   Sinha, A
AF Nangia, Vinay
   Jonas, Jost B.
   Gupta, Rajesh
   Khare, Anshu
   Sinha, Ajit
TI Visual impairment and blindness in rural central India: the Central
   India Eye and Medical Study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE blindness; Central India Eye and Medical Study; epidemiology; India;
   population-based study; visual acuity; visual impairment
ID ADULT-POPULATION; PREVALENCE; ASSOCIATIONS; VISION
AB . Purpose: The aim of the study was to investigate prevalence of visual impairment in rural central India. Methods: The population-based Central India Eye and Medical Study included 4711 subjects with an age of 30+ years. Presenting visual acuity (PRVA) and best-corrected visual acuity (BCVA) were recorded. Visual impairment and blindness were defined using the World Health Organization (WHO) standard and United States (US) standard. Results: On the basis of PRVA and using WHO and US standards, 1049 [22%; 95% confidence interval (CI): 21.1, 23.5] subjects and 1290 (27%; 95% CI: 26.1, 28.7) subjects, respectively, were visually impaired, and 35 (0.7%; 95% CI: 0.5, 1.0) subjects and 116 (2.5%; 95% CI: 2.0, 2.9) subjects, respectively, were blind. The corresponding age-standardized prevalence figures were 17%, 21%, 0.5% and 2%, respectively. Using best-correcting glasses could eliminate PRVA-visual impairment/blindness in 729 subjects (67% of all subjects with visual impairment/blindness). On the basis of BCVA and using WHO and US standards, 333 (7%; 95% CI: 6.3, 7.8) subjects and 473 (10%; 95% CI: 9.2, 10.9) subjects, respectively, had visual impairment, and 22 (0.5%; 95% CI: 0.3, 0.7) and 31 (0.7%; 95% CI: 0.4, 0.9) subjects, respectively, were blind. Corresponding age-standardized prevalence figures were 5%, 8%, 0.4% and 0.5%, respectively. Causes for BCVA-visual impairment/blindness were cataract (75%), postoperative posterior capsular opacification (4%), surgical complications (2%), corneal opacifications (2%), age-related macular degeneration (2%), other macular diseases (1%), and glaucoma (1%). Conclusions: Age-standardized prevalence of PRVA-visual impairment/blindness (WHO definition) in the adult population of rural central India was 17%. Most frequent cause was undercorrected refractive error. Supply of correct glasses is the most efficient way to improve vision in the rural central India.
C1 [Nangia, Vinay; Jonas, Jost B.; Gupta, Rajesh; Khare, Anshu; Sinha, Ajit] Suraj Eye Inst, Nagpur 440001, Maharashtra, India.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
C3 Suraj Eye Institute; Ruprecht Karls University Heidelberg
RP Nangia, V (通讯作者)，Suraj Eye Inst, Plot 559, Nagpur 440001, Maharashtra, India.
EM nagpursuraj@gmail.com
FU Om Drishti Trust Nagpur; Heidelberg Engineering Co. Heidelberg, Germany;
   Rotary Sight Saver Netherlands; ORBIS International; Carl Zeiss Meditec
   Co., Jena, Germany
FX Supported by an unrestricted grant from Om Drishti Trust Nagpur;
   Heidelberg Engineering Co. Heidelberg, Germany; Rotary Sight Saver
   Netherlands; ORBIS International; and Carl Zeiss Meditec Co., Jena,
   Germany.
CR Buch H, 2001, OPHTHALMOLOGY, V108, P2347, DOI 10.1016/S0161-6420(01)00823-5
   Dandona L, 1999, OPHTHALMOLOGY, V106, P497, DOI 10.1016/S0161-6420(99)90107-0
   Dandona L, 2001, INVEST OPHTH VIS SCI, V42, P908
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NR 12
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD AUG
PY 2013
VL 91
IS 5
BP 483
EP 486
DI 10.1111/j.1755-3768.2012.02447.x
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 180VD
UT WOS:000321626000038
PM 22682108
OA Bronze
DA 2022-11-30
ER

PT J
AU Chan, CM
   Chang, HH
   Wang, VC
   Huang, CL
   Hung, CF
AF Chan, Chi-Ming
   Chang, Hsun-Hsien
   Wang, Vin-Chi
   Huang, Chuen-Lin
   Hung, Chi-Feng
TI Inhibitory Effects of Resveratrol on PDGF-BB-Induced Retinal Pigment
   Epithelial Cell Migration via PDGFR beta, PI3K/Akt and MAPK pathways
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY; EXTRACELLULAR-MATRIX
   PROTEINS; VASCULAR SMOOTH-MUSCLE; GROWTH-FACTOR RECEPTOR; BREAST-CANCER
   CELLS; IN-VIVO; (-)-EPIGALLOCATECHIN GALLATE; DIABETIC-RETINOPATHY;
   ADJUNCTIVE TREATMENT; ARPE19 CELLS
AB Purpose: In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue.
   Methods: The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay.
   Results: Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor beta (PDGFR beta) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFR alpha and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration.
   Conclusions: These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRb, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin.
C1 [Chan, Chi-Ming] Cardinal Tien Hosp, Dept Ophthalmol, New Taipei City, Taiwan.
   [Chan, Chi-Ming; Wang, Vin-Chi; Hung, Chi-Feng] Fu Jen Catholic Univ, Sch Med, New Taipei City, Taiwan.
   [Chang, Hsun-Hsien; Hung, Chi-Feng] Harvard Univ, Childrens Hosp Informat Program, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol,Med Sch, Boston, MA USA.
   [Wang, Vin-Chi] Cardinal Tien Hosp, Neurol Ctr, New Taipei City, Taiwan.
   [Huang, Chuen-Lin] Cardinal Tien Hosp, Med Res Ctr, New Taipei City, Taiwan.
   [Huang, Chuen-Lin] Natl Def Med Ctr, Dept Physiol & Biophys, Grad Inst Physiol, Taipei, Taiwan.
C3 Cardinal Tien Hospital; Fu Jen Catholic University; Harvard University;
   Boston Children's Hospital; Harvard Medical School; Massachusetts
   Institute of Technology (MIT); Broad Institute; Cardinal Tien Hospital;
   Cardinal Tien Hospital; National Defense Medical Center
RP Hung, CF (通讯作者)，Fu Jen Catholic Univ, Sch Med, New Taipei City, Taiwan.
EM 054317@gmail.com
RI Hung, Chi-Feng/AAL-4977-2021; Chan, Chi-Ming/GWZ-3612-2022
OI Hung, Chi-Feng/0000-0003-3478-5451; Troughton,
   Richard/0000-0001-7484-4036
FU National Science Council, Taipei, Taiwan [NSC97-2320-B-030-001-MY3];
   Cardinal Tien Hospital, Taipei, Taiwan [FU10008]
FX This work was supported by the research grants from the National Science
   Council (NSC97-2320-B-030-001-MY3) and from Cardinal Tien Hospital
   (FU10008), Taipei, Taiwan. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript
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NR 64
TC 70
Z9 78
U1 0
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 14
PY 2013
VL 8
IS 2
AR e56819
DI 10.1371/journal.pone.0056819
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700096
PM 23844213
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Greenberg, PB
   Tseng, VL
   Wu, WC
   Liu, J
   Jiang, L
   Chen, CK
   Scott, IU
   Friedmann, PD
AF Greenberg, Paul B.
   Tseng, Victoria L.
   Wu, Wen-Chih
   Liu, Jeffrey
   Jiang, Lan
   Chen, Christine K.
   Scott, Ingrid U.
   Friedmann, Peter D.
TI Prevalence and Predictors of Ocular Complications Associated with
   Cataract Surgery in United States Veterans
SO OPHTHALMOLOGY
LA English
DT Article
ID INTRAOCULAR-LENS IMPLANTATION; PARS-PLANA VITRECTOMY; RESIDENTS
   PERFORMING PHACOEMULSIFICATION; CLINICAL-OUTCOMES; RETINAL-DETACHMENT;
   MARITAL-STATUS; HEALTH-STATUS; POSTOPERATIVE OUTCOMES; VISUAL OUTCOMES;
   VITREOUS LOSS
AB Purpose: To investigate the prevalence and predictors of intraoperative and 90-day postoperative ocular complications associated with cataract surgery performed in the United States Veterans Health Administration (VHA) system.
   Design: Retrospective cohort study.
   Participants: Forty-five thousand eighty-two veterans who underwent cataract surgery in the VHA.
   Methods: The National Patient Care Database was used to identify all VHA patients who underwent outpatient extracapsular cataract surgery and who underwent only 1 cataract surgery within 90 days of the index surgery between October 1, 2005, and September 30, 2007. Data collected include demographics, preoperative systemic and ocular comorbidities, intraoperative complications, and 90-day postoperative complications. Adjusted odds ratios (ORs) of factors predictive of complications were calculated using logistic regression modeling.
   Main Outcome Measures: Intraoperative and postoperative ocular complications within 90 days of cataract surgery.
   Results: During the study period, 53 786 veterans underwent cataract surgery; 45 082 met inclusion criteria. Common preoperative systemic and ocular comorbidities included diabetes mellitus (40.6%), chronic pulmonary disease (21.2%), age-related macular degeneration (14.4%), and diabetes with ophthalmic manifestations (14.0%). The most common ocular complications were posterior capsular tear, anterior vitrectomy, or both during surgery (3.5%) and posterior capsular opacification after surgery (4.2%). Predictors of complications included: black race (OR, 1.38; 95% confidence interval [CI], 1.28-1.50), divorced status (OR, 1.10; 95% CI, 1.03-1.18), never married (OR, 1.26; 95% CI, 1.14-1.38), diabetes with ophthalmic manifestations (OR, 1.33; 95% CI, 1.23-1.43), traumatic cataract (OR, 1.80; 95% CI, 1.40-2.31), previous ocular surgery (OR, 1.29; 95% CI, 1.02-1.63), and older age.
   Conclusions: In a cohort of United States veterans with a high preoperative disease burden, selected demographic factors and ocular comorbidities were associated with greater risks of cataract surgery complications. Further large-scale studies are warranted to investigate cataract surgery outcomes for non-VHA United States patient populations.
C1 [Greenberg, Paul B.; Tseng, Victoria L.; Chen, Christine K.] VA Med Ctr, Sect Ophthalmol, Providence, RI 02908 USA.
   [Greenberg, Paul B.; Tseng, Victoria L.; Chen, Christine K.] Brown Univ, Warren Alpert Med Sch, Div Ophthalmol, Providence, RI 02912 USA.
   [Greenberg, Paul B.; Tseng, Victoria L.; Wu, Wen-Chih; Liu, Jeffrey; Jiang, Lan; Chen, Christine K.; Friedmann, Peter D.] VA Med Ctr, Res Enhancement Award Program, Providence, RI 02908 USA.
   [Wu, Wen-Chih; Liu, Jeffrey; Friedmann, Peter D.] VA Med Ctr, Med Serv, Providence, RI 02908 USA.
   [Wu, Wen-Chih; Friedmann, Peter D.] Brown Univ, Dept Med, Warren Alpert Med Sch, Providence, RI 02912 USA.
   [Scott, Ingrid U.] Penn State Coll Med, Dept Ophthalmol, Hershey, PA USA.
   [Scott, Ingrid U.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Providence VA Medical Center; Brown University; US Department of
   Veterans Affairs; Veterans Health Administration (VHA); Providence VA
   Medical Center; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Providence VA Medical Center; Brown University;
   Pennsylvania Commonwealth System of Higher Education (PCSHE);
   Pennsylvania State University; Penn State Health; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Pennsylvania State
   University; Penn State Health
RP Greenberg, PB (通讯作者)，VA Med Ctr, Sect Ophthalmol, 830 Chalkstone Ave, Providence, RI 02908 USA.
EM paul_greenberg@brown.edu
OI Scott, Ingrid/0000-0002-3908-7153
FU Center on Systems, Outcomes, and Quality in Chronic Disease and
   Rehabilitation; Department of Veterans Affairs, Washington, DC (Health
   Service Research and Development Service) [REA08-263]
FX Supported by the Center on Systems, Outcomes, and Quality in Chronic
   Disease and Rehabilitation, Research Enhancement Award Program,
   Department of Veterans Affairs, Washington, DC (Health Service Research
   and Development Service Grant no.: REA08-263). The views expressed in
   this article are those of the authors and do not necessarily reflect the
   position or policy of the United States Department of Veterans Affairs
   or the United States government.
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NR 73
TC 101
Z9 110
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2011
VL 118
IS 3
BP 507
EP 514
DI 10.1016/j.ophtha.2010.07.023
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 729QA
UT WOS:000287964400014
PM 21035868
DA 2022-11-30
ER

PT J
AU Naveen, S
   Khanum, F
AF Naveen, S.
   Khanum, F.
TI ANTIDIABETIC, ANTIATHEROSCLEROTIC AND HEPATOPROTECTIVE PROPERTIES OF
   DECALEPIS HAMILTONII IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
SO JOURNAL OF FOOD BIOCHEMISTRY
LA English
DT Article
ID ANTIOXIDANT ACTIVITY; LIPID-PEROXIDATION; DNA-DAMAGE; AQUEOUS EXTRACT;
   IN-VITRO; ROOTS; INSULIN; WIGHT; GLUCOSE; ARN.
AB Decalepis root is consumed as ingredient in pickles and is a common ingredient in many of the ayurvedic preparation. Streptozotocin (STZ) is a potential source of oxidative stress that induces diabetes. In the present study, we have investigated the effect of Decalepis root extract (DRE) on antioxidant defence system in the body and other diabetic complications in rats. Rats were prefed with DRE (0.05 and 0.1%) and then injected with STZ (50 mg/kg bodyweight, i.p.). The results demonstrated that STZ injection lead to increased oxidation of tissue lipids apart from diabetic changes, decreased activities of the antioxidant enzymes causing liver and DNA damage. In rats, which were prefed with DRE, peroxidation of lipids was prevented to a significant level (heart 19%, kidney 42% and liver 88%). DRE protected the rats against STZ induced oxidative stress, reduced the risk of oxidative stress, DNA damage and ameliorated liver damage and diabetic condition.
   PRACTICAL APPLICATIONS
   The results obtained in this study clearly demonstrated that Decalepis root extract is plant-derived and nontoxic, it could be introduced in the cancer therapy regime in combination with conventional therapeutic agents, after some more detailed investigation. This extract could be used not only as food preservative (to replace for the toxic butylated hydroxyanisole and butylated hydroxytoluene currently under use) but also can be used in the preparation of nutraceutical and pharmaceutical products. Reactive oxygen species-mediated oxidative stress is now regarded as a major factor leading to degenerative diseases such as ageing, cardiovascular disease, cancer, diabetes, stroke, osteoporosis, diseases of the brain and nervous system and eye diseases such as cataract and age-related macular degeneration; a suitable antioxidant therapies with the extract could be one of the medicine to control these degenerative diseases. This study presents cost effective source of highly potent antioxidants that is safe and natural with antidiabetic, anti-atherosclerotic and hepatoprotective properties.
C1 [Naveen, S.; Khanum, F.] Def Food Res Lab, Dept Biochem & Nutr, Mysore 570011, Karnataka, India.
C3 Defence Research & Development Organisation (DRDO); Defence Food
   Research Laboratory (DFRL)
RP Khanum, F (通讯作者)，Def Food Res Lab, Dept Biochem & Nutr, Mysore 570011, Karnataka, India.
EM dr.farhathkhanum@gmail.com
RI S., Naveen/E-8678-2013
OI S., Naveen/0000-0001-6316-7973
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NR 57
TC 8
Z9 8
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-8884
EI 1745-4514
J9 J FOOD BIOCHEM
JI J. Food Biochem.
PD DEC
PY 2010
VL 34
IS 6
BP 1231
EP 1248
DI 10.1111/j.1745-4514.2010.00361.x
PG 18
WC Biochemistry & Molecular Biology; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Food Science & Technology
GA 691FC
UT WOS:000285064700008
DA 2022-11-30
ER

PT J
AU Leske, MC
   Wu, SY
   Nemesure, B
   Hennis, A
AF Leske, M. Cristina
   Wu, Suh-Yuh
   Nemesure, Barbara
   Hennis, Anselm
CA Barbados Eye Studies Grp
TI Causes of visual loss and their risk factors: an incidence summary from
   the Barbados Eye Studies
SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC
   HEALTH
LA English
DT Article
DE Vision disorders, vision, low; incidence; risk factors; Barbados
ID OPEN-ANGLE GLAUCOMA; LONG-TERM INCIDENCE; BEAVER DAM EYE;
   DIABETIC-RETINOPATHY; UNITED-STATES; MACULAR DEGENERATION;
   BLOOD-PRESSURE; 9-YEAR INCIDENCE; INTRAOCULAR-PRESSURE; LENS OPACITIES
AB Objectives. To summarize incidence and risk factors for each main cause of visual loss in an African-Caribbean population and discuss the implications of these data from a public health perspective.
   Methods. A nationally representative cohort (n = 4 709; ages 40-84 years at baseline) had ophthalmic and other examinations over 9 years. Incidence rates were estimated by the product-limit approach. Risk factors were evaluated from Cox regression models.
   Results. Average incidence was similar to 0.1% per year for blindness (< 6/120) and 0.7% per year for low vision (< 6/18 to 6/120), increasing steeply with age (P < 0.05) and affecting related quality of life (P < 0.05). Age-related cataract and open-angle glaucoma (OAG) accounted for 73.2% of blindness and diabetic retinopathy (DR) for 8.9%; cataract caused two-thirds of low vision. Average incidence was 5.1% per year for all lens changes (gradable/ungradable opacities or aphakia) and 0.4% per year for cataract surgery. Incidence of definite OAG was 0.5% per year (0.9% for suspect or probable); 53% of the affected were unaware. Persons with diabetes mellitus (DM) had a DR incidence of 4.4% per year. Age-related macular degeneration was rare (0.08% per year). Main cataract risk factors were age and DM. OAG incidence increased with age, intraocular pressure, family history, low ocular perfusion pressures, and thinner corneas. DR risk increased with early DM onset, DM duration, oral/insulin treatment, increased systolic and diastolic blood pressures, and hyperglycemia. Antihypertensive treatment halved DR risk.
   Conclusions. Incidence of visual impairment was high and significantly affected quality of life. Age-related cataract and OAG caused similar to 75% of blindness, indicating the need for public health action to increase appropriate cataract surgery and early OAG detection and treatment. Controlling DM and hypertension would help prevent DR-related complications and could lower cataract risk, further decreasing visual loss.
C1 [Leske, M. Cristina; Wu, Suh-Yuh; Nemesure, Barbara; Hennis, Anselm] SUNY Stony Brook, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA.
   [Hennis, Anselm] Minist Hlth, Bridgetown, Barbados.
   [Hennis, Anselm] Univ W Indies, Chron Dis Res Ctr, Res Inst Trop Med, Cave Hill, Barbados.
   [Barbados Eye Studies Grp] Johns Hopkins Univ, Wilmer Inst, Baltimore, MD USA.
C3 State University of New York (SUNY) System; SUNY Community College;
   State University of New York (SUNY) Stony Brook; University West Indies
   Mona Jamaica; University West Indies Cave Hill Campus; Johns Hopkins
   University
RP Leske, MC (通讯作者)，SUNY Stony Brook, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA.
EM cleske@notes.cc.sunysb.edu
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NR 67
TC 24
Z9 25
U1 0
U2 7
PU PAN AMER HEALTH ORGANIZATION
PI WASHINGTON
PA 525 23RD ST NW, WASHINGTON, DC 20037 USA
SN 1020-4989
J9 REV PANAM SALUD PUBL
JI Rev. Panam. Salud Publica
PD APR
PY 2010
VL 27
IS 4
BP 259
EP 267
DI 10.1590/S1020-49892010000400004
PG 9
WC Public, Environmental & Occupational Health
WE Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA 597NG
UT WOS:000277764200004
PM 20512228
OA gold
DA 2022-11-30
ER

PT J
AU Theoulakis, PE
   Lepidas, J
   Petropoulos, IK
   Livieratou, A
   Brinkmann, CK
   Katsimpris, JM
AF Theoulakis, P. E.
   Lepidas, J.
   Petropoulos, I. K.
   Livieratou, A.
   Brinkmann, C. K.
   Katsimpris, J. M.
TI Effect of Brimonidine/Timolol Fixed Combination on Preventing the
   Short-Term Intraocular Pressure Increase after Intravitreal Injection of
   Ranibizumab
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE intraocular pressure elevation; intravitreal injection; ranibizumab;
   brimonidine; timolol
ID MACULAR DEGENERATION; TRIAMCINOLONE ACETONIDE; BEVACIZUMAB; PEGAPTANIB;
   PARACENTESIS; ELEVATION; THERAPY
AB Background: The aim of this study was to evaluate the safety and efficacy of brimonidine 0.2% and timolol 0.5% instillation as a fixed combination (Combigan (TM), Allergan Inc.) to prevent acute intraocular pressure (IOP) increase occurring after intravitreal injection of ranibizumab (Lucentis (TM), Novartis Pharma AG).
   Patients and Methods: A prospective double-blind placebo-controlled study was carried out. One eye of 88 consecutive normotensive age-related macular degeneration patients receiving Lucentis (TM) was randomized into placebo drops (artificial tears, 44 patients) or Combigan (TM) drops (44 patients) given twice a day the day before and the day of injection. IOP was measured before and 5, 10, 15 minutes and 1 hour after the intravitreal injection.
   Results: The placebo group had the higher mean IOP at all time points after injection. Maximum IOP increase for both groups occurred at the 5-minutes time point. Mean post-injection IOP in the placebo group was 34.1 +/- 2.7 mmHg at 5 minutes post-injection versus 28.4 +/- 1.1 mmHg in the Combigan (TM) group (P < 0.001). IOP decreased to 24.9 +/- 1.8 mmHg (placebo group) and 19.9 +/- 1.1 mmHg (Combigan (TM) group) at 10 minutes post-injection. At 15 minutes post-injection, IOP was below 20 mmHg in all eyes of the Combigan (TM) group (100%), whereas at the same time point these IOP levels were reached only by 34% of the eyes of the placebo group (15 eyes). All eyes of both groups had a normal IOP 1 hour post-injection. No systemic or ocular side effect was recorded in either group.
   Conclusions: The use of Combigan (TM) drops twice a day the day before and the day of injection in eyes scheduled for intravitreal injection of Lucentis (TM) is a safe and effective prophylaxis to reduce the acute IOP spikes of the post-injection period.
C1 [Lepidas, J.; Livieratou, A.; Katsimpris, J. M.] Gen Hosp Patras Agios Andreas, Dept Ophthalmol, GR-26335 Patras, Greece.
   [Theoulakis, P. E.] Royal Free Hosp NHS Trust, Dept Ophthalmol, London, England.
   [Petropoulos, I. K.] Ophthalmol Ctr Terrassiere, Geneva, Switzerland.
   [Brinkmann, C. K.] Inselspital Bern, Univ Eye Clin, CH-3010 Bern, Switzerland.
C3 University of London; University College London; University of Bern;
   University Hospital of Bern
RP Katsimpris, JM (通讯作者)，Gen Hosp Patras Agios Andreas, Dept Ophthalmol, Ritsou & Empeirikou St 73, GR-26335 Patras, Greece.
EM jkatsimpris@yahoo.com
CR Bakri SJ, 2009, EYE, V23, P181, DOI 10.1038/sj.eye.6702938
   Bakri SJ, 2008, GRAEF ARCH CLIN EXP, V246, P955, DOI 10.1007/s00417-008-0819-2
   Benz MS, 2006, OPHTHALMOLOGY, V113, P1174, DOI 10.1016/j.ophtha.2005.10.061
   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   CODEN DJ, 1988, OPHTHALMIC SURG LAS, V19, P667
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   Spaide RF, 2006, RETINA-J RET VIT DIS, V26, P383, DOI 10.1097/00006982-200604000-00001
   Thompson JT, 2006, AM J OPHTHALMOL, V141, P629, DOI 10.1016/j.ajo.2005.11.050
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   Zamvar Usha, 2005, BMC Ophthalmol, V5, P24, DOI 10.1186/1471-2415-5-24
NR 23
TC 34
Z9 36
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 2010
VL 227
IS 4
BP 280
EP 284
DI 10.1055/s-0029-1245201
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 585XH
UT WOS:000276863200011
PM 20408074
DA 2022-11-30
ER

PT J
AU Zhao, SH
   Pan, DY
   Zhang, Y
   Wu, JH
   Liu, X
   Xu, Y
AF Zhao Shi-hong
   Pan Dong-yan
   Zhang Yuan
   Wu Jin-hui
   Liu Xin
   Xu Yu
TI Annexin A2 promotes choroidal neovascularization by increasing vascular
   endothelial growth factor expression in a rat model of argon laser
   coagulation-induced choroidal neovascularization
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE annexin A2; vascular endothelial growth factor; choroid
   neovascularization
ID MOUSE MODEL; PROTEIN; CELLS; ANGIOGENESIS; ACTIVATION; VEGF; THERAPY;
   PATHWAY; BINDING
AB Background Choroidal neovascularization (CNV) is a common cause of visual loss in the elderly patients with age-related macular degeneration and represents the growth of subretinal new vessels in the macular region. This study aimed to investigate the relationship between annexin A2 (ANXA2) and vascular endothelial growth factor (VEGF) in CNV.
   Methods In a rat model of argon laser coagulation-induced CNV, the mRNA expressions of the annexins and VEGF protein expression in the retina were detected using fluorescent real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. The interactions between ANXA2 and VEGF in both a retinal pigment epithelial cell line RPE-J and the rat model of CNV were examined by means of RNA interference, real-time PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA) and histopathological examinations.
   Results Fundus fluorescein angiography (FFA) showed that argon laser coagulation of the retina induced stable CNV models in the rats. Two to three weeks after the coagulation, ANXA2 and VEGF expressions in the coagulated area in the retina and choroid increased to the peak level, while the other annexin members (ANXA4, ANXA5, ANXA7 and ANXA11) showed no obvious changes. In RPE-J cells and the CNV model, RNA interference of ANXA2 gene significantly lowered the VEGF protein and mRNA expressions, and application of an adenoviral vector containing ANXA2 gene markedly increased VEGF expressions in the rat model of CNV, but produced no significant effects on the expressions of the kinase insert domain-containing receptor (KDR) or the fms-like tyrosine kinase (Flt-1). The expression of KDR inhibited the increment in ANXA2 expression, but VEGF and Flt-1 did not directly affect ANXA2 expression.
   Conclusion Besides the role as a plasminogen and the receptor of tissue plasminogen activator, ANXA2, which is under regulation of KDR via a negative feedback mechanism, also participates in neovascularization by regulating VEGF expression through a positive feedback mechanism. Chin Med J 2010;123(6):713-721
C1 [Zhao Shi-hong; Pan Dong-yan; Zhang Yuan; Wu Jin-hui; Liu Xin; Xu Yu] Second Mil Med Univ, Changhai Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
C3 Naval Medical University
RP Zhao, SH (通讯作者)，Second Mil Med Univ, Changhai Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
EM zhaosh2001@sina.com
FU National Natural Science Foundation of China [30572000, 30772395];
   Medical Research Foundation of Chinese People's Liberation Army [06Z025]
FX This study was supported by grants from the National Natural Science
   Foundation of China (No. 30572000 and No. 30772395) and Medical Research
   Foundation of Chinese People's Liberation Army (No. 06Z025).
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NR 42
TC 14
Z9 15
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0366-6999
EI 2542-5641
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD MAR 20
PY 2010
VL 123
IS 6
BP 713
EP 721
DI 10.3760/cma.j.issn.0366-6999.2010.06.014
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 577NO
UT WOS:000276230600014
PM 20368092
DA 2022-11-30
ER

PT J
AU Gismondi, M
   Salati, C
   Salvetat, ML
   Zeppieri, M
   Brusini, P
AF Gismondi, Maurizio
   Salati, Carlo
   Salvetat, Maria L.
   Zeppieri, Marco
   Brusini, Paolo
TI Short-term Effect of Intravitreal Injection of Ranibizumab (Lucentis) on
   Intraocular Pressure
SO JOURNAL OF GLAUCOMA
LA English
DT Article
DE intraocular pressure; intravitreal injection; ranibizumab; Lucentis;
   age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NEOVASCULARIZATION;
   PREVENTION; TONOMETER; GLAUCOMA; ANTIBODY; EYES
AB Purpose: To investigate short-term effect on intraocular pressure (IOP) after intravitreal injection of ranibizumab (Lucentis) (IVIL).
   Materials and Methods: This prospective study included 1 eye of 54 patients (64 +/- 12 y) with wet age-related macular degeneration treated with IVIL. IOP measurements with TonoPen were taken: immediately before and 5 seconds, 5, 10, 15, 30 60 minutes, and 1 day after IVIL. Axial length (with ultrasound biometry) was assessed in 24 eyes. The analysis included IOP difference at various time points and between phakic and pseudophakic eyes and the relationship between axial length and IOP increases after 5 seconds.
   Results: Mean IOP were 16.3 +/- 3.0 mm Hg (range: 12.0 to 21.3). 44.1 +/- 10.6 (22.0 to 59.3), 29.0 +/- 9.6 (15.0 to 49.0). 25.8 +/- 7.9 (16.0 to 45.0), 23.7 +/- 6.6 (15.7 to 39.0), 21.9 +/- 5.6 (14.7 to 37.0). 18.8 +/- 6.1 (10.0 to 35.0), and 16.1 +/- 3.0 (11.0 to 21.0), respectively, for time points immediately before, 5 seconds, 5, 10, 15, 30, 60 minutes, and I day after IVIL. Differences between before IVIL and after IVIL IOP were statistically significant after 5 seconds, 5. 10, 15, and 30 minutes (P = 0.0001); however, were not significant after 1 hour (P = 0.064) and I day (P = 0.449). Differences between phakic and pseudophakic eyes were not significant (P > 0.05). The relationship between shorter axial length and IOP increase after 5 seconds was significant (linear regression analysis; R-2 = 0.28, P = 0.007).
   Conclusions: IVIL causes a considerable short-term transient rise in IOP. The IOP increase after IVIL can be statistically significant at 0 to 30 minutes after injection in both phakic and pseudophakic eyes, and tends to be greater in shorter eyes.
C1 [Brusini, Paolo] Univ Santa Maria della Misericordia, SOC Oculist, Azienda Osped, Dept Ophthalmol, I-33100 Udine, Italy.
C3 Hospital Santa Maria della Misericordia
RP Brusini, P (通讯作者)，Univ Santa Maria della Misericordia, SOC Oculist, Azienda Osped, Dept Ophthalmol, P Le S Maria della Misericordia 15, I-33100 Udine, Italy.
EM brusini@libero.it
RI Zeppieri, Marco/ABA-8926-2020
OI Zeppieri, Marco/0000-0003-0999-5545
CR Aiello LP, 2004, RETINA-J RET VIT DIS, V24, pS3, DOI 10.1097/00006982-200410001-00002
   Benz MS, 2006, OPHTHALMOLOGY, V113, P1174, DOI 10.1016/j.ophtha.2005.10.061
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NR 26
TC 83
Z9 89
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-0829
EI 1536-481X
J9 J GLAUCOMA
JI J. Glaucoma
PD DEC
PY 2009
VL 18
IS 9
BP 658
EP 661
DI 10.1097/IJG.0b013e31819c4893
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 534MH
UT WOS:000272900900004
PM 20010243
DA 2022-11-30
ER

PT J
AU Jakobsdottir, J
   Gorin, MB
   Conley, YP
   Ferrell, RE
   Weeks, DE
AF Jakobsdottir, Johanna
   Gorin, Michael B.
   Conley, Yvette P.
   Ferrell, Robert E.
   Weeks, Daniel E.
TI Interpretation of Genetic Association Studies: Markers with Replicated
   Highly Significant Odds Ratios May Be Poor Classifiers
SO PLOS GENETICS
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY;
   OPERATING CHARACTERISTIC CURVE; CROHNS-DISEASE SUSCEPTIBILITY; MACULAR
   DEGENERATION; EDUCATIONAL PRIORITIES; GENERAL-PRACTITIONERS; LOC387715
   GENES; RISK
AB Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10(-13), 10-(13), and 10(-3), respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively), only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of personalized medicine before their time.
C1 [Jakobsdottir, Johanna; Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15261 USA.
   [Conley, Yvette P.; Ferrell, Robert E.; Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; University of California System; University of California
   Los Angeles; University of California Los Angeles Medical Center; David
   Geffen School of Medicine at UCLA; University of California System;
   University of California Los Angeles; University of California Los
   Angeles Medical Center; David Geffen School of Medicine at UCLA;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh
RP Jakobsdottir, J (通讯作者)，Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
EM joj8@pitt.edu
RI Weeks, Daniel E/B-2995-2012
OI Weeks, Daniel E/0000-0001-9410-7228; Jakobsdottir,
   Johanna/0000-0002-8019-9683
FU NEI [R01EY009859]; Steinbach Foundation, New York; Research to Prevent
   Blindness, New York; Eye and Ear Foundation of Pittsburgh; American
   Health Assistance Foundation, Clarksburg, Maryland; Jules Stein Eye
   Institute, Los Angeles, California; NATIONAL EYE INSTITUTE [R01EY009859]
   Funding Source: NIH RePORTER
FX This work was supported by NEI grant R01EY009859, The Steinbach
   Foundation, New York, Research to Prevent Blindness, New York, The Eye
   and Ear Foundation of Pittsburgh, the American Health Assistance
   Foundation, Clarksburg, Maryland, and the Jules Stein Eye Institute, Los
   Angeles, California (all to MBG). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
CR Calefato JM, 2008, GENET MED, V10, P99, DOI [10.1097/GIM.Ob013e3181614271, 10.1097/GIM.0b013e3181614271]
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   2007, NAT GENET, V39, P1415
NR 49
TC 192
Z9 198
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2009
VL 5
IS 2
AR e1000337
DI 10.1371/journal.pgen.1000337
PG 8
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 449GY
UT WOS:000266320000001
PM 19197355
OA gold, Green Published, Green Submitted, Green Accepted
DA 2022-11-30
ER

PT J
AU Kurzinger, GR
   Lang, GK
   Lang, GE
AF Kuerzinger, G. R.
   Lang, G. K.
   Lang, G. E.
TI Photedynamic therapy in retinal angiomatous proliferations
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularisation; retinal
   angiomatous proliferation; retinal choroidal anastomosis; intraretinal
   neovascularisation; photodynamic therapy
ID INDOCYANINE GREEN ANGIOGRAPHY; INTRAVITREAL TRIAMCINOLONE ACETONIDE;
   MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; SURGICAL ABLATION;
   NEOVASCULARIZATION; ANASTOMOSES; DETACHMENTS
AB Purpose: In age-related macular degeneration (ARMD) angiomatous proliferation can progress from the retina into the subretinal space. Retinal angiomatous proliferation (RAP) can be diagnosed by angiographic findings and optical coherence tomography (OCT). We investigated the outcome of photodynamic therapy in patients with RAP.
   Methods: 14 patients with ARMD and RAP were retrospectively analysed using a standardised protocol. The protocol included best corrected visual acuity (BCVA), ophthalmoscopy, OCT examination, fundus photography and fluorescein angiography (FAG). In a masked fashion the OCT and angiographic findings were independently graded in 3 stages (RAP 1: intraretinal neovascularisation, RAP 11: subretinal neovascularisation with a retinal-retinal anastomosis Or subretinal neovascularisation with a serous pigment epithelial detachment, RAP II: choroidal neovascularisation with vascularised pigment epithelial detachment and retinal-choroidal anastomosis). 15 eyes of these 14 patients were evaluated pre- and post-PDT with the standardised protocol and the data statistically analysed.
   Results: The age ranged from 58 to 90 years (median 76 years). In 15 eyes of 14 patients with RAP a PDT was performed. 6 of these 15 PDT cases were successfully treated and gained >= 2 lines (dry rnacula), 3 eyes with RAP I and 3 with RAP II. 4 eyes stablilised with +/- 1 line (persistent mcular oedema) under PDT with 2 RAP 1, 1 RAP 11 and 1 RAP III. 5 eyes showed a deterioration with loss of >= 2 lines (increasing macula oedema) with 2 RAP I and 3 RAP III. The median BCVA was pre-PDT in the successful cases 0.3, post-PDT 0.6, in the stable cases pre-PDT 0.2, post-PDT 0.2 and in the deterioration group pre-PDT 0.4 and post-PDT 0.01.
   Conclusions: According to our study PDT might be helpful in the treatment of RAP stages I and II in selected cases in ARMD patients. Further prospective studies are required to investigate the outcome of PDT in RAP.
C1 [Kuerzinger, G. R.; Lang, G. K.; Lang, G. E.] Univ Ulm Klinikum, Augenklin, D-89075 Ulm, Germany.
C3 Ulm University; University of Hamburg; University Medical Center
   Hamburg-Eppendorf
RP Lang, GK (通讯作者)，Univ Ulm Klinikum, Augenklin, Prittwitzstr 43, D-89075 Ulm, Germany.
EM gabriele.lang@uniklinik-ulm.de
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NR 33
TC 2
Z9 2
U1 0
U2 0
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 FEB
PY 2008
VL 225
IS 2
BP 159
EP 164
DI 10.1055/s-2008-1027198
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 279LC
UT WOS:000254355700007
PM 18293269
DA 2022-11-30
ER

PT J
AU Waes, JGV
   Smith, L
   Van Waes, M
   Wilberding, J
   Eudy, JD
   Bauer, LK
   Maddox, J
AF Waes, J. Gelineau-Van
   Smith, L.
   Van Waes, M.
   Wilberding, J.
   Eudy, J. D.
   Bauer, L. K.
   Maddox, J.
TI Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal
   development of the retinal pigment epithelium in
   microphthalmia-associated transcription factor Mitf(mi) and
   Mitf(vitiligo) mouse mutants
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelium (RPE); microphthalmia-associated
   transcription factor (Mitf); gene expression; Nramp1 (Slc11a1); iron
   homeostasis; melanosome; vitiligo mouse mutant; retinal degeneration
ID MACULAR DEGENERATION; MACROPHAGE PROTEIN-1; NATURAL-RESISTANCE; C-MYC;
   MELANOSOMAL PROTEINS; TRANSFERRIN-RECEPTOR; VITILIGO MICE; CELLS; GENE;
   MELANOCYTES
AB Microphthalmia-associated transcription factor (Mitf) is expressed in neural crest cell-derived melanocytes, and in the retinal pigment epithelium (RPE) during ocular development. Mutations in Mitf are associated with auditory/visual/pigmentary syndromes in humans. Mirf(mi/mi) mouse mutants lack pigmentation, and are microphthatmic, while Mitf(vit/vit) mouse mutants display abnormal RPE pigmentation, and progressive retinal degeneration. Microarray analysis was used to identify novel downstream gene targets/pathways in the RPE that are altered by mutations in the transcription factor Mitf. Using the Affymetrix platform, gene expression profiles were generated using the eyes of E13.5 mouse fetuses that were wildtype, heterozygous, or homozygous for the Mitf(mi) mutation. In a separate experiment, eyes from E13.5 mouse fetuses homozygous for the Mitf(vit) mutation were compared to eyes from the C57BL/6 control background strain. Statistical analyses were performed using robust multiarray average, mixed-effects ANOVA and random-variance t-tests. Altered expression of genes involved in pigment formation, melanosome biogenesis/transport, and redox homeostasis were observed. Twelve genes were commonly mis-regulated in the eyes of both Mitf mutants: 10 of these genes were downregulated in both mutants relative to controls, while 2 of the genes (Nramp1 (Slc11a1) and epoxide hydrolase) were downregulated in Mitf(mi/mi) mutants, and conversely, upregulated in Mitf(vit/vit) mutants. Quantitative RT-PCR and immunohistochemistry were used to confirm altered gene/protein expression. RPE expression of the Fe+2 iron transporter Nramp1 (Slc11a1) has not previously been reported. Fe+2 is an important co-factor utilized by the iron-dependent isomerohydrolase RPE65 in the retinoid visual cycle. However, excess accumulation of Fe+2 in the RPE has recently been associated with oxidative damage and age-related macular degeneration. Abnormal pigmentation and increased activity of Slc11a1 in the RPE of Mitf(vit) mice may contribute to the pathology and progressive retinal degeneration observed in these mutants. (C) 2007 Elsevier Ltd. All rights reserved.
C1 [Waes, J. Gelineau-Van; Wilberding, J.; Eudy, J. D.; Bauer, L. K.; Maddox, J.] Univ Nebraska, Med Ctr 985455, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA.
   [Smith, L.] Univ Nebraska, Med Ctr, Dept Prevent & Social Med, Omaha, NE 68198 USA.
   [Van Waes, M.] LI COR Biosci Inc, Lincoln, NE 68504 USA.
C3 University of Nebraska System; University of Nebraska Medical Center;
   University of Nebraska System; University of Nebraska Medical Center
RP Waes, JGV (通讯作者)，Univ Nebraska, Med Ctr 985455, Dept Genet Cell Biol & Anat, 600 S 42nd St, Omaha, NE 68198 USA.
EM jvanwaes@unmc.edu
FU NCRR NIH HHS [P20 RR 016469, P20 RR018788, P20 RR016469, P20 RR 018788,
   P20 RR018788-047476] Funding Source: Medline; NATIONAL CENTER FOR
   RESEARCH RESOURCES [P20RR016469, P20RR018788] Funding Source: NIH
   RePORTER
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NR 74
TC 6
Z9 7
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2008
VL 86
IS 2
BP 419
EP 433
DI 10.1016/j.exer.2007.11.015
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 278FY
UT WOS:000254271600030
PM 18191835
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lu, L
   Hackett, SF
   Mincey, A
   Lai, H
   Campochiaro, PA
AF Lu, L
   Hackett, SF
   Mincey, A
   Lai, H
   Campochiaro, PA
TI Effects of different types of oxidative stress in RPE cells
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; HYDROGEN-PEROXIDE; ANTIOXIDANT; RESISTANCE;
   MITOCHONDRIA; PROTECTS; RELEASE; DEFENSE; DAMAGE; MODEL
AB Oxidative damage to retinal pigmented epithelial ME) cells and photoreceptors has been implicated in the pathogenesis of age-related macular degeneration (AMD). In order to develop new treatments, it is necessary to characterize the antioxidant defense system in RPE cells to better define their vulnerabilities and how they can be remedied. In this study, we sought to investigate the effects of three different types of oxidative stress on cultured RPE cells. Carbonyl content in RPE cells increased with increasing concentrations of oxidants or increasing duration of exposure with high reproducibility, validating ELISA for carbonyl content as a valuable quantitative measure of oxidative damage. Compared to other cell types, RPE cells were able to survive exposure to H2O2 quite well and exposure to paraquat extremely well. Comparison of the total amount of oxidative damage at the IC50 for each type of stress showed a rank order of hyperoxia > paraquat > H2O2, and since these stressors primarily target different cellular compartments, it suggests that the endogenous defense system against oxidative damage in RPE cells protects well against damage to mitochondria and endoplasmic reticulum, and is less able to handle oxidative damage at the cell surface. Supplementation of media with ascorbic acid provided significant protection from H2O2-induced oxidative damage, but not that induced by paraquat or hyperoxia. Supplementation with docosahexaenoic acid or a-tocopherol significantly reduced oxidative damage from H2O2 or hyperoxia, but not that induced by paraquat. We conclude that exposure to different types of oxidative stress results in different patterns of accrual of oxidative damage to proteins in RPE cells, different patterns of loss of viability, and is differentially countered by antioxidants. This study suggests that multiple types of oxidant stress should be used to probe the vulnerabilities of the retina and RPE in vivo, and that ELISA for carbonyl content provides a valuable tool for quantitative assessment of oxidative damage for such studies.
C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhml.edu
FU NEI NIH HHS [EY12609, P30EY1765, EY05951] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [P30EY001765, R01EY012609] Funding Source: NIH
   RePORTER
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NR 31
TC 98
Z9 104
U1 0
U2 11
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 JAN
PY 2006
VL 206
IS 1
BP 119
EP 125
DI 10.1002/jcp.20439
PG 7
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA 989QX
UT WOS:000233689900014
PM 15965958
DA 2022-11-30
ER

