﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Ildefonso, CJ
   Jaime, H
   Rahman, MM
   Li, QH
   Boye, SE
   Hauswirth, WW
   Lucas, AR
   McFadden, G
   Lewin, AS
AF Ildefonso, Cristhian J.
   Jaime, Henrique
   Rahman, Masmudur M.
   Li, Qiuhong
   Boye, Shannon E.
   Hauswirth, William W.
   Lucas, Alexandra R.
   McFadden, Grant
   Lewin, Alfred S.
TI Gene Delivery of a Viral Anti-Inflammatory Protein to Combat Ocular
   Inflammation
SO HUMAN GENE THERAPY
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; ENDOTOXIN-INDUCED UVEITIS; PIGMENT
   EPITHELIAL-CELLS; ADENOASSOCIATED VIRUS; MACULAR DEGENERATION; NLRP3
   INFLAMMASOME; OXIDATIVE STRESS; MYXOMA VIRUS; ACTIVATION; INNATE
AB Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with the proinflammatory signaling pathways involving both the NLRP3 inflammasome and NF-kappa B. We have developed and characterized an adeno-associated viral (AAV) vector that delivers a secretable and cell-penetrating form of the M013 protein (TatM013). The expressed TatM013 protein was secreted and blocked the endotoxin-induced secretion of interleukin (IL)-1 beta in monocyte-derived cells and the reactive aldehyde-induced secretion of IL-1 beta in retinal pigment epithelium cells. The local anti-inflammatory effects of AAV-delivered TatM013 were evaluated in an endotoxin-induced uveitis (EIU) mouse model after intravitreal injection of mice with an AAV2-based vector carrying either TatM013 fused to a secreted green fluorescent protein (GFP) tag (sGFP-TatM013) or GFP. Expression of the sGFP-TatM013 transgene was demonstrated by fluorescence funduscopy in living mice. In EIU, the number of infiltrating cells and the concentration of IL-1 beta in the vitreous body were significantly lower in the eyes injected with AAV-sGFP-TatM013 compared with the eyes injected with control AAV-GFP. These results suggest that a virus-derived inhibitor of the innate immune response, when delivered via AAV, could be a generalized therapy for various inflammatory diseases of the eye.
C1 [Ildefonso, Cristhian J.; Rahman, Masmudur M.; McFadden, Grant; Lewin, Alfred S.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
   [Jaime, Henrique] Univ Florida, Dept Biol, Coll Liberal Arts & Sci, Gainesville, FL 32611 USA.
   [Li, Qiuhong; Boye, Shannon E.; Hauswirth, William W.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Lucas, Alexandra R.] Univ Florida, Coll Med, Dept Med, Div Cardiovasc Med, 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; State University System of
   Florida; University of Florida
RP Lewin, AS (通讯作者)，Univ Florida, Coll Med, Dept Mol Genet & Microbiol, 1200 Newell Dr,POB 100266, Gainesville, FL 32610 USA.
EM lewin@ufl.edu
RI Ildefonso, Cristhian/AAC-3576-2021
OI Ildefonso, Cristhian/0000-0001-6179-720X; Lewin,
   Alfred/0000-0002-4192-9727; McFadden, Grant/0000-0002-2556-3526;
   hauswirth, william/0000-0002-3244-4947; Boye,
   Shannon/0000-0002-7312-3197
FU National Eye Institute [R01 EY02025]; Florida Biomedical Research
   Foundation [e-10KG-s]; Macula Vision Research Foundation; NEI [P30
   EY02172]; NIAID [R01 AI100987]; NATIONAL EYE INSTITUTE [P30EY021721,
   R01EY024280, R24EY022023] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI100987] Funding
   Source: NIH RePORTER
FX The authors acknowledge the technical help of Mr. James Thomas, Jr. for
   the preparation of plasmids for viral packaging. The authors also thank
   Dr. Zhaoyang Wang and Brian Rossmiller for help with animal injections.
   The authors thank Mr. Vince Chiodo (UF Vector Core Laboratory) for
   production of the vectors used in these experiments. Finally, the
   authors appreciate the thoughtful review of this manuscript by Dr.
   Chulbul Ahmed. This research was funded by grants from the National Eye
   Institute (R01 EY02025) and the Florida Biomedical Research Foundation
   (e-10KG-s), and by the Macula Vision Research Foundation. Core
   facilities were supported by NEI grant P30 EY02172. The G.M. laboratory
   is supported by NIAID R01 AI100987. Author contributions: C.J.I. and
   A.S.L. designed experiments. C.J.I. and H.J. conducted the experiments
   and analyzed the data. C.J.I., H.J., M.M.R., Q.L., S.E.B., W.W.H.,
   A.R.L., G.M., and A.S.L. contributed to manuscript preparation and
   review.
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NR 48
TC 18
Z9 18
U1 0
U2 14
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JAN 1
PY 2015
VL 26
IS 1
BP 59
EP 68
DI 10.1089/hum.2014.089
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA AZ6DC
UT WOS:000348307700006
PM 25420215
OA Green Published
DA 2022-11-30
ER

PT J
AU Fraczek, LA
   Martin, CB
   Martin, BK
AF Fraczek, Laura A.
   Martin, Carol B.
   Martin, Brian K.
TI c-Jun and c-Fos regulate the complement factor H promoter in murine
   astrocytes
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Complement; Complement factor H; Astrocyte; c-Jun; c-Fos; Transcription
ID ANTIGEN-PRESENTING CELLS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES;
   HEMOLYTIC-UREMIC SYNDROME; POLYMERASE CHAIN-REACTION; MESSENGER-RNA
   EXPRESSION; ALTERNATIVE PATHWAY; ALZHEIMERS-DISEASE; DIFFERENTIAL
   MODULATION; MACULAR DEGENERATION; ENDOTHELIAL-CELLS
AB The complement system is a critical component of innate immunity that requires regulation to avoid inappropriate activation. This regulation is provided by many proteins, including complement factor H (CFH), a critical regulator of the alternative pathway of complement activation. Given its regulatory function, mutations in CFH have been implicated in diseases such as age-related macular degeneration and membranoproliferative glomerulonephritis, and central nervous system diseases such as Alzheimer's disease, Parkinson's disease, and a demyelinating murine model, experimental autoimmune encephalomyelitis (EAE). There have been few investigations on the transcriptional regulation of CFH in the brain and CNS. Our studies show that CFH mRNA is present in several CNS cell types. The murine CFH (mCFH) promoter was cloned and examined through truncation constructs and we show that specific regions throughout the promoter contain enhancers and repressors that are positively regulated by inflammatory cytokines in astrocytes. Database mining of these regions indicated transcription factor binding sites conserved between different species, which led to the investigation of specific transcription factor binding interactions in a 241 base pair (bp) region at -416 bp to -175 bp that showed the strongest activity. Through supershift analysis, it was determined that c-Jun and c-Fos interact with the CFH promoter in astrocytes in this region. These results suggest a relationship between cell cycle and complement regulation, and how these transcription factors and CFH affect disease will be a valuable area of investigation. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Martin, Carol B.; Martin, Brian K.] New Link Genet Corp, Ames, IA 50010 USA.
   [Fraczek, Laura A.] Univ Iowa, Interdisciplinary Program Immunol, Med Res Ctr 357, Iowa City, IA 52242 USA.
   [Fraczek, Laura A.] Iowa Canc Res Fdn, Urbandale, IA 50322 USA.
C3 University of Iowa
RP Martin, BK (通讯作者)，New Link Genet Corp, 2901 S Loop Dr Ste 3900, Ames, IA 50010 USA.
EM bmartin@linkp.com
OI Martin, Brian/0000-0002-4873-5351
FU NINDS NIH HHS [R21 NS056364-03] Funding Source: Medline; NATIONAL
   INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS056364] Funding
   Source: NIH RePORTER
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NR 78
TC 12
Z9 12
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD OCT-NOV
PY 2011
VL 49
IS 1-2
BP 201
EP 210
DI 10.1016/j.molimm.2011.08.013
PG 10
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA 862TU
UT WOS:000298117800023
PM 21920606
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Alcazar, O
   Cousins, SW
   Striker, GE
   Marin-Castano, ME
AF Alcazar, Oscar
   Cousins, Scott W.
   Striker, Gary E.
   Marin-Castano, Maria E.
TI (Pro)renin receptor is expressed in human retinal pigment epithelium and
   participates in extracellular matrix remodeling
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE (pro)renin receptor; prorenin; age-related macular degeneration; retinal
   pigment epithelium; hypertension
ID NONPROTEOLYTICALLY ACTIVATED PRORENIN; MACULAR DEGENERATION;
   RISK-FACTORS; ANGIOTENSIN-II; CHOROIDAL NEOVASCULARIZATION;
   RENIN/PRORENIN RECEPTOR; GEOGRAPHIC ATROPHY; TRANSGENIC RATS; MESANGIAL
   CELLS; OXIDANT INJURY
AB The (pro)renin receptor (PRR) is believed to potentiate the renin-angiotensin system (RAS), conferring to prorenin, a likely pathological role at tissue level. The PRR has been identified in the microvascular endothelial cells of the retina, in which it seems to be involved in pathological neovascularization processes. In the present study, we sought to explore PRR expression and prorenin action in human retinal pigment epithelium (RPE) cells, as well as its potential implication in extracellular matrix (ECM) turnover. Isolated RPE cells from donor human eyes as well as freshly isolated human retinas demonstrated expression of PRR at mRNA and protein levels. Moreover, we demonstrate that PRR expressed in the RPE cells is functional, as shown by prorenin-induced increases in Erk1/2 phosphorylation. PRR expression was also shown to be regulated by its main physiological agonist prorenin. We found evidence that the PRR may be involved in ECM-remodeling processes through a prorenin-induced upregulation of type I collagen. Immunostaining analysis of human retinas revealed higher PRR and type I collagen expression in the RPE of eye donors with dry age-related macular degeneration (AMD) and hypertension, supporting the in vitro findings using human-isolated RPE cells. Taken together, the present study demonstrates for the first time that the PRR is expressed in human RPE and suggests a molecular mechanism by which hypertension may exacerbate the pathology of dry AMD. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Alcazar, Oscar; Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Cousins, Scott W.] Duke Univ, Duke Ctr Macular Dis, Durham, NC 27710 USA.
   [Striker, Gary E.] Mt Sinai Sch Med, Div Diabet & Aging Res, New York, NY 10029 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Duke University; Icahn
   School of Medicine at Mount Sinai
RP Marin-Castano, ME (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM Mcastano@med.miami.edu
FU NIH [R01-EY015249-01A1, EY015249-01A1S1, P30-EY14801]; NATIONAL EYE
   INSTITUTE [R01EY015249, P30EY014801] Funding Source: NIH RePORTER
FX This study was supported by NIH Grants R01-EY015249-01A1 and
   EY015249-01A1S1, and an unrestricted grant by Research to Prevent
   Blindness P30-EY14801. Expert advice by Hinda Boutrid and Yolanda Pina
   is appreciated.
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NR 50
TC 23
Z9 25
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2009
VL 89
IS 5
BP 638
EP 647
DI 10.1016/j.exer.2009.06.014
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 507KA
UT WOS:000270850800006
PM 19580809
DA 2022-11-30
ER

PT J
AU Cano, MD
   Karagiannis, ED
   Soliman, M
   Bakir, B
   Zhuang, WJ
   Popel, AS
   Gehlbach, PL
AF Cano, Marisol del Valle
   Karagiannis, Emmanouil D.
   Soliman, Mohamed
   Bakir, Belal
   Zhuang, Wenjuan
   Popel, Aleksander S.
   Gehlbach, Peter L.
TI A Peptide Derived from Type 1 Thrombospondin Repeat-Containing Protein
   WISP-1 Inhibits Corneal and Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OCULAR NEOVASCULARIZATION; DIABETIC-RETINOPATHY; ENDOTHELIAL-CELLS;
   ANGIOGENESIS; MODEL; PROLIFERATION; MIGRATION; MICE
AB PURPOSE. Ocular neovascularization is the primary cause of blindness in a wide range of prevalent ocular diseases including proliferative diabetic retinopathy, exudative age-related macular degeneration, and retinopathy of prematurity, among others. Antiangiogenic therapies are starting to give promising results in these diseases. In the present study the antiangiogenic potential of an 18-mer peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 (wispostatin-1) was analyzed in vitro with human retinal endothelial cell proliferation and migration assays. The peptide was also tested in vivo in the corneal micropocket and the laser-induced choroidal neovascularization (CNV) mouse models.
   METHODS. Human retinal endothelial cells were treated with the WISP-1 peptide and in vitro migration and proliferation assays were performed. Also evaluated was the antiangiogenic effect of this peptide in vivo using the corneal micropocket assay and the laser-induced CNV model.
   RESULTS. Wispostatin-1 derived peptide demonstrated antimigratory and antiproliferative activity in vitro. Wispostatin-1 completely abolished bFGF-induced neovascularization in the corneal micropocket assay. The peptide also demonstrated significant inhibition of laser-induced CNV.
   CONCLUSIONS. An inhibitory effect of Wispostatin-1 on ocular neovascularization was found in vitro and in vivo. The identification of novel and potent endogenous peptide inhibitors provides insight into the pathogenesis of corneal and choroidal neovascularization. The results demonstrate potential for therapeutic application in prevalent ocular disease. (Invest Ophthalmol Vis Sci. 2009; 50: 3840-3845) DOI: 10.1167/iovs.08-2607
C1 [Gehlbach, Peter L.] Johns Hopkins Univ, Sch Med, Retina Div, Wilmer Eye Inst,Dept Ophthalmol, Baltimore, MD 21231 USA.
   [Karagiannis, Emmanouil D.; Popel, Aleksander S.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University
RP Gehlbach, PL (通讯作者)，Johns Hopkins Univ, Sch Med, Retina Div, Wilmer Eye Inst,Dept Ophthalmol, 1550 Orleans St, Baltimore, MD 21231 USA.
EM pgelbach@jhmi.edu
RI Popel, Aleksander S/A-6724-2009; Karagiannis, Emmanouil D./CAA-0759-2022
OI Karagiannis, Emmanouil/0000-0003-0131-6552; Popel,
   Aleksander/0000-0002-6706-9235
FU Fight for Sight (MdC); Sheila West Research Grant Award (MdC); JG
   Foundation (PLG); Prevent Blindness (Wilmer Eye Institute); Research to
   Prevent Blindness Career Development award (PLG); Jack and Gail Baylin
   Philanthropic Fund; Johns Hopkins University Fund for Medical Discovery
   (PLG); Kenneth and Brenda Richardson (PLG)
FX Supported by Fight for Sight (MdC), the Sheila West Research Grant Award
   (MdC), the JG Foundation (PLG); an unrestricted grant from Research to
   Prevent Blindness (Wilmer Eye Institute); a Research to Prevent
   Blindness Career Development award (PLG); the Jack and Gail Baylin
   Philanthropic Fund; the Johns Hopkins University Fund for Medical
   Discovery (PLG); a gift from Kenneth and Brenda Richardson (PLG), and a
   gift form Mr. and Mrs. George Laniado.
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NR 28
TC 16
Z9 16
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2009
VL 50
IS 8
BP 3840
EP 3845
DI 10.1167/iovs.08-2607
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 475XA
UT WOS:000268398000040
PM 19279315
DA 2022-11-30
ER

PT J
AU McLaughlin, BJ
   Fan, W
   Zheng, JJ
   Cai, H
   Del Priore, LV
   Bora, NS
   Kaplan, HJ
AF McLaughlin, BJ
   Fan, W
   Zheng, JJ
   Cai, H
   Del Priore, LV
   Bora, NS
   Kaplan, HJ
TI Novel role for a complement regulatory protein (CD46) in retinal pigment
   epithelial adhesion
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MEMBRANE COFACTOR PROTEIN; HUMAN BRUCHS MEMBRANE; MEASLES-VIRUS; MACULAR
   DEGENERATION; MULTIPLE ISOFORMS; SUPPRESSOR GENE; PLASMA-MEMBRANE;
   HUMAN-MELANOMA; CELL-ADHESION; PDZ DOMAINS
AB PURPOSE. There is increasing evidence that the complement system may play a significant role in one of the leading diseases causing blindness in the elderly population, age-related macular degeneration. In this study, a novel role in the retina for a regulatory protein in the complement system, CD46, is proposed.
   METHODS. The retinal pigment epithelium (RPE) was obtained from human donor eyes as well as human immortalized RPE cell lines (ARPE19). Immunohistochemistry and confocal microscopy were used to immunolocalize CD46 and beta1 integrin. Immunoprecipitation experiments with antibodies to either CD46 or beta1 integrin were performed on RPE cell lysates. A cell adhesion assay was used to determine the proportion of RPE cells that adhere to Bruch's membrane explants from donor eyes.
   RESULTS. Immunohistochemistry and confocal microscopy demonstrated that CD46 was polarized to the basal surface of the RPE along with beta1 integrin, shown previously to be involved in RPE adhesion. Immunoprecipitation experiments demonstrated that CD46 and 01 integrin coprecipitated from RPE cell lysates when either protein was used as the precipitating antibody. The adhesion assay showed that antibodies to either CD46 or beta1 integrin reduced RPE adhesion to the surface of Bruch's membrane compared with the control.
   CONCLUSIONS. These findings suggest that this complement regulatory protein, which protects host cells from autologous complement attack, may have a functional interaction with beta1 integrin in the eye that is related to RPE adhesion to its basement membrane and Bruch's membrane.
C1 Univ Louisville, Sch Med, Kentucky Lions Eye Ctr, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
   Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
C3 University of Louisville; Columbia University
RP McLaughlin, BJ (通讯作者)，Univ Louisville, Sch Med, Kentucky Lions Eye Ctr, Dept Ophthalmol & Visual Sci, 301 E Muhammad Ali Blvd, Louisville, KY 40292 USA.
FU NATIONAL EYE INSTITUTE [R01EY009730] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY09730] Funding Source: Medline
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NR 50
TC 40
Z9 40
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2003
VL 44
IS 8
BP 3669
EP 3674
DI 10.1167/iovs.02-0813
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 705EV
UT WOS:000184383500056
PM 12882822
DA 2022-11-30
ER

PT J
AU Ye, XQ
   Gaucher, JF
   Vidal, M
   Broussy, S
AF Ye, Xiaoqing
   Gaucher, Jean-Francois
   Vidal, Michel
   Broussy, Sylvain
TI A Structural Overview of Vascular Endothelial Growth Factors
   Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
SO MOLECULES
LA English
DT Review
DE vascular endothelial growth factors; ligands; structures;
   pharmacological inhibition; macromolecules; peptides
ID KINASE DOMAIN RECEPTOR; HEPARIN-BINDING DOMAIN; D-PROTEIN ANTAGONIST;
   ANTI-VEGF ANTIBODY; CRYSTAL-STRUCTURE; FACTOR-B; HIGH-AFFINITY; ORF
   VIRUS; TYROSINE KINASE; ANGSTROM RESOLUTION
AB The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed.
C1 [Ye, Xiaoqing; Vidal, Michel; Broussy, Sylvain] Univ Paris, CNRS, Fac Pharmacie Paris, CiTCoM,INSERM U 1268,CNRS 8038, F-75006 Paris, France.
   [Gaucher, Jean-Francois] Univ Paris, Fac Pharm Paris, Lab Cristallog & RMN Biol, CiTCoM,CNRS 8038, F-75006 Paris, France.
   [Vidal, Michel] Hop Cochin, AP HP, Serv Biol Medicament Toxicol, F-75014 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; Universite Paris Cite; UDICE-French Research
   Universities; Universite Paris Cite; Assistance Publique Hopitaux Paris
   (APHP); Hopital Universitaire Cochin - APHP; UDICE-French Research
   Universities; Universite Paris Cite
RP Broussy, S (通讯作者)，Univ Paris, CNRS, Fac Pharmacie Paris, CiTCoM,INSERM U 1268,CNRS 8038, F-75006 Paris, France.
EM xiaoqing.ye@etu.u-paris.fr; jean-francois.gaucher@u-paris.fr;
   michel.vidal@u-paris.fr; sylvain.broussy@u-paris.fr
RI Broussy, Sylvain/AAX-1833-2020
OI Broussy, Sylvain/0000-0003-3098-5317; YE, Xiaoqing/0000-0002-5912-3895
FU CNRS; INSERM; University of Paris; Chinese Scholarship Council
FX This research was funded by the CNRS, the INSERM, the University of
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NR 164
TC 1
Z9 1
U1 1
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD NOV
PY 2021
VL 26
IS 22
AR 6759
DI 10.3390/molecules26226759
PG 29
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 2I9OQ
UT WOS:000815300600001
PM 34833851
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Sanderson, E
   Spiller, W
   Bowden, J
AF Sanderson, Eleanor
   Spiller, Wes
   Bowden, Jack
TI Testing and correcting for weak and pleiotropic instruments in
   two-sample multivariable Mendelian randomization
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Cochran's Q-statistic; instrument strength; instrument validity;
   multivariable Mendelian randomization; two-sample Mendelian
   randomization
ID MACULAR DEGENERATION; INFERENCE; VARIABLES
AB Multivariable Mendelian randomization (MVMR) is a form of instrumental variable analysis which estimates the direct effect of multiple exposures on an outcome using genetic variants as instruments. Mendelian randomization and MVMR are frequently conducted using two-sample summary data where the association of the genetic variants with the exposures and outcome are obtained from separate samples. If the genetic variants are only weakly associated with the exposures either individually or conditionally, given the other exposures in the model, then standard inverse variance weighting will yield biased estimates for the effect of each exposure. Here, we develop a two-sample conditional F-statistic to test whether the genetic variants strongly predict each exposure conditional on the other exposures included in a MVMR model. We show formally that this test is equivalent to the individual level data conditional F-statistic, indicating that conventional rule-of-thumb critical values of F> 10, can be used to test for weak instruments. We then demonstrate how reliable estimates of the causal effect of each exposure on the outcome can be obtained in the presence of weak instruments and pleiotropy, by repurposing a commonly used heterogeneity Q-statistic as an estimating equation. Furthermore, the minimized value of this Q-statistic yields an exact test for heterogeneity due to pleiotropy. We illustrate our methods with an application to estimate the causal effect of blood lipid fractions on age-related macular degeneration.
C1 [Sanderson, Eleanor; Spiller, Wes; Bowden, Jack] Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England.
   [Sanderson, Eleanor; Spiller, Wes] Univ Bristol, Populat Hlth Sci, Bristol, Avon, England.
   [Bowden, Jack] Univ Exeter, Coll Med & Hlth, Exeter, Devon, England.
C3 University of Bristol; University of Bristol; University of Exeter
RP Sanderson, E (通讯作者)，Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England.
EM eleanor.sanderson@bristol.ac.uk
OI Bowden, Jack/0000-0003-2628-3304
FU Wellcome Trust [108902/B/15/Z]; Medical Research Council [MC_UU_00011/1,
   MC_UU_00011/2]
FX Medical Research Council, Grant/Award Numbers: MC_UU_00011/1,
   MC_UU_00011/2; Wellcome Trust, Grant/Award Number: 108902/B/15/Z
CR Alice R., 2019, 835819 BIORXIV
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U1 8
U2 8
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 10
PY 2021
VL 40
IS 25
BP 5434
EP 5452
DI 10.1002/sim.9133
EA AUG 2021
PG 19
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 WH8ZI
UT WOS:000679979100001
PM 34338327
OA Green Published, Green Submitted, hybrid
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Sikaroudi, MK
   Saraf-Bank, S
   Clayton, ZS
   Soltani, S
AF Khalighi Sikaroudi, Masoumeh
   Saraf-Bank, Sahar
   Clayton, Zachary S.
   Soltani, Sepideh
TI A positive effect of egg consumption on macular pigment and healthy
   vision: a systematic review and meta-analysis of clinical trials
SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
LA English
DT Review
DE egg; MPOD; lutein; meta&#8208; analysis
AB Increasing macular pigment optical density (MPOD) as a result of increased macular concentration of lutein and zeaxanthin may reduce the risk of age-related macular degeneration (AMD). The aim of the present study was to determine whether the consumption of eggs, a rich source of dietary lutein and zeaxanthin, influences MPOD and serum lutein. In this systematic review and meta-analysis we searched PubMed, Scopus, and ISI Web of Science up to July 2020, for relevant randomized clinical trials. Using a random-effects model, pooled weighted mean differences, and standard deviations (SDs) for each outcome were obtained. The quality of the eligible studies was assessed by the Cochrane Collaboration's tool. A meta-analysis of five trials (296 participants) revealed that egg consumption significantly increased MPOD (weighted mean differences (WMD): +0.037; 95% CI: 0.004, 0.069; P = 0.027) and serum lutein (WMD: +0.150 mu mol L-1; 95% CI: 0.037, 0.263; P = 0.009). Subgroup analyses showed that egg consumption: (a) had a larger effect on MPOD in studies with a parallel design; and (b) increased serum lutein to a greater extent in a healthy population. We did not detect any heterogeneity between studies. Daily egg consumption has beneficial effects on MPOD and serum lutein is inversely associated with reduced AMD progression. Further clinical trials are required to confirm the results of this study. (c) 2021 Society of Chemical Industry
C1 [Khalighi Sikaroudi, Masoumeh] Iran Univ Med Sci, Sch Publ Hlth, Dept Nutr, Tehran, Iran.
   [Saraf-Bank, Sahar] Isfahan Univ Med Sci, Sch Nutr & Food Sci, Dept Community Nutr, Food Secur Res Ctr, Esfahan, Iran.
   [Clayton, Zachary S.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA.
   [Soltani, Sepideh] Shahid Sadoughi Univ Med Sci, Nutr & Food Secur Res Ctr, Yazd 1449614535, Iran.
C3 Iran University of Medical Sciences; Isfahan University Medical Science;
   University of Colorado System; University of Colorado Boulder
RP Soltani, S (通讯作者)，Shahid Sadoughi Univ Med Sci, Nutr & Food Secur Res Ctr, Yazd 1449614535, Iran.
EM s.soltani1979@yahoo.com
OI Khalighi Sikaroudi, Masoumeh/0000-0002-1829-4591; Soltani,
   Sepideh/0000-0002-1591-2569
CR Berendschot TTJM, 2015, INVEST OPHTH VIS SCI, V56
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NR 42
TC 5
Z9 6
U1 2
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-5142
EI 1097-0010
J9 J SCI FOOD AGR
JI J. Sci. Food Agric.
PD AUG 15
PY 2021
VL 101
IS 10
BP 4003
EP 4009
DI 10.1002/jsfa.11109
EA FEB 2021
PG 7
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Chemistry; Food Science & Technology
GA SP6KI
UT WOS:000616112300001
PM 33491232
DA 2022-11-30
ER

PT J
AU Goldberg, RA
   Hill, LF
   Davis, T
   Ruiz, CQ
AF Goldberg, Roger A.
   Hill, Lauren F.
   Davis, Tatiana
   Quezada Ruiz, Carlos
TI Impact of Delayed Time to Treatment on Visual Outcomes in Neovascular
   AMD: Data From the HARBOR Study
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID 2.0 MG RANIBIZUMAB; MACULAR DEGENERATION; SUBGROUP ANALYSIS; EFFICACY;
   SAFETY
AB BACKGROUND AND OBJECTIVE: To determine the potential impact on visual outcomes of delayed treatment initiation in patients with neovascular age-related macular degeneration (nAMD).
   PATIENTS AND METHODS: Post hoc analysis of anti-vascular endothelial growth factor treatment-naive patients with nAMD from HARBOR. Time to treatment was defined as first ranibizumab injection date minus screening date. Comparisons were made between the prompt (<= 6 days) versus delayed (> 10 days) treatment groups. Main outcome measures were best-corrected visual acuity (BCVA) change over time, BCVA, number of ranibizumab injections, and proportion of 3-line gainers/losers.
   RESULTS: In HARBOR, more than 50% of patients received their first injection within 7 days of screening, with mean (median) time to treatment of 4.6 (5) and 15.9 (14) days for the prompt and delayed treatment groups, respectively. Mean (95% confidence interval [CI]) BCVA change from baseline to Month 24 was 9.1 (7.4-10.8) and 8.8 (6.7-10.8) Early Treatment Diabetic Retinopathy Study letters in the prompt (n = 395) and delayed (n = 230) treatment groups, respectively. Mean (95% CI) total number of ranibizumab injections for the as-needed arms was 12.4 (11.6-13.3) and 11.4 (10.3-12.4) for the prompt and delayed treatment groups, respectively.
   CONCLUSION: In HARBOR, time from screening to first ranibizumab injection did not seem to significantly affect mean BCVA change or number of injections.
C1 [Goldberg, Roger A.] Bay Area Retina Associates, 365 Lennon Lane,Suite 250, Walnut Creek, CA 94598 USA.
   [Hill, Lauren F.; Davis, Tatiana; Quezada Ruiz, Carlos] Genentech Inc, San Francisco, CA 94080 USA.
   [Quezada Ruiz, Carlos] Clin Ojos Garza Viejo, San Pedro Garza Garcia, Nuevo Leon, Mexico.
C3 Roche Holding; Genentech
RP Goldberg, RA (通讯作者)，Bay Area Retina Associates, 365 Lennon Lane,Suite 250, Walnut Creek, CA 94598 USA.
EM rgoldberg.eyemd@gmail.com
FU Genentech, Inc., a member of the Roche Group
FX Supported by Genentech, Inc., a member of the Roche Group, for the study
   and third-party writing assistance, which was provided by Jack W. Pike,
   PhD, of Envision Pharma Group.
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NR 17
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD FEB
PY 2021
VL 52
IS 2
BP 62
EP +
DI 10.3928/23258160-20210201-02
PG 9
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA QP0NF
UT WOS:000623533700002
PM 33626166
DA 2022-11-30
ER

PT J
AU Dietrich, M
   Hecker, C
   Nasiri, M
   Samsam, S
   Issberner, A
   Kohne, Z
   Hartung, HP
   Albrecht, P
AF Dietrich, Michael
   Hecker, Christina
   Nasiri, Milad
   Samsam, Sogol
   Issberner, Andrea
   Kohne, Zippora
   Hartung, Hans-Peter
   Albrecht, Philipp
TI Neuroprotective Properties of Dimethyl Fumarate Measured by Optical
   Coherence Tomography in Non-inflammatory Animal Models
SO FRONTIERS IN NEUROLOGY
LA English
DT Article
DE dimethyl fumarate; neuroprotection; optical coherence tomography; optic
   nerve crush; light-induced photoreceptor loss
ID PLACEBO-CONTROLLED PHASE-3; NERVE-FIBER LAYER; MULTIPLE-SCLEROSIS; ACID
   ESTERS; ORAL BG-12; PROTECTS; ACTIVATION; STRESS; RETINA; CELLS
AB While great advances have been made in the immunomodulatory treatment of multiple sclerosis (MS), there is still an unmet need for drugs with neuroprotective potential. Dimethyl fumarate (DMF) has been suggested to exert both immunomodulatory and neuroprotective effects in MS. To investigate if DMF has neuroprotective effects independent of immunomodulation we evaluated its effects in the non-inflammatory animal models of light-induced photoreceptor loss and optic nerve crush. This might also reveal applications for DMF besides MS, such as age related macular degeneration. Retinal neurodegeneration was longitudinally assessed by in vivo retinal imaging using optical coherence tomography (OCT), and glutathione (GSH) measurements as well as histological investigations were performed to clarify the mode of action. For light-induced photoreceptor loss, one eye of C57BL/6J mice was irradiated with a LED cold light lamp while for optic nerve crush the optic nerve was clamped behind the eye bulb. The other eye served as control. GSH was measured in the optic nerve, choroid and retina and immunohistological staining of retinal microglia (Iba1) was performed. Mice were treated with 15 or 30 mg DMF/kg bodyweight or vehicle. While no protective effects were observed in optic nerve crush, in the light-induced retinal degeneration model DMF treatment significantly reduced retinal degeneration. In these mice, GSH levels in the retina and surrounding choroid were increased and histological investigations revealed less microglial activation in the outer retinal layers, suggesting both antioxidant and anti-inflammatory effects.
C1 [Dietrich, Michael; Hecker, Christina; Nasiri, Milad; Samsam, Sogol; Issberner, Andrea; Kohne, Zippora; Hartung, Hans-Peter; Albrecht, Philipp] Heinrich Heine Univ Dusseldorf, Med Fac, Dept Neurol, Dusseldorf, Germany.
C3 Heinrich Heine University Dusseldorf
RP Albrecht, P (通讯作者)，Heinrich Heine Univ Dusseldorf, Med Fac, Dept Neurol, Dusseldorf, Germany.
EM phil.albrecht@gmail.com
RI Dietrich, Michael/GLR-9867-2022
FU Biogen; charitable Ilselore-Luckow Stiftung; charitable
   Dr.-Robert-Pfleger Stiftung
FX This work was supported by grants from Biogen, the charitable
   Ilselore-Luckow Stiftung and the charitable Dr.-Robert-Pfleger Stiftung
   to PA.
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NR 35
TC 3
Z9 3
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-2295
J9 FRONT NEUROL
JI Front. Neurol.
PD JAN 13
PY 2021
VL 11
AR 601628
DI 10.3389/fneur.2020.601628
PG 8
WC Clinical Neurology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA PY4BT
UT WOS:000611991500001
PM 33519681
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lee, WJA
   Yang, YHK
   Cheng, CL
AF Lee, Wan-Ju Annabelle
   Yang, Yea-Huei Kao
   Cheng, Ching-Lan
TI Risk ofage-relatedmacular degeneration in aspirin users
   andnon-aspirinusers: A population-based cohort study in Taiwan
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE age-related macular degeneration; AMD; aspirin; pharmacoepidemiology;
   population-based study
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; AGE-RELATED MACULOPATHY; ELDERLY
   CHINESE POPULATION; MACULAR DEGENERATION; PREVALENCE; STROKE; EYE
AB Background The association between cardioprotective aspirin and risk of age-related macular degeneration (AMD) is still controversial up to date. We aimed to analyze the risk of AMD between aspirin users and non-aspirin users. Method This was a retrospective cohort study by using claims data from the National Health Insurance Research Database. Patients aged more than 45 years old who initiated aspirin during 2002 to 2012 were followed till 2013. We first selected an age and sex-matched cohort, then identified aspirin users and non-aspirin users as propensity score-matched cohort. Cox proportional hazard regression model was applied to compare their hazards and 95% confidence intervals. Incidence of newly developed AMD, neovascular AMD, and other-AMD was calculated. Results We identified 204 085 regular aspirin users and 478 048 non-aspirin users from our datasets. The univariate HR was 2.85 (95% CI, 2.75-2.96), and the multivariate HR was 2.54 (95% CI, 2.44-2.65). In the PS-matched cohort, the HR was 2.38 (95% CI, 2.25-2.52). The incidence of aspirin users for AMD risk was 11.95 per 1000 person-year, while the incidence of non-aspirin users was only 3.92 per 1000 person-year. Conclusion Patients with regular use of aspirin had higher risk in developing AMD compared to non-aspirin users and suggest to have regular visual acuity and funduscopic examination.
C1 [Lee, Wan-Ju Annabelle] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Ophthalmol, Coll Med, Tainan, Taiwan.
   [Lee, Wan-Ju Annabelle; Yang, Yea-Huei Kao; Cheng, Ching-Lan] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Coll Med, Tainan, Taiwan.
   [Lee, Wan-Ju Annabelle] Chi Mei Med Ctr, Dept Ophthalmol, Tainan, Taiwan.
   [Yang, Yea-Huei Kao; Cheng, Ching-Lan] Natl Cheng Kung Univ, Sch Pharm, Coll Med, Tainan, Taiwan.
   [Yang, Yea-Huei Kao; Cheng, Ching-Lan] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan, Taiwan.
   [Cheng, Ching-Lan] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Pharm, Coll Med, 1 Univ Rd, Tainan 701, Taiwan.
C3 National Cheng Kung University; National Cheng Kung University Hospital;
   National Cheng Kung University; Chi Mei Hospital; National Cheng Kung
   University; National Cheng Kung University; National Cheng Kung
   University; National Cheng Kung University Hospital
RP Cheng, CL (通讯作者)，Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Pharm, Coll Med, 1 Univ Rd, Tainan 701, Taiwan.
EM clcheng@mail.ncku.edu.tw
RI Lee, Wan-Ju/AAC-7025-2020
OI Lee, Wan-Ju/0000-0002-9972-8899
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NR 40
TC 1
Z9 1
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD FEB
PY 2021
VL 30
IS 2
BP 178
EP 188
DI 10.1002/pds.5145
EA OCT 2020
PG 11
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA PO0HH
UT WOS:000577579600001
PM 33009703
DA 2022-11-30
ER

PT J
AU Huang, PR
   Sun, JR
   Wang, FH
   Luo, XT
   Zhu, H
   Gu, Q
   Sun, XJ
   Liu, T
   Sun, XD
AF Huang, Peirong
   Sun, Junran
   Wang, Fenghua
   Luo, Xueting
   Zhu, Hong
   Gu, Qing
   Sun, Xiangjun
   Liu, Te
   Sun, Xiaodong
TI DNMT1 and Sp1 competitively regulate the expression of BACE1 in
   A2E-mediated photo-oxidative damage in RPE cells
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Article
DE Age-related macular degeneration; Amyloid-beta; BACE1; DNA methylation;
   Sp1; Mithramycin A
ID RETINAL-PIGMENT EPITHELIUM; AMYLOID-BETA PRODUCTION; LIGHT-INDUCED
   DAMAGE; OXIDATIVE STRESS; LIPOFUSCIN FLUOROPHORE; MACULAR DEGENERATION;
   DNA METHYLATION; SECRETASE; ACCUMULATION; MECHANISMS
AB Numerous studies have focused on the deteriorate role of amyloid-beta (A beta) on retina, implying the potential pathogenic mechanism underlying age-related macular degeneration (AMD). However, the mechanism underlying the A beta deposition in AMD patients remains unknown. Beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), rate-limiting enzyme for A beta production, plays an important role in A beta deposition in the brain. In the current study, we aimed to clarify the regulation mechanism of BACE1 and explore potential drug targets using a lipofuscinfluorophore A2E-mediated photo-oxidation model. In this model, A beta(1.40) and A beta(1.42) levels increased simultaneously with the enhanced BACE1 expression. These changes were associated with the hypomethylation of specific loci within the BACE1 gene promoter and the decreased levels of DNA methyltransferase 1 (DNMT1). Furthermore, we noticed overlapping regions of differentially methylated CpG islands and specificity protein (Sp1) binding sites within the BACE1 promoter. We employed chromatin immunoprecipitation (ChIP) assay to verify that the decreased BACE1 promoter methylation by DNMT1 enabled increased binding between Sp1 and the BACE1 promoter, which further enhanced BACE1 transcription. The inhibition of Sp1 with mithramycin A (MTM) could down-regulate the expression of BACE1 as well as alleviate the RPE barrier morphology and function impairment. Our results for the first time show the competitive regulation of BACE1 by transcription factor Sp1 and DNMT1 after photo-oxidation and confirm the potential novel protective role of MTM on RPE cells.
C1 [Huang, Peirong; Sun, Junran; Wang, Fenghua; Luo, Xueting; Zhu, Hong; Gu, Qing; Sun, Xiaodong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Ophthalmol, 100 HaiNing Rd, Shanghai 200080, Peoples R China.
   [Huang, Peirong; Sun, Junran; Wang, Fenghua; Luo, Xueting; Zhu, Hong; Gu, Qing; Sun, Xiaodong] Shanghai Key Lab Fundus Dis, Shanghai, Peoples R China.
   [Sun, Xiangjun] Shanghai Jiao Tong Univ, Sch Biol & Agr, 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, Longhua Hosp, Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University; Yale
   University; Shanghai University of Traditional Chinese Medicine
RP Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Ophthalmol, 100 HaiNing Rd, Shanghai 200080, Peoples R China.; Liu, T (通讯作者)，Yale Univ, Sch Med, Dept Pathol, 10 Amistad St, New Haven, CT 06520 USA.
EM te.liu@yale.edu; xdsun@sjtu.edu.cn
OI Sun, Xiaodong/0000-0001-5015-0945
FU National Natural Science Foundation of China [81700843]; Shanghai
   Scholar Leadership Grant [XBR2013081]; Shanghai Jiao Tong University
   School of Medicine Precision Medicine Research Grant [15ZH4005];
   Shanghai Key Laboratory of Ocular Fundus Diseases [14DZ2272600]
FX This study was supported by the National Natural Science Foundation of
   China (81700843), a Shanghai Scholar Leadership Grant (XBR2013081), and
   a Shanghai Jiao Tong University School of Medicine Precision Medicine
   Research Grant (15ZH4005). Shanghai Key Laboratory of Ocular Fundus
   Diseases (14DZ2272600).
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NR 39
TC 6
Z9 6
U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
EI 1872-9754
J9 NEUROCHEM INT
JI Neurochem. Int.
PD DEC
PY 2018
VL 121
BP 59
EP 68
DI 10.1016/j.neuint.2018.09.001
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA HD5RD
UT WOS:000452586700007
PM 30273642
DA 2022-11-30
ER

PT J
AU Van den Brink, DM
   Cubizolle, A
   Chatelain, G
   Davoust, N
   Girard, V
   Johansen, S
   Napoletano, F
   Dourlen, P
   Guillou, L
   Angebault-Prouteau, C
   Bernoud-Hubac, N
   Guichardant, M
   Brabet, P
   Mollereau, B
AF Van den Brink, Daan M.
   Cubizolle, Aurelie
   Chatelain, Gilles
   Davoust, Nathalie
   Girard, Victor
   Johansen, Simone
   Napoletano, Francesco
   Dourlen, Pierre
   Guillou, Laurent
   Angebault-Prouteau, Claire
   Bernoud-Hubac, Nathalie
   Guichardant, Michel
   Brabet, Philippe
   Mollereau, Bertrand
TI Physiological and pathological roles of FATP-mediated lipid droplets in
   Drosophila and mice retina
SO PLOS GENETICS
LA English
DT Article
ID ACID TRANSPORT PROTEINS; PROGRAMMED CELL-DEATH; VISUAL CYCLE;
   PHOTORECEPTOR DIFFERENTIATION; PIGMENT EPITHELIUM; DISEASE; STORAGE;
   AGE; NEURODEGENERATION; ACYLTRANSFERASE
AB Increasing evidence suggests that dysregulation of lipid metabolism is associated with neurodegeneration in retinal diseases such as age-related macular degeneration and in brain disorders such as Alzheimer's and Parkinson's diseases. Lipid storage organelles (lipid droplets, LDs), accumulate in many cell types in response to stress, and it is now clear that LDs function not only as lipid stores but also as dynamic regulators of the stress response. However, whether these LDs are always protective or can also be deleterious to the cell is unknown. Here, we investigated the consequences of LD accumulation on retinal cell homeostasis under physiological and stress conditions in Drosophila and in mice. In wild-type Drosophila, we show that dFatp is required and sufficient for expansion of LD size in retinal pigment cells (RPCs) and that LDs in RPCs are required for photoreceptor survival during aging. Similarly, in mice, LD accumulation induced by RPC-specific expression of human FATP1 was non-toxic and promoted mitochondrial energy metabolism in RPCs and non-autonomously in photoreceptor cells. In contrast, the inhibition of LD accumulation by dFatp knockdown suppressed neurodegeneration in Aats-met(FB) Drosophila mutants, which carry elevated levels of reactive oxygen species (ROS). This suggests that abnormal turnover of LD may be toxic for photoreceptors cells of the retina under oxidative stress. Collectively, these findings indicate that FATP-mediated LD formation in RPCs promotes RPC and neuronal homeostasis under physiological conditions but could be deleterious for the photoreceptors under pathological conditions.
C1 [Van den Brink, Daan M.; Chatelain, Gilles; Davoust, Nathalie; Girard, Victor; Johansen, Simone; Mollereau, Bertrand] Univ Lyon, UCBL, ENSL, CNRS,LBMC,UMS 3444,Biosci Lyon Gerland, Lyon, France.
   [Cubizolle, Aurelie; Guillou, Laurent; Angebault-Prouteau, Claire; Brabet, Philippe] CHU St Eloi, INSERM, Inst Neurosci Montpellier, U1051, Montpellier, France.
   [Cubizolle, Aurelie; Guillou, Laurent; Brabet, Philippe] Univ Montpellier, Montpellier, France.
   [Napoletano, Francesco] Univ Trieste, Dept Life Sci, Mol Oncol Unit, Lab Nazl CIB, Area Sci Pk, Trieste, Italy.
   [Dourlen, Pierre] Inst Pasteur, Lille, France.
   [Dourlen, Pierre] INSERM, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, Lille, France.
   [Dourlen, Pierre] Univ Lille, U1167, Excellence Lab LabEx DISTALZ, Lille, France.
   [Angebault-Prouteau, Claire] Univ Montpellier, CHRU Montpellier, CNRS, INSERM,U1046,UMR 9214, Montpellier, France.
   [Bernoud-Hubac, Nathalie; Guichardant, Michel] Univ Claude Bernard Lyon 1, Univ Lyon, CarMeN Lab, INSA Lyon,INSERM,U1060,INRA,U1397, F-69621 Villeurbanne, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National
   Institute for Biology (INSB); UDICE-French Research Universities;
   Universite Claude Bernard Lyon 1; CHU Lyon; Ecole Normale Superieure de
   Lyon (ENS de LYON); Universite Jean Monnet; Institut National de la
   Sante et de la Recherche Medicale (Inserm); Universite de Montpellier;
   CHU de Montpellier; Universite de Montpellier; University of Trieste; Le
   Reseau International des Instituts Pasteur (RIIP); Universite de Lille -
   ISITE; Institut Pasteur Lille; Institut National de la Sante et de la
   Recherche Medicale (Inserm); Universite de Lille - ISITE; Universite de
   Lille; Universite de Lille - ISITE; Universite de Lille; Centre National
   de la Recherche Scientifique (CNRS); CNRS - National Institute for
   Biology (INSB); Institut National de la Sante et de la Recherche
   Medicale (Inserm); Universite de Montpellier; CHU de Montpellier; INRAE;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   Institut National des Sciences Appliquees de Lyon - INSA Lyon;
   UDICE-French Research Universities; Universite Claude Bernard Lyon 1
RP Mollereau, B (通讯作者)，Univ Lyon, UCBL, ENSL, CNRS,LBMC,UMS 3444,Biosci Lyon Gerland, Lyon, France.
EM bertrand.mollereau@ens-lyon.fr
RI Brabet, Philippe/AAO-8522-2020; Mollereau, Bertrand/S-4447-2017;
   Napoletano, Francesco/AAY-8755-2020
OI Brabet, Philippe/0000-0003-2739-1622; Mollereau,
   Bertrand/0000-0003-4710-8185; Napoletano, Francesco/0000-0002-0910-3167;
   GIRARD, Victor/0000-0002-5743-9503; Dourlen, Pierre/0000-0002-3562-1080;
   van den Brink, D/0000-0002-3048-5382; Johansen,
   Simone/0000-0002-6140-9366
FU French National Research Agency [ANR-12-BSV1-0019-02]; Association
   Francaise contre les Myopathies, a European Union's Seventh Framework
   Programme/AIRC (Associazione Italiana per la Ricerca sul cancro)
   Reintegration Grant; Bloomington Drosophila Stock Center [NIH
   P40OD018537]; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
   [P40OD018537] Funding Source: NIH RePORTER
FX This work was supported by the French National Research Agency award
   ANR-12-BSV1-0019-02 to BM, PB, DMVDB, and AC and by a postdoctoral
   fellowship to FN from the Association Francaise contre les Myopathies, a
   European Union's Seventh Framework Programme/AIRC (Associazione Italiana
   per la Ricerca sul cancro) Reintegration Grant. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; We are grateful to the ARTHRO-TOOLS and
   the PLATIM microscopy platform of SFR Biosciences (UMS3444/CNRS,
   US8/INSERM, ENS de Lyon, UCBL) and the Centre Technologique des
   Microstructures CT mu at Lyon1 for assistance with electron microscopy.
   We would like to thank Chantal Cazevieille from the COMET platform of
   RHEM for the transmission electron microscopy, the INM facility for the
   management and maintenance of mice, and Montpellier RIO Imaging for the
   use of imaging tools. We are grateful to Charlotte Scholtes for her help
   in the analysis of mitochondrial integrity on TEM images. Stocks were
   obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537).
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NR 56
TC 25
Z9 25
U1 1
U2 10
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 SEP
PY 2018
VL 14
IS 9
AR e1007627
DI 10.1371/journal.pgen.1007627
PG 25
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA GV5QO
UT WOS:000446157400018
PM 30199545
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kim, J
   Jin, HL
   Jang, DS
   Jeong, KW
   Choung, SY
AF Kim, Jun
   Jin, Hong Lan
   Jang, Dae Sik
   Jeong, Kwang Won
   Choung, Se-Young
TI Quercetin-3-O-alpha-L-arabinopyranoside protects against retinal cell
   death via blue light-induced damage in human RPE cells and Balb-c mice
SO FOOD & FUNCTION
LA English
DT Article
ID VACCINIUM-ULIGINOSUM L.; MACULAR DEGENERATION AMD; PIGMENT
   EPITHELIAL-CELLS; IN-VIVO; QUERCETIN GLYCOSIDES; INDUCED APOPTOSIS;
   OXIDATIVE STRESS; CHLOROGENIC ACID; A549 CELLS; LIPOFUSCIN
AB Age-related macular degeneration (AMD) is among the increasing number of diseases causing irreversible blindness in the elderly. Dry AMD is characterized by the accumulation of lipofuscin in retinal pigment epithelium (RPE) cells. N-Retinylidene-N-retinylethanolamine (A2E), a component of lipofuscin, is oxidized to oxo-A2E under blue light illumination, leading to retinal cell death. The aim of this study was to investigate the protective effect and mechanism of quercetin-3-O-alpha-L-arabinopyranoside (QA) against blue light (BL)-induced damage in both RPE cells and mice models. Treatment by QA inhibited A2E uptake in RPE cells, as determined by a decrease in fluorescence intensity. QA also protected A2E-laden RPE cells against BL-induced apoptosis. QA inhibited C3 complement activation and poly (ADP-ribose) polymerase (PARP) cleavage, as determined by western blotting. QA showed an inhibitory effect on AP1 and NF-kappa B activity as estimated in a reporter gene assay. In addition, QA activated the gene expression of aryl hydrocarbon receptor target genes (CYP1A1, CYP1B1) in TCDD-treated RPE cells. In the mice model, oral administration of QA protected against retinal degeneration induced by BL exposure as determined by histological analyses (thickness of retinal layers and immunostaining for caspase-3). In addition, QA inhibited apoptosis and inflammation via inhibition of NF-kappa B p65 translocation, C3 activation, and PARP cleavage. Collectively, these results revealed the protective mechanism of QA against BL-induced retinal damage both in vitro and in vivo.
C1 [Kim, Jun; Jang, Dae Sik; Choung, Se-Young] Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci, 26 Kyungheedae Ro, Seoul 02447, South Korea.
   [Jin, Hong Lan; Jeong, Kwang Won] Gachon Univ, Gachon Inst Pharmaceut Sci, Coll Pharm, 191 Hambakmoero, Incheon 21936, South Korea.
C3 Kyung Hee University; Gachon University
RP Choung, SY (通讯作者)，Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci, 26 Kyungheedae Ro, Seoul 02447, South Korea.; Jeong, KW (通讯作者)，Gachon Univ, Gachon Inst Pharmaceut Sci, Coll Pharm, 191 Hambakmoero, Incheon 21936, South Korea.
EM kwjeong@gachon.ac.kr; sychoung@khu.ac.kr
RI Choung, Young/AAH-9208-2020; Jang, Dae Sik/AAI-4526-2020
OI Kim, Jun/0000-0002-0535-8971
FU technology Innovation Industrial Program - Ministry of Trade, Industry
   and Energy (MOTIE, Korea) [10048028]; Korea Evaluation Institute of
   Industrial Technology (KEIT)
FX This study was supported by the technology Innovation Industrial Program
   (10048028) funded by the Ministry of Trade, Industry and Energy (MOTIE,
   Korea) & Korea Evaluation Institute of Industrial Technology (KEIT).
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NR 49
TC 27
Z9 29
U1 3
U2 12
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 2042-6496
EI 2042-650X
J9 FOOD FUNCT
JI Food Funct.
PD APR 1
PY 2018
VL 9
IS 4
BP 2171
EP 2183
DI 10.1039/c7fo01958k
PG 13
WC Biochemistry & Molecular Biology; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Food Science & Technology
GA GK3GV
UT WOS:000436031600022
PM 29541735
DA 2022-11-30
ER

PT J
AU McLeod, DS
   Bhutto, I
   Edwards, MM
   Gedam, M
   Baldeosingh, R
   Lutty, GA
AF McLeod, D. Scott
   Bhutto, Imran
   Edwards, Malia M.
   Gedam, Manasee
   Baldeosingh, Rajkumar
   Lutty, Gerard A.
TI Mast Cell-Derived Tryptase in Geographic Atrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; geographic atrophy; Bruch's membrane;
   RPE; choriocapillaris; choroid; degranulation; mast cells; tryptase;
   lipid
ID EPITHELIAL BARRIER DYSFUNCTION; APOLIPOPROTEIN-B; HUMAN EYES; BRUCHS
   MEMBRANE; BETA-TRYPTASE; AGE; HETEROGENEITY; ACCUMULATION; CHOLESTEROL;
   ACTIVATION
AB PURPOSE. Our previous study demonstrated significantly more degranulating mast cells (MCs) in choroids from subjects with age-related macular degeneration compared to aged controls. This study examined the immunolocalization of tryptase, the most abundant MC secretory granule-derived serine protease, in aged control eyes and eyes with geographic atrophy (GA).
   METHODS. Postmortem human eyes with and without GA were obtained from the National Disease Research Interchange. Tissue was fixed, cryopreserved, sectioned, and immunostained with a monoclonal antibody against tryptase. Sections were imaged on a Zeiss 710 Confocal Microscope.
   RESULTS. In the posterior pole of all aged control eyes, tryptase was confined to choroidal MCs, which were located primarily in Sattler's layer. In eyes with GA, many MCs were located in the inner choroid near choriocapillaris and Bruch's membrane (BM). Tryptase was found not only in MCs but also diffusely around them in stroma, suggesting they had degranulated. In contrast with aged control eyes, eyes with GA also had strong tryptase staining in BM. Tryptase was observed within BM in regions of RPE atrophy, at the border of atrophy, and extending well into the nonatrophic region.
   CONCLUSIONS. Our results demonstrate that tryptase, released during choroidal MC degranulation, binds to BM in GA in advance of RPE atrophy. Tryptase activates MMPs that can degrade extracellular matrix (ECM) and basement membrane components found in BM. ECM modifications are likely to have a profound effect on the function and health of RPE and choroidal thinning in GA.
C1 [McLeod, D. Scott; Bhutto, Imran; Edwards, Malia M.; Gedam, Manasee; Baldeosingh, Rajkumar; Lutty, Gerard A.] Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, M041 Smith Bldg,400 North Broadway, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Lutty, GA (通讯作者)，Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, M041 Smith Bldg,400 North Broadway, Baltimore, MD 21287 USA.
EM glutty@jhmi.edu
OI GEDAM, MANASEE/0000-0001-6877-4190
FU National Institutes of Health [EY016151, EY01765]; Arnold and Mabel
   Beckman Foundation; Altsheler-Durell Foundation; Bright Focus; Research
   to Prevent Blindness Unrestricted Grant; NATIONAL EYE INSTITUTE
   [R01EY016151] Funding Source: NIH RePORTER
FX Supported by National Institutes of Health Grants EY016151 (GL), and
   EY01765 (Wilmer), Arnold and Mabel Beckman Foundation (GL), the
   Altsheler-Durell Foundation, Bright Focus, and a Research to Prevent
   Blindness Unrestricted Grant (Wilmer).
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NR 39
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Z9 14
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2017
VL 58
IS 13
BP 5879
EP 5888
DI 10.1167/iovs.17-22989
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FR4YC
UT WOS:000419071600035
PM 29164232
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Park, TK
   Lee, SH
   Choi, JS
   Nah, SK
   Kim, HJ
   Park, HY
   Lee, H
   Lee, SHS
   Park, K
AF Park, Tae Kwann
   Lee, Si Hyung
   Choi, Jun Sub
   Nah, Seung Kwan
   Kim, Hee Jong
   Park, Ha Yan
   Lee, Heuiran
   Lee, Steven Hyun Seung
   Park, Keerang
TI Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin
   RNA Suppresses Laser-Induced Choroidal Neovascularization
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; LEBERS CONGENITAL AMAUROSIS; MACULAR
   DEGENERATION; GENE-THERAPY; AUTOPHAGY; VEGF; GROWTH; CELLS; MICE;
   PHOTOCOAGULATION
AB Choroidal neovascularization (CNV) is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD) and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF), the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA) after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV) delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control-and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV.
C1 [Park, Tae Kwann; Lee, Si Hyung; Nah, Seung Kwan] Soonchunhyang Univ, Coll Med, Dept Ophthalmol, Cheonan 31151, South Korea.
   [Park, Tae Kwann; Lee, Si Hyung; Nah, Seung Kwan; Park, Ha Yan] Soonchunhyang Univ Hosp Bucheon, Dept Ophthalmol, 170 Jomaru Ro, Bucheon 14584, South Korea.
   [Choi, Jun Sub; Kim, Hee Jong] Cdmogen Co Ltd, Cheongju 28751, South Korea.
   [Lee, Heuiran; Lee, Steven Hyun Seung] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Microbiol,Cellular Dysfunct Res Ctr, Seoul 05505, South Korea.
   [Park, Keerang] Chungbuk Hlth & Sci Univ, Dept Biopharm, Cheongju 28150, Chungbuk, South Korea.
C3 Soonchunhyang University; Soonchunhyang University; University of Ulsan
RP Park, TK (通讯作者)，Soonchunhyang Univ Hosp Bucheon, Dept Ophthalmol, 170 Jomaru Ro, Bucheon 14584, South Korea.; Park, K (通讯作者)，Chungbuk Hlth & Sci Univ, Dept Biopharm, 10 Deokam Gil, Cheongju 28150, Chungbuk, South Korea.
EM tkpark@schmc.ac.kr; krpark@chsu.ac.kr
RI Lee, Si Hyung/ABH-1408-2020
FU Soonchunhyang University
FX This work was supported in part by the Soonchunhyang University Research
   Fund.
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   Zarbin MA, 2004, ARCH OPHTHALMOL-CHIC, V122, P598, DOI 10.1001/archopht.122.4.598
   Zhang J, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.330
   Zhao C, 2011, J CLIN INVEST, V121, P369, DOI 10.1172/JCI44303
NR 53
TC 22
Z9 22
U1 0
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD SEP 15
PY 2017
VL 8
BP 26
EP 35
DI 10.1016/j.omtn.2017.05.012
PG 10
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EX8YX
UT WOS:000403537300003
PM 28918027
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kopic, A
   Biuk, D
   Barac, J
   Vinkovic, M
   Benasic, T
   Kopic, V
AF Kopic, Andrijana
   Biuk, Dubravka
   Barac, Josip
   Vinkovic, Maja
   Benasic, Tvrtka
   Kopic, Vlatko
TI RETINAL NERVE FIBER LAYER THICKNESS IN GLAUCOMA PATIENTS TREATED WITH
   MULTIPLE INTRAVITREAL ANTI-VEGF (BEVACIZUMAB) INJECTIONS
SO ACTA CLINICA CROATICA
LA English
DT Article
DE Intravitreal injections; Vascular endothelial growth factor A;
   Bevacizumab; Retinal degeneration; Macular edema; Diabetes mellitus;
   Glaucoma, primary open angle; Croatia
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; INTRAOCULAR-PRESSURE;
   DIABETIC-RETINOPATHY; RANIBIZUMAB; THERAPY; MANAGEMENT; AVASTIN; EDEMA
AB Over the past decade, intravitreal injections of anti-VEGF agents have been widely used and intensively developed as a treatment option for many ophthalmological indications. Due to its availability and low cost, the most frequently used anti-VEGF agent is bevacizumab. This type of therapy is often indicated in patients with exudative age-related macular degeneration (ARMD) and diabetic macular edema (DME). If, in addition to these two conditions, patients have a diagnosis of primary open angle glaucoma (POAG), they also present with optic nerve head (ONH) retinal nerve fiber layer (RNFL) thinning. The aim of this prospective study was to establish whether administering bevacizumab to patients with POAG leads to additional reduction of RNFL thickness. The study included 60 patients divided into two groups. First group comprised the eyes of patients with exudative ARMD and POAG, whereas second group comprised the eyes of patients with DME and POAG, all treated with bevacizumab. Control group comprised the fellow eye of each involved patient, which was not treated with bevacizumab. In a period of one year, all patients underwent optical coherence tomography (OCT) measurements of ONH RNFL thickness. The results of all patients were compared between the two study groups and then with control group results. Study results showed a decrease of RNFL in both groups of patients. Comparison of these two groups of patients after one year revealed a statistically more significant decrease in RNFL thickness in the second group (DME + POAG).
C1 [Kopic, Andrijana; Biuk, Dubravka; Barac, Josip; Vinkovic, Maja; Benasic, Tvrtka] Osijek Univ Hosp Ctr, Clin Dept Ophthalmol, Europska Ave Nija 14-16, HR-31000 Osijek, Croatia.
   [Kopic, Andrijana; Biuk, Dubravka; Barac, Josip; Vinkovic, Maja; Benasic, Tvrtka; Kopic, Vlatko] Josip Juraj Strossmayer Univ, Sch Med, Osijek, Croatia.
   [Kopic, Vlatko] Osijek Univ Hosp Ctr, Dept Maxillofacial & Oral Surg, Osijek, Croatia.
C3 University of JJ Strossmayer Osijek
RP Kopic, A (通讯作者)，Osijek Univ Hosp Ctr, Clin Dept Ophthalmol, Europska Ave Nija 14-16, HR-31000 Osijek, Croatia.
EM andrijanakopic@gmail.com
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NR 34
TC 9
Z9 11
U1 0
U2 1
PU SESTRE MILOSRDNICE UNIV HOSPITAL
PI ZAGREB
PA VINOGRADSKA C 29, ZAGREB, HR-10000, CROATIA
SN 0353-9466
EI 1333-9451
J9 ACTA CLIN CROAT
JI Acta Clin. Croat.
PD SEP
PY 2017
VL 56
IS 3
BP 406
EP 414
DI 10.20471/acc.2017.56.03.07
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA FT8JS
UT WOS:000423399700007
PM 29479906
OA gold
DA 2022-11-30
ER

PT J
AU Chong, V
AF Chong, V.
TI Ranibizumab for the treatment of wet AMD: a summary of real-world
   studies
SO EYE
LA English
DT Review
ID 2.0 MG RANIBIZUMAB; QUALITY-OF-LIFE; MACULAR DEGENERATION; INTRAVITREAL
   RANIBIZUMAB; VISUAL-ACUITY; CLINICAL-PRACTICE; OUTCOMES; SAFETY;
   VERTEPORFIN; EFFICACY
AB Data from real-world studies of ranibizumab in neovascular (wet) age-related macular degeneration suggest that outcomes in clinical practice fail to match those seen in clinical trials. These real-world studies follow treatment regimens that differ from the fixed dosing used in the pivotal clinical trial programme. To better understand the effectiveness of ranibizumab in clinical practice, we conducted a comprehensive evaluation of 12-month outcomes reported in peer-reviewed 'real-world' publications. Key measures included in our analysis were mean change in visual acuity (VA) and the proportion of patients gaining >= 15 letters or losing <= 15 letters. Twenty studies were eligible for inclusion in our study, with 18 358 eyes having sufficient data for analysis of 12-month outcomes. Mean baseline VA ranged from 48.8 to 61.6 Early Treatment Diabetic Retinopathy Study letters. Mean change in VA was between -2.0 and +5.5 letters, with a grand mean of +2.9 +/- 3.2, and a weighted mean (adjusted for the number of eyes in the study) of +1.95. Eleven studies reported that 19 +/- 7.5 (mean value) of patients gained >= 15 letters, while in 12 studies the mean percentage of patient losing <= 15 letters was 89 +/- 6.5%. Our comprehensive analysis of real-world ranibizumab study data confirm that patient outcomes are considerably poorer than those reported in randomised control trials of both fixed and pro re nata regimens.
C1 [Chong, V.] Oxford Univ Hosp, Oxford Eye Hosp, Headley Way, Oxford OX3 9DU, England.
RP Chong, V (通讯作者)，Oxford Univ Hosp, Oxford Eye Hosp, Headley Way, Oxford OX3 9DU, England.
EM victor@eretina.org
FU Bayer HealthCare Pharmaceuticals
FX I take full responsibility for the scope, direction, and the content of
   the manuscript, and has approved the submitted manuscript. Medical
   writing assistance was provided by Ana Tadeu of Porterhouse Medical
   Ltd., and was funded by Bayer HealthCare Pharmaceuticals.
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NR 38
TC 79
Z9 83
U1 1
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 FEB
PY 2016
VL 30
IS 2
BP 270
EP 286
DI 10.1038/eye.2015.217
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DE2HX
UT WOS:000370449500017
PM 26634711
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Jocic, JD
   Cukuranovic, R
   Jovanovic, P
   Djordjevic, V
   Mihajlovic, M
   Bogdanovic, D
   Cukuranovic-Kokoris, J
   Stefanovic, V
AF Jocic, Jasmina Djordjevic
   Cukuranovic, Rade
   Jovanovic, Predrag
   Djordjevic, Vidosava
   Mihajlovic, Marija
   Bogdanovic, Dragan
   Cukuranovic-Kokoris, Jovana
   Stefanovic, Vladisav
TI Ocular fundus abnormalities in patients with Balkan endemic nephropathy
   and other chronic kidney diseases
SO INTERNATIONAL UROLOGY AND NEPHROLOGY
LA English
DT Article
DE Balkan nephropathy; Chronic kidney disease; AMD; Retinopathy
ID RETINAL MICROVASCULAR ABNORMALITIES; MACULAR DEGENERATION;
   ATHEROSCLEROSIS RISK; POSITION STATEMENT; RENAL-FUNCTION; PREVALENCE;
   CLASSIFICATION; ASSOCIATIONS; RETINOPATHY; POPULATION
AB The aim of this study was to examine the ocular fundus pathology in patients with Balkan endemic nephropathy (BN) and chronic kidney diseases (CKD).
   The study included 51 patients with BN from the South Morava River region in Serbia, and 102 subjects with different stages of chronic renal diseases, matched according to age and gender, obtained from a database used in a recently published study. All patients had visited Outpatient Department of the Clinic of Nephrology, Clinical Center Nis. All patients underwent routine ophthalmic examinations.
   There were significantly more (P < 0.001) patients with age-related macular degeneration (AMD) in the group with BN (31.37 %) than in those with CKD (5.88 %). Multivariate logistic regression analysis confirmed that the significant factors related to AMD in the group with BN were albuminuria (P < 0.05) and proteinuria (P < 0.05); in CKD patients, the level of HDL (P < 0.05), while negative correlation with the level of triglyceride was registered (P < 0.05). There was no association between estimated glomerular filtration rate and AMD. The significant factors related to retinopathy in the group with BN are age (P < 0.05) and serum creatinine values (P < 0.05), in patients with CKD increasing age (P < 0.001) and DM (P < 0.05).
   Ocular fundus pathology in patients with BN is similar to the pathology of other CKD, but with significantly more AMD (about four times), probably related to the genetic/epigenetic factors.
C1 [Jocic, Jasmina Djordjevic; Jovanovic, Predrag] Univ Nis, Clin Ophthalmol, Fac Med, Nish 18000, Serbia.
   [Cukuranovic, Rade] Univ Nis, Clin Nephrol, Fac Med, Nish 18000, Serbia.
   [Djordjevic, Vidosava] Univ Nis, Inst Biochem, Fac Med, Nish 18000, Serbia.
   [Bogdanovic, Dragan; Stefanovic, Vladisav] State Univ Novi Pazar, Novi Pazar, Serbia.
   [Mihajlovic, Marija; Cukuranovic-Kokoris, Jovana] Univ Nis, Fac Med, Nish 18000, Serbia.
   [Stefanovic, Vladisav] Univ Nis, Res Dept, Fac Med, Nish 18000, Serbia.
C3 University of Nis; University of Nis; University of Nis; University of
   Nis; University of Nis
RP Jocic, JD (通讯作者)，Univ Nis, Clin Ophthalmol, Fac Med, Bul Zorana Djindjica 81, Nish 18000, Serbia.
EM jdjordjevic.jocic@gmail.com
RI Bogdanovic, Dragan/AAD-1384-2019; djordjevic, vidosava/AAP-1871-2020
OI Bogdanovic, Dragan/0000-0001-6300-7427
FU Ministry of Education, Science and Technological Development of Serbia
   [175092]
FX This work was supported by a Grant No. 175092, from the Ministry of
   Education, Science and Technological Development of Serbia.
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NR 40
TC 3
Z9 3
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-1623
EI 1573-2584
J9 INT UROL NEPHROL
JI Int. Urol. Nephrol.
PD OCT
PY 2015
VL 47
IS 10
BP 1693
EP 1701
DI 10.1007/s11255-015-1078-x
PG 9
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA CT2XJ
UT WOS:000362668800017
PM 26329737
DA 2022-11-30
ER

PT J
AU Mansour, AM
   Al-Ghadban, SI
   Yunis, MH
   El-Sabban, ME
AF Mansour, Ahmad M.
   Al-Ghadban, Sara I.
   Yunis, Muhammad H.
   El-Sabban, Marwan E.
TI Ziv-aflibercept in macular disease
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL AFLIBERCEPT; COST-EFFECTIVENESS; BEVACIZUMAB; DEGENERATION;
   RANIBIZUMAB; STABILITY; PHARMACOKINETICS; STERILITY; INJECTION; EFFICACY
AB Background/aims Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, zivaflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis.
   Methods Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA.
   Results There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p = 0.05) and central foveal thickness decreased in all patients (p = 0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4 degrees C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab.
   Conclusions Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept.
C1 [Mansour, Ahmad M.; Yunis, Muhammad H.] Amer Univ Beirut, Dept Ophthalmol, Beirut 1136044, Lebanon.
   [Mansour, Ahmad M.; Yunis, Muhammad H.] Rafic Hariri Univ Hosp, Beirut, Lebanon.
   [Al-Ghadban, Sara I.; El-Sabban, Marwan E.] Amer Univ Beirut, Dept Anat Cell Biol & Physiol Sci, Beirut 1136044, Lebanon.
C3 American University of Beirut; American University of Beirut
RP Mansour, AM (通讯作者)，Amer Univ Beirut, Dept Ophthalmol, Beirut 1136044, Lebanon.
EM ammansourmd@gmail.com
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NR 27
TC 56
Z9 56
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2015
VL 99
IS 8
BP 1055
EP 1059
DI 10.1136/bjophthalmol-2014-306319
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CN3BC
UT WOS:000358297200009
PM 25677668
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU White, UE
   Black, AA
   Wood, JM
   Delbaere, K
AF White, Ursula E.
   Black, Alex A.
   Wood, Joanne M.
   Delbaere, Kim
TI Fear of Falling in Vision Impairment
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Review
DE fear of falling; falls self-efficacy; falls; vision; visual impairment
ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; VISUAL IMPAIRMENT; COGNITIVE
   IMPAIRMENT; MOBILITY PERFORMANCE; ACTIVITY RESTRICTION; EFFICACY SCALE;
   PREVENT FALLS; ELDERLY-WOMEN; RISK-FACTORS
AB Falls are the leading cause of injury-related morbidity and mortality among older adults. In addition to the resulting physical injury and potential disability after a fall, there are also important psychological consequences, including depression, anxiety, activity restriction, and fear of falling. Fear of falling affects 20 to 43% of community-dwelling older adults and is not limited to those who have previously experienced a fall. About half of older adults who experience fear of falling subsequently restrict their physical and everyday activities, which can lead to functional decline, depression, increased falls risk, and reduced quality of life. Although there is clear evidence that older adults with visual impairment have higher falls risk, only a limited number of studies have investigated fear of falling in older adults with visual impairment and the findings have been mixed. Recent studies suggest increased levels of fear of falling among older adults with various eye conditions, including glaucoma and age-related macular degeneration, whereas other studies have failed to find differences. Interventions, which are still in their infancy in the general population, are also largely unexplored in those with visual impairment. The major aims of this review were to provide an overview of the literature on fear of falling, its measurement, and risk factors among older populations, with specific focus on older adults with visual impairment, and to identify directions for future research in this area.
C1 [White, Ursula E.; Black, Alex A.; Wood, Joanne M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Sch Optometry & Vis Sci, Brisbane, Qld 4001, Australia.
   [Delbaere, Kim] Univ New S Wales, Neurosci Res Australia, Randwick, NSW, Australia.
C3 Queensland University of Technology (QUT); Neuroscience Research
   Australia; University of New South Wales Sydney
RP White, UE (通讯作者)，Queensland Univ Technol, Inst Hlth & Biomed Innovat, Sch Optometry & Vis Sci, Brisbane, Qld 4001, Australia.
EM ursula.white@qut.edu.au
RI Black, Alex/I-9727-2012; Delbaere, Kim/D-6370-2011
OI Black, Alex/0000-0002-8671-5167; Delbaere, Kim/0000-0002-5655-0234; ,
   Joanne/0000-0002-0776-7736; White, Ursula/0000-0003-2112-2851
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NR 60
TC 28
Z9 31
U1 1
U2 34
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 JUN
PY 2015
VL 92
IS 6
BP 730
EP 735
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA CJ0DA
UT WOS:000355141900016
PM 25930978
OA Green Published
DA 2022-11-30
ER

PT J
AU Gaffney, AJ
   Margrain, TH
   Bunce, CV
   Binns, AM
AF Gaffney, Allannah J.
   Margrain, Tom H.
   Bunce, Catey V.
   Binns, Alison M.
TI How effective is eccentric viewing training? A systematic literature
   review
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Review
DE age-related macular degeneration; central visual loss; eccentric
   viewing; low vision; steady eye strategy; systematic literature review
ID PREFERRED RETINAL LOCUS; LOW-VISION REHABILITATION; AGE-RELATED
   MACULOPATHY; MACULAR DEGENERATION; VISUAL REHABILITATION; CENTRAL
   SCOTOMAS; RESIDUAL VISION; READING RATES; FIXATION; BIOFEEDBACK
AB Purpose: The global prevalence of age-related macular degeneration and associated central vision loss is rising. Central vision loss hinders the performance of many activities of daily living. Adaptive strategies such as eccentric viewing and steady eye strategy may be used to compensate for central vision loss. In order to establish the potential of these rehabilitation strategies, this systematic review evaluates current literature regarding the effectiveness of eccentric viewing and steady eye strategy training in people with central vision loss.
   Results: The search strategies identified 2605 publications, 36 of which met the inclusion criteria for the review, but only three of which were randomised controlled trials. This literature shows that eccentric viewing and steady eye strategy training can improve near visual acuity, reading speed, and performance of activities of daily living in people with central vision loss. However, there was insufficient literature to establish a relationship between training and distance visual acuity or quality of life. There is no conclusive evidence to show that a particular model of eccentric viewing training is superior to another, little clear evidence of a relationship between participant characteristics and training outcomes and no data regarding the cost effectiveness of training.
   Conclusion: This report highlights the need for further robust research to establish the true potential and cost effectiveness of eccentric viewing and steady eye strategy training as a rehabilitation strategy for individuals with central vision loss.
C1 [Gaffney, Allannah J.; Margrain, Tom H.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF10 3AX, S Glam, Wales.
   [Bunce, Catey V.] Moorfields Eye Hosp, London, England.
   [Binns, Alison M.] City Univ London, Div Optometry & Vis Sci, London EC1V 0HB, England.
C3 Cardiff University; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; City University London
RP Gaffney, AJ (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF10 3AX, S Glam, Wales.
EM gaffneyaj1@cf.ac.uk
OI Margrain, Tom/0000-0003-1280-0809; Bunce, Catey/0000-0002-0935-3713;
   Binns, Alison/0000-0001-8621-498X
FU Macular Society, UK
FX This study was funded by the Macular Society, UK. The authors would like
   to thank the following individuals for their helpful suggestions of
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   Susana Chung, Professor Christine Dickinson, Dr Michael Crossland, Dr
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NR 82
TC 23
Z9 24
U1 2
U2 29
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD JUL
PY 2014
VL 34
IS 4
SI SI
BP 427
EP 437
DI 10.1111/opo.12132
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA AL9UA
UT WOS:000339486100004
PM 24735182
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wang, L
   Cano, M
   Handa, JT
AF Wang, Lei
   Cano, Marisol
   Handa, James T.
TI p62 provides dual cytoprotection against oxidative stress in the retinal
   pigment epithelium
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Autophagy; Aging; Nrf2; Oxidative stress; p62
ID ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; MACULAR
   DEGENERATION; ALZHEIMERS-DISEASE; P62/SEQUESTOSOME 1; CELL-DEATH;
   AUTOPHAGY; ACTIVATION; P62/SQSTM1; PHOSPHORYLATION
AB As a signaling hub, p62/sequestosome plays important roles in cell signaling and degradation of misfolded proteins. p62 has been implicated as an adaptor protein to mediate autophagic clearance of insoluble protein aggregates in age-related diseases, including age-related macular degeneration (AMD), which is characterized by dysfunction of the retinal pigment epithelium (RPE). Our previous studies have shown that cigarette smoke (CS) induces oxidative stress and inhibits the proteasome pathway in cultured human RPE cells, suggesting that p62-mediated autophagy may become the major route to remove impaired proteins under such circumstances. In the present studies, we found that all p62 mRNA variants are abundantly expressed and upregulated by CS induced stress in cultured human RPE cells, yet isoform1 is the major translated form. We also show that p62 silencing exacerbated the CS induced accumulation of damaged proteins, both by suppressing autophagy and by inhibiting the Nrf2 antioxidant response, which in turn, increased protein oxidation. These effects of CS and p62 reduction were further confirmed in mice exposed to CS. We found that over-expression of p62 isoform1, but not its S403A mutant, which lacks affinity for ubiquitinated proteins, reduced misfolded proteins, yet simultaneously promoted an Nrf2-mediated antioxidant response. Thus, p62 provides dual, reciprocal enhancing protection to RPE cells from environmental stress induced protein misfolding and aggregation, by facilitating autophagy and the Nrf2 mediated antioxidant response, which might be a potential therapeutic target against AMD. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Wang, Lei; Cano, Marisol; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，400 N Broadway,Smith Bldg,Room 3015, Baltimore, MD 21287 USA.
EM leiwang.011@gmail.com; mcano1@jlmi.edu; jthanda@jhmi.edu
RI Wang, Lei/C-1902-2015
OI Wang, Lei/0000-0002-7957-1003
FU Beckman Foundation AMD Grant; Thome Foundation; Research to Prevent
   Blindness Senior Scientist Award [NIH P3OEY001765]; NIH [P3OEY001765];
   Robert Bond Welch Professorship; RPB;  [EY019904];  [EY14005]; NATIONAL
   EYE INSTITUTE [R01EY019904, P30EY001765, R01EY014005] Funding Source:
   NIH RePORTER
FX EY019904 (JTH), EY14005 (JTH), Beckman Foundation AMD Grant (JTH), Thome
   Foundation (JTH), Research to Prevent Blindness Senior Scientist Award
   (JTH), NIH P3OEY001765 core grant, the Robert Bond Welch Professorship
   (JTH), a gift from the Merlau family, and an Unrestricted grant from RPB
   to the Wilmer Eye Institute are acknowleged.
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NR 48
TC 64
Z9 65
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUL
PY 2014
VL 1843
IS 7
BP 1248
EP 1258
DI 10.1016/j.bbamcr.2014.03.016
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA AI2UM
UT WOS:000336713600002
PM 24667411
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU O'Connor, PM
   Harper, CA
   Brunton, CL
   Clews, SJ
   Haymes, SA
   Keeffe, JE
AF O'Connor, Patricia M.
   Harper, C. Alex
   Brunton, Cathy L.
   Clews, Sandra J.
   Haymes, Sharon A.
   Keeffe, Jill E.
TI Shared care for chronic eye diseases: perspectives of ophthalmologists,
   optometrists and patients
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Article
ID FOLLOW-UP; GLAUCOMA; MANAGEMENT
AB Objective: To report the perspectives of optometrists, ophthalmologists and patients on a model of shared care for patients with chronic eye diseases.
   Design, setting and participants: Qualitative study of a model of shared care between optometrists and ophthalmologists for patients with stable age-related macular degeneration, diabetic retinopathy and glaucoma, trialled by the Royal Victorian Eye and Ear Hospital in Melbourne during 2007-2009. Semi-structured interviews were conducted with optometrists, ophthalmologists and patients at completion of the project to obtain their perspectives on this model.
   Results: Seventeen optometrists submitted expressions of interest to participate, and 12 completed web-based training modules and clinical observerships and adhered to specified examination and reporting protocols. All five participating ophthalmologists and 11 of the optometrists were interviewed. Ninety-eight patients participated and 37 were interviewed. Optometrists not only met ophthalmologists' expectations but exceeded them, appropriately detecting and referring patients with additional, previously undetected conditions. Patients reported savings in travel time and were satisfied with the quality of care they received. Optometrists, ophthalmologists and patients indicated a general acceptance of shared care arrangements, although there were some issues relating to interprofessional trust.
   Conclusions: Shared care between local optometrists and hospital-based ophthalmologists can help to reduce patient waiting time for review and offers an opportunity for these two groups of eye care professionals to collaborate in providing localised care for the benefit of patients. However, trust and relationship building need to be further developed.
C1 [Keeffe, Jill E.] Royal Victorian Eye & Ear Hosp, Populat Hlth Unit, Melbourne, Vic 3002, Australia.
C3 Royal Victorian Eye & Ear Hospital
EM jillek@unimelb.edu.au
OI Bentley, Sharon/0000-0003-0146-4248
FU Australian Government Department of Health and Ageing; Victorian
   Department of Health; Royal Victorian Eye and Ear Hospital
FX This 2-year National Eye Health Demonstration Project was funded by the
   Australian Government Department of Health and Ageing, with additional
   funds from the Victorian Department of Health. This research was
   supported by the Royal Victorian Eye and Ear Hospital. The Centre for
   Eye Research Australia receives operational infrastructure support from
   the Victorian Government. We acknowledge the support and cooperation of
   all the ophthalmologists, optometrists, support staff and patients
   involved, and the contribution of the project manager, Bich Thai.
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NR 21
TC 36
Z9 36
U1 0
U2 11
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0025-729X
EI 1326-5377
J9 MED J AUSTRALIA
JI Med. J. Aust.
PD JUN 4
PY 2012
VL 196
IS 10
BP 646
EP 650
DI 10.5694/mja11.10856
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 957WR
UT WOS:000305198300025
PM 22676881
OA Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Wolkow, N
   Song, DL
   Song, Y
   Chu, S
   Hadziahmetovic, M
   Lee, JC
   Iacovelli, J
   Grieco, S
   Dunaief, JL
AF Wolkow, Natalie
   Song, Delu
   Song, Ying
   Chu, Sally
   Hadziahmetovic, Majda
   Lee, Jennifer C.
   Iacovelli, Jared
   Grieco, Steven
   Dunaief, Joshua L.
TI Ferroxidase Hephaestin's Cell-Autonomous Role in the Retinal Pigment
   Epithelium
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; IRON HOMEOSTASIS; TRANSFERRIN RECEPTORS;
   PHOTORECEPTOR CELLS; VERTEBRATE RETINA; KNOCKOUT MICE; CERULOPLASMIN;
   EXPRESSION; MOUSE; MODEL
AB Hephaestin (Heph) is a ferroxidase protein that converts ferrous to ferric iron to facilitate cellular iron export by ferroportin. Many tissues express either Heph or its homologue, ceruloplasmin (Cp), but the retina expresses both. In mice, a combined systemic mutation of Heph and systemic knockout of Cp (Cp-/-, Heph(sla/sla)) causes retinal iron accumulation and retinal degeneration, with features of human age-related macular degeneration; however, the role of Heph and Cp in the individual retinal cells is unclear. Herein, we used conditional knockout mice to study Heph's role in retinal pigment epithelial (RPE) and photoreceptor cells. Loss of both Heph and Cp from RPE cells alone results in RPE cell iron accumulation and degeneration. We found, however, that RPE iron accumulation in these conditional knockout mice is not as great as in systemic knockout mice. Photoreceptor-specific Heph knockout indicates that the additional iron in the RPE cells does not result from loss of ferroxidases in the photoreceptors, and Cp and Heph play minor roles in photoreceptors. Instead, loss of ferroxidases in other retinal cells causes retinal iron accumulation and transfer of iron to the RPE cells. Cp and Heph are necessary for iron export from the retina but are not essential for iron import into the retina. Thus, our studies, revise how we think about iron import and export from the retina. (Am J Pathol 2012, 180:1614-1624; DOI: 10.1016/j.ajpath.2011.12.041)
C1 [Dunaief, Joshua L.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med,Stellar Chance Lab 305, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med,Stellar Chance Lab 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
OI Wolkow, Natalie/0000-0003-1524-115X
FU NIH [F30 AG037289, RO1 EY015240]; Research to Prevent Blindness; F.M.
   Kirby Foundation; Paul and Evanina Bell Mackall Foundation Trust;
   NATIONAL EYE INSTITUTE [R01EY015240] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE ON AGING [F30AG037289] Funding Source: NIH RePORTER
FX Supported by a grant from the NIH (F30 AG037289 to N.W.; RO1 EY015240 to
   J.L.D.), an unrestricted grant from Research to Prevent Blindness
   (J.L.D.), the F.M. Kirby Foundation (J.L.D.), a gift in memory of Lee F.
   Mauger, M.D. (J.L.D.), and the Paul and Evanina Bell Mackall Foundation
   Trust (J.L.D.).
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NR 39
TC 31
Z9 31
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD APR
PY 2012
VL 180
IS 4
BP 1614
EP 1624
DI 10.1016/j.ajpath.2011.12.041
PG 11
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 919LO
UT WOS:000302329400029
PM 22342521
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Figurska, M
   Wierzbowska, J
   Robaszkiewicz, J
AF Figurska, Malgorzata
   Wierzbowska, Joanna
   Robaszkiewicz, Jacek
TI Severe decrease in visual acuity with choroidal hypoperfusion after
   photodynamic therapy
SO MEDICAL SCIENCE MONITOR
LA English
DT Article
DE occult wet AMD; photodynamic therapy; choroidal hypoperfusion;
   ranibizumab
ID VERTEPORFIN; NEOVASCULARIZATION; TAP
AB Background: Photodynamic therapy (PDT) is considered a selective method of treatment which works in areas of choroidal neovascularization (CNV); however, there are reports of choroidal hypoperfusion after PDT. This paper presents a clinical case of choroidal circulation disturbances caused by PDT, accompanied by CNV progression.
   Case Report: The patient, a 75-year-old woman, was qualified for PDT in the right eye - first treatment due to progression of occult CNV. Best corrected visual acuity (BCVA) in the right eye at baseline was +0.3 logMAR. After PDT, a rapid decrease in visual acuity to +0.7 logMAR in the right eye was observed, central choroidal hypoperfusion in fluorescein angiography (FA) with subretinal fluid appeared and, as a consequence, progression of neovascular age-related macular degeneration (AMD). After stabilizing the local state through conservative therapy, a decision was made to treat the right eye with intravitreal injections of vascular endothelial growth factor (VEGF) inhibitor. During a 12-month period of observation, 7 doses of ranibizumab were administered. A regression in activity of wet AMD was observed, with visual acuity of +0.6 logMAR.
   Conclusions: Choroidal circulation disturbance after PDT is possible and has to be taken into account. Sporadically, it can lead to an acute decrease in visual acuity and local state. After stabilization of AF and optical coherence tomography imaging, further treatment of neovascular AMD with intravitreal injections of anti-VEGF agents should be considered.
C1 [Figurska, Malgorzata; Wierzbowska, Joanna; Robaszkiewicz, Jacek] Mil Med Inst, Dept Ophthalmol, PL-04141 Warsaw, Poland.
C3 Military Medical Institute
RP Figurska, M (通讯作者)，Mil Med Inst, Dept Ophthalmol, 128 Szaserow Str, PL-04141 Warsaw, Poland.
EM malgorzata-figurska@wp.pl
OI Rekas, Marek/0000-0003-0429-6649; Wierzbowska,
   Joanna/0000-0002-6993-7518
CR Arnold JJ, 2004, AM J OPHTHALMOL, V137, P683, DOI 10.1016/j.ajo.2003.11.059
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   Michels S, 2003, INVEST OPHTH VIS SCI, V44, P2147, DOI 10.1167/iovs.02-0604
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   Schmidt-Erfurth U, 2002, ARCH OPHTHALMOL-CHIC, V120, P835
   Schmidt-Erfurth U, 2005, OPHTHALMOLOGY, V112, P2061, DOI 10.1016/j.ophtha.2005.09.007
   Schmidt-Erfurth U, 2002, INVEST OPHTH VIS SCI, V43, P830
   Schmidt-Erfurth U, 2003, INVEST OPHTH VIS SCI, V44, P4473, DOI 10.1167/iovs.02-1115
   Schmidt-Erfurth U, 2009, PROG RETIN EYE RES, V28, P145, DOI 10.1016/j.preteyeres.2009.01.001
   Schmidt-Erfurth UM, 2007, ACTA OPHTHALMOL SCAN, V85, P486, DOI 10.1111/j.1600-0420.2007.00979.x
NR 15
TC 10
Z9 11
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 JUN
PY 2011
VL 17
IS 6
BP CS75
EP CS79
DI 10.12659/MSM.881799
PG 5
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 775DG
UT WOS:000291437800015
PM 21629194
OA Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Siqueira, RC
   Nogueira, MC
AF Siqueira, Rubens Camargo
   Nogueira, Miriam Caparroz
TI Identifying early recurrence of choroidal neovascularization during
   treatment with ranibizumab using C-scan
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; C-scan; Choroidal neovascularization;
   OCT
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; INTRAVITREAL
   BEVACIZUMAB; RESOLUTION; VERTEPORFIN; TRIAL
AB Purpose. To demonstrate a new parameter to identify early recurrence of choroidal neovascularization (CNV) during treatment with ranibizumab using summated en face (C-scan).
   Methods. Seventeen patients with CNV secondary to age-related macular degeneration were enrolled in this retrospective study. Each patient received ranibizumab administered monthly for 3 months and their progress was monitored at 1 week and then at monthly intervals. RTVue spectral domain optical coherence tomography (OCT) was performed in all patients monthly using summated en face (C-scan) subanalysis and was compared with the standard programs for qualitative analysis (Line Scan) and quantitative analysis (macular thickness-MM5 Scan).
   Results. We observed during the control examination an increase of hyporeflective area (dark spot) mean early fluid accumulation in the layer corresponding to the outer segment of photoreceptors. We did not observe any morphologic characteristics of recurrence of CNV in the standard SD OCT examination. At this time, no treatment was done. We scheduled a new examination in 30 days. After 30 days, the patients presented initial signs of CNV recurrence, and ranibizumab reinjection was necessary. In all cases, we observed change in the C-scan 30 to 60 days before the recurrence signs in the standard OCT program.
   Conclusions. The data suggest that summated en face (C-scan) is useful to identify early recurrence of CNV during treatment with ranibizumab. Further studies are required to allow for appropriate clinical use of this new technique. (Eur J Ophthalmol 2010; 20: 559-64)
C1 [Siqueira, Rubens Camargo] Sch Med Catanduva, Dept Ophthalmol, Catanduva, SP, Brazil.
   [Nogueira, Miriam Caparroz] Rubens Siqueira Res Ctr, Sao Jose Do Rio Preto, SP, Brazil.
RP Siqueira, RC (通讯作者)，Rua Saldanha Marinho 2815 Sala 42, BR-15010100 Sao Jose Do Rio Preto, SP, Brazil.
EM rubenssiqueira@retinologia.com.br
OI Siqueira, Rubens/0000-0003-4563-1570
CR Bashshur ZF, 2008, AM J OPHTHALMOL, V145, P249, DOI 10.1016/j.ajo.2007.09.031
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NR 19
TC 2
Z9 2
U1 0
U2 0
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD MAY-JUN
PY 2010
VL 20
IS 3
BP 559
EP 564
DI 10.1177/112067211002000304
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 629JD
UT WOS:000280191400012
PM 20037904
DA 2022-11-30
ER

PT J
AU Kim, JH
   Kim, JH
   Jun, HO
   Yu, YS
   Min, BH
   Park, KH
   Kim, KW
AF Kim, Jeong Hun
   Kim, Jin Hyoung
   Jun, Hyoung Oh
   Yu, Young Suk
   Min, Bon Hong
   Park, Kyu Hyung
   Kim, Kyu-Won
TI Protective Effect of Clusterin from Oxidative Stress-Induced Apoptosis
   in Human Retinal Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; PHOSPHOINOSITIDE 3-KINASE; HEAT-SHOCK; ACTIVATION;
   SURVIVAL; KINASE; PROTEINS; DAMAGE
AB PURPOSE. Oxidative stress to retinal pigment epithelial (RPE) cells is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study was conducted to investigate whether clusterin protects human RPE cells from ROS-induced apoptosis through a PI3K/Akt survival pathway.
   METHODS. The preventive effect of clusterin on reactive oxygen species (ROS) production and RPE cell death induced by hydrogen peroxide was determined in ARPE-19 cells. The ability of clusterin to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and DAPI staining. Furthermore, the protective effect of clusterin via the PI3K/Akt pathway was determined by Western blot analysis.
   RESULTS. Clusterin prevented ARPE-19 cells from H2O2-induced cell death and ROS production. H2O2-induced oxidative stress increased caspase-3 activity, which was significantly inhibited by clusterin, as determined by the abrogation of apoptotic bodies. Interestingly, clusterin induced Akt phosphorylation in human RPE cells under oxidative stress, which contributed to cell viability in ARPE-19 cells. This cell survival by clusterin was blocked by a PI3K inhibitor.
   CONCLUSIONS. Clusterin may play a protective role in responding to the local redox environment of human RPE cells, which contributes to the cell survival via the PI3K/Akt pathway. Therefore, clusterin could be considered for the preventive approach to AMD. (Invest Ophthalmol Vis Sci. 2010;51:561-566) DOI:10.1167/iovs.09-3774
C1 [Kim, Jeong Hun; Kim, Jin Hyoung; Jun, Hyoung Oh; Yu, Young Suk] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Fight Angiogenesis Related Blindness Lab, Seoul, South Korea.
   [Kim, Jeong Hun; Kim, Jin Hyoung; Jun, Hyoung Oh; Yu, Young Suk] Seoul Natl Univ Hosp, Seoul Artificial Eye Ctr, Clin Res Inst, Seoul 110744, South Korea.
   [Min, Bon Hong] Korea Univ, Coll Med, Dept Pharmacol, Seoul 136705, South Korea.
   [Min, Bon Hong] Korea Univ, Coll Med, Program Med Sci BK21, Seoul 136705, South Korea.
   [Park, Kyu Hyung] Seoul Natl Univ, Bundang Hosp, Dept Ophthalmol, Songnam, South Korea.
   [Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea.
   [Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea.
C3 Seoul National University (SNU); Seoul National University (SNU); Seoul
   National University Hospital; Korea University; Korea University
   Medicine (KU Medicine); Korea University; Korea University Medicine (KU
   Medicine); Seoul National University (SNU); Seoul National University
   (SNU); Seoul National University (SNU)
RP Yu, YS (通讯作者)，Seoul Natl Univ, Coll Med, Dept Ophthalmol, Fight Angiogenesis Related Blindness Lab, Seoul, South Korea.
EM ysyu@snu.ac.kr
RI Yu, Young Suk/J-5551-2012; Park, Kyu Hyung/J-5481-2012; Kim, Jeong
   Hun/J-2748-2012; Kim, Kyu Won/AAJ-7213-2020
OI Kim, Jeong Hun/0000-0003-2957-1766
FU Bundang Seoul National University Hospital Research Fund [02-2007-007];
   Ministry of Science and Technology [M1064501001-06n4501-00110]; Korea
   Science and Engineering Foundation
FX Supported by Bundang Seoul National University Hospital Research Fund
   Grant 02-2007-007; Bio-signal Analysis Technology Innovation Program
   Grant M1064501001-06n4501-00110 of the Ministry of Science and
   Technology; and the Korea Science and Engineering Foundation.
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NR 20
TC 67
Z9 68
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 JAN
PY 2010
VL 51
IS 1
BP 561
EP 566
DI 10.1167/iovs.09-3774
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 539OI
UT WOS:000273264200074
PM 19710412
DA 2022-11-30
ER

PT J
AU Mauget-Faysse, M
   Mimoun, G
   Ruiz-Moreno, JM
   Quaranta-El Maftouhi, M
   De Laey, JJ
   Postelmans, L
   Soubrane, G
   Defauchy, M
   Leys, A
AF Mauget-Faysse, Martine
   Mimoun, Gerard
   Ruiz-Moreno, Jose M.
   Quaranta-El Maftouhi, Maddalena
   De Laey, Jean J.
   Postelmans, Laurence
   Soubrane, Gisele
   Defauchy, Michel
   Leys, Anita
TI Verteporfin photodynamic therapy for choroidal neovascularization
   associated with toxoplasmic retinochoroiditis
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal neovascularization; photodynamic therapy; retinochoroiditis;
   toxoplasma; verteporfin
ID RANDOMIZED CLINICAL-TRIAL; OCULAR TOXOPLASMOSIS; MACULAR DEGENERATION;
   SUBRETINAL NEOVASCULARIZATION; PATHOLOGICAL MYOPIA; LATE COMPLICATION;
   SURGICAL REMOVAL; SECONDARY; MEMBRANE; CHILDREN
AB Purpose: To evaluate the efficacy and safety of verteporfin photodynamic therapy (V-PDT) for young adults and children with subfoveal choroidal neovascularization (CNV) associated with toxoplasmic retinochoroiditis.
   Methods: Patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were treated with V-PDT and prospectively followed up. Before V-PDT and during follow-up, patients underwent visual acuity testing, complete ophthalmic examination including color photography, angiography with fluorescein and/or indocyanine green, and optical coherence tomography. The decision to retreat CNV was based on the criteria used in the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy investigation.
   Results: Eight patients (5 males and 3 females) were treated at a mean age of 15.3 years (range, 5-31 years). CNV was 100% classic or predominantly classic in all study patients. Mean visual acuity increased from 20/225 (range, 20/400 to 20/50) to 20/123 (range, 20/200 to 20/25) during a mean follow-up period of 25 months (range, 5-49 months). Persistent closure of CNV was achieved in all eight patients (mean number of treatments, 1.75). Vascular anastomosis developed in the treated area in two patients, but there was no additional visual loss. No significant adverse effects of V-PDT were observed.
   Conclusion: V-PDT for subfoveal CNV associated with toxoplasmic retinochoroiditis appears to be effective and safe even in young adults and children. However, a longer follow-up is recommended to confirm our observations.
C1 Ctr Ophtalmol Rabelais, F-69003 Lyon, France.
   Fac Med, Div Oftalmol, Dept Patol & Cirugia, Alacant, Spain.
   State Univ Ghent Hosp, Dept Ophthalmol, B-9000 Ghent, Belgium.
   Univ Hosp St Rafael, Dept Ophthalmol, Louvain, Belgium.
C3 Ghent University; Ghent University Hospital
RP Mauget-Faysse, M (通讯作者)，Ctr Ophtalmol Rabelais, 12-14 Rue Rabelais, F-69003 Lyon, France.
RI Ruiz-Moreno, José M/E-4644-2016
OI Ruiz-Moreno, Jose M/0000-0001-9636-0788
CR AABERG TM, 2004, INVEST OPHTH VIS SCI, P45
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NR 30
TC 30
Z9 36
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD APR
PY 2006
VL 26
IS 4
BP 396
EP 403
DI 10.1097/00006982-200604000-00003
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 100QX
UT WOS:000241684800003
PM 16603957
DA 2022-11-30
ER

PT J
AU Tong, W
   Stamp, M
   Apollo, NV
   Ganesan, K
   Meffin, H
   Prawer, S
   Garrett, DJ
   Ibbotson, MR
AF Tong, Wei
   Stamp, Melanie
   Apollo, Nicholas, V
   Ganesan, Kumaravelu
   Meffin, Hamish
   Prawer, Steven
   Garrett, David J.
   Ibbotson, Michael R.
TI Improved visual acuity using a retinal implant and an optimized
   stimulation strategy
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prosthesis; stimulation strategy; diamond electrode array
ID GANGLION-CELLS; ELECTRICAL-STIMULATION; VISION LOSS; DIAMOND;
   THRESHOLDS; ACTIVATION; DEGENERATION; PERFORMANCE; RESPONSES; DENSITY
AB Objective. Retinal prosthetic devices hold great promise for the treatment of retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Through electrical stimulation of the surviving retinal neurons, these devices evoke visual signals that are then relayed to the brain. Currently, the visual prostheses used in clinical trials have few electrodes, thus limiting visual acuity. Electrode arrays with high electrode densities have been developed using novel technologies, including diamond growth and laser machining, and these may provide a more promising route to achieve high visual acuity in blind patients. Approach. Here, we studied the potential spatial resolution of electrical stimulation using diamond electrodes. We did this by labeling retinal ganglion cells in whole mount retina with a calcium indicator in wild-type rats and those with retinal degeneration. We imaged the ganglion cell responses to a range of stimulation parameters, including pulse duration and return electrode configuration. Main results. With sub-retinal stimulation, in which electrodes were in contact with the intact or degenerated photoreceptor layer, we found that biphasic pulses of 0.1 ms phase duration and a local return configuration was the most effective in confining the retinal ganglion cell activation patterns, while also remaining within the safety limits of the materials and providing the best power efficiency. Significance. These results provide an optimized stimulation strategy for retinal implants, which if implemented in a retinal prosthetic is expected to improve the achievable visual acuity.
C1 [Tong, Wei; Meffin, Hamish; Ibbotson, Michael R.] Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.
   [Tong, Wei; Stamp, Melanie; Apollo, Nicholas, V; Ganesan, Kumaravelu; Prawer, Steven; Garrett, David J.] Univ Melbourne, Sch Phys, Parkville, Vic, Australia.
   [Tong, Wei; Meffin, Hamish; Ibbotson, Michael R.] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic, Australia.
   [Apollo, Nicholas, V] Univ Penn, Ctr Neural Engn & Therapeut, Philadelphia, PA 19104 USA.
C3 University of Melbourne; University of Melbourne; University of
   Pennsylvania
RP Ibbotson, MR (通讯作者)，Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.; Ibbotson, MR (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic, Australia.
EM mibbotson@nvri.org.au
OI Meffin, Hamish/0000-0003-4307-6841; Stamp, Melanie/0000-0002-6333-285X;
   PRAWER, STEVEN/0000-0002-4959-0828; Garrett, David/0000-0002-4676-8387
FU National Health and Medical Research Council (NHMRC) of Australia
   [GNT1118223]; NHMRC [GNT1101717]; Australian Nanofabrication Facility
   (ANFF)/Melbourne Centre for Nanofabrication (MCN) Technology Ambassador
   Fellowship
FX We thank the Melbourne Advanced Microscopy Facility housed within Bio21
   at The University of Melbourne for SEM Imaging. The research was
   supported by a Development Grant from The National Health and Medical
   Research Council (NHMRC, GNT1118223) of Australia. The work was
   performed in part at the Melbourne Centre for Nanofabrication (MCN) in
   the Victorian Node of the Australian National Fabrication Facility
   (ANFF). DJG is supported by NHMRC Project Grant GNT1101717 and by an
   Australian Nanofabrication Facility (ANFF)/Melbourne Centre for
   Nanofabrication (MCN) Technology Ambassador Fellowship. SP is cofounder
   and shareholder of iBIONICS, a company developing a diamond based
   retinal prothesis. SP, DJG and NVA are shareholders and executive
   officers of Carbon Cybernetics Pty Ltd, a company developing diamond and
   carbon-based medical device components. The other authors declare no
   conflict of interest.
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NR 71
TC 12
Z9 13
U1 3
U2 15
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 2020
VL 17
IS 1
AR 016018
DI 10.1088/1741-2552/ab5299
PG 14
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA KA4MF
UT WOS:000505770300006
PM 31665704
DA 2022-11-30
ER

PT J
AU Chen, D
   Chao, DL
   Rocha, L
   Kolar, M
   Huu, VAN
   Krawczyk, M
   Dasyani, M
   Wang, TN
   Jafari, M
   Jabari, M
   Ross, KD
   Saghatelian, A
   Hamilton, BA
   Zhang, K
   Skowronska-Krawczyk, D
AF Chen, Daniel
   Chao, Daniel L.
   Rocha, Lorena
   Kolar, Matthew
   Viet Anh Nguyen Huu
   Krawczyk, Michal
   Dasyani, Manish
   Wang, Tina
   Jafari, Maryam
   Jabari, Mary
   Ross, Kevin D.
   Saghatelian, Alan
   Hamilton, Bruce A.
   Zhang, Kang
   Skowronska-Krawczyk, Dorota
TI The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in
   the retina
SO AGING CELL
LA English
DT Article
DE age-related macular degeneration; aging; DNA methylation; ELOVL2;
   retina; PUFA
ID DNA METHYLATION; MACULAR DEGENERATION; SUBRETINAL MICROGLIA; BIOLOGICAL
   AGE; LONG-CHAIN; GENE; ACCUMULATION; WIDE; 5-AZA-2'-DEOXYCYTIDINE;
   DYSTROPHY
AB Methylation of the regulatory region of the elongation of very-long-chain fatty acids-like 2 (ELOVL2) gene, an enzyme involved in elongation of long-chain polyunsaturated fatty acids, is one of the most robust biomarkers of human age, but the critical question of whether ELOVL2 plays a functional role in molecular aging has not been resolved. Here, we report that Elovl2 regulates age-associated functional and anatomical aging in vivo, focusing on mouse retina, with direct relevance to age-related eye diseases. We show that an age-related decrease in Elovl2 expression is associated with increased DNA methylation of its promoter. Reversal of Elovl2 promoter hypermethylation in vivo through intravitreal injection of 5-Aza-2'-deoxycytidine (5-Aza-dc) leads to increased Elovl2 expression and rescue of age-related decline in visual function. Mice carrying a point mutation C234W that disrupts Elovl2-specific enzymatic activity show electrophysiological characteristics of premature visual decline, as well as early appearance of autofluorescent deposits, well-established markers of aging in the mouse retina. Finally, we find deposits underneath the retinal pigment epithelium in Elovl2 mutant mice, containing components found in human drusen, a pathologic hallmark of age related macular degeneration. These findings indicate that ELOVL2 activity regulates aging in mouse retina, provide a molecular link between polyunsaturated fatty acids elongation and visual function, and suggest novel therapeutic strategies for the treatment of age-related eye diseases.
C1 [Chen, Daniel; Chao, Daniel L.; Rocha, Lorena; Viet Anh Nguyen Huu; Krawczyk, Michal; Dasyani, Manish; Jafari, Maryam; Jabari, Mary; Zhang, Kang; Skowronska-Krawczyk, Dorota] Univ Calif San Diego, Shiley Eye Inst, Viterbi Family Dept Ophthalmol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Kolar, Matthew; Saghatelian, Alan] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Wang, Tina] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Ross, Kevin D.; Hamilton, Bruce A.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Hamilton, Bruce A.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
   [Skowronska-Krawczyk, Dorota] Univ Calif San Diego, Atkinson Lab Regenerat Med, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego;
   Salk Institute; University of California System; University of
   California San Diego; University of California System; University of
   California San Diego; University of California System; University of
   California San Diego; University of California System; University of
   California San Diego
RP Skowronska-Krawczyk, D (通讯作者)，Univ Calif San Diego, Shiley Eye Inst, Viterbi Family Dept Ophthalmol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM DorotaSK@health.ucsd.edu
RI Zhang, Kang/Y-2740-2019
OI Zhang, Kang/0000-0002-4549-1697; Hamilton, Bruce/0000-0001-5599-9139;
   Jafari, Maryam/0000-0001-5552-1127
FU RPB Special Scholar Award; RPB; Ruth L. Kirschstein National Research
   Service Award (NRSA) Institutional Predoctoral Training Grant [T32
   GM008666]; National Institute of General Medical Sciences; UCSD Vision
   Research Center Core Grant [P30EY022589];  [R01 EY02701]; 
   [K12EY024225];  [R01 GM086912]
FX We thank Dr. Trey Ideker for supporting work of T.W. We thank Ella
   Kothari and Jun Zhao in the UCSD Moores Cancer Center Transgenic Mouse
   Shared Resource for expert assistance in generation of edited mice. This
   work was supported by R01 EY02701 and RPB Special Scholar Award to
   D.S.K., by K12EY024225 to D.L.C., and by R01 GM086912 to B.A.H as well
   as by RPB Unrestricted Grant to Shiley Eye Institute. D.C., T. W., and
   K. D.R. were supported in part by a Ruth L. Kirschstein National
   Research Service Award (NRSA) Institutional Predoctoral Training Grant,
   T32 GM008666, from the National Institute of General Medical Sciences.
   Functional imaging and histology work were funded in part by the UCSD
   Vision Research Center Core Grant P30EY022589.
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NR 59
TC 29
Z9 30
U1 4
U2 15
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2020
VL 19
IS 2
AR e13100
DI 10.1111/acel.13100
EA JAN 2020
PG 13
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA KM0JX
UT WOS:000506933000001
PM 31943697
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Qian, XJ
   Li, RZ
   Li, Y
   Lu, GX
   He, YM
   Humayun, MS
   Chen, ZP
   Zhou, QF
AF Qian, Xuejun
   Li, Runze
   Li, Yan
   Lu, Gengxi
   He, Youmin
   Humayun, Mark S.
   Chen, Zhongping
   Zhou, Qifa
TI In vivo evaluation of posterior eye elasticity using shaker-based
   optical coherence elastography
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Shear wave elastography; optical coherence tomography; posterior eye
   elasticity
ID TOMOGRAPHY
AB Age-related macular degeneration (AMD) is a progressive retinal disease and becomes the leading cause of blindness. It is well established that early detection is the key to preservation of functional vision. However, it is very difficult to diagnose AMD in very early stages, before structural changes are evident. Consequently, investigating the biomechanical properties of the retina maybe essential for understanding its physiological function. In this study, we present a shear wave-based quantitative method for estimating the elasticity of the posterior eye using shaker-based optical coherence elastography. This technique has been developed and validated on both a homogeneous phantom and a healthy rabbit in vivo. The shear wave speed from the ganglion side to the photoreceptor side of the rabbit eye is 4.1 m/s, 4.9 m/s, and 6.7 m/s, respectively. In addition, the most stiff sclera region has an average shear wave speed of 9.1 m/s. The results demonstrate the feasibility of using this technique to quantify biomechanical properties of the posterior eye and its potential translation to the clinical study. Impact statement Herein, we propose a potentially clinical applicable shaker-based optical coherence elastography (OCE) technique to characterize the biomechanical properties of the posterior eye, including different layers of the retina. Compared with either acoustic radiation force OCE or air-puff OCE, the newly developed method can induce sufficient shear wave propagation at the posterior eye with high resolution and large field of view.
C1 [Qian, Xuejun; Li, Runze; Lu, Gengxi; Humayun, Mark S.; Zhou, Qifa] Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
   [Qian, Xuejun; Li, Runze; Lu, Gengxi; Humayun, Mark S.; Zhou, Qifa] Univ Southern Calif, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA.
   [Qian, Xuejun; Li, Runze; Lu, Gengxi; Humayun, Mark S.; Zhou, Qifa] Univ Southern Calif, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
   [Li, Yan; He, Youmin; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92612 USA.
C3 University of Southern California; National Institutes of Health (NIH) -
   USA; University of Southern California; University of Southern
   California; University of California System; University of California
   Irvine
RP Zhou, QF (通讯作者)，Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.; Zhou, QF (通讯作者)，Univ Southern Calif, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA.; Zhou, QF (通讯作者)，Univ Southern Calif, USC Roski Eye Inst, Los Angeles, CA 90033 USA.; Chen, ZP (通讯作者)，Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92612 USA.
EM z2chen@uci.edu; qifazhou@usc.edu
RI Lu, Gengxi/ABV-3995-2022; Li, Runze/ABF-1320-2020; Li,
   Runze/GMW-8665-2022
OI Lu, Gengxi/0000-0001-7497-050X; Li, Runze/0000-0002-0154-2202; Qian,
   Xuejun/0000-0003-3634-8757; Li, Runze/0000-0002-6642-5904
FU National Institutes of Health (NIH) [R01EY026091, R01EY028662,
   R01EY030126, R01CA211602, NIH P30EY029220]; research to prevent
   blindness
FX This work was supported by the National Institutes of Health (NIH) under
   grant R01EY026091, R01EY028662, R01EY030126, R01CA211602 and NIH
   P30EY029220. Unrestricted departmental grant from research to prevent
   blindness.
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NR 27
TC 8
Z9 8
U1 3
U2 16
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1535-3702
EI 1535-3699
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD FEB
PY 2020
VL 245
IS 4
SI SI
BP 282
EP 288
AR 1535370219897617
DI 10.1177/1535370219897617
EA JAN 2020
PG 7
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA LA2NJ
UT WOS:000507743200001
PM 31910651
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhang, YJ
   Jeffrey, J
   Dong, F
   Zhang, JH
   Kao, WWY
   Liu, CY
   Yuan, Y
AF Zhang, Yujin
   Jeffrey, Joseph
   Dong, Fei
   Zhang, Jianhua
   Kao, Winston W-Y
   Liu, Chia-Yang
   Yuan, Yong
TI Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; BETA-CATENIN; PSEUDOEXFOLIATION SYNDROME;
   LIFE-SPAN; PATHWAY; INHIBITION; GENERATION; MECHANISM; GLAUCOMA; PROTEIN
AB Purpose. Ocular aging is a natural process of functional decline in vision. When the process reaches a point that compromised vision affects normal daily activity, it manifests as age-related ocular diseases, such as age-related macular degeneration, cataracts, glaucoma, and pseudoexfoliation syndrome. We previously reported that repressed Wnt signaling accelerated the maturation of corneal epithelium during tissue development. Here, we explore the hypothesis that repressed Wnt signaling is associated with accelerated aging in mouse eyes. Methods. Wnt ligand antagonist secreted frizzled-related protein 1 (sFRP1) was expressed in the corneal stroma by a tissue-specific, inducible, bitransgenic system. Tissue structure was analyzed for signs of aging. Signal transduction analysis was performed to determine the cellular response to sFRP1. Results. Mouse eyes with sFRP1 expression showed signs of accelerated aging, resembling those found in pseudoexfoliation (PEX) syndrome, a known age-related disease. Specific findings include granular deposition on the surface of the anterior lens capsule, pigment loss from the anterior surface of the iris, the presence of fibrillary material in the anterior chamber, and changes in cell size (polymegethism) and shape (pleomorphism) of the corneal endothelial cells. In vitro studies demonstrated that sFRP1 did not inhibit Wnt5a function and that cells responded to sFRP1 and Wnt5a in a very similar manner. Conclusion. The expression of sFRP1 accelerates the aging process in mouse eyes and future studies are warranted to elucidate the underlying mechanisms.
C1 [Zhang, Yujin; Liu, Chia-Yang] Indiana Univ, Sch Optometry, 800 East Atwater Ave, Bloomington, IN 47405 USA.
   [Jeffrey, Joseph; Dong, Fei; Zhang, Jianhua; Kao, Winston W-Y; Yuan, Yong] Univ Cincinnati, Coll Med, Dept Ophthalmol, Crawley Vis Res Lab, Cincinnati, OH 45221 USA.
C3 Indiana University System; Indiana University Bloomington; University
   System of Ohio; University of Cincinnati
RP Liu, CY (通讯作者)，Indiana Univ, Sch Optometry, 800 East Atwater Ave, Bloomington, IN 47405 USA.; Yuan, Y (通讯作者)，Univ Cincinnati, Coll Med, Dept Ophthalmol, Crawley Vis Res Lab, Cincinnati, OH 45221 USA.
EM liuchia@iu.edu; yuany@ucmail.uc.edu
OI Liu, Chia-yang/0000-0002-8398-5516
FU Glaucoma Foundation; Ohio Lions Eye Research Foundation [NIH-EY013755,
   R01EY029071]
FX This study was supported in part by grants from the Glaucoma Foundation
   (YY), Ohio Lions Eye Research Foundation and NIH-EY013755 (WWK), and
   R01EY029071 (CYL).
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NR 39
TC 5
Z9 5
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PY 2019
VL 2019
AR 7604396
DI 10.1155/2019/7604396
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IG2ZA
UT WOS:000473668000001
PM 31318361
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Labrador-Velandia, SC
   Sanabria, MR
AF Labrador-Velandia, Sonia C.
   Sanabria, Maria R.
TI Fluorescein Angiography Indications: Changes after Optical Coherence
   Tomography and Antiangiogenics
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB
AB SIGNIFICANCE: The present study provides quantitative data regarding the change of indications of fluorescein angiography in a tertiary hospital. Exhaustively compiled data over more than 10 years concerning all the angiographic studies including diagnosis, first-visit/follow-up, possible relation with antiangiogenics approval, and optic coherence tomography (OCT) are presented.
   PURPOSE: The aim of this study was to determine the frequency and indications of fluorescein angiography before and after OCT and anti-vascular endothelial growth factor (anti-VEGF) treatment implantation.
   METHODS: This was a retrospective and descriptive study of all fluorescein angiographies performed in a tertiary hospital between 2005 and 2016. Demographic data, diagnosis, follow-up, and type of angiograms were analyzed in relation with the implantation of time domain OCT (2006), spectral domain OCT (SD-OCT) (2013), and anti-VEGF (2007).
   RESULTS: Of 3263 angiograms (2342 patients) analyzed, 72% were baseline angiograms, and 28% were follow-up angiograms. After anti-VEGF initiation, the number of angiograms per year increased progressively with peaks that matched with the approval of anti-VEGF for wet age-related macular degeneration (2007) (164.2%), macular edema secondary to retinal vein occlusions (2010) (102.2%), and diabetic macular edema (2011) (123.8%). After using SD-OCT, fluorescein angiographies decreased up to 57%.
   CONCLUSIONS: Anti-VEGF introduction led to an increase in the indication of angiograms, which did not vary significantly after time domain OCT. Nevertheless, since SD-OCT became available, the indication of fluorescein angiography has halved in the hospital of reference.
C1 [Labrador-Velandia, Sonia C.; Sanabria, Maria R.] Inst Univ Oftalmobiol Aplicada IOBA, Valladolid, Spain.
   [Sanabria, Maria R.] Complejo Asistencial Univ Palencia, Ophthalmol Unit, Palencia, Spain.
RP Labrador-Velandia, SC (通讯作者)，Inst Univ Oftalmobiol Aplicada IOBA, Valladolid, Spain.
EM sonia_labrador@hotmail.com
RI Sanabria, Maria Rosa/AAH-5766-2019
OI Sanabria, Maria Rosa/0000-0002-1818-9812
CR American Academy of Ophthalmology (AAO), 2003, DIAB RET OREF PRACT
   Androudi S, 2016, ADV THER, V33, P715, DOI 10.1007/s12325-016-0332-7
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NR 18
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD MAY
PY 2018
VL 95
IS 5
BP 435
EP 442
DI 10.1097/OPX.0000000000001212
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GE4IV
UT WOS:000431180000004
PM 29683983
DA 2022-11-30
ER

PT J
AU Nishi, T
   Saeki, K
   Obayashi, K
   Miyata, K
   Tone, N
   Tsujinaka, H
   Yamashita, M
   Masuda, N
   Mizusawa, Y
   Okamoto, M
   Hasegawa, T
   Maruoka, S
   Ueda, T
   Kojima, M
   Matsuura, T
   Kurumatani, N
   Ogata, N
AF Nishi, Tomo
   Saeki, Keigo
   Obayashi, Kenji
   Miyata, Kimie
   Tone, Nobuhiro
   Tsujinaka, Hiroki
   Yamashita, Mariko
   Masuda, Naonori
   Mizusawa, Yutarou
   Okamoto, Masahiro
   Hasegawa, Taiji
   Maruoka, Shinji
   Ueda, Tetsuo
   Kojima, Masashi
   Matsuura, Toyoaki
   Kurumatani, Norio
   Ogata, Nahoko
TI The effect of blue-blocking intraocular lenses on circadian biological
   rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour
   study)
SO BMJ OPEN
LA English
DT Article
ID AGE-RELATED MACULOPATHY; NIGHT-SHIFT WORK; URINARY MELATONIN EXCRETION;
   GENERAL ELDERLY POPULATION; GERIATRIC DEPRESSION SCALE; EYE
   CATARACT-SURGERY; HEIJO-KYO COHORT; LIGHT EXPOSURE; GANGLION-CELLS;
   NURSES HEALTH
AB Introduction: Blue light information plays an important role in synchronising internal biological rhythm within the external environment. Circadian misalignment is associated with the increased risk of sleep disturbance, obesity, diabetes mellitus, depression, ischaemic heart disease, stroke and cancer. Meanwhile, blue light causes photochemical damage to the retina, and may be associated with age-related macular degeneration (AMD). At present, clear intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for cataract surgery; there is currently a lack of randomised controlled trials to determine whether clear or blue-blocking IOLs should be used.
   Methods and analysis: This randomised controlled trial will recruit 1000 cataract patients and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio of 1:1. The primary outcomes are mortality and the incidence of cardiovascular disease, cancer and AMD. Secondary outcomes are fasting plasma glucose, triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime sleepiness depressive symptoms, light sensitivity, the circadian rhythm of physical activity, wrist skin temperature and urinary melatonin metabolite. Primary outcomes will be followed until 20 years after surgery, and secondary outcomes will be assessed at baseline and 1 year after surgery.
   Ethics and dissemination: Ethical approval has been obtained from the Institutional Review Board of Nara Medical University (No. 13-032). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) home page.
C1 [Nishi, Tomo; Miyata, Kimie; Tsujinaka, Hiroki; Yamashita, Mariko; Masuda, Naonori; Mizusawa, Yutarou; Okamoto, Masahiro; Hasegawa, Taiji; Maruoka, Shinji; Ueda, Tetsuo; Kojima, Masashi; Matsuura, Toyoaki; Ogata, Nahoko] Nara Med Univ, Sch Med, Dept Ophthalmol, Nara, Japan.
   [Saeki, Keigo; Obayashi, Kenji; Kurumatani, Norio] Nara Med Univ, Sch Med, Dept Epidemiol & Community Hlth, Nara, Japan.
   [Tone, Nobuhiro] Nara Med Univ, Sch Med, Ctr Acad Ind & Govt Relat, Nara, Japan.
C3 Nara Medical University; Nara Medical University; Nara Medical
   University
RP Saeki, K (通讯作者)，Nara Med Univ, Sch Med, Dept Epidemiol & Community Hlth, Nara, Japan.
EM saekik@naramed-u.ac.jp
RI Hasegawa, Taiji/ABG-8260-2021; SAEKI, KEIGO/GWU-5723-2022
FU Nara Medical University
FX present study is supported by a grant for collaboration study from Nara
   Medical University.
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NR 75
TC 10
Z9 11
U1 1
U2 14
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 e007930
DI 10.1136/bmjopen-2015-007930
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC General & Internal Medicine
GA CI3LB
UT WOS:000354648100060
PM 25968007
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU van Zeeburg, EJT
   Maaijwee, K
   van Meurs, JC
AF van Zeeburg, Elsbeth J. T.
   Maaijwee, Kristel
   van Meurs, Jan C.
TI There is no relation between the occurrence of proliferative
   vitreoretinopathy and the location of the donor site after
   transplantation of a free autologous retinal pigment epithelium-choroid
   graft
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE donor site retinotomy; age-related macular degeneration; translocation
   surgery; retinal pigment epithelium-choroid graft; proliferative
   vitreoretinopathy
ID MACULAR DEGENERATION; SILICONE OIL; TRANSLOCATION; TAMPONADE
AB Abstract.
   Purpose: A free autologous retinal pigment epithelium (RPE)-choroid graft can be harvested during transplantation surgery from a 6 or 12 o'clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro-inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy.
   Methods: Retrospective analysis of a prospective cohort of 246 patients with exudative age-related macular degeneration treated with an RPE-choroid graft transplantation and a lighter-than-water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two-tailed Fisher's exact test was used for statistical analysis.
   Results: Thirty-nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p = 0.8).
   Conclusion: Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR.
C1 [van Zeeburg, Elsbeth J. T.] Rotterdam Ophthalm Inst, NL-3011 BH Rotterdam, Netherlands.
   [van Zeeburg, Elsbeth J. T.; Maaijwee, Kristel; van Meurs, Jan C.] Rotterdam Eye Hosp, Rotterdam, Netherlands.
   [van Meurs, Jan C.] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands.
C3 Rotterdam Eye Hospital; Erasmus University Rotterdam; Erasmus MC
RP van Zeeburg, EJT (通讯作者)，Rotterdam Ophthalm Inst, Schiedamse Vest 160-D, NL-3011 BH Rotterdam, Netherlands.
EM e.vanzeeburg@oogziekenhuis.nl
FU Rotterdam Eye Hospital Flieringa Research Foundation, Rotterdam, the
   Netherlands; Royal Visio, Rotterdam, the Netherlands
FX This study has been funded/supported by The Rotterdam Eye Hospital
   Flieringa Research Foundation, Rotterdam, the Netherlands, and Royal
   Visio, Rotterdam, the Netherlands. We would like to thank L. Spielberg
   for manuscript editing.
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NR 16
TC 4
Z9 4
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 MAY
PY 2014
VL 92
IS 3
BP 228
EP 231
DI 10.1111/aos.12178
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AF2HJ
UT WOS:000334532900015
PM 23890210
DA 2022-11-30
ER

PT J
AU Bharathselvi, M
   Biswas, J
   Selvi, R
   Coral, K
   Narayanasamy, A
   Ramakrishnan, S
   Sulochana, KN
AF Bharathselvi, Muthuvel
   Biswas, Jyothirmay
   Selvi, Radhakrishnan
   Coral, Karunakaran
   Narayanasamy, Angayarkanni
   Ramakrishnan, Sivaramakrishnan
   Sulochana, Konerirajapuram N.
TI Increased homocysteine, homocysteine-thiolactone, protein
   homocysteinylation and oxidative stress in the circulation of patients
   with Eales' disease
SO ANNALS OF CLINICAL BIOCHEMISTRY
LA English
DT Article
DE Clinical studies; laboratory methods; statistics
ID PROLIFERATIVE DIABETIC-RETINOPATHY; PLASMA HOMOCYSTEINE; ANTIOXIDANT
   ENZYMES; LYSYL OXIDASE; COPPER; GLUTATHIONE; MECHANISM; LIPIDS;
   CONSEQUENCES; PEROXIDATION
AB Background: Eales' disease (ED) is an idiopathic retinal vascular disorder. It presents with inflammation and neovascularization in the retina. Adult men, aged between 15 and 40 years are more susceptible than women. Homocysteine has been implicated in other ocular diseases including age-related macular degeneration (ARMD), central retinal vein occlusion (CRVO) and optic neuropathy. The present study investigates the role of homocysteine in ED.
   Methods: Forty male subjects, 20 with ED and 20 healthy controls, were recruited to the study. Their blood samples were used to measure thiobarbituric acid reactive substances (TBARS), glutathione (GSH), homocysteine, homocysteine-thiolactone, extent of homocysteine conjugation with proteins and plasma copper concentration.
   Results: In the ED group, plasma homocysteine (18.6 +/- 1.77 mmol/L, P<0.001) and homocysteine-thiolactone (45.3 +/- 6.8 nmol/L, P<0.0001) concentrations were significantly higher compared to homocysteine (11.2 +/- 0.64 mmol/L) and homocysteine-thiolactone (7.1 +/- 0.94 nmol/L) concentrations in control subjects. TBARS (P<0.011) and protein homocysteinylation (P<0.030) were higher in the ED group while GSH (5.9 +/- 0.44 mmol/L, P<0.01) and copper (6.6 +/- 0.42 mmol/L, P<0.001) were lower compared to GSH (8.1 +/- 0.41 mmol/L) and copper (15.4 +/- 0.73 mmol/L) concentrations in control subjects.
   Conclusions: Increased homocysteine, and its metabolite thiolactone, is associated with the functional impairment of protein due to homocysteinylation in ED.
C1 [Bharathselvi, Muthuvel; Selvi, Radhakrishnan; Coral, Karunakaran; Narayanasamy, Angayarkanni; Ramakrishnan, Sivaramakrishnan; Sulochana, Konerirajapuram N.] Sankara Nethralaya, Vis Res Fdn, Dept Biochem & Cell Biol, Madras 600006, Tamil Nadu, India.
   [Biswas, Jyothirmay] Sankara Nethralaya, Med Res Fdn, Dept Uveitis, Madras 600006, Tamil Nadu, India.
RP Sulochana, KN (通讯作者)，Sankara Nethralaya, Vis Res Fdn, Dept Biochem & Cell Biol, 41 Coll Rd, Madras 600006, Tamil Nadu, India.
EM drkns@snmail.org
RI Narayanasamy, Angayarkanni/ABD-8584-2020; Coral,
   Karunakaran/AAK-2880-2021
FU (ICMR) Indian council of Medical research [ICMR/52/16/2007-BMS]
FX Grant from (ICMR) Indian council of Medical research
   (ICMR/52/16/2007-BMS).
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NR 48
TC 9
Z9 9
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0004-5632
EI 1758-1001
J9 ANN CLIN BIOCHEM
JI Ann. Clin. Biochem.
PD JUL
PY 2013
VL 50
IS 4
BP 330
EP 338
DI 10.1177/0004563213492146
PG 9
WC Medical Laboratory Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Medical Laboratory Technology
GA 297XP
UT WOS:000330288700006
PM 23761385
DA 2022-11-30
ER

PT J
AU Frampton, JE
AF Frampton, James E.
TI Ranibizumab In Diabetic Macular Oedema
SO DRUGS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINOPATHY; DEGENERATION; LASER
AB Ranibizumab, an intravitreally administered inhibitor of vascular endothelial growth factor (VEGF), is approved for the treatment of visual impairment associated with diabetic macular oedema (DME) in the EU.
   In four well designed, phase II or III trials (RESOLVE, RESTORE, RIDE and RISE), 1-2 years' treatment with ranibizumab was more effective than sham or focal/grid laser therapy in improving best corrected visual acuity (BCVA) and reducing central retinal thickness (CRT) in patients with visual impairment associated with DME.
   Additionally, in two well designed phase III trials (RESTORE and DRCR.net-1), 1 year of treatment with ranibizumab as an adjunct to laser therapy was more effective than laser monotherapy in improving BCVA and CRT in patients with visual impairment associated with DME.
   Improvements in BCVA with ranibizumab alone or as an adjunct to laser therapy were observed at the first follow-up visits in these studies (i.e. 1-4 weeks after the start of treatment), and were associated with gains in vision-related quality of life, as assessed using the National Eye Institute Visual Functioning Questionnaire-25.
   The ocular and non-ocular adverse event profile of ranibizumab in patients with DME is similar to that observed in patients with neovascular (wet) age-related macular degeneration or retinal vein occlusion.
   Based on tolerability data from clinical trials, there is no indication that ranibizumab alone or combined with laser is associated with an increased risk of cardiovascular or cerebrovascular events potentially related to systemic VEGF inhibition.
C1 Adis Int Ltd, Auckland 0754, New Zealand.
C3 Adis International
RP Frampton, JE (通讯作者)，Adis Int Ltd, 41 Centorian Dr,Private Bag 65901, Auckland 0754, New Zealand.
EM demail@adis.co.nz
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NR 45
TC 19
Z9 21
U1 0
U2 3
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 0012-6667
EI 1179-1950
J9 DRUGS
JI Drugs
PY 2012
VL 72
IS 4
BP 509
EP 523
PG 15
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA 910DV
UT WOS:000301618300005
PM 22356289
DA 2022-11-30
ER

PT J
AU Bernardes, R
   Santos, T
   Serranho, P
   Lobo, C
   Cunha-Vaz, J
AF Bernardes, Rui
   Santos, Torcato
   Serranho, Pedro
   Lobo, Conceicao
   Cunha-Vaz, Jose
TI Noninvasive Evaluation of Retinal Leakage Using Optical Coherence
   Tomography
SO OPHTHALMOLOGICA
LA English
DT Article
DE Optical coherence tomography; Retinal leakage analyzer; Fluorescein
   angiography; Blood-retinal barrier
ID BARRIER
AB Purpose: To demonstrate the association between changes in the blood-retinal barrier (BRB) identified by fluorescein leakage and those in the optical properties of the human retina determined by optical coherence tomography (OCT) and show how these changes can be quantified and their location identified within the retina. Methods: Two imaging techniques were applied: the retinal leakage analyzer, to map BRB function into intact or disrupted regions, and OCT, to measure refractive index changes along the light path within the human ocular fundus. Results: A total of 140 comparisons were made, 77 between areas of regions receiving the same classification (intact or disrupted BRB) and 63 between areas of regions receiving distinct classifications, from 4 pathological cases: 2 eyes with nonproliferative diabetic retinopathy and 2 eyes with wet age-related macular degeneration. In all cases, the distribution of OCT data between regions of intact and regions of disrupted BRB, identified by the retinal leakage analyzer, was quantified and was statistically significantly different (p < 0.001). In addition, it was found that the differences could be localized in the retina to specific structural sequences. Conclusions: Using a novel method to analyze OCT data, we showed that it may be possible to quantify differences in the extracellular compartment in eyes with retinal disease and alterations of the BRB. Based on quantitative techniques, our findings demonstrate the presence of indirect information on the BRB status within noninvasive OCT data. Copyright (C) 2011 S. Karger AG, Basel
C1 [Bernardes, Rui; Santos, Torcato; Lobo, Conceicao; Cunha-Vaz, Jose] Assoc Innovat & Biomed Res Light & Image AIBILI, Ctr New Technol Med, Coimbra, Portugal.
   [Bernardes, Rui; Serranho, Pedro; Lobo, Conceicao; Cunha-Vaz, Jose] Univ Coimbra, Fac Med, Inst Biomed Res Light & Image, Coimbra, Portugal.
   [Lobo, Conceicao] Coimbra Univ Hosp, Coimbra, Portugal.
C3 Universidade de Coimbra; Universidade de Coimbra; Universidade de
   Coimbra; Centro Hospitalar e Universitario de Coimbra (CHUC)
RP Bernardes, R (通讯作者)，Assoc Innovat & Biomed Res Light & Image, P-3000548 Coimbra, Portugal.
EM rcb@aibili.pt
RI Lobo, Conceição/ABB-8609-2021; Bernardes, Rui/M-4231-2013; Serranho,
   Pedro/N-6444-2019; Lobo, Conceicao/B-4122-2016
OI Bernardes, Rui/0000-0002-6677-2754; Serranho, Pedro/0000-0003-2176-3923;
   Lobo, Conceicao/0000-0001-5831-7711; Cunha-Vaz,
   Jose/0000-0002-0947-9850; Santos, Torcato/0000-0003-1873-4320
FU Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/SAU-BEB/103151/2008,
   FCOMP-01-0124-FEDER-010930]
FX The authors would like to thank Dr. Melissa Horne and Carl Zeiss Meditec
   (Dublin, Calif., USA) for their support on getting access to OCT data,
   and AIBILI Clinical Trial Center technicians for their support in
   managing data, working with patients and performing scans. This study is
   supported in part by the Fundacao para a Ciencia e a Tecnologia (FCT)
   under the research project PTDC/SAU-BEB/103151/2008 and program COMPETE
   (FCOMP-01-0124-FEDER-010930).
CR Alfaro V., 2006, RETINOPATIA DIABETIC
   Bernardes R, 2005, IEEE T BIO-MED ENG, V52, P106, DOI 10.1109/TBME.2004.839801
   Bouma B.E., 2002, HDB OPTICAL COHERENC
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   *RET STUD GROUP, 2010, AMD AG REL MAC DEG
   SHAKIB M, 1966, EXP EYE RES, V5, P229, DOI 10.1016/S0014-4835(66)80011-8
NR 7
TC 8
Z9 10
U1 0
U2 9
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2011
VL 226
IS 2
BP 29
EP 36
DI 10.1159/000326268
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 771JO
UT WOS:000291153200001
PM 21508651
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Brar, M
   Kozak, I
   Cheng, LY
   Bartsch, DUG
   Yuson, R
   Nigam, N
   Oster, SF
   Mojana, F
   Freeman, WR
AF Brar, Manpreet
   Kozak, Igor
   Cheng, Lingyun
   Bartsch, Dirk-Uwe G.
   Yuson, Ritchie
   Nigam, Nitin
   Oster, Stephen F.
   Mojana, Francesca
   Freeman, William R.
TI Correlation between Spectral-Domain Optical Coherence Tomography and
   Fundus Autofluorescence at the Margins of Geographic Atrophy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SCANNING LASER OPHTHALMOSCOPE; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; FLUORESCEIN ANGIOGRAPHY; JUNCTIONAL ZONE; PATTERNS;
   CLASSIFICATION; VISUALIZATION; MACULOPATHY; ENLARGEMENT
AB PURPOSE: To study the appearance of margins of geographic atrophy in high-resolution optical coherence tomography (OCT) images and to correlate those changes with fundus autofluorescence (FAF) imaging.
   DESIGN: Retrospective, observational case study.
   METHODS: Patients with geographic atrophy secondary to dry age related macular degeneration were assessed by means of spectral,domain OCT (Spectralis Heidelberg Retinal Angiograph/OCT; Heidelberg Engineering, Heidelberg, Germany; or OTI Inc, Toronto, Canada) as well as autofluorescence imaging (Heidelberg Retinal Angio graph or Spectralis; Heidelberg Engineering). The outer retinal layer alterations were analyzed in the junctional zone between normal retina and atrophic retina and were correlated with corresponding FAF.
   RESULTS: Twenty,three eyes of 16 patients between 62 and 96 years of age were examined. There was a significant association between OCT findings and the FAF findings (r = 0.67; P < .0001). Severe alterations of the outer retinal layers at margins on spectral domain OCT correspond significantly to increased autofluorescence; smooth margins on OCT correspond significantly to normal FAF (kappa, 0.7348; P < .0001).
   CONCLUSIONS: Spectral,domain OCT provides in vivo insight into the pathogenesis of geographic atrophy and its progression. Visualization of reactive changes in the retinal pigment epithelial cells at the junctional zone and correlation with increased FAF; secondary to increased lipofuscin, together these methods may serve as determinants of progression of geographic atrophy. (Am J Ophthalmol 2009;148:439-444. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 [Brar, Manpreet; Kozak, Igor; Cheng, Lingyun; Bartsch, Dirk-Uwe G.; Yuson, Ritchie; Nigam, Nitin; Oster, Stephen F.; Mojana, Francesca; Freeman, William R.] Univ Calif San Diego, Dept Ophthalmol, Shiley Eye Ctr, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego
RP Freeman, WR (通讯作者)，Shiley Eye Ctr, UCSD Dept Ophthalmol, Joan & Irwin Jacobs Retina Ctr 0946, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM freeman@eyecenter.ucsd.edu
RI Kozak, Igor/AAC-4645-2019
FU National Institutes of Health [EY16323, EY07366]; Prevent Blindness
   Physician Scientist Award; NATIONAL EYE INSTITUTE [R01EY016323,
   R01EY007366] Funding Source: NIH RePORTER
FX THIS STUDY WAS SUPPORTED BY RESEARCH TO PREVENT BLINDNESS INC, NEW YORK,
   NEW YORK; THE NATIONAL EYE INSTITUTE, National Institutes of Health,
   Grant No. EY16323, Betlic-,da, Maryland (Dr Bartsch); and the National
   Institutes of Health GrantNo. EY07366 (Dr Freeman). Dr Freeman is the
   recipient of a Research to Prevent Blindness Physician Scientist Award.
   Dr Bartsch has received diSCOUnted product: and specialized software
   from OTI Inc. Involved in design of study (W.R.F., M.B., I.K.);
   collection and management of data (M.B., I.K., F.M., R.Y.);
   interl)retation ofdata (I.K., L.C., WRT, M.B.); preparation of
   manuscript (M.B., N.N., D.-U.G.B.); and approval of final manuscript
   (W.R.F., S.F.O.). The University of California San Diego Institutional
   Review Board approval was obtained to conduct this study. The study is
   in accordance with Health IIISLIMIlCe Portability and Accountability
   Act.
CR Bartsch DU, 2005, BRIT J OPHTHALMOL, V89, P1026, DOI 10.1136/bjo.2004.057364
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NR 27
TC 64
Z9 67
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
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2009
VL 148
IS 3
BP 439
EP 444
DI 10.1016/j.ajo.2009.04.022
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 493RK
UT WOS:000269755400018
PM 19541290
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Das, R
   Shi, YY
   Silvestri, G
   Chakravarthy, U
AF Das, Radha
   Shi, Yanyun
   Silvestri, Guiliana
   Chakravarthy, Usha
TI DISTORTION MAPS FROM PREFERENTIAL HYPERACUITY PERIMETRY ARE HELPFUL IN
   MONITORING FUNCTIONAL RESPONSE TO LUCENTIS THERAPY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE optical coherence tomography; preferential hyperacuity perimetry;
   ranibizumab; visual function
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; VISUAL
   FUNCTION; PHOTODYNAMIC THERAPY; RANIBIZUMAB; ACUITY
AB Purpose: To use preferential hyperacuity perimetry to obtain a quantitative measure of central visual field distortion that would aid in the monitoring of functional responsiveness to ranibizumab treatment.
   Methods: This study is a retrospective analysis of data from patients with neovascular age-related macular degeneration treated with ranibizumab. Preferential hyperacuity perimetry (PHP) were performed before and within 10 days of treatment. Pre- and posttreatment PHP metamorphopsia maps of contours showing 6 levels of metamorphopsia severity (S1 through S6; least to most distortion) were analyzed. Optical coherence tomography (OCT) outputs were subjected to standardized grading to generate metrics on subretinal fluid height, maximum retinal thickness, outer high-reflectivity band thickness, and height of pigment epithelial detachment (OCT metrics).
   Results: Complete data were available from 17 patients. Statistically significant reductions were seen. between baseline and posttreatment in PHP contour areas and OCT metrics, except for maximum retinal thickness. Mean best-corrected visual acuity improved by two letters, but this was not statistically significant Change in PHP parameters correlated strongly with change in subretinal fluid height, with P values of <0.01 for most comparisons. Change in best-corrected visual acuity did not correlate with change in any of the OCT metrics or PHP distortion map areas.
   Conclusion: The reduction in the contour map area seen on PHP outputs occurs rapidly and correlates with the resolution of subretinal fluid, suggesting that this parameter may be used to monitor response to therapy.
C1 [Das, Radha; Silvestri, Guiliana; Chakravarthy, Usha] Queens Univ Belfast, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland.
C3 Queens University Belfast
RP Chakravarthy, U (通讯作者)，Queens Univ Belfast, Inst Clin Sci, Ctr Vis Sci, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM u.chakravarthy@qub.ac.uk
OI Silvestri, Giuliana/0000-0001-5662-5374; Chakravarthy,
   Usha/0000-0002-2606-3734
FU Shanxi Scholarship Council of the Peoples Republic of China;
   International Council for Ophthalmology
FX Yanyun Shi was supported by a fellowship from Shanxi Scholarship Council
   of the Peoples Republic of China. Radha Das is a recipient of a training
   fellowship from the International Council for Ophthalmology.
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NR 19
TC 12
Z9 12
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUL-AUG
PY 2009
VL 29
IS 7
BP 1013
EP 1018
DI 10.1097/IAE.0b013e3181a91dbf
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 470DT
UT WOS:000267955400016
PM 19584658
DA 2022-11-30
ER

PT J
AU Bravo, HC
   Lee, KE
   Klein, BEK
   Klein, R
   Iyengar, SK
   Wahba, G
AF Bravo, Hector Corrada
   Lee, Kristine E.
   Klein, Barbara E. K.
   Klein, Ronald
   Iyengar, Sudha K.
   Wahba, Grace
TI Examining the relative influence of familial, genetic, and environmental
   covariate information in flexible risk models
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE SS-ANOVA; retinal pigmentary abnormalities; RKHS; pedigrees
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; SMOOTHING SPLINE ANOVA;
   MACULAR DEGENERATION; VARIANT; POLYMORPHISM; PROGRESSION
AB We present a method for examining the relative influence of familial, genetic, and environmental covariate information in flexible nonparametric risk models. Our goal is investigating the relative importance of these three sources of information as they are associated with a particular outcome. To that end, we developed a method for incorporating arbitrary pedigree information in a smoothing spline ANOVA (SS-ANOVA) model. By expressing pedigree data as a positive semidefinite kernel matrix, the SS-ANOVA model is able to estimate a log-odds ratio as a multicomponent function of several variables: one or more functional components representing information from environmental covariates and/or genetic marker data and another representing pedigree relationships. We report a case study on models for retinal pigmentary abnormalities in the Beaver Dam Eye Study. Our model verifies known facts about the epidemiology of this eye lesion-found in eyes with early age-related macular degeneration-and shows significantly increased predictive ability in models that include all three of the genetic, environmental, and familial data sources. The case study also shows that models that contain only two of these data sources, that is, pedigree-environmental covariates, or pedigree-genetic markers, or environmental covariates-genetic markers, have comparable predictive ability, but less than the model with all three. This result is consistent with the notions that genetic marker data encode-at least in part-pedigree data, and that familial correlations encode shared environment data as well.
C1 [Bravo, Hector Corrada] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
   [Lee, Kristine E.; Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
   [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
   [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Ophthalmol, Cleveland, OH 44106 USA.
   [Wahba, Grace] Univ Wisconsin, Dept Stat Biostat & Med Informat, Madison, WI 53706 USA.
   [Wahba, Grace] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; University of Wisconsin System; University of Wisconsin Madison;
   Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; University of Wisconsin System; University
   of Wisconsin Madison; University of Wisconsin System; University of
   Wisconsin Madison
RP Bravo, HC (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
EM hcorrada@jhsph.edu; wahba@stat.wisc.edu
RI Corrada Bravo, Hector/G-6584-2011; /S-1190-2019
OI /0000-0001-7488-250X; Corrada Bravo, Hector/0000-0002-1255-4444; Klein,
   Ronald/0000-0002-4428-6237
FU National Institutes of Health (NIH) [EY09946, EY06594, 5R01 EY018510];
   National Science Foundation [DMS-0604572]; Office of Naval Research
   [N0014-06-0095]; Research to Prevent Blindness Senior Scientific
   Investigator Awards; NATIONAL EYE INSTITUTE [R01EY009946, U10EY006594]
   Funding Source: NIH RePORTER
FX This work was partially supported by National Institutes of Health (NIH)
   Grant EY09946, National Science Foundation Grant DMS-0604572 and Office
   of Naval Research Grant N0014-06-0095 (to H.C.B. and G.W.), NIH Grant
   EY06594 (to K.L., R.K. and B.K.), the Research to Prevent Blindness
   Senior Scientific Investigator Awards (to R.K. and B.K.), and NIH Grant
   5R01 EY018510 (to S.I.).
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NR 35
TC 18
Z9 18
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 19
PY 2009
VL 106
IS 20
BP 8128
EP 8133
DI 10.1073/pnas.0902906106
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 447RH
UT WOS:000266209000010
PM 19420224
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Eichler, W
   Reiche, A
   Yafai, Y
   Lange, J
   Wiedemann, P
AF Eichler, Wolfram
   Reiche, Anett
   Yafai, Yousef
   Lange, Johannes
   Wiedemann, Peter
TI Growth-related effects of oxidant-induced stress on cultured RPE and
   choroidal endothelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   angiogenesis; oxidative stress; bFGF; retinal pigment epithelium
ID OXIDATIVE STRESS; MACULAR DEGENERATION; FACTOR LOCALIZATION; INDUCED
   APOPTOSIS; IN-VITRO; PIGMENT; EXPRESSION; NEOVASCULARIZATION; RETINA;
   DRUSEN
AB Mounting evidence suggests that oxidative stress caused by reactive oxygen intermediates is a significant mechanism in the pathogenesis of age-related macular degeneration (AMD). Although vascular endothelial growth factor (VEGF) and other cytokines are involved in choroidal neovascularization (CNV) it is largely unknown whether oxidative stress may predispose the eye to increased levels of proangiogenic factors. In an in vitro study we have determined viability and proliferation of both human retinal pigment epithelial (RPE) cells and bovine choroidal endothelial cells (CECs) and assessed the release of basic fibroblast growth factor (bFGF) and VEGF from RPE cells after exposing them to oxidative stress. Permanent presence of tert-butyl-hydroperoxide (tBH), a pro-oxidative stressor, in the cell cultures resulted in decreasing viability and proliferation of RPE cells and CECs. Loss of RPE cell viability was associated with activation of apoptosis by tBH in a dose-dependent manner. The antioxidant, N-acetyl-L-cysteine (NAC), and secreted soluble mediators of RPE cells were appropriate to attenuate the effects of tBH-mediated oxidative stress. RPE cells exposed to tBH were found to release increasing amounts of bFGF but not VEGF after 24 h of culture, thereby supporting proliferation of CECs. These findings suggest that oxidative stress compromises the viability of RPE cells and CECs. However, increased bFGF levels concomitantly released from RPE cells may attenuate the CEC-directed effect, protect CECs from oxidative insults, and are likely to promote CNV. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Eichler, Wolfram; Reiche, Anett; Yafai, Yousef; Lange, Johannes; Wiedemann, Peter] Univ Leipzig, Hosp Eye, D-04103 Leipzig, Germany.
C3 Leipzig University
RP Eichler, W (通讯作者)，Univ Leipzig, Hosp Eye, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM eichwolf@rz.uni-leipzig.de
FU Deutsche Forschungsgemeinschaft (DFG) [SPP1088];
   Ernst-und-Berta-Grimmke-Stiftung
FX This work was supported by Deutsche Forschungsgemeinschaft (DFG)
   Priority Research Program SPP1088. Y.Y. and W.E. were supported by
   Ernst-und-Berta-Grimmke-Stiftung, Dusseldorf, Germany. J.L is a fellow
   of the Research Training School "Interneuro", Leipzig.
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NR 52
TC 19
Z9 22
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2008
VL 87
IS 4
BP 342
EP 348
DI 10.1016/j.exer.2008.06.017
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 356UC
UT WOS:000259802100007
PM 18640112
DA 2022-11-30
ER