PT J
AU Tsai, DC
   Charng, MJ
   Lee, FL
   Hsu, WM
   Chen, SJ
AF Tsai, Der-Chong
   Charng, Min-Ji
   Lee, Fenq-Lih
   Hsu, Wen-Ming
   Chen, Shih-Jen
TI Different plasma levels of vascular endothelial growth factor and nitric
   oxide between patients with choroidal and retinal neovascularization
SO OPHTHALMOLOGICA
LA English
DT Article
DE choroidal neovascularization; vascular endothelial growth factor; nitric
   oxide; age-related macular degeneration; proliferative diabetic
   retinopathy
ID PROLIFERATIVE DIABETIC-RETINOPATHY; MACULAR DEGENERATION; PERMEABILITY
   FACTOR; CHORIOCAPILLARIS; MEMBRANES; SERUM; FLUID; ANGIOGENESIS;
   EXPRESSION; MELLITUS
AB Because the blood flow is much more intense in the choroid than in the retina, it is interesting to explore whether choroidal neovascularization (CNV) is more influenced by plasma angiogenic factors than retinal neovascularization. The aim of this study was to investigate plasma profiles of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in patients with CNV due to age-related macular degeneration (AMD) and in those with retinal neovascularization due to proliferative diabetic retinopathy (PDR). Seventy-seven subjects with AMD, 22 with PDR, and 42 nondiabetic, non-AMD controls were enrolled in this comparative case series. AMD subjects were classified into three groups: dry type (dry AMD, n = 17), wet type with active CNV (CNV/AMD, n = 42), and disciform scar due to advanced wet AMD (scar/AMD, n = 18). Plasma VEGF and NO levels of each subject were measured with enzyme-linked immunosorbent assay and chemiluminescence, respectively. Plasma VEGF level in CNV/AMD (median 256.0 pg/ml, interquartile range 146.4-375.3 pg/ml) was significantly higher than in PDR (124.8 pg/ml, 75.7-215.3 pg/ml; p = 0.004) and controls (120.3 pg/ml, 82.8-168.2 pg/ml, p = 0.001). CNV/AMD also had the highest VEGF level among the AMD subgroups. Plasma NO level was significantly elevated in PDR (137.4 mu M, 63.7-240.1 mu M) when compared with CNV/AMD (71.8 mu M, 42.4-113.3 mu M; p = 0.004) and controls (62.6 mu M, 39.0-114.9 mu M; p = 0.002). There was no significant difference in NO levels among the AMD subgroups. No significant correlation between VEGF and NO levels was noted. These findings indicate that both circulating VEGF and NO may play different roles in the pathogenesis of retinal neovascularization and CNV. Copyright (c) 2006 S. Karger AG, Basel.
C1 Vet Gen Hosp, Dept Ophthalmol, Taipei 11217, Taiwan.
   Vet Gen Hosp, Dept Med, Taipei 11217, Taiwan.
   Natl Yang Ming Univ, Taipei 112, Taiwan.
   ILan Hosp, Dept Ophthalmol, Ilan, Taiwan.
C3 National Yang Ming Chiao Tung University
RP Chen, SJ (通讯作者)，Vet Gen Hosp, Dept Ophthalmol, 201,Sect 2,Shih Pai Rd, Taipei 11217, Taiwan.
EM sjchen@vghtpe.gov.tw
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NR 31
TC 30
Z9 33
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2006
VL 220
IS 4
BP 246
EP 251
DI 10.1159/000093079
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 057DR
UT WOS:000238577000007
PM 16785756
DA 2022-11-30
ER

PT J
AU Fujikado, T
   Shimojyo, H
   Hosohata, J
   Tsujikawa, K
   Fukui, T
   Ohji, M
   Tano, Y
AF Fujikado, T
   Shimojyo, H
   Hosohata, J
   Tsujikawa, K
   Fukui, T
   Ohji, M
   Tano, Y
TI Effect of simultaneous oblique muscle surgery in foveal translocation by
   360 degrees retinotomy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID VISUAL FUNCTION; CHOROIDAL NEOVASCULARIZATION; GLOBE
AB Purpose: To assess the effect of simultaneous oblique muscle surgery during foveal translocation surgery with 360degrees retinotomy in patients with neovascular maculopathy. Methods: Foveal translocation with 360degrees retinotomy was performed on 31 eyes of 31 patients with neovascular maculopathy (21 with age-related macular degeneration 9 with myopic neovascular maculopathy, and I with idiopathic neovascular maculopathy). All eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Visual acuity, binocular vision, and degree of cyclotorsion were assessed pre- and postoperatively. The angles of retinal and global rotation, distance of foveal shift, and surgical complications were also investigated. Results: With a mean postoperative follow-up of 10.0 months, vision improved (>0.2 log MAR units) in 13 eyes, was unchanged in 9 eyes, and worsened (>0.2 log MAR units) in 9 eyes, Ten of 31 eyes (32%) had a final visual acuity of 20/50 or better. Eleven patients had binocular fusion, 13 patients showed suppression, and 7 patients developed diplopia that was managed by spectacles with prisms or by secondary muscle surgery. The mean retinal and global rotations were 30.3degrees and 23.7degrees, respectively. The average size of the choroidal neovascular membrane was 1.3 disc diameters (DD), while the average shift of the fovea was 1.5 DD. After the primary surgery, six eyes developed retinal detachment, two eyes macular hole, and three eyes proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. Conclusion: Foveal translocation with 360degrees retinotomy is effective in restoring vision in 40% of patients with neovascular maculopathy. Simultaneous oblique muscle surgery was effective in rotating the globe by about 20degrees, corresponding to to a foveal shift of 1.5 DD. While the development of torsional diplopia is generally prevented by simultaneous oblique muscle surgery, the relatively high incidence of surgical complications with this procedure should be taken into account.
C1 Osaka Univ, Sch Med, Dept Appl Med Engn, Suita, Osaka 5650871, Japan.
   Osaka Univ, Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan.
C3 Osaka University; Osaka University
RP Fujikado, T (通讯作者)，Osaka Univ, Sch Med, Dept Appl Med Engn, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM fujikado@ophthal.med.osaka-u.ac.jp
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NR 15
TC 9
Z9 9
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 JAN
PY 2002
VL 240
IS 1
BP 21
EP 30
DI 10.1007/s00417-001-0401-7
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 528CJ
UT WOS:000174226300006
PM 11954777
DA 2022-11-30
ER

PT J
AU Johnen, S
   Harmening, N
   Marie, C
   Scherman, D
   Izsvak, Z
   Ivics, Z
   Walter, P
   Thumann, G
AF Johnen, Sandra
   Harmening, Nina
   Marie, Corinne
   Scherman, Daniel
   Izsvak, Zsuzsanna
   Ivics, Zoltan
   Walter, Peter
   Thumann, Gabriele
TI Electroporation-Based Genetic Modification of Primary Human Pigment
   Epithelial Cells using the Sleeping Beauty Transposon System
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
ID MACULAR DEGENERATION; VECTOR; PEDF; EXPRESSION; DELIVERY; VEGF;
   NEOVASCULARIZATION; TACHYPHYLAXIS; TRANSFECTION; INTEGRATION
AB Our increasingly aging society leads to a growing incidence of neurodegenerative diseases. So far, the pathological mechanisms are inadequately understood, thus impeding the establishment of defined treatments. Cell-based additive gene therapies for the increased expression of a protective factor are considered as a promising option to medicate neurodegenerative diseases, such as age-related macular degeneration (AMD). We have developed a method for the stable expression of the gene encoding pigment epithelium-derived factor (PEDF), which is characterized as a neuroprotective and anti-angiogenic protein in the nervous system, into the genome of primary human pigment epithelial (PE) cells using the Sleeping Beauty (SB) transposon system. Primary PE cells were isolated from human donor eyes and maintained in culture. After reaching confluence, 1 x 10(4) cells were suspended in 11 mu L of resuspension buffer and combined with 2 mu L of a purified solution containing 30 ng of hyperactive SB (SB100X) transposase plasmid and 470 ng of PEDF transposon plasmid. Genetic modification was carried out with a capillary electroporation system using the following parameters: two pulses with a voltage of 1,100 V and a width of 20 ms. Transfected cells were transferred into culture plates containing medium supplemented with fetal bovine serum; antibiotics and antimycotics were added with the first medium exchange. Successful transfection was demonstrated in independently performed experiments. Quantitative polymerase chain reaction (qPCR) showed the increased expression of the PEDF transgene. PEDF secretion was significantly elevated and remained stable, as evaluated by immunoblotting, and quantified by enzyme-linked immunosorbent assay (ELISA). SB100X-mediated transfer allowed for a stable PEDF gene integration into the genome of PE cells and ensured the continuous secretion of PEDF, which is critical for the development of a cell-based gene addition therapy to treat AMD or other retinal degenerative diseases. Moreover, analysis of the integration profile of the PEDF transposon into human PE cells indicated an almost random genomic distribution.
C1 [Johnen, Sandra; Walter, Peter] Univ Hosp RWTH Aachen, Dept Ophthalmol, Aachen, Germany.
   [Harmening, Nina; Thumann, Gabriele] Univ Geneva, Expt Ophthalmol, Geneva, Switzerland.
   [Harmening, Nina; Thumann, Gabriele] Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland.
   [Marie, Corinne; Scherman, Daniel] Univ Paris, CNRS, INSERM, UTCBS, Paris, France.
   [Marie, Corinne] PSL Res Univ, Chim ParisTech, Paris, France.
   [Izsvak, Zsuzsanna] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin, Germany.
   [Ivics, Zoltan] Paul Ehrlich Inst, Div Med Biotechnol, Langen, Germany.
C3 RWTH Aachen University; RWTH Aachen University Hospital; University of
   Geneva; University of Geneva; Centre National de la Recherche
   Scientifique (CNRS); Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Universite Paris
   Cite; UDICE-French Research Universities; PSL Research University Paris;
   Chimie ParisTech; Helmholtz Association; Max Delbruck Center for
   Molecular Medicine; Paul Ehrlich Institute
RP Johnen, S (通讯作者)，Univ Hosp RWTH Aachen, Dept Ophthalmol, Aachen, Germany.
EM sjohnen@ukaachen.de
RI Johnen, Sandra/ABA-9955-2020; Walter, Peter/L-5982-2018
OI Johnen, Sandra/0000-0003-0028-2557; Scherman,
   Daniel/0000-0003-1207-1298; MARIE, Corinne/0000-0001-9619-5700; Walter,
   Peter/0000-0001-8745-6593
FU European Union's Seventh Framework Programme for research, technological
   development and demonstration [305134]; European Research Council, ERC
   [ERC-2011-ADG 294742]
FX This work was supported by the European Union's Seventh Framework
   Programme for research, technological development and demonstration,
   grant agreement no. 305134. Zsuzsanna Izsvak was funded by the European
   Research Council, ERC Advanced (ERC-2011-ADG 294742). The authors would
   like to thank Anna Dobias and Antje Schiefer (Department of
   Ophthalmology, University Hospital RWTH Aachen) for excellent technical
   support, and the Aachen Cornea Bank (Department of Ophthalmology,
   University Hospital RWTH Aachen) for providing the human donor eyes.
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NR 58
TC 0
Z9 0
U1 0
U2 5
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2021
IS 168
AR e61987
DI 10.3791/61987
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA RV9XN
UT WOS:000646178300043
PM 33616098
DA 2022-11-30
ER

PT J
AU Hong, IH
   Jung, WH
   Lee, JH
   Chang, IB
AF Hong, In Hwan
   Jung, Woo Hyun
   Lee, Jae Hyup
   Chang, In Boem
TI Macular Pigment Optical Density in the Korean Population: a Cross
   Sectional Study
SO JOURNAL OF KOREAN MEDICAL SCIENCE
LA English
DT Article
DE Macular Pigment Optical Density; Dry Age-Related Macular Degeneration;
   Heterochromatic Flicker Photometry
ID SERUM LUTEIN; VITAMIN-C; DEGENERATION; ZEAXANTHIN; SUPPLEMENTATION;
   ASSOCIATION; PROTECTION; INSTRUMENT; CATARACTS; DAMAGE
AB Background: To evaluate the macular pigment optical density (MPOD) with age in the Korean population using the Macular Pigment Screener II (MPSII (R)).
   Methods: One hundred and twenty-six eyes were retrospectively reviewed. MPOD was measured using MPSII (R), which uses a heterochromatic flicker photometry method, and the estimated values were analyzed. Spearman's correlation test was used to evaluate correlations between MPOD and age. The association between MPOD and age was determined using a simple linear regression analysis. MPODs among the four groups were compared via the post hoc analysis with Bonferroni correction, MPODs between the age-related macular degeneration (AMD) group and aged-matched healthy subjects were compared via the Mann-Whitney U test. Other risk factors for AMD were identified via a logistic regression analysis.
   Results: Estimated MPOD decreased significantly with increasing age in the general population. In the simple regression analysis, a statistically significant linear regression model was observed, and the estimated values of MPOD decreased by -0.005 as age increased by 1 year. Aged (> 50 years) showed lower MPOD than younger (30-49 years) subjects. But, in the healthy population, the estimated MPOD values exhibited a decreasing trend with age, but there were no significant differences according to age, after excluding patients with AMD. MPOD was significantly lower in patients with AMD than in aged healthy controls. Furthermore, hypertension, dyslipidemia, and smoking were identified as risk factors for AMD.
   Conclusion: MPOD measured with MPSII (R) reflects the MP density in healthy individuals and patients with dry AMD. Aging was not significantly associated with low MPOD in healthy population, but the presence of dry AMD was significantly associated with low MPOD. Then, low MPOD may be a risk factor for development of dry AMD. Furthermore, routine screening with MPSII (R) for ages 50 and older is thought to help detect early low MPOD and identify individuals who should take supplements.
C1 [Hong, In Hwan] Hallym Univ, Dongtan Sacred Heart Hosp, Dept Ophthalmol, Med Ctr, Hwaseong, South Korea.
   [Jung, Woo Hyun; Lee, Jae Hyup; Chang, In Boem] Inje Univ, Busan Paik Hosp, Dept Ophthalmol, Coll Med, 75 Bokji Ro, Busan 47392, South Korea.
C3 Hallym University; Inje University
RP Chang, IB (通讯作者)，Inje Univ, Busan Paik Hosp, Dept Ophthalmol, Coll Med, 75 Bokji Ro, Busan 47392, South Korea.
EM ibeyebe0515@gmail.com
OI JUNG, WOOHYUN/0000-0002-9908-5483; Hong, In Hwan/0000-0002-3404-3901
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NR 40
TC 4
Z9 4
U1 0
U2 5
PU KOREAN ACAD MEDICAL SCIENCES
PI SEOUL
PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA
SN 1011-8934
EI 1598-6357
J9 J KOREAN MED SCI
JI J. Korean Med. Sci.
PD FEB 10
PY 2020
VL 35
IS 5
AR e30
DI 10.3346/jkms.2020.35.e30
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA KL9YT
UT WOS:000513774200001
PM 32030919
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Sun, Y
   Zheng, YF
   Wang, CX
   Liu, YZ
AF Sun, Yun
   Zheng, Yingfeng
   Wang, Chunxiao
   Liu, Yizhi
TI Glutathione depletion induces ferroptosis, autophagy, and premature cell
   senescence in retinal pigment epithelial cells
SO CELL DEATH & DISEASE
LA English
DT Article
ID STRESS-INDUCED APOPTOSIS; HUMAN RPE CELLS; OXIDATIVE STRESS; MACULAR
   DEGENERATION; MOLECULAR-MECHANISMS; DEATH; ACTIVATION; PATHWAYS; DAMAGE;
   MALONDIALDEHYDE
AB Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells. Briefly, cultured ARPE-19 cells were depleted of GSH using: (1) incubation in cystine (Cys(2))-free culture medium; (2) treatment with buthionine sulphoximine (BSO, 1000 mu M) to block de novo GSH synthesis for 24-48 h; or (3) treatment with erastin (10 mu M for 12-24 h) to inhibit Cys(2)/glutamate antiporter (system x(c)(-)). These treatments decreased cell viability and increased both soluble and lipid reactive oxygen species (ROS) generation but did not affect mitochondrial ROS or mitochondrial mass. Western blot analysis revealed decreased expression of ferroptotic modulator glutathione peroxidase 4 (GPX4). Increased autophagy was apparent, as reflected by increased LC3 expression, autophagic vacuoles, and autophagic flux. In addition, GSH depletion induced SIPS, as evidenced by increased percentage of the senescence-associated ss-galactosidase-positive cells, increased senescence-associated heterochromatin foci (SAHF), as well as cell cycle arrest at the G1 phase. GSH depletion-dependent cell death was prevented by selective ferroptosis inhibitors (8 mu M Fer-1 and 600 nM Lip-1), iron chelator DFO (80 mu M), as well as autophagic inhibitors Baf-A1 (75 nM) and 3-MA (10 mM). Inhibiting autophagy with Baf-A1 (75 nM) or 3-MA (10 mM) promoted SIPS. In contrast, inducing autophagy with rapamycin (100 nM) attenuated SIPS. Our findings suggest that GSH depletion induces ferroptosis, autophagy, and SIPS. In addition, we found that autophagy is activated in the process of ferroptosis and reduces SIPS, suggesting an essential role of autophagy in ferroptosis and SIPS.
C1 [Sun, Yun; Zheng, Yingfeng; Wang, Chunxiao; Liu, Yizhi] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Liu, YZ (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
EM liuyizh@mail.sysu.edu.cn
RI Zheng, Yingfeng/AAE-2983-2022; liu, yi/GXE-9662-2022; Zheng,
   Yingfeng/CAE-9225-2022
OI Zheng, Yingfeng/0000-0002-0914-7864; Liu, Yizhi/0000-0002-2067-2707;
   Liu, Yizhi/0000-0003-4108-9593
FU National Natural Science Foundation of China [81530028, 81721003];
   Guangdong Province Science & Technology Plan [2014B020228002]; National
   Key Basic Research and 973 Development Program of China [2015CB964600];
   Local Innovative and Research Teams Project of Guangdong Pearl River
   Talents Program
FX This work is funded by the National Natural Science Foundation of China
   (81530028; 81721003), the Guangdong Province Science & Technology Plan
   (2014B020228002), the National Key Basic Research and 973 Development
   Program of China (2015CB964600) and Local Innovative and Research Teams
   Project of Guangdong Pearl River Talents Program.
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NR 80
TC 198
Z9 202
U1 16
U2 71
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 JUL 9
PY 2018
VL 9
AR 753
DI 10.1038/s41419-018-0794-4
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA GM7KZ
UT WOS:000438367000001
PM 29988039
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chong, MF
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   Bentley, SA
AF Chong, Mae Fa
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TI An update on the characteristics of patients attending the Kooyong Low
   Vision Clinic
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE low vision; multidisciplinary care
AB Background Since 1972, the Australian College of Optometry has worked in partnership with Vision Australia to provide multidisciplinary low-vision care at the Kooyong Low Vision Clinic. In 1999, Wolffsohn and Cochrane reported on the demographic characteristics of patients attending Kooyong. Sixteen years on, the aim of this study is to review the demographics of the Kooyong patient cohort and prescribing patterns. Methods Records of all new patients (n = 155) attending the Kooyong Low Vision Clinic for optometry services between April and September 2012 were retrospectively reviewed. Results Median age was 84.3 years (range 7.7 to 98.1 years) with 59 per cent female. The majority of patients presented with late-onset degenerative pathology, 49 per cent with a primary diagnosis of age-related macular degeneration. Many (47.1 per cent) lived with their families. Mean distance visual acuity was 0.57 +/- 0.47 logMAR or approximately 6/24. The median spectacle-corrected near visual acuity was N8 (range N3 to worse than N80). Fifty patients (32.3 per cent) were prescribed new spectacles, 51 (32.9 per cent) low vision aids and five (8.3 per cent) were prescribed electronic magnification devices. Almost two-thirds (63.9 per cent) were referred for occupational therapy management and 12.3 per cent for orientation and mobility services. Conclusions The profile of patients presenting for low-vision services at Kooyong is broadly similar to that identified in 1999. Outcomes appear to be similar, aside from an expected increase in electronic devices and technological solutions; however, the nature of services is changing, as treatments for ocular diseases advance and assistive technology develops and becomes more accessible. Alongside the aging population and age-related ocular disease being the predominant cause of low vision in Australia, the health-funding landscape is becoming more restrictive. The challenge for the future will be to provide timely, high-quality care in an economically efficient model.
C1 [Chong, Mae Fa; Jackson, A. Jonathan; Bentley, Sharon A.] Australian Coll Optometry, Natl Vis Res Inst, Melbourne, Vic, Australia.
   [Jackson, A. Jonathan] Royal Grp Hosp, Belfast, Antrim, North Ireland.
   [Jackson, A. Jonathan; Bentley, Sharon A.] Univ Melbourne, Dept Optometry & Vis Sci, Melbourne, Vic, Australia.
   [Wolffsohn, James S.] Aston Univ, Sch Life & Hlth Sci, Birmingham, W Midlands, England.
C3 University of Melbourne; Aston University
RP Chong, MF (通讯作者)，Australian Coll Optometry, Natl Vis Res Inst, Melbourne, Vic, Australia.
EM mchong@aco.org.au
RI Jackson, Jonathan/ABH-1264-2021
OI Jackson, Jonathan/0000-0003-4675-0272; Bentley,
   Sharon/0000-0003-0146-4248; Wolffsohn, James/0000-0003-4673-8927
CR Australian Bureau of Statistics, 2015, AUSTR DEM STAT JUN Q
   Bailey, 1975, AUST J OPTOM, V58, P31
   Bentley SA, 2014, CLIN EXP OPTOM, V97, P214, DOI 10.1111/cxo.12139
   Deloitte Access Economics, 2011, EYES FUT CLEAR OUTL
   Robbins HG, 1994, LOW VISION RES NEW D
   Rosenfeld PJ, 2006, NEW ENGL J MED, V355, P1419, DOI 10.1056/NEJMoa054481
   Taylor HR, 2005, MED J AUSTRALIA, V182, P565, DOI 10.5694/j.1326-5377.2005.tb06815.x
   Thomas R, 2015, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD011350.pub2
   Wolffsohn JS, 1999, OPTOMETRY VISION SCI, V76, P747, DOI 10.1097/00006324-199911000-00023
NR 9
TC 7
Z9 8
U1 0
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD NOV 1
PY 2016
VL 99
IS 6
BP 555
EP 558
DI 10.1111/cxo.12395
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA VJ8RS
UT WOS:000640496600010
PM 27320822
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Ammar, DA
   Kahook, MY
AF Ammar, David A.
   Kahook, Malik Y.
TI In vitro effects of verteporfin on ocular cells
SO MOLECULAR VISION
LA English
DT Article
ID GLAUCOMA
AB Purpose: Photodynamic therapy (PDT) laser light in conjunction with the benzoporphyrin derivative verteporfin is a current clinical treatment for choroidal vascular diseases such as age-related macular degeneration. The aim of this study was to examine the effects of PDT laser-activated and inactive verteporfin on various cultured ocular cells.
   Methods: Primary human scleral fibroblasts (hFibro), primary human trabecular meshwork (TM) cells (hTMC), primary porcine TM cells (pTMC), and a human retinal pigment epithelial cell line (ARPE-19 cells) were treated with verteporfin with and without activation by PDT laser. Cell viability was determined according to mitochondrial enzyme activity (3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay).
   Results: PDT laser treatment alone was insufficient to cause significant cell death in any of the cell types tested. Twenty-four-hour exposure to inactive verteporfin (without PDT laser) caused a dose-dependent decrease in cell viability in hFibro and hTMC, and to a lesser extent ARPE-19 cells. Verteporfin (0.5 mu g/ml) without PDT laser activation caused a slight but statistically insignificant reduction in cell viability in hFibro (81.5%+/- 19.3%), pTMC (82.9%+/- 6.7%), hTMC (80.3%+/- 7.7%), and ARPE-19 cells (84.5%+/- 14.9%). Verteporfin (0.5 mu g/ml) plus 50 mu J/cm(2) PDT laser treatment significantly decreased viability in hFibro (13.5%+/- 3.3%), pTMC (7.1%+/- 1.5%), hTMC (11.1%+/- 5.2%), and ARPE-19 (44.5%+/- 7.8%). Similar results were obtained in cells where verteporfin incubation was followed by washout before PDT laser, indicating that verteporfin is internalized by the studied cell lines.
   Conclusions: PDT laser-induced cell death was obtained with coincubation of verteporfin or preincubation followed by washout. These results suggest a potential future use of PDT therapy for selective in vivo removal of targeted ocular cells beyond the current use for destroying vascular endothelial cells.
C1 Univ Colorado, Hosp Eye Ctr, Dept Ophthalmol, Aurora, CO 80045 USA.
   Univ Colorado Denver, Dept Ophthalmol, Aurora, CO USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; Children's Hospital Colorado; University of Colorado System;
   University of Colorado Anschutz Medical Campus
RP Kahook, MY (通讯作者)，Univ Colorado, Sch Med, Dept Ophthalmol, 1675 Aurora Court,MS F731, Aurora, CO 80045 USA.
EM Malik.Kahook@gmail.com
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   Tserentsoodol N, 2006, MOL VIS, V12, P1306
NR 12
TC 4
Z9 4
U1 1
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 20
PY 2013
VL 19
BP 424
EP 429
PG 6
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 097RX
UT WOS:000315492300002
PM 23441114
DA 2022-11-30
ER

PT J
AU Ablonczy, Z
   Crosson, CE
AF Ablonczy, Zsolt
   Crosson, Craig E.
TI VEGF modulation of retinal pigment epithelium resistance
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE RPE; resistance; VEGF; tight junction; macular edema; polarity; receptor
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   SIGNALING PATHWAY; FACTOR EXPRESSION; OXIDATIVE STRESS; TIGHT JUNCTIONS;
   NITRIC-OXIDE; CELL LINE; RECEPTORS
AB Fluid accumulation into the subretinal space and the development of macular edema is a common condition in age-related macular degeneration, diabetic retinopathy, and following ocular surgery, or injury. Vascular endothelial growth factor (VEGF) and other cytokines have been implicated in the disruption of retinal pigment epithelium (RPE) barrier function and a reduction in the regulated removal of subretinal fluid; however, the cellular and molecular events linking these agents to the disruption of barrier function have not been established. In the current study, cultures of ARPE-19 and primary porcine retinal pigment epithelium (RPE) cells were utilized to investigate the effects of the VEGF-induced modifications to the barrier properties of the RPE. The barrier function was determined by transepithelial resistance (TER) measurements and morphology of the RPE monolayers. In both ARPE-19 and primary porcine RPE cells the administration of VEGF produced a significant drop in TER, and this response was only observed following apical administration. Maximum reduction in TER was reached 5 h post VEGF administration. These responses were concentration-dependent with an EC50 of 502 pg/mL in ARPE-19 cells and 251 pg/mL in primary porcine cells. In both ARPE-19 and primary RPE cells, the response to VEGF was blocked by pretreatment with the relatively selective VEGF-R2 antagonists, SU5416 or ZM323881, or the protein tyrosine kinase inhibitor, genistein. Administration of the relatively selective VEGF-R2 agonist, VEGF-E, also reduced TER in a concentration-dependent manner (EC50 of 474 pg/mL), while VEGF-R1 agonist, placental growth factor (PIGF), did not significantly alter the TER. Immunolocalization studies demonstrated that confluent monolayers exhibited continuous cell-to-cell ZO-1 protein contacts and apical localization of the VEGF-R2 receptors. These data provide evidence that the VEGF-induced breakdown of RPE barrier function is mediated by the activation of apically-oriented VEGF-R2 receptors. Thus, VEGF-mediated increases in RPE permeability are initiated by a rise in intraocular levels of VEGF. (C) 2007 Elsevier Ltd. All rights reserved.
C1 [Ablonczy, Zsolt; Crosson, Craig E.] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
C3 Medical University of South Carolina
RP Ablonczy, Z (通讯作者)，Med Univ S Carolina, Dept Ophthalmol, SEI Room 518E,167 Ashley Ave, Charleston, SC 29425 USA.
EM ablonczy@musc.edu
FU NATIONAL EYE INSTITUTE [R01EY009741, R01EY013520, R24EY014793] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY 13520, R01 EY009741, R01 EY013520,
   R01 EY009741-15, EY 009741, EY 014793, R24 EY014793, R24 EY014793-01]
   Funding Source: Medline
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NR 37
TC 103
Z9 109
U1 0
U2 9
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2007
VL 85
IS 6
BP 762
EP 771
DI 10.1016/j.exer.2007.08.010
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 246VZ
UT WOS:000252037100004
PM 17915218
OA Green Accepted
DA 2022-11-30
ER

PT J
AU He, XN
   Hahn, P
   Iacovelli, J
   Wong, R
   King, C
   Bhisitkul, R
   Massaro-Giordano, M
   Dunaief, JL
AF He, Xining
   Hahn, Paul
   Iacovelli, Jared
   Wong, Robert
   King, Chih
   Bhisitkul, Robert
   Massaro-Giordano, Mina
   Dunaief, Joshua L.
TI Iron homeostasis and toxicity in retinal degeneration
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE iron; retina; age-related macular degeneration; oxidative stress;
   ferritin; ferroportin; chelator; ceruloplasmin; hephaestin
ID LENS EPITHELIAL-CELLS; GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED FORM;
   HANDLING PROTEINS FERRITIN; MACULAR DEGENERATION; TRANSFERRIN RECEPTOR;
   REGULATORY PROTEIN-2; INCREASED EXPRESSION; DEFICIENCY ANEMIA; OCULAR
   SIDEROSIS; OXIDATIVE STRESS
AB Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration.
   Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls.
   Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions.
   Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential. (C) 2007 Elsevier Ltd. All rights reserved.
C1 Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   California System; University of California San Francisco
RP Dunaief, JL (通讯作者)，Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, 305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
RI Iacovelli, Jared/G-3668-2011
OI Hahn, Paul/0000-0002-6574-388X
FU NATIONAL EYE INSTITUTE [R01EY015240] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY015240-04, EY015240, R01 EY015240] Funding Source:
   Medline
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NR 148
TC 171
Z9 177
U1 1
U2 14
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 2007
VL 26
IS 6
BP 649
EP 673
DI 10.1016/j.preteyeres.2007.07.004
PG 25
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 239EG
UT WOS:000251501000004
PM 17921041
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Denny, F
   Marshall, AH
   Stevenson, MR
   Hart, PM
   Chakravarthy, U
AF Denny, Frances
   Marshall, Adele H.
   Stevenson, Michael R.
   Hart, Patricia M.
   Chakravarthy, Usha
TI Rasch analysis of the Daily Livig Tasks Dependent on Vision (DLTV)
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VISUAL FUNCTIONING QUESTIONNAIRE; RATING-SCALE QUESTIONNAIRES;
   RANDOMIZED CONTROLLED-TRIAL; MACULAR DEGENERATION; OUTCOMES; ABILITY
AB PURPOSE. To examine internal consistency, refine the response scale, and obtain a linear scoring system for the visual function instrument, the Daily Living Tasks Dependent on Vision (DLTV).
   METHODS. Data were available from 186 participants with a clinical diagnosis of AMD who completed the 22-item DLTV (DLTV-22) according to four-point ordinal response scale. An independent group of 386 participants with AMD were administered a reduced version of the DLTV with 11 items (DLTV-11), according to a five-point response scale. Rasch analysis was performed on both datasets and used to generate item statistics for measure order; response odds ratios per item and per person, and infit and outfit mean square statistics. The Rasch output from the DLTV-22 was examined to identify redundant items and for factorial validity and person item measure separation reliabilities.
   RESULTS. The average rating for the DLTV-22 changed monotonically with the magnitude of the latent person trait. The expected versus observed average measures were extremely close, with step calibrations evenly separated for the four-point ordinal scale. In the case of the DLTV-11, step calibrations were not as evenly separated, suggesting that the five-point scale should be reduced to either a four- or three-point scale. Five items in the DLTV-22 were removed, and all 17 remaining items had good infit and outfit mean squares. PCA with residuals from Rasch analysis identified two domains containing 7 and 10 items each. The domains had high person separation reliabilities (0.86 and 0.77 for domains I and 2, respectively) and item measure reliabilities (0.99 and 0.98 for domains I and 2, respectively).
   CONCLUSIONS. With the improved internal consistency, establishment of the accuracy and precision of the rating scale for the DLTV and the establishment of a valid domain structure we believe that it constitutes a useful instrument for assessing visual function in older adults with age-related macular degeneration.
C1 Queens Univ Belfast, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland.
   Queens Univ Belfast, Ctr Stat Sci & Operat Res, Sch Math & Phys, Belfast BT12 6BA, Antrim, North Ireland.
C3 Queens University Belfast; Queens University Belfast
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Marshall, Adele/0000-0001-5306-2756; Chakravarthy,
   Usha/0000-0002-2606-3734
CR BOND TG, 2001, APPL RASCH MODEL FUN, pCH12
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NR 14
TC 8
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
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2007
VL 48
IS 5
BP 1976
EP 1982
DI 10.1167/iovs.06-0135
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 162DU
UT WOS:000246067800011
PM 17460249
DA 2022-11-30
ER

PT J
AU Ratra, D
   Gopalakrishnan, S
   Dalan, D
   Ratra, V
   Damkondwar, D
   Laxmi, G
AF Ratra, Dhanashree
   Gopalakrishnan, Sarika
   Dalan, Daleena
   Ratra, Vineet
   Damkondwar, Deepali
   Laxmi, Gella
TI Visual rehabilitation using microperimetric acoustic biofeedback
   training in individuals with central scotoma
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Article
DE acoustic biofeedback training; central scotoma; fixation stability;
   microperimetry; retinal sensitivity; visual rehabilitation
ID PREFERRED RETINAL LOCUS; FIXATION STABILITY; VISION REHABILITATION;
   MACULAR DEGENERATION; MP-1; PATIENT; ATROPHY
AB Background Patients with central scotoma have poor fixation stability and poor visual acuity. Acoustic biofeedback training can be an effective way to train such patients to eccentrically fixate. This study analyses the mean retinal sensitivity, saccadic velocity, and fixation stability after acoustic biofeedback training and shows correlation with age and scotoma size. Methods Patients with irreversible central scotoma in both the eyes secondary to macular diseases were selected. After undergoing comprehensive low vision assessment, 19 patients who were willing were recruited for the acoustic biofeedback training to the better eye in 10 sessions, using the MP-1 Microperimeter. Mean retinal sensitivity, saccadic velocity, fixation stability before and after the acoustic biofeedback were recorded. Results There were 17 men and two women. Ages ranged from 19-94 years (mean 54.63 +/- 24.66). The scotoma size ranged from four to 20 degrees. Ten patients had age-related macular degeneration, four had Stargardt disease, three had traumatic macular scar, two had scarred myopic choroidal neovascular membrane, and one had myopic macular degeneration. The vision improved from 1.06 +/- 0.36 to 0.86 +/- 0.33 logMAR (p < 0.0001). The mean retinal sensitivity improved from 2.1 +/- 2.9 dB to 2.7 +/- 3.1 dB (p = 0.01), with negative correlation with age (p = 0.01) and scotoma size (p = 0.02). Fixation stability improved with reduction in the bivariate contour ellipse area (p = 0.01). It showed negative correlation with age (p = 0.02) and scotoma size (p = 0.10). The saccadic velocity reduced from 0.34 degrees/second to 0.26 degrees/second but was not significant (p > 0.99). The majority (58 per cent) had their preferred retinal locus superior to the fovea. There was good agreement between bivariate contour ellipse area and MP-1 Microperimeter inbuilt fixation parameters. The effect was maintained at six months with slight reduction in fixation stability. Conclusion Acoustic biofeedback can improve fixation behaviour, visual acuity and retinal sensitivity in patients with central scotoma. The results are better with younger age and smaller scotoma size.
C1 [Ratra, Dhanashree] Med Res Fdn, Dept Vitreoretinal Dis, Chennai, Tamil Nadu, India.
   [Gopalakrishnan, Sarika] Shanmugha Arts Sci Technol & Res Acad, Dept Optometry, Low Vis Care Clin, Thanjavur, India.
   [Dalan, Daleena] Low Vis Care Clin, Dept Vitreoretinal Dis, Chennai, Tamil Nadu, India.
   [Ratra, Vineet; Damkondwar, Deepali] Med Res Fdn, Dept Comprehens Ophthalmol, Chennai, Tamil Nadu, India.
   [Laxmi, Gella] Univ Hyderabad, Sch Med Sci, Dept Optometry, Hyderabad, Telangana, India.
C3 Shanmugha Arts, Science, Technology & Research Academy (SASTRA);
   University of Hyderabad
RP Ratra, D (通讯作者)，Med Res Fdn, Dept Vitreoretinal Dis, Chennai, Tamil Nadu, India.
EM dhanashreeratra@gmail.com
RI Ratra, Dhanashree/AAE-2517-2020; Ratra, Vineet/AAM-4623-2021
OI Ratra, Dhanashree/0000-0001-5687-6384; G, Sarika/0000-0002-1848-0036
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NR 35
TC 12
Z9 12
U1 0
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD MAR
PY 2019
VL 102
IS 2
BP 172
EP 179
DI 10.1111/cxo.12834
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HM5IZ
UT WOS:000459510700012
PM 30253443
DA 2022-11-30
ER

PT J
AU Prins, D
   Hanekamp, S
   Cornelissen, FW
AF Prins, Doety
   Hanekamp, Sandra
   Cornelissen, Frans W.
TI Structural brain MRI studies in eye diseases: are they clinically
   relevant? A review of current findings
SO ACTA OPHTHALMOLOGICA
LA English
DT Review
DE eye diseases; magnetic resonance imaging; visual cortex; visual pathway
ID VOXEL-BASED MORPHOMETRY; OPEN-ANGLE GLAUCOMA; AGE-RELATED MACULOPATHY;
   ABNORMAL VISUAL-CORTEX; FIBER LAYER THICKNESS; MACULAR DEGENERATION;
   ALZHEIMERS-DISEASE; OPTIC RADIATION; GREY-MATTER; INTRAOCULAR-PRESSURE
AB Many eye diseases reduce visual acuity or are associated with visual field defects. Because of the well-defined retinotopic organization of the connections of the visual pathways, this may affect specific parts of the visual pathways and cortex, as a result of either deprivation or transsynaptic degeneration. For this reason, over the past several years, numerous structural magnetic resonance imaging(MRI) studies have examined the association of eye diseases with pathway and brain changes. Here, we review structural MRI studies performed in human patients with the eye diseases albinism, amblyopia, hereditary retinal dystrophies, age-related macular degeneration (AMD) and glaucoma. We focus on two main questions. First, what have these studies revealed? Second, what is the potential clinical relevance of their findings? We find that all the aforementioned eye diseases are indeed associated with structural changes in the visual pathways and brain. As such changes have been described in very different eye diseases, in our view the most parsimonious explanation is that these are caused by the loss of visual input and the subsequent deprivation of the visual pathways and brain regions, rather than by transsynaptic degeneration. Moreover, and of clinical relevance, for some of the diseases -in particular glaucoma and AMD -present results are compatible with the view that the eye disease is part of a more general neurological or neurodegenerative disorder that also affects the brain. Finally, establishing structural changes of the visual pathways has been relevant in the context of new therapeutic strategies to restore retinal function: it implies that restoring retinal function may not suffice to also effectively restore vision. Future structural MRI studies can contribute to (i) further establish relationships between ocular and neurological neurodegenerative disorders, (ii) investigate whether brain degeneration in eye diseases is reversible, (iii) evaluate the use of neuroprotective medication in ocular disease, (iv) determine optimal timing for retinal implant insertion and (v) establish structural MRI examination as a diagnostic tool in ophthalmology.
C1 [Prins, Doety; Hanekamp, Sandra; Cornelissen, Frans W.] Univ Groningen, Univ Med Ctr Groningen, Lab Expt Ophthalmol, Groningen, Netherlands.
C3 University of Groningen
RP Cornelissen, FW (通讯作者)，Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, Lab Expt Ophthalmol, POB 30-001,HPC BB61, NL-9700 RB Groningen, Netherlands.
EM f.w.cornelissen@umcg.nl
RI Hanekamp, Sandra/AAF-2852-2021
OI Hanekamp, Sandra/0000-0002-3677-1611
FU University Medical Center Groningen; Stichting UitZicht
FX DP was supported by the 'Junior Scientific Master-class MD/PhD
   Programme' of the University Medical Center Groningen. SH was supported
   by a grant from 'Stichting UitZicht'. The funding organizations had no
   role in the design or conduct of this research.
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NR 102
TC 39
Z9 41
U1 0
U2 19
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAR
PY 2016
VL 94
IS 2
BP 113
EP 121
DI 10.1111/aos.12825
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DE9KR
UT WOS:000370956800021
PM 26361248
OA Bronze
DA 2022-11-30
ER