PT J
AU Zhang, B
   Osborne, NN
AF Zhang, B.
   Osborne, N. N.
TI Oxidative-induced retinal degeneration is attenuated by epigallocatechin
   gallate
SO BRAIN RESEARCH
LA English
DT Article
DE lipid peroxidation; sodium nitroprusside; nitric oxide; retina;
   photoreceptor degeneration; epigallocatechin gallate; neuroprotection
ID GREEN TEA CATECHINS; PROGRAMMED CELL-DEATH; NITRIC-OXIDE;
   (-)-EPIGALLOCATECHIN GALLATE; MACULAR DEGENERATION; LIPID-PEROXIDATION;
   GANGLION-CELLS; DAMAGE; POLYPHENOLS; RAT
AB The aim of this investigation was to determine whether an ingredient of green tea, epigallocatechin gallate (EGCG) could attenuate oxidative stress-induced degeneration of the retina as occurs in age-related macular degeneration (AMD) and glaucoma. Initial in vitro studies on brain membranes showed that EGCG was approximately 10 times more potent than trolox (vitamin E analogue) at attenuating lipid peroxidation caused by the nitric oxide donor, sodium nitroprusside (SNP). Subsequent immunohistochemical studies revealed that following an intraocular injection of SNP retinal photoreceptors are affected. This was supported by electroretinogram (ERG) recordings which showed both the a- and b-wave amplitudes to be significantly reduced. RT-PCR and Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in the cell death marker caspase-3, and no change in the ganglion cell specific markers, neurofilament (NF-L) and Thy-1. Importantly, when EGCG was co-injected, the detrimental effects to the retina caused by SNP were significantly blunted. The conclusion reached from this study is that EGCG is a powerful antioxidant and when injected into the eye with SNP attenuated the detrimental influence of SNP to retinal photoreceptors. Since oxidative stress has been implicated in retinal diseases like AMD and glaucoma this study provides "proof of principle" for the idea that daily intake of EGCG may help individuals suffering from retinal diseases where oxidative stress is implicated. (c) 2006 Elsevier B.V. All rights reserved.
C1 Univ Oxford, Nuffield Lab Opthalmol, Oxford OX2 6AW, England.
C3 University of Oxford
RP Osborne, NN (通讯作者)，Univ Oxford, Nuffield Lab Opthalmol, Walton St, Oxford OX2 6AW, England.
EM neville.osborne@eye.ox.ac.uk
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NR 67
TC 68
Z9 71
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD DEC 8
PY 2006
VL 1124
BP 176
EP 187
DI 10.1016/j.brainres.2006.09.067
PG 12
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 119MQ
UT WOS:000243016800020
PM 17084820
DA 2022-11-30
ER

PT J
AU Cho, HM
   Jo, YD
   Choung, SY
AF Cho, Hye-Mi
   Jo, Ye-Dam
   Choung, Se-Young
TI Protective Effects of Spirulina maxima against Blue Light-Induced
   Retinal Damages in A2E-Laden ARPE-19 Cells and Balb/c Mice
SO NUTRIENTS
LA English
DT Article
DE Spirulina maxima; age-related macular degeneration; A2E; blue light;
   inflammation; oxidative stress
ID VACCINIUM-ULIGINOSUM L.; MACULAR DEGENERATION; C-PHYCOCYANIN;
   CYTOCHROME-C; ANTIOXIDANT; RPE; A2E; INFLAMMATION; MECHANISMS;
   LIPOFUSCIN
AB Age-related macular degeneration (AMD) is a significant visual impairment in older people, and there is no treatment for dry AMD. Spirulina maxima (S. maxima), a cyanobacterium, has inhibitory effects against oxidative stress. However, the protective effects of S. maxima and its underlying mechanisms on blue light (BL)-caused macular degeneration are unknown. We aimed to investigate the protective effects of S. maxima on blue light-caused retinal damage and demonstrate its underlying mechanisms in human retinal pigment epithelial (ARPE-19) cells and Balb/c retinas. Additionally, the active component of S. maxima was examined in the RPE cells. In vitro, S. maxima decreased BL-induced RPE cell death by inhibiting reactive oxygen species (ROS) production. S. maxima inhibited BL-induced inflammation via regulating the NF-kappa B pathway, inflammatory-related gene expression, and the apoptosis pathway in RPE cells. In vivo, administration of S. maxima inhibited BL-induced retinal degeneration by restoring the thicknesses of whole retina, ONL (outer nuclear layer), INL (inner nuclear layer), and PL (photoreceptor layer) by BL exposure. Phycocyanin exerted protective effects in the pre-and post-treatment system. Therefore, S. maxima could be a potential nutraceutical approach to intercept the patho-physiological processes leading to dry AMD and advancement to wet AMD. Moreover, phycocyanin was a major active compound of S. maxima. These findings need to be investigated in human studies, particularly through a clinical trial.
C1 [Cho, Hye-Mi; Choung, Se-Young] Kyung Hee Univ, Dept Biomed & Pharmaceut Sci, Grad Sch, 26 Kyungheedae Ro, Seoul 02447, South Korea.
   [Jo, Ye-Dam] Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci, 26 Kyungheedae Ro, Seoul, South Korea.
   [Choung, Se-Young] Kyung Hee Univ, Coll Pharm, Dept Prevent Pharm & Toxicol, 26 Kyungheedae Ro, Seoul 02447, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University
RP Choung, SY (通讯作者)，Kyung Hee Univ, Dept Biomed & Pharmaceut Sci, Grad Sch, 26 Kyungheedae Ro, Seoul 02447, South Korea.; Choung, SY (通讯作者)，Kyung Hee Univ, Coll Pharm, Dept Prevent Pharm & Toxicol, 26 Kyungheedae Ro, Seoul 02447, South Korea.
EM hyemb2@khu.ac.kr; whdpeka1004@naver.com; sychoung@khu.ac.kr
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TC 2
Z9 2
U1 0
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD FEB
PY 2022
VL 14
IS 3
AR 401
DI 10.3390/nu14030401
PG 15
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA ZA2CF
UT WOS:000755974000001
PM 35276761
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Huang, WC
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   Hsiao, CY
   Wu, SJ
AF Huang, Wen-Chung
   Liou, Chian-Jiun
   Shen, Szu-Chuan
   Hu, Sindy
   Hsiao, Chien-Yu
   Wu, Shu-Ju
TI Luteolin Attenuates IL-1 beta-Induced THP-1 Adhesion to ARPE-19 Cells
   via Suppression of NF-kappa B and MAPK Pathways
SO MEDIATORS OF INFLAMMATION
LA English
DT Article
ID MACULAR DEGENERATION; RETINAL DEGENERATION; SIGNALING PATHWAYS;
   OXIDATIVE STRESS; AQUEOUS-HUMOR; INFLAMMATION; MODULATION; CYTOKINES
AB Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1 beta-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) kappa B transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1 beta-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-kappa B signaling pathways, thus ameliorating the inflammatory response.
C1 [Huang, Wen-Chung] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Food & Cosmet Safety, Grad Inst Hlth Ind Technol, Taoyuan 33303, Taiwan.
   [Huang, Wen-Chung; Liou, Chian-Jiun] Chang Gung Mem Hosp, Dept Pediat, Div Allergy Asthma & Rheumatol, Taoyuan 33303, Taiwan.
   [Liou, Chian-Jiun] Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Dept Nursing, Div Basic Med Sci, Taoyuan 33303, Taiwan.
   [Liou, Chian-Jiun] Chang Gung Univ Sci & Technol, Grad Inst Hlth Ind Technol, Taoyuan 33303, Taiwan.
   [Shen, Szu-Chuan] Natl Taiwan Normal Univ, Grad Program Nutr Sci, 88 Ting Chow Rd,Sec 4, Taipei, Taiwan.
   [Hu, Sindy] Chang Gung Univ Sci & Technol, Coll Human Ecol, Dept Cosmet Sci, Taoyuan 33303, Taiwan.
   [Hu, Sindy; Hsiao, Chien-Yu; Wu, Shu-Ju] Chang Gung Mem Hosp, Aesthet Med Ctr, Dept Dermatol, Taoyuan 33303, Taiwan.
   [Hsiao, Chien-Yu; Wu, Shu-Ju] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Dept Nutr & Hlth Sci, Taoyuan 33303, Taiwan.
C3 Chang Gung University of Science & Technology; Chang Gung Memorial
   Hospital; Chang Gung University of Science & Technology; Chang Gung
   University of Science & Technology; National Taiwan Normal University;
   Chang Gung University of Science & Technology; Chang Gung Memorial
   Hospital; Chang Gung University of Science & Technology
RP Liou, CJ (通讯作者)，Chang Gung Mem Hosp, Dept Pediat, Div Allergy Asthma & Rheumatol, Taoyuan 33303, Taiwan.; Liou, CJ (通讯作者)，Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Dept Nursing, Div Basic Med Sci, Taoyuan 33303, Taiwan.; Liou, CJ (通讯作者)，Chang Gung Univ Sci & Technol, Grad Inst Hlth Ind Technol, Taoyuan 33303, Taiwan.; Wu, SJ (通讯作者)，Chang Gung Mem Hosp, Aesthet Med Ctr, Dept Dermatol, Taoyuan 33303, Taiwan.; Wu, SJ (通讯作者)，Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Dept Nutr & Hlth Sci, Taoyuan 33303, Taiwan.
EM nulycopene@gmail.com; sjwu@mail.cgust.edu.tw
OI Huang, Wen-Chung/0000-0001-7141-8971
FU Chang Gung Memorial Hospital [CMRPF1G0203, CMRPF1J0041]; Ministry of
   Science and Technology [MOST 108-2320-B-255-004-]; Chang Gung University
   of Science and Technology [ZRRPF3J0081]
FX This research was supported by grants from the Chang Gung Memorial
   Hospital (CMRPF1G0203, CMRPF1J0041), Ministry of Science and Technology
   (MOST 108-2320-B-255-004-), and Chang Gung University of Science and
   Technology (ZRRPF3J0081) of Taiwan.
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NR 44
TC 13
Z9 14
U1 2
U2 4
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 0962-9351
EI 1466-1861
J9 MEDIAT INFLAMM
JI Mediat. Inflamm.
PD OCT 16
PY 2020
VL 2020
AR 9421340
DI 10.1155/2020/9421340
PG 15
WC Cell Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Immunology
GA ON2UT
UT WOS:000586563400001
PM 33122970
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Pieramici, DJ
   Heimann, F
   Brassard, R
   Barteselli, G
   Ranade, S
AF Pieramici, Dante J.
   Heimann, Felix
   Brassard, Raymond
   Barteselli, Giulio
   Ranade, Shrirang
TI Virtual Reality Becomes a Reality for Ophthalmologic Surgical Clinical
   Trials
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE port delivery system with ranibizumab (PDS); virtual reality; surgical
   clinical trial
AB The Port Delivery System with ranibizumab (PDS) is an innovative, investigational drug delivery system designed for continuous delivery of ranibizumab into the vitreous to maintain therapeutic drug concentrations for extended durations. The phase 2 Ladder trial (NCT02510794) tested the efficacy of three customized formulations of ranibizumab in patients with neovascular age-related macular degeneration, and the phase 3 Archway trial (NCT03677934) will further assess the safety and efficacy of PDS 100 mg/mL with fixed 24-week refills. The insertion of the PDS implant into the vitreous cavity and subsequent refill-exchange of the drug require procedural skills that are not directly transferable from everyday experience for most eye surgeons today. Preoperative practice for the PDS implant insertion and refill-exchange procedures is therefore critical for achieving optimal surgical outcomes. Virtual reality (VR) as a training tool has long been used by the aeronautic industry and more recently adapted for physician training in medicine and surgery, with encouraging results. Besides the primary use of traditional training tools, physicians participating in Archway have an option to practice in computer-simulated environments provided by VR simulators before performing their first PDS implant insertion and refill-exchange procedures on patients. This Perspective article describes the unique advantages and technologic challenges that practice on VR simulators has to offer, and the experience of Archway physicians with VR technology as a first in any ophthalmic clinical trial.
C1 [Pieramici, Dante J.] Calif Retina Res Fdn, 525 E Micheltorena St,Suite D, Santa Barbara, CA 93103 USA.
   [Heimann, Felix] VRmagic, Mannheim, Germany.
   [Brassard, Raymond; Barteselli, Giulio; Ranade, Shrirang] Genentech Inc, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech
RP Pieramici, DJ (通讯作者)，Calif Retina Res Fdn, 525 E Micheltorena St,Suite D, Santa Barbara, CA 93103 USA.
EM dpieramici@yahoo.com
OI Ranade, Shrirang/0000-0002-9457-2477
FU Genentech, Inc.
FX Supported by Genentech, Inc., a member of the Roche Group, for the
   studies and third-party writing assistance, which was provided by
   Priyanka Narang, PhD, of Envision Pharma Group.
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NR 17
TC 2
Z9 2
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2020
VL 9
IS 7
AR 1
DI 10.1167/tvst.9.7.1
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QG6VF
UT WOS:000617721800001
PM 32832208
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Horton, MB
   Brady, CJ
   Cavallerano, J
   Abramoff, M
   Barker, G
   Chiang, MF
   Crockett, CH
   Garg, S
   Karth, P
   Liu, Y
   Newman, CD
   Rathi, S
   Sheth, V
   Silva, P
   Stebbins, K
   Zimmer-Galler, I
AF Horton, Mark B.
   Brady, Christopher J.
   Cavallerano, Jerry
   Abramoff, Michael
   Barker, Gail
   Chiang, Michael F.
   Crockett, Charlene H.
   Garg, Seema
   Karth, Peter
   Liu, Yao
   Newman, Clark D.
   Rathi, Siddarth
   Sheth, Veeral
   Silva, Paolo
   Stebbins, Kristen
   Zimmer-Galler, Ingrid
TI Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third
   Edition
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE teleophthalmology; telemedicine; telehealth; diabetic retinopathy;
   artificial intelligence
ID ACUTE-PHASE RETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY; CENTRAL CORNEAL
   THICKNESS; MACULAR EDEMA; FUNDUS PHOTOGRAPHY; INTRAOCULAR-PRESSURE;
   DIGITAL PHOTOGRAPHY; COST-EFFECTIVENESS; RETINAL IMAGES; PLUS DISEASE
AB Contributors
   The following document and appendices represent the third edition of the Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy. These guidelines were developed by the Diabetic Retinopathy Telehealth Practice Guidelines Working Group. This working group consisted of a large number of subject matter experts in clinical applications for telehealth in ophthalmology.
   The editorial committee consisted of Mark B. Horton, OD, MD, who served as working group chair and Christopher J. Brady, MD, MHS, and Jerry Cavallerano, OD, PhD, who served as cochairs. The writing committees were separated into seven different categories. They are as follows:
   1. Clinical/operational: Jerry Cavallerano, OD, PhD (Chair), Gail Barker, PhD, MBA, Christopher J. Brady, MD, MHS, Yao Liu, MD, MS, Siddarth Rathi, MD, MBA, Veeral Sheth, MD, MBA, Paolo Silva, MD, and Ingrid Zimmer-Galler, MD.
   2. Equipment: Veeral Sheth, MD (Chair), Mark B. Horton, OD, MD, Siddarth Rathi, MD, MBA, Paolo Silva, MD, and Kristen Stebbins, MSPH.
   3. Quality assurance: Mark B. Horton, OD, MD (Chair), Seema Garg, MD, PhD, Yao Liu, MD, MS, and Ingrid Zimmer-Galler, MD.
   4. Glaucoma: Yao Liu, MD, MS (Chair) and Siddarth Rathi, MD, MBA.
   5. Retinopathy of prematurity: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD.
   6. Age-related macular degeneration: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD.
   7. Autonomous and computer assisted detection, classification and diagnosis of diabetic retinopathy: Michael Abramoff, MD, PhD (Chair), Michael F. Chiang, MD, and Paolo Silva, MD.
C1 [Horton, Mark B.] Phoenix Indian Med Ctr, Indian Hlth Serv Joslin Vis Network IHS JVN Teleo, Phoenix, AZ USA.
   [Brady, Christopher J.] Univ Vermont, Dept Surg, Div Ophthalmol, Larner Coll Med, Burlington, VT 05405 USA.
   [Cavallerano, Jerry; Silva, Paolo] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA.
   [Cavallerano, Jerry; Silva, Paolo] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
   [Abramoff, Michael] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Abramoff, Michael] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
   [Abramoff, Michael] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
   [Abramoff, Michael] Univ Iowa, Dept Ophthalmol, Stephen A Wynn Inst Vis Res, Iowa City, IA 52242 USA.
   [Abramoff, Michael] Iowa City VA Hlth Care Syst, Iowa City, IA USA.
   [Abramoff, Michael] IDx, Coralville, IA USA.
   [Barker, Gail] Univ Arizona, Arizona Telemed Program, Phoenix, AZ USA.
   [Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA.
   [Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
   [Crockett, Charlene H.] Baylor Coll Med City, Dept Ophthalmol, Houston, TX USA.
   [Garg, Seema] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC 27515 USA.
   [Karth, Peter] Oregon Eye Consultants, Eugene, OR USA.
   [Liu, Yao] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
   [Newman, Clark D.] Plaza Vis Ctr, Dallas, TX USA.
   [Rathi, Siddarth] NYU Langone Hlth, Dept Ophthalmol, New York, NY USA.
   [Sheth, Veeral] Univ Illinois, Univ Retina & Macula Associates, Chicago, IL USA.
   [Stebbins, Kristen] Vis Care Dept, New York, NY USA.
   [Zimmer-Galler, Ingrid] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
C3 University of Vermont; Harvard University; Joslin Diabetes Center, Inc.;
   Harvard University; Harvard Medical School; University of Iowa;
   University of Iowa; University of Iowa; University of Iowa; US
   Department of Veterans Affairs; Veterans Health Administration (VHA);
   Iowa City VA Health Care System; University of Arizona; Oregon Health &
   Science University; Oregon Health & Science University; University of
   North Carolina; University of North Carolina Chapel Hill; University of
   Wisconsin System; University of Wisconsin Madison; NYU Langone Medical
   Center; University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; Johns Hopkins University; Johns
   Hopkins Medicine
RP Horton, MB (通讯作者)，50 Cessna Lane, Fredericksburg, VA 22405 USA.
EM markhrtn@msn.com
RI Abramoff, Michael/A-5836-2009
OI Abramoff, Michael/0000-0002-3490-0037; LIU, YAO/0000-0002-0700-0148
FU National Institute of General Medical Sciences of the National
   Institutes of Health [P20GM103644]
FX C.J.B. was supported by the National Institute of General Medical
   Sciences of the National Institutes of Health under Award Number
   P20GM103644. 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 292
TC 25
Z9 27
U1 4
U2 12
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 APR 1
PY 2020
VL 26
IS 4
BP 495
EP 543
DI 10.1089/tmj.2020.0006
EA MAR 2020
PG 49
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services
GA LF2SB
UT WOS:000524984500001
PM 32209018
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU McAnally, D
   Siddiquee, K
   Gomaa, A
   Szabo, A
   Vasile, S
   Maloney, PR
   Divlianska, DB
   Peddibhotla, S
   Morfa, CJ
   Hershberger, P
   Falter, R
   Williamson, R
   Terry, DB
   Farjo, R
   Pinkerton, AB
   Qi, XP
   Quigley, J
   Boulton, ME
   Grant, MB
   Smith, LH
AF McAnally, Danielle
   Siddiquee, Khandaker
   Gomaa, Ahmed
   Szabo, Andras
   Vasile, Stefan
   Maloney, Patrick R.
   Divlianska, Daniela B.
   Peddibhotla, Satyamaheshwar
   Morfa, Camilo J.
   Hershberger, Paul
   Falter, Rebecca
   Williamson, Robert
   Terry, David B.
   Farjo, Rafal
   Pinkerton, Anthony B.
   Qi, Xiaping
   Quigley, Judith
   Boulton, Michael E.
   Grant, Maria B.
   Smith, Layton H.
TI Repurposing antimalarial aminoquinolines and related compounds for
   treatment of retinal neovascularization
SO PLOS ONE
LA English
DT Article
ID INTRAVITREAL BEVACIZUMAB AVASTIN; PROTEIN-COUPLED RECEPTOR; VASCULAR
   SMOOTH-MUSCLE; ENDOGENOUS LIGAND APELIN; CALIBER SIZE REGULATION;
   ANTI-VEGF THERAPY; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   ENDOTHELIAL-CELLS; APJ RECEPTOR
AB Neovascularization is the pathological driver of blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. The loss of vision resulting from these diseases significantly impacts the productivity and quality of life of patients, and represents a substantial burden on the health care system. Current standard of care includes biologics that target vascular endothelial growth factor (VEGF), a key mediator of neovascularization. While anti-VGEF therapies have been successful, up to 30% of patients are non-responsive. Therefore, there is a need for new therapeutic targets, and small molecule inhibitors of angiogenesis to complement existing treatments. Apelin and its receptor have recently been shown to play a key role in both developmental and pathological angiogenesis in the eye. Through a cell-based high-throughput screen, we identified 4-aminoquinoline antimalarial drugs as potent selective antagonists of APJ. The prototypical 4-aminoquinoline, amodiaquine was found to be a selective, non-competitive APJ antagonist that inhibited apelin signaling in a concentration-dependent manner. Additionally, amodiaquine suppressed both apelin-and VGEF-induced endothelial tube formation. Intravitreal amodaiquine significantly reduced choroidal neovascularization (CNV) lesion volume in the laser-induced CNV mouse model, and showed no signs of ocular toxicity at the highest doses tested. This work firmly establishes APJ as a novel, chemically tractable therapeutic target for the treatment of ocular neovascularization, and that amodiaquine is a potential candidate for repurposing and further toxicological, and pharmacokinetic evaluation in the clinic.
C1 [McAnally, Danielle; Siddiquee, Khandaker; Szabo, Andras; Smith, Layton H.] Sanford Burnham Prebys Med Discovery Inst, Diabet & Obes Res Ctr, Cardiovasc Pathobiol Program, Orlando, FL 32827 USA.
   [McAnally, Danielle; Vasile, Stefan; Maloney, Patrick R.; Divlianska, Daniela B.; Peddibhotla, Satyamaheshwar; Morfa, Camilo J.; Hershberger, Paul; Falter, Rebecca; Williamson, Robert; Terry, David B.; Smith, Layton H.] Sanford Burnham Prebys Med Discovery Inst, Conrad Prebys Ctr Chem Genom, Orlando, FL 32827 USA.
   [Gomaa, Ahmed; Qi, Xiaping; Quigley, Judith; Boulton, Michael E.; Grant, Maria B.] Indiana Univ, Sch Med Indianapolis, Dept Ophthalmol, Indianapolis, IN 46204 USA.
   [Farjo, Rafal] EyeCRO LLC, Oklahoma City, OK USA.
   [Pinkerton, Anthony B.] Sanford Burnham Prebys Med Discovery Inst, Conrad Prebys Ctr Chem Genom, La Jolla, CA USA.
   [Qi, Xiaping; Boulton, Michael E.; Grant, Maria B.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 Sanford Burnham Prebys Medical Discovery Institute; Sanford Burnham
   Prebys Medical Discovery Institute; Indiana University System; Indiana
   University-Purdue University Indianapolis; Sanford Burnham Prebys
   Medical Discovery Institute; University of Alabama System; University of
   Alabama Birmingham
RP Smith, LH (通讯作者)，Sanford Burnham Prebys Med Discovery Inst, Diabet & Obes Res Ctr, Cardiovasc Pathobiol Program, Orlando, FL 32827 USA.; Smith, LH (通讯作者)，Sanford Burnham Prebys Med Discovery Inst, Conrad Prebys Ctr Chem Genom, Orlando, FL 32827 USA.
EM lhsmith@sbpdiscovery.org
OI Pinkerton, Anthony/0000-0003-4571-152X; Smith,
   Layton/0000-0003-2621-9740
FU Juvenile Diabetes Research Foundation [2-SRA-2014-146-Q-R]; Florida
   Department of Health James and Esther King grant [4KF01]; NIH [NS059422,
   EY018358, EY028861, HG005033]; Florida Translational Research Program
   (COHK8)
FX This work was funded by the Juvenile Diabetes Research Foundation
   (2-SRA-2014-146-Q-R), Florida Department of Health James and Esther King
   grant (4KF01), NIH NS059422, EY018358, EY028861 and HG005033. L.H.S.
   acknowledges support from the Florida Translational Research Program
   (COHK8), a contract administered by the Florida Department of Health,
   and for which L.H.S. is the Principal Investigator. The funders provided
   support in the form of salaries for authors [D.M., K.S., A.G., S.V.,
   P.R.M., D.B.D., S.P., C.J.M., P.H., R.F., R.W., D.B.T., A.B.P., X.Q.,
   J.Q., M.E.B., M.B.G., L.H.S.], but did not have any additional role in
   the study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. Rafal Farjo is an employee of EyeCRO,
   LLC. He provided subject matter expertise and his team provided contract
   research services on a fee-for-service basis. No employee of EyeCRO had
   any input regarding the interpretation of data, decision to publish, or
   preparation of the manuscript. This commercial affiliation does not
   alter our adherence to PLOS ONE policies on sharing data and materials.
   The specific roles of these authors are articulated in the 'author
   contributions' section.
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NR 90
TC 8
Z9 8
U1 1
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 SEP 12
PY 2018
VL 13
IS 9
AR e0202436
DI 10.1371/journal.pone.0202436
PG 23
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GT7EB
UT WOS:000444683000018
PM 30208056
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Nguyen, QD
   De Falco, S
   Behar-Cohen, F
   Lam, WC
   Li, X
   Reichhart, N
   Ricci, F
   Pluim, J
   Li, WW
AF Quan Dong Nguyen
   De Falco, Sandro
   Behar-Cohen, Francine
   Lam, Wai-Ching
   Li, Xuri
   Reichhart, Nadine
   Ricci, Federico
   Pluim, Jennifer
   Li, William W.
TI Placental growth factor and its potential role in diabetic retinopathy
   and other ocular neovascular diseases
SO ACTA OPHTHALMOLOGICA
LA English
DT Review
DE angiogenesis; diabetic retinopathy; neovascularization; placental growth
   factor; retina; vascular endothelial growth factor
ID RETINAL VEIN OCCLUSION; INTRAVITREAL AFLIBERCEPT INJECTION; MACULAR
   DEGENERATION; TUMOR ANGIOGENESIS; VASCULAR-PERMEABILITY; PROLONGED
   BLOCKADE; ENDOTHELIAL-CELLS; VEGF FAMILY; ANTI-VEGF; RANIBIZUMAB
AB The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.
C1 [Quan Dong Nguyen] Ocular Imaging Res & Reading Ctr, Omaha, NE 68198 USA.
   [De Falco, Sandro] CNR, Angiogenesis Lab, Inst Genet & Biophysics, Naples, Italy.
   [Behar-Cohen, Francine] UPMC Univ, Paris Descartes Univ, Sorbonne Paris Cite, Res Ctr Cordeliers,INSERM,U1138,UMR S 1138, Paris, France.
   [Behar-Cohen, Francine] Univ Lausanne, Asylum Fdn Blind, Dept Ophthalmol, Jules Gonin Hosp, Lausanne, Switzerland.
   [Lam, Wai-Ching] Univ Toronto, Dept Ophthalmol, Toronto, ON, Canada.
   [Li, Xuri] Sun Yat Sen Univ, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Reichhart, Nadine] Charite, Expt Ophthalmol, Eye Clin, Berlin, Germany.
   [Ricci, Federico] UOSD Retinal Dis Fdn PTV Polyclin Tor Vergata, Rome, Italy.
   [Pluim, Jennifer] Bayer Pharmaceut, Whippany, NJ USA.
   [Li, William W.] Angiogenesis Fdn, Cambridge, MA USA.
C3 Consiglio Nazionale delle Ricerche (CNR); Institut National de la Sante
   et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; University of
   Lausanne; University of Toronto; Sun Yat Sen University; Free University
   of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin
   Berlin; Bayer AG; Bayer Healthcare Pharmaceuticals
RP Nguyen, QD (通讯作者)，Ocular Imaging Res & Reading Ctr, Omaha, NE 68198 USA.
EM quan.nguyen@unmc.edu
RI ricci, federico/AAC-3836-2020
OI ricci, federico/0000-0002-4224-9280; De Falco,
   Sandro/0000-0002-6501-1697; Lam, Wai-Ching/0000-0003-2057-9374
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NR 94
TC 44
Z9 45
U1 0
U2 16
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 2018
VL 96
IS 1
BP E1
EP E9
DI 10.1111/aos.13325
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FT3SB
UT WOS:000423066600001
PM 27874278
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Rapino, C
   Tortolani, D
   Scipioni, L
   Maccarrone, M
AF Rapino, Cinzia
   Tortolani, Daniel
   Scipioni, Lucia
   Maccarrone, Mauro
TI Neuroprotection by (Endo)Cannabinoids in Glaucoma and Retinal
   Neurodegenerative Diseases
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Review
DE Neuroprotection; glaucoma; retinal diseases; retinal ganglion cells;
   endocannabinoids; phytocannabinoids
ID ACID AMIDE HYDROLASE; GANGLION-CELL DEATH; CANNABINOID CB2 RECEPTOR;
   OPEN-ANGLE GLAUCOMA; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER;
   NORMAL-TENSION GLAUCOMA; HUMOR OUTFLOW FACILITY; INTRAOCULAR-PRESSURE;
   RAT RETINA; ENDOCANNABINOID SYSTEM
AB Background: Emerging neuroprotective strategies are being explored to preserve the retina from degeneration, that occurs in eye pathologies like glaucoma, diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosa. Incidentally, neuroprotection of retina is a defending mechanism designed to prevent or delay neuronal cell death, and to maintain neural function following an initial insult, thus avoiding loss of vision.
   Methods: Numerous studies have investigated potential neuroprotective properties of plant-derived phytocannabinoids, as well as of their endogenous counterparts collectively termed endocannabinoids (eCBs), in several degenerative diseases of the retina. eCBs are a group of neuromodulators that, mainly by activating G protein-coupled type-1 and type-2 cannabinoid (CB1 and CB2) receptors, trigger multiple signal transduction cascades that modulate central and peripheral cell functions. A fine balance between biosynthetic and degrading enzymes that control the right concentration of eCBs has been shown to provide neuroprotection in traumatic, ischemic, inflammatory and neurotoxic damage of the brain.
   Results: Since the existence of eCBs and their binding receptors was documented in the retina of numerous species (from fishes to primates), their involvement in the visual processing has been demonstrated, more recently with a focus on retinal neurodegeneration and neuroprotection.
   Conclusion: The aim of this review is to present a modern view of the endocannabinoid system, in order to discuss in a better perspective available data from preclinical studies on the use of eCBs as new neuroprotective agents, potentially useful to prevent glaucoma and retinal neurodegenerative diseases.
C1 [Rapino, Cinzia; Tortolani, Daniel] Univ Teramo, Fac Vet Med, I-64100 Teramo, Italy.
   [Scipioni, Lucia; Maccarrone, Mauro] Campus BioMed Univ Rome, Dept Med, I-00128 Rome, Italy.
   [Maccarrone, Mauro] IRCCS Santa Lucia Fdn, European Ctr Brain Res, I-00164 Rome, Italy.
C3 University of Teramo; University Campus Bio-Medico - Rome Italy; IRCCS
   Santa Lucia
RP Rapino, C (通讯作者)，Univ Teramo, Fac Vet Med, I-64100 Teramo, Italy.; Maccarrone, M (通讯作者)，Campus BioMed Univ Rome, Dept Med, I-00128 Rome, Italy.
EM crapino@unite.it; m.maccarrone@unicampus.it
RI Tortolani, Daniel/AHE-7927-2022; Maccarrone, Mauro/K-5398-2012
OI Maccarrone, Mauro/0000-0002-3990-2963; TORTOLANI,
   DANIEL/0000-0002-6704-9023
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   Zhang M, 2008, NEUROSCIENCE, V152, P753, DOI 10.1016/j.neuroscience.2008.01.022
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NR 159
TC 32
Z9 33
U1 2
U2 12
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1570-159X
EI 1875-6190
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PY 2018
VL 16
IS 7
BP 959
EP 970
DI 10.2174/1570159X15666170724104305
PG 12
WC Neurosciences; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA GN1UB
UT WOS:000438778700006
PM 28738764
OA Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Demirel, S
   Yanik, O
   Nalci, H
   Batioglu, F
   Ozmert, E
AF Demirel, Sibel
   Yanik, Ozge
   Nalci, Hilal
   Batioglu, Figen
   Ozmert, Emin
TI The use of optical coherence tomography angiography in pachychoroid
   spectrum diseases: a concurrent comparison with dye angiography
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Flat irregular retinal pigment epithelium detachment; Optical coherence
   tomography angiography; Indocyanine green angiography; Pachychoroid
   neovasculopathy
ID CENTRAL SEROUS CHORIORETINOPATHY; PIGMENT EPITHELIAL DETACHMENTS;
   CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; NEOVASCULOPATHY
AB The study objective was to compare dye angiography and optical coherence tomography angiography (OCTA) in detecting choroidal neovascuarization (CNV) in patients presenting with pachychoroid features and flat irregular pigment epithelial detachment (PED).
   Nineteen eyes of 17 patients, presenting with flat PED and pachychoroid features, and without age-related macular degeneration or any other degenerative change, were analyzed. Fuorescein angiography (FA)/Indocyanine green angiography (ICGA) and OCTA were performed during the same visit. Subfoveal choroidal thickness was measured by enhanced depth imaging using spectral domain optical coherence tomography.
   The mean age of the patients was 59.1 years. Mean subfoveal choroidal thickness was 388 mu m. FA revealed non-patognomic features including RPE alterations, window defects, leaking points and leakage from an undetermined source. ICGA revealed choroidal vascular plaque in eight eyes (42%) and suspicious plaque in five eyes (26%). Nonneovascular features, such as hyperpermeability or dilated choroidal vessels, were observed in six eyes (32%). OCTA showed choroidal neovascularization in 14 (74%). For all of the eyes, which ICGA was positive for presence of CNV, OCTA also showed CNV, and in one case it also revealed polypoidal characteristics of the neovascular network. OCTA was also able to detect CNV in all of the eyes with suspicious plaque, and in one eye without CNV appearance using ICGA.
   OCTA demonstrated greater sensitivity in detecting type 1 CNV than conventional dye angiography in cases with pachychoroid spectrum disease.
C1 [Demirel, Sibel; Yanik, Ozge; Nalci, Hilal; Batioglu, Figen; Ozmert, Emin] Ankara Univ, Dept Ophthalmol, Vehbi Koc Goz Hastanesi, Fac Med, Mamak Caddesi, Ankara, Turkey.
C3 Ankara University
RP Demirel, S (通讯作者)，Ankara Univ, Dept Ophthalmol, Vehbi Koc Goz Hastanesi, Fac Med, Mamak Caddesi, Ankara, Turkey.
EM drsibeldemireltr@yahoo.com.tr
RI Yanık Odabaş, Özge/AAO-6777-2020; DEMIREL, SIBEL/GQH-3232-2022;
   Batıoğlu, Figen/AAQ-3727-2020; Demirel, Sibel/AAQ-4282-2020
OI Yanık Odabaş, Özge/0000-0002-1822-8703; DEMIREL,
   SIBEL/0000-0002-2477-9974; Batıoğlu, Figen/0000-0002-5834-7512; Demirel,
   Sibel/0000-0002-6430-6565
CR Azar G, 2016, ACTA OPHTHALMOL
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NR 20
TC 16
Z9 18
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 DEC
PY 2017
VL 255
IS 12
BP 2317
EP 2324
DI 10.1007/s00417-017-3793-8
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FN5JY
UT WOS:000416044900003
PM 28891028
DA 2022-11-30
ER

PT J
AU McGill, TJ
   Bohana-Kashtan, O
   Stoddard, JW
   Andrews, MD
   Pandit, N
   Rosenberg-Belmaker, LR
   Wiser, O
   Matzrafi, L
   Banin, E
   Reubinoff, B
   Netzer, N
   Irving, C
AF McGill, Trevor J.
   Bohana-Kashtan, Osnat
   Stoddard, Jonathan W.
   Andrews, Michael D.
   Pandit, Neelay
   Rosenberg-Belmaker, Lior R.
   Wiser, Ofer
   Matzrafi, Limor
   Banin, Eyal
   Reubinoff, Benjamin
   Netzer, Nir
   Irving, Charles
TI Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells
   Following Transplantation
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE RPE cells; transplantation; AMD; Xeno-free
ID RETINAL DEGENERATIVE DISEASE; PIGMENT EPITHELIUM-CELLS;
   FIBROBLAST-GROWTH-FACTOR; EMBRYONIC STEM-CELLS; RCS RATS; MACULAR
   DEGENERATION; ROYAL-COLLEGE; PHOTORECEPTOR PRECURSORS; HOST
   PHOTORECEPTORS; VISUAL FUNCTION
AB Purpose: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats.
   Methods: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells. BSS_(balanced salt solution) (vehicle) and unoperated eyes served as controls. Optomotor tracking (OKT) behavior was used to quantify functional efficacy. Histology and immunohistochemistry were used to evaluate photoreceptor rescue and transplanted cell survival at 60, 100, 150, and 200 days of age.
   Results: OKT was rescued in a dose-dependent manner. Outer nuclear layer (ONL) was significantly thicker in cell-treated eyes than controls up to P150. Transplanted RPE cells were identified in both the subretinal space and integrated into the host RPE monolayer in animals of all age groups, and often contained internalized photoreceptor outer segments. No pathology was observed.
   Conclusions: OpRegen RPE cells survived, rescued visual function, preserved rod and cone photoreceptors long-term in the RCS rat. Thus, these data support the use of OpRegen RPE cells for the treatment of human RPE cell disorders including
C1 [McGill, Trevor J.; Andrews, Michael D.; Pandit, Neelay] OHSU, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
   [McGill, Trevor J.; Stoddard, Jonathan W.] OHSU, Oregon Natl Primate Res Ctr, Dept Neurosci, Beaverton, OR USA.
   [Bohana-Kashtan, Osnat; Rosenberg-Belmaker, Lior R.; Wiser, Ofer; Matzrafi, Limor; Netzer, Nir; Irving, Charles] Cell Cure Neurosci Ltd, Jerusalem, Israel.
   [Banin, Eyal] Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, Ctr Retinal & Macular Degenerat, Jerusalem, Israel.
   [Reubinoff, Benjamin] Hadassah Hebrew Univ, Med Ctr, Sidney & Judy Swartz Embryon Stem Cell Res Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel.
   [Reubinoff, Benjamin] Hadassah Hebrew Univ, Med Ctr, Dept Obstet & Gynecol, Jerusalem, Israel.
C3 Oregon Health & Science University; Oregon Health & Science University;
   Oregon National Primate Research Center; Hebrew University of Jerusalem;
   Hadassah University Medical Center; Hebrew University of Jerusalem;
   Hadassah University Medical Center; Hebrew University of Jerusalem;
   Hadassah University Medical Center
RP McGill, TJ (通讯作者)，OHSU, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM mcgilltr@ohsu.edu
OI Reubinoff, Benjamin/0000-0003-0353-1299
FU 10572 from the National Institutes of Health (Bethesda, MD) [P30
   EY010572]; NATIONAL EYE INSTITUTE [P30EY010572] Funding Source: NIH
   RePORTER
FX Supported by grants from Cell Cure Neurosciences, Unrestricted
   departmental funding from Research to Prevent Blindness (New York, NY),
   departmental core grant P30 EY010572 from the National Institutes of
   Health (Bethesda, MD).
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NR 50
TC 32
Z9 34
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAY
PY 2017
VL 6
IS 3
AR 17
DI 10.1167/tvst.6.3.17
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FH2GT
UT WOS:000410957800017
PM 28626601
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU McHarg, S
   Brace, N
   Bishop, PN
   Clark, SJ
AF McHarg, Selina
   Brace, Nicole
   Bishop, Paul N.
   Clark, Simon J.
TI Enrichment of Bruch's Membrane from Human Donor Eyes
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 105; Human eye tissue; age-related macular
   degeneration; retinal disease; Bruch's membrane; drusen; western
   blotting
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; AGE
AB Age-related macular degeneration (AMD) is a leading cause of visual impairment in the developed world. The disease manifests itself by the destruction of the center of the retina, called the macula, resulting in the loss of central vision. Early AMD is characterised by the presence of small, yellowish lesions called soft drusen that can progress onto late AMD such as geographic atrophy (dry AMD) or neovascularisation (wet AMD). Although the clinical changes are well described, and the understanding of genetic influences on conferring AMD risk are getting ever more detailed, one area lacking major progress is an understanding of the biochemical consequences of genetic risk. This is partly due to difficulties in understanding the biochemistry of Bruch's membrane, a very thin extracellular matrix that acts as a biological filter of material from the blood supply and a scaffold on which the retinal pigment epithelial (RPE) cell monolayer resides. Drusen form within Bruch's membrane and their presence disrupts nutrient flow to the RPE cells. Only by investigating the protein composition of Bruch's membrane, and indeed how other proteins interact with it, can researchers hope to unravel the biochemical mechanisms underpinning drusen formation, development of AMD and subsequent vision loss. This paper details methodologies for enriching either whole Bruch's membrane, or just from the macula region, so that it can be used for downstream biochemical analysis, and provide examples of how this is already changing the understanding of Bruch's membrane biochemistry.
C1 [McHarg, Selina; Brace, Nicole; Bishop, Paul N.; Clark, Simon J.] Univ Manchester, Inst Human Dev, Ctr Ophthalmol & Vis Sci, Manchester M13 9PL, Lancs, England.
   [McHarg, Selina; Brace, Nicole; Bishop, Paul N.; Clark, Simon J.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Ctr Adv Discovery & Expt Therapeut, Manchester, Lancs, England.
C3 University of Manchester; University of Manchester
RP Clark, SJ (通讯作者)，Univ Manchester, Inst Human Dev, Ctr Ophthalmol & Vis Sci, Manchester M13 9PL, Lancs, England.
EM simon.clark-3@manchester.ac.uk
OI Brace, Nicole/0000-0002-6047-5193; Clark, Simon/0000-0001-8394-8355
FU Medical Research Council (MRC) [MR/K024418/1]; MRC [G0900538, K004441];
   Fight for Sight [1866]; Macular Society; MRC [MR/K024418/1,
   MR/K004441/1] Funding Source: UKRI; Medical Research Council
   [MR/K004441/1, G0900538, MR/K024418/1] Funding Source: researchfish;
   Fight for Sight [1517/18] Funding Source: researchfish
FX The Authors would like to acknowledge Dr. Isaac Zambrano and the staff
   at the Manchester Eye Hospital Eye Bank for the supply of human donor
   eye tissue, and Mr. Pete Walker of the Faculty of Life Sciences
   Histology facility for the H&E stained images. Special thanks goes to
   Mr. Roger Meadows for his help with the microscopy. SJC is a recipient
   of a Medical Research Council (MRC) Career Development Fellowship
   (MR/K024418/1) and the authors also acknowledge other recent research
   funding from MRC (G0900538 and K004441), Fight for Sight (1866) and The
   Macular Society.
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NR 15
TC 7
Z9 7
U1 0
U2 3
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD NOV
PY 2015
IS 105
AR e53382
DI 10.3791/53382
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DB5SM
UT WOS:000368573900062
PM 26650722
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Baid, R
   Upadhyay, AK
   Shinohara, T
   Kompella, UB
AF Baid, Rinku
   Upadhyay, Arun K.
   Shinohara, Toshimichi
   Kompella, Uday B.
TI Biosynthesis, Characterization, and Efficacy in Retinal Degenerative
   Diseases of Lens Epithelium-derived Growth Factor Fragment
   (LEDGF(1-326)), a Novel Therapeutic Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; ENDOPLASMIC-RETICULUM STRESS; VITAMIN-A
   SUPPLEMENTATION; MACULAR DEGENERATION; HIV-1 INTEGRASE; RHODOPSIN GENE;
   SURVIVAL; LEDGF; RPE; PREVALENCE
AB For vision-threatening retinitis pigmentosa and dry age-related macular degeneration, there are no United States Food and Drug Administration (FDA)-approved treatments. We identified, biosynthesized, purified, and characterized lens epithelium-derived growth factor fragment (LEDGF(1-326)) as a novel protein therapeutic. LEDGF(1-326) was produced at about 20 mg/liter of culture when expressed in the Escherichia coli system, with about 95% purity and aggregate-free homogeneous population with a mean hydrodynamic diameter of 9 +/- 1 nm. The free energy of unfolding of LEDGF(1-326) was 3.3 +/- 0.5 kcal mol(-1), and melting temperature was 44.8 +/- 0.2 degrees C. LEDGF(1-326) increased human retinal pigment epithelial cell viability from 48.3 +/- 5.6 to 119.3 +/- 21.1% in the presence of P23H mutant rhodopsin-mediated aggregation stress. LEDGF(1-326) also increased retinal pigment epithelial cell FluoSphere uptake to 140 +/- 10%. Eight weeks after single intravitreal injection in Royal College of Surgeons (RCS) rats, LEDGF(1-326) increased the b-wave amplitude significantly from 9.4 +/- 4.6 to 57.6 +/- 8.8 mu V for scotopic electroretinogram and from 10.9 +/- 5.6 to 45.8 +/- 15.2 mu V for photopic electroretinogram. LEDGF(1-326) significantly increased the retinal outer nuclear layer thickness from 6.34 +/- 1.6 to 11.7 +/- 0.7 mu m. LEDGF(1-326) is a potential new therapeutic agent for treating retinal degenerative diseases.
C1 [Baid, Rinku; Upadhyay, Arun K.; Kompella, Uday B.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO 80045 USA.
   [Kompella, Uday B.] Univ Colorado, Dept Ophthalmol, Aurora, CO 80045 USA.
   [Shinohara, Toshimichi] Univ Nebraska Med Ctr, Dept Ophthalmol, Omaha, NE 68198 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus; University of Colorado System; University of Colorado Anschutz
   Medical Campus; University of Nebraska System; University of Nebraska
   Medical Center
RP Kompella, UB (通讯作者)，Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Anschutz Med Campus,12850 E Montview Blvd,C238-V2, Aurora, CO 80045 USA.
EM uday.kompella@ucdenver.edu
RI Upadhyay, Arun/D-4510-2014
OI Shinohara, Toshimichi/0000-0002-7197-9039
FU National Institutes of Health [EY018940, RC1 EY020361, R21EY17360];
   NATIONAL EYE INSTITUTE [R21EY017360, R01EY018940, RC1EY020361] Funding
   Source: NIH RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY018940, RC1 EY020361, and R21EY17360 (to U. B. K.).
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NR 43
TC 3
Z9 4
U1 1
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI ROCKVILLE
PA 11200 ROCKVILLE PIKE, SUITE 302, ROCKVILLE, MD, UNITED STATES
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 14
PY 2013
VL 288
IS 24
BP 17372
EP 17383
DI 10.1074/jbc.M112.441618
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 164AH
UT WOS:000320380600030
PM 23640891
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Liu, MM
   Chan, CC
   Tuo, JS
AF Liu, Melissa M.
   Chan, Chi-Chao
   Tuo, Jingsheng
TI Epigenetics in Ocular Diseases
SO CURRENT GENOMICS
LA English
DT Article
DE Age-related macular generation; Cataract; Diabetic retinopathy;
   Epigenetics; DNA methylation; microRNA
ID DNA METHYLATION; GENE-EXPRESSION; MICRORNAS; DICER; AGE;
   DIFFERENTIATION; DEGENERATION; PROFILE; LENS
AB Epigenetics pertains to heritable alterations in gene expression that do not involve modification of the underlying genomic DNA sequence. Historically, the study of epigenetic mechanisms has focused on DNA methylation and histone modifications, but the concept of epigenetics has been more recently extended to include microRNAs as well. Epigenetic patterning is modified by environmental exposures and may be a mechanistic link between environmental risk factors and the development of disease. Epigenetic dysregulation has been associated with a variety of human diseases, including cancer, neurological disorders, and autoimmune diseases. In this review, we consider the role of epigenetics in common ocular diseases, with a particular focus on DNA methylation and microRNAs. DNA methylation is a critical regulator of gene expression in the eye and is necessary for the proper development and postmitotic survival of retinal neurons. Aberrant methylation patterns have been associated with age-related macular degeneration, susceptibility to oxidative stress, cataract, pterygium, and retinoblastoma. Changes in histone modifications have also been observed in experimental models of diabetic retinopathy and glaucoma. The expression levels of specific microRNAs have also been found to be altered in the context of ocular inflammation, retinal degeneration, pathological angiogenesis, diabetic retinopathy, and ocular neoplasms. Although the complete spectrum of epigenetic modifications remains to be more fully explored, it is clear that epigenetic dysregulation is an important contributor to common ocular diseases and may be a relevant therapeutic target.
C1 [Liu, Melissa M.; Chan, Chi-Chao; Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Liu, Melissa M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Johns Hopkins University
RP Tuo, JS (通讯作者)，10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tuoj@nei.nih.gov
FU NEI intramural Research Program; NATIONAL EYE INSTITUTE [T32EY007143]
   Funding Source: NIH RePORTER
FX The work was supported by NEI intramural Research Program.
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NR 59
TC 30
Z9 32
U1 2
U2 37
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1389-2029
EI 1875-5488
J9 CURR GENOMICS
JI Curr. Genomics
PD MAY
PY 2013
VL 14
IS 3
BP 166
EP 172
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 136FJ
UT WOS:000318347300002
PM 24179439
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Lieven, CJ
   Ribich, JD
   Crowe, ME
   Levin, LA
AF Lieven, Christopher J.
   Ribich, Jonathan D.
   Crowe, Megan E.
   Levin, Leonard A.
TI Redox Proteomic Identification of Visual Arrestin Dimerization in
   Photoreceptor Degeneration after Photic Injury
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL LIGHT DAMAGE; ROD; AMELIORATION; THIOREDOXIN; MECHANISMS;
   PROTECTION; SURVIVAL; MODEL; ACID
AB PURPOSE. Light-induced oxidative stress is an important risk factor for age-related macular degeneration, but the downstream mediators of photoreceptor and retinal pigment epithelium cell death after photic injury are unknown. Given our previous identification of sulfhydryl/disulfide redox status as a factor in photoreceptor survival, we hypothesized that formation of one or more disulfide-linked homo-or hetero-dimeric proteins might signal photoreceptor death after light-induced injury.
   METHODS. Two-dimensional (non-reducing/reducing) gel electrophoresis of Wistar rat retinal homogenates after 10 hours of 10,000 lux (4200 degrees K) light in vivo, followed by mass spectrometry identification of differentially oxidized proteins.
   RESULTS. The redox proteomic screen identified homodimers of visual arrestin (Arr1; S antigen) after toxic levels of light injury. Immunoblot analysis revealed a light duration-dependent formation of Arr1 homodimers, as well as other Arr1 oligomers. Immunoprecipitation studies revealed that the dimerization of Arr1 due to photic injury was distinct from association with its physiological binding partners, rhodopsin and enolase1. Systemic delivery of tris(2-carboxyethyl) phosphine, a specific disulfide reductant, both decreased Arr1 dimer formation and protected photoreceptors from light-induced degeneration in vivo.
   CONCLUSIONS. These findings suggest a novel arrestin-associated pathway by which oxidative stress could result in cell death, and identify disulfide-dependent dimerization as a potential therapeutic target in retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:3990-3998) DOI:10.1167/iovs.11-9321
C1 [Lieven, Christopher J.; Ribich, Jonathan D.; Crowe, Megan E.; Levin, Leonard A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53792 USA.
   [Levin, Leonard A.] Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada.
   [Levin, Leonard A.] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
C3 University of Wisconsin System; University of Wisconsin Madison;
   Universite de Montreal; Universite de Montreal
RP Levin, LA (通讯作者)，Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, 600 Highland Ave, Madison, WI 53792 USA.
FU NICHD; NIH [R21 EY017970, P30 EY016665]; Retina Research Foundation;
   Research to Prevent Blindness, Inc.; NATIONAL EYE INSTITUTE
   [P30EY016665, R21EY017970] Funding Source: NIH RePORTER
FX The authors thank Daniel Organisciak for plans and advice regarding
   construction of the light exposure chamber and a critical reading of an
   earlier version of the manuscript; Grzegorz Sabat for assistance with
   mass spectrometry, Kaitlyn Munsey and T. Michael Nork for help with
   glycomethacrylate sectioning; and W. Clay Smith of the University of
   Florida for Enol2-53 anti-enolase antibody. The anti-c-Myc antibody
   (9E10) developed by J.M. Bishop was obtained from the Developmental
   Studies Hybridoma Bank developed under the auspices of the NICHD and
   maintained by The University of Iowa, Department of Biology, Iowa City,
   IA 52242.; Supported by NIH Grants R21 EY017970 and P30 EY016665, Retina
   Research Foundation, and an unrestricted departmental grant from
   Research to Prevent Blindness, Inc.
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NR 37
TC 14
Z9 15
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2012
VL 53
IS 7
BP 3990
EP 3998
DI 10.1167/iovs.11-9321
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 971CM
UT WOS:000306181200085
PM 22599583
OA Green Published
DA 2022-11-30
ER

PT J
AU Neudorfer, M
   Weinberg, A
   Loewenstein, A
   Barak, A
AF Neudorfer, Meira
   Weinberg, Amit
   Loewenstein, Anat
   Barak, Adiel
TI Differential Optical Density of Subretinal Spaces
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-DETACHMENT; FLUID
AB PURPOSE. We investigated the optical density characteristics of 3subretinal spaces in neovascular age-related macular degeneration (AMD), diabetic retinopathy (DR), rhegmatogenous retinal detachment (RRD), central serous retinopathy (CSR), retinoschisis (RS), and pseudophakic cystoids macular edema (PCME).
   METHODS. Patients in whom subretinal fluid (SRF) was detected by optical coherence tomography (OCT), and whose earliest OCT scans showed sufficient SRF for sampling that did not include tissue edges, were chosen for study. The highest quality B-scan containing SRF (as graded by the OCT image acquisition software) was analyzed. Optical density measurements were obtained using ImageJ, an open code Java-based image processing software.
   RESULTS. The diagnoses of the 71 patients who met the inclusion criteria were AMD in 17, DR in 7, RRD in 18, CSR in 17, RS in 8, and PCME in 4. Optical density ratios (ODRs) were calculated as SRF OD divided by vitreous OD. ODRs were significantly higher in patients with AMD, DR, CSR, and PCME than in those with RRD and RS. No significant difference in vitreous reflectivity was detected between the former and latter patients.
   CONCLUSIONS. The finding that disease states produce significant changes in optical density ratios calls for further investigation of the possible usefulness of the parameter in differentiating between disease states, determining the outcome of various retinal diseases, and designing therapies aimed at treating the disease by correcting the abnormal density. (Invest Ophthalmol Vis Sci. 2012;53:3104-3110) DOI:10.1167/iovs.11-8700
C1 [Neudorfer, Meira; Weinberg, Amit; Loewenstein, Anat; Barak, Adiel] Tel Aviv Univ, Dept Ophthalmol, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, IL-64239 Tel Aviv, Israel.
C3 Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky
   Medical Center
RP Barak, A (通讯作者)，Tel Aviv Univ, Dept Ophthalmol, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, 6 Weizmann St, IL-64239 Tel Aviv, Israel.
EM adielbarak@gmail.com
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NR 15
TC 33
Z9 34
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2012
VL 53
IS 6
BP 3104
EP 3110
DI 10.1167/iovs.11-8700
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 953JY
UT WOS:000304864600068
PM 22499985
DA 2022-11-30
ER

PT J
AU Chen, M
   Copland, DA
   Zhao, JW
   Liu, J
   Forrester, JV
   Dick, AD
   Xu, HP
AF Chen, Mei
   Copland, David A.
   Zhao, Jiawu
   Liu, Jian
   Forrester, John V.
   Dick, Andrew D.
   Xu, Heping
TI Persistent Inflammation Subverts Thrombospondin-1-Induced Regulation of
   Retinal Angiogenesis and Is Driven by CCR2 Ligation
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ENDOTHELIAL GROWTH-FACTOR;
   PUNCTATE INNER CHOROIDOPATHY; 2 KNOCKOUT MICE; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; MULTIFOCAL CHOROIDITIS; IN-VIVO;
   SERPIGINOUS CHOROIDITIS; SYMPATHETIC OPHTHALMIA
AB Neovascular retinal disease is a leading cause of blindness orchestrated by inflammatory responses. Although noninfectious uveoretinitis is mediated by CD4(+) T cells, in the persistent phase of disease, angiogenic responses are observed, along with degeneration of the retina. Full clinical manifestation relies on myeloid-derived cells, which are phenotypically distinct from, but potentially sharing common effector responses to age-related macular degeneration. To interrogate inflammation-mediated angiogenesis, we investigated experimental autoimmune uveoretinitis, an animal model for human uveitis. After the initial acute phase of severe inflammation, the retina sustains a persistent low-grade inflammation with tissue-infiltrating leukocytes for over 4 months. During this persistent phase, angiogenesis is observed as retinal neovascular membranes that arise from inflamed venules and postcapillary venules, increase in size as the disease progresses, and are associated with infiltrating arginase-1(+) macrophages. In the absence of thrombospondin-1, retinal neovascular membranes are markedly increased and are associated with arginase-1(-) CD68(+) macrophages, whereas deletion of the chemokine receptor CCR2 resulted in reduced retinal neovascular membranes in association with a predominant neutrophil infiltrate. CCR2 is important for macrophage recruitment to the retina in experimental autoimmune uveoretinitis and promotes chronicity in the form of a persistent angiogenesis response, which in turn is regulated by constitutive expression of angiogenic inhibitors like thrombospondin-1. This model offers a new platform to dissect the molecular and cellular pathology of inflammation-induced ocular angiogenesis. (Am J. Pathol 2012, 180:235-245; DOI: 10.1016/j.ajpath.2011.09.020)
C1 [Xu, Heping] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Copland, David A.; Liu, Jian; Dick, Andrew D.] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.
   [Forrester, John V.; Xu, Heping] Univ Aberdeen, Sect Immunol & Infect, Div Appl Med, Inst Med Sci, Aberdeen, Scotland.
C3 Queens University Belfast; University of Bristol; University of Aberdeen
RP Xu, HP (通讯作者)，Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Vis & Vasc Sci, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM heping.xu@qub.ac.uk
RI Copland, David/AAE-5334-2020; Copland, David/AAG-2368-2019; Xu,
   Heping/A-4430-2008
OI Copland, David/0000-0002-2257-4270; Xu, Heping/0000-0003-4000-931X;
   Dick, Andrew/0000-0002-0742-3159
FU National Eye Research Centre (UK); Underwood Trust; Development Trust of
   Queen's University Belfast
FX Funded in part by National Eye Research Centre (UK), Underwood Trust,
   and the Development Trust of Queen's University Belfast.
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NR 67
TC 42
Z9 43
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JAN
PY 2012
VL 180
IS 1
BP 235
EP 245
DI 10.1016/j.ajpath.2011.09.020
PG 11
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 874RO
UT WOS:000298976000024
PM 22067906
OA Bronze
DA 2022-11-30
ER

PT J
AU Mackensen, F
   Heinz, C
   Becker, MD
   Heiligenhaus, A
AF Mackensen, Friederike
   Heinz, Carsten
   Becker, Matthias D.
   Heiligenhaus, Arnd
TI Intravitreal bevacizumab (avastin) as a treatment for refractory macular
   edema in patients with uveitis - A pilot study
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE bevacizumab; uveitis; macular edema; intravitreal injection
ID ANTI-VEGF ANTIBODY; DEGENERATION; TRIAMCINOLONE; RANIBIZUMAB; INJECTION
AB Purpose: Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) which has been successfully used for the treatment of age-related macular degeneration with choroidal neovascularization. As VEGF is involved in the pathomechanisms of inflammation and endothelial dysfunction the authors used bevacizumab as a last resort treatment in patients with persistent uveitic cystoid macular edema (CME).
   Patients and Methods: Persistent uveitic CME was defined by optical coherence tomography (OCT) measurements >250 mu m despite previous treatments. The authors reviewed patients with persistent CME who subsequently had been treated with intravitreous bevacizumab 1.25 or 2.5 mg. Improvement was judged by visual acuity (VA) gain >= 2 lines and thickness reduction in OCT.
   Results: Eleven eyes of 10 patients were injected since February 2006. Median follow-up was 70 days. Reduction in central retinal thickness could be seen as early as 2 weeks with a mean foveal thickness reduction of 127.2 mu m at 4 weeks. Concurrent improvement in VA was seen in 4 of 10 patients, and was unchanged in the others. Four patients received two injections and five patients received three injections. Except for progression of cataract in one eye no ocular or systemic adverse events were recorded.
   Conclusions: Intravitreal bevacizumab seems to be an effective and safe treatment in the management of refractory inflammatory CME. The effect is transient, and reinjections may be necessary, although the time until reinjection is needed differs individually.
C1 [Mackensen, Friederike; Becker, Matthias D.] Univ Heidelberg, Interdisciplinary Uveitis Ctr, Dept Ophthalmol, D-69120 Heidelberg, Germany.
   [Heinz, Carsten; Heiligenhaus, Arnd] St Franziskus Hosp, Uveitis Ctr, Munster, Germany.
C3 Ruprecht Karls University Heidelberg; St. Franziskus-Hospital
RP Mackensen, F (通讯作者)，Univ Heidelberg, Interdisciplinary Uveitis Ctr, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
EM friederike.mackensen@uveitiszentrum.de
RI Becker, Matthias/A-8733-2014; Heinz, Carsten/AAH-3629-2020
CR Aiello LP, 2004, RETINA-J RET VIT DIS, V24, pS3, DOI 10.1097/00006982-200410001-00002
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NR 17
TC 74
Z9 78
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 JAN
PY 2008
VL 28
IS 1
BP 41
EP 45
DI 10.1097/IAE.0b013e318156db75
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 251JT
UT WOS:000252370000004
PM 18185136
DA 2022-11-30
ER

PT J
AU Kim, SR
   He, J
   Yanase, E
   Jang, YP
   Berova, N
   Sparrow, JR
   Nakanishi, K
AF Kim, So R.
   He, Jiangtao
   Yanase, Emiko
   Jang, Young P.
   Berova, Nina
   Sparrow, Janet R.
   Nakanishi, Koji
TI Characterization of Dihydro-A2PE: An intermediate in the A2E
   biosynthetic pathway
SO BIOCHEMISTRY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; STARGARDTS MACULAR DEGENERATION;
   EXCITATION-ENERGIES; LIPOFUSCIN ACCUMULATION; OUTER SEGMENTS; VISUAL
   CYCLE; MOUSE MODEL; UV SPECTRA; FLUOROPHORES; DENSITY
AB Bisretinoid lipofuscin pigments that accumulate in retinal pigment epithelial cells are implicated in the etiology of several forms of macular degeneration, including juvenile onset Stargardt disease, Best vitelliform macular degeneration, and age-related macular degeneration. One of these compounds, A2E, is generated by phosphate hydrolysis of a phosphatidyl-pyridinium bisretinoid (A2PE) that forms within photoreceptor outer segments. Here, we demonstrate that the formation of the aromatic pyridinium ring of A2PE follows from the oxidation of a dihydropyridinium intermediate. Time-dependent density functional theory calculation, based on the structure of dihydro-A2E, produced a simulated UV-visible absorbance spectrum characterized by maxima of 494 and 344 nm. Subsequently, a compound exhibiting similar UV-visible absorbance maxima (lambda(max) 490 and 330 nm) was identified in the A2E biomimetic reaction mixture. By liquid chromatography-mass spectrometry (LC-MS) this bischromophore had the expected mass of the dihydro-pyridinium bisretinoid. The compound also exhibited the behavior of a biosynthetic intermediate since it formed in advance of the final product A2E and was consumed as A2E accumulated. Moreover, under deoxygenated conditions, conversion to the aromatic pyridinium bisretinoid was inhibited. Taken together, these findings indicate that A2E biosynthesis involves the oxidation of a dihydropyridinium intermediate dihydro-A2PE. An understanding of the biosynthetic pathways of retinal pigment epithelial lipofuscin pigments is critical to the development of therapies for macular degeneration that are based on limiting the formation of these damaging compounds.
C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   Columbia Univ, Dept Pathol, New York, NY 10032 USA.
   Columbia Univ, Dept Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Sparrow, JR (通讯作者)，630 W 168th St, New York, NY 10032 USA.
EM jrs88@columbia.edu; kn5@columbia.edu
RI Jang, Young Pyo/AAJ-8782-2020
OI Jang, Young Pyo/0000-0001-5865-9228; Yanase, Emiko/0000-0002-6652-4259;
   Kim, So Ra/0000-0001-8786-2815
FU NEI NIH HHS [R01 EY012951, EY 12951, R01 EY012951-11, R01 EY012951-07,
   R01 EY012951-10] Funding Source: Medline; NIGMS NIH HHS [GM 36564]
   Funding Source: Medline; NATIONAL EYE INSTITUTE [R01EY012951] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [R01GM036564] Funding Source: NIH RePORTER
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NR 37
TC 28
Z9 28
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 4
PY 2007
VL 46
IS 35
BP 10122
EP 10129
DI 10.1021/bi7009635
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 204CN
UT WOS:000249021100028
PM 17685561
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ramage, JM
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   Moss, RS
   Patton, DT
   Murray, JC
   Rees, RC
   Durrant, LG
AF Ramage, JM
   Metheringham, R
   Conn, A
   Spendlove, I
   Moss, RS
   Patton, DT
   Murray, JC
   Rees, RC
   Durrant, LG
TI Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific
   to the endothelial antigen Tie-2
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cytotoxic T lymphocyte; endothelial cell; tolerance; tumor immunity;
   vaccine
ID TUMOR ANGIOGENESIS; RHEUMATOID-ARTHRITIS; DNA VACCINE; EXPRESSION;
   PEPTIDE; GROWTH; CELLS; TOLERANCE; IMMUNOGENS; INHIBITION
AB Tie-2 stabilises pericyte-endothelial interactions during angiogenesis and is highly expressed on endothelium during several diseases, including arthritis, age-related macular degeneration and cancer. A vaccine that targets endothelium overexpressing Tie-2 may result in vessel damage and stimulate an inflammatory cascade resulting in disease regression. We have identified a region unique to Tie-2 (amino acids 1-196) that is homologous in humans and mice. Using computer algorithms, several HLA-A*0201 epitopes that are identical in mice and humans were predicted within this region; however, binding assays showed that the majority of these epitopes were of low affinity. Modification of the anchor residues of 4 epitopes enhanced HLA binding. These epitopes were incorporated by site-directed mutagenesis into a Tie-2 DNA construct. Immunisation of HLA*0201 transgenic mice with one of the modified Tie-2 constructs stimulated CTLs that recognised both wild-type and modified peptide-pulsed target cells. In contrast, no CTLs were generated in mice immunised with wild-type Tie-2 construct, demonstrating that the modified epitope was necessary in the generation of CTLs. Moreover, CTLs from mice immunised with the modified construct killed HLA-A*0201 endothelial cells overexpressing Tie-2. Our study demonstrates that it is possible to break tolerance to the endothelial antigen Tie-2, suggesting that it may be feasible to design a vaccine to activate CTLs to kill endothelial cells overexpressing Tie-2. (C) 2004 Wiley-Liss, Inc.
C1 Univ Nottingham, City Hosp Nottingham, CRUK, Acad Dept Clin Oncol,Acad Unit Clin Oncol, Nottingham NG5 1PB, England.
   Nottingham Trent Univ, Dept Life Sci, Nottingham, England.
C3 Nottingham University Hospital NHS Trust; Nottingham City Hospital;
   University of Nottingham; Nottingham Trent University
RP Ramage, JM (通讯作者)，Univ Nottingham, City Hosp Nottingham, CRUK, Acad Dept Clin Oncol,Acad Unit Clin Oncol, Hucknall Rd, Nottingham NG5 1PB, England.
EM judith.ramage@nottingham.ac.uk
OI Spendlove, Ian/0000-0002-7480-3768; Ramage, Judith/0000-0003-1948-7974
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NR 31
TC 11
Z9 12
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 10
PY 2004
VL 110
IS 2
BP 245
EP 250
DI 10.1002/ijc.20120
PG 6
WC Oncology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology
GA 817ML
UT WOS:000221181500014
PM 15069689
OA Bronze
DA 2022-11-30
ER

PT J
AU Schmitt, NJ
   Grover, DA
   Feldon, SE
AF Schmitt, NJ
   Grover, DA
   Feldon, SE
TI The Eger Macular Stressometer: Pilot study
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PHOTOSTRESS TEST; RECOVERY; RETINOPATHY
AB PURPOSE. To evaluate the sensitivity of the Eger Macular Stressometer (EMS) for early screening of age. related macular degeneration (AMD) in a clinical practice. We examined the null hypothesis that AMD eyes have EMS recovery times (RTs) that do not differ from eyes with cataract, diabetic retinopathy, or glaucoma.
   DESIGN: The design of this study was a nonrandomized clinical trial.
   METHODS: Ninety-two eyes from 92 patients with vision 20/80 or better, age 50 and older, of either gender, and any ethnic origin, were recruited into one of four groups: AMD (30 eyes), normal or mild cataract (30 eyes), diabetic retinopathy (16 eyes), and glaucoma (16 eyes). Recovery times were obtained with the EMS, according to manufacturer's instructions.
   RESULTS: The mean (SD) [median] RT for the AMD group was 11.8 (7.6) [9] seconds, the normal/cataract group 10.0 (4.3) [9] seconds, the diabetic retinopathy group 8.4 (3.0) [8] seconds, and glaucoma group 8.6 (2.4) [8] seconds. Recovery time did not appear to be related to group (P =.58), age (P =.50), visual acuity (P =.52), or sex (P =.23).
   CONCLUSION: We found EMS RT distributions did not differ between AMD, cataract, diabetic retinopathy, and glaucoma groups. The EMS in its current form is not a sensitive screening tool for AMD. Further testing is needed to examine EMS sensitivity with other macular diseases such as central serous choroidopathy and diabetic macular edema.
C1 Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA.
C3 University of Rochester
RP Feldon, SE (通讯作者)，Univ Rochester, Dept Ophthalmol, 601 Elmwood Ave,Box 659, Rochester, NY 14642 USA.
EM Steven_Feldon@urmcrochester.edu
OI Feldon, Steven/0000-0003-0603-9312
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NR 18
TC 9
Z9 9
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD AUG
PY 2003
VL 136
IS 2
BP 314
EP 317
DI 10.1016/S0002-9394(03)00208-3
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 702YT
UT WOS:000184253200014
PM 12888055
DA 2022-11-30
ER

PT J
AU Khin, SY
   Soe, HMSH
   Chansriniyom, C
   Pornputtapong, N
   Asasutjarit, R
   Loftsson, T
   Jansook, P
AF Khin, Soe Yadanar
   Soe, Hay Man Saung Hnin
   Chansriniyom, Chaisak
   Pornputtapong, Natapol
   Asasutjarit, Rathapon
   Loftsson, Thorsteinn
   Jansook, Phatsawee
TI Development of Fenofibrate/Randomly Methylated beta-Cyclodextrin-Loaded
   Eudragit (R) RL 100 Nanoparticles for Ocular Delivery
SO MOLECULES
LA English
DT Article
DE cyclodextrin; fenofibrate; complexation; eye drops: nanocarriers;
   permeation
ID WATER-SOLUBLE POLYMERS; IN-VITRO; AQUEOUS SOLUBILITY; PHARMACEUTICAL
   APPLICATIONS; SOLID-STATE; COMPLEXES; DISSOLUTION; CHITOSAN; SYSTEMS;
   TOOL
AB Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-beta-CD (RM beta CD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RM beta CD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RM beta CD complex. FE-loaded Eudragit (R) nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen's egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RM beta CD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.
C1 [Khin, Soe Yadanar; Soe, Hay Man Saung Hnin; Chansriniyom, Chaisak; Pornputtapong, Natapol; Jansook, Phatsawee] Chulalongkorn Univ, Fac Pharmaceut Sci, 254 Phyathai Rd, Bangkok 10330, Thailand.
   [Asasutjarit, Rathapon] Thammasat Univ, Fac Pharm, 99 Moo 18 Paholyothin Rd, Klongluang 12120, Rangsit, Thailand.
   [Loftsson, Thorsteinn] Univ Iceland, Fac Pharmaceut Sci, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
C3 Chulalongkorn University; Thammasat University; University of Iceland
RP Jansook, P (通讯作者)，Chulalongkorn Univ, Fac Pharmaceut Sci, 254 Phyathai Rd, Bangkok 10330, Thailand.
EM soeyadanarkhin1993@gmail.com; haymansaunghninsoe@gmail.com;
   chaisak.ch@chula.ac.th; natapol.p@chula.ac.th; rathapon@tu.ac.th;
   thorstlo@hi.is; phatsawee.j@chula.ac.th
RI Jansook, Phatsawee/AAW-5581-2021; Pornputtapong, Natapol/B-2335-2017
OI Jansook, Phatsawee/0000-0001-7114-8991; Pornputtapong,
   Natapol/0000-0002-3833-0537
FU Ratchadapiseksompotch Fund Chulalongkorn University; 90th Anniversary of
   Chulalongkorn University Scholarship under the Ratchadapisek Somphot
   Endowment Fund
FX This research was supported by the Ratchadapiseksompotch Fund
   Chulalongkorn University. The authors acknowledge the 90th Anniversary
   of Chulalongkorn University Scholarship under the Ratchadapisek Somphot
   Endowment Fund for providing partial financial support for this study.
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NR 91
TC 2
Z9 2
U1 1
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD AUG
PY 2022
VL 27
IS 15
AR 4755
DI 10.3390/molecules27154755
PG 27
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 3S8JF
UT WOS:000839835200001
PM 35897940
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Tschernoster, N
   Erger, F
   Walsh, PR
   McNicholas, B
   Fistrek, M
   Habbig, S
   Schumacher, AL
   Folz-Donahue, K
   Kukat, C
   Toliat, MR
   Becker, C
   Thiele, H
   Kavanagh, D
   Nurnberg, P
   Beck, BB
   Altmuller, J
AF Tschernoster, Nikolai
   Erger, Florian
   Walsh, Patrick R.
   McNicholas, Bairbre
   Fistrek, Margareta
   Habbig, Sandra
   Schumacher, Anna-Lena
   Folz-Donahue, Kat
   Kukat, Christian
   Toliat, Mohammad R.
   Becker, Christian
   Thiele, Holger
   Kavanagh, David
   Nuernberg, Peter
   Beck, Bodo B.
   Altmueller, Janine
TI Unraveling Structural Rearrangements of the CFH Gene Cluster in Atypical
   Hemolytic Uremic Syndrome Patients Using Molecular Combing and
   Long-Fragment Targeted Sequencing
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID COMPLEMENT FACTOR-H; C3 GLOMERULOPATHY; MACULAR DEGENERATION; DELETION;
   AUTOANTIBODIES; FAMILY; ASSOCIATION; ECULIZUMAB; DEFICIENCY; ACTIVATION
AB Complement factor H (CFH) and its related proteins have an essential role in regulating the alternative pathway of the complement system. Mutations and structural variants (SVs) of the CFH gene cluster, consisting of CFH and its five related genes (CFHR1-5), have been reported in renal pathologies as well as in complex immune diseases like age-related macular degeneration and systemic lupus erythematosus. SV analysis of this cluster is challenging because of its high degree of sequence homology. Following first-line next-generation sequencing gene panel sequencing, we applied Genomic Vision's Molecular Combing Technology to detect and visualize SVs within the CFH gene cluster and resolve its structural haplotypes completely. This approach was tested in three patients with atypical hemolytic uremic syndrome and known SVs and 18 patients with atypical hemolytic uremic syndrome or complement factor 3 glomerulopathy with unknown CFH gene cluster haplotypes. Three SVs, a CFH/CFHR1 hybrid gene in two patients and a rare heterozygous CFHR4/CFHR1 deletion in trans with the common CFHR3/CFHR1 deletion in a third patient, were newly identified. For the latter, the breakpoints were determined using a targeted enrichment approach for long DNA fragments (Samplix Xdrop) in combination with Oxford Nanopore sequencing. Molecular combing in addition to next-generation sequencing was able to improve the molecular genetic yield in this pilot study. This (cost-)effective approach warrants validation in larger cohorts with CFH/ j.jmoldx.2022.02.006)
C1 [Tschernoster, Nikolai; Toliat, Mohammad R.; Becker, Christian; Thiele, Holger; Nuernberg, Peter; Altmueller, Janine] Univ Cologne, Fac Med, Cologne Ctr Genom, Weyertal 115b, D-50931 Cologne, Germany.
   [Tschernoster, Nikolai; Erger, Florian; Nuernberg, Peter; Beck, Bodo B.; Altmueller, Janine] Univ Cologne, Fac Med, Ctr Mol Med Cologne, Cologne, Germany.
   [Tschernoster, Nikolai; Erger, Florian; Beck, Bodo B.; Altmueller, Janine] Univ Cologne, Fac Med, Inst Human Genet, Cologne, Germany.
   [Habbig, Sandra] Univ Cologne, Fac Med, Dept Pediat, Cologne, Germany.
   [Habbig, Sandra] Univ Hosp Cologne, Weyertal 115b, D-50931 Cologne, Germany.
   [Walsh, Patrick R.; Kavanagh, David] Royal Victoria Infirm, Natl Renal Complement Therapeut Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
   [Walsh, Patrick R.; Kavanagh, David] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England.
   [McNicholas, Bairbre] Natl Univ Ireland Galway, Sch Med, Galway, Ireland.
   [Fistrek, Margareta] Univ Zagreb, Univ Hosp Ctr Zagreb, Sch Med, Dept Internal Med,Div Nephrol Arterial Hypertens, Zagreb, Croatia.
   [Schumacher, Anna-Lena; Folz-Donahue, Kat; Kukat, Christian] Max Planck Inst Biol Ageing, FACS & Imaging Core Facil, Cologne, Germany.
   [Altmueller, Janine] Charite Univ Med Berlin, Berlin Inst Hlth, Berlin, Germany.
   [Altmueller, Janine] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Hannoversche Str 28, D-10115 Berlin, Germany.
C3 University of Cologne; University of Cologne; University of Cologne;
   University of Cologne; University of Cologne; Newcastle University - UK;
   Newcastle University - UK; Ollscoil na Gaillimhe-University of Galway;
   University of Zagreb; University of Zagreb, School of Dental Medicine;
   Max Planck Society; Berlin Institute of Health; Free University of
   Berlin; Humboldt University of Berlin; Charite Universitatsmedizin
   Berlin; Helmholtz Association; Max Delbruck Center for Molecular
   Medicine
RP Tschernoster, N (通讯作者)，Univ Cologne, Fac Med, Cologne Ctr Genom, Weyertal 115b, D-50931 Cologne, Germany.; Tschernoster, N (通讯作者)，Univ Hosp Cologne, Weyertal 115b, D-50931 Cologne, Germany.; Altmuller, J (通讯作者)，Helmholtz Assoc, Max Delbruck Ctr Mol Med, Hannoversche Str 28, D-10115 Berlin, Germany.
EM nikolai.tschernoster@uk-koeln.de; janine.altmueller@bih-charite.de
OI Altmuller, Janine/0000-0003-4372-1521; Walsh,
   Patrick/0000-0001-9852-0095; Tschernoster, Nikolai/0000-0002-6058-9342;
   Erger, Florian/0000-0002-2768-1702; Schumacher,
   Anna-Lena/0000-0001-7739-486X; Kukat, Christian/0000-0003-1508-0229
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NR 57
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD JUN
PY 2022
VL 24
IS 6
BP 619
EP 631
DI 10.1016/j.jmoldx.2022.02.006
PG 13
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 2E6KI
UT WOS:000812335400007
PM 35398599
OA hybrid, Green Accepted
DA 2022-11-30
ER

PT J
AU Zou, M
   Ke, Q
   Nie, Q
   Qi, RL
   Zhu, XF
   Liu, W
   Hu, XB
   Sun, Q
   Fu, JL
   Tang, XC
   Liu, YZ
   Li, DWC
   Gong, LL
AF Zou, Ming
   Ke, Qin
   Nie, Qian
   Qi, Ruili
   Zhu, Xingfei
   Liu, Wei
   Hu, Xuebin
   Sun, Qian
   Fu, Jia-Ling
   Tang, Xiangcheng
   Liu, Yizhi
   Li, David Wan-Cheng
   Gong, Lili
TI Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced
   retina inflammation and degeneration
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; CYCLIC GMP-AMP; SODIUM IODATE; DAMAGE;
   PATHWAY; ALIGNMENT; CELLS
AB Atrophic ("dry") form of age-related macular degeneration (AMD) is a leading cause of vision loss characterized by macular retinal pigment epithelium (RPE) and the ensuing photoreceptor degeneration. cGAS-STING signaling is a key cytosolic DNA sensor system in innate immunity and have recently been shown promotes RPE degeneration. However, expression regulation and therapeutic potential of cGAS and STING are not explored in retina under dry AMD pathogenic conditions. Our analysis shows upregulated STING RNA and increased chromatin accessibility around cGAS and STING promoters in macular retinas from dry AMD patients. cGAS-STING activation was detected in oxidative stress-induced mouse retina degeneration, accompanied with cytosolic leakage of damaged DNA in photoreceptors. Pharmaceutical or genetic approaches indicates STING promotes retina inflammation and degeneration upon oxidative damage. Drug screening reveals that BRD4 inhibitor JQ1 reduces cGAS-STING activation, inflammation and photoreceptor degeneration in the injured retina. BRD4 inhibition epigenetically suppresses STING transcription, and promotes autophagy-dependent cytosolic DNA clearance. Together, our results show that activation of cGAS-STING in retina may present pivotal innate immunity response in GA pathogenesis, whereas inhibition of cGAS-STING signaling by JQ1 could serve as a potential therapeutic strategy.
   Schematic summary of the mechanism underlying BRD4 inhibition on cGAS-STING signaling during retina degeneration. Cytosolic DNA accumulation and activation of cGAS-STING pathway were detected in retina photoreceptors after oxidative injury. BRD4 inhibition alleviates retinal inflammation and degeneration by epigenetically silencing STING transcription and by promoting autophagy-dependent cytosolic DNA clearance.
C1 [Zou, Ming; Ke, Qin; Nie, Qian; Qi, Ruili; Zhu, Xingfei; Liu, Wei; Hu, Xuebin; Sun, Qian; Fu, Jia-Ling; Tang, Xiangcheng; Liu, Yizhi; Li, David Wan-Cheng; Gong, Lili] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Li, DWC; Gong, LL (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
EM dwli1688@hotmail.com; gonglili@gzzoc.com
RI liu, yi/GXE-9662-2022
OI Gong, Lili/0000-0002-3129-3868
FU National Natural Science Foundation of China [82070969, 81970787,
   82000876]; Guangdong Natural Science Foundation [2021A1515011793]; Joint
   Key Project of Natural Science Foundation of Guangdong Province and
   Guangzhou City [2019B1515120014]; Fundamental Research Fund of the State
   Key Laboratory of Ophthalmology [3030901010111]; Zhongshan Ophthalmic
   Center, Sun Yat-Sen University in China
FX This work was supported by the National Natural Science Foundation of
   China (Grants #82070969, #81970787, #82000876), Guangdong Natural
   Science Foundation (2021A1515011793), the Joint Key Project of Natural
   Science Foundation of Guangdong Province and Guangzhou City
   (2019B1515120014), and the Fundamental Research Fund of the State Key
   Laboratory of Ophthalmology (3030901010111), Zhongshan Ophthalmic
   Center, Sun Yat-Sen University in China.
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NR 48
TC 3
Z9 3
U1 10
U2 18
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD SEP
PY 2022
VL 29
IS 9
BP 1816
EP 1833
DI 10.1038/s41418-022-00967-4
EA MAR 2022
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 4G7IL
UT WOS:000773847900001
PM 35347235
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Li, YT
   Lee, S
AF Li, Yatong
   Lee, Seunggeun
TI Integrating external controls in case-control studies improves power for
   rare-variant tests
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE case-control study; external control; GWAS; rare-variant test; SKAT
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; RISK; GENE;
   POLYMORPHISMS; SINGLE
AB Large-scale sequencing and genotyping data provide an opportunity to integrate external samples as controls to improve power of association tests. However, due to the systematic differences between genotyped samples from different studies, naively aggregating the controls could lead to inflation in Type I error rates. There has been recent effort to integrate external controls while adjusting for batch effect, such as the integrating External Controls into Association Test (iECAT) and its score-based single variant tests. Building on the original iECAT framework, we propose an iECAT-Score region-based test that increases power for rare-variant tests when integrating external controls. This method assesses the systematic batch effect between internal and external samples at each variant and constructs compound shrinkage score statistics to test for the joint genetic effect within a gene or a region, while adjusting for covariates and population stratification. Through simulation studies, we demonstrate that the proposed method controls for Type I error rates and improves power in rare-variant tests. The application of the proposed method to the association studies of age-related macular degeneration (AMD) from the International AMD Genomics Consortium and UK Biobank revealed novel rare-variant associations in gene DXO. Through the incorporation of external controls, the iECAT methods offer a powerful suite to identify disease-associated genetic variants, further shedding light on future directions to investigate roles of rare variants in human diseases.
C1 [Li, Yatong; Lee, Seunggeun] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Lee, Seunggeun] Seoul Natl Univ, Grad Sch Data Sci, Seoul 08826, South Korea.
C3 University of Michigan System; University of Michigan; Seoul National
   University (SNU)
RP Lee, S (通讯作者)，Seoul Natl Univ, Grad Sch Data Sci, Seoul 08826, South Korea.
EM lee7801@snu.ac.kr
OI Li, Yatong/0000-0003-2021-4076
FU National Institute of Health [R01-HG008773]; National Research
   Foundation of Korea [2020H1D3A2A03100666]
FX National Institute of Health, Grant/Award Number: R01-HG008773; National
   Research Foundation of Korea, Grant/Award Number: 2020H1D3A2A03100666
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NR 32
TC 0
Z9 0
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2022
VL 46
IS 3-4
BP 145
EP 158
DI 10.1002/gepi.22444
EA FEB 2022
PG 14
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 1A8AC
UT WOS:000755628300001
PM 35170803
DA 2022-11-30
ER

PT J
AU You, LT
   Peng, HLY
   Liu, J
   Cai, MR
   Wu, HM
   Zhang, ZQ
   Bai, J
   Yao, Y
   Dong, XX
   Yin, XB
   Ni, J
AF You, Longtai
   Peng, Hulinyue
   Liu, Jing
   Cai, Mengru
   Wu, Huimin
   Zhang, Zhiqin
   Bai, Jie
   Yao, Yu
   Dong, Xiaoxv
   Yin, Xingbin
   Ni, Jian
TI Catalpol Protects ARPE-19 Cells against Oxidative Stress via Activation
   of the Keap1/Nrf2/ARE Pathway
SO CELLS
LA English
DT Article
DE catalpol; oxidative stress; Nrf2; apoptosis; cell cycle arrest;
   age-related macular degeneration
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; DNA-DAMAGE; SIGNALING
   PATHWAY; APOPTOSIS; MITOCHONDRIAL; ANTIOXIDANT; EXPRESSION; TARGET; NQO1
AB Oxidative damage to retinal pigment epithelial (RPE) has been identified as one of the major regulatory factors in the pathogenesis of age-related macular degeneration (AMD). Catalpol is an iridoid glucoside compound that has been found to possess potential antioxidant activity. In the present study, we aimed to investigate the protective effect of catalpol on RPE cells under oxidative stress and to elucidate the potential molecular mechanism involved. We found that catalpol significantly attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, G0/G1 phase cell cycle arrest, and apoptosis in RPE cells. The overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) stimulated by oxidative stress and the corresponding reductions in antioxidant glutathione (GSH) and superoxide dismutase (SOD) levels were largely reversed by catalpol pretreatment. Moreover, catalpol pretreatment markedly activated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream antioxidant enzymes, catalase (CAT), heme oxygenase-1 (HO-1), and NADPH dehydrogenase (NQO1). It also increased the expression levels of cyclin E, Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK2) and decreased the expression levels of Bax, Fas, cleaved PARP, p-p53, and p21 cleaved caspase-3, 8, and 9. The oxidative stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by catalpol pretreatment. These results indicate that catalpol protected RPE cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE pathways and the inactivation of oxidative stress-mediated pathways of apoptosis.
C1 [You, Longtai; Peng, Hulinyue; Liu, Jing; Cai, Mengru; Wu, Huimin; Zhang, Zhiqin; Bai, Jie; Yao, Yu; Dong, Xiaoxv; Yin, Xingbin; Ni, Jian] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China.
C3 Beijing University of Chinese Medicine
RP Dong, XX; Yin, XB; Ni, J (通讯作者)，Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China.
EM 20190941307@bucm.edu.cn; 20200935154@bucm.edu.cn;
   20210941441@bucm.edu.cn; cmrtcm@bucm.edu.cn; 20190935128@bucm.edu.cn;
   20190935126@bucm.edu.cn; 20190935127@bucm.edu.cn;
   20190935142@bucm.edu.cn; 201801020@bucm.edu.cn; yxbtcm@bucm.edu.cn;
   602054@bucm.edu.cn
FU Fundamental Research Funds for the Central Universities
   [2020-JYB-ZDGG-046]
FX FundingThis work was funded by the Fundamental Research Funds for the
   Central Universities (No. 2020-JYB-ZDGG-046).
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NR 59
TC 3
Z9 3
U1 12
U2 26
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD OCT
PY 2021
VL 10
IS 10
AR 2635
DI 10.3390/cells10102635
PG 20
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA WP5YV
UT WOS:000713207700001
PM 34685615
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Sugita, S
   Mandai, M
   Kamao, H
   Takahashi, M
AF Sugita, Sunao
   Mandai, Michiko
   Kamao, Hiroyuki
   Takahashi, Masayo
TI Immunological aspects of RPE cell transplantation
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Retinal pigment epithelial cells; Immune rejection; Age-related macular
   degeneration; Stem cells; Transplantation
ID RETINAL-PIGMENT EPITHELIUM; PLURIPOTENT STEM-CELLS; AGE-RELATED
   MACULOPATHY; HUMAN BRUCHS MEMBRANE; LONG-TERM SAFETY; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; XENO-FREE; DIRECTED
   DIFFERENTIATION; BASAL DEPOSITS
AB Retinal pigment epithelial (RPE) cells have several functions, including support of the neural retina and choroid in the eye and immunosuppression. Cultured human RPE cells directly suppress inflammatory immune cells. For instance, they directly suppress the activation of T cells in vitro. In contrast, transplanted allogeneic human RPE cells are rejected by bystander immune cells such as T cells in vivo. Recently, human embryonic stem cell-derived RPE cells have been used in several clinical trials, and human induced pluripotent stem cell (iPSC)-RPE cells have also been tested in our clinical study in patients with retinal degeneration. Major safety concerns after stem cell -based transplantation surgery include hyper-proliferation, tumorigenicity, or ectopic tissue formation, but these events have currently not been seen in any of these patients. However, if RPE cells are allogeneic, there are concerns about immune rejection issues that have been raised in previous clinical trials. We therefore performed a preclinical study of allogeneic iPSC-RPE cell transplantation in animal rejection models. We then conducted autogenic or allogeneic iPSC-RPE cell transplantation in clinical studies of patients with age-related macular degeneration. In this review, we focus on immunological studies of RPE cells, including iPSC-derived cells. iPSC-RPE cells have unique inflammatory (immunosuppressive and immunogenic) characteristics like primary cultured RPE cells. The purpose of this review is to summarize the current findings obtained from preclinical (basic research) and clinical studies in iPSC-RPE cell transplantation, especially the immunological aspects.
C1 [Sugita, Sunao; Mandai, Michiko; Takahashi, Masayo] RIKEN Ctr Biosyst Dynam Res, Lab Retinal Regenerat, Kobe, Hyogo, Japan.
   [Sugita, Sunao; Mandai, Michiko; Takahashi, Masayo] Kobe City Eye Hosp, Dept Ophthalmol, Kobe, Hyogo, Japan.
   [Kamao, Hiroyuki] Kawasaki Med Sch, Dept Ophthalmol, Okayama, Japan.
C3 RIKEN; Kawasaki Medical School
RP Sugita, S (通讯作者)，RIKEN Ctr Biosyst Dynam Res, Lab Retinal Regenerat, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.
EM sunao.sugita@riken.jp
FU Japan Agency for Medical Research and Development (AMED) [JP18bm0204002,
   JP17bk0104002]; KAKENHI [18H02959]
FX This research was supported by Japan Agency for Medical Research and
   Development (AMED) under Grant Number JP18bm0204002 and JP17bk0104002 In
   addition, this study was also supported by grants from KAKENHI (B,
   18H02959) .
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NR 189
TC 13
Z9 14
U1 6
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD SEP
PY 2021
VL 84
AR 100950
DI 10.1016/j.preteyeres.2021.100950
EA SEP 2021
PG 24
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UR8XL
UT WOS:000697024800001
PM 33482342
OA hybrid
DA 2022-11-30
ER

PT J
AU Enzbrenner, A
   Zulliger, R
   Biber, J
   Pousa, AMQ
   Schafer, N
   Stucki, C
   Giroud, N
   Berrera, M
   Kortvely, E
   Schmucki, R
   Badi, L
   Grosche, A
   Pauly, D
   Enzmann, V
AF Enzbrenner, Anne
   Zulliger, Rahel
   Biber, Josef
   Pousa, Ana Maria Quintela
   Schaefer, Nicole
   Stucki, Corinne
   Giroud, Nicolas
   Berrera, Marco
   Kortvely, Elod
   Schmucki, Roland
   Badi, Laura
   Grosche, Antje
   Pauly, Diana
   Enzmann, Volker
TI Sodium Iodate-Induced Degeneration Results in Local Complement Changes
   and Inflammatory Processes in Murine Retina
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE retinal degeneration; geographic atrophy; sodium iodate; local
   complement; inflammation; innate immunity; mouse
ID MACULAR DEGENERATION; OXIDATIVE STRESS; CELL-DEATH; FACTOR B;
   EXPRESSION; ACTIVATION; DAMAGE; MICE; RPE; ABNORMALITIES
AB Age-related macular degeneration (AMD), one of the leading causes of blindness worldwide, causes personal suffering and high socioeconomic costs. While there has been progress in the treatments for the neovascular form of AMD, no therapy is yet available for the more common dry form, also known as geographic atrophy. We analysed the retinal tissue in a mouse model of retinal degeneration caused by sodium iodate (NaIO3)-induced retinal pigment epithelium (RPE) atrophy to understand the underlying pathology. RNA sequencing (RNA-seq), qRT-PCR, Western blot, immunohistochemistry of the retinas and multiplex ELISA of the mouse serum were applied to find the pathways involved in the degeneration. NaIO3 caused patchy RPE loss and thinning of the photoreceptor layer. This was accompanied by the increased retinal expression of complement components c1s, c3, c4, cfb and cfh. C1s, C3, CFH and CFB were complement proteins, with enhanced deposition at day 3. C4 was upregulated in retinal degeneration at day 10. Consistently, the transcript levels of proinflammatory ccl-2, -3, -5, il-1 beta, il-33 and tgf-beta were increased in the retinas of NaIO3 mice, but vegf-a mRNA was reduced. Macrophages, microglia and gliotic Muller cells could be a cellular source for local retinal inflammatory changes in the NaIO3 retina. Systemic complement and cytokines/chemokines remained unaltered in this model of NaIO3-dependent retinal degeneration. In conclusion, systemically administered NaIO3 promotes degenerative and inflammatory processes in the retina, which can mimic the hallmarks of geographic atrophy.
C1 [Enzbrenner, Anne; Schaefer, Nicole; Pauly, Diana] Univ Hosp Regensburg, Dept Ophthalmol, D-93053 Regensburg, Germany.
   [Zulliger, Rahel; Stucki, Corinne; Giroud, Nicolas; Berrera, Marco; Kortvely, Elod; Schmucki, Roland; Badi, Laura] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, CH-4070 Basel, Switzerland.
   [Biber, Josef; Grosche, Antje] Ludwig Maximilians Univ Munchen, Biomed Ctr, Dept Physiol Genom, D-82152 Planegg Martinsried, Germany.
   [Pousa, Ana Maria Quintela; Enzmann, Volker] Univ Hosp Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland.
   [Pousa, Ana Maria Quintela; Enzmann, Volker] Univ Bern, Dept Biomed Res, CH-3010 Bern, Switzerland.
   [Pauly, Diana] Univ Marburg, Expt Ophthalmol, D-35043 Marburg, Germany.
C3 University of Regensburg; Roche Holding; University of Munich;
   University of Bern; University Hospital of Bern; University of Bern;
   Philipps University Marburg
RP Pauly, D (通讯作者)，Univ Hosp Regensburg, Dept Ophthalmol, D-93053 Regensburg, Germany.; Pauly, D (通讯作者)，Univ Marburg, Expt Ophthalmol, D-35043 Marburg, Germany.
EM a.enzbrenner@googlemail.com; rahel.zulliger@roche.com;
   Josef.Biber@bmc.med.lmu.de; quintelapousa@gmail.com;
   Nicole.Schaefer@klinik.uni-regensburg.de; corinne.stucki@roche.com;
   nicolas.giroud@roche.com; marco.berrera@roche.com;
   elod.koertvely@roche.com; roland.schmucki@roche.com;
   laura.badi@roche.com; Antje.Grosche@bmc.med.lmu.de;
   diana.pauly@uni-marburg.de; volker.enzmann@insel.ch
RI Grosche, Antje/N-1978-2014
OI Grosche, Antje/0000-0003-0338-7530; Kortvely, Elod/0000-0003-1599-3116
FU Deutsche Forschungsgemeinschaft (DFG) [GR 4403/5-1, PA 1844/3-1]; F.
   Hoffmann-La Roche Ltd.
FX This project was supported by the Deutsche Forschungsgemeinschaft
   (DFG-GR 4403/5-1 to AG, and DFG-PA 1844/3-1 to DP). Partial research
   funding was provided by F. Hoffmann-La Roche Ltd., but the company did
   not have any influence in performing the study.
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NR 38
TC 8
Z9 8
U1 0
U2 2
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 SEP
PY 2021
VL 22
IS 17
AR 9218
DI 10.3390/ijms22179218
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA UN9IN
UT WOS:000694320700001
PM 34502128
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Luo, LJ
   Jian, HJ
   Harroun, SG
   Lai, JY
   Unnikrishnan, B
   Huang, CC
AF Luo, Li-Jyuan
   Jian, Hong-Jyuan
   Harroun, Scott G.
   Lai, Jui-Yang
   Unnikrishnan, Binesh
   Huang, Chih-Ching
TI Targeting nanocomposites with anti-oxidative/inflammatory/angiogenic
   activities for synergistically alleviating macular degeneration
SO APPLIED MATERIALS TODAY
LA English
DT Article
DE Gold-based nanomedicine; Nanomaterial biofunctionalization; Targeted
   delivery; Age-related macular degeneration
ID NF-KAPPA-B; GOLD NANOPARTICLES; OXIDATIVE STRESS; CELL-MIGRATION; MATRIX
   METALLOPROTEINASES; INTRAVITREAL INJECTION; MOLECULAR-MECHANISMS;
   ANIMAL-MODELS; METFORMIN; INFLAMMATION
AB Treatment of age-related macular degeneration (AMD) is a challenge due to frequent intravitreal injection of drugs, low retention time, risk of infection, need for drugs with multiple therapeutic efficacies, such as anti-inflammatory, anti-oxidant, and anti-angiogenesis. Herein, we demonstrate the synthesis and application of metformin-loaded gold-poly(catechin) core-shell nanoparticles (MF/Au@pCH NPs) as a potential nanocomposite for the treatment of AMD, via sustained drug release to the lesion site. To achieve targeted drug delivery to macula of the AMD eye, we immobilized the complement component protein C3 to form C3-MF/Au@pCH NPs. With this targeted nanocomposite, we aim to utilize the anti-oxidative and anti-inflammatory properties of phenol-rich poly(catechin) and the anti-angiogenic activity of metformin for the synergistic recovery from macular degeneration. The pharmacological efficacy of a single intravitreal dose of C3-MF/Au@pCH NPs is superior to Au@pCH NPs and MF/Au@pCH NPs. In addition, C3-MF/Au@pCH NPs exhibited good in vitro and in vivo biocompatibility. Our study suggests the potential of this multifunctional modality for translation into a clinical intervention for AMD therapy, due to the sustained release of drugs and targeted drug delivery. The findings of this work reveals that Au@pCH NPs could be extended to the treatment of various other diseases with the loading of relative drugs. (c) 2021 Elsevier Ltd. All rights reserved.
C1 [Luo, Li-Jyuan; Jian, Hong-Jyuan; Lai, Jui-Yang] Chang Gung Univ, Grad Inst Biomed Engn, Taoyuan 33302, Taiwan.
   [Harroun, Scott G.] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada.
   [Lai, Jui-Yang] Chang Gung Mem Hosp, Dept Ophthalmol, Taoyuan 33305, Taiwan.
   [Lai, Jui-Yang] Ming Chi Univ Technol, Dept Mat Engn, New Taipei 24301, Taiwan.
   [Lai, Jui-Yang] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Taoyuan 33303, Taiwan.
   [Unnikrishnan, Binesh; Huang, Chih-Ching] Natl Taiwan Ocean Univ, Dept Biosci & Biotechnol, Keelung 20224, Taiwan.
   [Huang, Chih-Ching] Natl Taiwan Ocean Univ, Ctr Excellence Oceans, Keelung 20224, Taiwan.
   [Huang, Chih-Ching] Kaohsiung Med Univ, Coll Pharm, Sch Pharm, Kaohsiung 80708, Taiwan.
C3 Chang Gung University; Universite de Montreal; Chang Gung Memorial
   Hospital; Ming Chi University of Technology; Chang Gung University of
   Science & Technology; National Taiwan Ocean University; National Taiwan
   Ocean University; Kaohsiung Medical University
RP Lai, JY (通讯作者)，Chang Gung Univ, Grad Inst Biomed Engn, Taoyuan 33302, Taiwan.; Lai, JY (通讯作者)，Chang Gung Mem Hosp, Dept Ophthalmol, Taoyuan 33305, Taiwan.; Lai, JY (通讯作者)，Ming Chi Univ Technol, Dept Mat Engn, New Taipei 24301, Taiwan.; Lai, JY (通讯作者)，Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Taoyuan 33303, Taiwan.; Huang, CC (通讯作者)，Natl Taiwan Ocean Univ, Dept Biosci & Biotechnol, Keelung 20224, Taiwan.; Huang, CC (通讯作者)，Natl Taiwan Ocean Univ, Ctr Excellence Oceans, Keelung 20224, Taiwan.; Huang, CC (通讯作者)，Kaohsiung Med Univ, Coll Pharm, Sch Pharm, Kaohsiung 80708, Taiwan.
EM jylai@mail.cgu.edu.tw; huanging@ntou.edu.tw
RI Harroun, Scott G./ABG-3694-2021; Huang, Chih-Ching/D-3103-2012; Lai,
   Jui-Yang/I-1166-2017; UNNIKRISHNAN, BINESH/E-6077-2016
OI Huang, Chih-Ching/0000-0002-0363-1129; Lai,
   Jui-Yang/0000-0002-9227-8549; UNNIKRISHNAN, BINESH/0000-0003-2886-5682
FU Ministry of Science and Technology of Taiwan
   [MOST107-2314-B-182-016-MY3, 108-2811-B-182-510, 110-2314-B-182-008-MY3,
   107-2113-M-019-004-MY3, 108-2638-M-002-001-MY2]; National Health
   Research Institutes of Taiwan [NHRI-EX110-10826EI]; Chang Gung Memorial
   Hospital, Linkou [CMRPD2K0161]
FX This work was supported by grants MOST107-2314-B-182-016-MY3,
   108-2811-B-182-510, 110-2314-B-182-008-MY3, 107-2113-M-019-004-MY3, and
   108-2638-M-002-001-MY2 from the Ministry of Science and Technology of
   Taiwan; grant NHRI-EX110-10826EI from the National Health Research
   Institutes of Taiwan; and grant CMRPD2K0161 from Chang Gung Memorial
   Hospital, Linkou. We are grateful for the assistance of Ms. Y.-Y. Yang
   and Ms. C.-Y. Lin from the Instrument Center of National Taiwan
   University for TEM measurements. We also thank Ms. S.-J. Ji and Ms.
   C.-Y. Chien of Precious Instrument Center (National Taiwan University)
   for their assistance in STEM analysis.
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NR 94
TC 3
Z9 3
U1 5
U2 16
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 2352-9407
J9 APPL MATER TODAY
JI Appl. Mater. Today
PD SEP
PY 2021
VL 24
AR 101156
DI 10.1016/j.apmt.2021.101156
EA AUG 2021
PG 14
WC Materials Science, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science
GA UO5EF
UT WOS:000694716600010
DA 2022-11-30
ER

PT J
AU Biswal, MR
   Wang, ZY
   Paulson, RJ
   Uddin, RR
   Tong, Y
   Zhu, P
   Li, H
   Lewin, AS
AF Biswal, Manas R.
   Wang, Zhaoyao
   Paulson, Ryan J.
   Uddin, Rukshana R.
   Tong, Yao
   Zhu, Ping
   Li, Hong
   Lewin, Alfred S.
TI Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from
   Oxidative Stress in the Retinal Pigment Epithelium
SO ANTIOXIDANTS
LA English
DT Article
DE age related macular degeneration; oxidative stress; MnSOD; RPE; retinal
   degeneration; erythropoietin; gene therapy; animal model; AAV; ERG
ID MACULAR DEGENERATION; GANGLION-CELLS; VISUAL FUNCTION; EXPRESSION;
   PROTECTS; LIGHT; INFLAMMATION; PRESERVES; NEUROINFLAMMATION;
   TRANSDUCTION
AB Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.
C1 [Biswal, Manas R.; Paulson, Ryan J.] Univ S Florida, Taneja Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33612 USA.
   [Biswal, Manas R.] Univ S Florida, Morsani Coll Med, Dept Ophthalmol, Tampa, FL 33612 USA.
   [Biswal, Manas R.] Univ S Florida, Morsani Coll Med, Dept Internal Med, Tampa, FL 33612 USA.
   [Biswal, Manas R.; Wang, Zhaoyao; Uddin, Rukshana R.; Tong, Yao; Li, Hong; Lewin, Alfred S.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
   [Wang, Zhaoyao] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200011, Peoples R China.
   [Uddin, Rukshana R.] Univ Florida, Dept Chem, Gainesville, FL 32603 USA.
   [Tong, Yao] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
   [Zhu, Ping; Lewin, Alfred S.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
C3 State University System of Florida; University of South Florida; State
   University System of Florida; University of South Florida; State
   University System of Florida; University of South Florida; State
   University System of Florida; University of Florida; Shanghai Jiao Tong
   University; State University System of Florida; University of Florida;
   Tulane University; State University System of Florida; University of
   Florida
RP Biswal, MR (通讯作者)，Univ S Florida, Taneja Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33612 USA.; Biswal, MR (通讯作者)，Univ S Florida, Morsani Coll Med, Dept Ophthalmol, Tampa, FL 33612 USA.; Biswal, MR (通讯作者)，Univ S Florida, Morsani Coll Med, Dept Internal Med, Tampa, FL 33612 USA.; Biswal, MR (通讯作者)，Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
EM biswal@usf.edu; zhaokekewzy@hotmail.com; rjpaulso@usf.edu;
   rukshana463@ufl.edu; ytong2@tulane.edu; pingz@ufl.edu; l712129@ufl.edu;
   lewin@UFL.EDU
OI Lewin, Alfred/0000-0002-4192-9727; Biswal, Manas/0000-0002-9685-2923;
   Tong, Yao/0000-0002-4132-5640
FU National Eye Institute (NEI) [EY027013, R01EY020825, R01EY026268]
FX This research was supported by grants from the National Eye Institute
   (NEI) EY027013 [M.R.B.], USF TCOP start up [M.R.B.], (R01EY020825;
   R01EY026268 [A.S.L.]).
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DI 10.3390/antiox10060842
PG 15
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 SX7BB
UT WOS:000665354500001
PM 34070383
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Vieira, LC
   Moreira, CPD
   Castro, BFM
   Cotta, OAL
   Silva, LM
   Fulgencio, GD
   Silva-Cunha, A
   Fialho, SL
AF Vieira, Lorena Carla
   Moreira, Carolina Paula de Souza
   Castro, Brenda Fernanda Moreira
   Cotta, Oliver Araujo Lacerda
   Silva, Luciana Maria
   Fulgencio, Gustavo de Oliveira
   Silva-Cunha, Armando
   Fialho, Silvia L.
TI Rosmarinic Acid Intravitreal Implants: A New Therapeutic Approach for
   Ocular Neovascularization
SO PLANTA MEDICA
LA English
DT Article
DE rosmarinic acid; implants; intravitreal; drug delivery;
   neovascularization; safety
ID BIODEGRADABLE IMPLANTS; ANGIOGENESIS; NANOPARTICLES; DELIVERY; RELEASE;
   DRUG
AB Rosmarinic acid, a plant-derived compound with antiangiogenic activity, can be applied for the treatment of ocular diseases related to neovascularization, such as diabetic retinopathy, macular edema, and age-related macular degeneration. These diseases represent the leading causes of blindness worldwide if they are not properly treated. Intravitreal devices allow for localized drug delivery to the posterior segment, increasing the drug bioavailability and promoting extended release, thus, reducing side effects and enhancing the patient's compliance to the treatment. In this work, rosmarinic acid-loaded poly lactic-co-glycolic acid intraocular implants were developed with a view for the treatment of ocular neovascularization. Physical-chemical, biocompatibility, and safety studies of the implants were carried outin vitroandin vivoas well as an evaluation of the antiangiogenic activity in a chorioallantoic membrane assay. Data obtained showed that rosmarinic acid released from the implants was quantified in the vitreous for 6 weeks, while when it was in the solution formulation, after 24 h, no drug was found in the vitreous. The delivery device did not show any sign of toxicity after clinical evaluation and in electroretinographic findings. Histological analysis showed normal eye tissue. Rosmarinic acid released from implants reduced 30% of new vessel's formation. The intravitreal implant successfully allowed for the prolonged release of rosmarinic acid, was safe to rabbits eyes, and demonstrated activity in vessel reduction, thus demonstrating potential in preventing neovascularization in ophthalmic diseases.
C1 [Vieira, Lorena Carla; Castro, Brenda Fernanda Moreira; Fulgencio, Gustavo de Oliveira; Silva-Cunha, Armando] Univ Fed Minas Gerais, Fac Pharm, Belo Horizonte, MG, Brazil.
   [Moreira, Carolina Paula de Souza; Cotta, Oliver Araujo Lacerda; Silva, Luciana Maria; Fialho, Silvia L.] Ezequiel Dias Fdn, Res & Dev, Belo Horizonte, MG, Brazil.
C3 Universidade Federal de Minas Gerais
RP Fialho, SL (通讯作者)，Ezequiel Dias Fdn, Res & Dev, Belo Horizonte, MG, Brazil.
EM silvia.fialho@funed.mg.gov.br
RI Silva, Luciana M/R-6340-2018; Silva, Luciana M/I-4353-2014; Fialho, S.
   L./G-1540-2012; Cunha, Armando/G-1157-2012; Castro, Brenda/AAO-6790-2021
OI Silva, Luciana M/0000-0002-2038-0405; Silva, Luciana
   M/0000-0002-2038-0405; Fialho, S. L./0000-0001-8068-5211; Cunha,
   Armando/0000-0002-1161-8936; Castro, Brenda/0000-0002-3604-8757;
   Moreira, Carolina Paula/0000-0001-9985-6252; Cotta,
   Oliver/0000-0002-9473-9775
FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG,
   Brazil); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
   (CNPq, Brazil); Coordenacao de Aperfeicoamento de Pessoal de Nivel
   Superior (CAPES/MEC, Brazil)
FX The authors thank Fundacao de Amparo a Pesquisa do Estado de Minas
   Gerais (FAPEMIG, Brazil), Conselho Nacional de Desenvolvimento
   Cientifico e Tecnologico (CNPq, Brazil), and Coordenacao de
   Aperfeicoamento de Pessoal de Nivel Superior (CAPES/MEC, Brazil) for
   financial support.
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NR 36
TC 6
Z9 6
U1 2
U2 10
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD NOV
PY 2020
VL 86
IS 17
BP 1286
EP 1297
DI 10.1055/a-1223-2525
EA AUG 2020
PG 12
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
   Medicine; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
   Medicine
GA OU9XV
UT WOS:000559509300001
PM 32797466
OA Bronze
DA 2022-11-30
ER

PT J
AU Tong, W
   Hejazi, M
   Garrett, DJ
   Esler, T
   Prawer, S
   Meffin, H
   Ibbotson, MR
AF Tong, Wei
   Hejazi, Maryam
   Garrett, David J.
   Esler, Timothy
   Prawer, Steven
   Meffin, Hamish
   Ibbotson, Michael R.
TI Minimizing axon bundle activation of retinal ganglion cells with
   oriented rectangular electrodes
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE retinal prostheses; retinal ganglion cells; electrical stimulation;
   stimulation strategy; axon bundle activation
ID ELECTRICAL-STIMULATION; THRESHOLDS
AB Objective. Retinal prostheses aim to restore vision in patients with retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. By implanting an array of microelectrodes, such a device creates percepts in patients through electrical stimulation of surviving retinal neurons. A challenge for retinal prostheses when trying to return high quality vision is the unintended activation of retinal ganglion cells through the stimulation of passing axon bundles, which leads to patients reporting large, elongated patches of light instead of focal spots.Approach.In this work, we used calcium imaging to record the responses of retinal ganglion cells to electrical stimulation in explanted retina using rectangular electrodes placed with different orientations relative to the axon bundles.Main results.We showed that narrow, rectangular electrodes oriented parallel to the axon bundles can achieve focal stimulation. To further improve the strategy, we studied the impact of different stimulation waveforms and electrode configurations. We found the selectivity for focal stimulation to be higher when using short (33 mu s), anodic-first biphasic pulses, with long electrode lengths and at least 50 mu m electrode-to-retinal separation. Focal stimulation was, in fact, less selective when the electrodes made direct contact with the retinal surface due to unwanted preferential stimulation of the proximal axon bundles.Significance. When employed in retinal prostheses, the proposed stimulation strategy is expected to provide improved quality of vision to the blind.
C1 [Tong, Wei; Meffin, Hamish; Ibbotson, Michael R.] Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.
   [Tong, Wei; Hejazi, Maryam; Garrett, David J.; Prawer, Steven] Univ Melbourne, Sch Phys, Parkville, Vic, Australia.
   [Tong, Wei; Meffin, Hamish; Ibbotson, Michael R.] Univ Melbourne, Dept Optometry & Vis Sci, Fac Med Dent & Hlth Sci, Parkville, Vic, Australia.
   [Esler, Timothy; Meffin, Hamish] Univ Melbourne, Dept Biomed Engn, Parkville, Vic, Australia.
C3 University of Melbourne; University of Melbourne; University of
   Melbourne
RP Meffin, H; Ibbotson, MR (通讯作者)，Australian Coll Optometry, Natl Vis Res Inst, Carlton, Vic, Australia.; Meffin, H; Ibbotson, MR (通讯作者)，Univ Melbourne, Dept Optometry & Vis Sci, Fac Med Dent & Hlth Sci, Parkville, Vic, Australia.; Meffin, H (通讯作者)，Univ Melbourne, Dept Biomed Engn, Parkville, Vic, Australia.
EM hmeffin@unimelb.edu.au; mibbotson@nvri.org.au
RI ; ibbotson, michael/F-9030-2011
OI PRAWER, STEVEN/0000-0002-4959-0828; Garrett, David/0000-0002-4676-8387;
   ibbotson, michael/0000-0002-3803-6653; Meffin,
   Hamish/0000-0003-4307-6841
FU National Health and Medical Research Council (NHMRC) of Australia
   [GNT1118223]; NHMRC [GNT1101717]; Australian Nanofabrication Facility
   (ANFF)/Melbourne Centre for Nanofabrication (MCN) Technology Ambassador
   Fellowship
FX The research was supported by a Development Grant from The National
   Health and Medical Research Council (NHMRC, GNT1118223) of Australia.
   The work was performed in part at the Melbourne Centre for
   Nanofabrication (MCN) in the Victorian Node of the Australian National
   Fabrication Facility (ANFF). D J G is supported by NHMRC Project Grant
   GNT1101717 and by an Australian Nanofabrication Facility
   (ANFF)/Melbourne Centre for Nanofabrication (MCN) Technology Ambassador
   Fellowship. S P is cofounder and shareholder of iBIONICS, a company
   developing a diamond based retinal prothesis. S P and D J G are
   shareholders and executive officers of Carbon Cybernetics Pty Ltd, a
   company developing diamond and carbon-based medical device components.
   The other authors declare no conflict of interest.
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NR 37
TC 4
Z9 4
U1 2
U2 5
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2020
VL 17
IS 3
AR 036016
DI 10.1088/1741-2552/ab909e
PG 15
WC Engineering, Biomedical; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Neurosciences & Neurology
GA MH5YW
UT WOS:000546805300001
PM 32375131
DA 2022-11-30
ER

PT J
AU Tu, LL
   Wang, JH
   Barathi, VA
   Prea, SM
   He, Z
   Lee, JH
   Bender, J
   King, AE
   Logan, GJ
   Alexander, IE
   Bee, YS
   Tai, MH
   Dusting, GJ
   Bui, BV
   Zhong, JX
   Liu, GS
AF Tu, Leilei
   Wang, Jiang-Hui
   Barathi, Veluchamy A.
   Prea, Selwyn M.
   He, Zheng
   Lee, Jia Hui
   Bender, James
   King, Anna E.
   Logan, Grant J.
   Alexander, Ian E.
   Bee, Youn-Shen
   Tai, Ming-Hong
   Dusting, Gregory J.
   Bui, Bang V.
   Zhong, Jingxiang
   Liu, Guei-Sheung
TI AAV-mediated gene delivery of the calreticulin anti-angiogenic domain
   inhibits ocular neovascularization
SO ANGIOGENESIS
LA English
DT Article
DE Ocular neovascularization; Gene therapy; AAV; Calreticulin
   anti-angiogenic domain; Diabetic retinopathy; Neovascular age-related
   macular degeneration
ID PROLIFERATIVE DIABETIC-RETINOPATHY; RANDOMIZED CLINICAL-TRIAL; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; TOPICAL APPLICATION;
   TUMOR-GROWTH; VEGF AGENTS; VASOSTATIN; THERAPY; RANIBIZUMAB
AB Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization.
C1 [Tu, Leilei; Zhong, Jingxiang; Liu, Guei-Sheung] Jinan Univ, Dept Ophthalmol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.
   [Tu, Leilei; Wang, Jiang-Hui; Lee, Jia Hui; Dusting, Gregory J.; Liu, Guei-Sheung] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
   [Wang, Jiang-Hui; Dusting, Gregory J.; Liu, Guei-Sheung] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
   [Barathi, Veluchamy A.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Translat Preclin Model Platform, Singapore, Singapore.
   [Barathi, Veluchamy A.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Barathi, Veluchamy A.] DUKE NUS Grad Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Prea, Selwyn M.; He, Zheng; Bui, Bang V.] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic, Australia.
   [Bender, James; King, Anna E.] Univ Tasmania, Wicking Dementia Res & Educ Ctr, Hobart, Tas, Australia.
   [Logan, Grant J.] Univ Sydney, Childrens Med Res Inst, Gene Therapy Res Unit, Sydney, NSW, Australia.
   [Alexander, Ian E.] Univ Sydney, Sydney Childrens Hosp Network, Sydney, NSW, Australia.
   [Alexander, Ian E.] Univ Sydney, Discipline Child & Adolescent Hlth, Westmead, NSW, Australia.
   [Bee, Youn-Shen] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Tai, Ming-Hong] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan.
   [Liu, Guei-Sheung] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia.
   [Liu, Guei-Sheung] Liverpool St, Hobart, Tas 7000, Australia.
C3 Jinan University; Centre for Eye Research Australia; Royal Victorian Eye
   & Ear Hospital; University of Melbourne; National University of
   Singapore; Singapore National Eye Center; National University of
   Singapore; National University of Singapore; University of Melbourne;
   University of Tasmania; Children's Medical Research Institute -
   Australia; University of Sydney; University of Sydney; University of
   Sydney; Kaohsiung Veterans General Hospital; National Sun Yat Sen
   University; University of Tasmania; Menzies Institute for Medical
   Research
RP Zhong, JX; Liu, GS (通讯作者)，Jinan Univ, Dept Ophthalmol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.; Liu, GS (通讯作者)，Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.; Liu, GS (通讯作者)，Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.; Liu, GS (通讯作者)，Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia.; Liu, GS (通讯作者)，Liverpool St, Hobart, Tas 7000, Australia.
EM zjx85221206@163.com; rickliu0817@gmail.com
RI Liu, Guei-Sheung/Q-6472-2018; Bui, Bang/AAD-2679-2021; Wang,
   Jiang-Hui/AAW-4653-2020; King, Anna/J-7927-2014
OI Liu, Guei-Sheung/0000-0003-3379-724X; Bui, Bang/0000-0001-7298-1352;
   Wang, Jiang-Hui/0000-0002-1551-9660; King, Anna/0000-0003-1792-0965;
   /0000-0001-9365-342X; Alexander, Ian E/0000-0002-6213-5627
FU National Health and Medical Research Council of Australia [1061912];
   Natural Science Foundation of Guangdong Province, China [2015A030310158,
   2014A030313359]; Science and Technology Planning Project of Guangdong
   Province, China [2015B020226003]; Scientific and Cultivation Foundation
   of the First Affiliated Hospital of Jinan University [2015201];
   fundamental Research Funds for the Central Universities [21611446];
   Ophthalmic Research Institute of Australia; Angior Family Foundation;
   Rebecca L. Cooper Medical Research Foundation; R.B. McComas Research
   Scholarship in Ophthalmology; Gordon P. Castles Scholarship; Melbourne
   Research Scholarship; NHMRC
FX This work was supported by grants from The National Health and Medical
   Research Council of Australia (#1061912), The Natural Science Foundation
   of Guangdong Province, China (2015A030310158 and 2014A030313359), The
   Science and Technology Planning Project of Guangdong Province, China
   (2015B020226003), The Scientific and Cultivation Foundation of the First
   Affiliated Hospital of Jinan University (2015201), The fundamental
   Research Funds for the Central Universities (21611446), The Ophthalmic
   Research Institute of Australia, The Angior Family Foundation and The
   Rebecca L. Cooper Medical Research Foundation. J.H.W. received a R.B.
   McComas Research Scholarship in Ophthalmology, a Gordon P. Castles
   Scholarship and a Melbourne Research Scholarship. G.J.D. received a
   Principal Research Fellowship from NHMRC. The Centre for Eye Research,
   Australia, received Operational Infrastructure Support from the
   Victorian Government.
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NR 44
TC 13
Z9 13
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD FEB
PY 2018
VL 21
IS 1
BP 95
EP 109
DI 10.1007/s10456-017-9591-4
PG 15
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA FW4JP
UT WOS:000425279800008
PM 29318471
DA 2022-11-30
ER

PT J
AU Hu, JY
   Yan, L
   Chen, YD
   Du, XH
   Li, TT
   Liu, DA
   Xu, DH
   Huang, YM
   Wu, Q
AF Hu, Jian-Yan
   Yan, Liang
   Chen, Yong-Dong
   Du, Xin-Hua
   Li, Ting-Ting
   Liu, De-An
   Xu, Dong-Hong
   Huang, Yi-Min
   Wu, Qiang
TI Population-based survey of prevalence, causes, and risk factors for
   blindness and visual impairment in an aging Chinese metropolitan
   population
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE blindness; visual impairment; prevalence; risk factor; cross-sectional
   study
ID ANGELES LATINO EYE; LOW-VISION; ADULT-POPULATION; CATARACT-SURGERY;
   RURAL-POPULATION; NORTHEAST CHINA; OLDER-ADULTS; SMOKING;
   CLASSIFICATION; RETINOPATHY
AB AIM: To assess the prevalence, causes, and risk factors for blindness and visual impairment among elderly (260 years of age) Chinese people in a metropolitan area of Shanghai, China.
   METHODS: Random cluster sampling was conducted to identify participants among residents MO years of age living in the Xietu Block, Xuhui District, Shanghai, China. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were checked by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual chart. All eligible participants underwent a comprehensive eye examination. Blindness and visual impairment were defined according to World Health Organization (WHO) criteria.
   RESULTS: A total of 4190 persons (1688 men and 2502 women) participated in the study, and the response rate was 91.1%. Based on PVA, the prevalence of blindness was 1.1% and that of visual impairment was 7.6%. Based on BCVA, the prevalence of blindness and visual impairment decreased to 0.9% and 3.9%, respectively. Older (>80 years of age) women, with low educational levels and smoking habits, exhibited a significantly greater chance for blindness and visual impairment than did those with high educational levels and no smoking habits (P<0.05). Based on PVA and BCVA, the main causes of blindness were cataract, myopic maculopathy, and age-related macular degeneration (AMD).
   CONCLUSION: Our findings help to identify the population in need of intervention, to highlight the need for additional eye healthcare services in urban China.
C1 [Hu, Jian-Yan; Yan, Liang; Chen, Yong-Dong; Du, Xin-Hua; Li, Ting-Ting; Wu, Qiang] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China.
   [Liu, De-An; Xu, Dong-Hong; Huang, Yi-Min] Community Hlth Ctr, Xietu St, Shanghai 200233, Peoples R China.
C3 Shanghai Jiao Tong University
RP Wu, Q (通讯作者)，Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Ophthalmol, 600 Yishan Rd, Shanghai 200233, Peoples R China.
EM qiang.wu@shsmu.edu.cn
FU Shanghai Municipal Health and Family Planning Commission Foundation
   [201440029]
FX Supported by Shanghai Municipal Health and Family Planning Commission
   Foundation (No.201440029).
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NR 30
TC 17
Z9 18
U1 0
U2 14
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD JAN 18
PY 2017
VL 10
IS 1
BP 140
EP 147
DI 10.18240/ijo.2017.01.23
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EH4XU
UT WOS:000391778000023
PM 28149791
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Choudhary, P
   Gutteridge, A
   Impey, E
   Storer, RI
   Owen, RM
   Whiting, PJ
   Bictash, M
   Benn, CL
AF Choudhary, Parul
   Gutteridge, Alex
   Impey, Emma
   Storer, R. Ian
   Owen, Robert M.
   Whiting, Paul J.
   Bictash, Magda
   Benn, Caroline L.
TI Targeting the cAMP and Transforming Growth Factor-beta Pathway Increases
   Proliferation to Promote Re-Epithelialization of Human Stem Cell-Derived
   Retinal Pigment Epithelium
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
ID TGF-BETA; MACULAR DEGENERATION; CYCLIC-AMP; MESENCHYMAL TRANSITION;
   MOLECULAR SIGNATURE; VISUAL FUNCTION; RPE CELLS; IN-VIVO; INHIBITION;
   VITREORETINOPATHY
AB Retinal pigment epithelium (RPE) cell integrity is critical to the maintenance of retinal function. Many retinopathies such as age-related macular degeneration (AMD) are caused by the degeneration or malfunction of the RPE cell layer. Replacement of diseased RPE with healthy, stem cell-derived RPE is a potential therapeutic strategy for treating AMD. Human embryonic stem cells (hESCs) differentiated into RPE progeny have the potential to provide an unlimited supply of cells for transplantation, but challenges around scalability and efficiency of the differentiation process still remain. Using hESC-derived RPE as a cellular model, we sought to understand mechanisms that could be modulated to increase RPE yield after differentiation. We show that RPE epithelialization is a density-dependent process, and cells seeded at low density fail to epithelialize. We demonstrate that activation of the CAMP pathway increases proliferation of dissociated RPE in culture, in part through inhibition of transforming growth factor-beta (TGF-beta) signaling. This results in enhanced uptake of epithelial identity, even in cultures seeded at low density. In line with these findings, targeted manipulation of the TGF-beta pathway with small molecules produces an increase in efficiency of RPE re-epithelialization. Taken together, these data highlight mechanisms that promote epithelial fate acquisition in stem cell derived RPE. Modulation of these pathways has the potential to favorably impact scalability and clinical translation of hESC-derived RPE as a cell therapy.
C1 [Choudhary, Parul; Gutteridge, Alex; Impey, Emma; Whiting, Paul J.; Bictash, Magda; Benn, Caroline L.] Pfizer Ltd, Pfizer Neurosci & Pain Res Unit, Cambridge, England.
   [Storer, R. Ian; Owen, Robert M.] Pfizer Ltd, Pfizer Worldwide Med Chem, Cambridge, England.
C3 Pfizer; Pfizer
RP Choudhary, P (通讯作者)，Pfizer Neurosci & Pain Res Unit, Granta Pk, Cambridge CB21 6GS, England.
EM parulc83@gmail.com
OI Gutteridge, Alex/0000-0001-7515-634X; Whiting, Paul/0000-0002-4121-1379
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NR 57
TC 10
Z9 10
U1 0
U2 9
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD JUL
PY 2016
VL 5
IS 7
BP 925
EP 937
DI 10.5966/sctm.2015-0247
PG 13
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA DQ1RY
UT WOS:000378979300015
PM 27112176
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Lorach, H
   Kung, J
   Beier, C
   Mandel, Y
   Dalal, R
   Huie, P
   Wang, J
   Lee, S
   Sher, A
   Jones, BW
   Palanker, D
AF Lorach, Henri
   Kung, Jennifer
   Beier, Corinne
   Mandel, Yossi
   Dalal, Roopa
   Huie, Philip
   Wang, Jenny
   Lee, Seungjun
   Sher, Alexander
   Jones, Bryan William
   Palanker, Daniel
TI Development of Animal Models of Local Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE geographic atrophy; animal model; AMD
ID RESTORING VISUAL FUNCTION; AMINO-ACID SIGNATURES; MACULAR DEGENERATION;
   RESTORATION; LASER; RESPONSES; DAMAGE; CAT; THERAPY; ATROPHY
AB PURPOSE. Development of nongenetic animal models of local retinal degeneration is essential for studies of retinal pathologies, such as chronic retinal detachment or age-related macular degeneration. We present two different methods to induce a highly localized retinal degeneration with precise onset time, that can be applied to a broad range of species in laboratory use.
   METHODS. A 30-mu m thin polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of chronic retinal separation from the RPE were studied using histology and immunohistochemistry. Another approach is applicable to species with avascular retina, such as rabbits, where the photoreceptors and RPE were thermally ablated over large areas, using a high power scanning laser.
   RESULTS. Photoreceptors above the subretinal implant in rats degenerated over time, with 80% of the outer nuclear layer disappearing within a month, and the rest by 3 months. Similar loss was obtained by selective photocoagulation with a scanning laser. Cells in the inner nuclear layer and ganglion cell layer were preserved in both cases. However, there were signs of rewiring and decrease in the size of the bipolar cell terminals in the damaged areas.
   CONCLUSIONS. Both methods induce highly reproducible degeneration of photoreceptors over a defined area, with complete preservation of the inner retinal neurons during the 3-month follow-up. They provide a reliable platform for studies of local retinal degeneration and development of therapeutic strategies in a wide variety of species.
C1 [Lorach, Henri; Mandel, Yossi; Huie, Philip; Wang, Jenny; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Lorach, Henri; Kung, Jennifer; Dalal, Roopa; Huie, Philip; Wang, Jenny; Lee, Seungjun; Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Lorach, Henri] Inst Vis, Paris, France.
   [Beier, Corinne; Sher, Alexander] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Santa Cruz, CA 95064 USA.
   [Mandel, Yossi] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.
   [Jones, Bryan William] Univ Utah, Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT USA.
C3 Stanford University; Stanford University; UDICE-French Research
   Universities; Sorbonne Universite; University of California System;
   University of California Santa Cruz; Bar Ilan University; Utah System of
   Higher Education; University of Utah
RP Lorach, H (通讯作者)，Hensen Expt Phys Lab, 452 Lomita Mall, Stanford, CA 94305 USA.
EM henri.lorach@gmail.com
OI Beier, Corinne/0000-0002-0698-7219; Sher, Alexander/0000-0001-6655-6456;
   Palanker, Daniel/0000-0002-0480-3025; LORACH, HENRI/0000-0003-4337-2798;
   Jones, Bryan/0000-0001-5527-6643
FU NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025744] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [P30EY014800, R01EY002576, R01EY015128,
   R01EY018608] Funding Source: NIH RePORTER; NCATS NIH HHS [UL1 TR001085]
   Funding Source: Medline; NCRR NIH HHS [UL1 RR025744] Funding Source:
   Medline; NEI NIH HHS [P30 EY014800, R01-EY-018608, R01 EY015128, R01
   EY018608, R01 EY002576] Funding Source: Medline
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NR 54
TC 18
Z9 18
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2015
VL 56
IS 8
BP 4644
EP 4652
DI 10.1167/iovs.14-16011
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT5WV
UT WOS:000362882700054
PM 26207299
OA Green Published
DA 2022-11-30
ER

PT J
AU Shang, JL
   Zhang, JY
   Sun, Y
   Zhang, YK
AF Shang, Junliang
   Zhang, Junying
   Sun, Yan
   Zhang, Yuanke
TI EpiMiner: A three-stage co-information based method for detecting and
   visualizing epistatic interactions
SO DIGITAL SIGNAL PROCESSING
LA English
DT Article
DE Epistatic interactions; Single nucleotide polymorphisms; Co-information;
   Genomic signal processing
ID GENE-GENE INTERACTIONS; STATISTICAL-METHODS; ENVIRONMENT; OPTIMIZATION;
   ASSOCIATIONS; POLYMORPHISM; ALGORITHM; INFERENCE; PATTERNS; MODELS
AB Detecting and visualizing nonlinear interactive effects of Single Nucleotide Polymorphisms (SNPs) or epistatic interactions are important topics of signal processing having great mathematical and computational challenges. To address these problems, a three-stage method, epiMiner (epistasis Miner), is proposed based on co-information theory. In screening stage, Co-Information Index (CII) is employed to visualize and rank contributions of individual SNPs to the phenotype, with the number of top ranking SNPs retained to next stage specified by users directly or a support vector machine classifier automatically. In testing stage, co-information and co-information based permutation test are conducted sequentially to search epistatic interactions within the retained SNPs, with the results then ranked by their p-values. For further characterizing broader epistasis landscape, a visualizing stage is designed to dynamically construct epistasis networks by linking pairs of the retained SNPs if their co-information values with respect to the phenotype are stronger than thresholds. The performance of epiMiner is compared with existing methods on a diverse range of simulated data sets containing several epistasis models. Results demonstrate that epiMiner is effective in detecting and visualizing epistatic interactions. In addition, the application of epiMiner on a real Age-related Macular Degeneration (AMD) data set provides several new clues for the exploration of causative factors of AMD. The Matlab version of epiMiner software is available free online at https://sourceforge.net/projects/epiminer/files/. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Shang, Junliang; Sun, Yan; Zhang, Yuanke] Qufu Normal Univ, Sch Comp Sci, Rizhao 276826, Peoples R China.
   [Shang, Junliang; Zhang, Junying] Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Peoples R China.
C3 Qufu Normal University; Xidian University
RP Shang, JL (通讯作者)，Qufu Normal Univ, Sch Comp Sci, Rizhao 276826, Peoples R China.
EM jishang@mail.xidian.edu.cn; jyzhang@mail.xidian.edu.cn;
   sunyan225@126.com; yuankezhang@163.com
FU Fundamental Research Funds for the Central Universities [K50513100014];
   National Natural Science Foundation of China [61070137]; Major Research
   Plan of the National Natural Science Foundation of China [91130006]; Key
   Program of the National Natural Science Foundation of China [60933009];
   Shandong Province Higher Educational Science and Technology Program
   [J13LN31]
FX This work was supported by the Fundamental Research Funds for the
   Central Universities (Grant No. K50513100014); the National Natural
   Science Foundation of China (Grant No. 61070137); the Major Research
   Plan of the National Natural Science Foundation of China (Grant No.
   91130006); the Key Program of the National Natural Science Foundation of
   China (Grant No. 60933009); a Project of Shandong Province Higher
   Educational Science and Technology Program (Grant No. J13LN31).
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NR 52
TC 25
Z9 25
U1 1
U2 20
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1051-2004
EI 1095-4333
J9 DIGIT SIGNAL PROCESS
JI Digit. Signal Prog.
PD JAN
PY 2014
VL 24
BP 1
EP 13
DI 10.1016/j.dsp.2013.08.007
PG 13
WC Engineering, Electrical & Electronic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 274GU
UT WOS:000328595600001
DA 2022-11-30
ER

PT J
AU Kang, S
   Roh, CR
   Cho, WK
   Park, KC
   Yang, KJ
   Choi, HS
   Kim, SH
   Roh, YJ
AF Kang, Seungbum
   Roh, Chang Rae
   Cho, Won-Kyung
   Park, Ki Cheol
   Yang, Keum-Jin
   Choi, Hyun-Su
   Kim, So-Hee
   Roh, Young-Jung
TI Antiangiogenic Effects of Axitinib, an Inhibitor of Vascular Endothelial
   Growth Factor Receptor Tyrosine Kinase, on Laser-Induced Choroidal
   Neovascularization in Mice
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Angiogenesis; Axitinib; Receptor tyrosine kinase; Vascular endothelial
   growth factor
ID MACULAR DEGENERATION; PHASE-II; DNA-SYNTHESIS; CANCER; CELLS;
   ACTIVATION; AG-013736; ANGIOGENESIS; RANIBIZUMAB; BEVACIZUMAB
AB Purpose: To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD).
   Methods: Experimental CNV lesions were induced in C57BL/6 mice by laser photocoagulation. Beginning 1 day after CNV induction, mice were treated with axitinib (5 mg/kg/day) or vehicle for 2 weeks. In other groups of mice, axitinib or vehicle treatment was started 7 days after the laser application to determine the effect of the drug on established CNV. Untreated mice were used as a baseline group. Two weeks after laser injury, the extent of CNV was assessed from choroidal flat mounts perfused with fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions.
   Results: Orally administered axitinib inhibited CNV growth in the laser-induced CNV model. Axitinib caused a 70.1% inhibition of CNV lesions compared to vehicle-treatment (p < 0.001). Axitinib also caused a significant regression of established CNV, reducing the area by 71.1% compared to vehicle treatment (p < 0.001). Moreover, immunofluorescence staining showed that the area of isolectin IB4 labeled vessels was smaller in the axitinib-treated group compared to the vehicle-treated group (p < 0.001).
   Conclusions: Axitinib effectively inhibits the progression of CNV in an experimental animal model. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of neovascular AMD.
C1 [Kang, Seungbum; Roh, Chang Rae; Cho, Won-Kyung; Roh, Young-Jung] Catholic Univ Korea, Daejeon St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, Taejon, South Korea.
   [Kang, Seungbum; Roh, Chang Rae; Cho, Won-Kyung; Park, Ki Cheol; Yang, Keum-Jin; Choi, Hyun-Su; Kim, So-Hee] Catholic Univ Korea, Daejeon St Marys Hosp, Coll Med, Clin Res Inst, Taejon, South Korea.
C3 Catholic University of Korea; Catholic University of Korea
RP Roh, YJ (通讯作者)，Catholic Univ Korea, Coll Med, St Marys Hosp, Dept Ophthalmol & Visual Sci, 62 Yoido Dong, Seoul, South Korea.
EM youngjungroh@hanmail.net
FU Clinical Research Institute; Catholic University of Korea, Daejeon St.
   Mary's Hospital [CMCDJ-201102]; Korea Institute for Advancement of
   Technology [M000004912-00192937]
FX This work was supported by Clinical Research Institute Grant funded by
   The Catholic University of Korea, Daejeon St. Mary's Hospital
   (CMCDJ-201102) and Korea Institute for Advancement of Technology
   (M000004912-00192937).
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NR 29
TC 17
Z9 18
U1 1
U2 7
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 JAN-FEB
PY 2013
VL 38
IS 1
BP 119
EP 127
DI 10.3109/02713683.2012.727520
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 067IV
UT WOS:000313288400018
PM 23013553
DA 2022-11-30
ER

PT J
AU Weikel, KA
   FitzGerald, P
   Shang, F
   Caceres, MA
   Bian, QN
   Handa, JT
   Stitt, AW
   Taylor, A
AF Weikel, Karen A.
   FitzGerald, Paul
   Shang, Fu
   Caceres, M. Andrea
   Bian, Qingning
   Handa, James T.
   Stitt, Alan W.
   Taylor, Allen
TI Natural History of Age-Related Retinal Lesions That Precede AMD in Mice
   Fed High or Low Glycemic Index Diets
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GLYCATION END-PRODUCTS; ENDOTHELIAL GROWTH-FACTOR; METHYLGLYOXAL-DERIVED
   HYDROIMIDAZOLONE; INCREASED SERUM-LEVELS; CARDIOVASCULAR-DISEASE
   MORTALITY; TYPE-2 DIABETES-MELLITUS; BASAL LAMINAR DEPOSIT; SUB-RPE
   DEPOSITS; MACULAR DEGENERATION; PIGMENT-EPITHELIUM
AB PURPOSE. Epidemiologic data indicate that people who consume low glycemic index (GI) diets are at reduced risk for the onset and progression of age-related macular degeneration (AMD). The authors sought corroboration of this observation in an animal model.
   METHODS. Five-and 16-month-old C57BL/6 mice were fed high or low GI diets until they were 17 and 23.5 months of age, respectively. Retinal lesions were evaluated by transmission electron microscopy, and advanced glycation end products (AGEs) were evaluated by immunohistochemistry.
   RESULTS. Retinal lesions including basal laminar deposits, loss of basal infoldings, and vacuoles in the retinal pigment epithelium were more prevalent in the 23.5-than in the 17-month-old mice. Within each age group, consumption of a high GI diet increased the risk for lesions and the risk for photoreceptor abnormalities and accumulation of AGEs.
   CONCLUSIONS. Consuming high GI diets accelerates the appearance of age-related retinal lesions that precede AMD in mice, perhaps by increasing the deposition of toxic AGEs in the retina. The data support the hypothesis that consuming lower GI diets, or simulation of their effects with nutraceuticals or drugs, may protect against AMD. The high GI-fed C57BL/6 mouse is a new model of age-related retinal lesions that precede AMD and mimic the early stages of disease and may be useful for drug discovery. (Invest Ophthalmol Vis Sci. 2012;53: 622-632) DOI:10.1167/iovs.11-8545
C1 [Weikel, Karen A.; Shang, Fu; Caceres, M. Andrea; Bian, Qingning; Taylor, Allen] Tufts Univ, Lab Nutr & Vis Res, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [FitzGerald, Paul] Univ Calif Davis, Sch Med, Dept Cell Biol & Human Anat, Davis, CA 95616 USA.
   [Handa, James T.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
   [Stitt, Alan W.] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
C3 Tufts University; United States Department of Agriculture (USDA);
   University of California System; University of California Davis; Johns
   Hopkins University; Johns Hopkins Medicine; Queens University Belfast
RP Taylor, A (通讯作者)，Tufts Univ, Lab Nutr & Vis Res, JM USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM allen.taylor@tufts.edu
RI Stitt, Alan/A-9842-2009
OI Stitt, Alan/0000-0002-8647-9918; Weikel, Karen/0000-0003-0317-7891
FU United States Department of Agriculture [1950-510000-060-01A]; Johnson &
   Johnson Focused Giving; American Health Assistance Foundation; National
   Institutes of Health [13250, 21212, NEI P30 EY12576 (UCD), EY14004,
   EY019904]; Thome Foundation; Robert Bond Welch Professorship; NATIONAL
   EYE INSTITUTE [R01EY014005, R01EY021212, R01EY019904, P30EY012576,
   R01EY013250] Funding Source: NIH RePORTER
FX Supported by United States Department of Agriculture Grant
   1950-510000-060-01A; Johnson & Johnson Focused Giving; American Health
   Assistance Foundation; National Institutes of Health Grants 13250,
   21212, NEI P30 EY12576 (UCD), EY14004, and EY019904; Thome Foundation
   Award; and Robert Bond Welch Professorship.
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NR 134
TC 40
Z9 40
U1 0
U2 13
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2012
VL 53
IS 2
BP 622
EP 632
DI 10.1167/iovs.11-8545
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 925VA
UT WOS:000302788600011
PM 22205601
OA Green Published
DA 2022-11-30
ER

PT J
AU Chaum, E
   Karnowski, TP
   Govindasamy, VP
   Abdelrahman, M
   Tobin, KW
AF Chaum, Edward
   Karnowski, Thomas P.
   Govindasamy, V. Priya
   Abdelrahman, Mohamed
   Tobin, Kenneth W.
TI AUTOMATED DIAGNOSIS OF RETINOPATHY BY CONTENT-BASED IMAGE RETRIEVAL
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE content-based image retrieval; computer-aided diagnosis; retina;
   retinopathy; diabetic retinopathy; age-related macular degeneration;
   image analysis
ID DIABETIC-RETINOPATHY; OPTIC DISC; RETINAL IMAGES; FUNDUS IMAGES;
   SEGMENTATION; LESIONS; SYSTEM; PHOTOGRAPHY; MODEL
AB Purpose: To describe a novel computer-based image analysis method that is being developed to assist and automate the diagnosis of retinal disease.
   Methods: Content-based image retrieval is the process of retrieving related images from large database collections using their pictorial content. The content feature list becomes the index for storage, search, and retrieval of related images from a library based upon specific visual characteristics. Low-level analyses use feature description models and higher-level analyses use perceptual organization and spatial relationships, including clinical metadata, to extract semantic information.
   Results: We defined, extracted, and tested a large number of region- and lesion-based features from a dataset of 395 retinal images. Using a statistical hold-one-out method, independent queries for each image were submitted to the system and a diagnostic prediction was formulated. The diagnostic sensitivity for all stratified levels of age-related macular degeneration ranged from 75% to 100%. Similarly, the sensitivity of detection and accuracy for proliferative diabetic retinopathy ranged from 75% to 91.7% and for nonproliferative diabetic retinopathy, ranged from 75% to 94.7%. The overall purity of the diagnosis (specificity) for all disease states in the dataset was 91.3%.
   Conclusions: The probabilistic nature of content-based image retrieval permits us to make statistically relevant predictions regarding the presence, severity, and manifestations of common retinal diseases from digital images in an automated and deterministic manner.
C1 [Chaum, Edward] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN USA.
   [Chaum, Edward] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN USA.
   [Chaum, Edward] Univ Tennessee, Hlth Sci Ctr, Dept Biomed Engn, Memphis, TN USA.
   [Chaum, Edward] Univ Tennessee, Hlth Sci Ctr, Dept Pediat, Memphis, TN USA.
   [Karnowski, Thomas P.; Govindasamy, V. Priya; Tobin, Kenneth W.] Oak Ridge Natl Lab, Image Sci & Machine Vis Grp, Oak Ridge, TN USA.
   [Abdelrahman, Mohamed] Tennessee Technol Univ, Cookeville, TN 38505 USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center; University of Tennessee System; University of Tennessee
   Health Science Center; University of Tennessee System; University of
   Tennessee Health Science Center; United States Department of Energy
   (DOE); Oak Ridge National Laboratory; Tennessee Technological University
RP Chaum, E (通讯作者)，Hamilton Eye Inst, 930 Madison Ave,Suite 731, Memphis, TN 38163 USA.
EM echaum@utmem.edu
RI Chaum, Edward/AAR-1512-2021
OI Chaum, Edward/0000-0003-3542-8376; Karnowski,
   Thomas/0000-0002-0376-4917; Tobin, Kenneth/0000-0003-3577-9520
FU Oak Ridge National Laboratory; National Eye Institute [EY017065]; United
   States Army Medical and Material Command; Telemedicine and Advanced
   Technology Research Center [W81XWH-05-1-0409]; Research to Prevent
   Blindness, New York, NY; Fight for Sight, New York, NY; Plough
   Foundation, Memphis, TN; NATIONAL EYE INSTITUTE [R01EY017065] Funding
   Source: NIH RePORTER
FX These studies were supported in part by grants from Oak Ridge National
   Laboratory, the National Eye Institute, (EY017065), the United States
   Army Medical and Material Command, Telemedicine and Advanced Technology
   Research Center (W81XWH-05-1-0409), by an unrestricted UTHSC
   Departmental grant from Research to Prevent Blindness, New York, NY,
   Fight for Sight, New York, NY, and by The Plough Foundation, Memphis,
   TN.
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NR 59
TC 51
Z9 53
U1 0
U2 11
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-DEC
PY 2008
VL 28
IS 10
BP 1463
EP 1477
DI 10.1097/IAE.0b013e31818356dd
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 373LH
UT WOS:000260972600013
PM 18997609
DA 2022-11-30
ER