PT J
AU Hollborn, M
   Vogler, S
   Reichenbach, A
   Wiedemann, P
   Bringmann, A
   Kohen, L
AF Hollborn, Margrit
   Vogler, Stefanie
   Reichenbach, Andreas
   Wiedemann, Peter
   Bringmann, Andreas
   Kohen, Leon
TI Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in
   retinal pigment epithelial cells: Involvement of NFAT5
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR 1-ALPHA HIF-1-ALPHA; NF-KAPPA-B;
   HYPERTONIC INDUCTION; DIABETIC-RETINOPATHY; DOWN-REGULATION;
   BLOOD-PRESSURE; MULLER CELLS; EXPRESSION; WATER
AB Purpose: High intake of dietary salt increases extracellular osmolarity, which results in hypertension, a risk factor of neovascular age-related macular degeneration. Neovascular retinal diseases are associated with edema. Various factors and channels, including vascular endothelial growth factor (VEGF) and aquaporins (AQPs), influence neovascularization and the development of edema. Therefore, we determined whether extracellular hyperosmolarity alters the expression of VEGF and AQPs in cultured human retinal pigment epithelial (RPE) cells.
   Methods: Human RPE cells obtained within 48 h of donor death were prepared and cultured. Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Alterations in gene expression and protein secretion were determined with real-time RT-PCR and ELISA, respectively. The levels of signaling proteins and nuclear factor of activated T cell 5 (NFAT5) were determined by western blotting. DNA binding of NFAT5 was determined with EMSA. NFAT5 was knocked down with siRNA.
   Results: Extracellular hyperosmolarity stimulated VEGF gene transcription and the secretion of VEGF protein. Hyperosmolarity also increased the gene expression of AQP5 and AQP8, induced the phosphorylation of p38 MAPK and ERK1/2, increased the expression of HIF-1 alpha and NFAT5, and induced the DNA binding of NFAT5. The hyperosmotic expression of VEGF was dependent on the activation of p38 MAPK, ERK1/2, JNK, PI3K, HIF-1, and NFAT5. The hyperosmotic induction of AQP5 was in part dependent on the activation of p38 MAPK, ERK1/2, NF-kappa B, and NFAT5. Triamcinolone acetonide inhibited the hyperosmotic expression of VEGF but not AQP5. The expression of AQP5 was decreased by hypoosmolarity, serum, and hypoxia.
   Conclusions: Hyperosmolarity induces the gene transcription of AQP5, AQP8, and VEGF, as well as the secretion of VEGF from RPE cells. The data suggest that high salt intake resulting in osmotic stress may aggravate neovascular retinal diseases and edema via the stimulation of VEGF production in RPE. The downregulation of AQP5 under hypoxic conditions may prevent the resolution of edema.
C1 [Hollborn, Margrit; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon] Univ Leipzig, Dept Ophthalmol, D-04103 Leipzig, Germany.
   [Hollborn, Margrit; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon] Univ Leipzig, Hosp Eye, D-04103 Leipzig, Germany.
   [Vogler, Stefanie; Reichenbach, Andreas] Univ Leipzig, Paul Flechsig Inst Brain Res, D-04103 Leipzig, Germany.
   [Kohen, Leon] Helios Klinikum Aue, Aue, Germany.
C3 Leipzig University; Leipzig University; Leipzig University; Helios
   Kliniken
RP Hollborn, M (通讯作者)，Univ Leipzig, Fac Med, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM hollbm@medizin.uni-leipzig.de
RI Reichenbach, Andreas/B-2510-2017
FU Deutsche Forschungsgemeinschaft [KO 1547/7-1, GRK 1097/1, RE 849/16-1];
   Geschwister Freter Stiftung (Hannover, Germany)
FX The authors thank Ute Weinbrecht for excellent technical assistance.
   This study was supported by grants from the Deutsche
   Forschungsgemeinschaft (KO 1547/7-1 to L.K; GRK 1097/1, RE 849/16-1, to
   A.R.) and the Geschwister Freter Stiftung (Hannover, Germany).
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NR 63
TC 38
Z9 39
U1 0
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 9
PY 2015
VL 21
BP 360
EP 377
PG 18
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA CG1GL
UT WOS:000353021000001
PM 25878490
DA 2022-11-30
ER

PT J
AU Terasaki, H
   Shirasawa, M
   Otsuka, H
   Yamashita, T
   Uchino, E
   Hisatomi, T
   Sonoda, S
   Sakamoto, T
AF Terasaki, Hiroto
   Shirasawa, Makoto
   Otsuka, Hiroki
   Yamashita, Takehiro
   Uchino, Eisuke
   Hisatomi, Toshio
   Sonoda, Shozo
   Sakamoto, Taiji
TI Different Effects of Thrombin on VEGF Secretion, Proliferation, and
   Permeability in Polarized and Non-polarized Retinal Pigment Epithelial
   Cells
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Barrier function; cell polarity; RPE; thrombin; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; SUBRETINAL HEMORRHAGE;
   FACTOR RECEPTORS; NATURAL-HISTORY; GAP FORMATION; TNF-ALPHA; RPE;
   EXPRESSION; BARRIER
AB We investigated the effect of thrombin on the secretion of vascular endothelial growth factor (VEGF), on cellular proliferation, and on the integrity of the barrier function of polarized retinal pigment epithelial (RPE) cells. In addition, we compared the responses of polarized to that of non-polarized RPE cells. Porcine polarized RPE cells were established using Transwell membranes. The polarization of the RPE cells was determined by their high transepithelial electrical resistance (TER>200 Omega cm(2)) and by their differential secretion of VEGF (basal direction >apical direction by 2.5x). RPE cells were incubated with thrombin (5-20 U/ml) for 24 h. The concentration of VEGF in the culture medium was measured by enzyme-linked immunosorbent assay, and the TER was measured. Cellular proliferation was assessed by Ki-67 immunostaining. The area of laser-induced choroidal naovascularization (CNV) was measured in rat eyes and compare to that of controls with or without thrombin. Our results showed that thrombin significantly increased VEGF secretion both in polarized and non-polarized RPE cells in a dose-dependent way. Thrombin did not significantly affect the TER or the expression of tight-junctional proteins in polarized RPE cells, but decreased it in non-polarized RPE cells by inducing intercellular gaps. Ki-67-positive cells were observed in non-polarized RPE cells but not in polarized RPE cells as controls. After thrombin exposure, the number of Ki-67-positive cells increased significantly in non-polarized RPE cells but not in polarized RPE cells. The area of CNV was larger in thrombin-injected eye than control eyes. Although thrombin increased VEGF secretion regardless of cell polarity, its effects on proliferation and barrier integrity were dependent upon cell polarity. Cell polarization is an important factor for determining the response of RPE cells to thrombin, and the different responsive patterns to thrombin upon cell polarity might explain the complicated pathology of such diseases as age-related macular degeneration.
C1 [Terasaki, Hiroto; Shirasawa, Makoto; Otsuka, Hiroki; Yamashita, Takehiro; Uchino, Eisuke; Sonoda, Shozo; Sakamoto, Taiji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Kagoshima 8908520, Japan.
   [Hisatomi, Toshio] Kyushu Univ, Dept Ophthalmol, Fukuoka 812, Japan.
C3 Kagoshima University; Kyushu 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
OI Hisatomi, Toshio/0000-0003-2552-9595
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NR 32
TC 11
Z9 11
U1 0
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2015
VL 40
IS 9
BP 936
EP 945
DI 10.3109/02713683.2014.964417
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CR4SA
UT WOS:000361327200010
PM 25310246
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Bird, AC
   Phillips, RL
   Hageman, GS
AF Bird, Alan C.
   Phillips, Rachel L.
   Hageman, Gregory S.
TI Geographic Atrophy A Histopathological Assessment
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; FUNDUS AUTOFLUORESCENCE;
   VITAMIN-A; VISUAL FUNCTION; DEGENERATION; DRUSEN; ACCUMULATION;
   REFLECTANCE; DYSFUNCTION
AB IMPORTANCE Geographic atrophy (GA) is the major cause of blind registration in Western communities, although, with few exceptions, it is less common than choroidal neovascular disease. The variation of phenotype implies that age-related macular degeneration (AMD) does not follow the same course from one case to another and that phenotyping may be important before initiating a therapeutic trial.
   OBJECTIVE To document photoreceptor and retinal pigment epithelium (RPE) cell loss and other changes at the RPE-choroid interface in donated human eyes in which visual loss was deemed to be due to GA.
   DESIGN. SETTING. AND PARTICIPANTS Histological study of a consecutive series of eyes donated by individuals previously diagnosed clinically as having GA. Donors were chosen on the basis of available clinical records (from MidAmerica Transplant Services, St Louis, Missouri; the Iowa Lions Eye Bank, Iowa City; and the Utah Lions Eye Bank, Salt Lake City) and selected were those considered to have GA due to AMD. Tissues in the regions of atrophy were examined with light, electron, and autofluorescence microscopy.
   RESULTS In most of the 37 donors examined, there was marked loss of photoreceptor cells for variable distances distal from the edge of the GA. Rod loss was greater than cone loss. An inverse relationship existed between the quantity of autofluorescent inclusions in the RPE and the thickness of sub-RPE basal laminar deposit. Integrity of the choroid varied from one eye to another and was not related strictly to photoreceptor survival. In some eyes, photoreceptor loss existed in the absence of obvious morphological changes in the Bruch membrane or RPE.
   CONCLUSIONS AND RELEVANCE The findings support the view that photoreceptor loss occurs early in AMD in a proportion of cases and imply that photoreceptor-cell loss may contribute to the functional loss recorded in early stages of AMD at least in part. The variation of changes from one eye to another implies that patients selected for a specific prophylactic therapy for early AMD should be chosen on the basis of the characteristics of their disease.
C1 [Bird, Alan C.] UCL, Inst Ophthalmol, London, England.
   [Phillips, Rachel L.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
   [Hageman, Gregory S.] Univ Utah, Moran Ctr Translat Med, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
C3 University of London; University College London; University of Iowa;
   Utah System of Higher Education; University of Utah
RP Bird, AC (通讯作者)，Moorfields Eye Hosp, Inst Ophthalmol, City Rd, London EC1V 2PD, England.
EM alan.bird@ucl.uk
RI Mitchell, Paul/P-1498-2014
FU National Institutes of Health [R24-EY017404]; American Macular
   Degeneration Foundation; Research to Prevent Blindness Inc.; NATIONAL
   EYE INSTITUTE [R24EY017404, P30EY014800] Funding Source: NIH RePORTER
FX This research was funded in part by National Institutes of Health grant
   R24-EY017404 (Dr Hageman), a grant from the American Macular
   Degeneration Foundation (Dr Hageman), and an unrestricted grant to the
   University of Utah Department of Ophthalmology and Visual Sciences
   (Moran Eye Center) from Research to Prevent Blindness Inc.
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NR 47
TC 115
Z9 118
U1 0
U2 6
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 MAR
PY 2014
VL 132
IS 3
BP 338
EP 345
DI 10.1001/jamaophthalmol.2013.5799
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AC8HL
UT WOS:000332774000016
PM 24626824
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wei, Y
   Wang, X
   Zhao, F
   Zhao, PQ
   Kang, XL
AF Wei, Yan
   Wang, Xu
   Zhao, Feng
   Zhao, Pei-quan
   Kang, Xiao-li
TI Cannabinoid receptor 1 blockade protects human retinal pigment
   epithelial cells from oxidative injury
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; ENDOCANNABINOID SYSTEM; MULTIDRUG-RESISTANCE;
   HYDROGEN-PEROXIDE; INDUCED APOPTOSIS; EYE TISSUES; IN-VIVO;
   NEUROTOXICITY; DAMAGE; NEUROPROTECTION
AB Background: Because oxidative stress is assumed to be a key mechanism in the pathological process of age-related macular degeneration (AMD), increasing numbers of studies have focused on discovering new pathways and treatments for reducing oxidative damage. Our work investigates the potential role of the cannabinoid receptor 1 (CB1) in oxidative stress of primary human retinal pigment epithelial (RPE) cells, a cellular model of AMD.
   Methods: Primary human RPE cells were cultured and exposed to hydrogen peroxide for 24 h to induce oxidative damage. The expression of and changes in the CB1 receptor were determined with western blot assay and confocal imaging. The CB1 receptor in the RPE cells was inhibited with small interfering RNA (siRNA) or rimonabant (SR141716). Cell viability, apoptosis, and reactive oxygen species production were measured by using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) and sulforhodamine B assay, annexin V and propidium iodide staining, and the dichlorofluorescein fluorescence assay, respectively. Intracellular superoxide dismutase activity was assayed with a commercially available assay kit. Phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) protein expression and activation of signaling molecules were assessed with western blot analysis.
   Results: We showed that human RPE cells express the CB1 receptor. In addition, oxidative stress upregulates the expression of the CB1 receptor. Deleting the CB1 receptor or treating with the CB1 receptor antagonist rimonabant (SR141716) rescued RPE cells from hydrogen peroxide-induced oxidative damage. Rimonabant pretreatment effectively reduced the apoptosis of RPE cells, inhibited the generation of intracellular reactive oxygen species and elevated the activity of superoxide dismutase. In addition, rimonabant significantly strengthened the oxidative stress-induced activation of the PI3K/Akt signaling pathway.
   Conclusions: The results demonstrate the expression and regulation of CB1 receptors in human RPE cells. Inhibiting the CB1 receptor may be an effective therapeutic strategy for AMD by downregulating oxidative stress signaling and facilitating PI3K/Akt activation.
C1 [Wei, Yan; Zhao, Pei-quan; Kang, Xiao-li] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Ophthalmol, Shanghai 200095, Peoples R China.
   [Wang, Xu] Shanghai Jiao Tong Univ, Sch Med, Dept Oral & Maxillofacial Head & Neck Oncol, Coll Stomatol,Peoples Hosp 9, Shanghai 200095, Peoples R China.
   [Zhao, Feng] Shanghai Tradit Chinese Med Univ, Shuguang Hosp, Dept Ophthalmol, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University
RP Kang, XL (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Ophthalmol, Shanghai 200095, Peoples R China.
EM clove_lau@hotmail.com
FU National Natural Science Foundation of China [81,100,680]; Shanghai
   Science and Technology Committee [114119b3000]
FX This work was supported by the National Natural Science Foundation of
   China (81,100,680) and Shanghai Science and Technology Committee
   (114119b3000). Drs. Pei-quan Zhao and Xiao-li Kang are co-corresponding
   author for this paper.
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NR 36
TC 15
Z9 17
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 13
PY 2013
VL 19
BP 357
EP 366
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 089LN
UT WOS:000314912100001
PM 23441106
DA 2022-11-30
ER

PT J
AU Hammond, CJ
   Liew, SHM
   Van Kuijk, FJ
   Beatty, S
   Nolan, JM
   Spector, TD
   Gilbert, CE
AF Hammond, Christopher J.
   Liew, S. H. Melissa
   Van Kuijk, Frederik J.
   Beatty, Stephen
   Nolan, John M.
   Spector, Tim D.
   Gilbert, Clare E.
TI The Heritability of Macular Response to Supplemental Lutein and
   Zeaxanthin: A Classic Twin Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT OPTICAL-DENSITY; FOOD-FREQUENCY QUESTIONNAIRE; SERUM
   CONCENTRATIONS; PRIMATE RETINAS; TISSUE CONCENTRATIONS;
   SPATIAL-DISTRIBUTION; PROTECTIVE ROLE; ADIPOSE-TISSUE; VITAMIN-C; AGE
AB PURPOSE. Antioxidant supplements may reduce age-related macular degeneration (AMD) progression. The macular carotenoids are of particular interest because of their biochemical, optical, and anatomic properties. This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z).
   METHODS. A total of 322 healthy female twin volunteers, aged 16-50 years (mean 40 +/- 8.7) was enrolled in a prospective, nonrandomized supplement study. Macular pigment optical density (MPOD) measurements using two techniques (2-wavelength fundus autofluorescence [AF] and heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z, were recorded at baseline, and at 3 and 6 months following daily supplementation with 18 mg L and 2.4 mg Z for a study period of 6 months.
   RESULTS. At baseline, mean MPOD was 0.44 density units (SD 0.21, range 0.04-1.25) using HFP, and 0.41 density units (SD 0.15) using AF. Serum L and Z levels were raised significantly from baseline following 3 months' supplementation (mean increase 223% and 633%, respectively, P < 0.0001 for both), with no MPOD increase. After 6 months' supplementation, a small increase in MPOD was seen (mean increase 0.025 +/- 0.16, P = 0.02, using HFP). Subdivision of baseline MPOD into quartiles revealed that baseline levels made no difference to the treatment effect. Genetic factors explained 27% (95% confidence interval [CI] 7-45) of the variation in MPOD response. Distribution profiles of macular pigment did not change in response to supplementation.
   CONCLUSIONS. MPOD response to supplemental L and Z for a period of 6 months was small (an increase over baseline of 5.7% and 3.7%, measured using HFP and AF, respectively), and was moderately heritable. Further study is indicated to investigate the functional and clinical impact of supplementation with the macular carotenoids. (Invest Ophthalmol Vis Sci. 2012;53:4963-4968) DOI:10.1167/iovs.12-9618
C1 [Hammond, Christopher J.; Liew, S. H. Melissa; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
   [Hammond, Christopher J.] Kings Coll London, St Thomas Hosp, Dept Ophthalmol, London WC2R 2LS, England.
   [Van Kuijk, Frederik J.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
   [Beatty, Stephen; Nolan, John M.] Waterford Inst Technol, Macular Pigment Res Grp, Waterford, Ireland.
   [Gilbert, Clare E.] London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1, England.
C3 University of London; King's College London; Guy's & St Thomas' NHS
   Foundation Trust; University of London; King's College London;
   University of Minnesota System; University of Minnesota Twin Cities;
   South East Technological University (SETU); University of London; London
   School of Hygiene & Tropical Medicine
RP Hammond, CJ (通讯作者)，Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Hosp Campus,Westminster Bridge Rd, London WC2R 2LS, England.
EM chris.hammond@kcl.ac.uk
RI Nolan, John/N-4921-2014
OI Nolan, John/0000-0002-5503-7084; Hammond,
   Christopher/0000-0002-3227-2620
FU Wellcome Trust; Research to Prevent Blindness; National Institute for
   Health Research [SRF/01/010] Funding Source: researchfish
FX Supported by Wellcome Trust and by a Research to Prevent Blindness
   unrestricted grant to University of Minnesota (FJVK).
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NR 55
TC 26
Z9 26
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2012
VL 53
IS 8
BP 4963
EP 4968
DI 10.1167/iovs.12-9618
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983DA
UT WOS:000307096400077
PM 22700713
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Bakri, SJ
   Risco, M
   Edwards, AO
   Pulido, JS
AF Bakri, Sophie J.
   Risco, Miguel
   Edwards, Albert O.
   Pulido, Jose S.
TI Bilateral Simultaneous Intravitreal Injections in the Office Setting
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; TRIAMCINOLONE INJECTION; RANIBIZUMAB;
   ENDOPHTHALMITIS
AB PURPOSE: To report the outcomes and complications of bilateral simultaneous intravitreal injections performed in the office.
   DESIGN: Retrospective case series.
   METHODS: Records of 35 patients receiving simultaneous bilateral intravitreal injections between November 2007 and November 2008 were reviewed. Data collected included indication for injection, preinjection and postinjection intraocular pressure (IOP), preinjection and postinjection visual acuity (VA), and complications/complaints after each injection. 0
   RESULTS: A total of 208 injections were administered to 35 patients, with a mean of 5.9 injections per patient (range, 2 to 14; standard deviation [SD], 3.68). One hundred and thirty-three eyes received bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) alone, 14 received bevacizumab plus preservative-free intravitreal triamcinolone or Triescence (Kenalog; Bristol-My. ers Squibb Co, New York, New York, USA), 56 received ranibizumab (Lucentis; Genentech Inc), and 5 received bevacizumab plus dexamethasone (Decadron; Merck, Whitehouse Station, New Jersey, USA). Mean time of postinjection follow-up was 39 days. Postinjection VA follow-up measurements were available for 194 injections. The indication for initiating therapy was choroidal neovascularization from age,related macular degeneration (49 eyes), diabetic macular edema (ME) (13 eyes), proliferative diabetic retinopathy (4 eyes), ME attributable to retinal vein occlusion (2 eyes), and ME attributable to autoimmune retinopathy (2 eyes). The mean VA before each injection was 20/96 and at the next follow-up was 20/91 (P =.40). One patient had a painless, culture-negative endophthalmitis in 1 eye 3 days after bilateral bevacizumab; at 1 year VA improved from 20/400 to 20/80.
   CONCLUSIONS. Simultaneous bilateral intravitreal injections in the office are well tolerated. A separate povidone-iodine preparation, speculum, needle, and syringe were used for each eye. None of the patients requested alternating unilateral injections, after receiving bilateral injections. Patients should be counseled as to the risk of complications. (Am J Ophthalmol 2009;148:66-69. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 [Bakri, Sophie J.; Risco, Miguel; Edwards, Albert O.; Pulido, Jose S.] Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA.
C3 Mayo Clinic
RP Bakri, SJ (通讯作者)，Mayo Clin, Dept Ophthalmol, 200 1st St SW, Rochester, MN 55905 USA.
EM bakri.sophie@mayo.edu
FU THE RESEARCH TO PREVENT BLINDNESS, NEW YORK, NEW YORK; Genentech Inc;
   Regeneron; Novartis; Potentia Pharmaceuticals
FX THIS STUDY WAS SUPPORTED BY THE RESEARCH TO PREVENT BLINDNESS, NEW YORK,
   NEW YORK. DR BAKRI HAS SERVED cm the advisory boards of Genentech Inc,
   Novartis, and Alcon Laboratories. The Mayo Clinic has received research
   funds for clinical trials from Genentech Inc, Regeneron, Novartis, and
   Potentia Pharmaceuticals. Involved in design and conduct of study
   (S.J.B.); collection, management, analysis, and interpretation of data
   (S.J.B., M.R., J.S.P., A.O.E.); and preparation, review, or approval of
   the manuscript (S.J.B., M.R., J.S.P., A.O.E.). Permission was obtained
   from the Institutional Review Board of the Mayo Clinic to conduct this
   retrospective review of patient records and to report these findings.
CR BAKRI SI, RETIN CASES IN PRESS
   Bhavsar AR, 2007, AM J OPHTHALMOL, V144, P454, DOI 10.1016/j.ajo.2007.04.011
   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
   DIAGO T, 2009, RETINA IN PRESS
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   Fung AE, 2007, AM J OPHTHALMOL, V143, P566, DOI 10.1016/j.ajo.2007.01.028
   Fung AE, 2009, OPHTHALMOLOGY, V116, P286, DOI 10.1016/j.ophtha.2008.09.014
   Maia M, 2007, BRIT J OPHTHALMOL, V91, P1122, DOI 10.1136/bjo.2007.115386
   Regillo CD, 2008, AM J OPHTHALMOL, V145, P239, DOI 10.1016/j.ajo.2007.10.004
   Rosenfeld Philip J, 2006, Ophthalmol Clin North Am, V19, P361
   Rosenfeld PJ, 2006, NEW ENGL J MED, V355, P1419, DOI 10.1056/NEJMoa054481
   Roth DB, 2008, AM J OPHTHALMOL, V146, P346, DOI 10.1016/j.ajo.2008.04.037
   Spaide R, 2007, AM J OPHTHALMOL, V143, P679, DOI 10.1016/j.ajo.2007.02.024
   Westfall AC, 2005, ARCH OPHTHALMOL-CHIC, V123, P1075, DOI 10.1001/archopht.123.8.1075
NR 14
TC 37
Z9 38
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 JUL
PY 2009
VL 148
IS 1
BP 66
EP 69
DI 10.1016/j.ajo.2009.02.013
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 464CE
UT WOS:000267481700011
PM 19403114
DA 2022-11-30
ER

PT J
AU Picard, E
   Fontaine, I
   Jonet, L
   Guillou, F
   Behar-Cohen, F
   Courtois, Y
   Jeanny, JC
AF Picard, Emilie
   Fontaine, Isabelle
   Jonet, Laurent
   Guillou, Florian
   Behar-Cohen, Francine
   Courtois, Yves
   Jeanny, Jean-Claude
TI The protective role of transferrin in Muller glial cells after
   iron-induced toxicity
SO MOLECULAR VISION
LA English
DT Article
ID GENE-EXPRESSION; MESSENGER-RNA; HUMAN RETINA; BRAIN; BINDING; MICE;
   DIFFERENTIATION; CERULOPLASMIN; PROTEINS; CULTURES
AB Purpose: Transferrin (Tf) expression is enhanced by aging and inflammation in humans. We investigated the role of transferrin in glial protection.
   Methods: We generated transgenic mice (Tg) carrying the complete human transferrin gene on a C57Bl/6J genetic background. We studied human (hTf) and mouse (mTf) transferrin localization in Tg and wild-type (WT) C57Bl/6J mice using immunochemistry with specific antibodies. Muller glial (MG) cells were cultured from explants and characterized using cellular retinaldehyde binding protein (CRALBP) and vimentin antibodies. They were further subcultured for study. We incubated cells with FeCl3-nitrilotriacetate to test for the iron-induced stress response; viability was determined by direct counting and measurement of lactate dehydrogenase (LDH) activity. Tf expression was determined by reverse transcriptase-quantitative PCR with human- or mouse-specific probes. hTf and mTf in the medium were assayed by ELISA or radioimmunoassay (RIA), respectively.
   Results: mTf was mainly localized in retinal pigment epithelium and ganglion cell layers in retina sections of both mouse lines. hTf was abundant in MG cells. The distribution of mTf and hTf mRNA was consistent with these findings. mTf and hTf were secreted into the medium of MG cell primary cultures. Cells from Tg mice secreted hTf at a particularly high level. However, both WT and Tg cell cultures lose their ability to secrete Tf after a few passages. Tg MG cells secreting hTf were more resistant to iron-induced stress toxicity than those no longer secreted hTf. Similarly, exogenous human apo-Tf, but not human holo-Tf, conferred resistance to iron-induced stress on MG cells from WT mice.
   Conclusions: hTf localization in MG cells from Tg mice was reminiscent of that reported for aged human retina and age-related macular degeneration, both conditions associated with iron deposition. The role of hTf in protection against toxicity in Tg MG cells probably involves an adaptive mechanism developed in neural retina to control iron-induced stress.
C1 [Picard, Emilie; Jonet, Laurent; Behar-Cohen, Francine; Courtois, Yves; Jeanny, Jean-Claude] INSERM, U872, Paris, France.
   [Picard, Emilie; Jonet, Laurent; Behar-Cohen, Francine; Courtois, Yves; Jeanny, Jean-Claude] Univ Paris 06, Ctr Rech Cordeliers, Paris, France.
   [Picard, Emilie; Jonet, Laurent; Behar-Cohen, Francine; Courtois, Yves; Jeanny, Jean-Claude] Univ Paris 05, Paris, France.
   [Fontaine, Isabelle; Guillou, Florian] Univ Tours, Ctr Natl Rech Sci, UMR 6175, Inst Natl Rech Agron, Nouzilly, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Universite Paris Cite; Institut
   National de la Sante et de la Recherche Medicale (Inserm); UDICE-French
   Research Universities; Sorbonne Universite; Universite Paris Cite;
   UDICE-French Research Universities; Universite Paris Cite; Centre
   National de la Recherche Scientifique (CNRS); Universite de Tours; INRAE
RP Picard, E (通讯作者)，CRC, UMRS 872 Eq 17, 15 Rue Ecole Med, F-75006 Paris 75, France.
EM e-picard@idf.inserm.fr
RI picard, Emilie/A-6919-2013
OI picard, Emilie/0000-0002-2689-0510
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NR 60
TC 24
Z9 25
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAY 20
PY 2008
VL 14
IS 111
BP 928
EP 941
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 327ST
UT WOS:000257749500001
PM 18509548
DA 2022-11-30
ER

PT J
AU Schlotzer-Schrehardt, U
   Viestenz, A
   Naumann, GOH
   Laqua, H
   Michels, S
   Schmidt-Erfurth, U
AF Schlotzer-Schrehardt, U
   Viestenz, A
   Naumann, GOH
   Laqua, H
   Michels, S
   Schmidt-Erfurth, U
TI Dose-related structural effects of photodynamic therapy on choroidal and
   retinal structures of human eyes
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; NEOVASCULARIZATION; VERTEPORFIN; OCCLUSION;
   PATHWAYS
AB Purpose: To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes. Methods: One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration. Two laser spots and two light doses (50 J/cm(2) and 100 J/cm(2)) were applied in unaffected chorioretinal areas. The effects of PDT were assessed by fluorescein and indocyanine-green angiography. The eyes were enucleated 1 week later, fixed in buffered paraformaldehyde/glutaraldehyde solution, bisected along the laser spots, and processed for light and electron microscopy. Results: In agreement with the clinical angiographic findings of hypofluorescence, a rather selective occlusion of the choriocapillary layer was observed in the 50-J/cm(2) PDT areas, whereas the 100-J/cm(2) PDT areas additionally revealed closure of deeper choroidal vessels and focal alterations of the retinal pigment epithelium. The overlying neurosensory retina, including photoreceptors and retinal capillaries, was well preserved in all PDT areas. Electron microscopy showed that alterations of the choriocapillary endothelium comprised swelling, shrinkage and fragmentation of endothelial cells, detachment from their basement membrane up to complete degeneration of the endothelial lining, leading to platelet aggregation, degranulation, and thrombus formation. Complete occlusion of capillary lumina by fibrin, thrombocytes, and cellular debris was observed. Remaining intact endothelial cells appeared to be reorganized into novel smaller vascular channels within occluded lumina. Conclusions: PDT with verteporfin at a dosage used clinically induces selective occlusion of the physiological choriocapillaris without affecting deeper choroidal, retinal, and optic nerve vessels or the overlying retinal pigment epithelium and neurosensory retina. The main mechanism of action appears to be vascular thrombosis induced by cytotoxic damage of endothelial cells and platelet activation. An increase in light dose enhances the occlusive effect with thrombosis within deeper choroidal layers and damage to the retinal pigment epithelium. However, photoreceptors remained intact at all light doses used.
C1 Univ Erlangen Nurnberg, Dept Ophthalmol, D-91054 Erlangen, Germany.
   Med Univ Lubeck, Hosp Eye, D-23538 Lubeck, Germany.
C3 University of Erlangen Nuremberg; University of Lubeck
RP Schlotzer-Schrehardt, U (通讯作者)，Univ Erlangen Nurnberg, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany.
EM ursula.schloetzer@augen.imed.uni-erlangen.de
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NR 26
TC 203
Z9 218
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 SEP
PY 2002
VL 240
IS 9
BP 748
EP 757
DI 10.1007/s00417-002-0517-4
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 607AT
UT WOS:000178768800011
PM 12271373
DA 2022-11-30
ER

PT J
AU Martinez-Camarillo, JC
   Spee, CK
   Trujillo-Sanchez, GP
   Rodriguez, A
   Hinton, DR
   Giarola, A
   Pikov, V
   Sridhar, A
   Humayun, MS
   Weitz, AC
AF Martinez-Camarillo, Juan Carlos
   Spee, Christine K.
   Trujillo-Sanchez, Gloria Paulina
   Rodriguez, Anthony
   Hinton, David R.
   Giarola, Alessandra
   Pikov, Victor
   Sridhar, Arun
   Humayun, Mark S.
   Weitz, Andrew C.
TI Blocking Ocular Sympathetic Activity Inhibits Choroidal
   Neovascularization
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE wet AMD; internal carotid nerve; choroidal neovascularization; ocular
   sympathetic activity; laser-induced CNV; beta-adrenoreceptor modulation
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR EXPRESSION; IN-VIVO; MACULAR
   DEGENERATION; PROPRANOLOL; HYPOXIA; VEGF; CATECHOLAMINES;
   GANGLIONECTOMY; ATTENUATION
AB Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the beta-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the beta-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.
C1 [Martinez-Camarillo, Juan Carlos; Trujillo-Sanchez, Gloria Paulina; Humayun, Mark S.; Weitz, Andrew C.] Univ Southern Calif, USC Roski Eye Inst, Keck Sch Med, Los Angeles, CA 90007 USA.
   [Martinez-Camarillo, Juan Carlos; Trujillo-Sanchez, Gloria Paulina; Hinton, David R.; Humayun, Mark S.; Weitz, Andrew C.] Univ Southern Calif, USC Ginsburg Inst Biomed Therapeut, Los Angeles, CA 90007 USA.
   [Spee, Christine K.; Rodriguez, Anthony; Hinton, David R.] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90007 USA.
   [Giarola, Alessandra; Pikov, Victor; Sridhar, Arun] Galvani Bioelect, Stevenage, Herts, England.
C3 University of Southern California; University of Southern California;
   University of Southern California
RP Humayun, MS (通讯作者)，Univ Southern Calif, USC Roski Eye Inst, Keck Sch Med, Los Angeles, CA 90007 USA.; Humayun, MS (通讯作者)，Univ Southern Calif, USC Ginsburg Inst Biomed Therapeut, Los Angeles, CA 90007 USA.
EM humayun@med.usc.edu
FU Galvani Bioelectronics; Research to Prevent Blindness
FX Supported by a grant from Galvani Bioelectronics as well as unrestricted
   departmental support to the USC Roski Eye Institute from Research to
   Prevent Blindness.
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NR 49
TC 0
Z9 0
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD JAN 10
PY 2022
VL 15
AR 780841
DI 10.3389/fnins.2021.780841
PG 9
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA YP1RG
UT WOS:000748404700001
PM 35082594
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Boyer, DS
   Gonzalez, VH
   Kunimoto, DY
   Maturi, RK
   Roe, RH
   Singer, MA
   Xavier, S
   Kornfield, JA
   Kuppermann, BD
   Quiroz-Mercado, H
   Aubel, J
   Karageozian, HL
   Park, JY
   Karageozian, VH
   Karageozian, L
   Sarayba, MA
   Kaiser, PK
AF Boyer, David S.
   Gonzalez, Victor H.
   Kunimoto, Derek Y.
   Maturi, Raj K.
   Roe, Richard H.
   Singer, Michael A.
   Xavier, Samantha
   Kornfield, Julie A.
   Kuppermann, Baruch D.
   Quiroz-Mercado, Hugo
   Aubel, Janine
   Karageozian, Hampar L.
   Park, John Y.
   Karageozian, Vicken H.
   Karageozian, Lisa
   Sarayba, Melvin A.
   Kaiser, Peter K.
TI Safety and Efficacy of Intravitreal Risuteganib for Non-Exudative AMD: A
   Multicenter, Phase 2a, Randomized, Clinical Trial
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; COMPLEMENT; RPE; PREVALENCE;
   PROTECTION; PATHWAY; VISION; MODELS
AB BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of 1.0 mg risuteganib in subjects with nonexudative age-related macular degeneration (AMD).
   PATIENTS AND METHODS: This was a phase 2a, prospective, double-masked, sham-controlled study. Eyes with nonexudative (dry) AMD and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/40 and 20/200 were included. Subjects were randomized to intravitreal 1.0 mg risuteganib or sham injection. At Week 16, subjects in the risuteganib group received a second 1.0-mg dose and the sham group crossed over to receive a dose of 1.0 mg risuteganib and were evaluated at Week 28. The primary endpoint was proportion of subjects with 8 letters ETDRS or more BCVA gain from baseline to Week 28 in the risuteganib group versus baseline to Week 12 for the sham group. BCVA was tested and subjects were observed for adverse events (AEs) every 4 weeks until completion of the study at 32 weeks.
   RESULTS: Forty-five subjects (risuteganib, n = 29; sham, n = 16) were enrolled in the study, of whom 39 (risuteganib, n = 25; sham, n = 14) completed the study and were included in the per protocol efficacy analysis. At baseline, mean age was 78.8 and 75.9 years and mean BCVA was 67.1 and 64.4 letters in the sham and risuteganib groups, respectively. The primary endpoint was met by 48% of the risuteganib group at Week 28 and 7% of the sham group at Week 12 (P = .013). Of the risuteganib subjects, 20% gained 15 letters or more at Week 28, whereas no patients in the sham group at Week 12 achieved this visual acuity gain. The only ocular treatment-related treatment-emergent AE was vitreous floaters, which spontaneously recovered without sequelae. No drug-related serious AE was reported.
   CONCLUSIONS: Risuteganib demonstrated significant BCVA improvement in patients with non-exudative AMD. No drug-related AEs were seen during a 32-week observation period.
C1 [Boyer, David S.; Roe, Richard H.] Retina Vitreous Associates Med Grp, Beverly Hills, CA USA.
   [Gonzalez, Victor H.] Valley Retinal Inst PA, Mcallen, TX USA.
   [Kunimoto, Derek Y.] Retinal Consultants Arizona, Gilbert, AZ USA.
   [Maturi, Raj K.] Midwest Eye Inst, Indianapolis, IN USA.
   [Singer, Michael A.] Med Ctr Ophthalmol Associates, San Antonio, TX USA.
   [Xavier, Samantha] Florida Eye Clin, Altamonte Springs, FL USA.
   [Kornfield, Julie A.] CALTECH, Pasadena, CA 91125 USA.
   [Kuppermann, Baruch D.] Univ Calif Irvine, Irvine, CA USA.
   [Quiroz-Mercado, Hugo] Assoc Evitar Ceguera Mexico, Mexico City, DF, Mexico.
   [Aubel, Janine; Karageozian, Hampar L.; Park, John Y.; Karageozian, Vicken H.; Karageozian, Lisa; Sarayba, Melvin A.] Allegro Ophthalm LLC, San Juan Capistrano, CA USA.
   [Kaiser, Peter K.] Cole Eye Inst, Cleveland, OH USA.
C3 Retina Vitreous Associates Medical Group; California Institute of
   Technology; University of California System; University of California
   Irvine
RP Boyer, DS (通讯作者)，9001 Wilshire Blvd,Suite 301, Beverly Hills, CA 90211 USA.
EM vitdoc@aol.com
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NR 27
TC 3
Z9 3
U1 1
U2 3
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 JUN
PY 2021
VL 52
IS 6
BP 327
EP 335
DI 10.3928/23258160-20210528-05
PG 9
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA TP8YK
UT WOS:000677879800005
PM 34185587
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Downie, LE
   Wormald, R
   Evans, J
   Virgili, G
   Keller, PR
   Lawrenson, JG
   Li, TJ
AF Downie, Laura E.
   Wormald, Richard
   Evans, Jennifer
   Virgili, Gianni
   Keller, Peter R.
   Lawrenson, John G.
   Li, Tianjing
TI Analysis of a Systematic Review About Blue Light-Filtering Intraocular
   Lenses for Retinal Protection: Understanding the Limitations of the
   Evidence
SO JAMA OPHTHALMOLOGY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; INTERVENTIONS
AB ImportanceCataract surgery, with intraocular lens (IOL) implantation, is the most common ocular surgical procedure worldwide. It has been suggested that IOLs that selectively attenuate short wavelength visible light (blue light-filtering IOLs) may be beneficial for macular health. Whether blue light-filtering IOLs impart retinal photoprotection is of public health relevance, particularly in the context of aging demographics and the increasing global prevalence of age-related macular degeneration. This review analyzes and interprets the key findings, including consideration of the implications for practice and future research, of a 2018 Cochrane systematic review that evaluated the efficacy and safety of blue light-filtering IOLs for providing protection to macular health and function. ObservationsThe Cochrane systematic review included 51 randomized controlled trials that were performed in 17 countries. The trials involved adults undergoing cataract surgery in which a blue light-filtering IOL was compared with an equivalent non-blue light-filtering IOL. Study follow-up periods ranged from 1 month to 5 years. Together, these studies considered clinical outcomes in more than 5000 eyes. There was limited ability to combine data across trials (to draw overall conclusions) because of the use of different measurement techniques for outcomes, incomplete reporting of data, and/or varied follow-up periods. We identified substantial shortcomings in the internal validity of many of the included studies, particularly regarding trial design, conduct, and reporting. We propose several avenues for improving the rigor of potential future research in the field, including developing a core set of outcome measures, the inclusion of sample size calculations, the masking of trial participants and outcome assessors, and prospective clinical trial registration. Conclusions and RelevanceUsing blue light-filtering IOLs to impart benefits to the macula is currently not supported by the best available clinical research evidence, and it is important that clinicians are mindful of this evidence limitation when adopting these devices in clinical practice.
   This Special Communication analyzes a 2018 Cochrane systematic review of studies that evaluated the efficacy and safety of blue light-filtering intraocular lenses for providing protection to macular health and function.
C1 [Downie, Laura E.; Keller, Peter R.] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3010, Australia.
   [Wormald, Richard] Moorfields Eye Hosp, Natl Hlth Serv Fdn Trust, London, England.
   [Wormald, Richard; Evans, Jennifer] London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Dept Clin Res, London, England.
   [Virgili, Gianni] Univ Florence, Dept Surg & Translat Med, Florence, Italy.
   [Lawrenson, John G.] Univ London, Div Optometry & Visual Sci, London, England.
   [Li, Tianjing] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
C3 University of Melbourne; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust; University of
   London; London School of Hygiene & Tropical Medicine; University of
   Florence; University of London; Johns Hopkins University; Johns Hopkins
   Bloomberg School of Public Health
RP Downie, LE (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3010, Australia.
EM ldownie@unimelb.edu.au
RI ; Virgili, Gianni/P-6607-2014
OI Downie, Laura/0000-0002-1596-2259; Lawrenson, John/0000-0002-2031-6390;
   Virgili, Gianni/0000-0002-9960-2989
FU 2015 NHMRC Translating Research Into Practice Fellowship [APP1091833];
   NATIONAL EYE INSTITUTE [UG1EY020522] Funding Source: NIH RePORTER
FX This work was partially supported by a 2015 NHMRC Translating Research
   Into Practice Fellowship (APP1091833, CIA, Dr Downie).
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NR 28
TC 16
Z9 16
U1 3
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2019
VL 137
IS 6
BP 694
EP 697
DI 10.1001/jamaophthalmol.2019.0019
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ID5XL
UT WOS:000471750500022
PM 30789642
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Pham, B
   Thomas, SM
   Lillie, E
   Lee, T
   Hamid, J
   Richter, T
   Janoudi, G
   Agarwal, A
   Sharpe, JP
   Scott, A
   Warren, R
   Brahmbhatt, R
   Macdonald, E
   Straus, SE
   Tricco, AC
AF Pham, Ba'
   Thomas, Sonia M.
   Lillie, Erin
   Lee, Taehoon
   Hamid, Jemila
   Richter, Trevor
   Janoudi, Ghayath
   Agarwal, Arnav
   Sharpe, Jane P.
   Scott, Alistair
   Warren, Rachel
   Brahmbhatt, Ronak
   Macdonald, Erin
   Straus, Sharon E.
   Tricco, Andrea C.
TI Anti-vascular endothelial growth factor treatment for retinal
   conditions: a systematic review and meta-analysis
SO BMJ OPEN
LA English
DT Review
ID MACULAR EDEMA SECONDARY; VEGF TRAP-EYE; INTRAVITREAL RANIBIZUMAB; VEIN
   OCCLUSION; VISUAL-ACUITY; CHOROIDAL NEOVASCULARIZATION;
   DIABETIC-RETINOPATHY; PATHOLOGICAL MYOPIA; RANDOMIZED-TRIAL; BEVACIZUMAB
AB Objectives To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).
   Design Systematic review and random-effects meta-analysis.
   Methods Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged >= 18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.
   Results 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6-9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.
   Conclusions Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (>= 15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.
   PROSPERO registration number CRD42015022041.
C1 [Pham, Ba'; Thomas, Sonia M.; Lillie, Erin; Lee, Taehoon; Hamid, Jemila; Sharpe, Jane P.; Scott, Alistair; Warren, Rachel; Brahmbhatt, Ronak; Macdonald, Erin; Straus, Sharon E.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Knowledge Translat Program, Toronto, ON, Canada.
   [Hamid, Jemila; Agarwal, Arnav] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
   [Richter, Trevor; Janoudi, Ghayath] Canadian Agcy Drugs & Technol Hlth, Ottawa, ON, Canada.
   [Agarwal, Arnav] Univ Toronto, Fac Med, Toronto, ON, Canada.
   [Macdonald, Erin] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
   [Straus, Sharon E.] Univ Toronto, Dept Geriatr Med, Toronto, ON, Canada.
   [Tricco, Andrea C.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Knowledge Translat Program, Toronto, ON, Canada.
   [Tricco, Andrea C.] Univ Toronto, Dalla Lana Sch Publ Hlth, Epidemiol Div, Toronto, ON, Canada.
C3 University of Toronto; Li Ka Shing Knowledge Institute; University
   Toronto Affiliates; Saint Michaels Hospital Toronto; McMaster
   University; University of Toronto; University of Toronto; University of
   Toronto; University of Toronto; Li Ka Shing Knowledge Institute;
   University Toronto Affiliates; Saint Michaels Hospital Toronto;
   University of Toronto
RP Tricco, AC (通讯作者)，St Michaels Hosp, Li Ka Shing Knowledge Inst, Knowledge Translat Program, Toronto, ON, Canada.; Tricco, AC (通讯作者)，Univ Toronto, Dalla Lana Sch Publ Hlth, Epidemiol Div, Toronto, ON, Canada.
EM triccoa@smh.ca
RI Agarwal, Arnav/J-1553-2014; Tricco, Andrea/B-9920-2011
OI Agarwal, Arnav/0000-0002-0931-7851; Tricco, Andrea/0000-0002-4114-8971;
   Janoudi, Ghayath/0000-0002-0790-047X
FU Canadian Institutes of Health Research/Drug Safety and Effectiveness
   Network (CIHR/DSEN); Tier 1 Canada Research Chair in Knowledge
   Translation; Tier 2 Canada Research Chair in Knowledge Synthesis;
   Canadian Institutes of Health Research Drug Safety and Effectiveness
   Network
FX This work was supported by the Canadian Institutes of Health
   Research/Drug Safety and Effectiveness Network (CIHR/DSEN). SES is
   funded by a Tier 1 Canada Research Chair in Knowledge Translation. ACT
   is funded by a Tier 2 Canada Research Chair in Knowledge Synthesis. The
   therapeutic review was commissioned by the Canadian Agency for Drugs and
   Technology in Health (CADTH) and funded by a grant from the Canadian
   Institutes of Health Research Drug Safety and Effectiveness Network. The
   funders had no role in 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.
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NR 57
TC 30
Z9 33
U1 0
U2 20
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PD MAY
PY 2019
VL 9
IS 5
AR e022031
DI 10.1136/bmjopen-2018-022031
PG 11
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA IC7YG
UT WOS:000471192800014
PM 31142516
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Munk, M
   Kiss, C
   Huf, W
   Sulzbacher, F
   Bolz, M
   Sayegh, R
   Eisenkolbl, S
   Simader, C
   Schmidt-Erfurth, U
AF Munk, Marion
   Kiss, Christopher
   Huf, Wolfgang
   Sulzbacher, Florian
   Bolz, Matthias
   Sayegh, Ramzi
   Eisenkoelbl, Stefan
   Simader, Christian
   Schmidt-Erfurth, Ursula
TI THERAPEUTIC INTERVENTIONS FOR MACULAR DISEASES SHOW CHARACTERISTIC
   EFFECTS ON NEAR AND DISTANCE VISUAL FUNCTION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE reading performance; neovascular age-related macular degeneration;
   distance visual acuity; cystoid macular edema; visual function; reading
   acuity
ID OPTICAL COHERENCE TOMOGRAPHY; READING PERFORMANCE; INTRAVITREAL
   TRIAMCINOLONE; RETINAL MORPHOLOGY; DEGENERATION; VISION; ACUITY; SPEED;
   EDEMA; SENSITIVITY
AB Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema.
   Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy.
   Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 +/- 0.28 to 0.39 +/- 0.3 (P = 0.018) and 0.71 +/- 0.53 to 0.56 +/- 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti-vascular endothelial growth factor therapy from 0.59 +/- 0.29 to 0.49 +/- 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 +/- 0.65 to 0.90 +/- 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease.
   Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.
C1 [Munk, Marion; Kiss, Christopher; Sulzbacher, Florian; Bolz, Matthias; Sayegh, Ramzi; Eisenkoelbl, Stefan; Simader, Christian; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
   [Huf, Wolfgang] Med Univ Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
C3 Medical University of Vienna; Medical University of Vienna
RP Kiss, C (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM christopher.kiss@meduniwien.ac.at
RI Bolz, Matthias/HCI-0622-2022
OI Bolz, Matthias/0000-0001-8691-5276; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Simader, Christian/0000-0002-1784-2883
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NR 27
TC 8
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD OCT
PY 2013
VL 33
IS 9
BP 1915
EP 1922
DI 10.1097/IAE.0b013e318285cc0c
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297DL
UT WOS:000330235500022
PM 23584693
DA 2022-11-30
ER