PT J
AU Krebs, I
   Ansari-Shahrezaei, S
   Goll, A
   Binder, S
AF Krebs, Ilse
   Ansari-Shahrezaei, Siamak
   Goll, Alexandra
   Binder, Susanne
TI Activity of neovascular lesions treated with bevacizumab: comparison
   between optical coherence tomography and fluorescein angiography
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; bevacizumab; choroidal
   neovascularisation; optical coherence tomography
ID INTRAVITREAL BEVACIZUMAB; AVASTIN
AB Purpose To investigate whether examination with the non-invasive optical coherence tomography (OCT) alone is sufficient to ascertain the need of re-treatment with bevacizumab for exudative age-related macular degeneration (AMD) or the invasive fluorescein angiography (FA) is needed.
   Method Two independent examiners reviewed FA and OCT images and performed a semi-quantitative assessment from 0=no activity to activity 1-3, mild, moderate and advanced, respectively. Weighted Kappa indices were performed to calculate the concordance between OCT and FA.
   Results A total of 153 OCT and FA examinations of 69 patients were evaluated, mean 2.2 examinations per patient. The mean age was 77.1 +/- 7.9 (55-89) years; 29.0% were male, 71.0% female. The weighted Kappa index showed concordance for activity in OCT and FA weak concerning the first investigation 4-6 weeks after initial treatment (0.3847) and obvious concerning the second investigation 8-10 weeks after initial treatment (0.4170). Higher values of activity were found with the OCT compared to FA. The most frequent reasons for discrepancies were detachment of the pigmentepithelium and fibrosis.
   Conclusion There is evidence of agreement between both examinations, the OCT was even more sensitive to detect activity of a lesion. In conducting studies based on OCT as single examination, it should be clearly defined how long fibrotic lesions or lesions with pigment epithelial detachment should be re-treated.
C1 [Krebs, Ilse; Ansari-Shahrezaei, Siamak; Binder, Susanne] Rudolf Fdn Clin, Dept Ophthalmol, A-1030 Vienna, Austria.
   [Krebs, Ilse; Ansari-Shahrezaei, Siamak; Binder, Susanne] Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, A-1030 Vienna, Austria.
   [Ansari-Shahrezaei, Siamak] Med Univ Graz, Dept Ophthalmol, Graz, Austria.
   [Goll, Alexandra] Med Univ Vienna, Core Unit Med Stat & Informat, A-1090 Vienna, Austria.
C3 Ludwig Boltzmann Institute; Medical University of Graz; Medical
   University of Vienna
RP Krebs, I (通讯作者)，Rudolf Fdn Clin, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
EM Ilse.Krebs@wienkav.at
OI Graf, Alexandra/0000-0003-0035-2658
CR Avery RL, 2006, OPHTHALMOLOGY, V113, P363, DOI 10.1016/j.ophtha.2005.11.019
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NR 14
TC 18
Z9 18
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUN
PY 2008
VL 246
IS 6
BP 811
EP 815
DI 10.1007/s00417-007-0755-6
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297PI
UT WOS:000255628200003
PM 18196261
DA 2022-11-30
ER

PT J
AU Baird, PN
   Robman, LD
   Richardson, AJ
   Dimitrov, PN
   Tikellis, G
   McCarty, CA
   Guymer, RH
AF Baird, Paul N.
   Robman, Luba D.
   Richardson, Andrea J.
   Dimitrov, Peter N.
   Tikellis, Gabriella
   McCarty, Catherine A.
   Guymer, Robyn H.
TI Gene-environment interaction in progression of AMD: the CFH gene,
   smoking and exposure to chronic infection
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CHLAMYDIA-PNEUMONIAE INFECTION; AGE-RELATED MACULOPATHY; FACTOR-H
   POLYMORPHISM; MACULAR DEGENERATION; DRUSEN FORMATION; CARDIOVASCULAR
   HEALTH; ASSOCIATION; DISEASE; RISK; VARIANT
AB A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.
C1 [Baird, Paul N.; Robman, Luba D.; Richardson, Andrea J.; Dimitrov, Peter N.; Tikellis, Gabriella; McCarty, Catherine A.; Guymer, Robyn H.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [McCarty, Catherine A.] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA.
C3 Centre for Eye Research Australia; University of Melbourne
RP Baird, PN (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM pnb@unimelb.edu.au
RI Robman, Liubov/N-9075-2013
OI McCarty, Catherine/0000-0003-1089-0142; Baird, Paul/0000-0002-1305-3502;
   Guymer, Robyn/0000-0002-9441-4356
CR Anderson DH, 2001, AM J OPHTHALMOL, V131, P767, DOI 10.1016/S0002-9394(00)00961-2
   Baird PN, 2006, INVEST OPHTH VIS SCI, V47, P4194, DOI 10.1167/iovs.05-1285
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   Bressler NM, 2003, ARCH OPHTHALMOL-CHIC, V121, P1621
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   Haines JL, 2005, SCIENCE, V308, P419, DOI 10.1126/science.1110359
   Ishida O, 2003, BRIT J OPHTHALMOL, V87, P523, DOI 10.1136/bjo.87.5.523
   Johnson LV, 2000, EXP EYE RES, V70, P441, DOI 10.1006/exer.1999.0798
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   Kalayoglu MV, 2003, ARCH OPHTHALMOL-CHIC, V121, P478, DOI 10.1001/archopht.121.4.478
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   Klein RJ, 2005, SCIENCE, V308, P385, DOI 10.1126/science.1109557
   Li M, 2006, NAT GENET, V38, P1049, DOI 10.1038/ng1871
   MAHDI O, 2002, P 10 INT S HUM CHLAM, P329
   Mahdi OS, 2002, CIRCULATION, V106, P1659, DOI 10.1161/01.CIR.0000031567.10814.D8
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   ROTHMAN K, 2005, EPISHEET EPIDEMIOLOG
   Rothman KJ., 2008, MODERN EPIDEMIOLOGY, V3
   Scholl HPN, 2007, MOL VIS, V13, P196
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NR 33
TC 67
Z9 69
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2008
VL 17
IS 9
BP 1299
EP 1305
DI 10.1093/hmg/ddn018
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 290VR
UT WOS:000255151300010
PM 18203751
OA Bronze
DA 2022-11-30
ER

PT J
AU Singh, RP
   Patel, C
   Sears, JE
AF Singh, RP
   Patel, C
   Sears, JE
TI Management of subretinal macular haemorrhage by direct administration of
   tissue plasminogen activator
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID THICK SUBMACULAR HEMORRHAGE; PARS-PLANA VITRECTOMY; RETINAL TOXICITY;
   ASSISTED REMOVAL; NATURAL-HISTORY; DEGENERATION; INJECTION; DRAINAGE;
   DISPLACEMENT; RABBITS
AB Background/aims: Recent studies on the treatment of acute subretinal macular haemorrhage have shown that the volume of the clot and the time to evacuation have strong prognostic factors for visual outcome. A novel technique for surgical evacuation of these lesions involves direct injection of tissue plasminogen activator (t-PA) into the haematoma using pars plana vitrectomy. The aim of this study was to evaluate the clinical outcomes of this recently described procedure.
   Methods: 17 consecutive patients with subretinal macular haemorrhages caused by age related macular degeneration were enrolled. Patient demographics, acuities, and fluorescein angiograms were obtained for all evaluations. All patients underwent complete three port pars plana vitrectomy to enable direct cannulation of the subretinal space and injection of 48 mu g of t-PA, partial fluid-air exchange, 1 hour face up supine positioning postoperatively, followed by upright positioning overnight.
   Results: 88% of patients within the study had stabilisation or improvement of visual acuity. Nine patients had total clearing of the macular haemorrhage and eight patients had subtotal clearing. Two patients had recurrence of the haemorrhage after the procedure and one patient underwent repair for retinal detachment. Occult lesions demonstrated similar outcomes to classic or predominately classic lesions. Nine patients required no therapy after the study to treat subfoveal neovascularisation.
   Conclusions: This study represents one of the largest case series to date showing that direct injection of subretinal t-PA with air-fluid exchange only and no intraoperative clot lysis period can have favourable results.
C1 Cleveland Clin Fdn, Vitreo Retinal Serv, Cole Eye Inst, Cleveland, OH 44195 USA.
   Kresge Eye Inst, Detroit, MI 48201 USA.
C3 Cleveland Clinic Foundation
RP Sears, JE (通讯作者)，Cleveland Clin Fdn, Vitreo Retinal Serv, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM searsj@ccf.org
RI Patel, Chetan Kantibhai/AAB-2130-2020
OI Patel, Chetan Kantibhai/0000-0002-1409-6045
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NR 29
TC 44
Z9 48
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2006
VL 90
IS 4
BP 429
EP 431
DI 10.1136/bjo.2005.085001
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 023CH
UT WOS:000236102400014
PM 16547320
OA Green Published
DA 2022-11-30
ER

PT J
AU THOMSON, RJ
   CHAZARO, J
   OTERO-MARQUEZ, O
   LEDESMA-GIL, G
   TONG, YH
   COUGHLIN, AC
   TEIBEL, ZR
   ALAUDDIN, S
   TAI, K
   LLOYD, H
   SCOLARO, M
   GOVINDAIAH, A
   BHUIYAN, A
   DHAMOON, MS
   DEOBHAKTA, A
   NARULA, J
   ROSEN, RB
   YANNUZZI, LA
   FREUND, KB
   SMITH, RT
AF THOMSON, R. O. B. E. R. T. J.
   CHAZARO, J. O. S. H. U. A.
   OTERO-MARQUEZ, O. S. C. A. R.
   LEDESMA-GIL, G. E. R. A. R. D. O.
   TONG, Y. U. E. H. O. N. G.
   COUGHLIN, A. R. I. E. L. L. E. C.
   TEIBEL, Z. A. C. H. A. R. Y. R.
   ALAUDDIN, S. H. A. R. M. I. N. A.
   TAI, K. A. T. Y.
   LLOYD, H. A. R. R. I. E. T.
   SCOLARO, M. A. R. I. A.
   GOVINDAIAH, A. R. U. N.
   BHUIYAN, A. L. A. U. D. D. I. N.
   DHAMOON, M. A. N. D. I. P. S.
   DEOBHAKTA, A. V. N. I. S. H.
   NARULA, J. A. G. A. T.
   ROSEN, R. I. C. H. A. R. D. B.
   YANNUZZI, L. A. W. R. E. N. C. E. A.
   FREUND, K. B. A. I. L. E. Y.
   SMITH, R. T. H. E. O. D. O. R. E.
TI SUBRETINAL DRUSENOID DEPOSITS AND SOFT DRUSEN Are They Markers for
   Distinct Retinal Diseases?
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; choroid; cardiovascular disease;
   drusen; genetics; risk factors; stroke; subretinal drusenoid deposits
ID RETICULAR MACULAR DISEASE; GEOGRAPHIC ATROPHY; DEGENERATION;
   PSEUDODRUSEN; EYES
AB Purpose: Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases. Methods: One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. Results: There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 +/- 18 vs. 69 +/- 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038). Conclusion: Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.
C1 [THOMSON, R. O. B. E. R. T. J.; CHAZARO, J. O. S. H. U. A.] Univ Texas Houston, McGovern Med Sch, Hlth Sci Ctr, Houston, TX USA.
   [CHAZARO, J. O. S. H. U. A.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA.
   [OTERO-MARQUEZ, O. S. C. A. R.; LEDESMA-GIL, G. E. R. A. R. D. O.; TONG, Y. U. E. H. O. N. G.; ALAUDDIN, S. H. A. R. M. I. N. A.; TAI, K. A. T. Y.; LLOYD, H. A. R. R. I. E. T.; DEOBHAKTA, A. V. N. I. S. H.; ROSEN, R. I. C. H. A. R. D. B.; SMITH, R. T. H. E. O. D. O. R. E.] New York Eye & Ear Infirm Mt Sinai, Dept Ophthalmol, New York, NY USA.
   [LEDESMA-GIL, G. E. R. A. R. D. O.; SCOLARO, M. A. R. I. A.; YANNUZZI, L. A. W. R. E. N. C. E. A.; FREUND, K. B. A. I. L. E. Y.] Vitreous Retina Macula Consultants New York, New York, NY USA.
   [LEDESMA-GIL, G. E. R. A. R. D. O.] Fdn Conde Valenciana, Inst Ophthalmol, Retina Dept, Mexico City, DF, Mexico.
   [TONG, Y. U. E. H. O. N. G.; BHUIYAN, A. L. A. U. D. D. I. N.; SMITH, R. T. H. E. O. D. O. R. E.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA.
   [COUGHLIN, A. R. I. E. L. L. E. C.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
   [TEIBEL, Z. A. C. H. A. R. Y. R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
   [GOVINDAIAH, A. R. U. N.] IHealthscreen Inc, New York, NY USA.
   [DHAMOON, M. A. N. D. I. P. S.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
   [NARULA, J. A. G. A. T.] Icahn Sch Med Mt Sinai, Dept Cardiol, New York, NY 10029 USA.
   [FREUND, K. B. A. I. L. E. Y.] NYU Grossman Sch Med, Dept Ophthalmol, New York, NY USA.
C3 University of Texas System; University of Texas Health Science Center
   Houston; Loyola University Chicago; New York Eye & Ear Infirmary of
   Mount Sinai; Vitreous Retina Macula Consultants of New York; Icahn
   School of Medicine at Mount Sinai; Icahn School of Medicine at Mount
   Sinai; Hackensack University Medical Center; Icahn School of Medicine at
   Mount Sinai; Icahn School of Medicine at Mount Sinai
RP SMITH, RT (通讯作者)，New York Eye & Ear Infirm Mt Sinai, 310 E 14th St, New York, NY 10003 USA.
EM rts1md@gmail.com
CR Ahmad M, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0175691
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   Colijn JM, 2019, OPHTHALMOLOGY, V126, P393, DOI 10.1016/j.ophtha.2018.09.045
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NR 29
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUL
PY 2022
VL 42
IS 7
BP 1311
EP 1318
DI 10.1097/IAE.0000000000003460
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2F9XK
UT WOS:000813255200012
PM 35213528
DA 2022-11-30
ER

PT J
AU Scholl, HPN
   Boyer, D
   Giani, A
   Chong, V
AF Scholl, Hendrik P. N.
   Boyer, David
   Giani, Andrea
   Chong, Victor
TI The Use of Neuroprotective Agents in Treating Geographic Atrophy
SO OPHTHALMIC RESEARCH
LA English
DT Review
DE Geographic atrophy; Neuroprotection; Age-related macular degeneration;
   Retina; Neurotrophic factors
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION AMD; COMPLEMENT
   FACTOR-H; C-REACTIVE PROTEIN; OXIDATIVE STRESS; EYE DISEASE; RETICULAR
   PSEUDODRUSEN; RISK-FACTORS; MOUSE MODEL; PROINFLAMMATORY CYTOKINES
AB Geographic atrophy (GA) secondary to age-related macular degeneration accounts for close to one-quarter of cases of legal blindness in the USA and the UK. Despite this notable disease burden, the pathophysiology of GA is complex and not fully understood, and there is currently no approved treatment to prevent or slow its progression. GA is heterogeneous in its appearance and extent, and underlying associated traits such as drusen and complement factor polymorphisms vary between patients and by ethnicity, posing a challenge for treatment development. The root cause of vision loss in GA is photoreceptor death; therefore, protecting photoreceptors from damage and delaying their degeneration are key to successful GA treatment. There are multiple neuroprotective pathways that may contribute to protecting photoreceptors from damage, and compounds that target these pathways include antioxidants, neurotrophic factors, and catalases. However, the efficacy of previously trialled neuroprotective therapies in GA, such as brimonidine, tandospirone, and NT-501, has been inconsistent; this may be due to their target of action, method of delivery, and/or suboptimal duration of action. Neurotrophic factors, or molecules involved in neuroprotective signalling cascades, may be ideal agents for further investigation for the treatment of GA. Future neuroprotective strategies in GA must focus on the development of agents with a long duration of action that can combat the progression of chronic damage in GA to provide clinically meaningful benefits for patients. (c) 2021 The Author(s) Published by S. Karger AG, Basel
C1 [Scholl, Hendrik P. N.] Inst Mol & Clin Ophthalmol, Basel, Switzerland.
   [Scholl, Hendrik P. N.] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Boyer, David] Retina Vitreous Associates Med Grp, Los Angeles, CA USA.
   [Giani, Andrea; Chong, Victor] Boehringer Ingelheim Int GmbH, Ingelheim, Germany.
C3 University of Basel; Retina Vitreous Associates Medical Group;
   Boehringer Ingelheim
RP Scholl, HPN (通讯作者)，Inst Mol & Clin Ophthalmol, Basel, Switzerland.; Scholl, HPN (通讯作者)，Univ Basel, Dept Ophthalmol, Basel, Switzerland.
EM hendrik.scholl@iob.ch
FU Boehringer Ingelheim
FX Funding was provided by Boehringer Ingelheim.
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NR 156
TC 3
Z9 3
U1 1
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD DEC
PY 2021
VL 64
IS 6
BP 888
EP 902
DI 10.1159/000517794
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZC4VR
UT WOS:000757520400002
PM 34153966
OA hybrid
DA 2022-11-30
ER

PT J
AU Grant, A
   Aubin, MJ
   Buhrmann, R
   Kergoat, MJ
   Freeman, EE
AF Grant, Alyssa
   Aubin, Marie-Josee
   Buhrmann, Ralf
   Kergoat, Marie-Jeanne
   Freeman, Ellen E.
TI Visual Impairment, Eye Disease, and the 3-year Incidence of Depressive
   Symptoms: The Canadian Longitudinal Study on Aging
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Visual impairment; age-related eye disease; cataract; CLSA; depression
ID VISION IMPAIRMENT; OLDER-ADULTS; ELDERLY POPULATION; ANXIETY; COHORT;
   AGE; GLAUCOMA; ONSET; PREDICTORS; CATARACT
AB Purpose Our goal was to explore the longitudinal association between vision-related variables and incident depressive symptoms in a community-dwelling sample of older adults and to examine whether sex, education, or hearing loss act as effect modifiers. Methods A 3-year prospective cohort study was performed using data from the Canadian Longitudinal Study on Aging consisting of 30,097 individuals aged 45-85 years. Visual acuity was evaluated with habitual distance correction using an illuminated Early Treatment of Diabetic Retinopathy Study chart. Visual impairment was defined as binocular presenting visual acuity worse than 20/40. Incident depressive symptoms was defined using a cut-off score of 10 or greater on the Center for Epidemiologic Studies Depression scale. Participants were asked if they had ever had a physician diagnosis of age-related macular degeneration (AMD), glaucoma, or cataract. Multivariable Poisson regression was used. Results Of 22,558 participants without depressive symptoms at baseline, 7.7% developed depressive symptoms within 3 years. Cataract was associated with incident depressive symptoms (relative risk = 1.20, 95% confidence interval 1.05, 1.37) after adjusting for age, sex, income, education, partner status, smoking, level of comorbidity, hearing loss, and province. Visual impairment, AMD, and glaucoma were not associated with incident depressive symptoms. No effect modification was detected. Conclusions Our longitudinal data confirm that the risk of depressive symptoms is higher in those who report ever having a cataract. Further research should confirm this and interventions should be considered.
C1 [Grant, Alyssa; Freeman, Ellen E.] Univ Ottawa, Sch Epidemiol & Publ Hlth, Ottawa, ON, Canada.
   [Aubin, Marie-Josee] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   [Aubin, Marie-Josee] Hop Maisonneuve Rosemt, Dept Ophthalmol, Ctr Univ Ophtalmol, Montreal, PQ, Canada.
   [Aubin, Marie-Josee] Univ Montreal, Dept Social & Prevent Med, ESPUM, Montreal, PQ, Canada.
   [Buhrmann, Ralf] Univ Ottawa, Dept Ophthalmol, Ottawa, ON, Canada.
   [Kergoat, Marie-Jeanne] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada.
   [Kergoat, Marie-Jeanne] Univ Montreal, Dept Med, Montreal, PQ, Canada.
   [Freeman, Ellen E.] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
C3 University of Ottawa; Universite de Montreal; Universite de Montreal;
   University of Ottawa; Universite de Montreal; Universite de Montreal;
   University of Ottawa; Ottawa Hospital Research Institute
RP Freeman, EE (通讯作者)，Univ Ottawa, Sch Epidemiol & Publ Hlth, Ottawa, ON, Canada.
EM efreeman@uottawa.ca
FU Canadian Institutes of Health Research [LSA 94473, ACD-170303]; Canada
   Foundation for Innovation
FX This work was supported by the Canadian Institutes of Health Research
   (Grants LSA 94473 and ACD-170303) and the Canada Foundation for
   Innovation.
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NR 44
TC 5
Z9 5
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 JAN 2
PY 2021
VL 28
IS 1
BP 77
EP 85
DI 10.1080/09286586.2020.1823425
EA SEP 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA PH8YM
UT WOS:000572521400001
PM 32970494
OA hybrid
DA 2022-11-30
ER

PT J
AU Furino, C
   Grassi, MO
   Bini, V
   Nacucchi, A
   Boscia, F
   Reibaldi, M
   Recchimurzo, N
   Alessio, G
AF Furino, Claudio
   Grassi, Maria Oliva
   Bini, Vito
   Nacucchi, Annalisa
   Boscia, Francesco
   Reibaldi, Michele
   Recchimurzo, Nicola
   Alessio, Giovanni
TI Intravitreal Injections in Arc Sterile Setting: Safety Profile after
   More Than 10,000 Treatments
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPERATING-ROOM; ENDOPHTHALMITIS
AB Purpose. To report the occurrence of endophthalmitis and other complications after intravitreal injections (IVIs) in the Arc Sterile setting. Methods. A retrospective study that enrolled all patients who underwent IVIs between November 2017 and March 2019, collecting data about the patient's gender and age, type of injected drug, diagnosis, other ocular pathologies, physician and possible occurrence of endophthalmitis, or other complications. Results. Ten thousand and eighty-three IVIs were performed during the study period, involving 2014 eyes of 1,670 patients with an average age of 71.37 +/- 11.63 years. The injected drugs included ranibizumab (54.6%), aflibercept (38.0%), dexamethasone (6.7%), pegaptanib (0.3%), bevacizumab (0.4%), and ocriplasmin (0.01%). The diagnosis included neovascular age-related macular degeneration (859), myopic choroidal neovascularization (154), diabetic macular edema (576), retinal vein occlusion (203), and miscellaneus diagnosis (222). No cases of endophthalmitis were recorded. One hundred and sixty-nine cases of ocular hypertension were detected, while the most frequent complication was subconjunctival hemorrhage, identified after 1,180 IVIs. The residents performed over 80% of IVIs, but there was no statistically significant difference in incidence of complications between the residents group and consultants group. Conclusions. Arc Sterile seems to be a safe setting in which IVIs can be carried out, regarding infective risk, and it is easy to set up compared to operation theatre and useful to improve intravitreal injections governance.
C1 [Furino, Claudio; Grassi, Maria Oliva; Bini, Vito; Nacucchi, Annalisa; Recchimurzo, Nicola; Alessio, Giovanni] Univ Bari, Eye Clin, Azienda Osped Univ Policlin, Bari, Italy.
   [Boscia, Francesco] Univ Sassari, Dept Ophthalmol, Eye Clin, Sassari, Italy.
   [Reibaldi, Michele] Univ Catania, Dept Ophthalmol, Eye Clin, Catania, Italy.
C3 Universita degli Studi di Bari Aldo Moro; University of Sassari;
   University of Catania
RP Furino, C (通讯作者)，Univ Bari, Eye Clin, Azienda Osped Univ Policlin, Bari, Italy.
EM claudiofurino@gmail.com; mariaolivagrassi@gmail.com; bin87v@gmail.com;
   annalisa.nacucchi@gmail.com; francescoboscia@hotmail.com;
   mreibaldi@libero.it; nicolarecchimurzo@hotmail.it;
   g.alessio@oftalmo.uniba.it
RI Boscia, Francesco/AAC-7729-2022; Reibaldi, Michele/AAL-1113-2021
OI Reibaldi, Michele/0000-0003-1368-6729
CR Abell RG, 2012, BRIT J OPHTHALMOL, V96, P1474, DOI 10.1136/bjophthalmol-2012-302030
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NR 17
TC 2
Z9 3
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD APR 15
PY 2020
VL 2020
AR 3680406
DI 10.1155/2020/3680406
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LJ7IZ
UT WOS:000530335800005
PM 32377417
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Fernandez-Vega, B
   Garcia, M
   Olivares, L
   Alvarez, L
   Gonzalez-Fernandez, A
   Artime, E
   Cueto, AFV
   Cobo, T
   Coca-Prados, M
   Vega, JA
   Gonzalez-Iglesias, H
AF Fernandez-Vega, Beatriz
   Garcia, Montserrat
   Olivares, Lorena
   Alvarez, Lydia
   Gonzalez-Fernandez, Adrian
   Artime, Enol
   Fernandez-Vega Cueto, Andres
   Cobo, Teresa
   Coca-Prados, Miguel
   Vega, Jose A.
   Gonzalez-Iglesias, Hector
TI The association study of lipid metabolism gene polymorphisms with AMD
   identifies a protective role for APOE-E2 allele in the wet form in a
   Northern Spanish population
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; genetic association; lipid metabolism
   genes; Northern Spanish population; single nucleotide polymorphism
ID APOLIPOPROTEIN-E GENE; POLYPOIDAL CHOROIDAL VASCULOPATHY; GENOME-WIDE
   ASSOCIATION; MACULAR DEGENERATION SUSCEPTIBILITY; AGE-RELATED
   MACULOPATHY; BODY-MASS INDEX; SCAVENGER RECEPTOR; BRUCHS MEMBRANE;
   CIGARETTE-SMOKING; EPSILON-4 ALLELE
AB Purpose To elucidate the potential role of eleven single nucleotide polymorphisms (SNPs) in the most relevant lipid metabolism genes in Northern Spanish patients with age-related macular degeneration (AMD). Methods A case-control study of 228 unrelated native Northern Spanish patients diagnosed with AMD (73 dry and 155 wet) and 95 healthy controls was performed. DNA was isolated from peripheral blood and genotyped for the SNPs APOE rs429358 and rs7412; CTEP rs3764261; LIPC rs10468017 and rs493258; LPL rs12678919; ABCA1 rs1883025; ABCA4 rs76157638, rs3112831 and rs1800555; and SCARB1 rs5888, using TaqMan probes. An additional association study of epsilon 2, epsilon 3 and epsilon 4 major isoforms of APOE gene with AMD has been carried out. Results The allele and genotype frequencies for each of the eleven sequence variants in the lipid metabolism genes did not show significant differences when comparing AMD cases and controls. Statistical analysis revealed that APOE-epsilon 2 carrier genotypes were less frequently observed in patients with wet AMD compared to controls (5.8% versus 13.7%, respectively: p = 3.28 x 10(-2); OR = 0.42, 95% CI: 0.19-0.95). The frequency of the allele T of rs10468017 (LIPC gene) was lower in dry AMD cases compared to controls (15.8 versus 27.9%, respectively: p = 8.4 x 10(-3) OR = 0.57, 95% CI: 0.33-0.98). Conclusions Our results suggest a protective role for APOE-epsilon 2 allele to wet AMD in the Northern Spanish population.
C1 [Fernandez-Vega, Beatriz; Garcia, Montserrat; Fernandez-Vega Cueto, Andres; Gonzalez-Iglesias, Hector] Inst Oftalmol Fernandez Vega, Avda Dres Fernandez Vega 34, Oviedo 33012, Spain.
   [Fernandez-Vega, Beatriz; Garcia, Montserrat; Olivares, Lorena; Alvarez, Lydia; Gonzalez-Fernandez, Adrian; Artime, Enol; Fernandez-Vega Cueto, Andres; Gonzalez-Iglesias, Hector] Univ Oviedo, Inst Univ Fernandez Vega, Fdn Invest Oftalmol, Oviedo, Spain.
   [Fernandez-Vega, Beatriz; Vega, Jose A.] Univ Oviedo, Dept Morfol & Biol Celular, Grp SINPOS, Oviedo, Spain.
   [Cobo, Teresa] Univ Oviedo, Dept Cirug & Especialidades Med Quirurg, Oviedo, Spain.
   [Coca-Prados, Miguel] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
   [Vega, Jose A.] Univ Autonoma Chile, Fac Ciencias Salud, Santiago, Chile.
C3 University of Oviedo; University of Oviedo; University of Oviedo; Yale
   University; Universidad Autonoma de Chile
RP Garcia, M (通讯作者)，Inst Oftalmol Fernandez Vega, Avda Dres Fernandez Vega 34, Oviedo 33012, Spain.
EM mgarciadiaz@fio.as; h.gonzalez@fio.as
RI Alvarez, Lydia/AAA-7736-2019; Vega, Jose A/AAG-3209-2021;
   Gonzalez-Iglesias, Hector/K-2447-2014; García Diaz,
   Montserrat/GXV-7857-2022; Gonzalez-Iglesias, Hector/AAB-5993-2019; COBO
   DIAZ, TERESA/GZG-8852-2022; Garcia, Montserrat/AAA-7781-2019; Artime,
   Enol/GVW-2359-2022
OI Gonzalez-Iglesias, Hector/0000-0001-5251-0967; Garcia,
   Montserrat/0000-0001-9983-546X; Alvarez Fernandez,
   Lydia/0000-0002-0604-7411
FU Agencia Estatal de Investigacion (Spain) [CTQ2016-79015-R]; FEDER;
   "Instituto de Desarrollo Economico del Principado de Asturias" (IDEPA)
   of Gobierno del Principado de Asturias; European FEDER
   [IDE/2018/000402]; Fundacion Rafael del Pino through "Catedra Rafael del
   Pino"
FX The Instituto Oftalmologico Fernandez-Vega and Fundacion de
   Investigacion Oftalmologica acknowledge financial support from the
   Fundacion Rafael del Pino (http://www.frdelpino.es) through the "Catedra
   Rafael del Pino". This work was supported by project CTQ2016-79015-R by
   Agencia Estatal de Investigacion (Spain) and FEDER, and the "Instituto
   de Desarrollo Economico del Principado de Asturias" (IDEPA) of Gobierno
   del Principado de Asturias and European FEDER co-financing, through the
   project IDE/2018/000402.
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NR 106
TC 6
Z9 8
U1 0
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAY
PY 2020
VL 98
IS 3
BP E282
EP E291
DI 10.1111/aos.14280
EA OCT 2019
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LH4QT
UT WOS:000492529700001
PM 31654486
DA 2022-11-30
ER

PT J
AU Alamri, A
   Biswas, L
   Watson, DG
   Shu, XH
AF Alamri, Abdulwahab
   Biswas, Lincoln
   Watson, David G.
   Shu, Xinhua
TI Deletion of TSPO Resulted in Change of Metabolomic Profile in Retinal
   Pigment Epithelial Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE TSPO; metabolites; retinal pigment epithelial cells; age related macular
   degeneration
ID LIPID-PEROXIDATION PRODUCTS; MACULAR DEGENERATION; TRANSLOCATOR PROTEIN;
   AGE; CHOLESTEROL; OXIDATION; ACID; RPE; PATHOPHYSIOLOGY; SUSCEPTIBILITY
AB Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD.
C1 [Alamri, Abdulwahab] Univ Hail, Dept Pharmacol, Coll Pharm Sci, Hail 55476, Saudi Arabia.
   [Alamri, Abdulwahab; Watson, David G.] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland.
   [Biswas, Lincoln; Shu, Xinhua] Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Shu, Xinhua] Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Lanark, Scotland.
C3 University Ha'il; University of Strathclyde; Glasgow Caledonian
   University; Glasgow Caledonian University
RP Watson, DG (通讯作者)，Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland.; Shu, XH (通讯作者)，Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.; Shu, XH (通讯作者)，Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Lanark, Scotland.
EM ph.whab@gmail.com; Lincoln.Biswas@gcu.ac.uk; d.g.watson@strath.ac.uk;
   Xinhua.Shu@gcu.ac.uk
RI Alamri, Abdulwahab/AAR-7735-2021
OI Alamri, Abdulwahab/0000-0001-8852-7517; Biswas,
   Lincoln/0000-0002-2288-341X; Watson, David/0000-0003-1094-7604; Shu,
   Xinhua/0000-0003-3760-3019
FU Rosetrees Trust [M160, M160-F1, M160-F2]; National Eye Research Centre
   [SAC037]; Saudi Government
FX This work was supported by the Rosetrees Trust (M160, M160-F1, M160-F2)
   and National Eye Research Centre (SAC037). We thank the Saudi Government
   for a studentship for A.A.
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NR 48
TC 9
Z9 9
U1 1
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAR 19
PY 2019
VL 20
IS 6
AR 1387
DI 10.3390/ijms20061387
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA HT1MB
UT WOS:000464326900021
PM 30893912
OA Green Submitted, gold, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Sheu, SJ
   Chen, JL
   Bee, YS
   Lin, SH
   Shu, CW
AF Sheu, Shwu-Jiuan
   Chen, Jiunn-Liang
   Bee, Youn-Shen
   Lin, Shi-Han
   Shu, Chih-Wen
TI ERBB2-modulated ATG4B and autophagic cell death in human ARPE19 during
   oxidative stress Shwu-Jiuan
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; ANTIOXIDANT RESPONSE; MECHANISMS; PHOSPHORYLATION;
   OVEREXPRESSION; ACTIVATION; DISEASE; MEMBER; DAMAGE; KEAP1
AB Age-related macular degeneration (AMD) is an ocular disease with retinal degeneration. Retinal pigment epithelium (RPE) degeneration is mainly caused by long-term oxidative stress. Kinase activity could be either protective or detrimental to cells during oxidative stress; however, few reports have described the role of kinases in oxidative stress. In this study, high-throughput screening of kinome siRNA library revealed that erb-b2 receptor tyrosine-protein kinase 2 (ERBB2) knockdown reduced reactive oxygen species (ROS) production in ARPE-19 cells during oxidative stress. Silencing ERBB2 caused an elevation in microtubule associated protein light chain C3-II (MAP1LC3B-II/I) conversion and sequesterone (SQSTM) 1 protein level. ERBB2 deprivation largely caused an increase in autophagy-regulating protease (ATG4B) expression, a protease that negatively recycles MAP1LC3-II at the fusion step between the autophagosome and lysosome, suggesting ERBB2 might modulate ATG4B for autophagy induction in oxidative stress-stimulated ARPE-19 cells. ERBB2 knockdown also caused an accumulation of nuclear factor erythroid 2-related factor 2 (NRF2) and enhanced its transcriptional activity. In addition, ERBB2 ablation or treatment with autophagy inhibitors reduced oxidative-induced cytotoxic effects in ARPE-19 cells. Furthermore, ERBB2 silencing had little or no additive effects in ATG5/7-deficient cells. Taken together, our results suggest that ERBB2 may play an important role in modulating autophagic RPE cell death during oxidative stress, and ERBB2 may be a potential target in AMD prevention.
C1 [Sheu, Shwu-Jiuan; Chen, Jiunn-Liang; Bee, Youn-Shen; Lin, Shi-Han] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Sheu, Shwu-Jiuan; Chen, Jiunn-Liang] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
   [Chen, Jiunn-Liang] Shu Zen Jr Coll Med & Management, Dept Optometry, Kaohsiung, Taiwan.
   [Bee, Youn-Shen] Yuh Ing Jr Coll Hlth Care & Management, Kaohsiung, Taiwan.
   [Bee, Youn-Shen] Natl Def Med Ctr, Taipei, Taiwan.
   [Shu, Chih-Wen] I Shou Univ, Sch Med Int Students, Kaohsiung, Taiwan.
   [Shu, Chih-Wen] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan.
C3 Kaohsiung Veterans General Hospital; National Yang Ming Chiao Tung
   University; National Defense Medical Center; I Shou University; National
   Sun Yat Sen University
RP Shu, CW (通讯作者)，I Shou Univ, Sch Med Int Students, Kaohsiung, Taiwan.; Shu, CW (通讯作者)，Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan.
EM vcwshu@gmail.com
RI Shu, Chih-Wen/AAE-9652-2019
OI Shu, Chih-Wen/0000-0002-7774-0002
FU Kaohsiung Veterans General Hospital [VGHKS105-094]; Ministry of Science
   and Technology [MOST 106-2314-B-075B-006, 107-2311-B-214-003]
FX This work was supported by Kaohsiung Veterans General Hospital
   (VGHKS105-094) and Ministry of Science and Technology (MOST
   106-2314-B-075B-006 and 107-2311-B-214-003).
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NR 43
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Z9 17
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 14
PY 2019
VL 14
IS 3
AR e0213932
DI 10.1371/journal.pone.0213932
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HO7YP
UT WOS:000461166300096
PM 30870514
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Weiss, M
   Sim, DA
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   Schumann, RG
   Liegl, R
   Kern, C
   Kreutzer, T
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   Priglinger, S
   Kortuem, KU
AF Weiss, Maximilian
   Sim, Dawn A.
   Herold, Tina
   Schumann, Ricarda G.
   Liegl, Raffael
   Kern, Christoph
   Kreutzer, Thomas
   Schiefelbein, Johannes
   Rottmann, Miriam
   Priglinger, Siegfried
   Kortuem, Karsten Ulrich
TI COMPLIANCE AND ADHERENCE OF PATIENTS WITH DIABETIC MACULAR EDEMA TO
   INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN DAILY
   PRACTICE
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE compliance; diabetic macular edema; adherence; anti-VEGF; intravitreal
   injection; age-related macular degeneration; continuity of therapy;
   database
ID PANRETINAL PHOTOCOAGULATION; GENDER-DIFFERENCES; RANIBIZUMAB;
   PREVALENCE; RETINOPATHY; OUTCOMES; CARE
AB Purpose: We assessed differences in compliance and adherence (lateness of patients, visual acuity, reasons for abstaining) between patients with diabetic macular edema (DME) and patients with age-related macular degeneration (AMD), both under anti-vascular endothelial growth factor therapy.
   Methods: We included 136 patients with DME (36% women, 65 years, 22 visits, 13.9 injections, and 29.9 months of follow-up) and 109 patients with AMD (59% women, 76 years, 20 visits, 14.7 injections, and 22.3 months of follow-up) (minimum follow-up of 12 months and at least 5 injections). We assessed missed appointments (lateness >14 days) and therapy break-offs (lateness >100 days). All delayed patients were called and interviewed for abstaining reasons.
   Results: Forty-six percent of patients with DME and 22% of patients with AMD had at least one break-off. Thirty-five percent of patients with DME and 50% of patients with AMD were always on schedule. In patients with DME, there was significant correlation (P = 0.017) between the number of break-offs and change of visual acuity. In 60% DME and 38% AMD of break-off cases, visual acuity was worse than the before break-off. The most common reason for abstaining was comorbidities (33% AMD and 20% DME).
   Conclusion: There are significant differences between patients with AMD and DME regarding compliance and adherence, which also affects outcome. Strategies to tie patients with DME to costly intravitreal therapy need to be developed to improve outcomes and efficacy.
C1 [Weiss, Maximilian; Herold, Tina; Schumann, Ricarda G.; Liegl, Raffael; Kern, Christoph; Kreutzer, Thomas; Schiefelbein, Johannes; Priglinger, Siegfried; Kortuem, Karsten Ulrich] Ludwig Maximilians Univ Munchen, Univ Eye Hosp Munich, Munich, Germany.
   [Sim, Dawn A.; Kortuem, Karsten Ulrich] Moorfields Eye Hosp, London, England.
   [Rottmann, Miriam] LMU, Univ Hosp Munich, Inst Med Informat Proc Biometry & Epidemiol IBE, MCR,Munich Tumour Ctr TZM, Munich, Germany.
C3 University of Munich; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of Munich
RP Kortuem, KU (通讯作者)，Univ Eye Hosp Munich, Mathildenstr 8, D-80333 Munich, Germany.
EM karsten.kortuem@med.uni-muenchen.de
FU Munich's Ludwig-Maximilian University
FX This study was conducted in Munich's University Eye Hospital and funded
   by Munich's Ludwig-Maximilian University.
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NR 43
TC 63
Z9 63
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD DEC
PY 2018
VL 38
IS 12
BP 2293
EP 2300
DI 10.1097/IAE.0000000000001892
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA HF1WG
UT WOS:000454008700008
PM 29068914
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chang, CC
   Huang, TY
   Chen, HY
   Huang, TC
   Lin, LC
   Chang, YJ
   Hsia, SM
AF Chang, Chih-Chao
   Huang, Tien-Yi
   Chen, Hsin-Yuan
   Huang, Tsui-Chin
   Lin, Li-Chun
   Chang, Yen-Jui
   Hsia, Shih-Min
TI Protective Effect of Melatonin against Oxidative Stress-Induced
   Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium
   Cells
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID MACULAR DEGENERATION; HYDROGEN-PEROXIDE; DNA-DAMAGE; RPE CELLS;
   PATHOGENESIS; ANTIOXIDANTS; ACTIVATION; EXPRESSION; PHYSIOLOGY; LEVEL
AB Age-related macular degeneration (AMD) affects the retinal macula and results in loss of vision, and AMD is the primary cause of blindness and severe visual impairment among elderly people worldwide. AMD is characterized by the accumulation of drusen in the Bruch's membrane and dysfunction of retinal pigment epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD remains unclear, and no effective treatment exists. Accumulating evidence indicates that oxidative stress plays a critical role in RPE cell degeneration and AMD. Melatonin is an antioxidant that scavenges free radicals, and it has anti-inflammatory, antitumor, and antiangiogenic effects. This study investigated the antioxidative, antiapoptotic, and autophagic effects of melatonin on oxidative damage to RPE cells. We used hydrogen peroxide (H2O2) to stimulate reactive oxygen species production to cause cell apoptosis in ARPE-19 cell lines. Our findings revealed that treatment with melatonin significantly inhibited H2O2-induced RPE cell damage, decreased the apoptotic rate, increased the mitochondrial membrane potential, and increased the autophagy effect. Furthermore, melatonin reduced the Bax/Bcl-2 ratio and the expression levels of the apoptosis-associated proteins cytochrome c and caspase 7. Additionally, melatonin upregulated the expression of the autophagy-related proteins LC3-II and Beclin-1 and downregulated the expression of p62. Thus, melatonin's effects on autophagy and apoptosis can protect against H2O2-induced oxidative damage in human RPE cells. Melatonin may have multiple protective effects on human RPE cells against H2O2-induced oxidative damage.
C1 [Chang, Chih-Chao; Huang, Tien-Yi; Chen, Hsin-Yuan; Hsia, Shih-Min] Taipei Med Univ, Sch Nutr & Hlth Sci, Taipei, Taiwan.
   [Huang, Tsui-Chin; Lin, Li-Chun] Taipei Med Univ, PhD Program Canc Biol & Drug Discovery, Coll Med Sci & Technol, Taipei, Taiwan.
   [Huang, Tsui-Chin; Lin, Li-Chun] Acad Sinica, Taipei, Taiwan.
   [Chang, Yen-Jui] Taipei City Hosp, Yangming Branch, Dept Ophthalmol, Taipei, Taiwan.
   [Chang, Yen-Jui] Univ Kang Ning, Dept Optometry, Taipei, Taiwan.
   [Chang, Yen-Jui] Univ Taipei, Dept Hlth & Welf, Coll City Management, Taipei, Taiwan.
   [Hsia, Shih-Min] Taipei Med Univ, Grad Inst Metab & Obes Sci, Taipei, Taiwan.
   [Hsia, Shih-Min] Taipei Med Univ, Sch Food & Safety, Taipei, Taiwan.
   [Hsia, Shih-Min] Taipei Med Univ Hosp, Nutr Res Ctr, Taipei, Taiwan.
C3 Taipei Medical University; Taipei Medical University; Academia Sinica -
   Taiwan; Taipei City Hospital; University of Taipei; Taipei Medical
   University; Taipei Medical University; Taipei Medical University; Taipei
   Medical University Hospital
RP Hsia, SM (通讯作者)，Taipei Med Univ, Sch Nutr & Hlth Sci, Taipei, Taiwan.; Hsia, SM (通讯作者)，Taipei Med Univ, Grad Inst Metab & Obes Sci, Taipei, Taiwan.; Hsia, SM (通讯作者)，Taipei Med Univ, Sch Food & Safety, Taipei, Taiwan.; Hsia, SM (通讯作者)，Taipei Med Univ Hosp, Nutr Res Ctr, Taipei, Taiwan.
EM bryanhsia@tmu.edu.tw
RI Hsia, Shih-Min/AAL-2026-2020
OI CHEN, HSIN YUAN/0000-0002-2411-426X; Hsia, Shih-Min/0000-0003-2888-2618
FU China Ministry of Science and Technology [MOST106-2320-B-038-064MY3,
   MOST103-2313-B-038-003-MY3, NSC102-2313-B-038-001]; Council of
   Agriculture, Taiwan, Republic of China [106AS-16.4.1-ST-a4]
FX This study was supported by the China Ministry of Science and Technology
   (Grant nos. MOST106-2320-B-038-064MY3, MOST103-2313-B-038-003-MY3, and
   NSC102-2313-B-038-001) and the Council of Agriculture, Taiwan, Republic
   of China (Grant no. 106AS-16.4.1-ST-a4).
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NR 59
TC 53
Z9 57
U1 3
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.
PY 2018
VL 2018
AR 9015765
DI 10.1155/2018/9015765
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA GQ7NU
UT WOS:000441930000001
PM 30174783
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Campbell, DJ
AF Campbell, Duncan J.
TI Long-term neprilysin inhibition - implications for ARNIs
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Review
ID NEUTRAL ENDOPEPTIDASE INHIBITION; ANGIOTENSIN-CONVERTING ENZYME;
   ATRIAL-NATRIURETIC-FACTOR; CEREBRAL AMYLOID ANGIOPATHY; MYOCARDIAL
   ISCHEMIA/REPERFUSION INJURY; INSULIN-DEGRADING ENZYME; CARCINOMA
   IN-VITRO; ALZHEIMERS-DISEASE; HEART-FAILURE; BLOOD-PRESSURE
AB Neprilysin has a major role in both the generation and degradation of bioactive peptides. LCZ696 (valsartan/sacubitril, Entresto), the first of the new ARNI (dual-acting angiotensin-receptor-neprilysin inhibitor) drug class, contains equimolar amounts of valsartan, an angiotensin-receptor blocker, and sacubitril, a prodrug for the neprilysin inhibitor LBQ657. LCZ696 reduced blood pressure more than valsartan alone in patients with hypertension. In the PARADIGM-HF study, LCZ696 was superior to the angiotensin-converting enzyme inhibitor enalapril for the treatment of heart failure with reduced ejection fraction, and LCZ696 was approved by the FDA for this purpose in 2015. This approval was the first for chronic neprilysin inhibition. The many peptides metabolized by neprilysin suggest many potential consequences of chronic neprilysin inhibitor therapy, both beneficial and adverse. Moreover, LBQ657 might inhibit enzymes other than neprilysin. Chronic neprilysin inhibition might have an effect on angio-oedema, bronchial reactivity, inflammation, and cancer, and might predispose to polyneuropathy. Additionally, inhibition of neprilysin metabolism of amyloid-beta peptides might have an effect on Alzheimer disease, age-related macular degeneration, and cerebral amyloid angiopathy. Much of the evidence for possible adverse consequences of chronic neprilysin inhibition comes from studies in animal models, and the relevance of this evidence to humans is unknown. This Review summarizes current knowledge of neprilysin function and possible consequences of chronic neprilysin inhibition that indicate a need for vigilance in the use of neprilysin inhibitor therapy.
C1 [Campbell, Duncan J.] St Vincents Inst Med Res, 41 Victoria Parade, Fitzroy, Vic 3065, Australia.
   [Campbell, Duncan J.] Univ Melbourne, Parkville, Vic 3010, Australia.
C3 St. Vincent's Institute of Medical Research; University of Melbourne
RP Campbell, DJ (通讯作者)，St Vincents Inst Med Res, 41 Victoria Parade, Fitzroy, Vic 3065, Australia.; Campbell, DJ (通讯作者)，Univ Melbourne, Parkville, Vic 3010, Australia.
EM dcampbell@svi.edu.au
FU Victorian Government's Operational Infrastructure Support Program
FX St Vincent's Institute of Medical Research is supported in part by the
   Victorian Government's Operational Infrastructure Support Program.
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NR 262
TC 86
Z9 89
U1 1
U2 22
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 1759-5002
EI 1759-5010
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD MAR
PY 2017
VL 14
IS 3
DI 10.1038/nrcardio.2016.200
PG 16
WC Cardiac & Cardiovascular Systems
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA EL0WJ
UT WOS:000394342200007
PM 27974807
DA 2022-11-30
ER

PT J
AU Li, P
   Sun, XF
   Ma, ZZ
   Liu, YN
   Jin, Y
   Ge, RM
   Hao, LM
   Ma, YL
   Han, S
   Sun, HJ
   Zhang, MZ
   Li, RZ
   Li, T
   Shen, L
AF Li, Peng
   Sun, Xiaofeng
   Ma, Zhizhong
   Liu, Yinan
   Jin, Ying
   Ge, Ruimin
   Hao, Limin
   Ma, Yanling
   Han, Shuo
   Sun, Haojie
   Zhang, Mingzhi
   Li, Ruizhi
   Li, Tao
   Shen, Li
TI Transcriptional Reactivation of OTX2, RX1 and SIX3 during Reprogramming
   Contributes to the Generation of RPE Cells from Human iPSCs
SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
LA English
DT Article
DE induced pluripotent stem cells; retinal pigment epithelium;
   reprogramming; epigenetic modification
ID PLURIPOTENT STEM-CELLS; DIRECT CONVERSION; PROGENITOR CELLS; DEFINED
   FACTORS; EPITHELIUM; FIBROBLASTS; DIFFERENTIATION; EXPRESSION; DISEASE;
   RETINA
AB Directed differentiation of human induced pluripotent stem cells (iPSCs) into retinal pigmented epithelium (RPE) holds great promise in cell replacement therapy for patients suffering from degenerative eye diseases, including age-related macular degeneration (AMD). In this study, we generated iPSCs from human dermal fibroblasts (HDFs) by electroporation with episomal plasmid vectors encoding OCT4, SOX2, KLF4, L-MYC together with p53 suppression. Intriguingly, cell reprogramming resulted in a metastable transcriptional activation and selective demethylation of neural and retinal specification -associated genes, such as OTX2, RXI and SIX3. In contrast, RPE progenitor genes were transcriptionally silent in HDFs and descendant iPSCs. Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RXI and SIX3 in HDFs and iPSCs. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified an OCT4- and two SOX2-binding sites located in the proximal promoter of OTX2. Histone acetylation and methylation on the local promoter also participated in the reactivation of OTX2. The transcriptional conversion of RXI and SIX3 genes partially attributed to DNA demethylation. Subsequently, iPSCs were induced into the RPE cells displaying the characteristics of polygonal shapes and pigments, and expressing typical RPE cell markers. Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RXI and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.
C1 [Li, Peng; Liu, Yinan; Han, Shuo; Sun, Haojie; Zhang, Mingzhi; Li, Ruizhi; Shen, Li] Peking Univ, Stem Cell Res Ctr, Dept Cell Biol, Sch Basic Med Sci, Beijing 100191, Peoples R China.
   [Sun, Xiaofeng] Hunan Univ Chinese Med, Dept Histol & Embryol, Inst Chinese Med, Sci Garden Dist Hanpu, Changsha 410208, Hunan, Peoples R China.
   [Ma, Zhizhong; Jin, Ying] Peking Univ, Hosp 3, Ctr Eye, Beijing 100191, Peoples R China.
   [Ge, Ruimin] Lund Univ, Univ Hosp, Lund Stem Cell Ctr, S-22242 Lund, Sweden.
   [Hao, Limin; Ma, Yanling] Beijing Cellonis Biotechnol Co Ltd, Zhongguancun Biomed Pk, Beijing 100191, Peoples R China.
   [Li, Tao] Zhejiang Normal Univ, Coll Chem & Life Sci, Dept Biol, Jinhua 321004, Zhejiang, Peoples R China.
C3 Peking University; Hunan University of Chinese Medicine; Peking
   University; Lund University; Skane University Hospital; Zhejiang Normal
   University
RP Shen, L (通讯作者)，Peking Univ, Stem Cell Res Ctr, Dept Cell Biol, Sch Basic Med Sci, Beijing 100191, Peoples R China.; Li, T (通讯作者)，Zhejiang Normal Univ, Coll Chem & Life Sci, Dept Biol, Jinhua 321004, Zhejiang, Peoples R China.
EM litao@zjnu.cn; shenli@bjmu.edu.cn
FU National Basic Research Program of China (973 program) [2011CB510200];
   National Natural Science Foundation of China [81303004, 31470082];
   Public Innovation Program [LY14C120001, 2014C37126]; Zhejiang Provincial
   Natural Science Foundation
FX This work was supported by Grant 2011CB510200 from the National Basic
   Research Program of China (973 program), the National Natural Science
   Foundation of China (81303004, 31470082), and Zhejiang Provincial
   Natural Science Foundation and Public Innovation Program (LY14C120001,
   2014C37126).
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NR 31
TC 10
Z9 10
U1 0
U2 11
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 5
BP 505
EP 517
DI 10.7150/ijbs.14212
PG 13
WC Biochemistry & Molecular Biology; Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics
GA DF9VD
UT WOS:000371709100003
PM 27019633
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Anderson, DMG
   Ablonczy, Z
   Koutalos, Y
   Spraggins, J
   Crouch, RK
   Caprioli, RM
   Schey, KL
AF Anderson, David M. G.
   Ablonczy, Zsolt
   Koutalos, Yiannis
   Spraggins, Jeffrey
   Crouch, Rosalie K.
   Caprioli, Richard M.
   Schey, Kevin L.
TI High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
DE Retina; Retinoids; Lipids; MALDI imaging
ID LASER-DESORPTION IONIZATION; LIPOFUSCIN FLUOROPHORE; RAT MODEL; A2E;
   ABCR; INSIGHTS; PHOTORECEPTORS; PHOSPHOLIPIDS; BIOSYNTHESIS; SUBLIMATION
AB Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism's surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 mu m retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4 (-/-) knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.
C1 [Anderson, David M. G.; Spraggins, Jeffrey; Caprioli, Richard M.; Schey, Kevin L.] Vanderbilt Univ, Sch Med, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA.
   [Anderson, David M. G.; Spraggins, Jeffrey; Caprioli, Richard M.; Schey, Kevin L.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA.
   [Ablonczy, Zsolt; Koutalos, Yiannis; Crouch, Rosalie K.] Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Caprioli, Richard M.] Vanderbilt Univ, Dept Chem Pharmacol & Med, Nashville, TN 37232 USA.
C3 Vanderbilt University; Vanderbilt University; Medical University of
   South Carolina; Vanderbilt University
RP Schey, KL (通讯作者)，Vanderbilt Univ, Sch Med, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA.
EM k.schey@vanderbilt.edu
OI Spraggins, Jeffrey/0000-0001-9198-5498
FU National Institute of General Medical Sciences [5 P41 GM103391-02];
   National Center for Research Resources [5P41RR031461-01]; NATIONAL
   CENTER FOR RESEARCH RESOURCES [P41RR031461] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P41GM103391]
   Funding Source: NIH RePORTER
FX This project was supported by a grant from the National Institute of
   General Medical Sciences (5 P41 GM103391-02), formerly the National
   Center for Research Resources (5P41RR031461-01). The authors thank Dr.
   G. H. Travis for providing the original breading pair of
   Abca4<SUP>-/-</SUP> mice.
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NR 58
TC 74
Z9 74
U1 1
U2 94
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1044-0305
EI 1879-1123
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD AUG
PY 2014
VL 25
IS 8
BP 1394
EP 1403
DI 10.1007/s13361-014-0883-2
PG 10
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
   Physical; Spectroscopy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA AM4FB
UT WOS:000339807400010
PM 24819461
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ma, HW
   Thapa, A
   Morris, L
   Redmond, TM
   Baehr, W
   Ding, XQ
AF Ma, Hongwei
   Thapa, Arjun
   Morris, Lynsie
   Redmond, T. Michael
   Baehr, Wolfgang
   Ding, Xi-Qin
TI Suppressing thyroid hormone signaling preserves cone photoreceptors in
   mouse models of retinal degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID CELL-DEATH; DEVELOPMENTAL EXPRESSION; RETINITIS-PIGMENTOSA; OPSIN
   EXPRESSION; DOWN-REGULATION; GENE DELIVERY; RECEPTOR; ACTIVATION;
   APOPTOSIS; METAMORPHOSIS
AB Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions.
C1 [Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Ding, Xi-Qin] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
   [Baehr, Wolfgang] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT 84132 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI); Utah System of Higher Education; University of Utah
RP Ding, XQ (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
EM xi-qin-ding@ouhsc.edu
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Center for Research Resources [P20RR017703]; National Eye
   Institute [P30EY12190, R01EY019490, R01EY08123]; Oklahoma Center for the
   Advancement of Science and Technology; NATIONAL CENTER FOR RESEARCH
   RESOURCES [P20RR017703] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY019490, P30EY014800, P30EY012190, ZIAEY000260,
   R01EY008123, P30EY021725] Funding Source: NIH RePORTER
FX We thank Drs. Cheryl Craft and Muna Naash for providing antibodies for
   M-opsin, cone arrestin, and S-opsin. This work was supported by grants
   from the National Center for Research Resources (P20RR017703), the
   National Eye Institute (P30EY12190, R01EY019490, and R01EY08123), and
   the Oklahoma Center for the Advancement of Science and Technology.
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NR 39
TC 35
Z9 36
U1 0
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3602
EP 3607
DI 10.1073/pnas.1317041111
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300087
PM 24550448
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Hulleman, JD
   Balch, WE
   Kelly, JW
AF Hulleman, John D.
   Balch, William E.
   Kelly, Jeffery W.
TI Translational attenuation differentially alters the fate of
   disease-associated fibulin proteins
SO FASEB JOURNAL
LA English
DT Article
DE eIF2 alpha; age-related macular degeneration; cutis laxa; malattia
   leventinese; proteostasis
ID ELASTIC FIBER HOMEOSTASIS; FACTOR 2-ALPHA KINASE; ENDOPLASMIC-RETICULUM;
   MACULAR DEGENERATION; ABERRANT ACCUMULATION; MALATTIA LEVENTINESE;
   VISUAL IMPAIRMENT; GENE-EXPRESSION; STRESS; MUTATION
AB Mutations in fibulin proteins that cause cellular secretion deficiencies are linked to a variety of diseases, ranging from retinopathies to cutis laxa (CL). One secretion-deficient fibulin mutant, R345W fibulin-3, causes the macular dystrophy malattia leventinese by increased endoplasmic reticulum retention and/or extracellular misfolding. Herein, we report that small-molecule activation of the PERK arm of the unfolded protein response partially rescues R345W secretion deficiencies through translational attenuation mediated by eIF2 alpha phosphorylation. Enhanced mutant fibulin-3 secretion can also be achieved by activation of a PERK-independent eIF2 alpha kinase through arsenite treatment and is independent of activating transcription factor 4 signaling and protein translation. However, this translational attenuation strategy was unsuccessful for enhancing the secretion deficiencies of fibulin-5 mutants associated with age-related macular degeneration or CL. While lowered growth temperature enhanced the secretion of mutants associated with CL (C217R and S227P), these effects were not mediated through translational attenuation. In stark contrast to the situation with fibulin-3, protein translation was required for efficient wild-type and mutant fibulin-5 secretion. These data suggest that alteration of specific cellular signaling pathways and proteostasis network components can differentially influence fibulin fate, a hypothesis that could be exploited as a therapy for fibulin-related diseases.-Hulleman, J. D., Balch, W. E., Kelly, J. W. Translational attenuation differentially alters the fate of disease-associated fibulin proteins. FASEB J. 26, 4548-4560 (2012). www.fasebj.org
C1 [Hulleman, John D.; Kelly, Jeffery W.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Hulleman, John D.; Balch, William E.; Kelly, Jeffery W.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Hulleman, John D.; Kelly, Jeffery W.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
   [Balch, William E.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute; Scripps Research
   Institute; Scripps Research Institute
RP Hulleman, JD (通讯作者)，Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM hulleman@scripps.edu; jkelly@scripps.edu
RI Hulleman, John D./AAV-8242-2020
OI Hulleman, John/0000-0001-8149-656X
FU Lita Annenberg Hazen Foundation; Skaggs Institute for Chemical Biology;
   Scripps Translational Science Institute [UL1 RR025774]; U.S. National
   Institutes of Health [AG018917]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [UL1RR025774] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK051870] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE ON AGING [R01AG018917] Funding Source:
   NIH RePORTER
FX The authors thank R. Luke Wiseman for his insightful review of the
   manuscript. This work was supported by the Lita Annenberg Hazen
   Foundation, the Skaggs Institute for Chemical Biology, grant UL1
   RR025774 from the Scripps Translational Science Institute (J. W. K.),
   and grant AG018917 from the U.S. National Institutes of Health (J. W.
   K.).
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NR 59
TC 19
Z9 20
U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD NOV
PY 2012
VL 26
IS 11
BP 4548
EP 4560
DI 10.1096/fj.11-202861
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 030MG
UT WOS:000310574200017
PM 22872678
OA Green Published
DA 2022-11-30
ER

PT J
AU Wang, YJ
   Shen, DF
   Wang, VM
   Yu, CR
   Wang, RX
   Tuo, JS
   Chan, CC
AF Wang, Yujuan
   Shen, Defen
   Wang, Vinson M.
   Yu, Cheng-Rong
   Wang, Ren-Xi
   Tuo, Jingsheng
   Chan, Chi-Chao
TI Enhanced apoptosis in retinal pigment epithelium under inflammatory
   stimuli and oxidative stress
SO APOPTOSIS
LA English
DT Article
DE Apoptosis; Retinal pigment epithelium (RPE); Inflammation; Oxidative
   stress; Fas ligand (FasL); Decoy receptor 3 (DcR3)
ID PHOTORECEPTOR CELL-DEATH; MACULAR DEGENERATION; FAS LIGAND;
   GENE-EXPRESSION; DNA-DAMAGE; MODELS; MICE; RPE; AMPLIFICATION;
   ACTIVATION
AB Age-related macular degeneration (AMD) is a neurodegenerative disease that causes irreversible central vision loss in the elderly. Retinal pigment epithelium (RPE) has been found to be a key component in AMD pathogenesis. The Ccl2 (-/-) /Cx3cr1 (-/-) (DKO) mouse on Crb1 (rd8) background is created as an AMD model, developing AMD-like retinal lesions. Our study aimed to examine RPE apoptosis in DKO mouse and human ARPE-19 cell line. DKO RPE expressed higher apoptotic proteins when compared with age-matched wild type (WT) RPE in physiological conditions. Apoptosis of primary cultured mouse RPE was evaluated under stimulation with lipopolysaccharide for inflammatory stimulation and 2,3,7,8-tetrachlorodibenzo-p-dioxin or H2O2 for oxidative stress. Compared with WT RPE, DKO RPE was more susceptible to Fas ligand (FasL)-mediated apoptosis under both inflammatory and oxidative stress, with less cell viability and higher expression of apoptotic transcripts and proteins. Decreased cell viability was also observed in ARPE-19 cells under each stimulus. Furthermore, we also investigated the anti-apoptotic effects of decoy receptor 3 (DcR3), a decoy receptor for FasL, on ARPE-19 cells under inflammatory and oxidative stress. DcR3 pre-incubated ARPE-19 cells showed decreased apoptosis, with increased cell viability and decreased expression of apoptotic transcripts and proteins under the stimuli. On the contrary, knockdown of DcR3 in ARPE-19 cells showed totally opposite results. Our study demonstrates that FasL-mediated RPE apoptosis may play a pivotal role in AMD pathogenesis.
C1 [Wang, Yujuan; Shen, Defen; Wang, Vinson M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China.
   [Yu, Cheng-Rong; Wang, Ren-Xi] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Sun Yat Sen University; National Institutes of Health (NIH) -
   USA; NIH National Eye Institute (NEI)
RP Chan, CC (通讯作者)，NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI Wang, Renxi/AAM-1326-2020; wang, yujuan/C-8428-2016
OI Wang, Renxi/0000-0003-4130-3334; Yu, Cheng-Rong/0000-0001-7246-0362;
   Tuo, Jingsheng/0000-0002-1372-7810
FU National Eye Institute Intramural Research Program; NATIONAL EYE
   INSTITUTE [ZIAEY000222, ZICEY000461, ZICEY000457, ZIAEY000418] Funding
   Source: NIH RePORTER
FX The National Eye Institute Intramural Research Program supported the
   study.
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NR 45
TC 35
Z9 38
U1 0
U2 16
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
J9 APOPTOSIS
JI Apoptosis
PD NOV
PY 2012
VL 17
IS 11
BP 1144
EP 1155
DI 10.1007/s10495-012-0750-1
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 016VL
UT WOS:000309547700002
PM 22911474
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lyzogubov, VV
   Tytarenko, RG
   Bora, NS
   Bora, PS
AF Lyzogubov, Valeriy V.
   Tytarenko, Ruslana G.
   Bora, Nalini S.
   Bora, Puran S.
TI Inhibitory role of adiponectin peptide I on rat choroidal
   neovascularization
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Adiponectin; Adiponectin receptors; VEGF; Angiogenesis; Macular
   degeneration; Neovascularization
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CELL-PROLIFERATION;
   FACTOR THERAPY; MOUSE MODEL; EXPRESSION; RECEPTORS; COMPLEMENT; PROTEIN;
   ADIPOCYTES
AB Age-related macular degeneration (AMD) is a leading cause of central blindness in the elderly population. The wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied the effects of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density were investigated by microscopy. Immunohistochemical staining (IHC) for von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 folds less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.] Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, Little Rock, AR 72205 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences
RP Bora, PS (通讯作者)，Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, 4301 W Markham, Little Rock, AR 72205 USA.
EM pbora@uams.edu
OI Bora, Puran/0000-0003-4781-1217
FU Pat and Willard Walker Eye Research Center, Jones Eye Institute;
   Arkansas Master Tobacco Settlement and Arkansas Biosciences Institute,
   University of Arkansas for Medical Sciences, Little Rock, AR; NIH [EY
   014623, EY 016205]; NATIONAL EYE INSTITUTE [R01EY016205, R01EY014623]
   Funding Source: NIH RePORTER
FX This study was supported in part by NIH grants EY 014623 and EY 016205,
   Pat and Willard Walker Eye Research Center, Jones Eye Institute and
   Arkansas Master Tobacco Settlement and Arkansas Biosciences Institute,
   University of Arkansas for Medical Sciences, Little Rock, AR.
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NR 38
TC 11
Z9 15
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD AUG
PY 2012
VL 1823
IS 8
BP 1264
EP 1272
DI 10.1016/j.bbamcr.2012.05.017
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 976YY
UT WOS:000306624500005
PM 22633972
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Gnana-Prakasam, JP
   Martin, PM
   Smith, SB
   Ganapathy, V
AF Gnana-Prakasam, Jaya P.
   Martin, Pamela M.
   Smith, Sylvia B.
   Ganapathy, Vadivel
TI Expression and Function of Iron-Regulatory Proteins in Retina
SO IUBMB LIFE
LA English
DT Review
DE hemochromatosis; age-related macular degeneration; iron toxicity;
   oxidative damage; retina
ID TRANSFERRIN RECEPTOR 2; HEPCIDIN EXPRESSION; MACULAR DEGENERATION;
   RESPONSIVE ELEMENT; PIGMENT EPITHELIUM; OXIDATIVE STRESS; CLASS-I; HFE;
   FERRITIN; HEMOCHROMATOSIS
AB Iron is essential for cell survival and function; yet excess iron is toxic to cells. Therefore, the cellular and whole-body levels of iron are regulated exquisitely. At least a dozen proteins participate in the regulation of iron homeostasis. Hemochromatosis, a genetic disorder of iron overload, is caused by mutations in at least five genes, namely HFE, hemojuvelin, Transferrin receptor 2, ferroportin, and hepcidin. Retina is separated from systemic circulation by inner and outer blood-retinal barriers; therefore it is widely believed that this tissue is immune to changes in systemic circulation. Even though hemochromatosis is associated with iron overload and dysfunction of a variety of systemic organs, little is known on the effects of this disease on the retina. Recent studies have shown that all five genes that are associated with hemochromatosis are expressed in the retina in a cell type-specific manner. The retinal pigment epithelium, which forms the outer blood-retinal barrier, expresses all of these five genes. It is therefore clearly evident that iron homeostasis in the retina is maintained locally by active participation of various iron-regulatory proteins. Excess iron is detrimental to the retina as evidenced from human studies and from mouse models of iron overload. Retinal iron homeostasis is disrupted in various clinical conditions such as hemochromatosis, aceruloplasminemia, age-related macular degeneration, and bacterial and viral infections. (C) 2010 IUBMB IUBMB Life, 62(5): 363-370, 2010
C1 [Gnana-Prakasam, Jaya P.; Martin, Pamela M.; Ganapathy, Vadivel] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
   [Smith, Sylvia B.] Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University
RP Ganapathy, V (通讯作者)，Med Coll Georgia, Dept Biochem & Mol Biol, 1120,15th St,CB2317, Augusta, GA 30912 USA.
EM vganapat@mail.mcg.edu
OI Gnana-Prakasam, Jaya P/0000-0003-2259-9213
FU National Institutes of Health [EY019672]; NATIONAL EYE INSTITUTE
   [R01EY019672] Funding Source: NIH RePORTER
FX This work was supported, in part, by the National Institutes of Health
   grant EY019672.
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NR 68
TC 37
Z9 37
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1521-6543
EI 1521-6551
J9 IUBMB LIFE
JI IUBMB Life
PD MAY
PY 2010
VL 62
IS 5
BP 363
EP 370
DI 10.1002/iub.326
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 595HT
UT WOS:000277602000006
PM 20408179
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Lindblad, AS
   Lloyd, PC
   Clemons, TE
   Gensler, GR
   Ferris, FL
   Klein, ML
   Armstrong, JR
AF Lindblad, Anne S.
   Lloyd, Patricia C.
   Clemons, Traci E.
   Gensler, Gary R.
   Ferris, Frederick L., III
   Klein, Michael L.
   Armstrong, Jane R.
CA AREDS Res Grp
TI Change in Area of Geographic Atrophy in the Age-Related Eye Disease
   Study AREDS Report Number 26
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID FUNDUS AUTOFLUORESCENCE; MACULAR DEGENERATION; NATURAL-HISTORY;
   PROGRESSION; ENLARGEMENT
AB Objective: To characterize progression of geographic atrophy (GA) associated with age-related macular degeneration in AREDS as measured by digitized fundus photographs.
   Methods: Fundus photographs from 181 of 4757 AREDS participants with a GA area of at least 0.5 disc areas at baseline or from participants who developed bilateral GA during follow-up were scanned, digitized, and evaluated longitudinally. Geographic atrophy area was determined using planimetry. Rates of progression from noncentral to central GA and of vision loss following development of central GA included the entire AREDS cohort.
   Results: Median initial lesion size was 4.3 mm(2). Average change in digital area of GA from baseline was 2.03 mm(2) standard error of the mean, 0.24 mm(2)) at 1 year, 3.78 mm(2) (0.24 mm(2)) at 2 years, 5.93 mm(2) (0.34 mm(2)) at 3 years, and 1.78 mm(2) (0.086 mm(2)) per year overall. Median time to developing central GA after any GA diagnosis was 2.5 years (95% confidence interval, 2.0-3.0). Average visual acuity decreased by 3.7 letters at first documentation of central GA, and by 22 letters at year 5.
   Conclusions: Growth of GA area can be reliably measured using standard fundus photographs that are digitized and subsequently graded at a reading center. Development of GA is associated with subsequent further growth of GA, development of central GA, and loss in central vision.
C1 [Lindblad, Anne S.] EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA.
   [Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA.
   [Klein, Michael L.] Casey Eye Inst, Portland, OR USA.
   [Armstrong, Jane R.] Fundus Photograph Reading Ctr, Madison, WI USA.
C3 Emmes Corporation; National Institutes of Health (NIH) - USA; NIH
   National Eye Institute (NEI)
RP Lindblad, AS (通讯作者)，EMMES Corp, AREDS Coordinating Ctr, 401 N Washington St,Ste 700, Rockville, MD 20850 USA.
EM aredspub@emmes.com
RI SanGiovanni, John Paul/AAU-3895-2020; Mitchell, Paul/P-1498-2014
OI Sunness, Janet/0000-0001-8823-0780; Klein, Ronald/0000-0002-4428-6237;
   Ferris, Frederick/0000-0002-4933-0639
FU National Eye Institute; National Institutes of Health; Department of
   Health and Human Services, Bethesda, Maryland; NATIONAL EYE INSTITUTE
   [R01EY011309] Funding Source: NIH RePORTER
FX This report was supported by contracts from the National Eye Institute,
   National Institutes of Health, Department of Health and Human Services,
   Bethesda, Maryland.
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NR 23
TC 156
Z9 156
U1 0
U2 14
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD SEP
PY 2009
VL 127
IS 9
BP 1168
EP 1174
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 493VD
UT WOS:000269765500008
PM 19752426
OA Bronze, Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Van Der Veen, RLP
   Ostendorf, S
   Hendrikse, F
   Berendschot, TTJM
AF Van Der Veen, Rob L. P.
   Ostendorf, Saskia
   Hendrikse, Fred
   Berendschot, Tos T. J. M.
TI Macular pigment optical density relates to foveal thickness
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Macula; Optical coherence tomography; Pigment; Retina; Thickness
ID COHERENCE TOMOGRAPHY; SPATIAL-DISTRIBUTION; PRIMATE RETINAS;
   DEGENERATION; LUTEIN; LOCALIZATION; INSTRUMENT; ZEAXANTHIN
AB PURPOSE. Macular pigment is composed of 2 dietary carotenoids, lutein and zeaxanthin, and is mainly present at the nerve fiber layers and ganglion cell layers of the retina, with peak concentrations in the fovea. It is thought to function as a blue-light filter and antioxidant, and therefore protect the retina from damaging influences that are thought to play a role in the pathogenesis of age-related macular degeneration. This study was performed to investigate the suggested positive relationship between foveal macular pigment optical density (MPOD) and foveal retinal thickness.
   METHODS. We determined MPOD and foveal thickness in the right eyes of 40 healthy Caucasian subjects (5 men, 35 women) recruited at the University of Maastricht, The Netherlands. Their mean age was 24.4+/-8.7 years. MPOD was determined by using a novel method of heterochromatic flicker photometry (HFP), where subjects have to detect flicker instead of conventionally minimizing a present flicker motion. Foveal thickness parameters were obtained using optical coherence tomography (OCT 3).
   RESULTS. We found a positively significant correlation between MPOD and central foveal thickness (r=0.359, p=0.027). In addition, we found a negatively significant correlation between foveal thickness and foveal width (r=-0.558, p<0.001).
   CONCLUSIONS. Our data confirm the previously suggested positively significant correlation between MPOD and central foveal thickness. The observed negative relationship between foveal thickness and foveal width may be explained by eccentric scans on the OCT. (Eur J Ophthalmol 2009; 19: 836-41)
C1 [Van Der Veen, Rob L. P.; Ostendorf, Saskia; Hendrikse, Fred; Berendschot, Tos T. J. M.] Univ Hosp Maastricht, Dept Ophthalmol, NL-6202 AZ Maastricht, Netherlands.
C3 Maastricht University; Maastricht University Medical Centre (MUMC)
RP Van Der Veen, RLP (通讯作者)，Univ Hosp Maastricht, Dept Ophthalmol, POB 5800, NL-6202 AZ Maastricht, Netherlands.
EM r.vander.veen@mumc.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X
FU Cognis Deutschland, GmbH Co. Kg.
FX Supported by a grant from Cognis Deutschland, GmbH & Co. Kg.
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NR 23
TC 27
Z9 27
U1 0
U2 9
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP-OCT
PY 2009
VL 19
IS 5
BP 836
EP 841
DI 10.1177/112067210901900524
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 520LF
UT WOS:000271845100023
PM 19787606
DA 2022-11-30
ER

PT J
AU Singh, SR
   Grossniklaus, HE
   Kang, SJ
   Edelhauser, HF
   Ambati, BK
   Kompella, UB
AF Singh, S. R.
   Grossniklaus, H. E.
   Kang, S. J.
   Edelhauser, H. F.
   Ambati, B. K.
   Kompella, U. B.
TI Intravenous transferrin, RGD peptide and dual-targeted nanoparticles
   enhance anti-VEGF intraceptor gene delivery to laser-induced CNV
SO GENE THERAPY
LA English
DT Article
DE nanoparticles; targeted delivery; gene delivery; choroidal
   neovascularization; anti-VEGF intraceptor
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; EXPERIMENTAL
   CHOROIDAL NEOVASCULARIZATION; ADENOASSOCIATED VIRUS VECTOR; MACULAR
   DEGENERATION; DRUG-DELIVERY; IN-VIVO; POLYSTYRENE MICROSPHERES;
   PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY
AB Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine-glycine-aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model. Gene Therapy (2009) 16, 645-659; doi: 10.1038/gt.2008.185; published online 5 February 2009
C1 [Kompella, U. B.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
   [Singh, S. R.; Kompella, U. B.] Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE USA.
   [Grossniklaus, H. E.; Kang, S. J.; Edelhauser, H. F.] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA.
   [Ambati, B. K.] Moran Eye Inst, Salt Lake City, UT USA.
C3 Children's Hospital Colorado; University of Colorado System; University
   of Colorado Anschutz Medical Campus; University of Nebraska System;
   University of Nebraska Medical Center; Emory University
RP Kompella, UB (通讯作者)，Univ Colorado Denver, Dept Pharmaceut Sci, 12700 E 19th Ave, Aurora, CO 80045 USA.
EM uday.kompella@uchsc.edu
RI Kompella, U/C-9789-2011
FU NIH [R24 EY017045, R21 EY017360, 5RO1EY017182]; NATIONAL EYE INSTITUTE
   [R01EY017182, R24EY017045, R21EY017360, P30EY006360] Funding Source: NIH
   RePORTER
FX This work was primarily supported by NIH grants R24 EY017045 and R21
   EY017360. Creation of VEGF intraceptor plasmid by Dr BK Ambati was
   supported by NIH grant 5RO1EY017182. We thank James R Talaska and Janice
   Taylor of the Confocal Laser Scanning Microscopy Core Facility at
   University of Nebraska Medical Center, which is supported by the
   Nebraska Research Initiative, for providing assistance with confocal
   microscopy. We thank Karen Dulany and Maureen Harman of the Eppley
   Histology Core Laboratory at University of Nebraska Medical Center, for
   their help in cryosectioning of the tissues. We also thank Dr
   Chandrasekar Durairaj and Rajendra S Kadam for their assistance during
   the study. We especially thank Dr Weiqing Gao, Emory Eye Center, Emory
   university, Atlanta, GA, for assistance with choroidal flatmounts.
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NR 61
TC 146
Z9 156
U1 3
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD MAY
PY 2009
VL 16
IS 5
BP 645
EP 659
DI 10.1038/gt.2008.185
PG 15
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Research & Experimental Medicine
GA 445CB
UT WOS:000266026100009
PM 19194480
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Fridley, BL
AF Fridley, Brooke L.
TI Bayesian Variable and Model Selection Methods for Genetic Association
   Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE Bayesian model averaging; Bayesian variable selection; candidate gene;
   Markov chain Monte Carlo; reversible jump MCMC; stochastic search
   variable selection
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E;
   HAPLOTYPE RECONSTRUCTION; MACULAR DEGENERATION; STRANDED-RNA;
   SUSCEPTIBILITY; POLYMORPHISM; RECOGNITION; DISEASE
AB Variable selection is growing in importance with the advent of high throughput genotyping methods requiring analysis of hundreds to thousands of single nucleotide polymorphisms (SNPs) and the increased interest in using these genetic studies to better understand common, complex diseases. Up to now, the standard approach has been to analyze the genotypes for each SNP individually to look for an association with a disease. Alternatively, combinations of SNPs or haplotypes are analyzed for association. Another added complication in studying complex diseases or phenotypes is that genetic risk for the disease is often due to multiple SNPs in various locations on the chromosome with small individual effects that may have a collectively large effect on the phenotype. Hence, multi-locus SNP models, as opposed to single SNP models, may better capture the true underlying genotypic-phenotypic relationship. Thus, innovative methods for determining which SNPs to include in the model are needed. The goal of this article is to describe several methods currently available for variable and model selection using Bayesian approaches and to illustrate their application for genetic association studies using both real and simulated candidate gene data for a complex disease. In particular, Bayesian model averaging (BMA), stochastic search variable selection (SSVS), and Bayesian variable selection (BVS) using a reversible jump Markov chain Monte Carlo (MCMC) for candidate gene association studies are illustrated using a Study of age-related macular degeneration (AMD) and simulated data. Genet. Epidemiol. 33:27-37, 2009. (C) 2008 Wiley-Liss, Inc.
C1 Mayo Clin, Div Biostat, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA.
C3 Mayo Clinic
RP Fridley, BL (通讯作者)，Mayo Clin, Div Biostat, Coll Med, Dept Hlth Sci Res, Harwick 766,200 1st St SW, Rochester, MN 55905 USA.
EM fridley.brooke@mayo.edu
RI Fridley, Brooke L/D-8315-2015
OI Fridley, Brooke L/0000-0001-7739-7956
FU NATIONAL EYE INSTITUTE [R01EY014467] Funding Source: NIH RePORTER
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NR 81
TC 33
Z9 34
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2009
VL 33
IS 1
BP 27
EP 37
DI 10.1002/gepi.20353
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 391PJ
UT WOS:000262244900004
PM 18618760
DA 2022-11-30
ER

PT J
AU Cheung, SH
   Legge, GE
AF Cheung, SH
   Legge, GE
TI Functional and cortical adaptations to central vision loss
SO VISUAL NEUROSCIENCE
LA English
DT Review
DE age-related macular degeneration; preferred retinal locus; primary
   visual cortex; retinotopic reorganization; brain plasticity
ID HUMAN VISUAL-CORTEX; PREFERRED RETINAL LOCI; SCANNING LASER
   OPHTHALMOSCOPE; QUALITY-OF-LIFE; SUPERIOR COLLICULUS; BEHAVING MONKEY;
   STRIATE CORTEX; RETINOTOPIC ORGANIZATION; MACULAR DEGENERATION;
   ECCENTRIC FIXATION
AB Age-related macular degeneration (AMD), affecting the retina, afflicts one out of ten people aged 80 years or older in the United States. AMD often results in vision loss to the central 15-20 deg of the visual field (i.e. central scotoma), and frequently afflicts both eyes. In most cases, when the central scotoma includes the fovea, patients will adopt an eccentric preferred retinal locus (PRL) for fixation. The onset of a central scotoma results in the absence of retinal inputs to corresponding regions of retinotopically mapped visual cortex. Animal studies have shown evidence for reorganization in adult mammals for such cortical areas following experimentally induced central scotomata. However, it is still unknown whether reorganization occurs in primary visual cortex (VI) of AMD patients. Nor is it known whether the adoption of a PRL corresponds to changes to the retinotopic mapping of V1. Two recent advances hold out the promise for addressing these issues and for contributing to the rehabilitation of AMD patients: improved methods for assessing visual function across the fields of AMD patients using the scanning laser ophthalmoscope, and the advent of brain-imaging methods for studying retinotopic mapping in humans. For the most part, specialists in these two areas come from different disciplines and communities, with few opportunities to interact. The purpose of this review is to summarize key findings on both the clinical and neuroscience issues related to questions about visual adaptation in AMD patients.
C1 Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Cheung, SH (通讯作者)，Univ Minnesota, Dept Psychol, 75 E River Rd, Minneapolis, MN 55455 USA.
EM sing@umn.edu
OI Legge, Gordon/0000-0002-3742-1680
FU NEI NIH HHS [EY02934, R01 EY002934] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R37EY002934, R01EY002934] Funding Source: NIH RePORTER
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NR 131
TC 123
Z9 128
U1 0
U2 25
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 MAR-APR
PY 2005
VL 22
IS 2
BP 187
EP 201
DI 10.1017/S0952523805222071
PG 15
WC Neurosciences; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology
GA 933ZJ
UT WOS:000229671300007
PM 15935111
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Dutt, K
   Sanford, G
   Harris-Hooker, S
   Brako, L
   Kumar, R
   Sroufe, A
   Melhado, C
AF Dutt, K
   Sanford, G
   Harris-Hooker, S
   Brako, L
   Kumar, R
   Sroufe, A
   Melhado, C
TI Three-dimensional model of angiogenesis: Coculture of human retinal
   cells with bovine aortic endothelial cells in the NASA bioreactor
SO TISSUE ENGINEERING
LA English
DT Article
ID FIBROBLAST GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; PROLIFERATIVE
   DIABETIC-RETINOPATHY; CAPILLARY-LIKE STRUCTURES; BLOOD-BRAIN-BARRIER;
   IN-VITRO; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION;
   GLIOMA-CELLS; INVITRO
AB Ocular angiogenesis is the leading cause of blindness and is associated with diabetic retinopathy and age-related macular degeneration. We describe, in this report, our preliminary studies using a horizontally rotating bioreactor (HRB), developed by the National Aeronautics and Space Administration (NASA), to explore growth and differentiation-associated events in the early phase of ocular angiogenesis. Human retinal (HRet) cells and bovine endothelial cells (ECs) were cocultured on laminin-coated Cytodex-3 microcarrier beads in an HRB; for 1-36 days. Endothelial cells grown alone in the HRB remained cuboidal and were well differentiated. However, when HRet cells were cocultured with ECs, cordlike structures formed as early as 18-36 h and were positive for von Willebrand factor. In addition to the formation of cords and capillary-like structures, ECs showed the beginning of sprouts. The HRB seems not only to promote accelerated capillary formation, but also to enhance differentiation of retinal precursor cells. This leads to the formation of rosette-like structures (which may be aggregates of photoreceptors that were positive for rhodopsin). Upregulation of vascular endothelial growth factor and basic fibroblast growth factor was seen in retinal cells grown in the HRB as compared with monolayers and could be one of the factors responsible for accelerated capillary formation. Hence, the HRB promotes three-dimensional assembly and differentiation, possibly through promoting cell-to-cell interaction and/or secretion of growth and differentiation factors.
C1 Morehouse Sch Med, Dept Pathol, Atlanta, GA 30310 USA.
   Morehouse Sch Med, Dept Biochem, Atlanta, GA 30310 USA.
   Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
   Morehouse Sch Med, Dept Anat, Atlanta, GA 30310 USA.
C3 Morehouse School of Medicine; Morehouse School of Medicine; Morehouse
   School of Medicine; Morehouse School of Medicine
RP Dutt, K (通讯作者)，Morehouse Sch Med, Dept Pathol, Atlanta, GA 30310 USA.
EM duttk@msm.edu
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NR 71
TC 20
Z9 22
U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2152-4947
J9 TISSUE ENG
JI Tissue Eng.
PD OCT
PY 2003
VL 9
IS 5
BP 893
EP 908
DI 10.1089/107632703322495547
PG 16
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 735MD
UT WOS:000186118400004
PM 14633374
DA 2022-11-30
ER

PT J
AU Shaikh, S
   Shaikh, N
   Chun, SH
   Spin, JM
   Blumenkranz, MS
   Marmor, MF
AF Shaikh, S
   Shaikh, N
   Chun, SH
   Spin, JM
   Blumenkranz, MS
   Marmor, MF
TI Retinal evaluation of patients on chronic amiodarone therapy
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE amiodarone; atrial fibrillation; cardiology; congestive heart failure;
   electroretinopathy; full-field electroretinogram; macular degeneration;
   multifocal electroretinogram; standard electroretinogram; toxicity;
   ventricular arrhythmias
ID OPTIC NEUROPATHY; ELECTRORETINOGRAPHY; AGE
AB Purpose: To determine whether retinal electrophysiologic changes can be detected and correlated with funduscopic findings in patients with the long-term use of amiodarone.
   Methods: Eleven patients ranging in age from 52 to 67 years were recruited from the Stanford University Medical Center Department of Cardiology for ophthalmologic examination. Patients had received amiodarone at various dosages ranging from 100 to 800 mg daily for at least 15 months. Clinical indications for the use of amiodarone included atrial fibrillation, ventricular arrhythmias, and congestive heart failure. All patients underwent retinal electrophysiology studies (full-field and multifocal electroretinograms) in addition to a complete ophthalmologic examination and fluorescein angiography.
   Results: No patients were found to have significant vision loss. Funduscopic examination and fluorescein angiography showed mild age-related changes in four patients, three of whom had nonspecific foveal pigmentary alterations. Multifocal and full-field electroretinograms were mostly unremarkable, and the mildly subnormal findings in a few patients showed no consistent pattern to suggest a toxic cause. Dosage, duration of amiodarone exposure, patient age, and underlying cardiac disease did not appear to correlate with these findings.
   Conclusions: No significant adverse retinal funduscopic changes or electrophysiologic effects could be correlated with amiodarone exposure in this small series of patients. Routine electrophysiologic and funduscopic screening of patients receiving amiodarone does not seem warranted, although future prospective controlled studies may be required to exclude the possibility of progressive abnormalities in patients with preexisting age-related macular degeneration.
C1 Stanford Univ, Med Ctr, Dept Ophthalmol, Stanford, CA 94305 USA.
   Stanford Univ, Med Ctr, Dept Cardiol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Shaikh, S (通讯作者)，Associated Retinal Consultants, Royal Oak, MI 48073 USA.
OI Spin, Joshua/0000-0002-4256-9161
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NR 25
TC 8
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUN
PY 2003
VL 23
IS 3
BP 354
EP 359
DI 10.1097/00006982-200306000-00011
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 697FY
UT WOS:000183932600011
PM 12824836
DA 2022-11-30
ER

PT J
AU Sghaier, R
   Perus, M
   Cornebise, C
   Courtaut, F
   Scagliarini, A
   Olmiere, C
   Aires, V
   Hermetet, F
   Delmas, D
AF Sghaier, Randa
   Perus, Maude
   Cornebise, Clarisse
   Courtaut, Flavie
   Scagliarini, Alessandra
   Olmiere, Celine
   Aires, Virginie
   Hermetet, Francois
   Delmas, Dominique
TI Resvega, a Nutraceutical Preparation, Affects NF kappa B Pathway and
   Prolongs the Anti-VEGF Effect of Bevacizumab in Undifferentiated ARPE-19
   Retina Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE AMD; angiogenesis; ocular diseases; anti-VEGF; Resvega; omega-3 fatty
   acids; resveratrol
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION AMD; ANGIOGENESIS;
   KINASE; NEOVASCULARIZATION; GAMMA
AB Age-related macular degeneration (AMD) is an irreversible chronic degenerative pathology that affects the retina. Despite therapeutic advances thanks to the use of anti-vascular endothelial growth factor (VEGF) agents, resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, called Resvega (R), was able to disrupt VEGF-A secretion in human ARPE-19 retina cells. We found that Resvega (R) inhibits VEGF-A secretion through decreases in both the PI3K-AKT-mTOR and NF kappa B signaling pathways. In NF kappa B signaling pathways, Resvega (R) inhibits the phosphorylation of the inhibitor of NF kappa B, I kappa B, which can bind NF kappa B dimers and sequester them in the cytoplasm. Thus, the NF kappa B subunits cannot migrate to the nucleus where they normally bind and stimulate the transcription of target genes such as VEGF-A. The I kappa B kinase complex (IKK) is also affected by Resvega (R) since the nutraceutical formulation decreases both IKK alpha and IKK beta subunits and the IKK gamma subunit which is required for the stimulation of IKK. Very interestingly, we highlight that Resvega (R) could prolong the anti-angiogenic effect of Avastin (R), which is an anti-VEGF agent typically used in clinical practice. Our results suggest that Resvega (R) may have potential interest as nutritional supplementation against AMD.
C1 [Sghaier, Randa; Perus, Maude; Cornebise, Clarisse; Courtaut, Flavie; Scagliarini, Alessandra; Aires, Virginie; Hermetet, Francois; Delmas, Dominique] Univ Bourgogne, UFR Sci Sante, F-21000 Dijon, France.
   [Sghaier, Randa; Perus, Maude; Cornebise, Clarisse; Courtaut, Flavie; Scagliarini, Alessandra; Aires, Virginie; Hermetet, Francois; Delmas, Dominique] INSERM, Bioact Mol & Hlth Res Grp, Canc & Adapt Immune Response Team, Res Ctr U1231, F-21000 Dijon, France.
   [Olmiere, Celine] Lab Thea, 12 Rue Louis Bleriot, F-63000 Clermont Ferrand, France.
   [Delmas, Dominique] Ctr Anticancereux Georges Francois Leclerc Ctr, F-21000 Dijon, France.
C3 Universite de Bourgogne; Universite de Franche-Comte; Institut Agro;
   AgroSup Dijon; Institut National de la Sante et de la Recherche Medicale
   (Inserm); Universite de Bourgogne
RP Delmas, D (通讯作者)，Univ Bourgogne, UFR Sci Sante, F-21000 Dijon, France.; Delmas, D (通讯作者)，INSERM, Bioact Mol & Hlth Res Grp, Canc & Adapt Immune Response Team, Res Ctr U1231, F-21000 Dijon, France.; Delmas, D (通讯作者)，Ctr Anticancereux Georges Francois Leclerc Ctr, F-21000 Dijon, France.
EM dominique.delmas@u-bourgogne.fr
FU ANRT [Nffi 2016/0003, nffi 2021/1248,]; French Government
   [ANR-11-LABX-0021]; Conseil Regional Bourgogne, FrancheComte (PARI
   grant); FEDER (European Funding for Regional Economic Development)
FX This work was supported by grants from the ANRT Nffi 2016/0003, ANRT
   Nffi nffi 2021/1248, by a French Government grant managed by the French
   National Research Agency under the program "Investissements d'Avenir",
   reference ANR-11-LABX-0021, the Conseil Regional Bourgogne, FrancheComte
   (PARI grant) and the FEDER (European Funding for Regional Economic
   Development).
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NR 44
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD OCT
PY 2022
VL 23
IS 19
AR 11704
DI 10.3390/ijms231911704
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 5H6IT
UT WOS:000867781600001
PM 36233006
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, BX
   Vachali, P
   Chang, FY
   Gorusupudi, A
   Arunkumar, R
   Shi, LJ
   Rognon, GT
   Frederick, JM
   Bernstein, PS
AF Li, Binxing
   Vachali, Preejith
   Chang, Fu-Yen
   Gorusupudi, Aruna
   Arunkumar, Ranganathan
   Shi, Linjia
   Rognon, Gregory T.
   Frederick, Jeanne M.
   Bernstein, Paul S.
TI HDL is the primary transporter for carotenoids from liver to retinal
   pigment epithelium in transgenic ApoA-I-/-/Bco2(-/-) mice
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE HDL; Carotenoids; ApoA-I; Zeaxanthin; 8-Carotene; Age-related macular
   degeneration
ID MACULAR PIGMENT; SCAVENGER RECEPTOR; BETA-CAROTENE; VITAMIN-A; LUTEIN;
   ZEAXANTHIN; METABOLISM; DENSITY; PLASMA; IDENTIFICATION
AB Supplementation with antioxidant carotenoids is a therapeutic strategy to protect against age-related macular degeneration (AMD); however, the transport mechanism of carotenoids from the liver to the retina is still not fully understood. Here, we investigate if HDL serves as the primary transporter for the macular carotenoids. ApoA-I, the key apolipoprotein of HDL, was genetically deleted from BCO2 knockout (Bco2(-/-)) mice, a macular pigment mouse model capable of accumulating carotenoids in the retina. We then conducted a feeding experiment with a mixed carotenoid chow (lutein:zeaxanthin:8-carotene = 1:1:1) for one month. HPLC data demonstrated that the total carotenoids were increased in the livers but decreased in the serum, retinal pigment epithelium (RPE)/choroids, and retinas of ApoA-I-/- /Bco2(-/-) mice compared to Bco2(-/-)- mice. In detail, ApoA-I deficiency caused a significant increase of 8-carotene but not lutein and zeaxanthin in the liver, decreased all three carotenoids in the serum, blocked the majority of zeaxanthin and 8-carotene transport to the RPE/choroid, and dramatically reduced 8-carotene and zeaxanthin but not lutein in the retina. Furthermore, surface plasmon resonance spectroscopy (SPR) data showed that the binding affinity between ApoA-I and 8-carotene >> zeaxanthin > lutein. Our results show that carotenoids are transported from the liver to the eye mainly by HDL, and ApoA-I may be involved in the selective delivery of macular carotenoids to the RPE.
C1 [Li, Binxing; Vachali, Preejith; Chang, Fu-Yen; Gorusupudi, Aruna; Arunkumar, Ranganathan; Shi, Linjia; Rognon, Gregory T.; Frederick, Jeanne M.; Bernstein, Paul S.] Univ Utah, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Sch Med, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
C3 Utah System of Higher Education; University of Utah
RP Bernstein, PS (通讯作者)，Univ Utah, Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
OI Rognon, Gregory/0000-0003-2659-3521; Chang, Fu-Yen/0000-0003-0921-9773;
   Bernstein, Paul/0000-0002-4228-7666
FU BrightFocus Foundation [M201606]; NIH [EY-11600, EY-14800]; Research to
   Prevent Blindness
FX Acknowledgments This work was supported by the BrightFocus Foundation
   M201606, by NIH grants EY-11600, EY-14800, and by unrestricted
   departmental funds from Research to Prevent Blindness.
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NR 36
TC 2
Z9 2
U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0003-9861
EI 1096-0384
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD FEB 15
PY 2022
VL 716
AR 109111
DI 10.1016/j.abb.2021.109111
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA ZR8BK
UT WOS:000768003000003
PM 34942193
DA 2022-11-30
ER

PT J
AU Li, S
   Jiang, YZ
   Xing, XA
   Lin, RH
   Li, Q
   Zhou, WS
   Qiu, W
   Zheng, WH
AF Li, Shuai
   Jiang, Yizhou
   Xing, Xingan
   Lin, Ruohong
   Li, Qin
   Zhou, Wenshu
   Qiu, Wei
   Zheng, Wenhua
TI Protective Mechanism of Berberine on Human Retinal Pigment Epithelial
   Cells against Apoptosis Induced by Hydrogen Peroxide via the Stimulation
   of Autophagy
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID INDUCED OXIDATIVE DAMAGE; PC12 CELLS; ACTIVATION; DEGENERATION; STRESS;
   MTOR; AMPK; RPE; PHOSPHORYLATION; NEUROPROTECTION
AB Age-related macular degeneration (AMD) is a major cause of severe and irreversible vision loss with limited effective therapies. Diminished autophagy and increased oxidative damage caused by ROS in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of AMD, and strategies aimed at enhancing autophagy are likely to protect these cells from oxidative damage. We have previously shown that berberine (BBR), an isoquinoline alkaloid isolated from Chinese herbs, was able to protect human RPE cells from H2O2-induced oxidative damage through AMPK activation. However, the precise mechanisms behind this protective effect remain unclear. Given the essential role of AMPK in autophagy activation, we postulated that BBR may confer protection against H2O2-induced oxidative damage by stimulating AMPK-dependent autophagy. Our results showed that BBR was able to induce autophagy in D407 cells, whereas autophagy inhibitor PIKIII or silencing of LC3B blocked the protective effect of BBR. Further analysis showed that BBR activated the AMPK/mTOR/ULK1 signaling pathways and that both pharmacological and genetic inhibitions of the AMPK pathway abolished the autophagy-stimulating effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrate that BBR is able to stimulate autophagy in D407 cells via the activation of AMPK pathway and that its protective effect against H2O2-induced oxidative damage relies on its autophagy-modulatory effect. Our findings also provide evidence to support the potential application of BBR in preventing and treating AMD.
C1 [Li, Shuai; Jiang, Yizhou; Xing, Xingan; Lin, Ruohong; Zhou, Wenshu; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Macau, Peoples R China.
   [Li, Shuai; Jiang, Yizhou; Xing, Xingan; Lin, Ruohong; Zhou, Wenshu; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Macau, Peoples R China.
   [Li, Qin] Hangzhou Med Coll, Hangzhou, Peoples R China.
   [Qiu, Wei] Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Dept, Guangzhou, Peoples R China.
C3 University of Macau; University of Macau; Hangzhou Medical College; Sun
   Yat Sen University
RP Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Macau, Peoples R China.; Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Macau, Peoples R China.; Qiu, W (通讯作者)，Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Dept, Guangzhou, Peoples R China.
EM qiuwei120@vip.163.com; wenhuazheng@um.edu.mo
RI Li, Shuai/ABC-5377-2021
FU National Natural Science Foundation of China [31771128]; Science and
   Technology Development Fund, Macau SAR [0127/2019/A3, 0044/2019/AGJ,
   0113/2018/A3]; University of Macau [MYRG2018-00134-FHS]
FX This research was supported by the National Natural Science Foundation
   of China (File No. 31771128), The Science and Technology Development
   Fund, Macau SAR (File Nos. 0127/2019/A3, 0044/2019/AGJ, and
   0113/2018/A3), and University of Macau (File No. MYRG2018-00134-FHS). We
   thank Dr. Marta Silva for a revision of the manuscript.
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NR 44
TC 4
Z9 4
U1 2
U2 8
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD AUG 13
PY 2021
VL 2021
AR 7654143
DI 10.1155/2021/7654143
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA UD9UU
UT WOS:000687546300004
PM 34422209
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Terheyden, JH
   Behning, C
   Luning, A
   Wintergerst, L
   Basile, PG
   Tavares, D
   Melicio, BA
   Leal, S
   Weissgerber, G
   Luhmann, UFO
   Crabb, DP
   Tufail, A
   Hoyng, C
   Berger, M
   Schmid, M
   Silva, R
   Martinho, CV
   Cunha-Vaz, J
   Holz, FG
   Finger, RP
AF Terheyden, Jan Henrik
   Behning, Charlotte
   Luening, Anna
   Wintergerst, Ludmila
   Basile, Pier G.
   Tavares, Diana
   Melicio, Beatriz A.
   Leal, Sergio
   Weissgerber, George
   Luhmann, Ulrich F. O.
   Crabb, David P.
   Tufail, Adnan
   Hoyng, Carel
   Berger, Moritz
   Schmid, Matthias
   Silva, Rufino
   Martinho, Cecilia V.
   Cunha-Vaz, Jose
   Holz, Frank G.
   Finger, Robert P.
CA MACUSTAR Consortium
TI Challenges, facilitators and barriers to screening study participants in
   early disease stages-experience from the MACUSTAR study
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Early disease stages; Age-related macular degeneration; Cohort study;
   Screening; Recruitment
ID RANDOMIZED CONTROLLED-TRIALS; MACULAR DEGENERATION; CLINICAL-TRIALS;
   RECRUITMENT STRATEGIES; POPULATIONS; PREVALENCE; RETENTION; RATES
AB Background: Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD).
   Methods: Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data. Only participants with intermediate AMD were considered.
   Results: A total of 766 individual screenings within 87 weeks were available for analysis. The mean screening rate was 0.6 +/- 0.9 screenings per week among all sites. The participation at investigator teleconferences (relative risk increase 1.466, 95% CI [1.018-2.112]), public holidays (relative risk decrease 0.466, 95% CI [0367-0.591]) and reaching 80% of the site's recruitment target (relative risk decrease 0.699, 95% CI [0.367-0.591]) were associated wIth the number of screenings at an individual site level.
   Conclusions: Careful planning of screening activities is necessary when recruiting early disease stages in multicentre observational or low-interventional studies. Conducting teleconferences with local investigators can increase screening rates. When planning recruitment, seasonal and saturation effects at clinical site level need to be taken into account.
C1 [Terheyden, Jan Henrik; Luening, Anna; Wintergerst, Ludmila; Holz, Frank G.; Finger, Robert P.] Univ Hosp Bonn, Dept Ophthalmol, Bonn, Germany.
   [Behning, Charlotte; Berger, Moritz; Schmid, Matthias] Univ Hosp Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany.
   [Basile, Pier G.; Tavares, Diana; Melicio, Beatriz A.; Silva, Rufino; Martinho, Cecilia V.; Cunha-Vaz, Jose] Assoc Innovat & Biomed Res Light & Image, Coimbra, Portugal.
   [Leal, Sergio] Bayer AG, Berlin, Germany.
   [Weissgerber, George] Novartis Pharma AG, Basel, Switzerland.
   [Luhmann, Ulrich F. O.] Roche Innovat Ctr, Roche Pharmaceut Res & Early Dev, Translat Med Ophthalmol, Roche Pharma Res & Early Dev, Basel, Switzerland.
   [Crabb, David P.] City Univ London, Div Optometry & Visual Sci, Sch Hlth Sci, London, England.
   [Tufail, Adnan] Moorfields Eye Hosp, London, England.
   [Hoyng, Carel] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands.
   [Silva, Rufino] Univ Coimbra, Coimbra Inst Clin & Biomed Res iCBR, Fac Med, Coimbra, Portugal.
   [Silva, Rufino] Ctr Hosp & Univ Coimbra CHUC, Dept Ophthalmol, Coimbra, Portugal.
C3 University of Bonn; University of Bonn; Universidade de Coimbra; Bayer
   AG; Novartis; Roche Holding; City University London; University of
   London; University College London; Moorfields Eye Hospital NHS
   Foundation Trust; Radboud University Nijmegen; Universidade de Coimbra;
   Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra
   (CHUC)
RP Terheyden, JH; Finger, RP (通讯作者)，Univ Hosp Bonn, Dept Ophthalmol, Bonn, Germany.
EM Jan.Terheyden@ukbonn.de; Robert.Finger@ukbonn.de
RI Berger, Moritz/ABD-2233-2021
OI Silva, Rufino/0000-0001-8676-0833; Brazier, John/0000-0001-8645-4780;
   Schmid, Matthias/0000-0002-0788-0317; Hogg, Ruth/0000-0001-9413-2669;
   Behning, Charlotte/0000-0002-9310-3804; Tufail,
   Adnan/0000-0001-6131-7640; Terheyden, Jan Henrik/0000-0002-0174-4066;
   Cunha-Vaz, Jose/0000-0002-0947-9850
FU Innovative Medicines Initiative 2 Joint Undertaking [116076]; European
   Union; EFPIA; Projekt DEAL
FX This project has received funding from the Innovative Medicines
   Initiative 2 Joint Undertaking under grant agreement No 116076.This
   Joint Undertaking receives support from the European Union's Horizon
   2020 research and innovation programme and EFPIA. Open Access funding
   enabled and organized by Projekt DEAL.
CR Barton K, 2015, MUMIN
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NR 30
TC 1
Z9 1
U1 0
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD MAR 17
PY 2021
VL 21
IS 1
AR 54
DI 10.1186/s12874-021-01243-8
PG 8
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA QY4KP
UT WOS:000630010700001
PM 33731014
OA gold, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Mansour, AM
   Charbaji, A
   Farah, ME
   Mansour, HA
   Chhablani, J
AF Mansour, Ahmad M.
   Charbaji, Abdulrazzak
   Farah, Michel Eid
   Mansour, Hana A.
   Chhablani, Jay
TI Long-term outcome of treat and extend intravitreal ziv-aflibercept
   therapy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Macula; Retina; Treatment other
ID DIABETIC MACULAR EDEMA; DEGENERATION; BEVACIZUMAB; RANIBIZUMAB; REGIMEN
AB Aim To assess the 30-month outcome of treat and extend (TAE) intravitreal ziv-aflibercept therapy in eyes with macular diseases. Methods In this prospective study, consecutive subjects received intravitreal 0.05 mL ziv-aflibercept (1.25 mg) injections for various macular diseases. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) and central macular thickness (CMT) on spectral domain optical coherence tomography. Paired comparison was done using Wilcoxon signed-rank test calculator. Results Fifty-three eyes of 48 subjects (33 naive eyes) received intravitreal ziv-aflibercept and were followed between 12 and 30 months following TAE included neovascular age-related macular degeneration (nAMD) (35 eyes) and diabetic macular oedema (DMO) (18 eyes). In eyes with nAMD, CMT decreased by 107.8 mu m at the 30-month follow-up (p=0.012) with BCVA gain of 0.52 (p=0.001). In eyes with DMO, CMT decreased by 224.3 mu m at the 30-month follow-up (p=0.027) with BCVA gain of 0.46 (p=0.042). Combining all disease categories, the mean number of injections was 9.2 at month 12, 2.5 between 12 and 18 months, 1.6 between 18 and 24 months and 1.0 between 24 and 30 months. Conclusions Using TAE regimen, intravitreal ziv-aflibercept appeared efficacious at managing retinal disease through month 30 using the TAE regimen.
C1 [Mansour, Ahmad M.; Mansour, Hana A.] Amer Univ Beirut, Dept Ophthalmol, Beirut, Lebanon.
   [Mansour, Ahmad M.] Rafic Hariri Univ Hosp, Dept Ophthalmol, Beirut, Lebanon.
   [Charbaji, Abdulrazzak] Lebanese Amer Univ, Dept Stat & Res Methodol, Beirut, Lebanon.
   [Charbaji, Abdulrazzak] Lebanese Univ, Dept Stat & Res Methodol, Beirut, Lebanon.
   [Farah, Michel Eid] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil.
   [Chhablani, Jay] LV Prasad Eye Inst, Smt Kanuri Santhamma Ctr Vitreoretinal Dis, Hyderabad, Andhra Pradesh, India.
C3 American University of Beirut; American University of Beirut; Lebanese
   American University; Lebanese University; Universidade Federal de Sao
   Paulo (UNIFESP); L. V. Prasad Eye Institute
RP Chhablani, J (通讯作者)，LV Prasad Eye Inst, Smt Kanuri Santhamma Ctr Vitreoretinal Dis, Hyderabad, Andhra Pradesh, India.
EM jay.chhablani@gmail.com
RI Farah, Michel Eid E/F-3285-2012
OI Farah, Michel Eid E/0000-0001-5951-0193; Chhablani,
   Jay/0000-0003-1772-3558
CR Abedi F, 2014, RETINA-J RET VIT DIS, V34, P1531, DOI 10.1097/IAE.0000000000000134
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NR 22
TC 4
Z9 4
U1 1
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2019
VL 103
IS 7
BP 938
EP 941
DI 10.1136/bjophthalmol-2018-312593
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IF4HJ
UT WOS:000473042100013
PM 30072436
DA 2022-11-30
ER

PT J
AU Tom, J
   Chang, D
   Wuster, A
   Mukhyala, K
   Cuenco, K
   Cowgill, A
   Vogel, J
   Reeder, J
   Yaspan, B
   Hunkapiller, J
   Brauer, M
   Behrens, T
   Forrest, W
   Bhangale, T
AF Tom, Jennifer
   Chang, Diana
   Wuster, Art
   Mukhyala, Kiran
   Cuenco, Karen
   Cowgill, Amy
   Vogel, Jan
   Reeder, Jens
   Yaspan, Brian
   Hunkapiller, Julie
   Brauer, Matt
   Behrens, Tim
   Forrest, William
   Bhangale, Tushar
TI Enabling genome-wide association testing with multiple diseases and no
   healthy controls
SO GENE
LA English
DT Article
DE Bayesian; Genetics; Reverse regression; Spike and slab prior
ID MACULAR DEGENERATION; RARE VARIANTS; HIGH-RISK; CFI GENE; GWAS
AB Motivation: While large-scale whole genome sequencing is feasible the high costs compel investigators to focus on disease subjects. As a result large sequencing datasets of samples with different diseases are often readily available, but not healthy controls to contrast them with. While it is possible to perform an association study using only diseases, the associations could be driven by a disease acting as a control and not the focal disease.
   Methods: We developed a genotype-on-phenotype reverse regression with a Bayesian spike and slab prior to enable association testing in datasets with multiple diseases. This method, referred to as revreg, flagged associations (both common and rare) that were driven by diseases that were not of primary interest.
   Results: Based on simulations, revreg had 80% power to detect an odds ratio of 1.74 for common variants (3500 samples total) and 3.73 for rare variants (14,000 samples total), with minimal type I error. For common variants, we tested this method on 3657 whole genome sequenced samples aimed at discovering variants associated with disease risk of Chronic Obstructive Pulmonary Disease using three other diseases as controls. We demonstrated detection of six highly significant associations likely due to Age-Related Macular Degeneration. In an exome dataset of 8836 samples aimed at characterizing rare variants associated with disease risk of Asthma, using five other diseases as controls, we detected and removed genic regions due to AMD (C3, CFH, CFHR5, CFI, and DNMT3A) and RA (KRTAP13-4).
C1 [Tom, Jennifer; Mukhyala, Kiran; Cowgill, Amy; Vogel, Jan; Reeder, Jens; Brauer, Matt; Forrest, William; Bhangale, Tushar] Genentech Inc, Bioinformat & Computat Biol Dept, 1 DNA Way, San Francisco, CA 94080 USA.
   [Chang, Diana; Wuster, Art; Cuenco, Karen; Yaspan, Brian; Hunkapiller, Julie] Genentech Inc, Human Genet Dept, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding; Genentech
RP Tom, J; Bhangale, T (通讯作者)，Genentech Inc, Bioinformat & Computat Biol Dept, 1 DNA Way, San Francisco, CA 94080 USA.
EM tom.jennifer@gene.com
OI Yaspan, Brian/0000-0002-3787-2510; Wuster, Arthur/0000-0003-4162-5931
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NR 35
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
EI 1879-0038
J9 GENE
JI Gene
PD FEB 5
PY 2019
VL 684
BP 118
EP 123
DI 10.1016/j.gene.2018.10.047
PG 6
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA HI1TM
UT WOS:000456227900014
PM 30366082
OA hybrid
DA 2022-11-30
ER

PT J
AU Zhang, Y
   Zhang, DD
   Wei, W
   Shen, BQ
   Wang, YY
   Zhang, YJ
   Zhang, YD
   Ji, J
   Sun, H
   Luo, M
   Gu, P
AF Zhang, Yi
   Zhang, Dandan
   Wei, Wei
   Shen, Bingqiao
   Wang, Yuyao
   Zhang, Yingjie
   Zhang, Yidan
   Ji, Jing
   Sun, Hao
   Luo, Min
   Gu, Ping
TI Effects of RPE-conditioned medium on the differentiation of hADSCs into
   RPE cells, and their proliferation and migration
SO EXPERIMENTAL AND THERAPEUTIC MEDICINE
LA English
DT Article
DE mesenchymal stromal cells; differentiation; proliferation; migration
ID RETINAL-PIGMENT EPITHELIUM; MESENCHYMAL STEM-CELLS; BONE-MARROW; STROMAL
   CELLS; TRANSPLANTATION; MODEL
AB Age-related macular degeneration (AMD) is associated with the dysfunction and death of the retinal pigment epithelium (RPE). Recently, there has been increasing interest in stem cell-derived RPE cells for cell replacement therapies, such as those for AMD. The present study investigated whether RPE-conditioned medium (RPECM) could promote the differentiation of human adipose tissue-derived mesenchymal stromal cells (hADSCs) into RPE cells, and enhance the proliferation and migration of these cells. Reverse-transcription quantitative polymerase chain reaction analysis demonstrated that RPECM induced hADSCs to differentiate into cells expressing RPE markers, including retinoid isomerohydrolase (RPE65), cytokeratin (CK8) and Bestrophin, which were identified to be significantly upregulated by similar to 10-fold, 3.5-fold and 2.4-fold, respectively, compared with the control group [hADSCs cultured in ADSC-conditioned medium (ADSCCM)]. The immunocytochemistry and western blot analysis results demonstrated that the protein levels of RPE65, CK8 and Bestrophin were significantly increased in RPECM-treated hADSCs. In addition, Cell Counting Kit-8 analysis demonstrated that RPECM promoted the proliferation of induced cells. RPECM also increased the expression level of the cell proliferative marker Ki-67. Furthermore, to evaluate the migration potential, cell migration assays were performed. These assays demonstrated that following RPECM treatment hADSCs migrated more quickly compared with the control group. The results of the present study suggest that RPECM induces hADSCs to differentiate into RPE cells with higher proliferative and migratory potentials, which may aid in applications for hADSCs in RPE regenerative therapy.
C1 [Zhang, Yi; Zhang, Dandan; Wei, Wei; Shen, Bingqiao; Wang, Yuyao; Zhang, Yingjie; Zhang, Yidan; Ji, Jing; Sun, Hao; Luo, Min; Gu, Ping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Ophthalmol, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China.
C3 Shanghai Jiao Tong University
RP Luo, M; Gu, P (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Ophthalmol, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China.
EM qiangson@sh163.net; guping2009@126.com
RI Sun, Hao/AAX-1653-2020
FU National High Technology Research and Development 863 Program
   [2015AA020311]; National Natural Science Foundation of China [81570883,
   31300810, 31500835]; Science and Technology Commission of Shanghai
   [14JC1493103]; Education Commission of Shanghai [14ZZ115]
FX The present study was supported by the National High Technology Research
   and Development 863 Program (grant no. 2015AA020311), the National
   Natural Science Foundation of China (grant nos. 81570883, 31300810 and
   31500835), the Science and Technology Commission of Shanghai (grant no.
   14JC1493103) and the Education Commission of Shanghai (grant no.
   14ZZ115).
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NR 34
TC 4
Z9 4
U1 0
U2 4
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-0981
EI 1792-1015
J9 EXP THER MED
JI Exp. Ther. Med.
PD OCT
PY 2017
VL 14
IS 4
BP 3699
EP 3707
DI 10.3892/etm.2017.4997
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA FG9BE
UT WOS:000410732400138
PM 29042966
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Kearns, VR
   Tasker, J
   Zhuola
   Akhtar, R
   Bachhuka, A
   Vasilev, K
   Sheridan, CM
   Williams, RL
AF Kearns, Victoria R.
   Tasker, Jack
   Zhuola
   Akhtar, Riaz
   Bachhuka, Akash
   Vasilev, Krasimir
   Sheridan, Carl M.
   Williams, Rachel L.
TI The formation of a functional retinal pigment epithelium occurs on
   porous polytetrafluoroethylene substrates independently of the surface
   chemistry
SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
LA English
DT Article
ID HUMAN BRUCHS MEMBRANE; MACULAR DEGENERATION; PLASMA TREATMENT;
   MOLECULAR-WEIGHT; CELLS; PTFE; CONTACT; BEHAVIOR
AB Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells may have the potential to preserve or restore vision in patients affected by blinding diseases such as age-related macular degeneration (AMD). One of the critical steps in achieving this is the ability to grow a functioning retinal pigment epithelium, which may need a substrate on which to grow and to aid transplantation. Tailoring the physical and chemical properties of the substrate should help the engineered tissue to function in the long term. The purpose of the study was to determine whether a functioning monolayer of RPE cells could be produced on expanded polytetrafluoroethylene substrates modified by either an ammonia plasma treatment or an n-Heptylamine coating, and whether the difference in surface chemistries altered the extracellular matrix the cells produced. Primary human RPE cells were able to form a functional, cobblestone monolayer on both substrates, but the formation of an extracellular matrix to exhibit a network structure took months, whereas on non-porous substrates with the same surface chemistry, a similar appearance was observed after a few weeks. This study suggests that the surface chemistry of these materials may not be the most critical factor in the development of growth of a functional monolayer of RPE cells as long as the cells can attach and proliferate on the surface. This has important implications in the design of strategies to optimise the clinical outcomes of subretinal transplant procedures.
C1 [Kearns, Victoria R.; Sheridan, Carl M.; Williams, Rachel L.] Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
   [Tasker, Jack; Zhuola; Akhtar, Riaz] Univ Liverpool, Dept Mech Mat & Aerosp Engn, Sch Engn, Liverpool, Merseyside, England.
   [Bachhuka, Akash; Vasilev, Krasimir] Univ South Australia, Sch Engn, Adelaide, SA 5095, Australia.
C3 University of Liverpool; University of Liverpool; University of South
   Australia
RP Kearns, VR (通讯作者)，Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
EM vkearns@liverpool.ac.uk
RI Bachhuka, Akash/AAA-6963-2022; Sheridan, Carl/AAH-3607-2021; Vasilev,
   Krasimir/C-5248-2008; Kearns, Victoria/I-3271-2012
OI Bachhuka, Akash/0000-0003-1253-8126; Sheridan, Carl/0000-0003-0100-9587;
   Kearns, Victoria/0000-0003-1426-6048; Vasilev,
   Krasimir/0000-0003-3534-4754
FU private local charity; Engineering and Physical Sciences Research
   Council [EP/M002209/1] Funding Source: researchfish; EPSRC
   [EP/M002209/1] Funding Source: UKRI
FX This work was supported by a private local charity (who had no
   involvement in the conduct of the research and/or preparation of the
   article).
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NR 41
TC 4
Z9 4
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-4530
EI 1573-4838
J9 J MATER SCI-MATER M
JI J. Mater. Sci.-Mater. Med.
PD AUG
PY 2017
VL 28
IS 8
AR 124
DI 10.1007/s10856-017-5926-3
PG 14
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA FB5QE
UT WOS:000406196100013
PM 28707136
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Sun, YX
   Shang, JL
   Liu, JX
   Li, SJ
   Zheng, CH
AF Sun, Yingxia
   Shang, Junliang
   Liu, Jin-Xing
   Li, Shengjun
   Zheng, Chun-Hou
TI epiACO - a method for identifying epistasis based on ant Colony
   optimization algorithm
SO BIODATA MINING
LA English
DT Article
DE Epistatic interactions; Ant colony optimization; Bayesian network;
   Mutual information
ID MULTIFACTOR-DIMENSIONALITY REDUCTION; DETECTING GENE-GENE; MUTUAL
   INFORMATION; INFERENCE; NETWORKS
AB Background: Identifying epistasis or epistatic interactions, which refer to nonlinear interaction effects of single nucleotide polymorphisms (SNPs), is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Though many works have been done for identifying epistatic interactions, due to their methodological and computational challenges, the algorithmic development is still ongoing.
   Results: In this study, a method epiACO is proposed to identify epistatic interactions, which based on ant colony optimization algorithm. Highlights of epiACO are the introduced fitness function Svalue, path selection strategies, and a memory based strategy. The Svalue leverages the advantages of both mutual information and Bayesian network to effectively and efficiently measure associations between SNP combinations and the phenotype. Two path selection strategies, i.e., probabilistic path selection strategy and stochastic path selection strategy, are provided to adaptively guide ant behaviors of exploration and exploitation. The memory based strategy is designed to retain candidate solutions found in the previous iterations, and compare them to solutions of the current iteration to generate new candidate solutions, yielding a more accurate way for identifying epistasis.
   Conclusions: Experiments of epiACO and its comparison with other recent methods epiMODE, TEAM, BOOST, SNPRuler, AntEpiSeeker, AntMiner, MACOED, and IACO are performed on both simulation data sets and a real data set of age-related macular degeneration. Results show that epiACO is promising in identifying epistasis and might be an alternative to existing methods.
C1 [Sun, Yingxia; Shang, Junliang; Liu, Jin-Xing; Li, Shengjun; Zheng, Chun-Hou] Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.
   [Shang, Junliang] Qufu Normal Univ, Inst Network Comp, Rizhao 276826, Peoples R China.
   [Zheng, Chun-Hou] Anhui Univ, Coll Elect Engn & Automat, Hefei 230601, Peoples R China.
C3 Qufu Normal University; Qufu Normal University; Anhui University
RP Shang, JL; Liu, JX (通讯作者)，Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.; Shang, JL (通讯作者)，Qufu Normal Univ, Inst Network Comp, Rizhao 276826, Peoples R China.
EM shangjunliang110@163.com; sdcavell@126.com
RI Liu, Jin-Xing/AAU-7257-2020
FU National Natural Science Foundation of China [61502272, 61572284];
   Science and Technology Planning Project of Qufu Normal University
   [xkj201410]; Scientific Research Foundation of Qufu Normal University
   [BSQD20130119]
FX We are grateful to the anonymous reviewers whose suggestions and
   comments contributed to the significant improvement of this paper. This
   work was in part supported by the National Natural Science Foundation of
   China (61502272, 61572284), the Science and Technology Planning Project
   of Qufu Normal University (xkj201410), the Scientific Research
   Foundation of Qufu Normal University (BSQD20130119).
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NR 37
TC 44
Z9 44
U1 0
U2 15
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1756-0381
J9 BIODATA MIN
JI BioData Min.
PD JUL 6
PY 2017
VL 10
AR 23
DI 10.1186/s13040-017-0143-7
PG 17
WC Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematical & Computational Biology
GA FA0AA
UT WOS:000405091200002
PM 28694848
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hao, XF
   Xie, LK
   Tang, YZ
   Xie, WK
   Zhang, ZF
   Qi, YX
   Xiao, WZ
   Zhang, J
AF Hao, Xiao-Feng
   Xie, Li-Ke
   Tang, You-Zhi
   Xie, Wan-Kun
   Zhang, Zhi-Fang
   Qi, Yi-Xin
   Xiao, Wen-Zheng
   Zhang, Jing
TI Association of complement factor H gene polymorphisms with age-related
   macular egeneration susceptibility
SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
LA English
DT Article
DE CFH; AMD; polymorphism; susceptibility
ID VARIANT INCREASES; CHINESE PATIENTS; DEGENERATION; MACULOPATHY; RISK;
   Y402H; PREVALENCE; EPIDEMIOLOGY; POPULATION; LOC387715
AB Objective: This study was aimed to confirm whether I62V and Y402H polymorphisms of complement factor H (CFH) were risk factors for age-related macular degeneration (AMD). Method: 109 AMD patients and 165 AMD-free controls were enrolled in the study. The I62V and Y402H polymorphisms were analyzed by polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the X-2 test to assess the relationship of I62V and Y402H polymorphisms with AMD risk. Analysis of haplotype and stratification by age and smoking status was conducted as well. Results: AA genotype and A allele of I62V polymorphism was significantly associated with increased risk for AMD (OR = 3.75, 95% CI = 1.70-8.30; OR = 1.64, 95% CI = 1.14-2.36). For Y402H polymorphism, CT genotype showed strong effects on the occurrence of AMD (OR = 2.10, 95% CI = 1.04-4.27). Moreover, C allele was also a risk factor for AMD (OR = 1.95, 95% CI = 1.02-3.72). The haplotypes analysis suggested that the risk for AT haplotype carriers was high, compared with GT haplotype (OR = 3.91, 95% CI = 2.58-5.94). In addition, we found that smoking status could affect the genotype distribution of Y402H polymorphism (P < 0.05). Conclusions: Our results revealed that CFH polymorphisms I62V and Y402H might be associated with the susceptibility to AMD in Chinese population.
C1 [Hao, Xiao-Feng; Xie, Li-Ke; Tang, You-Zhi; Xie, Wan-Kun; Zhang, Zhi-Fang; Qi, Yi-Xin; Xiao, Wen-Zheng; Zhang, Jing] China Acad Chinese Med Sci, Hosp Eye, Beijing 100040, Peoples R China.
C3 China Academy of Chinese Medical Sciences
RP Xie, LK (通讯作者)，China Acad Chinese Med Sci, Hosp Eye, Beijing 100040, Peoples R China.
EM xieliike@yeah.net
RI Xie, Wankun/K-8623-2017
OI Xie, Wankun/0000-0003-0178-3361
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NR 25
TC 7
Z9 8
U1 1
U2 3
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 2015
VL 8
IS 3
BP 3186
EP 3191
PG 6
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA CJ2KD
UT WOS:000355312200105
PM 26045838
DA 2022-11-30
ER

PT J
AU Huang, JD
   Amaral, J
   Lee, JW
   Rodriguez, IR
AF Huang, Jiahn-Dar
   Amaral, Juan
   Lee, Jung Wha
   Rodriguez, Ignacio R.
TI 7-Ketocholesterol-Induced Inflammation Signals Mostly through the TLR4
   Receptor Both In Vitro and In Vivo
SO PLOS ONE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; BIOLOGICAL-ACTIVITY; CYTOKINE
   PRODUCTION; WNT PATHWAY; INHIBITOR; OXYSTEROLS; CELLS; MECHANISMS;
   OXIDATION
AB The cholesterol oxide 7-ketocholesterol (7KCh) has been implicated in numerous age-related diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer and age-related macular degeneration. It is formed by the autooxidation of cholesterol and especially cholesterol-fatty acid esters found in lipoprotein deposits. This molecule causes complex and potent inflammatory responses in vitro and in vivo. It is suspected of causing chronic inflammation in tissues exposed to oxidized lipoprotein deposits. In this study we have examined the inflammatory pathways activated by 7KCh both in cultured ARPE19 cells and in vivo using 7KCh-containing implants inserted into the anterior chamber of the rat eye. Our results indicate that 7KCh-induced inflammation is mediated mostly though the TLR4 receptor with some cross-activation of EGFR-related pathways. The majority of the cytokine inductions seem to signal via the TRIF/TRAM side of the TLR4 receptor. The MyD88/TIRAP side only significantly effects IL-1 beta inductions. The 7KCh-induced inflammation also seems to involve a robust ER stress response. However, this response does not seem to involve a calcium efflux-mediated UPR. Instead the ER stress response seems to be mediated by yet identified kinases activated through the TLR4 receptor. Some of the kinases identified are the RSKs which seem to mediate the cytokine inductions and the cell death pathway but do not seem to be involved in the ER stress response.
C1 [Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Rodriguez, Ignacio R.] NEI, Retinal Cell & Mol Biol Lab, Mech Retinal Dis Sect, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Rodriguez, IR (通讯作者)，NEI, Retinal Cell & Mol Biol Lab, Mech Retinal Dis Sect, NIH, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
OI Amaral, Juan/0000-0001-8755-9170
FU National Eye Institute Intramural Research Program; NATIONAL EYE
   INSTITUTE [ZIAEY000307] Funding Source: NIH RePORTER
FX This research was supported by the National Eye Institute Intramural
   Research Program. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 69
TC 30
Z9 30
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 18
PY 2014
VL 9
IS 7
AR e100985
DI 10.1371/journal.pone.0100985
PG 26
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AM1OC
UT WOS:000339615200011
PM 25036103
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, YY
   Liu, SL
   Hu, DP
   Xing, YQ
   Shen, Y
AF Chen, Yuan-Yuan
   Liu, Shi-Liang
   Hu, Dan-Ping
   Xing, Yi-Qiao
   Shen, Yin
TI N -methyl- N -nitrosourea-induced retinal degeneration in mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE N -methyl- N -nitrosourea; photoreceptor; remodelling; retinal
   degeneration; ribbon synapse; retinal vessel
ID SPRAGUE-DAWLEY RATS; PHOTORECEPTOR APOPTOSIS; ROD PHOTORECEPTORS;
   PIGMENT-EPITHELIUM; RIBBON SYNAPSES; MOUSE RETINA; CELL LOSS; RCS RAT;
   NEURONS; PROTEINS
AB Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Chen, Yuan-Yuan; Liu, Shi-Liang; Hu, Dan-Ping; Xing, Yi-Qiao; Shen, Yin] Wuhan Univ, Renmin Hosp, Dept Ophthalmol, Wuhan 430060, Peoples R China.
   Wuhan Univ, Inst Eye, Wuhan 430060, Peoples R China.
C3 Wuhan University; Wuhan University
RP Xing, YQ (通讯作者)，Wuhan Univ, Renmin Hosp, Inst Eye, Dept Ophthalmol, Jiefang Rd 238, Wuhan 430060, Peoples R China.
EM xyqdr07@gmail.com; yinshen@whu.edu.cn
RI Chen, Yuanyuan/GXG-2130-2022
FU National Natural Science Foundation of China [81000395, 81270998,
   81271025]; Ministry of Health Public Welfare Scientific Research
   [201302015]
FX This study was funded by the National Natural Science Foundation of
   China (No: 81000395, 81270998 and 81271025) and the Ministry of Health
   Public Welfare Scientific Research (201302015). We sincerely thank
   Professor Zhiyin Song (Life Sciences College, Wuhan University, Wuhan,
   China) for the generous gift of the anti-HSP60 and anti-COX4 antibodies,
   Hong Xia (Key Laboratory of Hubei Province for Digestive System Disease,
   Wuhan, China) for his technical support, and Dr. Scott Nawy (Albert
   Einstein College of Medicine, USA) for his critical reading of the
   manuscript.
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NR 40
TC 50
Z9 55
U1 0
U2 15
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2014
VL 121
BP 102
EP 113
DI 10.1016/j.exer.2013.12.019
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AG0LI
UT WOS:000335106600014
PM 24509257
DA 2022-11-30
ER

PT J
AU Monestam, EI
   Lundqvist, B
AF Monestam, Eva I.
   Lundqvist, Britta
TI Extended long-term outcomes of cataract surgery
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE cataract surgery; longitudinal outcome study; long-term outcome;
   population-based
ID RANDOMIZED CONTROLLED-TRIAL; AGE-RELATED MACULOPATHY; BEAVER DAM EYE;
   MACULAR DEGENERATION; VISUAL FUNCTION; ELDERLY-WOMEN; HEALTH-STATUS;
   POPULATION; RISK; DISEASE
AB Purpose: To longitudinally report the changes in visual acuity (VA) and subjective visual function, 10 years after cataract surgery.
   Methods: This population-based prospective study reviewed 335 patients (85% of survivors) who underwent cataract surgery during a 1-year period in 199798, 289 of whom were also re-examined. The patients underwent a routine eye examination and answered the same visual function questionnaire (VF-14), preoperatively, 4 months postoperatively, 5 years and 10 years after surgery.
   Results: Ten years after surgery, the best corrected VA (BCVA) of the operated eye had deteriorated to a median of 0.06 (logMAR) (Snellen acuity: 20/23) from 0.046 (logMAR) (20/22) postoperatively (p = 0.001). More than two-thirds of the patients had <0.1 logMAR units worsening of BCVA compared with postoperatively. Approximately half of the patients had no deterioration in subjective visual function, and 77% had 10 points decline or less. Twelve per cent of the patients (42/335) had a worsening of more than 30 points. Effect size was calculated for the VF-14 total score at all three occasions of follow-up after surgery and was largest approximately 4 months postoperatively. Long-time follow-up of 10 years shows still moderate effect size.
   Conclusion: These results confirm the effectiveness of cataract extraction, offering good long-term visual rehabilitation for the majority of the patients. The most common cause for large functional loss after 10 years is age-related macular degeneration.
C1 [Monestam, Eva I.; Lundqvist, Britta] Norrlands Univ Hosp, Dept Clin Sci Ophthalmol, Umea, Sweden.
C3 Umea University
RP Monestam, EI (通讯作者)，Umea Univ, Dept Clin Sci Ophthalmol, S-90185 Umea, Sweden.
EM eva.monestam@vll.se
FU Crown Princess Margareta's Committee for the Blind, Stockholm, Sweden;
   Swedish Medical Society, Stockholm, Sweden; Vasterbottens County Council
   Research Fund, Umea, Sweden
FX Presented at the EVER meeting (European Association for Vision and Eye
   Research) at Crete October 6-9 2010. Grants from Crown Princess
   Margareta's Committee for the Blind, Stockholm, Sweden, The Swedish
   Medical Society, Stockholm, Sweden, and from the Vasterbottens County
   Council Research Fund, Umea, Sweden, are acknowledged. The authors have
   no proprietary interest in the development or marketing of any product
   mentioned and do not receive grants from any company.
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NR 29
TC 14
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD NOV
PY 2012
VL 90
IS 7
BP 651
EP 656
DI 10.1111/j.1755-3768.2011.02138.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 030DG
UT WOS:000310548500022
PM 21449927
OA Bronze
DA 2022-11-30
ER

PT J
AU Sparrow, JR
   Ueda, K
   Zhou, J
AF Sparrow, Janet R.
   Ueda, Keiko
   Zhou, Jilin
TI Complement dysregulation in AMD: RPE-Bruch's membrane-choroid
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE Age-related macular degeneration; Complement system; Drusen; Retinal
   pigment epithelium
ID CHLAMYDIA-PNEUMONIAE INFECTION; RETINAL-PIGMENT EPITHELIUM;
   SINGLET-OXYGEN GENERATION; MITOCHONDRIAL-DNA DAMAGE; GENOME-WIDE
   ASSOCIATION; FACTOR-H POLYMORPHISM; LIGHT-INDUCED DAMAGE; C-REACTIVE
   PROTEIN; MACULAR DEGENERATION; AMYLOID-BETA
AB The question as to why the macula of the retina is prone to an aging disease (age-related macular degeneration) remains unanswered. This unmet challenge has implications since AMD accounts for approximately 54% of blindness in the USA (Swaroop, Chew, Bowes Rickman and Abecasis, 2009). While AMD has onset in the elder years, it likely develops over time. Genetic discovery to date has accounted for approximately 50% of the inheritable component of AMD. The polymorphism that has been most widely studied is the Y402H allele in the complement factor H gene. The implication of this genetic association is that in a subset of AMD cases, unregulated complement activation is permissive for AMD. Given that this gene variant results in an amino acid substitution, it is assumed that this change will have functional consequences although the precise mechanisms are still unknown. Genetic predisposition is not the only factor however, since in this complex disease there is substantial evidence that lifestyle factors such as diet and smoking contribute to risk. Here we provide an overview of current knowledge with respect to factors involved in AMD pathogenesis. Interwoven with these issues is a discussion of the significant role played by aging processes, some of which are unique to the retina and retinal pigment epithelium. One recurring theme is the potential for disease promotion by diverse types of oxidation products. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   Columbia Univ, Dept Pathol, New York, NY 10032 USA.
   Columbia Univ, Dept Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Sparrow, JR (通讯作者)，Columbia Univ, Dept Ophthalmol, 630 W 168th St, New York, NY 10032 USA.
EM jrs88@columbia.edu
FU National Institutes of Health [EY12951, P30EY019007]; Research to
   Prevent Blindness; NATIONAL EYE INSTITUTE [P30EY019007, R01EY012951]
   Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants EY12951
   (JRS) and P30EY019007 and a grant from Research to Prevent Blindness to
   the Department of Ophthalmology.
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NR 117
TC 48
Z9 50
U1 0
U2 13
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0098-2997
EI 1872-9452
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 436
EP 445
DI 10.1016/j.mam.2012.03.007
PG 10
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 983WR
UT WOS:000307149900007
PM 22504022
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Eldaly, MA
   Styles, C
AF Eldaly, Mohamed A.
   Styles, Caroline
TI FIRST VERSUS SECOND EYE INTRAVITREAL RANIBIZUMAB THERAPY FOR WET AMD
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; ranibizumab; wet; intravitreal; vision
ID MACULAR DEGENERATION; NEOVASCULARIZATION; VERTEPORFIN
AB Purpose: To evaluate the short-term visual outcomes after intravitreal Ranibizumab for wet age-related macular degeneration, when used in first eyes (good vision in the untreated eye) compared with second eyes (significant visual impairment in the untreated eye).
   Methods: Seventy-five consecutive patients who received intravitreal ranibizumab injection were divided into Group A, comprising 35 first eyed patients and Group B, comprising 40 second eyes. Visual acuity and contrast sensitivity was compared before treatment, and 3 months after the 3rd injection. Results were compared at 95% confidence interval.
   Results: Mean pretreatment logMar visual acuity was 0.86 (standard deviation 0.28) in Group A whereas Group B was 0.66 (standard deviation 0.36) (P = 0.007). Posttreatment the mean visual acuity in Group A was 0.63 (standard deviation 0.37) and in Group B was 0.44 (standard deviation 0.33) (P = 0.02). The mean numbers of letters gained per patient were 11.1 (Group A) and 10.6 (Group B). Half of all patients showed significant improvement of visual acuity (>= 15 letters gain). Contrast sensitivity significantly improved in both groups and was usually, but not always, associated with visual gain.
   Conclusion: Second eye patients tend to present to clinical diagnosis at a better visual acuity than first ones and subsequently have better chances for better posttreatment visual acuity. However, both groups have an equal chance of significant visual improvement.
C1 [Eldaly, Mohamed A.] Cairo Univ, Dept Ophthalmol, Giza, Egypt.
   [Styles, Caroline] NHS Fife, Queen Margaret Hosp, Dept Ophthalmol, Leven, Scotland.
C3 Egyptian Knowledge Bank (EKB); Cairo University
RP Eldaly, MA (通讯作者)，36 Gameat Eldowal Elarabia St, Giza 12411, Cairo, Egypt.
EM mohamedahmedeldaly@yahoo.com
RI Eldaly, Mohamed/Q-1246-2019
OI Eldaly, Mohamed/0000-0001-7578-4362
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   Moutray T, 2008, BRIT J OPHTHALMOL, V92, P361, DOI 10.1136/bjo.2007.123976
   Regillo CD, 2008, AM J OPHTHALMOL, V145, P239, DOI 10.1016/j.ajo.2007.10.004
   Rosenfeld PJ, 2006, NEW ENGL J MED, V355, P1419, DOI 10.1056/NEJMoa054481
   Steinbrook R, 2006, NEW ENGL J MED, V355, P1409, DOI 10.1056/NEJMp068185
NR 10
TC 8
Z9 9
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2009
VL 29
IS 3
BP 325
EP 328
DI 10.1097/IAE.0b013e31819a6154
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 420RK
UT WOS:000264306700007
PM 19287289
DA 2022-11-30
ER

PT J
AU Saw, CLL
   Heng, PWS
   Olivo, M
AF Saw, Constance Lay Lay
   Heng, Paul Wan Sia
   Olivo, Malini
TI Potentiation of the photodynamic action of hypericin
SO JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY
LA English
DT Article
DE hypericin; photodynamic therapy; photodynamic diagnosis; cancer;
   chemical modifications; light dosimetry; formulations; oxygen;
   anti-angiogenesis; adjuvant therapy
ID CHICK CHORIOALLANTOIC MEMBRANE; N-METHYL PYRROLIDONE; BLADDER-CARCINOMA;
   5-AMINOLEVULINIC ACID; LEUPROLIDE ACETATE; SUSTAINED-RELEASE;
   INTRAVESICAL INSTILLATION; SUBCELLULAR-DISTRIBUTION; FLUORESCENCE
   DIAGNOSIS; EXTENDED-RELEASE
AB Hypericin (HY) is an interesting photosensitizer with dark activity and photodynamic therapy (PDT) effects via p53-independent pathway. In photodynamic diagnosis (PDD) of bladder cancer using HY, very high sensitivity and specificity were reported, in comparison with its counterpart, 5-aminolevulinic acid (5-ALA). HY was tested for the detection of human gastric cancer. It was also studied for treating some cancers and age-related macular degeneration and showed some promising findings. Several strategies to enhance the efficacy of HY-PDD and HY-PDT are reviewed. Using fractionated light dosing, fractionated drug dosing, hyperthermia, adjuvants such as oxygen carrier/antiangiogenesis, chemical modifications, and formulation approaches to enhance the PDT effects of HY are topics of this review. Despite cutting-edge technology approach such as preparing transferring-mediated targeting HY liposomes and nanoparticles of HY, such preparations did not always offer the desired enhanced treatment effects. It turns out that simple solutions of HY, especially those prepared without using plasma protein, were more successful in enhancing the delivery of HY for in vitro and in vivo systems. Thus, the HY-PDT with these formulations performed better. It is anticipated that HY-PDD and HY-PDT can be enhanced and optimized with the right combination of light dosimetry and drug dose in an effective formulation containing a suitable adjuvant. Hyperoxygenation and hyperthermia can also be used to further enhance the efficacy of HY-PDT.
C1 [Olivo, Malini] Natl Canc Ctr, Div Med Sci, Singapore 169610, Singapore.
   [Saw, Constance Lay Lay; Heng, Paul Wan Sia] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore.
C3 National Cancer Centre Singapore (NCCS); National University of
   Singapore
RP Olivo, M (通讯作者)，Natl Canc Ctr, Div Med Sci, Singapore 169610, Singapore.
EM dmsmcd@nccs.com.sg
RI Heng, Paul W/G-7134-2012; Saw, Constance Lay Lay/B-3959-2018
OI Saw, Constance Lay Lay/0000-0002-7631-8395
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NR 79
TC 2
Z9 2
U1 0
U2 22
PU BEGELL HOUSE INC
PI DANBURY
PA 50 NORTH ST, DANBURY, CT 06810 USA
SN 0731-8898
EI 2162-6537
J9 J ENVIRON PATHOL TOX
JI J. Environ. Pathol. Toxicol. Oncol.
PY 2007
VL 27
IS 1
BP 23
EP 33
PG 11
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA 286YM
UT WOS:000254882700003
DA 2022-11-30
ER

PT J
AU Binns, A
   Margrain, TH
AF Binns, A
   Margrain, TH
TI Evaluation of retinal function using the dynamic focal cone ERG
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Article
DE cone; electroretinogram; function; macular; recovery
ID VISUAL-EVOKED-POTENTIALS; DARK-ADAPTATION; GLARE RECOVERY; A-WAVE;
   PHOTOSTRESS RECOVERY; MACULAR FUNCTION; FELLOW EYES; ROD; FLICKER;
   PATTERN
AB The development of effective means of assessing visual function in retinal disease holds the key to improved understanding of pathogenesis, and better monitoring of treatment outcomes. In diseases such as age-related macular degeneration, in which the primary locus of dysfunction is the outer retina, tests which provide a direct measure of the functional integrity of the photoreceptor/retinal pigment epithelium (RPE) complex are of great importance. Recovery of retinal function following adaptation to a bright light requires the healthy function of photoreceptors, RPE, Bruch's membrane and choroidal circulation, making an assessment of this recovery a potentially useful clinical tool. However, current techniques are either subjective in nature, or are influenced by post-retinal processing of visual information. This report describes a novel technique, the 'Dynamic Focal Cone Electro-retinogram (ERG)', which allows direct, objective assessment of the recovery of macular function following photopigment bleach. A series of 41 Hz ERGs was recorded, and ERG amplitude was plotted as a function of time following cessation of the bleach. Normative data was collected from 10 healthy subjects. For all subjects, there was no measurable ERG immediately after the bleach, but the amplitude had returned to a pre-bleach level within 4 min. The amplitude recovery data were adequately described both by an exponential recovery function and by a model based on a rate-limited recovery process. We conclude that this technique provides a clinically applicable, objective measure of outer retinal recovery.
C1 Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF10 3XF, Wales.
C3 Cardiff University
RP Binns, A (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, POB 905, Cardiff CF10 3XF, Wales.
EM BinnsAM@cardiff.ac.uk
OI Margrain, Tom/0000-0003-1280-0809; Binns, Alison/0000-0001-8621-498X
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NR 62
TC 14
Z9 15
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-5408
EI 1475-1313
J9 OPHTHAL PHYSL OPT
JI Ophthalmic Physiol. Opt.
PD NOV
PY 2005
VL 25
IS 6
BP 492
EP 500
DI 10.1111/j.1475-1313.2005.00338.x
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 983AR
UT WOS:000233204000003
PM 16343125
DA 2022-11-30
ER

PT J
AU Werner, L
   Kaskaloglu, M
   Apple, DJ
   Pandey, SK
   Macky, TA
   Izak, AM
   Trivedi, RH
   Heredia, M
   Morse, SE
AF Werner, L
   Kaskaloglu, M
   Apple, DJ
   Pandey, SK
   Macky, TA
   Izak, AM
   Trivedi, RH
   Heredia, M
   Morse, SE
TI Aqueous infiltration into an implantable miniaturized telescope
SO OPHTHALMIC SURGERY AND LASERS
LA English
DT Article
ID MACULAR DEGENERATION; SURGICAL PREVENTION; REHABILITATION
AB The implantable miniaturized telescope (IMT(TM)) is the first intraocular magnifying system proposed for optical correction in patients with age-related macular degeneration (ARMD). The optical component is embedded in a carrying device designed as an intraocular lens that is implanted after cataract surgery. In this study, we report findings on an IMT(TM) that was explanted because of aqueous infiltration into its optic and describe the configuration of this device and the surgical technique required for its implantation. The patient, a 75-year-old mate with bilateral cataract and nonexudative ARMD, underwent phacoemulsification with implantation of an IMT(TM) in the right eye. The rigid device, weighing 46.1 mg in aqueous, has an overall diameter of 13.5 mm and requires implantation through a large limbal incision. It is fixated at the 6 to 12 o'clock meridian. Follow-up examination revealed the presence of numerous droplets inside the IMT(TM) optic. The device was explanted and sent to our center for evaluation. A large Fissure was found on the carrying device. However, it was unlikely the site for aqueous infiltration. Microdefects at the level of the sealing of the optical cylinder appeared to provide the opening for the inflow of aqueous that formed droplets. Based on the findings of this report the manufacturer has modified the sea-ling technique to avoid this complication. Current clinical trials are now ongoing to assess the efficacy of this device in providing visual rehabilitation for ARMD patients.
C1 Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
   Ege Univ, Izmir, Turkey.
C3 Medical University of South Carolina; Ege University
RP Werner, L (通讯作者)，Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, 167 Ashley Ave,POB 250676, Charleston, SC 29425 USA.
RI Trivedi, Rupal H/A-5243-2013; Macky, Tamer A/I-8716-2019
OI Macky, Tamer A/0000-0002-9767-8912; Trivedi, Rupal/0000-0001-9786-7062
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NR 20
TC 0
Z9 0
U1 0
U2 2
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0022-023X
J9 OPHTHALMIC SURG LAS
JI Ophthalmic Surg. Lasers
PD JUL-AUG
PY 2002
VL 33
IS 4
BP 343
EP 348
PG 6
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA 573KF
UT WOS:000176828100018
PM 12135001
DA 2022-11-30
ER