PT J
AU Perkins, SJ
   Nan, RD
   Li, KY
   Khan, S
   Miller, A
AF Perkins, Stephen J.
   Nan, Ruodan
   Li, Keying
   Khan, Sanaullah
   Miller, Ami
TI Complement Factor H-ligand interactions: Self-association, multivalency
   and dissociation constants
SO IMMUNOBIOLOGY
LA English
DT Review
DE Analytical ultracentrifugation; Surface plasmon resonance; X-ray
   scattering; Complement Factor H; Complement C3
ID C-REACTIVE PROTEIN; REGULATOR FACTOR-H; X-RAY-SCATTERING; BINDING-SITES;
   MACULAR DEGENERATION; STRUCTURAL BASIS; C3B; DOMAIN; ZINC; POLYMORPHISM
AB Factor H (FH) is the major plasma regulator of the central complement protein C3b in the alternative pathway of complement activation.The elucidation of the FH interactions with five major ligands (below) is complicated by their weak mu M dissociation constants K-D and FH multivalency. We present the first survey of all the K-D values for the major FH-ligand interactions and critically review their physiological significance.
   (i) FH self-association is presently well-established. We review multiple data sets that show that 5-14% of FH is self-associated in physiological conditions. FH self-association is significant for both laboratory investigations and physiological function.
   (ii) The FH-C3b complex shows low mu M affinity, meaning that the complex is not fully formed in plasma. In addition. C3, its hydrolysed form C3u, and its cleaved forms C3b and C3d show multimerisation. Current data favour a model when two C3b molecules bind independently to one FH molecule, as opposed to a 1:1 stoichiometry where FH wraps itself around C3b.
   (iii) Heparin is often used as an analogue of the polyanionic host cell surface. The FH-heparin complex also shows a low mu M affinity, again meaning that complexes are not fully formed in vivo. The oligomeric FH-heparin complexes clarify a two-site interaction model of FH with host-cell surfaces.
   (iv) Reinvestigation of the FH and C-reactive protein (CRP) interaction revealed that this can only occur in plasma when CRP levels are elevated during acute-phase conditions. Given that CRP binds more weakly to the His402 allotype of FH than the Tyr402 allotype, this suggested a link with age-related macular degeneration (AMD).
   (v) FH activity is inhibited by zinc, which causes FH to aggregate strongly. High levels of bioavailable zinc occur in sub-retinal pigment epithelial deposits which lead to AMD. Excess zinc binds weakly to a central region of FH, explaining how zinc inhibits FH regulation of C3b. (C) 2011 Elsevier GmbH. All rights reserved.
C1 [Perkins, Stephen J.; Nan, Ruodan; Li, Keying; Khan, Sanaullah; Miller, Ami] UCL, Dept Struct & Mol Biol, 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
RI KHAN, SANAULLAH/A-8386-2015
OI KHAN, SANAULLAH/0000-0003-2480-6239
FU University College London; Medical Research Council; Biotechnology and
   Biological Sciences Research Council; Mercer Fund of the Fight For Sight
   Charity; Henry Smith Charity; Higher Education Commission of Pakistan;
   Medical Research Council [G0801724] Funding Source: researchfish; MRC
   [G0801724] Funding Source: UKRI
FX We thank University College London, the Medical Research Council, the
   Biotechnology and Biological Sciences Research Council, the Mercer Fund
   of the Fight For Sight Charity, the Henry Smith Charity and the Higher
   Education Commission of Pakistan for studentships and grant funding. We
   are particularly grateful to Dr Zuby Okemefuna and Dr Daniel Gale at
   UCL, and Dr Imre Lengyel and Prof Alan Bird of the UCL Institute of
   Ophthalmology for useful discussions, and Jayesh Gor, Dr Theyencheri
   Narayanan, Dr Anuj Shukla and Dr Shirley Callow for invaluable
   instrumental support during our recent projects.
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NR 78
TC 61
Z9 64
U1 0
U2 28
PU ELSEVIER GMBH
PI MUNICH
PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD FEB
PY 2012
VL 217
IS 2
SI SI
BP 281
EP 297
DI 10.1016/j.imbio.2011.10.003
PG 17
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 902GI
UT WOS:000301026200019
PM 22137027
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Xie, P
   Kamei, M
   Suzuki, M
   Matsumura, N
   Nishida, K
   Sakimoto, S
   Sakaguchi, H
   Nishida, K
AF Xie, Ping
   Kamei, Motohiro
   Suzuki, Mihoko
   Matsumura, Nagakazu
   Nishida, Kentaro
   Sakimoto, Susumu
   Sakaguchi, Hirokazu
   Nishida, Kohji
TI Suppression and Regression of Choroidal Neovascularization in Mice by a
   Novel CCR2 Antagonist, INCB3344
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE
   RECEPTOR 2; MACULAR DEGENERATION; SIGNAL-TRANSDUCTION; PHARMACOLOGICAL
   CHARACTERIZATION; SOD1-DEFICIENT MICE; MACROPHAGES; ACTIVATION;
   EXPRESSION
AB Purpose: To investigate the effect of an intravitreally administered CCR2 antagonist, INCB3344, on a mouse model of choroidal neovascularization (CNV).
   Methods: CNV was induced by laser photocoagulation on Day 0 in wild type mice. INCB3344 or vehicle was administered intravitreally immediately after laser application. On Day 14, CNV areas were measured on retinal pigment epithelium (RPE)-choroid flat mounts and histopathologic examination was performed on 7 mu m-thick sections. Macrophage infiltration was evaluated by immunohistochemistry on RPE-choroid flat mounts and quantified by flow cytometry on Day 3. Expression of vascular endothelial growth factor (VEGF) protein in RPE-choroid tissue was examined by immunohistochemistry and ELISA, VEGF mRNA in sorted macrophages in RPE-choroid tissue was examine by real-time PCR and expression of phosphorylated extracellular signal-regulated kinase (p-ERK 1/2) in RPE-choroid tissue was measured by Western blot analysis on Day 3. We also evaluated the efficacy of intravitreal INCB3344 to spontaneous CNV detected in Cu, Zn-superoxide dismutase (SOD1) deficient mice. Changes in CNV size were assessed between pre- and 1week post-INCB3344 or vehicle administration in fundus photography and fluorescence angiography (FA).
   Results: The mean CNV area in INCB3344-treated mice decreased by 42.4% compared with the vehicle-treated control mice (p<0.001). INCB3344 treatment significantly inhibited macrophage infiltration into the laser-irradiated area (p<0.001), and suppressed the expression of VEGF protein (p = 0.012), VEGF mRNA in infiltrating macrophages (p<0.001) and the phosphorylation of ERK1/2 (p<0.001). The area of spontaneous CNV in Sod1(-/-) mice regressed by 70.35% in INCB3344-treated animals while no change was detected in vehicle-treated control mice (p<0.001).
   Conclusions: INCB3344 both inhibits newly forming CNV and regresses established CNV. Controlling inflammation by suppressing macrophage infiltration and angiogenic ability via the CCR-2/MCP-1 signal may be a useful therapeutic strategy for treating CNV associated with age-related macular degeneration.
C1 [Xie, Ping; Kamei, Motohiro; Suzuki, Mihoko; Matsumura, Nagakazu; Nishida, Kentaro; Sakimoto, Susumu; Sakaguchi, Hirokazu; Nishida, Kohji] Osaka Univ, Dept Ophthalmol, Grad Sch Med, Suita, Osaka, Japan.
C3 Osaka University
RP Xie, P (通讯作者)，Osaka Univ, Dept Ophthalmol, Grad Sch Med, Suita, Osaka, Japan.
EM mkamei@ophthal.med.osaka-u.ac.jp
OI Nishida, Kohji/0000-0001-9069-3610; Xie, Ping/0000-0003-4257-8970
FU Ministry of Education, Science and Culture of Japan [15591853];
   Grants-in-Aid for Scientific Research [21592231] Funding Source: KAKEN
FX This work was supported by a Grant-in-Aid for Scientific Research
   (#15591853) from the Ministry of Education, Science and Culture of
   Japan. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
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NR 51
TC 32
Z9 36
U1 0
U2 1
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 9
PY 2011
VL 6
IS 12
AR e28933
DI 10.1371/journal.pone.0028933
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 870JO
UT WOS:000298665600017
PM 22205983
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Meyer, CH
   Scholl, HP
   Eter, N
   Helb, HM
   Holz, FG
AF Meyer, Carsten H.
   Scholl, Hendrik P.
   Eter, Nicole
   Helb, Hans-Martin
   Holz, Frank G.
TI Combined treatment of acute subretinal haemorrhages with intravitreal
   recombined tissue plasminogen activator, expansile gas and bevacizumab:
   a retrospective pilot study
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE bevacizumab; choroidal neovascularization; expansile gas; intravitreal
   injection; recombined tissue plasminogen activator; subretinal
   haemorrhages
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; NATURAL-HISTORY;
   INJECTION; PRESSURE; AVASTIN
AB Purpose: To assess the effectiveness of consecutive intravitreal injections of recombined tissue plasminogen activator (rtPA), expansile gas and bevacizumab in eyes with acute subretinal haemorrhage (SRH).
   Methods: A retrospective, non-randomized consecutive case series included 19 eyes in 19 patients with SRH related to exudative age-related macular degeneration (AMD). The initial size of the subfoveal SRH was 1-3 disc diameters. Each patient received a triple procedure using 0.05 ml rtPA (50 mu g), 0.3 ml of sulphur hexafluoride (SF6) gas and 0.05 ml bevacizumab (1.25 mg). Lesion size, location of the SRH and early treatment in diabetic retinopathy study (ETDRS) visual acuity were evaluated pretreatment as well as 1 and 3 months after the procedure.
   Results: At the initial presentation, the patients' mean age was 77 years (range 63-88 years) and the mean duration of symptoms was 9.3 days (range 4-12 days). The mean visual acuity pretreatment (20/133) improved significantly to 20/86 at 1 month and to 20/74 at 3 months. The mean ETDRS visual acuity improved from baseline by 2.1 lines at 1 month (Wilcoxon ranks test; P < 0.005) and 3.7 lines at 3 months after treatment (Wilcoxon ranks test; P < 0.005). None of our patients had reading visual acuity prior to treatment, with visual acuity below 0.3. One month after the triple procedure, 25% of our patients had reading visual acuity (>= 0.4); at 3 months, the figure was 35%. A successful inferior displacement of the SRH was achieved in 17/19 eyes. Eyes with elevated intraocular pressure were treated immediately by a corneal paracentesis.
   Conclusion: The intravitreal application of rtPA, gas and bevacizumab appears to be beneficial and well tolerated in the treatment of SRH in the short term. The triple approach seems a logical alternative to the current combined dual approach in limiting the progression of the underlying disease and achieving better visual outcome. Further randomized evaluations are warranted.
C1 [Meyer, Carsten H.; Scholl, Hendrik P.; Eter, Nicole; Helb, Hans-Martin; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
C3 University of Bonn
RP Meyer, CH (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe St 2, D-53127 Bonn, Germany.
EM meyer_eye@yahoo.com
RI Meyer, Carsten/A-3981-2017
OI Meyer, Carsten/0000-0002-0530-5298
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   Lincoff H, 2001, RETINA-J RET VIT DIS, V21, P191, DOI 10.1097/00006982-200104000-00021
   Luke M, 2007, BRIT J OPHTHALMOL, V91, P1077, DOI 10.1136/bjo.2006.111260
   Niemeyer M, 2007, OPHTHALMOLOGE, V104, P158, DOI 10.1007/s00347-006-1425-5
   Rodrigues EB, 2007, AM J OPHTHALMOL, V143, P1035, DOI 10.1016/j.ajo.2007.01.035
   Schmidt JC, 2004, OPHTHALMOLOGE, V101, P584, DOI 10.1007/s00347-003-0912-1
   Schulze SD, 2002, GRAEF ARCH CLIN EXP, V240, P717, DOI 10.1007/s00417-002-0516-5
   Scupola A, 1999, OPHTHALMOLOGICA, V213, P97, DOI 10.1159/000027400
   Soliman W, 2006, ACTA OPHTHALMOL SCAN, V84, P707, DOI 10.1111/j.1600-0420.2006.00736.x
   Spaide RF, 2006, RETINA-J RET VIT DIS, V26, P383, DOI 10.1097/00006982-200604000-00001
   THOMAS MA, 1992, INT OPHTHALMOL CLIN, V32, P173, DOI 10.1097/00004397-199203220-00016
   Yoganathan P, 2006, RETINA-J RET VIT DIS, V26, P994, DOI 10.1097/01.iae.0000244380.34082.67
NR 22
TC 74
Z9 76
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD AUG
PY 2008
VL 86
IS 5
BP 490
EP 494
DI 10.1111/j.1600-0420.2007.01125.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 329AP
UT WOS:000257839600004
PM 18221499
DA 2022-11-30
ER

PT J
AU Karacorlu, SA
   Ozdemir, H
   Senturk, F
   Karacorlu, M
AF Karacorlu, Serra Arf
   Ozdemir, Hakan
   Senturk, Fevzi
   Karacorlu, Murat
TI Optical coherence tomography after photodynamic therapy for patients
   with pathologic myopia
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION
AB Purpose: To evaluate early changes after photodynamic therapy (PDT) for patients with subfoveal choroidal neovascularization (CNV) due to pathologic myopia by optical coherence tomography (OCT).
   Methods: PDT was performed on 10 eyes of 10 patients who presented with subfoveal CNV due to pathologic myopia. OCT was used to evaluate changes 1 day, 3 days, and 7 days after therapy. Changes in intraretinal and subretinal fluid and CNV were examined on the images obtained. The retinal elevation and the height of the neurosensory retinal detachment were calculated. From these two values, the thickness of the neurosensory retina was obtained. The thickness of the neurosensory retina was measured to ascertain the intraretinal fluid change, and the height of the neurosensory retinal detachment was measured to ascertain the subretinal fluid change.
   Results: The mean pretherapy retinal elevation +/- SD increased from 211 +/- 28 mu m to 230 +/- 39 mu m 1 day after PDT and decreased to 221 +/- 36 mu m 3 days after therapy. At 7 days after therapy, the mean retinal elevation +/- SD was 211 +/- 22 mu m. The retinal elevation was due to a subretinal fluid accumulation, whereas the thickness of the neurosensory retina increased only to a minor extent (range, 0-22 mu m) and the foveal architecture remained unchanged. The mean pretherapy height +/- SD of the neurosensory retinal detachment was 6 +/- 11 mu m. It was 18 +/- 20 mu m, 12 +/- 12 mu m, and 3 +/- 6 /mu m 1 day, 3 days, and 7 days after therapy, respectively. No change in CNV was observed during follow-up.
   Conclusion: The results of our study indicate that the acute infiltration observed in patients with pathologic myopia after PDT occurs in the first day and regresses during the first week. Yet, it should be noted that, unlike in patients with age-related macular degeneration, the acute infiltration phase can be observed by OCT only to a limited extent.
C1 Istanbul Retina Inst Inc, TR-34349 Istanbul, Turkey.
C3 Istanbul Retina Enstitusu
RP Karacorlu, M (通讯作者)，Istanbul Retina Inst Inc, Hakki Yeten Cad 8,K7, TR-34349 Istanbul, Turkey.
EM retina@pobox.com
RI Karaçorlu, Murat/AFK-0782-2022; Karaçorlu, Murat/AAF-7763-2022
CR AVILA MP, 1984, OPHTHALMOLOGY, V91, P1573
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NR 11
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 SEP
PY 2006
VL 26
IS 7
BP 752
EP 756
DI 10.1097/01.iae.0000231382.83491.c1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 180TQ
UT WOS:000247389300007
PM 16963847
DA 2022-11-30
ER

PT J
AU Varma, R
   Paz, SH
   Azen, SP
   Klein, R
   Globe, D
   Torres, M
   Shufelt, C
   Preston-Martin, S
AF Varma, R
   Paz, SH
   Azen, SP
   Klein, R
   Globe, D
   Torres, M
   Shufelt, C
   Preston-Martin, S
CA Los Angeles Latino Eye Study
TI The Los Angeles Latino eye study - Design, methods, and baseline data
SO OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; MEXICAN-AMERICAN POPULATION;
   OPEN-ANGLE GLAUCOMA; VISUAL IMPAIRMENT; DIABETIC-RETINOPATHY; LENS
   OPACITIES; HEALTH SURVEY; BARBADOS EYE; CLASSIFICATION-SYSTEM
AB Objective: To describe the study design, operational strategies, procedures, and baseline characteristics of the Los Angeles Latino Eye Study (LALES), a population-based assessment of the prevalence of visual impairment, ocular disease, and visual functioning in Latinos.
   Design: Population-based, cross-sectional study.
   Participants: Six thousand three hundred fifty-seven Latinos 40 years and older from 6 census tracts in Los Angeles, California.
   Methods: A detailed interview and eye examination were performed on each eligible participant. The interview included an assessment of demographic, behavioral, and ocular risk factors and health-related and vision-related quality of life. The eye examination included a measurement of visual acuity, intraocular pressure, and visual fields; fundus and optic disc photography; a detailed anterior and posterior segment examination; and measurement of blood pressure, glycosylated hemoglobin levels, and blood glucose levels. Main Outcome Measures: Prevalence of visual impairment, blindness, cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration constitute the study's primary outcome variables. Secondary outcomes include odds ratios for risk factors associated with eye disease, health-related quality of life, and vision-related quality of life. Response rates and baseline characteristics are presented.
   Results: Of the 7789 individuals eligible for LALES, 6357 (82%) had a clinical examination; an additional 524 completed only an in-home interview. The majority of participants were female (58%), the average (+/-standard deviation) age was 54.9 (+/-10.8) years, and 80.0% were of Mexican origin and 0.4% self-identified as American Indian or Alaskan Native. The age distribution of LALES participants was similar to that of Latinos of Mexican origin in the rest of the United States.
   Conclusion: The LALES has recruited Latinos 40 and older for an ophthalmic epidemiologic study. The LALES cohort will provide information about the prevalence and risk factors of ocular disease in the largest and fastest growing minority in the United States. (C) 2004 by the American Academy of Ophthalmology.
C1 Doheny Eye Inst, Los Angeles, CA 90033 USA.
   Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA.
   Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
   Univ So Calif, Sch Pharm, Dept Pharmaceut Econ, Madison, WI USA.
   Univ So Calif, Sch Pharm, Dept Policy, Madison, WI USA.
C3 Doheny Eye Institute; University of Southern California; University of
   Southern California; University of Southern California; University of
   Southern California
RP Varma, R (通讯作者)，Doheny Eye Inst, 1450 San Pablo St,Suite 4900, Los Angeles, CA 90033 USA.
EM rvarma@usc.edu
OI Shufelt, Chrisandra/0000-0001-6886-9210
FU NEI NIH HHS [P30 EY003040, U10 EY011753, EY03040, EY11753] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [P30EY003040] Funding Source:
   NIH RePORTER
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NR 47
TC 124
Z9 129
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2004
VL 111
IS 6
BP 1121
EP 1131
DI 10.1016/j.ophtha.2004.02.001
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 824SY
UT WOS:000221708100009
PM 15177962
DA 2022-11-30
ER

PT J
AU Joseph, DP
   Uemura, A
   Thomas, MA
AF Joseph, DP
   Uemura, A
   Thomas, MA
TI Subretinal surgery for juxtafoveal choroidal neovascularization
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID SURGICAL REMOVAL
AB Purpose: To report visual outcome, rate of recurrence, and complications for patients who underwent subretinal surgery as treatment of classic juxtafoveal choroidal neovascularization (CNV).
   Methods: This study was a noncomparative case series of 46 patients who underwent subretinal surgery for juxtafoveal CNV that appeared to be pure classic without angiographic or clinical evidence of occult neovascularization between 1993 and 2000, with best-corrected preoperative and postoperative Snellen visual acuity reported.
   Results: The mean follow-up period +/- SD was 20.4 +/- 12.9 months (range, 6-57 months). Etiologic categories included ocular histoplasmosis syndrome (37%), age-related macular degeneration (20%), idiopathic (15%), myopic degeneration (11%), mixed features of ocular histoplasmosis syndrome and myopia (11%), and other miscellaneous causes (6%). Thirty-three percent (15) of 46 eyes that underwent surgery had previously been treated with thermal laser photocoagulation at least once. Most patients (89%) had membranes with the posterior edge located 200 mum or closer to the center of the foveal avascular zone. The median preoperative visual acuity was 20/70 compared with the median postoperative visual acuity of 20/40. Significant improvement of visual acuity, measured as an increase of two or more lines of vision, occurred in 26 eyes (56%). In 10 (22%) of the remaining eyes, postoperative visual acuity was within one line of the preoperative visual acuity. Visual acuity decreased by two to five lines in seven eyes (15%). Severe vision loss, defined as a decrease of six or more lines, occurred in three eyes (7%). Recurrence was observed in 26 patients (56.5%).
   Conclusion: The results indicated that subretinal surgery for juxtafoveal CNV improved or stabilized vision in most cases (78%), but in the absence of controls with a limited number of eyes and variable follow-up, it is impossible to determine with certainty if this improvement or stabilization is greater than what might be seen with laser photocoagulation or observation.
C1 Washington Univ, Sch Med, Barnes Retina Inst, St Louis, MO 63144 USA.
   Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63144 USA.
   Kagoshima Univ, Fac Med, Dept Ophthalmol, Kagoshima 890, Japan.
C3 Washington University (WUSTL); Washington University (WUSTL); Kagoshima
   University
RP Joseph, DP (通讯作者)，Washington Univ, Sch Med, Barnes Retina Inst, 1600 S Brentwood Blvd,8th Floor, St Louis, MO 63144 USA.
EM josephd@vision.wustl.edu
RI Thomas, Megan/GWQ-4391-2022
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NR 15
TC 7
Z9 8
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 AUG
PY 2003
VL 23
IS 4
BP 463
EP 468
DI 10.1097/00006982-200308000-00003
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 718DQ
UT WOS:000185130200003
PM 12972755
DA 2022-11-30
ER

PT J
AU Biehlmaier, O
   Neuhauss, SCF
   Kohler, K
AF Biehlmaier, O
   Neuhauss, SCF
   Kohler, K
TI Double cone dystrophy and RPE degeneration in the retina of the
   zebrafish gnn mutant
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VISUAL-SYSTEM; INTERPHOTORECEPTOR MATRIX; PHOTORECEPTOR CELLS;
   BEHAVIORAL SCREEN; PEANUT AGGLUTININ; ROD; MUTATIONS; DIFFERENTIATION;
   BLINDNESS; BINDING
AB PURPOSE. To characterize morphologic alterations in the retina of the visual mutant zebrafish gantenbein (gnn) and to examine whether these alterations correlate with those present in human hereditary eye diseases.
   METHODS. The gnn mutant was isolated by behavioral and macroscopic screening. Retinas of gnn zebrafish larvae were examined at different developmental stages from 2 to 9 days postfertilization (dpf) by standard histologic staining techniques and by immunocytochemistry. Ultrastructural alterations were examined by electron microscopy. The genetic map position of the induced mutation was identified by mapping with two candidate primer pairs on single larvae.
   RESULTS. The gnn mutant exhibited shortened outer photoreceptor segments and altered RPE morphology. In the photoreceptor layer of the mutant, the total number of lectin-labeled cones was reduced in all developmental stages from 2 to 7 dpf, whereas the amount of rhodopsin-positive cells remained at the wild-type (WT) level. Labeling with zebrafish opsin antibodies revealed dystrophic red cones at 5 dpf, whereas the morphology of all other cone types was largely unaffected. Electron microscopy unveiled electron-dense deposits between the discs of the double cone outer segments. In addition, the onset of progressive RPE degeneration was observed at this stage of development. At later stages, all cone types and the RPE became degenerative. The morphology of distinct second-order neurons remained largely unaffected by the mutation. The gnn mutation was located approximately 4.3 cM from the simple sequence length polymorphism (SSLP) marker Z15453 on linkage group 16.
   CONCLUSIONS. In gnn mutant zebrafish, cones, and especially red cones, are dystrophic in early retinal development. Subsequent to this cone dystrophy, the RPE becomes dysfunctional and starts to degenerate in later stages of development. Thus, the early developmental morphology of gnn exhibits similarities to cone dystrophies most commonly seen in age-related macular degeneration (AMD) among humans, whereas the later stages of degeneration in gnn resemble RPE alterations in retinitis pigmentosa (RP) in humans. The grin zebrafish mutant may therefore be a useful model for examining the possible interplay and connection between cone dystrophy and RPE degeneration.
C1 Univ Tubingen, Hosp Eye, Dept Expt Ophthalmol, D-72076 Tubingen, Germany.
   Univ Zurich, Brain Res Inst, Dept Neuromorphol, Zurich, Switzerland.
   Swiss Fed Inst Technol, Zurich, Switzerland.
C3 Eberhard Karls University of Tubingen; University of Zurich; Swiss
   Federal Institutes of Technology Domain; ETH Zurich
RP Kohler, K (通讯作者)，Univ Tubingen, Hosp Eye, Dept Expt Ophthalmol, Rontgenweg 11, D-72076 Tubingen, Germany.
EM konrad.kohler@uni-tuebingen.de
RI Neuhauss, Stephan/AAX-9915-2020
OI Neuhauss, Stephan/0000-0002-9615-480X; Biehlmaier,
   Oliver/0000-0003-0825-8500
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NR 50
TC 24
Z9 25
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 MAR
PY 2003
VL 44
IS 3
BP 1287
EP 1298
DI 10.1167/iovs.02-0363
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 649TD
UT WOS:000181223300049
PM 12601061
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zhuang, XN
   Ma, J
   Xu, GZ
   Sun, ZC
AF Zhuang, Xiaonan
   Ma, Jun
   Xu, Gezhi
   Sun, Zhongcui
TI SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates
   mitochondria-dependent apoptosis induced by all trans retinal through
   the STING/AMPK pathways
SO MOLECULAR MEDICINE
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; All trans
   retinal; Src-homology 2 domain-containing phosphatase-1; Stimulator of
   interferon genes; Adenosine monophosphate-activated protein kinase;
   Mitochondrial biogenesis
ID PROTEIN-TYROSINE-PHOSPHATASE; ENDOPLASMIC-RETICULUM STRESS; PIGMENT
   EPITHELIUM; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; ACTIVATION;
   INFLAMMATION; INVOLVEMENT; RETINOPATHY; REGULATOR
AB Background Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved. Methods In the all trans retinal (atRAL)-induced oxidative stress model, we used the vector of lentivirus to knockdown the expression of SHP-1 in ARPE-19 cells. CCK-8 assay, Annexin V/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis. Results We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes. Conclusions These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal diseases including AMD.
C1 [Zhuang, Xiaonan; Xu, Gezhi; Sun, Zhongcui] Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, 83 Fenyang Rd, Shanghai 200031, Peoples R China.
   [Ma, Jun] Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai, Peoples R China.
   [Zhuang, Xiaonan; Ma, Jun; Xu, Gezhi; Sun, Zhongcui] Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China.
   [Zhuang, Xiaonan; Ma, Jun; Xu, Gezhi; Sun, Zhongcui] Fudan Univ, NHC Key Lab Myopia, Shanghai, Peoples R China.
C3 Fudan University; Fudan University; Fudan University; Fudan University
RP Sun, ZC (通讯作者)，Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, 83 Fenyang Rd, Shanghai 200031, Peoples R China.; Sun, ZC (通讯作者)，Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China.; Sun, ZC (通讯作者)，Fudan Univ, NHC Key Lab Myopia, Shanghai, Peoples R China.
EM zhongcui.sun@aliyun.com
FU Clinical Research Plan of SHDC [SHDC2020CR2041B]; Youth Project of the
   National Natural Science Fund [81700851]
FX This study was granted by the Clinical Research Plan of SHDC
   (SHDC2020CR2041B) and the Youth Project of the National Natural Science
   Fund (81700851).
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NR 57
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 1076-1551
EI 1528-3658
J9 MOL MED
JI Mol. Med.
PD DEC
PY 2022
VL 28
IS 1
AR 125
DI 10.1186/s10020-022-00554-w
PG 16
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 5M6GM
UT WOS:000871191000001
PM 36273174
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, L
   Zhu, YQ
   Zhou, J
   Wu, R
   Yang, N
   Bao, QB
   Xu, XR
AF Chen, Lan
   Zhu, Yanqing
   Zhou, Jie
   Wu, Rui
   Yang, Ning
   Bao, Qinbin
   Xu, Xinrong
TI Luteolin Alleviates Epithelial-Mesenchymal Transformation Induced by
   Oxidative Injury in ARPE-19 Cell via Nrf2 and AKT/GSK-3 beta Pathway
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; PREVALENCE; TRANSITION
AB Oxidative stress plays a critical role in age-related macular degeneration (AMD), and epithelial-mesenchymal transition (EMT) is involved in this process. The aim of this study was to investigate the protective effects of luteolin, a natural flavonoid with strong antioxidant activity, on H2O2-induced EMT in ARPE-19 cells. ARPE-19 cells were incubated with H2O2 at 200 mu M to induce oxidative stress-associated injury. Cell viability assay showed that luteolin at 20 and 40 mu M significantly promoted cell survival in H2O2-treated ARPE-19 cells. Luteolin also markedly protected ARPE-19 cells from H2O2-induced apoptosis. Cell migration assay presented that luteolin significantly reduced H2O2-induced migration in APRE-19 cells. EMT in ARPE-19 cells was detected by western blotting and immunofluorescence. The results showed that H2O2 significantly upregulated the expression of alpha-SMA and vimentin and downregulated the expression of ZO-1 and E-cadherin, while cells pretreated with luteolin showed a reversal. Meanwhile, the assessment of effects of luteolin on the Nrf2 pathway indicated that luteolin promoted Nrf2 nuclear translocation and upregulated the expressions of HO-1 and NQO-1. In addition, luteolin significantly increased the activities of SOD and GSH-PX and decreased intracellular levels of ROS and MDA in H2O2-treated ARPE-19 cells. Meanwhile, we observed that the expression of TGF-beta 2, p-AKT, and p-GSK-3 beta was upregulated in H2O2-treated ARPE-19 cells and downregulated in luteolin-treated cells, revealing that luteolin inhibited the activation of the AKT/GSK-3 beta pathway. However, these effects of luteolin were all annulled by transfecting ARPE-19 cells with Nrf2 siRNA. Our current data collectively indicated that inhibition of luteolin on EMT was induced by oxidative injury in ARPE-19 cell through the Nrf2 and AKT/GSK-3 beta pathway, suggesting that luteolin could be a potential drug for the treatment of dry AMD.
C1 [Chen, Lan; Zhu, Yanqing; Zhou, Jie; Wu, Rui; Yang, Ning; Bao, Qinbin; Xu, Xinrong] Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Ophthalmol, Nanjing 210029, Peoples R China.
C3 Nanjing University of Chinese Medicine
RP Xu, XR (通讯作者)，Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Ophthalmol, Nanjing 210029, Peoples R China.
EM fjmucl@126.com; 522857923@qq.com; 1960950360@qq.com; 1725485744@qq.com;
   13875869072@163.com; 1483548533@qq.com; 13851641312@qq.com
FU National Natural Science Foundation of China [82074177]; Jiangsu
   Provincial Key Research and Development Program [BE2018757]
FX AcknowledgmentsWe thank Dr. Xuewen Yang for the assistance in the
   laboratory work. The work was supported by the National Natural Science
   Foundation of China (Grant No. 82074177) and the Jiangsu Provincial Key
   Research and Development Program (Grant No. BE2018757).
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NR 42
TC 4
Z9 4
U1 2
U2 6
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD FEB 14
PY 2022
VL 2022
AR 2265725
DI 10.1155/2022/2265725
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA ZR0ZV
UT WOS:000767523200001
PM 35198094
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wu, HH
   Xu, J
   Du, XY
   Cui, JG
   Zhang, T
   Chen, Y
AF Wu, Hanhan
   Xu, Jing
   Du, Xiaoye
   Cui, Jingang
   Zhang, Teng
   Chen, Yu
TI Shihu Yeguang Pill protects against bright light-induced photoreceptor
   degeneration in part through suppressing photoreceptor apoptosis
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE Shihu Yeguang Pill; Retinopathies; Photoreceptor degeneration; Apoptosis
ID LYCIUM-BARBARUM POLYSACCHARIDES; MOUSE MODEL; RETINA
AB Photoreceptor cells are first-order retinal neurons that directly contribute to the formation of vision. Photoreceptor degeneration is the primary cause of vision impairment during the course of retinopathies such as retinitis pigmentosa and age-related macular degeneration, for which photoreceptor-targeted therapies are currently unavailable. Shihu Yeguang Pill (SYP), a classic formula in traditional Chinese medicine, has a long histology of clinical application for the treatment of a wide range of retinopathies in China. However, whether SYP is pharmacological effective at protecting photoreceptor cells is unclear. The current study thus directly addressed the pharmacological implications of SYP in photoreceptor degeneration in a mouse model characterized by bright light-induced retinal degeneration. Non-invasive full-retinal assessment was carried out to evaluate the effect of SYP on the retinal structure and function through optical coherence tomography and electroretinography, respectively. In addition, photoreceptor apoptosis, second-order neuron impairment and reactive changes in retinal microglial and muller cells, hallmark pathologies associated with photoreceptor degeneration, were assessed using immunohistochemistry and real-time PCR analyses. The results showed that SYP treatment attenuated bright light-induced impairment of the retinal structure and function. Moreover, SYP treatment suppressed photoreceptor apoptosis, alleviated the impairment of bipolar and horizontal cells and mitigated the reactive changes of muller and microglial cells in the bright light-exposed retinas. Real-time PCR analyses showed that dysregulated expression of pro-apoptotic c-fos and c-jun and anti-apoptotic bcl-2 as well as proinflammatory TNF-alpha in the bright light-exposed retinas was partially normalized as a result of SYP treatment. In summary, the work here demonstrates for the first time that SYP treatment protects the retinas from developing bright light-induced photoreceptor degeneration and associated alterations in second-order neurons and glial cells. The findings here thus provide experimental evidence to better support the mechanism-guided clinical application of SYP in the treatment of related retinal degenerative diseases.
C1 [Wu, Hanhan; Xu, Jing; Du, Xiaoye; Cui, Jingang; Zhang, Teng; Chen, Yu] Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Shanghai, Peoples R China.
   [Xu, Jing; Du, Xiaoye; Cui, Jingang; Zhang, Teng; Chen, Yu] Shanghai Acad Tradit Chinese Med, Clin Res Inst Integrat Med, Shanghai, Peoples R China.
   [Chen, Yu] Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Lab Clin & Mol Pharmacol, Shanghai, Peoples R China.
C3 Shanghai University of Traditional Chinese Medicine; Shanghai University
   of Traditional Chinese Medicine
RP Chen, Y (通讯作者)，Shanghai Univ Tradit Chinese Med, 110 Ganhe Rd, Shanghai 200437, Peoples R China.
EM chenyu@shyueyanghospital.com
FU National Natural Science Foundation of China [81673790, 81473732];
   Program of Shanghai Academic/Technology Research Leader [19XD1403700];
   Shanghai Municipal Education Commission [GZ2017064, GZ2015011]; Science
   Foundation of Yueyang Hospital, Shanghai University of Traditional
   Chinese Medicine [2019YYZ02]
FX This work was supported by the National Natural Science Foundation of
   China (81673790 and 81473732, Y.C), Program of Shanghai
   Academic/Technology Research Leader (19XD1403700, Y.C), Program of
   Eastern Scholar supported by Shanghai Municipal Education Commission
   (GZ2017064, Y.C and GZ2015011, T.Z) and Science Foundation of Yueyang
   Hospital, Shanghai University of Traditional Chinese Medicine
   (2019YYZ02, Y.C).
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NR 27
TC 2
Z9 2
U1 1
U2 13
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 JUN
PY 2020
VL 126
AR 110050
DI 10.1016/j.biopha.2020.110050
PG 13
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA LE5UI
UT WOS:000526785500064
PM 32135462
OA gold
DA 2022-11-30
ER

PT J
AU Jeon, HL
   Lee, H
   Yoon, D
   Lee, Y
   Kim, JH
   Jee, D
   Shin, JY
AF Jeon, Ha-Lim
   Lee, Hyesung
   Yoon, Dongwon
   Lee, Yeonkyung
   Kim, Jae Hui
   Jee, Donghyun
   Shin, Ju-Young
TI Burden of diabetic macular oedema in patients receiving antivascular
   endothelial growth factor therapy in South Korea: a healthcare resource
   use and cost analysis
SO BMJ OPEN
LA English
DT Article
DE diabetic retinopathy; public health; vitreoretinal
ID ANTI-VEGF TREATMENT; REAL-WORLD; ECONOMIC BURDEN; RETINOPATHY;
   DEGENERATION; COMORBIDITY
AB Objective To examine healthcare resource utilisation (HRU) and direct medical costs for patients with diabetic macular oedema (DME) treated with antivascular endothelial growth factor (anti-VEGF) in Korea by comparing with those for (1) patients with diabetes mellitus (DM) without retinopathy and (2) patients with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF. Design Retrospective cohort study. Setting The Korean National Health Insurance (NHI) database from 1 January 2014 to 31 December 2016. Participants We identified 1398 patients older than 30 years of age who received anti-VEGF treatment for DME in 2015 after excluding patients who had a diagnosis of nAMD in 2015 and any cancer in the preceding year. Main outcome measures One-year healthcare resource use and direct medical costs of patients with DME treated with anti-VEGF. Results In total, 1398 patients with DME receiving anti-VEGF, 12 813 patients with DM without retinopathy and 12 222 patients with nAMD receiving anti-VEGF were identified. Hospital admissions and outpatient visits were highest in patients with DME, while the number of licensed anti-VEGF injections in those with DME was about half that of those with nAMD (2.1 vs 3.9 per patient per year). Mean 1-year medical costs were also higher in patients with DME (US$6723) than in those with DM without retinopathy (US$2687) and nAMD (US$4980). In a multivariable analysis with matched cohorts, DME was associated with 66% higher medical costs for comorbid diseases (adjusted OR (aOR), 1.66; 95% CI 1.45 to 1.90) and 50% lower anti-VEGF injections (aOR, 0.50; 95% CI 0.46 to 0.54) compared with nAMD. Conclusions The overall HRU and economic burden for DME treated with anti-VEGF were higher than for DM without retinopathy or for nAMD treated with anti-VEGF. Meanwhile, the lower number of licensed anti-VEGF injections compared with nAMD may reflect a potential lack of ophthalmological treatment for DME supported by the NHI in Korea.
C1 [Jeon, Ha-Lim; Lee, Hyesung; Yoon, Dongwon; Shin, Ju-Young] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea.
   [Lee, Yeonkyung] Bayer Korea Ltd, Seoul, South Korea.
   [Kim, Jae Hui] Konyang Univ, Kims Eye Hosp, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Jee, Donghyun] Catholic Univ Korea, Coll Med, St Vincents Hosp, Dept Ophthalmol, Seoul, South Korea.
C3 Sungkyunkwan University (SKKU); Bayer AG; Konyang University; Konyang
   University Hospital; Catholic University of Korea
RP Shin, JY (通讯作者)，Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea.
EM shin.jy@skku.edu
RI Lee, Hyesung/GPC-5111-2022
OI Yoon, Dongwon/0000-0002-9369-0789; Kim, Jae Hui/0000-0001-8121-6353;
   Lee, Hyesung/0000-0001-6556-9984
FU Bayer Korea
FX This study was funded by Bayer Korea.
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NR 30
TC 5
Z9 5
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2020
VL 10
IS 12
AR e042484
DI 10.1136/bmjopen-2020-042484
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA PQ3ZA
UT WOS:000606484000041
PM 33376178
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Nassisi, M
   Baghdasaryan, E
   Borrelli, E
   Ip, M
   Sadda, SR
AF Nassisi, Marco
   Baghdasaryan, Elmira
   Borrelli, Enrico
   Ip, Michael
   Sadda, Srinivas R.
TI Choriocapillaris flow impairment surrounding geographic atrophy
   correlates with disease progression
SO PLOS ONE
LA English
DT Article
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; QUANTITATIVE FUNDUS AUTOFLUORESCENCE;
   AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; MORPHOMETRIC-ANALYSIS;
   ADAPTIVE OPTICS; GROWTH-RATES; DRUSEN; IMAGE; RPE
AB Purpose
   To evaluate the correlation between the choriocapillaris (CC) flow alterations around geographic atrophy (GA) and the GA yearly growth rate (yGR) in patients with dry age-related macular degeneration (AMD).
   Methods
   We retrospectively reviewed and analyzed spectral domain optical coherence tomography (SD-OCT) and SD-OCT angiography images of consecutive patients with GA acquired using the Cirrus OCT at the Doheny Eye Centers between 2015 and 2017. All eligible patients had one 6 x 6 mm OCTA scan acquired during the first visit (considered as baseline) and two fovea-centered 512 x 128 macular cubes (6 x 6 mm) acquired at baseline and after a minimum of 12 months.
   Main outcome measures
   The fundus images from the OCT volumes were used to manually delineate the GA area and calculate the yGR after square root transformation. The en-face angiogram at the level of the CC was analyzed for the percentage of flow voids (FV) outside the atrophic lesion (FVOUT) and in the para-and peri-atrophy regions (FV500 and FV1000 respectively; two concentric 500 mu m wide rings around the atrophy edge). These values, together with the difference between FV500 and FV1000 (Delta FV), were then correlated with the corresponding yGR.
   Results
   Thirty-three eyes of 23 patients were eligible for the analysis. The mean yGR was 0.23 +/- 0.17 mm/years.
   At baseline, the mean FVOUT was 41.86 +/- 2.71%, while FV500 and FV1000 were 46.4 +/- 4.17% and 42.51 +/- 2.65% respectively. The mean Delta FV was 3.89 +/- 2.6%. While in the univariable analysis, the yGR was significantly associated with FV500 and with Delta FV (both p < 0.001), in multivariable model the association remained significant only with Delta FV (p < 0.001).
   Conclusions
   Our study reports a correlation between the CC flow impairment around the atrophic lesions and their yGR in patients with GA. If replicated in future longitudinal studies, the choriocapillaris FV in the para-and peri-atrophy regions may prove to be useful parameters for evaluating the prognosis of these eyes.
C1 [Nassisi, Marco; Baghdasaryan, Elmira; Borrelli, Enrico; Ip, Michael; Sadda, Srinivas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Nassisi, Marco; Baghdasaryan, Elmira; Borrelli, Enrico; Ip, Michael; Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Borrelli, Enrico] Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalmol Clin, Chieti, Italy.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; G d'Annunzio University
   of Chieti-Pescara
RP Sadda, SR (通讯作者)，Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.; Sadda, SR (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
EM SSadda@doheny.org
RI Nassisi, Marco/P-9939-2019; Borrelli, Enrico/AAR-3693-2020
OI Nassisi, Marco/0000-0002-9354-9005; Borrelli, Enrico/0000-0003-2815-5031
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NR 43
TC 57
Z9 57
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2019
VL 14
IS 2
AR e0212563
DI 10.1371/journal.pone.0212563
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HM8DR
UT WOS:000459709100089
PM 30794627
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Chen, C
   Zhong, YM
   Wang, JSJ
   Yu, Q
   Plafker, K
   Plafker, S
   Zhang, SX
AF Chen, Chen
   Zhong, Yimin
   Wang, Joshua J.
   Yu, Qiang
   Plafker, Kendra
   Plafker, Scott
   Zhang, Sarah X.
TI Regulation of Nrf2 by X Box-Binding Protein 1 in Retinal Pigment
   Epithelium
SO FRONTIERS IN GENETICS
LA English
DT Article
DE retinal pigment epithelium; NF-E2-related factor 2; X-box binding
   protein 1; endoplasmic reticulum stress; oxidative stress; cell death
ID ENDOPLASMIC-RETICULUM STRESS; ANSAMYCIN GROUP COMPOUND; INDUCED XBP1
   ACTIVATION; OXIDATIVE STRESS; ER STRESS; NRF2-MEDIATED ANTIOXIDANT;
   MACULAR DEGENERATION; DIETARY ANTIOXIDANTS; MOLECULAR-MECHANISMS;
   GENETIC RISK
AB Normal function of the retinal pigment epithelium (RPE) is essential for maintaining the structural integrity of retinal photoreceptors and the visual process. Sustained oxidative damage of the RPE due to aging and other risk factors contributes to the development of age-related macular degeneration (AMD). The transcription factor NF-E2-related factor 2 (Nrf2) is a central regulator of cellular antioxidant and detoxification responses. Enhancing Nrf2 function protects RPE cells from oxidation-related apoptosis and cell death. Previously, we demonstrated that Nrf2 activation can be induced by endoplasmic reticulum (ER) stress; however, the mechanisms are not fully understood. In the present study, we examined the role of X box-binding protein 1 (XBP1), an ER stress-inducible transcription factor, in regulation of Nrf2 in the RPE. We found that RPE-specific XBP1 conditional knockout (cKO) mice exhibit a significant reduction in Nrf2 mRNA and protein levels, along with decreased expression of major Nrf2 target genes, in the RPE/choroid complex. Using primary RPE cells isolated from XBP1 cKO mice and human ARPE-19 cell line, we confirmed that loss of XBP1 gene or pharmacological inhibition of XBP1 splicing drastically reduces Nrf2 levels in the RPE. Conversely, overexpression of spliced XBP1 results in a modest but significant increase in cytosolic and nuclear Nrf2 protein levels without affecting the transcription of Nrf2 gene. Moreover, induction of ER stress by tunicamycin and thapsigargin markedly increases Nrf2 expression, which is abolished in cells pretreated with XBP1 splicing inhibitors 4 mu 8C and quinotrierixin. Mechanistic studies indicate that quinotrierixin reduces Nrf2 expression likely through inhibition of protein translation. Finally, we demonstrate that overexpression of Nrf2 protected RPE cells against oxidative injury but appeared to be insufficient to rescue from XBP1 deficiency-induced cell death. Taken together, our results indicate that XBP1 modulates Nrf2 activity in RPE cells and that XBP1 deficiency contributes to oxidative injury of the RPE.
C1 [Chen, Chen] Second Peoples Hosp Yunnan Prov, Dept Ophthalmol, Kunming, Yunnan, Peoples R China.
   [Chen, Chen] Yunnan Eye Inst, Key Lab Yunnan Prov Prevent & Treatment Ophthalm, Kunming, Yunnan, Peoples R China.
   [Chen, Chen; Zhong, Yimin; Wang, Joshua J.; Zhang, Sarah X.] Univ Oklahoma, Dept Med, Oklahoma City, OK 73104 USA.
   [Zhong, Yimin; Yu, Qiang] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China.
   [Wang, Joshua J.; Zhang, Sarah X.] Univ Buffalo State Univ New York, Dept Ophthalmol, Buffalo, NY 14260 USA.
   [Plafker, Kendra; Plafker, Scott] Oklahoma Med Res Fdn, Aging & Metab Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; Sun Yat Sen University; State University of New York (SUNY)
   System; State University of New York (SUNY) Buffalo; Oklahoma Medical
   Research Foundation
RP Chen, C (通讯作者)，Second Peoples Hosp Yunnan Prov, Dept Ophthalmol, Kunming, Yunnan, Peoples R China.; Chen, C (通讯作者)，Yunnan Eye Inst, Key Lab Yunnan Prov Prevent & Treatment Ophthalm, Kunming, Yunnan, Peoples R China.; Chen, C; Zhang, SX (通讯作者)，Univ Oklahoma, Dept Med, Oklahoma City, OK 73104 USA.; Zhang, SX (通讯作者)，Univ Buffalo State Univ New York, Dept Ophthalmol, Buffalo, NY 14260 USA.
EM chencheamd@aliyun.com; xzhang38@buffalo.edu
OI Chen, Chen/0000-0001-6741-7036
FU NIH/NEI [EY019949, EY025061]; Bright Focus Foundation [M2010088];
   Research to Prevent Blindness; National Natural Science Foundation of
   China (NSFC) [81660167]; NATIONAL EYE INSTITUTE [R01EY019949,
   R01EY024944, R21EY025061] Funding Source: NIH RePORTER
FX This work was supported by NIH/NEI grants EY019949 and EY025061,
   Research Grant M2010088 from American Health Assistance Foundation
   (Currently Bright Focus Foundation), and an Unrestricted Grant to the
   Department of Ophthalmology, SUNY-Buffalo, from Research to Prevent
   Blindness. This work was also supported by National Natural Science
   Foundation of China (NSFC, Grant No. 81660167).
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NR 55
TC 9
Z9 9
U1 0
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-8021
J9 FRONT GENET
JI Front. Genet.
PD DEC 20
PY 2018
VL 9
AR 658
DI 10.3389/fgene.2018.00658
PG 14
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA HF1DL
UT WOS:000453905700002
PM 30619478
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ishihara, T
   Kaidzu, S
   Kimura, H
   Koyama, Y
   Matsuoka, Y
   Ohira, A
AF Ishihara, Tomoe
   Kaidzu, Sachiko
   Kimura, Hideto
   Koyama, Yasurou
   Matsuoka, Yotaro
   Ohira, Akihiro
TI Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed
   Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against
   Light-Induced Oxidative Damage in Rat Retina
SO NUTRIENTS
LA English
DT Article
DE retina protection; Japanese horse chestnut; Aesculus turbinata BLUME;
   polyphenolic compound; antioxidant; proanthocyanidin
ID N-TERT-BUTYLNITRONE; MACULAR DEGENERATION; AGE; APOPTOSIS; STRESS;
   CELLS; MODEL
AB Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.
C1 [Ishihara, Tomoe; Kaidzu, Sachiko; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro] Shimane Univ, Sch Med, Dept Ophthalmol, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan.
   [Ishihara, Tomoe; Kimura, Hideto] Kotobuki Seika Co Ltd, Dept Res & Dev, 2028 Hatagasaki, Yonago, Tottori 6830845, Japan.
C3 Shimane University
RP Ohira, A (通讯作者)，Shimane Univ, Sch Med, Dept Ophthalmol, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan.
EM t-ishihara@kozuchi-net.jp; kecha@med.shimane-u.ac.jp;
   h-kimura@kozuchi-net.jp; ykoyama@med.shimane-u.ac.jp;
   ymatsu@med.shimane-u.ac.jp; aohira@med.shimane-u.ac.jp
RI ohira, akihiro/G-8352-2017
OI ohira, akihiro/0000-0002-1307-5592; Kimura, Hideto/0000-0003-1483-3401
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NR 31
TC 10
Z9 10
U1 0
U2 8
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2072-6643
J9 NUTRIENTS
JI Nutrients
PD MAY
PY 2018
VL 10
IS 5
AR 593
DI 10.3390/nu10050593
PG 14
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA GJ3LI
UT WOS:000435196000067
PM 29748512
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Vizzarri, F
   Palazzo, M
   Bartollino, S
   Casamassima, D
   Parolini, B
   Troiano, P
   Caruso, C
   Costagliola, C
AF Vizzarri, F.
   Palazzo, M.
   Bartollino, S.
   Casamassima, D.
   Parolini, B.
   Troiano, P.
   Caruso, C.
   Costagliola, C.
TI Effects of an Antioxidant Protective Topical Formulation on Eye Exposed
   to Ultraviolet-Irradiation: a Study in Rabbit Animal Model
SO PHYSIOLOGICAL RESEARCH
LA English
DT Article
DE UV exposure; Oxidative stress; Antioxidant eye-drops
ID RISK-FACTOR; GLUTATHIONE-PEROXIDASE; HYDROGEN-PEROXIDE; LENS; RADIATION;
   DAMAGE; ACID; FLUORESCENCE; EPITHELIUM; CORNEA
AB Ultraviolet-radiation exerts a well-known role in the development of various ocular diseases and may contribute to the progress of age-related macular degeneration. Therefore, the use of compounds able to protect the eyes from UV-induced cellular damage is challenging. The aim of this study has been to test the protective effects of an antioxidant topical formulation against UV-induced damage in rabbit eyes. Twelve male rabbits were used. Animals were divided into 4 groups of 3 animals each. Control group (CG) did not receive any irradiation and/or eye drop. The other three experimental groups were treated as follows: the first group received only UVR irradiation for 30 min, without eye drop supplementation (Irradiation group, IG), the second (G30) and the third (G60) groups received UV irradiation for 30' and 60', respectively, and eye drop supplementation (riboflavin, d-a-tocopheryl polyethylene glycol, proline, glycine, lysine and leucine solution) every 15 min for three hours. In the IG group a significant increase of oxidized glutathione (GSSG) and hydrogen peroxide (H2O2) was recorded in the aqueous humor, whereas ascorbic acid levels were significantly lower when compared to control eyes. In the groups exposed to UVR rays for 30 min, and treated with the topical antioxidant formulation, the GSSG, H2O2 and ascorbic acid levels were similar to those recorded in controls, whereas in the G60 group the three markers significantly differ from control group. In the lens, a significant decrease of alpha tocopherol and total antioxidant capacity (TAC) was recorded in IG-animals as compared to control group, whereas malondialdehyde (MDA) levels were significantly higher in UV-induced eye than in control eyes. In the G30 groups the alpha tocopherol, MDA and TAC levels do not significantly differ from those recorded in controls, whereas in the G60 group these three markers significantly differ from control group. Present findings demonstrate that topical treatment with the antioxidant formulation used herein protects ocular structures from oxidative stress induced by UV exposure in in vivo animal model.
C1 [Vizzarri, F.; Palazzo, M.; Casamassima, D.] Univ Molise, Dept Agr Environm & Food Sci, Campobasso, Italy.
   [Bartollino, S.; Costagliola, C.] Univ Molise, Dept Med & Hlth Sci V Tiberio, Campobasso, Italy.
   [Parolini, B.] St Anna Inst, Dept Ophthalmol, Brescia, Italy.
   [Troiano, P.] Fatebenefratelli Sacred Family Hosp, Dept Ophthalmol, Erba, Italy.
   [Caruso, C.] Pellegrini Hosp, Corneal Transplant Ctr, Naples, Italy.
C3 University of Molise; University of Molise
RP Vizzarri, F (通讯作者)，Univ Molise, Dept Agr Environm & Food Sci, Campobasso, Italy.
EM francesco.vizzarri@unimol.it
RI Bartollino, Silvia/M-6271-2019; Vizzarri, Francesco/ABE-5109-2020;
   Parolini, Barbara/AAH-9913-2019
OI Bartollino, Silvia/0000-0001-7105-6392; Vizzarri,
   Francesco/0000-0003-1316-7937; Parolini, Barbara/0000-0002-7838-6834;
   Palazzo, Marisa/0000-0002-9116-9420
FU Servimed Industrial s.p.a. (Rome, Italy)
FX The investigation was conducted with the collaboration and contribution
   of all co-authors. Authors would like to thank Servimed Industrial
   s.p.a. (Rome, Italy) in funding the present work.
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NR 38
TC 8
Z9 8
U1 0
U2 1
PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY
PI PRAGUE 4
PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC
SN 0862-8408
EI 1802-9973
J9 PHYSIOL RES
JI Physiol. Res.
PY 2018
VL 67
IS 3
BP 457
EP 464
DI 10.33549/physiolres.933759
PG 8
WC Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Physiology
GA GN8ZA
UT WOS:000439466000010
PM 29527920
OA Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Danyliv, A
   Glanville, J
   McCool, R
   Ferreira, A
   Skelly, A
   Jacob, RP
AF Danyliv, Andriy
   Glanville, Julie
   McCool, Rachael
   Ferreira, Alberto
   Skelly, Adrian
   Jacob, Ruth Pulikottil
TI The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in
   nAMD: Systematic Review and Network Meta-Analysis
SO ADVANCES IN THERAPY
LA English
DT Review
DE Aflibercept; Neovascular age-related macular degeneration; Network
   meta-analysis; Ophthalmology; Ranibizumab Systematic; review; Treat and
   extend; Vascular endothelial growth factor inhibitors
ID MIXED TREATMENT COMPARISONS; MACULAR DEGENERATION; VISUAL IMPAIRMENT;
   UNITED-STATES; PREVALENCE; THERAPY; UPDATE; UK
AB Introduction: Neovascular age-related macular degeneration (nAMD) is a chronic eye condition that causes severe deterioration of vision and ultimately blindness. Two vascular endothelial growth factor inhibitors are approved for nAMD treatment in Europe: ranibizumab and aflibercept. The European license for ranibizumab was updated with an individualized ``treat and extend'' (T& E) regimen, which involves more proactive treatment based on changes in best corrected visual acuity (BCVA) and/or anatomical outcomes. The aim of this publication is to compare the efficacy of the ranibizumab T& E regimen with other approved dosing regimens for nAMD on the basis of outcomes identified from a systematic review and subsequent NMA.
   Methods: Following a systematic search of publications, to identify relevant studies, a repeated-measures network meta-analysis (NMA) was performed to estimate the relative effectiveness of ranibizumab T& E versus approved dosing regimens of ranibizumab and aflibercept. The analysis focused on licensed treatment regimens for nAMD. We examined mean change from baseline in BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.
   Results: The systematic literature review identified 22,949 records, of which 23 studies were included in the NMA. At 12 months, the ranibizumab T& E dosing regimen vs ranibizumab pro re nata (PRN) was associated with small differences in change in BCVA, between 1.86 letter gain at 12 months and 2.35 letter gain at 24 months. A similar difference was observed in the aflibercept dosing regimen versus ranibizumab T& E; 1.94 letter gain at 12 months and 3.31 letter gain at 24 months. All doses of ranibizumab and aflibercept showed similar effectiveness, and the differences between treatment options were not significant.
   Conclusion: This study used novel repeated-measures NMA to synthesize efficacy results when treatment effects were reported at multiple follow-up times. This repeated-measures NMA suggests that treating patients with the ranibizumab T& E regimen yields similar effectiveness compared to other approved ranibizumab and aflibercept dosing regimens for nAMD treatment.
C1 [Danyliv, Andriy] Novartis Ireland Ltd, Dublin, Ireland.
   [Glanville, Julie; McCool, Rachael] Univ York, York Hlth Econ Consortium, York, N Yorkshire, England.
   [Ferreira, Alberto; Skelly, Adrian] Novartis Pharma AG, Basel, Switzerland.
   [Jacob, Ruth Pulikottil] Novartis Pharmaceut UK Ltd, Camberley, Surrey, England.
C3 Novartis; University of York - UK; Novartis; Novartis
RP Danyliv, A (通讯作者)，Novartis Ireland Ltd, Dublin, Ireland.
EM andrii.danyliv@novartis.com
OI Pulikottil-Jacob, Ruth/0000-0003-0630-960X
FU Novartis Pharmaceuticals UK Ltd, Surrey, UK
FX Novartis Pharmaceuticals UK Ltd, Surrey, UK.
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NR 26
TC 18
Z9 19
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0741-238X
EI 1865-8652
J9 ADV THER
JI Adv. Ther.
PD MAR
PY 2017
VL 34
IS 3
BP 611
EP 619
DI 10.1007/s12325-017-0484-0
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA EQ3NB
UT WOS:000397978600003
PM 28188433
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Tahir, HJ
   Rodrigo-Diaz, E
   Parry, NRA
   Kelly, JMF
   Carden, D
   Murray, IJ
AF Tahir, Humza J.
   Rodrigo-Diaz, Elena
   Parry, Neil R. A.
   Kelly, Jeremiah M. F.
   Carden, David
   Murray, Ian J.
TI Slowed dark adaptation in older eyes; effect of location
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal sensitivity; Psychophysics;
   Scotopic function
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; PHOTORECEPTOR TOPOGRAPHY;
   BRUCHS-MEMBRANE; ROD
AB Purpose: The rate of rod sensitivity recovery following a photobleach is a basic measure of the integrity of the outer retina. Rods are selectively impaired in aging and many disorders of the retina, notably Age Related Macular Degeneration (AMD). It is not known for certain whether the age-related deficit is a pan retinal effect or if there are localised regions of impaired rod function. To address this important issue a dual arc stimulus was developed that samples sensitivity recovery in two retinal locations.
   Methods: Arc-shaped stimuli were presented on a black CRT screen at two locations, in the inferior visual field. Following a bleach, which was localised to the stimuli, recovery of sensitivity was measured using a modified method of adjustment technique. Neutral density filters were used to extend the luminance range of the CRT. Sensitivity recovery functions were fitted by non-linear regression to a seven parameter model.
   Results: Pairs of sensitivity recovery functions were generated from the stimuli. The cone phases of these functions were identical. The slopes of the S2 sections of the curves were steeper for the outer stimuli for both young (p < 0.001) and older (p = 0.003) observers. The difference between the two was the same for the two groups. The a point was reached slightly earlier for the young observers and with the outer stimulus but neither of these effects reached statistical significance. The p point occurred earlier for the outer stimuli and this effect was statistically significant only for the older group.
   Conclusions: The method places minimal demands on observers. The fact that rod sensitivity recovery is slowed in the older normal eye to the same extent in the two locations suggests that this deficit may be uniform across the retina. As there are localised losses in scotopic function in AMD, the technique is ideally suited to distinguishing impaired recovery dynamics due to normal ageing from those caused by disease. (C) 2017 Elsevier Ltd. All rights reserved.
C1 [Tahir, Humza J.; Rodrigo-Diaz, Elena; Kelly, Jeremiah M. F.; Carden, David; Murray, Ian J.] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England.
   [Parry, Neil R. A.] Univ Manchester, Ctr Hearing & Vision Res, Manchester M13 9PL, Lancs, England.
   [Parry, Neil R. A.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Royal Eye Hosp, Vision Sci Ctr, Manchester, Lancs, England.
C3 University of Manchester; University of Manchester; Manchester Royal Eye
   Hospital; University of Manchester
RP Tahir, HJ (通讯作者)，Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England.
EM humza.tahir@manchester.ac.uk
OI Rodrigo Diaz de Cerio, Elena/0000-0002-9643-8634
FU Newtricious RD B.V.; NIHR [II-LB-0712-20001]; National Institute for
   Health Research [II-LB-0712-20001] Funding Source: researchfish
FX NRAP's participation was facilitated by the Manchester Biomedical
   Research Centre and the Greater Manchester Comprehensive Local Research
   Network. HJT and ERD were supported by Newtricious R&D B.V. MJK was
   supported by NIHR grant reference II-LB-0712-20001.
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NR 27
TC 10
Z9 10
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2017
VL 155
BP 47
EP 53
DI 10.1016/j.exer.2016.11.016
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EQ4BF
UT WOS:000398017000005
PM 27890475
DA 2022-11-30
ER

PT J
AU Guo, JH
   Linetsky, M
   Yu, AO
   Zhang, L
   Howell, SJ
   Folkwein, HJ
   Wang, H
   Salomon, RG
AF Guo, Junhong
   Linetsky, Mikhail
   Yu, Annabelle O.
   Zhang, Liang
   Howell, Scott J.
   Folkwein, Heather J.
   Wang, Hua
   Salomon, Robert G.
TI 4-Hydroxy-7-oxo-5-heptenoic Acid Lactone Induces Angiogenesis through
   Several Different Molecular Pathways
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; OXIDATIVE STRESS; REACTIVE OXYGEN; IN-VITRO; ETHANOLAMINE
   PHOSPHOLIPIDS; OXIDIZED PHOSPHOLIPIDS; ARPE-19 CELLS; UP-REGULATION
AB Oxidative stress and angiogenesis have been implicated not only in normal phenomena such as tissue healing and remodeling but also in many pathological processes. However, the relationships between oxidative stress and angiogenesis still remain unclear, although oxidative stress has been convincingly demonstrated to influence the progression of angiogenesis under physiological and pathological conditions. The retina is particularly susceptible to oxidative stress because of its intensive oxygenation and high abundance of polyunsaturated fatty acyls. In particular, it has high levels of docosahexanoates, whose oxidative fragmentation produces 4-hydroxy-7-oxo-5-heptenoic acid lactone (HOHA-lactone). Previously, we found that HOHA-lactone is a major precursor of 2-(omega-carboxyethyl)pyrrole (CEP) derivatives, which are tightly linked to age-related macular degeneration (AMD). CEPs promote the pathological angiogenesis of late-stage AMD. We now report additional mechanisms by which HOHA-lactone promotes angiogenesis. Using cultured ARPE-19 cells, we observed that HOHA-lactone induces secretion of vascular endothelial growth factor (VEGF), which is correlated to increases in reactive oxygen species and decreases in intracellular glutathione (GSH). Wound healing and tube formation assays provided, for the first time, in vitro evidence that HOHA-lactone induces the release of VEGF from ARPE-19 cells, which promotes angiogenesis by human umbilical vein endothelial cells (HUVEC) in culture. Thus, HOHA-lactone can stimulate vascular growth through a VEGF-dependent pathway. In addition, results from MTT and wound healing assays as well as tube formation experiments showed that GSH-conjugated metabolites of HOHA-lactone stimulate HUVEC proliferation and promote angiogenesis in vitro. Previous studies demonstrated that HOHA-lactone, through its CEP derivatives, promotes angiogenesis in a novel Toll-like receptor 2-dependent manner that is independent of the VEGF receptor or VEGF expression. The new studies show that HOHA-lactone also participates in other angiogenic signaling pathways that include promoting the secretion of VEGF from retinal pigmented epithelial cells.
C1 [Guo, Junhong; Linetsky, Mikhail; Folkwein, Heather J.; Wang, Hua; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Yu, Annabelle O.] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA.
   [Zhang, Liang] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
   [Howell, Scott J.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; Case Western Reserve University
RP Salomon, RG (通讯作者)，Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
EM rgs@case.edu
RI Guo, Junhong/O-6316-2017
OI Guo, Junhong/0000-0003-0005-4837; Folkwein, Heather/0000-0002-2951-5863;
   Salomon, Robert/0000-0001-9456-3557
FU NIH [R01-EY016813]; NATIONAL EYE INSTITUTE [R01EY016813] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported by NIH Grant R01-EY016813 to R.G.S.
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NR 43
TC 9
Z9 9
U1 0
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD DEC
PY 2016
VL 29
IS 12
BP 2125
EP 2135
DI 10.1021/acs.chemrestox.6b00233
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA EF4KR
UT WOS:000390294700017
PM 27806561
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Domalpally, A
   Danis, R
   Agorn, E
   Blodi, B
   Clemons, T
   Chew, E
AF Domalpally, Amitha
   Danis, Ronald
   Agorn, Elvira
   Blodi, Barbara
   Clemons, Traci
   Chew, Emily
CA Age-Related Eye Dis Study Res Grp
TI Evaluation of Geographic Atrophy from Color Photographs and Fundus
   Autofluorescence Images Age-Related Eye Disease Study 2 Report Number 11
SO OPHTHALMOLOGY
LA English
DT Article
ID VISUAL-ACUITY LOSS; MACULAR DEGENERATION; NATURAL-HISTORY; PROGRESSION;
   ENLARGEMENT; PATTERNS; RATES
AB Purpose: To compare measurements of area of geographic atrophy (GA) and change in GA area from color photographs and fundus autofluorescence (FAF) images.
   Design: The Age-Related Eye Disease Study 2 (AREDS2) was a prospective multicenter randomized clinical trial evaluating progression of dry age-related macular degeneration (AMD) using color photographs at annual visits over a 5-year study period. The FAF images were acquired in a subset of participants who joined the FAF ancillary study at any of the annual visits over the study period.
   Participants: The AREDS2 FAF ancillary study included 8070 corresponding color and FAF visits of 2202 participants with variable follow-up.
   Methods: Corresponding color and FAF images were independently evaluated at a central reading center for GA area measurement, lesion growth, and involvement of the macula center.
   Main Outcome Measures: Presence, area, growth rate of GA, and involvement of center of macula from color and FAF images.
   Results: Hypoautofluorescence was visible in 2048 visits (25.4%). Agreement for the presence of GA between the 2 modalities had a kappa of 0.79, with 23% of visits with hypoautofluorescence not presenting with GA on color photographs. Percentage agreement for GA presence ranged from 43% at baseline to 81% at year 5 with improving agreement over time. The mean difference in GA area between the 2 modalities was 0.5 mm(2), with larger areas on FAF. Growth rate of GA was 1.45 mm(2) from color photographs and 1.43 mm2 from FAF images. The center of the macula was involved in 51% of color photographs and 56% with FAF images.
   Conclusions: Geographic atrophy may be detected earlier by the use of FAF images, but over the course of the study, the 2 modalities become comparable. Progression of GA area is comparable between color photographs and FAF images, but evaluating involvement of the center of the macula may differ, probably because of macular pigmentation blocking autofluorescence. (C) 2016 by the American Academy of Ophthalmology.
C1 [Domalpally, Amitha; Danis, Ronald; Blodi, Barbara] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA.
   [Clemons, Traci] EMMES Corp, Rockville, MD USA.
   [Agorn, Elvira; Chew, Emily] NEI, Bethesda, MD 20892 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Emmes
   Corporation; National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI)
RP Domalpally, A (通讯作者)，Univ Wisconsin, Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, 2828 Marshall Court,Suite 200, Madison, WI 53705 USA.
EM adomalpally@rc.ophth.wisc.edu
RI SanGiovanni, John Paul/AAU-3895-2020
OI Domalpally, Amitha/0000-0002-8145-9619
FU National Eye Institute [HHS-N-260-2005-00007-C]; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [ZIAEY000489] Funding Source: NIH
   RePORTER
FX The author(s) have made the following disclosure(s): A.D., R.D., E.A.,
   B.B., E.C. and T.C.: Grant National Eye Institute grant no.
   HHS-N-260-2005-00007-C (TEC). Supported in part by an unrestricted grant
   from Research to Prevent Blindness to the Department of Ophthalmology
   and Visual Sciences, University of Wisconsin-Madison (A.D., R.D., and
   B.B.).
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NR 35
TC 30
Z9 31
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2016
VL 123
IS 11
BP 2401
EP 2407
DI 10.1016/j.ophtha.2016.06.025
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EE3QK
UT WOS:000389509500025
PM 27448832
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ghosh, W
   Wickstead, R
   Claxton, L
   Kusel, J
   Taylor, M
   Fleetwood, K
   Pulikottil-Jacob, R
AF Ghosh, Wrik
   Wickstead, Rose
   Claxton, Lindsay
   Kusel, Jeanette
   Taylor, Matthew
   Fleetwood, Kelly
   Pulikottil-Jacob, Ruth
TI The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus
   Aflibercept in the UK
SO ADVANCES IN THERAPY
LA English
DT Article
DE Age-related macular degeneration; Aflibercept; Cost-effectiveness;
   Ophthalmology; Ranibizumab; Treat and extend
ID MACULAR DEGENERATION; VISUAL-ACUITY; AGE; OUTCOMES; THERAPY; TRIAL
AB Wet age-related macular degeneration (AMD) is a chronic eye condition that causes severe deterioration of vision and even blindness. Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept. Patients with wet AMD require frequent and long-term monitoring for treatment to be effective, contributing to a substantial resource burden at wet AMD centers. The European license for ranibizumab was recently updated with an individualized 'treat and extend' (T&E) regimen, comprising a structured monitoring and treatment protocol. This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting.
   An individual patient-level simulation model was developed utilizing treatment effects from a network meta-analysis of randomized controlled trials. The model was conducted from a UK National Health Service (NHS) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model. Additional scenario analyses were conducted to assess the impact of changes to the model inputs.
   Ranibizumab T&E was found to be more effective and less costly than aflibercept, providing, on average, an additional 1.058 quality-adjusted life years (QALYs) and a cost-saving of A 19,604 pound over a lifetime horizon. At list price, ranibizumab T&E was found to be cost-effective versus aflibercept in 100% of simulations at a willingness-to-pay threshold of A 20,000 pound per QALY. The robustness of the results was tested in several scenario analyses; ranibizumab T&E was found to be more effective, and less costly, than aflibercept in the vast majority of cases.
   This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS resources than aflibercept, and could, therefore, be considered as a first-line regimen for patients with wet AMD in the UK.
   Novartis Pharmaceuticals UK Limited.
C1 [Ghosh, Wrik; Wickstead, Rose; Kusel, Jeanette] Costello Med Consulting Ltd, Cambridge, England.
   [Claxton, Lindsay; Taylor, Matthew] Univ York, York Hlth Econ Consortium, York, N Yorkshire, England.
   [Fleetwood, Kelly] Quantics, Edinburgh, Midlothian, Scotland.
   [Pulikottil-Jacob, Ruth] Novartis Pharmaceut UK Ltd, Camberley, Surrey, England.
C3 Costello Medical Consulting; University of York - UK; Novartis
RP Pulikottil-Jacob, R (通讯作者)，Novartis Pharmaceut UK Ltd, Camberley, Surrey, England.
EM Ruth.jacob@novartis.com
OI Pulikottil-Jacob, Ruth/0000-0003-0630-960X
FU Novartis Pharmaceuticals UK Limited
FX Novartis Pharmaceuticals UK Limited.
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NR 39
TC 10
Z9 13
U1 0
U2 4
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 SEP
PY 2016
VL 33
IS 9
BP 1660
EP 1676
DI 10.1007/s12325-016-0367-9
PG 17
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DX6XX
UT WOS:000384530500015
PM 27457470
DA 2022-11-30
ER