PT J
AU Arik, YB
   Buijsman, W
   Loessberg-Zahl, J
   Cuartas-Velez, C
   Veenstra, C
   Logtenberg, S
   Grobbink, AM
   Bergveld, P
   Gagliardi, G
   den Hollander, AI
   Bosschaart, N
   van den Berg, A
   Passier, R
   van der Meer, AD
AF Arik, Yusuf B.
   Buijsman, Wesley
   Loessberg-Zahl, Joshua
   Cuartas-Velez, Carlos
   Veenstra, Colin
   Logtenberg, Sander
   Grobbink, Anne M.
   Bergveld, Piet
   Gagliardi, Giuliana
   den Hollander, Anneke, I
   Bosschaart, Nienke
   van den Berg, Albert
   Passier, Robert
   van der Meer, Andries D.
TI Microfluidic organ-on-a-chip model of the outer blood-retinal barrier
   with clinically relevant read-outs for tissue permeability and vascular
   structure
SO LAB ON A CHIP
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; ENDOTHELIAL-CELLS;
   OXIDATIVE STRESS; NEOVASCULARIZATION; ARPE-19; ANGIOGRAPHY; PLATFORM;
   ASSAY
AB The outer blood-retinal barrier (oBRB) tightly controls the transport processes between the neural tissue of the retina and the underlying blood vessel network. The barrier is formed by the retinal pigment epithelium (RPE), its basal membrane and the underlying choroidal capillary bed. Realistic three-dimensional cell culture based models of the oBRB are needed to study mechanisms and potential treatments of visual disorders such as age-related macular degeneration that result from dysfunction of the barrier tissue. Ideally, such models should also include clinically relevant read-outs to enable translation of experimental findings in the context of pathophysiology. Here, we report a microfluidic organ-on-a-chip model of the oBRB that contains a monolayer of human immortalized RPE and a microvessel of human endothelial cells, separated by a semi-permeable membrane. Confluent monolayers of both cell types were confirmed by fluorescence microscopy. The three-dimensional vascular structures within the chip were imaged by optical coherence tomography: a medical imaging technique, which is routinely applied in ophthalmology. Differences in diameters and vessel density could be readily detected. Upon inducing oxidative stress by treating with hydrogen peroxide (H2O2), a dose dependent increase in barrier permeability was observed by using a dynamic assay for fluorescence tracing, analogous to the clinically used fluorescence angiography. This organ-on-a-chip of the oBRB will allow future studies of complex disease mechanisms and treatments for visual disorders using clinically relevant endpoints in vitro.
C1 [Arik, Yusuf B.; Buijsman, Wesley; Logtenberg, Sander; Grobbink, Anne M.; Passier, Robert; van der Meer, Andries D.] Univ Twente, Appl Stem Cell Technol, Tech Med Ctr, POB 217, NL-7500 AE Enschede, Netherlands.
   [Arik, Yusuf B.; Buijsman, Wesley; Loessberg-Zahl, Joshua; Bergveld, Piet; van den Berg, Albert] Univ Twente, BIOS Lab Chip Grp, Tech Med Ctr, MESA Inst Nanotechnol, Enschede, Netherlands.
   [Cuartas-Velez, Carlos; Veenstra, Colin; Logtenberg, Sander; Bosschaart, Nienke] Univ Twente, Tech Med Ctr, Biomed Photon Imaging Grp, Enschede, Netherlands.
   [Gagliardi, Giuliana; den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands.
   [den Hollander, Anneke, I] Radboud Univ Nijmegen, Dept Human Genet, Donders Inst Brain Cognit & Behav, Med Ctr, Nijmegen, Netherlands.
   [Passier, Robert] Leiden Univ, Dept Anat & Embryol, Med Ctr, Leiden, Netherlands.
C3 University of Twente; University of Twente; University of Twente;
   Radboud University Nijmegen; Radboud University Nijmegen; Leiden
   University; Leiden University Medical Center (LUMC); Leiden University -
   Excl LUMC
RP Arik, YB (通讯作者)，Univ Twente, Appl Stem Cell Technol, Tech Med Ctr, POB 217, NL-7500 AE Enschede, Netherlands.; Arik, YB (通讯作者)，Univ Twente, BIOS Lab Chip Grp, Tech Med Ctr, MESA Inst Nanotechnol, Enschede, Netherlands.
EM y.b.arik@utwente.nl
OI Loessberg-Zahl, Joshua/0000-0002-4491-5179; van den Berg,
   Albert/0000-0001-9019-933X; Bosschaart, Nienke/0000-0001-9232-1079;
   Buijsman, Wesley/0000-0002-2135-3863
FU Stichting Toegepast Wetenschappelijk Instituut voor Neuromodulatie
   (TWIN) under the project 'Inflammation and Edema in an Organ-on-a-Chip
   Model of Wet Age-Related Macular Degeneration'; Top sector 'Life
   Sciences and Health' Health - Holland under the 'PLURIMACULA' grant
   [LSHM19001]; Dutch Science Foundation (NWO) under the Gravitation Grant
   'NOCI' Program [024.003.001]; Dutch Science Foundation (NWO) under the
   Gravitation Grant 'VESCEL' Program [669768]
FX We acknowledge Duco Schriemer and Karin Roelofs for kindly providing
   ARPE-19 cells. The authors acknowledge the funding received from
   Stichting Toegepast Wetenschappelijk Instituut voor Neuromodulatie
   (TWIN) under the project 'Inflammation and Edema in an Organ-on-a-Chip
   Model of Wet Age-Related Macular Degeneration', from Top sector 'Life
   Sciences and Health' Health - Holland under the 'PLURIMACULA' grant
   (grant no. LSHM19001) of Dr. Andries van der Meer, from the Dutch
   Science Foundation (NWO) under the Gravitation Grant 'NOCI' Program
   (grant no. 024.003.001) of Prof. Christine Mummery and 'VESCEL' Program
   (grant no. 669768) of Prof. Albert van den Berg.
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NR 70
TC 14
Z9 14
U1 7
U2 18
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PD JAN 21
PY 2021
VL 21
IS 2
BP 272
EP 283
DI 10.1039/d0lc00639d
PG 12
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Chemistry,
   Analytical; Nanoscience & Nanotechnology; Instruments & Instrumentation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
   Other Topics; Instruments & Instrumentation
GA PY6VR
UT WOS:000612181000003
PM 33346294
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Alic, L
   Papac-Milicevic, N
   Czamara, D
   Rudnick, RB
   Ozsvar-Kozma, M
   Hartmann, A
   Gurbisz, M
   Hoermann, G
   Haslinger-Hutter, S
   Zipfel, PF
   Skerka, C
   Binder, EB
   Binder, CJ
AF Alic, Lejla
   Papac-Milicevic, Nikolina
   Czamara, Darina
   Rudnick, Ramona B.
   Ozsvar-Kozma, Maria
   Hartmann, Andrea
   Gurbisz, Michael
   Hoermann, Gregor
   Haslinger-Hutter, Stefanie
   Zipfel, Peter F.
   Skerka, Christine
   Binder, Elisabeth B.
   Binder, Christoph J.
TI A genome-wide association study identifies key modulators of complement
   factor H binding to malondialdehyde-epitopes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE complement factor H; complement factor H-related protein 1; complement
   factor H-related protein 3; malondialdehyde; genome-wide association
   study
ID OXIDATION-SPECIFIC EPITOPES; TRANSLATIONAL MINIREVIEW SERIES;
   LOW-DENSITY-LIPOPROTEIN; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   PROTEINS; POLYMORPHISM; HEPARIN; ANTIBODIES; SURFACE
AB Genetic variants within complement factor H (CFH), a major alternative complement pathway regulator, are associated with the development of age-related macular degeneration (AMD) and other complementopathies. This is explained with the reduced binding of CFH or its splice variant factor H-like protein 1 (FHL-1) to self-ligands or altered self-ligands (e.g., malondialdehyde [MDA]-modified molecules) involved in homeostasis, thereby causing impaired complement regulation. Considering the critical role of CFH in inhibiting alternative pathway activation on MDA-modified surfaces, we performed an unbiased genome-wide search for genetic variants that modify the ability of plasma CFH to bind MDA in 1,830 individuals and characterized the mechanistic basis and the functional consequences of this. In a cohort of healthy individuals, we identified rs1061170 in CFH and the deletion of CFHR3 and CFHR1 as dominant genetic variants that modify CFH/FHL-1 binding to MDA. We further demonstrated that FHR1 and FHR3 compete with CFH for binding to MDA-epitopes and that FHR1 displays the highest affinity toward MDA-epitopes compared to CFH and FHR3. Moreover, FHR1 bound to MDA-rich areas on necrotic cells and prevented CFH from mediating its cofactor activity on MDA-modified surfaces, resulting in enhanced complement activation. These findings provide a mechanistic explanation as to why the deletion of CFHR3 and CFHR1 is protective in AMD and highlight the importance of genetic variants within the CFH/CFHR3/CFHR1 locus in the recognition of altered-self in tissue homeostasis.
C1 [Alic, Lejla; Papac-Milicevic, Nikolina; Ozsvar-Kozma, Maria; Gurbisz, Michael; Hoermann, Gregor; Haslinger-Hutter, Stefanie; Binder, Christoph J.] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.
   [Alic, Lejla; Papac-Milicevic, Nikolina; Ozsvar-Kozma, Maria; Binder, Christoph J.] Austrian Acad Sci, Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Alic, Lejla] Univ Sarajevo, Fac Med, Dept Med Biochem, Sarajevo 71000, Bosnia & Herceg.
   [Czamara, Darina; Binder, Elisabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany.
   [Rudnick, Ramona B.; Hartmann, Andrea; Zipfel, Peter F.; Skerka, Christine] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, D-07745 Jena, Germany.
   [Hoermann, Gregor] Univ Hosp Innsbruck, Cent Inst Med & Chem Lab Diag, A-6020 Innsbruck, Austria.
   [Zipfel, Peter F.] Friedrich Schiller Univ, Inst Microbiol, D-07743 Jena, Germany.
C3 Medical University of Vienna; Austrian Academy of Sciences; University
   of Sarajevo; Max Planck Society; Hans Knoll Institute (HKI); Medical
   University of Innsbruck; Friedrich Schiller University of Jena
RP Papac-Milicevic, N; Binder, CJ (通讯作者)，Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.; Papac-Milicevic, N; Binder, CJ (通讯作者)，Austrian Acad Sci, Res Ctr Mol Med, A-1090 Vienna, Austria.
EM nikolina.papac@meduniwien.ac.at; christoph.binder@meduniwien.ac.at
RI Alic, Lejla/AAC-1149-2021; Hoermann, Gregor/B-8832-2016
OI Alic, Lejla/0000-0003-0197-0837; Hoermann, Gregor/0000-0002-7374-4380;
   Papac-Milicevic, Nikolina/0000-0002-8187-7677; Binder, Christoph
   J./0000-0001-8313-7050; Gurbisz, Michael/0000-0002-7773-8228
FU Vienna Science and Technology Fund (WWTF) [LS16-019]; Austrian Science
   Fund (FWF) [F5402-B21]; Collaborative Research Center 1192 from the
   Deutsche Forschungsgemeinschaft; Kidneeds; Deutsche
   Forschungsgemeinschaft [PR905/12-1]
FX We thank Petra Jurkowitsch, Vesna Krajina, Harald Esterbauer, Mate G.
   Kiss, Monika von der Heide, and Mateo Markovi~c. This work was supported
   by The Vienna Science and Technology Fund (WWTF) Project LS16-019 and by
   the Austrian Science Fund (FWF) Project F5402-B21 (to C.J.B.),
   Collaborative Research Center 1192 from the Deutsche
   Forschungsgemeinschaft (to P.F.Z.), Deutsche Forschungsgemeinschaft
   Grant PR905/12-1 (to C.S.), and Kidneeds (to P.F.Z. and C.S.).
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NR 53
TC 15
Z9 15
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 5
PY 2020
VL 117
IS 18
BP 9942
EP 9951
DI 10.1073/pnas.1913970117
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA LK7UR
UT WOS:000531067600046
PM 32321835
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Bhattarai, N
   Korhonen, E
   Toppila, M
   Koskela, A
   Kaarniranta, K
   Mysore, Y
   Kauppinen, A
AF Bhattarai, Niina
   Korhonen, Eveliina
   Toppila, Maija
   Koskela, Ali
   Kaarniranta, Kai
   Mysore, Yashavanthi
   Kauppinen, Anu
TI Resvega Alleviates Hydroquinone-Induced Oxidative Stress in ARPE-19
   Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE hydroquinone; Resvega; retinal pigment epithelial cell; ROS; ARPE-19;
   cell viability; inflammation; antioxidant; NF-kappa B; NADPH oxidase
ID RETINAL-PIGMENT EPITHELIUM; NF-KAPPA-B; MACULAR DEGENERATION; REACTIVE
   METABOLITE; INFLAMMASOME ACTIVATION; BENZENE; INTERLEUKIN-4; PROTECTION;
   SMOKING; INJURY
AB Retinal pigment epithelial (RPE) cells maintain homeostasis at the retina and they are under continuous oxidative stress. Cigarette smoke is a prominent environmental risk factor for age-related macular degeneration (AMD), which further increases the oxidant load in retinal tissues. In this study, we measured oxidative stress and inflammatory markers upon cigarette smoke-derived hydroquinone exposure on human ARPE-19 cells. In addition, we studied the effects of commercial Resvega product on hydroquinone-induced oxidative stress. Previously, it was observed that Resvega induces autophagy during impaired protein clearance in ARPE-19 cells, for which it has the potential to alleviate pro-inflammatory pathways. Cell viability was determined while using the lactate dehydrogenase (LDH) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and the cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) production were measured using the 2 ',7 '-dichlorofluorescin diacetate (H(2)DCFDA) probe. Hydroquinone compromised the cell viability and increased ROS production in ARPE-19 cells. Resvega significantly improved cell viability upon hydroquinone exposure and reduced the release of interleukin (IL)-8 and monocytic chemoattractant protein (MCP)-1 from RPE cells. Resvega, N-acetyl-cysteine (NAC) and aminopyrrolidine-2,4-dicarboxylic acid (APDC) alleviated hydroquinone-induced ROS production in RPE cells. Collectively, our results indicate that hydroquinone induces cytotoxicity and increases oxidative stress through NADPH oxidase activity in RPE cells, and resveratrol-containing Resvega products prevent those adverse effects.
C1 [Bhattarai, Niina; Korhonen, Eveliina; Toppila, Maija; Mysore, Yashavanthi; Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, Kuopio 70210, Finland.
   [Korhonen, Eveliina] Helsinki Univ Hosp, Dept Clin Chem, HUSLAB, Helsinki 00290, Finland.
   [Koskela, Ali; 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 Helsinki; Helsinki
   University Central Hospital; University of Eastern Finland; Kuopio
   University Hospital; University of Eastern Finland
RP Bhattarai, N; Kauppinen, A (通讯作者)，Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, Kuopio 70210, Finland.
EM niina.bhattarai@uef.fi; eveliina.korhonen@uef.fi; maija.toppila@uef.fi;
   ali.koskela@uef.fi; kai.kaarniranta@uef.fi; yashavanthi.mysore@uef.fi;
   anu.kauppinen@uef.fi
RI Harju, Niina/ABA-7085-2020; Mysore, Yashavanthi/O-2190-2016
OI Harju, Niina/0000-0001-9031-5353; Mysore,
   Yashavanthi/0000-0001-8279-0998; Korhonen, Eveliina/0000-0002-5360-7258;
   Toppila, Maija/0000-0002-8754-0266
FU Academy of Finland [297267, 307341, 328443, 296840]; Emil Aaltonen
   Foundation; Paivikki and Sakari Sohlberg Foundation; Finnish Eye
   Foundation; Sigrid Juselius Foundation; Sokeain Ystavat ry, Silma-ja
   Kudospankkisaatio
FX This research was funded by the Academy of Finland (297267, 307341,
   328443, and 296840), the Emil Aaltonen Foundation, the Paivikki and
   Sakari Sohlberg Foundation, The Finnish Eye Foundation, The Sigrid
   Juselius Foundation, Sokeain Ystavat ry, Silma-ja Kudospankkisaatio. The
   APC was funded by the Academy of Finland (328443).
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NR 57
TC 9
Z9 9
U1 1
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAR
PY 2020
VL 21
IS 6
AR 2066
DI 10.3390/ijms21062066
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LJ0UU
UT WOS:000529890200162
PM 32192228
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Colomer, A
   Naranjo, V
   Janvier, T
   Mossi, JM
AF Colomer, Adrian
   Naranjo, Valery
   Janvier, Thomas
   Mossi, Jose M.
TI Evaluation of fractal dimension effectiveness for damage detection in
   retinal background
SO JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS
LA English
DT Article
DE Retinal fundus image; Fractal analysis; Diabetic retinopathy;
   Age-related macular degeneration; Local binary patterns
ID DIABETIC-RETINOPATHY; AUTOMATIC DETECTION; TRABECULAR BONE; IMAGES;
   ACCURACY; TEXTURE
AB This work investigates the characterization of bright lesions in retinal fundus images using texture analysis techniques. Exudates and drusen are evidences of retinal damage in diabetic retinopathy (DR) and age-related macular degeneration (AMD) respectively. An automatic detection of pathological tissues could make possible an early detection of these diseases. In this work, fractal analysis is explored in order to discriminate between pathological and healthy retinal texture. After a deep preprocessing step, in which spatial and colour normalization are performed, the fractal dimension is extracted locally by computing the Hurst exponent (H) along different directions. The greyscale image is described by the increments of the fractional Brownian motion model and the H parameter is computed by linear regression in the frequency domain. The ability of fractal dimension to detect pathological tissues is demonstrated using a home-made system, based on fractal analysis and Support Vector Machine, able to achieve around a 70% and 83% of accuracy in E-OPHTHA and DIARETDB1 public databases respectively. In a second experiment, the fractal descriptor is combined with texture information, extracted by the Local Binary Patterns, improving the bright lesion detection. Accuracy, sensitivity and specificity values higher than 89%, 80% and 90% respectively suggest that the method presented in this paper is a robust algorithm for describing retina texture and can be useful in the automatic detection of DR and AMD. (C) 2018 Elsevier B.V. All rights reserved.
C1 [Colomer, Adrian; Naranjo, Valery] Univ Politecn Valencia, Inst Invest & Innovac Bioingn I3B, Camino Vera S-N, E-46022 Valencia, Spain.
   [Colomer, Adrian; Naranjo, Valery] UPV FISABIO, Unidad Conjunta, Grp Tecnol Informat Aplicadas Oftalmol, Valencia, Spain.
   [Janvier, Thomas] Univ Orleans, Lab I3MTO, Rue Chartres,BP 6759, F-45067 Orleans 2, France.
   [Mossi, Jose M.] Univ Politecn Valencia, ITEAM Res Inst, Camino Vera S-N, E-46022 Valencia, Spain.
C3 Universitat Politecnica de Valencia; Universite de Orleans
RP Colomer, A (通讯作者)，Univ Politecn Valencia, Inst Invest & Innovac Bioingn I3B, Camino Vera S-N, E-46022 Valencia, Spain.
EM adcogra@i3b.upv.es; vnaranjo@i3b.upv.es; thomas.janvier@univ-orleans.fr;
   jmmossi@dcom.upv.es
RI Colomer Granero, Adrián/GZM-7967-2022; Mossi, Jose M./F-9777-2016
OI Colomer Granero, Adrián/0000-0002-7616-6029; Mossi, Jose
   M./0000-0001-9083-3476; Naranjo, Valery/0000-0002-0181-3412
FU European Union's Horizon research and innovation programme under the
   Project GALAHAD [H-ICT] [732613]; Ministerio de Economia y
   Competitividad of Spain, Project SICAP [DPI2016-77869-C2-1-R]; Spanish
   Government under a FPI Grant [BES-2014-067889]
FX This paper was supported by the European Union's Horizon 2020 research
   and innovation programme under the Project GALAHAD [H2020-ICT-2016-2017,
   732613]. In addition, this work was partially funded by the Ministerio
   de Economia y Competitividad of Spain, Project SICAP
   [DPI2016-77869-C2-1-R]. The work of Adrian Colomer has been supported by
   the Spanish Government under a FPI Grant [BES-2014-067889]. We
   gratefully acknowledge the support of NVIDIA Corporation with the
   donation of the Titan Xp GPU used for this research.
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NR 42
TC 7
Z9 7
U1 1
U2 22
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0377-0427
EI 1879-1778
J9 J COMPUT APPL MATH
JI J. Comput. Appl. Math.
PD AUG 1
PY 2018
VL 337
BP 341
EP 353
DI 10.1016/j.cam.2018.01.005
PG 13
WC Mathematics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Mathematics
GA GA8RR
UT WOS:000428607900022
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Fogli, S
   Del Re, M
   Rofi, E
   Posarelli, C
   Figus, M
   Danesi, R
AF Fogli, Stefano
   Del Re, Marzia
   Rofi, Eleonora
   Posarelli, Chiara
   Figus, Michele
   Danesi, Romano
TI Clinical pharmacology of intravitreal anti-VEGF drugs
SO EYE
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; OCCLUSION 12-MONTH OUTCOMES; RETINAL VEIN
   OCCLUSIONS; MACULAR EDEMA; INTRAOCULAR PHARMACOKINETICS; IN-VITRO;
   SUSTAINED BENEFITS; FACTOR-TRAP; 0.5 MG; RANIBIZUMAB
AB Clinical efficacy of intravitreal anti-VEGF drugs has been widely demonstrated in several angiogenesis-driven eye diseases including diabetic macular edema and the neovascular form of age-related macular degeneration. Pegaptanib, ranibizumab, and aflibercept have been approved for use in the eye, whereas bevacizumab is widely used by ophthalmologists to treat patients "off-label". These drugs are active in the nanomolar to picomolar range; however, caution is required when establishing the rank order of affinity and potency due to in vitro inter-experimental variation. Despite the small doses used for eye diseases and the intravitreal route of administration may limit systemic side effects, these drugs can penetrate into blood circulation and alter systemic VEGF with unknown clinical consequences, particularly in vulnerable groups of patients. Clinical pharmacokinetics of ocular anti-VEGF agents should therefore be taken into account when choosing the right drug for the individual patient. The gaps in current understanding that leave open important questions are as follows: (i) uncertainty about which drug should be given first, (ii) how long these drugs can be used safely, and (iii) the choice of the best pharmacological strategy after first-line treatment failure. The current review article, based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and available on the PubMed database, describes in detail the clinical pharmacology of this class of drugs to provide a sound pharmacological basis for their proper use in ophthalmology clinical practice.
C1 [Fogli, Stefano; Del Re, Marzia; Rofi, Eleonora; Danesi, Romano] Univ Pisa, Dept Clin & Expt Med, Clin Pharmacol & Pharmacogenet Unit, Pisa, Italy.
   [Posarelli, Chiara; Figus, Michele] Univ Hosp, Ophthalmol Unit, Dept Surg, Pisa, Italy.
C3 University of Pisa; University of Pisa; Azienda Ospedaliero
   Universitaria Pisana
RP Fogli, S (通讯作者)，Univ Pisa, Dept Clin & Expt Med, Clin Pharmacol & Pharmacogenet Unit, Pisa, Italy.
EM stefano.fogli@unipi.it
RI Figus, Michele/AAD-6850-2020; Fogli, Stefano/AAB-5874-2022; Danesi,
   Romano/AAC-9410-2019; Fogli, Stefano/AAC-1939-2019; Danesi,
   Romano/J-7239-2018; Figus, Michele/AAA-9808-2019; Posarelli,
   Chiara/AAW-9528-2020; Posarelli, Chiara/AAA-8278-2019; Del Re,
   Marzia/J-6468-2018
OI Fogli, Stefano/0000-0002-7845-2598; Danesi, Romano/0000-0002-4414-8934;
   Danesi, Romano/0000-0002-4414-8934; Figus, Michele/0000-0003-2243-9033;
   Posarelli, Chiara/0000-0003-0222-5177; Del Re,
   Marzia/0000-0001-7343-6161
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NR 100
TC 81
Z9 83
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JUN
PY 2018
VL 32
IS 6
BP 1010
EP 1020
DI 10.1038/s41433-018-0021-7
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GJ0ZH
UT WOS:000434982700003
PM 29398697
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Einarsdottir, AB
   Hardarson, SH
   Kristjansdottir, JV
   Bragason, DT
   Snaedal, J
   Stefansson, E
AF Einarsdottir, Anna Bryndis
   Hardarson, Sveinn Hakon
   Kristjansdottir, Jona Valgerdur
   Bragason, David Thor
   Snaedal, Jon
   Stefansson, Einar
TI Retinal Oximetry Imaging in Alzheimer's Disease
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Alzheimer's disease; blood vessels; diagnosis; hemoglobin; oxygen;
   retina; retinal oximetry; vessel diameter
ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; OXYGEN-SATURATION;
   MACULAR DEGENERATION; MULTIPLE-SCLEROSIS; EYE; RETINOPATHY; VESSELS;
   BRAIN; LIGHT
AB Background: Structural and physiological abnormalities have been reported in the retina in Alzheimer's disease (AD). Retinal oximetry detects changes in retinal oxygen metabolism in many eye diseases, where structural changes are seen.
   Objective: To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort.
   Methods: Oxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. 18 individuals with mild to moderate dementia of the Alzheimer-type (stage 3-5 according to the Global Deterioration Scale) and 18 healthy subjects underwent retinal oximetry in a case control study.
   Results: Retinal oxygen saturation in arterioles and venules in patients with moderate AD was significantly elevated compared to healthy individuals. Retinal arterioles have 94.2 +/- 5.4% oxygen saturation in moderate AD compared with 90.5 +/- 3.1% in healthy subjects (mean +/- SD, n = 10, p = 0.028). Retinal venules were 51.9 +/- 6.0% saturated in moderate AD compared with 49.7 +/- 7.0% in healthy subjects (mean +/- SD, n = 10, p = 0.02).
   Conclusion: This is the first study of retinal oxygen metabolism in any central nervous system disease. It discovers abnormalities in retinal oxygen metabolism in AD. The findings are similar to those seen in age-related macular degeneration and diabetic retinopathy. Noninvasive retinal oximetry may offer new insights into pathophysiology of AD. Further studies are needed to confirm and expand these findings.
C1 [Einarsdottir, Anna Bryndis] Natl Univ Hosp Reykjavik, Landspitali, Dept Neurol, Reykjavik, Iceland.
   [Hardarson, Sveinn Hakon; Kristjansdottir, Jona Valgerdur; Bragason, David Thor; Stefansson, Einar] Natl Univ Hosp Reykjavik, Landspitali, Dept Ophthalmol, Reykjavik, Iceland.
   [Snaedal, Jon] Natl Univ Hosp Reykjavik, Landspitali, Dept Geriatr, Reykjavik, Iceland.
   [Hardarson, Sveinn Hakon; Kristjansdottir, Jona Valgerdur; Stefansson, Einar] Univ Iceland, Reykjavik, Iceland.
C3 Landspitali National University Hospital; Landspitali National
   University Hospital; Landspitali National University Hospital;
   University of Iceland
RP Einarsdottir, AB (通讯作者)，Landspitali, Dept Neurol, IS-108 Reykjavik, Iceland.
EM abe1@hi.is
OI Hardarson, Sveinn Hakon/0000-0001-5865-6756
FU Helga Jonsdottir and Sigurlidi Kristjansson Memorial Fund
FX This study was presented in part at the Alzheimer Association
   International Conference in Copenhagen in June 2014. ES and SHH are
   shareholders in Oxymap ehf, which produces retinal oximeters. The study
   was supported by Helga Jonsdottir and Sigurlidi Kristjansson Memorial
   Fund.
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NR 22
TC 58
Z9 61
U1 2
U2 15
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 2016
VL 49
IS 1
BP 79
EP 83
DI 10.3233/JAD-150457
PG 5
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA CV6VH
UT WOS:000364409100009
PM 26444785
DA 2022-11-30
ER

PT J
AU Bertolotti, E
   Neri, A
   Camparini, M
   Macaluso, C
   Marigo, V
AF Bertolotti, Evelina
   Neri, Alberto
   Camparini, Monica
   Macaluso, Claudio
   Marigo, Valeria
TI Stem cells as source for retinal pigment epithelium transplantation
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Retinal stem cells; Retinal neurospheres; RPE65; LRAT; Bestrophin 1;
   Beta5-integrin; OA1; CRALBP; MITF
ID OUTER SEGMENT PHAGOCYTOSIS; OCULAR ALBINISM TYPE-1; ENDOTHELIAL
   GROWTH-FACTOR; IN-VITRO DIFFERENTIATION; LONG-TERM SAFETY; HUMAN RPE
   CELLS; MACULAR DEGENERATION; BINDING-PROTEIN; OCULOCUTANEOUS ALBINISM;
   DIRECTED DIFFERENTIATION
AB Inherited maculopathies, age related macular degeneration and some forms of retinitis pigmentosa are associated with impaired function or loss of the retinal pigment epithelium (RPE). Among potential treatments, transplantation approaches are particularly promising. The arrangement of RPE cells in a well-defined tissue layer makes the RPE amenable to cell or tissue sheet transplantation. Different cell sources have been suggested for RPE transplantation but the development of a clinical protocol faces several obstacles. The source should provide a sufficient number of cells to at least recover the macula area. Secondly, cells should be plastic enough to be able to integrate in the host tissue. Tissue sheets should be considered as well, but the substrate on which RPE cells are cultured needs to be carefully evaluated. Immunogenicity can also be an obstacle for effective transplantation as well as tumorigenicity of not fully differentiated cells. Finally, ethical concerns may represent drawbacks when embryo-derived cells are proposed for RPE transplantation. Here we discuss different cell sources that became available in recent years and their different properties. We also present data on a new source of human RPE. We provide a protocol for RPE differentiation of retinal stem cells derived from adult ciliary bodies of postmortem donors. We show molecular characterization of the in vitro differentiated RPE tissue and demonstrate its functionality based on a phagocytosis assay. This new source may provide tissue for allogenic transplantation based on best matches through histocompatibility testing. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Bertolotti, Evelina; Marigo, Valeria] Univ Modena & Reggio Emilia, Dept Life Sci, I-41125 Modena, Italy.
   [Neri, Alberto; Camparini, Monica; Macaluso, Claudio] Univ Parma, SBiBiT Dept, I-43100 Parma, Italy.
C3 Universita di Modena e Reggio Emilia; University of Parma
RP Marigo, V (通讯作者)，Univ Modena & Reggio Emilia, Dept Life Sci, Via Campi 287, I-41125 Modena, Italy.
EM valeria.marigo@unimore.it
RI Marigo, Valeria/B-7947-2015
OI Marigo, Valeria/0000-0002-4428-2084; Neri, Alberto/0000-0001-7273-8571
FU Italian "Istituto Superiore di Sanita"-ERARE; Programma Strategico
   RARER-Programma di ricerca Regione-Universita; Vision of Children
   Foundation
FX This study was funded by the Italian "Istituto Superiore di
   Sanita"-ERARE, Programma Strategico RARER-Programma di ricerca
   Regione-Universita 2010-2012, and the Vision of Children Foundation. The
   authors would like to acknowledge the CIGS of University of Modena and
   Reggio Emilia for providing confocal microscopy assistance and E.
   Nandrot, K. Palczewski and M. Redmond for reagents.
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NR 159
TC 36
Z9 39
U1 0
U2 23
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 2014
VL 42
BP 130
EP 144
DI 10.1016/j.preteyeres.2014.06.002
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AO6NT
UT WOS:000341469500006
PM 24933042
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Sharma, S
   Sayanagi, K
   Kaiser, PK
AF Sharma, Sumit
   Sayanagi, Kaori
   Kaiser, Peter K.
TI Pathology detection rate of spectral domain optical coherence tomography
   devices
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
AB Background Spectral domain optical coherence tomography (SDOCT) allows for higher resolution scans and higher scanning speeds compared to time domain OCT (TDOCT). The purpose of this study is to compare the pathology detection rates of various SDOCT devices to the Stratus TDOCT.
   Methods Patients with neovascular age-related macular degeneration were imaged on the Stratus and one of four SDOCT devices. The images were then analysed in a masked manner evaluating for the presence of epiretinal membrane (ERM), pigment epithelial detachment (PED) and subretinal fluid (SRF). After determining that low scan density with one of the devices was likely the cause of missed PED and SRF compared to the other SDOCT devices the study was repeated with a higher scan density.
   Results 60 eyes from 60 patients with neovascular macular degeneration were imaged on each SDOCT device, for a total of 240 eyes from 240 patients imaged on Stratus. There were no instances where pathology was visible on Stratus but was missed on SDOCT. The highest incidence of missed pathology was with SRF, followed by ERM and PED.
   Conclusions The increased resolution and image quality of SDOCT devices over TDOCT allows for finer discrimination of retinal structures. The increased speed of SDOCT allows for dense coverage of the macula resulting in the ability to see smaller areas of PED and SRF. There was a critical threshold for the distance between B-scans in the three-dimensional cube scan for detection of pathology.
C1 [Sharma, Sumit; Sayanagi, Kaori; Kaiser, Peter K.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation
RP Kaiser, PK (通讯作者)，Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave,Desk i13, Cleveland, OH 44195 USA.
EM pkkaiser@gmail.com
OI Kaiser, Peter/0000-0001-5126-045X
FU Research to Prevent Blindness
FX Supported by Research to Prevent Blindness; no other competing
   interests.
CR Cense B, 2006, Bull Soc Belge Ophtalmol, P123
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NR 10
TC 1
Z9 1
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUN
PY 2014
VL 98
SU 1
BP 3
EP 6
DI 10.1136/bjophthalmol-2013-303846
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AI4MX
UT WOS:000336840600002
PM 24568868
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Yuda, K
   Takahashi, H
   Inoue, T
   Ueta, T
   Iriyama, A
   Kadonosono, K
   Tamaki, Y
   Aburatani, H
   Nagai, R
   Yanagi, Y
AF Yuda, Kentaro
   Takahashi, Hidenori
   Inoue, Tatsuya
   Ueta, Takashi
   Iriyama, Aya
   Kadonosono, Kazuaki
   Tamaki, Yasuhiro
   Aburatani, Hiroyuki
   Nagai, Ryozo
   Yanagi, Yasuo
TI Adrenomedullin Inhibits Choroidal Neovascularization via CCL2 in the
   Retinal Pigment Epithelium
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY;
   MACULAR DEGENERATION; AMYLOID-BETA; IMMUNOREACTIVE ADRENOMEDULLIN;
   BINDING-PROTEIN; GENE-EXPRESSION; RAT-HEART; CELLS
AB The molecular mechanism that leads to age-related macular degeneration (AMD) is poorly understood. Gene expression profiling identified adrenomedullin (ADM) as a possible molecular target for the treatment of AMD and expression of ADM was upregulated in eyes with laser-induced choroidal neovascularization (CNV). In vivo experiments strongly indicated that ADM inhibits laser-induced CNV. In vitro tube formation assay demonstrated that neither ADM nor conditioned medium from the retinal pigment epithelial (RPE) cells, D407 cells, treated with ADM affected the capillary-formation of human umbilical vein endothelial cells. In contrast, in vitro macrophage migration assay clearly demonstrated that the conditioned medium of D407 inhibited macrophage migration. Furthermore, the expression of C-C motif chemokine 2 (CCL2) was significantly inhibited in D407 cells after ADM treatment. In vivo experiments using a laser-induced CNV model in ADM(+/-) mice demonstrated that CCL2 expression was upregulated in ADM(+/-) mice with concomitant increase in macrophage migration in the subretinal space. Additionally, the effect of ADM was abrogated in CCL2 knockout mice. These results suggest that administration of ADM inhibits macrophage migration in the subretinal space and leads to the suppression of laser-induced CNV in an animal model. The inhibition of macrophage migration occurred through the CCL2 from RPE. This study provides a novel potential therapeutic target for AMD which does not substantially disrupt VEGF-A signaling mediated vasculogenesis. (Am J Pathol 2012, 181:14641472 http://dx.dot.org/10.1016/j.ajpath.2012.06.028)
C1 [Yanagi, Yasuo] Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138655, Japan.
   [Nagai, Ryozo] Univ Tokyo, Sch Med, Dept Cardiovasc Med, Tokyo 1138655, Japan.
   [Kadonosono, Kazuaki] Yokohama City Univ, Med Ctr, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan.
   [Aburatani, Hiroyuki] Univ Tokyo, Adv Sci & Technol Res Ctr, Genome Sci Div, Tokyo 1138655, Japan.
C3 University of Tokyo; University of Tokyo; Yokohama City University;
   University of Tokyo
RP Yanagi, Y (通讯作者)，Univ Tokyo, Sch Med, Dept Ophthalmol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM yanagi-tky@umin.ac.jp
RI Yanagi, Yasuo/AAA-5441-2022; Yanagi, Yasuo/AAF-2670-2020; Takahashi,
   Hidenori/H-2945-2019
OI Takahashi, Hidenori/0000-0001-5331-4730; Yanagi,
   Yasuo/0000-0002-0362-7285
FU Ministry of Education, Science, Sports and Culture of Japan [21592217]
FX Supported in part by a grant-in-aid from the Ministry of Education,
   Science, Sports and Culture of Japan (grant 21592217).
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NR 94
TC 16
Z9 18
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD OCT
PY 2012
VL 181
IS 4
BP 1464
EP 1472
DI 10.1016/j.ajpath.2012.06.028
PG 9
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 017DK
UT WOS:000309570100036
PM 22841816
OA Bronze
DA 2022-11-30
ER

PT J
AU Nicholson, BP
   Schachat, AP
AF Nicholson, Benjamin P.
   Schachat, Andrew P.
TI A review of clinical trials of anti-VEGF agents for diabetic retinopathy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Diabetic retinopathy; Pegaptanib; Ranibizumab; Bevacizumab; Vascular
   endothelial growth factor (VEGF)
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB AVASTIN;
   INTERCELLULAR-ADHESION MOLECULE-1; MACULAR EDEMA; LASER
   PHOTOCOAGULATION; PEGAPTANIB SODIUM; CATARACT-SURGERY; RANDOMIZED-TRIAL;
   HUMAN RETINA; RISK-FACTORS
AB Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population worldwide. Many observational and preclinical studies have implicated vascular endothelial growth factor (VEGF) in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration (AMD) have prompted research into the application of anti-VEGF drugs to DR. Here we review the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of diabetic retinopathy.
   For diabetic macular edema, phase II trials of intravitreal pegaptanib and intravitreal ranibizumab have shown short-term benefit in visual acuity. Intravitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness. For proliferative diabetic retinopathy (PDR), early studies suggest that intravitreal bevacizumab temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment (TRD). Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy (PPV) for TRD. Finally, three small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of DME after cataract surgery. Use of anti-VEGF medications for any of these indications is off-label. Despite promising early reports on the safety of these medications, we eagerly await the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy.
C1 [Nicholson, Benjamin P.; Schachat, Andrew P.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation
RP Nicholson, BP (通讯作者)，Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM nicholb2@ccf.org
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NR 92
TC 195
Z9 209
U1 0
U2 42
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 JUL
PY 2010
VL 248
IS 7
BP 915
EP 930
DI 10.1007/s00417-010-1315-z
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 602JB
UT WOS:000278134300001
PM 20174816
DA 2022-11-30
ER

PT J
AU Ritter, M
   Bolz, M
   Sacu, S
   Deak, GG
   Kiss, C
   Pruente, C
   Schmidt-Erfurth, UM
AF Ritter, M.
   Bolz, M.
   Sacu, S.
   Deak, G. G.
   Kiss, C.
   Pruente, C.
   Schmidt-Erfurth, U. M.
TI Effect of intravitreal ranibizumab in avascular pigment epithelial
   detachment
SO EYE
LA English
DT Article
DE age-related macular degeneration; optical coherence tomography; pigment
   epithelial detachment; ranibizumab; VEGF
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; OPTICAL COHERENCE TOMOGRAPHY;
   MACULAR DEGENERATION; BRUCHS MEMBRANE; CLASSIFICATION; ANGIOGRAPHY;
   INJECTION; THERAPY; DRUSEN; TEAR
AB Purpose To evaluate long-term morphologic and functional changes after intravitreal ranibizumab in avascular pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD).
   Patients and methods Interventional, prospective case series; the first group of six patients received three and the second group of six patients received six intravitreal injections of ranibizumab (0.5 mg) at monthly intervals. Outcome measures included the change of PED and retinal volume as determined by spectral domain optical coherence tomography (Cirrus), best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), and macular sensitivity using microperimetry (MP-1; Nidek Co. Ltd).
   Results The mean baseline PED volume of 1.33 mm(3) decreased significantly by 42% at month 6 (-0.55 mm(3), P < 0.05). Compared to baseline no significant change was observed at months 9 and 12. BCVA, retinal volume, and macular sensitivity remained stable during the entire follow-up. In one case a tear of the retinal pigment epithelium was observed after five injections with a consequent decrease of BCVA of four lines.
   Conclusion Treatment with intravitreal injections of ranibizumab may temporarily decrease the volume of avascular PED secondary to AMD, however this effect was not maintained over the 1-year study period. The treatment was ineffective for improving retinal function as measured with BCVA and microperimetry. Eye (2010) 24, 962-968; doi: 10.1038/eye.2009.265; published online 13 November 2009
C1 [Ritter, M.; Bolz, M.; Sacu, S.; Deak, G. G.; Kiss, C.; Pruente, C.; Schmidt-Erfurth, U. M.] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, UM (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
RI Bolz, Matthias/HCI-0622-2022
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Ritter,
   Markus/0000-0003-1406-8340
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NR 27
TC 27
Z9 30
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD JUN
PY 2010
VL 24
IS 6
BP 962
EP 968
DI 10.1038/eye.2009.265
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 608YX
UT WOS:000278623000003
PM 19911018
OA Bronze
DA 2022-11-30
ER

PT J
AU Bruban, J
   Glotin, AL
   Dinet, V
   Chalour, N
   Sennlaub, F
   Jonet, L
   An, N
   Faussat, AM
   Mascarelli, F
AF Bruban, Julien
   Glotin, Anne-Lise
   Dinet, Virginie
   Chalour, Naima
   Sennlaub, Florian
   Jonet, Laurent
   An, Na
   Faussat, Anne Marie
   Mascarelli, Frederic
TI Amyloid-beta(1-42) alters structure and function of retinal pigmented
   epithelial cells
SO AGING CELL
LA English
DT Article
DE aging; degeneration; oxidative stress; retina; tight junction
ID BETA-AMYLOID PEPTIDE; AGE-RELATED MACULOPATHY; FACTOR-H POLYMORPHISM;
   OXIDATIVE STRESS; MACULAR DEGENERATION; BINDING PROTEIN; PRECURSOR
   PROTEIN; PATHOGENESIS; PREVALENCE; EXPRESSION
AB Age-related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid-beta (A beta) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of A beta(1-42) - OA beta(1-42) - on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OA beta(1-42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OA beta(1-42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OA beta(1-42)-induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens-1 and of the visual cycle proteins cellular retinaldehyde-binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of A beta in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting A beta may help develop selective methods for treating diseases involving retinal degeneration, such as AMD.
C1 [Mascarelli, Frederic] Univ Paris 06, INSERM, UMR S872, Ctr Rech Cordeliers, F-75006 Paris, France.
   [Bruban, Julien; Glotin, Anne-Lise; Dinet, Virginie; Chalour, Naima; Sennlaub, Florian; Jonet, Laurent; Mascarelli, Frederic] Univ Paris 05, UMR S 872, F-75006 Paris, France.
   [Bruban, Julien; Glotin, Anne-Lise; Dinet, Virginie; Chalour, Naima; Sennlaub, Florian; Jonet, Laurent; Mascarelli, Frederic] INSERM, U872, F-75006 Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; UDICE-French Research Universities; Universite Paris Cite;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Universite Paris Cite
RP Mascarelli, F (通讯作者)，Univ Paris 06, INSERM, UMR S872, Ctr Rech Cordeliers, 15 Rue Ecole Med, F-75006 Paris, France.
EM mascarelli@idf.inserm.fr
RI Sennlaub, Florian/F-2756-2017; Mascarelli, Frederic/L-8916-2018
OI Sennlaub, Florian/0000-0003-4412-1341; Dinet,
   virginie/0000-0002-5458-0253
FU EVI-GenoRET [LSHG-CT-2005-512036]; RETINA France; Ministere de la
   Recherche; FEdEration des Aveugles et HandicapEs Visuels de France;
   Agence Nationale de la Recherche Scientifique (ANR)
FX This study was supported by grant LSHG-CT-2005-512036 from EVI-GenoRET
   (FrEdEric Mascarelli and Virginie Dinet), RETINA France (FrEdEric
   Mascarelli), the Ministere de la Recherche (Julien Bruban and Naima
   Chalour) and the FEdEration des Aveugles et HandicapEs Visuels de France
   (Anne-Lise Glotin), Agence Nationale de la Recherche Scientifique (ANR)
   (FrEdEric Mascarelli and Virginie Dinet).
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NR 54
TC 94
Z9 96
U1 1
U2 8
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD APR
PY 2009
VL 8
IS 2
BP 162
EP 177
DI 10.1111/j.1474-9726.2009.00456.x
PG 16
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 424ZQ
UT WOS:000264607200008
PM 19239420
OA Bronze
DA 2022-11-30
ER

PT J
AU O'Connor, PM
   Lamoureux, EL
   Keeffe, JE
AF O'Connor, P. M.
   Lamoureux, E. L.
   Keeffe, J. E.
TI Predicting the need for low vision rehabilitation services
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VISUAL IMPAIRMENT; QUESTIONNAIRE; PARTICIPATION; PERFORMANCE; ABILITY;
   PEOPLE; IMPACT; URBAN; FALLS; CARE
AB Aims: To determine the independent predictors of rehabilitation needs for people with low vision using the Impact of Vision Impairment questionnaire (IVI) to measure the quality-of-life consequences of vision-specific restrictions on participation in activities of daily living.
   Methods: Patients attending low vision clinics completed the IVI and provided personal and clinical information such as co-morbidities and visual acuity. Rasch analysis was used to generate person measures for the IVI total and three domain scores. Rehabilitation needs were based on '' mild '', '' moderate '' or '' severe '' levels of restriction in participation as determined by the lower, moderate and higher tertiles of persons measures. Logistic regression analyses were used to determine independent predictors of rehabilitation needs.
   Results: 477 patients (56% women) with a mean age 72 years (SD 15.3) were recruited. Most (74%) had moderate or severe vision loss ( presenting visual acuity (VA)< 6/18), and 43% had age-related macular degeneration (AMD). Females, shorter duration of vision impairment, having AMD, worse VA, a greater impact of co-morbidities on daily living and reliance on family or friends were univariately associated with poorer IVI scores (p < 0.05). In all regression models, VA, the impact of comorbidities on daily living and dependence on family/friends emerged as the three strongest independent predictors of rehabilitation needs.
   Conclusion: In addition to vision, clinicians also need to consider issues relating to dependency when assessing rehabilitation needs. A more holistic approach to patient referral and rehabilitation provision is therefore warranted.
C1 [O'Connor, P. M.; Lamoureux, E. L.; Keeffe, J. E.] Univ Melbourne, Ctr Eye Res Australia, Melbourne 8002, Australia.
   [O'Connor, P. M.; Lamoureux, E. L.; Keeffe, J. E.] Vis CRC, Sydney, NSW, Australia.
C3 Centre for Eye Research Australia; University of Melbourne
RP O'Connor, PM (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Locked Bag 8, Melbourne 8002, Australia.
EM ocp@unimelb.edu.au
RI Lamoureux, Ecosse/Z-5482-2019
CR Baker RS, 2005, OPHTHAL EPIDEMIOL, V12, P1, DOI 10.1080/09286580590921330
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NR 24
TC 22
Z9 22
U1 3
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 FEB
PY 2008
VL 92
IS 2
BP 252
EP 255
DI 10.1136/bjo.2007.125955
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 256GH
UT WOS:000252715200021
PM 18227205
DA 2022-11-30
ER

PT J
AU Sagara, N
   Kawaji, T
   Takano, A
   Inomata, Y
   Inatani, M
   Fukushima, M
   Tanihara, H
AF Sagara, Nina
   Kawaji, Takahiro
   Takano, Akiomi
   Inomata, Yasuya
   Inatani, Masaru
   Fukushima, Mikiko
   Tanihara, Hidenobu
TI Effect of pitavastatin on experimental choroidal neovascularization in
   rats
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE choroidal neovascularization; HMG-CoA reductase inhibitor; pitavastatin;
   age-related macular degeneration
ID AGE-RELATED MACULOPATHY; ENDOTHELIAL GROWTH-FACTOR; C-REACTIVE PROTEIN;
   MACULAR DEGENERATION; 5-YEAR INCIDENCE; STATIN USE; EXPRESSION; THERAPY;
   CELLS; ANGIOGENESIS
AB The association between the use of statins and age-related macular degeneration (AMD), a leading cause of blindness, has been evaluated in many clinical studies; however, the results have been contradictory. We evaluated the effect of pitavastatin administration on laser-induced experimental choroidal neovascularization (CNV) in rats. Brown Norway rats received pitavastatin (1.0 mg/kg per day) for I day prior to laser-induced CNV and continued to receive the drug for 14 days. Fluorescein angiograms were graded by masked observers. CNV area and thickness were assessed by fluorescein isothiocyanate-labeled dextran angiography and histology, respectively. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protem-1 (Ccl-2; also known as MCP-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA levels were measured using reverse-transcription polymerase, chain reaction (RT-PCR) and real-time quantitative RT-CR. Pitavastatin-treated rats had significantly less fluorescence leakage compared with the vehicle-treated rats estimated by CNV score using fluorescein angiography. Both the area and the thickness of CNV in pitavastatin-treated rats were significantly reduced compared with the vehicle-treated rats. Gene expression of VEGF, Ccl-2, and ICAM-1 were significantly decreased by pitavastatin administration in experimental CNV. Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolernia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients. (c) 2007 Elsevier Ltd. All rights reserved.
C1 Kumamoto Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Kumamoto 8608556, Japan.
C3 Kumamoto University
RP Kawaji, T (通讯作者)，Kumamoto Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, 1-1-1 Honjo, Kumamoto 8608556, Japan.
EM kawag@white.plala.or.jp
RI Kawaji, Takahiro/AAH-2481-2020
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NR 40
TC 20
Z9 22
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 JUN
PY 2007
VL 84
IS 6
BP 1074
EP 1080
DI 10.1016/j.exer.2007.02.005
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 179HC
UT WOS:000247279300008
PM 17418120
DA 2022-11-30
ER

PT J
AU Jonas, JB
   Jager, M
AF Jonas, JB
   Jager, M
TI Perfluorohexyloctane endotamponade for treatment of subfoveal hemorrhage
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; pars plana vitrectomy;
   perfluorohexyloctane; subfoveal hemorrhage
ID REMOVING SILICONE OIL; INTRAOCULAR LENSES; TAMPONADE
AB PURPOSE. To report on the use of perfluorohexyloctane as a heavy liquid to temporarily tamponade the fovea for the prevention of recurrent massive subfoveal hemorrhage in patients with exudative age-related macular degeneration (ARMD).
   METHODS. The case series comprised seven patients with acute massive subfoveal hemorrhage due to exudative ARMD. The patients underwent pars plana vitrectomy, drainage of the subretinal blood, and foveal endotamponade with perfluorohexyloctane. The perfluorohexyloctane was removed 80.4 +/- 38.1 days (median 98 days; range 22-118 days) after the primary surgery in a second pars plana intervention.
   RESULTS. In six patients (85.7%) the subretinal hemorrhage removed during the first pars plana vitrectomy did not recur after removal of perfluorohexyloctane. In the seventh, however, a subretinal hemorrhage re-developed five days after release of perfluorohexyloctane. No large epiretinal membranes were observed. In six eyes (85.7%), the retina remained attached after removal of perfluorohexyloctane but in one eye proliferative vitreoretinopathy developed, with central retinal detachment. After the first pars plana vitrectomy, visual acuity increased slightly but not significantly (p=0.25), from 0.03 +/- 0.03 to 0.05 +/- 0.07. Intraocular pressure rose from 15.0 +/- 1.9 mm Hg to 24.9 +/- 16.9 mm Hg. After a follow-up of 69.7 +/- 121.0 days after removal of the perfluorohexyloctane, final visual acuity was 0.02 +/- 0.04.
   CONCLUSIONS. Perfluorohexyloctane may be a useful additional tool for preventing the recurrence of subfoveal re-bleeding in exudative ARMD.
C1 Heidelberg Univ, Fac Clin Med, Dept Ophthalmol, Augenklin, D-68167 Mannheim, Germany.
   Heidelberg Univ, Hosp Eye, Fac Clin Med, Augenklin, D-68167 Mannheim, Germany.
C3 Ruprecht Karls University Heidelberg; University of Hamburg; University
   Medical Center Hamburg-Eppendorf; Ruprecht Karls University Heidelberg;
   University of Hamburg; University Medical Center Hamburg-Eppendorf
RP Jonas, JB (通讯作者)，Heidelberg Univ, Fac Clin Med, Dept Ophthalmol, Augenklin, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM Jost.Jonas@augen.ma.uni-heidelberg.de
CR Dick HB, 2000, J CATARACT REFR SURG, V26, P1667
   Hiscott P, 2001, BRIT J OPHTHALMOL, V85, P179, DOI 10.1136/bjo.85.2.179
   Kirchhof B, 2002, AM J OPHTHALMOL, V133, P95, DOI 10.1016/S0002-9394(01)01295-8
   Langefeld S, 1999, GRAEF ARCH CLIN EXP, V237, P201, DOI 10.1007/s004170050219
   Zeana D, 1999, INT OPHTHALMOL, V23, P17, DOI 10.1023/A:1006444615412
   Zeana D, 2000, J CATARACT REFR SURG, V26, P301, DOI 10.1016/S0886-3350(99)00350-8
NR 6
TC 9
Z9 9
U1 0
U2 0
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD NOV-DEC
PY 2002
VL 12
IS 6
BP 534
EP 536
DI 10.1177/112067210201200614
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 629CL
UT WOS:000180032800014
PM 12510723
DA 2022-11-30
ER

PT J
AU Omidkhoda, SF
   Hosseinzadeh, H
AF Omidkhoda, Seyedeh Farzaneh
   Hosseinzadeh, Hossein
TI Saffron and its active ingredients against human disorders: A literature
   review on existing clinical evidence
SO IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
LA English
DT Review
DE Clinical trial; Crocin; Disease; Disorder; Saffron; Therapy
ID CROCUS-SATIVUS-L.; TO-MODERATE DEPRESSION; TYPE-2 DIABETES-MELLITUS;
   DOUBLE-BLIND; METABOLIC SYNDROME; AQUEOUS EXTRACT; ERECTILE DYSFUNCTION;
   ALCOHOLIC EXTRACT; RAT MODEL; PREMENSTRUAL-SYNDROME
AB Saffron, the stigmas of Crocus sativus L., has been mentioned extensively in the traditional reference texts as a herbal medicine. Many clinical trials have been conducted on this valuable herbal substance and its main constituents following numerous cellular and animal assessments. In the present review, we have collected almost all of these clinical studies to clarify how much knowledge has clinically been achieved in this field so far and which scientific gaps are needed to be filled by more studies. A comprehensive literature review was conducted through a two-round search. First, we performed a general search for identifying the human disorders against which saffron was studied. Then, we searched specifically for the combination of saffron keywords and each disease name. Scientific databases including Scopus, PubMed, and Web of science were used for this search. Studies were collected through electronic databases from their inception up to August 2021. The largest number of these clinical studies represent the investigations into saffron efficacy in different neurological and mental disorders, particularly depression. This substance has clinically revealed significant protective effects against various types of depression, age-related macular degeneration, and allergic asthma. In some cases, such as sexual dysfunction, cognitive and metabolic disorder, the effects of saffron are still clinically open to dispute, or there are limited data on its positive influences. Overall, saffron and its constituents have promising effects on human disorders; however, it needs more clinical evidence or meta-analyses to be confirmed.
C1 [Omidkhoda, Seyedeh Farzaneh; Hosseinzadeh, Hossein] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Pharmaceut Res Ctr, Mashhad, Razavi Khorasan, Iran.
   [Hosseinzadeh, Hossein] Mashhad Univ Med Sci, Sch Pharm, Dept Pharmacodynam & Toxicol, Mashhad, Razavi Khorasan, Iran.
C3 Mashhad University Medical Science; Mashhad University Medical Science
RP Hosseinzadeh, H (通讯作者)，Mashhad Univ Med Sci, Pharmaceut Technol Inst, Pharmaceut Res Ctr, Mashhad, Razavi Khorasan, Iran.; Hosseinzadeh, H (通讯作者)，Mashhad Univ Med Sci, Sch Pharm, Dept Pharmacodynam & Toxicol, Mashhad, Razavi Khorasan, Iran.
EM hosseinzadehh@mums.ac.ir
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NR 152
TC 0
Z9 0
U1 3
U2 3
PU MASHHAD UNIV MED SCIENCES
PI MASHHAD
PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 -
   445, MASHHAD, 00000, IRAN
SN 2008-3866
EI 2008-3874
J9 IRAN J BASIC MED SCI
JI Iran. J. Basic Med. Sci.
PD AUG
PY 2022
VL 25
IS 8
BP 913
EP 933
DI 10.22038/IJBMS.2022.63378.13985
PG 21
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 3Z1HD
UT WOS:000844170200001
PM 36159329
DA 2022-11-30
ER

PT J
AU Bulirsch, LM
   Sassmannshausen, M
   Nadal, J
   Liegl, R
   Thiele, S
   Holz, FG
AF Bulirsch, Louisa Maria
   Sassmannshausen, Marlene
   Nadal, Jennifer
   Liegl, Raffael
   Thiele, Sarah
   Holz, Frank G.
TI Short-term real-world outcomes following intravitreal brolucizumab for
   neovascular AMD: SHIFT study
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Brolucizumab; drugs; imaging; macula; neovascularisation
ID MACULAR DEGENERATION; VISUAL-ACUITY; RANIBIZUMAB; TACHYPHYLAXIS;
   BEVACIZUMAB; AFLIBERCEPT; THERAPY
AB Background Brolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients. Methods Patients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (mu m)), central subfield retinal thickness (CSRT (mu m)) and macular volume (mm(3)). Results Sixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (+/- SD) age of 79.5 +/- 6.7 years were included. Mean change of BCVA was 0.03 +/- 0.14 logMAR (p=0.115). Significant reductions were recorded for FCP with a mean (+/- SD) change of -66.81 +/- 72.63 mu m, -66.76 +/- 60.71 mu m for CSRT and -0.27 +/- 0.24 mm(3) for macular volume (all p<0.001). Intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis. Conclusions The results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.
C1 [Bulirsch, Louisa Maria; Sassmannshausen, Marlene; Liegl, Raffael; Thiele, Sarah; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
   [Nadal, Jennifer] Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany.
C3 University of Bonn; University of Bonn
RP Holz, FG (通讯作者)，Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany.
EM Frank.Holz@ukbonn.de
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NR 31
TC 30
Z9 30
U1 2
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2022
VL 106
IS 9
BP 1288
EP 1294
DI 10.1136/bjophthalmol-2020-318672
EA APR 2021
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4D0ZF
UT WOS:000726803100001
PM 33846161
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Tosi, GM
   Giustarini, D
   Franci, L
   Minetti, A
   Imperatore, F
   Caldi, E
   Fiorenzani, P
   Aloisi, AM
   Sparatore, A
   Rossi, R
   Chiariello, M
   Orlandini, M
   Galvagni, F
AF Tosi, Gian Marco
   Giustarini, Daniela
   Franci, Lorenzo
   Minetti, Alberto
   Imperatore, Francesco
   Caldi, Elena
   Fiorenzani, Paolo
   Aloisi, Anna Maria
   Sparatore, Anna
   Rossi, Ranieri
   Chiariello, Mario
   Orlandini, Maurizio
   Galvagni, Federico
TI Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl
   Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE oxidative stress; retinopathy; retinal pigment epithelium; age-related
   macular degeneration; N-acetyl-L-cysteine; N-acetyl-L-cysteine ethyl
   ester
ID MACULAR DEGENERATION; ANTIOXIDANT; ZEAXANTHIN; LUTEIN
AB Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats' eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.
C1 [Tosi, Gian Marco] Univ Siena, Ophthalmol Unit, Dept Med Surg & Neurosci, I-53100 Siena, Italy.
   [Giustarini, Daniela; Minetti, Alberto; Caldi, Elena; Rossi, Ranieri; Orlandini, Maurizio; Galvagni, Federico] Univ Siena, Dept Biotechnol Chem & Pharm, I-53100 Siena, Italy.
   [Franci, Lorenzo; Imperatore, Francesco; Chiariello, Mario] Ist Studio Prevenz & Rete Oncol ISPRO, Core Res Lab, I-53100 Siena, Italy.
   [Franci, Lorenzo; Imperatore, Francesco; Chiariello, Mario] CNR, Ist Fisiol Clin, I-53100 Siena, Italy.
   [Fiorenzani, Paolo; Aloisi, Anna Maria] Univ Siena, Dept Med Surg & Neurosci, I-53100 Siena, Italy.
   [Sparatore, Anna] Univ Milan, Dept Pharmaceut Sci, I-20133 Milan, Italy.
C3 University of Siena; University of Siena; Consiglio Nazionale delle
   Ricerche (CNR); University of Siena; University of Milan
RP Orlandini, M; Galvagni, F (通讯作者)，Univ Siena, Dept Biotechnol Chem & Pharm, I-53100 Siena, Italy.
EM gianmarco.tosi@unisi.it; daniela.giustarini@unisi.it;
   lorenzofranci4@gmail.com; alberto.minetti@student.unisi.it;
   imperatore@ifc.cnr.it; elenac84@hotmail.it; paolo.fiorenzani@unisi.it;
   annamaria.aloisi@unisi.it; anna.sparatore@unimi.it;
   ranieri.rossi@unisi.it; mario.chiariello@cnr.it;
   maurizio.orlandini@unisi.it; federico.galvagni@unisi.it
RI Chiariello, Mario/O-3642-2014; Giustarini, Daniela/AAV-6629-2021;
   Sparatore, Anna/J-8634-2015; Rossi, Ranieri/C-8743-2011
OI Chiariello, Mario/0000-0001-8434-5177; Sparatore,
   Anna/0000-0003-2135-2649; Galvagni, Federico/0000-0003-1967-9554; Rossi,
   Ranieri/0000-0002-0187-4530; Giustarini, Daniela/0000-0003-4929-5316;
   Franci, Lorenzo/0000-0001-6300-1746; Aloisi, Anna
   Maria/0000-0002-9136-9983; IMPERATORE, Francesco/0000-0001-5883-4727
FU MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca) grant
   "Dipartimento di Eccellenza" 2018-2022; I.Ri.Fo.R Onlus (Institute for
   Research, Training, and Rehabilitation) [2747]
FX This study was partially supported by MIUR (Ministero dell'Istruzione,
   dell'Universita e della Ricerca) grant "Dipartimento di Eccellenza"
   2018-2022 to the Department of Biotechnology, Chemistry and Pharmacy,
   and by the I.Ri.Fo.R Onlus (Institute for Research, Training, and
   Rehabilitation), grant number prot.2747, 08/08/2019. The funding sources
   had no involvement in study design; in the collection, analysis, and
   interpretation of data; in the writing of the report; in the decision to
   submit the article for publication.
CR Abokyi S, 2020, OXID MED CELL LONGEV, V2020, DOI 10.1155/2020/7901270
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NR 26
TC 5
Z9 5
U1 2
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JAN
PY 2021
VL 22
IS 2
AR 600
DI 10.3390/ijms22020600
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA PY2OE
UT WOS:000611887300001
PM 33435325
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Di Maggio, I
   Virgili, G
   Giacomelli, G
   Murro, V
   Sato, G
   Amore, F
   Villani, GM
   Fortini, S
   Turco, S
   Pece, A
   Rizzo, R
   Galan, A
   Giordani, L
   Mucciolo, DP
   Nota, L
AF Di Maggio, Ilaria
   Virgili, Gianni
   Giacomelli, Giovanni
   Murro, Vittoria
   Sato, Giovanni
   Amore, Filippo
   Villani, Gianfrancesco Maria
   Fortini, Stefania
   Turco, Simona
   Pece, Alfredo
   Rizzo, Roberta
   Galan, Alessandro
   Giordani, Lucia
   Mucciolo, Dario Pasquale
   Nota, Laura
TI The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 (VA
   LV VFQ-48): Performance of the Italian version
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Low-vision; rehabilitation; quality of life; activities of daily living;
   questionnaires
ID PSYCHOMETRIC PROPERTIES; REHABILITATION; OUTCOMES
AB Purpose: The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 is among the most validated tools to collect patient-reported outcomes in a low-vision population. We have aimed to conduct a pilot validation of the Italian version of the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48. Methods: The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 was translated using a standardized procedure and then administered to consecutive low-vision patients attending rehabilitation services in three centers. Patients were interviewed by a trained psychologist regarding the individual items of the tool. Results: We included 131 patients with a mean visual acuity of 0.91 logMAR (standard deviation: 0.42 logMAR), mostly affected by age-related macular degeneration. The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 showed high internal consistency (Cronbach's alpha: 0.98) and good item-test and item-rest correlation (median: 0.73 and 0.71, respectively). Both the overall score and the subscale (reading, visual motor, mobility and visual information) scores significantly correlated with visual acuity, reading acuity and speed. Reading speed achieved the best absolute correlation with the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 scores (Spearman r: 0.39-0.49). Conclusion: The Italian version of the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 is a valid tool to assess patients attending low-vision services. Revising a few items may further improve the tool.
C1 [Di Maggio, Ilaria; Nota, Laura] Univ Padua, Univ Ctr Disabil Rehabil & Inclus, Dept Philosophy Sociol Pedag & Appl Psychol, Padua, Italy.
   [Virgili, Gianni; Giacomelli, Giovanni; Murro, Vittoria; Giordani, Lucia; Mucciolo, Dario Pasquale] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Careggi Teaching Hosp, Largo Brambilla 3, I-50134 Florence, Italy.
   [Sato, Giovanni; Rizzo, Roberta; Galan, Alessandro] Ctr Reg Riabilitaz Vis Ipovis Complesso Sociosani, AULSS6, Padua, Italy.
   [Amore, Filippo; Fortini, Stefania; Turco, Simona] WHO Collaborating Ctr, Natl Ctr Serv & Res Prevent Blindness & Rehabil V, Rome, Italy.
   [Villani, Gianfrancesco Maria] Ambulatorio Sanit Profess San Vito Srls, Cerea, VR, Italy.
   [Pece, Alfredo] Fdn Retina 3000, Milan, Italy.
C3 University of Padua; University of Florence; Azienda Ospedaliero
   Universitaria Careggi; World Health Organization
RP Mucciolo, DP (通讯作者)，Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Careggi Teaching Hosp, Largo Brambilla 3, I-50134 Florence, Italy.
EM dario.mucciolo@gmail.com
RI Mucciolo, Dario Pasquale/K-1307-2018; giacomelli,
   giovanni/ABC-6173-2020; Virgili, Gianni/P-6607-2014; MURRO,
   VITTORIA/K-1309-2018
OI Mucciolo, Dario Pasquale/0000-0002-1661-5312; Virgili,
   Gianni/0000-0002-9960-2989; MURRO, VITTORIA/0000-0002-9249-4460; Di
   Maggio, Ilaria/0000-0002-1019-2232
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NR 19
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP
PY 2020
VL 30
IS 5
BP 1014
EP 1018
DI 10.1177/1120672119852016
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA OB6JS
UT WOS:000578575700048
PM 31113297
DA 2022-11-30
ER

PT J
AU Buyandelger, U
   Walker, DG
   Yanagisawa, D
   Morimura, T
   Tooyama, I
AF Buyandelger, Undral
   Walker, Douglas G.
   Yanagisawa, Daijiro
   Morimura, Toshifumi
   Tooyama, Ikuo
TI Effects of FTMT Expression by Retinal Pigment Epithelial Cells on
   Features of Angiogenesis
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE mitochondrial ferritin; vascular endothelial growth factor;
   angiogenesis; retinal pigment epithelium; age-related macular
   degeneration; differentiation
ID NF-KAPPA-B; MITOCHONDRIAL FERRITIN; MACULAR DEGENERATION;
   GENE-EXPRESSION; TNF-ALPHA; OXIDATIVE STRESS; AGE; IRON; PROTECTS;
   ARPE-19
AB Aberrant angiogenesis is a pathological feature of a number of diseases and arises from the uncoordinated expression of angiogenic factors as response to different cellular stresses. Age-related macular degeneration (AMD), a leading cause of vision loss, can result from pathological angiogenesis. As a mutation in the mitochondrial ferritin (FTMT) gene has been associated with AMD, its possible role in modulating angiogenic factors and angiogenesis was investigated. FTMT is an iron-sequestering protein primarily expressed in metabolically active cells and tissues with high oxygen demand, including retina. In this study, we utilized the human retinal pigment epithelial cell line ARPE-19, both as undifferentiated and differentiated cells. The effects of proinflammatory cytokines, FTMT knockdown, and transient and stable overexpression of FTMT were investigated on expression of pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial-derived factor (PEDF). Proinflammatory cytokines induced FTMT and VEGF expression, while NF-kappa B inhibition significantly reduced FTMT expression. VEGF protein and mRNA expression were significantly increased in FTMT-silenced ARPE-19 cells. Using an in vitro angiogenesis assay with endothelial cells, we showed that conditioned media from FTMT-overexpressing cells had significant antiangiogenic effects. Collectively, our findings indicate that increased levels of FTMT inhibit angiogenesis, possibly by reducing levels of VEGF and increasing PEDF expression. The cellular models developed can be used to investigate if increased FTMT may be protective in angiogenic diseases, such as AMD.
C1 [Buyandelger, Undral; Walker, Douglas G.; Yanagisawa, Daijiro; Morimura, Toshifumi; Tooyama, Ikuo] Shiga Univ Med Sci, Mol Neurosci Res Ctr, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan.
C3 Shiga University of Medical Science
RP Tooyama, I (通讯作者)，Shiga Univ Med Sci, Mol Neurosci Res Ctr, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan.
EM undral@belle.shiga-med.ac.jp; walker@belle.shiga-med.ac.jp;
   yanisagawa@belle.shiga-med.ac.jp; morimura@belle.shiga-med.ac.jp;
   kinchan@belle.shiga-med.ac.jp
FU JSPS KAKENHI [JP17H03560]; Japan Society for the Promotion of Science
FX This study was supported by JSPS KAKENHI grant number JP17H03560 (I.T.)
   from Japan Society for the Promotion of Science.
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NR 70
TC 3
Z9 3
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAY
PY 2020
VL 21
IS 10
DI 10.3390/ijms21103635
PG 19
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LW7GO
UT WOS:000539312100231
PM 32455741
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wright, CB
   Becker, SM
   Low, LA
   Tagle, DA
   Sieving, PA
AF Wright, Charles B.
   Becker, Steven M.
   Low, Lucie A.
   Tagle, Danilo A.
   Sieving, Paul A.
TI Improved Ocular Tissue Models and Eye-On-A-Chip Technologies Will
   Facilitate Ophthalmic Drug Development
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Review
DE organoid; tissue chip; microphysiological systems
ID PLURIPOTENT STEM-CELLS; TARGETED MOUSE MODELS; RETINAL ORGANOIDS;
   DIFFERENTIATION; GENERATION; EPITHELIUM; RPE
AB In this study, we describe efforts by the National Eye Institute (NEI) and National Center for Advancing Translational Science (NCATS) to catalyze advances in 3-dimensional (3-D) ocular organoid and microphysiological systems (MPS). We reviewed the recent literature regarding ocular organoids and tissue chips. Animal models, 2-dimensional cell culture models, and postmortem human tissue samples provide the vision research community with insights critical to understanding pathophysiology and therapeutic development. The advent of induced pluripotent stem cell technologies provide researchers with enticing new approaches and tools that augment study in more traditional models to provide the scientific community with insights that have previously been impossible to obtain. Efforts by the National Institutes of Health (NIH) have already accelerated the pace of scientific discovery, and recent advances in ocular organoid and MPS modeling approaches have opened new avenues of investigation. In addition to more closely recapitulating the morphologies and physiological responses of in vivo human tissue, key breakthroughs have been made in the past year to resolve long-standing scientific questions regarding tissue development, molecular signaling, and pathophysiological mechanisms that promise to provide advances critical to therapeutic development and patient care. 3-D tissue culture modeling and MPS offer platforms for future high-throughput testing of therapeutic candidates and studies of gene interactions to improve models of complex genetic diseases with no well-defined etiology, such as age-related macular degeneration and Fuchs' dystrophy.
C1 [Wright, Charles B.; Becker, Steven M.; Sieving, Paul A.] NEI, NIH, 31 Ctr Dr,Rm 6A03, Bethesda, MD 20892 USA.
   [Low, Lucie A.; Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Center
   for Advancing Translational Sciences (NCATS)
RP Becker, SM (通讯作者)，NEI, NIH, 31 Ctr Dr,Rm 6A03, Bethesda, MD 20892 USA.
EM steven.becker@nih.gov
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NR 38
TC 6
Z9 6
U1 1
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JAN 1
PY 2020
VL 36
IS 1
BP 25
EP 29
DI 10.1089/jop.2018.0139
PG 5
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA KF7IY
UT WOS:000509414100006
PM 31166829
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Liu, Y
   Kanda, A
   Wu, D
   Ishizuka, ET
   Kase, S
   Noda, K
   Ichihara, A
   Ishida, S
AF Liu, Ye
   Kanda, Atsuhiro
   Wu, Di
   Ishizuka, Erdal Tan
   Kase, Satoru
   Noda, Kousuke
   Ichihara, Atsuhiro
   Ishida, Susumu
TI Suppression of Choroidal Neovascularization and Fibrosis by a Novel RNAi
   Therapeutic Agent against (Pro) renin Receptor
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
ID ENDOTOXIN-INDUCED UVEITIS; NONPROTEOLYTIC ACTIVATION;
   SIGNAL-TRANSDUCTION; OCULAR INFLAMMATION; GROWTH-FACTOR; PRORENIN;
   INHIBITION; CONTRIBUTES; MACROPHAGES; MECHANISMS
AB The receptor-associated prorenin system refers to the pathogenic mechanism whereby prorenin binding to (pro) renin receptor [(P) RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent signaling, and its activation contributes to the molecular pathogenesis of various ocular diseases. We recently developed a new single-stranded RNAi agent targeting both human and mouse (P) RR ((P) RR-proline-modified short hairpin RNA [(P) RR-PshRNA]), and confirmed its therapeutic effect on murine models of ocular inflammation. Here, we investigated the efficacy of (P) RR-PshRNA against laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which are involved in the pathogenesis of age-related macular degeneration (AMD). Administration of (P) RR-PshRNA in mice significantly reduced CNV formation, together with the expression of inflammatory molecules, macrophage infiltration, and extracellular signal-regulated kinase (ERK) 1/2 activation. In addition, (P) RR-PshRNA attenuated subretinal fibrosis, together with epithelial-mesenchymal transition (EMT)-related markers including phosphorylated SMAD2. The suppressive effect of (P) RR-PshRNA is comparable with aflibercept, an anti-vascular endothelial growth factor drug widely used for AMD therapy. AMD patient specimens demonstrated (P) RR co-localization with phosphorylated ERK1/2 in neovascular endothelial cells and retinal pigment epithelial cells. These results indicate that (P) RR contributes to the ocular pathogenesis of both inflammation-related angiogenesis and EMT-driven fibrosis, and that (P) RR-PshRNA is a promising therapeutic agent for AMD.
C1 [Liu, Ye; Kanda, Atsuhiro; Wu, Di; Ishizuka, Erdal Tan; Kase, Satoru; Noda, Kousuke; Ishida, Susumu] Hokkaido Univ, Lab Ocular Cell Biol & Visual Sci, Dept Ophthalmol, Fac Med, Sapporo, Hokkaido 0608638, Japan.
   [Liu, Ye; Kanda, Atsuhiro; Wu, Di; Ishizuka, Erdal Tan; Kase, Satoru; Noda, Kousuke; Ishida, Susumu] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido 0608638, Japan.
   [Ichihara, Atsuhiro] Tokyo Womens Med Univ, Dept Endocrinol & Hypertens, Tokyo 1628666, Japan.
C3 Hokkaido University; Hokkaido University; Tokyo Women's Medical
   University
RP Kanda, A (通讯作者)，Hokkaido Univ, Lab Ocular Cell Biol & Visual Sci, Dept Ophthalmol, Fac Med,Kita Ku, N-15,W-7, Sapporo, Hokkaido 0608638, Japan.; Kanda, A (通讯作者)，Hokkaido Univ, Grad Sch Med, Kita Ku, N-15,W-7, Sapporo, Hokkaido 0608638, Japan.
EM kanda@med.hokudai.ac.jp
FU Bayer Japan Retina Award; Institute of Science of Blood Pressure and
   Hormone; New Energy and Industrial Technology Development Organization
   (NEDO); MEXT KAKENHI [16K11279, 16H05484]; China Scholarship Council
   [201508210220]; Otsuka Toshimi Scholarship Foundation
FX We thank Ikuyo Hirose, Shiho Yoshida, and Miyuki Murata (Hokkaido
   University) for their skilled technical assistance. This work was
   supported in part by the Bayer Japan Retina Award (to A.K.), the
   Institute of Science of Blood Pressure and Hormone (to A.K.), the New
   Energy and Industrial Technology Development Organization (NEDO), and
   MEXT KAKENHI grant numbers 16K11279 (to A.K.) and 16H05484 (to S.I.).
   Y.L. and D.W. are recipients of a scholarship from the China Scholarship
   Council (201508210220) and Otsuka Toshimi Scholarship Foundation,
   respectively.
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NR 49
TC 11
Z9 11
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD SEP 6
PY 2019
VL 17
BP 113
EP 125
DI 10.1016/j.omtn.2019.05.012
PG 13
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA JA6XF
UT WOS:000487984400010
PM 31254924
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Treister, AD
   Nesper, PL
   Fayed, AE
   Gill, MK
   Mirza, RG
   Fawzi, AA
AF Treister, Alison D.
   Nesper, Peter L.
   Fayed, Alaa E.
   Gill, Manjot K.
   Mirza, Rukhsana G.
   Fawzi, Amani A.
TI Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in
   Fellow Eyes of Unilateral Exudative AMD on OCT Angiography
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; choriocapillaris; choroidal
   neovascularization; OCT; optical coherence tomography angiography
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; INDOCYANINE-GREEN VIDEOANGIOGRAPHY;
   RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; RETICULAR PSEUDODRUSEN; BRUCHS MEMBRANE;
   RISK-FACTORS; THICKNESS; DISEASE
AB Purpose: To determine the prevalence of subclinical choroidal neovascularization (CNV) in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and to quantify choriocapillaris nonperfusion adjacent to CNV.
   Methods: We retrospectively reviewed all patients with AMD who underwent OCTA and identified eyes with unilateral exudative AMD. We determined the presence of subclinical CNV on custom en face macular slabs of the outer retina and choriocapillaris and confirmed on cross-sectional scans. Two graders quantified the percent choriocapillaris area of nonperfusion (PCAN) in the entire choriocapillaris slab as well as in the "halo'' zone (200 mu m) surrounding subclinical and exudative CNV lesions.
   Results: Of 140 AMD patients who underwent OCTA, 34 had unilateral exudative AMD, with five of the 34 fellow eyes (14.7%) having subclinical CNV. Compared with PCAN in the entire slab (10.333 +/- 4.288%), we found that "halo'' PCAN, surrounding CNV, was significantly higher (13.045 +/- 5.809%; P < 0.001). Further, there was a trend for higher PCAN in exudative CNV eyes (15.267 +/- 7.230%) compared with their fellow subclinical CNV eyes (10.823 +/- 3.365%, P = 0.115).
   Conclusions: There is a notable prevalence of subclinical CNV in fellow eyes with unilateral exudative CNV, and significantly greater choriocapillaris nonperfusion adjacent to all CNV lesions. We identified a trend for increased choriocapillaris nonperfusion in exudative AMD eyes as compared with their fellow subclinical CNV eyes, which deserves further study.
C1 [Treister, Alison D.; Nesper, Peter L.; Fayed, Alaa E.; Gill, Manjot K.; Mirza, Rukhsana G.; Fawzi, Amani A.] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, 645 N Michigan Ave,Suite 440, 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, Feinberg Sch Med, Dept Ophthalmol, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
EM afawzimd@gmail.com
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558; Fayed, Alaa E./0000-0003-2634-3880
FU NIH [DP3-DK108248]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND
   KIDNEY DISEASES [DP3DK108248] Funding Source: NIH RePORTER
FX Supported by NIH grant DP3-DK108248(AAF) and research instrument support
   by OptoVue, Inc.
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NR 38
TC 34
Z9 37
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD OCT
PY 2018
VL 7
IS 5
AR 19
DI 10.1167/tvst.7.5.19
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GW9UU
UT WOS:000447352100007
PM 30280004
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Manousaridis, K
   Peter-Reichart, S
   Mennel, S
AF Manousaridis, Kleanthis
   Peter-Reichart, Silvia
   Mennel, Stefan
TI Ocriplasmin treatment for vitreomacular traction in real life: can the
   indication spectrum be expanded?
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Macular hole; Ocriplasmin; Optical coherence tomography; Vitreomacular
   traction syndrome
ID DIABETIC MACULAR EDEMA; INTRAVITREAL OCRIPLASMIN; VITRECTOMY; ADHESION;
   OUTCOMES; THICKNESS; EXPERIENCE; INTERFACE; SAFETY; EYES
AB To evaluate the efficacy of intravitreal ocriplasmin for the resolution of vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) in the clinical setting and to assess whether the indication spectrum of this treatment modality can be expanded beyond that of the MIVI-TRUST trials.
   The records of patients with VMT with or without FTMH, who were treated with intravitreal ocriplasmin were reviewed. Patients were divided in two groups. In the first group, VMT with or without FTMH was present without any other macular pathology. In the second group, VMT with or without FTMH occurred alongside of other macular disease including age-related macular degeneration, diabetic maculopathy and post-operative pseudophakic cystoid macular edema.
   Release of the VMT was achieved in 12/20 patients (12/20 eyes) of the first group. 16 eyes in this group met 3 or more criteria known to be associated with favorable prognosis after intravitreal ocriplasmin treatment. No cases of release of the VMT were observed in the second group, which included 15 patients (15 eyes). Significant improvement of visual acuity and reduction of the central macular thickness was observed only in the subgroup of eyes which responded to treatment.
   Concomitant macular pathology was a significant factor for treatment failure and we suggest that ocriplasmin should be regarded with caution in these cases. Careful patient selection for treatment with ocriplasmin using specific criteria in the clinical setting can provide superior results to those reported in the MIVI-TRUST trials.
C1 [Manousaridis, Kleanthis; Peter-Reichart, Silvia; Mennel, Stefan] Acad Teaching Hosp, State Hosp Feldkirch, Dept Ophthalmol, Carinagasse 47, A-6800 Feldkirch, Austria.
RP Manousaridis, K (通讯作者)，Acad Teaching Hosp, State Hosp Feldkirch, Dept Ophthalmol, Carinagasse 47, A-6800 Feldkirch, Austria.
EM kleanthis.manousaridis@googlemail.com
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NR 44
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2017
VL 255
IS 10
BP 1907
EP 1916
DI 10.1007/s00417-017-3731-9
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FG9JV
UT WOS:000410756000006
PM 28681138
DA 2022-11-30
ER

PT J
AU Zhu, C
   Dong, YC
   Liu, HL
   Ren, H
   Cui, ZH
AF Zhu, Chao
   Dong, Yuchen
   Liu, Haile
   Ren, Hua
   Cui, Zhihua
TI Hesperetin protects against H2O2- triggered oxidative damage via
   upregulation of the Keap1-Nrf2/ HO-1 signal pathway in ARPE-19 cells
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE AMD; Hesperetin; Oxidative stress; Nrf2; HO-1
ID PIGMENT EPITHELIAL-CELLS; HEME OXYGENASE-1 EXPRESSION; NF-KAPPA-B;
   ANTIOXIDANT RESPONSE; HYDROGEN-PEROXIDE; STRESS; ACTIVATION; NRF2;
   STABILITY; APOPTOSIS
AB Age-related macular degeneration (AMD) is an irreversible vision loss disease that primarily results from oxidative stress that causes oxidative damage to the retinal pigment epithelial (RPE) cells. Hesperetin (Hesp) is a common flavanone glycoside compound that has been demonstrated to exhibit a variety of biological and pharmacological properties that include anti-inflammatory and antioxidant properties. The aim of this study is to explore the ability of Hesp to attenuate oxidative damage in hydrogen peroxide (H2O2)-stimulated ARPE-19 cells. The results indicated that Hesp treatment not only increased cell survival but also decreased reactive oxygen species (ROS) generation, whereas these roles were effectively enhanced the superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced malondialdehyde (MDA) formation. Importantly, the level of heme oxygenase-1 (HO-1) expression was increased by Hesp exposure, which resulted in a decrease after the transfection of cells with Nrf2-siRNA. Additionally, further results revealed that Hesp treatment significantly elevated Keap-1 protein expression, Nrf2 nuclear translocation and ARE activities. These observations indicated that Hesp treatment effectively protected against H2O2-induced oxidative damage in ARPE-19 cells by inhibiting cell apoptosis, ROS overproduction and MDA formation as well as enhancing the SOD and GSH levels. The underlying mechanisms may be related to the activation of the Keap1-Nrf2/ HO-1 signal pathway, which may provide biological evidence to further encourage the investigation of the protective effect of Hesp in AMD disease. (C) 2016 Elsevier Masson SAS. All rights reserved.
C1 [Liu, Haile; Ren, Hua; Cui, Zhihua] Jilin Univ, Dept Ophthalmol, Hosp 1, Changchun 130021, Peoples R China.
   [Zhu, Chao; Dong, Yuchen] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130041, Peoples R China.
C3 Jilin University; Jilin University
RP Ren, H; Cui, ZH (通讯作者)，Jilin Univ, Dept Ophthalmol, Hosp 1, Changchun 130021, Peoples R China.
EM lvhm63251@163.com; cz3531@163.com
FU Natural Science Foundation of Jilin [20150520050JH]
FX This work supported by a grant from the Natural Science Foundation of
   Jilin (No. 20150520050JH).
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NR 39
TC 88
Z9 101
U1 9
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 APR
PY 2017
VL 88
BP 124
EP 133
DI 10.1016/j.biopha.2016.11.089
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA EM7YJ
UT WOS:000395528000015
PM 28103505
DA 2022-11-30
ER

PT J
AU Libertini, G
   Ferrara, N
AF Libertini, Giacinto
   Ferrara, Nicola
TI Aging of perennial cells and organ parts according to the programmed
   aging paradigm
SO AGE
LA English
DT Review
DE Aging; Cell turnover; Cell senescence; Parkinson disease; Alzheimer
   disease; Age-related macular degeneration
ID AMYLOID BETA-PROTEIN; GLOBOSE BASAL-CELLS; PARKINSONS-DISEASE;
   RISK-FACTORS; STATIN USE; OLFACTORY DYSFUNCTION; MACULAR DEGENERATION;
   VASCULAR DEMENTIA; HEARING-LOSS; MULTIPOTENT PROGENITORS
AB If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.
C1 [Libertini, Giacinto; Ferrara, Nicola] Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy.
C3 University of Naples Federico II
RP Libertini, G (通讯作者)，Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy.
EM giacinto.libertini@tin.it
RI Ferrara, Nicola/ABG-2180-2021; Ferrara, Nicola/A-2904-2014
OI Ferrara, Nicola/0000-0001-8200-4942
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NR 113
TC 4
Z9 12
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD APR
PY 2016
VL 38
IS 2
AR 35
DI 10.1007/s11357-016-9895-0
PG 13
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA DG7GM
UT WOS:000372252800007
PM 26957493
OA Green Published
DA 2022-11-30
ER

PT J
AU Muller, PL
   Muller, S
   Gliem, M
   Kupper, K
   Holz, FG
   Harmening, WM
   Issa, PC
AF Mueller, Philipp L.
   Mueller, Simone
   Gliem, Martin
   Kuepper, Kristina
   Holz, Frank G.
   Harmening, Wolf M.
   Issa, Peter Charbel
TI Perception of Haidinger Brushes in Macular Disease Depends on Macular
   Pigment Density and Visual Acuity
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE Haidinger brush; macular pigment; macular disease; entoptic phenomenon;
   visual acuity
ID OPTICAL-DENSITY; TELANGIECTASIA TYPE-2; POLARIZED-LIGHT; HUMAN RETINA;
   HUMAN EYE; CAROTENOIDS; ZEAXANTHIN; VISION; LUTEIN; MODEL
AB PURPOSE. To optimize the perceptibility of Haidinger brushes (HB) and to investigate its association with visual acuity and macular pigment density.
   METHODS. In this prospective cross-sectional study, each subject underwent best-corrected visual acuity (BCVA) testing, funduscopy, and assessment of macular pigment optical density (MPOD) using the two-wavelength fundus autofluorescence method. Haidinger brush visibility was tested with a rotating linear polarizer and a controllable three-color light-emitting diode (LED) panel as light source. A simple model of macular pigment absorption was used to predict HB visibility as a function of stimulus wavelength and MPOD.
   RESULTS. All control eyes (n = 92) and 34% of the 198 eyes of subjects with macular disease (age-related macular degeneration, n = 40; macular telangiectasia type 2, n = 52; Stargardt disease, n = 58; other retinal dystrophies, n = 48) perceived HB when an optimized test setup (464-nm LED light) was applied. The degree of psychophysical perception and the dependency on different wavelengths were in accordance with the absorptance model. In eyes of subjects with macular disease, minimum thresholds of MPOD and BCVA required for HB perception were identified. Subjects with macular telangiectasia type 2 showed lowest values of MPOD and were mostly unable to perceive HB despite relatively preserved BCVA.
   CONCLUSIONS. Macular pigment and a relatively preserved foveal function are necessary for the perception of HB. Haidinger brushes are usually not perceived by subjects with macular telangiectasia type 2, likely due to their characteristic foveal depletion of macular pigment.
C1 [Mueller, Philipp L.; Mueller, Simone; Gliem, Martin; Kuepper, Kristina; Holz, Frank G.; Harmening, Wolf M.; Issa, Peter Charbel] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
   [Mueller, Philipp L.; Gliem, Martin; Holz, Frank G.; Issa, Peter Charbel] Univ Bonn, Ctr Rare Dis, D-53127 Bonn, Germany.
C3 University of Bonn; University of Bonn
RP Issa, PC (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM peter.issa@ukb.uni-bonn.de
RI Issa, Peter Charbel/E-8935-2018; Müller, Philipp L./P-3350-2019; Issa,
   Peter Charbel/O-2580-2019
OI Issa, Peter Charbel/0000-0002-0351-6673; Issa, Peter
   Charbel/0000-0002-0351-6673; Harmening, Wolf/0000-0001-7053-1198
FU ProRetina Deutschland, Aachen, Germany; German Research Foundation [DFG
   Ha 5323/5-1]; Carl Zeiss Forderfonds
FX Supported by the ProRetina Deutschland, Aachen, Germany; the German
   Research Foundation (DFG Ha 5323/5-1; WMH); and the Carl Zeiss
   Forderfonds ( WMH). The Department of Ophthalmology, University of Bonn,
   receives imaging devices from Heidelberg Engineering, Zeiss, and Optos.
   The sponsor or funding organization had no role in the design or conduct
   of this research.
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NR 59
TC 19
Z9 21
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2016
VL 57
IS 3
BP 1448
EP 1456
DI 10.1167/iovs.15-19004
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DK4BE
UT WOS:000374860600090
PM 27028066
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Li, T
   Aredo, B
   Zhang, KY
   Zhong, X
   Pulido, JS
   Wang, SS
   He, YG
   Huang, XM
   Brekken, RA
   Ufret-Vincenty, RL
AF Li, Tao
   Aredo, Bogale
   Zhang, Kaiyan
   Zhong, Xin
   Pulido, Jose S.
   Wang, Shusheng
   He, Yu-Guang
   Huang, Xianming
   Brekken, Rolf A.
   Ufret-Vincenty, Rafael L.
TI Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium:
   PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex
   Vivo
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroidal neovascularization; phosphatidylserine; PS-targeting antibody;
   choroidal angiogenesis; choroidal sprouting; PS-exposure
ID BINDS ANIONIC PHOSPHOLIPIDS; TUMOR BLOOD-VESSELS; MONOCLONAL-ANTIBODY;
   MACULAR DEGENERATION; AUTOANTIBODY BIOMARKERS; PLASMA-MEMBRANE; SURFACE;
   VEGF; MODEL; MICE
AB PURPOSE. Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV.
   METHODS. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts.
   RESULTS. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis.
   CONCLUSIONS. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.
C1 [Li, Tao; Aredo, Bogale; Zhang, Kaiyan; Zhong, Xin; He, Yu-Guang; 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.
   [Zhang, Kaiyan] Hainan Prov Peoples Hosp, Dept Ophthalmol, Haikou, Hainan, Peoples R China.
   [Pulido, Jose S.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA.
   [Pulido, Jose S.] Mayo Clin, Dept Mol Med, Rochester, MN USA.
   [Wang, Shusheng] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
   [Wang, Shusheng] Tulane Univ, Dept Ophthalmol, New Orleans, LA 70118 USA.
   [Huang, Xianming; Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Huang, Xianming; Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
   [Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical
   Center Dallas; Huazhong University of Science & Technology; Mayo Clinic;
   Mayo Clinic; Tulane University; 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
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 EYE INSTITUTE [P30EY020799] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY020799, P30 EY020799] Funding Source: Medline
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NR 60
TC 7
Z9 9
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2015
VL 56
IS 12
BP 7137
EP 7145
DI 10.1167/iovs.15-17302
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DB0ZS
UT WOS:000368238200019
PM 26529048
OA Green Published
DA 2022-11-30
ER

PT J
AU Li, J
   Cai, XH
   Xia, QQ
   Yao, K
   Chen, JM
   Zhang, YL
   Naranmandura, H
   Liu, X
   Wu, YL
AF Li, Jie
   Cai, Xianhui
   Xia, Qingqing
   Yao, Ke
   Chen, Jingmeng
   Zhang, Yanli
   Naranmandura, Hua
   Liu, Xin
   Wu, Yalin
TI Involvement of Endoplasmic Reticulum Stress in All-Trans-Retinal-Induced
   Retinal Pigment Epithelium Degeneration
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE all-trans-retinal; retinal pigment epithelium; endoplasmic reticulum;
   reactive oxygen species; mitochondrial dysfunction
ID UNFOLDED PROTEIN RESPONSE; ER STRESS; INDUCED APOPTOSIS; MACULAR
   DEGENERATION; ROD PHOTORECEPTORS; REDOX HOMEOSTASIS; TARGET ORGANELLE;
   OXIDATIVE STRESS; CELL-SURVIVAL; EXPRESSION
AB Excess accumulation of endogenous all-trans-retinal (atRAL) contributes to degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, and plays a role in the etiologies of age-related macular degeneration (AMD) and Stargardt's disease. In this study, we reveal that human RPE cells tolerate exposure of up to 5 A mu M atRAL without deleterious effects, but higher concentrations are detrimental and induce cell apoptosis. atRAL treatment significantly increased production of intracellular reactive oxygen species (ROS) and up-regulated mRNA expression of Nrf2, HO-1, and gamma-GCSh within RPE cells, thereby causing oxidative stress. ROS localized to mitochondria and endoplasmic reticulum (ER). ER-resident molecular chaperone BiP, a marker of ER stress, was up-regulated at the translational level, and meanwhile, the PERK-eIF2 alpha-ATF4 signaling pathway was activated. Expression levels of ATF4, CHOP, and GADD34 in RPE cells increased in a concentration-dependent manner after incubation with atRAL. Salubrinal, a selective inhibitor of ER stress, alleviated atRAL-induced cell death. The antioxidant N-acetylcysteine (NAC) effectively blocked RPE cell loss and ER stress activation, suggesting that atRAL-induced ROS generation is responsible for RPE degeneration and is an early trigger of ER stress. Furthermore, the mitochondrial transmembrane potential was lost after atRAL exposure, and was followed by caspase-3 activation and poly (ADP-ribose) polymerase cleavage. The results demonstrate that atRAL-driven ROS overproduction-induced ER stress is involved in cellular mitochondrial dysfunction and apoptosis of RPE cells.
C1 [Li, Jie; Cai, Xianhui; Zhang, Yanli; Wu, Yalin] Zhejiang Univ, Coll Pharmaceut Sci, 866 Yu Hang Tang Rd, Hangzhou 310058, Zhejiang, Peoples R China.
   [Xia, Qingqing] Zhejiang Univ, Sch Med, Ctr Stem Cell & Tissue Engn, Hangzhou 310058, Zhejiang, Peoples R China.
   [Yao, Ke; Liu, Xin; Wu, Yalin] Zhejiang Univ, Sch Med, Ctr Eye, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China.
   [Chen, Jingmeng] Zhejiang Univ City Coll, Sch Med, Hangzhou 310015, Zhejiang, Peoples R China.
   [Naranmandura, Hua] Zhejiang Univ, Sch Med & Publ Hlth, Dept Toxicol, Hangzhou 310058, Zhejiang, Peoples R China.
C3 Zhejiang University; Zhejiang University; Zhejiang University; Zhejiang
   University City College; Zhejiang University
RP Wu, YL (通讯作者)，Zhejiang Univ, Coll Pharmaceut Sci, 866 Yu Hang Tang Rd, Hangzhou 310058, Zhejiang, Peoples R China.
EM yalinw@zju.edu.cn
RI Yao, Ke/AAM-6866-2021; Naranmandura, Hua/C-6499-2015
OI Li, Jie/0000-0001-5463-3995; Naranmandura, Hua/0000-0003-0799-2340
FU China National Natural Science Foundation [21202146, 81271018]; Zhejiang
   Key Laboratory Funds of China [2011E10006]; Zhejiang Key Innovation Team
   Project of China [2009R50039]; Project of National Clinical Key
   Discipline of Chinese Ministry of Health Grant
FX China National Natural Science Foundation (grants 21202146 and 81271018
   to Y.W.); Zhejiang Key Laboratory Funds of China (grant 2011E10006 to
   K.Y.); Zhejiang Key Innovation Team Project of China (grant 2009R50039
   to K.Y.); and Project of National Clinical Key Discipline of Chinese
   Ministry of Health Grant (to K.Y.).
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NR 42
TC 30
Z9 31
U1 0
U2 27
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JAN
PY 2015
VL 143
IS 1
BP 196
EP 208
DI 10.1093/toxsci/kfu223
PG 13
WC Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Toxicology
GA CC1LH
UT WOS:000350101700021
PM 25331497
OA Bronze
DA 2022-11-30
ER

PT J
AU Rodriguez, IR
   Clark, ME
   Lee, JW
   Curcio, CA
AF Rodriguez, Ignacio R.
   Clark, Mark E.
   Lee, Jung Wha
   Curcio, Christine A.
TI 7-ketocholesterol accumulates in ocular tissues as a consequence of
   aging and is present in high levels in drusen
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE 7-Ketocholesterol; Monkey; Retina; Drusen; Aging; Human; Cholesterol;
   Age-related macular degeneration
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; BASAL DEPOSITS; CHOLESTEROL;
   INFLAMMATION; EYES; PREVALENCE; MEMBRANE
AB We analyzed by LCMS lipid extracts of lens, retina (MNR) and RPE/Choroid (MPEC) from macaque monkeys 2-25 yr in age to determine their content of 7-ketocholesterol (7KCh) as function of age. In addition we also analyzed drusen capped with retinal pigment epithelium (RPE), RPE, and neural retina from human donors age 72-95 yr. The lowest 7KCh levels were found in monkey lens (<0.5-3.5 pmol 7KCh per nmol Ch), the second highest in MNR (1-15 pmol/nmol), and the highest in MPEC (1 to >60 pmol/nmol). Despite individual variability all three tissues demonstrated a strong age-related increase. In older human donors 7KCh levels were significantly higher. The levels in human neural retina ranged from 8 to 20 pmol/nmol, similar to the oldest monkeys, but 7-KCh levels in RPE ranged from 200 to 17,000 pmol/nmol, and in RPE-capped drusen from 200 to 2000 pmol/nmol, levels that would be lethal in most cultured cell systems. Most of the 7KCh is sequestered and not readily available to the surrounding tissue, based on published histochemical evidence that extracellular cholesterol (Ch) and cholesteryl fatty acid esters (CEs) are highly concentrated in Bruch's membrane and drusen. However, adjacent tissues, especially RPE but also choriocapillaris endothelium, could be chronically inflamed and in peril of receiving a lethal exposure. Implications for initiation and progression of age-related macular degeneration are discussed. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Rodriguez, Ignacio R.; Lee, Jung Wha] NEI, Lab Retinal Cell & Mol Biol, Mech Retinal Dis Sect, NIH, Bethesda, MD USA.
   [Clark, Mark E.; Curcio, Christine A.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); University of Alabama System; University of Alabama Birmingham
RP Curcio, CA (通讯作者)，Univ Alabama Birmingham, EyeSight Fdn, Sch Med, Dept Ophthalmol,Alabama Vision Res Labs, 1670 Univ Blvd Room 360, Birmingham, AL 35294 USA.
EM curcio@uab.edu
FU National Eye Institute Intramural Research program; NIH [EY06109];
   Arnold and Mabel Beckman Initiative for Macular Research; Research to
   Prevent Blindness, Inc.; EyeSight Foundation of Alabama; NATIONAL EYE
   INSTITUTE [R01EY006109] Funding Source: NIH RePORTER
FX National Eye Institute Intramural Research program (IRR); NIH grant
   EY06109, Arnold and Mabel Beckman Initiative for Macular Research (D.
   Stambolian MD PhD; co-PI), unrestricted funds to the UAB Department of
   Ophthalmology from Research to Prevent Blindness, Inc., and from
   EyeSight Foundation of Alabama (CAC).
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NR 27
TC 40
Z9 41
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 2014
VL 128
BP 151
EP 155
DI 10.1016/j.exer.2014.09.009
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AS5LL
UT WOS:000344312300019
PM 25261634
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Fang, IM
   Yang, CH
   Yang, CM
AF Fang, I-Mo
   Yang, Chang-Hao
   Yang, Chung-May
TI Docosahexaenoic acid reduces linoleic acid induced monocyte
   chemoattractant protein-1 expression via PPAR gamma and nuclear
   factor-kappa B pathway in retinal pigment epithelial cells
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE Docosahexaenoic acid; Linoleic acid; Monocyte chemoattractant protein-1;
   Neovascularization; Peroxisome proliferator-activated receptors
ID PROLIFERATOR-ACTIVATED RECEPTORS; DIETARY FATTY-ACIDS; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; KINASE; GENE; INFLAMMATION;
   ADHESION; ALPHA; INHIBITION
AB Scope: To investigate whether docosahexaenoic acid (DHA) could inhibit linoleic acid (LA) induced monocyte chemoattractant protein (MCP)-1 expression in human retinal pigment epithelial (RPE) cells.
   Methods and results: ARPE-19 cells were pretreated with DHA and then exposed to LA. The expression of MCP-1 and PPAR gamma was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 mu M induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05). DHA at 50 and 100 mu M effectively inhibited LA-induced MCP-1 expression and production (p < 0.05) and NF-kappa B activation. In addition, the culture medium from LA-stimulated ARPE-19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 mu M DHA inhibited tube formation. DHA at 100 mu M increased the expression and activity of PPAR gamma (p < 0.05). Pretreatment with PPAR gamma inhibitor (GW9662) abolished the inhibitory effect of DHA (100 mu M) on LA-induced I kappa B degradation, p65 translocation, and MCP-1 expression in ARPE-19 cells (p < 0.05), as well as tube formation in RF6A.
   Conclusion: DHA reduced LA-induced MCP-1 expression via a PPAR gamma- and NF-kappa B-dependent pathway in ARPE-19 cells. These results suggest the molecular mechanisms underlying the beneficial effects of increased consumption of DHA and reduced consumption of LA on age-related macular degeneration.
C1 [Fang, I-Mo] Taipei City Hosp, Dept Ophthalmol, Zhongxiao Branch, Taipei, Taiwan.
   [Fang, I-Mo; Yang, Chang-Hao; Yang, Chung-May] Natl Taiwan Univ Hosp, Dept Ophthalmol, Taipei 10041, Taiwan.
C3 Taipei City Hospital; National Taiwan University; National Taiwan
   University Hospital
RP Yang, CH (通讯作者)，Natl Taiwan Univ Hosp, Dept Ophthalmol, 7 Chung Shan South Rd, Taipei 10041, Taiwan.
EM chyangoph@ntu.edu.tw
RI Yang, Chung-May/AAV-3737-2020; Yang, Chang-Hao/AAR-3759-2021
OI YANG, CHUNG-MAY/0000-0003-4082-420X; YANG, CHANG-HAO/0000-0002-4328-8716
FU Department of Health, Taipei City Government [101-056]
FX This study was supported by research grant from the Department of
   Health, Taipei City Government (101-056).
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NR 41
TC 18
Z9 19
U1 0
U2 8
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1613-4125
EI 1613-4133
J9 MOL NUTR FOOD RES
JI Mol. Nutr. Food Res.
PD OCT
PY 2014
VL 58
IS 10
BP 2053
EP 2065
DI 10.1002/mnfr.201400196
PG 13
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA AQ6DN
UT WOS:000342898900013
PM 25044948
DA 2022-11-30
ER

PT J
AU Wang, L
   Kondo, N
   Cano, M
   Ebrahimi, K
   Yoshida, T
   Barnett, BP
   Biswal, S
   Handa, JT
AF Wang, Lei
   Kondo, Naoshi
   Cano, Marisol
   Ebrahimi, Katayoon
   Yoshida, Takeshi
   Barnett, Bradley P.
   Biswal, Shyam
   Handa, James T.
TI Nrf2 signaling modulates cigarette smoke-induced complement activation
   in retinal pigmented epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Aging-related disease; Complement; Innate immunity; Nrf2; Oxidative
   stress; Free radicals
ID FACTOR-H POLYMORPHISM; NF-KAPPA-B; MACULAR DEGENERATION; OXIDATIVE
   STRESS; GLUTATHIONE SYNTHESIS; NLRP3 INFLAMMASOME; MEDIATED INJURY; 3RD
   COMPONENT; RISK; PATHWAY
AB Whereas cigarette smoking (CS) and dysregulated complement are thought to play central roles in age-related macular degeneration (AMD), their exact roles are unknown. The aim of this study was to determine if CS activates complement and if the antioxidant transcription factor Nrf2 modulates this response. In AMD specimens, Nrf2 immunolabeling was strong in the cytoplasm, with scattered nuclear labeling of macular retinal pigmented epithelial (RPE) cells that appeared normal, but was decreased and without nuclear labeling in dysmorphic cells overlying drusen, a hallmark AMD lesion. Cigarette smoke extract (CSE) induced Nrf2 nuclear translocation in RPE cells with increased antioxidant and complement gene expression. Whereas CFH protein was not altered by CSE, the cell membrane regulator proteins CD46, CD55, and CD59 were decreased, and C3a and Ob, but not iC3b, were increased compared to controls. C5b-9 was increased by CSE, but at sublytic levels, only after addition of normal human serum. Nrf2 knockdown enhanced the increase in C3a and C3b from CSE, but not iC3b, C5a, or C5b-9. CSE also increased IL-lb expression and secretion after C3a generation and was reduced by a C3aR antagonist. In contrast, the Nrf2 activator CDDO-Im restored complement gene expression in RPE cells exposed to CSE. We provide evidence of altered Nrf2 in human AMD and that CSE induces a proinflammatory environment specifically by generating C3a and Ob, and Nrf2 deficiency magnifies this specific complement response. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Wang, Lei; Kondo, Naoshi; Cano, Marisol; Ebrahimi, Katayoon; Yoshida, Takeshi; Barnett, Bradley P.; Handa, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
   [Biswal, Shyam] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Bloomberg School of Public
   Health; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins
   Bloomberg School of Public Health
RP Handa, JT (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
RI Wang, Lei/C-1902-2015; Barnett, Bradley/AAN-1628-2020
OI Wang, Lei/0000-0002-7957-1003; Barnett, Bradley/0000-0002-8301-404X;
   Kondo, Naoshi/0000-0001-6025-3876
FU Thome Foundation Award in AMD; Research to Prevent Blindness Senior
   Scientist Award; Wilmer Core Grant [EY001765]; Research to Prevent
   Blindness;  [EY14005];  [EY019904];  [P50HL107169];  [R01CA140492];
   NATIONAL CANCER INSTITUTE [R01CA140492] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY014005, P30EY001765, R01EY019904] Funding
   Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [P50HL107169] Funding Source: NIH RePORTER
FX We thank Mike Sporn, M.D., Dartmouth School of Medicine, for providing
   CDDO-Im. This work was supported by EY14005 (J.T.H.), EY019904 (J.T.H.),
   P50HL107169 (S.B.), R01CA140492 (S.B.), a Thome Foundation Award in AMD
   (J.T.H.), a Research to Prevent Blindness Senior Scientist Award
   (J.T.H.), a Wilmer Core Grant, EY001765, an unrestricted grant from
   Research to Prevent Blindness, and gifts from the Merlau family and
   Aleda Wright. J.T.H. is a Robert Bond Welch Professor.
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NR 44
TC 64
Z9 65
U1 0
U2 13
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 MAY
PY 2014
VL 70
BP 155
EP 166
DI 10.1016/j.freeradbiomed.2014.01.015
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AG5VP
UT WOS:000335487100015
PM 24440594
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Hua, J
   Gross, N
   Schulze, B
   Michaelis, U
   Bohnenkamp, H
   Guenzi, E
   Hansen, LL
   Martin, G
   Agostini, HT
AF Hua, Jing
   Gross, Nikolai
   Schulze, Brita
   Michaelis, Uwe
   Bohnenkamp, Hermann
   Guenzi, Eric
   Hansen, Lutz L.
   Martin, Gottfried
   Agostini, Hansjuergen T.
TI In vivo imaging of choroidal angiogenesis using fluorescence-labeled
   cationic liposomes
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB; EFFICACY; GROWTH; CANCER;
   NEOVASCULARIZATION; CHEMOTHERAPY; EXPRESSION; SODIUM; MODEL
AB Purpose: Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration (AMD) enables sensitive use of antiangiogenic drugs and reduces adverse side effects. So far, no in vivo imaging methods are available to specifically label active angiogenesis. Here, we report such a technique using fluorophore-labeled cationic liposomes (CL) detected with a standard clinical in vivo scanning laser ophthalmoscope (SLO).
   Methods: C57Bl/6 mice underwent laser coagulations at day 0 (d0) to induce choroidal neovascularization (CNV). Liposomes labeled with Oregon green, rhodamine (Rh), or indocyanine green (ICG) were injected into the tail vein at various time points after laser coagulation, and their fluorescence was observed in vivo 60 min later using an SLO, or afterwards in choroidal flatmounts or cryosections.
   Results: SLO detected accumulated fluorescence only in active CNV lesions with insignificant background noise. The best signal was obtained with CL-ICG. Choroidal flatmounts and cryosections of the eye confirmed the location of retained CL in CNV lesions. Neutral liposomes, in contrast, showed no accumulation.
   Conclusions: These results establish fluorophore-labeled CL as high affinity markers to selectively stain active CNV. This novel, non-invasive SLO imaging technique could improve risk assessment and indication for current intraocular antiangiogenic drugs in neovascular eye diseases, as well as monitor therapeutic outcomes. Labeling of angiogenic vessels using CL can be of interest not only for functional imaging in ophthalmology but also for other conditions where localization of active angiogenesis is desirable.
C1 [Hua, Jing; Gross, Nikolai; Hansen, Lutz L.; Martin, Gottfried; Agostini, Hansjuergen T.] Univ Freiburg, Univ Eye Hosp, D-79106 Freiburg, Germany.
   [Schulze, Brita; Michaelis, Uwe; Bohnenkamp, Hermann; Guenzi, Eric] MediGene AG, Martinsried, Germany.
C3 University of Freiburg
RP Agostini, HT (通讯作者)，Univ Freiburg, Univ Eye Hosp, Killianstr 5, D-79106 Freiburg, Germany.
EM hansjuergen.agostini@uniklinik-freiburg.de
FU German Bundesministerium fur Bildung und Forschung (BMBF)
FX The technical help of Anne Mattes, Beatrix Flugel, and Marc Leinweber is
   gratefully acknowledged. The authors' research was generously supported
   by the German Bundesministerium fur Bildung und Forschung (BMBF).
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NR 25
TC 20
Z9 23
U1 0
U2 12
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 26
PY 2012
VL 18
IS 111
BP 1045
EP 1054
PG 10
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 947MS
UT WOS:000304434700001
PM 22605917
DA 2022-11-30
ER

PT J
AU Sung, HK
   Michael, IP
   Nagy, A
AF Sung, Hoon-Ki
   Michael, Iacovos P.
   Nagy, Andras
TI Multifaceted role of vascular endothelial growth factor signaling in
   adult tissue physiology: an emerging concept with clinical implications
SO CURRENT OPINION IN HEMATOLOGY
LA English
DT Article
DE angiogenesis; antiangiogenic therapy; cancer; organ homeostasis; side
   effects; vascular endothelial growth factor
ID POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; METASTATIC COLORECTAL-CANCER;
   FACTOR-A; VEGF-A; ANGIOGENESIS INHIBITION; PHASE-II; BEVACIZUMAB;
   EXPRESSION; SURVIVAL; HYPOXIA
AB Purpose of review
   In addition to the crucial role of vascular endothelial growth factor (VEGF) A in vessel development, it has become apparent that the VEGF signaling pathway (VSP) plays an important role during adulthood in the maintenance of tissue homeostasis in normal physiological processes, as well as in pathological conditions. This review will focus on the role of the VSP for proper function of many organs in adult life.
   Recent findings
   Although adult angiogenesis is essentially quiescent-with the exception for wound healing and the menstrual cycle-manipulations of the VSP in mice have revealed its much broader and essential role in adult physiology and pathological conditions. Although suppression of the VSP is a promising clinical approach to treat cancer and age-related macular degeneration, it is associated with severe side effects. These adverse reactions caused by systemic VSP suppression in patients and the knowledge that has been gained from mouse models have contributed to our increasing understanding of the vast spectrum of functions that can be attributed to VEGF.
   Summary
   We will review the multifaceted role of VEGF signaling in adult life and highlight how genetic approaches have verified and explained the spectrum of side effects of antiangiogenic therapies using systemic modulation of the VSP. The fascinating parallels that become evident calls for the development of further animal models to address specific questions that could have implications in disease treatments targeting the VSP.
C1 [Sung, Hoon-Ki; Michael, Iacovos P.; Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3H7, Canada.
   [Michael, Iacovos P.; Nagy, Andras] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
C3 University of Toronto; University Toronto Affiliates; Sinai Health
   System Toronto; Lunenfeld Tanenbaum Research Institute; University of
   Toronto
RP Nagy, A (通讯作者)，Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 25 Orde St,5th Floor, Toronto, ON M5T 3H7, Canada.
EM nagy@lunenfeld.ca
RI Nagy, Andras/G-6465-2013; Sung, Hoon-Ki/A-1922-2016; Michael, Iacovos
   P/C-8695-2016; Sung, Hoon-Ki/G-3049-2013
OI Nagy, Andras/0000-0003-4311-0413; Sung, Hoon-Ki/0000-0001-6677-9385;
   Michael, Iacovos P/0000-0001-7674-1233; 
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NR 90
TC 20
Z9 22
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1065-6251
EI 1531-7048
J9 CURR OPIN HEMATOL
JI Curr. Opin. Hematol.
PD MAY
PY 2010
VL 17
IS 3
BP 206
EP 212
DI 10.1097/MOH.0b013e32833865e6
PG 7
WC Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology
GA 591NH
UT WOS:000277307300008
PM 20216210
DA 2022-11-30
ER

PT J
AU Jiang, W
   Chiou, GCY
AF Jiang, Wei
   Chiou, George C. Y.
TI Effects of hydralazine on ocular blood flow laser-induced choroidal
   neovascularization
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE hydralazine; choroid; neovascularization; human umbilical vein
   endothelial cell; age-related macular degeneration
ID AGE; EYES
AB AIM: To investigate the effect of hydralazine on choroidal blood flow in rabbits and laser-induced choroidal neovascularization (CNV) in rats and on tube formation of human umbilical vein endothelial cells (HUVEC).
   METHODS: Female New Zealand white rabbits were used with raised intraocular pressure (TOP) of the left eye to 40mmHg. Hydralazine (10g/L) eye drops were instilled and ocular blood flow was measured with colored microspheres technique. Male Brown Norway rats were treated with Nd: YAG laser to break Bruch's membrane. Hydralazine (5, 10, 20g/L) eye drops or saline alone was instilled three times a day for 4 weeks after laser treatment. Fluorescein angiography (FA) and choroidal flat mount were used to measure the area of CNV. Tube formation of HUVEC was studied at different concentrations of hydralazine.
   RESULTS: With raised IOP to 40mmHg on rabbits, 10g/L hydralazine eye drops enhanced the choroidal blood flow significantly at 30 and 60 minutes after drug instillation. After 4 weeks of drug treatment, 5, 10 and 20g/L hydralazine eye drops all reduced the CNV formation dramatically measured by fluorescein angiography and choroidal flat mount. When HUVEC was cultured on matrix gel for 48 hours, the tube formation of HUVEC were prevented.by hydralazine at 3-30mg /L.
   CONCLUSION: Hydralazine prevents CNV formation in vivo and HUVEC tube formation in vitro, and enhances rabbits' choroidal blood flow after ischemia. It is hoped that hydralazine could be used to treat age-related macular degeneration in the future.
C1 [Jiang, Wei; Chiou, George C. Y.] Texas A&M Hlth Sci Ctr, Coll Med, 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, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
EM chiou@medicine.tamhsc.edu
CR CHELLY JE, 1986, J PHARMACOL EXP THER, V238, P665
   Daiber A, 2005, AM J CARDIOL, V96, p25I, DOI 10.1016/j.amjcard.2005.07.030
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NR 14
TC 2
Z9 2
U1 0
U2 1
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD DEC 18
PY 2009
VL 2
IS 4
BP 324
EP 327
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 664BN
UT WOS:000282934000011
DA 2022-11-30
ER

PT J
AU Martinez-Barricarte, R
   de Jorge, EG
   Montes, T
   Layana, AG
   de Cordoba, SR
AF Martinez-Barricarte, R.
   Goicoechea de Jorge, E.
   Montes, T.
   Layana, A. G.
   Rodriguez de Cordoba, S.
TI Lack of association between polymorphisms in C4b-binding protein and
   atypical haemolytic uraemic syndrome in the Spanish population
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE age-related macular degeneration; atypical haemolytic uraemic syndrome;
   C4b-binding protein; complement; polymorphism
ID HUMAN C4-BINDING PROTEIN; FACTOR-H MUTATIONS; MEMBRANE COFACTOR PROTEIN;
   COMPLEMENT FACTOR-H; MACULAR DEGENERATION; MOLECULAR-BASIS;
   GENE-CLUSTER; ALPHA-CHAIN; S-BINDING; FACTOR-B
AB Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding factor H, membrane co-factor protein, factor I or factor B, is associated strongly with predisposition to atypical haemolytic uraemic syndrome (aHUS). C4b-binding protein (C4BP), a major regulator of the classical pathway of complement activation, also has capacity to regulate the alternative pathway. Interestingly, the C4BP polymorphism p.Arg240His has been associated recently with predisposition to aHUS and the risk allele His240 showed decreased capacity to regulate the alternative pathway. Identification of novel aHUS predisposition factors has important implications for diagnosis and treatment in a significant number of aHUS patients; thus, we sought to replicate these association studies in an independent cohort of aHUS patients. In this study we show that the C4BP His240 allele corresponds to the C4BP*2 allele identified previously by isoelectric focusing in heterozygosis in 1.9-3.7% of unrelated Caucasians. Crucially, we found no differences between 102 unrelated Spanish aHUS patients and 128 healthy age-matched Spanish controls for the frequency of carriers of the His240 C4BP allele. This did not support an association between the p.Arg240His C4BP polymorphism and predisposition to aHUS in the Spanish population. In a similar study, we also failed to sustain an association between C4BP polymorphisms and predisposition to age-related macular degeneration, another disorder which is associated strongly with polymorphisms in factor H, and is thought to involve alternative pathway dysregulation.
C1 [Martinez-Barricarte, R.; Goicoechea de Jorge, E.; Montes, T.; Rodriguez de Cordoba, S.] Ctr Invest Biol, Dept Fisiopatol Celular & Mol, Madrid 28040, Spain.
   [Martinez-Barricarte, R.; Goicoechea de Jorge, E.; Montes, T.; Rodriguez de Cordoba, S.] Ciber Enfermedades Raras, Madrid, Spain.
   [Layana, A. G.] Univ Navarra, Clin Univ, Dept Oftalmol, E-31080 Pamplona, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de
   Investigaciones Biologicas (CIB); CIBER - Centro de Investigacion
   Biomedica en Red; CIBERER; University of Navarra
RP de Cordoba, SR (通讯作者)，Ctr Invest Biol, Dept Fisiopatol Celular & Mol, Ramiro Maeztu 9, Madrid 28040, Spain.
EM SRdeCordoba@cib.csic.es
RI de Cordoba, Santiago Rodriguez/K-6727-2014; Barricarte, Ruben
   Martinez/W-8695-2019; de Jorge, Elena Goicoechea/L-4580-2016
OI de Cordoba, Santiago Rodriguez/0000-0001-6401-1874; Barricarte, Ruben
   Martinez/0000-0001-7925-449X; de Jorge, Elena
   Goicoechea/0000-0002-4978-2483
FU Spanish Ministerio de Educacion y Cultura [SAF2005-00913]; Ciber de
   Enfermedades Raras; Fundacion Renal Inigo Alvarez de Toledo
FX We are grateful to the patients for their participation in this study.
   We thank the members of Secugen SL and the DNA sequencing laboratory at
   the CIB for invaluable technical assistance. S. R. de C. is supported by
   the Spanish Ministerio de Educacion y Cultura (SAF2005-00913), the Ciber
   de Enfermedades Raras and the Fundacion Renal Inigo Alvarez de Toledo.
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NR 40
TC 11
Z9 11
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
EI 1365-2249
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD JAN
PY 2009
VL 155
IS 1
BP 59
EP 64
DI 10.1111/j.1365-2249.2008.03798.x
PG 6
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 378YP
UT WOS:000261361400008
PM 19076829
OA Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU de Moura, FF
   Ho, CC
   Getachew, G
   Hickenbottom, S
   Clifford, AJ
AF de Moura, FF
   Ho, CC
   Getachew, G
   Hickenbottom, S
   Clifford, AJ
TI Kinetics of C-14 distribution after tracer dose of C-14-lutein in an
   adult woman
SO LIPIDS
LA English
DT Article
ID LC-APCI-MS; BETA-CAROTENE; MACULAR DEGENERATION; VITAMIN-A; LUTEIN
   BIOAVAILABILITY; PLASMA APPEARANCE; MASS-SPECTROMETRY; HUMANS;
   ZEAXANTHIN; ABSORPTION
AB Lutein is an oxygenated carotenoid (xanthophyll) found in dark green leafy vegetables. High intakes of lutein may lower the risk of age-related macular degeneration. Current understanding of human lutein metabolism as it might occur in vivo is incomplete. Therefore, we conducted a feasibility study where we dosed a normal adult woman with C-14-lutein (125 nmol, 36 nCi C-14), dissolved in olive oil (0.5 g/kg body weight) and mixed in a banana shake. Blood, urine, and feces collected before the dose was administered served to establish baseline values. Thereafter, blood was collected for 63 d following the dose, while feces and urine were collected for 2 wk post-dose. The 14C contents in plasma, urine, and feces were measured by accelerator MS. The C-14 first appeared in plasma 1 h after dosing and reached its highest level, approximate to 2.08% of dose/L plasma, at 14 h post-dose. The plasma pattern of 14 C did not include a chylomicrons/VLDL (intestinal) peak like that when the same subject received C-14-beta-carotene (a previous test), suggesting that lutein was handled differently from P-carotene by plasma lipoproteins. Lutein had an elimination half-life (t(1/2)) of approximate to 10 d. Forty-five percent of the dose of C-14 was eliminated in feces and 10% in urine in the first 2 d after dosing. Quantifying human lutein metabolism is a fertile area for future research.
C1 Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Clifford, AJ (通讯作者)，Univ Calif Davis, Dept Nutr, 1 Shields Ave, Davis, CA 95616 USA.
EM ajclifford@ucdavis.edu
OI De Moura, Fabiana F./0000-0001-8176-5352
FU PHS HHS [048307] Funding Source: Medline
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NR 35
TC 19
Z9 19
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0024-4201
EI 1558-9307
J9 LIPIDS
JI Lipids
PD OCT
PY 2005
VL 40
IS 10
BP 1069
EP 1073
DI 10.1007/s11745-005-1471-4
PG 5
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 986YV
UT WOS:000233486500012
PM 16382580
DA 2022-11-30
ER

PT J
AU Hatz, K
   Zimmermann, F
   Lazaridis, E
   Kardamakis, D
   Guichard, M
   Turksever, C
   Pruente, C
   Schmidt-Erfurth, UM
   Gerendas, BS
AF Hatz, Katja
   Zimmermann, Frank
   Lazaridis, Emmanouil
   Kardamakis, Dimitrios
   Guichard, Magdalena
   Turksever, Cengiz
   Pruente, Christian
   Schmidt-Erfurth, Ursula Margarethe
   Gerendas, Bianca S.
TI Microvascular abnormalities and long-term efficacy after stereotactic
   radiotherapy under continued intravitreal anti-VEGF treatment for
   neovascular AMD
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GROWTH-FACTOR THERAPY; NERVE-FIBER LAYER; MACULAR DEGENERATION;
   EPIMACULAR BRACHYTHERAPY; VISUAL IMPAIRMENT; CONTROLLED-TRIAL; OUTCOMES;
   RANIBIZUMAB; UPDATE
AB Background For treatment of neovascular age-related macular degeneration (nAMD), multiple intravitreal injections of drugs targeting vascular endothelial growth factors (VEGF) result in a high burden for patients and healthcare systems. Low-energy stereotactic radiotherapy (SRT) might reduce the anti-VEGF need. This study evaluated the long-term efficacy and safety of adjunct SRT to anti-VEGF injections in a treat-and-extend regimen in nAMD.
   Methods 50 consecutive patients were followed 3 years after single-session SRT, a safety analysis including standardised study imaging, and a reading centre based image analysis was performed after 2 years.
   Results After increase from baseline (4.24 +/- 0.66 weeks) to 12 months (7.52 +/- 3.05 weeks, p<0.001), mean recurrence-free anti-VEGF treatment interval remained stable at 24 (7.40 +/- 3.17, p=0.746) and 36 months (6.89 +/- 3.00, p=0.175). Mean visual acuity change was -5.8 +/- 15.9 and -11.0 +/- 20.1 letters at 24 and 36 months, respectively. 36% of eyes showed microvascular abnormalities (MVAs) on colour fundus photography and/or fluoresceine angiography most frequently located in parafoveal inferior and nasal regions.
   Conclusion In real life, low-energy SRT was associated with a reduced anti-VEGF injection frequency through year 3. However, due to an observed visual acuity reduction and remarkable number of MVAs, a close follow-up of these patients is recommended. The real-life use, optimal treatment schedule and dose should be rediscussed critically.
C1 [Hatz, Katja; Guichard, Magdalena; Turksever, Cengiz] Vista Klin, Binningen, Switzerland.
   [Hatz, Katja] Univ Basel, Fac Med, Basel, Switzerland.
   [Zimmermann, Frank] Univ Basel Hosp, Dept Radiat Oncol, Basel, Switzerland.
   [Lazaridis, Emmanouil] EyeRAD Swiss Med Ctr, Binningen, Switzerland.
   [Kardamakis, Dimitrios] Univ Patras, Dept Radiat Oncol, Dept Med, Patras, Greece.
   [Pruente, Christian] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Pruente, Christian] Inst Mol & Clin Ophthalmol, Basel, Switzerland.
   [Schmidt-Erfurth, Ursula Margarethe; Gerendas, Bianca S.] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna, Austria.
C3 University of Basel; University of Geneva; University of Basel;
   University of Patras; University of Basel; Medical University of Vienna
RP Hatz, K (通讯作者)，Vista Klin, Binningen, Switzerland.
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311; Gerendas, Bianca
   S./0000-0001-8940-8130
FU Carl Zeiss Meditec AG Germany
FX This study has been supported in part by Carl Zeiss Meditec AG Germany.
   The authors would like to thank the study coordinator Mrs Susanne
   Mueller and the chief photographer Mrs Christine Knodel for their
   support.
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NR 39
TC 1
Z9 1
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2022
VL 106
IS 3
BP 415
EP 421
DI 10.1136/bjophthalmol-2020-317563
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZH4UL
UT WOS:000760935500020
PM 33355151
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Sreekumar, PG
   Hinton, DR
   Kannan, R
AF Sreekumar, Parameswaran G.
   Hinton, David R.
   Kannan, Ram
TI The Emerging Role of Senescence in Ocular Disease
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Review
ID ONCOGENE-INDUCED SENESCENCE; SMALL EXTRACELLULAR VESICLES; CELLULAR
   SENESCENCE; SECRETORY PHENOTYPE; OXIDATIVE STRESS; HUMAN FIBROBLASTS;
   DNA-DAMAGE; MITOCHONDRIAL BIOGENESIS; PREMATURE SENESCENCE; RPE CELLS
AB Cellular senescence is a state of irreversible cell cycle arrest in response to an array of cellular stresses. An important role for senescence has been shown for a number of pathophysiological conditions that include cardiovascular disease, pulmonary fibrosis, and diseases of the skin. However, whether senescence contributes to the progression of age-related macular degeneration (AMD) has not been studied in detail so far and the present review describes the recent research on this topic. We present an overview of the types of senescence, pathways of senescence, senescence-associated secretory phenotype (SASP), the role of mitochondria, and their functional implications along with antisenescent therapies. As a central mechanism, senescent cells can impact the surrounding tissue microenvironment via the secretion of a pool of bioactive molecules, termed the SASP. An updated summary of a number of new members of the ever-growing SASP family is presented. Further, we introduce the significance of mechanisms by which mitochondria may participate in the development of cellular senescence. Emerging evidence shows that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Based on recent studies, there is reasonable evidence that senescence could be a modifiable factor, and hence, it may be possible to delay age-related diseases by modulating basic aging mechanisms using SASP inhibitors/senolytic drugs. Thus, antisenescent therapies in aging and age-related diseases appear to have a promising potential.
C1 [Sreekumar, Parameswaran G.; Kannan, Ram] Doheny Eye Inst, Stephen J Ryan Initiat Macular Res RIMR, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Hinton, David R.] Univ Southern Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Hinton, David R.] Univ Southern Calif, Dept Ophthalmol, Keck Sch Med, Roski Eye Inst, Los Angeles, CA 90033 USA.
   [Kannan, Ram] Univ Calif Los Angeles, Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
C3 Doheny Eye Institute; University of Southern California; University of
   Southern California; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Kannan, R (通讯作者)，Doheny Eye Inst, Stephen J Ryan Initiat Macular Res RIMR, 1355 San Pablo St, Los Angeles, CA 90033 USA.; Kannan, R (通讯作者)，Univ Calif Los Angeles, Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
EM rkannan@doheny.org
RI kannan, ram/ABB-7154-2020
OI kannan, ram/0000-0002-1583-3414; /0000-0002-9425-3986
FU Stephen J. Ryan Initiative for Macular Research (RIMR)
FX This work was supported by funding from the Stephen J. Ryan Initiative
   for Macular Research (RIMR). We thank Dr. Chandra Nagineni, National
   Cancer Institute, for helpful discussions.
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NR 234
TC 25
Z9 24
U1 0
U2 7
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD MAR 9
PY 2020
VL 2020
AR 2583601
DI 10.1155/2020/2583601
PG 19
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA KY0NP
UT WOS:000522271400001
PM 32215170
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, YJ
   Sun, RP
   Zou, JR
   Ying, Y
   Luo, ZJ
AF Li, Yuanjun
   Sun, Ruipu
   Zou, Junrong
   Ying, Ying
   Luo, Zhijun
TI Dual Roles of the AMP-Activated Protein Kinase Pathway in Angiogenesis
SO CELLS
LA English
DT Review
DE angiogenesis; tumorigenesis; retinopathy; AMPK; mTOR; TGF-beta; VEGF;
   HIF-1 alpha
ID ENDOTHELIAL GROWTH-FACTOR; BONE MORPHOGENETIC PROTEIN-6; PROSTATE-CANCER
   CELLS; TGF-BETA; SIGNALING PATHWAY; BREAST-CANCER; NITRIC-OXIDE;
   IN-VITRO; MESENCHYMAL TRANSITION; PROMOTES ANGIOGENESIS
AB Angiogenesis plays important roles in development, stress response, wound healing, tumorigenesis and cancer progression, diabetic retinopathy, and age-related macular degeneration. It is a complex event engaging many signaling pathways including vascular endothelial growth factor (VEGF), Notch, transforming growth factor-beta/bone morphogenetic proteins (TGF-beta/BMPs), and other cytokines and growth factors. Almost all of them eventually funnel to two crucial molecules, VEGF and hypoxia-inducing factor-1 alpha (HIF-1 alpha) whose expressions could change under both physiological and pathological conditions. Hypoxic conditions stabilize HIF-1 alpha, while it is upregulated by many oncogenic factors under normaxia. HIF-1 alpha is a critical transcription activator for VEGF. Recent studies have shown that intracellular metabolic state participates in regulation of sprouting angiogenesis, which may involve AMP-activated protein kinase (AMPK). Indeed, AMPK has been shown to exert both positive and negative effects on angiogenesis. On the one hand, activation of AMPK mediates stress responses to facilitate autophagy which stabilizes HIF-1 alpha, leading to increased expression of VEGF. On the other hand, AMPK could attenuate angiogenesis induced by tumor-promoting and pro-metastatic factors, such as the phosphoinositide 3-kinase /protein kinase B (Akt)/mammalian target of rapamycin (PI3K/Akt/mTOR), hepatic growth factor (HGF), and TGF-beta/BMP signaling pathways. Thus, this review will summarize research progresses on these two opposite effects and discuss the mechanisms behind the discrepant findings.
C1 [Li, Yuanjun; Zou, Junrong; Ying, Ying; Luo, Zhijun] Nanchang Univ, Jiangxi Med Coll, Jiangxi Prov Key Lab Tumor Pathogens & Mol Pathol, Dept Pathophysiol,Sch Basic Med Sci, Nanchang 330006, Jiangxi, Peoples R China.
   [Sun, Ruipu; Luo, Zhijun] Nanchang Univ, Jiangxi Med Coll, Queen Mary Sch, Nanchang 30006, Jiangxi, Peoples R China.
C3 Nanchang University; Nanchang University
RP Luo, ZJ (通讯作者)，Nanchang Univ, Jiangxi Med Coll, Jiangxi Prov Key Lab Tumor Pathogens & Mol Pathol, Dept Pathophysiol,Sch Basic Med Sci, Nanchang 330006, Jiangxi, Peoples R China.; Luo, ZJ (通讯作者)，Nanchang Univ, Jiangxi Med Coll, Queen Mary Sch, Nanchang 30006, Jiangxi, Peoples R China.
EM zluo559914@ncu.edu.cn
RI Sun, Ruipu/GYR-3422-2022; Zou, Junrong/AGF-6491-2022; Luo,
   Zhijun/AAE-9302-2019
OI Luo, Zhijun/0000-0001-8105-5289
FU National Nature Science Foundation of China [81572753, 31660332,
   81560299]; Innovation and Entrepreneurship grant from Jiangxi Province
   Bureau of Foreign Experts
FX This work was supported by National Nature Science Foundation of China
   (81572753, 31660332, 81560299) and Innovation and Entrepreneurship grant
   from Jiangxi Province Bureau of Foreign Experts.
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NR 134
TC 43
Z9 45
U1 2
U2 18
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD JUL
PY 2019
VL 8
IS 7
AR 752
DI 10.3390/cells8070752
PG 16
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA IN8AC
UT WOS:000478902000020
PM 31331111
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Velez, G
   Yang, J
   Li, AS
   Tsang, SH
   Bassuk, AG
   Mahajan, VB
AF Velez, Gabriel
   Yang, Jing
   Li, Angela S.
   Tsang, Stephen H.
   Bassuk, Alexander G.
   Mahajan, Vinit B.
TI Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIABETIC-RETINOPATHY; PERSONALIZED PROTEOMICS; GLUTAMATE RECEPTORS;
   VITREOUS FLUID; GROWTH-FACTOR; SERUM-LEVELS; INFLAMMATION; CALPAIN;
   DEGENERATION; MECHANISMS
AB CAPN5 Neovascular Inflammatory Vitreoretinopathy (CAPN5-NIV; OMIM 193235) is a poorly-understood rare, progressive inflammatory intraocular disease with limited therapeutic options. To profile disease effector proteins in CAPN5-NIV patient vitreous, liquid vitreous biopsies were collected from two groups: eyes from control subjects (n = 4) with idiopathic macular holes (IMH) and eyes from test subjects (n = 12) with different stages of CAPN5-NIV. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein expression changes were evaluated by principal component analysis, 1-way ANOVA (significant p-value < 0.05), hierarchical clustering, gene ontology, and pathway representation. There were 216 differentially-expressed proteins (between CAPN5-NIV and control vitreous), including those unique to and abundant in each clinical stage. Gene ontology analysis revealed decreased synaptic signaling proteins in CAPN5-NIV vitreous compared to controls. Pathway analysis revealed that inflammatory mediators of the acute phase response and the complement cascade were highly-represented. The CAPN5-NIV vitreous proteome displayed characteristic enrichment of proteins and pathways previously-associated with non-infectious posterior uveitis, rhegmatogenous retinal detachment (RRD), age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and proliferative vitreoretinopathy (PVR). This study expands our knowledge of affected molecular pathways in CAPN5-NIV using unbiased, shotgun proteomic analysis rather than targeted detection platforms. The high-levels and representation of acute phase response proteins suggests a functional role for the innate immune system in CAPN5-NIV pathogenesis.
C1 [Velez, Gabriel; Yang, Jing; Li, Angela S.; Mahajan, Vinit B.] Stanford Univ, Om Lab, Palo Alto, CA 94304 USA.
   [Velez, Gabriel; Yang, Jing; Li, Angela S.; Mahajan, Vinit B.] Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Palo Alto, CA 94304 USA.
   [Velez, Gabriel] Univ Iowa, Med Scientist Training Program, Iowa City, IA USA.
   [Mahajan, Vinit B.] Palo Alto Vet Adm, Palo Alto, CA 94304 USA.
   [Tsang, Stephen H.] Columbia Univ, Jonas Childrens Vis Care, New York, NY USA.
   [Tsang, Stephen H.] Columbia Univ, Dept Ophthalmol, Bernard & Shirlee Brown Glaucoma Lab, Columbia Stem Cell Initiat,Inst Human Nutr, New York, NY 10027 USA.
   [Tsang, Stephen H.] Columbia Univ, Bernard & Shirlee Brown Glaucoma Lab, Columbia Stem Cell Initiat, Dept Pathol,Inst Human Nutr, New York, NY USA.
   [Tsang, Stephen H.] Columbia Univ, Bernard & Shirlee Brown Glaucoma Lab, Columbia Stem Cell Initiat, Dept Cell Biol,Inst Human Nutr, New York, NY USA.
   [Tsang, Stephen H.] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USA.
   [Bassuk, Alexander G.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
C3 Stanford University; Stanford University; University of Iowa; Columbia
   University; Columbia University; Columbia University; Columbia
   University; Columbia University; University of Iowa
RP Mahajan, VB (通讯作者)，Stanford Univ, Om Lab, Palo Alto, CA 94304 USA.; Mahajan, VB (通讯作者)，Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Palo Alto, CA 94304 USA.; Mahajan, VB (通讯作者)，Palo Alto Vet Adm, Palo Alto, CA 94304 USA.
EM vinit.mahajan@stanford.edu
OI Li, Angela/0000-0002-0397-2193; Velez, Gabriel/0000-0003-0819-5933;
   Mahajan, Vinit/0000-0003-1886-1741; Bassuk,
   Alexander/0000-0002-4067-2157
FU NIH [K08EY020530, R01EY024665, R01EY025225, R01EY024698, R21AG050437,
   P30EY026877, F30EYE027986, T32GM007337]; Doris Duke Charitable
   Foundation [2013103]; Research to Prevent Blindness (RPB); Stanford
   ChEM-H Testing Molecular Hypotheses in Human Subjects Seed Grant; CDMRP
   TSCRP [TS080017]; National Institute of Health [R01EY024698,
   R21AG050437, 5P30EY019007, R01EY018213, R01EY026682]; National Cancer
   Institute Core [5P30CA013696]; Research to Prevent Blindness (RPB)
   Physician-Scientist Award; RPB, New York, NY, USA; Tistou and Charlotte
   Kerstan Foundation; Crowley Family Fund; Schneeweiss Stem Cell Fund; New
   York State [C029572]; Gebroe Family Foundation; NATIONAL CANCER
   INSTITUTE [P30CA013696] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY018213, R01EY026682, F30EY027986, R01EY024698,
   P30EY026877, P30EY019007, R01EY025225, R01EY024665] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007337]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING [R21AG050437]
   Funding Source: NIH RePORTER
FX We thank Emily Chen and Rajesh Soni for technical assistance. V.B.M. and
   A.G.B. are supported by NIH grants [K08EY020530, R01EY024665,
   R01EY025225, R01EY024698, R21AG050437, P30EY026877], Doris Duke
   Charitable Foundation Grant #: 2013103, Research to Prevent Blindness
   (RPB) and the Stanford ChEM-H Testing Molecular Hypotheses in Human
   Subjects Seed Grant. The Barbara & Donald Jonas Laboratory of
   Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory
   are supported by the CDMRP TSCRP: TS080017, National Institute of Health
   [5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437];
   National Cancer Institute Core [5P30CA013696]; the Research to Prevent
   Blindness (RPB) Physician-Scientist Award; unrestricted funds from RPB,
   New York, NY, USA; the Tistou and Charlotte Kerstan Foundation; the
   Crowley Family Fund; the Schneeweiss Stem Cell Fund; New York State
   [C029572]; and the Gebroe Family Foundation. G. V. is supported by NIH
   grants [F30EYE027986 and T32GM007337]. The funding organizations 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 58
TC 4
Z9 4
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAY 20
PY 2019
VL 9
AR 7608
DI 10.1038/s41598-019-44031-7
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HY7AA
UT WOS:000468281500038
PM 31110225
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Leleu, I
   Penaud, B
   Blumen-Ohana, E
   Rodallec, T
   Adam, R
   Laplace, O
   Akesbi, J
   Nordmann, JP
AF Leleu, I
   Penaud, B.
   Blumen-Ohana, E.
   Rodallec, T.
   Adam, R.
   Laplace, O.
   Akesbi, J.
   Nordmann, J-P
TI Late and sustained intraocular pressure elevation related to
   intravitreal anti-VEGF injections: Cases requiring filtering surgery
SO JOURNAL FRANCAIS D OPHTALMOLOGIE
LA English
DT Article
DE Anti-VEGF; Intravitreal injection; Elevated intraocular pressure;
   Glaucoma; Filtering surgery; Non-penetrating deep sclerectomy
ID ENDOTHELIAL GROWTH-FACTOR; SILICONE OIL DROPLETS; MACULAR DEGENERATION;
   OCULAR HYPERTENSION; BEVACIZUMAB INJECTIONS; RANIBIZUMAB INJECTIONS;
   FACTOR THERAPY; GLAUCOMA; AFLIBERCEPT; PEGAPTANIB
AB We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IV!), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1 % and 13 % according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery. (C) 2018 Elsevier Masson SAS. All rights reserved.
C1 [Leleu, I; Penaud, B.; Blumen-Ohana, E.; Rodallec, T.; Adam, R.; Laplace, O.; Akesbi, J.; Nordmann, J-P] Ctr Hosp Natl Ophtalmol 15 20, 28 Rue Charenton, F-75012 Paris, France.
C3 CHNO des Quinze-Vingts; UDICE-French Research Universities; Sorbonne
   Universite
RP Leleu, I (通讯作者)，10 Rue Roi de Sicile, F-75004 Paris, France.
EM leleu.igor@gmail.com
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   Zhou YD, 2016, SCI REP-UK, V6, DOI 10.1038/srep39301
NR 45
TC 2
Z9 2
U1 0
U2 1
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 OCT
PY 2018
VL 41
IS 8
BP E329
EP E340
DI 10.1016/j.jfo.2018.07.002
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GW4AC
UT WOS:000446851200001
PM 30197188
DA 2022-11-30
ER

PT J
AU Csincsi, AI
   Szabo, Z
   Banlaki, Z
   Uzonyi, B
   Cserhalmi, M
   Karpati, E
   Tortajada, A
   Caesar, JJE
   Prohaszka, Z
   Jokiranta, TS
   Lea, SM
   de Cordoba, SR
   Jozsi, M
AF Csincsi, Adam I.
   Szabo, Zsoka
   Banlaki, Zsofia
   Uzonyi, Barbara
   Cserhalmi, Marcell
   Karpati, Eva
   Tortajada, Agustin
   Caesar, Joseph J. E.
   Prohaszka, Zoltan
   Jokiranta, T. Sakari
   Lea, Susan M.
   de Cordoba, Santiago Rodriguez
   Jozsi, Mihaly
TI FHR-1 Binds to C-Reactive Protein and Enhances Rather than Inhibits
   Complement Activation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; H-RELATED PROTEIN; REGULATOR FACTOR-H;
   APOPTOTIC CELLS; MOLECULAR-BASIS; AUTOANTIBODIES; CFHR1; RECOGNITION;
   TERMINUS; DOMAINS
AB Factor H-related protein (FHR) 1 is one of the five human FHRs that share sequence and structural homology with the alternative pathway complement inhibitor FH. Genetic studies on disease associations and functional analyses indicate that FHR-1 enhances complement activation by competitive inhibition of FH binding to some surfaces and immune proteins. We have recently shown that FHR-1 binds to pentraxin 3. In this study, our aim was to investigate whether FHR-1 binds to another pentraxin, C-reactive protein (CRP), analyze the functional relevance of this interaction, and study the role of FHR-1 in complement activation and regulation. FHR-1 did not bind to native, pentameric CRP, but it bound strongly to monomeric CRP via its C-terminal domains. FHR-1 at high concentration competed with FH for CRP binding, indicating possible complement deregulation also on this ligand. FHR-1 did not inhibit regulation of solid-phase C3 convertase by FH and did not inhibit terminal complement complex formation induced by zymosan. On the contrary, by binding C3b, FHR-1 allowed C3 convertase formation and thereby enhanced complement activation. FHR-1/CRP interactions increased complement activation via the classical and alternative pathways on surfaces such as the extracellular matrix and necrotic cells. Altogether, these results identify CRP as a ligand for FHR-1 and suggest that FHR-1 enhances, rather than inhibits, complement activation, which may explain the protective effect of FHR-1 deficiency in age-related macular degeneration.
C1 [Csincsi, Adam I.; Szabo, Zsoka; Banlaki, Zsofia; Cserhalmi, Marcell; Karpati, Eva; Jozsi, Mihaly] Eotvos Lorand Univ, Hungarian Acad Sci, Lendiilet Complement Res Grp, Dept Immunol,MTA,ELTE, Pazmany Peter Setany 1-C, H-1117 Budapest, Hungary.
   [Uzonyi, Barbara] Eotvos Lorand Univ, Hungarian Acad Sci, Immunol Res Grp, Dept Immunol,MTA,ELTE, H-1117 Budapest, Hungary.
   [Tortajada, Agustin; de Cordoba, Santiago Rodriguez] Ctr Invest Biol, Dept Med Celular & Mol, Madrid 28040, Spain.
   [Tortajada, Agustin; de Cordoba, Santiago Rodriguez] Ctr Invest Biomed Red Enfermedades Raras, Madrid 28040, Spain.
   [Caesar, Joseph J. E.; Lea, Susan M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Prohaszka, Zoltan] Semmelweis Univ, Dept Internal Med 3, Res Lab, H-1125 Budapest, Hungary.
   [Jokiranta, T. Sakari] Univ Helsinki, Haartman Inst, Immunobiol, Res Programs Unit, FI-00014 Helsinki, Finland.
C3 Eotvos Lorand University; Hungarian Academy of Sciences; Eotvos Lorand
   University; Hungarian Academy of Sciences; Consejo Superior de
   Investigaciones Cientificas (CSIC); CSIC - Centro de Investigaciones
   Biologicas (CIB); CIBER - Centro de Investigacion Biomedica en Red;
   CIBERER; University of Oxford; Semmelweis University; University of
   Helsinki
RP Jozsi, M (通讯作者)，Eotvos Lorand Univ, Hungarian Acad Sci, Lendiilet Complement Res Grp, Dept Immunol,MTA,ELTE, Pazmany Peter Setany 1-C, H-1117 Budapest, Hungary.
EM mihalyjozsi@gmx.net
RI Jozsi, Mihaly/I-7872-2018; Tortajada, Agustín/H-2857-2015; Uzonyi,
   Barbara/J-3973-2018; Lea, Susan M/B-7678-2009; Prohaszka,
   Zoltan/F-2191-2010; Rodriguez de Cordoba, Santiago/K-6727-2014
OI Jozsi, Mihaly/0000-0002-5520-5535; Tortajada,
   Agustín/0000-0002-2131-2594; Uzonyi, Barbara/0000-0002-9680-1974; Lea,
   Susan M/0000-0001-9287-8053; Prohaszka, Zoltan/0000-0003-1761-7982;
   Rodriguez de Cordoba, Santiago/0000-0001-6401-1874
FU National Research, Development and Innovation Office [K 109055];
   Lendulet Program of the Hungarian Academy of Sciences [LP2012-43];
   Spanish Ministerio e Economia y Competitividad [SAF2011-26583];
   Autonomous Region of Madrid [S2010BMD-2316]; European Union
   (Eurenomics); Sigrid Juselius Foundation; Academy of Finland [128646,
   255922, 259793]
FX This work was supported by the National Research, Development and
   Innovation Office (Grant K 109055) and the Lendulet Program of the
   Hungarian Academy of Sciences (Grant LP2012-43 to M.J.). S.R.d.C. is
   supported by the Spanish Ministerio e Economia y Competitividad (Grant
   SAF2011-26583), the Autonomous Region of Madrid (Grant S2010BMD-2316),
   and the European Union (Eurenomics). T.S.J. acknowledges research grants
   from the Sigrid Juselius Foundation and the Academy of Finland (Grants
   128646, 255922, and 259793).
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NR 64
TC 30
Z9 33
U1 0
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2017
VL 199
IS 1
BP 292
EP 303
DI 10.4049/jimmunol.1600483
PG 12
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA FA2LD
UT WOS:000405272000031
PM 28533443
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Miller, CG
   Budoff, G
   Prenner, JL
   Schwarzbauer, JE
AF Miller, Charles G.
   Budoff, Greg
   Prenner, Jonathan L.
   Schwarzbauer, Jean E.
TI Fibronectin in retinal disease
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Fibronectin; retina; fibrosis; neovascularization; extracellular matrix;
   diabetic retinopathy; age-related macular degeneration; proliferative
   vitreoretinopathy
ID EXTRACELLULAR-MATRIX COMPONENTS; PROLIFERATIVE VITREORETINOPATHY;
   MACULAR DEGENERATION; BASEMENT-MEMBRANE; GROWTH-FACTOR; BRUCHS MEMBRANE;
   HIGH-GLUCOSE; PROTEOMIC ANALYSIS; VASCULAR-LESIONS; IV COLLAGEN
AB Retinal fibrosis, characterized by dysregulation of extracellular matrix (ECM) protein deposition by retinal endothelial cells, pigment epithelial cells, and other resident cell-types, is a unifying feature of several common retinal diseases. Fibronectin is an early constituent of newly deposited ECM and serves as a template for assembly of other ECM proteins, including collagens. Under physiologic conditions, fibronectin is found in all layers of Bruch's membrane. Proliferative vitreoretinopathy (PVR), a complication of retinal surgery, is characterized by ECM accumulation. Among the earliest histologic manifestations of diabetic retinopathy (DR) is capillary basement membrane thickening, which occurs due to perturbations in ECM homeostasis. Neovascularization, the hallmark of late stage DR as well as exudative age-related macular degeneration (AMD), involves ECM assembly as a scaffold for the aberrant new vessel architecture. Rodent models of retinal injury demonstrate a key role for fibronectin in complications characteristic of PVR, including retinal detachment. In mouse models of DR, reducing fibronectin gene expression has been shown to arrest the accumulation of ECM in the capillary basement membrane. Alterations in matrix metalloproteinase activity thought to be important in the pathogenesis of AMD impact the turnover of fibronectin matrix as well as collagens. Growth factors involved in PVR, AMD, and DR, such as PDGF and TGFb, are known to stimulate fibronectin matrix assembly. A deeper understanding of how pathologic ECM deposition contributes to disease progression may help to identify novel targets for therapeutic intervention.
C1 [Miller, Charles G.; Budoff, Greg; Prenner, Jonathan L.] Rutgers Robert Wood Johnson Med Sch, Dept Ophthalmol, Piscataway, NJ 08854 USA.
   [Prenner, Jonathan L.] NJ Retina, New Brunswick, NJ 08901 USA.
   [Schwarzbauer, Jean E.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center; Princeton University
RP Miller, CG (通讯作者)，Rutgers Robert Wood Johnson Med Sch, Dept Ophthalmol, Piscataway, NJ 08854 USA.
EM charlesgmiller@gmail.com
OI Schwarzbauer, Jean/0000-0003-1012-7593
FU NCI; NIDDK; NATIONAL CANCER INSTITUTE [R01CA160611] Funding Source: NIH
   RePORTER
FX The authors would like to thank the NCI (to JES) and NIDDK (to CGM) for
   funding.
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NR 93
TC 32
Z9 32
U1 2
U2 10
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1535-3702
EI 1535-3699
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD JAN
PY 2017
VL 242
IS 1
BP 1
EP 7
DI 10.1177/1535370216675245
PG 7
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA EK9SA
UT WOS:000394263000001
PM 27798121
OA Green Published
DA 2022-11-30
ER