PT J
AU Wang, H
   Linetsky, M
   Guo, JH
   Choi, J
   Hong, L
   Chamberlain, AS
   Howell, SJ
   Howes, AM
   Salomon, RG
AF Wang, Hua
   Linetsky, Mikhail
   Guo, Junhong
   Choi, Jaewoo
   Hong, Li
   Chamberlain, Amanda S.
   Howell, Scott J.
   Howes, Andrew M.
   Salomon, Robert G.
TI 4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone is a Biologically Active
   Precursor for the Generation of 2-(omega-Carboxyethyl)pyrrole (CEP)
   Derivatives of Proteins and Ethanolamine Phospholipids
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CELLS
AB 2-(omega-Carboxyethyl)pyrrole (CEP) derivatives of proteins were previously shown to have significant pathological and physiological relevance to age-related macular degeneration, cancer and wound healing. Previously, we showed that CEPs are generated in the reaction of omega-amino groups of protein lysyl residues With 1-palmityl-2-(4-hydroxy-7- oxo-5-heptenoyl)-sn-glycero-3-phosphatidylcholine (HOHA-PC), a lipid oxidation product uniquely generated by oxidative truncation of docosahexanenate-containing phosphatidylcholine. More recently, we found that HOHA-PC rapidly releases HOHA-lactone and 2-lyso-PC (t(1/2) = 30 min at 37 degrees C) by nonenzymatic transesterification/deacylation. Now we report that HOHA-lactone reacts with Ac-Gly-Lys-OMe or human serum albumin to form CEP derivatives in vitro. Incubation of human red blood cell ghosts with HOHA-lactone generates CEP derivatives of membrane proteins and ethanolamine phospholipids. Quantitative analysis of the products generated in the reaction HOHA-PC with Ac-Gly-Lys-OMe showed that HOHA-PC mainly forms CEP-dipeptide that is not esterified to 2-lysophosphalidycholine. Thus, the HOHA-lactone pathway predominates over the direct reaction of HOHA-PC to produce the CEP-PC-dipeptide derivative. Myleoperoxidase/H2O2/NO2- promoted in vitro oxidation of either 1-palmity1-2docosahexaneoyl-sn-glycero-3-phosphatidylcholine (DHA-PC) or docosahexaenoic acid (DHA) generates HOHA-lactone in yields of 0.45% and 0.78%, respectively. Lipid oxidation in human red blood cell ghosts also releases HOHA-lactone. Oxidative injury of ARPE-19 human retinal pigmented epithelial cells by exposure to H2O2 generated CEP derivatives. Treatment of ARPE-19 cells with HOHA-lactone generated CEP-modified proteins. Low (submicromolar), but not high, concentrations of HOHA-lactone promote increased vascular endothelial growth factor (VEGF) secretion by ARPE-19 cells. Therefore, HOHA-lactone not only serves as an intermediate for the generation of CEPs but also is a biologically active oxidative truncation product from docosahexaenoate lipids.
C1 [Wang, Hua; Linetsky, Mikhail; Guo, Junhong; Choi, Jaewoo; Hong, Li; Chamberlain, Amanda S.; Howell, Scott J.; Howes, Andrew M.; Salomon, Robert G.] 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@case.edu
RI Wang, Hua/N-9400-2015; Guo, Junhong/O-6316-2017
OI Wang, Hua/0000-0002-2109-5497; Guo, Junhong/0000-0003-0005-4837; Howes,
   Andrew/0000-0003-2365-3592; Salomon, Robert/0000-0001-9456-3557
FU NIH [EY011373, EY016813, GM021249]; NATIONAL EYE INSTITUTE [P30EY011373,
   R01EY016813] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL
   MEDICAL SCIENCES [R01GM021249] Funding Source: NIH RePORTER
FX This work was supported by NIH Grants EY011373, EY016813, and GM021249.
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NR 22
TC 15
Z9 15
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD MAY
PY 2015
VL 28
IS 5
BP 967
EP 977
DI 10.1021/acs.chemrestox.5b00001
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA CI6XM
UT WOS:000354907500014
PM 25793308
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lawley, E
   Baranov, P
   Young, M
AF Lawley, Elodie
   Baranov, Petr
   Young, Michael
TI Hybrid vitronectin-mimicking polycaprolactone scaffolds for human
   retinal progenitor cell differentiation and transplantation
SO JOURNAL OF BIOMATERIALS APPLICATIONS
LA English
DT Article
DE Tissue engineering; polycaprolactone; vitronectin; retinal progenitor
   cells; photoreceptors
ID SELF-RENEWAL; PROLIFERATION; DEGRADATION; SURVIVAL; PROMOTE; SURFACE;
   GROWTH; REPAIR; FILM
AB Many advances have been made in an attempt to treat retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. The irreversible loss of photoreceptors is common to both, and currently no restorative clinical treatment exists. It has been shown that retinal progenitor and photoreceptor precursor cell transplantation can rescue the retinal structure and function. Importantly, retinal progenitor cells can be collected from the developing neural retina with further expansion and additional modification invitro, and the delivery into the degenerative host can be performed as a single-cell suspension injection or as a complex graft transplantation. Previously, we have described several polymer scaffolds for culture and transplantation of retinal progenitor cells of both mouse and human origin. This tissue engineering strategy increases donor cell survival and integration. We have also shown that biodegradable poly(-caprolactone) induces mature photoreceptor differentiation from human retinal progenitor cells. However, poor adhesive properties limit its use, and therefore it requires additional surface modification. The aim of this work was to study vitronectin-mimicking oligopeptides (Synthemax II-SC) poly(-caprolactone) films and their effects on human retinal progenitor cell adhesion, proliferation, and differentiation. Here, we show that the incorporation of vitronectin-mimicking oligopeptide into poly(-caprolactone) leads to dose-dependent increases in cell adhesion; the optimum dose identified as 30 mu g/ml. Inhibition of human retinal progenitor cells proliferation was seen on poly(-caprolactone) and was maintained with the hybrid scaffold. This has been shown to be beneficial for driving cell differentiation. Additionally, we observed equal expression of Nrl, rhodopsin, recoverin, and rod outer membrane 1 after differentiation on the hybrid scaffold as compared to the standard fibronectin coating of poly(-caprolactone). After transplantation into rd1 retina degenerative mice, human retinal progenitor cells were able to migrate to the outer nuclear layer and survive for three weeks. We conclude that Synthemax II-SC can be incorporated into poly(-caprolactone) to create a hybrid chemically defined scaffold for clinical application.
C1 [Lawley, Elodie; Baranov, Petr; Young, Michael] Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute
RP Baranov, P (通讯作者)，Harvard Univ, Massachusetts Eye & Ear, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM petr_baranov@meei.harvard.edu
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NR 31
TC 26
Z9 27
U1 0
U2 18
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0885-3282
EI 1530-8022
J9 J BIOMATER APPL
JI J. Biomater. Appl.
PD JAN
PY 2015
VL 29
IS 6
BP 894
EP 902
DI 10.1177/0885328214547751
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA AX2II
UT WOS:000346766400009
PM 25145988
DA 2022-11-30
ER

PT J
AU Hogg, RE
   Dimitrov, PN
   Dirani, M
   Varsamidis, M
   Chamberlain, MD
   Baird, PN
   Guymer, RH
   Vingrys, AJ
AF Hogg, Ruth E.
   Dimitrov, Peter N.
   Dirani, Mohamed
   Varsamidis, Mary
   Chamberlain, Matthew D.
   Baird, Paul N.
   Guymer, Robyn H.
   Vingrys, Algis J.
TI Gene-Environment Interactions and Aging Visual Function A Classical Twin
   Study
SO OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; MACULAR DEGENERATION; DARK-ADAPTATION;
   COLOR-VISION; RISK-FACTORS; AGE; CLASSIFICATION; ACCUMULATION;
   SENSITIVITY; PERFORMANCE
AB Objective: To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging.
   Design: A classical twin study.
   Participants. Forty-two twin pairs (21 monozygotic and 21 dizygotic; age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry.
   Methods: Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap resampling was used to return robust intrapair correlations for each parameter.
   Main Outcome Measures: Psychophysical thresholds and adaptational time constants.
   Results: The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83; P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime.
   Conclusions: Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention.
   Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:263-269 (C) 2009 by the American Academy of Ophthalmology.
C1 [Hogg, Ruth E.; Vingrys, Algis J.] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3052, Australia.
   [Dimitrov, Peter N.; Dirani, Mohamed; Varsamidis, Mary; Chamberlain, Matthew D.; Baird, Paul N.; Guymer, Robyn H.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
   [Dirani, Mohamed; Baird, Paul N.] Vis Cooperat Res Ctr, Sydney, NSW, Australia.
C3 University of Melbourne; Centre for Eye Research Australia; Royal
   Victorian Eye & Ear Hospital; University of Melbourne; Visa Inc
RP Hogg, RE (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM rh.guymer@unimelb.edu.au
RI Hogg, Ruth E./ABC-9602-2020
OI Hogg, Ruth E./0000-0001-9413-2669; Vingrys, Algis/0000-0001-5920-4604;
   Guymer, Robyn/0000-0002-9441-4356; Baird, Paul/0000-0002-1305-3502
FU NHMRC [1350224]
FX Partially funded by NHMRC grant (1350224 RHG/AJV).
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NR 56
TC 10
Z9 10
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2009
VL 116
IS 2
BP 263
EP 269
DI 10.1016/j.ophtha.2008.09.002
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 403QW
UT WOS:000263098100015
PM 19019448
DA 2022-11-30
ER

PT J
AU Jin, XH
   Ohgami, K
   Shiratori, K
   Suzuki, Y
   Hirano, T
   Koyama, Y
   Yoshida, K
   Ilieva, I
   Iseki, K
   Ohno, S
AF Jin, Xue-Hai
   Ohgami, Kazubiro
   Shiratori, Kenji
   Suzuki, Yukari
   Hirano, Takeshi
   Koyama, Yoshikazu
   Yoshida, Kazubiko
   Ilieva, Iliyana
   Iseki, Ken
   Ohno, Shigeaki
TI Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; KAPPA-B; EXPRESSION; CYCLOOXYGENASE-2;
   INTERLEUKIN-6; INFLAMMATION; CAROTENOIDS; MECHANISMS; ZEAXANTHIN
AB PURPOSE. Lutein deposits in the macula and lens of human eyes with high concentration and is well known as an eye-protective nutrient for its beneficial effects on eye disease such as age-related macular degeneration and cataract. The purpose of the present study was to investigate the effects of lutein on endotoxin-induced uveitis (EIU) in rats.
   METHODS. EIU was induced in male Lewis rats by subcutaneous injection of 200 mu g lipopolysaccharide. Lutein or dexamethasone was administered intravenously at 30 minutes before, at the same time as, and at 30 minutes after LPS treatment. The aqueous humor was collected at 24 hours after LPS injection, the number of infiltrating cells, the protein concentration, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, prostaglandin (PG)-E2, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-2 in the aqueous humor were determined. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappa B was performed to evaluate the effect of lutein on NF-kappa B activation in the iris-ciliary body (ICB) of rats. A mouse macrophage cell line (RAW264.7 cells) was stimulated with LPS, in the presence or absence of lutein. Expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and degradation of inhibitor kappa B (I kappa B) were analyzed by Western blot analysis.
   RESULTS. Lutein suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg lutein was as strong as that of I mg/kg dexamethasone. Treatment with lutein reduced the concentrations of NO, TNF-alpha, IL-6, PGE2, MCP-1, and MIP-2 in aqueous humor. Lutein also suppressed the activation of NF-kappa B in the ICB as well as iNOS and COX-2 expression and I kappa B degradation in RAW cells. C
   CONCLUSIONS. These findings indicate that lutein has anti-inflammatory effects on EIU by inhibiting the NF-kappa B dependent signaling pathway and the subsequent production of proinflammatory mediators.
C1 Hokkaido Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kita Ku, Sapporo, Hokkaido 0608638, Japan.
   Hokkaido Univ, Grad Sch Med, Dept Biochem, Kita Ku, Sapporo, Hokkaido 0608638, Japan.
   Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Clin Pharmaceut & Therapeut, Sapporo, Hokkaido 060, Japan.
C3 Hokkaido University; Hokkaido University; Hokkaido University
RP Ohgami, K (通讯作者)，Hokkaido Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM kohgami@med.hokudai.ac.jp
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NR 35
TC 91
Z9 98
U1 1
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2006
VL 47
IS 6
BP 2562
EP 2568
DI 10.1167/iovs.05-1429
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 048LQ
UT WOS:000237949000041
PM 16723471
DA 2022-11-30
ER

PT J
AU Wang, BY
   Chen, ZC
   Bhuckory, M
   Goldstein, AK
   Palanker, D
AF Wang, Bing-Yi
   Chen, Zhijie Charles
   Bhuckory, Mohajeet
   Goldstein, Anna Kochnev
   Palanker, Daniel
TI Pixel size limit of the PRIMA implants: from humans to rodents and back
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; restoration of sight; neural stimulation;
   electrophysiology; photovoltaic
ID MORPHOMETRIC-ANALYSIS; MACULAR DEGENERATION; BIPOLAR CELLS; PROSTHESIS;
   PREVALENCE; RETINA; SIGHT; EYES
AB Objective. Retinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic age-related macular degeneration using the PRIMA subretinal implant, a 2 x 2 mm array of 100 mu m-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which, with the current bipolar design, necessitates more intense stimulation. Approach. We examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, and using animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials measured in Royal College of Surgeons rats with photovoltaic implants composed of 100 mu m and 75 mu m pixels were compared to clinical thresholds with 100 mu m pixels. Electrical stimulation model calibrated by the clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main results. PRIMA implants with 75 mu m bipolar pixels under the maximum safe near-infrared (880 nm) illumination of 8 mW mm(-2) with 30% duty cycle (10 ms pulses at 30 Hz) should provide a similar perceptual brightness as with 100 mu m pixels under 3 mW mm(-2) irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75 mu m pixels is also similar under such illumination to that with 100 mu m pixels, increasing the maximum acuity from 20/420 to 20/315. Significance. Computational modeling defines the minimum pixel size of the PRIMA implants as 75 mu m. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75 mu m will nearly quadrupole the number of pixels, which should be very beneficial for patients. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.
C1 [Wang, Bing-Yi] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Chen, Zhijie Charles; Goldstein, Anna Kochnev] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Bhuckory, Mohajeet; Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Bhuckory, Mohajeet; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford
   University
RP Wang, BY (通讯作者)，Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
EM bingyiw@stanford.edu
OI Wang, Bing-Yi/0000-0001-8336-3285; Chen, Zhijie/0000-0003-2705-065X;
   Kochnev Goldstein, Anna/0000-0003-4674-688X; Palanker,
   Daniel/0000-0002-0480-3025; Bhuckory, Mohajeet
   Balveer/0000-0002-2824-1899
FU National Institutes of Health [R01EY-027786, P30-EY-026877]; Department
   of Defense [W81XWH-19-1-0738]; AFOSR [FA9550-19-1-0402]; Research to
   Prevent Blindness; Wu Tsai Institute of Neurosciences at Stanford
FX The authors wish to thank Pixium Vision for providing the PRIMA implants
   with 100 mu m and 75 mu m pixels. The financial support was provide in
   part by the National Institutes of Health (Grants R01EY-027786 and
   P30-EY-026877), the Department of Defense (Grant W81XWH-19-1-0738),
   AFOSR (Grant FA9550-19-1-0402), Wu Tsai Institute of Neurosciences at
   Stanford, and an unrestricted grant from Research to Prevent Blindness.
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NR 30
TC 1
Z9 1
U1 0
U2 0
PU IOP Publishing Ltd
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD OCT 1
PY 2022
VL 19
IS 5
AR 055003
DI 10.1088/1741-2552/ac8e31
PG 11
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA 4N0ZS
UT WOS:000853748900001
PM 36044878
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Demeter, C
   Nagy, J
   Huzsvai, L
   Zelenak, A
   Szabo, A
   Szeles, A
AF Demeter, Cintia
   Nagy, Janos
   Huzsvai, Laszlo
   Zelenak, Annabella
   Szabo, Atala
   Szeles, Adrienn
TI Analysis of the Content Values of Sweet Maize (Zea mays L. Convar
   Saccharata Koern) in Precision Farming
SO AGRONOMY-BASEL
LA English
DT Article
DE sweet maize; precision farming; minerals; sugars; lutein; zeaxanthin
ID CORN; HYBRIDS; YIELD; PARAMETERS; INDEX
AB The global precision farming area is constantly increasing, and precision sweet maize production developed the most. Sweet maize yield is above average in precision farming. Additionally, its role in healthy nutrition is becoming increasingly important due to new hybrids with high carotenoid content. Precision farming techniques are needed to produce healthy food. In particular, nutrient supply and irrigation, sowing, crop management and harvesting need to be carried out with precision techniques. These factors are all prerequisites for effective and healthy growing and processing. The aim was to use the yields of the four sweet maize hybrids grown on the largest area to examine their nutritional values and concentrations (mg kg(-1) dry matter) and to analyse their yield per hectare. Concentration is important for the consumer because K, P, Mg, Ca, Fe, Zn, and Na play an important role in metabolism, skin protection, and bone and tooth health. The new results obtained show that the amount of lutein and zeaxanthin per hectare is important for the processing industry, especially for use in food supplements. Their anti-inflammatory effects and their role in disease prevention (cardiovascular diseases, Age-Related Macular Degeneration (AMD)) have been demonstrated. Consumers choose sweet maize mainly on the basis of its palatability, which is why the sugar content of the hybrids was also studied. We assumed that the element concentration in the yield of new hybrids with higher yield per hectare does not decrease with increasing yield. The concentrations of zeaxanthin, beta-cryptoxanthin and beta-carotene appear in one principal component and they are in close positive correlation with each other. The lutein concentration was independent of the former three compounds. The independence of the lutein concentration means that it is not possible to estimate its amount based on the other three components. For yield per unit area, the correlation is one-dimensional. Yield determines the lutein, zeaxanthin, beta-cryptoxanthin and beta-carotene concentrations per hectare.
C1 [Demeter, Cintia; Nagy, Janos; Zelenak, Annabella; Szabo, Atala; Szeles, Adrienn] Univ Debrecen, Fac Agr & Food Sci & Environm Management, Inst Land Use Engn & Precis Farming Technol, 138 Boszormenyi Str, H-4032 Debrecen, Hungary.
   [Huzsvai, Laszlo] Univ Debrecen, Inst Stat & Methodol, Fac Econ & Business, 138 Boszormenyi Str, H-4032 Debrecen, Hungary.
C3 University of Debrecen; University of Debrecen
RP Nagy, J (通讯作者)，Univ Debrecen, Fac Agr & Food Sci & Environm Management, Inst Land Use Engn & Precis Farming Technol, 138 Boszormenyi Str, H-4032 Debrecen, Hungary.
EM szintia.demeter@gmail.com; nagyjanos@agr.unideb.hu;
   huzsvai.laszlo@econ.unideb.hu; zelenak@agr.unideb.hu;
   szabo.atala@agr.unideb.hu; szelesa@agr.unideb.hu
RI Széles, Adrienn/AAE-8912-2022
OI Szeles, Adrienn/0000-0003-4101-3177; Szabo, Atala/0000-0002-5166-5868;
   Huzsvai, Laszlo/0000-0003-1267-2835
FU National Research, Development and Innovation Fund [TKP2020-IKA-04]
FX This research was funded by the National Research, Development and
   Innovation Fund, grant number: TKP2020-IKA-04.
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NR 35
TC 0
Z9 0
U1 2
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4395
J9 AGRONOMY-BASEL
JI Agronomy-Basel
PD DEC
PY 2021
VL 11
IS 12
AR 2596
DI 10.3390/agronomy11122596
PG 12
WC Agronomy; Plant Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Plant Sciences
GA XW6ES
UT WOS:000735710600001
OA gold
DA 2022-11-30
ER

PT J
AU Pondorfer, SG
   Terheyden, JH
   Overhoff, H
   Stasch-Bouws, J
   Holz, FG
   Finger, RP
AF Pondorfer, Susanne G.
   Terheyden, Jan H.
   Overhoff, Helen
   Stasch-Bouws, Jana
   Holz, Frank G.
   Finger, Robert P.
TI Development of the Vision Impairment in Low Luminance Questionnaire
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE vision-related quality of life; age-related macular degeneration (AMD);
   questionnaire development
ID QUALITY-OF-LIFE; MEDIATED DARK-ADAPTATION; VISUAL FUNCTION; HEALTH;
   IMPACT; ACUITY; PART; MICROPERIMETRY; DEGENERATION; BIOMARKERS
AB Purpose: The purpose of this study was to design and evaluate an instrument for assessing vision-related quality of life appropriate for the specific visual impairment characteristic for all stages of age-related macular degeneration (AMD), with a focus on the low luminance deficit in early/intermediate stages. Methods: A standardized questionnaire was developed in three steps with participants with early, intermediate, and late AMD: (1) based on in-depth interviews (n = 19) and two focus group discussions (n = 5 each), content was developed followed by 2. (2) The questionnaire development using cognitive debriefing interviews (n = 3) and leading to a preliminary version of the questionnaire. (3) This version was then administered to 127 participants with early, intermediate, and late AMD. Psychometric properties, such as response category functioning (floor and ceiling effects) and targeting of item difficulty to patient ability of the pilot Vision Impairment in Low Luminance (VILL) questionnaire were evaluated using Rasch analysis. Results: The preliminary VILL questionnaire consisted of 68 items with a 5-step response scale. Several items were removed based on floor/ceiling effects or misfit and a final pool of 37 items remained. The response scale was collapsed to four categories as one category was underutilized. The targeting of the instrument was good with minimal difference in person and item means (0.52 logits). Precision was also good with a person separation index of 3.55 and reliability of 0.93. There was evidence of multidimensionality (eigenvalue of the first contrast = 5.95) in the scale, which could be resolved by splitting the items into subscales including a reading, mobility, and emotional well-being subscale. Conclusions: Individuals with AMD report difficulties with vision-related activities and functioning under visually challenging conditions at all stages of the disease. These aspects were considered when developing the 37-item VILL, which demonstrates promising psychometric characteristics. Further assessments of reliability and validity are warranted. Translational Relevance: The VILL questionnaire is a new patient-reported outcome (PRO) measure developed for future use in AMD studies.
   <comment>Superscript/Subscript Available</comment
C1 [Pondorfer, Susanne G.; Terheyden, Jan H.; Holz, Frank G.; Finger, Robert P.] Univ Hosp Bonn, Dept Ophthalmol, Bonn, Germany.
   [Overhoff, Helen] Forschungszentrum Julich, Julich, Germany.
   [Stasch-Bouws, Jana] AMD Netz eV, Munster, Germany.
C3 University of Bonn; Helmholtz Association; Research Center Julich
RP Finger, RP (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM robert.finger@ukbonn.de
FU German Scholars Organization/Else Krohner Fresenius Stiftung [GSO/EKFS
   16]; Jackstadt Foundation
FX Supported by the German Scholars Organization/Else Krohner Fresenius
   Stiftung (GSO/EKFS 16) and the Jackstadt Foundation.
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NR 57
TC 3
Z9 3
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 JAN
PY 2021
VL 10
IS 1
DI 10.1167/tvst.10.1.5
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RF6JV
UT WOS:000634949300005
PM 33505772
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lo, YC
   Lin, KH
   Bair, H
   Sheu, WHH
   Chang, CS
   Shen, YC
   Hung, CL
AF Lo, Ying-Chih
   Lin, Keng-Hung
   Bair, Henry
   Sheu, Wayne Huey-Herng
   Chang, Chi-Sen
   Shen, Ying-Cheng
   Hung, Che-Lun
TI Epiretinal Membrane Detection at the Ophthalmologist Level using Deep
   Learning of Optical Coherence Tomography
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIABETIC-RETINOPATHY; RISK-FACTORS; CLASSIFICATION; VITRECTOMY;
   VALIDATION; DISEASES
AB Purpose: Previous deep learning studies on optical coherence tomography (OCT) mainly focused on diabetic retinopathy and age-related macular degeneration. We proposed a deep learning model that can identify epiretinal membrane (ERM) in OCT with ophthalmologist-level performance. Design: Cross-sectional study. Participants: A total of 3,618 central fovea cross section OCT images from 1,475 eyes of 964 patients. Methods: We retrospectively collected 7,652 OCT images from 1,197 patients. From these images, 2,171 were normal and 1,447 were ERM OCT. A total of 3,141 OCT images was used as training dataset and 477 images as testing dataset. DL algorithm was used to train the interpretation model. Diagnostic results by four board-certified non-retinal specialized ophthalmologists on the testing dataset were compared with those generated by the DL model. Main Outcome Measures: We calculated for the derived DL model the following characteristics: sensitivity, specificity, F1 score and area under curve (AUC) of the receiver operating characteristic (ROC) curve. These were calculated according to the gold standard results which were parallel diagnoses of the retinal specialist. Performance of the DL model was finally compared with that of non-retinal specialized ophthalmologists. Results: Regarding the diagnosis of ERM in OCT images, the trained DL model had the following characteristics in performance: sensitivity: 98.7%, specificity: 98.0%, and F1 score: 0.945. The accuracy on the training dataset was 99.7% (95% CI: 99.4 - 99.9%), and for the testing dataset, diagnostic accuracy was 98.1% (95% CI: 96.5 - 99.1%). AUC of the ROC curve was 0.999. The DL model slightly outperformed the average non-retinal specialized ophthalmologists. Conclusions: An ophthalmologist-level DL model was built here to accurately identify ERM in OCT images. The performance of the model was slightly better than the average non-retinal specialized ophthalmologists. The derived model may play a role to assist clinicians to promote the efficiency and safety of healthcare in the future.
C1 [Lo, Ying-Chih] Taichung Vet Gen Hosp, Dept Internal Med, Div Nephrol, Taichung, Taiwan.
   [Lo, Ying-Chih] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA.
   [Lo, Ying-Chih] Harvard Med Sch, Boston, MA 02115 USA.
   [Lo, Ying-Chih] Providence Univ, Dept Data Sci & Big Data Analyt, Taichung, Taiwan.
   [Lin, Keng-Hung; Shen, Ying-Cheng] Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan.
   [Lin, Keng-Hung] Cent Taiwan Univ Sci & Technol, Taichung, Taiwan.
   [Lin, Keng-Hung] Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, Taichung, Taiwan.
   [Bair, Henry] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Sheu, Wayne Huey-Herng] Taichung Vet Gen Hosp, Dept Med, Div Endocrinol & Metab, Taichung, Taiwan.
   [Sheu, Wayne Huey-Herng] NationalYang Ming Univ, Coll Med, Taipei, Taiwan.
   [Sheu, Wayne Huey-Herng] Natl Def Med Ctr, Coll Med, Taipei, Taiwan.
   [Sheu, Wayne Huey-Herng] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung, Taiwan.
   [Chang, Chi-Sen] Taichung Vet Gen Hosp, Dept Internal Med, Div Gastroenterol, Taichung, Taiwan.
   [Hung, Che-Lun] Natl Yang Ming Univ, Inst Biomed Informat, Taipei, Taiwan.
   [Hung, Che-Lun] Providence Univ, Dept Comp Sci & Commun Engn, Taichung, Taiwan.
   [Hung, Che-Lun] Chang Gung Univ, Dept Comp Sci & Informat Engn, Taoyuan, Taiwan.
   [Hung, Che-Lun] Chang Gung Univ, AI Innovat Res Ctr, Taoyuan, Taiwan.
C3 Taichung Veterans General Hospital; Harvard University; Brigham &
   Women's Hospital; Harvard University; Harvard Medical School; Providence
   University - Taiwan; Taichung Veterans General Hospital; Central Taiwan
   University Science & Technology; National Chung Hsing University;
   Stanford University; Taichung Veterans General Hospital; National
   Defense Medical Center; National Chung Hsing University; Taichung
   Veterans General Hospital; National Yang Ming Chiao Tung University;
   Providence University - Taiwan; Chang Gung University; Chang Gung
   University
RP Hung, CL (通讯作者)，Natl Yang Ming Univ, Inst Biomed Informat, Taipei, Taiwan.; Hung, CL (通讯作者)，Providence Univ, Dept Comp Sci & Commun Engn, Taichung, Taiwan.; Hung, CL (通讯作者)，Chang Gung Univ, Dept Comp Sci & Informat Engn, Taoyuan, Taiwan.; Hung, CL (通讯作者)，Chang Gung Univ, AI Innovat Res Ctr, Taoyuan, Taiwan.
EM clhung@mail.cgu.edu.tw
OI Bair, Henry/0000-0002-3422-0373
FU Taichung Veterans General Hospital [TCVGH- 1070105D,
   MOST108-2218-E-126-003, MOST108-2221-E-010-013-MY3]
FX We highly appreciate the participated ophthalmologists CC Chou, LC Wei,
   YS Cheng and YC Wu for their assistance in providing a baseline
   interpretation as the benchmark for evaluating the DL model. Supported
   by Taichung Veterans General Hospital (grant TCVGH- 1070105D),
   MOST108-2218-E-126-003, and MOST108-2221-E-010-013-MY3.
CR [Anonymous], 2015, TZUT LAB FREE SOFTW
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NR 36
TC 8
Z9 8
U1 1
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAY 21
PY 2020
VL 10
IS 1
AR 8424
DI 10.1038/s41598-020-65405-2
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA NB3UQ
UT WOS:000560441900004
PM 32439844
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Giorgis, AT
   Alemu, AM
   Arora, S
   Gessesse, GW
   Melka, F
   Woldeyes, A
   Amin, S
   Kassam, F
   Kurji, AK
   Damji, KF
AF Giorgis, Abeba T.
   Alemu, Abiye M.
   Arora, Sourabh
   Gessesse, Girum W.
   Melka, Fikru
   Woldeyes, Alemayehu
   Amin, Samreen
   Kassam, Faazil
   Kurji, Ayaz K.
   Damji, Karim F.
TI Results From the First Teleglaucoma Pilot Project in Addis Ababa,
   Ethiopia
SO JOURNAL OF GLAUCOMA
LA English
DT Article
DE glaucoma; teleglaucoma; telemedicine; ophthalmology; case finding
ID GLAUCOMA; AFRICA; TELEOPHTHALMOLOGY; IDENTIFICATION; PREVALENCE; CARE
AB Precis: A teleglaucoma case-finding model was utilized in Ethiopia using a high-risk case identification approach. An overall 7.9% of patients had definite glaucoma, and 13.8% were glaucoma suspects. Most cases could be managed medically. Background: This study was carried out to analyze disease prevalence and clinical referral pathways for high-risk patients assessed through a hospital-based teleglaucoma case-finding program. Methods: Patients over the age of 35 years were referred from outpatient diabetic and hypertensive clinics. Through a teleglaucoma consultation, a glaucoma specialist provided remote diagnosis and management recommendations. Patient referral pathways were analyzed. Part way through the program, frontline ophthalmic nurses and optometrists were empowered to refer patients to be seen by general ophthalmologists within a week if patients met high-risk criteria. Qualitative stakeholder feedback was also obtained. Results: A total of 1002 patients (53% female) were assessed with a mean age of 51.0 +/- 11.7 years. The prevalence of glaucoma and glaucoma suspects was 7.9% (79 cases) and 13.8% (138 cases), respectively. Retinopathy was found in 9.1%, with hypertensive retinopathy (2.7%) and diabetic retinopathy (2.5%) representing the majority of cases. Age-related macular degeneration was present in 1.5% and cataract in 16%. An overall 63% of cases were without organic eye disease. 35% of patients were referred to a general ophthalmologist, 0.7% to a glaucoma specialist (for surgery), 1.5% to a retina specialist, and 17.7% to an optometrist for further care. Qualitative analysis revealed that stakeholders felt the value of teleglaucoma would be in triaging patients requiring more urgent management and in identifying disease at an earlier stage. Conclusions: There is a high prevalence of glaucoma in Ethiopian patients assessed through this teleglaucoma program. This model and study have also demonstrated various principles behind telemedicine, such as the development of an intelligent triage system, case-finding for a variety of diseases, and consideration of optimal patient flow/referral pathways.
C1 [Giorgis, Abeba T.; Alemu, Abiye M.] Addis Ababa Univ, Dept Ophthalmol, Addis Ababa, Ethiopia.
   [Gessesse, Girum W.] St Pauls Hosp, Millennium Med Coll, Addis Ababa, Ethiopia.
   [Melka, Fikru] Ras Desta Hosp, Addis Ababa, Ethiopia.
   [Woldeyes, Alemayehu] WGGA Eye Ctr, Addis Ababa, Ethiopia.
   [Arora, Sourabh; Amin, Samreen; Damji, Karim F.] Univ Alberta, Dept Ophthalmol & Visual Sci, Edmonton, AB, Canada.
   [Kassam, Faazil] Calgary Retina Consultants, Calgary, AB, Canada.
   [Kurji, Ayaz K.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
C3 Addis Ababa University; University of Alberta; University of Toronto
RP Damji, KF (通讯作者)，Royal Alexandra Hosp, 2320,10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada.
EM kdamji@ualberta.ca
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   World Health Organization, 2003, BLIND VIS 2020 GLOB
NR 25
TC 7
Z9 8
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-0829
EI 1536-481X
J9 J GLAUCOMA
JI J. Glaucoma
PD AUG
PY 2019
VL 28
IS 8
BP 701
EP 707
DI 10.1097/IJG.0000000000001271
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IV5XP
UT WOS:000484343800014
PM 31082882
DA 2022-11-30
ER

PT J
AU Wei, QQ
   Liang, XW
   Peng, Y
   Yu, DH
   Zhang, RL
   Jin, HZ
   Fan, JQ
   Cai, WT
   Ren, CD
   Yu, J
AF Wei, Qingquan
   Liang, Xiuwei
   Peng, Ye
   Yu, Donghui
   Zhang, Ruiling
   Jin, Huizi
   Fan, Jiaqi
   Cai, Wenting
   Ren, Chengda
   Yu, Jing
TI 17 beta-estradiol ameliorates oxidative stress and blue light-emitting
   diode-induced retina degeneration by decreasing apoptosis and enhancing
   autophagy
SO DRUG DESIGN DEVELOPMENT AND THERAPY
LA English
DT Article
DE 17 beta-estradiol; hydrogen peroxide; retinal blue light-emitting diode
   degeneration; oxidative stress; apoptosis; autophagy
ID ESTROGEN-RECEPTOR-BETA; MACULAR DEGENERATION; EPITHELIAL-CELLS;
   GENE-EXPRESSION; GANGLION-CELLS; PIGMENT EPITHELIUM; RAT RETINA;
   ACTIVATION; AGE; PROTECTS
AB Purpose: This study aimed to assess the effects of 17 beta-estradiol (beta E-2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of beta E-2 underlying these processes.
   Methods: Female ovariectomized (OVX) rats were intravitreally injected with beta E2 before blue LED exposure (3,000 lux, 2 hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy.
   Results: Female OVX rats were exposed to blue LED, inducing RD. beta E-2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. beta E-2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, f1E, reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, beta E-2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and lax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. beta E-2 also increased the number of autophagosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.
   Conclusion: beta E-2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; beta E-2 may be a novel and effective therapy for age-related macular degeneration.
C1 [Wei, Qingquan; Yu, Donghui; Zhang, Ruiling; Jin, Huizi; Fan, Jiaqi; Cai, Wenting; Ren, Chengda; Yu, Jing] Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, 301 Middle Yanchang Rd, Shanghai 200072, Peoples R China.
   [Liang, Xiuwei] Nanchang Univ, Dept Ophthalmol, Nanchang, Jiangxi, Peoples R China.
   [Peng, Ye] Tongji Univ, Shanghai Peoples Hosp 10, Dept Clin Lab, Shanghai, Peoples R China.
   [Yu, Jing] Ninghai First Hosp, Dept Ophthalmol, Ninghai, Zhejiang, Peoples R China.
C3 Tongji University; Nanchang University; Tongji University
RP Ren, CD; Yu, J (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, 301 Middle Yanchang Rd, Shanghai 200072, Peoples R China.
EM curiec@sina.cn; dryujing@aliyun.com
RI Yu, Donghui/HCH-5897-2022
OI Yu, Donghui/0000-0001-5360-6186; Cai, Wenting/0000-0002-2880-302X
FU National Natural Science Foundation of China in 2014 [81470648];
   Fundamental Research Funds for the Central Universities
FX This work was supported by the National Natural Science Foundation of
   China in 2014 (project number: 81470648) and the Fundamental Research
   Funds for the Central Universities. The authors also thank AJE for
   English editing. An abstract of this paper was presented at the 10th
   Chinese Congress of Research in Vision and Ophthalmology (CCRVO) as a
   poster presentation.
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NR 60
TC 16
Z9 17
U1 1
U2 8
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 2018
VL 12
BP 2715
EP 2730
DI 10.2147/DDDT.S176349
PG 16
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GS5ZO
UT WOS:000443759000001
PM 30233136
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Alten, F
   Lauermann, JL
   Clemens, CR
   Heiduschka, P
   Eter, N
AF Alten, F.
   Lauermann, J. L.
   Clemens, C. R.
   Heiduschka, P.
   Eter, N.
TI Signal reduction in choriocapillaris and segmentation errors in spectral
   domain OCT angiography caused by soft drusen
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Drusen; Soft drusen; OCT-angiography;
   Optical coherence tomography angiography; Spectral domain optical
   coherence tomography; Swept source optical coherence tomography;
   Choriocapillaris; Image artifacts; Segmentation
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; SWEPT-SOURCE; GEOGRAPHIC ATROPHY;
   ULTRAHIGH-SPEED; IMAGE ARTIFACTS; CLASSIFICATION; DEGENERATION; LAYERS;
   EYES
AB To analyze signal reduction in choriocapillaris (CC) and segmentation errors in spectral domain optical coherence tomography angiography (OCT-A) caused by soft drusen due to age-related macular degeneration (AMD).
   Twenty-four eyes of 24 patients underwent multimodal retinal imaging including central 3 x 3mm(2) OCT-A (AngioVue, Optovue). Three drusen per study eye were randomly chosen and evaluated regarding drusen height, diameter, and accuracy of OCT-A layer segmentation in lesion proximity. Structural en-face OCT CC images were graded qualitatively and quantitatively regarding signal loss underneath the individual drusen area. Those drusen that showed no distinct signal loss in structural en-face OCT CC images were further evaluated in OCT-A. CC decorrelation signal index was measured within a 30-mu m OCT-A CC slab in the exact area of drusen affection. Data were compared to healthy age-matched control subjects. Accuracy of layer segmentation, OCT CC data, and OCT-A CC data were correlated to morphological drusen parameters.
   Mean drusen height and diameter were 91.57 +/- 19.5 mu m and 315.17 +/- 116.7 mu m. OCT-A layer segmentation of the inner plexiform layer (IPL) was disturbed by more than 50 mu m in proximity to 26 drusen (36.1%). In these patients, drusen height was significantly higher compared to those with accurate IPL segmentation (p = 0.0126). Sixty-six out of 72 drusen (91.7%) caused a distinct signal loss in the structural en-face OCT CC image. Drusen height and drusen diameter were significantly higher in this group compared to the six drusen with a sufficient signal (p = 0.0276, p = 0.0025). CC decorrelation signal index measured in the area of these six drusen without OCT signal loss (8.3%) was reduced compared to age-matched healthy controls (73.6 vs. 100.1; p = 0.001).
   Signal attenuation in CC slabs and segmentation errors of the IPL depend on drusen morphology. Both are frequent artifacts in OCT-A imaging in patients with soft drusen and must be considered during image analysis.
C1 [Alten, F.; Lauermann, J. L.; Clemens, C. R.; Heiduschka, P.; Eter, N.] Univ Munster, Dept Ophthalmol, Med Ctr, Domagkstr 15, D-48149 Munster, Germany.
C3 University of Munster
RP Alten, F (通讯作者)，Univ Munster, Dept Ophthalmol, Med Ctr, Domagkstr 15, D-48149 Munster, Germany.
EM florian.alten@ukmuenster.de; jost.lauermann@ukmuenster.de;
   christoph.clemens@ukmuenster.de; peter.heiduschka@ukmuenster.de;
   eter@uni-muenster.de
RI Heiduschka, Peter/AAX-3882-2021
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NR 38
TC 22
Z9 23
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD DEC
PY 2017
VL 255
IS 12
BP 2347
EP 2355
DI 10.1007/s00417-017-3813-8
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FN5JY
UT WOS:000416044900007
PM 28983695
DA 2022-11-30
ER