PT J
AU Austeng, D
   Morken, TS
   Bolme, S
   Follestad, T
   Halsteinli, V
AF Austeng, Dordi
   Morken, Tora Sund
   Bolme, Stine
   Follestad, Turid
   Halsteinli, Vidar
TI Nurse-administered intravitreal injections of anti-VEGF: study protocol
   for noninferiority randomized controlled trial of safety, cost and
   patient satisfaction
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF; Intravitreal injection; Nurse; Randomized controlled trial;
   Age-related macular degeneration; Retinal vein occlusion; Diabetic
   macular edema
ID MACULAR DEGENERATION; RANIBIZUMAB; OPHTHALMOLOGISTS
AB Background: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) now improve or stabilize visual acuity in a number of previously untreatable eye diseases, of which the main are age-related macular degeneration, retinal vein occlusion and diabetic macular edema. Most patients require multiple injections over lengthy periods of time and the prevalence of treatable conditions is increasing. Anti-VEGF IVI normally administered by physicians, therefore represent a considerable workload on ophthalmologic clinics and will continue to do so in the near future. Nurse-administered IVI may relieve this workload, but the safety, cost and patient satisfaction of such an extended role for nurses in ophthalmologic clinics has not earlier been investigated. To investigate these outcomes following independent anti-VEGF IVI by trained nurses, a noninferiority randomized controlled trial is being conducted.
   Methods/Design: Patients eligible for anti-VEGF treatment, minimum 304, are recruited and randomized to IVI administration by either trained nurses or physicians. The primary outcome is safety, measured by difference in mean change in visual acuity between the two groups during an observation period of 12 months. Secondary outcomes are incidence of ocular adverse events, cost per patient and patient satisfaction.
   Discussion: This study protocol describes the design of the first randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is designed to examine safety, cost and patient satisfaction during 12 months follow-up.
C1 [Austeng, Dordi; Morken, Tora Sund; Bolme, Stine] Univ Trondheim Hosp, St Olavs Hosp, Dept Ophthalmol, Trondheim, Norway.
   [Halsteinli, Vidar] Univ Trondheim Hosp, St Olavs Hosp, Reg Ctr Healthcare Improvement, Trondheim, Norway.
   [Austeng, Dordi] Norwegian Univ Sci & Technol NTNU, Dept Neurosci, Trondheim, Norway.
   [Morken, Tora Sund] Norwegian Univ Sci & Technol NTNU, Childrens & Womens Hlth, Dept Lab Med, Trondheim, Norway.
   [Follestad, Turid] Norwegian Univ Sci & Technol NTNU, Dept Publ Hlth & Gen Practice, Trondheim, Norway.
C3 Norwegian University of Science & Technology (NTNU); Norwegian
   University of Science & Technology (NTNU); Norwegian University of
   Science & Technology (NTNU); Norwegian University of Science &
   Technology (NTNU); Norwegian University of Science & Technology (NTNU)
RP Austeng, D (通讯作者)，Univ Trondheim Hosp, St Olavs Hosp, Dept Ophthalmol, Trondheim, Norway.; Austeng, D (通讯作者)，Norwegian Univ Sci & Technol NTNU, Dept Neurosci, Trondheim, Norway.
EM dordi.austeng@ntnu.no
FU St. Olavs Hospital, Trondheim University Hospital; Central Norway
   Regional Health Authority
FX The study is supported by St. Olavs Hospital, Trondheim University
   Hospital, and the Central Norway Regional Health Authority. It has not
   received external funding.
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NR 18
TC 9
Z9 10
U1 0
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD OCT 1
PY 2016
VL 16
AR 169
DI 10.1186/s12886-016-0348-4
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DY9MR
UT WOS:000385458500001
PM 27716253
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, RS
   Liu, ZL
   Zhang, H
   Zhang, Y
   Lin, D
AF Zhang, Ruoshuang
   Liu, Zheli
   Zhang, Han
   Zhang, Yi
   Lin, Dong
TI The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal
   Neovascularization and Subretinal Fibrosis
SO PLOS ONE
LA English
DT Article
ID CYCLOOXYGENASE-2 GENE-EXPRESSION; PLATELET-ACTIVATING-FACTOR;
   ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; UP-REGULATION;
   ANIMAL-MODEL; COX-2; RANIBIZUMAB; MACROPHAGE; LOCALIZATION
AB Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium-choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-beta(2) in the retinal pigment epithelium-choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-beta(2) in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis.
C1 [Zhang, Ruoshuang; Liu, Zheli; Zhang, Han; Zhang, Yi; Lin, Dong] China Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Shenyang 110001, Liaoning Provin, Peoples R China.
C3 China Medical University
RP Liu, ZL (通讯作者)，China Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Shenyang 110001, Liaoning Provin, Peoples R China.
EM zheli_liu@163.com
OI Zhang, Han/0000-0002-9338-0051
FU Liaoning Science and Technology Project [2013225303]; Fund for
   Scientific Research of The First Hospital Of China Medical University
   [2014-04]
FX This work was supported by Liaoning Science and Technology Project (No.
   2013225303, H. Z.) and Fund for Scientific Research of The First
   Hospital Of China Medical University (No. 2014-04, H. Z.). 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 29
Z9 31
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 JAN 13
PY 2016
VL 11
IS 1
AR e0146808
DI 10.1371/journal.pone.0146808
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DA8CX
UT WOS:000368033100042
PM 26760305
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Chen, Q
   de Sisternes, L
   Leng, T
   Zheng, LL
   Kutzscher, L
   Rubin, DL
AF Chen, Qiang
   de Sisternes, Luis
   Leng, Theodore
   Zheng, Luoluo
   Kutzscher, Lauren
   Rubin, Daniel L.
TI Semi-automatic geographic atrophy segmentation for SD-OCT images
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID AGE-RELATED MACULOPATHY; OPTICAL COHERENCE TOMOGRAPHY; FUNDUS
   AUTOFLUORESCENCE; AUTOMATIC SEGMENTATION; MACULAR DEGENERATION;
   RISK-FACTORS; PROGRESSION; QUANTIFICATION; DRUSEN
AB Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively. (C) 2013 Optical Society of America
C1 [Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [Chen, Qiang; de Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Dept Radiol & Med Biomed Informat Res, Stanford, CA 94305 USA.
   [Leng, Theodore; Zheng, Luoluo; Kutzscher, Lauren] Stanford Univ, Sch Med, Byers Eye Inst Stanford, Palo Alto, CA 94303 USA.
C3 Nanjing University of Science & Technology; Stanford University;
   Stanford University
RP Chen, Q (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
EM chen2qiang@njust.edu.cn; dlrubin@standford.edu
RI Leng, Theodore/AAQ-7459-2020; chen, qiang/GWZ-7308-2022
OI Leng, Theodore/0000-0002-8461-3562
FU Bio-X Interdisciplinary Initiatives Program of Stanford University;
   National Cancer Institute, National Institutes of Health
   [U01-CA-142555]; Programme of Introducing Talents of Discipline to
   Universities [B13022]; Qing Lan Project
FX The authors wish to thank Dr. Mary Durbin from Carl Zeiss Meditec as
   well as Dr. Gordon, Dr. Pearlman, Dr. Lit and Dr. Boyer for their help
   preparing and providing sample cases and results obtained from FAF
   images and the Cirrus software. This work was supported by a grant from
   the Bio-X Interdisciplinary Initiatives Program of Stanford University,
   a grant from the National Cancer Institute, National Institutes of
   Health, grant No. U01-CA-142555, and grants from the Programme of
   Introducing Talents of Discipline to Universities under Grant No. B13022
   and Qing Lan Project.
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NR 37
TC 41
Z9 44
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 2013
VL 4
IS 12
BP 2729
EP 2750
DI 10.1364/BOE.4.002729
PG 22
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 267EA
UT WOS:000328078300002
PM 24409376
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Flammer, J
   Konieczka, K
   Bruno, RM
   Virdis, A
   Flammer, AJ
   Taddei, S
AF Flammer, Josef
   Konieczka, Katarzyna
   Bruno, Rosa M.
   Virdis, Agostino
   Flammer, Andreas J.
   Taddei, Stefano
TI The eye and the heart
SO EUROPEAN HEART JOURNAL
LA English
DT Review
DE Retinal vessels; Cardiovascular risk; Vascular dysregulation;
   Endothelial function; Systemic hypertension; Systemic hypotension;
   Retinal venous pressure; Retinal vein occlusion; Glaucoma
ID ENDOTHELIN-1 PLASMA-LEVELS; OCULAR BLOOD-FLOW; BODY-MASS INDEX; RETINAL
   VEIN OCCLUSIONS; NORMAL-TENSION GLAUCOMA; SMALL-ARTERY STRUCTURE;
   RISK-FACTOR; MATRIX METALLOPROTEINASES; VASCULAR DYSREGULATION; SYSTEMIC
   HYPOTENSION
AB The vasculature of the eye and the heart share several common characteristics. The easily accessible vessels of the eye are thereforeuto some extentua window to the heart. There is interplay between cardiovascular functions and risk factors and the occurrence and progression of many eye diseases. In particular, arteriovenous nipping, narrowing of retinal arteries, and the dilatation of retinal veins are important signs of increased cardiovascular risk. The pressure in the dilated veins is often markedly increased due to a dysregulation of venous outflow from the eye. Besides such morphological criteria, functional alterations might be even more relevant and may play an important role in future diagnostics. Via neurovascular coupling, flickering light dilates capillaries and small arterioles, thus inducing endothelium-dependent, flow-mediated dilation of larger retinal vessels. Risk factors for arteriosclerosis, such as dyslipidaemia, diabetes, or systemic hypertension, are also risk factors for eye diseases such as retinal arterial or retinal vein occlusions, cataracts, age-related macular degeneration, and increases in intraocular pressure (IOP). Functional alterations of blood flow are particularly relevant to the eye. The primary vascular dysregulation syndrome (PVD), which often includes systemic hypotension, is associated with disturbed autoregulation of ocular blood flow (OBF). Fluctuation of IOP on a high level or blood pressure on a low level leads to instable OBF and oxygen supply and therefore to oxidative stress, which is particularly involved in the pathogenesis of glaucomatous neuropathy. Vascular dysregulation also leads to a barrier dysfunction and thereby to small retinal haemorrhages.
C1 [Flammer, Josef; Konieczka, Katarzyna] Univ Basel, Dept Ophthalmol, CH-4031 Basel, Switzerland.
   [Bruno, Rosa M.; Virdis, Agostino; Taddei, Stefano] Univ Pisa, Dept Internal Med, Pisa, Italy.
   [Flammer, Andreas J.] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland.
C3 University of Basel; University of Pisa; University of Zurich;
   University Zurich Hospital
RP Flammer, J (通讯作者)，Univ Basel, Dept Ophthalmol, Mittlere Str 91, CH-4031 Basel, Switzerland.
EM jflammer@uhbs.ch
RI Flammer, Andreas/AAJ-1328-2021; Taddei, Stefano/AAB-2828-2019; Virdis,
   Agostino/K-5315-2016; Bruno, Rosa Maria/C-3594-2015
OI Bruno, Rosa Maria/0000-0002-6107-3356; Flammer,
   Andreas/0000-0002-1373-0630
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NR 115
TC 207
Z9 210
U1 1
U2 33
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD MAY
PY 2013
VL 34
IS 17
BP 1270
EP +
DI 10.1093/eurheartj/eht023
PG 11
WC Cardiac & Cardiovascular Systems
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 139AR
UT WOS:000318554300009
PM 23401492
OA hybrid, Green Accepted, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Maruotti, J
   Wahlin, K
   Gorrell, D
   Bhutto, I
   Lutty, G
   Zack, DJ
AF Maruotti, Julien
   Wahlin, Karl
   Gorrell, David
   Bhutto, Imran
   Lutty, Gerard
   Zack, Donald J.
TI A Simple and Scalable Process for the Differentiation of Retinal Pigment
   Epithelium From Human Pluripotent Stem Cells
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Retinal pigment epithelium; Pluripotent stem cells; Serum-free; Defined
ID DIRECTED DIFFERENTIATION; AUTOLOGOUS TRANSLOCATION; MACULAR
   DEGENERATION; EXTRACELLULAR-MATRIX; TRANSCRIPTION FACTOR; IN-VITRO; RPE;
   TRANSPLANTATION; GENERATION; EXPRESSION
AB Age-related macular degeneration (AMD), the leading cause of irreversible vision loss and blindness among the elderly in industrialized countries, is associated with the dysfunction and death of the retinal pigment epithelial (RPE) cells. As a result, there has been significant interest in developing RPE culture systems both to study AMD disease mechanisms and to provide substrate for possible cell-based therapies. Because of their indefinite self-renewal, human pluripotent stem cells (hPSCs) have the potential to provide an unlimited supply of RPE-like cells. However, most protocols developed to date for deriving RPE cells from hPSCs involve time- and labor-consuming manual steps, which hinder their use in biomedical applications requiring large amounts of differentiated cells. Here, we describe a simple and scalable protocol for the generation of RPE cells from hPSCs that is less labor-intensive. After amplification by clonal propagation using a myosin inhibitor, differentiation was induced in monolayers of hPSCs, and the resulting RPE cells were purified by two rounds of whole-dish single-cell passage. This approach yields highly pure populations of functional hPSC-derived RPE cells that display many characteristics of native RPE cells, including proper pigmentation and morphology, cell type-specific marker expression, polarized membrane and vascular endothelial growth factor secretion, and phagocytic activity. This work represents a step toward mass production of RPE cells from hPSCs. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:341-354
C1 [Maruotti, Julien; Wahlin, Karl; Gorrell, David; Bhutto, Imran; Lutty, Gerard; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21231 USA.
   [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21231 USA.
   [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Baltimore, MD 21231 USA.
   [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Inst Genet Med, Baltimore, MD 21231 USA.
   [Zack, Donald J.] Univ Paris 06, Inst Vis, Paris, France.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins University; Johns Hopkins University;
   UDICE-French Research Universities; Sorbonne Universite
RP Zack, DJ (通讯作者)，Johns Hopkins Univ, Sch Med, 400 North Broadway, Baltimore, MD 21231 USA.
EM dzack@jhmi.edu
OI Zack, Don/0000-0002-7966-1973
FU Foundation Fighting Blindness Wynn-Gund Translational Acceleration
   Program grant; American Health Assistance Foundation Macular
   Degeneration Research grant; NIH [P30EY001765]; Research to Prevent
   Blindness, Inc.; Maryland Stem Cell Research Fund [RFA-MD-11-3];
   NATIONAL EYE INSTITUTE [P30EY001765] Funding Source: NIH RePORTER
FX We thank Dr. Alice Jouneau (INRA BDR) and Dr. Vinod Ranganathan (Johns
   Hopkins University) for help in reviewing the manuscript, Dr. Michael
   Young (Harvard Medical School) for fruitful discussions, Dr. Zara
   Melkoumian (Corning Life Sciences) for useful advice regarding the use
   of VN-PAS, and Dr. Tomohiro Matsuda (Johns Hopkins University) for
   assistance with quantitative PCR experiments. This work was supported by
   a Foundation Fighting Blindness Wynn-Gund Translational Acceleration
   Program grant, an American Health Assistance Foundation Macular
   Degeneration Research grant, NIH Core Grant P30EY001765 to the Wilmer
   Eye Institute, unrestricted funds from Research to Prevent Blindness,
   Inc., and generous gifts from Mr. and Mrs. Robert and Clarice Smith, the
   Raab Family Foundation, and the Guerrieri Family Foundation. J.M. was
   supported by Post-Doctoral Fellowship Grant RFA-MD-11-3 from the
   Maryland Stem Cell Research Fund.
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NR 63
TC 74
Z9 80
U1 1
U2 36
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD MAY
PY 2013
VL 2
IS 5
BP 341
EP 354
DI 10.5966/sctm.2012-0106
PG 14
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 139MB
UT WOS:000318585700010
PM 23585288
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Buttner-Mainik, A
   Parsons, J
   Jerome, H
   Hartmann, A
   Lamer, S
   Schaaf, A
   Schlosser, A
   Zipfel, PF
   Reski, R
   Decker, EL
AF Buettner-Mainik, Annette
   Parsons, Juliana
   Jerome, Hanna
   Hartmann, Andrea
   Lamer, Stephanie
   Schaaf, Andreas
   Schlosser, Andreas
   Zipfel, Peter F.
   Reski, Ralf
   Decker, Eva L.
TI Production of biologically active recombinant human factor H in
   Physcomitrella
SO PLANT BIOTECHNOLOGY JOURNAL
LA English
DT Article
DE complement factor H; FH; moss; Physcomitrella patens; recombinant
   biopharmaceuticals
ID COMPLEMENT-FACTOR-H; HEMOLYTIC-UREMIC-SYNDROME; TRANSLATIONAL MINIREVIEW
   SERIES; TUBULAR PHOTOBIOREACTOR; HUMAN-ERYTHROPOIETIN; ALTERNATIVE
   PATHWAY; ENDOTHELIAL-CELLS; MOSS BIOREACTORS; N-GLYCOSYLATION;
   HIGHER-PLANTS
AB The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma.
C1 [Buettner-Mainik, Annette; Parsons, Juliana; Jerome, Hanna; Schaaf, Andreas; Reski, Ralf; Decker, Eva L.] Univ Freiburg, Fac Biol, Freiburg, Germany.
   [Parsons, Juliana; Reski, Ralf; Decker, Eva L.] Ctr Biol Signalling Studies BIOSS, Freiburg, Germany.
   [Hartmann, Andrea; Zipfel, Peter F.] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
   [Lamer, Stephanie; Schlosser, Andreas] Ctr Syst Biol ZBSA, Core Facil Prote, Freiburg, Germany.
   [Lamer, Stephanie; Schlosser, Andreas; Reski, Ralf] Feiburg Initiat Syst Biol FRISYS, Freiburg, Germany.
C3 University of Freiburg; Hans Knoll Institute (HKI)
RP Decker, EL (通讯作者)，Univ Freiburg, Fac Biol, Freiburg, Germany.
EM eva.decker@biologie.uni-freiburg.de
RI Parsons, Juliana/K-4652-2015
OI Reski, Ralf/0000-0002-5496-6711
FU German Chemical Industry Foundation (FCI); German Federal Ministry of
   Education and Research (BMBF) [0312624, FRISYS: 0313921]; Excellence
   Initiative of the German Federal and State Governments [EXC 294]
FX A.B-M. is particularly thankful for her support through a
   Kekule-scholarship by the German Chemical Industry Foundation (FCI).
   Funding of this work by the German Federal Ministry of Education and
   Research (BMBF; 0312624, FRISYS: 0313921) and the Excellence Initiative
   of the German Federal and State Governments (EXC 294) is gratefully
   acknowledged. We highly appreciate the excellent technical assistance
   provided by Ulrike Lanner, Gertrud Wiedemann, Dagmar Krischke, and Linh
   Da Minh Phan. We thank Anne Katrin Prowse for proof-reading of the
   manuscript.
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NR 59
TC 63
Z9 70
U1 0
U2 26
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1467-7644
EI 1467-7652
J9 PLANT BIOTECHNOL J
JI Plant Biotechnol. J.
PD APR
PY 2011
VL 9
IS 3
BP 373
EP 383
DI 10.1111/j.1467-7652.2010.00552.x
PG 11
WC Biotechnology & Applied Microbiology; Plant Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Plant Sciences
GA 738HM
UT WOS:000288630900008
PM 20723134
DA 2022-11-30
ER

PT J
AU Canavese, M
   Altruda, F
   Ruzicka, T
   Schauber, J
AF Canavese, Miriam
   Altruda, Fiorella
   Ruzicka, Thomas
   Schauber, Juergen
TI Vascular endothelial growth factor (VEGF) in the pathogenesis of
   psoriasis-A possible target for novel therapies?
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Review
DE VEGF; Inflammation; Skin; Psoriasis; Angiogenesis
ID PERMEABILITY FACTOR; SKIN INFLAMMATION; PLAQUE PSORIASIS; T-CELLS;
   ANGIOGENESIS; OVEREXPRESSION; KERATINOCYTES; INHIBITION; EXPRESSION;
   RECEPTORS
AB Angiogenesis is defined as the formation of new capillaries from pre-existing blood vessels. The process of angiogenesis is tightly regulated by a balance between pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor and several anti-VEGF therapies are used in the treatment of diseases that are characterized by abnormal formation of blood vessels such as certain cancers and age-related macular degeneration. In addition, dysregulated angiogenesis has been observed in inflammatory diseases and might underly chronic cutaneous inflammation in psoriasis. Several experimental studies and clinical reports suggest that VEGF is involved in psoriasis pathogenesis. Among those, transgenic over-expression of VEGF in keratinocytes in mice resulted in skin inflammation and a phenotype resembling human psoriasis. In different psoriasis models, anti-VEGF antibody treatment of mice, already displaying disease symptoms, resulted in an overall improvement of the cutaneous lesions. On the molecular level human keratinocytes produce VEGF after stimulation with cytokines involved in psoriasis pathogenesis. Finally, patients with psoriasis receiving anti-VEGF treatment for cancer showed complete remission of their cutaneous symptoms. Therefore, VEGF might be an underappreciated proinflammatory factor in the pathogenesis of psoriasis. In this review, current knowledge on the significance of VEGF in psoriasis pathogenesis is summarized. Furthermore, current reports on treatments directed against VEGF or its receptors and their potential as future therapy for psoriasis are discussed. (C) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Schauber, Juergen] Univ Munich, Dept Dermatol & Allergy, Klin & Poliklin Dermatol & Allergol, D-80337 Munich, Germany.
   [Altruda, Fiorella] Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, Turin, Italy.
C3 University of Munich; University of Turin
RP Schauber, J (通讯作者)，Univ Munich, Dept Dermatol & Allergy, Klin & Poliklin Dermatol & Allergol, Frauenlobstr 9-11, D-80337 Munich, Germany.
EM juergen.schauber@med.uni-muenchen.de
FU Fritz Thyssen Stiftung; Deutsche Forschungsgemeinschaft [979/3-1]
FX Some of the data on K14-VEGF transgenic mice reported in this review
   were part of MC's Ph.D. thesis at the University of Torino, Italy. MC is
   supported by a postdoctoral fellowship from the Fritz Thyssen Stiftung.
   JS has received grants from the Deutsche Forschungsgemeinschaft (Emmy
   Noether Programm; Scha 979/3-1; www.dfg.de) and the Fritz Thyssen
   Stiftung (www.fritzthyssen-stiftung.de).
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NR 45
TC 72
Z9 82
U1 0
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD JUN
PY 2010
VL 58
IS 3
BP 171
EP 176
DI 10.1016/j.jdermsci.2010.03.023
PG 6
WC Dermatology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Dermatology
GA 610ZW
UT WOS:000278781000001
PM 20430590
DA 2022-11-30
ER

PT J
AU Campbell, M
   Nguyen, ATH
   Kiang, AS
   Tam, LCS
   Gobbo, OL
   Kerskens, C
   Dhubhghaill, SN
   Humphries, MM
   Farrar, GJ
   Kenna, PF
   Humphries, P
AF Campbell, Matthew
   Nguyen, Anh T. H.
   Kiang, Anna-Sophia
   Tam, Lawrence C. S.
   Gobbo, Oliviero L.
   Kerskens, Christian
   Dhubhghaill, Sorcha Ni
   Humphries, Marian M.
   Farrar, G. -Jane
   Kenna, Paul F.
   Humphries, Peter
TI An experimental platform for systemic drug delivery to the retina
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE blood-retina barrier; retinitis pigmentosa; RNAi; tight junctions;
   claudin-5
ID BLOOD-BRAIN-BARRIER; MOLECULAR-GENETICS; TIGHT JUNCTION; EXPRESSION;
   APOPTOSIS; CLAUDIN-5; DEGENERATION; INVOLVEMENT; DYSFUNCTION; OCCLUDIN
AB Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders-major causes of world blindness-are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized'' approach to therapy for conditions with little or no current forms of treatment.
C1 [Campbell, Matthew; Nguyen, Anh T. H.; Kiang, Anna-Sophia; Tam, Lawrence C. S.; Dhubhghaill, Sorcha Ni; Humphries, Marian M.; Farrar, G. -Jane; Kenna, Paul F.; Humphries, Peter] Univ Dublin Trinity Coll, Dept Genet, Ocular Genet Unit, Dublin 2, Ireland.
   [Gobbo, Oliviero L.] Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland.
   [Kerskens, Christian] Univ Dublin Trinity Coll, Trinity Coll Inst Neurosci, Dublin 2, Ireland.
C3 Trinity College Dublin; Trinity College Dublin; Trinity College Dublin
RP Campbell, M (通讯作者)，Univ Dublin Trinity Coll, Dept Genet, Ocular Genet Unit, Dublin 2, Ireland.
EM matthew.campbell@tcd.ie
RI Ní Dhubhghaill, Sorcha/D-4278-2015; Bateson, Jane Farrar/AAO-6147-2020;
   Gobbo, Oliviero L/R-1763-2016; Farrar, G Jane/B-9832-2011; Kerskens,
   Christian/AAJ-6202-2020; Gobbo, Oliviero/S-2043-2019
OI Ní Dhubhghaill, Sorcha/0000-0002-1115-7834; Gobbo, Oliviero
   L/0000-0003-4629-9485; Kerskens, Christian/0000-0003-0823-4648; Gobbo,
   Oliviero/0000-0003-4629-9485
FU Science Foundation Ireland; Wellcome Trust; European Vision Institute;
   EVI-Genoret [LSHG-CT-2005-512036]; Fighting Blindness Ireland, and
   Enterprise Ireland
FX We thank Caroline Woods, David Flynn, and Rebecca Robertson for animal
   husbandry. IMPDH1<SUP>-/-</SUP> mice were kindly donated by Dr. Beverly
   Mitchell. The Ocular Genetics Unit at TCD is supported by Science
   Foundation Ireland, The Wellcome Trust, European Vision Institute,
   EVI-Genoret Grant LSHG-CT-2005-512036, Fighting Blindness Ireland, and
   Enterprise Ireland.
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NR 43
TC 55
Z9 56
U1 0
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 20
PY 2009
VL 106
IS 42
BP 17817
EP 17822
DI 10.1073/pnas.0908561106
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 508UR
UT WOS:000270963100040
PM 19822744
OA Green Published, Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Cousins, S
   Bearelly, S
   Reinoso, M
   Chi, S
   Espinosa-Heidmann, D
AF Cousins, Scott W.
   Bearelly, Srilaxmi
   Reinoso, Maria A.
   Chi, Sulene L.
   Espinosa-Heidmann, Diego G.
TI Dynamic indocyanine green angiography-guided focal thermal laser
   treatment of fibrotic choroidal neovascularization
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Fibrotic choroidal neovascularization;
   Indocyanine green angiography; Focal thermal laser
ID MACULAR DEGENERATION; FEEDER VESSELS; PHOTOCOAGULATION; ANGIOGENESIS;
   DISEASES
AB Fibrotic choroidal neovascular membranes (CNV) are the end-stage outcomes of neovascular age-related macular degeneration (AMD). No treatment is currently available for fibrotic CNV. We investigated the role of focal thermal laser ablation of the perfusing afferent arteriole as determined by dynamic indocyanine green angiography (ICGA).
   We conducted a retrospective study of 20 patients with fibrotic CNV associated with significant subretinal fluid or retinal edema, who also demonstrated well-defined perfusing arterioles by dynamic ICGA. Patients underwent focal thermal laser occlusion of the perfusing afferent arteriole. Six, 12 and 24 weeks post-treatment, eyes underwent repeat examination with optical coherence tomography (OCT) and visual acuity testing, and ICGA at 12 weeks.
   Therapeutic closure of the perfusing afferent arterioles was achieved in 17 of 20 eyes immediately post-treatment. All 17 of these eyes demonstrated significant resolution of retinal edema and subretinal fluid, as evidenced by OCT, which was dramatic in some cases. Seven eyes demonstrated an improvement in visual acuity of 1 line or more. While most eyes demonstrated reperfusion within 3 months, many lesions suggested reduced vascularity and flow.
   Eyes with fibrotic CNV and associated retinal edema often demonstrate well-defined vascularity of the fibrosis with discrete perfusing arterioles when imaged by dynamic ICGA. Thermal laser occlusion of these arterioles can result in resolution of subretinal fluid, and occasionally an improvement in vision. This represents a potential therapeutic intervention for an advanced stage of AMD currently regarded as stable.
C1 [Cousins, Scott W.; Bearelly, Srilaxmi; Chi, Sulene L.] Duke Univ, Ctr Eye, Duke Ctr Macular Dis, Durham, NC 27706 USA.
   [Cousins, Scott W.; Bearelly, Srilaxmi; Chi, Sulene L.] Duke Univ, Ctr Eye, Albert Eye Res Inst, Durham, NC USA.
   [Cousins, Scott W.; Reinoso, Maria A.; Espinosa-Heidmann, Diego G.] Univ Miami, Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA.
   [Reinoso, Maria A.] Louisiana State Univ Ochsner Hlth Syst, Dept Ophthalmol, New Orleans, LA USA.
   [Espinosa-Heidmann, Diego G.] Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA.
C3 Duke University; Duke University; Bascom Palmer Eye Institute;
   University of Miami; Ochsner Health System; University System of
   Georgia; Augusta University
RP Cousins, S (通讯作者)，Duke Univ, Ctr Eye, Duke Ctr Macular Dis, Durham, NC 27706 USA.
EM scott.cousins@duke.edu
FU Research to Prevent Blindness
FX The authors have no proprietary interest in any aspect of this report.
   This work has been supported in part by an unrestricted grant from
   Research to Prevent Blindness.
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NR 19
TC 2
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD DEC
PY 2008
VL 246
IS 12
BP 1677
EP 1683
DI 10.1007/s00417-008-0905-5
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 368QM
UT WOS:000260637600004
PM 18682971
DA 2022-11-30
ER

PT J
AU Klein, BEK
   Knudtson, MD
   Lee, KE
   Reinke, JO
   Danforth, LG
   Wealti, AM
   Moore, E
   Klein, R
AF Klein, Barbara E. K.
   Knudtson, Michael D.
   Lee, Kristine E.
   Reinke, Jennifer O.
   Danforth, Lorraine G.
   Wealti, Angela M.
   Moore, Emily
   Klein, Ronald
TI Supplements and age-related eye conditions - The Beaver Dam Eye Study
SO OPHTHALMOLOGY
LA English
DT Article
ID ALTERNATIVE MEDICINE USE; UNITED-STATES; VISUAL-ACUITY;
   DIETARY-SUPPLEMENTS; HERBAL MEDICINES; MACULAR DEGENERATION;
   NATIONAL-HEALTH; US ADULTS; COMPLEMENTARY; POPULATION
AB Objective: To investigate the association of use of vitamin, mineral, and nonvitamin nonmineral supplements with common age-related eye diseases.
   Design: Population-based prospective study with incidence data.
   Participants: Subjects were participants in the Beaver Dam Eye Study who contributed data in 1988 to 1990 (n = 4926), 1993 to 1995 (n = 3722), 1998 to 2000 (n = 2962), and 2003 to 2005 (n = 2375).
   Methods: Use of all medications and supplements were collected from study participants at each of 4 examinations. Intraocular pressure (IOP) measurement and fundus and lens photography were done at each visit. Visual field data are available only from baseline. Photographs of the lenses, retina, and discs were graded using standard protocols by trained graders.
   Main Outcome Measures: Incidence of age-related cataracts, macular degeneration (AMD), and high IOP for one set of analyses and incidence of supplement use for the second set of analyses.
   Results: There was little evidence of any significant associations between supplement use and incident ocular outcomes except for a small protective effect for cortical cataracts by vitamins A and D, zinc, and multivitamins and increased odds of late AMD. Late AMD was associated with incident use of vitamins A, C, and E and zinc.
   Conclusions: Age-related macular degeneration seems to precede use of vitamins A, C, and E and zinc. This may reflect advice by family, friends, and health care providers about the benefits of Age-Related Eye Disease Study-like supplements.
C1 [Klein, Barbara E. K.; Knudtson, Michael D.; Lee, Kristine E.; Reinke, Jennifer O.; Danforth, Lorraine G.; Wealti, Angela M.; Moore, Emily; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53726 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Klein, BEK (通讯作者)，Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, 610 N Walnut St,4th Floor WARF, Madison, WI 53726 USA.
EM kleinb@epi.ophth.wisc.edu
OI Klein, Ronald/0000-0002-4428-6237
FU NEI NIH HHS [EY06594, U10 EY006594] Funding Source: Medline
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NR 46
TC 25
Z9 25
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2008
VL 115
IS 7
BP 1203
EP 1208
DI 10.1016/j.ophtha.2007.09.011
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 320CK
UT WOS:000257211100016
PM 17997484
DA 2022-11-30
ER

PT J
AU Marques, JP
   Bernardes, J
   Geada, S
   Soares, M
   Teixeira, D
   Farinha, C
   Pires, I
   Cachulo, ML
   Silva, R
AF Marques, Joao Pedro
   Bernardes, Joao
   Geada, Sara
   Soares, Mario
   Teixeira, Dora
   Farinha, Claudia
   Pires, Isabel
   Cachulo, Maria Luz
   Silva, Rufino
TI Non-exudative macular neovascularization in pseudoxanthoma elasticum
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Pseudoxanthoma elasticum; Angioid streaks; Non-exudative macular
   neovascularization; Optical coherence tomography; Optical coherence
   tomography angiography; Quiescent
ID CHOROIDAL NEOVASCULARIZATION; ANGIOID STREAKS; SPECTRUM
AB Purpose To characterize morphological changes in the retina and to report the frequency and natural history of non-exudative macular neovascularization (MNV) in a cohort of pseudoxanthoma elasticum (PXE). Methods A single-center, retrospective study was complemented by a cross-sectional examination. Consecutive patients with a definitive genetic and/or clinical diagnosis of PXE, visiting our department between January 2019 and December 2019, and with a minimum follow-up of 6 months were recruited. Baseline data were retrieved from each patient file. Additionally, a cross-sectional examination comprising color fundus photography, spectral-domain optical coherence tomography (SD-OCT), OCT-Angiography (OCT-A), and fundus autofluorescence was performed. The presence of typical PXE-related findings, as well as related complications, was multimodally evaluated. The prevalence and natural history of non-exudative MNV were assessed. All images were graded by two independent graders. Results Forty-eight eyes from 24 patients (mean age 59.11 +/- 18.14) with a median follow-up of 53.00 months were included. Angioid streaks andpeau d'orangewere observed in 46/48 and 42/48 eyes, while MNV was present in 75.00% of the cohort. The prevalence of non-exudative MNV was 33.33% (6/18). In the 2 eyes that developed exudation, time to conversion was 9.50 +/- 4.95 months. No significant difference in visual acuity was found between eyes with non-exudative MNV and those with no signs of MNV. Conclusion We have shown that non-exudative MNV is a frequent finding in PXE but the majority of eyes did not develop exudation during follow-up. Our results are a clear evidence of the utility of OCT-A in the management of PXE.
C1 [Marques, Joao Pedro; Bernardes, Joao; Geada, Sara; Soares, Mario; Teixeira, Dora; Farinha, Claudia; Pires, Isabel; Cachulo, Maria Luz; Silva, Rufino] Ctr Hosp & Univ Coimbra CHUC, Ctr Responsabilidade Integrado Oftalmol CRIO, Ophthalmol Unit, Praceta Prof Mota Pinto, P-3000075 Coimbra, Portugal.
   [Marques, Joao Pedro; Farinha, Claudia; Pires, Isabel; Cachulo, Maria Luz; Silva, Rufino] Univ Coimbra FMUC, Fac Med, Univ Clin Ophthalmol, Coimbra, Portugal.
   [Marques, Joao Pedro; Farinha, Claudia; Pires, Isabel; Cachulo, Maria Luz] Clin Acad Ctr Coimbra CACC, Coimbra, Portugal.
   [Marques, Joao Pedro; Farinha, Claudia; Pires, Isabel; Cachulo, Maria Luz] Univ Coimbra, Univ Coimbra FMUC, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal.
C3 Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra
   (CHUC); Universidade de Coimbra; Universidade de Coimbra; Universidade
   de Coimbra
RP Marques, JP (通讯作者)，Ctr Hosp & Univ Coimbra CHUC, Ctr Responsabilidade Integrado Oftalmol CRIO, Ophthalmol Unit, Praceta Prof Mota Pinto, P-3000075 Coimbra, Portugal.; Marques, JP (通讯作者)，Univ Coimbra FMUC, Fac Med, Univ Clin Ophthalmol, Coimbra, Portugal.; Marques, JP (通讯作者)，Clin Acad Ctr Coimbra CACC, Coimbra, Portugal.; Marques, JP (通讯作者)，Univ Coimbra, Univ Coimbra FMUC, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal.
EM marquesjoaopedro@gmail.com
RI Marques, João Pedro/J-3584-2012; Farinha, Claudia/R-1392-2017
OI Marques, João Pedro/0000-0002-1014-0483; Silva,
   Rufino/0000-0001-8676-0833; Pires, Isabel/0000-0002-5764-0178; Batista,
   Sara/0000-0002-6851-6201; Farinha, Claudia/0000-0003-4596-0913;
   Bernardes, Joao/0000-0002-4609-1302
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NR 24
TC 1
Z9 1
U1 1
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 APR
PY 2021
VL 259
IS 4
BP 873
EP 882
DI 10.1007/s00417-020-04979-z
EA OCT 2020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RH0XW
UT WOS:000581054600002
PM 33074374
DA 2022-11-30
ER

PT J
AU Rego-Lorca, D
   Valverde-Megias, A
   Fernandez-Vigo, JI
   Oribio-Quinto, C
   Murciano-Cespedosa, A
   Sanchez-Quiros, J
   Donate-Lopez, J
   Garcia-Feijoo, J
AF Rego-Lorca, Daniela
   Valverde-Megias, Alicia
   Ignacio Fernandez-Vigo, Jose
   Oribio-Quinto, Carlos
   Murciano-Cespedosa, Antonio
   Sanchez-Quiros, Julia
   Donate-Lopez, Juan
   Garcia-Feijoo, Julian
TI Long-Term Consequences of COVID-19 Lockdown in Neovascular AMD Patients
   in Spain: Structural and Functional Outcomes after 1 Year of Standard
   Follow-Up and Treatment
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Article
DE COVID-19; pandemic; lockdown effects; nAMD; anti-VEGF
ID MACULAR DEGENERATION; TREATMENT DELAY; RANIBIZUMAB; THERAPY; IMPACT
AB Consequences of the COVID-19 pandemic on medical care have been extensively analyzed. Specifically, in ophthalmology practice, patients suffering age-related macular degeneration (AMD) represent one of the most affected subgroups. After reporting the acute consequences of treatment suspension in neovascular AMD, we have now evaluated these same 242 patients (270 eyes) to assess if prior functional and anatomical situations can be restored after twelve months of regular follow-up and treatment. We compared data from visits before COVID-19 outbreak and the first visit after lockdown with data obtained in subsequent visits, until one year of follow-up was achieved. For each patient, rate of visual loss per year before COVID-19 pandemic, considered "natural history of treated AMD", was calculated. This rate of visual loss significantly increased during the lockdown period and now, after twelve months of regular follow-up, is still higher than before COVID outbreak (3.1 vs. 1.6 ETDRS letters/year, p < 0.01). Percentage of OCT images showing active disease is now lower than before the lockdown period (51% vs. 65.3%, p = 0.0017). Although anatomic deterioration, regarding signs of active disease, can be apparently fully restored, our results suggest that functional consequences of temporary anti-VEGF treatment suspension are not entirely reversible after 12 months of treatment, as BCVA remains lower and visual loss rate is still higher than before the COVID-19 pandemic.
C1 [Rego-Lorca, Daniela; Valverde-Megias, Alicia; Ignacio Fernandez-Vigo, Jose; Oribio-Quinto, Carlos; Sanchez-Quiros, Julia; Donate-Lopez, Juan; Garcia-Feijoo, Julian] San Carlos Clin Hosp, Inst Invest Sanitaria, Dept Ophthalmol, Hosp Clin San Carlos IdISSC, Madrid 28040, Spain.
   [Ignacio Fernandez-Vigo, Jose] Ctr Int Oftalmol Avanzada, Madrid 28010, Spain.
   [Murciano-Cespedosa, Antonio] Univ Complutense Madrid, Fac Biol, Dept Biodivers Ecol & Evolut, Madrid 28040, Spain.
   [Murciano-Cespedosa, Antonio] Univ Complutense Madrid, Modeling Data Anal & Computat Tools Biol Res Grp, Madrid 28040, Spain.
   [Murciano-Cespedosa, Antonio] Univ Complutense Madrid, Neurocomp & Neurorobot Res Grp, Madrid 28037, Spain.
   [Murciano-Cespedosa, Antonio] Hosp Clin San Carlos IdISSC, Brain Plast Grp, Inst Invest Sanitaria, Madrid 28040, Spain.
C3 Hospital Clinico San Carlos; Complutense University of Madrid;
   Complutense University of Madrid; Complutense University of Madrid;
   Hospital Clinico San Carlos
RP Rego-Lorca, D (通讯作者)，San Carlos Clin Hosp, Inst Invest Sanitaria, Dept Ophthalmol, Hosp Clin San Carlos IdISSC, Madrid 28040, Spain.
EM dpregolorca@gmail.com
RI ; Fernandez-Vigo, Jose Ignacio/G-9779-2017
OI Oribio-Quinto, Carlos/0000-0003-3577-6880; DONATE,
   JUAN/0000-0002-9944-6736; Rego-Lorca, Daniela/0000-0002-8076-0522;
   Fernandez-Vigo, Jose Ignacio/0000-0001-8745-3464
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NR 27
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 SEP
PY 2022
VL 11
IS 17
AR 5063
DI 10.3390/jcm11175063
PG 10
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 4J2JN
UT WOS:000851095200001
PM 36078993
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shen, G
   Li, YM
   Hong, FY
   Zhang, J
   Fang, ZZ
   Xiang, W
   Qi, WW
   Yang, X
   Gao, GQ
   Zhou, T
AF Shen, Gang
   Li, Yanmei
   Hong, Fuyan
   Zhang, Jing
   Fang, Zhenzhen
   Xiang, Wei
   Qi, Weiwei
   Yang, Xia
   Gao, Guoquan
   Zhou, Ti
TI A role for Snail-MnSOD axis in regulating epithelial-to-mesenchymal
   transition markers expression in RPE cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Age-related macular degeneration (AMD); Epithelial-mesenchymal
   transition (EMT); Manganese superoxide dismutase (MnSOD); Snail;
   Reactive oxygen species (ROS); Retinal pigment epithelium (RPE)
ID RETINAL-PIGMENT EPITHELIUM; OXIDATIVE STRESS; EMT; OVEREXPRESSION;
   DEGENERATION; MODEL
AB Age-related macular degeneration (AMD) is a common cause of vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, accompanied by oxidative damage, plays a crucial role in AMD. It is well known that manganese superoxide dismutase (MnSOD) encoded by SOD2 is a critical molecule in fighting against oxidative stress, and Snail encoded by SNAIL is the essential transcription factor for EMT. However, the effect of MnSOD on EMT and the underlying mechanism in RPE cells remains unknown. In this study, we found that MnSOD knockdown triggered the EMT by upregulating Snail, while MnSOD overexpression reversed EMT even with TGF beta treatment in RPE cells, and the anti-oxidative stress activity of MnSOD mediated this observation. In addition, Snail depletion increased both expression and activity of MnSOD while Snail overexpression decreased MnSOD expression and activity, and Dual-luciferase reporter and ChIP assays showed that Snail directly bound to E-box (CACCTG) in the SOD2 promoter. Moreover, MnSOD over-expression and Snail interference co-treatment strengthened the anti-oxidation and EMT reversing. Therefore, our findings demonstrate that MnSOD prevents EMT of RPE cells in AMD through inhibiting oxidative injury to RPE. Moreover, a critical EMT transcription factor, Snail, functions as a new negative transcriptional factor of SOD2. Herein, the Snail-MnSOD axis forms a mutual loop in the development of AMD, which may be a novel systemic treatment target for preventing AMD. (C) 2021 Elsevier Inc. All rights reserved.
C1 [Shen, Gang; Qi, Weiwei; Yang, Xia; Gao, Guoquan; Zhou, Ti] Sun Yat Sen Univ, Affiliated Guangzhou Women & Childrens Hosp, Zhongshan Sch Med, Program Mol Med, Guangzhou, Peoples R China.
   [Shen, Gang; Li, Yanmei; Hong, Fuyan; Zhang, Jing; Fang, Zhenzhen; Xiang, Wei; Qi, Weiwei; Yang, Xia; Gao, Guoquan; Zhou, Ti] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou, Peoples R China.
   [Shen, Gang] Sun Yat Sen Univ, Dept Lab Med, Affiliated Hosp 3, Guangzhou, Peoples R China.
   [Gao, Guoquan] Sun Yat Sen Univ, Guangdong Engn & Technol Res Ctr Gene Manipulat &, Guangzhou, Peoples R China.
   [Yang, Xia] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou, Peoples R China.
   [Zhou, Ti] Sun Yat Sen Univ, Minist Educ, China Key Lab Trop Dis Control, Guangzhou, Peoples R China.
C3 Sun Yat Sen University; Sun Yat Sen University; Sun Yat Sen University;
   Sun Yat Sen University; Sun Yat Sen University; Sun Yat Sen University
RP Zhou, T (通讯作者)，Sun Yat Sen Univ, Zhongshan Med Sch, Dept Biochem, 74 Zhongshan Rd 2, Guangzhou 510080, Peoples R China.
EM zhouti2@mail.sysu.edu.cn
FU Guangdong Special Support Program for Young Top Scientist [201629046];
   National Natural Science Foundation of China [82070888, 82070882,
   81770808, 81872165, 81701414, 81871211, 81702879]; National Key R&D
   Program of China [2018YFA0800403]; Guangdong Provincial Key RD Program
   [2018B030337001, 2019B020227003]; Key Project of Nature Science
   Foundation of Guangdong Province, China [2019B1515120077]; Guangdong
   Natural Science Fund [2019A1515011810, 2021A1515010434]; Guangdong
   Science Technology Project [2017A020215075]; Key Sci-Tech Research
   Project of Guangzhou Municipality, China [201803010017, 201807010069,
   202002020022]; 2019 Milstein Medical Asian American Partnership
   Foundation Research Project Award in Translational Medicine; 2017
   Milstein Medical Asian American Partnership Foundation Research Project
   Award in Translational Medicine
FX This study was supported by Guangdong Special Support Program for Young
   Top Scientist (Grant 201629046); The National Natural Science Foundation
   of China (Grants 82070888, 82070882, 81770808, 81872165, 81701414,
   81871211, and 81702879); National Key R&D Program of China (Grant
   2018YFA0800403); Guangdong Provincial Key R&D Program (Grants
   2018B030337001 and 2019B020227003); Key Project of Nature Science
   Foundation of Guangdong Province, China (Grant 2019B1515120077);
   Guangdong Natural Science Fund (Grant 2019A1515011810, 2021A1515010434);
   Guangdong Science Technology Project (Grant 2017A020215075); Key
   Sci-Tech Research Project of Guangzhou Municipality, China (Grants
   201803010017, 201807010069, and 202002020022); 2017 and 2019 Milstein
   Medical Asian American Partnership Foundation Research Project Award in
   Translational Medicine.
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U2 8
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 DEC 31
PY 2021
VL 585
BP 146
EP 154
DI 10.1016/j.bbrc.2021.11.039
EA NOV 2021
PG 9
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA XN4DA
UT WOS:000729456100009
PM 34808498
DA 2022-11-30
ER

PT J
AU Aninye, IO
   Digre, K
   Hartnett, ME
   Baldonado, K
   Shriver, EM
   Periman, LM
   Grutzmacher, J
   Clayton, JA
AF Aninye, Irene O.
   Digre, Kathleen
   Hartnett, M. Elizabeth
   Baldonado, Kira
   Shriver, Erin M.
   Periman, Laura M.
   Grutzmacher, Julie
   Clayton, Janine A.
CA Soc Women's Hlth Res Women's Eye
TI The roles of sex and gender in women's eye health disparities in the
   United States
SO BIOLOGY OF SEX DIFFERENCES
LA English
DT Review
DE Dry eye; Retinopathy; Gender inequity; Health disparities; Macular
   degeneration; Telehealth; Patient and provider education; Population
   health; Thyroid eye disease; Vision loss
ID TEAR FILM; DRY EYE; DISEASE; RETINOPATHY; PATHOPHYSIOLOGY; PREVALENCE;
   PREGNANCY; MIGRAINE; ADULTS
AB Background In the United States, women are at a higher risk of developing vision impairment or a serious eye disease (such as age-related macular degeneration, thyroid eye disease, or chronic dry eye disease) than men. Disparities in eye diseases due to biology widen even further when considering factors such as social determinants of health; gaps in research data, literature, and policy; insufficient provider and patient education; and limitations in screening and treatment options. Sex and gender disparities in eye health are clinically under-addressed and burdensome on both patient quality of life and the health care and economic systems, resulting in a pressing population health issue that negatively impacts women. Design The Society for Women's Health Research convened a working group of expert clinicians, researchers, and patient advocates to review the current state of science regarding sex and gender disparities in women's eye health, identify knowledge gaps and unmet needs, and explore better means to advance research, improve patient care, and raise awareness of key issues. Discussion The SWHR Women's Eye Health Working Group identified priority areas in research, clinical care, and education to reduce disparities and improve patient care in women's eye health. The working group recommends using a systems approach that incorporates a comprehensive research framework with a sex and gender lens to guide future work and that increases health care provider and public education, as well as engagement by expanding partnerships among ophthalmologic providers, researchers, and non-vision stakeholders.
C1 [Aninye, Irene O.; Soc Women's Hlth Res Women's Eye] Soc Womens Hlth Res, 1025 Connecticut Ave NW,Suite 1104, Washington, DC 20036 USA.
   [Digre, Kathleen; Hartnett, M. Elizabeth] Univ Utah, Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   [Baldonado, Kira; Grutzmacher, Julie] Prevent Blindness, Chicago, IL USA.
   [Shriver, Erin M.] Univ Iowa, Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Periman, Laura M.] Periman Eye Inst, Seattle, WA USA.
   [Clayton, Janine A.] NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA.
C3 Utah System of Higher Education; University of Utah; University of Iowa;
   National Institutes of Health (NIH) - USA
RP Aninye, IO (通讯作者)，Soc Womens Hlth Res, 1025 Connecticut Ave NW,Suite 1104, Washington, DC 20036 USA.
EM science@swhr.org
RI Periman MD, Laura M/GPF-5866-2022
OI Aninye, Irene/0000-0002-1747-9148
FU SWHR Women's Eye Health Program; Horizon Pharmaceuticals
FX The SWHR Women's Eye Health Program and development of this manuscript
   were supported by programmatic sponsorship from Horizon Pharmaceuticals.
   The funder had no role in the writing of this review or the decision to
   submit it for publication.
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NR 57
TC 2
Z9 2
U1 1
U2 3
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 2042-6410
J9 BIOL SEX DIFFER
JI Biol. Sex Differ.
PD OCT 20
PY 2021
VL 12
IS 1
AR 57
DI 10.1186/s13293-021-00401-3
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism; Genetics & Heredity
GA WJ8WL
UT WOS:000709318600001
PM 34670620
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Clemens, CR
   Lauermann, JL
   Schmitz, B
   Eter, N
   Alten, F
AF Clemens, Christoph R.
   Lauermann, Jost L.
   Schmitz, Boris
   Eter, Nicole
   Alten, Florian
TI Longitudinal choriocapillaris changes in the presence of reticular
   pseudodrusen
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; GEOGRAPHIC-ATROPHY; MACULAR DEGENERATION;
   SEGMENTATION ERRORS; FEATURES; RISK; EYES
AB To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4 mm diameter and a circle of 6 mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36 +/- 8.39 mm(2) at baseline to 37.77 +/- 9.03 mm(2) at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p < 0.001; ring: p < 0.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p < 0.001; ring: p < 0.001). Evaluation of CC parameters suggested significant group x time interaction effects for CC FD (p = 0.04) and mean intensity signal (p = 0.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5 years in both RPD-affected and RPD-unaffected macular areas.
C1 [Clemens, Christoph R.; Lauermann, Jost L.; Alten, Florian] Univ Munster, Dept Ophthalmol, Med Ctr, Domagkstr 15, D-48149 Munster, Germany.
   [Schmitz, Boris] Univ Witten Herdecke, Fac Hlth, Dept Rehabil Sci, Witten, Germany.
   [Schmitz, Boris] Klin Konigsfeld DRV, Ctr Med Rehabil, Ennepetal, Germany.
C3 University of Munster; Witten Herdecke University
RP Alten, F (通讯作者)，Univ Munster, Dept Ophthalmol, Med Ctr, Domagkstr 15, D-48149 Munster, Germany.
EM florian.alten@ukmuenster.de
RI Schmitz, Boris/M-3205-2019
OI Schmitz, Boris/0000-0001-7041-7424
FU Open Access Publication Fund of University of Muenster
FX We acknowledge support by the Open Access Publication Fund of University
   of Muenster.
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NR 38
TC 1
Z9 1
U1 1
U2 1
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 14
PY 2021
VL 11
IS 1
AR 18227
DI 10.1038/s41598-021-97771-w
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA UR3IG
UT WOS:000696645100056
PM 34521974
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Li, Y
   Cai, YT
   Huang, Q
   Tan, W
   Li, BY
   Zhou, HX
   Wang, ZC
   Zou, JL
   Ding, C
   Jiang, B
   Yoshida, S
   Zhou, YD
AF Li, Yun
   Cai, Yuting
   Huang, Qian
   Tan, Wei
   Li, Bingyan
   Zhou, Haixiang
   Wang, Zicong
   Zou, Jingling
   Ding, Chun
   Jiang, Bing
   Yoshida, Shigeo
   Zhou, Yedi
TI Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal
   Neovascularization
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Article
DE choroidal neovascularization; age-related macular degeneration; gut
   microbiome; metabolomics; mouse model
ID GUT MICROBIOTA; PATHOLOGICAL ANGIOGENESIS; CHOLESTEROL; OBESITY; EFFLUX;
   SYSTEM
AB PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.
C1 [Li, Yun; Cai, Yuting; Huang, Qian; Tan, Wei; Li, Bingyan; Zhou, Haixiang; Wang, Zicong; Zou, Jingling; Ding, Chun; Jiang, Bing; Zhou, Yedi] Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Peoples R China.
   [Li, Yun; Cai, Yuting; Huang, Qian; Tan, Wei; Li, Bingyan; Zhou, Haixiang; Wang, Zicong; Zou, Jingling; Ding, Chun; Jiang, Bing; Zhou, Yedi] Hunan Clin Res Ctr Ophthalm Dis, Changsha, Peoples R China.
   [Yoshida, Shigeo] Kurume Univ, Dept Ophthalmol, Sch Med, Kurume, Fukuoka, Japan.
C3 Central South University; Kurume University
RP Zhou, YD (通讯作者)，Cent South Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Peoples R China.; Zhou, YD (通讯作者)，Hunan Clin Res Ctr Ophthalm Dis, Changsha, Peoples R China.
EM zhouyedi@csu.edu.cn
OI Zhou, Yedi/0000-0002-8948-1108
FU National Natural Science Foundation of China [81800855]; Natural Science
   Foundation of Hunan Province [2019JJ50885]; Hunan Provincial Science and
   Technology Department [2020SK2086]
FX Funding. This work was supported by the National Natural Science
   Foundation of China (No. 81800855), Natural Science Foundation of Hunan
   Province (No. 2019JJ50885), and Hunan Provincial Science and Technology
   Department (No. 2020SK2086).
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NR 40
TC 4
Z9 4
U1 11
U2 23
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PD AUG 26
PY 2021
VL 12
AR 738796
DI 10.3389/fmicb.2021.738796
PG 10
WC Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Microbiology
GA XI8PS
UT WOS:000726366800001
PM 34512615
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Abokyi, S
   Shan, SW
   Lam, CHI
   Catral, KP
   Pan, F
   Chan, HHL
   To, CH
   Tse, DYY
AF Abokyi, Samuel
   Shan, Sze-Wan
   Lam, Christie Hang-, I
   Catral, Kirk Patrick
   Pan, Feng
   Chan, Henry Ho-Lung
   To, Chi-Ho
   Tse, Dennis Yan-Yin
TI Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects
   and Oxidative Damage in Human Retinal Pigment Epithelial Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; hydroquinone; oxidative stress;
   autophagy; ubiquitin-proteasome system (UPS); lysosomal alkalization
ID SUB-RPE DEPOSITS; OXIDANT INJURY; CULTURED HUMAN; STRESS; PROTEASOME;
   METABOLISM; CROSSTALK; DYNAMICS; PATHWAY; BLOOD
AB In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ. In comparison to hydrogen peroxide (H2O2), HQ induced fewer reactive oxygen species (ROS) but more oxidative damage as characterized by protein carbonyl levels, mitochondrial dysfunction, and the loss of cell viability. HQ blocked the autophagy flux and increased proteasome activity, whereas H2O2 did the opposite. Moreover, the lysosomal membrane-stabilizing protein LAMP2 and cathepsin D levels declined with HQ exposure, suggesting loss of lysosomal membrane integrity and function. Accordingly, HQ induced lysosomal alkalization, thereby compromising the acidic pH needed for optimal lysosomal degradation. Pretreatment with MG132, a proteasome inhibitor and lysosomal stabilizer, upregulated LAMP2 and autophagy and prevented HQ-induced oxidative damage in wildtype RPE cells but not cells transfected with shRNA against ATG5. This study demonstrated that lysosomal dysfunction underlies autophagy defects and oxidative damage induced by HQ in human RPE cells and supports lysosomal stabilization with the proteasome inhibitor MG132 as a potential remedy for oxidative damage in RPE and AMD.
C1 [Abokyi, Samuel; Shan, Sze-Wan; Lam, Christie Hang-, I; Catral, Kirk Patrick; Pan, Feng; Chan, Henry Ho-Lung; To, Chi-Ho; Tse, Dennis Yan-Yin] Hong Kong Polytech Univ, Sch Optometry, Hung Hom, Hong Kong, Peoples R China.
   [Abokyi, Samuel] Univ Cape Coast, Coll Hlth & Allied Sci, Dept Optometry & Vis Sci, Cape Coast 00233, Ghana.
   [Pan, Feng; Chan, Henry Ho-Lung; To, Chi-Ho; Tse, Dennis Yan-Yin] Ctr Eye & Vis Res, 17W Hong Kong Sci Pk, Hong Kong, Peoples R China.
C3 Hong Kong Polytechnic University; University of Cape Coast
RP Tse, DYY (通讯作者)，Hong Kong Polytech Univ, Sch Optometry, Hung Hom, Hong Kong, Peoples R China.; Tse, DYY (通讯作者)，Ctr Eye & Vis Res, 17W Hong Kong Sci Pk, Hong Kong, Peoples R China.
EM samuel.abokyi@connect.polyu.hk; samantha.shan@polyu.edu.hk;
   christie.h.lam@connect.polyu.hk; kirk-patrick.catral@polyu.edu.hk;
   feng.a.pan@polyu.edu.hk; henryhl.chan@polyu.edu.hk;
   chi-ho.to@polyu.edu.hk; dennis.tse@polyu.edu.hk
RI TSE, Dennis Yan-yin/B-9949-2011
OI TSE, Dennis Yan-yin/0000-0001-7561-9121; PAN, Feng/0000-0002-5256-4380;
   To, Chi-ho/0000-0002-1938-8397; Lam, Christie
   Hang-i/0000-0001-8517-8796; ABOKYI, SAMUEL/0000-0001-8808-1340; Catral,
   Kirk Patrick/0000-0001-6458-4875; CHAN, Henry HL/0000-0002-8516-4711;
   SHAN, SW/0000-0001-6876-9914
FU RGC Hong Kong Ph.D. Fellowship [UGC/GEN/456/08, UGC/456/09]; RGC General
   Research Fund [151060/18M]; Government of the Hong Kong Special
   Administrative Region & Innovation and Technology Fund, PolyU Central
   Research Grant UAG1; Henry G. Leong Endowed Professorship in Elderly
   Vision Health; UAHD; PolyU Dean's Reserve (ZVN2)
FX This work was funded by the RGC Hong Kong Ph.D. Fellowship
   UGC/GEN/456/08, UGC/456/09, RGC General Research Fund (151060/18M), The
   Government of the Hong Kong Special Administrative Region & Innovation
   and Technology Fund, PolyU Central Research Grant UAG1, UAHD, PolyU
   Dean's Reserve (ZVN2), and Henry G. Leong Endowed Professorship in
   Elderly Vision Health.
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NR 66
TC 1
Z9 1
U1 1
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD AUG
PY 2021
VL 22
IS 16
AR 9042
DI 10.3390/ijms22169042
PG 21
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA UG4UC
UT WOS:000689248500001
PM 34445748
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Maunz, A
   Benmansour, F
   Li, Y
   Albrecht, T
   Zhang, YP
   Arcadu, F
   Zheng, YL
   Madhusudhan, S
   Sahni, J
AF Maunz, Andreas
   Benmansour, Fethallah
   Li, Yvonna
   Albrecht, Thomas
   Zhang, Yan-Ping
   Arcadu, Filippo
   Zheng, Yalin
   Madhusudhan, Savita
   Sahni, Jayashree
TI Accuracy of a Machine-Learning Algorithm for Detecting and Classifying
   Choroidal Neovascularization on Spectral-Domain Optical Coherence
   Tomography
SO JOURNAL OF PERSONALIZED MEDICINE
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   classification; machine learning; optical coherence tomography
ID VERTEPORFIN PHOTODYNAMIC THERAPY; 2.0 MG RANIBIZUMAB; MACULAR
   DEGENERATION; EFFICACY; SAFETY; LEAKAGE
AB Background: To evaluate the performance of a machine-learning (ML) algorithm to detect and classify choroidal neovascularization (CNV), secondary to age-related macular degeneration (AMD) on spectral-domain optical coherence tomography (SD-OCT) images. Methods: Baseline fluorescein angiography (FA) and SD-OCT images from 1037 treatment-naive study eyes and 531 fellow eyes, without advanced AMD from the phase 3 HARBOR trial (NCT00891735), were used to develop, train, and cross-validate an ML pipeline combining deep-learning-based segmentation of SD-OCT B-scans and CNV classification, based on features derived from the segmentations, in a five-fold setting. FA classification of the CNV phenotypes from HARBOR was used for generating the ground truth for model development. SD-OCT scans from the phase 2 AVENUE trial (NCT02484690) were used to externally validate the ML model. Results: The ML algorithm discriminated CNV absence from CNV presence, with a very high accuracy (area under the receiver operating characteristic [AUROC] = 0.99), and classified occult versus predominantly classic CNV types, per FA assessment, with a high accuracy (AUROC = 0.91) on HARBOR SD-OCT images. Minimally classic CNV was discriminated with significantly lower performance. Occult and predominantly classic CNV types could be discriminated with AUROC = 0.88 on baseline SD-OCT images of 165 study eyes, with CNV from AVENUE. Conclusions: Our ML model was able to detect CNV presence and CNV subtypes on SD-OCT images with high accuracy in patients with neovascular AMD.
C1 [Maunz, Andreas; Benmansour, Fethallah; Li, Yvonna; Albrecht, Thomas; Zhang, Yan-Ping; Arcadu, Filippo; Sahni, Jayashree] F Hoffmann La Roche Ltd, Roche Innovat Ctr, Pharma Res & Early Dev, CH-4070 Basel, Switzerland.
   [Zheng, Yalin; Madhusudhan, Savita] Univ Liverpool, Dept Eye & Vis Sci, Liverpool L7 8XP, Merseyside, England.
   [Zheng, Yalin; Madhusudhan, Savita] Royal Liverpool Univ Hosp, Liverpool Ophthalm Reading Ctr NetwORC, St Pauls Eye Unit, Liverpool L7 8XP, Merseyside, England.
C3 Roche Holding; University of Liverpool; Royal Liverpool & Broadgreen
   University Hospitals NHS Trust; Royal Liverpool University Hospital;
   University of Liverpool
RP Maunz, A (通讯作者)，F Hoffmann La Roche Ltd, Roche Innovat Ctr, Pharma Res & Early Dev, CH-4070 Basel, Switzerland.
EM andreas.maunz@roche.com; fethallah.benmansour@roche.com;
   yvonna.li@roche.com; tom.albrecht@roche.com;
   yan-ping.zhang_schaerer@roche.com; filippo.arcadu@roche.com;
   Yalin.Zheng@liverpool.ac.uk; Savita.Madhusudhan@liverpoolft.nhs.uk;
   jayashreesahni@yahoo.co.uk
RI ; Zheng, Yalin/N-6432-2017
OI Maunz, Andreas/0000-0002-2784-9456; Zhang, Yan-Ping/0000-0001-7602-4453;
   Zheng, Yalin/0000-0002-7873-0922
FU F. Hoffmann-La Roche Ltd., Basel, Switzerland
FX Funding was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland,
   for the study and third-party writing assistance.
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NR 34
TC 3
Z9 3
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-4426
J9 J PERS MED
JI J. Pers. Med.
PD JUN
PY 2021
VL 11
IS 6
AR 524
DI 10.3390/jpm11060524
PG 20
WC Health Care Sciences & Services; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; General & Internal Medicine
GA SZ7WR
UT WOS:000666771000001
PM 34201045
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Pan, Y
   Huang, XL
   Wu, ZF
   Lu, S
   Chen, TT
   Zou, WJ
AF Pan, Ying
   Huang, Xiaoli
   Wu, Zhifeng
   Lu, Shui
   Chen, Tiantian
   Zou, Wenjun
TI Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for
   Exudative Macular Degeneration
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
AB SIGNIFICANCE
   Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss. PURPOSE
   This study aimed to report a case of ARN after IVR in a patient with exudative AMD. CASE REPORT
   A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment. CONCLUSIONS
   This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.
C1 [Pan, Ying; Huang, Xiaoli; Wu, Zhifeng; Lu, Shui; Chen, Tiantian; Zou, Wenjun] Nantong Univ, Dept Ophthalmol, Affiliated Wuxi Clin Coll, Nantong, Jiangsu, Peoples R China.
   [Pan, Ying; Huang, Xiaoli; Wu, Zhifeng; Lu, Shui; Chen, Tiantian; Zou, Wenjun] Nanjing Med Univ, Affiliated Wuxi 2 Peoples Hosp, Dept Ophthalmol, Wuxi, Jiangsu, Peoples R China.
C3 Nantong University; Nanjing Medical University
RP Zou, WJ (通讯作者)，Nantong Univ, Dept Ophthalmol, Affiliated Wuxi Clin Coll, Nantong, Jiangsu, Peoples R China.; Zou, WJ (通讯作者)，Nanjing Med Univ, Affiliated Wuxi 2 Peoples Hosp, Dept Ophthalmol, Wuxi, Jiangsu, Peoples R China.
EM wendyzwj0805@njmu.edu.cn
RI wu, zhi/GXH-3041-2022
FU National Natural Science Foundation of China [81700852]; Top Talent
   Support Program for young and middle-aged people of Wuxi Health
   Committee [BJ2020031]
FX National Natural Science Foundation of China (81700852; to WZ) and Top
   Talent Support Program for young and middle-aged people of Wuxi Health
   Committee (BJ2020031; to WZ).
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NR 12
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD MAR
PY 2021
VL 98
IS 3
BP 206
EP 211
DI 10.1097/OPX.0000000000001649
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RI1FH
UT WOS:000636655100005
PM 33633018
DA 2022-11-30
ER

PT J
AU Xie, LQ
   Wang, Y
   Li, Q
   Ji, XY
   Tu, YY
   Du, S
   Lou, H
   Zeng, XW
   Zhu, LL
   Zhang, J
   Zhu, MH
AF Xie, Laiqing
   Wang, Ying
   Li, Quan
   Ji, Xiaoyan
   Tu, Yuanyuan
   Du, Shu
   Lou, Hui
   Zeng, Xinwei
   Zhu, Linling
   Zhang, Ji
   Zhu, Manhui
TI The HIF-1 alpha/p53/miRNA-34a/Klotho axis in retinal pigment epithelial
   cells promotes subretinal fibrosis and exacerbates choroidal
   neovascularization
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE choroidal neovascularization; hypoxia-inducible factor-1 alpha (HIF-1
   alpha); Klotho; microRNA-34a (miRNA-34a); p53; subretinal fibrosis
ID MESENCHYMAL TRANSITION; KLOTHO; P53; CONTRIBUTES; INJECTION; FEEDBACK;
   RISK; RPE
AB Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti-vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia-inducible factor-1 alpha (HIF-1 alpha) increases the stability and activation of p53, which activates microRNA-34a (miRNA-34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA-34a that inhibits fibrosis. This study aimed to explore the role of the HIF-1 alpha/p53/miRNA-34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia-induced HIF-1 alpha promoted p53 stability, phosphorylation and nuclear translocation in ARPE-19 cells (a human RPE cell line). HIF-1 alpha-dependent p53 activation up-regulated miRNA-34a expression in ARPE-19 cells following hypoxia. Moreover, hypoxia-induced p53-dependent miRNA-34a inhibited the expression of Klotho in ARPE-19 cells. Additionally, the HIF-1 alpha/p53/miRNA-34a/Klotho axis facilitated hypoxia-induced EMT in ARPE-19 cells. In vivo, blockade of the HIF-1 alpha/p53/miRNA-34a/Klotho axis alleviated the formation of mouse laser-induced CNV and subretinal fibrosis. In short, the HIF-1 alpha/p53/miRNA-34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.
C1 [Xie, Laiqing; Ji, Xiaoyan; Lou, Hui; Zeng, Xinwei; Zhang, Ji] Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou, Jiangsu, Peoples R China.
   [Wang, Ying] Nanjing Med Univ, Affiliated Suzhou Hosp, Suzhou Municipal Hosp, Dept Ophthalmol, Suzhou, Peoples R China.
   [Wang, Ying; Tu, Yuanyuan; Du, Shu; Zhu, Linling; Zhu, Manhui] Soochow Univ, Dept Ophthalmol, Lixiang Eye Hosp, Suzhou, Peoples R China.
   [Li, Quan] Soochow Univ, Ctr Stomatol, Affiliated Hosp 2, Suzhou, Peoples R China.
C3 Soochow University - China; Nanjing Medical University; Soochow
   University - China; Soochow University - China
RP Zhang, J (通讯作者)，Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou, Jiangsu, Peoples R China.; Zhu, MH (通讯作者)，Soochow Univ, Lixiang Eye Hosp, Suzhou, Jiangsu, Peoples R China.
EM jizhang@suda.edu.cn; zhumanhuieye@126.com
RI 涂, 园园/AGE-3991-2022
OI Zhang, Ji/0000-0002-3999-2196
FU Natural Science Foundation of China [SDFEYGJ1905]; Suzhou Science and
   Technology Bureau [SYS2018005, SYS2018060]; Open Subject of the State
   Key Laboratory of Radiation Medicine and Radiation Protection
   [GZK1201912]; Jiangsu Provincial Natural Science Foundation Project
   [SBK2020040630]
FX Natural Science Foundation of China, Grant/Award Number: SDFEYGJ1905;
   Suzhou Science and Technology Bureau, Grant/Award Number: SYS2018005 and
   SYS2018060; Open Subject of the State Key Laboratory of Radiation
   Medicine and Radiation Protection, Grant/Award Number: GZK1201912;
   Jiangsu Provincial Natural Science Foundation Project, Grant/Award
   Number: SBK2020040630
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NR 39
TC 4
Z9 4
U1 1
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD FEB
PY 2021
VL 25
IS 3
BP 1700
EP 1711
DI 10.1111/jcmm.16272
EA JAN 2021
PG 12
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA QF2IF
UT WOS:000607086000001
PM 33438362
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Shwetha, HJ
   Shilpa, S
   Mukherjee, MB
   Ambedkar, R
   Raichur, AM
   Lakshminarayana, R
AF Shwetha, Hulikere Jagdish
   Shilpa, Shivaprasad
   Mukherjee, Mousumi Beto
   Ambedkar, Rudrappa
   Raichur, Ashok M.
   Lakshminarayana, Rangaswamy
TI Fabrication of chitosan nanoparticles with phosphatidylcholine for
   improved sustain release, basolateral secretion, and transport of lutein
   in Caco-2 cells
SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
LA English
DT Article
DE Chitosan-phosphatidylcholine based nanoparticles; Lutein
   bioavailability; SRB-1 mediated transport
ID BETA-CAROTENE; IN-VITRO; CELLULAR UPTAKE; BIOAVAILABILITY; ABSORPTION;
   ZEAXANTHIN; DELIVERY; STABILITY; HUMANS; SIZE
AB Biopolymers-based nanoparticles delivery emerged alternatively to improve nutraceuticals and drug bioavailability. The intestinal physiology suggested a prerequisite of lipid moiety for carotenoid absorption. This study aimed to fabricate chitosan-based nanoparticleswith phosphatidylcholine (PC) to enhance lutein bioavailability. Lutein encapsulated chitosan nanoparticles with PC (LCNPC) or without PC (LCN) were assessed for bioaccessibility, sustain release, cellular uptake/internalization, and basolateral secretion of lutein in Caco-2 cells. Standard lutein mixed micelles (LMM), and micelles derived through in vitro digestion of green leafy vegetables (GMM) treated as controls. The LCNPC showed reduced particle size, higher colloidal stability, homogeneous dispersion, and suitable for oral administration compared to LCN. The cellular uptake of lutein (20 h) in LCNPC was higher than LCN, LMM, and GMM, respectively. Interestingly, lutein uptake was maximum at 8 h in LMMand gradually decreased against sustain-release response in LCNPC and LCN, whereas considerably low lutein uptake from GMMat all time points. Further, LCNPC significantly increased basolateral secretion of triglyceride (TG) and positively correlated enhanced lutein uptake/internalization process than LCN and micelles. Also, LCNPC demonstrated the upregulation of endocytosis, paracellular, scavenger receptor class B type 1 (SRB-1), and peroxisome proliferator-activated receptor gamma (PPAR.) mediated lutein transportmechanism. These results suggested that fabrication of biopolymer-based nanoparticles with PC could provide greater insight to improve lutein bioavailability at enterocyte levels, to avoid age-related macular degeneration and other chronic diseases. (C) 2020 Elsevier B.V. All rights reserved.
C1 [Shwetha, Hulikere Jagdish; Shilpa, Shivaprasad; Ambedkar, Rudrappa; Lakshminarayana, Rangaswamy] Bangalore Univ, Dept Microbiol & Biotechnol, Jnana Bharathi Campus, Bengaluru 560056, India.
   [Mukherjee, Mousumi Beto; Raichur, Ashok M.] Indian Inst Sci, Dept Mat Engn, Bengaluru 560012, India.
C3 Bangalore University; Indian Institute of Science (IISC) - Bangalore
RP Lakshminarayana, R (通讯作者)，Bangalore Univ, Dept Biotechnol, Jnana Bharathi Campus, Bengaluru 560056, India.
EM rlnarn21@gmail.com
RI Raichur, Ashok/N-6842-2019
FU ICMR (Govt. of India) [3/1/2/159/2019 - (Nut)]; Department
   ofMicrobiology and Biotechnology, Bangalore University; UGC-SAP
   [F.4-8/2018/DRS-II/SAP-II]; DST-PURSE [SR/PURSE Phase-2/36 (C) (G)];
   DHR-ICMR [GIA/54/2014-DHR]
FX Mrs. Shwetha H.J. acknowledges ICMR (Govt. of India) for the awarding
   Senior Research Fellowship (F. No. 3/1/2/159/2019 - (Nut) Dated.
   21.06.2019). Authors acknowledge theDepartment ofMicrobiology and
   Biotechnology, Bangalore University, UGC-SAP (No.
   F.4-8/2018/DRS-II/SAP-II), DST-PURSE (Sanction order No. SR/PURSE
   Phase-2/36 (C) & (G), Dated. 08.03.2017 & 12.04.2018), and DHR-ICMR
   (GIA/54/2014-DHR, Dated. 29/12/2014) for facilities and support. Also,
   the authors acknowledge Dr. V. Baskaran (Dept of Biochemistry,
   CFTRI-CSIR, Mysore) for providing antibodies and Dr. Ganesh Nagaraju
   (Dept of Biochemistry, IISc, Bangalore) for western blotting facilities.
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NR 49
TC 8
Z9 9
U1 2
U2 32
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29a, 1043 NX AMSTERDAM, NETHERLANDS
SN 0141-8130
EI 1879-0003
J9 INT J BIOL MACROMOL
JI Int. J. Biol. Macromol.
PD NOV 15
PY 2020
VL 163
BP 2224
EP 2235
DI 10.1016/j.ijbiomac.2020.09.040
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA OD4RK
UT WOS:000579839600217
PM 32918957
DA 2022-11-30
ER

PT J
AU Feldman, TB
   Yakovleva, MA
   Larichev, AV
   Arbukhanova, PM
   Radchenko, AS
   Borzenok, SA
   Kuzmin, VA
   Ostrovsky, MA
AF Feldman, Tatiana B.
   Yakovleva, Marina A.
   Larichev, Andrey, V
   Arbukhanova, Patimat M.
   Radchenko, Alexandra Sh
   Borzenok, Sergey A.
   Kuzmin, Vladimir A.
   Ostrovsky, Mikhail A.
TI Spectral analysis of fundus autofluorescence pattern as a tool to detect
   early stages of degeneration in the retina and retinal pigment
   epithelium
SO EYE
LA English
DT Article
ID LIFETIME IMAGING OPHTHALMOSCOPY; RECESSIVE STARGARDT-DISEASE; HUMAN
   CADAVER EYES; FLUORESCENCE LIFETIME; MACULAR DEGENERATION; LIPOFUSCIN
   FLUOROPHORES; OUTER SEGMENTS; A2E; AGE; OXIDATION
AB Purpose The aim of this work is the determination of quantitative diagnostic criteria based on the spectral characteristics of fundus autofluorescence to detect early stages of degeneration in the retina and retinal pigment epithelium (RPE).
   Methods RPE cell suspension samples were obtained from the cadaver eyes with and without signs of age-related macular degeneration (AMD). Fluorescence analysis at an excitation wavelength of 488 nm was performed. The fluorescence lifetimes of lipofuscin-granule fluorophores were measured by counting time-correlated photon method.
   Results Comparative analysis of fluorescence spectra of RPE cell suspensions from the cadaver eyes with and without signs of AMD showed a significant difference in fluorescence intensity at 530-580 nm in response to fluorescence excitation at 488 nm. It was notably higher in eyes with visual pathology than in normal eyes regardless of the age of the eye donor. Measurements of fluorescence lifetimes of lipofuscin fluorophores showed that the contribution of photooxidation and photodegradation products of bisretinoids to the total fluorescence at 530-580 nm of RPE cell suspensions was greater in eyes with visual pathology than in normal eyes.
   Conclusion Because photooxidation and photodegradation products of bisretinoids are markers of photodestructive processes, which can cause RPE cell death and initiate degenerative processes in the retina, quantitative determination of increases in these bisretinoid products in lipofuscin granules may be used to establish quantitative diagnostic criteria for degenerative processes in the retina and RPE.
C1 [Feldman, Tatiana B.; Ostrovsky, Mikhail A.] Lomonosov Moscow State Univ, Biol Fac, Dept Mol Physiol, Leninskie Gory 1, Moscow 119991, Russia.
   [Feldman, Tatiana B.; Yakovleva, Marina A.; Radchenko, Alexandra Sh; Kuzmin, Vladimir A.; Ostrovsky, Mikhail A.] Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygin St 4, Moscow 119334, Russia.
   [Larichev, Andrey, V] Lomonosov Moscow State Univ, Dept Med Phys, Fac Phys, Leninskie Gory 1, Moscow 119991, Russia.
   [Larichev, Andrey, V] Russian Acad Sci, Fed Sci Res Ctr Crystallog & Photon, Inst Laser & Informat Technol, Svyatoozerskaya St 1, Shatura 140700, Moscow Region, Russia.
   [Arbukhanova, Patimat M.; Borzenok, Sergey A.] Sv Fyodorov Eye Microsurg Complex, Beskudnikovsky Bld 59a, Moscow 127486, Russia.
C3 Lomonosov Moscow State University; Russian Academy of Sciences; Emanuel
   Institute of Biochemical Physics; Lomonosov Moscow State University;
   Russian Academy of Sciences; FSRC Crystallography & Photonics RAS
RP Feldman, TB (通讯作者)，Lomonosov Moscow State Univ, Biol Fac, Dept Mol Physiol, Leninskie Gory 1, Moscow 119991, Russia.; Feldman, TB (通讯作者)，Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygin St 4, Moscow 119334, Russia.
EM feldmantb@mail.ru
RI Borzenok, Sergey/ABF-9757-2021; Larichev, Andrey V/J-1514-2012; Feldman,
   Tatiana/F-2286-2014
OI Borzenok, Sergey/0000-0001-9160-6240; Kuzmin,
   Vladimir/0000-0001-6586-3251; Feldman, Tatiana/0000-0003-2613-056X
FU Russian Foundation for Basic Research [15-29-03831]
FX This work was supported by the Russian Foundation for Basic Research
   (No. 15-29-03831).
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NR 49
TC 12
Z9 13
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 SEP
PY 2018
VL 32
IS 9
BP 1440
EP 1448
DI 10.1038/s41433-018-0109-0
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GT3MQ
UT WOS:000444407600004
PM 29786089
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Kumar, V
AF Kumar, Vinod
TI Reticular Pseudodrusen and Thin Choroid are Associated With Angioid
   Streaks
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID PSEUDOXANTHOMA ELASTICUM; BRUCH MEMBRANE; THICKNESS; MUTATIONS;
   DYSTROPHY; UPDATE; EYES
AB BACKGROUND AND OBJECTIVE: To report the association of angioid streaks in patients with Pseudo-xanthoma elasticum (PXE) with reticular pseudo-drusen (RPD), thin choroid, and retinal pigment epithelium (RPE) atrophy using swept-source optical coherence tomography (SS-OCT) and short-wave autofluorescence (SWAF).
   PATIENTS AND METHODS: Retrospective cross-sectional study. Records of consecutive patients with angioid streaks due to PXE, who presented with a decrease of vision due to choroidal neovascularization (CNV), were reviewed for best-corrected visual acuity, color fundus photographs, SS-OCT, SWAF, and red-free images with special emphasis on presence or absence of RPD, subfoveal choroidal thickness (SFCT), and RPE atrophy.
   RESULTS: Sixteen eyes of eight patients with a mean age of 45.5 years +/- 9.4 years were enrolled in the study. RPD were seen in 10 of the 16 eyes and were seen commonly along the superotemporal quadrant. Mean subfoveal thickness in study eyes (175.7 mu m +/- 37.2 mu m) was significantly reduced when compared to controls (286.4 mu m +/- 40.8 mu m). The mean SFCT was similar between the eyes with and without CNV. Four eyes had RPE atrophy in the macular area, whereas four eyes had peripapillary RPE atrophy.
   CONCLUSIONS: Angioid streaks in PXE are associated with RPD, thin choroid, and RPE atrophy. These features occur at a younger age as compared to age-related macular degeneration and appear to be interrelated because of single pathophysiological mechanism.
C1 [Kumar, Vinod] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences
RP Kumar, V (通讯作者)，57 Sadar Apartments,Mayur Vihar Phase 1 Extens, New Delhi 110091, India.
EM drvinod_agg@yahoo.com
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NR 20
TC 2
Z9 2
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD JUN
PY 2018
VL 49
IS 6
BP 402
EP 408
DI 10.3928/23258160-20180601-04
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA GK4EJ
UT WOS:000436108300004
PM 29927467
DA 2022-11-30
ER

PT J
AU Ma, L
   Liu, R
   Du, JH
   Liu, T
   Wu, SS
   Liu, XH
AF Ma, Le
   Liu, Rong
   Du, Jun Hui
   Liu, Tao
   Wu, Shan Shan
   Liu, Xiao Hong
TI Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with
   Macular Pigment Optical Density
SO NUTRIENTS
LA English
DT Article
DE lutein; zeaxanthin; meso-zeaxanthin; macular pigment optical density
ID AGE-RELATED MACULOPATHY; VISUAL-ACUITY; DOUBLE-BLIND; DIETARY
   SUPPLEMENTATION; DOCOSAHEXAENOIC ACID; BINDING PROTEIN; HUMAN RETINA;
   DEGENERATION; SERUM; CAROTENOIDS
AB The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (r(AMD) = -0.43, p = 0.06; r(healthy subjects) = -0.71, p < 0.001) and blood xanthophyll carotenoids concentration (r(AMD) = 0.40, p = 0.07; r(healthy) (subjects) = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship.
C1 [Ma, Le; Liu, Xiao Hong] Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.
   [Ma, Le; Liu, Rong] Xi An Jiao Tong Univ, Sch Publ Hlth, Hlth Sci Ctr, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.
   [Liu, Rong; Liu, Tao] Xi An Jiao Tong Univ, Coll Med, Hosp 3201, 783 Tianhan Rd, Hanzhong 723000, Shaanxi, Peoples R China.
   [Du, Jun Hui] Xi An Jiao Tong Univ, Coll Med, Hosp 9, 151 East South Second Ring Rd, Xian 710054, Shaanxi, Peoples R China.
   [Wu, Shan Shan] Capital Med Univ, Natl Clin Res Ctr Digest Dis, Beijing Friendship Hosp, 95 Yongan Rd, Beijing 100050, Peoples R China.
C3 Xi'an Jiaotong University; Xi'an Jiaotong University; Xi'an Jiaotong
   University; Xi'an Jiaotong University; Capital Medical University
RP Ma, L; Liu, XH (通讯作者)，Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.; Ma, L (通讯作者)，Xi An Jiao Tong Univ, Sch Publ Hlth, Hlth Sci Ctr, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.; Wu, SS (通讯作者)，Capital Med Univ, Natl Clin Res Ctr Digest Dis, Beijing Friendship Hosp, 95 Yongan Rd, Beijing 100050, Peoples R China.
EM male@mail.xjtu.edu.cn; liu.rong@stu.xjtu.edu.cn; djh79918@163.com;
   taoliustone@163.com; wss@bjmu.edu.cn; liuxiaoh@mail.xjtu.edu
RI Du, junhui/P-3183-2019
OI Du, junhui/0000-0001-6692-3877; ma, le/0000-0001-7592-9779
FU National Natural Science Foundation of China [NSFC-81202198,
   NSFC-81473059]; Natural Science Foundation of Shaanxi Province of China
   [2013JQ4008]; New-star Plan of Science and Technology of Shaanxi
   Province [2015LJXX-07]; China Postdoctoral Science Special Foundation
   [2015T81036]; Fundamental Research Funds for the Central Universities
   [qngz2016004]; China Postdoctoral Science Foundation [2014M560790]
FX This study was partially supported by grants from the National Natural
   Science Foundation of China (NSFC-81202198, NSFC-81473059); the Natural
   Science Foundation of Shaanxi Province of China (2013JQ4008); New-star
   Plan of Science and Technology of Shaanxi Province (2015LJXX-07); the
   China Postdoctoral Science Special Foundation (2015T81036); the
   Fundamental Research Funds for the Central Universities (qngz2016004);
   and the China Postdoctoral Science Foundation Funded Project
   (2014M560790).
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NR 66
TC 57
Z9 61
U1 2
U2 33
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD JUL
PY 2016
VL 8
IS 7
AR 426
DI 10.3390/nu8070426
PG 14
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA DS4QP
UT WOS:000380766200043
PM 27420092
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Bhoiwala, DL
   Song, Y
   Cwanger, A
   Clark, E
   Zhao, LL
   Wang, CG
   Li, YF
   Song, DL
   Dunaief, JL
AF Bhoiwala, Devang L.
   Song, Ying
   Cwanger, Alyssa
   Clark, Esther
   Zhao, Liang-liang
   Wang, Chenguang
   Li, Yafeng
   Song, Delu
   Dunaief, Joshua L.
TI CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron
   Diet
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE iron overload; hemochromatosis; retinal damage; retinal degeneration;
   oxidation; free radical; retinal pigment epithelium; metabolism; AMD
ID CHELATOR DEFERIPRONE PROTECTS; HEPCIDIN KNOCKOUT MICE; MACULAR
   DEGENERATION; EPITHELIAL-CELLS; POTENTIAL FACTOR; SERUM IRON;
   HOMEOSTASIS; METABOLISM; EXPRESSION; TOXICITY
AB PURPOSE. High RPE iron levels have been associated with age-related macular degeneration. Mutation of the ferroxidase ceruloplasmin leads to RPE iron accumulation and degeneration in patients with aceruloplasminemia; mice lacking ceruloplasmin and its homolog hephaestin have a similar RPE degeneration. To determine whether a high iron diet (HID) could cause RPE iron accumulation, possibly contributing to RPE oxidative stress in AMD, we tested the effect of dietary iron on mouse RPE iron.
   METHODS. Male CD1 strain mice were fed either a standard iron diet (SID) or the same diet with extra iron added (HID) for either 3 months or 10 months. Mice were analyzed with immunofluorescence and Perls' histochemical iron stain to assess iron levels. Levels of ferritin, transferrin receptor, and oxidative stress gene mRNAs were measured by quantitative PCR (qPCR) in neural retina (NR) and isolated RPE. Morphology was assessed in plastic sections.
   RESULTS. Ferritin immunoreactivity demonstrated a modest increase in the RPE in 10-month HID mice. Analysis by qPCR showed changes in mRNA levels of iron-responsive genes, indicating moderately increased iron in the RPE of 10-month HID mice. However, even by age 18 months, there was no Perls' signal in the retina or RPE and no retinal degeneration.
   CONCLUSIONS. These findings indicate that iron absorbed from the diet can modestly increase the level of iron deposition in the wild-type mouse RPE without causing RPE or retinal degeneration. This suggests regulation of retinal iron uptake at the blood-retinal barriers.
C1 [Bhoiwala, Devang L.; Song, Ying; Cwanger, Alyssa; Clark, Esther; Zhao, Liang-liang; Wang, Chenguang; Li, Yafeng; Song, Delu; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Bhoiwala, Devang L.] Albany Med Coll, Albany, NY 12208 USA.
   [Zhao, Liang-liang; Wang, Chenguang] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun, Jilin, Peoples R China.
C3 University of Pennsylvania; Pennsylvania Medicine; Albany Medical
   College; Jilin University
RP Dunaief, JL (通讯作者)，305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
OI Bhoiwala, Devang/0000-0001-5864-0607
FU NEI NIH HHS [P30 EY001583, R01 EY015240] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [P30EY001583, R01EY015240] Funding Source: NIH
   RePORTER
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NR 35
TC 9
Z9 9
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2015
VL 56
IS 9
BP 5344
EP 5352
DI 10.1167/iovs.15-17026
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT5WW
UT WOS:000362882800041
PM 26275132
OA Green Published
DA 2022-11-30
ER

PT J
AU Li, FL
   Xu, HW
   Zeng, YX
   Yin, ZQ
AF Li, Fuliang
   Xu, Haiwei
   Zeng, Yuxiao
   Yin, Zheng Qin
TI Overexpression of Fibulin-5 in Retinal Pigment Epithelial Cells Inhibits
   Cell Proliferation and Migration and Downregulates VEGF, CXCR4, and
   TGFB1 Expression in Cocultured Choroidal Endothelial Cells
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; choroidal neovascularization;
   choroidal endothelial cells; Fibulin 5; retinal pigment epithelium
ID MACULAR DEGENERATION; GROWTH-FACTOR; CUTIS LAXA; HUMAN EYES; IN-VIVO;
   NEOVASCULARIZATION; TRANSMIGRATION; ANGIOGENESIS; MODEL; GENE
AB Purpose of the study: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss. Fibulin-5 (FBLN5) plays a pleiotropic role in the pathogenesis of AMD. We examined whether the in vitro overexpression of FBLN5 in retinal pigment epithelial (RPE) cells alters the proliferation and migration of cocultured choroidal endothelial cells (CECs) and explored the possible mechanisms involved.
   Materials and methods: A recombinant lentiviral vector carrying the Fbln5 gene was generated to transduce rat RPE cells. The expression of FBLN5 in transduced RPE cells was detected by quantitative real-time PCR and Western blot. The transduced RPE cells were then cocultured with rhesus macaque CECs in a Transwell coculture system. The impact of overexpression of FBLN5 in RPE cells on CEC proliferation and migration was assessed, as well as the impact on the mRNA expressions of vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), and transforming growth factor beta 1 (TGFB1).
   Results: Our results showed that a recombinant lentivirus carrying the Fbln5 gene, which could induce overexpression of FBLN5 in RPE cells, was successfully generated. Overexpression of FBLN5 in RPE cells inhibited cell proliferation and migration and downregulated the mRNA expressions of VEGF, CXCR4, and TGFB1 in cocultured CECs.
   Conclusions: These findings suggest that FBLN5 may interfere with choroidal neovascularization by downregulating VEGF, CXCR4, and TGFB1 expression and inhibiting CEC proliferation and invasion, intensifying interest in FBLN5 as a target for therapeutic intervention in neovascular AMD.
C1 [Li, Fuliang; Xu, Haiwei; Zeng, Yuxiao; Yin, Zheng Qin] Third Mil Med Univ, Southwest Hosp, SW Eye Hosp, Chongqing 400038, Peoples R China.
C3 Army Medical University
RP Yin, ZQ (通讯作者)，Third Mil Med Univ, Southwest Hosp, SW Eye Hosp, 30 Gaotanyan St, Chongqing 400038, Peoples R China.
EM haiweixu2001@yahoo.com.cn; qinzyin@yahoo.com.cn
OI Li, Fuliang/0000-0001-8002-1298
FU National Natural Science Foundation of China [30801270]; National Basic
   Research Program of China [2007CB512203]
FX The authors thank Shujia Huo, Jing Xie, Yaochen Li, Chuanhuang Weng,
   Jianrong He for their excellent technical support. This work was
   supported by grants from the National Natural Science Foundation of
   China (No. 30801270) and National Basic Research Program of China (No.
   2007CB512203).
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NR 32
TC 14
Z9 16
U1 0
U2 7
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 540
EP 548
DI 10.3109/02713683.2012.665561
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 942RH
UT WOS:000304064200013
PM 22369482
DA 2022-11-30
ER

PT J
AU Mukerjee, A
   Shankardas, J
   Ranjan, AP
   Vishwanatha, JK
AF Mukerjee, Anindita
   Shankardas, Jwalitha
   Ranjan, Amalendu P.
   Vishwanatha, Jamboor K.
TI Efficient nanoparticle mediated sustained RNA interference in human
   primary endothelial cells
SO NANOTECHNOLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; ANNEXIN-II; IN-VITRO; BIODEGRADABLE
   NANOPARTICLES; POLYMERIC NANOPARTICLES; ENHANCED EXPRESSION; SIRNA
   DELIVERY; DRUG-DELIVERY; ORAL DELIVERY; GENE-TRANSFER
AB Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (similar to 97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.
C1 [Mukerjee, Anindita] Univ N Texas Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA.
   Univ N Texas Hlth Sci Ctr, Inst Canc Res, Grad Sch Biomed Sci, Ft Worth, TX 76107 USA.
C3 University of North Texas System; University of North Texas Health
   Science Center; University of North Texas System; University of North
   Texas Health Science Center
RP Mukerjee, A (通讯作者)，Univ N Texas Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA.
EM Jamboor.vishwanatha@unthsc.edu
RI Mukerjee, Anindita/D-3427-2014
OI Vishwanatha, Jamboor/0000-0002-0266-6020
FU Department of Defense [BC075097]; National Institutes of Health
   [R21CA109593]; Susan G Komen Post Doctoral Fellowship [KG101213];
   NATIONAL CANCER INSTITUTE [R21CA109593] Funding Source: NIH RePORTER
FX This research was supported in parts by grants from the Department of
   Defense Breast Cancer Research Program (BC075097), National Institutes
   of Health (R21CA109593) to Dr Jamboor K Vishwanatha and Susan G Komen
   Post Doctoral Fellowship (KG101213) to Anindita Mukerjee.
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NR 49
TC 14
Z9 14
U1 0
U2 23
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD NOV 4
PY 2011
VL 22
IS 44
AR 445101
DI 10.1088/0957-4484/22/44/445101
PG 10
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
   Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science; Physics
GA 844LW
UT WOS:000296749700001
PM 21990205
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lee, KH
AF Lee, Keyong Ho
TI Pre- and co-treatment with xanthophyll enhances the anti-leukemic
   activity of adriamycin
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE Xanthophyll; Antioxidant; Oxidative stress; Anti-leukemia
ID OXIDATIVE STRESS; 1,25-DIHYDROXYVITAMIN D-3; DIETARY LUTEIN;
   LEUKEMIA-CELLS; CARNOSIC ACID; DNA-DAMAGE; CAROTENOIDS; DIFFERENTIATION;
   ANTIOXIDANT; ZEAXANTHIN
AB Xanthophyll (lutein) is one of the most potent known antioxidants. It has been shown that dietary intake of xanthophyll helps to prevent age-related macular degeneration and the development of cataracts. It may also reduce the risk of developing various types of cancer. Here we showed that xanthophyll efficiently scavenged the stable free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) with an IC50 of 0.5 mM and effectively countered the cytotoxic effect of tert-butylhydroperoxide (tBuOOH) on various leukemic cell lines. In contrast, oxidized xanthophyll did not have these effects. We then examined whether dietary intake of xanthophyll inhibited leukemic tumor growth in mice injected subcutaneously with the leukemic cell line L1210. After one month, treatment with 13 mg/kg xanthophyll had inhibited tumor growth by about 20%. Xanthophyll also enhanced the anti-leukemic activity of adriamycin in the L1210 mouse model as it extended the duration of adriamycin-induced suppression of tumor growth. Moreover, the two agents together reduced tumor volume by about 50% whereas treatment with adriamycin alone only stalled growth for a few days. Oxidized xanthophyll did not have any anti-leukemic effects on its own or in combination with adriamycin. Thus, the radical scavenging activity of the food supplement xanthophyll prevents oxidative stress, inhibits leukemic tumor growth, and enhances the anti-leukemic activities of a common chemotherapeutic agent in a synergistic manner. (C) 2008 Elsevier B.V. All rights reserved.
C1 Inst Kolon Life Sci Inc, Yongin 446797, South Korea.
RP Lee, KH (通讯作者)，Inst Kolon Life Sci Inc, 207-2 Mabuk Dong, Yongin 446797, South Korea.
EM keyho625@hotmail.com
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NR 39
TC 6
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD SEP 18
PY 2008
VL 92
IS 3
BP 175
EP 179
DI 10.1016/j.jphotobiol.2008.06.008
PG 5
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 358ZA
UT WOS:000259954800006
PM 18653355
DA 2022-11-30
ER

PT J
AU Thomas, G
   Grassi, MA
   Lee, JR
   Edwards, AO
   Gorin, MB
   Klein, R
   Casavant, TL
   Scheetz, TE
   Stone, EM
   Williams, AB
AF Thomas, George
   Grassi, Michael A.
   Lee, John R.
   Edwards, Albert O.
   Gorin, Michael B.
   Klein, Ronald
   Casavant, Thomas L.
   Scheetz, Todd E.
   Stone, Edwin M.
   Williams, Andrew B.
TI IDOCS: Intelligent distributed ontology consensus system - The use of
   machine learning in retinal drusen phenotyping
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   FAMILIAL AGGREGATION; GENE; DYSTROPHY; SUSCEPTIBILITY; RISK;
   CLASSIFICATION; POLYMORPHISM
AB PURPOSE. To use the power of knowledge acquisition and machine learning in the development of a collaborative computer classification system based on the features of age-related macular degeneration (AMD).
   METHODS. A vocabulary was acquired from four AMD experts who examined 100 ophthalmoscopic images. The vocabulary was analyzed, hierarchically structured, and incorporated into a collaborative computer classification system called IDOCS. Using this system, three of the experts examined images from a second set of digital images compiled,from more than 1000 patients with AMD. Images were annotated, and features were identified and defined. Decision trees, a machine learning method, were trained on the data collected and used to extract patterns. Interrelationships between the data from the different clinicians were investigated.
   RESULTS. Six drusen classes in the structured vocabulary were largely sufficient to describe all the identified features. The decision trees classified the data with 76.86% to 88.5% accuracy and distilled patterns in the form of hierarchical trees composed of 5 to 15 nodes. Experts v, ere largely consistent in their characterization of soft, and to a lesser extent, hard drusen, but diverge in definition of other drusen. Size and crystalline morphology were the main determinants of drusen type across all experts.
   CONCLUSIONS. Machine learning is a powerful tool for the characterization of disease phenotypes. The creation of a defined feature set for AMD will facilitate the development of an IDOCS-based classification system.
C1 Spelman Coll, Dept Comp & Informat Sci, Atlanta, GA 30314 USA.
   Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA.
   Univ Chicago, Ctr Bioinformat & Computat Biol, Chicago, IL 60637 USA.
   Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA.
   Univ Chicago, Dept Biomed Engn, Chicago, IL 60637 USA.
   Univ Chicago, Dept Ophthalmol, Chicago, IL 60637 USA.
   Assist Intelligence Inc, Iowa City, IA USA.
   Mayo Clin, Dept Ophthalmol, Rochester, MN USA.
   Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
   Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
   Howard Hughes Med Inst, Chevy Chase, MD USA.
C3 Spelman College; University of Chicago; University of Chicago;
   University of Chicago; University of Chicago; University of Chicago;
   Mayo Clinic; 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 Wisconsin System;
   University of Wisconsin Madison; Howard Hughes Medical Institute
RP Williams, AB (通讯作者)，Spelman Coll, Dept Comp & Informat Sci, 350 Spelman Lane SW,Campus Box 1257, Atlanta, GA 30314 USA.
EM williams@spelman.edu
RI Williams, Andrew/AAU-4856-2020
OI Scheetz, Todd/0000-0002-1965-5811; Stone, Edwin M./0000-0003-3343-4414
FU NEI NIH HHS [EY014467, EY013688-03] Funding Source: Medline; NIMHD NIH
   HHS [5 P20 MD000215] Funding Source: Medline; NATIONAL CENTER ON
   MINORITY HEALTH AND HEALTH DISPARITIES [P20MD000215] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R33EY013688, R01EY014467] Funding
   Source: NIH RePORTER
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NR 22
TC 3
Z9 4
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 MAY
PY 2007
VL 48
IS 5
BP 2278
EP 2284
DI 10.1167/iovs.06-1022
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 162DU
UT WOS:000246067800054
PM 17460291
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Alam, S
   Zawadzki, RJ
   Choi, S
   Gerth, C
   Park, SS
   Morse, L
   Werner, JS
AF Alam, Suhail
   Zawadzki, Robert J.
   Choi, Stacey
   Gerth, Christina
   Park, Susanna S.
   Morse, Lawrence
   Werner, John S.
TI Clinical application of rapid serial Fourier-domain optical coherence
   tomography for macular imaging
SO OPHTHALMOLOGY
LA English
DT Article
ID ULTRAHIGH-RESOLUTION; IN-VIVO; HIGH-SPEED; HUMAN RETINA; TRANSVERSAL;
   PATHOLOGY
AB Purpose: To introduce and examine the utility of a retinal imaging technique using high-speed optical coherence tomography (OCT) for creating a more complete retinal structural map to aid in the evaluation of patients with macular pathology.
   Design: Prospective observational case series.
   Participants: Five patients with a variety of macular pathologies.
   Methods: Patients were imaged with a Fourier-domain high-speed high-resolution OCT system built at our institution. A sweeping serial OCT B-scan of the macula was acquired to create a detailed retinal structural map. The data were then used to make individual clinical observations.
   Results: Rapid serial OCT B-scans produced detailed macular maps for all 5 patients. Diagnoses of imaged patients included macular hole, lamellar macular hole, regressed macular hole or macular microhole, choroidal neovascular membrane (CNV) from age-related macular degeneration, and CNV from presumed ocular histoplasmosis syndrome. Reconstructed B-scans and C-scans are shown for selected patients to illustrate the additional perspectives gained by obtaining a detailed retinal map.
   Conclusions: Rapid serial Fourier-domain OCT B-scanning can be used to create a detailed retinal structural map. This technique provides additional information that can be missed on single OCT images and provides an accurate way to image large or complex lesions, and allows B-scan and C-scan reconstructions to be made that provide additional perspectives into retinal structures that may be missed using traditional imaging methods. (c) 2006 by the American Academy of Ophthalmology.
C1 Univ Calif Davis, Dept Ophthalmol & Visual Sci, Sacramento, CA 95817 USA.
C3 University of California System; University of California Davis
RP Werner, JS (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Visual Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
EM jswerner@ucdavis.edu
RI Zawadzki, Robert/E-7534-2011; Zawadzki, Robert J./S-3236-2019
OI Zawadzki, Robert/0000-0002-9574-156X; Zawadzki, Robert
   J./0000-0002-9574-156X; Gerth-Kahlert, Christina/0000-0001-6298-615X;
   Morse, Lawrence/0000-0002-1758-2348
FU NATIONAL EYE INSTITUTE [R01EY014743] Funding Source: NIH RePORTER; NEI
   NIH HHS [R01 EY014743-04, R01 EY014743] Funding Source: Medline; PHS HHS
   [014743] Funding Source: Medline
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NR 28
TC 129
Z9 142
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2006
VL 113
IS 8
BP 1425
EP 1431
DI 10.1016/j.ophtha.2006.03.020
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 070OF
UT WOS:000239531400024
PM 16766031
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Ergun, E
   Abramov, A
   Zawinka, C
   Stur, M
AF Ergun, E
   Abramov, A
   Zawinka, C
   Stur, M
TI Incidence of patients presenting with exudative maculopathy and
   neovascular retinal disease in an urban population
SO WIENER KLINISCHE WOCHENSCHRIFT
LA English
DT Article
DE clinical epidemiology; age-related macular degeneration; diabetic
   retinopathy; venous occlusive disease; choroidal neovascularization;
   vasoproliferative retinal disease
ID AGE-RELATED MACULOPATHY; DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   RISK-FACTORS; 10-YEAR INCIDENCE; VEIN OCCLUSION; EYE DISEASE; RURAL
   AREA; FOLLOW-UP; PROGRESSION
AB Purpose: To determine the incidence of exudative macular and neovascular retinal disease presenting within a defined urban population. Study design: prospective, observational, consecutive case series.
   Patients and methods: Patients referred to ten ophthalmic centers within a defined 10-week period with a newly diagnosed exudative macular and/or neovascular retinal disease were examined fundoscopically, angiographically and quantified according to age and underlying disease.
   Results: A total of 527 eyes of 426 patients were referred. The most frequent disease was neovascular age-related macular degeneration (AMD, 199/527, 37.8%, 184 patients), followed by diabetic maculopathy and/or proliferative diabetic retinopathy (199/527, 37.8%, 128 patients) and venous occlusive disease (67/527, 12.7%, 67 patients).
   The majority of neovascular AMD consisted of occult without classic choroidal neovascularization (CNV, 115/199, 57.8%); predominantly classic CNV was seen more often than minimally classic CNV (43/199, 21.6% vs. 27/199, 13.6%). The overwhelming majority of the diabetic cases had diabetic macular edema (179/199, 89.9%); only 10.1% had vasoproliferative disease. All other causes of CNV, macular edema/exudation, and retinal neovascularization were observed in <5% of all patients.
   Conclusion: The main causes of exudative maculopathy are CNV due to neovascular AMD and diabetic macular edema. Proliferative diabetic retinopathy is the main cause of retinal neovascularization. The number of patients with neovascular AMD presents a future challenge for ophthalmologists.
C1 Univ Vienna, Sch Med, Dept Ophthalmol, A-1090 Vienna, Austria.
   Univ Basel, Dept Ophthalmol, Basel, Switzerland.
C3 University of Vienna; University of Basel
RP Ergun, E (通讯作者)，Univ Vienna, Sch Med, Dept Ophthalmol, Waehringer Guertel 18, A-1090 Vienna, Austria.
EM erdem.ergun@meduniwien.ac.at
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NR 46
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0043-5325
EI 1613-7671
J9 WIEN KLIN WOCHENSCHR
JI Wien. Klin. Wochen.
PD NOV 30
PY 2004
VL 116
IS 21-22
BP 737
EP 743
DI 10.1007/s00508-004-0262-2
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 880XK
UT WOS:000225823200007
PM 15628644
DA 2022-11-30
ER

PT J
AU Subin, PG
   Muthukannan, P
AF Subin, P. Glaret
   Muthukannan, P.
TI Optimized convolution neural network based multiple eye disease
   detection
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Age-related macular degeneration; Convolution neural network; Diabetic
   retinopathy; FPOA; Multiclass support vector machine
ID MACULAR DEGENERATION; AUTOMATIC DETECTION
AB World health organization (WHO) reports around 2.2 billion people in the world as visually challenged which is mostly due to the age-related eye diseases such as age-related macular degeneration (AMD), cataract, diabetic retinopathy (DR) and glaucoma. These diseases lead to blindness if not diagnosed at an early stage. This paper focuses on the identification of the age-related eye diseases at an early stage using retinal fundus images taken from online dataset and pre-processed using maximum entropy transformation. The pre-processed images were fed to a convolution neural network (CNN), which was optimized using a flower pollination optimization algorithm (FPOA) for feature extraction. Hyperparameters were optimized using FPOA for training the CNN. This increased the speed and the accuracy of the network. The CNN output was fed to a Multiclass Support Vector Machine (MSVM) classifier for the classification of the type of disease. The proposed CNN-based multiple disease detection (CNN-MDD) was tested with the online dataset, namelyOcular Disease Intelligent Recognition (ODIR). The proposed model performance was analysed with the other optimized models which yielded the best performance in terms of precision, accuracy, specificity, recall, and F1 score of 98.30%, 95.27%, 95.21%, and 93.3%, respectively. The proposed method assisted automatic detection of the type of disease. Overall, this approach can be of great assistance to the medical professionals concerned in the treatment of eye diseases.
C1 [Subin, P. Glaret; Muthukannan, P.] Saveetha Univ, Saveetha Inst Med & Tech Sci, Saveetha Sch Engn, Dept Elect & Commun Engn, Chennai 602105, India.
C3 Saveetha Institute of Medical & Technical Science; Saveetha School of
   Engineering
RP Subin, PG (通讯作者)，Saveetha Univ, Saveetha Inst Med & Tech Sci, Saveetha Sch Engn, Dept Elect & Commun Engn, Chennai 602105, India.
EM glaretsubin.p@gmail.com; muthukannan@saveetha.com
RI C, Chellaswamy/GWQ-5009-2022; subin, glaret/GLR-1919-2022
OI subin, glaret/0000-0002-2210-4500
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NR 55
TC 1
Z9 1
U1 5
U2 5
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 JUL
PY 2022
VL 146
AR 105648
DI 10.1016/j.compbiomed.2022.105648
PG 11
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
   Engineering; Mathematical & Computational Biology
GA 1W5CA
UT WOS:000806790100001
PM 35751184
DA 2022-11-30
ER

PT J
AU Lv, B
   Li, S
   Liu, Y
   Wang, W
   Li, HY
   Zhang, XY
   Sha, YH
   Yang, XF
   Yang, Y
   Wang, Y
   Zhang, CF
   Wang, YL
   Lv, CF
   Xie, GT
   Wang, K
AF Lv, Bin
   Li, Shuang
   Liu, Yang
   Wang, Wei
   Li, Hongyang
   Zhang, Xiaoyue
   Sha, Yanhui
   Yang, Xiufen
   Yang, Yang
   Wang, Yue
   Zhang, Chengfen
   Wang, Yanling
   Lv, Chuanfeng
   Xie, Guotong
   Wang, Kang
TI DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE
   FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE
   TOMOGRAPHY IMAGES
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE deep learning; macular disease diagnosis; optical coherence tomography
ID DEGENERATION; FLUID
AB Purpose: To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images. Methods: A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts. Results: On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971-0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis. Conclusion: The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.
C1 [Lv, Bin; Liu, Yang; Zhang, Xiaoyue; Wang, Yue; Zhang, Chengfen; Lv, Chuanfeng; Xie, Guotong] Ping Healthcare Technol, Beijing, Peoples R China.
   [Li, Shuang; Wang, Wei; Li, Hongyang; Sha, Yanhui; Yang, Xiufen; Yang, Yang; Wang, Yanling; Wang, Kang] Capital Med Univ, Beijing Friendship Hosp, Dept Ophthalmol, Beijing 100050, Peoples R China.
   [Xie, Guotong] Ping Hlth Cloud Co Ltd, Shenzhen, Peoples R China.
   [Xie, Guotong] Ping An Int Smart City Technol Co Ltd, Shenzhen, Peoples R China.
C3 Capital Medical University
RP Wang, K (通讯作者)，Capital Med Univ, Beijing Friendship Hosp, Dept Ophthalmol, Beijing 100050, Peoples R China.
EM wangkang@ccmu.edu.cn
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NR 31
TC 0
Z9 0
U1 3
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2022
VL 42
IS 3
BP 456
EP 464
DI 10.1097/IAE.0000000000003325
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZD6KA
UT WOS:000758305500013
PM 34723902
DA 2022-11-30
ER

PT J
AU Bouskila, J
   Bleau, M
   Micaelo-Fernandes, C
   Bouchard, JF
   Ptito, M
AF Bouskila, Joseph
   Bleau, Maxime
   Micaelo-Fernandes, Catarina
   Bouchard, Jean-Francois
   Ptito, Maurice
TI The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated
   by Typical and Atypical Cannabinoid Receptors
SO CELLS
LA English
DT Review
DE retina; typical cannabinoid receptors; atypical cannabinoid receptors;
   immunohistochemistry; electroretinography; monkeys; visual system
ID ACID AMIDE HYDROLASE; CB1 RECEPTORS; CELLS EXPRESS; LOCALIZATION;
   ENDOCANNABINOIDS; ACTIVATION; TRPV1; NEUROPROTECTION; CANNABIDIOL;
   DEGRADATION
AB The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.
C1 [Bouskila, Joseph; Bleau, Maxime; Micaelo-Fernandes, Catarina; Bouchard, Jean-Francois; Ptito, Maurice] Univ Montreal, Sch Optometry, Montreal, PQ H3Y 1P1, Canada.
   [Ptito, Maurice] Behav Sci Fdn, Eastern Caribbean KN0101, Estridge, St Kitts & Nevi.
   [Ptito, Maurice] Univ Copenhagen, Dept Neurosci, DK-2200 Copenhagen, Denmark.
   [Ptito, Maurice] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
C3 Universite de Montreal; University of Copenhagen; McGill University
RP Ptito, M (通讯作者)，Univ Montreal, Sch Optometry, Montreal, PQ H3Y 1P1, Canada.; Ptito, M (通讯作者)，Behav Sci Fdn, Eastern Caribbean KN0101, Estridge, St Kitts & Nevi.; Ptito, M (通讯作者)，Univ Copenhagen, Dept Neurosci, DK-2200 Copenhagen, Denmark.; Ptito, M (通讯作者)，McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
EM joseph.bouskila@umontreal.ca; maxime.bleau.1@umontreal.ca;
   catarina.fernandes@umontreal.ca; jean-francois.bouchard@umontreal.ca;
   maurice.ptito@umontreal.ca
OI Micaelo Fernandes, Catarina Sofia/0000-0003-4978-4304; Bleau,
   Maxime/0000-0002-5117-9368; Bouskila, Joseph/0000-0002-5132-4051;
   Bouchard, Jean-Francois/0000-0001-9622-6239
FU National Science and Engineering Research Council of Canada [6362-2017,
   RGPIN- 2020-05739]; Canadian Institutes of Health Research [163014-2019,
   PJT-156029]
FX This research was funded by the National Science and Engineering
   Research Council of Canada (6362-2017: M.P.; RGPIN- 2020-05739:
   J.-F.B.), and the Canadian Institutes of Health Research (163014-2019:
   M.P. and J.-F.B., PJT-156029: J.-F.B.).
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NR 81
TC 1
Z9 1
U1 2
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD NOV
PY 2021
VL 10
IS 11
AR 3160
DI 10.3390/cells10113160
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA XI3NF
UT WOS:000726022100001
PM 34831383
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Sindal, MD
   Chhabra, K
   Khanna, V
AF Sindal, Manavi D.
   Chhabra, Kanika
   Khanna, Vaibhav
TI Profile of patients receiving intravitreal anti-vascular endothelial
   growth factor injections during COVID-19-related lockdown
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; anti-VEGF; COVID-19; diabetic macular
   edema; retinal vein occlusion
AB Purpose: The aim of this study was to analyze the impact on vision due to delay in presentation of patients requiring intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, consequent to COVID-19-related travel restrictions. Methods: Data were collected retrospectively of patients who received anti-VEGF injections during four months of the COVID-19 pandemic. Visual acuities, indication for treatment were noted along with basic demographic characteristics. Results: Data were analyzed for 303 eyes of 263 patients. The indication for treatment was age-related macular degeneration (AMD) in 60 eyes (19.8%), while 162 eyes (53.5%) had Diabetic Macular Edema, 71 eyes (23.4%) had Retinal Vein Occlusion and 10 eyes (3.3%) had other diagnosis. The visual acuity in the treatment naive eyes (Group A, n = 168) was significantly worse (P < 0.001) than those who presented for retreatment (Group B, n = 135). In Group B, there was a significant decline in vision for the entire cohort (P = 0.009) and those with AMD (P = 0.036). Those in Group B presented at a mean interval of 19.1 +/- 10.6 (range, 4-64) weeks for retreatment. Conclusion: The COVID-19 pandemic has led to a delay in patients receiving anti-VEGF injections. The visual acuity is worse in both treatment naive as well as those requiring retreatment. This could have long-term impact on vision of patients requiring this vision preserving treatment.
C1 [Sindal, Manavi D.] Aravind Eye Hosp, Clin Retina & Training, Vitreoretinal Serv, Pondicherry, India.
   [Chhabra, Kanika] Aravind Eye Hosp, Vitreoretinal Serv, Cuddalore Main Rd, Pondicherry 605007, India.
   [Khanna, Vaibhav] Aravind Eye Hosp, Cornea Serv, Pondicherry, India.
   [Khanna, Vaibhav] Postgrad Inst Ophthalmol, Pondicherry, India.
RP Sindal, MD (通讯作者)，Aravind Eye Hosp, Vitreoretinal Serv, Cuddalore Main Rd, Pondicherry 605007, India.
EM mdsindal@gmail.com
CR [Anonymous], 2020, COR DIS 2019
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NR 16
TC 7
Z9 7
U1 0
U2 1
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD MAR
PY 2021
VL 69
IS 3
BP 730
EP 733
DI 10.4103/ijo.IJO_2807_20
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QQ3ZW
UT WOS:000624463600058
PM 33595512
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sharma, K
   Singh, R
   Sharma, SK
   Anand, A
AF Sharma, Kaushal
   Singh, Ramandeep
   Sharma, Suresh Kumar
   Anand, Akshay
TI Sleeping pattern and activities of daily living modulate protein
   expression in AMD
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; ALZHEIMERS-DISEASE;
   STEM-CELLS; AGE; ACCUMULATION; EPIGENETICS; MECHANISMS; RECEPTOR-3;
   DURATION
AB Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.
C1 [Sharma, Kaushal; Anand, Akshay] Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India.
   [Sharma, Kaushal] Post Grad Inst Med Educ & Res, Adv Pediat Ctr, Dept Pediat, Chandigarh, India.
   [Singh, Ramandeep] Post Grad Inst Med Educ & Res, Dept Ophthalmol, Chandigarh, India.
   [Sharma, Suresh Kumar] Panjab Univ, Dept Stat, Chandigarh, India.
C3 Post Graduate Institute of Medical Education & Research (PGIMER),
   Chandigarh; Post Graduate Institute of Medical Education & Research
   (PGIMER), Chandigarh; Post Graduate Institute of Medical Education &
   Research (PGIMER), Chandigarh; Panjab University
RP Anand, A (通讯作者)，Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India.
EM akshay1anand@rediffmail.com
OI Anand, Akshay/0000-0001-9003-3532
FU Department of Biotechnology, New Delhi, India
   [BT/PR17550/MED/30/1755/2016]; CSIR-UGC, New Delhi; Indian Council of
   Medical Research (ICMR), New Delhi, India; Department of Science and
   Technology (DST), New Delhi, India
FX This study was funded by the Department of Biotechnology, New Delhi,
   India to AA (No. BT/PR17550/MED/30/1755/2016). We also acknowledge
   CSIR-UGC, New Delhi for providing fellowship during PhD to KS,
   Department of Science and Technology (DST), New Delhi, India and Indian
   Council of Medical Research (ICMR), New Delhi, India to provide the
   travel funds to KS. 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 2
Z9 2
U1 1
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
PY 2021
VL 16
IS 6
AR e0248523
DI 10.1371/journal.pone.0248523
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA SL3JC
UT WOS:000656813600020
PM 34061866
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Masaeli, E
   Forster, V
   Picaud, S
   Karamali, F
   Nasr-Esfahani, MH
   Marquette, C
AF Masaeli, Elahe
   Forster, Valerie
   Picaud, Serge
   Karamali, Fereshte
   Nasr-Esfahani, Mohammad Hossein
   Marquette, Christophe
TI Tissue engineering of retina through high resolution 3-dimensional
   inkjet bioprinting
SO BIOFABRICATION
LA English
DT Article
DE bioprinting; photoreceptors; retina pigmented epithelium; tissue
   engineering
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIUM; CELL SHEETS; STEM-CELLS;
   RPE CELLS; PHAGOCYTOSIS; SECRETION; SURVIVAL; DIFFERENTIATION;
   TRANSPLANTATION
AB The mammalian retina contains multiple cellular layers, each carrying out a specific task. Such a controlled organization should be considered as a crucial factor for designing retinal therapies. The maintenance of retinal layered complexity through the use of scaffold-free techniques has recently emerged as a promising approach for clinical ocular tissue engineering. In an attempt to fabricate such layered retinal model, we are proposing herein a unique inkjet bioprinting system applied to the deposition of a photoreceptor cells (PRs) layer on top of a bioprinted retinal pigment epithelium (RPE), in a precise arrangement and without any carrier material. The results showed that, after bioprinting, both RPE and PRs were well positioned in a layered structure and expressed their structural markers, which was further demonstrated by ZO1, MITF, rhodopsin, opsin B, opsin R/G and PNA immunostaining, three days after bioprinting. We also showed that considerable amounts of human vascular endothelial growth factors (hVEGF) were released from the RPE printed layer, which confirmed the formation of a functional RPE monolayer after bioprinting. Microstructures of bioprinted cells as well as phagocytosis of photoreceptor outer segments by apical RPE microvilli were finally established through transmission electron microscopy (TEM) imaging. In summary, using this carrier-free bioprinting method, it was possible to develop a reasonable in vitro retina model for studying some sight-threatening diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
C1 [Masaeli, Elahe; Karamali, Fereshte; Nasr-Esfahani, Mohammad Hossein] ACECR, Royan Inst Biotechnol, Dept Cellular Biotechnol, Cell Sci Res Ctr, Esfahan, Iran.
   [Masaeli, Elahe; Marquette, Christophe] Univ Lyon, Univ Lyon1, CNRS, 3d FAB,INSA,CPE Lyon,ICBMS,UMR 5246, Bat Lederer,1 Rue Victor Grignard, F-69100 Villeurbanne, France.
   [Forster, Valerie; Picaud, Serge] Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
C3 Academic Center for Education, Culture & Research (ACECR); Centre
   National de la Recherche Scientifique (CNRS); CNRS - Institute of
   Chemistry (INC); Institut National des Sciences Appliquees de Lyon -
   INSA Lyon; UDICE-French Research Universities; Sorbonne Universite
RP Masaeli, E (通讯作者)，ACECR, Royan Inst Biotechnol, Dept Cellular Biotechnol, Cell Sci Res Ctr, Esfahan, Iran.; Masaeli, E; Marquette, C (通讯作者)，Univ Lyon, Univ Lyon1, CNRS, 3d FAB,INSA,CPE Lyon,ICBMS,UMR 5246, Bat Lederer,1 Rue Victor Grignard, F-69100 Villeurbanne, France.
EM elahe.masaeli@royaninstitute.org; christophe.marquette@univ-lyon1.fr
RI , Nasr-Esfahani/AAR-2434-2021; Nasr-Esfahani, Mohammad
   Hossein/AAN-2577-2020; Picaud, Serge/H-4012-2014
OI Nasr-Esfahani, Mohammad Hossein/0000-0003-1983-3435; Marquette,
   Christophe/0000-0003-3019-0696; Picaud, Serge/0000-0002-0548-5145
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NR 54
TC 39
Z9 41
U1 3
U2 60
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1758-5082
EI 1758-5090
J9 BIOFABRICATION
JI Biofabrication
PD APR
PY 2020
VL 12
IS 2
AR 025006
DI 10.1088/1758-5090/ab4a20
PG 12
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA KH5RU
UT WOS:000510708300001
PM 31578006
OA Green Published
DA 2022-11-30
ER

PT J
AU Borrelli, E
   Costanzo, E
   Parravano, M
   Viggiano, P
   Varano, M
   Giorno, P
   Marchese, A
   Sacconi, R
   Mastropasqua, L
   Bandello, F
   Querques, G
AF Borrelli, Enrico
   Costanzo, Eliana
   Parravano, Mariacristina
   Viggiano, Pasquale
   Varano, Monica
   Giorno, Paola
   Marchese, Alessandro
   Sacconi, Riccardo
   Mastropasqua, Leonardo
   Bandello, Francesco
   Querques, Giuseppe
TI Impact of Bleaching on Photoreceptors in Different Intermediate AMD
   Phenotypes
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; optical coherence tomography;
   photoreceptors
ID ROD OUTER SEGMENT; SUBRETINAL DRUSENOID DEPOSITS; RETICULAR
   PSEUDODRUSEN; MACULAR DEGENERATION; DARK-ADAPTATION; FUNDUS
   AUTOFLUORESCENCE; A-WAVE; MICROPERIMETRY; CLASSIFICATION; PREVALENCE
AB Purpose: To investigate photoreceptors' structural changes after photobleaching exposure in intermediate age-related macular degeneration (iAMD) eyes with and without reticular pseudodrusen (RPD).
   Methods: In this prospective, cross-sectional study, were enrolled iAMD patients and healthy controls. Patients and controls underwent repeated imaging with spectraldomain optical coherence tomography (SD-OCT), at baseline and at three intervals after bleaching, during the subsequent recovery in darkness. Structural changes in photoreceptors were investigated in the foveal region and in four perifoveal areas.
   Results: Twenty eyes of 20 iAMD patients (12 with RPD and 8 without RPD) and 15 age-matched healthy controls were enrolled. At baseline, the photoreceptor outer segment (OS) volume was significantly reduced in iAMD eyes with RPD compared with controls, in the foveal and perifoveal regions. In healthy subjects, a precocious increase in OS volume was observed after bleaching in the foveal region, and a rapid recovery to baseline values was recorded. In the perifoveal regions, an increase in OS volume was observed 10 minutes after light onset. In contrast, in iAMD subjects with RPD an altered response to photobleaching, in the foveal and superior and inferior perifoveal regions, was recorded.
   Conclusions: Our imaging evidences support the hypothesis that dark adaptation is more altered in eyes with RPD. The structural modifications may explain the functional increased damage of the retinal pigment epithelium and photoreceptors reported in eyes with RPD.
   Translational Relevance: OCT imaging may be used to assess dark adaptation in AMD eyes.
C1 [Borrelli, Enrico; Marchese, Alessandro; Sacconi, Riccardo; Bandello, Francesco; Querques, Giuseppe] San Raffaele Univ Hosp, Ophthalmol Dept, Milan, Italy.
   [Costanzo, Eliana; Parravano, Mariacristina; Varano, Monica; Giorno, Paola] IRCCS Fdn Bietti, Rome, Italy.
   [Viggiano, Pasquale; Mastropasqua, Leonardo] Univ G dAnnunzio, Dept Med & Sci Ageing, Ophthalmol Clin, 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)，Univ Vita Salute San Raffaele, Dept Ophthalmol, Via Olgettina 60, Milan, Italy.
EM giuseppe.querques@hotmail.it
RI Borrelli, Enrico/AAR-3693-2020; Marchese, Alessandro/AAG-7231-2019;
   bandello, francesco/AAH-2405-2019; Costanzo, Eliana/AAA-7690-2020
OI Borrelli, Enrico/0000-0003-2815-5031; bandello,
   francesco/0000-0003-3238-9682; Querques, Giuseppe/0000-0002-3292-9581;
   Varano, Monica/0000-0002-6530-1563; Marchese,
   Alessandro/0000-0001-7716-7261; Sacconi, Riccardo/0000-0003-2891-2012;
   Viggiano, Pasquale/0000-0002-0323-967X
FU Italian Ministry of Health; Fondazione Roma
FX Supported by grants from the Italian Ministry of Health and Fondazione
   Roma.
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NR 44
TC 4
Z9 4
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD NOV
PY 2019
VL 8
IS 6
AR 5
DI 10.1167/tvst.8.6.5
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA JM1RN
UT WOS:000495999700003
PM 31737429
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhou, J
   Liu, Z
   Chen, M
   Luo, ZH
   Li, YQ
   Qi, GY
   Liu, T
AF Zhou, Jun
   Liu, Zheng
   Chen, Meng
   Luo, Zhi-Heng
   Li, Yun-Qiu
   Qi, Guang-Ying
   Liu, Tao
TI Concentrations of VEGF and PlGF Decrease in Eyes After Intravitreal
   Conbercept Injection
SO DIABETES THERAPY
LA English
DT Article
DE Aqueous humor; Conbercept; Placental growth factor; Vascular endothelial
   growth factor; Vitreous humor
AB IntroductionConbercept is a new anti-vascular endothelial growth factor drug approved for the treatment of age-related macular degeneration by the China Food and Drug Administration (CFDA) in 2013. In this study, we for the first time evaluated the concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) after patients with proliferative diabetic retinopathy were treated with intravitreal conbercept (IVC) injection.MethodsSixteen patients with proliferative diabetic retinopathy were randomly divided into two equal groups (A and B). Nine patients with rhegmatogenous retinal detachment were used as the control group. The patients in group A received 0.5mg IVC and their aqueous humor was collected. After 7days, all patients underwent vitrectomy, and their aqueous and vitreous humor were collected.ResultsIn the aqueous humor, the concentrations of VEGF and PlGF were higher pre- than post-IVC injection in group A. Similarly, the concentrations of VEGF and PlGF in group A (pre-IVC) and group B were higher than those in the control group. In vitreous humor, the concentrations of VEGF and PlGF were higher in group B than those in the control group, and the concentrations of VEGF were lower in group A (post-IVC) than those in group B.ConclusionsOur study proved that the concentration of VEGF and PlGF reduced after IVC injection in aqueous humor. However, the concentration of PlGF did not reduce after IVC injection in vitreous humor.
C1 [Zhou, Jun; Liu, Zheng; Chen, Meng; Liu, Tao] Xi An Jiao Tong Univ, Dept Ophthalmol, Hosp 3201, Hlth Sci Ctr, Hanzhong, Shaanxi, Peoples R China.
   [Zhou, Jun] Hanzhong Cent Hosp, Dept Ophthalmol, Hanzhong, Shaanxi, Peoples R China.
   [Liu, Zheng; Li, Yun-Qiu; Qi, Guang-Ying] Guilin Med Univ, Coll Med Lab Sci, Guilin, Guangxi, Peoples R China.
   [Luo, Zhi-Heng] Shaanxi Univ Technol, Vitamin Res Inst D, Hanzhong, Shaanxi, Peoples R China.
C3 Xi'an Jiaotong University; Guilin Medical University; Shaanxi University
   of Technology
RP Liu, T (通讯作者)，Xi An Jiao Tong Univ, Dept Ophthalmol, Hosp 3201, Hlth Sci Ctr, Hanzhong, Shaanxi, Peoples R China.
EM taoliustone@hz3201.com
RI Liu, Zheng/GVU-3695-2022
OI Liu, Zheng/0000-0003-4158-6768; Liu, Tao/0000-0001-9246-7430
FU key research and development program of Shaanxi province
   [2017ZDXM-SF-067]
FX Sponsorship for this study and article processing charges were funded by
   the key research and development program of Shaanxi province
   (2017ZDXM-SF-067). All authors had full access to all of the data in
   this study and take complete responsibility for the integrity of the
   data and accuracy of the data analysis.
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NR 15
TC 7
Z9 7
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1869-6953
EI 1869-6961
J9 DIABETES THER
JI Diabetes Ther.
PD DEC
PY 2018
VL 9
IS 6
BP 2393
EP 2398
DI 10.1007/s13300-018-0527-9
PG 6
WC Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism
GA HB4NY
UT WOS:000451031400019
PM 30377995
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Will-Orrego, A
   Qiu, YB
   Fassbender, ES
   Shen, SY
   Aranda, J
   Kotagiri, N
   Maker, M
   Liao, SM
   Jaffee, BD
   Poor, SH
AF Will-Orrego, Adrian
   Qiu, Yubin
   Fassbender, Elizabeth S.
   Shen, Siyuan
   Aranda, Jorge
   Kotagiri, Namrata
   Maker, Michael
   Liao, Sha-Mei
   Jaffee, Bruce D.
   Poor, Stephen H.
TI Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of
   Experimental Choroidal Neovascularization (CNV)
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE microglia; MNPs; CNV; anti-VEGF; TLR-2; angiogenesis
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; RETINAL DEGENERATION; MACULAR
   DEGENERATION; INNATE IMMUNITY; MICROGLIAL ACTIVATION; OXIDATIVE STRESS;
   INFLAMMATION; MACROPHAGES; RECEPTORS; PHENOTYPE
AB Purpose: Mononuclear phagocytes (MNPs) are present in neovascular age-related macular degeneration (nv AMD) which is also called choroidal neovascularization (CNV). The number and phenotype of the MNPs depend upon the local environment in the CNV and effect of nv AMD therapy. We investigated ocular cell infiltration and conditions that modulate angiogenesis in a laser-induced mouse CNV model. Methods: We developed assays to quantify MNPs in our established mouse CNV model. One MNP assay quantified the number of subretinal cells peripheral to the CNV lesions. A second assay semiquantitatively assesses the number of MNPs localized to the CNV lesion. We used these assays to measure the effect of toll-like receptor-2 (TLR-2) activation, anti-vascular endothelial growth factor (VEGF) therapy, and chemokine (C-C motif) ligand 2 (Ccl2) genetic deletion on MNP infiltration after laser injury. Results: Laser injury induced blood vessel growth and infiltration of MNPs. Systemic administration of a TLR-2 activating peptide increased laser-induced CNV area, MNP cell numbers, and MNP density over the CNV lesions. Systemic administration of a VEGF antibody reduced CNV area, while Ccl2 genetic deletion increased CNV area. Despite the change in amount of angiogenesis, MNP infiltration was, surprisingly, unchanged in these 2 conditions. Conclusions: MNP quantification provides biological insights for candidate AMD therapies. The number of infiltrating MNP cells does not correlate with the amount of laser-induced CNV area.
C1 [Will-Orrego, Adrian; Qiu, Yubin; Fassbender, Elizabeth S.; Shen, Siyuan; Aranda, Jorge; Kotagiri, Namrata; Maker, Michael; Liao, Sha-Mei; Jaffee, Bruce D.; Poor, Stephen H.] Novartis Inst Biomed Res, Dept Ophthalmol, 22 Windsor St, Cambridge, MA 02139 USA.
C3 Novartis
RP Poor, SH (通讯作者)，Novartis Inst Biomed Res, Dept Ophthalmol, 22 Windsor St, Cambridge, MA 02139 USA.
EM stephen.poor@novartis.com
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NR 59
TC 4
Z9 4
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD SEP
PY 2018
VL 34
IS 7
BP 489
EP 499
DI 10.1089/jop.2017.0131
PG 11
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA GS6PA
UT WOS:000443818600002
PM 30188257
OA Green Published
DA 2022-11-30
ER

PT J
AU Kim, Y
   Griffin, JM
   Nor, MNM
   Zhang, J
   Freestone, PS
   Danesh-Meyer, HV
   Rupenthal, ID
   Acosta, M
   Nicholson, LFB
   O'Carroll, SJ
   Green, CR
AF Kim, Yeri
   Griffin, Jarred M.
   Nor, Mohd N. Mat
   Zhang, Jie
   Freestone, Peter S.
   Danesh-Meyer, Helen V.
   Rupenthal, Ilva D.
   Acosta, Monica
   Nicholson, Louise F. B.
   O'Carroll, Simon J.
   Green, Colin R.
TI Tonabersat Prevents Inflammatory Damage in the Central Nervous System by
   Blocking Connexin43 Hemichannels
SO NEUROTHERAPEUTICS
LA English
DT Article
DE Tonabersat; connexin43; connexin hemichannel; gap junction; CNS disease
ID CORTICAL SPREADING DEPRESSION; IMPROVES FUNCTIONAL RECOVERY;
   GAP-JUNCTIONAL HEMICHANNELS; RAT SPINAL-CORD; ATP RELEASE; MIMETIC
   PEPTIDE; CELL-DEATH; INTRACELLULAR CALCIUM; EXTRACELLULAR CALCIUM;
   CHANNEL PERMEABILITY
AB The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
C1 [Kim, Yeri; Zhang, Jie; Danesh-Meyer, Helen V.; Rupenthal, Ilva D.; Green, Colin R.] Univ Auckland, Fac Med & Hlth Sci, Dept Ophthalmol, Auckland 1142, New Zealand.
   [Kim, Yeri; Nor, Mohd N. Mat; Zhang, Jie; Danesh-Meyer, Helen V.; Rupenthal, Ilva D.; Acosta, Monica; Green, Colin R.] Univ Auckland, Fac Med & Hlth Sci, New Zealand Natl Eye Ctr, Auckland 1142, New Zealand.
   [Griffin, Jarred M.; Nicholson, Louise F. B.; O'Carroll, Simon J.] Univ Auckland, Fac Med & Hlth Sci, Ctr Brain Res, Auckland 1142, New Zealand.
   [Nor, Mohd N. Mat; Acosta, Monica] Univ Auckland, Fac Med & Hlth Sci, Sch Optometry & Vis Sci, Auckland 1142, New Zealand.
   [Freestone, Peter S.] Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, Auckland 1142, New Zealand.
   [Rupenthal, Ilva D.] Univ Auckland, Fac Med & Hlth Sci, Buchanan Ocular Therapeut Unit, Auckland 1142, New Zealand.
   [Nor, Mohd N. Mat] Univ Sultan Zainal Abidin, Fac Med, Kuala Terengganu, Malaysia.
C3 University of Auckland; University of Auckland; University of Auckland;
   University of Auckland; University of Auckland; University of Auckland;
   Universiti Sultan Zainal Abidin
RP Green, CR (通讯作者)，Univ Auckland, Fac Med & Hlth Sci, Dept Ophthalmol, Auckland 1142, New Zealand.; Green, CR (通讯作者)，Univ Auckland, Fac Med & Hlth Sci, New Zealand Natl Eye Ctr, Auckland 1142, New Zealand.
EM c.green@auckland.ac.nz
RI Zhang, Jie/I-6135-2019; Rupenthal, Ilva D/M-5340-2016; Acosta,
   Monica/H-2700-2019; Green, Colin R/B-5663-2012
OI Zhang, Jie/0000-0003-1572-8339; Rupenthal, Ilva D/0000-0001-5997-5994;
   Acosta, Monica/0000-0002-5018-339X; Green, Colin R/0000-0003-3459-6298
FU University of Auckland; CatWalk Spinal Cord Injury Trust; Ministry of
   Higher Education, Malaysia; Auckland UniServices Ltd; New Zealand Return
   on Science fund; WB Hadden
FX We thank Professor P.J. Donaldson for the generous loan of his
   electrophysiology equipment. This work was supported by a University of
   Auckland Doctoral Scholarship to Y.K. J.M.G was supported by the CatWalk
   Spinal Cord Injury Trust, and M.N.M.N by a PhD scholarship from the
   Ministry of Higher Education, Malaysia. C.R.G is a founding scientist of
   CoDa Therapeutics, Inc. USA, which holds intellectual property around
   the use of connexin channel modulators for the treatment of injury and
   disease. C.R.G and Y.K are named as inventors on patent application(s)
   related to uses of tonabersat. We acknowledge support from Auckland
   UniServices Ltd and the New Zealand Return on Science fund. C.R.G is the
   W&B Hadden Professor of Ophthalmology and Translational Research and
   acknowledges the generous support of W&B Hadden.
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NR 116
TC 29
Z9 32
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 1933-7213
EI 1878-7479
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD OCT
PY 2017
VL 14
IS 4
BP 1148
EP 1165
DI 10.1007/s13311-017-0536-9
PG 18
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA FP5XB
UT WOS:000417695200029
PM 28560708
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Bian, MJ
   Zhang, Y
   Du, XY
   Xu, J
   Cui, JG
   Gu, JP
   Zhu, WL
   Zhang, T
   Chen, Y
AF Bian, Minjuan
   Zhang, Yong
   Du, Xiaoye
   Xu, Jing
   Cui, Jingang
   Gu, Jiangping
   Zhu, Weiliang
   Zhang, Teng
   Chen, Yu
TI Apigenin-7-diglucuronide protects retinas against bright light-induced
   photoreceptor degeneration through the inhibition of retinal oxidative
   stress and inflammation
SO BRAIN RESEARCH
LA English
DT Article
DE Apigenin-7-diglucuronide; Photoreceptor degeneration; Oxidative stress;
   Retinal inflammation
ID APOPTOSIS IN-VITRO; MACULAR DEGENERATION; MICROGLIAL ACTIVATION;
   PERILLA-FRUTESCENS; CELLS; DAMAGE; CONSTITUENTS; HYDROETHIDINE;
   MECHANISMS; RPE
AB Vision impairment in retinal degenerative diseases such as age-related macular degeneration is primarily associated with photoreceptor degeneration, in which oxidative stress and inflammatory responses are mechanistically involved as central players. Therapies with photoreceptor protective properties remain to be developed. Apigenin-7-diglucuronide (A7DG), a flavonoid glycoside, is present in an assortment of medicinal plants with anti-inflammatory or ant-oxidant activities. However, the pharmacological significance of A7DG remains unknown in vivo. The current study isolated A7DG from Glechoma longituba (Nakai) Kuprian and investigated the retinal protective effect A7DG in mice characterized by bright light-induced photoreceptor degeneration. The results showed that A7DG treatment led to remarkable photoreceptor protection in bright light-exposed BALB/c mice. Moreover, A7DG treatment alleviated photoreceptor apoptosis, mitigated oxidative stress, suppressed reactive gliosis and microglial activation and attenuated the expression of proinflammatory genes in bright light-exposed retinas. The results demonstrated for the first time remarkable photoreceptor protective activities of A7DG in vivo. Inhibition of bright light-induced retinal oxidative stress and retinal inflammatory responses was associated with the retinal protection conferred by A7DG. The work here warrants further evaluation of A7DG as a pharmacological candidate for the treatment of vision-threatening retinal degenerative disorders. Moreover, given the general implication of oxidative stress and inflammation in the pathogenesis of neurodegeneration, A7DG could be further tested for the treatment of other neurodegenerative disorders. (C) 2017 Elsevier B.V. All rights reserved.
C1 [Bian, Minjuan; Du, Xiaoye; Cui, Jingang; Zhang, Teng; Chen, Yu] Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Shanghai 200437, Peoples R China.
   [Bian, Minjuan; Du, Xiaoye; Cui, Jingang; Zhang, Teng; Chen, Yu] Shanghai Univ Tradit Chinese Med, Clin Res Inst Integrat Med, Shanghai 200437, Peoples R China.
   [Zhang, Yong; Zhu, Weiliang] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China.
   [Xu, Jing; Gu, Jiangping] East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China.
C3 Shanghai University of Traditional Chinese Medicine; Shanghai University
   of Traditional Chinese Medicine; Chinese Academy of Sciences; Shanghai
   Institute of Materia Medica, CAS; East China University of Science &
   Technology
RP Zhang, T; Chen, Y (通讯作者)，Shanghai Univ Tradit Chinese Med, 110 Ganhe Rd, Shanghai 200437, Peoples R China.
EM zhangteng501@hotmail.com; chenyu6639@hotmai.com
FU National Natural Science Foundation of China [81473732, 81673790];
   Program of Eastern Scholar - Shanghai Municipal Education Commission
   [Hu201188, GZ2015011]; Shuguang Project - Shanghai Municipal Education
   Commission [13SG42]; Budget Project from Shanghai Municipal Education
   Commission [2014YSN49]; Shanghai Sailing Program [16YF1414100]
FX This work was supported by the National Natural Science Foundation of
   China (81473732, 81673790, Y.C); the Program of Eastern Scholar
   supported by Shanghai Municipal Education Commission (Hu201188, Y.O and
   GZ2015011, T.Z); the Shuguang Project supported by Shanghai Municipal
   Education Commission (13SG42, Y. C); the Budget Project from Shanghai
   Municipal Education Commission (2014YSN49, M.B) and the Shanghai Sailing
   Program (16YF1414100, Y.Z).
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NR 36
TC 14
Z9 14
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD MAY 15
PY 2017
VL 1663
BP 141
EP 150
DI 10.1016/j.brainres.2017.03.019
PG 10
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA EU5BL
UT WOS:000401046500016
PM 28336272
DA 2022-11-30
ER