PT J
AU Gaddipati, S
   Lu, QX
   Kasetti, RB
   Miller, MC
   Lu, QJ
   Trent, JO
   Kaplan, HJ
   Li, QT
AF Gaddipati, Subhash
   Lu, Qingxian
   Kasetti, Ramesh Babu
   Miller, M. Clarke
   Lu, Qingjun
   Trent, John O.
   Kaplan, Henry J.
   Li, Qiutang
TI IKK2 Inhibition Using TPCA-1-Loaded PLGA Microparticles Attenuates
   Laser-Induced Choroidal Neovascularization and Macrophage Recruitment
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; MACULAR DEGENERATION; BETA; MICROSPHERES; INFLAMMATION;
   CELLS; MODEL; MICE; RANIBIZUMAB; RETINOPATHY
AB The inhibition of NF-kappa B by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 1/4m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retro-bulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR) tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of TPCA-1 delivered by microparticles in treatment of CNV in the patients with age-related macular degeneration and other retinal neovascularization diseases.
C1 [Gaddipati, Subhash; Lu, Qingxian; Kasetti, Ramesh Babu; Kaplan, Henry J.; Li, Qiutang] Univ Louisville, Sch Med, Dept Ophthalmol, Louisville, KY 40292 USA.
   [Gaddipati, Subhash; Lu, Qingxian; Kasetti, Ramesh Babu; Kaplan, Henry J.; Li, Qiutang] Univ Louisville, Sch Med, Dept Visual Sci, Louisville, KY 40292 USA.
   [Gaddipati, Subhash; Lu, Qingxian; Miller, M. Clarke; Trent, John O.; Li, Qiutang] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
   [Miller, M. Clarke] Univ North Georgia, Dept Chem & Biochem, Oakwood, GA USA.
   [Lu, Qingjun] Capital Med Univ, Beijing Tong Ren Eye Ctr, Beijing Inst Ophthalmol, Beijing, Peoples R China.
   [Trent, John O.] Univ Louisville, Sch Med, Dept Med, Louisville, KY 40292 USA.
C3 University of Louisville; University of Louisville; University of
   Louisville; University of North Georgia; Capital Medical University;
   University of Louisville
RP Li, QT (通讯作者)，Univ Louisville, Sch Med, Dept Ophthalmol, Louisville, KY 40292 USA.
EM q.li@louisville.edu
RI Miller, M. Clarke/C-9483-2011; Kasetti, Ramesh Babu/H-5157-2019
OI Miller, M. Clarke/0000-0002-9877-6581; KASETTI,
   RAMESH/0000-0001-7874-3988; trent, John/0000-0002-7346-4231; Gaddipati,
   Subhash/0000-0002-5323-5466
FU National Eye Institute [R01-EY019891, EY021548]; National Institute of
   General Medical Sciences [1P30GM106396]; Research to Prevent Blindness
   Ernest & Elizabeth Althouse Special Scholar Award; NATIONAL EYE
   INSTITUTE [R01EY019891] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF GENERAL MEDICAL SCIENCES [P30GM106396] Funding Source: NIH RePORTER
FX This work was supported by National Eye Institute grants R01-EY019891
   and EY021548, National Institute of General Medical Sciences grant
   1P30GM106396, and a Research to Prevent Blindness Ernest & Elizabeth
   Althouse Special Scholar Award. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 39
TC 14
Z9 14
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2015
VL 10
IS 3
AR e0121185
DI 10.1371/journal.pone.0121185
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CH2XV
UT WOS:000353889600135
PM 25803615
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Chavali, VRM
   Diniz, B
   Huang, JY
   Ying, GS
   Sadda, SR
   Stambolian, D
AF Chavali, Venkata Ramana Murthy
   Diniz, Bruno
   Huang, Jiayan
   Ying, Gui-Shuang
   Sadda, SriniVas R.
   Stambolian, Dwight
TI Association of OCT-Derived Drusen Measurements with AMD-Associated
   Genotypic SNPs in the Amish Population
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE age-related macular degeneration; AMD; Older Order Amish; CFH; SYN3;
   OCT; drusen area; drusen volume; RPE atrophy; Cirrus HD-OCT
ID COMPLEMENT FACTOR-H; OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; BRUCHS MEMBRANE; FACTOR-B; VARIANTS;
   RISK; GENE; SUSCEPTIBILITY
AB Purpose: To investigate the association of optical coherence tomography (OCT)-derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC) of 3 mm in diameter and a surrounding perifoveal ring (PR) of 3 to 5 mm in diameter using the Cirrus OCT RPE analysis software. Other demographic information, including age, gender and smoking status, were collected. Study subjects were further genotyped to determine their risk for the AMD-associated SNPs in the SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. Results: 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status) confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for the drusen area (the area increased 0.12 mm(2) for a risk allele increase, p < 0.01), drusen volume (the volume increased 0.01 mm(3) for a risk allele increase, p = 0.05) and the area of RPE atrophy (the area increased 0.43 mm(2) for a risk allele increase, p = 0.003). SYN3 risk allele G is significantly associated with larger area PR (the area increased 0.09 mm(2) for a risk allele increase, p = 0.03) and larger drusen volume in the central circle (the volume increased 0.01 mm(3) for a risk allele increase, p = 0.04). Conclusion: Among the genotyped SNPs tested, the CFH risk genotype appears to play a major role in determining the drusen phenotype in the Amish AMD population.
C1 [Chavali, Venkata Ramana Murthy; Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Stellar Chance Labs 313B, 422 Curie Blvd, Philadelphia, PA 19104 USA.
   [Diniz, Bruno; Sadda, SriniVas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Diniz, Bruno] Univ Fed Sao Paulo, Dept Ophthalmol, BR-09920 Sao Paulo, Brazil.
   [Huang, Jiayan; Ying, Gui-Shuang] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
   [Sadda, SriniVas R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
C3 University of Pennsylvania; Doheny Eye Institute; Universidade Federal
   de Sao Paulo (UNIFESP); University of Pennsylvania; University of
   Southern California
RP Stambolian, D (通讯作者)，Univ Penn, Dept Ophthalmol, Stellar Chance Labs 313B, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM vchavali@mail.med.upenn.edu; bdinizlt@hotmail.com;
   huangjiayan@gmail.com; gsying@mail.med.upenn.edu; vassadda@gmail.com;
   stamboli@mail.med.upenn.edu
FU NIH [RO1 EY023164]; NATIONAL EYE INSTITUTE [P30EY001583, R01EY023164]
   Funding Source: NIH RePORTER
FX This work is supported in part by NIH grant RO1 EY023164 to Stambolian
   and Sadda.
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NR 51
TC 13
Z9 13
U1 0
U2 1
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 FEB
PY 2015
VL 4
IS 2
BP 304
EP 317
DI 10.3390/jcm4020304
PG 14
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA CT9IY
UT WOS:000363131700006
PM 25893111
OA Green Submitted, Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Wang, LC
   Yang, CM
   Yang, CH
   Huang, JS
   Ho, TC
   Lin, CP
   Chen, MS
AF Wang, Lu-Chun
   Yang, Chung-May
   Yang, Chang-Hao
   Huang, Jen-Sheng
   Ho, Tzyy-Chang
   Lin, Chang-Ping
   Chen, Muh-Shy
TI Clinical characteristics and visual outcome of non-traumatic
   suprachoroidal haemorrhage in Taiwan
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; expulsive haemorrhage; haemorrhagic
   choroidal detachment; ocular surgical complications; suprachoroidal
   haemorrhage
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; PARS-PLANA VITRECTOMY; EXPULSIVE
   HEMORRHAGE; RISK-FACTORS; SURGICAL-MANAGEMENT; SURGERY; SEVERITY;
   GLAUCOMA; FEATURES; EFFUSION
AB This study aimed to evaluate the clinical features and visual outcomes of non-traumatic suprachoroidal haemorrhage (SH) in Taiwan.
   We report a retrospective, non-comparative, interventional case series study carried out in an institutional setting. Thirty-nine eyes with non-traumatic SH were studied using a new system for grading the severity of SH. The aetiologies of SH were analysed. The correlations between grades and prognoses of SH were studied. Multiple logistic regression was used to assess factors associated with final visual outcome.
   Conditions causing SH in the eyes considered in this study included cataract surgery (43.59%), age-related macular degeneration (AMD) (17.95%), filtering operation and vitrectomy (both 10.26%), scleral buckling (5.13%) and others. Twelve eyes (12/39, 30.77%) had a final visual outcome of no light perception. Only 12 eyes (12/39, 30.77%) had final visual acuity (VA) > 4/200. Grade of SH correlated significantly with need for surgical drainage and with final visual outcome (Spearman rank correlations 0.313 and - 0.408, p = 0.010 and p = 0.00317, respectively). 'Good' and 'poor' final VA was significantly associated with VA at the time of SH (multiple logistic regression coefficients 2.132 and - 2.809, p = 0.015 and p = 0.008, respectively), as well as initial retinal detachment (multiple logistic regression coefficients - 2.267 and 2.223, p = 0.036 and p = 0.006, respectively). Higher grades of SH and increased age were associated with poor final visual outcome (multiple logistic regression coefficients - 1.332 and - 0.122, p = 0.013 and p = 0.022, respectively).
   Suprachoroidal haemorrhage is a devastating ocular problem. Complications of intraoperative surgery and AMD are common causes. The new SH grading system provides a simple method for evaluating the need for drainage and for predicting visual prognosis. Visual acuity and retinal detachment at the time of SH are major factors associated with good and poor final VA, respectively.
C1 [Yang, Chung-May] Natl Taiwan Univ, Coll Med, Dept Ophthalmol, Natl Taiwan Univ Hosp, Taipei 10764, Taiwan.
   [Wang, Lu-Chun] Natl Taiwan Univ Hosp, Yun Lin Branch, Dept Ophthalmol, Yunlin, Taiwan.
C3 National Taiwan University; National Taiwan University Hospital;
   National Taiwan University; National Taiwan University Hospital
RP Yang, CM (通讯作者)，Natl Taiwan Univ, Coll Med, Dept Ophthalmol, Natl Taiwan Univ Hosp, 7 Chung Shan S Rd, Taipei 10764, Taiwan.
EM chungmay@ntu.edu.tw
RI Yang, Chang-Hao/AAR-3759-2021; Yang, Chung-May/AAV-3737-2020
OI LIN, CHANG-PING/0000-0003-0302-7711; YANG,
   CHANG-HAO/0000-0002-4328-8716; YANG, CHUNG-MAY/0000-0003-4082-420X
FU National Centre of Excellence for General Clinical Trials; National
   Taiwan University Hospital
FX We thank the National Centre of Excellence for General Clinical Trials
   and Research, National Taiwan University Hospital, for statistical
   consultation.
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NR 30
TC 14
Z9 17
U1 0
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD DEC
PY 2008
VL 86
IS 8
BP 908
EP 912
DI 10.1111/j.1755-3768.2008.01266.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 377IA
UT WOS:000261243700019
PM 18631331
OA Bronze
DA 2022-11-30
ER

PT J
AU Fernando, AN
   Furtado, PB
   Clark, SJ
   Gilbert, HE
   Day, AJ
   Sim, RB
   Perkins, SJ
AF Fernando, Anira N.
   Furtado, Patricia B.
   Clark, Simon J.
   Gilbert, Hannah E.
   Day, Anthony J.
   Sim, Robert B.
   Perkins, Stephen J.
TI Associative and structural properties of the region of complement factor
   H encompassing the Tyr402His disease-related polymorphism and its
   interactions with heparin
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE factor H; X-ray scattering; homology modelling; ultracentrifugation
ID HEMOLYTIC-UREMIC SYNDROME; ANGLE X-RAY; NEUTRON-SCATTERING;
   CRYSTAL-STRUCTURE; BINDING DOMAIN; ANALYTICAL ULTRACENTRIFUGATION;
   HYDRODYNAMIC PROPERTIES; CONTROL PROTEIN; IDENTIFICATION; MUTATIONS
AB Factor H (FH) is a major complement control protein in serum. The seventh short complement regulator (SCR-7) domain of the 20 in FH is associated with age-related macular degeneration through a Tyr402His polymorphism. The recombinant SCR-6/8 domains containing either His402 or Tyr402 and their complexes with a heparin decasaccharide were studied by analytical ultracentrifugation and X-ray scattering. The sedimentation coefficient is concentration dependent, giving a value of 2.0 S at zero concentration and a frictional ratio f/f(o) of 1.2 for both allotypes. The His402 allotype showed a slightly greater self-association than the Tyr402 allotype, and small amounts of dimeric SCR-6/8 were found for both allotypes in 50 mM, 137 mM and 250 mM NaCl buffers. Sedimentation equilibrium data were interpreted in terms of a monomer-dimer equilibrium with a dissociation constant of 40 mu M for the His402 form. The Guinier radius of gyration R-G of 3.1-3.3 nrn and. the R-G/R-O ratio of 2.0-2.1 showed that SCR6/8 is relatively extended in solution. The distance distribution function P(r) showed a maximum dimension of 10 nm, which is less than the length expected for a linear domain arrangement. The constrained scattering and sedimentation modelling of FH SCR-6/8 showed that bent SCR arrangements fit the data better than linear arrangements. Previously identified heparin-binding residues were exposed on the outside curvature of this bent domain structure. Heparin caused the formation of a more linear structure, possibly by binding to residues in the linker. It was concluded that the His402 allotype may self-associate more readily than the Tyr402 allotype, SCR-6/8 is partly responsible for the folded-back structure of intact FH, and SCR-6/8 changes conformation upon heparin binding. (c) 2007 Elsevier Ltd. All rights reserved.
C1 UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England.
   Univ Oxford, MRC, Dept Biochem, Immunochem Unit, Oxford OX1 3QU, England.
   Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England.
C3 University of London; University College London; University of Oxford;
   University of Manchester
RP Perkins, SJ (通讯作者)，UCL, Dept Biochem & Mol Biol, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM s.perkins@medsch.ucl.ac.uk
RI Day, Anthony/O-1658-2015; Sim, Bob/A-1354-2008
OI Day, Anthony/0000-0002-1415-3134; Sim, Bob/0000-0002-2855-7455; Clark,
   Simon/0000-0001-8394-8355
FU Medical Research Council [MC_U138274352] Funding Source: Medline;
   Wellcome Trust Funding Source: Medline; MRC [MC_U138274352] Funding
   Source: UKRI
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NR 58
TC 42
Z9 43
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD APR 27
PY 2007
VL 368
IS 2
BP 564
EP 581
DI 10.1016/j.jmb.2007.02.038
PG 18
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 159WD
UT WOS:000245897400023
PM 17362990
DA 2022-11-30
ER

PT J
AU Orosz, K
   Gupta, S
   Hassink, M
   Abdel-Rahman, M
   Moldovan, L
   Davidorf, FH
   Moldovan, NI
AF Orosz, K
   Gupta, S
   Hassink, M
   Abdel-Rahman, M
   Moldovan, L
   Davidorf, FH
   Moldovan, NI
TI Delivery of antiangiogenic and antioxidant drugs of ophthalmic interest
   through a nanoporous inorganic filter
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ASCORBIC-ACID; OXIDATIVE STRESS; CELLS;
   ANGIOGENESIS; RETINA; NEOVASCULARIZATION; INHIBITION; EXPRESSION;
   ALUMINUM
AB Purpose: We propose a novel method of administration of antiangiogenic and antioxidant drugs, with potential clinical application in the treatment of proliferative diabetic retinopathy (PDR) and age-related macular degeneration (AMD). We suggest the encapsulation of drugs in implantable sustained release devices, limited by membranes with pores in the tens of nanometers diameter range, which display a slower, quasi-linear release kinetics, and a better selectivity than other membranes. In this paper we explored the feasibility of this approach by testing in vitro several key elements of the nanofilter system: diffusion of drugs of interest, efficacy in producing desirable effects on cells, and biocompatibility of used material with some of the cells encountered in the ocular cavity.
   Methods: We used an aluminum oxide filter (AnoporeTM) with pores of 20 nm as a limiting medium for the administration of drugs. First, we induced an oxidative stress in human retinal endothelial cells (HREC) by treating them with hydrogen peroxide diffused across the filter, in the absence or in the presence of catalase. HREC attached to the culture plate, or emerging as angiogenic sprouts from aggregates embedded in collagen gels, were also exposed to vitamin C or to endostatin delivered across the nanoporous filter. Direct exposure of the cells to the agents served as positive controls. Growth of cells on the filter was considered an indication for biocompatibility.
   Results: Catalase diffused across the nanoporous membrane counteracted the cytotoxic effect of hydrogen peroxide on HREC. We also found that vitamin C, acting directly or after diffusion across the filter, up to concentrations physiologically present in the eye, was a concentration dependent modulator of HREC's ability to survive and sprout. Additionally, we confirmed the ability of endostatin to block the growth of HREC either attached or sprouting from cell aggregates, after diffusion across the AnoporeTM nanofilter.
   Conclusions: The drug delivery method based on the administration of angiostatic and antioxidant agents across the inorganic aluminum oxide nanoporous filter passed the key in vitro tests for diffusibility and biocompatibility, opening the way for medical applications.
C1 Ohio State Univ, Med Ctr, Dept Internal Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
   Ohio State Univ, Div Ophthalmol, Columbus, OH 43210 USA.
   Ohio State Univ, Ctr Biomed Engn, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; University System of
   Ohio; Ohio State University; University System of Ohio; Ohio State
   University
RP Moldovan, NI (通讯作者)，Ohio State Univ, Med Ctr, Dept Internal Med, Davis Heart & Lung Res Inst, Room 305A,473 W 12th Ave, Columbus, OH 43210 USA.
EM moldovan-1@medctr.osu.edu
RI Abdel-rahman, Mohamed/E-2608-2011; Abdel-Rahman, Mohamed/A-8197-2013
OI Abdel-Rahman, Mohamed/0000-0002-9493-7894; Moldovan,
   Leni/0000-0003-1967-2408
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NR 52
TC 34
Z9 38
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD AUG 18
PY 2004
VL 10
IS 68
BP 555
EP 565
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 849LI
UT WOS:000223539700001
PM 15332016
DA 2022-11-30
ER

PT J
AU Ahn, J
   Cha, S
   Choi, KE
   Kim, SW
   Yoo, Y
   Goo, YS
AF Ahn, Jungryul
   Cha, Seongkwang
   Choi, Kwang-Eon
   Kim, Seong-Woo
   Yoo, Yongseok
   Goo, Yong Sook
TI Correlated Activity in the Degenerate Retina Inhibits Focal Response to
   Electrical Stimulation
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE retinal degeneration; electrical stimulation; rd1 mice; rd10 mice;
   non-human primate model; retinal ganglion cell; retinal network;
   correlation analysis
ID GANGLION-CELLS; PARKINSONS-DISEASE; PRIMATE RETINA; MOUSE; RD1; LIGHT;
   OSCILLATIONS; ACTIVATION; NETWORK; MECHANISMS
AB Retinal prostheses have shown some clinical success in patients with retinitis pigmentosa and age-related macular degeneration. However, even after the implantation of a retinal prosthesis, the patient's visual acuity is at best less than 20/420. Reduced visual acuity may be explained by a decrease in the signal-to-noise ratio due to the spontaneous hyperactivity of retinal ganglion cells (RGCs) found in degenerate retinas. Unfortunately, abnormal retinal rewiring, commonly observed in degenerate retinas, has rarely been considered for the development of retinal prostheses. The purpose of this study was to investigate the aberrant retinal network response to electrical stimulation in terms of the spatial distribution of the electrically evoked RGC population. An 8 x 8 multielectrode array was used to measure the spiking activity of the RGC population. RGC spikes were recorded in wild-type [C57BL/6J; P56 (postnatal day 56)], rd1 (P56), rd10 (P14 and P56) mice, and macaque [wild-type and drug-induced retinal degeneration (RD) model] retinas. First, we performed a spike correlation analysis between RGCs to determine RGC connectivity. No correlation was observed between RGCs in the control group, including wild-type mice, rd10 P14 mice, and wild-type macaque retinas. In contrast, for the RD group, including rd1, rd10 P56, and RD macaque retinas, RGCs, up to approximately 400-600 mu m apart, were significantly correlated. Moreover, to investigate the RGC population response to electrical stimulation, the number of electrically evoked RGC spikes was measured as a function of the distance between the stimulation and recording electrodes. With an increase in the interelectrode distance, the number of electrically evoked RGC spikes decreased exponentially in the control group. In contrast, electrically evoked RGC spikes were observed throughout the retina in the RD group, regardless of the inter-electrode distance. Taken together, in the degenerate retina, a more strongly coupled retinal network resulted in the widespread distribution of electrically evoked RGC spikes. This finding could explain the low-resolution vision in prosthesis-implanted patients.
C1 [Ahn, Jungryul; Cha, Seongkwang; Goo, Yong Sook] Chungbuk Natl Univ, Dept Physiol, Sch Med, Cheongju, South Korea.
   [Choi, Kwang-Eon; Kim, Seong-Woo] Korea Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Yoo, Yongseok] Incheon Natl Univ, Dept Elect Engn, Incheon, South Korea.
C3 Chungbuk National University; Korea University; Korea University
   Medicine (KU Medicine); Incheon National University
RP Goo, YS (通讯作者)，Chungbuk Natl Univ, Dept Physiol, Sch Med, Cheongju, South Korea.; Kim, SW (通讯作者)，Korea Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.; Yoo, Y (通讯作者)，Incheon Natl Univ, Dept Elect Engn, Incheon, South Korea.
EM ksw64724@korea.ac.kr; yyoo@inu.ac.kr; ysgoo@chungbuk.ac.kr
OI Cha, SeongKwang/0000-0002-0859-2368
FU Bio and Medical Technology Development Program [NRF-2017M3A9E2056460,
   NRF-2017M3A9E2056458]; National Research Foundation of Korea (NRF) -
   Ministry of Science and ICT (MSIP) [NRF-2020R1A2C1005729,
   NRF-2021R1A6A3A01086439, NRF-2022R1A2C2004793]; Ministry of Education
FX This research was supported in part by the Bio and Medical Technology
   Development Program (NRF-2017M3A9E2056460 and NRF-2017M3A9E2056458) and
   the Basic Science Research Program (NRF-2020R1A2C1005729,
   NRF-2021R1A6A3A01086439, and NRF-2022R1A2C2004793) through the National
   Research Foundation of Korea (NRF) funded by the Ministry of Science and
   ICT (MSIP) and the Ministry of Education.
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NR 106
TC 1
Z9 1
U1 6
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD MAY 4
PY 2022
VL 16
AR 889663
DI 10.3389/fncel.2022.889663
PG 18
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 1J1KH
UT WOS:000797682700001
PM 35602554
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ma, JN
   Xu, XL
   Li, MD
   Zhang, Y
   Zhang, L
   Ma, P
   Hou, J
   Lei, YL
   Liu, JG
   Huangfu, XJ
   Yang, Y
   Yi, XL
   Cheng, G
   Bai, J
   Zhong, XW
   Xu, XM
   Wang, Y
AF Ma, Jiaonan
   Xu, Xueli
   Li, Mengdi
   Zhang, Yan
   Zhang, Lin
   Ma, Ping
   Hou, Jie
   Lei, Yulin
   Liu, Jianguo
   Huangfu, Xiaojin
   Yang, Yang
   Yi, Xianglong
   Cheng, George
   Bai, Ji
   Zhong, Xingwu
   Xu, Ximing
   Wang, Yan
TI Predictive models of aging of the human eye based on ocular anterior
   segment morphology
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Aging; Machine learning; Eye; Anterior segment; Morphology
ID AGE; AGREEMENT
AB Aging is a major risk factor for various eye diseases, such as cataract, glaucoma, and age-related macular degeneration. Age-related changes are observed in almost all structures of the human eye. Considerable individual variations exist within a group of similarly aged individuals, indicating the need for more informative biomarkers for assessing the aging of the eyes. The morphology of the ocular anterior segment has been reported to vary across age groups, focusing on only a few corneal parameters, such as keratometry and thickness of the cornea, which could not provide accurate estimation of age. Thus, the association between eye aging and the morphology of the anterior segment remains elusive. In this study, we aimed to develop a predictive model of age based on a large number of anterior segment morphology-related features, measured via the high-resolution ocular anterior segment analysis system (Pentacam). This approach allows for an integrated assessment of age-related changes in corneal morphology, and the identification of important morphological features associated with different eye aging patterns. Three machine learning methods (neural networks, Lasso regression and extreme gradient boosting) were employed to build predictive models using 276 anterior segment features of 63,753 participants from 10 ophthalmic centers in 10 different cities of China. The best performing age prediction model achieved a median absolute error of 2.80 years and a mean absolute error of 3.89 years in the validation set. An external cohort of 100 volunteers was used to test the performance of the prediction model. The developed neural network model achieved a median absolute error of 3.03 years and a mean absolute error of 3.40 years in the external cohort. In summary, our study revealed that the anterior segment morphology of the human eye may be an informative and non-invasive indicator of eye aging. This could prompt doctors to focus on age-related medical interventions on ocular health.
C1 [Ma, Jiaonan; Li, Mengdi; Zhang, Yan; Wang, Yan] Tianjin Med Univ, Clin Coll Ophthalmol, 4 Gansu Rd, Tianjin 300020, Peoples R China.
   [Xu, Xueli; Xu, Ximing] Nankai Univ, Sch Stat & Data Sci, Tianjin, Peoples R China.
   [Zhang, Lin; Wang, Yan] Nankai Univ, Affiliated Eye Hosp, Tianjin Key Lab Ophthalmol & Visual Sci, Tianjin Eye Inst,Tianjin Eye Hosp, 4 Gansu Rd, Tianjin 300020, Peoples R China.
   [Ma, Ping] Univ Georgia, Dept Stat, Athens, GA 30602 USA.
   [Hou, Jie; Lei, Yulin] Jinan Mingshui Eye Hosp, Dept Ophthalmol, Jinan, Shandong, Peoples R China.
   [Liu, Jianguo] Xian 4 Hosp, Xian, Shaanxi, Peoples R China.
   [Huangfu, Xiaojin] 4th Peoples Hosp Shenyang, Shenyang, Liaoning, Peoples R China.
   [Yang, Yang] Yanan Hosp Kunming City, Kunming, Yunnan, Peoples R China.
   [Yi, Xianglong] Xinjiang Med Univ, Affiliated Hosp 1, Urumqi, Xinjiang, Peoples R China.
   [Cheng, George] Hong Kong Laser Eye Ctr, Hong Kong, Peoples R China.
   [Bai, Ji] Daping Hosp, Chongqing, Peoples R China.
   [Zhong, Xingwu] Sun Yat Sen Univ, Hainan Eye Hosp, Zhongshan Ophthalm Ctr, Haikou, Guangdong, Peoples R China.
   [Xu, Ximing] Key Lab Med Data Anal & Stat Res Tianjin, Tianjin, Peoples R China.
C3 Tianjin Medical University; Nankai University; Nankai University;
   Tianjin Medical University; University System of Georgia; University of
   Georgia; Xinjiang Medical University; Army Medical University; Sun Yat
   Sen University
RP Wang, Y (通讯作者)，Tianjin Med Univ, Clin Coll Ophthalmol, 4 Gansu Rd, Tianjin 300020, Peoples R China.; Wang, Y (通讯作者)，Nankai Univ, Affiliated Eye Hosp, Tianjin Key Lab Ophthalmol & Visual Sci, Tianjin Eye Inst,Tianjin Eye Hosp, 4 Gansu Rd, Tianjin 300020, Peoples R China.; Xu, XM (通讯作者)，Nankai Univ, Sch Stat & Data Sci, Key Lab Med Data Anal & Stat Res Tianjin, 94 Weijin Rd, Tianjin 300071, Peoples R China.
EM ximing@nankai.edu.cn; wangyan7143@vip.sina.com
FU National Natural Science Foundation of China [81873684, 11701294]
FX This study was supported by grants from by the National Natural Science
   Foundation of China (No. 81873684 and 11701294).
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NR 43
TC 2
Z9 3
U1 2
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2021
VL 120
AR 103855
DI 10.1016/j.jbi.2021.103855
EA JUL 2021
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Medical Informatics
GA TY1JL
UT WOS:000683539900007
PM 34216803
OA Bronze
DA 2022-11-30
ER

PT J
AU Schori, C
   Trachsel, C
   Grossmann, J
   Barben, M
   Klee, K
   Storti, F
   Samardzija, M
   Grimm, C
AF Schori, Christian
   Trachsel, Christian
   Grossmann, Jonas
   Barben, Maya
   Klee, Katrin
   Storti, Federica
   Samardzija, Marijana
   Grimm, Christian
TI A chronic hypoxic response in photoreceptors alters the vitreous
   proteome in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Vitreous; Hypoxia; Proteomics; Rod photoreceptors; Cone photoreceptors;
   Retina
ID RECEPTOR-RELATED PROTEIN-1; SET ENRICHMENT ANALYSIS; MAJOR VAULT
   PROTEIN; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; COMPLEMENT-SYSTEM;
   NEURAL CELLS; MOUSE MODEL; BLOOD-FLOW; EXPRESSION
AB Reduced oxygenation of the outer retina in the aging eye may activate a chronic hypoxic response in RPE and photoreceptor cells and is considered as a risk factor for the development of age-related macular degeneration (AMD). In mice, a chronically active hypoxic response in the retinal pigment epithelium (RPE) or photoreceptors leads to age-dependent retinal degeneration. To identify proteins that may serve as accessible markers for a chronic hypoxic insult to photoreceptors, we used proteomics to determine the protein composition of the vitreous humor in genetically engineered mice that lack the von Hippel-Lindau tumor suppressor (Vhl) specifically in rods (rod(Delta Vhl)) or cones (all-cone(Delta Vhl)). Absence of VHL leads to constitutively active hypoxia-inducible transcription factors (HIFs) and thus to a molecular response to hypoxia even in normal room air. To discriminate between the consequences of a local response in photoreceptors and systemic hypoxic effects, we also evaluated the vitreous proteome of wild type mice after exposure to acute hypoxia.
   1'043 of the identified proteins were common to all three hypoxia models. 257, 258 and 356 proteins were significantly regulated after systemic hypoxia, in rod(Delta Vhl) and in all-cone(Delta Vhl) mice, respectively, at least at one of the analyzed time points. Only few of the regulated proteins were shared by the models indicating that the vitreous proteome is differentially affected by systemic hypoxia and the rod or cone-specific hypoxic response. Similarly, the distinct protein compositions in the individual genetic models at early and late time points suggest regulated, cell-specific and time-dependent processes. Among the proteins commonly regulated in the genetic models, guanylate binding protein 2 (GBP2) showed elevated levels in the vitreous that were accompanied by increased mRNA expression in the retina of both rod(Delta Vhl) and all-cone(Delta Vhl) mice. We hypothesize that some of the differentially regulated proteins at early time points may potentially be used as markers for the detection of a chronic hypoxic response of photoreceptors.
C1 [Schori, Christian; Barben, Maya; Klee, Katrin; Storti, Federica; Samardzija, Marijana; Grimm, Christian] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Zurich, Switzerland.
   [Schori, Christian; Klee, Katrin; Grimm, Christian] Univ Zurich, Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland.
   [Trachsel, Christian; Grossmann, Jonas] Swiss Fed Inst Technol, Funct Genom Ctr Zurich FGCZ, Zurich, Switzerland.
   [Trachsel, Christian; Grossmann, Jonas] Univ Zurich, Zurich, Switzerland.
   [Barben, Maya; Grimm, Christian] Univ Zurich, Neurosci Ctr Zurich ZNZ, Zurich, Switzerland.
C3 University of Zurich; University of Zurich; Zurich Center Integrative
   Human Physiology (ZIHP); ETH Zurich; University of Zurich; University of
   Zurich
RP Grimm, C (通讯作者)，Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Wagistr 14, CH-8952 Schlieren, Switzerland.
EM cgrimm@opht.uzh.ch
RI Samardzija, Marijana/B-9245-2008
OI Samardzija, Marijana/0000-0003-0991-4653; Grimm,
   Christian/0000-0001-9318-4352
FU Novartis Pharma, Switzerland; Robert and Rosa Pulfer Foundation
   (Switzerland); Swiss National Science Foundation [31003A_149311,
   31003A_173008]
FX We thank Sarah Notzli, Andrea Gubler and Coni Imsand for excellent
   technical assistance. This work was supported by a grant from Novartis
   Pharma, Switzerland, the Robert and Rosa Pulfer Foundation (Switzerland)
   and by the Swiss National Science Foundation (31003A_149311 and
   31003A_173008). The authors declare no competing interests.
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NR 93
TC 3
Z9 3
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2019
VL 185
AR 107690
DI 10.1016/j.exer.2019.107690
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IT8NU
UT WOS:000483140000022
PM 31181196
OA hybrid, Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Gao, XX
   Park, CH
   Dedrick, K
   Borkar, DS
   Obeid, A
   Reber, S
   Federman, J
AF Gao, Xinxiao
   Park, Carl H.
   Dedrick, Krista
   Borkar, Durga S.
   Obeid, Anthony
   Reber, Shae
   Federman, Jay
TI Use of Telehealth Screening to Detect Diabetic Retinopathy and Other
   Ocular Findings in Primary Care Settings
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE diabetic retinopathy; screening; telehealth; ocular pathology
ID EYE DISEASE; TELEMEDICINE; AGE; TELEOPHTHALMOLOGY; SURVEILLANCE;
   MANAGEMENT; PROGRAM; NETWORK
AB Purpose: To determine the incidence of diabetic retinopathy (DR) and other ocular findings in previously diagnosed diabetes using telehealth retinal screening with nonmydriatic fundus photography (nFP) in primary care physicians' offices. Methods: A retrospective study based on electronic chart review was performed. All diabetic patients who participated in the Wills Eye Hospital (WEH) telehealth retinal screening program from July 1, 2012 to February 20, 2017 were included. In addition to evaluation of DR, other eye pathologies of the retina were detected using nFP. Results: Overall, 9,946 diabetics participated in the WEH telehealth screening system. After exclusion of missing or unreadable images, 15,180 eyes of 7,624 (76.7%) patients were eligible for final analysis. A total of 1,269 (16.6%) patients were noted to have DR changes in at least one eye. Of those, 475 (37.4%) had mild nonproliferative DR (NPDR) in the more severely affected eye, 712 (56.1%) had moderate NPDR, 33 (2.6%) had severe NPDR, 19 (1.5%) had proliferative DR, and 30 (2.4%) have received pan-retinal photocoagulation previously. In addition, there was evidence of diabetic macular edema detectable on nFP in 34 eyes of 29 patients. Other ocular findings included hypertensive retinopathy (709, 9.3%), increased or asymmetric cup-to-disc ratio (562, 7.4%), age-related cataract (379, 5.0%), cotton-wool spots (221, 2.9%), choroidal nevus (74, 1.0%), age-related macular degeneration (AMD) (66, 0.9%), and epiretinal membrane (48, 0.6%). Patients with hypertensive retinopathy, glaucomatous findings, cataract, or AMD were significantly older (p < 0.001) than those without these ocular pathologies. Conclusion: The WEH Telehealth Screening Program identified DR in approximately one out of six patients and other ocular pathologies in over 25% of the diabetic population that received screenings in Philadelphia area primary care offices. Given the importance of early detection and routine eye care to prevent vision loss for DR patients, these findings have a significant impact.
C1 [Gao, Xinxiao; Park, Carl H.; Dedrick, Krista; Borkar, Durga S.; Obeid, Anthony; Reber, Shae; Federman, Jay] Thomas Jefferson Univ, Wills Eye Hosp, Suite 1020,840 Walnut St, Philadelphia, PA 19107 USA.
   [Gao, Xinxiao] Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China.
C3 Jefferson University; Capital Medical University
RP Federman, J (通讯作者)，Thomas Jefferson Univ, Wills Eye Hosp, Suite 1020,840 Walnut St, Philadelphia, PA 19107 USA.
EM jayfederman@gmail.com
CR Asbell PA, 2005, LANCET, V365, P599
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NR 32
TC 4
Z9 4
U1 0
U2 6
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 SEP 1
PY 2019
VL 25
IS 9
BP 802
EP 807
DI 10.1089/tmj.2018.0016
EA NOV 2018
PG 6
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA IX9SH
UT WOS:000451289500001
PM 30481134
DA 2022-11-30
ER

PT J
AU Busch, M
   Wasmuth, S
   Spital, G
   Lommatzsch, A
   Pauleikhoff, D
AF Busch, Martin
   Wasmuth, Susanne
   Spital, Georg
   Lommatzsch, Albrecht
   Pauleikhoff, Daniel
TI Activation of the ERK1/2-MAPK Signaling Pathway by Complement Serum in
   UV-POS-Pretreated ARPE-19 Cells
SO OPHTHALMOLOGICA
LA English
DT Article
DE ERK1/2-MAPK; Retinal pigment epithelial cells; Complement stimulation;
   Oxidative stress; Age-related macular degeneration
ID PIGMENT EPITHELIAL-CELLS; PHOTORECEPTOR OUTER SEGMENTS; ENDOTHELIAL
   GROWTH-FACTOR; MEMBRANE-ATTACK-COMPLEX; LIPID-PEROXIDATION PRODUCTS;
   FACTOR-H POLYMORPHISM; NF-KAPPA-B; MACULAR DEGENERATION; REGULATED
   KINASE; OXIDATIVE-STRESS
AB Background: Retinal pigment epithelial (RPE) cells undergo functional changes upon complement stimulation, which play a role in the pathogenesis of age-related macular degeneration (AMD). These effects are in part enhanced by pretreating ARPE-19 cells with UV-irradiated photoreceptor outer segments (UV-POS) in vitro. The aim of this study was to investigate the effects of human complement serum (HCS) treatment on p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2 [ERK1/2]) activation in ARPE-19 cells pretreated with UV-POS. Methods: UV-POS-pretreated ARPE-19 cells were stimulated with 5% HCS or heat-inactivated HCS (HI-HCS) as a control. Protein expression of phosphorylated (activated) ERK1/2, total ERK1/2, Bax, and Bcl-2 was analyzed by Western blotting. Cell culture supernatants were analyzed for IL-6, IL-8, MCP-1, and VEGF by enzyme-linked immunosorbent assay (ELISA). Furthermore, extra-and intracellular reactive oxygen species (ROS) were determined. Results: The amount of phosphory-lated ERK1/2 was increased in UV-POS-pretreated ARPE-19 cells, especially in combination with HCS stimulation, compared to non-pretreated ARPE-19 cells incubated with HCS alone or HI-HCS. The same observation was made for Bax and Bcl-2 expression. Furthermore, an increase in extra-and intracellular ROS was detected in UV-POS-pretreated ARPE-19 cells. The ELISA data showed that the production of IL-6, IL-8, and MCP-1 tended to increase in response to HCS in both UV-POS-pretreated and non-pretreated ARPE-19 cells. Conclusions: Our data imply that ERK1/2 activation in ARPE-19 cells may represent a response mechanism to cellular and oxidative stress, associated with apoptosis-regulating factors such as Bax and Bcl-2, which might play a role in AMD, while ERK1/2 seems not to represent the crucial signaling pathway mediating the functional changes in RPE cells in response to complement stimulation. (C) 2018 S. Karger AG, Basel
C1 [Busch, Martin; Wasmuth, Susanne] St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, Hohenzollemring 74, DE-48145 Munster, Germany.
   [Spital, Georg; Lommatzsch, Albrecht; Pauleikhoff, Daniel] St Franziskus Hosp, Dept Ophthalmol, Munster, Germany.
   [Lommatzsch, Albrecht; Pauleikhoff, Daniel] Univ Duisburg Essen, Dept Ophthalmol, Essen, Germany.
C3 St. Franziskus-Hospital; St. Franziskus-Hospital; University of Duisburg
   Essen
RP Busch, M (通讯作者)，St Franziskus Hosp, Dept Ophthalmol, Ophtha Lab, Hohenzollemring 74, DE-48145 Munster, Germany.
EM martin.busch@uveitis-zentrum.de
FU Dr. Werner Jackstadt Foundation; Voltmann Foundation
FX This work was supported by the Dr. Werner Jackstadt Foundation and the
   Voltmann Foundation.
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NR 54
TC 7
Z9 8
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2018
VL 239
IS 4
BP 215
EP 224
DI 10.1159/000486404
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GH9GB
UT WOS:000433976300004
PM 29486466
DA 2022-11-30
ER

PT J
AU Baek, SU
   Park, IW
   Suh, W
AF Baek, Sung Uk
   Park, In Won
   Suh, Wool
TI Long-term intraocular pressure changes after intravitreal injection of
   bevacizumab
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Bevacizumab; glaucoma; intraocular pressure
ID GROWTH-FACTOR THERAPY; DIABETIC MACULAR EDEMA; SUSTAINED ELEVATION;
   REFRACTIVE ERROR; DEGENERATION; RANIBIZUMAB; PEGAPTANIB; EYE
AB Purpose: To assess the long-term intraocular pressure (IOP) changes after the intravitreal injection of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for treatment of age-related macular degeneration (AMD) and diabetic macular edema (DME) patients and evaluate the correlation factors.Material and methods: Patients with neovascular AMD or DME underwent treat-and-extended anti-VEGF regimen in one eye and followed more than 12 months were enrolled in this study. We set three criteria of IOP elevation: (1) the IOP of the treated eye increased above the contralateral eye for at least two consecutive visits; (2) the IOP of the treated eye increased above the pre-injection IOP for at least two consecutive visits; (3) and the IOP of the treated eye increased more than 5mmHg above the baseline IOP for at least two consecutive visits. We used mixed model univariate and multivariate analysis to assess the association between IOP elevation and independent parameters including age, sex, lens status, the number of injections, and underlying disease.Results: In total 152 patients, 83 patients with AMD and 69 patients with DME, were included in this study. Mean follow-up time was 18.7 months, with a maximum of 50 months. In IOP elevation, 54 eyes (35.6%) showed an IOP increase above that of the contralateral eye (criteria 1), 50 eyes (33.4%) showed an IOP increase above the baseline IOP (criteria 2), and an IOP increase greater than 5mmHg above the baseline IOP observed in nine eyes (5.9%) (criteria 3). In the univariate analysis, lens status and total number of injections were statistically significant for criteria 2 and 3 (all ps<0.05). However, in the multivariable analysis, only the number of intravitreal injections was statistically correlated with sustained IOP elevation for criteria 2 and 3 (p<0.001 and p=0.039, respectively).Conclusions: Our results suggest that under long-term monitoring, with a treat-and-extended regimen, intravitreal bevacizumab injections were associated with sustained IOP elevation. In particular, multiple intravitreal injections could be associated with sustained IOP elevation.
C1 [Baek, Sung Uk] Armed Forces Daegu Hosp, Dept Ophthalmol, Dae Gu, South Korea.
   [Park, In Won] Hallym Univ, Dept Ophthalmol, Sacred Heart Hosp, Anyang, South Korea.
   [Suh, Wool] Hallym Univ, Dongtan Sacred Heart Hosp, Hwaseong, South Korea.
C3 Hallym University; Hallym University
RP Suh, W (通讯作者)，Hallym Univ, Dongtan Sacred Heart Hosp, Hwaseong, South Korea.
EM being111@hotmail.com
CR Adelman RA, 2010, J OCUL PHARMACOL TH, V26, P105, DOI 10.1089/jop.2009.0076
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NR 34
TC 22
Z9 22
U1 0
U2 33
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1556-9527
EI 1556-9535
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD DEC
PY 2016
VL 35
IS 4
BP 310
EP 314
DI 10.3109/15569527.2015.1124886
PG 5
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA DX5NZ
UT WOS:000384429000008
PM 26820610
DA 2022-11-30
ER