PT J
AU Moon, SW
   Kim, W
   Choi, S
   Shin, JH
AF Moon, Sang Woong
   Kim, Wansun
   Choi, Samjin
   Shin, Jae-Ho
TI Label-free optical detection of age-related and diabetic oxidative
   damage in human aqueous humors
SO MICROSCOPY RESEARCH AND TECHNIQUE
LA English
DT Article
DE age-related macular degeneration; cataract; diabetic retinopathy; human
   aqueous humors; oxidative damage; Raman spectroscopy
ID ATOMIC-FORCE MICROSCOPY; RAMAN MICROSCOPY; PAPER PLATFORM; STRESS;
   DISEASES
AB In this study, we investigate the biochemical characteristics of oxidative stress in age-related macular degeneration (AMD) and diabetic retinopathy (DR) by analyzing aqueous humors. Nondiabetic cataract aqueous humor was used as the control. The level of oxidative damage was evaluated based on changes in Raman spectral intensity. Seven prominent peaks were detected at 1002, 1043, 1062, 1352, 1419, 1454, and 1656 cm(-1). We proposed four multimodal biomarkers to distinguish these peaks based on the ratios of Raman intensities in two wavelengths, including CHO (C-O stretching or C-O-H bending modes), AG (adenine and guanine), PRO-AG (protein and AG), and PHEa (phenylalanine symmetric ring breath and amide I alpha-helix) markers. The presence of oxidative damage was detected by CHO and AG markers associated with C-O stretching, C-O-H bending modes in carbohydrates (1043 cm(-1)), and the nucleic acids adenine and guanine (1352 cm(-1)), respectively. DR-related oxidative damage was identified by PRO-AG and PHEa markers associated with adenine, guanine, and protein components (1419 and 1454 cm(-1)) and amide I alpha-helix protein structure (1656 cm(-1)), respectively. AMD-related oxidative damage was identified by four biomarkers. Four multimodal biomarkers with simple linear threshold values achieved high sensitivity of 100% and high specificity of 100% for classifying oxidative stressinduced AMD and DR diseases. Therefore, Raman-based label-free optical detection is effective for detecting the presence of age-related or diabetic oxidative damage in aqueous humor.
C1 [Moon, Sang Woong; Shin, Jae-Ho] Kyung Hee Univ, Dept Ophthalmol, Coll Med, Seoul 052778, South Korea.
   [Kim, Wansun; Choi, Samjin] Kyung Hee Univ, Grad Sch, Dept Med Engn, Seoul 02447, South Korea.
   [Choi, Samjin] Kyung Hee Univ, Dept Biomed Engn, Coll Med, 26 Kyungheedae Ro, Seoul 02447, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University
RP Choi, S (通讯作者)，Kyung Hee Univ, Dept Biomed Engn, Coll Med, 26 Kyungheedae Ro, Seoul 02447, South Korea.; Shin, JH (通讯作者)，Kyung Hee Univ, Dept Ophthalmol, 23 Kyunghee dae Ro, Seoul 02447, South Korea.
EM medchoi@khu.ac.kr; pbloadsky@naver.com
OI KIM, Wansun/0000-0001-9186-6448; Choi, Samjin/0000-0003-3498-0652
FU Basic Science Research Program through the National Research Foundation
   of Korea (NRF) - Ministry of Education [2014R1A1A2054452]; NRF grant -
   Korean government (MSIP) [2015R1A5A1037656]
FX This research was supported by the Basic Science Research Program
   through the National Research Foundation of Korea (NRF) funded by the
   Ministry of Education (Grant 2014R1A1A2054452) and by an NRF grant
   funded by the Korean government (MSIP) (Grant 2015R1A5A1037656).
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NR 27
TC 5
Z9 5
U1 0
U2 5
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-910X
EI 1097-0029
J9 MICROSC RES TECHNIQ
JI Microsc. Res. Tech.
PD NOV
PY 2016
VL 79
IS 11
BP 1050
EP 1055
DI 10.1002/jemt.22743
PG 6
WC Anatomy & Morphology; Biology; Microscopy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics;
   Microscopy
GA EA2VF
UT WOS:000386452900007
PM 27507597
DA 2022-11-30
ER

PT J
AU Shang, JL
   Sun, YX
   Liu, JX
   Xia, JF
   Zhang, JY
   Zheng, CH
AF Shang, Junliang
   Sun, Yingxia
   Liu, Jin-Xing
   Xia, Junfeng
   Zhang, Junying
   Zheng, Chun-Hou
TI CINOEDV: a co-information based method for detecting and visualizing
   n-order epistatic interactions
SO BMC BIOINFORMATICS
LA English
DT Article
DE Epistatic interactions; Co-information; Single nucleotide polymorphisms;
   Particle swarm optimization; Hypergraph
ID ASSOCIATION INTERACTION NETWORK; GENE-GENE INTERACTIONS; MISSING
   HERITABILITY; STATISTICAL-METHODS; INFERENCE; VARIANTS; PATTERNS
AB Background: Detecting and visualizing nonlinear interaction effects of single nucleotide polymorphisms (SNPs) or epistatic interactions are important topics in bioinformatics since they play an important role in unraveling the mystery of "missing heritability". However, related studies are almost limited to pairwise epistatic interactions due to their methodological and computational challenges.
   Results: We develop CINOEDV (Co-Information based N-Order Epistasis Detector and Visualizer) for the detection and visualization of epistatic interactions of their orders from 1 to n (n >= 2). CINOEDV is composed of two stages, namely, detecting stage and visualizing stage. In detecting stage, co-information based measures are employed to quantify association effects of n-order SNP combinations to the phenotype, and two types of search strategies are introduced to identify n-order epistatic interactions: an exhaustive search and a particle swarm optimization based search. In visualizing stage, all detected n-order epistatic interactions are used to construct a hypergraph, where a real vertex represents the main effect of a SNP and a virtual vertex denotes the interaction effect of an n-order epistatic interaction. By deeply analyzing the constructed hypergraph, some hidden clues for better understanding the underlying genetic architecture of complex diseases could be revealed.
   Conclusions: Experiments of CINOEDV and its comparison with existing state-of-the-art methods are performed on both simulation data sets and a real data set of age-related macular degeneration. Results demonstrate that CINOEDV is promising in detecting and visualizing n-order epistatic interactions.
C1 [Shang, Junliang; Sun, Yingxia; Liu, Jin-Xing] Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.
   [Shang, Junliang] Qufu Normal Univ, Inst Network Comp, Rizhao 276826, Peoples R China.
   [Liu, Jin-Xing] Harbin Inst Technol, Shenzhen Grad Sch, Biocomp Res Ctr, Shenzhen 518055, Peoples R China.
   [Xia, Junfeng] Anhui Univ, Inst Hlth Sci, Hefei 230601, Anhui, Peoples R China.
   [Zhang, Junying] Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Peoples R China.
   [Zheng, Chun-Hou] Anhui Univ, Coll Elect Engn & Automat, Hefei 230039, Anhui, Peoples R China.
C3 Qufu Normal University; Qufu Normal University; Harbin Institute of
   Technology; University Town of Shenzhen; Anhui University; Xidian
   University; Anhui University
RP Shang, JL (通讯作者)，Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao 276826, Peoples R China.; Shang, JL (通讯作者)，Qufu Normal Univ, Inst Network Comp, Rizhao 276826, Peoples R China.
EM shangjunliang110@163.com
RI Liu, Jin-Xing/AAU-7257-2020; Xia, Junfeng/S-2456-2019
OI Xia, Junfeng/0000-0003-3024-1705
FU National Natural Science Foundation of China [61502272, 61572284,
   61572283]; Scientific Research Reward Foundation for Excellent Young and
   Middle-age Scientists of Shandong Province [BS2014DX004]; Opening
   Laboratory Fund of Qufu Normal University [sk201416]; Science and
   Technology Planning Project of Qufu Normal University [xkj201410];
   Shenzen Municipal Science and Technology Innovation Council
   [JCYJ20140417172417174]; Scientific Research Foundation of Qufu Normal
   University [BSQD20130119]
FX This work was supported by the National Natural Science Foundation of
   China (61502272, 61572284, 61572283), the Scientific Research Reward
   Foundation for Excellent Young and Middle-age Scientists of Shandong
   Province (BS2014DX004), the Opening Laboratory Fund of Qufu Normal
   University (sk201416), the Science and Technology Planning Project of
   Qufu Normal University (xkj201410), the Shenzen Municipal Science and
   Technology Innovation Council (No. JCYJ20140417172417174), and the
   Scientific Research Foundation of Qufu Normal University (BSQD20130119).
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NR 56
TC 22
Z9 22
U1 2
U2 18
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAY 17
PY 2016
VL 17
AR 214
DI 10.1186/s12859-016-1076-8
PG 15
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 DL8ND
UT WOS:000375897800001
PM 27184783
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Santana-Blank, L
   Rodriguez-Santana, E
   Santana-Rodriguez, KE
   Reyes, H
AF Santana-Blank, Luis
   Rodriguez-Santana, Elizabeth
   Santana-Rodriguez, Karin E.
   Reyes, Heberto
TI "Quantum Leap'' in Photobiomodulation Therapy Ushers in a New Generation
   of Light-Based Treatments for Cancer and Other Complex Diseases:
   Perspective and Mini-Review
SO PHOTOMEDICINE AND LASER SURGERY
LA English
DT Review
ID PULSED-LASER DEVICE; MOUSE MODEL; ENERGY; CELL; MITOCHONDRIAL; WATER;
   APOPTOSIS; IRRADIATION; MECHANISMS; PATHOLOGY
AB Objective: Set within the context of the 2015 International Year of Light and Light-Based Technologies,and of a growing and aging world population with ever-rising healthcare needs, this perspective and mini-review focuses on photobiomodulation (PBM) therapy as an emerging, cost-effective, treatment option for cancer (i.e., solid tumors) and other complex diseases, particularly, of the eye (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa) and the central nervous system (e.g., Alzheimer's and Parkinson's disease). Background data: Over the last decades, primary and secondary mechanisms of PBM have been revealed. These include oxygen-dependent and oxygen-independent structural and functional action pathways. Signal and target characteristics determine biological outcome, which is optimal (or even positive) only within a given set of parameters. Methods: This study was a perspective and nonsystematic literature mini-review. Results: Studies support what we describe as a paradigm shift or quantum leap in the understanding and use of light and its interaction with water and other relevant photo-cceptors to restore physiologic function. Conclusions: Based on existing evidence, it is argued that PBM therapy can raise the standard of care and improve the quality of life of patients for a fraction of the cost of many current approaches. PBM therapy can, therefore,benefit large, vulnerable population groups, including the elderly and the poor, whilehaving a major impact on medical practice and public finances.
C1 [Santana-Blank, Luis; Rodriguez-Santana, Elizabeth; Santana-Rodriguez, Karin E.; Reyes, Heberto] Fundalas, Fdn Interdisciplinary Res & Dev, Caracas, Venezuela.
RP Santana-Blank, L (通讯作者)，Fundalas, Luis Santana Blank, Calle Las Flores,CC Carabel PB Local 2 MUN, Puerto La Cruz 1262, Venezuela.
EM luissantanablank@gmail.com
FU Fundalas, Foundation for Interdisciplinary Research and Development
FX We thank Jesus Alberto Santana-Rodriguez for reviewing and editing this
   article, and Luis Rafael Santana-Rodriguez for design and technical
   support. This study was supported by Fundalas, Foundation for
   Interdisciplinary Research and Development.
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NR 101
TC 22
Z9 22
U1 0
U2 21
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-5418
EI 1557-8550
J9 PHOTOMED LASER SURG
JI Photomed. Laser Surg.
PD MAR 1
PY 2016
VL 34
IS 3
BP 93
EP 101
DI 10.1089/pho.2015.4015
PG 9
WC Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Surgery
GA DG2CA
UT WOS:000371872600002
PM 26890728
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhong, YM
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AF Zhong, Yimin
   Li, Jingming
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   Yu, Qiang
   Le, Yun-zheng
   Mandal, Md Nawajes A.
   Anderson, Robert E.
   Zhang, Sarah X.
TI X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and
   Cell Survival in the Retinal Pigment Epithelium
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTOR XBP-1; ENDOPLASMIC-RETICULUM STRESS; MACULAR
   DEGENERATION; LIGHT DAMAGE; SOD1-DEFICIENT MICE; MOUSE MODEL; ER STRESS;
   EXPRESSION; DYSFUNCTION; ACTIVATION
AB Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD.
C1 [Zhong, Yimin; Li, Jingming; Wang, Joshua J.; Chen, Chen; Le, Yun-zheng; Zhang, Sarah X.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Sect Endocrinol & Diabet, Oklahoma City, OK 73190 USA.
   [Zhong, Yimin; Li, Jingming; Wang, Joshua J.; Chen, Chen; Le, Yun-zheng; Zhang, Sarah X.] Univ Oklahoma, Harold Hamm Diabet Ctr, Oklahoma City, OK USA.
   [Tran, Julie-Thu A.; Saadi, Anisse; Mandal, Md Nawajes A.; Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA.
   [Tran, Julie-Thu A.; Saadi, Anisse; Mandal, Md Nawajes A.; Anderson, Robert E.] Dean A McGee Eye Inst, Oklahoma City, OK USA.
   [Le, Yun-zheng; Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA.
   [Zhang, Sarah X.] Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
   [Zhong, Yimin] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Oklahoma System; University of Oklahoma
   Health Sciences Center; University of Oklahoma System; University of
   Oklahoma Health Sciences Center; Sun Yat Sen University
RP Zhong, YM (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Dept Med, Sect Endocrinol & Diabet, Oklahoma City, OK 73190 USA.
EM xin-zhang@ouhsc.edu
RI li, jingming/J-5760-2012
OI li, jingming/0000-0003-2300-8614; Chen, Chen/0000-0001-6741-7036
FU National Institutes of Health [EY019949, RR17703, RR024215]; American
   Diabetes Association [7-11-BS-182]; Oklahoma Center for the Advancement
   of Science and Technology [HR10-060]; American Health Assistance
   Foundation [M2010088]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [P20RR024215, P20RR017703] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [R01EY019949] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants
   EY019949, RR17703, and RR024215; Research Award 7-11-BS-182 from
   American Diabetes Association; Research Grant HR10-060 from Oklahoma
   Center for the Advancement of Science and Technology; and Research Grant
   M2010088 from American Health Assistance Foundation. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
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NR 46
TC 45
Z9 45
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 JUN 8
PY 2012
VL 7
IS 6
AR e38616
DI 10.1371/journal.pone.0038616
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 959TQ
UT WOS:000305336800037
PM 22715395
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Vossmerbaeumer, U
   Ohnesorge, S
   Kuehl, S
   Haapalahti, M
   Kluter, H
   Jonas, J
   Thierse, HJ
   Bieback, K
AF Vossmerbaeumer, Urs
   Ohnesorge, Stefanie
   Kuehl, Sandra
   Haapalahti, Minna
   Kluter, Harald
   Jonas, Jost B.
   Thierse, Hermann-Josef
   Bieback, Karen
TI Retinal pigment epithelial phenotype induced in human adipose
   tissue-derived mesenchymal stromal cells
SO CYTOTHERAPY
LA English
DT Article
DE Adipose tissue; age-related macular degeneration; epithelial
   differentiation; mesenchymal stromal cells
ID STEM-CELLS; MACULAR DEGENERATION; BONE-MARROW; PROGENITOR CELLS; EYE;
   DIFFERENTIATION; EXPRESSION; INDUCTION; TRANSDIFFERENTIATION;
   TRANSPLANTATION
AB Background aims The non-exudative form of age-related macular degeneration (ARMD) is characterized by a progressive decay of retinal pigment epithelium cells at the posterior pole of the eye. As mesenchymal stromal cells (MSC) have been shown to differentiate into various cell types from the mesodermal and ectodermal lineages, we investigated whether we can induce a phenotype displaying retinal pigment epithelium (RPE) characteristics. Methods The differentiation of human lipo-aspirate-derived MSC toward the RPE lineage was triggered by exposure to conditioned medium from either human or porcine RPE cells. In a second approach we tested whether adding vasoactive intestinal peptide (VIP) is capable of further modifying differentiation processes. Resulting cell populations were assessed for expression of RPE-specific markers by immunofluorescence, quantitative real time (RT)-polymerase chain reaction (PCR) and Western blotting. The potential for pigment synthesis was assessed by the response to melanocyte-stimulating hormone (MSH). Results Following culture of undifferentiated MSC with RPE-conditioned medium and/or VIP, expression of typical RPE markers bestrophin, cytokeratins 8 and 18 and RPE 65 was induced. MSH induced the formation of pigmented granula in differentiated MSC. Conclusions MSC are shown to express RPE markers upon induction with either RPE-conditioned medium and/or VIP. The gain of basic functional features of RPE cells was indicated by melanin synthesis. This alludes to a differentiation potential of MSC into the neuroectodermal lineage, yielding cells with phenotypic characteristics of RPE cells.
C1 [Vossmerbaeumer, Urs; Kuehl, Sandra; Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Univ Eye Hosp, Univ Augenklin, D-68167 Mannheim, Germany.
   [Ohnesorge, Stefanie; Thierse, Hermann-Josef] Heidelberg Univ, Res Grp Immunol & Prote, Dept Dermatol, D-68167 Mannheim, Germany.
   [Haapalahti, Minna; Kluter, Harald; Bieback, Karen] Heidelberg Univ, Inst Transfus Med & Immunol, German Red Cross Blood Serv Baden Wuerttemberg He, Med Fac Mannheim, D-68167 Mannheim, Germany.
C3 Ruprecht Karls University Heidelberg; University of Hamburg; University
   Medical Center Hamburg-Eppendorf; Ruprecht Karls University Heidelberg;
   Ruprecht Karls University Heidelberg
RP Vossmerbaeumer, U (通讯作者)，Heidelberg Univ, Dept Ophthalmol, Univ Augenklin, Med Fac Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM urs.vossmerbaeumer@gmx.de
OI Thierse, PD Dr. Hermann-Josef/0000-0001-9655-681X
FU Gertrud-Kusen-Stiftung ( Hamburg, Germany)
FX We gratefully acknowledge the generous support received through a grant
   from Gertrud-Kusen-Stiftung ( Hamburg, Germany) that has made possible
   the work presented in this paper.
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NR 35
TC 54
Z9 58
U1 0
U2 15
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PY 2009
VL 11
IS 2
BP 177
EP 188
AR PII 909026256
DI 10.1080/14653240802714819
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
   Biology; Hematology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
   & Experimental Medicine
GA 421FK
UT WOS:000264344600008
PM 19241195
DA 2022-11-30
ER

PT J
AU Dinu, V
   Miller, PL
   Zhao, HY
AF Dinu, Valentin
   Miller, Perry L.
   Zhao, Hongyu
TI Evidence for association between multiple complement pathway genes and
   AMD
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE age related macular degeneration (AMD); complement pathway; false
   discovery rate (FDR); pathway-based disease association; single
   nucleotide polymorphisms (SNP)
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; EXTENDED FAMILIES; C7
   DEFICIENCY; GENOME SCAN; SUSCEPTIBILITY; VARIANT
AB In this paper we explore the use of biological knowledge to supplement statistical analysis in identifying genes associated with disease. It has been previously found that the 402H variant in complement factor H (CFH) is associated with risk for developing age related macular degeneration (AMD). By focusing on the single nucleotide polymorphisms (SNPs) in the complement pathway, we were able to use the genotype data from a recently published AMD genome wide association study to identify two additional genes, C7 and MBL2, as potentially associated with subtypes of AMD. Two SNPs situated in introns of C7 and MBL2 could help differentiate between two forms of AMD: wet (more severe form of AMD) and dry (milder form of AMD). We identified a C7 haplotype associated with protection against developing wet AMD among individuals with homozygous CFH risk allele 402H (p-value 0.001 for wet AMD versus dry AMD, odds ratio (OR) 0.16, OR 95% Cl 0.05-0.49) as well as among individuals with at least one CFH risk allele (p-value 0.007 for wet AMD versus dry AMD, OR 0.35, OR 95% CI 0.16-0.77). The fact that the statistical scores for the C7 and MBL2 SNPs were significant (low false discovery rate) at the pathway level, but not significant at the genome level suggests that focusing at the pathway level can be beneficial for identifying SNP signals that would be lost at the genome-wide level.
C1 Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA.
   Yale Univ, Sch Med, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   Yale Univ, Sch Med, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06520 USA.
   Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
   Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
C3 Yale University; Yale University; Yale University; Yale University; Yale
   University; Yale University
RP Dinu, V (通讯作者)，Yale Univ, Sch Med, Ctr Med Informat, POB 208009, New Haven, CT 06520 USA.
EM valentin.dinu@yale.edu
RI Dinu, Valentin/C-4213-2013
OI Dinu, Valentin/0000-0001-6192-7836
FU NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM059507] Funding
   Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND
   STROKE [U24NS051869] Funding Source: NIH RePORTER; NATIONAL LIBRARY OF
   MEDICINE [P20LM007253, T15LM007056] Funding Source: NIH RePORTER; NIGMS
   NIH HHS [GM59507] Funding Source: Medline; NINDS NIH HHS [U24 NS051869]
   Funding Source: Medline; NLM NIH HHS [T15 LM07056, P20 LM07253] Funding
   Source: Medline
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NR 22
TC 36
Z9 39
U1 0
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2007
VL 31
IS 3
BP 224
EP 237
DI 10.1002/gepi.20204
PG 14
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA 149DW
UT WOS:000245128200005
PM 17266113
DA 2022-11-30
ER

PT J
AU Li, B
   Tang, SB
   Hu, J
   Gao, Y
   Zhang, G
   Lin, SF
   Chen, EH
   Li, BJ
AF Li, Bin
   Tang, Shi-bo
   Hu, Jie
   Gao, Yi
   Zhang, Ge
   Lin, Shao-fen
   Chen, Ean-hong
   Li, Bao-jin
TI Protective effects of transcription factor HESR1 on retinal vasculature
SO MICROVASCULAR RESEARCH
LA English
DT Article
DE HESR1 gene; retinal vasculature; VEGFR-2
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; HEY GENES; RECEPTOR;
   ANGIOGENESIS; CELLS; EXPRESSION; TIGHT; VEGF; IDENTIFICATION
AB HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch signaling pathway in vertebrate and Drosophila embryos, and is related to the HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial cells and could be an effector of Notch signaling in these cells. HESR1 is necessary for the induction of a tubular network and for continued maintenance of mature and quiescent blood vessels. To examine the role of HESR1 in retinal neovascularization, we transfected retinal vascular endothelial cells (HRCECs) with the HESR1 gene and studied its effects on the expression of angiogenic factors, on the proliferation and migration of endothelial cells, and on the formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated VEGFR-2 expression, upregulated occludin expression, inhibited the migration and proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a key role in the finely tuned network of molecules involved in the regulation of retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects of VEGF, shift endothelial cells from a proliferative state to a quiescent state, and restore normal vessel structures. Expression of the HESR1 gene in retinal vascular endothelial cells may protect retinal blood vessels and may be useful in the treatment of diseases involving damage to the retinal vasculature, including diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion. (c) 2006 Elsevier Inc. All rights reserved.
C1 Sun Yat Sen Univ, Zhongshan Opthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China.
   Sun Yat Sen Univ, Mol Med Ctr, Guangzhou, Peoples R China.
   Sun Yat Sen Univ, Hosp 1, Guangzhou, Peoples R China.
C3 Sun Yat Sen University; Sun Yat Sen University; Sun Yat Sen University
RP Tang, SB (通讯作者)，Sun Yat Sen Univ, Zhongshan Opthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China.
EM tangsb@mail.sysu.edu.cn
RI TANG, Shi/GXH-5719-2022
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NR 47
TC 18
Z9 22
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0026-2862
EI 1095-9319
J9 MICROVASC RES
JI Microvasc. Res.
PD NOV
PY 2006
VL 72
IS 3
BP 146
EP 152
DI 10.1016/j.mvr.2006.07.002
PG 7
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA 115FY
UT WOS:000242721400008
PM 17028039
DA 2022-11-30
ER

PT J
AU Clemons, TE
   Rankin, MW
   McBee, WL
AF Clemons, TE
   Rankin, MW
   McBee, WL
CA Age-Related Eye Dis Study Res Grp
TI Cognitive impairment in the age-related eye disease study - AREDS report
   No. 16
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; DEPRESSIVE SYMPTOMS; VISION IMPAIRMENT; DECLINE;
   RISK; MEMORY; MACULOPATHY; POPULATION; DYSFUNCTION; DEMENTIA
AB Objective: To investigate potential associations between cognitive function and/or impairment and age-related macular degeneration (AMD) and visual impairment in the Age-Related Eye Disease Study (AREDS).
   Methods: The AREDS is an 11-center natural history study of AMD and age-related cataract. The AREDS Cognitive Function Battery was administered to 2946 participants. The battery consists of 6 neuropsychological tests measuring performance in several cognitive domains. The Dunnett multiple comparison test was used to identify differences by AMD and visual acuity severity. The relationship with cognitive impairment was also assessed using logistic regression.
   Results: Mean scores of instruments in the AREDS Cognitive Function Battery declined with increased macular abnormalities and reduced visual acuity. After adjustment for age, sex, race, education, smoking status, diabetes mellitus, hypertension, and depression, increased macular abnormalities (trend P value <. 05) reduced mean cognitive function scores as measured by the Modified Mini-Mental State Examination and the Wechsler Logical Memory Scale. Reduced vision was found to be associated with reduced mean cognitive function scores as measured by the Modified Mini-Mental State Examination and letter and verbal fluency tasks. Persons with vision worse than 20/40 OU were more likely to be cognitively impaired (Modified Mini-Mental State Examination score < 80) (odds ratio, 2.88 [95% confidence interval, 1.75-4.76]) compared with persons with visual acuity of 20/40 or better OU.
   Conclusion: These data suggest a possible association of advanced AMD and visual acuity with cognitive impairment in older persons.
C1 EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA.
C3 Emmes Corporation
RP Clemons, TE (通讯作者)，EMMES Corp, AREDS Coordinating Ctr, 401 N Washington St,Suite 700, Rockville, MD 20850 USA.
EM aredspub@emmes.com
FU NATIONAL EYE INSTITUTE [Z01EY000394] Funding Source: NIH RePORTER; NEI
   NIH HHS [Z01 EY000394-03] Funding Source: Medline
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NR 40
TC 110
Z9 112
U1 1
U2 13
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD APR
PY 2006
VL 124
IS 4
BP 537
EP 543
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 031CB
UT WOS:000236680600012
PM 16606880
DA 2022-11-30
ER

PT J
AU Jiang, YL
   Escano, MFT
   Sasaki, R
   Fujii, S
   Kusuhara, S
   Matsumoto, A
   Sugimura, K
   Negi, A
AF Jiang, YL
   Escano, MFT
   Sasaki, R
   Fujii, S
   Kusuhara, S
   Matsumoto, A
   Sugimura, K
   Negi, A
TI Ionizing radiation induces a p53-dependent apoptotic mechanism in
   ARPE-19 cells
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE apoptosis; ARPE-19 cells; ionizing radiation; p53
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; RETINAL-PIGMENT
   EPITHELIUM; X-RAY-IRRADIATION; P53 GENE-THERAPY; FACTOR VEGF; HUMAN
   FIBROBLASTS; UP-REGULATION; CANCER-CELLS; DNA-DAMAGE
AB Purpose: To investigate the molecular mechanisms for cell growth inhibition or apoptosis in human retinal pigment epithelium (RPE) cells after ionizing radiation.
   Methods: Cell survival studies, a TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay, and a caspase-3 immunocytochemical analysis were performed on irradiated ARPE-19 cell cultures at different time periods. Transcriptional levels of p53, p21, Bax, Fas/Fas-L, vascular endothelial growth factor (VEGF), and pigment epithelium-derived growth factor (PEDF) were evaluated by semiquantitative reverse transcriptional polymerase chain reaction. Mutations in the p53 gene were analyzed by DNA sequencing. Protein levels of p53, VEGF, and PEDF were evaluated by Western blot.
   Results: Cell viability was inversely related to radiation close. TUNEL-positive cells were detected 6 h after radiation exposure. Caspase-3 immunomocytochemical analysis revealed increased immunoreactivity in the TUNEL-positive cells. Levels of p53, p21, and Bax mRNA were greatest at the 2-h postradiation period. VEGF and PEDF mRNA and protein levels were constant. Protein levels of p53 were increased at the 4- and 6-h postradiation period.
   Conclusions: Ionizing radiation induces apoptosis in normal proliferating RPE cells through p53 activation, without affecting expression of VEGF or PEDF. We documented a molecular basis for explaining the decrease in effectiveness of radiation therapy. particularly, for age-related macular degeneration. In the clinical setting, selection of appropriate radiation therapy methods and the doses for specific diseases need careful evaluation. (C) Japanese Ophthalmological Society 2004.
C1 Kobe Univ, Grad Sch Med, Dept Organ Therapeut, Div Ophthalmol, Kobe, Hyogo 6500017, Japan.
   Kobe Univ, Grad Sch Med, Dept Synchrotron Radiol Med, Kobe, Hyogo 6500017, Japan.
   Kobe Univ, Grad Sch Med, Dept Mol & Cell Biol, Div Cell Biol, Kobe, Hyogo 6500017, Japan.
C3 Kobe University; Kobe University; Kobe University
RP Jiang, YL (通讯作者)，Kobe Univ, Grad Sch Med, Dept Organ Therapeut, Div Ophthalmol, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
EM jiangyanlin00@hotmail.com
OI Kusuhara, Sentaro/0000-0002-6458-539X
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NR 48
TC 10
Z9 11
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0021-5155
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAR-APR
PY 2004
VL 48
IS 2
BP 106
EP 114
DI 10.1007/s10384-003-0043-x
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 810VB
UT WOS:000220730700004
PM 15064971
DA 2022-11-30
ER

PT J
AU Johnson, M
   Dabholkar, A
   Huang, JD
   Presley, JB
   Chimento, MF
   Curcio, CA
AF Johnson, Mark
   Dabholkar, Arun
   Huang, Jiahn-Dar
   Presley, J. Brett
   Chimento, Melissa F.
   Curcio, Christine A.
TI Comparison of morphology of human macular and peripheral Bruch's
   membrane in older eyes
SO CURRENT EYE RESEARCH
LA English
DT Article
DE AMD; basal lamina; collagen; elastin; lipoprotein; morphology
ID QUICK-FREEZE/DEEP-ETCH; DEEP-ETCH; AGE; DEGENERATION; DRUSEN;
   ACCUMULATION; DEPOSITS; RETINA
AB Deposits in macular human Bruch's membrane (BrM) increase with age and have been postulated to be associated with age-related maculopathy. We used two ultrastructural methods to compare these deposits by electron microscopy in macular and peripheral BrM of eight eyes from donors 63-86 years of age. Quick-freeze/deep-etch (QFDE) was used to prepare replicas that showed the ultrastructure of deposits, and osmium-tannic acid-paraphenylenediamine (OTAP) was used to preserve small extracellular lipid particles. We found that an accumulation of lipoprotein-like particles(LLPs) occurred in the peripheral BrM just as it does in the macular region, but with perhaps a somewhat slower time course. The '' lipid wall,'' reported in macular BrM, was also found occasionally in the peripheral regions. The same processes that lead to age-related accumulation of LLPs in macular BrM appear to also occur in the peripheral regions.
C1 Tech E378, Evanston, IL 60208 USA.
   Northwestern Univ, Evanston, IL USA.
   Univ Alabama, Birmingham, AL USA.
C3 Northwestern University; University of Alabama System; University of
   Alabama Birmingham
RP Johnson, M (通讯作者)，Tech E378, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM m-johnson2@northwestern.edu
RI Johnson, Mark/B-6921-2009
FU NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR016701] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY014662, R01EY006109] Funding
   Source: NIH RePORTER; NCRR NIH HHS [S10 RR016701-01] Funding Source:
   Medline; NEI NIH HHS [R01 EY014662-02, EY 014662, R01 EY014662, R01
   EY014662-03, EY 06109, R01 EY006109, R01 EY014662-01, R01 EY014662-04]
   Funding Source: Medline
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NR 22
TC 32
Z9 32
U1 0
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0271-3683
J9 CURR EYE RES
JI Curr. Eye Res.
PY 2007
VL 32
IS 9
BP 791
EP 799
DI 10.1080/02713680701550660
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 217RL
UT WOS:000249964900009
PM 17882712
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nittala, MG
   Metlapally, R
   Ip, M
   Chakravarthy, U
   Holz, FG
   Staurenghi, G
   Waheed, N
   Velaga, SB
   Lindenberg, S
   Karamat, A
   Koester, J
   Ribeiro, R
   Sadda, S
AF Nittala, Muneeswar Gupta
   Metlapally, Ravi
   Ip, Michael
   Chakravarthy, Usha
   Holz, Frank G.
   Staurenghi, Giovanni
   Waheed, Nadia
   Velaga, Swetha Bindu
   Lindenberg, Sophiana
   Karamat, Ayesha
   Koester, John
   Ribeiro, Ramiro
   Sadda, SriniVas
TI Association of Pegcetacoplan With Progression of Incomplete Retinal
   Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular
   Degeneration A Post Hoc Analysis of the FILLY Randomized Clinical Trial
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID GEOGRAPHIC ATROPHY; END-POINTS; SECONDARY
AB IMPORTANCE Change in areas of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) within eyes with geographic atrophy (GA) might reflect similar changes among eyes with drusen but no GA.
   OBJECTIVE To evaluate the potential association of pegcetacoplan with progression of iRORA in eyes with GA secondary to AMD.
   DESIGN, SETTING, AND PARTICIPANTS This post hoc analysis of the phase 2 multicenter, randomized, single-masked, sham-controlled FILLY trial of intravitreal pegcetacoplan for 12 months took place from February 2 to July 7, 2020. Participants comprised 167 patients with GA secondary to AMD who received pegcetacoplan monthly (n = 41) or every other month (n = 56) or a sham injection (n = 70) in the FILLY trial, completed the month 12 study visit, and did not develop exudative AMD.
   INTERVENTIONS Intravitreal pegcetacoplan, 15 mg, or sham injection, monthly or every other month for 12 months.
   MAIN OUTCOMES AND MEASURES Masked readers analyzed spectral-domain optical coherence tomography scans in regions beyond a perimeter of 500 pm from the GA border according to the Classification of Atrophy Meetings criteria. Primary outcome measures were progression from iRORA to complete RPE and outer retina atrophy (cRORA) from baseline to 6 and 12 months.
   RESULTS Among the 167 patients in the study, at baseline, iRORA was present in 45.0% of study eyes (18 of 40) in the pegcetacoplan monthly group, 61.8% of study eyes (34 of 55) in the pegcetacoplan every other month group, and 50.7% of study eyes (34 of 67) in the sham group. At 12 months, progression from iRORA to cRORA occurred in 50.0% of study eyes (9 of 18) in the pegcetacoplan monthly group (P = .02 vs sham), 60.6% of study eyes (20 of 33) in the pegcetacoplan every other month group (A = .06 vs sham), and 81.8% of study eyes (27 of 33) in the sham group. Compared with sham treatment, the relative risk of progression at 12 months from iRORA to cRORA was 0.61(95% CI, 0.37-1.00) for eyes in the pegcetacoplan monthly group and 0.74 (95% CI, 0.54-1.02) for eyes in the pegcetacoplan every other month group.
   CONCLUSIONS AND RELEVANCE Eyes receiving intravitreal pegcetacoplan had lower rates of progression from iRORA to cRORA compared with controls, suggesting a potential role for pegcetacoplan therapy earlier in the progression of AMD prior to the development of GA.
C1 [Nittala, Muneeswar Gupta; Velaga, Swetha Bindu; Lindenberg, Sophiana; Karamat, Ayesha; Sadda, SriniVas] Doheny Eye Inst, Doheny Image Reading Res Lab, 1355 San Pablo St,DVRC 211, Los Angeles, CA 90033 USA.
   [Metlapally, Ravi; Ribeiro, Ramiro] Dept Clin Dev Apellis Pharmaceut, Waltham, MA USA.
   [Ip, Michael; Sadda, SriniVas] Univ Calif Los Angeles, David Geffen Sch Med, UCLA, Dept Ophthalmol, Los Angeles, CA USA.
   [Chakravarthy, Usha] Queens Univ, Dept Ophthalmol & Vis Sci, Royal Victoria Hosp, Belfast, Antrim, North Ireland.
   [Holz, Frank G.] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Staurenghi, Giovanni] Univ Eye Clin, Luigi Sacco Hosp, Dept Biomed & Clin Sci, Milan, Italy.
   [Waheed, Nadia] Tufts Univ, New England Eye Ctr, Sch Med, Boston, MA USA.
   [Koester, John] JMK Stat, Goodyear, Tempe, AZ 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; Queens University
   Belfast; University of Bonn; University of Milan; Luigi Sacco Hospital;
   Tufts University
RP Sadda, S (通讯作者)，Doheny Eye Inst, Doheny Image Reading Res Lab, 1355 San Pablo St,DVRC 211, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
FU Apellis Pharmaceuticals
FX This study was supported by Apellis Pharmaceuticals.
CR Ardeljan D, 2013, PROG RETIN EYE RES, V37, P68, DOI 10.1016/j.preteyeres.2013.07.003
   Boyer DS, 2017, RETINA-J RET VIT DIS, V37, P819, DOI 10.1097/IAE.0000000000001392
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   Corvi F, 2021, RETINA-J RET VIT DIS, V41, P1851, DOI 10.1097/IAE.0000000000003158
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NR 24
TC 6
Z9 6
U1 0
U2 0
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 2022
VL 140
IS 3
BP 243
EP 249
DI 10.1001/jamaophthalmol.2021.6067
EA FEB 2022
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZV2WK
UT WOS:000750998800003
PM 35113137
DA 2022-11-30
ER

PT J
AU Schroeder, M
   Westborg, I
   Adrian, ML
AF Schroeder, Marion
   Westborg, Inger
   Adrian, Monica Loevestam
TI Twelve per cent of 6142 eyes treated for neovascular age-related macular
   degeneration (nAMD) presented with low visual outcome within 2 years.
   Analysis from the Swedish Macula Registry (SMR)
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE aflibercept; bevacizumab; neovascular age-related macular degeneration;
   ranibizumab; Swedish Macula Registry
ID RANIBIZUMAB; THERAPY; EFFICACY; ATROPHY
AB Purpose To analyse characteristics from the SMR to explore the risk factors for visual acuity (VA) below <= 35 letters of the Early Treatment Diabetic Retinopathy Study (ETDRS) due to nAMD during a two-year follow-up. Methods This study evaluates 6142 treatment-naive eyes, with focus on a subgroup of 780 eyes with final VA outcome of <= 35 letters, regarding differences of baseline characteristics, change of VA, number of injections and choice of drug to predict visual outcome. Results Patients with final VA <= 35 letters were older; p < 0.0001, and received fewer injections, 6.2 +/- 3.8 vs. 8.7 +/- 5.4; p 35 letters presented the following baseline lesion locations; p = 0.001; 61% vs. 57% subfoveal, 18% vs. 21% juxtafoveal and 4% vs. 6% extrafoveal. Lesion size, in the group with final VA <= 35 letters, was 2805 +/- 2093 mu m vs. 2440 +/- 1637 mu m in the group with a VA of > 35 letters; p = 0.005. A logistic regression analysis including baseline VA, best- or worse-seeing eye, age, membrane size, membrane location, symptom duration showed VA; p = < 0.0001, best- or worse-seeing eye; p = 0.026, age; p = < 0.0001, and membrane size; p = 0.002 to predict a decline of VA within 2 years. Conclusions In eyes treated for wet AMD and studied for 2 years, 12.7% of eyes declined to a final VA of <= 35 letters. Visual acuity, worse-seeing eye treated, age and membrane size turned out as the baseline characteristics that had significantly influenced visual decline to <= 35 letters during the two-year follow-up.
C1 [Schroeder, Marion; Adrian, Monica Loevestam] Lund Univ, Dept Ophthalmol, SE-22185 Lund, Sweden.
   [Westborg, Inger] Uppsala Univ, Dept Neurosci, Ophthalmol, Uppsala, Sweden.
C3 Lund University; Uppsala University
RP Schroeder, M (通讯作者)，Lund Univ, Dept Ophthalmol, SE-22185 Lund, Sweden.
EM marion.schroeder@med.lu.se
RI Westborg, Inger/AAD-7108-2021
FU Skane University Hospital (SUS) Research Grants; Foundation for the
   Visually Impaired in the County of Malmohus; Swedish Eye Foundation
FX This study was supported by the Skane University Hospital (SUS) Research
   Grants, the Foundation for the Visually Impaired in the County of
   Malmohus, and the Swedish Eye Foundation. The authors have full control
   of all primary data and agree to allow the journal to review the data on
   request. The authors have no conflicts of interest to disclose. The
   following clinics have contributed with data to the Swedish Macula
   Register: (1) Akademiska Uppsala, (2) Boras SAS, (3) Capio Malmo, (4)
   Eksjo, (5) Eskilstuna, (6) Falu lasarett, (7) Gavle sjukhus, (8)
   Helsingborg, (9) Jonkoping, (10) Kalmar, (11) Karlskrona, (12) Karlstad,
   (13) Kristianstad, (14) Landskrona, (15) Linkoping, (16) Lund, Skanes
   Universitetssjukhus, (17) Lycksele, (18) Malmo, Skanes
   Universitetssjukhus, (19) Norrkoping Vrinnevisjukhuset, (20) Nykoping,
   (21) Skelleftea, (22) Simrishamn, (23) Skovde, (24) Solleftea, (25) St.
   Eriks Ogonsjukhus, (26) Stock-holms Ogonklinik, (27) Sunderby, (28)
   Sundsvall-Harnosand, (29) Sodersjukhuset, (30) Uddevalla, (31) Umea NUS,
   (32) Varnamo, (33) Vastervik, (34) Vasteras, (35) Vaxjo, (36) Angelholm,
   (37) Orebro, (38) Ornskoldsvik, (39) Ostersund.
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NR 21
TC 5
Z9 5
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 MAY
PY 2020
VL 98
IS 3
BP 274
EP 278
DI 10.1111/aos.14239
EA SEP 2019
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LH4QT
UT WOS:000486412900001
PM 31517440
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Vingolo, EM
   Cavarretta, S
   Domanico, D
   Parisi, F
   Malagola, R
AF Vingolo, Enzo M.
   Cavarretta, Sonia
   Domanico, Daniela
   Parisi, Francesca
   Malagola, Romualdo
TI Microperimetric biofeedback in AMD patients
SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK
LA English
DT Article
DE biofeedback AMD; retina microperimetry
ID SCANNING LASER OPHTHALMOSCOPE; MACULAR DEGENERATION; SCOTOMA; VISION
AB To analyse biofeedback training by microperimeter MP-1 (Nidek Technologies) on patients with Age Related Maculopathy (AMD). We enrolled 15 patients (10 female and 5 male) and examined total of 27 eyes with AMD. All the patient underwent 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student's t-test. p values less than 0.05 were considered statistically significant. All patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity an reading speed. The mean character size value improved from 36.4 to 11.7; this result was statistically significant (p = 0.031). A biofeedback examination using the MP-1 microperimeter can help the brain to memorize the final fixation location by increasing attention modulation, thereby providing an efficient preferred retinal locus for visual tasks in patients with macular disease and central scotoma.
C1 Univ Roma La Sapienza, Inherited Retinal Dis Unit, Dept Ophthalmol, Osped A Fiorini, Terracina, Italy.
C3 Sapienza University Rome
RP Vingolo, EM (通讯作者)，Univ Roma La Sapienza, Inherited Retinal Dis Unit, Dept Ophthalmol, Osped A Fiorini, Terracina, Italy.
EM evingolo@rdn.it
RI Vingolo, Enzo Maria/E-6674-2010
OI Vingolo, Enzo Maria/0000-0002-8363-5866
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NR 13
TC 49
Z9 54
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-0586
J9 APPL PSYCHOPHYS BIOF
JI Appl. Psychophysiol. Biofeedback
PD DEC
PY 2007
VL 32
IS 3-4
BP 185
EP 189
DI 10.1007/s10484-007-9038-6
PG 5
WC Psychology, Clinical
WE Social Science Citation Index (SSCI)
SC Psychology
GA 230LW
UT WOS:000250879000006
PM 17574525
DA 2022-11-30
ER

PT J
AU Lam, D
   Semoun, O
   Blanco-Garavito, R
   Jung, C
   Nguyen, DT
   Souied, EH
   Mimoun, G
AF Lam, Delphine
   Semoun, Oudy
   Blanco-Garavito, Rocio
   Jung, Camille
   Nguyen, Diem T.
   Souied, Eric H.
   Mimoun, Gerard
TI WRINKLED VASCULARIZED RETINAL PIGMENT EPITHELIUM DETACHMENT PROGNOSIS
   AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; vascularized retinal pigment
   epithelial detachment; choroidal neovascularization; anti-vascular
   endothelial growth factor; wrinkled pigment epithelium detachment;
   optical coherence tomography
ID OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULAR MEMBRANES; SENILE
   MACULAR DEGENERATION; DAILY CLINICAL-PRACTICE; BRUCHS MEMBRANE;
   NATURAL-HISTORY; VISUAL-ACUITY; SWITCHING TREATMENT; AGE; RANIBIZUMAB
AB Background/Purpose: Neovascular age-related macular degeneration (nAMD) is frequently associated with vascularized pigment epithelial detachment (v-PED). We observed a peculiar characteristic of v-PED characterized by small lacy folds of the retinal pigment epithelium, appearing as a wrinkled PED (w-PED) on spectral domain optical coherence tomography (SD-OCT). Our purpose was to describe the visual prognosis and number of intravitreal injections in w-PED compared with non-w-PED.
   Methods: In this retrospective, case-control series, we reviewed retrospectively medical records of 52 eyes of 51 patients who were consecutively included between November 1 and 30, 2015 with a previous minimum 3-year follow-up. Inclusion criteria were: neovascular age-related macular degeneration, affected with w-PED. Baseline characteristics, best-corrected visual acuity (BVCA), number of intravitreal anti-vascular endothelial growth factor injections (anti-VEGF IVT) and maximal recurrence-free interval, that is, without intravitreal anti-vascular endothelial growth factor injection, were analyzed. A w-PED was defined as a v-PED >= 200 mm in height on SD-OCT imaging, presenting with at least 4 small lacy folds on the surface of the retinal pigment epithelium. Patients were compared with a control group, that is, patients harboring PED without wrinkle shape (non-w-PED). All patients had been treated by intravitreal anti-vascular endothelial growth factor injection of either ranibizumab (IVR) or aflibercept (IVA) using a pro re nata (PRN) protocol after three initial monthly treatments, with a minimum of follow-up of 3 years.
   Results: Two groups of patients were compared, w-PED (29 eyes, from 29 patients), and non-w-PED (23 eyes from 22 patients). In the w-PED group, mean BCVA evolved from 0.28 (+/- 0.18) log MAR (20/40, range 20/25-20/63) at baseline, to 0.29 (+/- 0.21) log MAR (20/40, range 20/25-20/63) at 1 year (P = 0.41), 0.34 (+/- 0.26) log MAR (20/40, range 20/25-20/80) at 2 years (P = 0.49), 0.35 (+/- 0.28) log MAR (20/40, range 20/25-20/80) at 3 years (P = 0.54). In the non-w-PED group, mean BCVA was 0.40 (+/- 0.28) log MAR (20/50, range 20/25-20/100) at baseline and decreased to 0.48 (+/- 0.46) log MAR (20/63, range 20/20-20/160) at 1 year (P = 0.19), 0.48 (+/- 0.35) log MAR (20/63, range 20/25-20/125) at 2 years (P = 0.02), 0.60 (+/- 0.38) log MAR (20/80, range 20/32-20/200) at 3 years (P = 0.002). In the w-PED group, the mean maximal documented recurrence-free interval was 7.87 (+/- 2.94) months at Year 1, 13.5 (+/- 7.52) at Year 2 and 14.78 (+/- 10.70) at Year 3, versus 4.59 (+/- 2.95) months at Year 1, 7.83 (+/- 6.62) at Year 2, 8.57 (+/- 11.18) at Year 3 in the non-w-PED group (P = 0.0004; 0.0101; 0.0168 respectively at Years 1, 2 and 3).
   Discussion: The evolution of v-PED after intravitreal anti-vascular endothelial growth factor injection is still difficult to predict despite intense clinical research in this topic. In our study, we noticed that w-PED might be a phenotypic prognosis factor for better visual acuity and longer maximal recurrence-free interval.
C1 [Lam, Delphine; Semoun, Oudy; Blanco-Garavito, Rocio; Nguyen, Diem T.; Souied, Eric H.; Mimoun, Gerard] Univ Paris Est, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, GRC Macula, Creteil, France.
   [Blanco-Garavito, Rocio; Jung, Camille] Ctr Hosp Intercommunal, Clin Res Ctr, Creteil, France.
   [Mimoun, Gerard] Ecole Mil Retinal Ctr, Paris, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Souied, EH (通讯作者)，Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM eric.souied@chicreteil.fr
RI Nguyen, Diem/GYI-8534-2022
OI JUNG, Camille/0000-0001-8486-8939
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NR 59
TC 5
Z9 7
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JUN
PY 2018
VL 38
IS 6
BP 1100
EP 1109
DI 10.1097/IAE.0000000000001698
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GP2CC
UT WOS:000440627100008
PM 28520639
DA 2022-11-30
ER

PT J
AU Kannarkat, GT
   Lee, JK
   Ramsey, CP
   Chung, J
   Chang, JJ
   Porter, I
   Oliver, D
   Shepherd, K
   Tansey, MG
AF Kannarkat, George T.
   Lee, Jae-Kyung
   Ramsey, Chenere P.
   Chung, Jaegwon
   Chang, Jianjun
   Porter, Isadora
   Oliver, Danielle
   Shepherd, Kennie
   Tansey, Malu G.
TI Age-related changes in regulator of G-protein signaling (RGS)-10
   expression in peripheral and central immune cells may influence the risk
   for age-related degeneration
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Aging; Dopamine; Immune cells; Midbrain; Oxidative stress; RGS10;
   Tyrosine hydroxylase
ID GTPASE-ACTIVATING PROTEINS; ASSOCIATION; COMPLEX; GENES; MOUSE; RGS
AB Inflammation in the aging brain increases risk for neurodegenerative disease. In humans, the regulator of G-protein signaling-10 (RGS10) locus has been associated with age-related maculopathy. Chronic peripheral administration of lipopolysaccharide in the RGS10-null mice induces nigral dopaminergic (DA) degeneration, suggesting that RGS10 modulates neuroimmune interactions and may influence susceptibility to neurodegeneration. Because age is the strongest risk factor for neurodegenerative disease, we assessed whether RGS10 expression changes with age and whether aged RGS10-null mice have altered immune cell profiles. Loss of RGS10 in aged mice does not alter the regulation of nigral DA neurons but does alter B-cell, monocyte, microglial, and CD4+ T-cell populations and inflammatory cytokine levels in the cerebrospinal fluid. These results suggest that loss of RGS10 is associated with an age-dependent dysregulation of peripheral and central immune cells rather than dysregulation of DA neuron function. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Kannarkat, George T.; Lee, Jae-Kyung; Ramsey, Chenere P.; Chung, Jaegwon; Chang, Jianjun; Porter, Isadora; Oliver, Danielle; Tansey, Malu G.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
   [Shepherd, Kennie] Morehouse Sch Med, Dept Pharmacol & Toxicol, Atlanta, GA 30310 USA.
C3 Emory University; Morehouse School of Medicine
RP Tansey, MG (通讯作者)，Emory Univ, Sch Med, Dept Physiol, 615 Michael St,605L Whitehead Biomed Res Bldg, Atlanta, GA 30322 USA.
EM malu.tansey@emory.edu
RI Kannarkat, George/ABB-6064-2021
OI Ramsey, Chenere/0000-0002-4179-6098; LEE, JAE-KYUNG/0000-0003-0104-8623
FU University Research Committee (URC) at Emory University; Emory
   University Fellowships in Research and Science Teaching Program's
   Institutional and Academic Career Development Award [K12GM000680]; NINDS
   at the National Institutes of Health [R01NS072467]; NATIONAL INSTITUTE
   OF GENERAL MEDICAL SCIENCES [K12GM000680, T32GM008169] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
   [F31NS081830, R01NS072467] Funding Source: NIH RePORTER; National
   Institute on Minority Health and Health Disparities [S21MD000101]
   Funding Source: NIH RePORTER
FX We thank members of the Tansey lab for useful discussions. This work was
   supported by a grant from the University Research Committee (URC) at
   Emory University (J.K.L.), fellowship award K12GM000680 from the Emory
   University Fellowships in Research and Science Teaching Program's
   Institutional and Academic Career Development Award (C.P.R.), and grant
   R01NS072467 (M.G.T.) from the NINDS at the National Institutes of
   Health.
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NR 33
TC 14
Z9 15
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2015
VL 36
IS 5
BP 1982
EP 1993
DI 10.1016/j.neurobiolaging.2015.02.006
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CI9PA
UT WOS:000355100900019
PM 25784210
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Manayath, GJ
   Verghese, S
   Jain, N
   Ranjan, R
   Narendran, V
AF Manayath, George Joseph
   Verghese, Shishir
   Jain, Nidhee
   Ranjan, Ratnesh
   Narendran, Venkatapathy
TI Safety of photodynamic therapy involving optic nerve head
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Optic nerve head; photodynamic therapy; polypoidal choroidal
   vasculopathy
AB We present a case of large peripapillary polypoidal choroidal vasculopathy treated with standard-fluence photodynamic therapy (PDT) as other treatment options were unsuccessful or not justified. Due to large lesion size, treatment spot included part of optic disc also. PDT resulted in regression of polyp and visual improvement (from 20/300 to 20/20) without any collateral damage to optic nerve as evidenced by visual-field test and visual-evoked potential with a follow-up till 2 years. This case highlights the role of PDT as a safe alternative for treatment of large peripapillary lesion, even though the treatment spot encompasses part of the optic nerve head.
C1 [Manayath, George Joseph; Verghese, Shishir; Jain, Nidhee; Ranjan, Ratnesh; Narendran, Venkatapathy] Aravind Eye Hosp, Avinashi Rd, Coimbatore 641004, Tamil Nadu, India.
RP Verghese, S (通讯作者)，Aravind Eye Hosp, Avinashi Rd, Coimbatore 641004, Tamil Nadu, India.
EM shishirverghese@gmail.com
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NR 10
TC 0
Z9 0
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 MAR
PY 2020
VL 68
IS 3
BP 530
EP +
AR PMID 32057026
DI 10.4103/ijo.IJO_1081_19
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KQ7VG
UT WOS:000517127900036
PM 32057026
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Faynus, MA
   Bailey, JK
   Pennington, BO
   Katsura, M
   Proctor, DA
   Yeh, AK
   Menon, S
   Choi, DG
   Lebkowski, JS
   Johnson, LV
   Clegg, DO
AF Faynus, Mohamed A.
   Bailey, Jeffrey K.
   Pennington, Britney O.
   Katsura, Mika
   Proctor, Duncan A.
   Yeh, Ashley K.
   Menon, Sneha
   Choi, Dylan G.
   Lebkowski, Jane S.
   Johnson, Lincoln, V
   Clegg, Dennis O.
TI Microcarrier-Based Culture of Human Pluripotent Stem-Cell-Derived
   Retinal Pigmented Epithelium
SO BIOENGINEERING-BASEL
LA English
DT Article
DE microcarriers; stem cells; retinal pigment epithelium
AB Dry age-related macular degeneration (AMD) is estimated to impact nearly 300 million individuals globally by 2040. While no treatment options are currently available, multiple clinical trials investigating retinal pigmented epithelial cells derived from human pluripotent stem cells (hPSC-RPE) as a cellular replacement therapeutic are currently underway. It has been estimated that a production capacity of >10(9) RPE cells annually would be required to treat the afflicted population, but current manufacturing protocols are limited, being labor-intensive and time-consuming. Microcarrier technology has enabled high-density propagation of many adherent mammalian cell types via monolayer culture on surfaces of uM-diameter matrix spheres; however, few studies have explored microcarrier-based culture of RPE cells. Here, we provide an approach to the growth, maturation, and differentiation of hPSC-RPE cells on Cytodex 1 (C1) and Cytodex 3 (C3) microcarriers. We demonstrate that hPSC-RPE cells adhere to microcarriers coated with Matrigel, vitronectin or collagen, and mature in vitro to exhibit characteristic epithelial cell morphology and pigmentation. Microcarrier-grown hPSC-RPE cells (mcRPE) are viable; metabolically active; express RPE signature genes including BEST1, RPE65, TYRP1, and PMEL17; secrete the trophic factors PEDF and VEGF; and demonstrate phagocytosis of photoreceptor outer segments. Furthermore, we show that undifferentiated hESCs also adhere to Matrigel-coated microcarriers and are amenable to directed RPE differentiation. The capacity to support hPSC-RPE cell cultures using microcarriers enables efficient large-scale production of therapeutic RPE cells sufficient to meet the treatment demands of a large AMD patient population.
C1 [Faynus, Mohamed A.] Univ Calif Santa Barbara, Program Biomol Sci & Engn, Santa Barbara, CA 93106 USA.
   [Faynus, Mohamed A.; Bailey, Jeffrey K.; Pennington, Britney O.; Katsura, Mika; Proctor, Duncan A.; Yeh, Ashley K.; Menon, Sneha; Choi, Dylan G.; Clegg, Dennis O.] Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Proctor, Duncan A.; Yeh, Ashley K.; Menon, Sneha; Clegg, Dennis O.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Choi, Dylan G.] Univ Calif Santa Barbara, Coll Creat Studies Chem & Biochem, Santa Barbara, CA 93106 USA.
   [Lebkowski, Jane S.; Johnson, Lincoln, V; Clegg, Dennis O.] Regenerat Patch Technol LLC, Portola Valley, CA 94028 USA.
   [Clegg, Dennis O.] Univ Calif Santa Barbara, Program Biol Engn, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara
RP Faynus, MA (通讯作者)，Univ Calif Santa Barbara, Program Biomol Sci & Engn, Santa Barbara, CA 93106 USA.; Faynus, MA (通讯作者)，Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
EM faynus@ucsb.edu; jkbailey@ucsb.edu; bop@ucsb.edu; mikakatsura@ucsb.edu;
   duncan@ucsb.edu; ashleyyeh@umail.ucsb.edu; snehamenon@ucsb.edu;
   dylanchoi@ucsb.edu; jane@regenerativepatch.com;
   linc@regenerativepatch.com; clegg@ucsb.edu
OI Choi, Dylan/0000-0003-1509-0574
FU Garland Initiative for Vision; California Institute for Regenerative
   Medicine (CIRM) [DR1-01444, CL1-00521, TB1-1177, FA1-00616, TG2-01151];
   Breaux Foundation; Foundation Fighting Blindness Wynn-Gund Translational
   Research Acceleration Program; Regenerative Patch Technologies
FX This research was funded by Garland Initiative for Vision, the
   California Institute for Regenerative Medicine (CIRM; Grants DR1-01444,
   CL1-00521, TB1-1177, FA1-00616, TG2-01151), Regenerative Patch
   Technologies, the Breaux Foundation and the Foundation Fighting
   Blindness Wynn-Gund Translational Research Acceleration Program.
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NR 42
TC 0
Z9 0
U1 4
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2306-5354
J9 BIOENGINEERING-BASEL
JI Bioengineering-Basel
PD JUL
PY 2022
VL 9
IS 7
AR 297
DI 10.3390/bioengineering9070297
PG 15
WC Biotechnology & Applied Microbiology; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Engineering
GA 3H6MA
UT WOS:000832147100001
PM 35877348
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chawla, R
   Bhattacharyya, J
   Moksha, L
   Phour, A
   Velpandian, T
   Kashyap, S
   Kalyanasundaram, D
AF Chawla, Rohan
   Bhattacharyya, Jayanta
   Moksha, Laxmi
   Phour, Anjali
   Velpandian, Thirumurthy
   Kashyap, Seema
   Kalyanasundaram, Dinesh
TI A novel, minimally invasive implant to assist in repeated intraocular
   drug delivery
SO BIOMEDICAL MICRODEVICES
LA English
DT Article
DE Ophthalmic implants; Intravitreal injection; Drug delivery; Ocular pain;
   Inflammation; Endophthalmitis
ID MACULAR DEGENERATION; PHARMACOKINETICS; RANIBIZUMAB; MULTICENTER;
   RETISERT; RELEASE
AB The standard of care for posterior segment disorders such as wet age-related macular degeneration, diabetic macular oedema and retinal vascular occlusions is pharmacotherapy by intravitreal drug delivery. Since the therapeutic effect of these drugs lasts only around 4 to 8 weeks, repeated intravitreal injections are required. Pain is experienced by the patients during injection as the needle courses through the sclera and choroid. The current work describes the design and development of a novel anodized titanium alloy implant that allows for intravitreal injections through the implant so that the needle transverses only the conjunctiva, thus minimizing discomfort to the patient. Both ex-vivo testing of the implant in enucleated goat's eye as well as in-vivo validation in rabbit eyes was carried out. The implant was placed through pars plana via a minor surgical procedure and was sutured to the sclera and covered with conjunctiva. Subsequent intravitreal injections were administered under topical anaesthesia with a 30-gauge needle through the implant thus delivering the drug into the vitreous cavity. Repeated intravitreal injections were administered every 2 weeks via the implant for 3 months in 4 rabbits. Apart from cataract in 1 rabbit, no complications were observed. There was no evidence of intra-ocular inflammation or infection at final follow-up. Histopathological analysis did not reveal any inflammation or necrosis around the area of implant. The implants were subsequently removed at 5 months and scleral wound was closed with a single suture. The sclera and overlying conjunctiva healed well and no intraocular complications were observed after removal.
C1 [Chawla, Rohan] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi 110029, India.
   [Bhattacharyya, Jayanta; Phour, Anjali; Kalyanasundaram, Dinesh] Indian Inst Technol Delhi, Ctr Biomed Engn, New Delhi 110016, India.
   [Bhattacharyya, Jayanta; Kalyanasundaram, Dinesh] All India Inst Med Sci, Dept Biomed Engn, New Delhi 110029, India.
   [Moksha, Laxmi; Velpandian, Thirumurthy] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pharmacol, New Delhi 110029, India.
   [Kashyap, Seema] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pathol, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences; Indian Institute of Technology
   System (IIT System); Indian Institute of Technology (IIT) - Delhi; All
   India Institute of Medical Sciences (AIIMS) New Delhi; All India
   Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra Prasad
   Centre for Ophthalmic Sciences; All India Institute of Medical Sciences
   (AIIMS) New Delhi; Dr. Rajendra Prasad Centre for Ophthalmic Sciences
RP Kalyanasundaram, D (通讯作者)，Indian Inst Technol Delhi, Ctr Biomed Engn, New Delhi 110016, India.; Kalyanasundaram, D (通讯作者)，All India Inst Med Sci, Dept Biomed Engn, New Delhi 110029, India.
EM dr.rohanrpc@gmail.com; jayanta@cbme.iitd.ac.in; mokshakou147@gmail.com;
   tvelpandian@hotmail.com; dr_skashyap@hotmail.com;
   dineshk@cbme.iitd.ac.in
FU IRD [MI01884 (IITD)/A-05]; IIT Delhi [MI01884 (IITD)/A-05]; AIIMS
   [MI01884 (IITD)/A-05]
FX The authors would like to acknowledge the funding agencies, IRD, IIT
   Delhi and AIIMS for partial financial support to the project via
   multi-institutional project:MI01884 (IITD)/A-05 (AIIMS).
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NR 40
TC 0
Z9 0
U1 6
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1387-2176
EI 1572-8781
J9 BIOMED MICRODEVICES
JI Biomed. Microdevices
PD JUN
PY 2022
VL 24
IS 2
AR 17
DI 10.1007/s10544-022-00618-y
PG 8
WC Engineering, Biomedical; Nanoscience & Nanotechnology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Science & Technology - Other Topics
GA 1J2OE
UT WOS:000797760500001
PM 35587289
DA 2022-11-30
ER

PT J
AU Faes, L
   Islam, M
   Bachmann, LM
   Lienhard, KR
   Schmid, MK
   Sim, DA
AF Faes, Livia
   Islam, Meriam
   Bachmann, Lucas M.
   Lienhard, Kenny R.
   Schmid, Martin K.
   Sim, Dawn A.
TI False alarms and the positive predictive value of smartphone-based
   hyperacuity home monitoring for the progression of macular disease: a
   prospective cohort study
SO EYE
LA English
DT Article
ID DEGENERATION; PERIMETER; ACCURACY
AB Background Home monitoring of hyperacuity allows early detection of progression in exudative neovascular age-related macular degeneration (nvAMD) and diabetic macular oedema (DMO). However, false alarms may pose a significant burden to both patients and healthcare professionals alike.
   Purpose To assess the false alarm rate and positive predictive value of smartphone-based home monitoring of nvAMD and DMO.
   Methods Patients treated with anti-angiogenic therapy in a pro re nata scheme for nvAMD or DMO at the Medical Retina service (Lucerne, Switzerland) between March and June 2016 were included in this prospective cohort study. The home monitoring test Alleye (Oculocare Ltd, Switzerland) provided a session score from 0-100 in addition to a traffic-light system feedback via the smartphone application. Three consecutive "red" scores were considered as a positive test or alarm signal. Specificity, 1-specificity (false alarm rate) and the predictive value for optical coherence tomography-based disease progression were analysed.
   Results 73 eyes of 56 patients performed 2258 tests in 222 "follow-up periods". Progression was observed in 141 periods (63.5%). The specificity of the test was 93.8% (95% CI: 86.2-98.0%), the false alarm rate 6.1% (95% CI: 2.0-13.8%), and the positive predictive value 80.0% (95% CI: 59.3-93.2%) for the detection of progression.
   Conclusion False alarm rates for the detection of progression in macular disease via home monitoring is low. These findings suggest that home monitoring may be a useful adjunct for remote management of nvAMD and DMO.
C1 [Faes, Livia; Islam, Meriam; Sim, Dawn A.] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Faes, Livia; Islam, Meriam; Sim, Dawn A.] UCL Inst Ophthalmol, London, England.
   [Faes, Livia; Schmid, Martin K.] Cantonal Hosp Lucerne, Luzern, Switzerland.
   [Bachmann, Lucas M.; Lienhard, Kenny R.] Medignition Inc, Zurich, Switzerland.
   [Bachmann, Lucas M.; Lienhard, Kenny R.; Schmid, Martin K.] Oculocare Med Inc, Zurich, Switzerland.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Lucerne Cantonal Hospital
RP Bachmann, LM (通讯作者)，Medignition Inc, Zurich, Switzerland.; Bachmann, LM (通讯作者)，Oculocare Med Inc, Zurich, Switzerland.
EM bachmann@medignition.com
OI Sim, Dawn/0000-0002-6363-7805
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NR 22
TC 6
Z9 6
U1 0
U2 0
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD NOV
PY 2021
VL 35
IS 11
BP 3035
EP 3040
DI 10.1038/s41433-020-01356-2
EA JAN 2021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WJ3DG
UT WOS:000605863200001
PM 33414531
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Gualino, V
   Fourmaux, E
   Grenet, T
   Zerbib, J
   Wolff, B
AF Gualino, V
   Fourmaux, E.
   Grenet, T.
   Zerbib, J.
   Wolff, B.
TI Ocular manifestations of Crohn's disease
SO JOURNAL FRANCAIS D OPHTALMOLOGIE
LA English
DT Article
DE Intravitreal injections; Anti-VEGF; Patient; Stress; Anxiety; AMD
ID OCCLUSION 12-MONTH OUTCOMES; DIABETIC MACULAR EDEMA; ANTI-VEGF
   TREATMENT; SUSTAINED BENEFITS; LEGAL BLINDNESS; RANIBIZUMAB;
   DEGENERATION; EXPERIENCES; ANXIETY; INJECTION
AB Intravitreal anti-vascular epithelial growth factor (anti-VEGF) injections have revolutionised the treatment of macular diseases, but can be stressful for the patient. We surveyed 904 patients receiving injections at 5 centres in France regarding their feelings toward anti-VEGF injections. The mean age was 77.4 years, and the injections were performed mostly for age related macular degeneration (72%). Half of the patients had previously received > 10 injections, 35.6% had received 3-10 injections, and 14.2% had received < 3 injections. The mean (SD) stress score was 4.2 [on a scale from 1-10 (0 = least stressful, 10 = extremely stressful)]. Most patients (70%) reported low to moderate stress (score <= 5). The number of previous injections did not influence stress scores. Paradoxically, 61.2% of patients reported finding injections to be less stressful over time. Most patients found injections to be less traumatic than expected (64%) or just as they had anticipated (25%). Most patients (88%) were not bothered by the presence of other patients in the waiting room. Most patients (78.8%) preferred to be injected quickly before they had time to feel stressed about the procedure. Injections were generally well accepted; most patients would prefer to maintain their current schedule of injections and their current vision (55.7%), or would be willing to have more frequent injections for better vision (39.5%). Our results suggest that stress appears to be more related to the patient's psychological make-up than to the treatment experience or the number of injections received. (C) 2020 Elsevier Masson SAS. All rights reserved.
C1 [Gualino, V] Clin Honore Cave, 406 Blvd Montauriol, F-82000 Montauban, Tarn & Garonne, France.
   [Fourmaux, E.] Ctr Retine Gallien, 68 Rue Palais Gallien, F-33000 Bordeaux, France.
   [Grenet, T.] CIL, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
   [Zerbib, J.] Nice Retina, 5 Rue Eugene Emmanuel, F-06000 Nice, France.
   [Wolff, B.] Ctr Ophtalmol Maison Rouge, 6 Rue Eglise, F-67000 Strasbourg, France.
RP Gualino, V (通讯作者)，Clin Honore Cave, 406 Blvd Montauriol, F-82000 Montauban, Tarn & Garonne, France.
EM vincent.gualino@gmail.com; eric.fourmaux@retinegalfien.com;
   typhaine_grenet@yahoo.fr; jennyfer.zerbib@hotmail.com; bwolff@hotmail.fr
OI Gualino, Vincent/0000-0002-3941-1304
CR AFSSAPS, 2011, GOOD PRACT INTR INJ
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NR 31
TC 2
Z9 2
U1 0
U2 1
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 0181-5512
EI 1773-0597
J9 J FR OPHTALMOL
JI J. Fr. Ophthamol.
PD DEC
PY 2020
VL 43
IS 10
BP 1047
EP 1053
DI 10.1016/j.jfo.2020.02.006
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OW5CC
UT WOS:000592903500027
PM 33004191
DA 2022-11-30
ER

PT J
AU Jung, J
   Jeong, J
   Hong, HS
AF Jung, Jihyun
   Jeong, Junha
   Hong, Hyun Sook
TI Substance P improves MSC-mediated RPE regeneration by modulating PDGF-BB
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Substance P; Mesenchymal stem cells; Retinal pigmented epithelial cells;
   PDGF-BB
ID STEM-CELLS; RETINAL CELLS; DIFFERENTIATE; MICE
AB Stem cells have regenerative potentials that can be used for the treatment of critical and incurable diseases. Age-related macular degeneration (ARMD) and diabetic retinopathy are one of the most severe retinal disorders, which are mostly attributed to impairment of retinal pigmented epithelium (RPE). Thus, restoration of RPE is the main therapeutic approach to prevent the development of ocular diseases, such as ARMD. In this study, we have investigated the role of substance P (SP) on bone marrow mesenchymal stem cell (MSC)-mediated RPE regeneration in vitro. The MSCs were primed with SP followed by the addition of conditioned medium (MSCSP-CM) to RPE. The effects of MSCSP-CM on RPE activity was evaluated by assessing viability, proliferation rate, and migration of RPE. Ex vivo long-term culture led to altered cellular characteristics of MSCs by weakening cell viability, cytokine secretion, and differentiation potential. The conditioned medium of early passage MSC (E-MSCCM) enhanced the RPE viability and migration, whereas the late passage MSC (L-MSCCM) hardly influenced the RPE activity. SP priming, however, facilitated the inductive effects of MSC, and SP effect was more distinct in the late passage than in the early passage. Moreover, it was revealed that SP could exert its effects by modulating PDGF-BB secretion in the MSCs.
   Taken together, these results suggested that SP could restore the therapeutic effects of MSCs on retinal diseases by elevating their proliferative and paracrine activities through PDGF-PDGFR signaling in ex vivo culture. (C) 2019 Elsevier Inc. All rights reserved.
C1 [Jung, Jihyun; Jeong, Junha; Hong, Hyun Sook] Kyung Hee Univ, Med Ctr, Med Sci Res Inst, Kyung Hee Inst Regenerat Med KIRM, Seoul 02447, South Korea.
   [Hong, Hyun Sook] Kyung Hee Univ, Grad Sch, East West Med Res Inst, Dept Biomed Sci & Technol, Seoul 02447, South Korea.
C3 Kyung Hee University; Kyung Hee University
RP Hong, HS (通讯作者)，Kyung Hee Univ, Coll Med, Seoul, South Korea.
EM hshong@khu.ac.kr
RI HONG, HYUN SOOK/AAI-3017-2020
OI HONG, HYUN SOOK/0000-0003-3659-1386
FU Korean Health Technology R&D Project grant from the Ministry of Health &
   Welfare, Republic of Korea [HI18C1492, HI13C1479]
FX This study was supported by a Korean Health Technology R&D Project grant
   from the Ministry of Health & Welfare, Republic of Korea (HI18C1492,
   HI13C1479).
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NR 25
TC 2
Z9 2
U1 1
U2 13
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 6
PY 2019
VL 515
IS 4
BP 524
EP 530
DI 10.1016/j.bbrc.2019.05.186
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA IG1ND
UT WOS:000473557400002
PM 31176487
DA 2022-11-30
ER

PT J
AU Chen, HC
   Lee, CY
   Sun, CC
   Huang, JY
   Lin, HY
   Yang, SF
AF Chen, Hung-Chi
   Lee, Chia-Yi
   Sun, Chi-Chin
   Huang, Jing-Yang
   Lin, Hung-Yu
   Yang, Shun-Fa
TI Risk factors for the occurrence of visual-threatening posterior capsule
   opacification
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Posterior capsule opacification; Cataract surgery; Nd:YAG capsulotomy;
   Intraocular lens; Population-based
ID INTRAOCULAR-LENS IMPLANTATION; CATARACT-SURGERY; PHACOEMULSIFICATION
AB BackgroundTo evaluate the potential risk factor of visual-threatening posterior capsule opacification (PCO) via the analysis of National Health Insurance Research Database in Taiwan.Patients and methodsA total of 8571 patients (3767 male and 4804 female) were recruited in the study group and 17,142 patients (7534 male and 9608 female) in the control group. Patients undergoing cataract surgery, acrysof single-piece intraocular lens implantation and Nd:YAG capsulotomy were selected as the study group. After exclusion which aimed to standardize the ocular condition and exclude the possibility that patients undergoing cataract surgery and Nd:YAG capsulotomy in different eyes, each patient in the study group was age-gender matched to two patients undergoing cataract surgery but without Nd:YAG capsulotomy. The demographic data, systemic disease, and ocular co-morbidities were obtained and analyzed. Adjusted odds ratio (OR) of each demographic data and co-morbidities to the development of visual-threatening PCO, and adjusted OR of co-morbidities to visual-threatening PCO develop within 1year postoperatively.ResultsThe dry eye disease (DED), glaucoma, uveitis, age-related macular degeneration (AMD), hyperlipidemia, peptic ulcer disease and liver disease showed significant crude OR while the DED, glaucoma, AMD, hyperlipidemia and peptic ulcer disease revealed a significant adjusted OR. In the subgroup analysis, the DED, glaucoma, AMD, and hyperlipidemia still illustrated a higher adjusted OR to develop visual-threatening PCO within 1year after the cataract surgery.ConclusionThe DED, glaucoma, AMD, hyperlipidemia and peptic ulcer disease may serve as the risk factor for the developing of visual-threatening PCO.
C1 [Chen, Hung-Chi] Chang Gung Mem Hosp, Dept Ophthalmol, Linkou, Taiwan.
   [Chen, Hung-Chi] Chang Gung Univ, Coll Med, Dept Med, Taoyuan, Taiwan.
   [Chen, Hung-Chi] Chang Gung Mem Hosp, Ctr Tissue Engn, Linkou, Taiwan.
   [Lee, Chia-Yi; Lin, Hung-Yu] Show Chwan Mem Hosp, Dept Ophthalmol, 2,Ln 530,Sec 1,Zhongshan Rd, Changhua 50093, Changhua, Taiwan.
   [Lee, Chia-Yi] Chung Hwa Univ Med Technol, Dept Optometry, Coll Med & Life Sci, Tainan, Taiwan.
   [Sun, Chi-Chin] Chang Gung Mem Hosp, Dept Ophthalmol, Keelung, Taiwan.
   [Sun, Chi-Chin] Chang Gung Univ, Dept Chinese Med, Taoyuan, Taiwan.
   [Huang, Jing-Yang; Yang, Shun-Fa] Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan.
   [Lin, Hung-Yu; Yang, Shun-Fa] Chung Shan Med Univ, Inst Med, 110,Sec 1,Chien Kuo N Rd, Taichung 40201, Taiwan.
   [Lin, Hung-Yu] Chung Shan Med Univ, Dept Optometry, Taichung, Taiwan.
   [Lin, Hung-Yu] Chung Chou Univ Sci & Technol, Dept Exercise & Hlth Promot, Changhua, Taiwan.
C3 Chang Gung Memorial Hospital; Chang Gung University; Chang Gung Memorial
   Hospital; Show Chwan Memorial Hospital; Chung Hua University; Chang Gung
   Memorial Hospital; Chang Gung University; Chung Shan Medical University;
   Chung Shan Medical University Hospital; Chung Shan Medical University;
   Chung Shan Medical University
RP Lin, HY (通讯作者)，Show Chwan Mem Hosp, Dept Ophthalmol, 2,Ln 530,Sec 1,Zhongshan Rd, Changhua 50093, Changhua, Taiwan.; Lin, HY; Yang, SF (通讯作者)，Chung Shan Med Univ, Inst Med, 110,Sec 1,Chien Kuo N Rd, Taichung 40201, Taiwan.
EM anthonyhungyulin@hotmail.com; ysf@csmu.edu.tw
RI Yang, Shun-Fa/AAN-1519-2020
OI Yang, Shun-Fa/0000-0002-0365-7927; Chen, Hung-Chi/0000-0002-1117-7878
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NR 29
TC 13
Z9 13
U1 0
U2 2
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUN 20
PY 2019
VL 17
AR 209
DI 10.1186/s12967-019-1956-6
PG 8
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA IE7DI
UT WOS:000472534200001
PM 31221170
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ramos, CJ
   Lin, CM
   Liu, XW
   Antonetti, DA
AF Ramos, Carla J.
   Lin, Chengmao
   Liu, Xuwen
   Antonetti, David A.
TI The EPAC-Rap1 pathway prevents and reverses cytokine-induced retinal
   vascular permeability
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Ras-related protein 1 (Rap1); small GTPase; tight junction; tumor
   necrosis factor (TNF); vascular endothelial growth factor (VEGF); EPAC;
   blood-retinal barrier
ID ENDOTHELIAL BARRIER FUNCTION; TIGHT JUNCTION TRAFFICKING; EXCHANGE
   FACTOR; OCCLUDIN PHOSPHORYLATION; CELL JUNCTIONS; CYCLIC-AMP; CAMP;
   RAP1; EPAC; PROTEIN
AB Increased retinal vascular permeability contributes to macular edema, a leading cause of vision loss in eye pathologies such as diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusions. Pathological changes in vascular permeability are driven by growth factors such as VEGF and pro-inflammatory cytokines such as TNF-. Identifying the pro-barrier mechanisms that block vascular permeability and restore the blood-retinal barrier (BRB) may lead to new therapies. The cAMP-dependent guanine nucleotide exchange factor (EPAC) exchange-protein directly activated by cAMP promotes exchange of GTP in the small GTPase Rap1. Rap1 enhances barrier properties in human umbilical endothelial cells by promoting adherens junction assembly. We hypothesized that the EPAC-Rap1 signaling pathway may regulate the tight junction complex of the BRB and may restore barrier properties after cytokine-induced permeability. Here, we show that stimulating EPAC or Rap1 activation can prevent or reverse VEGF- or TNF--induced permeability in cell culture and in vivo. Moreover, EPAC activation inhibited VEGF receptor (VEGFR) signaling through the Ras/MEK/ERK pathway. We also found that Rap1B knockdown or an EPAC antagonist increases endothelial permeability and that VEGF has no additive effect, suggesting a common pathway. Furthermore, GTP-bound Rap1 promoted tight junction assembly, and loss of Rap1B led to loss of junctional border organization. Collectively, our results indicate that the EPAC-Rap1 pathway helps maintain basal barrier properties in the retinal vascular endothelium and activation of the EPAC-Rap1 pathway may therefore represent a potential therapeutic strategy to restore the BRB.
C1 [Ramos, Carla J.; Lin, Chengmao; Liu, Xuwen; Antonetti, David A.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan
RP Antonetti, DA (通讯作者)，Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM dantonet@med.umich.edu
RI LIU, XUWEN/AAR-9250-2020
OI antonetti, david/0000-0003-1130-6577; Ramos, Carla
   Jhoana/0000-0001-5041-6758; Lin, Cheng-mao/0000-0003-2409-9423
FU National Institutes of Health [EY012021, P30EY007003]; Research to
   Prevent Blindness; Kellogg Eye Center Core Center for Vision Research;
   Michigan Diabetes Research and Training Center [DK020572]; NATIONAL EYE
   INSTITUTE [R01EY012021, P30EY007003] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
   [P60DK020572, P30DK020572] Funding Source: NIH RePORTER
FX This work was supported by National Institutes of Health Grant EY012021
   (to D. A. A.), grants from the Research to Prevent Blindness (to D. A.
   A.) and Kellogg Eye Center Core Center for Vision Research, National
   Institutes of Health Grant P30EY007003, and Michigan Diabetes Research
   and Training Center Grant DK020572. The authors declare that they have
   no conflicts of interest with the contents of this article. The content
   is solely the responsibility of the authors and does not necessarily
   represent the official views of the National Institutes of Health.
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Z9 34
U1 2
U2 16
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 JAN 12
PY 2018
VL 293
IS 2
BP 717
EP 730
DI 10.1074/jbc.M117.815381
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA FS6NZ
UT WOS:000419915400025
PM 29158262
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Baker, QB
   Podgorski, GJ
   Vargis, E
   Flann, NS
AF Baker, Qanita Bani
   Podgorski, Gregory J.
   Vargis, Elizabeth
   Flann, Nicholas S.
TI A computational study of VEGF production by patterned retinal epithelial
   cell colonies as a model for neovascular macular degeneration
SO JOURNAL OF BIOLOGICAL ENGINEERING
LA English
DT Article
DE Micropatterning; Auto-regulation; Vascular endothelial growth factor;
   Age-related macular degeneration; Retinal pigment epithelial cells;
   Age-related macular degeneration
ID MICROPATTERNED SURFACES; MECHANISMS; EXPRESSION; SECRETION; SIZE
AB Background: The configuration of necrotic areas within the retinal pigmented epithelium is an important element in the progression of age-related macular degeneration (AMD). In the exudative (wet) and non-exudative (dry) forms of the disease, retinal pigment epithelial (RPE) cells respond to adjacent atrophied regions by secreting vascular endothelial growth factor (VEGF) that in turn recruits new blood vessels which lead to a further reduction in retinal function and vision. In vitro models exist for studying VEGF expression in wet AMD (Vargis et al., Biomaterials 35(13): 3999-4004, 2014), but are limited in the patterns of necrotic and intact RPE epithelium they can produce and in their ability to finely resolve VEGF expression dynamics.
   Results: In this work, an in silico hybrid agent-based model was developed and validated using the results of this cell culture model of VEGF expression in AMD. The computational model was used to extend the cell culture investigation to explore the dynamics of VEGF expression in different sized patches of RPE cells and the role of negative feedback in VEGF expression. Results of the simulation and the cell culture studies were in excellent qualitative agreement, and close quantitative agreement.
   Conclusions: The model indicated that the configuration of necrotic and RPE cell-containing regions have a major impact on VEGF expression dynamics and made precise predictions of VEGF expression dynamics by groups of RPE cells of various sizes and configurations. Coupled with biological studies, this model may give insights into key molecular mechanisms of AMD progression and open routes to more effective treatments.
C1 [Baker, Qanita Bani] Jordan Univ Sci & Technol, Irbid, Jordan.
   [Podgorski, Gregory J.] Utah State Univ, Dept Biol, Logan, UT 84322 USA.
   [Podgorski, Gregory J.] Utah State Univ, Ctr Integrated BioSyst, Logan, UT 84322 USA.
   [Vargis, Elizabeth] Utah State Univ, Biol Engn Dept, Logan, UT 84322 USA.
   [Flann, Nicholas S.] Synthet Biomfg Inst, Logan, UT 84322 USA.
   [Flann, Nicholas S.] Inst Syst Biol, Seattle, WA 98109 USA.
   [Flann, Nicholas S.] Utah State Univ, Dept Comp Sci, Logan, UT 84335 USA.
C3 Jordan University of Science & Technology; Utah System of Higher
   Education; Utah State University; Utah System of Higher Education; Utah
   State University; Utah System of Higher Education; Utah State
   University; Institute for Systems Biology (ISB); Utah System of Higher
   Education; Utah State University
RP Flann, NS (通讯作者)，Synthet Biomfg Inst, Logan, UT 84322 USA.; Flann, NS (通讯作者)，Inst Syst Biol, Seattle, WA 98109 USA.; Flann, NS (通讯作者)，Utah State Univ, Dept Comp Sci, Logan, UT 84335 USA.
RI Baker, Qanita Bani/Y-6531-2019
OI Baker, Qanita Bani/0000-0003-4722-6632
FU National Institute Of General Medical Sciences of the National
   Institutes of Health [P50GM076547]; Luxembourg Centre for Systems
   Biomedicine; University of Luxembourg; Institute for Systems Biology,
   Seattle, USA; Knights Templar Eye Foundation; Oak Ridge Associated
   Universities; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
   [P50GM076547] Funding Source: NIH RePORTER
FX Research reported in this publication was supported by the National
   Institute Of General Medical Sciences of the National Institutes of
   Health under Award Number P50GM076547, Luxembourg Centre for Systems
   Biomedicine, the University of Luxembourg, the Institute for Systems
   Biology, Seattle, USA, the Knights Templar Eye Foundation and a Ralph E.
   Powe Junior Faculty Award from the Oak Ridge Associated Universities.
   The content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Institutes of
   Health.
CR Ambati J, 2012, NEURON, V75, P26, DOI 10.1016/j.neuron.2012.06.018
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NR 32
TC 1
Z9 1
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1754-1611
J9 J BIOL ENG
JI J. Biol. Eng.
PD AUG 2
PY 2017
VL 11
AR 26
DI 10.1186/s13036-017-0063-6
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA FC6NW
UT WOS:000406958200001
PM 28775765
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ou, WC
   Brown, DM
   Payne, JF
   Wykoff, CC
AF Ou, William C.
   Brown, David M.
   Payne, John F.
   Wykoff, Charles C.
TI Relationship Between Visual Acuity and Retinal Thickness During
   Anti-Vascular Endothelial Growth Factor Therapy for Retinal Diseases
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC MACULAR EDEMA; 2.0 MG
   RANIBIZUMAB; VEIN-OCCLUSION; RANDOMIZED-TRIAL; TIME-DOMAIN; PATTERNS;
   TREAT; PARAMETERS; MORPHOLOGY
AB PURPOSE: To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases.
   DESIGN: Retrospective analysis of clinical trial data.
   METHODS: Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression.
   RESULTS: At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data.
   CONCLUSION: DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO. (C) 2017 Elsevier Inc. All rights reserved.
C1 [Ou, William C.; Brown, David M.; Wykoff, Charles C.] Retina Consultants Houston, Houston, TX USA.
   [Brown, David M.; Wykoff, Charles C.] Houston Methodist Hosp, Blanton Eye Inst, Houston, TX USA.
   [Brown, David M.; Wykoff, Charles C.] Weill Cornell Med Coll, Houston, TX USA.
   [Payne, John F.] Palmetto Retina Ctr, W Columbia, SC USA.
C3 The Methodist Hospital System; The Methodist Hospital - Houston; Cornell
   University
RP Wykoff, CC (通讯作者)，6560 Fannin St,Suite 750, Houston, TX 77030 USA.
EM ccwmd@houstonretina.com
OI Ou, William/0000-0003-1997-1360
FU Alcon; Allegro Ophthalmics (San Juan Capistrano, California, USA);
   Allergan; Apellis Pharmaceuticals (Crestwood, Kentucky, USA); Clearside;
   Iconic Therapeutics (South San Francisco, California, USA); Genentech;
   Regeneron; DRCR Network (Jaeb Center for Health Research, Tampa,
   Florida, USA); Ophthotech (Princeton, New Jersey, USA); ThromboGenics;
   Tryogenex (West Palm Beach, Florida, USA); Aerpio (Cincinnati, Ohio,
   USA); Alcon (Hunenberg, Switzerland); EMMES (Rockville, MD); Allegro
   Ophthalmics; Apellis Pharmaceuticals; DRCR Network; Iconic Therapeutics;
   Novartis; Ophthotech; Tryogenex
FX DAVID M. BROWN: CONSULTANT: ADERVUM (Menlo Park, California, USA),
   Allergan (Parsippany-Troy Hills, New Jersey, USA), Alimera Sciences
   (Alpharetta, Georgia, USA), Bayer (Leverkusen, Germany), Clearside
   (Alpharetta, Georgia, USA), Genentech (South San Francisco, California,
   USA), Heidelberg (Heidelberg, Germany), Novartis (Basel, Switzerland),
   Ohr (New York, New York, USA), Optos (Dunfermline, United Kingdom),
   Regeneron (Tarrytown, New York, USA), Regenxbio (Rockville, Maryland,
   USA), Stealth Peptides (Newton, Massachusetts, USA), ThromboGenics
   (Leuven, Belgium);, Research Support: Alcon, Allegro Ophthalmics (San
   Juan Capistrano, California, USA), Allergan, Apellis Pharmaceuticals
   (Crestwood, Kentucky, USA), Clearside, Iconic Therapeutics (South San
   Francisco, California, USA), Genentech, Regeneron, DRCR Network (Jaeb
   Center for Health Research, Tampa, Florida, USA), Ophthotech (Princeton,
   New Jersey, USA), ThromboGenics, Tryogenex (West Palm Beach, Florida,
   USA). John F. Payne: Research support: Aerpio (Cincinnati, Ohio, USA),
   Alcon (Hunenberg, Switzerland), EMMES (Rockville, MD), Genentech,
   Regeneron. Charles C. Wykoff: Consultant: Alcon, Allergan, Alimera
   Sciences, Alnylam (Cambridge, Massachusetts, USA), Bayer, Clearside,
   DORC International (Zuidland, Netherlands), Genentech, ONL Therapeutics
   (Ann Arbor, Michigan, USA), Regeneron, Thrombogenics, Valeant (Laval,
   Canada); Research Support: Alcon, Allegro Ophthalmics, Allergan, Apellis
   Pharmaceuticals, Clearside, DRCR Network, Genentech, Iconic
   Therapeutics, Novartis, Ophthotech, Regeneron, ThromboGenics, Tryogenex;
   Speaker Bureau: Allergan, Regeneron. The following author has no
   financial disclosures: William C. Ou. All authors attest that they meet
   the current ICMJE criteria for authorship.
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NR 40
TC 46
Z9 47
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD AUG
PY 2017
VL 180
BP 8
EP 17
DI 10.1016/j.ajo.2017.05.014
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FC6ZK
UT WOS:000406990000004
PM 28549848
DA 2022-11-30
ER

PT J
AU Chen, WJ
   Wu, CY
   Xu, ZH
   Kuse, Y
   Hara, H
   Duh, EJ
AF Chen, Wan-Ju
   Wu, Caiying
   Xu, Zhenhua
   Kuse, Yoshiki
   Hara, Hideaki
   Duh, Elia J.
TI Nrf2 protects photoreceptor cells from photo-oxidative stress induced by
   blue light
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Photoreceptor; Oxidative stress; Nrf2; Neuroprotection
ID RETINAL ISCHEMIA-REPERFUSION; MACULAR DEGENERATION; OXIDATIVE STRESS;
   NEURODEGENERATIVE DISEASES; RETINITIS-PIGMENTOSA; TRANSGENIC MICE;
   IN-VITRO; DAMAGE; CONE; DEATH
AB Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6-24 h resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Chen, Wan-Ju; Wu, Caiying; Xu, Zhenhua; Duh, Elia J.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 400 N Broadway,Smith Bldg Room 3011, Baltimore, MD 21287 USA.
   [Chen, Wan-Ju] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kong Univ Hosp, Dept Ophthalmol, Tainan, Taiwan.
   [Kuse, Yoshiki; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
C3 Johns Hopkins University; National Cheng Kung University; Gifu
   Pharmaceutical University
RP Duh, EJ (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 400 N Broadway,Smith Bldg Room 3011, Baltimore, MD 21287 USA.
EM eduh@jhmi.edu
RI Kuse, Yoshiki/AAB-7445-2021
OI Hara, Hideaki/0000-0003-2046-9001
FU National Institutes of Health [EY022383, EY022683, P30EY001765];
   NATIONAL EYE INSTITUTE [R01EY022383, R01EY022683, P30EY001765] Funding
   Source: NIH RePORTER
FX This work was supported by research grants from the National Institutes
   of Health (EY022383 and EY022683; to E.J.D.) and Core Grant P30EY001765,
   Imaging and Microscopy Core Module. We thank Cindy Berlinicke for her
   help with the quantitative analysis of the cell staining with the
   CellomicsArrayScan VTI HCS reader.
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NR 28
TC 44
Z9 44
U1 2
U2 20
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2017
VL 154
BP 151
EP 158
DI 10.1016/j.exer.2016.12.001
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EP7HF
UT WOS:000397548100016
PM 27923559
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kelly, D
   Nolan, JM
   Howard, AN
   Stack, J
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   Moran, R
   Thurnham, DI
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   Beatty, S
AF Kelly, David
   Nolan, John M.
   Howard, Alan N.
   Stack, Jim
   Akuffo, Kwadwo O.
   Moran, Rachel
   Thurnham, David I.
   Dennison, Jessica
   Meagher, Katherine A.
   Beatty, Stephen
TI Serum and macular response to carotenoid-enriched egg supplementation in
   human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT)
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Lutein; Zeaxanthin; Meso-zeaxanthin; Macular pigment;
   Carotenoid-enriched eggs; Serum carotenoids; Cholesterol
ID PIGMENT OPTICAL-DENSITY; HETEROCHROMATIC FLICKER PHOTOMETRY;
   POLYUNSATURATED FATTY-ACIDS; MESO-ZEAXANTHIN; VISUAL FUNCTION; CONTRAST
   SENSITIVITY; COGNITIVE FUNCTION; LIPOPROTEIN CHOLESTEROL; LUTEIN
   SUPPLEMENTATION; TISSUE CONCENTRATIONS
AB The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P < 0.001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6.5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and / or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.
C1 [Kelly, David; Nolan, John M.; Stack, Jim; Akuffo, Kwadwo O.; Moran, Rachel; Dennison, Jessica; Meagher, Katherine A.; Beatty, Stephen] Waterford Inst Technol, Sch Hlth Sci, Nutr Res Ctr Ireland, Macular Pigment Res Grp, Waterford X91 K236, Ireland.
   [Howard, Alan N.] Howard Fdn, Cambridge CB25 ONW, England.
   [Howard, Alan N.] Univ Cambridge, Downing Coll, Cambridge CB2 1DQ, England.
   [Thurnham, David I.] Univ Ulster, Northern Ireland Ctr Food & Hlth NICHE, Coleraine BT52 1SA, Londonderry, North Ireland.
C3 South East Technological University (SETU); University of Cambridge;
   Ulster University
RP Kelly, D (通讯作者)，Waterford Inst Technol, Sch Hlth Sci, Nutr Res Ctr Ireland, Macular Pigment Res Grp, Waterford X91 K236, Ireland.
EM davidkelly_24@yahoo.co.uk
RI Akuffo, Kwadwo Owusu/J-2036-2019; Dennison, Jessica/AAG-1199-2020;
   Nolan, John/N-4921-2014
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; Nolan,
   John/0000-0002-5503-7084; Dennison, Jessica/0000-0001-8793-9237
FU Howard Foundation, Cambridge [285822]; European Research Council Starter
   grant [281096]
FX The EXIT clinical trial was supported by the Howard Foundation (English
   Charity reg. no. 285822), Cambridge, UK. D. K., K. O. A. and J. M. N.
   are funded by the European Research Council Starter grant (ref. 281096).
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NR 92
TC 12
Z9 13
U1 0
U2 11
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 2017
VL 117
IS 1
BP 108
EP 123
DI 10.1017/S0007114516003895
PG 16
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA EM7QZ
UT WOS:000395508700010
PM 28122649
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Park, SI
   Jang, YP
AF Park, Sang-Il
   Jang, Young Pyo
TI The Protective Effect of Brown-, Gray-, and Blue -Tinted Lenses against
   Blue LED Light -Induced Cell Death in A2E-Laden Human Retinal Pigment
   Epithelial Cells
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Age-related macular degeneration; A2E; Blue light; Tinted lenses;
   ARPE-19 cells
ID MACULAR DEGENERATION; LIPOFUSCIN FLUOROPHORE; INDUCED DAMAGE; A2E; RPE;
   MECHANISMS; RADIATION; COMPONENT; CULTURE; ISO-A2E
AB A2E-laden ARPE-19 cells were exposed to a blue light to induce cytotoxicity, in order to investigate the protective effects of various tinted ophthalmic lenses against photo -induced cytotoxicity in human retinal pigment epithelial (RPE) cells laden with A2E, known to be among the etiologies of age -related macular degeneration (AMD). Different -colored tinted lenses with varying levels of tint and different filtering characteristics, such as polarized, blue -cut, and photochromatic lenses, were placed over the cells, and the protective efficacies thereof were evaluated by lactate dehydrogenase assay. When tinted lenses were placed over ARPE-19 cells, there were different reductions in cytotoxicity according to the colors and tint levels. The level of protection afforded by brown -tinted lenses was 6.9, 36.1, and 49% with a tint level of 15, 50, and 80%, respectively. For gray -tinted lenses, the protective effect was 16.3,35, and 43.4% for the corresponding degree of tint, respectively. In the case of blue-tinted lenses, a protective effect of 20% was observed with 80% tinted lenses, but 15 and 50% tinted lenses provided no sig-nificant protection. In addition, photochromic lenses showed a protective effect but blue-cut lenses and polarized lenses provided no significant protection. Tinted lenses significantly reduced cytotoxicity in RPE cells irradiated with blue light. The protection was more efficient in lenses with a brown or gray tint than in blue -tinted lenses. Tinted glasses may provide significant protection against potential blue-light-induced photochemical and photo-oxidative damage in RPE cells. (C) 2016 S. Karger AG, Basel
C1 [Park, Sang-Il; Jang, Young Pyo] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Coll Pharm, Seoul, South Korea.
   [Jang, Young Pyo] Kyung Hee Univ, Dept Oriental Pharmaceut Sci, Coll Pharm, Seoul, South Korea.
C3 Kyung Hee University; Kyung Hee University
RP Jang, YP (通讯作者)，Kyung Hee Univ, Coll Pharm, Div Pharmacognosy, Seoul 130701, South Korea.
EM ypjang@khu.ac.kr
RI Jang, Young Pyo/AAJ-8782-2020
OI Jang, Young Pyo/0000-0001-5865-9228
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NR 29
TC 7
Z9 8
U1 0
U2 12
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2017
VL 57
IS 2
BP 118
EP 124
DI 10.1159/000452174
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EK2BY
UT WOS:000393733500006
PM 27880954
DA 2022-11-30
ER

PT J
AU Hong, HS
   Kim, S
   Kim, YH
   Park, JH
   Jin, Y
   Son, Y
AF Hong, Hyun Sook
   Kim, Suna
   Kim, Yeong Hoon
   Park, Ju Hyeong
   Jin, Yinji
   Son, Youngsook
TI Substance-P Blocks Degeneration of Retina by Stimulating Migration and
   Proliferation of Retinal Pigmented Epithelial Cells
SO TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE Substance-P; retinal pigment epithelium; proliferation; migration
ID PREVALENCE; GROWTH
AB The retinal pigment epithelium (RPE) is a monolayer to function as a compact barrier between photoreceptor and choroid and also a regulator of the overlying photoreceptor layer by providing nutrients. If RPE is damaged, choroidal neovascularization is occurred, accompanied by inflammation, which leads to degeneration of whole retina layer and furthermore, loss of vision. Thus, the preservation of RPE layer is very critical treatment to block the progression and occurrence of diverse ocular disease, inducing age-related macular degeneration (AMD). In this study, we explored the new role of SP in RPE regeneration. After confirming the expression of NK-1R on ARPE-19 cells, we treated SP to ARPE-19 cells in vitro to evaluate the effect of SP on proliferation rate and migratory capacity. SP could promote proliferation and migration of ARPE-19 in dose-dependent manner in vitro. Based on the in vitro data, 5nmole/kg of SP was intravitreally treated to laser-induced RPE damaged mice in vivo, showing that PBS-injected mice had severed disturbed retina layer, whereas SP-injected mice maintained retina layer more intact without detachment of RPE. In addition to histological comparison, the efficacy of SP was assessed according to the score that indicate the severity of retina degeneration. This confirmed that SP can exert the beneficial effect on laser-induced RPE damage. Collectively, our findings suggest that SP can stimulate the regeneration of RPE layer and thus, it may be possible that SP is used as the new therapeutics for RPE-damaged disease including AMD.
C1 [Hong, Hyun Sook] Kyung Hee Univ, East West Med Res Inst, Coll Med, Seoul 130702, South Korea.
   [Kim, Suna; Park, Ju Hyeong; Jin, Yinji; Son, Youngsook] Kyung Hee Univ, Dept Genet Engn, Coll Life Sci, Seochun Dong 441706, Yong In, South Korea.
   [Kim, Suna; Park, Ju Hyeong; Jin, Yinji; Son, Youngsook] Kyung Hee Univ, Grad Sch Biotechnol, Seochun Dong 441706, Yong In, South Korea.
   [Kim, Yeong Hoon] Catholic Univ Korea, Coll Med, Dept Ophthalmol, St Pauls Hosp, Seoul 130709, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University;
   Catholic University of Korea
RP Son, Y (通讯作者)，Kyung Hee Univ, Dept Genet Engn, Coll Life Sci, Seochun Dong 441706, Yong In, South Korea.
EM ysson@khu.ac.kr
RI HONG, HYUN SOOK/AAI-3017-2020
OI HONG, HYUN SOOK/0000-0003-3659-1386
FU Korean Health Technology R&D Project grant from the Ministry of Health &
   Welfare, Republic of Korea [A120627, HI13C1479]; Bio & Medical
   Technology Development Program of the National Research Foundation
   [NRF-2012-050485]
FX This study was supported by a Korean Health Technology R&D Project grant
   from the Ministry of Health & Welfare, Republic of Korea (A120627,
   HI13C1479) and the Bio & Medical Technology Development Program
   (NRF-2012-050485) of the National Research Foundation.
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NR 19
TC 6
Z9 6
U1 0
U2 4
PU KOREAN TISSUE ENGINEERING REGENERATIVE MEDICINE SOC
PI SEOCHO-GU
PA 1414 SEOCHO WORLD OFFICETEL 19, SEOUN-RO, SEOCHO-GU, SEOUL 06732, SOUTH
   KOREA
SN 1738-2696
EI 2212-5469
J9 TISSUE ENG REGEN MED
JI Tissue Eng. Regen. Med.
PD APR
PY 2015
VL 12
IS 2
BP 121
EP 127
DI 10.1007/s13770-014-0088-6
PG 7
WC Cell & Tissue Engineering; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Engineering
GA CF5QG
UT WOS:000352611400007
DA 2022-11-30
ER

PT J
AU Shiroma, HF
   Farah, ME
   Takahashi, WY
   Gomes, AMV
   Goldbaum, M
   Rodrigues, EB
AF Shiroma, Helio F.
   Farah, Michel E.
   Takahashi, Walter Y.
   Gomes, Andre M. V.
   Goldbaum, Mauro
   Rodrigues, Eduardo Buchele
TI Survey: technique of performing intravitreal injection among members of
   the Brazilian Retina and Vitreous Society (SBRV)
SO ARQUIVOS BRASILEIROS DE OFTALMOLOGIA
LA English
DT Article
DE Intravitreal injections; Retinal diseases; Angiogenesis inhibitors;
   Topical anesthesia
ID MACULAR DEGENERATION; BEVACIZUMAB; ENDOPHTHALMITIS; RANIBIZUMAB; THERAPY
AB Objective: To evaluate and describe the precautions involved in the technique of intravitreal injection of antiangiogenic drugs adopted by the ophthalmologists who are members of the Brazilian Society of Retina and Vitreous (SBRV).
   Method: A questionnaire containing 22 questions related to precautions taken before, during, and after intravitreal injection was sent electronically to 920 members of SBRV between November 15, 2013 and April 31, 2014.
   Results: 352 responses (38%) were obtained. There was a predominance of men (76%) from the southwest region of Brazil (51%). The professional experience varied between 6 and 15 years after medical specialization (50%). Most professionals (76%) performed an average of 1 to 10 intravitreal injections a week, and 88% of the procedures were performed in the operating room using povidone iodine (99%), sterile gloves, and blepharostat (94%). For inducing topical anesthesia, usage of anesthetic eye drops was the most used technique (65%). Ranibizumab (Lucentis (R)) was the most common drug (55%), and age-related macular degeneration (AMD) was the most treated disease (57%). Regarding the complications treated, 6% of the ophthalmologists had treated at least one case of retinal detachment, 20% had treated cases of endophthalmitis, 9% had treated cases of vitreous hemorrhage, and 12% had encountered cases of crystalline lens touch.
   Conclusion: Intravitreal injection is a procedure routinely performed by retina specialists and has a low incidence of complications. Performing the procedure in the operating room using an aseptic technique was preferred by most of the respondents. Ranibizumab was the most used drug, and AMD was the most treated disease.
C1 [Shiroma, Helio F.; Farah, Michel E.; Rodrigues, Eduardo Buchele] Fed Univ Sao Paulo UNIFESP, Paulista Sch Med EPM, Dept Ophthalmol & Visual Sci, Sao Paulo, Brazil.
   [Takahashi, Walter Y.; Gomes, Andre M. V.; Goldbaum, Mauro] Univ Sao Paulo, Sch Med, Dept Ophthalmol, BR-09500900 Sao Paulo, SP, Brazil.
C3 Universidade Federal de Sao Paulo (UNIFESP); Universidade de Sao Paulo
RP Shiroma, HF (通讯作者)，Rua Pastor William Richard Schisler 900, BR-88034100 Florianopolis, SC, Brazil.
EM helioshiroma@hotmail.com
RI Farah, Michel Eid E/F-3285-2012; Rodrigues, Eduardo Büchele/C-6852-2015
OI Farah, Michel Eid E/0000-0001-5951-0193; Buchele Rodrigues,
   Eduardo/0000-0002-4224-0921
CR Aiello LP, 2011, OPHTHALMOLOGY, V118, pE5, DOI 10.1016/j.ophtha.2011.09.058
   Bhavsar AR, 2009, ARCH OPHTHALMOL-CHIC, V127, P1581, DOI 10.1001/archophthalmol.2009.304
   Engelbert M, 2009, RETINA-J RET VIT DIS, V29, P1424, DOI 10.1097/IAE.0b013e3181bfbd46
   Fagan XJ, 2013, CLIN EXP OPHTHALMOL, V41, P500, DOI 10.1111/ceo.12026
   Fung AE, 2006, BRIT J OPHTHALMOL, V90, P1344, DOI 10.1136/bjo.2006.099598
   Green-Simms AE, 2011, AM J OPHTHALMOL, V151, P329, DOI 10.1016/j.ajo.2010.08.039
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   Martin DF, 2011, NEW ENGL J MED, V364, P1897, DOI 10.1056/NEJMoa1102673
   Michels S, 2005, OPHTHALMOLOGY, V112, P1035, DOI 10.1016/j.ophtha.2005.02.007
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   Sampat KM, 2003, OPHTHAL SURG LAS IM, V44, P385
   Solomon SD, 2014, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD005139.pub3
   Stone TW, 2013, PREFERENCES TRENDS P
   Storey P, 2014, OPHTHALMOLOGY, V121, P283, DOI 10.1016/j.ophtha.2013.08.037
   Tesniere Antoine, 2003, Anesthesiol Clin North Am, V21, P273, DOI 10.1016/S0889-8537(02)00081-0
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   Yannuzzi NA, 2014, AM J OPHTHALMOL, V6, P233
NR 20
TC 7
Z9 9
U1 0
U2 1
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 JAN-FEB
PY 2015
VL 78
IS 1
BP 32
EP 35
DI 10.5935/0004-2749.20150009
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CC4OO
UT WOS:000350332900009
PM 25714535
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hsu, J
   Gerstenblith, AT
   Garg, SJ
   Vander, JF
AF Hsu, Jason
   Gerstenblith, Adam T.
   Garg, Sunir J.
   Vander, James F.
TI Conjunctival Flora Antibiotic Resistance Patterns After Serial
   Intravitreal Injections Without Postinjection Topical Antibiotics
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DRUG INJECTION; ENDOPHTHALMITIS; RANIBIZUMAB; RISK; BEVACIZUMAB
AB PURPOSE: To report conjunctival bacterial flora antibiotic resistance patterns after serial intravitreal injections performed using a povidone-iodine preparation without the use of preinjection or postinjection topical antibiotics.
   DESIGN: Prospective, interventional case series.
   METHODS: Setting: Single-center clinical practice in Pennsylvania. Study Population: Thirteen eyes of 13 treatment-naive patients undergoing serial intravitreal anti vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration or macular edema attrihutable to retinal vein occlusion. Intervention: Conjunctival cultures from the treatment eye were performed prior to each injection preparation. A minimum of 3 monthly 'conjunctival cultures were obtained per eye over the course of the study. Ocular surface preparation consisted of topical anesthetic and povidone-iodine 5% without the use of preinjection or postinjection topical antibiotics. Main Outcome Measures: Conjunctival flora growth patterns and antibiotic resistance patterns to several common antibiotics tested over the course of the study.
   RESULTS: A total of 48 cultures were performed with a 77% culture positivity rate. Over the course of the serial conjunctival cultures in each patient, there was no evidence for emergence of resistant bacteria to any of the tested antibiotics (including fluoroquinolones and azithromycin) or significant alteration from baseline conjunctival flora. Of the 47 bacterial isolates, the most commonly isolated organism was coagulase-negative Staphylococcus both at baseline (73%) and following serial intravitreal injections (78%, P = .73).
   CONCLUSIONS: Ocular surface preparation for intravitreal injection using povidone-iodine 5% alone in the absence of postinjection topical antibiotics does not appear to promote bacterial resistance or a discernible change in conjunctival flora.
C1 [Hsu, Jason; Gerstenblith, Adam T.; Garg, Sunir J.; Vander, James F.] Mid Atlantic Retina, Retina Serv, Wills Eye Hosp, Philadelphia, PA 19107 USA.
C3 Jefferson University
RP Hsu, J (通讯作者)，Wills Eye Hosp & Res Inst, Retina Serv, 840 Walnut St,Suite 1020, Philadelphia, PA 19107 USA.
EM jhsu@midatlanticretina.com
FU Santen, Ophthotech; Genentech, Regeneron, Eyegate; J. Arch McNamara
   Memorial Fund for Retina Research (Wills Eye Hospital, Philadelphia,
   Pennsylvania, USA)
FX The authors indicate the following financial disclosures: J.H.: grant
   support (Santen, Ophthotech); S.J.G.: grant support (Genentech,
   Regeneron, Eyegate), speaker bureau (Allergan). Funding support was
   received from J. Arch McNamara Memorial Fund for Retina Research (Wills
   Eye Hospital, Philadelphia, Pennsylvania, USA).
CR Bhatt SS, 2011, RETINA-J RET VIT DIS, V31, P2032, DOI 10.1097/IAE.0b013e31820f4b4f
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NR 28
TC 50
Z9 53
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 MAR
PY 2014
VL 157
IS 3
BP 514
EP 518
DI 10.1016/j.ajo.2013.10.003
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AC2QX
UT WOS:000332350100003
PM 24332373
DA 2022-11-30
ER

PT J
AU Sohn, EH
   Khanna, A
   Tucker, BA
   Abramoff, MD
   Stone, EM
   Mullins, RF
AF Sohn, Elliott H.
   Khanna, Aditi
   Tucker, Budd A.
   Abramoff, Michael D.
   Stone, Edwin M.
   Mullins, Robert F.
TI Structural and Biochemical Analyses of Choroidal Thickness in Human
   Donor Eyes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE choroid; age-related macular degeneration; protease
ID OPTICAL COHERENCE TOMOGRAPHY; CENTRAL SEROUS CHORIORETINOPATHY; PUNCTATE
   INNER CHOROIDOPATHY; SORSBYS FUNDUS DYSTROPHY; LARGE GENE LISTS; MACULAR
   DEGENERATION; TISSUE INHIBITOR; METALLOPROTEINASES-3 TIMP3; BRUCHS
   MEMBRANE; MYOPIC EYES
AB PURPOSE. The choroid plays a vital role in the health of the outer retina. While measurements of choroid using optical coherence tomography show altered thickness in aging and macular disease, detailed histopathologic and proteomic analyses are lacking. In this study we sought to evaluate biochemical differences in human donor eyes between very thin and thick choroids.
   METHODS. One hundred forty-one eyes from 104 donors (mean age 6 standard deviation, 81.5 +/- 12.2) were studied. Macular sections were collected, and the distance between Bruch's membrane and the inner surface of the sclera was measured in control, early/dry age-related macular degeneration (AMD), neovascular AMD, and geographic atrophy eyes. Proteins from the RPE-choroid of eyes with thick and thin choroids were analyzed using two-dimensional electrophoresis and/or mass spectrometry. Two proteins with altered abundance were confirmed using Western blot analysis.
   RESULTS. Donor eyes showed a normal distribution of thicknesses. Eyes with geographic atrophy had significantly thinner choroids than age-matched controls or early AMD eyes. Proteomic analysis showed higher levels of the serine protease SERPINA3 in thick choroids and increased levels of tissue inhibitor of metalloproteinases-3 (TIMP3) in thin choroids.
   CONCLUSIONS. Consistent with clinical imaging observations, geographic atrophy was associated with choroidal thinning. Biochemical data suggest an alteration in the balance between proteases and protease inhibitors in eyes that lie at the extremes of choroidal thickness. An improved understanding of the basic mechanisms associated with choroidal thinning may guide the development of new therapies for AMD.
C1 [Sohn, Elliott H.; Khanna, Aditi; Tucker, Budd A.; Abramoff, Michael D.; Stone, Edwin M.; Mullins, Robert F.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
   [Sohn, Elliott H.; Khanna, Aditi; Tucker, Budd A.; Abramoff, Michael D.; Stone, Edwin M.; Mullins, Robert F.] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
C3 University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，4135E MERF,375 Newton Rd, Iowa City, IA 52242 USA.
EM robert-mullins@uiowa.edu
RI Abramoff, Michael D/A-5836-2009; Mullins, Robert F/I-6717-2013
OI Abramoff, Michael D/0000-0002-3490-0037; Stone, Edwin
   M./0000-0003-3343-4414; Mullins, Robert/0000-0002-5006-0891; Sohn,
   Elliott/0000-0002-3778-9362; Tucker, Budd/0000-0003-2178-1742
FU National Institutes of Health [EY017451, EY016822, 1-DP2-OD007483-01];
   Howard Hughes Medical Institute; Elmer and Sylvia Sramek Charitable
   Foundation; Stephen A. Wynn Foundation; NATIONAL EYE INSTITUTE
   [R01EY016822, R01EY017451] Funding Source: NIH RePORTER; OFFICE OF THE
   DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP2OD007483] Funding Source:
   NIH RePORTER
FX Supported in part by National Institutes of Health Grants EY017451
   (RFM), EY016822 (EMS), and 1-DP2-OD007483-01 (BAT); Howard Hughes
   Medical Institute (EMS); Elmer and Sylvia Sramek Charitable Foundation
   (RFM/BAT); the Stephen A. Wynn Foundation; and the Hansjoerg EJW Kolder
   MD, PhD Professorship for Best Disease (RFM).
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NR 59
TC 64
Z9 66
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 2014
VL 55
IS 3
BP 1352
EP 1360
DI 10.1167/iovs.13-13754
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AD2BA
UT WOS:000333036500023
PM 24519422
OA Green Published
DA 2022-11-30
ER

PT J
AU Ugarte, M
   Osborne, NN
   Brown, LA
   Bishop, PN
AF Ugarte, Marta
   Osborne, Neville N.
   Brown, Laurence A.
   Bishop, Paul N.
TI Iron, zinc, and copper in retinal physiology and disease
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE iron; zinc; copper; retina; metal homeostasis interactions; trace metal
   deficiency and overload; trace metal toxicity; age-related macular
   degeneration; iron chelators; zinc supplements
ID PIGMENT EPITHELIAL-CELLS; HANDLING PROTEINS FERRITIN;
   CYTOCHROME-C-OXIDASE; X-RAY-MICROANALYSIS; MACULAR DEGENERATION; SERUM
   FERRITIN; IN-VITRO; DEFICIENCY ANEMIA; OPTIC NEUROPATHY; FINGER PROTEIN
AB The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of "free" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Ugarte, Marta; Bishop, Paul N.] Univ Manchester, Inst Human Dev, Ctr Adv Discovery & Expt Therapeut, Manchester M13 9PT, Lancs, England.
   [Ugarte, Marta; Bishop, Paul N.] Manchester Royal Eye Hosp, Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 9PT, Lancs, England.
   [Osborne, Neville N.] Fdn Invest Oftalmol, Inst Oftalmol Fernandes Vega, Oviedo, Asturias, Spain.
   [Osborne, Neville N.; Brown, Laurence A.] Univ Oxford, John Radcliffe Hosp, Nuffield Lab Ophthalmol NDCN, Oxford OX3 9DU, England.
C3 University of Manchester; Manchester Royal Eye Hospital; University of
   Manchester; University of Oxford
RP Ugarte, M (通讯作者)，AV Hill Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
EM mugarte@doctors.org.uk
OI Brown, Laurence/0000-0001-8116-4100; Bishop, Paul/0000-0001-7937-7932;
   Ugarte, Marta/0000-0002-8132-5004
FU NIHR Manchester Biomedical Research Centre
FX M.U. is a National Institute of Health Research (NIHR) Clinical
   Lecturer. We acknowledge support from the NIHR Manchester Biomedical
   Research Centre. We are most grateful to Dr. Kalotina Geraki from Ion
   beam I18 at Diamond Light Source (Harwell Science and Innovation Campus,
   Didcot, Oxfordshire OX11 0DE, UK) for her help with the synchrotron XRF
   analysis of rat retina (Fig. 1).
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NR 410
TC 83
Z9 85
U1 1
U2 51
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0039-6257
EI 1879-3304
J9 SURV OPHTHALMOL
JI Surv. Ophthalmol.
PD NOV-DEC
PY 2013
VL 58
IS 6
BP 585
EP 609
DI 10.1016/j.survophthal.2012.12.002
PG 25
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 244ZO
UT WOS:000326428900006
PM 24160731
DA 2022-11-30
ER

PT J
AU Notomi, S
   Hisatomi, T
   Murakami, Y
   Terasaki, H
   Sonoda, S
   Asato, R
   Takeda, A
   Ikeda, Y
   Enaida, H
   Sakamoto, T
   Ishibashi, T
AF Notomi, Shoji
   Hisatomi, Toshio
   Murakami, Yusuke
   Terasaki, Hiroto
   Sonoda, Shozo
   Asato, Ryo
   Takeda, Atsunobu
   Ikeda, Yasuhiro
   Enaida, Hiroshi
   Sakamoto, Taiji
   Ishibashi, Tatsuro
TI Dynamic Increase in Extracellular ATP Accelerates Photoreceptor Cell
   Apoptosis via Ligation of P2RX7 in Subretinal Hemorrhage
SO PLOS ONE
LA English
DT Article
ID BRILLIANT BLUE-G; RETINAL GANGLION-CELLS; MACULAR DEGENERATION; P2X(7)
   RECEPTORS; INTRACEREBRAL HEMORRHAGE; IN-VIVO; RAT MODEL; CHOROIDAL
   NEOVASCULARIZATION; MITOCHONDRIAL APOPTOSIS; VITREOUS HEMORRHAGE
AB Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.
C1 [Notomi, Shoji; Hisatomi, Toshio; Murakami, Yusuke; Asato, Ryo; Takeda, Atsunobu; Ikeda, Yasuhiro; Enaida, Hiroshi; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan.
   [Hisatomi, Toshio; Asato, Ryo] Natl Hosp Org, Clin Res Inst, Kyushu Med Ctr, Fukuoka, Japan.
   [Terasaki, Hiroto; Sonoda, Shozo; Sakamoto, Taiji] Kagoshima Univ, Dept Ophthalmol, Grad Sch Med Sci, Kagoshima 890, Japan.
C3 Kyushu University; Kagoshima University
RP Hisatomi, T (通讯作者)，Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan.
EM hisatomi@med.kyushu-u.ac.jp
OI Hisatomi, Toshio/0000-0003-2552-9595
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan
   [21791690]
FX This study was supported by a Grant-In-Aid for Scientific Research
   (number 21791690) from the Ministry of Education, Culture, Sports,
   Science, and Technology, 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 70
TC 55
Z9 59
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 JAN 8
PY 2013
VL 8
IS 1
AR e53338
DI 10.1371/journal.pone.0053338
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 069IY
UT WOS:000313429800040
PM 23308196
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Ermini, L
   Wilson, IJ
   Goodship, THJ
   Sheerin, NS
AF Ermini, L.
   Wilson, I. J.
   Goodship, T. H. J.
   Sheerin, N. S.
TI Complement polymorphisms: Geographical distribution and relevance to
   disease
SO IMMUNOBIOLOGY
LA English
DT Article
DE Complement polymorphisms; Human diseases; Evolutionary and population
   genetics
ID GENOME-WIDE ASSOCIATION; BINDING LECTIN GENOTYPE; FACTOR-H POLYMORPHISM;
   NATURAL-SELECTION; IDENTIFIES VARIANTS; CONFERS PROTECTION; MACULAR
   DEGENERATION; FUNDAMENTAL-CONCEPTS; FALCIPARUM-MALARIA; GENETICS
   GENETICS
AB The evolution of man has been characterised by recurrent episodes of migration and settlement with infectious disease a constant threat. This long history of demographic change, together with the action of evolutionary forces such as natural selection and genetic drift, has shaped human genetic diversity. In particular, the interaction between humans, pathogens and the environment has played a crucial role in generating patterns of human genetic variation. The complement system plays a crucial role in the early protective immune response after exposure to a pathogen. Pathogens, over time, have developed mechanisms to circumvent the effects of complement which in turn has led to development of a more complex complement system. During the evolution of the complement system genes coding complement proteins have evolved polymorphisms, some of which have a functional effect, and this may reflect human-pathogen interaction and geographical origin. An example is the polymorphism Ile62Val (rs800292 (A>G)) in the complement regulator Factor H gene which alters the susceptibility to age-related macular degeneration (AMD), with the Ile62 polymorphism protecting against AMD. When sub-Saharan African and European populations are compared, the frequency of this polymorphism shows a very marked geographical distribution. Polymorphisms in other complement genes such as complement factor B show similar trends. This paper describes the geographical variation present in complement genes and discusses the implications of these observations. The analysis of genetic variation in complement genes is a promising tool to unravel mechanisms of host-pathogen interaction and can provide new insights into the evolution of the human immune system. (C) 2011 Elsevier GmbH. All rights reserved.
C1 [Sheerin, N. S.] Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Wilson, I. J.; Goodship, T. H. J.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle University - UK
RP Sheerin, NS (通讯作者)，Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM neil.sheerin@ncl.ac.uk
RI Ermini, Luca/O-4813-2016
OI Ermini, Luca/0000-0001-8109-6021; Wilson, Ian/0000-0001-6893-2873
FU MRC [G0701320] Funding Source: UKRI; Medical Research Council [G0701320]
   Funding Source: Medline
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NR 67
TC 11
Z9 11
U1 0
U2 8
PU ELSEVIER GMBH
PI MUNICH
PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY
SN 0171-2985
EI 1878-3279
J9 IMMUNOBIOLOGY
JI Immunobiology
PD FEB
PY 2012
VL 217
IS 2
SI SI
BP 265
EP 271
DI 10.1016/j.imbio.2011.07.020
PG 7
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 902GI
UT WOS:000301026200017
PM 21899915
DA 2022-11-30
ER

PT J
AU Mahajan, VB
   Elkins, KA
   Russell, SR
   Boldt, HC
   Gehrs, KM
   Weingeist, TA
   Stone, EM
   Abramoff, MD
   Liu, DW
   Folk, JC
AF Mahajan, Vinit B.
   Elkins, Kori A.
   Russell, Stephen R.
   Boldt, H. Culver
   Gehrs, Karen M.
   Weingeist, Thomas A.
   Stone, Edwin M.
   Abramoff, Michael D.
   Liu, Dawei
   Folk, James C.
TI BILATERAL INTRAVITREAL INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH
   FACTOR THERAPY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; anti-VEGF
ID MACULAR DEGENERATION; LASER PHOTOCOAGULATION; CLINICAL-TRIALS;
   RANIBIZUMAB
AB Purpose: The purpose of this study was to review adverse events and patient preference after bilateral intravitreal injection of antibodies to vascular endothelial growth factor.
   Methods: A retrospective case-control study. Patients with exudative age-related macular degeneration who received intravitreal antivascular endothelial growth factor agent injections in both eyes (bilateral group) on the same day over a 23-month period were compared with patients who received injections in only 1 eye. The occurrence of endophthalmitis, cerebrovascular accident, myocardial infarction, death, patient discomfort, and patient preference was compared between the two groups.
   Results: One hundred and two patients received an average of 4.43 bilateral injections (range 1-13). A case-control group of 102 patients received an average of 10.2 unilateral injections, (range 2-28). Bevacizumab was injected 45.5%, ranibizumab 45.5%, and a combination of bevacizumab and ranibizumab 9% of the time for bilateral injections. Bevacizumab was used 50.3% and ranubizumab 49.7% of the time in unilateral injections. The follow-up of both groups averaged 18.4 months (range 4.7-36.5 months). There were no cases of endophthalmitis or cerebrovascular accident in either group. There was a single case of myocardial infarction in each group. There were two deaths in the bilateral group and three deaths in the unilateral group. More than 90% strongly preferred bilateral injections to unilateral injections.
   Conclusion: Bilateral injections of antivascular endothelial growth factor agents on the same day did not increase the rate of adverse events and was preferred by the majority of patients. RETINA 31:31-35, 2011
C1 [Mahajan, Vinit B.; Elkins, Kori A.; Russell, Stephen R.; Boldt, H. Culver; Gehrs, Karen M.; Weingeist, Thomas A.; Stone, Edwin M.; Abramoff, Michael D.; Folk, James C.] Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci, Vitreoretinal Serv, Iowa City, IA 52242 USA.
   [Mahajan, Vinit B.] Omics Lab, Iowa City, IA USA.
   [Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA.
   [Abramoff, Michael D.] VAMC, Iowa City, IA USA.
   [Liu, Dawei] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA.
C3 University of Iowa; Howard Hughes Medical Institute; University of Iowa;
   US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Iowa City VA Health Care System; University of Iowa
RP Mahajan, VB (通讯作者)，Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci, Vitreoretinal Serv, 200 Hawkins Dr, Iowa City, IA 52242 USA.
EM mahajanlab@gmail.com
RI Abramoff, Michael D/A-5836-2009
OI Abramoff, Michael D/0000-0002-3490-0037; Stone, Edwin
   M./0000-0003-3343-4414; Mahajan, Vinit/0000-0003-1886-1741; Gehrs,
   Karen/0000-0003-4510-9678; Russell, Stephen/0000-0003-3776-1367; Folk,
   James/0000-0002-6271-2906; Boldt, H. Culver/0000-0002-7292-2093
FU Research to Prevent Blindness, Inc., New York, NY
FX An unrestricted grant from Research to Prevent Blindness, Inc., New
   York, NY. Dr. J.C.F. is The Judith (Gardner) and Donald H. Beisner, MD,
   Professor of Vitreoretinal Diseases and Surgery.
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   2010, STUDY RANIBIZUMAB AD
NR 11
TC 23
Z9 23
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD JAN
PY 2011
VL 31
IS 1
BP 31
EP 35
DI 10.1097/IAE.0b013e3181ed8c80
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 699TG
UT WOS:000285685100005
PM 21187731
DA 2022-11-30
ER

PT J
AU Dreyfuss, JL
   Regatieri, CV
   Lima, MA
   Paredes-Gamero, EJ
   Brito, AS
   Chavante, SF
   Belfort, R
   Farah, ME
   Nader, HB
AF Dreyfuss, J. L.
   Regatieri, C. V.
   Lima, M. A.
   Paredes-Gamero, E. J.
   Brito, A. S.
   Chavante, S. F.
   Belfort, R., Jr.
   Farah, M. E.
   Nader, H. B.
TI A heparin mimetic isolated from a marine shrimp suppresses
   neovascularization
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE angiogenesis; endothelial cell; glycosaminoglycans; growth factors;
   heparin mimetic; proliferation
ID FIBROBLAST GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; MATRIX
   METALLOPROTEINASES; 3-DIMENSIONAL STRUCTURE; ENDOTHELIAL-CELLS; TUBE
   FORMATION; IN-VIVO; VEGF(165); GLYCOSAMINOGLYCANS; ANGIOGENESIS
AB Background: Choroidal neovascularization (CNV) is the main cause of severe visual loss in age-related macular degeneration (AMD). Heparin/heparan sulfate are known to play important roles in neovascularization due to their abilities to bind and modulate angiogenic growth factors and cytokines. Previously, we have isolated from marine shrimp a heparin-like compound with striking anti-inflammatory action and negligible anticoagulant and hemorrhagic activities. Objectives: To investigate the role of this novel heparin-like compound in angiogenic processes. Methods and Results: The anti-angiogenic effect of this heparinoid in laser-induced CNV and in vitro models is reported. The compound binds to growth factors (FGF-2, EGF and VEGF), blocks endothelial cell proliferation and shows no cytotoxic effect. The decrease in proliferation is not related to cell death either by apoptosis or secondary necrosis. The results also showed that the heparinoid modified the 2-D network organization in capillary-like structures of endothelial cells in Matrigel and reduced the CNV area. The effect on CNV area correlates with decreases in the levels of VEGF and TGF-beta 1 in the choroidal tissue. The low content of 2-O-sulfate groups in this heparinoid may explain its potent anti-angiogenic effect. Conclusions: The properties of the shrimp heparinoid, such as potent anti-angiogenic and anti-inflammatory activities but insignificant anticoagulant or hemorrhagic actions, point to this compound as a compelling drug candidate for treating neovascular AMD and other angioproliferative diseases. A mechanism for the anti-angiogenic effect of the heparinoid is proposed.
C1 [Dreyfuss, J. L.; Regatieri, C. V.; Lima, M. A.; Paredes-Gamero, E. J.; Brito, A. S.; Nader, H. B.] Univ Fed Sao Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, BR-04044020 Sao Paulo, Brazil.
   [Regatieri, C. V.; Belfort, R., Jr.; Farah, M. E.] Univ Fed Sao Paulo, Dept Oftalmol, BR-04044020 Sao Paulo, Brazil.
   [Brito, A. S.; Chavante, S. F.] Univ Fed Rio Grande do Norte, UFRN, Dept Bioquim, BR-59072970 Natal, RN, Brazil.
C3 Universidade Federal de Sao Paulo (UNIFESP); Universidade Federal de Sao
   Paulo (UNIFESP); Universidade Federal do Rio Grande do Norte
RP Nader, HB (通讯作者)，Univ Fed Sao Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, Rua Tres Maio 100, BR-04044020 Sao Paulo, Brazil.
EM hbnader.bioq@cpm.br
RI Dreyfuss, Juliana L. L/H-8660-2012; Nader, Helena Bonciani/D-9253-2012;
   Brito, Adriana Silva/AAS-7365-2020; Regatieri, Caio/G-8152-2014;
   Belfort, Rubens/E-2252-2012; Paredes-Gamero, Edgar J/C-4791-2012; Farah,
   Michel Eid E/F-3285-2012; Lima, Marcelo/E-6841-2012
OI Dreyfuss, Juliana L. L/0000-0002-9825-1072; Regatieri,
   Caio/0000-0003-1511-8696; Belfort, Rubens/0000-0002-8422-3898;
   Paredes-Gamero, Edgar J/0000-0003-3686-8402; Farah, Michel Eid
   E/0000-0001-5951-0193; da Silva Brito, Adriana/0000-0002-4291-8456;
   NADER, HELENA/0000-0002-7569-2166
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP);
   Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES);
   Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
FX This work was supported by Fundacao de Amparo a Pesquisa do Estado de
   Sao Paulo (FAPESP), Coordenacao de Aperfeicoamento de Pessoal de Nivel
   Superior (CAPES). J. L. Dreyfuss and C. V. Regatieri are recipients of
   fellowships from Conselho Nacional de Desenvolvimento Cientifico e
   Tecnologico (CNPq).
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NR 41
TC 27
Z9 29
U1 0
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD AUG
PY 2010
VL 8
IS 8
BP 1828
EP 1837
DI 10.1111/j.1538-7836.2010.03916.x
PG 10
WC Hematology; Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Cardiovascular System & Cardiology
GA 635HN
UT WOS:000280646300022
PM 20492474
DA 2022-11-30
ER

PT J
AU Hasan, SM
   Vugler, AA
   Miljan, EA
   Sinden, JD
   Moss, SE
   Greenwood, J
AF Hasan, Shazeen M.
   Vugler, Anthony A.
   Miljan, Erik A.
   Sinden, John D.
   Moss, Stephen E.
   Greenwood, John
TI Immortalized Human Fetal Retinal Cells Retain Progenitor Characteristics
   and Represent a Potential Source for the Treatment of Retinal
   Degenerative Disease
SO CELL TRANSPLANTATION
LA English
DT Article
DE Retina; Progenitor cells; Conditional immortalization; Cellular therapy
ID EMBRYONIC STEM-CELLS; LEBERS CONGENITAL AMAUROSIS; VISUAL FUNCTION;
   SUBRETINAL TRANSPLANTATION; PHOTORECEPTOR PRECURSORS; DYSTROPHIC RATS;
   RCS RATS; DIFFERENTIATION; LINES; INTEGRATION
AB Human fetal retinal cells have been widely advocated for the development of cellular replacement therapies in patients with retinal dystrophies and age-related macular degeneration. A major limitation, however, is the lack of an abundant and renewable source of cells to meet therapeutic demand, although theoretically this may be addressed through the use of immortalized retinal progenitor cell lines. Here, we have used the temperature-sensitive tsA58 simian virus SV40 T antigen to conditionally immortalize human retinal progenitor cells isolated from retinal tissue at 10-12 weeks of gestation. We show that immortalized human fetal retinal cells retain their progenitor cell properties over many passages, and are comparable with nonimmortalized human fetal retinal cultures from the same gestational period with regard to expression of certain retinal genes. To evaluate the capacity of these cells to integrate into the diseased retina and to screen for potential tumorigenicity, cells were grafted into neonatal hooded Lister rats and RCS dystrophic rats. Both cell lines exhibited scarce integration into the host retina and failed to express markers of mature differentiated retinal cells. Moreover, although immortalized cells showed a greater propensity to survive, the cell lines demonstrated poor long-term survival. All grafts were infiltrated with host macrophage/microglial cells throughout their duration of survival. This study demonstrates that immortalized human fetal retinal progenitor cells retain their progenitor characteristics and may therefore have therapeutic potential in strategies that demand a renewable and consistent supply of donor cells for the treatment of degenerative retinal diseases.
C1 [Hasan, Shazeen M.; Vugler, Anthony A.; Moss, Stephen E.; Greenwood, John] UCL Inst Ophthalmol, Dept Cell Biol, London EC1V 9EL, England.
   [Miljan, Erik A.; Sinden, John D.] ReNeuron, Guildford, Surrey, England.
C3 University of London; University College London
RP Greenwood, J (通讯作者)，UCL Inst Ophthalmol, Dept Cell Biol, 11-43 Bath St, London EC1V 9EL, England.
EM j.greenwood@ucl.ac.uk
RI Miljan, Erik/AAH-7424-2020
OI Greenwood, John/0000-0003-4496-2984
FU Medical Research Council, UK; MRC [G0300308] Funding Source: UKRI;
   Medical Research Council [G0300308] Funding Source: researchfish
FX This work was supported by grants from the Medical Research Council, UK.
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NR 39
TC 13
Z9 14
U1 0
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-6897
EI 1555-3892
J9 CELL TRANSPLANT
JI Cell Transplant.
PY 2010
VL 19
IS 10
BP 1291
EP 1306
DI 10.3727/096368910X505477
PG 16
WC Cell & Tissue Engineering; Medicine, Research & Experimental;
   Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine; Transplantation
GA 696LK
UT WOS:000285442700007
PM 20447347
DA 2022-11-30
ER

PT J
AU Tatar, O
   Shinoda, K
   Kaiserling, E
   Pertile, G
   Eckardt, C
   Mohr, A
   Yoeruek, E
   Szurman, P
   Bartz-Schmidt, KU
   Grisanti, S
AF Tatar, Olcay
   Shinoda, Kei
   Kaiserling, Edwin
   Pertile, Grazia
   Eckardt, Claus
   Mohr, Andreas
   Yoeruek, Efdal
   Szurman, Peter
   Bartz-Schmidt, Karl U.
   Grisanti, Salvatore
TI Early effects of triamcinolone on vascular endothelial growth factor and
   endostatin in human choroidal neovascularization
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID VERTEPORFIN PHOTODYNAMIC THERAPY; LIMITED MACULAR TRANSLOCATION;
   RANDOMIZED CLINICAL-TRIAL; PIGMENT EPITHELIAL-CELLS; TREATED RAT MODEL;
   INTRAVITREAL TRIAMCINOLONE; IN-VITRO; PROLIFERATIVE VITREORETINOPATHY;
   VISUAL IMPAIRMENT; DEGENERATION
AB Objective: To evaluate the early effects of triamcinolone acetonide as monotherapy or as an adjuvant to ocular verteporfin photodynamic therapy (PDT) on angiogenesis in human choroidal neovascularization (CNV) secondary to age-related macular degeneration.
   Methods: Retrospective review of an interventional series of 55 patients who underwent CNV extraction. Eleven patients were treated with intravitreal triamcinolone acetonide (4 mg) monotherapy (triamcinolone-treated CNV group [n=5]) or with PDT-triamcinolone combination therapy (PDT-triamcinolone-treated CNV group [n=6]) 3 to 9 days before surgery. Forty patients who underwent CNV extraction without previous therapy (control CNV group) and 4 patients who underwent CNV extraction 3 days after PDT (PDT CNV group) served as control subjects. The CNV samples were stained for CD34, endostatin, cytokeratin 18, and vascular endothelial growth factor (VEGF).
   Results: Vascular endothelial growth factor expression was stronger in the PDT CNV samples (P <. 001), triamcinolone CNV samples (P=.01), and PDT-triamcinolone CNV samples (P=.007) compared with the control CNV samples. There were no statistically significant differences in VEGF expression among the PDT CNV samples, triamcinolone CNV samples, and PDT-triamcinolone CNV samples. Endostatin expression was weaker in the PDT CNV samples than in the control CNV samples ( P=.008). Endostatin expression was stronger in the triamcinolone CNV samples and the PDT-triamcinolone CNV samples compared with the control CNV samples (P=.001 and P <. 001, respectively) and the PDT CNV samples (P <. 001 for both).
   Conclusion: To some extent, triamcinolone monotherapy seems to exert its angiogenesis inhibitory effects on CNV by enhancing endostatin expression rather than by suppressing VEGF expression.
C1 [Tatar, Olcay; Yoeruek, Efdal; Bartz-Schmidt, Karl U.; Grisanti, Salvatore] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, D-72076 Tubingen, Germany.
   [Kaiserling, Edwin] Univ Tubingen, Dept Pathol, D-72076 Tubingen, Germany.
   [Eckardt, Claus] Augenklin Staedtischen Klin, Frankfurt, Germany.
   [Mohr, Andreas] St Joseph Stift Augenklin, Bremen, Germany.
   [Shinoda, Kei] Natl Inst Sensory Organs, Lab Vis Physiol, Tokyo, Japan.
   [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)，Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Schleichstr 12-15, D-72076 Tubingen, Germany.
EM Salvatore.Grisanti@med.uni-tuebingen.de
RI Pertile, Grazia/AAC-4956-2022; Shinoda, Kei/ABC-7993-2020
OI Shinoda, Kei/0000-0002-1543-9345
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NR 76
TC 13
Z9 15
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD FEB
PY 2008
VL 126
IS 2
BP 193
EP 199
DI 10.1001/archophthalmol.2007.40
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 261DQ
UT WOS:000253059700005
PM 18268209
OA Bronze
DA 2022-11-30
ER

PT J
AU Wu, WC
   Kao, YH
   Hu, PS
   Chen, JH
AF Wu, Wen-Chuan
   Kao, Ying-Hsien
   Hu, Pei-Shin
   Chen, Jiun-Hwan
TI Geldanamycin, a HSP90 inhibitor, attenuates the hypoxia-induced vascular
   endothelial growth factor expression in retinal pigment epithelium cells
   in vitro
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retinal pigment epithelial cells; hypoxia; vascular endothelial growth
   factor; heat shock proteins; geldanamycin
ID PROTEIN; OXYGEN; INDUCTION; RECEPTOR; ANGIOGENESIS; BINDING; VEGF
AB Hypoxia is the most common factor contributing to the pathogenesis of choroidal neovascularization, which is the major cause for blindness and occurs in proliferative diabetic retinopathy and age-related macular degeneration. The purpose of this study is to investigate the role of retinal pigment epithelial (RPE) cells in the regulation of subretinal neovascularization under hypoxia and the possible function of a heat shock protein 90 (HSP90) inhibitor, geldanamycin (GA), in the regulation of VEGF expression. An in vitro hypoxic experimental model was used to mimic the ischemic microenvironment of RPE cells. The cell growth was measured by proliferation assay and the morphological observation was documented by microscope. The gene expression of VEGF, hsp70, hsp90 alpha and hsp90 beta were measured using semi-quantitative RT-PCR. The VEGF release from RPE cells were detected by ELISA. No alteration in growth rate and cell morphology under 1% O-2 condition for 24 h was noticed. The proangiogenic growth factor VEGF, but not bFGF, released from hypoxia-treated cells were significantly higher than those of normoxic controls. A similar tendency of VEGF(165) isoform gene expression, detected by RT-PCR, was noticed in hypoxia-treated cells. Heat shock pretreatment elevated hsp70 and VEGF(165) gene expression and augmented the hypoxia-induced VEGF gene expression and protein release. Pretreatment with GA can significantly suppress the hypoxia-induced VEGF gene expression in and peptide release from RPE cells. These in vitro findings suggest that HSP90 inhibitors could be considered as novel anti-angiogenesis agents for diseases with intraocular neovascularization. (C) 2007 Elsevier Ltd. All rights reserved.
C1 Chi Mei Med Ctr, Dept Ophthalmol, Yung Kang 710, Tainan County, Taiwan.
   Kaohsiung Med Univ Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   Chang Gung Univ, Chang Gung Mem Hosp, Kaohsiung Med Ctr, Coll Med,Dept Surg, Kaohsiung, Taiwan.
   Kaohsiung Christian Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
C3 Chi Mei Hospital; Kaohsiung Medical University; Kaohsiung Medical
   University Hospital; Chang Gung Memorial Hospital; Chang Gung University
RP Chen, JH (通讯作者)，Chi Mei Med Ctr, Dept Ophthalmol, 901 Chung Hwa Rd, Yung Kang 710, Tainan County, Taiwan.
EM jiunhwan@gmaii.com
RI Kao, Ying-Hsien/H-4134-2019; Wu, Wen-Chuan/D-5296-2009
OI Kao, Ying-Hsien/0000-0001-7803-9384
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NR 41
TC 34
Z9 38
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2007
VL 85
IS 5
BP 721
EP 731
DI 10.1016/j.exer.2007.08.005
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 238JU
UT WOS:000251444500016
PM 17870069
DA 2022-11-30
ER

PT J
AU Zhou, JL
   Jang, YP
   Kim, SR
   Sparrow, JR
AF Zhou, Jilin
   Jang, Young Pyo
   Kim, So Ra
   Sparrow, Janet R.
TI Complement activation by photooxidation products of A2E, a lipofuscin
   constituent of the retinal pigment epithelium
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE inflammation; macular degeneration
ID AGE-RELATED MACULOPATHY; C-REACTIVE PROTEIN; FACTOR-H POLYMORPHISM;
   MACULAR DEGENERATION; FLUOROPHORE; DRUSEN; ACCUMULATION; CELLS; RISK;
   RPE
AB Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial (RPE) cells, contribute to the disease process. In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of products resulting from photooxidation of A2E might include a range of fragments that could be recognized by the complement system as "foreign" and that could serve to activate the complement system, leading to low-grade inflammation. To this end, we established an in vitro assay by using human serum as a source of complement, and we measured products of C3 activation by enzyme immunoassay. Accordingly, we found that the C3 split products inactivated C3b (iC3b) and C3a were elevated in serum, overlying ARPE-19 cells that had accumulated A2E and were irradiated to induce A2E photooxidation. Precoating of microtiter plates with two species of oxidized A2E, peroxy-A2E, and furano-A2E, followed by incubation with serum, also activated complement. We suggest that products of the photooxidation of bis-retinoid lipofuscin pigments in RPE cells could serve as a trigger for the complement system, a trigger than would predispose the macula to disease and that, over time, could contribute to chronic inflammation. These findings link four factors that have been posited as being associated with AMD: inflammation, oxidative damage, drusen, and RPE lipofuscin.
C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   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, New York, NY 10032 USA.
EM jrs88@columbia.edu
RI Jang, Young Pyo/AAJ-8782-2020; Mohammed, Imran/J-8271-2012
OI Jang, Young Pyo/0000-0001-5865-9228; Mohammed,
   Imran/0000-0002-8412-0768; Kim, So Ra/0000-0001-8786-2815
FU NEI NIH HHS [EY 12951, R01 EY012951] Funding Source: Medline; NATIONAL
   EYE INSTITUTE [R01EY012951] Funding Source: NIH RePORTER
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NR 60
TC 275
Z9 292
U1 0
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 31
PY 2006
VL 103
IS 44
BP 16182
EP 16187
DI 10.1073/pnas.0604255103
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 103IS
UT WOS:000241879500024
PM 17060630
OA Green Published
DA 2022-11-30
ER

PT J
AU Orr, PR
   Marsh, MJ
   Hawkins, BS
   Hawse, PL
   Bressler, NM
AF Orr, PR
   Marsh, MJ
   Hawkins, BS
   Hawse, PL
   Bressler, NM
CA Submacular Surg Trials
TI Evaluation of the Traveling Vision Examiner Program in the Submacular
   Surgery Trials Pilot Study
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE visual acuity screening; Submacular Surgery Trials Pilot Study;
   Traveling Vision Examiner Program; choroical neovascularization; masked
   vision measurements; age-related macular degenration; ocular
   histoplasmosis; reading speed; contrast threshold
ID VISUAL-ACUITY; REFRACTION; DESIGN
AB Purpose: To describe methods and results and to assess the value of a Traveling Vision Examiner (TVE) Program designed to provide masked vision measurements by expert vision examiners who were independent of, and traveled to, local clinical centers.
   Methods: The Submacular Surgery Trials (SST) Pilot Study was conducted to refine the design and methods for a set of multicenter, randomized clinical trials to evaluate submacular surgery in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) or ocular histoplasmosis (OHS), or idiopathic CNV in which the primary study outcome would be change in 2-year best-corrected vision from baseline. As part of the SST Pilot Study, the feasibility and value of a TVE Program was assessed. The goal of the program was to obtain unbiased vision measurements, according to a standard protocol, of best-corrected visual acuity, reading speed, and contrast threshold, of each patient at 2 and 4 years after enrollment.
   Results: Eighty-three visits by TVEs were made to 16 centers participating in the SST Pilot Study; 239 patients had at least one masked vision examination. Comparison of pairs of vision measurements of the traveling vision examiners and local vision examiners for 71 patients made on the same day showed good agreement overall (intraclass correlation coefficient >= 0.81).
   Conclusions: The proposed TVE Program was judged to be a feasible and useful method of providing standardized, unbiased, masked vision measurements. This approach was incorporated into the larger clinical trials conducted by the SST Research Group.
C1 Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Orr, PR (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, 550 N Broadway,Suite 115, Baltimore, MD 21205 USA.
EM pegorr@jhmi.edu
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NR 24
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2005
VL 12
IS 1
BP 47
EP 57
DI 10.1080/09286580490907814
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 911HU
UT WOS:000227994000007
PM 15848920
DA 2022-11-30
ER

PT J
AU Khani, SC
   Karoukis, AJ
   Young, JE
   Ambasudban, R
   Burch, T
   Stockton, R
   Lewis, RA
   Sullivan, LS
   Daiger, SP
   Reichel, E
   Ayyagari, R
AF Khani, SC
   Karoukis, AJ
   Young, JE
   Ambasudban, R
   Burch, T
   Stockton, R
   Lewis, RA
   Sullivan, LS
   Daiger, SP
   Reichel, E
   Ayyagari, R
TI Late-onset autosomal dominant macular dystrophy with choroidal
   neovascularization and nonexudative maculopathy associated with mutation
   in the RDS gene
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HONEYCOMB RETINAL DYSTROPHY; SORSBYS-FUNDUS-DYSTROPHY; DEGENERATION SLOW
   GENE; RETINITIS-PIGMENTOSA; PERIPHERIN/RDS GENE; PATTERN DYSTROPHY;
   CLINICAL-FEATURES; TISSUE INHIBITOR; DISK MEMBRANE; CHROMOSOME 6Q
AB PURPOSE. To examine the molecular genetic basis and phenotypic characteristics of an unusual late-onset autosomal dominant macular dystrophy with features of age-related macular degeneration (AMD) in a large family (SUNY901), by using linkage and mutation analyses.
   METHODS. Blood samples were collected from 17 affected members, 17 clinically unaffected members, and 5 unrelated spouses. Clinical analyses included a review of medical history and standard ophthalmic examination with fundus photography, fluorescein angiography, and electroretinography. Linkage and haplotype analyses were performed with microsatellite markers. Mutation analysis was performed by amplification of exons followed by sequencing.
   RESULTS. A wide spectrum of clinical phenotypes including exudative and nonexudative maculopathy was observed, with onset in the late fifth decade. Linkage analysis excluded most of the previously known maculopathy loci. Markers D6S1604 (Z(max) of 3.18 at theta = 0), and D6S282 (Z(max) of 3.18 at theta = 0) gave significant positive LOD scores and haplotype analysis localized the disease gene to a 9-centimorgan (cM) interval between markers D6S1616 and D6S459. Mutation analysis excluded the GUCA1A and GUCA1B genes and revealed a missense mutation in the RDS/peripherin gene leading to a Tyr141Cys substitution. A phenotype and haplotype comparison between this and a separate family with the Tyr141Cys mutation suggested the presence of a common ancestral haplotype.
   CONCLUSIONS. The RDS mutation in codon 141 is associated with an unusual AMD-like late-onset maculopathy. An apparent selective bias was noted favoring the transmission of the mutant allele. These observations broaden the spectrum of phenotypes associated with RDS gene mutations.
C1 SUNY Buffalo, Dept Ophthalmol, Buffalo, NY 14260 USA.
   Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   Baylor Coll Med, Dept Ophthalmol, 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 Mol & Human Genet, Houston, TX 77030 USA.
   Univ Texas, Hlth Sci Ctr, Ctr Human Genet, San Antonio, TX 78285 USA.
   Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78285 USA.
   Tufts Univ, New England Med Ctr, Dept Ophthalmol, Boston, MA 02111 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo; University of Michigan System; University of Michigan;
   Baylor College of Medicine; Baylor College of Medicine; Baylor College
   of Medicine; Baylor College of Medicine; University of Texas System;
   University of Texas Health San Antonio; University of Texas System;
   University of Texas Health San Antonio; Tufts Medical Center; Tufts
   University
RP Ayyagari, R (通讯作者)，Univ Michigan, WK Kellogg Eye Ctr, 1000 Wall St,Room 325, Ann Arbor, MI 48105 USA.
EM ayyagari@umich.edu
FU NATIONAL EYE INSTITUTE [R01EY013198, R01EY005235, R01EY007142,
   P30EY007003, F31EY007003] Funding Source: NIH RePORTER; NEI NIH HHS
   [EY13198, R01 EY007142-12A2, R01 EY007142, EY07003, EY07142, R01
   EY013198, P30 EY007003, F31 EY007003, R01 EY005235] Funding Source:
   Medline
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NR 46
TC 27
Z9 28
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 AUG
PY 2003
VL 44
IS 8
BP 3570
EP 3577
DI 10.1167/iovs.02-1287
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 705EV
UT WOS:000184383500043
PM 12882809
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Han, IC
   Bohrer, LR
   Gibson-Corley, KN
   Wiley, LA
   Shrestha, A
   Harman, BE
   Jiao, CH
   Sohn, EH
   Wendland, R
   Allen, BN
   Worthington, KS
   Mullins, RF
   Stone, EM
   Tucker, BA
AF Han, Ian C.
   Bohrer, Laura R.
   Gibson-Corley, Katherine N.
   Wiley, Luke A.
   Shrestha, Arwin
   Harman, Brynnon E.
   Jiao, Chunhua
   Sohn, Elliott H.
   Wendland, Rion
   Allen, Brittany N.
   Worthington, Kristan S.
   Mullins, Robert F.
   Stone, Edwin M.
   Tucker, Budd A.
TI Biocompatibility of Human Induced Pluripotent Stem Cell-Derived Retinal
   Progenitor Cell Grafts in Immunocompromised Rats
SO CELL TRANSPLANTATION
LA English
DT Article
DE systemic toxicity; autologous cell replacement; subretinal
   transplantation; iPSC-derived retinal cell graft; human retinal
   engineering
ID VISUAL FUNCTION; TRANSPLANTATION; PHOTORECEPTORS; DIFFERENTIATION;
   INTEGRATION; DEGENERATION; SURVIVAL; MODELS; REPAIR
AB Loss of photoreceptor cells is a primary feature of inherited retinal degenerative disorders including age-related macular degeneration and retinitis pigmentosa. To restore vision in affected patients, photoreceptor cell replacement will be required. The ideal donor cells for this application are induced pluripotent stem cells (iPSCs) because they can be derived from and transplanted into the same patient obviating the need for long-term immunosuppression. A major limitation for retinal cell replacement therapy is donor cell loss associated with simple methods of cell delivery such as subretinal injections of bolus cell suspensions. Transplantation with supportive biomaterials can help maintain cellular integrity, increase cell survival, and encourage proper cellular alignment and improve integration with the host retina. Using a pig model of retinal degeneration, we recently demonstrated that polycaprolactone (PCL) scaffolds fabricated with two photon lithography have excellent local and systemic tolerability. In this study, we describe rapid photopolymerization-mediated production of PCL-based bioabsorbable scaffolds, a technique for loading iPSC-derived retinal progenitor cells onto the scaffold, methods of surgical transplantation in an immunocompromised rat model and tolerability of the subretinal grafts at 1, 3, and 6 months of follow-up (n = 150). We observed no local or systemic toxicity, nor did we observe any tumor formation despite extensive clinical evaluation, clinical chemistry, hematology, gross tissue examination and detailed histopathology. Demonstrating the local and systemic compatibility of biodegradable scaffolds carrying human iPSC-derived retinal progenitor cells is an important step toward clinical safety trials of this approach in humans.
C1 [Han, Ian C.; Bohrer, Laura R.; Wiley, Luke A.; Shrestha, Arwin; Harman, Brynnon E.; Jiao, Chunhua; Sohn, Elliott H.; Wendland, Rion; Allen, Brittany N.; Worthington, Kristan S.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.] Univ Iowa, Inst Vis Res, Iowa City, IA USA.
   [Han, Ian C.; Bohrer, Laura R.; Wiley, Luke A.; Shrestha, Arwin; Harman, Brynnon E.; Jiao, Chunhua; Sohn, Elliott H.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.] Univ Iowa, Dept Ophthalmol & Visual Sci, Carver Coll Med, Iowa City, IA USA.
   [Gibson-Corley, Katherine N.] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN USA.
   [Wendland, Rion; Allen, Brittany N.; Worthington, Kristan S.] Univ Iowa, Coll Engn, Dept Biomed Engn, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa; Vanderbilt University;
   University of Iowa
RP Tucker, BA (通讯作者)，Univ Iowa, Inst Vis Res, Dept Ophthalmol & Visual Sci, Carver Coll Med, 375 Newton Rd, Iowa City, IA 52242 USA.
EM budd-tucker@uiowa.edu
FU University of Iowa Institute for Vision Research, University of Iowa,
   Iowa City, IA, USA; Elmer and Sylvia Sramek Charitable Trust, Research
   to Prevent Blindness; National Institutes of Health Grant (NIH;
   Bethesda, MD, USA) [R01 EY 024605, P30 EY025580]
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This work
   was supported by the University of Iowa Institute for Vision Research,
   University of Iowa, Iowa City, IA, USA; the Elmer and Sylvia Sramek
   Charitable Trust, Research to Prevent Blindness; and National Institutes
   of Health Grant (NIH; Bethesda, MD, USA): R01 EY 024605 and P30
   EY025580.
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NR 71
TC 1
Z9 1
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-6897
EI 1555-3892
J9 CELL TRANSPLANT
JI Cell Transplant.
PD JUN
PY 2022
VL 31
AR 09636897221104451
DI 10.1177/09636897221104451
PG 25
WC Cell & Tissue Engineering; Medicine, Research & Experimental;
   Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine; Transplantation
GA 2O7SM
UT WOS:000819254600001
PM 35758274
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Xu, YH
   Feng, YF
   Zou, R
   Yuan, F
   Yuan, YZ
AF Xu, Ya-hui
   Feng, Yi-fan
   Zou, Rong
   Yuan, Fei
   Yuan, Yuan-zhi
TI Silencing of YAP attenuates pericyte-myofibroblast transition and
   subretinal fibrosis in experimental model of choroidal
   neovascularization
SO CELL BIOLOGY INTERNATIONAL
LA English
DT Article
DE extracellular matrix; fibrosis; hypoxia; pericyte-myofibroblast
   transition; Yes-associated protein
ID CELL-CELL ADHESION; MACULAR DEGENERATION; HIPPO PATHWAY; SIZE-CONTROL;
   FILAMIN-A; EXPRESSION; GENE; BETA; ANGIOGENESIS; MIGRATION
AB Age-related macular degeneration (AMD) is the main reason of irreversible vision loss in the elderly. The subretinal fibrosis subsequent to choroidal neovascularization (CNV) is an important feature in the late stage of wet AMD and is considered to be one reason for incomplete response to anti-VEGF drugs. Recent studies have shown that pericyte-myofibroblast transition (PMT) is an important pathological process involving fibrotic diseases of various organs. However, the specific role and mechanism of PMT in the subretinal fibrosis of CNV have not been clarified. It has been clear that the Hippo pathway along with its downstream effector Yes-associated protein (YAP) plays an important role in both epithelial and endothelial myofibroblast development. Therefore, we speculate whether YAP participates in PMT of pericytes and promotes fibrosis of CNV. In this study, experimental CNV was induced by laser photocoagulation in C57BL/6J (B6) mice, and aberrant YAP overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of the laser-injured eyes. YAP knockdown reduced the proliferation, migration, and differentiation of human retinal microvascular pericytes in vitro. It also reduced subretinal fibrosis of laser-induced CNV in vivo. Moreover, by proteomics-based analysis of pericyte conditioned medium (PC-CM) and bioinformatic analyses, we identified that the crosstalk between Hippo/YAP and MAPK/Erk was involved in expression of filamin A in hypoxic pericytes. These findings suggest that Hippo/YAP and MAPK/Erk are linked together to mediate pericyte proliferation, migration as well as differentiation, which may embody potential implications for treatment in diseases related to CNV.
C1 [Xu, Ya-hui; Feng, Yi-fan; Zou, Rong; Yuan, Fei; Yuan, Yuan-zhi] Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.
   [Xu, Ya-hui] Northern Jiangsu Peoples Hosp, Dept Ophthalmol, Yangzhou, Jiangsu, Peoples R China.
   [Yuan, Yuan-zhi] Fudan Univ, Zhongshan Hosp, Xiamen Branch, Dept Ophthalmol, Xiamen 361000, Peoples R China.
C3 Fudan University; Fudan University
RP Zou, R; Yuan, YZ (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.; Yuan, YZ (通讯作者)，Fudan Univ, Zhongshan Hosp, Xiamen Branch, Dept Ophthalmol, Xiamen 361000, Peoples R China.
EM m18300671679@163.com; yuan.yuanzhi@zs-hospital.sh.cn
OI Yuan, Yuan-zhi/0000-0002-5240-3915
FU National Nature Science Foundation of China [81970817, 81873680,
   81600735, 81600703]
FX This study was supported by grants from the National Nature Science
   Foundation of China (Grants 81970817, 81873680, 81600735, and 81600703).
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NR 70
TC 0
Z9 0
U1 2
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-6995
EI 1095-8355
J9 CELL BIOL INT
JI Cell Biol. Int.
PD AUG
PY 2022
VL 46
IS 8
BP 1249
EP 1263
DI 10.1002/cbin.11809
EA APR 2022
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 3C3UC
UT WOS:000787740900001
PM 35475568
DA 2022-11-30
ER

PT J
AU Burgaletto, C
   Platania, CBM
   Di Benedetto, G
   Munafo, A
   Giurdanella, G
   Federico, C
   Caltabiano, R
   Saccone, S
   Conti, F
   Bernardini, R
   Bucolo, C
   Cantarella, G
AF Burgaletto, Chiara
   Platania, Chiara Bianca Maria
   Di Benedetto, Giulia
   Munafo, Antonio
   Giurdanella, Giovanni
   Federico, Concetta
   Caltabiano, Rosario
   Saccone, Salvatore
   Conti, Federica
   Bernardini, Renato
   Bucolo, Claudio
   Cantarella, Giuseppina
TI Targeting the miRNA-155/TNFSF10 network restrains inflammatory response
   in the retina in a mouse model of Alzheimer's disease
SO CELL DEATH & DISEASE
LA English
DT Article
ID UP-REGULATION; NITRIC-OXIDE; EXPRESSION; BETA; NEUTRALIZATION;
   ASTROCYTES; PATHWAY; PLAQUES; GENES; BRAIN
AB Age-related disorders, such as Alzheimer's disease (AD) and age-related macular degeneration (AMD) share common features such as amyloid-beta (A beta) protein accumulation. Retinal deposition of A beta aggregates in AMD patients has suggested a potential link between AMD and AD. In the present study, we analyzed the expression pattern of a focused set of miRNAs, previously found to be involved in both AD and AMD, in the retina of a triple transgenic mouse model of AD (3xTg-AD) at different time-points. Several miRNAs were differentially expressed in the retina of 3xTg-AD mice, compared to the retina of age-matched wild-type (WT) mice. In particular, bioinformatic analysis revealed that miR-155 had a central role in miRNA-gene network stability, regulating several pathways, including apoptotic and inflammatory signaling pathways modulated by TNF-related apoptosis-inducing ligand (TNFSF10). We showed that chronic treatment of 3xTg-AD mice with an anti-TNFSF10 monoclonal antibody was able to inhibit the retinal expression of miR-155, which inversely correlated with the expression of its molecular target SOCS-1. Moreover, the fine-tuned mechanism related to TNFSF10 immunoneutralization was tightly linked to modulation of TNFSF10 itself and its death receptor TNFRSF10B, along with cytokine production by microglia, reactive gliosis, and specific AD-related neuropathological hallmarks (i.e., A beta deposition and Tau phosphorylation) in the retina of 3xTg-AD mice. In conclusion, immunoneutralization of TNFSF10 significantly preserved the retinal tissue in 3xTg-AD mice, suggesting its potential therapeutic application in retinal degenerative disorders.
C1 [Burgaletto, Chiara; Platania, Chiara Bianca Maria; Di Benedetto, Giulia; Munafo, Antonio; Conti, Federica; Bernardini, Renato; Bucolo, Claudio; Cantarella, Giuseppina] Univ Catania, Pharmacol Sect, Dept Biomed & Biotechnol Sci, Sch Med, Catania, Italy.
   [Giurdanella, Giovanni] Univ Catania, Biochem Sect, Dept Biomed & Biotechnol Sci, Sch Med, Catania, Italy.
   [Federico, Concetta; Saccone, Salvatore] Univ Catania, Sect Anim Biol, Dept Biol Geol & Environm Sci, Catania, Italy.
   [Caltabiano, Rosario] Univ Catania, Sect Anat Pathol, Dept Gian Filippo Ingrassia, Catania, Italy.
   [Bernardini, Renato] Univ Catania, Univ Hosp, Clin Toxicol Unit, Catania, Italy.
C3 University of Catania; University of Catania; University of Catania;
   University of Catania; University of Catania
RP Bernardini, R (通讯作者)，Univ Catania, Pharmacol Sect, Dept Biomed & Biotechnol Sci, Sch Med, Catania, Italy.; Bernardini, R (通讯作者)，Univ Catania, Univ Hosp, Clin Toxicol Unit, Catania, Italy.
EM bernardi@unict.it
RI Cantarella, Giuseppina/AHD-9609-2022; Platania, Chiara BM/AHE-1140-2022;
   Burgaletto, Chiara/AHD-9628-2022; Di Benedetto, Giulia/AHE-8905-2022
OI Platania, Chiara Bianca Maria/0000-0002-8630-5993; Burgaletto,
   Chiara/0000-0002-5517-8223; MUNAFO', ANTONIO/0000-0003-1370-2880;
   bernardini, renato/0000-0002-4765-0663; Di Benedetto,
   Giulia/0000-0001-5060-6244
FU Grant PIano inCEntivi RIcerca Ateneo 2020/2022 -Linea Intervento 2
FX This study was supported by Grant PIano inCEntivi RIcerca Ateneo
   2020/2022 -Linea Intervento2.
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NR 71
TC 8
Z9 8
U1 3
U2 7
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD OCT 5
PY 2021
VL 12
IS 10
AR 905
DI 10.1038/s41419-021-04165-x
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA WC0XQ
UT WOS:000703988200006
PM 34611142
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ozkan, J
   Coroneo, M
   Sandbach, J
   Subedi, D
   Willcox, M
   Thomas, T
AF Ozkan, Jerome
   Coroneo, Minas
   Sandbach, Jennifer
   Subedi, Dinesh
   Willcox, Mark
   Thomas, Torsten
TI Bacterial contamination of intravitreal needles by the ocular surface
   microbiome
SO OCULAR SURFACE
LA English
DT Article
DE Intravitreal needle; Bacterial contamination; Ocular microbiome; 16S
   rRNA gene sequencing; Microbiology; Conjunctiva; Age-related macular
   degeneration
AB Purpose: The ocular surface microbiota are recognised as one of causative microorganisms in post-procedural endophthalmitis but in many cases the vitreous tap is culture negative. This study investigated bacterial contamination of intravitreal (IVT) needles using multiple approaches covering culturing, 16S rRNA gene sequencing, fluorescent in situ hybridisation (FISH) and scanning electron microscopy (SEM).
   Methods: IVT needles were obtained immediately after injection from patients undergoing treatment for predominantly age-related macular degeneration. Eighteen needles were analysed by culturing on chocolate blood agar. In addition, 40 needles were analysed by extracting DNA and paired-end sequencing of the 16S rRNA gene. Sequences were quality filtered (USEARCH), taxonomically classified (SILVA) and contaminant filtered (DECONTAM). Nine needles were analysed by either FISH using the bacterial probe EUB338 or SEM.
   Results: Using culturing, three bacteria were identified from 5 of 18 needles (28%) Kocuria kristinae, Staphylococcus hominis and Sphingomonas paucimobilis. The negative control needles showed no growth. Following rigorous data filtering, bacterial community analysis using 16S rRNA gene sequencing showed the presence of predominantly Corynebacterium but also Pseudomonas, Acinetobacter, Sphingomonas, Staphylococcus and Bacillus on the needles. Cocci-shaped cells in a tetrad formation were observed using FISH, while SEM images showed cocci-shaped bacteria in pairs and irregular tetrads.
   Conclusions: The study showed evidence for a large diversity of bacteria on IVT needles and visually confirmed their adherence. The diversity was similar to that found on the ocular surface and in conjunctival tissue. This suggests the risk of exogenous endophthalmitis remains even with sterilization of the conjunctival surface.
C1 [Ozkan, Jerome; Subedi, Dinesh; Willcox, Mark] Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia.
   [Ozkan, Jerome; Thomas, Torsten] Univ New South Wales, Sch Biol Earth & Environm Sci, Sydney, NSW, Australia.
   [Coroneo, Minas; Sandbach, Jennifer] Univ New South Wales, Prince Wales Hosp, Dept Ophthalmol, Sydney, NSW, Australia.
C3 University of New South Wales Sydney; University of New South Wales
   Sydney; University of New South Wales Sydney
RP Ozkan, J (通讯作者)，Lab 263, Biol Sci Bldg D26, Sydney, NSW 2052, Australia.; Ozkan, J (通讯作者)，Sch Optometry & Vis Sci, Lab 3 071, Sydney, NSW 2052, Australia.
EM j.ozkan@unsw.edu.au
RI Subedi, Dinesh/R-1686-2017
OI Subedi, Dinesh/0000-0002-1357-9520; Ozkan, Jerome/0000-0001-6194-1128;
   willcox, mark/0000-0003-3842-7563
FU Faculty of Science Research Grant, University of New South Wales;
   Australian Government National Health and Medical Research Council
   (NHMRC) Peter Doherty Biomedical Fellowship [GNT1112537]
FX This research was supported by a Faculty of Science Research Grant,
   University of New South Wales. JO is supported by an Australian
   Government National Health and Medical Research Council (NHMRC) Peter
   Doherty Biomedical Fellowship (GNT1112537). The contents of the
   published material are solely the responsibility of the authors and do
   not reflect the views of the NHMRC.
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NR 47
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 1542-0124
EI 1937-5913
J9 OCUL SURF
JI Ocul. Surf.
PD JAN
PY 2021
VL 19
BP 169
EP 175
DI 10.1016/j.jtos.2020.05.010
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QE3TK
UT WOS:000616131400019
PM 32497656
DA 2022-11-30
ER

PT J
AU Ji, Z
   Liu, X
   Wang, X
   Ren, Y
   Liu, Y
   Han, SY
   Zhao, JK
   Gou, XC
   He, Y
AF Ji, Zhi
   Liu, Xu
   Wang, Xia
   Ren, Yuan
   Liu, Ying
   Han, Shuangyu
   Zhao, Jingkang
   Gou, Xingchun
   He, Yuan
TI Changes in Mitochondrial Morphology and Mitochondrial Fission/Fusion
   Gene Expression in Retinal Pigment Epithelial Cells During Oxidative
   Stress
SO NANOSCIENCE AND NANOTECHNOLOGY LETTERS
LA English
DT Article
DE Retinal Pigment Epithelium; Mitochondrial Fission/Fusion Gene; Oxidative
   Stress
ID DNA DAMAGE; INCREASED SUSCEPTIBILITY; MACULAR DEGENERATION; FUSION; RPE;
   DYNAMICS; ANTIOXIDANTS; PATHOGENESIS; INFLAMMATION; ENZYMES
AB Age-related macular degeneration (AMD) represents a serious impairment for the elderly. Because the pathogenesis of AMD has not been completely defined, the available therapeutic treatments are not ideal. Retinal pigment epithelial (RPE) cells are essential for photoreceptor cell maintenance and survival; however, the mechanisms underlying RPE cell damage and AMD remains to be elucidated. It is known that abnormal mitochondrial gene expression causes mitochondrial dysfunction, induces cell damage, and results in disease. In this study, ARPE-19 cells were treated with different concentrations of H2O2. It was found that excessive H2O2 concentration resulted in significant contraction of ARPE-19 cells and increased cell death, and destruction of mitochondrial structure as well as membrane and crest. RT-PCR results showed that decreased expression of the Fis1 gene was evident in H2O2-treated cells. There were no significant differences observed among the different H2O2 concentration groups. The expression of the fission genes, MTP18 and Dnmp1, and the fusion genes, Mnf1 and Mnf2, was not significantly different. Real-time PCR results revealed that the expression of the Fis1 gene decreased concomitantly with different concentrations of H2O2, whereas the expression of the Mfn2 gene increased by treatment with 200 mu MH2O2. There were no significant differences in the expression of the other genes. These results indicate that abnormal expression of the mitochondrial Fis1 fission gene, and the Mfn2 fusion gene caused mitochondrial dysfunction in ARPE-19 cells. This indicates that the imbalance of mitochondrial dynamics may contribute to cell death in an oxidative stress environment.
C1 [Ji, Zhi; Liu, Xu; Wang, Xia; Ren, Yuan; Liu, Ying; Han, Shuangyu; Zhao, Jingkang; He, Yuan] Xian Med Univ, Dept Ophthalmol, Affiliated Hosp 2, Xian 710038, Shaanxi, Peoples R China.
   [Gou, Xingchun] Xian Med Univ, Lab Cell Biol & Translat Med, Xian 710021, Shaanxi, Peoples R China.
C3 Xi'an Medical University; Xi'an Medical University
RP He, Y (通讯作者)，Xian Med Univ, Dept Ophthalmol, Affiliated Hosp 2, Xian 710038, Shaanxi, Peoples R China.
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NR 45
TC 0
Z9 0
U1 1
U2 3
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1941-4900
EI 1941-4919
J9 NANOSCI NANOTECH LET
JI Nanosci. Nanotechnol. Lett.
PD OCT
PY 2020
VL 12
IS 10
BP 1192
EP 1199
DI 10.1166/nnl.2020.3229
PG 8
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
   Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science; Physics
GA PV6FB
UT WOS:000610080900007
DA 2022-11-30
ER

PT J
AU Claessen, H
   Kvitkina, T
   Narres, M
   Trautner, C
   Bertram, B
   Icks, A
AF Claessen, Heiner
   Kvitkina, Tatjana
   Narres, Maria
   Trautner, Christoph
   Bertram, Bernd
   Icks, Andrea
TI Markedly decreasing incidence of cause-specific blindness in Saxony
   (Eastern Germany)
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Blindness; Incidence; Germany; Cause-specific blindness; Cause of
   blindness; Time trend
ID MACULAR DEGENERATION; VISUAL IMPAIRMENT; DIABETIC-RETINOPATHY; TRENDS;
   PROJECTIONS; POPULATION; PREVALENCE; PEOPLE
AB Purpose To analyze the recent time trend in Saxony.
   Methods Data were based on administrative files in Saxony (Eastern Germany) to assess recipients of blindness allowance newly registered between January 1, 2009, and December 31, 2017. We estimated age-sex standardized incidence of all-cause and cause-specific blindness and used Poisson regression to examine age- and sex-adjusted time trends.
   Results We identified 5114 new cases of blindness (63.3% female, 59.9% >= 80 years). We observed a markedly decrease in incidence of blindness: all-causes 2009: 15.7 per 100,000 person years [95% confidence interval: 14.6-17.0]; 2017: 8.9 [8.1-9.8]; age-related macular degeneration 2009: 6.9 [6.1-7.7], 2017: 3.8 [3.3-4.3]; glaucoma 2009: 2.6 [2.2-3.1], 2017: 1.8 [1.4-2.2]; diabetic retinopathy 2009: 1.5 [1.2-1.9], 2017: 0.7 [0.5-1.0]; myopia 2009: 0.7 [0.5-1.1], 2017: 0.4 [0.2-0.5]; optic atrophy 2009: 0.9 [0.6-1.2], 2017: 0.5 [0.3-0.7]; and cataract 2009: 0.5 [0.3-0.8], 2017: 0.1 [0.1-0.3]. The annual reduction was between 5 (glaucoma, relative risk 0.95 [0.92-0.98]) and 16% (cataract, relative risk 0.84 [0.78-0.91]).
   Conclusion The age- and sex-standardized incidence of blindness decreased among all common causes of blindness in Saxony in the last decade.
C1 [Claessen, Heiner; Kvitkina, Tatjana; Narres, Maria; Icks, Andrea] German Diabet Ctr, Inst Hlth Serv Res & Hlth Econ, Dusseldorf, Germany.
   [Claessen, Heiner; Kvitkina, Tatjana; Narres, Maria; Icks, Andrea] Heinrich Heine Univ Dusseldorf, Inst Hlth Serv Res & Hlth Econ, Ctr Hlth & Soc, Fac Med, Dusseldorf, Germany.
   [Claessen, Heiner; Kvitkina, Tatjana; Narres, Maria; Icks, Andrea] German Ctr Diabet Res DZD, Munich, Germany.
   [Trautner, Christoph] Med Sci Consulting, Berlin, Germany.
   [Bertram, Bernd] Ophthalmol Off, Aachen, Germany.
C3 Deutsches Diabetes-Zentrum (DDZ); Heinrich Heine University Dusseldorf
RP Claessen, H (通讯作者)，German Diabet Ctr, Inst Hlth Serv Res & Hlth Econ, Dusseldorf, Germany.; Claessen, H (通讯作者)，Heinrich Heine Univ Dusseldorf, Inst Hlth Serv Res & Hlth Econ, Ctr Hlth & Soc, Fac Med, Dusseldorf, Germany.; Claessen, H (通讯作者)，German Ctr Diabet Res DZD, Munich, Germany.
EM heiner.claessen@ddz.de
FU German Federal Ministry of Health [2516DIA001]
FX This study was funded by the German Federal Ministry of Health (grant
   number 2516DIA001). The funding organization had no role in the study
   design, collection, analysis, or interpretation of data.
CR American Academy of Ophthalmology, 2015, AGE RELATED MACULAR
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NR 34
TC 3
Z9 3
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAY
PY 2021
VL 259
IS 5
BP 1089
EP 1101
DI 10.1007/s00417-020-04885-4
EA SEP 2020
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RY3DR
UT WOS:000572627800001
PM 32974733
DA 2022-11-30
ER

PT J
AU Young, BK
   Kovacs, KD
   Adelman, RA
AF Young, Benjamin K.
   Kovacs, Kyle D.
   Adelman, Ron A.
TI Fractal Dimension Analysis of Widefield Choroidal Vasculature as
   Predictor of Stage of Macular Degeneration
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE fractal analysis; choroid; age-related macular degeneration
AB Purpose: To evaluate the fractal dimension (D-f) of the choroidal vasculature using widefield indocyanine green (ICG) angiography and correlate it with the stage of age-related macular degeneration (AMD).
   Methods: Widefield ICG angiography performed on 38 eyes was retrospectively analyzed using the FracLac application within the National Institutes of Health ImageJ software to determine regional fractal dimensions in the macular field and widefield. These values were then associated with a diagnosis of no AMD, non-exudative AMD (subdivided into early/intermediate stage vs. advanced stage), or exudative AMD(subdivided into with or without geographic atrophy). The mean values were compared using Wilcoxon's test.
   Results: Early/intermediate non-exudative AMD and exudative AMD without geographic atrophy were found to have statistically significantly lower D-f values compared to an absence of AMD when examining the macular field. Exudative AMD with geographic atrophy was found to have a statistically significant lower choroidal fractal dimension compared to no AMD when studied in the widefield.
   Conclusions: Advanced stages of macular degeneration were found to have significantly decreased the fractal dimensions of choroidal vasculature on widefield ICG compared to early/intermediate stages, possibly implying a generalized reduction in complexity and/or vessel caliber of the choroid with advancing stage of AMD. This finding agrees with previous understanding of the development of choriocapillaris atrophy in advanced macular degeneration.
   Translational Relevance: These findings suggest that using automated fractal analysis techniques can aid in differentiating stages of macular degeneration and, with further study, may be used to predict advancement of macular degeneration.
C1 [Young, Benjamin K.; Kovacs, Kyle D.; Adelman, Ron A.] Yale Univ, Dept Ophthalmol & Visual Sci, Sch Med, New Haven, CT 06510 USA.
C3 Yale University
RP Adelman, RA (通讯作者)，Yale Univ, Sch Med, Yale Eye Ctr, Dept Ophthalmol & Visual Sci, 40 Temple St, New Haven, CT 06510 USA.
EM ron.adelman@yale.edu
FU American Society of Cataract & Refractive Surgery Foundation; Leir
   Foundation
FX Supported by Grants from the American Society of Cataract & Refractive
   Surgery Foundation and Leir Foundation.
CR Arya M, 2018, EYE VISION, V5, DOI 10.1186/s40662-018-0118-x
   Cheung E, 2009, INVEST OPHTH VIS SCI, V50, P312
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NR 9
TC 0
Z9 0
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2020
VL 9
IS 7
AR 22
DI 10.1167/tvst.9.7.22
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QG6VK
UT WOS:000617722300005
PM 32832228
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nassisi, M
   Shi, Y
   Fan, WY
   Borrelli, E
   Uji, A
   Ip, MS
   Sadda, SR
AF Nassisi, Marco
   Shi, Yue
   Fan, Wenying
   Borrelli, Enrico
   Uji, Akihito
   Ip, Michael S.
   Sadda, Srinivas R.
TI Choriocapillaris impairment around the atrophic lesions in patients with
   geographic atrophy: a swept-source optical coherence tomography
   angiography study
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE macula; retina; imaging; geographic atrophy
ID SPECTRAL-DOMAIN; MACULAR DEGENERATION; SOURCE OCT; IMAGE; THICKNESS;
   DRUSEN; EYES
AB Aims To evaluate the choriocapillaris (CC) flow alterations around geographic atrophy (GA) in eyes with dry age-related macular degeneration. Methods Using a swept-source optical coherence tomography angiography (SS-OCTA) device, two volume 6x6 mm scans were acquired in patients with GA presenting between June and December 2017 at the Doheny-UCLA Eye Centers. The area of GA was delineated on the en face structural OCT fundus images. For each eye, the en face OCTA slabs at the level of the CC from the two acquisitions were averaged and compensated for signal loss using the corresponding structural en face images. The resulting images were binarised and analysed for the percentage of flow voids in the para-atrophy zone (a 500 mu m wide ring around the immediate edge of the atrophy) and in the peri-atrophy zone (a 500 mu m wide ring around the para-atrophy zone edge), the latter considered as a reference in the comparative analysis. Results Thirty eyes of 20 patients were enrolled. The percentage of flow voids in the para-atrophy zone was 27.23%+/- 6.29% and was significantly higher than in the surrounding peri-atrophy zone (23.4%+/- 6.01%; p<0.001). There was no significant correlation between the flow void percentage in these regions and age, visual acuity, extent of the atrophic area or central choroidal thickness. Conclusions A significant impairment of the CC flow is present in the zone immediately surrounding the GA lesions strengthening the hypothesis that CC alterations may be relevant to the progression of GA.
C1 [Nassisi, Marco; Shi, Yue; Fan, Wenying; Borrelli, Enrico; Uji, Akihito; Ip, Michael S.; Sadda, Srinivas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Nassisi, Marco; Shi, Yue; Fan, Wenying; Borrelli, Enrico; Uji, Akihito; Ip, Michael S.; Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Fan, Wenying] Capital Med Univ, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
   [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; Capital Medical
   University; 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.
EM ssadda@doheny.org
RI Borrelli, Enrico/AAR-3693-2020; fan, wenying/GSI-5125-2022; Nassisi,
   Marco/P-9939-2019
OI Borrelli, Enrico/0000-0003-2815-5031; Nassisi, Marco/0000-0002-9354-9005
CR Ahn J, 2018, GRAEF ARCH CLIN EXP, V256, P11, DOI 10.1007/s00417-017-3814-7
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   Choi W, 2015, OPHTHALMOLOGY, V122, P2532, DOI 10.1016/j.ophtha.2015.08.029
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   Yehoshua Z, 2015, OSLI RETINA, V46, P413, DOI 10.3928/23258160-20150422-03
   Yehoshua Z, 2013, OSLI RETINA, V44, P127, DOI 10.3928/23258160-20130313-05
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   Zhang QQ, 2017, INVEST OPHTH VIS SCI, V58, P1506, DOI 10.1167/iovs.16-20977
NR 38
TC 62
Z9 62
U1 1
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2019
VL 103
IS 7
BP 911
EP 917
DI 10.1136/bjophthalmol-2018-312643
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IF4HJ
UT WOS:000473042100008
PM 30131381
OA Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Chirco, KR
   Lewis, CJ
   Scheetz, TE
   Johnston, RM
   Tucker, BA
   Stone, EM
   Fingert, JH
   Mullins, RF
AF Chirco, Kathleen R.
   Lewis, Carly J.
   Scheetz, Todd E.
   Johnston, Rebecca M.
   Tucker, Budd A.
   Stone, Edwin M.
   Fingert, John H.
   Mullins, Robert F.
TI Evaluation of sFLT1 protein levels in human eyes with the FLT1 rs9943922
   polymorphism
SO OPHTHALMIC GENETICS
LA English
DT Article
DE Age-related macular degeneration; choroid; FLT1; retina; VEGF receptor
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; RANIBIZUMAB; BLINDNESS;
   MEMBRANE; THERAPY
AB Purpose: Age-related macular degeneration (AMD) is a devastating disease characterized by central vision impairment in individuals with advanced age. Neovascular AMD is a form of end-stage disease in which choroidal vessel outgrowth occurs beneath the retina. While many hypotheses have been raised as to what triggers the formation of pathological choroidal neovascular membranes, the exact mechanism for their initiation remains unresolved. Polymorphisms in the FLT1 gene have previously been associated with neovascular AMD risk, including the rs9943922 single nucleotide polymorphism (SNP). Here, we aimed to determine the association between the high-risk FLT1 genotype and FLT1 protein levels in human retina or retinal pigment epithelium (RPE)/choroid tissue.
   Methods: Retina and RPE/choroid tissue from 10 human donor eyes was selected from a collection of eyes genotyped for the rs9943922 SNP. Differences in soluble and membrane bound FLT1 protein levels were assessed for retina versus RPE/choroid donor tissue using ELISA and Western blotting analyses. Genotype-associated changes in FLT1 protein levels were also evaluated.
   Results: We found soluble FLT1 levels in the RPE/choroid tissue to be approximately three times higher than that of the retina (p < 0.001), while both samples have similar levels of the membrane bound form. When tissue with the rs9943922 SNP was compared with controls, no significant genotypic differences in FLT1 protein levels were observed.
   Conclusions: Based on these data, we conclude that the rs9943922 SNP in the FLT1 gene does not result in a large difference in FLT1 protein levels, regardless of whether it is the soluble or the membrane bound form.
C1 Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
   Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
C3 University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Stephen A Wynn Inst Vis Res, 375 Newton Rd, Iowa City, IA 52242 USA.
EM Robert-Mullins@uiowa.edu
RI Mullins, Robert F/I-6717-2013; Fingert, John/AAX-4750-2021
OI Fingert, John/0000-0002-0377-0479; van der Heide,
   Carly/0000-0003-1761-8635; Tucker, Budd/0000-0003-2178-1742; Mullins,
   Robert/0000-0002-5006-0891; Scheetz, Todd/0000-0002-1965-5811; Stone,
   Edwin M./0000-0003-3343-4414
FU NIH [EY-024605]; Elmer and Sylvia Sramek Charitable Foundation; NATIONAL
   EYE INSTITUTE [R01EY024605, P30EY025580, R01EY026087, R01EY017673]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [T32GM007337] Funding Source: NIH RePORTER
FX Supported in part by NIH grant EY-024605 and the Elmer and Sylvia Sramek
   Charitable Foundation.
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   Bora NS, 2015, MOL IMMUNOL, V63, P176, DOI 10.1016/j.molimm.2014.07.012
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   Brown DM, 2006, NEW ENGL J MED, V355, P1432, DOI 10.1056/NEJMoa062655
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NR 27
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1381-6810
EI 1744-5094
J9 OPHTHALMIC GENET
JI Ophthalmic Genet.
PY 2018
VL 39
IS 1
BP 68
EP 72
DI 10.1080/13816810.2017.1369550
PG 5
WC Genetics & Heredity; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Ophthalmology
GA GA7MM
UT WOS:000428520500013
PM 28949775
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Van Lancker, L
   Petrarca, R
   Moutsouris, K
   Masaoutis, P
   Kampougeris, G
AF Van Lancker, Lauren
   Petrarca, Robert
   Moutsouris, Kyros
   Masaoutis, Panos
   Kampougeris, George
TI Clinical experience of switching anti-VEGF therapy from ranibizumab to
   aflibercept in age-related choroidal neovascularization
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Anti-VEGF; Intravitreal therapy; Neovascular age-related
   macular degeneration; Ranibizumab
ID MACULAR DEGENERATION; INTRAVITREAL AFLIBERCEPT; BEVACIZUMAB; OUTCOMES;
   EYES; CONVERSION; INJECTION; RECURRENT; FLUID; AMD
AB Purpose: To report the response of participants switching from ranibizumab to aflibercept treatment for neovascular age-related macular degeneration (nAMD) requiring further anti-vascular endothelial growth factor treatment.
   Methods: In this retrospective case review of 68 participants treated in a single hospital, all participants, prior to switching, received ranibizumab injections only. Best-corrected visual acuity (BCVA), clinical examination, and optical coherence tomography (OCT) were performed at each visit. Active nAMD was defined as persistent intraretinal or subretinal fluid on OCT. Participants had their first aflibercept injection at baseline and 2 more injections at 2 monthly intervals. Afterwards, they were followed up every 6-8 weeks and given injections as needed. The main outcome measures were visual acuity and the OCT central retinal thickness (CRT), average thickness (AT), and total macular volume (TMV).
   Results: The BCVA at baseline visit was 0.57 +/- 0.33 log MAR and the final BCVA was 0.54 +/- 0.37 log MAR (p = 0.215). The CRT mean change was -75.6 +/- 85.6 (p = 0.001), the AT mean change was -24.2 +/- 27.2 (p = 0.001), and TMV mean change was -0.69 +/- 0.78 (p = 0.001). There were no significant ophthalmic complications related to treatments.
   Conclusions: Intravitreal aflibercept improved anatomic outcomes (as measured by OCT) in eyes with nAMD that were previously treated with intravitreal ranibizumab and were still active. There was no statistically significant difference in logMAR visual acuity in participants who switched to aflibercept with a follow-up of at least 6 months.
C1 [Van Lancker, Lauren; Petrarca, Robert; Moutsouris, Kyros; Masaoutis, Panos; Kampougeris, George] Moorfields Eye Hosp NHS Trust, Croydon Univ Hosp, Croydon CR7 7YE, Surrey, England.
C3 Croydon University Hospital
RP Kampougeris, G (通讯作者)，Moorfields Eye Hosp NHS Trust, Croydon Univ Hosp, Croydon CR7 7YE, Surrey, England.
EM gkampougeris@yahoo.gr
RI Moutsouris, Kyros/M-8861-2015
OI Moutsouris, Kyros/0000-0001-7301-6589; Petrarca,
   Robert/0000-0001-8693-3423
CR Arcinue CA, 2015, AM J OPHTHALMOL, V159, P426, DOI 10.1016/j.ajo.2014.11.022
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   Martin DF, 2012, OPHTHALMOLOGY, V119, DOI 10.1016/j.ophtha.2012.03.053
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   Sarao V, 2015, RETINA
   Schaal S, 2008, OPHTHALMOLOGY, V115, P2199, DOI 10.1016/j.ophtha.2008.07.007
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NR 21
TC 7
Z9 7
U1 0
U2 2
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-JUN
PY 2017
VL 27
IS 3
BP 342
EP 345
DI 10.5301/ejo.5000861
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EV8RI
UT WOS:000402050000079
PM 27739561
DA 2022-11-30
ER

PT J
AU Ayala-Pena, VB
   Pilotti, F
   Volonte, Y
   Rotstein, NP
   Politi, LE
   German, OL
AF Belen Ayala-Pena, Victoria
   Pilotti, Fiorella
   Volonte, Yanel
   Rotstein, Nora P.
   Politi, Luis E.
   Lorena German, Olga
TI Protective effects of retinoid x receptors on retina pigment epithelium
   cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Retina pigment epithelium cells; Retinoid x receptors; Hydrogen
   peroxide; Oxidative stress; Peroxisome proliferator-activated receptor
ID NF-KAPPA-B; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; MACULAR
   DEGENERATION; HYDROGEN-PEROXIDE; RXR-ALPHA; ACTIVATION; EXPRESSION;
   APOPTOSIS; GAMMA
AB Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and has currently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in the progressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays an important role in this process. We have previously determined that activation of RXRs protects rat photoreceptor neurons from oxidative stress-induced apoptosis. In this study we investigated whether RXR ligands prevented apoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407 cells, promoting p65NE kappa B nuclear translocation, increasing Bax mRNA expression, activating caspase-3 and altering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells from H2O2-induced apoptosis, preventing p65NF kappa B nuclear translocation, increasing Bclxl and PPAR gamma mRNA levels and simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonist blocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist of RXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPAR gamma were protective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-induced apoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPAR gamma. These data also imply that RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Belen Ayala-Pena, Victoria; Pilotti, Fiorella; Volonte, Yanel; Rotstein, Nora P.; Politi, Luis E.; Lorena German, Olga] Univ Nacl Sur UNS CONICET, Dept Biol Bioquim & Farm, Inst Invest Bioquim Bahia Blanca INIBIBB, B8000FWB, Bahia Blanca, Buenos Aires, Argentina.
RP German, OL (通讯作者)，Univ Nacl Sur UNS CONICET, Inst Invest Bioquim Bahia Blanca, B8000FWB, Bahia Blanca, Buenos Aires, Argentina.
EM olgerman@criba.edu.ar
OI Volonte, Yanel Andrea/0000-0002-1214-2562
FU Secretaria de Ciencia y Tecnologia, Universidad Nacional del Sur
   [24/ZB60]; Agencia Nacional Para la Ciencia y Tecnologia (ANPCYT)
   [PICT-2012 2491, PICT-2012 2278]; Subsidio Florencio Fiorini Para
   Investigacion En Ciencias Biomedicas-Academia Nacional de Medicina;
   Consejo Nacional de Investigaciones Cientificas y Tecnicas (PIP)
   [112-201101-00827]
FX This work was supported by funds from: Secretaria de Ciencia y
   Tecnologia, Universidad Nacional del Sur (Grant 24/ZB60, to Olga Lorena
   German, OLG); Agencia Nacional Para la Ciencia y Tecnologia (ANPCYT)
   (PICT-2012 2491, to OLG, PICT-2012 2278, to LEP); Subsidio Florencio
   Fiorini Para Investigacion En Ciencias Biomedicas-Academia Nacional de
   Medicina 2014 (to OLG) and Consejo Nacional de Investigaciones
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NR 77
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 1879-2596
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUN
PY 2016
VL 1863
IS 6
BP 1134
EP 1145
DI 10.1016/j.bbamcr.2016.02.010
PN A
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA DL8IN
UT WOS:000375885800006
PM 26883505
OA Bronze
DA 2022-11-30
ER

PT J
AU Chen, M
   Rajapakse, D
   Fraczek, M
   Luo, C
   Forrester, JV
   Xu, HP
AF Chen, Mei
   Rajapakse, Dinusha
   Fraczek, Monika
   Luo, Chang
   Forrester, John V.
   Xu, Heping
TI Retinal pigment epithelial cell multinucleation in the aging eye - a
   mechanism to repair damage and maintain homoeostasis
SO AGING CELL
LA English
DT Article
DE aging; cytokinesis; multinucleation; phagocytosis; photoreceptor outer
   segments; retinal pigment epithelium
ID MACULAR DEGENERATION; GIANT-CELLS; MACROPHAGE FUSION; OXIDATIVE STRESS;
   MICROGLIA; DISEASE; INFLAMMATION; MICE; ACCUMULATION; CYTOKINESIS
AB Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells invitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate invivo and to repair defects in the monolayer. We further propose that the conventionally accepted "postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.
C1 [Chen, Mei; Rajapakse, Dinusha; Luo, Chang; Xu, Heping] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Med Expt, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
   [Fraczek, Monika; Forrester, John V.] Univ Aberdeen, Sect Immunol & Infect, Div Appl Med, Sch Med & Dent,Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland.
   [Forrester, John V.] Univ Western Australia, Ocular Immunol Program, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
   [Forrester, John V.] Lions Eye Inst, Ctr Expt Immunol, Nedlands, WA 6009, Australia.
C3 Queens University Belfast; University of Aberdeen; University of Western
   Australia; Lions Eye Institute; University of Western Australia
RP Xu, HP (通讯作者)，Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Ctr Med Biol, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM heping.xu@qub.ac.uk
RI Xu, Heping/A-4430-2008
OI Xu, Heping/0000-0003-4000-931X; Rajapakse, Dinusha/0000-0002-5210-6494
FU Fight for Sight [1361/1362, 1425/1426]; Development Trust of the
   University of Aberdeen; Department of Trade and Industry; Office of
   Science and Technology; Chief Scientist Office [ETM/351] Funding Source:
   researchfish; Fight for Sight [1361/62] Funding Source: researchfish
FX The study was funded by Fight for Sight (1361/1362, 1425/1426) and the
   Development Trust of the University of Aberdeen. Dr Heping Xu was a
   Research Council UK (2005-2009) (RCUK) academic fellow funded by the
   Department of Trade and Industry and Office of Science and Technology.
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NR 44
TC 73
Z9 73
U1 1
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD JUN
PY 2016
VL 15
IS 3
BP 436
EP 445
DI 10.1111/acel.12447
PG 10
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA DL8AA
UT WOS:000375860500006
PM 26875723
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lin, SL
AF Lin, Shili
TI Kullback-Leibler divergence for detection of rare haplotype common
   disease association
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID UNCOMMON CAUSAL VARIANTS; LOGISTIC BAYESIAN LASSO; MACULAR DEGENERATION;
   ENVIRONMENT INTERACTION; LINKAGE PHASE; POLYMORPHISM; TRAITS; TESTS;
   SNPS
AB Rare haplotypes may tag rare causal variants of common diseases; hence, detection of such rare haplotypes may also contribute to our understanding of complex disease etiology. Because rare haplotypes frequently result from common single-nucleotide polymorphisms (SNPs), focusing on rare haplotypes is much more economical compared with using rare single-nucleotide variants (SNVs) from sequencing, as SNPs are available and 'free' from already amassed genome-wide studies. Further, associated haplotypes may shed light on the underlying disease causal mechanism, a feat unmatched by SNV-based collapsing methods. In recent years, data mining approaches have been adapted to detect rare haplotype association. However, as they rely on an assumed underlying disease model and require the specification of a null haplotype, results can be erroneous if such assumptions are violated. In this paper, we present a haplotype association method based on Kullback-Leibler divergence (hapKL) for case-control samples. The idea is to compare haplotype frequencies for the cases versus the controls by computing symmetrical divergence measures. An important property of such measures is that both the frequencies and logarithms of the frequencies contribute in parallel, thus balancing the contributions from rare and common, and accommodating both deleterious and protective, haplotypes. A simulation study under various scenarios shows that hapKL has well-controlled type I error rates and good power compared with existing data mining methods. Application of hapKL to age-related macular degeneration (AMD) shows a strong association of the complement factor H (CFH) gene with AMD, identifying several individual rare haplotypes with strong signals.
C1 Ohio State Univ, Dept Stat, Columbus, OH 43210 USA.
C3 Ohio State University
RP Lin, SL (通讯作者)，Ohio State Univ, Dept Stat, 1958 Neil Ave,404 Cokins Hall, Columbus, OH 43210 USA.
EM shili@stat.osu.edu
FU NSF [DMS-1208968]; NATIONAL CANCER INSTITUTE [R03CA171011] Funding
   Source: NIH RePORTER
FX We thank the editor and two anonymous reviewers for their helpful
   comments and suggestions. This work was partially supported by NSF Grant
   DMS-1208968. The MAD data set used for the analyses described in this
   manuscript was obtained from the NEI Study of Age-Related Macular
   Degeneration (NEI-AMD) Database found at
   http://www.ncbi.nlm.nih.gov/gap.
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   Wang M, 2014, BIOINFORMATICS, V30, P2611, DOI 10.1093/bioinformatics/btu347
   Wu MC, 2011, AM J HUM GENET, V89, P82, DOI 10.1016/j.ajhg.2011.05.029
   Zhu XF, 2010, GENET EPIDEMIOL, V34, P171, DOI 10.1002/gepi.20449
NR 26
TC 3
Z9 4
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD OCT
PY 2015
VL 23
IS 11
BP 1558
EP 1565
DI 10.1038/ejhg.2015.25
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CT6IH
UT WOS:000362916200022
PM 25735482
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Azzolini, C
   Torreggiani, A
   Eandi, C
   Donati, S
   Al Oum, M
   Vinciguerra, R
   Bartalena, L
   Tartaglia, V
AF Azzolini, Claudio
   Torreggiani, Aldo
   Eandi, Chiara
   Donati, Simone
   Al Oum, Muna
   Vinciguerra, Riccardo
   Bartalena, Luigi
   Tartaglia, Valerio
TI A teleconsultation network improves the efficacy of anti-VEGF therapy in
   retinal diseases
SO JOURNAL OF TELEMEDICINE AND TELECARE
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; RISK-FACTORS;
   FOLLOW-UP; EYE; DIAGNOSIS
AB We investigated the care of patients with age-related macular degeneration (AMD) managed via a physician-to-physician teleconsultation network for ophthalmology. Eleven groups of ophthalmologists took part in the study. The groups were located in 10 cities across Italy. Each group was based on a Retina Centre located at a university or hospital, with one or two expert ophthalmologists (20 expert ophthalmologists in total). In each region containing a Retina Centre, 6-10 general ophthalmologists (94 ophthalmologists in total) referred patients via the network for a period of three months between June 2011 and December 2012. An automatic grading system quantified the risk of disease progression, and a remote booking system allowed the referring ophthalmologist to make appointments directly with the appropriate Retina Centre. There were 360 network patients and 318 control patients (consecutive patients undergoing usual care during the previous three months). The time delay before therapy was significantly shorter in the network patients (mean 5.5 days) compared with the usual care patients (mean 28.7 days; P < 0.0001). There was a significant improvement in visual acuity in the network patients after treatment (first visit = 0.29 logMAR; after treatment = 0.22 logMAR; P < 0.05). In contrast, there was no improvement in the usual care patients (first visit = 0.29 logMAR; after treatment = 0.27 logMAR; P > 0.05). The telemedicine network allows regional ophthalmologists to quantify the risk of disease progression, and to send patients to a Retina Centre quickly and easily, when required.
C1 [Azzolini, Claudio; Donati, Simone; Al Oum, Muna; Vinciguerra, Riccardo; Tartaglia, Valerio] Univ Insubria, Osped Circolo, Dept Surg & Morphol Sci, Sect Ophthalmol, I-21100 Varese, Italy.
   [Torreggiani, Aldo] Torreggiani & Cancellieri Co, Milan, Italy.
   [Eandi, Chiara] Univ Turin, Dept Ophthalmol, I-10124 Turin, Italy.
   [Bartalena, Luigi] Univ Insubria, Osped Circolo, Dept Clin & Expt Med, Endocrine Unit, I-21100 Varese, Italy.
C3 Ospedale Circolo & Fondazione Macchi; University of Insubria; University
   of Turin; Ospedale Circolo & Fondazione Macchi; University of Insubria
RP Azzolini, C (通讯作者)，Univ Insubria, Osped Circolo, Dept Surg & Morphol Sci, Sect Ophthalmol, Viale Borri 57, I-21100 Varese, Italy.
EM claudio.azzolini@uninsubria.it
RI Donati, Simone/K-4382-2019
OI Donati, Simone/0000-0002-6920-7021; Vinciguerra,
   Riccardo/0000-0002-2280-9981; Azzolini, Claudio/0000-0002-1334-0974;
   Eandi, Chiara Maria/0000-0003-3656-1689
FU Novartis Farma S.p.A. Italy
FX We thank the consulting ophthalmologists at the Retinal Centres and the
   94 general ophthalmologists. We also thank Michael John for his
   assistance. The work was supported by Andrea Marazzi through an
   educational grant from Novartis Farma S.p.A. Italy.
CR Azzolini C, 2011, J TELEMED TELECARE, V17, P20, DOI 10.1258/jtt.2010.100305
   Bressler NM, 2009, OPHTHALMOLOGY, V116, pS15, DOI 10.1016/j.ophtha.2009.06.048
   Brody BL, 2012, OPHTHAL EPIDEMIOL, V19, P190, DOI 10.3109/09286586.2012.672618
   Cook HL, 2008, BRIT MED BULL, V85, P127, DOI 10.1093/bmb/ldn012
   Framme C, 2012, KLIN MONATSBL AUGENH, V229, P812, DOI 10.1055/s-0031-1299405
   Friberg TR, 2012, OPHTHALMOLOGY, V119, DOI 10.1016/j.ophtha.2012.02.048
   Jager RD, 2008, NEW ENGL J MED, V358, P2606, DOI 10.1056/NEJMra0801537
   John S, 2012, TELEMED E-HEALTH, V18, P382, DOI 10.1089/tmj.2011.0190
   Karcic S, 1999, Med Arh, V53, P73
   Lichtinger A, 2012, ISR MED ASSOC J, V14, P363
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   Pece A, 2012, EXPERT REV OPHTHALMO, V7, P219, DOI 10.1586/EOP.12.24
   Quinn GE, 2010, CHINESE MED J-PEKING, V123, P2929, DOI 10.3760/cma.j.issn.0366-6999.2010.20.033
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NR 15
TC 11
Z9 11
U1 0
U2 8
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1357-633X
EI 1758-1109
J9 J TELEMED TELECARE
JI J. Telemed. Telecare
PD DEC
PY 2013
VL 19
IS 8
BP 437
EP 442
DI 10.1177/1357633X13501760
PG 6
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA 263BW
UT WOS:000327782600001
PM 24162839
DA 2022-11-30
ER

PT J
AU Shmueli, RB
   Ohnaka, M
   Miki, A
   Pandey, NB
   Silva, RLE
   Koskimaki, JE
   Kim, J
   Popel, AS
   Campochiaro, PA
   Green, JJ
AF Shmueli, Ron B.
   Ohnaka, Masayuki
   Miki, Akiko
   Pandey, Niranjan B.
   Lima e Silva, Raquel
   Koskimaki, Jacob E.
   Kim, Jayoung
   Popel, Aleksander S.
   Campochiaro, Peter A.
   Green, Jordan J.
TI Long-term suppression of ocular neovascularization by intraocular
   injection of biodegradable polymeric particles containing a
   serpin-derived peptide
SO BIOMATERIALS
LA English
DT Article
DE Angiogenesis; Controlled drug release; Drug delivery; Microsphere;
   Ophthalmology; Peptide
ID CHOROIDAL NEOVASCULARIZATION; CONTROLLED-RELEASE; VEGF-TRAP; DELIVERY;
   ANGIOGENESIS; FORMULATIONS; BEVACIZUMAB; SAFETY; CELLS; GENE
AB Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Shmueli, Ron B.; Pandey, Niranjan B.; Koskimaki, Jacob E.; Kim, Jayoung; Popel, Aleksander S.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA.
   [Shmueli, Ron B.; Kim, Jayoung; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21231 USA.
   [Ohnaka, Masayuki; Miki, Akiko; Lima e Silva, Raquel; Campochiaro, Peter A.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21231 USA.
   [Koskimaki, Jacob E.; Popel, Aleksander S.; Green, Jordan J.] Johns Hopkins Univ, Sch Med, Inst Nanobiotechnol, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   University; Johns Hopkins University
RP Green, JJ (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA.
EM green@jhu.edu
RI Green, Jordan/B-9001-2009; Popel, Aleksander S/A-6724-2009
OI Green, Jordan/0000-0003-4176-3808; Popel, Aleksander/0000-0002-6706-9235
FU Edward N. & Della L. Thome Memorial Foundation (Bank of America,
   Trustee) Awards Program in AMD Research; NIH [1R21EY022986-01,
   R01EY012609]; Wallace H. Coulter Foundation; NATIONAL EYE INSTITUTE
   [R01EY012609, R21EY022986] Funding Source: NIH RePORTER
FX The authors thank the Edward N. & Della L. Thome Memorial Foundation
   (Bank of America, Trustee) Awards Program in AMD Research, the NIH
   (1R21EY022986-01 and R01EY012609), and the Wallace H. Coulter Foundation
   for support of this work.
CR Bressler SB, 2009, OPHTHALMOLOGY, V116, pS1, DOI 10.1016/j.ophtha.2009.06.045
   Campochiaro PA, 2010, OPHTHALMOLOGY, V117, P1393, DOI 10.1016/j.ophtha.2009.11.024
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NR 28
TC 43
Z9 45
U1 1
U2 77
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD OCT
PY 2013
VL 34
IS 30
BP 7544
EP 7551
DI 10.1016/j.biomaterials.2013.06.044
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 198OJ
UT WOS:000322931900033
PM 23849876
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Barteselli, G
   Chhablani, J
   Lee, SN
   Wang, HY
   El Emam, S
   Kozak, I
   Cheng, LY
   Bartsch, DU
   Azen, S
   Freeman, WR
AF Barteselli, Giulio
   Chhablani, Jay
   Lee, Su Na
   Wang, Haiyan
   El Emam, Sharif
   Kozak, Igor
   Cheng, Lingyun
   Bartsch, Dirk-Uwe
   Azen, Stanley
   Freeman, William R.
TI SAFETY AND EFFICACY OF ORAL FLUORESCEIN ANGIOGRAPHY IN DETECTING MACULAR
   EDEMA IN COMPARISON WITH SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE oral fluorescein angiography; spectral-domain optical coherence
   tomography; macular edema
ID SCANNING LASER OPHTHALMOSCOPE; CHOROIDAL NEOVASCULARIZATION; FEATURES;
   LEAKAGE; RETINA
AB Purpose: To evaluate the safety of oral fluorescein angiography (FA) and to compare its efficacy in detection of macular edema (ME) with spectral-domain optical coherence tomography (SD-OCT).
   Methods: Results of imaging studies for 1,928 eyes of 1,019 patients who had simultaneously undergone both oral FA and SD-OCT by a confocal laser ophthalmoscope were reviewed. Sensitivity in detecting ME, discrepancy rate, and "kappa" agreement were determined for both the techniques and with eyes stratified by disease diagnosis.
   Results: No allergic reactions occurred after oral FA. Mild gastric discomfort was noted in <1% of the patients; 1,840 eyes (95.4%) showed concordance between the two techniques, and kappa agreement was 90.3%. For ME, oral FA showed an overall sensitivity of 0.97 and SD-OCT of 0.91. Equivalent sensitivity was found in cases of wet age-related macular degeneration (0.99). Oral FA was more sensitive than SD-OCT in cases of retinovascular diseases. The SD-OCT showed higher sensitivity in cases of macular holes. Detection of ME by SD-OCT was significantly higher in cases of intense leakage on oral FA (P < 0.001).
   Conclusion: Oral FA proved to be a safe and an adequate technique to evaluate ME. It is more sensitive than SD-OCT in detection of ME in cases of retinovascular diseases but can fail to detect ME in cases of macular holes. A noninvasive examination with simultaneous oral FA and SD-OCT may be considered to obtain a comprehensive evaluation of the presence of ME from different pathologies.
C1 [Barteselli, Giulio; Chhablani, Jay; Lee, Su Na; Wang, Haiyan; El Emam, Sharif; Kozak, Igor; Cheng, Lingyun; Bartsch, Dirk-Uwe; Freeman, William R.] Univ Calif San Diego, Shiley Eye Ctr, Jacobs Retina Ctr, Dept Ophthalmol, La Jolla, CA 92037 USA.
   [Barteselli, Giulio] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dipartimento Sci Clin & Comunita, UO Oculist, Milan, Italy.
   [Azen, Stanley] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
C3 University of California System; University of California San Diego;
   IRCCS Ca Granda Ospedale Maggiore Policlinico; University of Milan;
   University of Southern California
RP Freeman, WR (通讯作者)，Univ Calif San Diego, Shiley Eye Ctr, 0946,9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM freeman@eyecenter.ucsd.edu
RI Kozak, Igor/AAC-4645-2019; Emam, Sharif El/AAA-6627-2020
OI Emam, Sharif El/0000-0001-6357-0471; Chhablani, Jay/0000-0003-1772-3558;
   Barteselli, Giulio/0000-0003-0533-1135
FU NIH [R01EY007366, R01EY018589, R01EY020617, R01EY016323]; RPB
   incorporated; Jacobs Retina Center; NATIONAL EYE INSTITUTE [R01EY020617,
   R01EY018589, R01EY007366, R01EY016323, P30EY022589] Funding Source: NIH
   RePORTER
FX Supported by NIH grants R01EY007366 and R01EY018589 (WRF), R01EY020617
   (LC), and R01EY016323 (DUB) and by "RPB incorporated and unrestricted
   funds from Jacobs Retina Center." The funding organizations had no role
   in the design or conduct of this research.
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NR 27
TC 8
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2013
VL 33
IS 8
BP 1574
EP 1583
DI 10.1097/IAE.0b013e318285cd84
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297CP
UT WOS:000330233200012
PM 23584697
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Favret, S
   Binet, F
   Lapalme, E
   Leboeuf, D
   Carbadillo, J
   Rubic, T
   Picard, E
   Mawambo, G
   Tetreault, N
   Joyal, JS
   Chemtob, S
   Sennlaub, F
   SanGiovanni, JP
   Guimond, M
   Sapieha, P
AF Favret, Sandra
   Binet, Francois
   Lapalme, Eric
   Leboeuf, Dominique
   Carbadillo, Jose
   Rubic, Tina
   Picard, Emilie
   Mawambo, Gaelle
   Tetreault, Nicolas
   Joyal, Jean-Sebastien
   Chemtob, Sylvain
   Sennlaub, Florian
   SanGiovanni, John Paul
   Guimond, Martin
   Sapieha, Przemyslaw
TI Deficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer
   retinal lesions
SO AGING-US
LA English
DT Article
DE AMD; GPR91; geographic atrophy; microglia; succinate; metabolite
   receptor
ID PROTEIN-COUPLED RECEPTORS; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   UNITED-STATES; DISEASE; PREVALENCE; DEPOSITS; DRUSEN; CELLS;
   PATHOGENESIS
AB Age-related macular degeneration (AMD) is a prominent cause of blindness in the Western world. To date, its molecular pathogenesis as well as the sequence of events leading to retinal degeneration remain largely ill-defined. While the invasion of choroidal neovasculature in the retina is the primary mechanism that precipitates loss of sight, an earlier dry form may accompany it. Here we provide the first evidence for the protective role of the Retinal Pigment Epithelium (RPE)-resident metabolite receptor, succinate receptor 1 (SUCNR1; G-Protein coupled Receptor-91 (GPR91), in preventing dry AMD-like lesions of the outer retina. Genetic analysis of 925 patients with geographic atrophy and 1199 AMD-free peers revealed an increased risk of developing geographic atrophy associated with intronic variants in the SUCNR1 gene. In mice, outer retinal expression of SUCNR1 is observed in the RPE as well as microglial cells and decreases progressively with age. Accordingly, Sucnr1-/- mice show signs of premature sub-retinal dystrophy with accumulation of oxidized-LDL, abnormal thickening of Bruch's membrane and a buildup of subretinal microglia. The accumulation of microglia in Sucnr1-deficient mice is likely triggered by the inefficient clearance of oxidized lipids by the RPE as bone marrow transfer of wildtype microglia into Sucnr1-/- mice did not salvage the patho-phenotype and systemic lipolysis was equivalent between wild-type and control mice. Our findings suggest that deficiency in SUCNR1 is a possible contributing factor to the pathogenesis of dry AMD and thus broaden our understanding of this clinically unmet need.
C1 [Favret, Sandra; Binet, Francois; Lapalme, Eric; Joyal, Jean-Sebastien; Chemtob, Sylvain; Sapieha, Przemyslaw] Univ Montreal, Res Ctr, Dept Ophthalmol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
   [Lapalme, Eric; Mawambo, Gaelle; Tetreault, Nicolas; Sapieha, Przemyslaw] Univ Montreal, Res Ctr, Dept Biochem, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
   [Leboeuf, Dominique] Univ Montreal, Res Ctr, Dept Immunol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
   [Carbadillo, Jose; Rubic, Tina] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
   [Picard, Emilie] Univ Paris 06, Paris, France.
   [Picard, Emilie] Univ Descartes, Paris, France.
   [Picard, Emilie] 2 INSERM, CRC UMRS872, Team 17, Paris, France.
   [Sennlaub, Florian] INSERM, U968, F-75012 Paris, France.
   [Sennlaub, Florian] CNRS, UMR 7210, Paris, France.
   [Sennlaub, Florian] UPMC Univ Paris 06, UMR S 968, Inst Vis, Paris, France.
   [Sennlaub, Florian] Hop Hotel Dieu, AP HP, Serv Ophtalmol, Ctr Rech Ophtalmol, F-75006 Paris, France.
   [Favret, Sandra; Binet, Francois; SanGiovanni, John Paul] NEI, Clin Trials Branch, Bethesda, MD 20892 USA.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal;
   Novartis; UDICE-French Research Universities; Sorbonne Universite;
   UDICE-French Research Universities; Universite Paris Cite; Institut
   National de la Sante et de la Recherche Medicale (Inserm); UDICE-French
   Research Universities; Universite Paris Cite; Institut National de la
   Sante et de la Recherche Medicale (Inserm); Centre National de la
   Recherche Scientifique (CNRS); CNRS - National Institute for Biology
   (INSB); UDICE-French Research Universities; Universite Paris Cite;
   UDICE-French Research Universities; Sorbonne Universite; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire Hotel-Dieu - APHP;
   UDICE-French Research Universities; Universite Paris Cite; National
   Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
RP Sapieha, P (通讯作者)，Univ Montreal, Res Ctr, Dept Ophthalmol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
EM Mike.Sapieha@umontreal.ca
RI SanGiovanni, John Paul/AAU-3895-2020; Leboeuf, Dominique/U-9674-2017;
   Sennlaub, Florian/F-2756-2017; picard, Emilie/A-6919-2013
OI Sennlaub, Florian/0000-0003-4412-1341; picard,
   Emilie/0000-0002-2689-0510; Leboeuf, Dominique/0000-0001-5386-3510
FU Canada Research Chair in Retinal Cell Biology; Alcon Research Institute
   New Investigator Award; Canadian Institutes of Health Research [221478];
   Canadian Diabetes Association [OG-3-11-3329-PS]; Natural Sciences and
   Engineering Research Council of Canada [418637]; Foundation Fighting
   Blindness Canada; Reseau de Recherche en Sante de la Vision du Quebec;
   Fonds de la Recherche en Sante du Quebec (FRSQ) fellowship;
   Maisonneuve-Rosemont Hospital Foundation
FX PS holds a Canada Research Chair in Retinal Cell Biology and the Alcon
   Research Institute New Investigator Award. This work was supported by
   grants from the Canadian Institutes of Health Research (221478), the
   Canadian Diabetes Association (OG-3-11-3329-PS), the Natural Sciences
   and Engineering Research Council of Canada (418637) and The Foundation
   Fighting Blindness Canada. Support was also provided by the Reseau de
   Recherche en Sante de la Vision du Quebec. FB holds a Fonds de la
   Recherche en Sante du Quebec (FRSQ) fellowship. Additional funding was
   provided by the Maisonneuve-Rosemont Hospital Foundation. We would like
   to thank Johanne Ouellette and Dr. Ribeiro-Da-Silva for electron
   microscopy. We thank Dr. Emily Chew for comments on the manuscript.
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NR 42
TC 23
Z9 25
U1 4
U2 17
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUN
PY 2013
VL 5
IS 6
BP 427
EP 444
DI 10.18632/aging.100563
PG 18
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 195CS
UT WOS:000322679600007
PM 23833031
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Goldstein, JE
   Massof, RW
   Deremeik, JT
   Braudway, S
   Jackson, ML
   Kehler, KB
   Primo, SA
   Sunness, JS
AF Goldstein, Judith E.
   Massof, Robert W.
   Deremeik, James T.
   Braudway, Sonya
   Jackson, Mary Lou
   Kehler, K. Bradley
   Primo, Susan A.
   Sunness, Janet S.
CA Low Vision Res Network Study Grp
TI Baseline Traits of Low Vision Patients Served by Private Outpatient
   Clinical Centers in the United States
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID BLUE-MOUNTAINS-EYE; AGE-RELATED MACULOPATHY; QUALITY-OF-LIFE; BEAVER DAM
   EYE; VISUAL IMPAIRMENT; OLDER-ADULTS; MACULAR DEGENERATION;
   HEARING-LOSS; REHABILITATION SERVICES; COGNITIVE IMPAIRMENT
AB Objective: To characterize the traits of low vision patients who seek outpatient low vision rehabilitation (LVR) services in the United States.
   Methods: In a prospective observational study, we enrolled 764 new low vision patients seeking outpatient LVR services from 28 clinical centers in the United States. Before their initial appointment, multiple questionnaires assessing daily living and vision, physical, psychological, and cognitive health states were administered by telephone. Baseline clinical visual impairment measures and disorder diagnoses were recorded.
   Results: Patients had a median age of 77 years, were primarily female (66%), and had macular disease (55%), most of which was nonneovascular age-related macular degeneration. More than one-third of the patients (37%) had mild vision impairment with habitual visual acuity (VA) of 20/60 or greater. The VA correlated well with contrast sensitivity (r=-0.52) but poorly with self-reported vision quality. The intake survey revealed self-reported physical health limitations, including decreased endurance (68%) and mobility problems (52%). Many patients reported increased levels of frustration (42%) and depressed mood (22%); memory and cognitive impairment (11%) were less frequently endorsed. Patients relied on others for daily living support (87%), but many (31%) still drove.
   Conclusions: Most patients seeking LVR are geriatric and have macular disease with relatively preserved VA. The disparity between VA and subjective quality of vision suggests that LVR referrals are based on symptoms rather than on VA alone. Patients seen for LVR services have significant physical, psychological, and cognitive disorders that can amplify vision disabilities and decrease rehabilitation potential.
C1 [Goldstein, Judith E.; Massof, Robert W.; Deremeik, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Lions Vis Res & Rehabil Ctr, Baltimore, MD 21205 USA.
   [Braudway, Sonya] Ctr Retina & Macular Dis, Winter Haven, FL USA.
   [Jackson, Mary Lou] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
   [Kehler, K. Bradley] Vanderbilt Eye Inst, Nashville, TN USA.
   [Primo, Susan A.] Emory Eye Ctr, Atlanta, GA USA.
   [Sunness, Janet S.] Greater Baltimore Med Ctr, Hoover Low Vis Rehabil Serv, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Harvard University;
   Harvard Medical School; Massachusetts Eye & Ear Infirmary; Vanderbilt
   University; Greater Baltimore Medical Center
RP Goldstein, JE (通讯作者)，Lions Vis Ctr, 6th Floor,550 N Broadway, Baltimore, MD 21205 USA.
EM jgolds28@jhmi.edu
OI Sunness, Janet/0000-0001-8823-0780
FU National Eye Institute, National Institutes of Health [EY012045,
   EY018696]; Reader's Digest Partners for Sight Foundation; Research to
   Prevent Blindness; National Eye Institute [P30EY006360]; NATIONAL EYE
   INSTITUTE [R34EY018696, P30EY006360, R01EY012045] Funding Source: NIH
   RePORTER
FX This study was supported by grants EY012045 and EY018696 from the
   National Eye Institute, National Institutes of Health, and by a grant
   from Reader's Digest Partners for Sight Foundation. Dr Kehler was
   supported by an unrestricted grant from Research to Prevent Blindness.
   Dr Primo was supported in part by an unrestricted departmental grant
   from Research to Prevent Blindness and National Eye Institute Core Grant
   for Vision Research P30EY006360.
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NR 71
TC 60
Z9 62
U1 0
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD AUG
PY 2012
VL 130
IS 8
BP 1028
EP 1037
DI 10.1001/archophthalmol.2012.1197
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 987YU
UT WOS:000307455800011
PM 22893074
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Burt, AJ
   Grainger, CM
   Smid, MP
   Shelp, BJ
   Lee, EA
AF Burt, Andrew J.
   Grainger, Christopher M.
   Smid, Matthew P.
   Shelp, Barry J.
   Lee, Elizabeth A.
TI Allele Mining of Exotic Maize Germplasm to Enhance Macular Carotenoids
SO CROP SCIENCE
LA English
DT Article
ID BETA-CAROTENE; SUBSTRATE-SPECIFICITY; PHYTOENE DESATURASE; MOLECULAR
   MARKERS; GENETIC-VARIATION; VITAMIN-A; IDENTIFICATION; ACCUMULATION;
   CLEAVAGE; PIGMENT
AB Lutein and zeaxanthin are commonly referred to as the macular carotenoids, as they are localized to ocular tissues and their loss is associated with age-related macular degeneration. Thirty-four high-carotenoid (HiC) lines exhibiting uniquely high concentrations of carotenoids resulted from allele mining of the Orange Flint race using traditional breeding techniques and visual selection for deep orange endosperm color. Total carotenoid concentrations of the HiC lines ranged from 50 to 101 mu g g(-1) dry weight (DW) with lutein and zeaxanthin concentrations as high as 66 and 65 mu g g(-1) DW, respectively, levels higher than reported in previous germplasm surveys. The HiC lines fall into three classes based on the accumulation of the major carotenoid: "high-lutein," "high-zeaxanthin," and "balanced." Significant year effects were observed for carotenoid concentrations but not for profiles. During kernel development the pattern of carotenoid accumulation in the HiC lines did not appear to be different than in yellow corn belt dent lines. Collectively, the HiC lines represented only one y1 haplotype, 10 unique haplotypes of lcyE, and two unique haplotypes at crtRB1. Interestingly, previously identified diagnostic polymorphisms within lcyE did not appear to be useful in distinguishing between high-lutein and high-zeaxanthin HiC lines, and high beta-carotene levels were achieved despite the presence of a suboptimal crtRB1 allele. The HiC lines illustrate the utility of mining allelic variation from exotic sources coupled with the power of simple visual selection and the potential limitations of diagnostic polymorphisms.
C1 [Burt, Andrew J.; Grainger, Christopher M.; Smid, Matthew P.; Shelp, Barry J.; Lee, Elizabeth A.] Univ Guelph, Dept Plant Agr, Guelph, ON N1G 2W1, Canada.
C3 University of Guelph
RP Lee, EA (通讯作者)，Univ Guelph, Dept Plant Agr, Crop Sci Bldg, Guelph, ON N1G 2W1, Canada.
EM lizlee@uoguelph.ca
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   [No title captured]
   2010, PLANTS GI BLAST SEAR
NR 72
TC 28
Z9 28
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0011-183X
EI 1435-0653
J9 CROP SCI
JI Crop Sci.
PD MAY
PY 2011
VL 51
IS 3
BP 991
EP 1004
DI 10.2135/cropsci2010.06.0335
PG 14
WC Agronomy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture
GA 752SJ
UT WOS:000289713900009
DA 2022-11-30
ER

PT J
AU Falkenstein, IA
   Cheng, LY
   Jones, TR
   Freeman, WR
   Babson, B
   Kozak, I
   Tammewar, AM
   Barron, EC
AF Falkenstein, Iryna A.
   Cheng, Lingyun
   Jones, Terence R.
   Freeman, William R.
   Babson, Bruce
   Kozak, Igor
   Tammewar, Ajay M.
   Barron, Erin C.
TI Intraocular Properties of a Repository Urokinase Receptor Antagonist
   angstrom 36 Peptide in Rabbits
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Anti-angiogenesis; Ocular drug delivery; Ocular toxicity; Rat CNV model;
   Urokinase receptor antagonist
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; PLASMINOGEN-ACTIVATOR SYSTEM;
   MACULAR DEGENERATION; RETINAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY;
   SUBMACULAR SURGERY; TUMOR-GROWTH; MOUSE MODEL; INHIBITION; CANCER
AB Purpose: To evaluate the intraocular properties of angstrom 36, a peptide that directly antagonizes the cell surface urokinase receptor and so prevents pericellular urokinase plasminogen activator activity.
   Methods: A total of 41 rabbits were used. The toxicity study tested three doses of angstrom 36: 1 mg/eye, 0.3 mg/eye, and 0.1 mg/eye. At 2 and 12 weeks, eyes were evaluated by ERG and histology. Pharmacokinetics were studied in rabbit eyes with the dose of 1 mg/eye in two different formulations: a micronized preparation and a non-micronized formulation. Eyes were enucleated at months 1, 2, 3, 4, and 5. Vitreous, retina, and choroid were collected separately for active angstrom 36 analysis.
   Results: We did not find ocular toxicity with low and medium doses. At the highest dose, there was a transient toxicity at 2 weeks but was not notable at 3 months. The target choroid concentration of angstrom 36 was chosen as >= 100 nM. The micronized formulation at months 1, 2, and 3 combined, showed variable levels in the choroid giving 5/10 (50%) of the therapeutic level; the non-micronized formulation at months 4 and 5 combined, gave 6/7 (86%) of the therapeutic level, although this difference was not statistically significant.
   Conclusion: angstrom 36 appears to be long lasting; the non-micronized formulation of angstrom 36 gave concentrations above therapeutic level in the choroid at months 4 and 5. Optimization of the formulation of angstrom 36, particularly the particle size, may result in a promising new compound for exudative age-related macular degeneration treatment.
C1 [Falkenstein, Iryna A.; Cheng, Lingyun; Freeman, William R.; Kozak, Igor; Tammewar, Ajay M.; Barron, Erin C.] Univ Calif San Diego, Shiley Eye Ctr, Dept Ophthalmol, Joan & Irwin Jacobs Retina Ctr, La Jolla, CA 92037 USA.
   [Jones, Terence R.] Angstrom Pharmaceut Inc, San Diego, CA USA.
   [Babson, Bruce] MicroConstants, San Diego, CA USA.
C3 University of California System; University of California San Diego
RP Cheng, LY (通讯作者)，Univ Calif San Diego, Shiley Eye Ctr, Dept Ophthalmol, Joan & Irwin Jacobs Retina Ctr, 9415 Campus Point Dr, La Jolla, CA 92037 USA.
EM cheng@eyecenter.ucsd.edu
RI Kozak, Igor/AAC-4645-2019
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NR 41
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD AUG
PY 2010
VL 35
IS 8
BP 742
EP 750
DI 10.3109/02713683.2010.486519
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 663PO
UT WOS:000282900000010
PM 20673051
DA 2022-11-30
ER

PT J
AU Nakanishi, H
   Gotoh, N
   Yamada, R
   Yamashiro, K
   Otani, A
   Hayashi, H
   Tsujikawa, A
   Shimada, N
   Ohno-Matsui, K
   Mochizuki, M
   Saito, M
   Saito, K
   Iida, T
   Matsuda, F
   Yoshimura, N
AF Nakanishi, H.
   Gotoh, N.
   Yamada, R.
   Yamashiro, K.
   Otani, A.
   Hayashi, H.
   Tsujikawa, A.
   Shimada, N.
   Ohno-Matsui, K.
   Mochizuki, M.
   Saito, M.
   Saito, K.
   Iida, T.
   Matsuda, F.
   Yoshimura, N.
TI ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal
   neovascularization in highly myopic eyes of the elderly Japanese
   population
SO EYE
LA English
DT Article
DE age-related macular degeneration; myopia; choroidal neovascularization;
   single nucleotide polymorphism; case-control association study; clinical
   genetics
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; HTRA1 PROMOTER
   POLYMORPHISM; MACULAR DEGENERATION; VARIANT INCREASES; Y402H VARIANT;
   SUSCEPTIBILITY; GENE; RISK; LOC387715
AB Purpose The purpose of this study was to investigate whether the genetic risk factors of age-related macular degeneration (AMD) are associated with the development of choroidal neovascularization (CNV) in highly myopic eyes of elderly Japanese.
   Methods Highly myopic elderly Japanese patients with and without CNV were genotyped for three AMD-associated single nucleotide polymorphisms (SNPs), namely rs10490924 (A69S) of ARMS2, rs11200638 of HTRA1, and rs1061170 (Y402H) of complement factor H (CFH), with the TaqMan SNP assay. One hundred and eighty-three unrelated highly myopic (axial lengths >26.00 mm or refractive errors > -6.0 diopters) Japanese patients with CNV who were >= 50 years of age (mean age +/- standard deviation of 62.7 +/- 6.3 years) and 170 highly myopic patients without CNV who were >= 50 years old (62.3 +/- 7.1 years) were studied. The differences in the genotypic distributions for the three SNPs between the two groups were tested with the Trend chi(2) test, and logistic regression analyses were performed for age and gender adjustment.
   Results No significant difference was detected in the distribution of the three SNPs, rs10490924 (P>0.1), rs11200638 (P>0.1), and rs1061170 (P>0.5), between the two groups even after adjustments for age and gender differences.
   Conclusion The genetic risk factors of AMD related to these SNPs do not contribute significantly to the development of CNV in a highly myopic elderly Japanese population. Eye (2010) 24, 1078-1084; doi: 10.1038/eye.2009.215; published online 14 August 2009
C1 [Nakanishi, H.] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Kyoto 6068507, Japan.
   [Nakanishi, H.; Gotoh, N.; Yamada, R.; Hayashi, H.; Matsuda, F.] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto 6068507, Japan.
   [Yamada, R.] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Tokyo, Japan.
   [Shimada, N.; Ohno-Matsui, K.; Mochizuki, M.] Tokyo Med & Dent Univ, Grad Sch, Dept Ophthalmol & Visual Sci, Tokyo, Japan.
   [Saito, M.; Saito, K.; Iida, T.] Fukushima Med Univ, Dept Ophthalmol, Fukushima, Japan.
   [Matsuda, F.] Ctr Natl Genotypage, Evry, France.
C3 Kyoto University; Kyoto University; University of Tokyo; Tokyo Medical &
   Dental University (TMDU); Fukushima Medical University; CEA;
   UDICE-French Research Universities; Universite Paris Saclay
RP Nakanishi, H (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, Shogoinkawaharacho 54, Kyoto 6068507, Japan.
EM hideon@kuhp.kyoto-u.ac.jp
RI Matsuda, Fumihiko/B-9893-2009; Saito, Masaaki/ABI-2783-2020
OI Saito, Masaaki/0000-0003-1494-6350; Yamashiro,
   Kenji/0000-0001-9354-8558; Yamada, Ryo/0000-0002-1587-630X; Tsujikawa,
   Akitaka/0000-0003-0779-7799
FU Ministry of Education, Culture, Sports, Science, and Technology of
   Japan; Japanese National Society for the Prevention of Blindness
FX The study was supported in part by the Ministry of Education, Culture,
   Sports, Science, and Technology of Japan and by the Japanese National
   Society for the Prevention of Blindness.
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NR 49
TC 16
Z9 16
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JUN
PY 2010
VL 24
IS 6
BP 1078
EP 1084
DI 10.1038/eye.2009.215
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 608YX
UT WOS:000278623000023
PM 19680273
OA Bronze
DA 2022-11-30
ER

PT J
AU De Marco, R
   Aurilia, P
   Mele, A
AF De Marco, Rocco
   Aurilia, Pasquale
   Mele, Alessandro
TI Massive spontaneous choroidal hemorrhage in a patient with chronic renal
   failure and coronary artery disease treated with Plavix
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Choroidal hemorrhage; Chronic renal failure; Evacuative sclerotomy;
   Plavix
ID SUPRACHOROIDAL HEMORRHAGE; CLOPIDOGREL; SECONDARY; ASPIRIN
AB PURPOSE. To report a case of massive spontaneous choroidal hemorrhage in a patient with chronic renal failure and coronary artery disease treated with clopidogrel bisulfate ( Plavix).
   METHODS. Case report.
   RESULTS. A 75-year-old man presented with pain and loss of vision in the left eye for 1 week. His medical history was remarkable for systemic hypertension, chronic renal failure, and artery coronary disease. For 6 months, he had been taking 75 mg/day of Plavix after coronary angioplasty. Ocular examination revealed the patient to be in angle closure. Ultrasonography and computed tomography scan revealed a massive choroidal hemorrhage pushing the iris-lens diaphragm forward. Pain and intraocular pressure were treated successfully with evacuative sclerotomies, but the final exitus after 6 months was bulbar phthisis.
   CONCLUSIONS. Massive spontaneous choroidal hemorrhage is an extremely rare event that usually has been described in older patients (65-87 years old) receiving anticoagulants or thrombolytic agents. Systemic hypertension, generalized atherosclerosis, and age-related macular degeneration are additional risk factors. In the present case, massive choroidal hemorrhage was associated with use of clopidogrel bisulfate (Plavix) in a patient with chronic renal failure. Our report indicates that Plavix should be administered with caution in patients with chronic renal failure owing to the risk of serious choroidal bleeding. Chronic renal failure should be also included in the list of risk factors for massive spontaneous choroidal hemorrhage. Evacuative sclerotomies may have value in the relief of pain and elevated intraocular pressure but has not been shown to be beneficial in visual and anatomic outcomes. (Eur J Ophthalmol 2009; 19: 883-6)
C1 [De Marco, Rocco; Aurilia, Pasquale; Mele, Alessandro] Cardinale Ascalesi Hosp ASLNA1, Dept Ophthalmol, Naples, Italy.
RP De Marco, R (通讯作者)，Via Spirito Santo 17, I-80049 Somma Vesuviana, NA, Italy.
EM roccodemarco@tin.it
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NR 8
TC 10
Z9 11
U1 0
U2 1
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1120-6721
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD SEP-OCT
PY 2009
VL 19
IS 5
BP 883
EP 886
DI 10.1177/112067210901900534
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 520LF
UT WOS:000271845100033
PM 19787616
DA 2022-11-30
ER

PT J
AU Leung, KW
   Barnstable, CJ
   Tombran-Tink, J
AF Leung, Kar Wah
   Barnstable, Colin J.
   Tombran-Tink, Joyce
TI Bacterial endotoxin activates retinal pigment epithelial cells and
   induces their degeneration through IL-6 and IL-8 autocrine signaling
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Cytokine; Cytokine receptor; Inflammation; Lipopolysaccharide; Retinal
   degenerative diseases; Retinal pigment epithelial cells
ID GROWTH-FACTOR-BETA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MESSENGER-RNA
   EXPRESSION; NITRIC-OXIDE; INDUCED UVEITIS; AQUEOUS-HUMOR; INFLAMMATORY
   MEDIATORS; CELLULAR-LOCALIZATION; IMMUNE PRIVILEGE; GENE-EXPRESSION
AB Inflammation is a major contributing factor to many blinding disorders including uveitis, diabetic retinopathy, and age-related macular degeneration. Here we examined the response of the retinal pigment epithelium (RPE) to physiological levels of lipopolysaccharide (LPS) to understand the role of this epithelium in inflammatory retinal conditions. Expression of a group of inflammatory mediators was identified by gene array analysis and confirmed by PCR and immunocytochemistry in primary human RPE cultures and ARPE19. The effects of LPS on the expression of these cytokines and RPE survival were examined by PCR, Luminex bead, and MTT assays. RPE cells express many cytokine receptors including IL-1R, -4R, -6R, -8RA, IFNAR1, IFNGR1/2 and secrete a range of pro- and anti-inflammatory cytokines including IL-4,-6,-8,-10,-17, IFN-gamma, MCP-1, and VEGF. LPS increases IL-13RA1 and IFNAR1, and decreases IL-7R receptor expression. It also increases RPE secretion of IL-4,-6,-8, -10, IFN-gamma and MCP-1, and is toxic to RPE cells at LC50 = 17.7 mu g/ml. LPS toxicity is mediated by IL-6 and IL-8 through an autocrine feedback loop. Silencing IL-6R and IL-8RA gene expression by siRNA blocks death by their respective ligands or LPS. These findings imply that RPE cells are acutely sensitive to inflammatory stress and that over secretion of IL-6 and IL-8 by this epithelium during inflammatory stimulus may be an underlying factor in the progression of some retinal pathologies. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Leung, Kar Wah; Barnstable, Colin J.; Tombran-Tink, Joyce] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA USA.
   [Barnstable, Colin J.; Tombran-Tink, Joyce] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE);
   Pennsylvania State University; Penn State Health; Yale University
RP Tombran-Tink, J (通讯作者)，Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA USA.
EM Jttink@aol.com
RI Barnstable, Colin/ABB-4822-2021; Barnstable, Colin/GLU-9219-2022; Leung,
   Kar Wah/I-3844-2012
OI Barnstable, Colin/0000-0002-7011-4068
FU Ben Franklin Award; David Woods Kemper Foundation
FX This study was supported by the Ben Franklin Award and the David Woods
   Kemper Foundation.
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NR 83
TC 80
Z9 90
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD APR
PY 2009
VL 46
IS 7
BP 1374
EP 1386
DI 10.1016/j.molimm.2008.12.001
PG 13
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA 435CS
UT WOS:000265321600011
PM 19157552
DA 2022-11-30
ER

PT J
AU Zhong, M
   Molday, LL
   Molday, RS
AF Zhong, Ming
   Molday, Laurie L.
   Molday, Robert S.
TI Role of the C Terminus of the Photoreceptor ABCA4 Transporter in Protein
   Folding, Function, and Retinal Degenerative Diseases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STARGARDT MACULAR DYSTROPHY; CONE-ROD DYSTROPHY; GENE ABCR;
   RETINITIS-PIGMENTOSA; TANGIER-DISEASE; RIM PROTEIN; SYNTHETIC PEPTIDES;
   CHOLESTEROL EFFLUX; MEMBRANE TOPOLOGY; LOCALIZATION
AB ABCA4 is an ATP-binding cassette transporter that is expressed in rod and cone photoreceptor cells and implicated in the removal of retinal derivatives from outer segments following photoexcitation. Mutations in the ABCA4 gene are responsible for a number of related retinal degenerative diseases, including Stargardt macular degeneration, cone-rod dystrophy, retinitis pigmentosa, and age-related macular degeneration. In order to determine the role of the C terminus of ABCA4 in protein structure and function and understand mechanisms by which C-terminal mutations cause retinal degenerative diseases, we have expressed and purified a series of deletion and substitution mutants of ABCA4 and ABCA1 in HEK 293T cells for analysis of their cellular localization and biochemical properties. Removal of the C-terminal 30 amino acids of ABCA4, including a conserved VFVNFA motif, resulted in a loss in N-retinylidene-phosphatidylethanolamine substrate binding, ATP photoaffinity labeling, and retinal-stimulated ATPase activity. This mutant was also retained in the endoplasmic reticulum of cells. Replacement of the VFVNFA motif with alanine residues also resulted in loss in function and cellular mislocalization. In contrast, C-terminal deletion mutants that retain the VFVNFA motif were functionally active and localized to intracellular vesicles similar to wild-type ABCA4. Our studies indicated that the VFVNFA motif is required for the proper folding of ABCA4 into a functionally active protein. This motif also contributes to the efficient folding of ABCA1 into an active protein. Our results provide a molecular based rationale for the disease phenotype displayed by individuals with mutations in the C terminus of ABCA4.
C1 [Molday, Robert S.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
   Univ British Columbia, Dept Ophthalmol & Visual Sci, Ctr Macular Res, Vancouver, BC V6T 1Z3, Canada.
C3 University of British Columbia; University of British Columbia
RP Molday, RS (通讯作者)，Univ British Columbia, Dept Biochem & Mol Biol, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada.
EM molday@interchange.ubc.ca
FU Canadian Institutes for Health Research [MT5822]; University of British
   Columbia
FX This work was supported by Canadian Institutes for Health Research Grant
   MT5822. The costs of publication of this article were defrayed in part
   by the payment of page charges. This article must therefore be hereby
   marked "advertisement" in accordance with 18 U. S. C. Section 1734
   solely to indicate this fact.; Supported by a University of British
   Columbia predoctoral studentship.
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NR 42
TC 40
Z9 40
U1 0
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 6
PY 2009
VL 284
IS 6
BP 3640
EP 3649
DI 10.1074/jbc.M806580200
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 400MO
UT WOS:000262872500032
PM 19056738
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Jiang, W
   Ko, WC
   Hsiao, SH
   Chiou, GCY
AF Jiang, Wei
   Ko, Wun-Chang
   Hsiao, Shu-Huei
   Chiou, George C. Y.
TI Effect of Z,E-butylidedephthalide on experimental choroidal
   neovascularization in rat and ocular blood flow in rabbits
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Z,E-butylidedephthalide; choroid; neovascularization; blood flow;
   age-related macular degeneration
AB AIM: To investigate the effect of Z,E-butylidedephthalide (Bdph)on laser-induced experimental choroidal neovascularization (CNV) in rat model and choroid blood flow in rabbits' eyes.
   METHODS: Male Brown Norway rats were treated with Nd: YAG laser to break Bruch's membrane. 30mg/kg and 15mg/kg Bdph were given daily through intraperitoneal injection for 4 weeks after laser treatment. Fluorescein angiography (FA) and choroidal flat mount were used to measure the development of CNV. Female New Zealand white rabbits' eyes were instilled with 10g/L Z,E-BdPh solution, and ocular blood flow was measured with colored microsphere technique.
   RESULTS: The intensity of fluorescein leakage, indicating the ocular lesion, decreased significantly in group Bdph 30mg/kg and 15mg/kg, as compared to the control at P<0.01. The area of neovascularization checked by FA in both groups of Bdph, at 30mg/kg and 15mg/kg decreased significantly compared to the control group at P<0.05. On the choroid flat mount, the areas of CNV were also smaller in both Bdph groups than that in control group. One percent drug solution instilled into rabbits eyes could improve the choroid blood flow at 30 and 60 minutes after drug instillation ( P<0.05).
   CONCLUSION: Z,E-butylidedephthalide can inhibit the development of CNV in the rat eyes and increase the choroid blood flow in the rabbit eyes. These results suggest that Z, E-butylidedephthalide may be a good agent for the treatment of age-related macular degeneration (AMD).
C1 [Jiang, Wei; Chiou, George C. Y.] Texas A&M Univ Syst Hlth Sci Ctr, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
   [Jiang, Wei; Chiou, George C. Y.] Texas A&M Univ Syst Hlth Sci Ctr, Dept Neurosci & Expt Therapeut, College Stn, TX 77843 USA.
   [Ko, Wun-Chang] Taipei Med Univ, Grad Inst Med Sci, Taipei 110, Taiwan.
   [Ko, Wun-Chang] Taipei Med Univ, Sch Pharm, Taipei 110, Taiwan.
   [Hsiao, Shu-Huei] Natl Chung Cheng Univ, Coll Sci, Dept Life Sci, Chiayi, Taiwan.
C3 Texas A&M University System; Texas A&M University College Station; Texas
   A&M Health Science Center; Texas A&M University System; Texas A&M
   University College Station; Texas A&M Health Science Center; Taipei
   Medical University; Taipei Medical University; National Chung Cheng
   University
RP Chiou, GCY (通讯作者)，Texas A&M Univ Syst Hlth Sci Ctr, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
EM chiou@medicine.tamhsc.edu
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NR 14
TC 0
Z9 0
U1 0
U2 1
PU IJO PRESS
PI XI AN
PA NO 269 YOUYI EAST RD, XI AN, 710054, PEOPLES R CHINA
SN 2222-3959
EI 2227-4898
J9 INT J OPHTHALMOL-CHI
JI Int. J. Ophthalmol.
PD DEC 18
PY 2008
VL 1
IS 4
BP 293
EP 296
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V13QZ
UT WOS:000207682600002
DA 2022-11-30
ER

PT J
AU Wu, JM
   Seregard, S
   Algvere, PV
AF Wu, Jiangmei
   Seregard, Stefan
   Algvere, Peep V.
TI Photochemical damage of the retina
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE age-related macular degeneration; blue light; chromophore; light
   exposure; optical radiation; photochemical damage; photo-oxidation;
   photoreceptor; retina; retinal pigment epithelium
ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; LIGHT-INDUCED DAMAGE;
   SENILE MACULAR DEGENERATION; BLUE MOUNTAINS EYE; FIBROBLAST
   GROWTH-FACTOR; OUTER-SEGMENT MEMBRANE; SHORT-WAVELENGTH LIGHT; N-3
   FATTY-ACIDS; RAT RETINA
AB Visual perception occurs when radiation with a wavelength between 400 and 760 nm reaches the retina. The retina has evolved to capture photons efficiently and initiate visual transduction. The retina, however, is vulnerable to damage by light, a vulnerability that has long been recognized. Photochemical damage has been widely studied, because it can cause retinal damage within the intensity range of natural light. Photochemical lesions are primarily located in the outer layers at the central region of the retina. Two classes of photochemical damage have been recognized: Class I damage, which is characterized by the rhodopsin action spectrum, is believed to be mediated by Visual pigments, with the primary lesions located in the photoreceptors; whereas Class 11 damage is generally confined to the retinal pigment epithelium. The action spectrum peaks in the short wavelength region, providing the basis for the concept of blue light hazard. Several factors can modify the susceptibility of the retina to photochemical damage. Photochemical mechanisms, in particular mechanisms that arise from illumination with blue light, are responsible for solar retinitis and for iatrogenic retinal insult from ophthalmological instruments. Further, blue light may play a role in the pathogenesis of age-related macular degeneration. Laboratory studies have suggested that photochemical damage includes oxidative events. Retinal cells die by apoptosis in response to photic injury, and the process of cell death is operated by diverse damaging mechanisms. Modern molecular biology techniques help to study in-depth the basic mechanism of photochemical damage of the retina and to develop strategies of neuroprotection.
C1 St Eriks Eye Hosp, Karolinska Inst, Dept Vitreoretinal Dis, SE-11282 Stockholm, Sweden.
C3 Karolinska Institutet
RP Wu, JM (通讯作者)，St Eriks Eye Hosp, Karolinska Inst, Dept Vitreoretinal Dis, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
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NR 301
TC 241
Z9 265
U1 2
U2 79
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6257
EI 1879-3304
J9 SURV OPHTHALMOL
JI Surv. Ophthalmol.
PD SEP-OCT
PY 2006
VL 51
IS 5
BP 461
EP 481
DI 10.1016/j.survophthal.2006.06.009
PG 21
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 089KR
UT WOS:000240880000002
PM 16950247
DA 2022-11-30
ER

PT J
AU Watson, GR
   Maino, J
   De l'Aune, W
AF Watson, GR
   Maino, J
   De l'Aune, W
TI Comparison of low-vision reading with spectacle-mounted magnifiers
SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT
LA English
DT Article
DE diffraction; literacy; low vision; magnifier; optical devices; optics;
   reading; refraction; spectacle; vision rehabilitation
ID IMPAIRED VISION; COMPREHENSION; DEPRESSION; DISABILITY
AB Reading is the most common goal among persons with age-related macular degeneration and other retinal diseases that lead to macular loss, as well as the functional task most affected by the resulting central scotomas. This project determined whether reading ability is different when persons with macular loss read with a new hybrid-diffractive spectacle magnifier versus a refractive-aspheric spectacle magnifier and an aplanatic spectacle magnifier. After Subjects completed a low-vision examination, we assigned them to groups that compared different types of spectacle magnifiers and assessed their reading acuity, speed, critical print size (print size large enough to provide a subject's best fluent reading), accuracy, and comprehension. Subjects completed visual analog scales to indicate their perceptions of satisfaction with reading, comfort with reading, and cosmesis (comfort with allowing others to see them read) and were asked which of the compared spectacle magnifiers they preferred for prescription. We subjected the data to paired t-tests to ascertain whether differences existed in subjects' reading ability and perceptions between the types of reading devices. Subjects' reading comprehension, perception of satisfaction, and perception of cosmesis were significantly better with the hybrid-diffractive lens than with the refractiveaspheric lens. Although subjects' critical print size was significantly better with the aplanatic lens than with the hybrid-diffractive lens, functional reading ability was not significantly different. More subjects preferred the hybrid-diffractive lenses for prescription. The hybrid-diffractive spectacle magnifiers are an important addition to the optical-device armamentarium for reading with low vision.
C1 Altanta Dept Vet Affairs VA Med Ctr, Ctr Aging & Vis Loss, Atlanta, GA USA.
   Kansas City VA Med Ctr, Kansas City, KS USA.
   Atlanta Res & Educ Fdn, Atlanta, GA USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Atlanta VA Health Care System
RP Watson, GR (通讯作者)，Atlanta VA Med Ctr, 151-R,1600 Clairmont Rd, Atlanta, GA 30033 USA.
EM Gale.Watson@med.va.gov
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NR 27
TC 6
Z9 7
U1 0
U2 3
PU JOURNAL REHAB RES & DEV
PI BALTIMORE
PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET,
   BALTIMORE, MD 21202-4051 USA
SN 0748-7711
EI 1938-1352
J9 J REHABIL RES DEV
JI J. Rehabil. Res. Dev.
PD JUL-AUG
PY 2005
VL 42
IS 4
BP 459
EP 469
DI 10.1682/JRRD.2004.11.0137
PG 11
WC Rehabilitation
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Rehabilitation
GA 995NB
UT WOS:000234105900010
PM 16320142
DA 2022-11-30
ER

PT J
AU Nirmal, J
   Barathi, VA
   Dickescheid, A
   Wey, YS
   Nirmal, S
   Raja, MM
   Venkatraman, S
   Agrawal, R
AF Nirmal, Jayabalan
   Barathi, Veluchamy A.
   Dickescheid, Andreas
   Wey, Yeo Sia
   Nirmal, Sonali
   Raja, Miguel Moreno
   Venkatraman, Subbu
   Agrawal, Rupesh
TI Potential of subconjunctival aflibercept in treating choroidal
   neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Subconjunctival; Aflibercept; Vascular endothelial growth factor (VEGF);
   Pharmacokinetics; Efficacy; Choroidal neovascularization
ID NEONATAL FC-RECEPTOR; PHARMACOKINETICS; DELIVERY; PROTEIN; AGE;
   PERMEABILITY; RANIBIZUMAB; BEVACIZUMAB; PENETRATION; STABILITY
AB The study aimed to evaluate the intraocular pharmacokinetics and efficacy of aflibercept after subconjunctival injection in animal models for treating choroidal neovascularization (CNV) associated with Age-Related Macular Degeneration (AMD). New Zealand albino rabbits received aflibercept (2000 mu g/50 mu l) in one eye, and the other eye was used as control. At 7, 14, 21 and 28 days, the animals were sacrificed to dissect the ocular tissues, and serum was collected at lhr, 3 h, 1, 7, 14, 21 and 28 days. The concentration of aflibercept in various ocular tissues and serum were measured using the immunoassay technique. The concentration maximum (C-max) at the Retinal Pigment Epithelium (RPE)-choroid complex and retina in treated eyes was 261.55 and 33.83 ng/gm, respectively. The area under the curve (ALIC(0-last)) for RPE-Choroid and retina were 2094.02 and 290.33 days. ng/gm respectively. The time maximum (T-max) for the ocular tissues was reached on day 7. In the vitreous humour, a lower level of aflibercept was retrieved. The C-max (1766.84 ng/mL) in the serum was reached on day 1, followed by a decline in the concentration till the end of the study period. In treated eyes, the levels of aflibercept in most of the ocular tissues were maintained for at least 21 days above the invitro IC50 concentration. The results of the efficacy study show that subconjunctival aflibercept could reach the therapeutic target to inhibit CNV. The subconjunctival aflibercept could be a less invasive route for treating CNV with AMD.
C1 [Nirmal, Jayabalan] Birla Inst Technol & Sci, Dept Pharm, Translat Pharmaceut Lab, Hyderabad Campus, Hyderabad, India.
   [Nirmal, Jayabalan; Dickescheid, Andreas; Nirmal, Sonali; Raja, Miguel Moreno; Venkatraman, Subbu; Agrawal, Rupesh] Nanyang Technol Univ, Northwestern Inst Nanomed, Sch Mat Sci & Engn, Singapore, Singapore.
   [Barathi, Veluchamy A.; Wey, Yeo Sia; Agrawal, Rupesh] Singapore Eye Res Inst, Singapore, Singapore.
   [Barathi, Veluchamy A.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Barathi, Veluchamy A.] DUKE NUS Grad Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
   [Agrawal, Rupesh] Tan Tock Seng Hosp, Singapore, Singapore.
C3 Birla Institute of Technology & Science Pilani (BITS Pilani); Nanyang
   Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; National University of
   Singapore; Singapore National Eye Center; National University of
   Singapore; National University of Singapore; Tan Tock Seng Hospital
RP Agrawal, R (通讯作者)，Tan Tock Seng Hosp, Natl Healthcare Grp, Dept Ophthalmol, Eye Inst, Singapore 308433, Singapore.; Nirmal, J (通讯作者)，Birla Inst Technol & Sci Pilani, Dept Pharm, Hyderabad Campus, Hyderabad, Telangana, India.
EM nirmaljayabalan@gmail.com; Rupesh_agrawal@ttsh.com.sg
RI J, Nirmal/AAO-5138-2020
OI J, Nirmal/0000-0001-7864-6053
FU National Thematic Research Grant; Ageing Research Grant;
   NMRC/CG-INCEPTOR/Pre-Clinical Core Platform/2017_SERI
FX The project was funded by the National Thematic Research Grant and the
   Ageing Research Grant administered by National Healthcare Group,
   Singapore. Dr Rupesh Agrawal is the Principal clinical investigator, and
   Prof Subbu Venkatraman is the Principal technical investigator, and
   pre-clinical facility and equipment were supported by
   NMRC/CG-INCEPTOR/Pre-Clinical Core Platform/2017_SERI to VAB.
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NR 28
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 OCT
PY 2020
VL 199
AR 108187
DI 10.1016/j.exer.2020.108187
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OH0ED
UT WOS:000582245300016
PM 32795527
DA 2022-11-30
ER

PT J
AU Kusunose, N
   Akamine, T
   Kobayashi, Y
   Yoshida, S
   Kimoto, K
   Yasukochi, S
   Matsunaga, N
   Koyanagi, S
   Ohdo, S
   Kubota, T
AF Kusunose, Naoki
   Akamine, Takahiro
   Kobayashi, Yoshiyuki
   Yoshida, Shigeo
   Kimoto, Kenichi
   Yasukochi, Sai
   Matsunaga, Naoya
   Koyanagi, Satoru
   Ohdo, Shigehiro
   Kubota, Toshiaki
TI Contribution of the clock gene DEC2 to VEGF mRNA upregulation by
   modulation of HIF1 protein levels in hypoxic MIO-M1 cells, a human cell
   line of retinal glial (Muller) cells
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Clock genes; DEC2; HIF1; VEGF; Muller cells
ID ENDOTHELIAL GROWTH-FACTOR; CIRCADIAN-RHYTHMS; EXPRESSION; ACTIVATION;
   ANGIOGENESIS; MANAGEMENT; PERIOD; PER2
AB PurposeClock genes are components of the molecular clock. Their malfunction is thought to increase the risk of numerous diseases, including cancer. Vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis, and its expression levels are controlled by clock genes in tumor cells. Ophthalmic diseases such as age-related macular degeneration, proliferative diabetic retinopathy, and neovascular glaucoma are also associated with abnormal angiogenesis followed by upregulation of VEGF in the eye. In the present study, we aimed to uncover the relationship between clock genes and VEGF in the eye.Study designLaboratory investigationMethodsOxygen-induced retinopathy (OIR) mice were prepared to mimic hypoxic conditions in the eye. Deferoxamine (DFO) was used to mimic hypoxic conditions in human Muller cell line MIO-M1 cells. Expression levels of mRNA and protein were quantified by quantitative reverse transcription polymerase chain reaction and Western blot analysis, respectively.ResultsIn the retinas of OIR mice, the expression levels of Vegf and the clock gene Dec2 increased transiently, and their temporal profiles were correlated. Knockdown of DEC2 resulted in a significant (26.7%) reduction of VEGF expression in MIO-M1 cells under hypoxia-mimicking conditions induced by DFO (P < .05). Levels of HIF1 protein were also reduced significantly, by 60.2%, in MIO-M1 cells treated with siRNA against the DEC2 gene (P < .05). Moreover, HIF1 levels showed a significant (2.5-fold) increase in MIO-M1 cells overexpressing DEC2 (P < .05).ConclusionDEC2 could upregulate retinal VEGF gene expression through modulation of HIF1 levels under hypoxic conditions.
C1 [Kusunose, Naoki; Akamine, Takahiro; Kimoto, Kenichi; Kubota, Toshiaki] Oita Univ, Dept Ophthalmol, Fac Med, 1-1 Yufu Shi, Oita 8795593, Japan.
   [Kusunose, Naoki; Akamine, Takahiro; Yasukochi, Sai; Ohdo, Shigehiro] Kyushu Univ, Fac Pharmaceut Sci, Dept Pharmaceut, Fukuoka, Fukuoka, Japan.
   [Kobayashi, Yoshiyuki; Yoshida, Shigeo] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka, Japan.
   [Matsunaga, Naoya; Koyanagi, Satoru] Kyushu Univ, Fac Pharmaceut Sci, Dept Glocal Healthcare, Fukuoka, Fukuoka, Japan.
C3 Oita University; Kyushu University; Kyushu University; Kyushu University
RP Kusunose, N (通讯作者)，Oita Univ, Dept Ophthalmol, Fac Med, 1-1 Yufu Shi, Oita 8795593, Japan.; Kusunose, N (通讯作者)，Kyushu Univ, Fac Pharmaceut Sci, Dept Pharmaceut, Fukuoka, Fukuoka, Japan.
EM naoki-0207@umin.ac.jp
RI Koyanagi, Satoru/AAE-6843-2020; Kubota, Toshiaki/AAN-4334-2021
FU Japan Society for the Promotion of Science [26861456]
FX This work was supported by a Grant-in-Aid for Young Scientists (B) (no.
   26861456) from the Japan Society for the Promotion of Science.
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NR 45
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD NOV
PY 2018
VL 62
IS 6
BP 677
EP 685
DI 10.1007/s10384-018-0622-5
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GZ1GI
UT WOS:000449115200009
PM 30250985
DA 2022-11-30
ER

PT J
AU Tan, ACS
   Tan, GS
   Denniston, AK
   Keane, PA
   Ang, M
   Milea, D
   Chakravarthy, U
   Cheung, CMG
AF Tan, A. C. S.
   Tan, G. S.
   Denniston, A. K.
   Keane, P. A.
   Ang, M.
   Milea, D.
   Chakravarthy, U.
   Cheung, C. M. G.
TI An overview of the clinical applications of optical coherence tomography
   angiography
SO EYE
LA English
DT Review
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; INDOCYANINE GREEN ANGIOGRAPHY; FOVEAL
   AVASCULAR ZONE; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; FLUORESCEIN
   ANGIOGRAPHY; TYPE-3 NEOVASCULARIZATION; QUANTITATIVE-ANALYSIS; OCT
   ANGIOGRAPHY; IMAGE ARTIFACTS
AB Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.
C1 [Tan, A. C. S.; Tan, G. S.; Ang, M.; Milea, D.; Cheung, C. M. G.] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Level 8,11 Third Hosp Ave, Singapore 168751, Singapore.
   [Tan, A. C. S.; Tan, G. S.; Ang, M.; Milea, D.; Cheung, C. M. G.] Singapore Eye Res Inst, Singapore, Singapore.
   [Tan, A. C. S.; Tan, G. S.; Ang, M.; Milea, D.; Cheung, C. M. G.] Duke NUS Med Sch, Singapore, Singapore.
   [Denniston, A. K.] Univ Hosp Birmingham NHS Fdn Trust, Dept Ophthalmol, Birmingham, W Midlands, England.
   [Denniston, A. K.] Univ Birmingham, Inst Inflammat & Ageing, Acad Unit Ophthalmol, Birmingham, W Midlands, England.
   [Denniston, A. K.; Keane, P. A.] Moorfields Eye Hosp NHS Fdn Trust, NIHR, Biomed Res Ctr, London, England.
   [Denniston, A. K.; Keane, P. A.] UCL Inst Ophthalmol, London, England.
   [Chakravarthy, U.] Queens Univ Belfast, Royal Victoria Hosp, Dept Ophthalmol, Belfast, Antrim, North Ireland.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Singapore National Eye Center;
   National University of Singapore; University of Birmingham; University
   of Birmingham; University of London; King's College London; University
   College London; Moorfields Eye Hospital NHS Foundation Trust; University
   of London; University College London; Queens University Belfast
RP Cheung, CMG (通讯作者)，Singapore Eye Res Inst, Singapore Natl Eye Ctr, Level 8,11 Third Hosp Ave, Singapore 168751, Singapore.
EM gemmy.cheung.c.m@singhealth.com.sg
RI Keane, Pearse/AAE-5709-2019; Denniston, Alastair/ABD-1238-2020; Milea,
   Dan/AAT-8661-2021
OI Keane, Pearse/0000-0002-9239-745X; Denniston,
   Alastair/0000-0001-7849-0087; Chakravarthy, Usha/0000-0002-2606-3734;
   Cheung, Chui Ming Gemmy/0000-0003-3358-3516
FU Bayer; Allergan; Mandarin Optics; National Institute for Health Research
   (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS
   Foundation Trust; Clinician Scientist award from the National Institute
   for Health Research [CS-2014-14-023]; Heidelberg Engineering; Topcon;
   Haag-Streit; Novartis; Alimera Sciences; Santen; UCL Institute of
   Ophthalmology; National Institute for Health Research [CS-2014-14-023]
   Funding Source: researchfish
FX Dr Raymond Najjar and Dr Sourabh Sharma for help with the figures. ACT
   is a consultant for Zeiss and has received travel grants and sponsorship
   from Bayer, Allergan and Mandarin Optics. GT is a consultant for
   Novartis and Abbott medical, a speaker and receives travel support from
   Allergan, Alcon, Zeiss and Bayer; in addition to grant and travel
   support from Santen. AKD receive a proportion of their funding from the
   National Institute for Health Research (NIHR) Biomedical Research Centre
   based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
   of Ophthalmology. PAK is funded by a Clinician Scientist award
   (CS-2014-14-023) from the National Institute for Health Research. The
   views expressed in this publication are those of the authors and not
   necessarily those of the NHS, the National Institute for Health Research
   or the Department of Health. PAK has received speaker fees from
   Heidelberg Engineering, Topcon, Haag-Streit, Allergan, Novartis, and
   Bayer. He has served on advisory boards for Novartis and Bayer, and is
   an external consultant for DeepMind and Optos. UC receives grant funding
   from Alimera Sciences, lectures and speaking events for Allergan. GC is
   a consultant, speaker and receives grant funding from Novartis and
   Bayer, is also a speaker for Allergan and Topcon.
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NR 108
TC 115
Z9 119
U1 2
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD FEB
PY 2018
VL 32
IS 2
BP 262
EP 286
DI 10.1038/eye.2017.181
PG 25
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FV5VK
UT WOS:000424650300019
PM 28885606
OA Bronze, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Pedersen, HR
   Gilson, SJ
   Dubra, A
   Munch, IC
   Larsen, M
   Baraas, RC
AF Pedersen, Hilde R.
   Gilson, Stuart J.
   Dubra, Alfredo
   Munch, Inger Christine
   Larsen, Michael
   Baraas, Rigmor C.
TI Multimodal imaging of small hard retinal drusen in young healthy adults
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ADAPTIVE OPTICS; CLASSIFICATION; DEGENERATION; DENSITY; EYES
AB Background Small hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen.
   Methods Retinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SDOCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised.
   Results Small hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22-61 mu m where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex.
   Conclusion High lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1-4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.
C1 [Pedersen, Hilde R.; Gilson, Stuart J.; Baraas, Rigmor C.] Univ Coll Southeast Norway, Fac Hlth Sci, Natl Ctr Opt Vis & Eye Care, Hasbergsvei 36, N-3616 Kongsberg, Norway.
   [Dubra, Alfredo] Stanford Univ, Dept Ophthlmol, Palo Alto, CA 94304 USA.
   [Munch, Inger Christine] Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.
   [Munch, Inger Christine; Larsen, Michael] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Larsen, Michael] Rigshosp, Dept Ophthalmol, Copenhagen, Denmark.
C3 University College of Southeast Norway; Stanford University; University
   of Copenhagen; Rigshospitalet; University of Copenhagen
RP Baraas, RC (通讯作者)，Univ Coll Southeast Norway, Fac Hlth Sci, Natl Ctr Opt Vis & Eye Care, Hasbergsvei 36, N-3616 Kongsberg, Norway.
EM rigmor.baraas@usn.no
RI Larsen, Michael/E-9620-2010; Baraas, Rigmor C./N-5707-2019
OI Larsen, Michael/0000-0002-5172-5891; Baraas, Rigmor
   C./0000-0003-3259-7617; Pedersen, Hilde R./0000-0003-3946-6687; Dubra,
   Alfredo/0000-0002-6506-9020
FU University College of Southeast Norway
FX The study was funded by the University College of Southeast Norway.
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NR 33
TC 15
Z9 16
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JAN
PY 2018
VL 102
IS 1
BP 146
EP 152
DI 10.1136/bjophthalmol-2017-310719
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FQ2NY
UT WOS:000418194700027
PM 29051326
OA Green Submitted, Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Niu, SJ
   Chen, Q
   de Sisternes, L
   Leng, T
   Rubin, DL
AF Niu, Sijie
   Chen, Qiang
   de Sisternes, Luis
   Leng, Theodore
   Rubin, Daniel L.
TI Automated detection of foveal center in SD-OCT images using the saliency
   of retinal thickness maps
SO MEDICAL PHYSICS
LA English
DT Article
DE foveal center; macular fovea; retinal thickness map; saliency; SD-OCT
   image
ID FEATURE-EXTRACTION; VISUAL-ATTENTION; OPTIC DISC; SEGMENTATION; LAYERS;
   LOCALIZATION; MODEL
AB Purpose: To develop an automated method based on saliency map of the retinal thickness map to determine foveal center in spectral-domain optical coherence tomography (SD-OCT) images.
   Methods: This paper proposes an automatic method for the detection of the foveal center in SD-OCT images. Initially, a retinal thickness map is generated by considering the axial distance between the internal limiting membrane (ILM) and the Bruch's membrane (BM). Both the ILM and BM boundaries are automatically segmented by a known retinal segmentation technique. The macular foveal region is identified as a salient feature in the retinal thickness map, and segmented by the saliency detection method based on a human vision attention model. Finally, the foveal center is identified by searching for the lowest point from the determined macular fovea region.
   Results: Experimental results in 39 scans from 35 healthy eyes and 58 scans from 29 eyes diagnosed with several stages of age-related macular degeneration (AMD), from mild or intermediate stages to severe dry or wet stages, demonstrated that the proposed method achieves good performance. The mean radial distance error of the automatically detected foveal center locations when compared to consensus manual determination established by repeated sessions from two expert readers was 52 +/- 56 mu m for the normal eyes and 73 +/- 63 mu m for AMD eyes.
   Conclusions: The proposed algorithm was more effective for detecting the foveal center automatically in SD-OCT images than the state-of-art methods. (C) 2017 American Association of Physicists in Medicine
C1 [Niu, Sijie] Univ Jinan, Sch Informat Sci & Engn, Jinan 250022, Shandong, Peoples R China.
   [Niu, Sijie; Chen, Qiang] Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
   [Chen, Qiang] Minjiang Univ, Fujian Prov Key Lab Informat Proc & Intelligent C, Fuzhou 350121, Fujian, Peoples R China.
   [de Sisternes, Luis; Rubin, Daniel L.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
   [Leng, Theodore] Stanford Univ, Sch Med, Byers Eye Inst Stanford, Palo Alto, CA 94303 USA.
C3 University of Jinan; Nanjing University of Science & Technology;
   Minjiang University; Stanford University; Stanford University
RP Niu, SJ (通讯作者)，Univ Jinan, Sch Informat Sci & Engn, Jinan 250022, Shandong, Peoples R China.; Niu, SJ; Chen, Q (通讯作者)，Nanjing Univ Sci & Technol, Sch Comp Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.; Chen, Q (通讯作者)，Minjiang Univ, Fujian Prov Key Lab Informat Proc & Intelligent C, Fuzhou 350121, Fujian, Peoples R China.
EM sjniu@hotmail.com; chen2qiang@njust.edu.cn
RI chen, qiang/GWZ-7308-2022; Leng, Theodore/AAQ-7459-2020
FU National Science Foundation of China [61671242, 61701192, 61701222];
   Shandong Province Natural Science Foundation, China [ZR2017QF004]; China
   Postdoctoral Science Foundation [2017M612178]; China Scholarship Council
   [201406840031]; Six Talent Peaks project in Jiangsu Province
   [2014-SWYY-024]; Fundamental Research Funds for the Central Universities
   [30920140111004]; Open Fund Project of Fujian Provincial Key Laboratory
   of Information Processing and Intelligent Control (Minjiang University)
   [MJUKF201706]; Spectrum/SPADA grant
FX The authors thank H. L. Shen and W. Fan for the statistical analysis of
   foveal center identification results, and S. T. Lu for his contribution
   in developing the implementation of the traditional 3-D Graph search.
   National Science Foundation of China under Grant No. 61671242, 61701192
   and 61701222, Shandong Province Natural Science Foundation, China, under
   Grant No. ZR2017QF004, China Postdoctoral Science Foundation under
   Grants No. 2017M612178, China Scholarship Council, 201406840031, the Six
   Talent Peaks project in Jiangsu Province (2014-SWYY-024), the
   Fundamental Research Funds for the Central Universities under Grant no.
   30920140111004, the Open Fund Project of Fujian Provincial Key
   Laboratory of Information Processing and Intelligent Control (Minjiang
   University) (No. MJUKF201706) and Spectrum/SPADA grant.
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NR 45
TC 9
Z9 9
U1 1
U2 15
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD DEC
PY 2017
VL 44
IS 12
BP 6390
EP 6403
DI 10.1002/mp.12614
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Radiology, Nuclear Medicine & Medical Imaging
GA FW5SQ
UT WOS:000425379200027
PM 28976639
DA 2022-11-30
ER

PT J
AU Toutounchian, JJ
   Pagadala, J
   Miller, DD
   Baudry, J
   Park, F
   Chaum, E
   Yates, CR
AF Toutounchian, Jordan J.
   Pagadala, Jayaprakash
   Miller, Duane D.
   Baudry, Jerome
   Park, Frank
   Chaum, Edward
   Yates, Charles R.
TI Novel Small Molecule JP-153 Targets the Src-FAK-Paxillin Signaling
   Complex to Inhibit VEGF-Induced Retinal Angiogenesis
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ENDOTHELIAL-GROWTH-FACTOR; FOCAL ADHESION KINASE; OXYGEN-INDUCED
   RETINOPATHY; TUMOR ANGIOGENESIS; TYROSINE PHOSPHORYLATION; RADIATION
   RETINOPATHY; MACULAR DEGENERATION; VISUAL FUNCTION; CELL-ADHESION; LD
   MOTIFS
AB Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited. In this study, we demonstrated that VEGFdependent activation of the Src/FAK/paxillin signalsome is required for human retinal endothelial cell migration and proliferation. Specifically, the disruption of focal adhesion kinase (FAK) and paxillin interactions using the small molecule JP-153 inhibited Src-dependent phosphorylation of paxillin (Y118) and downstream activation of Akt (S473), resulting in reduced migration and proliferation of retinal endothelial cells stimulated with VEGF. However, this effect did not prevent the initial activation of either Src or FAK. Furthermore, topical application of a JP-153-loaded microemulsion affected the hallmark features of pathologic retinal angiogenesis, reducing neovascular tuft formation and increased avascular area, in a dose-dependent manner. In conclusion, our results suggest that using small molecules to modulate the focal adhesion protein paxillin is an effective strategy for treating pathologic retinal neovascularization. To our knowledge, this is the first paradigm validating modulation of paxillin to inhibit angiogenesis. As such, we have identified and developed a novel class of small molecules aimed at targeting focal adhesion protein interactions that are essential for pathologic neovascularization in the eye.
C1 [Toutounchian, Jordan J.; Pagadala, Jayaprakash; Miller, Duane D.; Park, Frank; Yates, Charles R.] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA.
   [Chaum, Edward; Yates, Charles R.] Univ Tennessee, Dept Ophthalmol, Memphis, TN 38163 USA.
   [Baudry, Jerome] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
   [Baudry, Jerome] Oak Ridge Natl Lab, UT ORNL Ctr Mol Biophys, Oak Ridge, TN USA.
C3 University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center; University of Tennessee System; University of Tennessee
   Knoxville; United States Department of Energy (DOE); Oak Ridge National
   Laboratory; University of Tennessee System; University of Tennessee
   Knoxville
RP Yates, CR (通讯作者)，Univ Tennessee, Dept Pharmaceut Sci, 881 Madison Ave,Pharm Bldg Room 446, Memphis, TN 38163 USA.
EM cyates4@uthsc.edu
RI Park, Frank/I-4590-2019; Chaum, Edward/AAR-1512-2021
OI Park, Frank/0000-0003-2324-2937; Chaum, Edward/0000-0003-3542-8376
FU University of Tennessee College of Pharmacy; University of Tennessee
   Research Foundation
FX The authors thank Drs. Bilal Aleiwi and Shivaputra Patil for help with
   the synthetic chemistry of JP-153 and the University of Tennessee
   College of Pharmacy and the University of Tennessee Research Foundation
   for financial support.
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NR 64
TC 14
Z9 17
U1 0
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JAN 1
PY 2017
VL 91
IS 1
BP 1
EP 13
DI 10.1124/mol.116.105031
PG 13
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA EE4WZ
UT WOS:000389607600001
PM 27913654
OA Bronze
DA 2022-11-30
ER

PT J
AU Cabrera, AP
   Bhaskaran, A
   Xu, J
   Yang, X
   Scott, HA
   Mohideen, U
   Ghosh, K
AF Cabrera, Andrea P.
   Bhaskaran, Arun
   Xu, Jun
   Yang, Xiao
   Scott, Harry A.
   Mohideen, Umar
   Ghosh, Kaustabh
TI Senescence Increases Choroidal Endothelial Stiffness and Susceptibility
   to Complement Injury: Implications for Choriocapillaris Loss in AMD
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aging; Rho; membrane attack complex; cell lysis; vessels
ID MACULAR-DEGENERATION; CELLULAR SENESCENCE; VASCULAR-DISEASE; CELLS;
   ACTIVATION; DRUSEN; EXPRESSION; THROMBIN; INFLAMMATION; MACROPHAGES
AB PURPOSE. Age-related macular degeneration (AMD) commonly causes blindness in the elderly. Yet, it is untreatable in the large fraction of all AMD patients that develop the early dry form. Dry AMD is marked by the deposition of membrane attack complex (MAC) on choriocapillaris (CC), which is implicated in CC degeneration and subsequent atrophy of overlying retinal pigment epithelium. Since MAC is also found on the CC of young eyes, here we investigated whether and how aging increases choroidal endothelial susceptibility to MAC injury.
   METHODS. Monkey chorioretinal endothelial cells (ECs, RF/6A) were cultured to high passages (> P60) to achieve replicative senescence. We treated ECs with complement-competent human serum to promote MAC deposition and injury, which were assessed by flow cytometry and trypan blue exclusion assay, respectively. Stiffness of EC was measured by atomic force microscopy indentation while Rho GTPase activity was quantified by Rho G-LISA assay.
   RESULTS. Our findings reveal that senescent ECs are significantly stiffer than their normal counterparts, which correlates with higher cytoskeletal Rho activity in these cells and their greater susceptibility to complement (MAC) injury. Importantly, inhibition of Rho activity in senescent ECs significantly reduced cell stiffness and MAC-induced lysis.
   CONCLUSIONS. By revealing an important role of senescence-associated choroidal EC stiffening in complement injury, these findings implicate CC stiffening as an important determinant of age-related CC atrophy seen in dry AMD. Future studies are needed to validate these findings in appropriate animal models so new therapeutic targets can be identified for treatment of dry AMD.
C1 [Cabrera, Andrea P.; Bhaskaran, Arun; Yang, Xiao; Scott, Harry A.; Ghosh, Kaustabh] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
   [Xu, Jun; Mohideen, Umar] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside;
   University of California System; University of California Riverside
RP Ghosh, K (通讯作者)，Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
EM kghosh@engr.ucr.edu
RI Xu, Jun/N-8564-2018
OI Xu, Jun/0000-0001-7735-9554
FU UC Riverside Bourns College of Engineering
FX Supported by Initial Complement Funds provided by the UC Riverside
   Bourns College of Engineering.
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NR 58
TC 31
Z9 31
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2016
VL 57
IS 14
BP 5910
EP 5918
DI 10.1167/iovs.16-19727
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EI3HG
UT WOS:000392380000008
PM 27802521
OA gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Sulzbacher, F
   Kiss, C
   Munk, M
   Deak, G
   Sacu, S
   Schmidt-Erfurth, U
AF Sulzbacher, Florian
   Kiss, Christopher
   Munk, Marion
   Deak, Gabor
   Sacu, Stefan
   Schmidt-Erfurth, Ursula
TI Diagnostic Evaluation of Type 2 (Classic) Choroidal Neovascularization:
   Optical Coherence Tomography, Indocyanine Green Angiography, and
   Fluorescein Angiography
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; VISUAL-ACUITY; RANIBIZUMAB; THERAPY
AB PURPOSE: To evaluate the diagnostic characteristics of type 2 (classic) choroidal neovascularizations secondary to age-related macular degeneration using spectral domain-optical coherence tomography (SD OCT), indocyanine green angiography (ICGA), and fluorescein angiography (FA).
   DESIGN: Observational case series.
   METHODS: SETTING: Institutional. STUDY POPULATION: Thirteen treatment-naive eyes with type 2 choroidal neovascularization without an occult component. MAIN OUTCOME MEASURES: Greatest horizontal dimension, based on the anatomic features of the neovascular complex by SD OCT (Spectra lis; Heidelberg Engineering), ICGA, and FA; retinal leakage area in late-phase FA and ICGA; and the area of retinal edema in SD OCT. OBSERVATION PROCEDURES: For direct comparison, ICGA and FA images were overlaid manually on infrared plus SD OCT images using Virtual Dub and Paint.NET software. Greatest horizontal dimension was measured using Image J software (National Institutes of Health).
   RESULTS: The mean greatest horizontal dimension of the neovascular complex and the retinal leakage area consistently were smaller on ICGA compared with the area of retinal edema on SD OCT. According to FA, the greatest horizontal dimension of early, well-demarcated hyperfluorescence was significantly smaller than the neovascular complex on SD OCT. In addition, the greatest horizontal dimension of the retinal leakage area in late-phase FA consistently was smaller than the area of retinal edema on SD OCT.
   CONCLUSIONS: In classic choroidal neovascularization, ICGA and FA seem to underestimate the extension of the neovascular complex and the associated retinal pathologic features compared with SD OCT imaging. (Am J Ophthalmol 2011;152:799-806. (C) 2011 by Elsevier Inc. All rights reserved.)
C1 [Sulzbacher, Florian; Kiss, Christopher; Munk, Marion; Deak, Gabor; Sacu, Stefan; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Kiss, C (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM christopher.kiss@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311
FU ALCON; Bayer Healthcare; Novartis; Regeneron; Pfizer
FX THE AUTHORS INDICATE NO FINANCIAL SUPPORT. URSULA SCHMIDT-ERFURTH HAS
   RECEIVED LECTURE FEES FROM ALCON, Bayer Healthcare, Novartis, Regeneron,
   and Pfizer and consulting fees from Alcon, Bayer Healthcare, and
   Novartis. The remaining authors have no financial support or financial
   conflict of interests to disclose. Involved in Conception and design
   (F.S., C.K.); analysis and interpretation of data (F.S., G.D., S.S.);
   Provision of patients and other resources (C.K., M.M., U.S.-E.);
   Literature search (F.S., C.K., M.M); Writing the article (F.S.);
   Critical revision of the article (C.K., S.S., U.S.-E.); and Final
   approval of article (U.S.-E.). All procedures conformed to the tenets of
   the Declaration of Helsinki and were in compliance with the national
   Institutional Review Board of the Medical University of Vienna, Vienna,
   Austria. Patients provided written informed consent for use of their
   data. The trial is registered at www.clinicaltrials.gov with the
   following number: EudraCT-Nr.: 2006-005684-26.
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NR 20
TC 41
Z9 42
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 NOV
PY 2011
VL 152
IS 5
BP 799
EP 806
DI 10.1016/j.ajo.2011.04.011
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 840BK
UT WOS:000296413100015
PM 21742302
DA 2022-11-30
ER

PT J
AU Jin, J
   Zhou, KK
   Park, K
   Hu, Y
   Xu, X
   Zheng, Z
   Tyagi, P
   Kompella, UB
   Ma, JX
AF Jin, Ji
   Zhou, Kevin K.
   Park, Kyoungmin
   Hu, Yang
   Xu, Xun
   Zheng, Zhi
   Tyagi, Puneet
   Kompella, Uday B.
   Ma, Jian-xing
TI Anti-inflammatory and Antiangiogenic Effects of Nanoparticle-Mediated
   Delivery of a Natural Angiogenic Inhibitor
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; PLASMINOGEN KRINGLE-5; VASCULAR LEAKAGE; RETINAL
   NEOVASCULARIZATION; RAT MODELS; IN-VIVO; CELLS; PATHOGENESIS
AB PURPOSE. The purpose of this study was to evaluate the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5) on choroidal neovascularization (CNV) and retinal inflammation.
   METHODS. CNV was induced by laser in adult rats. Nanoparticles with an expression plasmid of K5 (K5-NP) were injected into the vitreous. K5 expression was detected by immunohistochemistry. The CNV area was measured after fluorescein angiography. Retinal vascular permeability was quantified with Evans blue as a tracer. Expression of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 was measured by Western blot analysis or ELISA and real-time RT-PCR.
   RESULTS. Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. The expression of VEGF was downregulated by K5-NP at both the protein and mRNA levels. Moreover, K5-NP also inhibited expression of TNF-alpha and ICAM-1. Similarly, K5-NP decreased retinal levels of total beta-catenin. In cultured cells, K5-NP suppressed hypoxia-induced secretion of MCP-1 and TNF-alpha.
   CONCLUSIONS. K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV and thus has therapeutic potential for age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2011; 52: 6230-6237) DOI: 10.1167/iovs.10-6229
C1 [Jin, Ji] Zhejiang Univ, Sch Med, Dept Ophthalmol, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China.
   [Jin, Ji; Zhou, Kevin K.; Park, Kyoungmin; Hu, Yang; Ma, Jian-xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA.
   [Xu, Xun; Zheng, Zhi] Shanghai Jiao Tong Univ, Peoples Hosp 1, Shanghai 200080, Peoples R China.
   [Tyagi, Puneet; Kompella, Uday B.] Univ Colorado, Dept Pharmaceut Sci, Hlth Sci Ctr, Aurora, CO USA.
C3 Zhejiang University; University of Oklahoma System; University of
   Oklahoma Health Sciences Center; Shanghai Jiao Tong University;
   University of Colorado System; University of Colorado Anschutz Medical
   Campus
RP Ma, JX (通讯作者)，941 Stanton L Young Blvd,BSEB 328B, Oklahoma City, OK 73104 USA.
EM zzheng8@yahoo.com.cn; jian-xing-ma@ouhsc.edu
RI Zhou, Kelu/C-1322-2017; Kompella, U/C-9789-2011
OI Zhou, Kelu/0000-0001-6751-942X; 
FU National Center for Research Resources [EY012231, EY018659, EY019309,
   P20RR024215]; American Diabetes Association; Centers of Biomedical
   Research Excellence (COBRE), NIH [P20RR024215]; NATIONAL CENTER FOR
   RESEARCH RESOURCES [P20RR024215] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [R01EY018659, R01EY012231, R01EY019309] Funding Source:
   NIH RePORTER
FX Supported by National Institutes of Health (NIH) Grants EY012231,
   EY018659, EY019309, and P20RR024215 from the National Center for
   Research Resources, grants from the American Diabetes Association, and
   Grant P20RR024215 to the Diabetic Animal Core Facility from the Centers
   of Biomedical Research Excellence (COBRE), NIH.
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NR 26
TC 35
Z9 38
U1 0
U2 24
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2011
VL 52
IS 9
BP 6230
EP 6237
DI 10.1167/iovs.10-6229
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 806XC
UT WOS:000293849400024
PM 21357401
OA Green Published
DA 2022-11-30
ER

PT J
AU Kalariya, NM
   Ramana, KV
   Srivastava, SK
   van Kuijk, FJGM
AF Kalariya, Nilesh M.
   Ramana, Kota V.
   Srivastava, Satish K.
   van Kuijk, Frederik J. G. M.
TI Post-translational protein modification by carotenoid cleavage products
SO BIOFACTORS
LA English
DT Article
DE carotenoid; aldehyde; protein adduct; Schiff's base Linkage; thioether
   linkage
ID AGE-RELATED MACULOPATHY; PIGMENT EPITHELIAL-CELLS; HUMAN MACULAR
   PIGMENT; BETA-CAROTENE; OXIDATION-PRODUCTS; VITAMIN-E; ZEAXANTHIN
   SUPPLEMENTATION; NUTRITIONAL MANIPULATION; BREAKDOWN PRODUCTS;
   HYPOCHLOROUS ACID
AB Carotenoids are known to generate various aldehydes, known as carotenoid-derived aldehydes (CDAs), which could efficiently react with protein or DNA. In this in vitro model study, interaction between CDA and protein has been studied. Various proteins were incubated with CDA, and protein modification and adduct formation were confirmed by using matrix-assisted laser desorption and ionization time-of-flight, amino acid analysis, and measuring enzyme activity on modification with CDA. Using radiolabeled NaB(H-3)H-4 and Raney nickel as well as sulfhydryl assay (Ellman's reagent), we confirmed that CDA could conjugate with cysteine through a thioether linkage. The carbonyl assay using 2,4-dinitrophenylhydrazine revealed the possible involvement of Schiff's base reaction between CDA and lysine. The adducts formed between beta-apo-8-carotenal (BA8C) and N-acetylcysteine and BA8C and N-acetyllysine were confirmed by HPLC and ESI-MS. Our results suggest that CDA could alter protein function by post-translational interaction with cysteine and lysine by thioether linkage and by schiff's based bonds, respectively. Thus, the formation of CDA adducts with proteins could alter functional properties of proteins responsible for maintaining cell homeostasis and thereby cause cellular toxicity. In view of these observations, further studies are required to understand the delicate balance between beneficial and/or harmful effects of carotenoids as a dietary supplement to slow age-related macular degeneration progression. (C) 2011 International Union of Biochemistry and Molecular Biology, Inc. Volume 37, Number 2, March/April 2011, Pages 104-116 . E-mail: fjvankui@utmb.edu
C1 [Kalariya, Nilesh M.; van Kuijk, Frederik J. G. M.] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, AMD Ctr, Galveston, TX 77555 USA.
   [Ramana, Kota V.; Srivastava, Satish K.] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
   [Kalariya, Nilesh M.] Univ Texas Med Branch, Sch Nursing, Galveston, TX 77555 USA.
C3 University of Texas System; University of Texas Medical Branch
   Galveston; University of Texas System; University of Texas Medical
   Branch Galveston; University of Texas System; University of Texas
   Medical Branch Galveston
RP van Kuijk, FJGM (通讯作者)，Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, AMD Ctr, Room 2-100,700 Univ Blvd, Galveston, TX 77555 USA.
EM fjvankui@utmb.edu
RI Ramana, Kota/C-5460-2012
OI Ramana, Kota/0000-0001-6502-7800
FU Wilkins AMD Fund; National Institutes of Health (NIH) [GM71036,
   EY018591, DK36118]; Research to Prevent Blindness, NY; NATIONAL EYE
   INSTITUTE [R01EY018591] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK036118, R01DK036118]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [R01GM071036] Funding Source: NIH RePORTER
FX This work was supported by Wilkins AMD Fund (to FJGMvK) and National
   Institutes of Health (NIH) Grants GM71036 and EY018591 (to K.V.R.),
   DK36118 (to S.K.S.). This work was also supported by Research to Prevent
   Blindness, NY. The authors thank staff of Protein Chemistry Core and
   Mass Spectrometry Core Facilities at UTMB for technical assistance with
   MALDI-TOF, ESI-MS, and amino acid analysis.
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NR 73
TC 8
Z9 8
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-6433
J9 BIOFACTORS
JI Biofactors
PD MAR-APR
PY 2011
VL 37
IS 2
BP 104
EP 116
DI 10.1002/biof.152
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 756GK
UT WOS:000289999500005
PM 21488133
DA 2022-11-30
ER

PT J
AU Gangalum, RK
   Atanasov, IC
   Zhou, ZH
   Bhat, SP
AF Gangalum, Rajendra K.
   Atanasov, Ivo C.
   Zhou, Z. Hong
   Bhat, Suraj P.
TI alpha B-Crystallin Is Found in Detergent-resistant Membrane Microdomains
   and Is Secreted via Exosomes from Human Retinal Pigment Epithelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEAT-SHOCK-PROTEIN; MACULAR DEGENERATION; MULTIPLE-SCLEROSIS; LIPID
   RAFTS; EXPRESSION; LENS; DRUSEN; MATURATION; PATHOLOGY; BIOMARKER
AB alpha B-crystallin (alpha B) is known as an intracellular Golgi membrane- associated small heat shock protein. Elevated levels of this protein have been linked with a myriad of neurodegenerative pathologies including Alzheimer disease, multiple sclerosis, and age-related macular degeneration. The membrane association of alpha B has been known for more than 3 decades, yet its physiological import has remained unexplained. In this investigation we show that alpha B is secreted from human adult retinal pigment epithelial cells via microvesicles (exosomes), independent of the endoplasmic reticulum-Golgi protein export pathway. The presence of alpha B in these lipoprotein structures was confirmed by its susceptibility to digestion by proteinase K only when exosomes were exposed to Triton X-100. Transmission electron microscopy was used to localize alpha B in immuno-gold- labeled intact and permeabilized microvesicles. The saucer- shaped exosomes, with a median diameter of 100-200 nm, were characterized by the presence of flotillin-1, alpha-enolase, and Hsp70, the same proteins that associate with detergent-resistant membrane microdomains (DRMs), which are known to be involved in their biogenesis. Notably, using polarized adult retinal pigment epithelial cells, we show that the secretion of alpha B is predominantly apical. Using OptiPrep gradients we demonstrate that alpha B resides in the DRM fraction. The secretion of alpha B is inhibited by the cholesterol-depleting drug, methyl beta-cyclodextrin, suggesting that the physiological function of this protein and the regulation of its export through exosomes may reside in its association with DRMs/lipid rafts.
C1 [Bhat, Suraj P.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
   [Bhat, Suraj P.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Gangalum, Rajendra K.; Bhat, Suraj P.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Atanasov, Ivo C.; Zhou, Z. Hong] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
   [Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, 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 System; University of
   California Los Angeles; University of California System; University of
   California Los Angeles; University of California System; University of
   California Los Angeles
RP Bhat, SP (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, 100 Stein Plaza,Rm BH 623, Los Angeles, CA 90095 USA.
EM Bhat@jsei.ucla.edu
RI Zhou, Z Hong/HDN-0747-2022; Gangalum, Rajendra K/H-1369-2013
OI Gangalum, Rajendra K/0000-0002-8746-0266; Bhat, Suraj
   P/0000-0003-4707-5870
FU National Institutes of Health through NEI; National Institutes of Health
   [1S10RR23057]; NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR023057]
   Funding Source: NIH RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health grants, through the NEI (to S. P. B.). This work was also
   supported by National Institutes of Health Grant 1S10RR23057 (to the
   Electron Imaging Center for Nanomachines and Z. H. Z.). A preliminary
   account was presented at the Association for Research in Vision and
   Ophthalmology Annual Meeting, Ft. Lauderdale, FL, May 3-7, 2009 (Bhat,
   S. P., Gangalum, R. K., and Jing, Z. (2009) Invest. Ophthalmol. Vis.
   Sci. 50, E-Abstr. 4183).
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NR 50
TC 82
Z9 84
U1 0
U2 14
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 FEB 4
PY 2011
VL 286
IS 5
BP 3261
EP 3269
DI 10.1074/jbc.M110.160135
PG 9
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 712GE
UT WOS:000286653200011
PM 21097504
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Ryhanen, T
   Hyttinen, JMT
   Kopitz, J
   Rilla, K
   Kuusisto, E
   Mannermaa, E
   Viiri, J
   Holmberg, CI
   Immonen, I
   Meri, S
   Parkkinen, J
   Eskelinen, EL
   Uusitalo, H
   Salminen, A
   Kaarniranta, K
AF Ryhanen, Tuomas
   Hyttinen, Juha M. T.
   Kopitz, Juergen
   Rilla, Kirsi
   Kuusisto, Erkki
   Mannermaa, Eliisa
   Viiri, Johanna
   Holmberg, Carina I.
   Immonen, Ilkka
   Meri, Seppo
   Parkkinen, Jussi
   Eskelinen, Eeva-Liisa
   Uusitalo, Hannu
   Salminen, Antero
   Kaarniranta, Kai
TI Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes
   in autophagy-mediated proteolysis in human retinal pigment epithelial
   cells
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE autophagosome; Hsp70; lysosome; proteasome; proteolysis; retinal pigment
   epithelium
ID INTRACELLULAR PROTEIN-DEGRADATION; HEAT-SHOCK PROTEINS; MACULAR
   DEGENERATION; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; RPE CELLS;
   LIPOFUSCIN; UBIQUITIN; ACTIVATION; INHIBITION
AB The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells.
C1 [Ryhanen, Tuomas; Hyttinen, Juha M. T.; Viiri, Johanna; Uusitalo, Hannu; Kaarniranta, Kai] Univ Kuopio, Dept Ophthalmol, FIN-70211 Kuopio, Finland.
   [Kopitz, Juergen] Heidelberg Univ, Fac Med, Inst Mol Pathol, Heidelberg, Germany.
   [Rilla, Kirsi] Univ Kuopio, Dept Anat, FIN-70211 Kuopio, Finland.
   [Kuusisto, Erkki; Salminen, Antero] Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland.
   [Mannermaa, Eliisa] Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland.
   [Holmberg, Carina I.] Univ Helsinki, Inst Biomed, Mol & Canc Biol Program, Helsinki, Finland.
   [Immonen, Ilkka] Helsinki Univ Hosp, Dept Ophthalmol, Helsinki, Finland.
   [Meri, Seppo] Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, Helsinki, Finland.
   [Parkkinen, Jussi] Univ Joensuu, Dept Comp Sci & Stat, FIN-80101 Joensuu, Finland.
   [Eskelinen, Eeva-Liisa] Univ Helsinki, Div Biochem, Dept Biol & Environm Sci, Helsinki, Finland.
C3 University of Eastern Finland; Ruprecht Karls University Heidelberg;
   University of Eastern Finland; University of Eastern Finland; University
   of Eastern Finland; University of Helsinki; University of Helsinki;
   Helsinki University Central Hospital; University of Helsinki; University
   of Eastern Finland; University of Helsinki
RP Kaarniranta, K (通讯作者)，Univ Kuopio, Dept Ophthalmol, POB 1627, FIN-70211 Kuopio, Finland.
EM kaarnira@messi.uku.fi
RI Eskelinen, Eeva-Liisa/AAF-3496-2019
OI Eskelinen, Eeva-Liisa/0000-0003-0006-7785; Holmberg-Still,
   Carina/0000-0001-9645-2009; Rilla, Kirsi/0000-0002-7862-5727;
   Kaarniranta, Kai/0000-0003-2600-8679; Meri, Seppo/0000-0001-9142-501X;
   Hyttinen, Juha/0000-0002-3414-4032
FU Academy of Finland; Emil Aaltonen Foundation; Finnish Cultural
   Foundation and its North Savo Fund; Finnish Eye Foundation; Finnish Eye
   and Tissue Bank Foundation; Finnish Eye Science Society; Finnish Funding
   Agency for Technology; Kuopio University Foundation; National Institutes
   of Health [EY11515]; NATIONAL EYE INSTITUTE [R01EY011515] Funding
   Source: NIH RePORTER
FX This work was supported by the Academy of Finland, the Emil Aaltonen
   Foundation, the Finnish Cultural Foundation and its North Savo Fund, the
   Finnish Eye Foundation, the Finnish Eye and Tissue Bank Foundation, the
   Finnish Eye Science Society, the Finnish Funding Agency for Technology,
   the Kuopio University Foundation and the National Institutes of Health
   (EY11515). The authors wish to thank Dr. Ewen MacDonald and Vivian
   Paganuzzi for checking the language and Paivi Perttula, Virpi Miettinen
   and Sunna Lappalainen for technical assistance.
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NR 53
TC 105
Z9 107
U1 1
U2 17
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD SEP
PY 2009
VL 13
IS 9B
BP 3616
EP 3631
DI 10.1111/j.1582-4934.2008.00577.x
PG 16
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA 551BC
UT WOS:000274179300054
PM 19017362
OA Green Published
DA 2022-11-30
ER