PT J
AU Nie, C
   Zhang, MN
   Zhao, HW
   Olsen, TD
   Jackman, K
   Hu, LN
   Ma, WP
   Chen, XF
   Wang, J
   Zhang, Y
   Gao, TS
   Uehara, H
   Ambati, BK
   Luo, L
AF Nie, Chuang
   Zhang, Mao-Nian
   Zhao, Hong-Wei
   Olsen, Thomas D.
   Jackman, Kyle
   Hu, Lian-Na
   Ma, Wen-Ping
   Chen, Xiao-Fei
   Wang, Juan
   Zhang, Ying
   Gao, Tie-Shan
   Uehara, Hiro
   Ambati, Balamurali K.
   Luo, Ling
TI Correlation of In Vivo and In Vitro Methods in Measuring Choroidal
   Vascularization Volumes Using a Subretinal Injection Induced Choroidal
   Neovascularization Model
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE Choroidal Flatmount; Choroidal Neovascularization; Correlation;
   Spectral-domain Optical Coherence Tomography
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; SD-OCT; RETINAL
   DEGENERATION; SCHEMATIC EYE; MOUSE; MICE; INFLAMMATION; INHIBITION;
   FIBROSIS
AB Background: In vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.
   Methods: CNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (m/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at ). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.
   Results: The CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R (2) =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001).
   Conclusions: There is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection. The result might provide a useful evaluation of CNV both for the studies using CNV models induced by subretinal injection and human AMD studies.
C1 [Nie, Chuang; Zhang, Mao-Nian; Chen, Xiao-Fei; Zhang, Ying] Chinese Peoples Liberat Army Gen Hosp, Dept Ophthalmol, Beijing 100853, Peoples R China.
   [Zhao, Hong-Wei; Hu, Lian-Na; Gao, Tie-Shan; Luo, Ling] PLA, Dept Ophthalmol, Hosp 306, Beijing 100101, Peoples R China.
   [Olsen, Thomas D.; Jackman, Kyle; Uehara, Hiro; Ambati, Balamurali K.] Univ Utah, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Ma, Wen-Ping; Wang, Juan] PLA, Dept Ophthalmol, Hosp 261, Beijing 100094, Peoples R China.
C3 Chinese People's Liberation Army General Hospital; Utah System of Higher
   Education; University of Utah
RP Luo, L (通讯作者)，PLA, Dept Ophthalmol, Hosp 306, Beijing 100101, Peoples R China.
EM bambati@gmail.com; Ling.luoling1208@gmail.com
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NR 37
TC 1
Z9 1
U1 0
U2 4
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD JUN 5
PY 2015
VL 128
IS 11
BP 1516
EP 1522
DI 10.4103/0366-6999.157681
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA CJ7RF
UT WOS:000355695200017
PM 26021510
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Choudhary, M
   Kazmin, D
   Hu, P
   Thomas, RS
   McDonnell, DP
   Malek, G
AF Choudhary, Mayur
   Kazmin, Dmitri
   Hu, Peng
   Thomas, Russell S.
   McDonnell, Donald P.
   Malek, Goldis
TI Aryl hydrocarbon receptor knock-out exacerbates choroidal
   neovascularization via multiple pathogenic pathways
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE age-related macular degeneration; aryl hydrocarbon receptor; choroidal
   neovascularization; RNA sequencing; inflammation; extracellular matrix;
   angiogenesis
ID MONOCYTE-CHEMOATTRACTANT PROTEIN-1; RETINAL-PIGMENT EPITHELIUM;
   GROWTH-FACTOR-BETA; MACULAR DEGENERATION; DIOXIN-RECEPTOR; AH RECEPTOR;
   TGF-BETA; CELL-DIFFERENTIATION; INDUCED ANGIOGENESIS; MATRIX METABOLISM
AB The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+)) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-1 (TGF1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116. (c) 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
C1 [Choudhary, Mayur; Hu, Peng; Malek, Goldis] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA.
   [Kazmin, Dmitri] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Thomas, Russell S.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA.
   [McDonnell, Donald P.] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Malek, Goldis] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA.
C3 Duke University; Emory University; The Hamner Institutes for Health
   Sciences; Duke University; Duke University
RP Malek, G (通讯作者)，Duke Univ, Sch Med, Dept Ophthalmol, Duke Eye Ctr, 2351 Erwin Rd,AERI Room 4006, Durham, NC 27710 USA.
EM gmalek@duke.edu
RI Choudhary, Mayur/AAU-3497-2021
OI Choudhary, Mayur/0000-0001-8056-011X; Malek, Goldis/0000-0003-0026-2388;
   Thomas, Russell/0000-0002-2340-0301
FU International Retinal Research Foundation Loris and David Rich
   Postdoctoral Scholar Award; US National Institutes of Health [EY02868,
   R37DK048807, P30 EY005722]; Research to Prevent Blindness Inc (RPB); RPB
   Sybil B Harrington Scholar Award; NATIONAL EYE INSTITUTE [P30EY005722,
   R01EY020868] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK048807, R37DK048807]
   Funding Source: NIH RePORTER
FX We thank Mr Peter Saloupis and Mrs Amanda Bednar for technical support
   and Dr Krzysztof Palczewski for valuable advice. We thank Dr Scott
   Cousins for allowing us to use his diode red laser and slit-lamp
   biomicroscope. This study was funded by an International Retinal
   Research Foundation Loris and David Rich Postdoctoral Scholar Award (to
   MC), the US National Institutes of Health (Grant Nos EY02868, to GM;
   R37DK048807, to DPM; and P30 EY005722, to Duke Eye Center), Research to
   Prevent Blindness Inc (RPB), core grant (to Duke Eye Center) and an RPB
   Sybil B Harrington Scholar Award (to GM).
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NR 80
TC 33
Z9 34
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD JAN
PY 2015
VL 235
IS 1
BP 101
EP 112
DI 10.1002/path.4433
PG 12
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA AW3LX
UT WOS:000346189200009
PM 25186463
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Kennedy, RD
   Spafford, MM
   Douglas, O
   Brule, J
   Hammond, D
   Fong, GT
   Thompson, ME
   Schultz, ASH
AF Kennedy, Ryan David
   Spafford, Marlee M.
   Douglas, Ornell
   Brule, Julie
   Hammond, David
   Fong, Geoffrey T.
   Thompson, Mary E.
   Schultz, Annette S. H.
TI Patient Tobacco Use in Optometric Practice: A Canada-Wide Study
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE public health; tobacco; cessation; prevention; age-related macular
   degeneration
ID MACULAR DEGENERATION; CIGARETTE-SMOKING; RISK-FACTORS; CESSATION;
   BLINDNESS; HEALTH; INTERVENTIONS; ADOLESCENTS; CHILDREN
AB Purpose. A national census survey of optometrists in Canada measured knowledge of ocular diseases associated with smoking cigarettes and current practice behaviors related to addressing tobacco use with patients, including prevention and cessation. Optometrists were also asked to identify tools to assist addressing tobacco use with patients.
   Methods. An online bilingual (English/French) survey was developed and an e-mail with a link to the survey was sent to all 4528 optometrists registered in Canada. No participation incentives were provided. Frequency data were tabulated for survey items. Logistic regression models were fit to understand respondent characteristics associated with discussing tobacco use prevention and cessation with patients.
   Results. The response rate was 19% (850 responses). Almost all respondents (98%) believed that smoking cigarettes was a risk factor for developing age-related macular degeneration; approximately half (55%) assessed the smoking status of patients during their initial visit; 7% reported that they discussed the benefits of tobacco use prevention with patients younger than 19 years; and 33% reported that they always or regularly assess their patients' interest in quitting smoking. Respondents who completed the survey in English were more likely (odds ratio, 2.4; 95% confidence interval, 1.01 to 5.65) to deliver prevention messaging, compared with respondents who completed the survey in French. Male respondents were less likely to assess patients' interest in quitting (odds ratio, 0.7; 95% confidence interval, 0.50 to 0.97) than female respondents. Most respondents (90%) were interested in a continuing education program about the impact of smoking on vision and eye health as well as strategies for discussing tobacco cessation and prevention.
   Conclusions. Optometrists are aware of the impact of smoking on ocular health; however, most respondents do not systematically engage in tobacco use prevention and cessation practices. Providing optometrists with tools, including continuing education, may help support patient conversations about the risks of tobacco use and improve public health.
C1 [Kennedy, Ryan David] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA.
   [Kennedy, Ryan David; Douglas, Ornell] Univ Waterloo, Propel Ctr Populat Hlth Impact, Waterloo, ON N2L 3G1, Canada.
   [Spafford, Marlee M.] Univ Waterloo, Sch Optometry & Vis Sci, Waterloo, ON N2L 3G1, Canada.
   [Hammond, David] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada.
   [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada.
   [Thompson, Mary E.] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada.
   [Brule, Julie] Univ Montreal, Ecole Optometrie, Montreal, PQ H3C 3J7, Canada.
   [Hammond, David] Sch Publ Hlth & Hlth Syst, Waterloo, ON, Canada.
   [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada.
   [Schultz, Annette S. H.] Univ Manitoba, Fac Nursing, Winnipeg, MB, Canada.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; University of Waterloo; University of Waterloo; University of
   Waterloo; University of Waterloo; University of Waterloo; Universite de
   Montreal; Ontario Institute for Cancer Research; University of Toronto;
   University Toronto Affiliates; University of Manitoba
RP Kennedy, RD (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Dept Hlth Behav & Soc, 2213 McElderry St,4th Floor, Baltimore, MD 21205 USA.
EM rkennedy@jhsph.edu
RI Kennedy, Ryan David/U-3794-2017; Fong, Geoffrey T/H-2810-2014
OI Kennedy, Ryan David/0000-0002-9448-5234; Fong, Geoffrey
   T/0000-0001-9098-6472; Schultz, Annette/0000-0002-7944-2180
FU Federal Tobacco Control Strategy from Health Canada; Canadian Cancer
   Society Research Initiative (CCSRI grant) [701019]; Ontario Institute
   for Cancer Research (Senior Investigator Award); 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 by an operating grant from the Canadian Cancer
   Society Research Initiative (CCSRI grant #701019). Data were collected
   by the Survey Research Centre at the University of Waterloo. GTF is
   supported by the Ontario Institute for Cancer Research (Senior
   Investigator Award). Additional support was provided by the 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 43
TC 8
Z9 8
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD JUL
PY 2014
VL 91
IS 7
BP 769
EP 777
DI 10.1097/OPX.0000000000000303
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AK9WD
UT WOS:000338778400014
PM 24927140
DA 2022-11-30
ER

PT J
AU Zhuge, CC
   Xu, JY
   Zhang, JF
   Li, WY
   Li, P
   Li, ZY
   Chen, L
   Liu, XQ
   Shang, P
   Xu, H
   Lu, YJ
   Wang, F
   Lu, LX
   Xu, GT
AF Zhuge, Chun-Chun
   Xu, Jing-Ying
   Zhang, Jingfa
   Li, Weiye
   Li, Peng
   Li, Zongyi
   Chen, Ling
   Liu, Xiaoqing
   Shang, Peng
   Xu, Hua
   Lu, Yanjun
   Wang, Fang
   Lu, Lixia
   Xu, Guo-Tong
TI Fullerenol Protects Retinal Pigment Epithelial Cells From Oxidative
   Stress-Induced Premature Senescence via Activating SIRT1
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE fullerenol; RPE senescence; SIRT1; DNA damage; oxidative stress
ID MACULAR DEGENERATION; DNA-DAMAGE; RPE CELLS; P53; PHOSPHORYLATION;
   SUPPRESSION; EXPRESSION; C-60
AB PURPOSE. Oxidative stress-induced retinal pigment epithelium (RPE) senescence is one of the important factors in the pathogenesis of age-related macular degeneration (AMD). This study aimed to develop a new antisenescence-based intervention and clarify its possible molecular mechanism.
   METHODS. A cell premature senescence model was established in both primary RPE cells and ARPE-19 cells by exposure of the cells to pulsed H2O2 stress for 5 days, and confirmed with senescence-associated beta-galactosidase (SA-beta-gal) staining. The final concentration of fullerenol (Fol) in the cell culture system was 5 mu g/mL. Cellular redox status was determined by the examination of cellular reactive oxygen species (ROS) staining, catalase activity, and the ratio of reduced to oxidized glutathione, respectively. Deoxyribonucleic acid double-strand breaks were determined by quantitative analysis of gamma H(2)AX. Cell cycle analysis was performed with flow cytometry. SIRT1 activity was examined with SIRT1 Assay Kit. SIRT1 overexpression and knockdown in ARPE-19 cells were performed with lentiviral-mediated infection.
   RESULTS. Pulsed H2O2 exposure triggered the acetylation of p53 at lysine 382 (K382) and subsequent increase in its target p21(Waf1/Cip1). It also increased the number of accumulated phospho-gamma H(2)AX foci and the level of phosphor-ATM in RPE cells. Fullerenol protected the RPE cells, as it reduced the number of positive SA-beta-gal-staining cells, alleviated the depletion of cellular antioxidants, and reduced genomic DNA damage. Its mechanism might involve the activation of deacetylase SIRT1, resulting in decreased levels of acetyl-p53 and p21(Waf1/Cip1). The roles of SIRT1 in protecting cells in response to Fol were further confirmed by applications of SIRT1 activator (resveratrol) and inhibitors (nicotinamide and sirtinol), and through SIRT1 overexpression and knockdown.
   CONCLUSIONS. Fullerenol could rescue RPE cells from oxidative stress-induced senescence through its antioxidation activity and the activation of SIRT1. The protective effect of Fol is useful for the development of new strategies to treat oxidative stress-related retinal diseases like AMD.
C1 [Zhuge, Chun-Chun; Xu, Guo-Tong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Lab Clin Visual Sci, Shanghai, Peoples R China.
   [Xu, Jing-Ying; Zhang, Jingfa; Li, Weiye; Chen, Ling; Liu, Xiaoqing; Wang, Fang; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R China.
   [Xu, Jing-Ying; Zhang, Jingfa; Li, Weiye; Chen, Ling; Liu, Xiaoqing; Wang, Fang; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Shanghai 200092, Peoples R China.
   [Xu, Jing-Ying; Zhang, Jingfa; Li, Weiye; Li, Peng; Li, Zongyi; Chen, Ling; Liu, Xiaoqing; Shang, Peng; Xu, Hua; Lu, Yanjun; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Dept Regenerat Med, Shanghai 200092, Peoples R China.
   [Xu, Jing-Ying; Zhang, Jingfa; Li, Weiye; Li, Peng; Li, Zongyi; Chen, Ling; Liu, Xiaoqing; Shang, Peng; Xu, Hua; Lu, Yanjun; Lu, Lixia; Xu, Guo-Tong] Tongji Univ, Sch Med, Stem Cell Res Ctr, Shanghai 200092, Peoples R China.
   [Li, Weiye] Drexel Univ, Coll Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Xu, Guo-Tong] Tongji Univ, Inst Nutr Sci, Shanghai 200092, Peoples R China.
C3 Chinese Academy of Sciences; Shanghai Institutes for Biological
   Sciences, CAS; Tongji University; Tongji University; Tongji University;
   Tongji University; Drexel University; Chinese Academy of Sciences;
   Tongji University
RP Xu, GT (通讯作者)，Tongji Univ, Sch Med, Tongji Eye Inst, Shanghai Peoples Hosp 10,Dept Ophthalmol, 1239 Siping Rd,Med Sch Bldg,Room 521, Shanghai 200092, Peoples R China.
EM dreyemilwang_122@163.com; lulixia@tongji.edu.cn; gtxu@tongji.edu.cn
OI /0000-0002-3780-5641
FU Key State Basic Research Development Program of China (973 Projects)
   [2013CB967501, 2011CB965102, 2012CBA01308, 2011DFB30010]; National
   Natural Science Foundation of China [31171419, 31071199]; Shanghai
   Science and Technology Committee Grant [12ZR1434400]; Shanghai Health
   Bureau Scientific Research Grant [2010Y011]
FX Supported by the following research grants: the Key State Basic Research
   Development Program of China (973 Projects, 2013CB967501, 2011CB965102,
   2012CBA01308, and 2011DFB30010); National Natural Science Foundation of
   China (31171419 and 31071199); Shanghai Science and Technology Committee
   Grant 12ZR1434400; and Shanghai Health Bureau Scientific Research Grant
   2010Y011.
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NR 40
TC 44
Z9 46
U1 2
U2 30
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 2014
VL 55
IS 7
BP 4628
EP 4638
DI 10.1167/iovs.13-13732
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AL9UI
UT WOS:000339487000075
PM 24845634
DA 2022-11-30
ER

PT J
AU Thampi, P
   Rao, HV
   Mitter, SK
   Cai, J
   Mao, HY
   Li, H
   Seo, S
   Qi, XP
   Lewin, AS
   Romano, C
   Boulton, ME
AF Thampi, Prajitha
   Rao, Haripriya Vittal
   Mitter, Sayak K.
   Cai, Jun
   Mao, Haoyu
   Li, Hong
   Seo, Soojung
   Qi, Xiaoping
   Lewin, Alfred S.
   Romano, Carl
   Boulton, Michael E.
TI The 5HT(1a) Receptor Agonist 8-Oh DPAT Induces Protection from
   Lipofuscin Accumulation and Oxidative Stress in the Retinal Pigment
   Epithelium
SO PLOS ONE
LA English
DT Article
ID BAY X 3702; MITOCHONDRIAL-DNA DAMAGE; GLOBAL CEREBRAL-ISCHEMIA; FUNDUS
   AUTOFLUORESCENCE; SEROTONIN(1A) RECEPTOR; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; IN-VIVO; PROTEIN-KINASE; MOUSE MODEL
AB Age-related macular degeneration (AMD), a major cause of blindness in the elderly, is associated with oxidative stress, lipofuscin accumulation and retinal degeneration. The aim of this study was to determine if a 5-HT1A receptor agonist can reduce lipofuscin accumulation, reduce oxidative damage and prevent retinal cell loss both in vitro and in vivo. Autophagy-derived and photoreceptor outer segment (POS)-derived lipofuscin formation was assessed using FACS analysis and confocal microscopy in cultured retinal pigment epithelial (RPE) cells in the presence or absence of the 5-HT1A receptor agonist, 8-OH DPAT. 8-OH DPAT treatment resulted in a dose-dependent reduction in both autophagy-and POS-derived lipofuscin compared to control. Reduction in autophagy-induced lipofuscin was sustained for 4 weeks following removal of the drug. The ability of 8-OH DPAT to reduce oxidative damage following exposure to 200 mu M H2O2 was assessed. 8-OH DPAT reduced superoxide generation and increased mitochondrial superoxide dismutase (MnSOD) levels and the ratio of reduced glutathione to the oxidized form of glutathione in H2O2-treated cells compared to controls and protected against H2O2-initiated lipid peroxidation, nitrotyrosine levels and mitochondrial damage. SOD2 knockdown mice, which have an AMD-like phenotype, received daily subcutaneous injections of either saline, 0.5 or 5.0 mg/kg 8-OH DPAT and were evaluated at monthly intervals. Systemic administration of 8-OH DPAT improved the electroretinogram response in SOD2 knockdown eyes of mice compared to knockdown eyes receiving vehicle control. There was a significant increase in the ONL thickness in mice treated with 8-OH DPAT at 4 months past the time of MnSOD knockdown compared to untreated controls together with a 60% reduction in RPE lipofuscin. The data indicate that 5-HT1A agonists can reduce lipofuscin accumulation and protect the retina from oxidative damage and mitochondrial dysfunction. 5-HT1A receptor agonists may have potential as therapeutic agents in the treatment of retinal degenerative disease.
C1 [Thampi, Prajitha; Rao, Haripriya Vittal; Mitter, Sayak K.; Cai, Jun; Qi, Xiaoping; Boulton, Michael E.] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
   [Mao, Haoyu; Li, Hong; Seo, Soojung; Lewin, Alfred S.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
   [Romano, Carl] Alcon Labs Inc, Retina Res, Ft Worth, TX 76101 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida; Novartis; Alcon
RP Thampi, P (通讯作者)，Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
EM meboulton@ufl.edu
OI Lewin, Alfred/0000-0002-4192-9727
FU National Institutes of Health [EY019688]; Alcon Labs, Inc; NATIONAL EYE
   INSTITUTE [P30EY021721, R01EY019688] Funding Source: NIH RePORTER
FX This work was funded by National Institutes of Health grant EY019688
   (MEB) and a grant from Alcon Labs, Inc (MEB & ASL). CR is an employee of
   Alcon Labs, Inc. and contributed to the study design and preparation of
   the manuscript. The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
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NR 56
TC 33
Z9 33
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 3
PY 2012
VL 7
IS 4
AR e34468
DI 10.1371/journal.pone.0034468
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 952PZ
UT WOS:000304805900035
PM 22509307
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Pons, M
   Marin-Castano, ME
AF Pons, Marianne
   Marin-Castano, Maria E.
TI Cigarette Smoke-Related Hydroquinone Dysregulates MCP-1, VEGF and PEDF
   Expression in Retinal Pigment Epithelium in Vitro and in Vivo
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; NONLETHAL OXIDANT
   INJURY; SUB-RPE DEPOSITS; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   CHOROIDAL NEOVASCULARIZATION; OXIDATIVE STRESS; PROTEIN-1 MCP-1;
   GENE-EXPRESSION
AB Background: Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s) linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial derived factor (PEDF) in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ), a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.
   Principal Findings: MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.
   Conclusion: We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and progression to CNV in smoker patients with dry AMD.
C1 [Pons, Marianne; Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
C3 Bascom Palmer Eye Institute; University of Miami
RP Pons, M (通讯作者)，Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
EM Mcastano@med.miami.edu
FU Flight Attendant Medical Research Institute [072100_CIA]; Research to
   Prevent Blindness [P30-EY14801]; NATIONAL EYE INSTITUTE [P30EY014801]
   Funding Source: NIH RePORTER
FX This study was supported by a Flight Attendant Medical Research
   Institute 072100_CIA grant and an unrestricted grant from Research to
   Prevent Blindness to the University of Miami P30-EY14801. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript file.
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NR 73
TC 57
Z9 59
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 FEB 28
PY 2011
VL 6
IS 2
AR e16722
DI 10.1371/journal.pone.0016722
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 729EM
UT WOS:000287931400011
PM 21386905
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Woo, SJ
   Kim, JH
   Yu, HG
AF Woo, Se Joon
   Kim, Joo Hoon
   Yu, Hyeong Gon
TI Ursodeoxycholic Acid and Tauroursodeoxycholic Acid Suppress Choroidal
   Neovascularization in a Laser-Treated Rat Model
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; VISUAL IMPAIRMENT;
   REDUCES APOPTOSIS; MOUSE; ANGIOGENESIS; CHAPERONES; VEGF; PRESERVATION;
   INFLAMMATION
AB Purpose: The aim of this study was to investigate the suppressing effects of systemically administered ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) on choroidal neovascularization (CNV) in a laser-treated rat model.
   Methods: CNV was induced by argon laser photocoagulation in the right eye of each animal. UDCA 500 mg/kg, TUDCA 100 mg/kg, or vehicle was intraperitoneally injected at 24 h before and daily after laser treatment. Fourteen days after laser treatment, fluorescein angiography was performed to evaluate leakage from CNV and eyes were enucleated for histologic evaluation. Vascular endothelial growth factor (VEGF) levels in the retina were measured using enzyme-linked immunosorbent assay at 3 days after laser treatment and were compared between the UDCA, TUDCA, and control groups.
   Results: The proportion of CNV lesions showing clinically significant fluorescein leakage was lower in the UDCA and TUDCA groups (42%, P = 0.0124; and 46%, P = 0.0292) than in the control group (67%). CNV lesion dimensions including CNV area and CNV/choroid thickness ratio were also significantly reduced in the UDCA and TUDCA groups (7,664 +/- 630 mu m(2), P < 0.001 and 8,558 +/- 570 mu m(2), P < 0.001; 2.35 +/- 0.16, P = 0.026 and 2.27 +/- 0.15, P = 0.003) compared with the control group (12,147 +/- 661 mu m(2) and 3.10 +/- 0.27). The VEGF level in the retina after laser treatment was lower in the TUDCA group than that in the control group (9.0 +/- 2.7 pg/mg vs. 29.4 +/- 8.2 pg/mg, P = 0.032), whereas the UDCA group showed no difference.
   Conclusions: The systemic administration of UDCA and TUDCA suppressed laser-induced CNV formation in rats, which might be associated with anti-inflammatory action. The result indicates that UDCA and TUDCA are potential candidate drugs for the treatment of many CNV-related retinal diseases, including age-related macular degeneration.
C1 [Kim, Joo Hoon; Yu, Hyeong Gon] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul Natl Univ Hosp, Seoul 110744, South Korea.
   [Woo, Se Joon] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Bundang Hosp, Seoul 110744, South Korea.
   [Yu, Hyeong Gon] Seoul Natl Univ, Med Res Ctr, Res Inst Sensory Organs, Seoul 110744, 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, Dept Ophthalmol, Coll Med, Seoul Natl Univ Hosp, 28 Yongon Dong, Seoul 110744, South Korea.
EM hgonyu@snu.ac.kr
RI Yu, Hyeong Gon/J-2772-2012; Woo, Joon/I-7357-2013
OI Woo, Joon/0000-0003-3692-7169; Yu, Hyeong Gon/0000-0002-1795-202X
FU Daewoong Pharmaceutical Company [0411-20070024]
FX This research was supported by a research fund from the Daewoong
   Pharmaceutical Company, Grant Number 0411-20070024. The authors thank
   Young Joo Kim for VEGF quantification by ELISA and Hyo Jin Shin for her
   assistance during the animal treatments.
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NR 35
TC 35
Z9 35
U1 0
U2 5
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 223
EP 229
DI 10.1089/jop.2010.0012
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 614CW
UT WOS:000279033800001
PM 20565307
DA 2022-11-30
ER

PT J
AU Madill, SA
   Lascaratos, G
   Arden, GB
   Ffytche, DH
AF Madill, Stephen A.
   Lascaratos, Gerassimos
   Arden, Geoffrey B.
   Ffytche, Dominic H.
TI Perceived Color of Hallucinations in the Charles Bonnet Syndrome Is
   Related to Residual Color Contrast Sensitivity
SO JOURNAL OF NEURO-OPHTHALMOLOGY
LA English
DT Article
ID ACQUIRED CEREBRAL DYSCHROMATOPSIA; COMPLEX VISUAL HALLUCINATIONS;
   COMPUTER-GRAPHICS SYSTEM; VISION; GLAUCOMA; DEFECTS; ANATOMY
AB Background: We sought to determine whether the change in cortical excitability secondary to deafferentation in patients with Charles Bonnet Syndrome (CBS) who hallucinate in a predominant color or combination of colors is related to an alteration in color contrast thresholds and whether the change is specific to the color of the hallucination.
   Methods: We prospectively categorized each patient's hallucinations using the Institute of Psychiatry Visual Hallucinations Interview. We measured color contrast thresholds with a computerized test designed to assess red-green and blue-yellow color confusion axes against a background of luminance noise. We calculated the ratio of red-green threshold to blue-yellow threshold (R-G/B-Y ratio) for each patient. Because central vision was impaired in all patients, we used a sectoral annular stimulus that projected to the retina at 12.5 degrees eccentricity.
   Results: There were 10 patients with age-related macular degeneration and CBS who were hallucinating in a predominant color or combination of colors at the time of recruitment. Patients hallucinating in red, green, or a combination of red and green had R-G/B-Y ratios of less than 1.0 (n = 5). Patients hallucinating in blue, yellow, or a combination of blue and yellow had R-G/B-Y ratios of greater than 1.0 (n = 2). Patients hallucinating in purple had ratios between the red-green and blue-yellow hallucinators (n = 2). The I patient hallucinating in white had the lowest thresholds for red-green and blue-yellow confusion axes. Comparing the R-G/B-Y ratios for the "red/green hallucinators" and "blue/yellow hallucinators" returned a significant result with Fisher's exact test (P = 0.047, n = 7).
   Conclusions: Deafferentation and secondary cortical hyperexcitability in CBS have a correlate in psychophysical threshold. This change in sensitivity relates specifically to the hallucinated color axis rather than across all colors. This is the first published evidence for cerebral hyperexcitability leading to a decrease in color contrast thresholds.
C1 [Madill, Stephen A.; Lascaratos, Gerassimos] Princess Alexandra Eye Pavil, Edinburgh EH3 9HA, Midlothian, Scotland.
   [Arden, Geoffrey B.] City Univ London, Dept Visual Sci, Henry Wellcome Labs, London EC1V 0HB, England.
   [Ffytche, Dominic H.] Inst Psychiat, London, England.
C3 City University London; University of London; King's College London
RP Madill, SA (通讯作者)，Princess Alexandra Eye Pavil, Chalmers St, Edinburgh EH3 9HA, Midlothian, Scotland.
EM samadill@hotmail.com
RI ffytche, Dominic/ABD-8214-2021; Lascaratos, Gerassimos/AAL-6344-2020
OI ffytche, Dominic/0000-0002-4214-9642; Arden,
   Geoffrey/0000-0001-7334-2026
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NR 27
TC 5
Z9 5
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1070-8022
EI 1536-5166
J9 J NEURO-OPHTHALMOL
JI J. Neuro-Ophthal.
PD SEP
PY 2009
VL 29
IS 3
BP 192
EP 196
DI 10.1097/WNO.0b013e3181b1b2bf
PG 5
WC Clinical Neurology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Neurosciences & Neurology; Ophthalmology
GA 497HF
UT WOS:000270048700005
PM 19726940
DA 2022-11-30
ER

PT J
AU Brown, MM
   Brown, GC
   Brown, HC
   Peet, J
AF Brown, Melissa M.
   Brown, Gary C.
   Brown, Heidi C.
   Peet, Jonathan
TI A value-based medicine analysis of ranibizumab for the treatment of
   subfoveal neovascular macular degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID INCREMENTAL COST-EFFECTIVENESS; QUALITY-OF-LIFE; TIME TRADE-OFF;
   CHOROIDAL NEOVASCULARIZATION; LASER PHOTOCOAGULATION; PHOTODYNAMIC
   THERAPY; UTILITY VALUES; DIABETIC-RETINOPATHY; CLINICAL-TRIALS;
   SECONDARY
AB Objective: To assess the conferred value and average cost-utility (cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD).
   Design: Value-based medicine cost-utility analysis.
   Participants: MARINA (Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD) Study patients utilizing published primary data.
   Methods: Reference case, third-party insurer perspective, cost-utility analysis using 2006 United States dollars.
   Main Outcome Measures: Conferred value in the forms of (1) quality-adjusted life-years (QALYs) and (2) percent improvement in health-related quality of life. Cost-utility is expressed in terms of dollars expended per QALY gained. All outcomes are discounted at a 3% annual rate, as recommended by the Panel on Cost-effectiveness in Health and Medicine. Data are presented for the second-eye model, first-eye model, and combined model.
   Results: Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization. The reference case treatment cost is $52 652, and the cost-utility for the second-eye model is $50 691/QALY. The quality-of-life gain from the first-eye model is 6.4% and the cost-utility is $123 887, whereas the most clinically simulating combined model yields a quality-of-life gain of 10.4% and cost-utility of $74 169.
   Conclusions: By conventional standards and the most commonly used second-eye and combined models, intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in randomized clinical trials.
C1 [Brown, Melissa M.; Brown, Gary C.; Brown, Heidi C.; Peet, Jonathan] Ctr Value Based Med, Flourtown, PA 19031 USA.
   [Brown, Melissa M.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Brown, Melissa M.; Brown, Gary C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
   [Brown, Gary C.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Retina Serv, Philadelphia, PA 19107 USA.
   [Brown, Melissa M.; Brown, Gary C.] Eye Res Inst, Philadelphia, PA USA.
C3 University of Pennsylvania; University of Pennsylvania; Jefferson
   University
RP Brown, MM (通讯作者)，Ctr Value Based Med, Box 335, Flourtown, PA 19031 USA.
EM mbrown@valuebasedmedicine.com
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NR 48
TC 76
Z9 76
U1 0
U2 10
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 JUN
PY 2008
VL 115
IS 6
BP 1039
EP 1045
DI 10.1016/j.ophtha.2007.08.033
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 306XX
UT WOS:000256282800018
PM 17976724
DA 2022-11-30
ER

PT J
AU Efstathiou, NE
   Moustafa, GA
   Maidana, DE
   Konstantinou, EK
   Notomi, S
   Barbisan, PRT
   Georgakopoulos, CD
   Miller, JW
   Vavvas, DG
AF Efstathiou, Nikolaos E.
   Moustafa, Giannis A.
   Maidana, Daniel E.
   Konstantinou, Eleni K.
   Notomi, Shoji
   Barbisan, Paulo R. T.
   Georgakopoulos, Constantine D.
   Miller, Joan W.
   Vavvas, Demetrios G.
TI Acadesine suppresses TNF-alpha induced complement component 3 (C3), in
   retinal pigment epithelial (RPE) cells
SO PLOS ONE
LA English
DT Article
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; HIGH-RISK;
   5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE; CHOROIDAL NEOVASCULARIZATION;
   GENE-EXPRESSION; RARE VARIANTS; FACTOR-B; ACTIVATION; AMPK
AB Rationale
   Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-alpha) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-alpha induced C3 in RPE cells.
   Methods
   ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-alpha was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis.
   Results
   Acadesine suppresses TNF-alpha induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine's effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it's action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn't prevent acadesine from decreasing TNF-alpha induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK alpha catalytic subunit did not affect the inhibitory effect of acadesine on TNF-alpha upregulation of C3.
   Conclusions
   Our results suggest that acadesine suppresses TNF-alpha induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.
C1 [Efstathiou, Nikolaos E.; Moustafa, Giannis A.; Maidana, Daniel E.; Konstantinou, Eleni K.; Notomi, Shoji; Barbisan, Paulo R. T.; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Med Sch, Massachusetts Eye & Ear, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA.
   [Georgakopoulos, Constantine D.] Univ Patras, Med Sch, Dept Ophthalmol, Patras, Greece.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; University of Patras
RP Vavvas, DG (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA.
EM Demetrios_Vavvas@MEEI.HARVARD.EDU
OI Efstathiou, Nikolaos/0000-0002-6635-0391
FU STAMATIOU Foundation; New England Hellenic Medical and Dental Society;
   National Eye Institute [R01EY025362-01, R21EY023079-01/A1]
FX This work was supported by STAMATIOU Foundation Scholarship (N.E.E), New
   England Hellenic Medical and Dental Society Scholarship (N.E.E),
   National Eye Institute, R01EY025362-01 (D.G.V), National Eye Institute,
   R21EY023079-01/A1 (D.G.V).
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NR 87
TC 2
Z9 2
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 DEC 23
PY 2020
VL 15
IS 12
AR e0244307
DI 10.1371/journal.pone.0244307
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA PL4CI
UT WOS:000603071600062
PM 33362238
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Zhu, ZT
   Liao, H
   Wang, W
   Scheetz, J
   Zhang, J
   He, MG
AF Zhu, Zhuoting
   Liao, Huan
   Wang, Wei
   Scheetz, Jane
   Zhang, Jian
   He, Mingguang
TI Visual Impairment and Major Eye Diseases in Chronic Kidney Disease: The
   National Health and Nutrition Examination Survey, 2005-2008
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL MICROVASCULAR ABNORMALITIES; AGE-RELATED MACULOPATHY;
   CYSTATIN-C; VISION IMPAIRMENT; CATARACT-SURGERY; UNITED-STATES; MACULAR
   DEGENERATION; RENAL-INSUFFICIENCY; VESSEL DIAMETERS; RISK-FACTOR
AB PURPOSE: To investigate the prevalence and associations of visual impairment (VI) and major eye diseases with chronic kidney disease (CKD) in the United States.
   DESIGN: Cross-sectional study.
   METHODS: We investigated the prevalence and associations of VI and major eye diseases with CKD among 5,518 participants aged 40 years or older in the 2005-2008 National Health and Nutrition Examination Survey. An estimated glomerular filtration rate of lower than 60 mL/min/1.73 m(2) was defined as CKD. Corrected visual acuity of worse than 20/40 in the better-seeing eye was defined as VI. Major eye diseases, including any ocular disease, any objectively determined ocular disease, cataract surgery, any retinopathy, diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma were evaluated from questionnaire or retinal photographs using standardized grading protocols.
   RESULTS: The prevalence of VI and major eye diseases were approximately 2- to 7-fold higher in participants with CKD than in those without (all P < .05). After controlling for multiple confounders, the presence of CKD was associated with VI (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.14-3.54), any ocular disease (OR: 1.65, 95% CI: 1.22-2.22), any objectively determined ocular disease (OR: 1.52, 95% CI: 1.06-2.19), any retinopathy (OR: 1.70, 95% CI: 1.18-2.45), and DR (OR: 2.34, 95% CI: 1.23-4.42). There was no association of CKD with cataract surgery, AMD, or glaucoma. A significant association between CKD and any ocular disease was observed among nondiabetic participants. The presence of CKD was closely related to VI and any retinopathy among diabetic participants.
   CONCLUSIONS: This nationally representative sample of the US population demonstrated high prevalence and strong associations of VI and major eye diseases with CKD, highlighting the importance of ocular screening among CKD patients and potential common pathogenesis underlying these conditions. (C) 2020 Elsevier Inc. All rights reserved.
C1 [Zhu, Zhuoting; Wang, Wei; Zhang, Jian; He, Mingguang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China.
   [Liao, Huan] Univ Bonn, Inst Reconstruct Neurobiol, Neural Regenerat Grp, Bonn, Germany.
   [Scheetz, Jane] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Australia.
C3 Sun Yat Sen University; University of Bonn; Centre for Eye Research
   Australia; University of Melbourne
RP He, MG (通讯作者)，Zhongshan Ophthalm Ctr, Guangzhou 510060, Peoples R China.
EM mingguang.he@unimelb.edu.au
RI He, Mingguang/AAY-5239-2020; Wang, Wei/J-4000-2016
OI He, Mingguang/0000-0002-6912-2810; Wang, Wei/0000-0002-5273-3332
FU FUNDAMENTAL RESEARCH FUNDS OF THE STATE KEY Laboratory in Ophthalmology;
   University of Melbourne at Research Accelerator Program; CERA Foundation
FX THE PRESENT WORK WAS SUPPORTED BY FUNDAMENTAL RESEARCH FUNDS OF THE
   STATE KEY Laboratory in Ophthalmology. Mingguang He receives support
   from the University of Melbourne at Research Accelerator Program and the
   CERA Foundation. The Centre for Eye Research Australia receives
   Operational Infrastructure Support from the Victorian State Government.
   The sponsor or funding organization had no role in the design or conduct
   of this research.
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NR 62
TC 7
Z9 7
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAY
PY 2020
VL 213
BP 24
EP 33
DI 10.1016/j.ajo.2020.01.002
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LK8GN
UT WOS:000531098400006
PM 31945332
DA 2022-11-30
ER

PT J
AU Brown, EE
   DeWeerd, AJ
   Ildefonso, CJ
   Lewin, AS
   Ash, JD
AF Brown, Emily E.
   DeWeerd, Alexander J.
   Ildefonso, Cristhian J.
   Lewin, Alfred S.
   Ash, John D.
TI Mitochondrial oxidative stress in the retinal pigment epithelium (RPE)
   led to metabolic dysfunction in both the RPE and retinal photoreceptors
SO REDOX BIOLOGY
LA English
DT Article
DE Retina; SOD2; AMD; Mitochondria
ID MACULAR DEGENERATION; CONE SURVIVAL; DNA; MICE; BEVACIZUMAB; EXPRESSION;
   RESISTANCE; MUTATION; DAMAGE; CELLS
AB Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world. Recent evidence suggests that RPE and photoreceptors have an interconnected metabolism and that mitochondrial damage in RPE is a trigger for degeneration in both RPE and photoreceptors in AMD. To test this hypothesis, this study was designed to induce mitochondrial damage in RPE in mice to determine whether this is sufficient to cause RPE and photoreceptor damage characteristic of AMD. In this study, we conditionally deleted the gene encoding the mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD encoded by Sod2) in the retinal pigment epithelium (RPE) of albino BALB/cJ mice. VMD2-Cre;Sod2(flox/flox) BALB/cJ mice were housed in either 12-h dark, 12-h 200 lux white lighting (normal light), or 12-h dark, 12-h < 10 lux red lighting (dim light). Electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT) were performed to assess retinal function and morphology. Immunofluorescence was used to examine protein expression; quantitative RT-PCR was used to measure gene expression. Sod2 knockout (KO) mice had reduced RPE function with age and increased oxidative stress compared to wild type (WT) controls as expected by the cell-specific deletion of Sod2. This was associated with alterations in RPE morphology and the structure and function of RPE mitochondria. In addition, data show a compensatory increase in RPE glycolytic metabolism. The metabolic shift in RPE correlated with severe disruption of photoreceptor mitochondria including a reduction in TOMM20 expression, mitochondrial fragmentation, and reduced COXIII/beta-actin levels. These findings demonstrate that mitochondrial oxidative stress can lead to RPE dysfunction and metabolic reprogramming of RPE. Secondary to these changes, photoreceptors also undergo metabolic stress with increased mitochondrial damage. These data are consistent with the hypothesis of a linked metabolism between RPE and photoreceptors and suggest a mechanism of retinal degeneration in dry AMD.
C1 [Brown, Emily E.; DeWeerd, Alexander J.; Ildefonso, Cristhian J.; Ash, John D.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Brown, Emily E.] Univ Florida, Clin & Translat Sci Inst, Gainesville, FL 32610 USA.
   [Lewin, Alfred S.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of Florida; State
   University System of Florida; University of Florida; State University
   System of Florida; University of Florida
RP Ash, JD (通讯作者)，Univ Florida, 1600 SW Archer Rd, Gainesville, FL 32610 USA.
EM jash@ufl.edu
RI Ildefonso, Cristhian/AAC-3576-2021
OI Brown, Emily/0000-0003-0658-074X; Lewin, Alfred/0000-0002-4192-9727
FU National Center for Advancing Translational Sciences of the National
   Institutes of Health [UL1TR001427, R01 EY026268, R01 EYO16459];
   Foundation Fighting Blindness; Research to Prevent Blindness; NATIONAL
   CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001427] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [R01EY016459, R01EY026268]
   Funding Source: NIH RePORTER
FX Research reported in this publication was supported by the National
   Center for Advancing Translational Sciences of the National Institutes
   of Health under Award Number UL1TR001427, R01 EY026268 and R01 EYO16459.
   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 comes from the Foundation Fighting Blindness
   and an unrestricted grant from Research to Prevent Blindness. These
   funding organizations had no role in the design or conduct of this
   research.
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NR 45
TC 85
Z9 86
U1 4
U2 11
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD JUN
PY 2019
VL 24
AR 101201
DI 10.1016/j.redox.2019.101201
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA IC8TS
UT WOS:000471255400032
PM 31039480
OA Green Published, gold
DA 2022-11-30
ER

EF