PT J
AU Vives-Bauza, C
   Anand, M
   Shirazi, AK
   Magrane, J
   Gao, JP
   Vollmer-Snarr, HR
   Manfredi, G
   Finnemann, SC
AF Vives-Bauza, Cristofol
   Anand, Monika
   Shirazi, Arash K.
   Magrane, Jordi
   Gao, Junping
   Vollmer-Snarr, Heidi R.
   Manfredi, Giovanni
   Finnemann, Silvia C.
TI The age lipid A2E and mitochondrial dysfunction synergistically impair
   phagocytosis by retinal pigment epithelial cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-RETINYLIDENE ETHANOLAMINE; LIPOFUSCIN FLUOROPHORE; MACULAR
   DEGENERATION; RPE CELLS; DNA; DYSTROPHY; COMPONENT; BINDING; GENE;
   BIOSYNTHESIS
AB Accumulation of indigestible lipofuscin and decreased mitochondrial energy production are characteristic age-related changes of post-mitotic retinal pigment epithelial (RPE) cells in the human eye. To test whether these two forms of age-related impairment have interdependent effects, we quantified the ATP dependent phagocytic function of RPE cells loaded or not with the lipofuscin component A2E and inhibiting or not mitochondrial ATP synthesis either pharmacologically or genetically. We found that physiological levels of lysosomal A2E reduced mitochondrial membrane potential and inhibited oxidative phosphorylation (OXPHOS) of RPE cells. Furthermore, in media with physiological concentrations of glucose or pyruvate, A2E significantly inhibited phagocytosis. Antioxidants reversed these effects of A2E, suggesting that A2E damage is mediated by oxidative processes. Because mitochondrial mutations accumulate with aging, we generated novel genetic cellular models of RPE carrying mitochondrial DNA point mutations causing either moderate or severe mitochondrial dysfunction. Exploring these mutant RPE cells we found that, by itself, only the severe but not the moderate OXPHOS defect reduces phagocytosis. However, sub-toxic levels of lysosomal A2E are sufficient to reduce phagocytic activity of RPE with moderate OXPHOS defect and cause cell death of RPE with severe OXPHOS defect. Taken together, RPE cells rely on OXPHOS for phagocytosis when the carbon energy source is limited. Our results demonstrate that A2E accumulation exacerbates the effects of moderate mitochondrial dysfunction. They suggest that synergy of sub-toxic lysosomal and mitochondrial changes in RPE cells with age may cause RPE dysfunction that is known to contribute to human retinal diseases like age-related macular degeneration.
C1 [Vives-Bauza, Cristofol; Magrane, Jordi; Manfredi, Giovanni] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, New York, NY 10065 USA.
   [Anand, Monika; Shirazi, Arash K.; Finnemann, Silvia C.] Cornell Univ, Dept Ophthalmol, Weill Med Coll, Dyson Vis Res Inst, New York, NY 10065 USA.
   [Finnemann, Silvia C.] Cornell Univ, Dept Physiol & Biophys, Weill Med Coll, New York, NY 10065 USA.
   [Finnemann, Silvia C.] Cornell Univ, Dept Cell & Dev Biol, Weill Med Coll, New York, NY 10065 USA.
   [Gao, Junping; Vollmer-Snarr, Heidi R.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
C3 Cornell University; Cornell University; Dyson; Cornell University;
   Cornell University; Brigham Young University
RP Finnemann, SC (通讯作者)，Weill Cornell Med Coll, Dyson Vis Res Inst, LC305,Box 233,1300 York Ave, New York, NY 10065 USA.
EM sfinne@med.cornell.edu
RI Vives-Bauza, Cristofol/N-7044-2015; Magrané, Jordi/AAJ-2967-2020;
   Vives-Bauza, Cristofol/AAS-1301-2021
OI Magrané, Jordi/0000-0002-6785-2166; Vives-Bauza,
   Cristofol/0000-0001-5735-8335; Vollmer-Snarr, Heidi/0000-0002-7312-4907
FU National Institutes of Health [R01-EY13295, K02-NS47306]; NATIONAL EYE
   INSTITUTE [R01EY013295] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF NEUROLOGICAL DISORDERS AND STROKE [K02NS047306] Funding Source: NIH
   RePORTER
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants R01-EY13295 (to S. C. F.) and K02-NS47306 (to G. M.). The
   costs of publication of this article were defrayed in part by the
   payment of page charges. This article must therefore be hereby marked
   "advertisement" in accordance with 18 U. S. C. Section 1734 solely to
   indicate this fact. 1 Both authors contributed equally to this study.
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NR 53
TC 119
Z9 122
U1 1
U2 15
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 5
PY 2008
VL 283
IS 36
BP 24770
EP 24780
DI 10.1074/jbc.M800706200
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 342YR
UT WOS:000258820000045
PM 18621729
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Paimela, T
   Ryhanen, T
   Mannermaa, E
   Ojala, J
   Kalesnykas, G
   Salminen, A
   Kaarniranta, K
AF Paimela, Tuomas
   Ryhanen, Tuomas
   Mannermaa, Eliisa
   Ojala, Johanna
   Kalesnykas, Giedrius
   Salminen, Antero
   Kaarniranta, Kai
TI The effect of 17 beta-estradiol on IL-6 secretion and NF-kappa B
   DNA-binding activity in human retinal pigment epithelial cells
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE 17 beta-estradiol; IL-6; LPS; NF-kappa B; RPE; TLR
ID HORMONE REPLACEMENT THERAPY; ESTROGEN-RECEPTOR-ALPHA; MACULAR
   DEGENERATION; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; PROINFLAMMATORY
   CYTOKINE; INNATE IMMUNITY; AGE; INTERLEUKIN-6; DISEASE
AB Toll-like receptors (TLRs) and inflammatory cascades participate in the pathology of age-related macular degeneration (AMD). The effect of estrogens on the development of AMD is poorly understood, although many studies indicate that these compounds can modulate inflammatory responses. In this study, we investigated the regulatory role of TLR agonists and 17 beta-estradiol (E-2) on IL-6 expression and NF-kappa B DNA-binding activity in human retinal pigment epithelial cells (ARPE-19). The inflammatory response of ARPE-19 cells to various TLR agonists, e.g. Pam, zymosan, flagellin, SLTA and lipopolysaccharide (LPS) exposures were examined via the secretion of IL-6 cytokine as analyzed by ELISA. In addition, the IL-6 responses to the estrogen-receptor agonist, E-2, and to the estrogen-receptor antagonist ICI 182.780 as well as to the NF-kappa B inhibitor helenalin were compared. The DNA-binding activity of NF-kappa B transcription factor of nuclear cell extracts was analyzed by the gel mobility shift assay (EMSA). TLR4 gene expression was studied by quantitave PCR. The TLR4 agonist, LPS, caused a clear IL-6 response that was attenuated by E-2 in ARPE-19-cells. The anti-inflammatory properties of E-2 were mediated through estrogen receptors and were associated with decreased NF-kappa B DNA-binding activity. The level of TLR4 gene expression was not affected by LPS exposure. Our results indicate that IL-6 expression is regulated through NF-kappa B transcription factor and stereoid-receptor signalling pathways in ARPE-19 cells. (c) 2007 Elsevier B.V. All rights reserved.
C1 Univ Kuopio, Dept Ophthalmol, FIN-70211 Kuopio, Finland.
   Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland.
   Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland.
   Kuopio Univ Hosp, Dept Neurol, FIN-70211 Kuopio, Finland.
C3 University of Eastern Finland; University of Eastern Finland; University
   of Eastern Finland; Kuopio University Hospital
RP Kaarniranta, K (通讯作者)，Univ Kuopio, Dept Ophthalmol, POB 1627, FIN-70211 Kuopio, Finland.
EM kaarnira@messi.uku.fi
RI Kalesnykas, Giedrius/AAG-4084-2021
OI Ojala, Johanna/0000-0002-8528-1387; Kaarniranta, Kai/0000-0003-2600-8679
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NR 36
TC 47
Z9 53
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD JUN 15
PY 2007
VL 110
IS 2
BP 139
EP 144
DI 10.1016/j.imlet.2007.04.008
PG 6
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 185IL
UT WOS:000247704500007
PM 17532054
DA 2022-11-30
ER

PT J
AU Tomita, M
   Yamada, H
   Adachi, Y
   Cui, YZ
   Yamada, E
   Higuchi, A
   Minamino, K
   Suzuki, Y
   Matsumura, M
   Ikehara, S
AF Tomita, M
   Yamada, H
   Adachi, Y
   Cui, YZ
   Yamada, E
   Higuchi, A
   Minamino, K
   Suzuki, Y
   Matsumura, M
   Ikehara, S
TI Choroidal neovascularization is provided by bone marrow cells
SO STEM CELLS
LA English
DT Article
DE choroidal neovascularization; bone marrow cells; age-related macular
   degeneration; bone marrow transplantation
ID ENDOTHELIAL GROWTH-FACTOR; HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS;
   GENE-TRANSFER; DIFFERENTIATE; ENGRAFTMENT; ASTROCYTES; INJECTION;
   BRAINS; BLOOD
AB Choroidal neovascularization (CNV) is a known cause of age-related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.
C1 Kansai Med Univ, Dept Pathol, Moriguchi, Osaka 5708506, Japan.
   Kansai Med Univ, Dept Ophthalmol, Moriguchi, Osaka 5708506, Japan.
   Kansai Med Univ, Regenerat Res Ctr Intractable Dis, Moriguchi, Osaka 5708506, Japan.
C3 Kansai Medical University; Kansai Medical University; Kansai Medical
   University
RP Ikehara, S (通讯作者)，Kansai Med Univ, Dept Pathol, Moriguchi, Osaka 5708506, Japan.
EM ikehara@takii.kmu.ac.jp
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NR 39
TC 42
Z9 46
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PY 2004
VL 22
IS 1
BP 21
EP 26
DI 10.1634/stemcells.22-1-21
PG 6
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 756TE
UT WOS:000187497200003
PM 14688388
DA 2022-11-30
ER

PT J
AU Pan, CD
   Banerjee, K
   Lehmann, GL
   Almeida, D
   Hajjar, KA
   Benedicto, I
   Jiang, ZC
   Radu, RA
   Thompson, DH
   Rodriguez-Boulan, E
   Nociari, MM
AF Pan, Chendong
   Banerjee, Kalpita
   Lehmann, Guillermo L.
   Almeida, Dena
   Hajjar, Katherine A.
   Benedicto, Ignacio
   Jiang, Zhichun
   Radu, Roxana A.
   Thompson, David H.
   Rodriguez-Boulan, Enrique
   Nociari, Marcelo M.
TI Lipofuscin causes atypical necroptosis through lysosomal membrane
   permeabilization
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE Lipofuscin; necroptosis; LMP; lipid-bisretinoids; aging
ID RETINAL-PIGMENT EPITHELIUM; QUANTITATIVE FUNDUS AUTOFLUORESCENCE; MIXED
   LINEAGE KINASE; CELL-DEATH; RPE CELLS; A2E; ACCUMULATION; DISRUPTION;
   PROTEIN; MICE
AB Lipofuscin granules enclose mixtures of cross-linked proteins and lipids in proportions that depend on the tissue analyzed. Retinal lipofuscin is unique in that it contains mostly lipids with very little proteins. However, retinal lipofuscin also presents biological and physicochemical characteristics indistinguishable from conventional granules, including indigestibility, tendency to cause lysosome swelling that results in rupture or defective functions, and ability to trigger NLRP3 inflammation, a symptom of low-level disruption of lysosomes. In addition, like conventional lipofuscins, it appears as an autofluorescent pigment, considered toxic waste, and a biomarker of aging. Ocular lipofuscin accumulates in the retinal pigment epithelium (RPE), whereby it interferes with the support of the neuroretina. RPE cell death is the primary cause of blindness in the most prevalent incurable genetic and age-related human disorders, Stargardt disease and age-related macular degeneration (AMD), respectively. Although retinal lipofuscin is directly linked to the cell death of the RPE in Stargardt, the extent to which it contributes to AMD is a matter of debate. Nonetheless, the number of AMD clinical trials that target lipofuscin formation speaks for the potential relevance for AMD as well. Here, we show that retinal lipofuscin triggers an atypical necroptotic cascade, amenable to pharmacological intervention. This pathway is distinct from canonic necroptosis and is instead dependent on the destabilization of lysosomes. We also provide evidence that necroptosis is activated in aged human retinas with AMD. Overall, this cytotoxicity mechanism may offer therapeutic targets and markers for genetic and age-related diseases associated with lipofuscin buildups.
C1 [Pan, Chendong; Banerjee, Kalpita; Lehmann, Guillermo L.; Benedicto, Ignacio; Rodriguez-Boulan, Enrique; Nociari, Marcelo M.] Margaret Dyson Vis Res Inst, Dept Ophthalmol, Weill Cornell Med, New York, NY 10065 USA.
   [Almeida, Dena; Hajjar, Katherine A.] Weill Cornell Med, Dept Pediat, New York, NY 10065 USA.
   [Benedicto, Ignacio] Ctr Nacl Invest Cardiovasc, Madrid 47907, Spain.
   [Jiang, Zhichun; Radu, Roxana A.] Univ Calif Los Angeles, UCLA Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Thompson, David H.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
C3 Cornell University; Cornell University; Centro Nacional de
   Investigaciones Cardiovasculares (CNIC); University of California
   System; University of California Los Angeles; Purdue University System;
   Purdue University; Purdue University West Lafayette Campus
RP Nociari, MM (通讯作者)，Margaret Dyson Vis Res Inst, Dept Ophthalmol, Weill Cornell Med, New York, NY 10065 USA.
EM mnociari@med.cornell.edu
OI Radu, Roxana/0000-0002-5064-6403; Thompson, David H/0000-0002-0746-1526;
   , Katherine/0000-0003-3977-4356
FU BrightFocus [M2016124]; National Eye Institute [R01EY027422, R01EY08538,
   GM34107]; Research to Prevent Blindness
FX Funding was provided by the following grants: BrightFocus-M2016124 to
   M.M.N.; National Eye Institute, R01EY027422 to M.M.N.; and R01EY08538
   and GM34107 to E.R.-B. Research to Prevent Blindness grants to the
   Departments of Ophthalmology at Weill Cornell Medicine (WCM) and
   University of California, Los Angeles, Stein Eye Institute. Thanks to
   Sheldon Miller and Maminishkis for providing hfRPE; Sushmita Mukherjee
   at WCM for setup ONL-thickness analysis; Vera Bonilha, Cleveland Clinic
   for invaluable help with human specimens; and Zelda Salfati for
   maintaining the colony.
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NR 78
TC 9
Z9 9
U1 2
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
EI 1091-6490
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 23
PY 2021
VL 118
IS 47
AR e2100122118
DI 10.1073/pnas.2100122118
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA XD9SL
UT WOS:000723039500003
PM 34782457
OA Green Published
DA 2022-11-30
ER

PT J
AU Flieger, J
   Dolar-Szczasny, J
   Rejdak, R
   Majerek, D
   Tatarczak-Michalewska, M
   Proch, J
   Blicharska, E
   Flieger, W
   Baj, J
   Niedzielski, P
AF Flieger, Jolanta
   Dolar-Szczasny, Joanna
   Rejdak, Robert
   Majerek, Dariusz
   Tatarczak-Michalewska, Malgorzata
   Proch, Jedrzej
   Blicharska, Eliza
   Flieger, Wojciech
   Baj, Jacek
   Niedzielski, Przemyslaw
TI The Multi-Elemental Composition of the Aqueous Humor of Patients
   Undergoing Cataract Surgery, Suffering from Coexisting Diabetes,
   Hypertension, or Diabetic Retinopathy
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE elemental analysis; aqueous humor (AH); cataract; diabetes;
   hypertension; diabetic retinopathy; age-related macular degeneration
   (AMD); ICP-OES
ID INTRAOCULAR-LENS; TRACE-ELEMENTS; COBALT; TRANSPORT; NA,K-ATPASE;
   EXPRESSION; HYPOXIA; NUCLEAR; BINDING; PROTEIN
AB The aim of the study was the multi-elemental analysis of aqueous humor (AH) collected from patients undergoing cataract surgery. The study included: 16 patients with age-related macular degeneration AMD (99 controls), 10 patients with retinopathy (105 controls), 61 patients with hypertension (54 controls), and 33 patients with coexisting diabetes (82 controls). The control groups were recruited from patients with a lack of co-existing disease characterizing the specified studied group. The measurements were performed by the use of inductively coupled plasma optical emission spectrometry (ICP-OES). The statistical analysis was carried out using non-parametric testing (Mann-Whitney U). The level of significance was set at p = 0.05. The data obtained revealed substantial variations in elemental composition between the test groups in comparison to the controls. However, the significant variations concerned only a few elements. The phosphorous (P) level and the ratio of P/Ca were significant in retinopathy and diabetes, whereas cobalt (0.091 +/- 0.107 mg/L vs. 0.031 +/- 0.075 mg/L; p = 0.004) was significant in AMD. In co-existing hypertension, the levels of tin (0.293 +/- 0.409 mg/L vs. 0.152 +/- 0.3 mg/L; p = 0.031), titanium (0.096 +/- 0.059 mg/L vs. 0.152 +/- 0.192 mg/L; p = 0.045), and ruthenium (0.035 +/- 0.109 mg/L vs. 0.002 +/- 0.007 mg/L; p = 0.006) varied in comparison to the controls. The study revealed inter-elemental interactions. The correlation matrices demonstrated the domination of the positive correlations, whereas negative correlations mainly concerned sodium.
C1 [Flieger, Jolanta; Tatarczak-Michalewska, Malgorzata; Blicharska, Eliza] Med Univ Lublin, Dept Analyt Chem, Chodzki 4A, PL-20093 Lublin, Poland.
   [Dolar-Szczasny, Joanna; Rejdak, Robert] Med Univ Lublin, Dept Gen & Pediat Ophthalmol, Chmielna 1, PL-20079 Lublin, Poland.
   [Majerek, Dariusz] Univ Technol, Dept Appl Math, Nadbystrzycka 38D, PL-20618 Lublin, Poland.
   [Proch, Jedrzej; Niedzielski, Przemyslaw] Adam Mickiewicz Univ, Fac Chem, Dept Analyt Chem, 89B Umultowska St, PL-61614 Poznan, Poland.
   [Flieger, Wojciech; Baj, Jacek] Med Univ Lublin, Dept Anat, PL-20090 Lublin, Poland.
C3 Medical University of Lublin; Medical University of Lublin; Lublin
   University of Technology; Adam Mickiewicz University; 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; joannaszczasny@op.pl; robert.rejdak@umlub.pl;
   majerek@gmail.com; malgorzatatatarczakmichalewska@umlub.pl;
   jed.proch@gmail.com; eliza.blicharska@umlub.pl; wwoj24@umgmail.com;
   jacek.baj@umlub.pl; pnied@amu.edu.pl
RI Proch, Jędrzej/AAB-9429-2020; Majerek, Dariusz/D-3457-2017; Niedzielski,
   Przemyslaw/A-6316-2009
OI Proch, Jędrzej/0000-0003-0023-044X; Majerek,
   Dariusz/0000-0002-0035-7187; Niedzielski,
   Przemyslaw/0000-0002-2787-9057; Baj, Jacek/0000-0002-1372-8987;
   Tatarczak-Michalewska, Malgorzata/0000-0001-5353-9091; Flieger,
   Jolanta/0000-0001-6881-3161; Dolar-Szczasny, Joanna/0000-0003-4206-4371;
   Rejdak, Robert/0000-0003-3321-2723
FU Polish Ministry of Science and Higher Education
FX The authors are grateful for the financial support given from the Polish
   Ministry of Science and Higher Education by subvention activity for the
   Department of Analytical Chemistry of Medical University of Lublin.
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NR 76
TC 5
Z9 5
U1 2
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD SEP
PY 2021
VL 22
IS 17
AR 9413
DI 10.3390/ijms22179413
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Biochemistry & Molecular Biology; Chemistry
GA UO0RR
UT WOS:000694412100001
PM 34502323
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Krytkowska, E
   Grabowicz, A
   Mozolewska-Piotrowska, K
   Ulanczyk, Z
   Safranow, K
   Machalinska, A
AF Krytkowska, Elzbieta
   Grabowicz, Aleksandra
   Mozolewska-Piotrowska, Katarzyna
   Ulanczyk, Zofia
   Safranow, Krzysztof
   Machalinska, Anna
TI The impact of vascular risk factors on the thickness and volume of the
   choroid in AMD patients
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; PHYSICAL-ACTIVITY;
   EXERCISE
AB Disturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (beta=+0.18, p=0.0007, beta=+0.18, p=0.0008, respectively) and to dry AMD (beta=+0.17, p=0.00003 for both ATC and AVC and beta=-0.30 p<0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs=-0.13, p<0.05; Rs=-0.12; p<0.05, Rs=-0.12; p<0.05, respectively) while IHD duration negatively correlated with AV (Rs=-0.15, p<0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.
C1 [Krytkowska, Elzbieta; Grabowicz, Aleksandra; Mozolewska-Piotrowska, Katarzyna; Machalinska, Anna] Pomeranian Med Univ, Dept Ophthalmol 1, Al Powstancow Wlkp 72, PL-70111 Szczecin, Poland.
   [Ulanczyk, Zofia] Pomeranian Med Univ, Dept Gen Pathol, Al Powstancow Wlkp 72, PL-70111 Szczecin, Poland.
   [Safranow, Krzysztof] Pomeranian Med Univ, Dept Biochem & Med Chem, Al Powstancow Wlkp 72, PL-70111 Szczecin, Poland.
C3 Pomeranian Medical University; Pomeranian Medical University; Pomeranian
   Medical University
RP Machalinska, A (通讯作者)，Pomeranian Med Univ, Dept Ophthalmol 1, Al Powstancow Wlkp 72, PL-70111 Szczecin, Poland.; Ulanczyk, Z (通讯作者)，Pomeranian Med Univ, Dept Gen Pathol, Al Powstancow Wlkp 72, PL-70111 Szczecin, Poland.
EM zofia.litwinska@pum.edu.pl; annam@pum.edu.pl
FU Polish National Centre for Research and Development
   [STRATEGMED1/234261/2NCBR/2014]; European Union funds from the European
   Union Regional Development Fund; Interreg Cooperation Program V A
   Mecklenburg-Western Pomerania/Brandenburg/Poland
FX This work was supported by Polish National Centre for Research and
   Development (grant number: STRATEGMED1/234261/2NCBR/2014) and European
   Union funds from the European Union Regional Development Fund, Interreg
   Cooperation Program V A Mecklenburg-Western Pomerania/Brandenburg/Poland
   for 2014-2020: "Consolidating cross-border cooperation through ex-change
   of knowledge and skills in the field of modern diagnostic imaging
   methods in ophthalmology".
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NR 56
TC 0
Z9 0
U1 0
U2 10
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 23
PY 2021
VL 11
IS 1
AR 15106
DI 10.1038/s41598-021-94676-6
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA TS0YZ
UT WOS:000679385000004
PM 34302055
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Luu, W
   Zangerl, B
   Kalloniatis, M
   Palmisano, S
   Kim, J
AF Luu, Wilson
   Zangerl, Barbara
   Kalloniatis, Michael
   Palmisano, Stephen
   Kim, Juno
TI Vision Impairment Provides New Insight Into Self-Motion Perception
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE virtual reality; vection; presence; age-related macular degeneration;
   glaucoma
ID STIMULUS ECCENTRICITY; PERIPHERAL-VISION; VIEWPOINT JITTER; GLAUCOMA;
   VECTION; PREVALENCE; AUSTRALIA; ANGLE; SIZE
AB PURPOSE. Leading causes of irreversible blindness such as age-related macular degeneration (AMD) and glaucoma can, respectively, lead to central or peripheral vision loss. The ability of sufferers to process visual motion information can be impacted even during early stages of eye disease. We used head-mounted display virtual reality as a tool to better understand how vision changes caused by eye diseases directly affect the processing of visual information critical for self-motion perception.
   METHODS. Participants with intermediate AMD or early manifest glaucoma with near-normal visual acuities and visual fields were recruited for this study. We examined their experiences of self-motion in depth (linear vection), spatial presence, and cybersickness when viewing radially expanding patterns of optic flow simulating different speeds of self-motion in depth. Viewing was performed with the head stationary (passive condition) or while making lateral-sway head movements (active conditions).
   RESULTS. Participants with AMD (i.e., central visual field loss) were found to have greater vection strength and spatial presence, compared to participants with normal visual fields. However, participants with glaucoma (i.e., peripheral visual field loss) were found to have lower vection strength and spatial presence, compared to participants with normal visual fields. Both AMD and glaucoma groups reported reduced severity in cybersickness compared to healthy normals.
   CONCLUSIONS. These findings strongly support the view that perceived self-motion is differentially influenced by peripheral versus central vision loss, and that patients with different visual field defects are oppositely biased when processing visual cues to self-motion perception.
C1 [Luu, Wilson; Zangerl, Barbara; Kalloniatis, Michael; Kim, Juno] Univ New South Wales, Sch Optometry & Vis Sci, Level 3,Room 3-006,North Wing,Rupert Myers Bldg, Sydney, NSW 2052, Australia.
   [Luu, Wilson; Zangerl, Barbara; Kalloniatis, Michael] Univ New South Wales, Ctr Eye Hlth, Sydney, NSW, Australia.
   [Palmisano, Stephen] Univ Wollongong, Sch Psychol, Wollongong, NSW, Australia.
C3 University of New South Wales Sydney; University of New South Wales
   Sydney; University of Wollongong
RP Kim, J (通讯作者)，Univ New South Wales, Sch Optometry & Vis Sci, Level 3,Room 3-006,North Wing,Rupert Myers Bldg, Sydney, NSW 2052, Australia.; Luu, W (通讯作者)，UNSW, Ctr Eye Hlth, Sch Optometry & Vis Sci, South Wing,Rupert Myers Bldg, Sydney, NSW 2052, Australia.
EM wilson.luu@unsw.edu.au; juno.kim@unsw.edu.au
RI Palmisano, Stephen/O-1553-2018
OI Palmisano, Stephen/0000-0002-9140-5681; Luu, Wilson/0000-0002-5751-274X
FU Sensory Processes Innovation Network (SPINet); Australian Government
   Research Training Program; Guide Dogs NSW/ACT; ARC Future Fellowship
   [FT140100535]
FX Supported by the Sensory Processes Innovation Network (SPINet) and a
   travel award for WL to present the findings at the 2019 Asia Pacific
   Conference on Vision (APCV'19). W.L. is a PhD candidate supported by the
   Australian Government Research Training Program and a scholarship from
   Guide Dogs NSW/ACT. B.Z. and M.K. receive salary support from Guide Dogs
   NSW/ACT. J.K. was supported by an ARC Future Fellowship (FT140100535).
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NR 75
TC 3
Z9 3
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2021
VL 62
IS 2
AR 4
DI 10.1167/iovs.62.2.4
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA QQ5MM
UT WOS:000624567800004
PM 33533880
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gonzalez-Gonzalo, C
   Liefers, B
   van Ginneken, B
   Sanchez, CI
AF Gonzalez-Gonzalo, Cristina
   Liefers, Bart
   van Ginneken, Bram
   Sanchez, Clara I.
TI Iterative Augmentation of Visual Evidence for Weakly-Supervised Lesion
   Localization in Deep Interpretability Frameworks: Application to Color
   Fundus Images
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Interpretability; deep learning; visualization; weakly-supervised
   detection; lesion localization; color fundus imaging
ID DIABETIC-RETINOPATHY; MACULAR DEGENERATION; DISEASE; CLASSIFICATION;
   DRUSEN
AB Interpretability of deep learning (DL) systems is gaining attention in medical imaging to increase experts' trust in the obtained predictions and facilitate their integration in clinical settings. We propose a deep visualization method to generate interpretability of DL classification tasks in medical imaging by means of visual evidence augmentation. The proposed method iteratively unveils abnormalities based on the prediction of a classifier trained only with image-level labels. For each image, initial visual evidence of the prediction is extracted with a given visual attribution technique. This provides localization of abnormalities that are then removed through selective inpainting. We iteratively apply this procedure until the system considers the image as normal. This yields augmented visual evidence, including less discriminative lesions which were not detected at first but should be considered for final diagnosis. We apply the method to grading of two retinal diseases in color fundus images: diabetic retinopathy (DR) and age-related macular degeneration (AMD). We evaluate the generated visual evidence and the performance of weakly-supervised localization of different types of DR and AMD abnormalities, both qualitatively and quantitatively. We show that the augmented visual evidence of the predictions highlights the biomarkers considered by experts for diagnosis and improves the final localization performance. It results in a relative increase of 11.2 +/- 2.0% per image regarding sensitivity averaged at 10 false positives/image on average, when applied to different classification tasks, visual attribution techniques and network architectures. This makes the proposed method a useful tool for exhaustive visual support of DL classifiers in medical imaging.
C1 [Gonzalez-Gonzalo, Cristina; Liefers, Bart; Sanchez, Clara I.] Radboudumc, Eye Res Grp A, Diagnost Image Anal Grp, Dept Radiol & Nucl Med, NL-6525 Nijmegen, Netherlands.
   [Gonzalez-Gonzalo, Cristina; Liefers, Bart; Sanchez, Clara I.] Radboudumc, Donders Inst Brain Cognit & Behav, NL-6525 Nijmegen, Netherlands.
   [van Ginneken, Bram] Radboudumc, Dept Radiol & Nucl Med, Diagnost Image Anal Grp, NL-6525 Nijmegen, Netherlands.
   [Sanchez, Clara I.] Radboudumc, Dept Ophthalmol, NL-6525 Nijmegen, Netherlands.
RP Gonzalez-Gonzalo, C (通讯作者)，Radboudumc, Eye Res Grp A, Diagnost Image Anal Grp, Dept Radiol & Nucl Med, NL-6525 Nijmegen, Netherlands.; Gonzalez-Gonzalo, C (通讯作者)，Radboudumc, Donders Inst Brain Cognit & Behav, NL-6525 Nijmegen, Netherlands.
EM cristina.gonzalezgonzalo@radboudumc.nl; bart.liefers@radboudumc.nl;
   bram.vanginneken@radboudumc.nl; clara.sanchezgutierrez@radboudumc.nl
RI van Ginneken, Bram/A-3728-2012; Sanchez Gutierrez, Clara
   Isabel/B-3800-2014
OI van Ginneken, Bram/0000-0003-2028-8972; Gonzalez-Gonzalo,
   Cristina/0000-0001-8413-3297; Sanchez Gutierrez, Clara
   Isabel/0000-0001-9787-8319
FU Dutch Technology Foundation STW, Netherlands Organisation for Scientific
   Research (NWO); Ministry of Economic Affairs [P15-26]
FX This work was supported by the Dutch Technology Foundation STW, which is
   part of the Netherlands Organisation for Scientific Research (NWO) and
   partly funded by the Ministry of Economic Affairs (Perspectief programme
   P15-26 'DLMedIA: Deep Learning for Medical Image Analysis').
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NR 51
TC 9
Z9 9
U1 3
U2 19
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD NOV
PY 2020
VL 39
IS 11
BP 3499
EP 3511
DI 10.1109/TMI.2020.2994463
PG 13
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA OM9RL
UT WOS:000586352000022
PM 32746093
OA Green Submitted, hybrid
DA 2022-11-30
ER

PT J
AU Oddone, E
   Taino, G
   Vita, S
   Schimd, M
   Frigerio, F
   Imbriani, M
AF Oddone, Enrico
   Taino, Giuseppe
   Vita, Silvia
   Schimd, Monica
   Frigerio, Francesco
   Imbriani, Marcello
TI Macular degeneration: peculiar sunlight exposure in an agricultural
   worker
SO MEDICINA DEL LAVORO
LA English
DT Article
DE Age-related macular degeneration; sunlight exposure; blue light;
   agriculture; occupational exposure; personal protective equipment
ID AGE-RELATED MACULOPATHY; RISK-FACTOR; LIGHT; PHOTOREACTIVITY; RADIATION;
   ARC
AB Background: Occupational exposure to sunlight, in particular to blue light (wavelength of 380-550 nm), is a risk factor for several pathologies, including chronic retinal photochemical damage and, more specifically, age-related macular degeneration (AMD). Moreover, in addition to the effect of blue light, there is evidence about the role of near ultraviolet light (UV-A) as a risk factor for AMD since, given the wavelength, a precise "turning point" between effect and no effect is not definable. Methods and results: This work reports the case of a woman employed in the agricultural sector from 15 to 25 years of age, with no significant occupational exposure to other risk factors for AMD, who later developed this pathology. The case is of particular interest given that she worked as a "mondina", a task involving the transplanting of young rice seedlings into water flooded fields and manual weed control. Ibis practice, although replaced by the introduction of pesticides, entailed the exposure to sunlight reflection on the water surface in addition to direct exposure to natural light. Conclusion: This brief case-report points out that occupational exposure to the short wavelength component of visible light and UV-A deserve further attention regarding preventive measures and the adoption of adequate personal protective equipment, in particular in productive sectors involving lengthy eye exposure to solar radiation and to the reflectance of surrounding surfaces. Furthermore, the cases of AMD and cataract should receive a complete and accurate occupational anamnesis for a more proper recognition of the possible role of occupational solar radiation exposure in the induction of the disease.
C1 [Oddone, Enrico; Imbriani, Marcello] Univ Pavia, Occupat Med Unit Salvatore Maugeri, Dept Publ Hlth Expt & Forens Med, Via Severino Boezio 24, I-27100 Pavia, Italy.
   [Oddone, Enrico; Frigerio, Francesco; Imbriani, Marcello] IRCCS Salvatore Maugeri Fdn, Dept Occupat Med Toxicol & Environm Risks, Pavia, Italy.
   [Taino, Giuseppe] IRCCS Salvatore Maugeri Fdn, Hosp Occupat Med Unit UOOML, Dept Occupat Med Toxicol & Environm Risks, Pavia, Italy.
   [Vita, Silvia; Schimd, Monica] IRCCS Salvatore Maugeri Fdn, Ophthalmol Rehabil Unit, Pavia, Italy.
C3 University of Pavia; Istituti Clinici Scientifici Maugeri IRCCS;
   Istituti Clinici Scientifici Maugeri IRCCS; Istituti Clinici Scientifici
   Maugeri IRCCS
RP Oddone, E (通讯作者)，Univ Pavia, Occupat Med Unit Salvatore Maugeri, Dept Publ Hlth Expt & Forens Med, Via Severino Boezio 24, I-27100 Pavia, Italy.
EM enrico.oddone@unipv.it
RI Imbriani, Marcello/AAB-1171-2021; oddone, enrico/H-1682-2013; Taino,
   Giuseppe/W-5959-2019; Frigerio, Francesco/AAC-1613-2021
OI Imbriani, Marcello/0000-0002-2752-1565; oddone,
   enrico/0000-0001-8503-6560; Taino, Giuseppe/0000-0002-8995-100X;
   Frigerio, Francesco/0000-0003-3164-3933
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PU MATTIOLI 1885
PI FIDENZA
PA VIA DELLA LODESANA 649-SX, FIDENZA, 43046 PR, ITALY
SN 0025-7818
J9 MED LAV
JI Med. Lav.
PD MAY-JUN
PY 2019
VL 110
IS 3
BP 241
EP 245
DI 10.23749/mdl.v110i3.8125
PG 5
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Public, Environmental & Occupational Health
GA IG3HR
UT WOS:000473695900008
PM 31268431
DA 2022-11-30
ER

PT J
AU Low, A
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AF Low, Allison
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TI Comparative effectiveness and harms of intravitreal antivascular
   endothelial growth factor agents for three retinal conditions: a
   systematic review and meta-analysis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID DIABETIC MACULAR EDEMA; VEGF TRAP-EYE; VISUAL-ACUITY;
   COST-EFFECTIVENESS; VEIN OCCLUSION; RANIBIZUMAB; BEVACIZUMAB;
   DEGENERATION; AFLIBERCEPT; INJECTION
AB Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on bestcorrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (>= 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.
C1 [Low, Allison; Freeman, Michele; Paynter, Robin; Kondo, Karli; Kansagara, Devan] VA Portland Hlth Care Syst, Evidence Based Synth Program, Portland, OR 97239 USA.
   [Faridi, Ambar; Bhavsar, Kavita V.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA.
   [Faridi, Ambar; Bhavsar, Kavita V.] VA Portland Hlth Care Syst, Dept Ophthalmol, Operat Care Div, Portland, OR USA.
   [Cockerham, Glenn C.] Dept Vet Affairs, Vet Hlth Adm Ophthalmol Serv, Palo Alto, CA USA.
   [Fu, Rochelle; Kansagara, Devan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
   [Fu, Rochelle; Kondo, Karli] Oregon Hlth & Sci Univ Portland State Univ Sch Pu, Portland, OR USA.
   [Kansagara, Devan] VA Portland Healthcare Syst, Dept Med, Portland, OR USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   VA Portland Health Care System; Oregon Health & Science University; US
   Department of Veterans Affairs; Veterans Health Administration (VHA); VA
   Portland Health Care System; US Department of Veterans Affairs; Veterans
   Health Administration (VHA); VA Palo Alto Health Care System; Oregon
   Health & Science University; Oregon Health & Science University;
   Portland State University; US Department of Veterans Affairs; Veterans
   Health Administration (VHA); VA Portland Health Care System
RP Low, A (通讯作者)，VA Portland Hlth Care Syst, Evidence Based Synth Program, Portland, OR 97239 USA.
EM low@oakland.edu
RI Kondo, Karli/R-3994-2019
OI Kondo, Karli/0000-0002-4635-5056; Paynter, Robin/0000-0002-6969-4261
FU Department of Veterans Affairs, Veterans Health Administration, Office
   of Research and Development, Quality Enhancement Research Initiative
FX This research was funded by the Department of Veterans Affairs, Veterans
   Health Administration, Office of Research and Development, Quality
   Enhancement Research Initiative.
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NR 67
TC 20
Z9 20
U1 0
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2019
VL 103
IS 4
BP 442
EP 451
DI 10.1136/bjophthalmol-2018-312691
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ID7OE
UT WOS:000471871400002
PM 30409915
DA 2022-11-30
ER

PT J
AU Schmidt-Erfurth, U
   Waldstein, SM
   Klimscha, S
   Sadeghipour, A
   Hu, XF
   Gerendas, BS
   Osborne, A
   Bogunovic, H
AF Schmidt-Erfurth, Ursula
   Waldstein, Sebastian M.
   Klimscha, Sophie
   Sadeghipour, Amir
   Hu, Xiaofeng
   Gerendas, Bianca S.
   Osborne, Aaron
   Bogunovic, Hrvoje
TI Prediction of Individual Disease Conversion in Early AMD Using
   Artificial Intelligence
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration; optical coherence tomography; machine
   learning; artificial intelligence; choroidal neovascularization
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; IMAGING BIOMARKERS;
   DRUSEN VOLUME; PROGRESSION; MORPHOLOGY; ATROPHY
AB PURPOSE. While millions of individuals show early age-related macular degeneration (AMD) signs, yet have excellent vision, the risk of progression to advanced AMD with legal blindness is highly variable. We suggest means of artificial intelligence to individually predict AMD progression.
   METHODS. In eyes with intermediate AMD, progression to the neovascular type with choroidal neovascularization (CNV) or the dry type with geographic atrophy (GA) was diagnosed based on standardized monthly optical coherence tomography (OCT) images by independent graders. We obtained automated volumetric segmentation of outer neurosensory layers and retinal pigment epithelium, drusen, and hyperreflective foci by spectral domain-OCT image analysis. Using imaging, demographic, and genetic input features, we developed and validated a machine learning-based predictive model assessing the risk of conversion to advanced AMD.
   RESULTS. Of a total of 495 eyes, 159 eyes (32%) had converted to advanced AMD within 2 years, 114 eyes progressed to CNV, and 45 to GA. Our predictive model differentiated converting versus nonconverting eyes with a performance of 0.68 and 0.80 for CNV and GA, respectively. The most critical quantitative features for progression were outer retinal thickness, hyperreflective foci, and drusen area. The features for conversion showed pathognomonic patterns that were distinctly different for the neovascular and the atrophic pathways. Predictive hallmarks for CNV were mostly drusen-centric, while GA markers were associated with neurosensory retina and age.
   CONCLUSIONS. Artificial intelligence with automated analysis of imaging biomarkers allows personalized prediction of AMD progression. Moreover, pathways of progression may be specific in respect to the neovascular/atrophic type.
C1 [Schmidt-Erfurth, Ursula; Waldstein, Sebastian M.; Klimscha, Sophie; Sadeghipour, Amir; Hu, Xiaofeng; Gerendas, Bianca S.; Bogunovic, Hrvoje] Med Univ Vienna, Dept Ophthalmol, Vienna Reading Ctr, Christian Doppler Lab Ophthalm Image Anal, Vienna, Austria.
   [Osborne, Aaron] Genentech Inc, San Francisco, CA 94080 USA.
C3 Medical University of Vienna; Roche Holding; Genentech
RP Schmidt-Erfurth, U (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Spitalgasse 23, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
RI Bogunovic, Hrvoje/J-3445-2014
OI Bogunovic, Hrvoje/0000-0002-9168-0894; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311; Riedl, Sophie/0000-0003-0003-0886; Gerendas,
   Bianca S./0000-0001-8940-8130
FU Austrian Federal Ministry of Science, Research and Economy
FX Supported by the Austrian Federal Ministry of Science, Research and
   Economy.
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NR 30
TC 82
Z9 86
U1 0
U2 18
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2018
VL 59
IS 8
BP 3199
EP 3208
DI 10.1167/iovs.18-24106
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GL9II
UT WOS:000437547100002
PM 29971444
OA gold
DA 2022-11-30
ER

PT J
AU Hariri, A
   Wang, JX
   Kim, Y
   Jhunjhunwala, A
   Chao, DL
   Jokerst, JV
AF Hariri, Ali
   Wang, Junxin
   Kim, Yeji
   Jhunjhunwala, Anamik
   Chao, Daniel L.
   Jokerst, Jesse V.
TI In vivo photoacoustic imaging of chorioretinal oxygen gradients
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE photoacoustic ocular imaging; chorioretina oxygen saturation; oxygen
   tension; ischemia reperfusion
ID OPTICAL COHERENCE TOMOGRAPHY; HIGH-RESOLUTION; FUNDUS CAMERA; HUMAN EYE;
   SATURATION; OPHTHALMOSCOPY; ULTRASOUND; MICROSCOPY; OXIMETRY; DISEASE
AB Chorioretinal imaging has a crucial role for the patients with chorioretinal vascular diseases, such as neovascular age-related macular degeneration. Imaging oxygen gradients in the eye could better diagnose and treat ocular diseases. Here, we describe the use of photoacoustic ocular imaging (PAOI) in measuring chorioretinal oxygen saturation (CR - sO(2)) gradients in New Zealand white rabbits (n = 5) with ocular ischemia. We observed good correlation (R-2 = 0.98) between pulse oximetry and PAOI as a function of different oxygen percentages in inhaled air. We then used an established ocular ischemia model in which intraocular pressure is elevated to constrict ocular blood flow, and notice a positive correlation (R-2 = 0.92) between the injected volume of phosphate buffered saline (PBS) and intraocular pressure (IOP) as well as a negative correlation (R-2 = 0.98) between CR - sO2 and injected volume of PBS. The CR - sO(2) was measured before (baseline), during (ischemia), and after the infusion (600-mu L PBS). The ischemia-reperfusion model did not affect the measurement of the sO(2) using a pulse oximeter on the animal's paw, but the chorioretinal PAOI signal showed a nearly sixfold decrease in CR - sO(2) (n = 5, p = 0.00001). We also observe a sixfold decrease in CR - sO(2) after significant elevation of IOP during ischemia, with an increase close to baseline during reperfusion. These data suggest that PAOI can detect changes in chorioretinal oxygenation and may be useful for application to imaging oxygen gradients in ocular disease. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Hariri, Ali; Wang, Junxin; Jokerst, Jesse V.] Univ Calif San Diego, Nanoengn Dept, La Jolla, CA 92093 USA.
   [Kim, Yeji] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
   [Jhunjhunwala, Anamik] Univ Calif San Diego, Bioengn Dept, La Jolla, CA 92093 USA.
   [Chao, Daniel L.] Univ Calif San Diego, Shiley Eye Inst, Dept Ophthalmol, La Jolla, CA 92093 USA.
   [Jokerst, Jesse V.] Univ Calif San Diego, Mat Sci & Engn Program, La Jolla, CA 92093 USA.
   [Jokerst, Jesse V.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego;
   University of California System; University of California San Diego;
   University of California System; University of California San Diego;
   University of California System; University of California San Diego;
   University of California System; University of California San Diego;
   University of California System; University of California San Diego
RP Jokerst, JV (通讯作者)，Univ Calif San Diego, Nanoengn Dept, La Jolla, CA 92093 USA.; Jokerst, JV (通讯作者)，Univ Calif San Diego, Mat Sci & Engn Program, La Jolla, CA 92093 USA.; Jokerst, JV (通讯作者)，Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
EM jjokerst@ucsd.edu
FU NIH [HL117048, HL137187]; American Cancer Society Institutional Research
   through the Moores Cancer Center, University of California, San Diego
   [14-250-42]; UC San Diego via the Frontiers of Innovation Scholars
   Program (FISP) [3-G3005];  [S10 OD021821]; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R00HL117048, DP2HL137187] Funding Source: NIH RePORTER;
   OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD021821]
   Funding Source: NIH RePORTER
FX Jesse V. Jokerst acknowledges funding from NIH HL117048 and HL137187 and
   infrastructure from S10 OD021821. The authors also thank the American
   Cancer Society Institutional Research (Grant No. 14-250-42) provided
   through the Moores Cancer Center, University of California, San Diego.
   We also knowledge UC San Diego for funding via the Frontiers of
   Innovation Scholars Program (FISP #3-G3005). The authors acknowledge
   Kristyn Huffman from Dr. Cheng's Lab at UC San Diego for her assistance
   with measuring IOP in this study.
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NR 59
TC 32
Z9 32
U1 0
U2 10
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAR
PY 2018
VL 23
IS 3
AR 036005
DI 10.1117/1.JBO.23.3.036005
PG 8
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA GB7IT
UT WOS:000429248800019
PM 29524321
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hasegawa, E
   Inafuku, S
   Mulki, L
   Okunuki, Y
   Yanai, R
   Smith, KE
   Kim, CB
   Klokman, G
   Bielenberg, DR
   Puli, N
   Falck, JR
   Husain, D
   Miller, JW
   Edin, ML
   Zeldin, DC
   Lee, KSS
   Hammock, BD
   Schunck, WH
   Connor, KM
AF Hasegawa, Eiichi
   Inafuku, Saori
   Mulki, Lama
   Okunuki, Yoko
   Yanai, Ryoji
   Smith, Kaylee E.
   Kim, Clifford B.
   Klokman, Garrett
   Bielenberg, Diane R.
   Puli, Narender
   Falck, John R.
   Husain, Deeba
   Miller, Joan W.
   Edin, Matthew L.
   Zeldin, Darryl C.
   Lee, Kin Sing Stephen
   Hammock, Bruce D.
   Schunck, Wolf-Hagen
   Connor, Kip M.
TI Cytochrome P450 monooxygenase lipid metabolites are significant second
   messengers in the resolution of choroidal neovascularization
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE P450; choroidal neovascularization; oxylipin; omega-3 fatty acids; lipid
   metabolites
ID POLYUNSATURATED FATTY-ACIDS; LOWERS BLOOD-PRESSURE; MACULAR
   DEGENERATION; DIETARY OMEGA-3-FATTY-ACIDS; EPOXYEICOSATRIENOIC ACIDS;
   ENDOTHELIAL EXPRESSION; TARGETED DISRUPTION; EPOXIDE; INHIBITION;
   DISEASE
AB Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.
C1 [Hasegawa, Eiichi; Inafuku, Saori; Mulki, Lama; Okunuki, Yoko; Yanai, Ryoji; Smith, Kaylee E.; Kim, Clifford B.; Klokman, Garrett; Husain, Deeba; Miller, Joan W.; Connor, Kip M.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA.
   [Bielenberg, Diane R.] Harvard Med Sch, Dept Surg, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.
   [Puli, Narender; Falck, John R.] Univ Texas Southwestern, Dept Biochem, Dallas, TX 75390 USA.
   [Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
   [Lee, Kin Sing Stephen; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
   [Lee, Kin Sing Stephen; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA.
   [Schunck, Wolf-Hagen] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Harvard University; Boston Children's Hospital; Harvard
   Medical School; University of Texas System; University of Texas
   Southwestern Medical Center Dallas; National Institutes of Health (NIH)
   - USA; NIH National Institute of Environmental Health Sciences (NIEHS);
   University of California System; University of California Davis;
   University of California System; University of California Davis;
   Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Connor, KM (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Boston, MA 02114 USA.; Hammock, BD (通讯作者)，Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.; Hammock, BD (通讯作者)，Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA.
EM bdhammock@ucdavis.edu; kip_connor@meei.harvard.edu
RI Edin, Matthew/AAI-1934-2019; Okunuki, Yoko/ABE-8090-2020; Smith, Kevin
   M/G-1453-2011; Zeldin, Darryl C/Y-7091-2018; Lee, Kin Sing
   Stephen/I-9476-2012
OI Okunuki, Yoko/0000-0002-1612-7925; Smith, Kevin M/0000-0002-6736-4779;
   Zeldin, Darryl C/0000-0002-2087-7307; Edin, Matthew/0000-0002-7042-500X;
   Husain, Deeba/0000-0002-8494-0950; Lee, Kin Sing
   Stephen/0000-0003-4541-3063; Connor, Kip/0000-0002-2048-9080
FU Research to Prevent Blindness; Department of Ophthalmology, Harvard
   University; Massachusetts Eye and Ear Infirmary; Massachusetts Lions Eye
   Research Fund; BrightFocus Foundation; West Coast Metabolomics Center
   [NIH 1U24DK097154]; Japan Society for the Promotion of Science
   Postdoctoral Fellowships; NIH, National Institute of Environmental
   Health Sciences (NIEHS) [Z01 E5025034]; Robert A. Welch Foundation
   [1-0011]; NIH [HL111392, K99ES024806, R00ES024806]; NIEHS [R01ES002710];
   NIEHS/Superfund Research Program [P42 E5004699]; Special Scholar Award;
   Medical Student Fellowship;  [R01EY022084/S1]; NATIONAL EYE INSTITUTE
   [R01EY022084] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U24DK097154] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
   [R01ES002710, K99ES024806, Z01ES025034, ZIAES025034, R00ES024806,
   P42ES004699] Funding Source: NIH RePORTER
FX This study was supported by a Special Scholar Award (to K.M.C.), a
   Medical Student Fellowship Grant (to C.B.K.), and an unrestricted grant
   (to J.W.M.) from Research to Prevent Blindness. Special thanks go to
   Department of Ophthalmology, Harvard University, and Massachusetts Eye
   and Ear Infirmary for supporting this research (K.M.C.); the
   Massachusetts Lions Eye Research Fund (K.M.C.); the BrightFocus
   Foundation (K.M.C.); Grant R01EY022084/S1 (to K.M.C.); partial support
   (to K.M.C.) from the West Coast Metabolomics Center (NIH 1U24DK097154);
   a fellowship from the Japan Society for the Promotion of Science
   Postdoctoral Fellowships for Research Abroad (to E.H.); the Intramural
   Program of the NIH, National Institute of Environmental Health Sciences
   (NIEHS) (Z01 E5025034 to D.C.Z.); the Robert A. Welch Foundation (1-0011
   to J.R.F.); and NIH (HL111392 to J.R.F.). Partial support was supplied
   by NIEHS (R01ES002710 to B.D.H.), NIEHS/Superfund Research Program (P42
   E5004699 to B.D.H.), and the NIH (K99ES024806 and R00ES024806 to
   K.S.S.L.).
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NR 60
TC 22
Z9 24
U1 0
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 5
PY 2017
VL 114
IS 36
BP E7545
EP E7553
DI 10.1073/pnas.1620898114
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FF7FP
UT WOS:000409182200016
PM 28827330
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Shan, Y
   Tromp, G
   Kuivaniemi, H
   Smelser, DT
   Verma, SS
   Ritchie, MD
   Elmore, JR
   Carey, DJ
   Conley, YP
   Gorin, MB
   Weeks, DE
AF Shan, Ying
   Tromp, Gerard
   Kuivaniemi, Helena
   Smelser, Diane T.
   Verma, Shefali S.
   Ritchie, Marylyn D.
   Elmore, James R.
   Carey, David J.
   Conley, Yvette P.
   Gorin, Michael B.
   Weeks, Daniel E.
TI Genetic risk models: Influence of model size on risk estimates and
   precision
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE disease risk estimation; confidence interval; model size;
   reclassification
ID ABDOMINAL AORTIC-ANEURYSM; POLYMORPHISMS; DISEASE; ASSOCIATION;
   PREDICTION; VARIANT; ATHEROSCLEROSIS; SUSCEPTIBILITY; UNCERTAINTY;
   INFORMATION
AB Disease risk estimation plays an important role in disease prevention. Many studies have found that the ability to predict risk improves as the number of risk single-nucleotide polymorphisms (SNPs) in the risk model increases. However, the width of the confidence interval of the risk estimate is often not considered in the evaluation of the risk model. Here, we explore how the risk and the confidence interval width change as more SNPs are added to the model in the order of decreasing effect size, using both simulated data and real data from studies of abdominal aortic aneurysms and age-related macular degeneration. Our results show that confidence interval width is positively correlated with model size and the majority of the bigger models have wider confidence interval widths than smaller models. Once the model size is bigger than a certain level, the risk does not shift markedly, as 100% of the risk estimates of the one-SNP-bigger models lie inside the confidence interval of the one-SNP-smaller models. We also created a confidence interval-augmented reclassification table. It shows that both more effective SNPs with larger odds ratios and less effective SNPs with smaller odds ratios contribute to the correct decision of whom to screen. The best screening strategy is selected and evaluated by the net benefit quantity and the reclassification rate. We suggest that individuals whose upper bound of their risk confidence interval is above the screening threshold, which corresponds to the population prevalence of the disease, should be screened.
C1 [Shan, Ying; Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, 130 De Soto St, Pittsburgh, PA 15261 USA.
   [Tromp, Gerard; Kuivaniemi, Helena; Smelser, Diane T.; Carey, David J.] Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.
   [Tromp, Gerard; Kuivaniemi, Helena] Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa.
   [Verma, Shefali S.; Ritchie, Marylyn D.] Geisinger Hlth Syst, Dept Biomed & Translat Informat, Danville, PA USA.
   [Elmore, James R.] Geisinger Hlth Syst, Dept Vasc & Endovasc Surg, Danville, PA USA.
   [Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15261 USA.
   [Conley, Yvette P.; Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, 130 De Soto St, 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, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Gorin, Michael B.] Stein Eye Inst, Los Angeles, CA USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Geisinger Health System; Stellenbosch University;
   Geisinger Health System; Geisinger Health System; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh; 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
RP Weeks, DE (通讯作者)，Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, 130 De Soto St, Pittsburgh, PA 15261 USA.; Weeks, DE (通讯作者)，Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, 130 De Soto St, Pittsburgh, PA 15261 USA.
EM weeks@pitt.edu
RI Tromp, Gerard/B-2677-2017; Weeks, Daniel E/B-2995-2012; Kuivaniemi,
   Helena/Q-8178-2019
OI Tromp, Gerard/0000-0002-7761-0806; Weeks, Daniel E/0000-0001-9410-7228;
   Kuivaniemi, Helena/0000-0001-5753-8766; Conley,
   Yvette/0000-0002-1784-6067; Shan, Ying/0000-0003-3253-3197
FU Commonwealth Universal Research Enhancement (CURE) program of the
   Commonwealth of Pennsylvania [1120101]; National Institutes of Health
   [R01 EY009859]; National Institutes of Health American Recovery and
   Reinvestment Act [R01 EY009859-14S1]; NATIONAL EYE INSTITUTE
   [R01EY009859] Funding Source: NIH RePORTER
FX Grant sponsor: The Commonwealth Universal Research Enhancement (CURE)
   program of the Commonwealth of Pennsylvania; Grant number: 1120101;
   Grant sponsor: National Institutes of Health; Grant number: R01
   EY009859; Grant sponsor: National Institutes of Health American Recovery
   and Reinvestment Act; Grant number: R01 EY009859-14S1.
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NR 42
TC 2
Z9 2
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2017
VL 41
IS 4
BP 282
EP 296
DI 10.1002/gepi.22035
PG 15
WC Genetics & Heredity; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Mathematical & Computational Biology
GA ES7EN
UT WOS:000399712600001
PM 28198095
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Bonet-Ponce, L
   Saez-Atienzar, S
   da Casa, C
   Sancho-Pelluz, J
   Barcia, JM
   Martinez-Gil, N
   Nava, E
   Jordan, J
   Romero, FJ
   Galindo, MF
AF Bonet-Ponce, Luis
   Saez-Atienzar, Sara
   da Casa, Carmen
   Sancho-Pelluz, Javier
   Barcia, Jorge M.
   Martinez-Gil, Natalia
   Nava, Eduardo
   Jordan, Joaquin
   Romero, Francisco J.
   Galindo, Maria F.
TI Rotenone Induces the Formation of 4-Hydroxynonenal Aggresomes. Role of
   ROS-Mediated Tubulin Hyperacetylation and Autophagic Flux Disruption
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Autophagy; Mitochondria; Reactive oxygen species; Tubulin
ID OXIDATIVE STRESS; SH-SY5Y CELLS; NEURODEGENERATIVE DISEASE; MONITORING
   AUTOPHAGY; DJ-1-DEFICIENT MICE; PARKINSON DISEASE; INCLUSION-BODIES;
   DEATH; DEACETYLASE; CLEARANCE
AB Oxidative stress causes cellular damage by (i) altering protein stability, (ii) impairing organelle function, or (iii) triggering the formation of 4-HNE protein aggregates. The catabolic process known as autophagy is an antioxidant cellular response aimed to counteract these stressful conditions. Therefore, autophagy might act as a cytoprotective response by removing impaired organelles and aggregated proteins. In the present study, we sought to understand the role of autophagy in the clearance of 4-HNE protein aggregates in ARPE-19 cells under rotenone exposure. Rotenone induced an overproduction of reactive oxygen species (ROS), which led to an accumulation of 4-HNE inclusions, and an increase in the number of autophagosomes. The latter resulted from a disturbed autophagic flux rather than an activation of the autophagic synthesis pathway. In compliance with this, rotenone treatment induced an increase in LC3-II while upstream autophagy markers such as Beclin- 1, Vsp34 or Atg5-Atg12, were decreased. Rotenone reduced the autophagosome-to-lysosome fusion step by increasing tubulin acetylation levels through a ROS-mediated pathway. Proof of this is the finding that the free radical scavenger, N-acetylcysteine, restored autophagy flux and reduced rotenone-induced tubulin hyperacetylation. Indeed, this dysfunctional autophagic response exacerbates cell death triggered by rotenone, since 3-methyladenine, an autophagy inhibitor, reduced cell mortality, while rapamycin, an inductor of autophagy, caused opposite effects. In summary, we shed new light on the mechanisms involved in the autophagic responses disrupted by oxidative stress, which take place in neurodegenerative diseases such as Huntington or Parkinson diseases, and age-related macular degeneration.
C1 [Bonet-Ponce, Luis; Saez-Atienzar, Sara; Sancho-Pelluz, Javier; Barcia, Jorge M.; Martinez-Gil, Natalia; Romero, Francisco J.] Univ Catolia Valencia San Vicente Martir, Fac Med Odontol, Valencia, Spain.
   [Saez-Atienzar, Sara; Galindo, Maria F.] Univ Albacete, Complejo Hosp, Unidad Neuropsicofarmacol Traslac, Albacete, Spain.
   [Saez-Atienzar, Sara; da Casa, Carmen; Nava, Eduardo; Jordan, Joaquin] Univ Castilla La Mancha, IDINE, Fac Med Albacete, Grp Neurofarmacol,Dpto Cienicas Med, Albacete, Spain.
C3 Universidad Catolica de Valencia San Vicente Martir; Universidad de
   Castilla-La Mancha; Universidad de Castilla-La Mancha
RP Galindo, MF (通讯作者)，Univ Albacete, Complejo Hosp, Unidad Neuropsicofarmacol Traslac, Albacete, Spain.
EM mgalindoa@sescam.jccm.es
RI JM, Barcia/ABH-2932-2020; Sancho-Pelluz, Javier/AAB-2786-2019;
   Bonet-Ponce, Luis/GPW-9357-2022; Bonet-Ponce, Luis/ADT-4664-2022
OI Sancho-Pelluz, Javier/0000-0001-5409-5760; Bonet-Ponce,
   Luis/0000-0001-9276-059X; nava, eduardo/0000-0003-3259-0511; Romero,
   Francisco J/0000-0001-8701-5907; da Casa, Carmen/0000-0002-2290-126X;
   Saez-Atienzar, Sara/0000-0002-1524-9584; Martinez Gil,
   Natalia/0000-0001-8882-5602; Barcia, Jorge M./0000-0002-3660-7977;
   Galindo Anaya, Maria Francisca/0000-0002-7789-7341
FU Ministerio de Ciencia e Innovacion, Spain [SAF2010-21317]; Universidad
   Catolica de Valencia; JCCM
FX We thank Carlos Garrido for his technical help and Dr E. Knecht for
   providing the mRFP-GFP-LC3 vector. This work was supported by a grant
   from the Ministerio de Ciencia e Innovacion, Spain (SAF2010-21317),
   funds from the Universidad Catolica de Valencia to FJR, and JCCM to JJ.
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NR 68
TC 28
Z9 29
U1 2
U2 13
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD NOV
PY 2016
VL 53
IS 9
BP 6194
EP 6208
DI 10.1007/s12035-015-9509-3
PG 15
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA EB2ZO
UT WOS:000387231300033
PM 26558631
DA 2022-11-30
ER

PT J
AU Peng, CH
   Chuang, JH
   Wang, ML
   Jhan, YY
   Chien, KH
   Chung, YC
   Hung, KH
   Chang, CC
   Lee, CK
   Tseng, WL
   Hwang, DK
   Hsu, CH
   Lin, TC
   Chiou, SH
   Chen, SJ
AF Peng, Chi-Hsien
   Chuang, Jen-Hua
   Wang, Mong-Lien
   Jhan, Yong-Yu
   Chien, Ke-Hung
   Chung, Yu-Chien
   Hung, Kuo-Hsuan
   Chang, Chia-Ching
   Lee, Chao-Kuei
   Tseng, Wei-Lien
   Hwang, De-Kuang
   Hsu, Chia-Hsien
   Lin, Tai-Chi
   Chiou, Shih-Hwa
   Chen, Shih-Jen
TI Laminin modification subretinal bio-scaffold remodels retinal pigment
   epithelium-driven microenvironment in vitro and in vivo
SO ONCOTARGET
LA English
DT Article
DE age-related macular degeneration; biomimetic scaffold; pluripotent stem
   cells; pigment epithelium cells; pigment epithelium-derived factor;
   Pathology Section
ID PLURIPOTENT STEM-CELLS; BRUCHS MEMBRANE; MACULAR DEGENERATION;
   AUTOLOGOUS TRANSPLANTATION; MATRIX; IDENTIFICATION; PHAGOCYTOSIS;
   IMPLANTATION; GENERATION; MOLECULES
AB Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear. Herein we generated a biomimetic scaffold mimicking subretinal Bruch's basement from plasma modified polydimethylsiloxane (PDMS) sheet with laminin coating (PDMS-PmL), and investigated its potential functions to provide a subretinal environment for dRPE-monolayer grown on it. Firstly, compared to non-modified PDMS, PDMS-PmL enhanced the attachment, proliferation, polarization, and maturation of dRPEs. Second, PDMS-PmL increased the polarized tight junction, PEDF secretion, melanosome pigment deposit, and phagocytotic-ability of dRPEs. Third, PDMS-PmL was able to carry a dRPEs/ photoreceptor-precursors multilayer retina tissue. Finally, the in vivo subretinal implantation of PDMS-PmL in porcine eyes showed well-biocompatibility up to 2-year follow-up. Notably, multifocal ERGs at 2-year follow-up revealed well preservation of macular function in PDMS-PmL, but not PDMS, transplanted porcine eyes. Trophic PEDF secretion of macular retina in PDMS-PmL group was also maintained to preserve retinal microenvironment in PDMS-PmL eyes at 2 year. Taken together, these data indicated that PDMS-PmL is able to sustain the physiological morphology and functions of polarized RPE monolayer, suggesting its potential of rescuing macular degeneration in vivo.
C1 [Peng, Chi-Hsien; Jhan, Yong-Yu; Chung, Yu-Chien; Hung, Kuo-Hsuan; Hwang, De-Kuang; Lin, Tai-Chi; Chiou, Shih-Hwa; Chen, Shih-Jen] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Chuang, Jen-Hua; Wang, Mong-Lien; Tseng, Wei-Lien; Chiou, Shih-Hwa] Taipei Vet Gen Hosp, Dept Med Res, Taipei, Taiwan.
   [Peng, Chi-Hsien] Shin Kong Wu Ho Mem Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Peng, Chi-Hsien] Fu Jen Catholic Univ, Taipei, Taiwan.
   [Chien, Ke-Hung] Triserv Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Chien, Ke-Hung] Natl Def Med Ctr, Taipei, Taiwan.
   [Chang, Chia-Ching] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu, Taipei, Taiwan.
   [Lee, Chao-Kuei] Natl Sun Yat Sen Univ, Dept Photon, Kaohsiung, Taiwan.
   [Hsu, Chia-Hsien] Natl Hlth Res Inst, Hsinchu, Taiwan.
   [Lin, Tai-Chi; Chiou, Shih-Hwa] Natl Yang Ming Univ, Inst Clin Med, Taipei, Taiwan.
   [Chiou, Shih-Hwa] Natl Yang Ming Univ, Inst Pharmacol, Taipei, Taiwan.
   [Chiou, Shih-Hwa; Chen, Shih-Jen] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
C3 Taipei Veterans General Hospital; Taipei Veterans General Hospital; Shin
   Kong Wu Ho Su Memorial Hospital; Fu Jen Catholic University; Tri-Service
   General Hospital; National Defense Medical Center; National Yang Ming
   Chiao Tung University; National Sun Yat Sen University; National Health
   Research Institutes - Taiwan; National Yang Ming Chiao Tung University;
   National Yang Ming Chiao Tung University; National Yang Ming Chiao Tung
   University
RP Chen, SJ (通讯作者)，Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.; Chen, SJ (通讯作者)，Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.
EM sjchen@vghtpe.gov.tw
RI Hsu, Chia-Hsien/E-4957-2010; Jhan, Yong-Yu/GLV-3718-2022; Chung,
   Yu-Chien/CAJ-1823-2022; Hwang, DK De-Kuang/J-3931-2016; Chang,
   Chia-Ching/F-1247-2011
OI Hsu, Chia-Hsien/0000-0002-0752-3133; Jhan, Yong-Yu/0000-0002-1131-166X;
   Hwang, DK De-Kuang/0000-0001-6346-8485; Chang,
   Chia-Ching/0000-0002-3444-0894
FU Ministry of Science and Technology [104-2627-M-010-004 /
   104-2325-B-010-006 / 104-2325-B-001-010 / 105-2633-B-009-003 /
   105-2325-B-010-005]; Taipei Veterans General Hospital (Stem Cell
   Project) [E99-104]; Yen-Tjing-Ling Medical Foundation [CI-100-104];
   Department of Health Cancer Center Research of Excellence
   [MOHW104-TDU-B-211-124-001 / TD-B-111-02 / MOHW104-TDU-B-211-113-003];
   National Health Research Institutes [NHRI-EX102-10258SI]; Academia
   Sinica [VTA105-V1-5-1]; Genomic / Cancer Center Project of National
   Yang-Ming University (Ministry of Education, Aim for the Top University
   Plan), Taiwan
FX This study was funded by the Ministry of Science and Technology
   (104-2627-M-010-004 / 104-2325-B-010-006 / 104-2325-B-001-010 /
   105-2633-B-009-003 / 105-2325-B-010-005), Taipei Veterans General
   Hospital (Stem Cell Project E99-104), Yen-Tjing-Ling Medical Foundation
   (CI-100-104), the Department of Health Cancer Center Research of
   Excellence (MOHW104-TDU-B-211-124-001 / TD-B-111-02 /
   MOHW104-TDU-B-211-113-003), National Health Research Institutes
   (NHRI-EX102-10258SI), Academia Sinica (VTA105-V1-5-1), and the Genomic /
   Cancer Center Project of National Yang-Ming University (Ministry of
   Education, Aim for the Top University Plan), Taiwan.
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NR 50
TC 19
Z9 20
U1 0
U2 11
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
EI 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 4
PY 2016
VL 7
IS 40
BP 64631
EP 64648
DI 10.18632/oncotarget.11502
PG 18
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA EB3QQ
UT WOS:000387281000008
PM 27564261
OA Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Gouras, P
   Ivert, L
   Neuringer, M
   Nagasaki, T
AF Gouras, Peter
   Ivert, L.
   Neuringer, M.
   Nagasaki, T.
TI Mitochondrial elongation in the macular RPE of aging monkeys, evidence
   of metabolic stress
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Retina; Macula; Epithelium; Monkey; Mitochondria; Morphology; Electron
   microscopy
ID RETINAL-PIGMENT EPITHELIUM; OXIDATIVE STRESS; GIANT MITOCHONDRIA;
   DEGENERATION; FUSION; CELLS; SENESCENCE; FISSION; FIS1; MORPHOLOGY
AB This study was conducted to determine whether mitochondria of the macular retinal pigment epithelium (RPE) change with age in rhesus monkeys (Macaca mulatta). Mitochondria are the main instigators of oxidative stress, which has often been considered to play a role in the pathogenesis of age-related macular degeneration (AMD). Any pathological changes in the mitochondria of aging macular RPE, the main target of AMD, would be a clue to the pathogenesis of this common retinal degeneration afflicting both monkey and man.
   Transmission electron microscopy was used to identify mitochondria and to determine their appearance, their density per unit area of RPE cytoplasm and their length. The eyes of seven monkeys, 1, 2, 6.5, 23, 26, 27 and 35 years of age, were studied. Measurements were kept separate for the basal, middle and apical third of each cell. The basal third of the macular RPE had many more mitochondria than the middle third, and the apical third was almost devoid of mitochondria.
   Mitochondrial number decreased and length increased with age. The increase in length was associated with an unusual clustering of mitochondria into parallel arrays of elongated mitochondria, with their long axis orthogonal to the basal membrane of the cell, structures not described before in RPE.
   Mitochondrial elongation is associated with metabolic and/or oxidative stress, which implies that age produces stress in macular RPE. The increased clustering of very elongated mitochondria suggests that pathological changes occur in mitochondrial organization with age. These changes support the hypothesis that age-related mitochondrial dysfunction plays a role in the pathogenesis of AMD.
C1 [Gouras, Peter; Nagasaki, T.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   [Gouras, Peter] Edward S Harkness Eye Inst, Res Annex, 635 West 165th St,Box 76, New York, NY 10032 USA.
   [Ivert, L.] Karolinska Inst, St Eriks Eye Hosp, Stockholm, Sweden.
   [Neuringer, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
C3 Columbia University; Karolinska Institutet; Oregon Health & Science
   University
RP Gouras, P (通讯作者)，Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.; Gouras, P (通讯作者)，Edward S Harkness Eye Inst, Res Annex, 635 West 165th St,Box 76, New York, NY 10032 USA.
EM pg10@columbia.edu
FU Foundation Fighting Blindness; Research to Prevent Blindness, Inc.; NIH
   [P51-OD011092, R01-EY015293, P30-EY019007]; Eye Surgery Fund; NATIONAL
   EYE INSTITUTE [P30EY019007, R01EY015293] Funding Source: NIH RePORTER;
   OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P51OD011092]
   Funding Source: NIH RePORTER
FX We thank Krissty Brown for her assistance with electron microscopy,
   Julie Mattison from the National Institute on Aging for providing the
   elderly monkeys, and the Foundation Fighting Blindness and Research to
   Prevent Blindness, Inc., for their support. This work was also supported
   in part by NIH grants P51-OD011092 ( MN), R01-EY015293 ( PG), and
   P30-EY019007 ( PG, TN) and a grant from the Eye Surgery Fund ( TN).
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NR 38
TC 22
Z9 22
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 2016
VL 254
IS 6
BP 1221
EP 1227
DI 10.1007/s00417-016-3342-x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DN4GR
UT WOS:000377022400025
PM 27106622
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Thederan, L
   Steinmetz, S
   Kampmann, S
   Koob-Matthes, AM
   Grehn, F
   Klink, T
AF Thederan, Luisa
   Steinmetz, Susanne
   Kampmann, Sabine
   Koob-Matthes, Anna-Maria
   Grehn, Franz
   Klink, Thomas
TI The Prevalence of Visual Impairment in Retirement Home Residents
SO DEUTSCHES ARZTEBLATT INTERNATIONAL
LA English
DT Article
ID BLINDNESS; GERMANY; RISK; POPULATION; FRACTURES; VISION
AB Background: Elderly persons often have eye diseases causing either reversible or irreversible visual loss. The prevalence of such problems among retirement home residents is unknown.
   Methods: 203 residents of retirement homes in and around Wurzberg, Germany, were examined. Clinical histories were taken, including information on prior ophthalmological care, and ophthalmological examinations were performed, including visual acuity, slit-lamp examination of the anterior segment of the eye, fundoscopy (with optical coherence tomography), and measurement of the intraocular pressure.
   Results: 119 women and 84 men aged 55 to 101 were examined in 6 retirement homes. 44 (21.7%) had ophthalmological findings that required acute treatment. The most common diagnoses in the anterior segment of the eye were keratoconjunctivitis sicca (160; 78.8%), cataract (88; 43.3%), secondary cataract (15; 7.4%), glaucoma (33; 12.3%), and eyelid malpositions (25; 12.3%). In the fundus, 45 residents (22.2%) had dry age-related macular degeneration (AMD), 7 (3.4%) had fresh wet AMD, and 7 (3.4%) had epiretinal gliosis. 81 (39.9%) could give no information about earlier ophthalmologic examinations, and 42 (20.7%) had not been to an ophthalmologist for at least 5 years. After correction of refractive errors, their mean decimal visual acuity improved from 0.25 to 0.33.
   Conclusion: The retirement home residents that we examined were not receiving adequate ophthalmological care; in particular, some of them had irreversible eye diseases that were not being treated. The ophthalmological care of retirement home residents needs to be improved through better collaboration of all types of personnel taking care of them.
C1 [Thederan, Luisa; Steinmetz, Susanne; Grehn, Franz] Univ Hosp Wurzburg, Dept Ophthalmol, Wurzburg, Germany.
   [Kampmann, Sabine; Koob-Matthes, Anna-Maria] Blindeninst Stiftung Wurzburg, Wurzburg, Germany.
   [Klink, Thomas] Herzog Carl Theodor Eye Hosp, Munich, Germany.
C3 University of Wurzburg
RP Thederan, L (通讯作者)，Univ Augenklin Wurzburg, Josef Schneider Str 11, D-97080 Wurzburg, Germany.
FU Caritas Association for the Diocese of Wurzberg; Bavarian Blind and
   Visually-Impaired Association (BBSB, Bayerische Blinden- und
   Sehbehindertenbund e.V.); LowVision Foundation (LowVision-Stiftung
   gGmbH); Johann Wilhelm Klein Akademie GmbH; Bavarian State Ministry of
   Health and Nursing Care; "Daheim im Heim" Foundation; Edith-Muhlschlegal
   Foundation; Heidelberg Engineering (Heidelberg, Germany)
FX We would like to thank the Caritas Association for the Diocese of
   Wurzberg, the Bavarian Blind and Visually-Impaired Association (BBSB,
   Bayerische Blinden- und Sehbehindertenbund e.V.), the LowVision
   Foundation (LowVision-Stiftung gGmbH), and the Johann Wilhelm Klein
   Akademie GmbH for sponsoring this project.; The project received funding
   from the Bavarian State Ministry of Health and Nursing Care as well as
   the "Daheim im Heim" Foundation and the Edith-Muhlschlegal Foundation.
   Furthermore, it was supported by Heidelberg Engineering (Heidelberg,
   Germany) which provided an spectral-domain optical coherence tomography
   (SD OCT) scanner free of charge.
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NR 20
TC 17
Z9 17
U1 0
U2 5
PU DEUTSCHER AERZTE-VERLAG GMBH
PI COLOGNE
PA DIESELSTRABE 2, POSTFACH 400265, D-50859 COLOGNE, GERMANY
SN 1866-0452
J9 DTSCH ARZTEBL INT
JI Dtsch. Arztebl. Int.
PD MAY 6
PY 2016
VL 113
IS 18
BP 323
EP +
DI 10.3238/arztebl.2016.0323
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA DN6EC
UT WOS:000377164000003
PM 27215597
OA Green Published
DA 2022-11-30
ER

PT J
AU Ciferri, C
   Lipari, MT
   Liang, WC
   Estevez, A
   Hang, JL
   Stawicki, S
   Wu, Y
   Moran, P
   Elliott, M
   Eigenbrot, C
   Katschke, KJ
   Campagne, MV
   Kirchhofer, D
AF Ciferri, Claudio
   Lipari, Michael T.
   Liang, Wei-Ching
   Estevez, Alberto
   Hang, Julie
   Stawicki, Scott
   Wu, Yan
   Moran, Paul
   Elliott, Mike
   Eigenbrot, Charles
   Katschke, Kenneth J.
   Campagne, Menno van Lookeren
   Kirchhofer, Daniel
TI The trimeric serine protease HtrA1 forms a cage-like inhibition complex
   with an anti-HtrA1 antibody
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE age-related macular degeneration; antibody; HtrA1; phage display; serine
   protease
ID RETINAL-PIGMENT EPITHELIUM; SMALL-VESSEL DISEASE; MACULAR DEGENERATION;
   INCREASED EXPRESSION; FUNCTIONAL-ANALYSIS; GENETIC-VARIANTS; PDZ
   DOMAINS; SYSTEM; SUSCEPTIBILITY; POLYMORPHISM
AB High temperature requirement A1 (HtrA1) is a trypsin-fold serine protease implicated in the progression of age-related macular degeneration (AMD). Our interest in an antibody therapy to neutralize HtrA1 faces the complication that the target adopts a trimeric arrangement, with three active sites in close proximity. In the present study, we describe antibody 94, obtained from a human antibody phage display library, which forms a distinct macromolecular complex with HtrA1 and inhibits the enzymatic activity of recombinant and native HtrA1 forms. Using biochemical methods and negative-staining EM we were able to elucidate the molecular composition of the IgG94 and Fab94 complexes and the associated inhibition mechanism. The 246-kDa complex between the HtrA1 catalytic domain trimer (HtrA1_Cat) and Fab94 had a propeller-like organization with one Fab bound peripherally to each protomer. Low-resolution EM structures and epitope mapping indicated that the antibody binds to the surface-exposed loops B and C of the catalytic domain, suggesting an allosteric inhibition mechanism. The HtrA1_Cat-IgG94 complex (636 kDa) is a cage-like structure with three centrally located IgG94 molecules co-ordinating two HtrA1_Cat trimers and the six active sites pointing into the cavity of the cage. In both complexes, all antigen-recognition regions (paratopes) are found to bind one HtrA1 protomer and all protomers are bound by a paratope, consistent with the complete inhibition of enzyme activity. Therefore, in addition to its potential therapeutic usefulness, antibody 94 establishes a new paradigm of multimeric serine protease inhibition.
C1 [Ciferri, Claudio; Estevez, Alberto; Eigenbrot, Charles] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA.
   [Lipari, Michael T.; Moran, Paul; Kirchhofer, Daniel] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA.
   [Liang, Wei-Ching; Stawicki, Scott; Wu, Yan] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
   [Hang, Julie; Elliott, Mike] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Katschke, Kenneth J.; Campagne, Menno van Lookeren] Genentech Inc, Dept Immunol, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Roche Holding;
   Genentech; Roche Holding; Genentech; Roche Holding; Genentech
RP Campagne, MV (通讯作者)，Genentech Inc, Dept Immunol, 1 DNA Way, San Francisco, CA 94080 USA.
EM vanlookeren.menno@gene.com; dak@gene.com
OI Estevez, Alberto/0000-0002-9141-5003
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NR 44
TC 13
Z9 16
U1 0
U2 13
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 DEC 1
PY 2015
VL 472
BP 169
EP 181
DI 10.1042/BJ20150601
PN 2
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DC4DY
UT WOS:000369171700005
PM 26385991
DA 2022-11-30
ER

PT J
AU Rhee, KD
   Nusinowitz, S
   Chao, K
   Yu, F
   Bok, D
   Yang, XJ
AF Rhee, Kun Do
   Nusinowitz, Steven
   Chao, Kevin
   Yu, Fei
   Bok, Dean
   Yang, Xian-Jie
TI CNTF-mediated protection of photoreceptors requires initial activation
   of the cytokine receptor gp130 in Muller glial cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID CILIARY NEUROTROPHIC FACTOR; RETINAL GANGLION-CELLS; LIGHT-INDUCED
   DEGENERATION; INTRAOCULAR IMPLANTS; ROD PHOTORECEPTORS; SIGNALING
   PATHWAYS; TRANSGENIC MICE; GROWTH-FACTORS; UP-REGULATION; DELIVERY
AB Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in multiple retinal degeneration animal models. Recently, CNTF has been evaluated in clinical trials for the inherited degenerative disease retinitis pigmentosa (RP) and for dry age-related macular degeneration (AMD). Despite its potential as a broad-spectrum therapeutic treatment for blinding diseases, the target cells of exogenous CNTF and its mechanism of action remain poorly understood. We have shown previously that constitutive expression of CNTF prevents photoreceptor death but alters the retinal transcriptome and suppresses visual function. Here, we use a lentivirus to deliver the same secreted human CNTF used in clinical trials to a mouse model of RP. We found that low levels of CNTF halt photoreceptor death, improve photoreceptor morphology, and correct opsin mislocalization. However, we did not detect corresponding improvement of retinal function as measured by the electroretinogram. Disruption of the cytokine receptor gp130 gene in Muller glia reduces CNTF-dependent photoreceptor survival and prevents phosphorylation of STAT3 and ERK in Muller glia and the rest of the retina. Targeted deletion of gp130 in rods also demolishes neuroprotection by CNTF and prevents further activation of Muller glia. Moreover, CNTF elevates the expression of LIF and endothelin 2, thus positively promoting Muller and photoreceptor interactions. We propose that exogenous CNTF initially targets Muller glia, and subsequently induces cytokines acting through gp130 in photoreceptors to promote neuronal survival. These results elucidate a cellular mechanism for exogenous CNTF-triggered neuroprotection and provide insight into the complex cellular responses induced by CNTF in diseased retinas.
C1 [Rhee, Kun Do; Nusinowitz, Steven; Chao, Kevin; Yu, Fei; Bok, Dean; Yang, Xian-Jie] Univ Calif Los Angeles, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
   [Bok, Dean] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA.
   [Yang, Xian-Jie] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California System; University of California Los Angeles;
   University of California System; University of California Los Angeles
RP Yang, XJ (通讯作者)，Univ Calif Los Angeles, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
EM yang@jsei.ucla.edu
OI Chao, Kevin/0000-0002-8457-2318
FU National Institutes of Health [EY019052]; Oppenheimer Family Foundation;
   Ernest G. Herman Endowed Chair in Ophthalmology; Macula Vision Research
   Foundation; Dolly Green Endowed Chair in Ophthalmology; National Eye
   Institute Core Grant for vision research at UCLA [EY00331]; NATIONAL EYE
   INSTITUTE [P30EY000331, R01EY019052] Funding Source: NIH RePORTER
FX We thank Jane Coffman, Shannan Eddington, Samir Habib, Tania Hioe, Paul
   Kim, Josephine Lee, Marcia Lloyd, Hitomi Suzuki, and Carrie Zhao for
   excellent technical support. We thank Dr. William W. Hauswirth for the
   secretable human CNTF plasmid, Dr. Jason C.-K. Chen for the Rho-iCre
   mouse, and Dr. Robert Molday for the rhodopsin antibody. The work was in
   part supported by grants from National Institutes of Health EY019052,
   the Oppenheimer Family Foundation, and the Ernest G. Herman Endowed
   Chair in Ophthalmology (to X.-J.Y.), Macula Vision Research Foundation
   and Dolly Green Endowed Chair in Ophthalmology (to D.B.), and National
   Eye Institute Core Grant EY00331 for vision research at UCLA.
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NR 59
TC 56
Z9 57
U1 0
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 19
PY 2013
VL 110
IS 47
BP E4520
EP E4529
DI 10.1073/pnas.1303604110
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 253PD
UT WOS:000327100600017
PM 24191003
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Nakajima, T
   Nakajima, E
   Shearer, TR
   Azuma, M
AF Nakajima, Takeshi
   Nakajima, Emi
   Shearer, Thomas R.
   Azuma, Mitsuyoshi
TI Concerted inhibition of HIF-1 alpha and-2 alpha expression markedly
   suppresses angiogenesis in cultured RPE cells
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Hypoxia-inducible factor-1 alpha and-2 alpha; Retinal pigment epithelial
   cells; Hypoxia; Vascular endothelial growth factor; Age-related macular
   degeneration
ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-2-ALPHA; MACULAR
   DEGENERATION; CHOROIDAL NEOVASCULARIZATION; ANGIOPOIETIN-LIKE-4;
   FACTOR-1-ALPHA; TRANSCRIPTION; HIF-2-ALPHA; GENES; VEGF
AB HIF-1 alpha is known to play an important role in the induction of VEGF by hypoxia in retinal pigment epithelial (RPE) cells. However, the involvement of the other isoform, HIF-2 alpha, in RPE cells remains unclear. Thus, the purpose of present study was to clarify the role of HIF-2 alpha during induction of angiogenic genes in hypoxic RPE cells. When human RPE cells (ARPE-19) were cultured under hypoxic conditions, HIF-1 alpha and HIF-2 alpha proteins increased. This induced an increase in mRNA for VEGF, causing secretion of VEGF protein into the medium. This conditioned medium induced tube formation in human vascular endothelial cells (HUVEC). The increased expression of mRNA for VEGF in hypoxic RPE cells was partially inhibited by HIF-1 alpha siRNA, but not by HIF-2 alpha siRNA. However, co-transfection of HIF-1 alpha siRNA and HIF-2 alpha siRNA augmented downregulation of VEGF mRNA and protein in hypoxic RPE cells and inhibited formation of tube-like structures in HUVEC. GeneChip and PCR array analyses revealed that not only VEGF, but also expression of other angiogenic genes were synergistically downregulated by co-transfection of hypoxic RPE cells with HIF-1 alpha and HIF-2 alpha siRNAs. These findings suggest an important compensatory role for the HIF-2 alpha isoform in the regulation of angiogenic gene expression. Thus, suppression of angiogenic genes for HIF-1 alpha and HIF-2 alpha may be a possible therapeutic strategy against retinal angiogenesis in Age-related macular degeneration (ARMD).
C1 [Nakajima, Takeshi; Nakajima, Emi; Azuma, Mitsuyoshi] Senju Pharmaceut Co Ltd, Senju Lab Ocular Sci, Kobe, Hyogo, Japan.
   [Shearer, Thomas R.; Azuma, Mitsuyoshi] Oregon Hlth & Sci Univ, Dept Integrat Biosci, Portland, OR 97201 USA.
   [Azuma, Mitsuyoshi] Senju Pharmaceut Co Ltd, Senju Lab Ocular Sci, Beaverton, OR 97006 USA.
C3 Senju Pharmaceutical Co. Ltd.; Oregon Health & Science University; Senju
   Pharmaceutical Co. Ltd.
RP Azuma, M (通讯作者)，Senju Pharmaceut Co Ltd, Senju Lab Ocular Sci, OHSU West Campus,20000 NW Walker Rd,Suite JM508, Beaverton, OR 97006 USA.
EM mitsuyoshi-azuma@senju.co.jp
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NR 30
TC 11
Z9 11
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD NOV
PY 2013
VL 383
IS 1-2
BP 113
EP 122
DI 10.1007/s11010-013-1760-1
PG 10
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 227TC
UT WOS:000325136400013
PM 23873332
DA 2022-11-30
ER

PT J
AU Shao, Z
   Friedlander, M
   Hurst, CG
   Cui, ZH
   Pei, DT
   Evans, LP
   Juan, AM
   Tahir, H
   Duhamel, F
   Chen, J
   Sapieha, P
   Chemtob, S
   Joyal, JS
   Smith, LEH
AF Shao, Zhuo
   Friedlander, Mollie
   Hurst, Christian G.
   Cui, Zhenghao
   Pei, Dorothy T.
   Evans, Lucy P.
   Juan, Aimee M.
   Tahir, Houda
   Duhamel, Francois
   Chen, Jing
   Sapieha, Przemyslaw
   Chemtob, Sylvain
   Joyal, Jean-Sebastien
   Smith, Lois E. H.
TI Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL-CELLS; PHENOTYPIC HETEROGENEITY; MACULAR DEGENERATION;
   EXPRESSION; RETINOPATHY; MICROGLIA; CHANNELS; EXPLANT
AB Angiogenesis of the microvasculature is central to the etiology of many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model of microvascular angiogenesis would be very valuable and enable access to a wide range of genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured in vitro are widely used, however, isolating pure vascular murine endothelial cells is technically challenging. A microvascular mouse explant model that is robust, quantitative and can be reproduced without difficulty would overcome these limitations. Here we characterized and optimized for reproducibility an organotypic microvascular angiogenesis mouse and rat model from the choroid, a microvascular bed in the posterior of eye. The choroidal tissues from C57BL/6J and 129S6/SvEvTac mice and Sprague Dawley rats were isolated and incubated in Matrigel. Vascular sprouting was comparable between choroid samples obtained from different animals of the same genetic background. The sprouting area, normalized to controls, was highly reproducible between independent experiments. We developed a semi-automated macro in ImageJ software to allow for more efficient quantification of sprouting area. Isolated choroid explants responded to manipulation of the external environment while maintaining the local interactions of endothelial cells with neighboring cells, including pericytes and macrophages as evidenced by immunohistochemistry and fluorescence-activated cell sorting (FACS) analysis. This reproducible ex vivo angiogenesis assay can be used to evaluate angiogenic potential of pharmacologic compounds on microvessels and can take advantage of genetically manipulated mouse tissue for microvascular disease research.
C1 [Shao, Zhuo; Friedlander, Mollie; Hurst, Christian G.; Cui, Zhenghao; Pei, Dorothy T.; Evans, Lucy P.; Juan, Aimee M.; Chen, Jing; Joyal, Jean-Sebastien; Smith, Lois E. H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02114 USA.
   [Duhamel, Francois; Sapieha, Przemyslaw; Chemtob, Sylvain] Univ Montreal, Dept Ophthalmol, Res Ctr, Hop Maisonneuve Rosemont, Montreal, PQ, Canada.
   [Tahir, Houda; Duhamel, Francois; Chemtob, Sylvain] CHU St Justine, Res Ctr, Dept Pediat Ophthalmol, Montreal, PQ, Canada.
   [Tahir, Houda; Duhamel, Francois; Chemtob, Sylvain] CHU St Justine, Res Ctr, Dept Pharmacol, Montreal, PQ, Canada.
C3 Harvard University; Boston Children's Hospital; Harvard Medical School;
   Universite de Montreal; Universite de Montreal; Centre Hospitalier
   Universitaire Sainte-Justine; Universite de Montreal; Centre Hospitalier
   Universitaire Sainte-Justine
RP Smith, LEH (通讯作者)，Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02114 USA.
EM Lois.Smith@childrens.harvard.edu
OI Qian, Mollie/0000-0001-7536-9054; Juan, Aimee/0000-0002-0221-2280
FU National Institutes of Health (NIH) [EY017017-04S1, EY017017-05]; V.
   Kann Rasmussen Foundation; Boston Children's Hospital Mental Retardation
   and Developmental Disabilities Research Center [PO1HD18655]; Research to
   Prevent Blindness; Alcon Research Institute Award; Lowy Medical
   Foundation; Canadian Institute of Health Research (CIHR); CIHR Banting &
   Best PhD Scholarship; Fonds de la Recherche en Sante du Quebec (FRSQ);
   Boston Children's Hospital Ophthalmology Foundation; Charles H. Hood
   Foundation; Blind Children's Center; BrightFocus Foundation; EUNICE
   KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
   [P30HD018655] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY017017, R01EY022275] Funding Source: NIH RePORTER
FX This work is supported by funding from National Institutes of Health
   (NIH) (EY017017-04S1, EY017017-05), V. Kann Rasmussen Foundation, Boston
   Children's Hospital Mental Retardation and Developmental Disabilities
   Research Center PO1HD18655, Research to Prevent Blindness Senior
   Investigator Award, Alcon Research Institute Award and Lowy Medical
   Foundation (LEHS). ZS is supported by Canadian Institute of Health
   Research (CIHR) System Biology Training Scholarship and Travel Grant. FD
   is supported by CIHR Banting & Best PhD Scholarship and Health
   Professional PhD Scholarship from the Fonds de la Recherche en Sante du
   Quebec (FRSQ). JC is supported by Boston Children's Hospital
   Ophthalmology Foundation, Charles H. Hood Foundation Child Health
   Research Award, Blind Children's Center, and BrightFocus Foundation. PS
   holds a Canada Research Chair tier II. SC holds a Canada Research chair
   tier I (Vision science) and the Leopoldine Wolfe Chair in translational
   research in macular degeneration (U Montreal). The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 43
TC 74
Z9 78
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 26
PY 2013
VL 8
IS 7
AR e69552
DI 10.1371/journal.pone.0069552
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 197GU
UT WOS:000322838900055
PM 23922736
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Craword, SE
   Fitchev, P
   Veliceasa, D
   Volpert, OV
AF Craword, Susan E.
   Fitchev, Philip
   Veliceasa, Dorina
   Volpert, Olga V.
TI The many facets of PEDF in drug discovery and disease: a diamond in the
   rough or split personality disorder?
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE angiogenesis; bone disease; cancer; lipid metabolism; metabolic disease;
   neuronal differentiation; ocular neovascular disease; pigment
   epithelium-derived factor; stem cell niche
ID EPITHELIUM-DERIVED FACTOR; ENDOTHELIAL GROWTH-FACTOR; ORTHOTOPIC
   OSTEOSARCOMA GROWTH; RETINAL-PIGMENT EPITHELIUM; TOTAL ANTIOXIDANT
   CAPACITY; ANTI-ANGIOGENIC ACTIVITY; MEDIATED GENE-TRANSFER;
   INSULIN-RESISTANCE; AQUEOUS-HUMOR; CHOROIDAL NEOVASCULARIZATION
AB Introduction: Pigment epithelium-derived factor (PEDF) was discovered as a neurotrophic factor secreted by retinal pigment epithelial cells. A decade later, it re-emerged as a powerful angiogenesis inhibitor guarding ocular function. Since then, significant advances were made identifying PEDF's mechanisms, targets and biomedical applications.
   Areas covered: The authors review several methodologies that have generated significant new information about the potential of PEDF as a drug. Furthermore, the authors review and discuss mechanistic and structure-function analyses combined with the functional mapping of active fragments, which have yielded several short bioactive PEDF peptides. Additionally, the authors present functional studies in knockout animals and human correlates that have provided important information about conditions amenable to PEDF-based therapies.
   Expert opinion: Through its four known receptors, PEDF causes a wide range of cellular events vitally important for the organism, which include survival and differentiation, migration and invasion, lipid metabolism and stem cell maintenance. These processes are deregulated in multiple pathological conditions, including cancer, metabolic and cardiovascular disease. PEDF has been successfully used in countless preclinical models of these conditions and human correlates suggest a wide utility of PEDF-based drugs. The most significant clinical application of PEDF, to date, is its potential therapeutic use for age-related macular degeneration. Moreover, PEDF-based gene therapy has advanced to early stage clinical trials. PEDF active fragments have been mapped and used to design short peptide mimetics conferring distinct functions of PEDF, which may address specific clinical problems and become prototype drugs.
C1 [Craword, Susan E.; Fitchev, Philip] St Louis Univ, Dept Pathol, Sch Med, St Louis, MO USA.
   [Veliceasa, Dorina; Volpert, Olga V.] RH Lurie Comprehens Canc Ctr, Chicago, IL USA.
C3 Saint Louis University; Robert H. Lurie Comprehensive Cancer Center
RP Veliceasa, D (通讯作者)，Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA.
EM olgavolp@northwestern.edu
OI Volpert, Olga/0000-0003-1381-5543
FU Herman L Ketchmer Fund; St. Louis University Department of Pathology and
   Prostate Cancer SPORE [P50-CA090386]; NRSA; NATIONAL CANCER INSTITUTE
   [P50CA090386] Funding Source: NIH RePORTER
FX OV Volpert is supported by the Herman L Ketchmer Fund. Furthermore, SE
   Crawford and PS Fitchev are supported by the St. Louis University
   Department of Pathology and Prostate Cancer SPORE award P50-CA090386,
   while D Veliceasa has been funded by the NRSA scholarship in urology.
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NR 213
TC 38
Z9 40
U1 1
U2 15
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD JUL
PY 2013
VL 8
IS 7
BP 769
EP 792
DI 10.1517/17460441.2013.794781
PG 24
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 169WE
UT WOS:000320810600002
PM 23642051
DA 2022-11-30
ER

PT J
AU Sparrow, JM
   Taylor, H
   Qureshi, K
   Smith, R
   Birnie, K
   Johnston, RL
AF Sparrow, J. M.
   Taylor, H.
   Qureshi, K.
   Smith, R.
   Birnie, K.
   Johnston, R. L.
CA UK EPR User Grp
TI The Cataract National Dataset electronic multi-centre audit of 55 567
   operations: risk indicators for monocular visual acuity outcomes
SO EYE
LA English
DT Article
DE cataract surgery; visual acuity outcome; risk factors; Cataract National
   Dataset; electronic patient record
ID POSTERIOR CAPSULE RUPTURE; SURGERY
AB Aims To report risk factors for visual acuity (VA) improvement and harm following cataract surgery using electronically collected multi-centre data conforming to the Cataract National Dataset (CND).
   Methods Routinely collected anonymised data were remotely extracted from the electronic patient record systems of 12 participating NHS Trusts undertaking cataract surgery. Following data checks and cleaning, analyses were performed to identify risk indicators for: (1) a good acuity outcome (VA 6/12 or better), (2) the pre- to postoperative change in VA, and (3) VA loss (doubling or worse of the visual angle).
   Results In all, 406 surgeons from 12 NHS Trusts submitted data on 55 567 cataract operations. Preoperative VA was known for 55 528 (99.9%) and postoperative VA outcome for 40 758 (73.3%) operations. Important adverse preoperative risk indicators found in at least 2 of the 3 analyses included older age (3), short axial length (3), any ocular comorbidity (3), age-related macular degeneration (2), diabetic retinopathy (3), amblyopia (2), corneal pathology (2), previous vitrectomy (2), and posterior capsule rupture (PCR) during surgery (3). PCR was the only potentially modifiable adverse risk indicator and was powerfully associated with VA loss (OR = 5.74).
   Conclusion Routinely collected electronic data conforming to the CND provide sufficient detail for identification and quantification of preoperative risk indicators for VA outcomes of cataract surgery. The majority of risk indicators are intrinsic to the patient or their eye, with a notable exception being PCR during surgery. Eye (2012) 26, 821-826; doi:10.1038/eye.2012.51; published online 23 March 2012
C1 [Sparrow, J. M.] Bristol Eye Hosp, Dept Ophthalmol, Bristol BS1 2LX, Avon, England.
   [Sparrow, J. M.] London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1, England.
   [Taylor, H.] Bristol Royal Infirm & Gen Hosp, R&E Off, Res & Dev Support Unit, Bristol, Avon, England.
   [Qureshi, K.] Royal Coll Ophthalmologists, London, England.
   [Qureshi, K.] Royal Bolton Hosp, Bolton, England.
   [Smith, R.] Stoke Mandeville Hosp, Aylesbury HP21 8AL, Bucks, England.
   [Birnie, K.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
   [Johnston, R. L.] Cheltenham Gen Hosp, Gloucestershire Eye Dept, Cheltenham, Glos, England.
C3 Bristol Eye Hospital; University of London; London School of Hygiene &
   Tropical Medicine; Bristol Royal Infirmary; Royal Bolton Hospital;
   University of Bristol; Gloucestershire Hospitals NHS Foundation Trust;
   Cheltenham General Hospital
RP Sparrow, JM (通讯作者)，Bristol Eye Hosp, Dept Ophthalmol, Lower Maudlin St, Bristol BS1 2LX, Avon, England.
EM John.Sparrow@doctors.org.uk
OI Taylor, Hazel/0000-0003-3430-5278
FU Academy of Medical Royal Colleges
FX This work was supported by a grant from the Academy of Medical Royal
   Colleges entitled 'Developing a defensible decision making algorithm for
   revalidation based on case mix adjusted measures of surgical
   performance', which was administered through the Royal College of
   Ophthalmologists.
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NR 12
TC 87
Z9 87
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD JUN
PY 2012
VL 26
IS 6
BP 821
EP 826
DI 10.1038/eye.2012.51
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 960LL
UT WOS:000305389400010
PM 22441022
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Burns-Whitmore, BL
   Haddad, EH
   Sabate, J
   Jaceldo-Siegl, K
   Tanzman, J
   Rajaram, S
AF Burns-Whitmore, B. L.
   Haddad, E. H.
   Sabate, J.
   Jaceldo-Siegl, K.
   Tanzman, J.
   Rajaram, S.
TI Effect of n-3 fatty acid enriched eggs and organic eggs on serum lutein
   in free-living lacto-ovo vegetarians
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE n-3 fatty acid egg; organic egg; age-related macular degeneration;
   lutein
ID PIGMENT OPTICAL-DENSITY; ZEAXANTHIN CONCENTRATIONS; CAROTENOIDS; PLASMA;
   CHOLESTEROL; SUPPLEMENTATION; CONSUMPTION
AB Background/Objective: Lutein is a xanthophyll found in the chloroplasts of dark green leafy vegetables, chromoplasts of fruits, and egg yolk. Dietary, serum and macular lutein are inversely related to the risk of age-related macular degeneration. Although the lutein from egg is known to be more bioavailable than that from spinach, not much is known about lutein bioavailability from n-3 fatty acid enriched eggs and organic eggs, both of which are increasingly available to consumers.
   Subjects/Methods: We determined the effects of feeding n-3 fatty acid-enriched eggs and organic eggs on serum lutein, zeaxanthin and beta-carotene in 20 healthy lacto-ovo-vegetarian (LOV) adults using a single-blind, randomized, crossover study design with a 4-week washout between treatments: six organic eggs or six n-3 fatty acid enriched eggs per week or no egg control for 8weeks each.
   Results: Serum lutein was significantly higher in both egg treatments (P<0.009) compared with the control, but was not different between the two egg treatments. Serum beta-carotene was also higher in the egg groups compared with control but only approached significance (P = 0.066). Serum zeaxanthin increased in both egg treatments compared with control but did not reach statistical significance (P = 0.139).
   Conclusion: n-3 fatty acid enriched eggs and organic eggs may both significantly increase serum lutein in healthy LOV consuming a predominately plant-based diet. European Journal of Clinical Nutrition (2010) 64, 1332-1337; doi: 10.1038/ejcn.2010.140; published online 28 July 2010
C1 [Burns-Whitmore, B. L.; Haddad, E. H.; Sabate, J.; Jaceldo-Siegl, K.; Tanzman, J.; Rajaram, S.] Loma Linda Univ, Dept Nutr, Sch Publ Hlth, Loma Linda, CA 92350 USA.
   [Burns-Whitmore, B. L.] Calif State Polytech Univ Pomona, Coll Agr, Dept Human Nutr & Food Sci, Pomona, CA 91768 USA.
C3 Loma Linda University; California State University System; California
   State Polytechnic University Pomona
RP Rajaram, S (通讯作者)，Loma Linda Univ, Dept Nutr, Sch Publ Hlth, Loma Linda, CA 92350 USA.
EM srajaram@llu.edu
RI Rajaram, Sujatha/AAC-1465-2020
OI Tanzman, Jay/0000-0002-8361-9292; Sabate, Joan/0000-0002-9063-9785
FU American Egg Board
FX We would like to extend special thanks to Lisa Forde-Griffith for her
   technical laboratory assistance, the American Egg Board for their
   Graduate Fellowship Grant, the California State Polytechnic University
   for the Agriculture Research Initiative, and Chino Valley Ranchers
   (Irvine, CA) for supplying the eggs at no cost to the study.
CR Anderson HA, 2008, CHEMOSPHERE, V73, P187, DOI 10.1016/j.chemosphere.2008.05.052
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NR 25
TC 17
Z9 19
U1 0
U2 6
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD NOV
PY 2010
VL 64
IS 11
BP 1332
EP 1337
DI 10.1038/ejcn.2010.140
PG 6
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 674MM
UT WOS:000283749800012
PM 20664616
DA 2022-11-30
ER

PT J
AU Sanfilippo, PG
   Hewitt, AW
   Hammond, CJ
   Mackey, DA
AF Sanfilippo, Paul G.
   Hewitt, Alex W.
   Hammond, Chris J.
   Mackey, David A.
TI The Heritability of Ocular Traits
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE familial aggregation; family study; heritability; pedigree
ID CENTRAL CORNEAL THICKNESS; OPEN-ANGLE GLAUCOMA; AGE-RELATED MACULOPATHY;
   ANTERIOR-CHAMBER DEPTH; RETINAL VESSEL DIAMETERS; FIBER LAYER THICKNESS;
   OPTIC DISC PARAMETERS; GENOME-WIDE LINKAGE; INTRAOCULAR-PRESSURE;
   REFRACTIVE ERROR
AB Heritability is the proportion of phenotypic variation in a population that is attributable to genetic variation. among individuals. Many ophthalmic disorders and biometric traits are known to have a genetic basis and consequently much work has been published in the literature estimating the heritability of various ocular parameters. We collated and summarized the findings of heritability studies conducted in the field of ophthatmology. We grouped the various Studies broadly by phenotype as follows refract primary open-angle glaucoma, age-related macular degeneration (AMD), cataract, diabetic retinopathy, and others A total of 82 articles were retrieved from the literature relating to estimation of heritability loran ocular disease or biometric trait; of these, 37 papers were concerned with glaucoma, 28 with refraction, 4 with AM D, 5 with diabetic reunopathy, and 4 with cataract. The highest reported heritability for an ophthalmic trait is 0.99 for the phenotype >= 20 small hard, drusen, indicating that observed variation in this parameter is largely governed by genetic factors. Over 60% of the studies employed a twin study design and a similar percentage utilized variance components methods and structural equation modeling (SEM) to derive their heritability values. Using modern SEM techniques, heritability estimates derived from twin subjects were generally higher than those from family data. Many oldie estimates are in the moderate to high range, but to date the majority of genetic variants accounting for these findings have not been uncovered, hence in much work remains to be undertaken to elucidate fully their molecular etiology. (Surv Ophthalmol 55:561-583,2010. (c) 2010 Elsevier Inc All rights reserved)
C1 [Sanfilippo, Paul G.; Hewitt, Alex W.; Mackey, David A.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia.
   [Hammond, Chris J.] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
   [Mackey, David A.] Univ Tasmania, Discipline Med, Hobart, Tas, Australia.
   [Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; Guy's & St Thomas' NHS Foundation Trust;
   University of London; King's College London; University of Tasmania;
   Lions Eye Institute; University of Western Australia
RP Sanfilippo, PG (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 8006, Australia.
RI Mackey, David A/H-5340-2014; Hewitt, Alex W/D-1936-2013
OI Mackey, David A/0000-0001-7914-4709; Hewitt, Alex W/0000-0002-5123-5999;
   Hammond, Christopher/0000-0002-3227-2620; Sanfilippo,
   Paul/0000-0002-1778-9154
FU Ophthalmic Research Institute of Australia; Victorian Government; UK
   National Institute for Health Research; NHMRC; Australian National
   Health and Medical Research Council
FX Publication of this article was financially supported by the Ophthalmic
   Research Institute of Australia and the Australian National Health and
   Medical Research Council. The Centre for Eye Research Australia (CERA)
   receives Operational Infrastructure support from the Victorian
   Government D A M is a Pfizer Australia research fellow C J H is funded
   by UK National Institute for Health Research P G S is the recipient of
   an NHMRC postgraduate scholarship P G S, A W H. C J H, and D A M are
   authors of studies included in this review. The authors reported no
   proprietary or commercial interest in any product mentioned of concept
   discussed in this article
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NR 153
TC 106
Z9 106
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0039-6257
EI 1879-3304
J9 SURV OPHTHALMOL
JI Surv. Ophthalmol.
PD NOV-DEC
PY 2010
VL 55
IS 6
BP 561
EP 583
DI 10.1016/j.survophthal.2010.07.003
PG 23
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 673WG
UT WOS:000283694300005
PM 20851442
DA 2022-11-30
ER

PT J
AU Rutar, M
   Provis, JM
   Valter, K
AF Rutar, Matt
   Provis, Jan M.
   Valter, Krisztina
TI Brief Exposure to Damaging Light Causes Focal Recruitment of
   Macrophages, and Long-Term Destabilization of Photoreceptors in the
   Albino Rat Retina
SO CURRENT EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Blood-retinal barrier; Light damage;
   Macrophages; Photoreceptor dystrophy; Retina
ID AGE-RELATED MACULOPATHY; CHOROIDAL BLOOD-FLOW; MACULAR DEGENERATION;
   GEOGRAPHIC ATROPHY; SUNLIGHT EXPOSURE; RHODOPSIN CONTENT; OXIDATIVE
   DAMAGE; BRUCHS MEMBRANE; IRIS COLOR; CELLS
AB Purpose: To characterize the long-term spatiotemporal features of light-mediated retinal degeneration.
   Methods: Sprague-Dawley rats were exposed to 1000 lux for 24 h, then kept in dim light (5 lux), for up to 56 days. Animals were killed at 0, 3, 7, 28, and 56 days post-exposure, and retinas were prepared for immunohistochemistry. Outer nuclear layer (ONL) thickness and TUNEL labeling were used to quantify photoreceptor death. Antibodies to opsins, glial fibrillary acidic protein (GFAP), fibroblast growth factor-2 (FGF-2), and ED1 were used to assess the retina.
   Results: At 0 days post-exposure, we detected photoreceptor death 2 mm superior to the optic disc (the "hotspot"), and ED1-positive macrophages in the retinal vasculature and underlying choroid. By 3 days, the ONL was thinner and there was gliosis in the outer retina, where ED1 positive macrophages were also present. Few ED1 positive cells remained at 28 days. At 56 days, there were TUNEL-positive nuclei in the penumbra, and increased FGF-2, and GFAP expression by Muller cells (MCs). In inferior retina, outer segment length was initially reduced, but recovered to near-normal by 28 days.
   Conclusions: Short exposure to damaging light destabilizes the retina adjacent to a hotspot of degeneration, so that the damaged region expands in size over time. Recruitment of macrophages is associated with the early phase of damage, but not with the longer term photoreceptor loss in the penumbra. Features of the focal and progressive retinal damage in this model are reminiscent of the progression of age-related macular degeneration (AMD).
C1 [Rutar, Matt; Provis, Jan M.; Valter, Krisztina] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia.
   [Rutar, Matt; Provis, Jan M.; Valter, Krisztina] Australian Natl Univ, ARC Ctr Excellence Vis Sci, Canberra, ACT 0200, Australia.
   [Provis, Jan M.] Australian Natl Univ, ANU Med Sch, Canberra, ACT 0200, Australia.
C3 Australian National University; Australian National University;
   Australian National University
RP Rutar, M (通讯作者)，Australian Natl Univ, Res Sch Biol, GPO Box 4, Canberra, ACT 0200, Australia.
EM matt.rutar@rsbs.anu.edu.au
RI Valter, Krisztina/C-9743-2009; 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
FU Australian Research Council Centres of Excellence [CE0561903];
   Ophthalmic Research Institute of Australia
FX This work was supported by Australian Research Council Centres of
   Excellence Program (CE0561903); Ophthalmic Research Institute of
   Australia/Brenda Mitchell grant.
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NR 85
TC 70
Z9 72
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD JUL
PY 2010
VL 35
IS 7
BP 631
EP 643
DI 10.3109/02713681003682925
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 663OU
UT WOS:000282898000010
PM 20597649
OA Green Published
DA 2022-11-30
ER

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   Duggan, C
   Madden, BJ
   Edwards, AO
AF Chen, Dequan
   Langford, Marlyn P.
   Duggan, Chris
   Madden, Benjamin J.
   Edwards, Albert O.
TI Expression of recombinant protein encoded by LOC387715 in Escherichia
   coli
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE LOC387715; age-related macular degeneration (AMD); single nucleotide
   polymorphism (SNP); non-synonymous coding; synonymous modification;
   recombinant protein; rare codon; Shine-Dalgarno-like sequence; ribosome
   binding site complementary sequence; nano-flow liquid chromatography
   electrospray tandem mass spectrometry
ID AGE-RELATED MACULOPATHY; HIGH-LEVEL EXPRESSION; RARE ARGININE CODONS;
   COMPLEMENT FACTOR-H; MACULAR DEGENERATION; TRANSFER-RNA;
   GENOMEWIDE-SCAN; MESSENGER-RNA; SUSCEPTIBILITY LOCI; SECONDARY STRUCTURE
AB LOC387715 is a hypothetical gene located on human chromosome 10q26.13 that is associated with the development of age-related macular degeneration (AMD). The native open reading frame (ORF) of LOC387715 cDNA - LOC387715(ORF), contains a large number of Escherichia coli (E. coli) rare codons (RC) including 5.6% and 15.0% Group-I and IIa translational problem causative (TPC) RCs, respectively, which forms 3 and 4 simple E coli rare codon clusters (RCC) where RCs are spaced by 1 and 2 respective non-TPC codons and one complex E. coli RCC where RCs and RCCs are spaced by < 5 non-TPC codons. We modified the entire 35 E. coli RCs (6, 16 and 13 Group 1, IIa and IIb RCs, respectively) present in LOC387715(ORF) with their optimal or sub-optimal synonymous degenerate codons, and the resulted LOC387715(ORF)m was free from Shine-Dalgarno-like sequence (SDLS) and ribosome binding site complementary sequence (RBSCS). SDS-PAGE and Western blotting analysis demonstrated that LOC387715(ORF)m was capable of highly expressing the recombinant protein rLOC387715 in E. coli. Mass spectrometry analysis indicated that the bacterial expressed rLOC387715 contained the correct and expected amino acid (aa) sequence without aa misincorporation, aa missing or frame-shift. The results suggest that high and authentic expression of LOC387715 recombinant protein in E. coli was achieved by the synonymous modification of its native ORF cDNA sequence for all the 3 groups of bacterial RCs and the simultaneous elimination of SDLS and RBSCS sequences. (C) 2007 Elsevier Inc. All rights reserved.
C1 Mayo Clin, Coll Med, Dept Ophthalmol, Rochester, MN 55905 USA.
   Presbyterian Med Ctr, Inst Retina Res, Dallas, TX 75231 USA.
   Louisiana State Univ, Hlth Sci Ctr, Dept Ophthalmol, Shreveport, LA 71130 USA.
   Mayo Clin, Coll Med, Mayo Proteom Res Ctr, Rochester, MN 55905 USA.
C3 Mayo Clinic; Louisiana State University System; Louisiana State
   University Health Sciences Center at Shreveport; Mayo Clinic
RP Chen, DQ (通讯作者)，Mayo Clin, Coll Med, Dept Ophthalmol, Guggenheim Bldg,Room Gu 9-11,200 1st St SW, Rochester, MN 55905 USA.
EM chen.dequan@mayo.edu
FU NATIONAL EYE INSTITUTE [R01EY014467] Funding Source: NIH RePORTER; NEI
   NIH HHS [EY014467, R01 EY014467-03, R01 EY014467] Funding Source:
   Medline
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NR 48
TC 2
Z9 3
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD AUG
PY 2007
VL 54
IS 2
BP 275
EP 282
DI 10.1016/j.pep.2007.03.017
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 182YZ
UT WOS:000247541200012
PM 17485225
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Altintas, M
   Ulas, F
   Celebi, S
   Uyar, E
AF Altintas, Melek
   Ulas, Fatih
   Celebi, Serdal
   Uyar, Enes
TI Effect of quadrant switch on intraocular pressure change in intravitreal
   aflibercept or ranibizumab injection applications
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Intraocular pressure; Intravitreal injection; Quadrant
   switch; Ranibizumab; Vitreous reflux
ID REFLUX; BEVACIZUMAB; IMPACT
AB Objective To evaluate the effect of injection quadrant switch on the intraocular pressure (IOP) change in intravitreal aflibercept or ranibizumab applications. Methods 123 eyes of 123 patients who received intravitreal injection (IVE) into the superotemporal quadrant at least 10 times for age-related macular degeneration or diabetic macular edema have been recruited. The demographic data, lens status, IOP values (preoperative, postoperative 0th min, and postoperative 30th min), and amount of vitreous reflux (VR) following IVE have been recorded. Next IVE application was performed into the inferotemporal quadrant of the patient, which had never been injected before. Results The mean IOP value at postoperative 0th min was 50.24 +/- 7.66 mmHg after injections into the superotemporal quadrant and was 34.85 +/- 4.96 mmHg after injections into the inferotemporal quadrant. No significant difference was observed between the preoperative and postoperative 30th min-IOP values (p > 0.05), while a significant difference was found between the postoperative 0th min-IOP values among quadrants (p < 0.001). VR was significantly higher in applications into the inferotemporal quadrant than those into the superotemporal quadrant (p < 0.001). Conclusion One of the most principal factors affecting the postoperative short-term IOP increase is the amount of VR, and this amount decreases the IOP following an IVE. The high amount of VR produced in the quadrant where the injection was applied for the first time caused a low-level IOP, while the low amount of VR formed in the quadrant where the repeated injections were applied caused a higher IOP.
C1 [Altintas, Melek; Ulas, Fatih; Celebi, Serdal] Abant Izzet Baysal Univ, Fac Med, Dept Ophthalmol, Bolu, Turkey.
   [Altintas, Melek] Diyarbakir Dagkapi State Hosp, Dept Ophthalmol, Diyarbakir, Turkey.
   [Uyar, Enes] Aksaray Univ, Aksaray Training & Res Hosp, Dept Ophthalmol, Aksaray, Turkey.
C3 Abant Izzet Baysal University; Aksaray University
RP Altintas, M (通讯作者)，Abant Izzet Baysal Univ, Fac Med, Dept Ophthalmol, Bolu, Turkey.
EM dr.melek.altintas@gmail.com; fatihu44@yahoo.com; scelebi_63@yahoo.com;
   enuyar@gmail.com
OI Uyar, Enes/0000-0003-2544-3580; Ulas, Fatih/0000-0003-4468-3985
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NR 15
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0165-5701
EI 1573-2630
J9 INT OPHTHALMOL
JI Int. Ophthalmol.
PD SEP
PY 2022
VL 42
IS 9
BP 2841
EP 2846
DI 10.1007/s10792-022-02274-w
EA MAR 2022
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4C2LU
UT WOS:000782219600003
PM 35357637
DA 2022-11-30
ER

PT J
AU Suchetha, M
   Ganesh, NS
   Raman, R
   Dhas, DE
AF Suchetha, M.
   Ganesh, N. Sai
   Raman, Rajiv
   Dhas, D. Edwin
TI Region of interest-based predictive algorithm for subretinal hemorrhage
   detection using faster R-CNN
SO SOFT COMPUTING
LA English
DT Article
DE Macular Edema; Optical Coherence Tomography; Convolutional Neural
   Network; Region of Interest; Subretinal fluid; Subretinal hemorrhage
ID DIABETIC MACULAR EDEMA; VESSELS SEGMENTATION; PATHOLOGY; MODELS
AB Macular edema (ME) is an essential sort of macular issue caused due to the storing of fluid underneath the macula. Age-related Macular Degeneration (AMD) and diabetic macular edema (DME) are the two customary visual contaminations that can lead to fragmentary or complete vision loss. This paper proposes a deep learning-based predictive algorithm that can be used to detect the presence of a Subretinal hemorrhage. Region Convolutional Neural Network (R-CNN) and faster R-CNN are used to develop the predictive algorithm that can improve the classification accuracy. This method initially detects the presence of Subretinal hemorrhage, and it then segments the Region of Interest (ROI) by a semantic segmentation process. The segmented ROI is applied to a predictive algorithm which is derived from the Fast Region Convolutional Neural Network algorithm, that can categorize the Subretinal hemorrhage as responsive or non-responsive. The dataset, provided by a medical institution, comprised of optical coherence tomography (OCT) images of both pre- and post-treatment images, was used for training the proposed Faster Region Convolutional Neural Network (Faster R-CNN). We also used the Kaggle dataset for performance comparison with the traditional methods that are derived from the convolutional neural network (CNN) algorithm. The evaluation results using the Kaggle dataset and the hospital images provide an average sensitivity, selectivity, and accuracy of 85.3%, 89.64%, and 93.48% respectively. Further, the proposed method provides a time complexity in testing as 2.64s, which is less than the traditional schemes like CNN, R-CNN, and Fast R-CNN.
C1 [Suchetha, M.] VIT Chennai, Ctr Healthcare Adv Innovat & Res, Chennai, Tamil Nadu, India.
   [Ganesh, N. Sai; Dhas, D. Edwin] VIT Chennai, Sch Elect Engn, Chennai, Tamil Nadu, India.
   [Raman, Rajiv] Shri Bhagwan Mahavir Vitreo Retinal Serv, Sankara Nethralaya, Chennai, Tamil Nadu, India.
C3 VIT Chennai; VIT Chennai
RP Suchetha, M (通讯作者)，VIT Chennai, Ctr Healthcare Adv Innovat & Res, Chennai, Tamil Nadu, India.
EM suchetha.m@vit.ac.in; sganesh154@gmail.com; rajivpgraman@gmail.com;
   edwindhas.dhason@vit.ac.in
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NR 52
TC 0
Z9 0
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 1432-7643
EI 1433-7479
J9 SOFT COMPUT
JI Soft Comput.
PD DEC
PY 2021
VL 25
IS 24
BP 15255
EP 15268
DI 10.1007/s00500-021-06098-1
EA AUG 2021
PG 14
WC Computer Science, Artificial Intelligence; Computer Science,
   Interdisciplinary Applications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science
GA WR3GG
UT WOS:000686093800001
PM 34421341
OA Green Submitted, Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Movahedan, A
   Barba, H
   Spedale, M
   Deng, NN
   Arvans, D
   Nadeem, U
   Leone, V
   Chang, EB
   Theriault, B
   Skondra, D
AF Movahedan, Asadolah
   Barba, Hugo
   Spedale, Melanie
   Deng, Nini
   Arvans, Donna
   Nadeem, Urooba
   Leone, Vanessa
   Chang, Eugene B.
   Theriault, Betty
   Skondra, Dimitra
TI Gnotobiotic Operations and Assembly for Development of Germ-Free Animal
   Model of Laser-Induced Choroidal Neovascularization
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; microbiome; choroidal
   neovascularization; germ-free; gnotobiotic; animal model
ID GUT MICROBIOTA; MACULAR DEGENERATION; PATHOLOGICAL ANGIOGENESIS;
   OBESITY; RETINA; MICE
AB Purpose: Compelling new evidence reveals a close link between the gut microbiome and the pathogenesis of neovascular age-related macular degeneration (nAMD). Germ free (GF) animal models are the current gold standard for studying host the microbe interactions in vivo; yet, no GF animal models of nAMD are available today. This protocol describes gnotobiotic operations and assembly for a laser-induced choroidal neovascularization (CNV) model in GF mice to study the gut microbiome in neovascular AMD. Methods: We developed a step-wise approach to performing retinal laser photocoagulation in GF C57BL/6J mice that were bred and maintained at the gnotobiotic facility. Following a strict sterility protocol, we administered laser photocoagulation via an Argon 532-nm laser attached to a customized slit-lamp delivery system. Sterility was confirmed by weekly fecal cultures and reverse transcriptase-polymerase chain reaction. Results: The experiment was repeated twice at different time points using seven mice (14 eyes). Stool cultures and RT-PCR remained negative for 14 days post-procedure in all mice. Lectin immunostaining performed on choroidal flatmounts confirmed the presence of CNV lesions 2 weeks after laser treatment. Conclusions: We established a GF mouse model of nAMD with detailed guidelines to deliver retinal laser in GF mice maintaining sterility after the laser procedure. Translational Relevance: To our knowledge, this is the first protocol that describes a GF murine model of laser-induced CNV. In addition to nAMD, this animal model can be used to investigate host-microbial interactions in other eye diseases with laser-induced mouse models such as glaucoma and retinal vein occlusion.
C1 [Movahedan, Asadolah; Barba, Hugo; Deng, Nini; Arvans, Donna; Skondra, Dimitra] Univ Chicago, Dept Ophthalmol & Visual Sci, 5841 S Maryland Ave, Chicago, IL 60637 USA.
   [Spedale, Melanie; Theriault, Betty] Univ Chicago, Anim Resources Ctr, Chicago, IL 60637 USA.
   [Nadeem, Urooba] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   [Leone, Vanessa; Chang, Eugene B.] Univ Chicago, Dept Med, Sect Gastroenterol & Nutr, Chicago, IL 60637 USA.
   [Leone, Vanessa; Chang, Eugene B.] Univ Chicago, Microbiome Ctr, Chicago, IL 60637 USA.
   [Theriault, Betty] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago;
   University of Chicago; University of Chicago; University of Chicago
RP Skondra, D (通讯作者)，Univ Chicago, Dept Ophthalmol & Visual Sci, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM dskondra@bsd.uchicago.edu
FU Bright Focus Foundation [M2018042]; University of Chicago Women's Board;
   Illinois Society of Prevention of Blindness [FP067271-01-PR]; National
   Institute of Diabetes and Digestive and Kidney Diseases Diges-tive
   Disease Core Research Center [P30 DK42086]
FX Supported by grants from the Bright Focus Foundation (M2018042 to DS) ,
   University of Chicago Women's Board (DS), Illinois Society of Prevention
   of Blindness (FP067271-01-PR to DS) National Institute of Diabetes and
   Digestive and Kidney Diseases Diges-tive Disease Core Research Center
   (P30 DK42086) .
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NR 47
TC 2
Z9 2
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD AUG
PY 2021
VL 10
IS 9
AR 14
DI 10.1167/tvst.10.9.14
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UW7XM
UT WOS:000700367100007
PM 34388237
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Krytkowska, E
   Ulanczyk, Z
   Grabowicz, A
   Mozolewska-Piotrowska, K
   Safranow, K
   Palucha, A
   Krawczyk, M
   Sikora, P
   Matczynska, E
   Stahl, A
   Machalinski, B
   Machalinska, A
AF Krytkowska, Elzbieta
   Ulanczyk, Zofia
   Grabowicz, Aleksandra
   Mozolewska-Piotrowska, Katarzyna
   Safranow, Krzysztof
   Palucha, Andrzej
   Krawczyk, Mariusz
   Sikora, Piotr
   Matczynska, Ewa
   Stahl, Andreas
   Machalinski, Boguslaw
   Machalinska, Anna
TI Retinal Vessel Functionality Is Linked With ARMS2 A69S and CFH Y402H
   Polymorphisms and Choroidal Status in AMD Patients
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE age-related macular degeneration (AMD); CFH; ARMS2; retinal vasculature;
   choroid
ID COMPLEMENT FACTOR-H; CORONARY-ARTERY-DISEASE; MACULAR DEGENERATION; EYE
   DISEASE; RISK-FACTORS; CALIBER; ATHEROSCLEROSIS; HYPERTENSION;
   ARTERIOLAR; INSIGHTS
AB PURPOSE. We aimed to investigate the reactivity of retinal vessels to a flickering stimulus in patients with age-related macular degeneration (AMD) and healthy participants. We also assessed whether the parameters of retinal vessels are dependent on genetic predisposition.
   METHODS. A total of 354 patients with AMD and 121 controls were recruited for the study. All participants underwent thorough ophthalmologic examination and static and dynamic retinal vessel analysis. AMD risk polymorphisms were genotyped in the CFH and ARMS2 genes.
   RESULTS. We found no differences between the AMD group and controls in central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriovenous ratio (AVR), dynamic analysis of arteries (DAAs), or dynamic analysis of veins (DAVs). Eyes with early AMD presented with significantly higher AVR values than eyes with late AMD. In the AMD group, DAA correlated positively with both choroidal thickness (Rs = 0.14, P = 0.00096) and choroidal volume (Rs = 0.23, P < 0.0001), and no such associations were observed in the controls. We found significantly lower DAA (1.47 +/- 1.50) in TT homozygotes for the ARMS2 A69S polymorphism in comparison with GG homozygotes (2.38 +/- 1.79) and patients with GG + GT genotypes (2.28 +/- 1.84). We also observed less prominent DAV (3.24 +/- 1.71) in patients with TC + CC genotypes in the CFH Y402H polymorphism compared with TT homozygotes (3.83 +/- 1.68).
   CONCLUSIONS. Our findings suggest that retinal microcirculation appears to be associated with the genetic background, choroidal parameters, and clinical features of the patients with AMD.
C1 [Krytkowska, Elzbieta; Grabowicz, Aleksandra; Mozolewska-Piotrowska, Katarzyna; Machalinska, Anna] Pomeranian Med Univ, Dept Ophthalmol 1, Szczecin, Poland.
   [Ulanczyk, Zofia; Machalinski, Boguslaw] Pomeranian Med Univ, Dept Gen Pathol, Szczecin, Poland.
   [Safranow, Krzysztof] Pomeranian Med Univ, Dept Biochem & Med Chem, Szczecin, Poland.
   [Palucha, Andrzej; Krawczyk, Mariusz; Sikora, Piotr; Matczynska, Ewa] Genomed SA, Warsaw, Poland.
   [Stahl, Andreas] Univ Med Greifswald, Dept Ophthalmol, Greifswald, Germany.
C3 Pomeranian Medical University; Pomeranian Medical University; Pomeranian
   Medical University; Greifswald Medical School
RP Machalinska, A (通讯作者)，Pomeranian Med Univ, Dept Ophthalmol 1, Al Powstancow Wielkopolskich 72, PL-70111 Szczecin, Poland.
EM annam@pum.edu.pl
FU Polish National Centre for Research and Development
   [STRATEGMED1/234261/2NCBR/2014]; European Union funds from the European
   Union Regional Development Fund; Interreg Cooperation Program V A
   Mecklenburg-Western Pomerania/Brandenburg/Poland
FX Supported by the Polish National Centre for Research and Development
   (grant number: STRATEGMED1/234261/2NCBR/2014) and European Union funds
   from the European Union Regional Development Fund, Interreg Cooperation
   Program V A Mecklenburg-Western Pomerania/Brandenburg/Poland for
   2014-2020: "Consolidating cross-border cooperation through exchange of
   knowledge and skills in the field of modern diagnostic imaging methods
   in ophthalmology."
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NR 63
TC 0
Z9 0
U1 2
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2021
VL 62
IS 4
AR 30
DI 10.1167/iovs.62.4.30
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UQ5HH
UT WOS:000696094600016
PM 33900362
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wang, SB
   Liu, CX
   Ouyang, WJ
   Liu, Y
   Li, CY
   Cheng, YQ
   Su, YR
   Liu, C
   Yang, L
   Liu, YR
   Wang, ZC
AF Wang, Shoubi
   Liu, Chengxiu
   Ouyang, Weijie
   Liu, Ying
   Li, Chaoyang
   Cheng, Yaqi
   Su, Yaru
   Liu, Chang
   Yang, Liu
   Liu, Yurun
   Wang, Zhichong
TI Common Genes Involved in Autophagy, Cellular Senescence and the
   Inflammatory Response in AMD and Drug Discovery Identified via
   Biomedical Databases
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; autophagy; cellular senescence;
   inflammatory response; common genes; drugs
AB Purpose: Retinal pigment epithelial cell autophagy dysfunction, cellular senescence, and the retinal inflammatory response are key pathogenic factors in age-related macular degeneration (AMD), which has been reviewed in our previously work in 2019. This study aims to identify genes collectively involved in these three biological processes and target drugs in AMD.
   Methods: The pubmed2ensembl database was used to perform text mining. The GeneCodis database was applied to analyze gene ontology biological process and the KEGG pathway. The STRING database was used to analyze protein?protein interaction analysis and hub genes were identified by the Cytoscape software. The Drug Gene Interaction Database was used to perform drug?gene interactions.
   Results: We identified 62 genes collectively involved in AMD, autophagy, cellular senescence, and inflammatory response, 19 biological processes including 42 genes, 11 enriched KEGG pathways including 37 genes, and 12 hub genes step by step via the above biomedical databases. Finally, five hub genes (IL-6, VEGF-A, TP53, IL-10, and transforming growth factor [TGF]-01) and their specific interaction modes were identified, corresponding with 24 target drugs with therapeutic potential for AMD.
   Conclusions: IL-6, VEGF-A, TP53, IL-10, and TGF-01 are pivotal in autophagy, cellular senescence, and the inflammatory response in AMD, corresponding with 24 drugs with therapeutic potential for AMD, providing definite molecular mechanisms for further research and new possibilities for AMD treatment in the future.
   Translational Relevance: IL-6, VEGF-A, TP53, IL-10, and TGF-01 may be new targets for AMD gene therapy and drug development.
C1 [Wang, Shoubi; Liu, Ying; Li, Chaoyang; Cheng, Yaqi; Su, Yaru; Liu, Chang; Yang, Liu; Liu, Yurun; Wang, Zhichong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 Xian Lie Nan Rd, Guangzhou 510060, Peoples R China.
   [Liu, Chengxiu] Qingdao Univ, Med Coll, Affiliated Hosp, Dept Ophthalmol, Qingdao, Peoples R China.
   [Ouyang, Weijie] Xiamen Univ, Eye Inst, Sch Med, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Peoples R China.
C3 Sun Yat Sen University; Qingdao University; Xiamen University
RP Wang, ZC (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 Xian Lie Nan Rd, Guangzhou 510060, Peoples R China.
EM wangzhichong@gzzoc.com
RI Li, Chao/GSM-8117-2022
OI Li, Chao/0000-0001-6110-6210
FU National Key R&D program of China [2018YFC1106000]
FX Supported by The National Key R&D program of China (2018YFC1106000).
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NR 90
TC 2
Z9 3
U1 3
U2 8
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
AR 14
DI 10.1167/tvst.10.1.14
PG 21
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA RC7SP
UT WOS:000632996300005
PM 33510953
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, J
   Cho, K
   Choung, SY
AF Kim, Jun
   Cho, Kyoungwon
   Choung, Se-Young
TI Protective effect of Prunella vulgaris var. L extract against blue light
   induced damages in ARPE-19 cells and mouse retina
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Age-related macular degeneration; Retinal degeneration; Prunella
   vulgaris; Blue light; Oxidative stress; Inflammation
ID MACULAR DEGENERATION; PHOTOOXIDATIVE STRESS; EPITHELIUM-CELLS; OXIDATIVE
   STRESS; IN-VITRO; A2E; ACTIVATION; FRACTIONS; NRF2
AB Age -related macular degeneration (AMD) is one of leading causes that induce severe visual impairment and loss in the elderly. Previous studies have suggested that blue light (BL) could induce retinal degeneration, which is a major cause of the onset and development of severe AMD. In the retinal pigment epithelium (RPE) cells, A2E, a lipofuscin fluorophore, is accumulated with aging. When A2E is exposed to BL, it is easily oxidized to A2E- epoxides, leading to oxidative stress and inflammatory response in retina. The aim of this study was to in- vestigate protective effect of Prunella vulagris (P.V) extract against oxidative stress and inflammation caused by BL, and to elucidate the underlying mechanisms in the cultured RPE cells and balb-c mice. In both model studies, P.V extract activated NF -E2 related factor 2 (Nrf-2)/hemeoxygenase-1 (HO -1) signaling pathway, followed by inhibition of ROS/MDA production, GSH depletion and reduction in SOD activity. Furthermore, P.V extract inhibited upregulation of inflammatory related genes (interlukin (IL)-1beta, IL -6, monocyte chemoattractant protein -1 (MCP -1), vascular endothelial growth factor A (VEGF A)) and BL induced RPE cell death, determined by cell viability and histological analyses. The mechanism of protection against inflammation by P.V extract involves inhibition of nuclear translocation of nuclear factor kappa beta (NF-kB) along with degradation of NF- kB inhibitor alpha (IkB alpha). The results suggest that P.V extract could be a potential intervention to prevent the onset and development of severe AMD.
C1 [Kim, Jun; Choung, Se-Young] Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci, 26 Kyungheedae Ro, Seoul 02447, South Korea.
   [Cho, Kyoungwon] Chong Kun Dang Healthcare Corp, 47 Beodeunaru Ro, Seoul 07249, South Korea.
C3 Kyung Hee University
RP Choung, SY (通讯作者)，Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci, 26 Kyungheedae Ro, Seoul 02447, South Korea.
EM Jun2@khu.ac.kr; sychoung@khu.ac.kr
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NR 36
TC 14
Z9 17
U1 6
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAY 20
PY 2020
VL 152
BP 622
EP 631
DI 10.1016/j.freeradbiomed.2019.12.003
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA MB9XD
UT WOS:000542949900007
PM 31811921
DA 2022-11-30
ER

PT J
AU Song, JH
   Moon, KY
   Lee, SC
   Kim, SS
AF Song, Ji Hun
   Moon, Ka Young
   Lee, Sung Chul
   Kim, Sung Soo
TI Inhibition of Hypoxia-Inducible Factor-1 alpha and Vascular Endothelial
   Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; chrysin; choroidal neovascularization;
   hypoxia-inducible factor-1 alpha; vascular endothelial growth factor
ID MACULAR DEGENERATION; CELL-PROLIFERATION; NUCLEAR-FACTOR; EXPRESSION;
   RANIBIZUMAB; OVEREXPRESSION; ACTIVATION; FLAVONOIDS; APOPTOSIS; ANTIBODY
AB Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Vascular endothelial growth factor (VEGF) is essential for choroidal neovascularization (CNV) development in advanced, wet AMD. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with anti-inflammatory, anti-oxidative, and anti-angiogenic effects. We hypothesized that intravitreally injected chrysin may inhibit CNV due to its inhibitory effect on angiogenesis. To determine the effects of chrysin on an experimental CNV model, we induced CNV in Brown Norway rats with a diode laser. One week later, rats were injected intravitreally with chrysin in the right eye and vehicle in the left eye. The following week, we evaluated chrysin's effects via the CNV grade assessed with fluorescein angiography and histologic analyses. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and VEGF expression in the retina/choroid complex were also measured in both eyes. The mean CNV grade was significantly lower in chrysin-treated vs. control eyes (2.34 +/- 1.14 vs. 2.97 +/- 1.05, p < 0.001), as was the mean CNV thickness (33.90 +/- 4.89 vs. 38.50 +/- 5.43 mu m, p < 0.001) and mean HIF-1 alpha and VEGF levels (both p < 0.001). Compared to chrysin-treated eyes, the relative risk of control eyes developing high-leakage lesions was 2.03 (95% confidence interval: 1.46-2.83). Since chrysin inhibited laser-induced CNV and downregulated HIF-1 alpha and VEGF expression, it is a candidate for treating wet AMD and other CNV-associated conditions.
C1 [Song, Ji Hun; Moon, Ka Young] Ajou Univ, Dept Ophthalmol, Sch Med, 164 World Cup Ro, Suwon 16499, South Korea.
   [Lee, Sung Chul; Kim, Sung Soo] Yonsei Univ, Coll Med, Inst Vis Res, Dept Ophthalmol, 134 Shinchon Dong, Seoul 03722, South Korea.
C3 Ajou University; Yonsei University; Yonsei University Health System
RP Song, JH (通讯作者)，Ajou Univ, Dept Ophthalmol, Sch Med, 164 World Cup Ro, Suwon 16499, South Korea.
EM dreyesong@naver.com
OI Kim, Sung Soo/0000-0002-0574-7993; , Sung Chul/0000-0001-9438-2385
FU National Research Foundation of Korea (NRF) - Korea government (MSIT)
   [NRF-2018RICIB5044824]
FX This work was supported by the National Research Foundation of Korea
   (NRF) grant funded by the Korea government (MSIT) (No.
   NRF-2018RICIB5044824).
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NR 41
TC 7
Z9 7
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 APR
PY 2020
VL 21
IS 8
AR 2842
DI 10.3390/ijms21082842
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LR3AC
UT WOS:000535565300184
PM 32325771
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Tang, WY
   Guo, JL
   Gu, RP
   Lei, BY
   Ding, XY
   Ma, J
   Xu, GZ
AF Tang, Wenyi
   Guo, Jingli
   Gu, Ruiping
   Lei, Boya
   Ding, Xinyi
   Ma, Jun
   Xu, Gezhi
TI MicroRNA-29b-3p inhibits cell proliferation and angiogenesis by
   targeting VEGFA and PDGFB in retinal microvascular endothelial cells
SO MOLECULAR VISION
LA English
DT Article
ID MACULAR DEGENERATION; GROWTH-FACTORS; LUNG-CANCER; CYCLIN-E; EXPRESSION;
   PROTEIN; MIR-29; FAMILY; RECRUITMENT; RESISTANCE
AB Purpose: Excessive angiogenesis, also known as neovascularization, has considerable pathophysiologic roles in several retinal diseases, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. Accumulated evidence has revealed that miRNAs play important roles in endothelial cell dysfunction and angiogenesis. However, the role of microRNA-29b-3p (miR-29b-3p) in retinal angiogenesis is still unclear. Therefore, we investigated whether and how miR-29b-3p affects the function of retinal microvascular endothelial cells (RMECs).
   Methods: The overexpression and inhibition of miR-29b-3p were achieved by transfecting rat RMECs with an miR-29b-3p mimic and inhibitor, respectively. The proliferation, migration, and angiogenesis of RMECs were evaluated using a Cell Counting Kit-8 assay, Ki67 staining, western blotting (of proliferating cell nuclear antigen, cyclin A2, cyclin D1, and cyclin E1), wound healing test, and tube formation assay. The expression levels of vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB) were examined with quantitative real-time PCR and western blotting, respectively.
   Results: Overexpression of miR-29b-3p statistically significantly inhibited the function of RMECs in cell proliferation and angiogenesis, while inhibition of miR-29b-3p increased the proliferative and angiogenic activities of RMECs. Moreover, VEGFA and PDGFB, as the targets of miR-29b-3p, were statistically significantly downregulated by the miR-29b mimic, whereas the miR-29b-3p inhibitor had the opposite effects.
   Conclusions: miR-29b-3p negatively regulates RMEC proliferation and angiogenesis, at least partly by targeting VEGFA and PDGFB. These data may provide a potential therapeutic strategy for treating ocular neovascular diseases.
C1 [Tang, Wenyi; Guo, Jingli; Gu, Ruiping; Lei, Boya; Ding, Xinyi; Xu, Gezhi] Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, 83 Fen Yang Rd, Shanghai 200031, Peoples R China.
   [Ma, Jun; Xu, Gezhi] Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China.
   [Ma, Jun] Fudan Univ, Res Ctr, Eye & ENT Hosp, Shanghai, Peoples R China.
   [Xu, Gezhi] Fudan Univ, NHC Key Lab Myopia, Shanghai, Peoples R China.
   [Xu, Gezhi] Chinese Acad Med Sci, Lab Myopia, Shanghai, Peoples R China.
C3 Fudan University; Fudan University; Fudan University; Fudan University;
   Chinese Academy of Medical Sciences - Peking Union Medical College
RP Xu, GZ (通讯作者)，Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, 83 Fen Yang Rd, Shanghai 200031, Peoples R China.
EM ma886615@126.com; xugezhi@sohu.com
FU National Key Basic Research Program of 355 China [2013CB967503];
   National Natural Science Foundation of China [81570854]; Youth Project
   of the National Natural Science Fund [81600739, 81700861, 81700863,
   81800846]; Shanghai Sailing Program [16YF1401300]; Science and
   Technology Commission of Shanghai Municipality [16411953700]
FX This work was supported by grants from the National Key Basic Research
   Program of 355 China (2013CB967503), the National Natural Science
   Foundation of China (81570854), the Youth Project of the National
   Natural Science Fund (81600739, 81700861, 81700863, 81800846), Shanghai
   Sailing Program (16YF1401300) and Science and Technology Commission of
   Shanghai Municipality (16411953700). Gezhi Xu (xugezhi@sohu.com) and Jun
   Ma (ma886615@126.com) are both the co-corresponding authors of this
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NR 41
TC 13
Z9 14
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 24
PY 2020
VL 26
BP 64
EP 75
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA KU2VU
UT WOS:000519566800001
PM 32165827
DA 2022-11-30
ER

PT J
AU Bhuachalla, BN
   McGarrigle, CA
   O'Leary, N
   Akuffo, KO
   Peto, T
   Beatty, S
   Kenny, RA
AF Bhuachalla, Blaithin Ni
   McGarrigle, Christine A.
   O'Leary, Neil
   Akuffo, Kwadwo Owusu
   Peto, Tunde
   Beatty, Stephen
   Kenny, Rose Anne
TI Orthostatic blood pressure variability is associated with lower visual
   contrast sensitivity function: Findings from The Irish Longitudinal
   Study on Aging
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Eye; Contrast sensitivity; Blood pressure variability; End-organ damage;
   Orthostatic hypotension; Orthostatic hypertension
ID CARDIOVASCULAR RISK; FLOW; HYPERTENSION; PERFORMANCE; HYPOTENSION;
   IMPAIRMENT; PREVALENCE; CATARACT; BEHAVIOR
AB Background: Hypertension is established to cause vascular end-organ damage. Other forms of dysregulated blood pressure (BP) behaviour, such as orthostatic hypotension have also been associated with cardiovascular (CV) events. The eye is potentially vulnerable to dysregulated systemic BP if ocular circulation autoregulation is impaired. We investigated whether phenotypes of abnormal BP stabilisation after orthostasis, an autonomic stressor, had a relationship with contrast sensitivity (CS), an outcome measure of subtle psychophysical visual function.
   Methods: This was a cross-sectional study from wave 1 of The Irish Longitudinal Study on Ageing (TILDA). From beat-to-beat orthostatic BP (BP), measured by digital photoplethysmography during active stand, 4 phenotypes have been defined 1) normal stabilisation 2) orthostatic hypotension, 3) orthostatic hypertension 4) BP variability. Contrast sensitivity was measured using a Functional Visual Analyzer. Multivariable linear regression models investigated the relationship between orthostatic BP phenotypes and contrast sensitivity in 4289 adults aged >= 50 years adjusting for, demographics, cardiovascular risk factors, self-reported eye pathologies, objective hypertension and antihypertensives. A sensitivity analysis adjusted for age-related macular degeneration, glaucoma, diabetic retinopathy and maculopathy identified on retinal photographs. Finally models were compared, adjusting for alternative measures of cataract versus not, to examine the potential effect of cataract on any associations.
   Results: Systolic orthostatic BP variability was associated with worse contrast sensitivity, in the primary and the sensitivity analysis. Adjusting for alternative measures of clinical cataract attenuated the association by 18%.
   Conclusions: Orthostatic BP variability is associated with worse contrast sensitivity, independent of hypertension and retinal pathology and may be a cardiovascular biomarker of early ocular pathology.
C1 [Bhuachalla, Blaithin Ni; Kenny, Rose Anne] Univ Dublin, St Jamess Hosp, Trinity Coll Dublin, Sch Med,Dept Med Gerontol,Trinity Ctr Hlth Sci, Old Stone Bldg,Jamess St, Dublin 8, Ireland.
   [McGarrigle, Christine A.; O'Leary, Neil; Kenny, Rose Anne] Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Aging TILDA, Dublin 2, Ireland.
   [Akuffo, Kwadwo Owusu] Kwame Nkrumah Univ Sci & Technol, Coll Sci, Dept Optometry & Visual Sci, Kumasi, Ghana.
   [Peto, Tunde] Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth, Res Biomed Res Ctr, Reading Ctr,Dept Res & Dev, London, England.
   [Peto, Tunde] UCL Inst Ophthalmol, London, England.
   [Beatty, Stephen] Waterford Inst Technol, Vis Res Ctr, Macular Pigment Res Grp, Carriganore House, Waterford, Ireland.
C3 Trinity College Dublin; Trinity College Dublin; Kwame Nkrumah University
   Science & Technology; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of London;
   University College London; South East Technological University (SETU)
RP McGarrigle, CA (通讯作者)，Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Aging TILDA, Dublin 2, Ireland.
EM nibhuacb@tcd.ie; Christine.McGarrigle@tcd.ie; olearyne@tcd.ie;
   akuffokwadwoowusu@knust.edu.gh; Tunde.Peto@moorfields.nhs.uk;
   sbeatty@wit.ie; rkenny@tcd.ie
RI Akuffo, Kwadwo Owusu/J-2036-2019; McGarrigle, Christine/J-8331-2017
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; McGarrigle,
   Christine/0000-0001-5814-5673; Kenny, Rose Anne/0000-0002-9336-8124;
   O'Leary, Neil/0000-0002-2765-7016
FU Atlantic Philanthropies; Irish Life plc; Irish Government; NIHR BMRC at
   Moorfields Eye Hospital Foundation Trust and the UCL Institute of
   Ophthalmology
FX The authors report no conflicts of interest. Informed consent was
   obtained for all participants, and all protocols and procedures were
   approved by the institutional review board. TILDA is funded by The
   Atlantic Philanthropies (research grant), Irish Life plc and the Irish
   Government (research grant). Dr. Peto was funded by the NIHR BMRC at
   Moorfields Eye Hospital Foundation Trust and the UCL Institute of
   Ophthalmology. No funder played a role in the design, execution,
   analysis and interpretation of data or in the writing of this paper. The
   authors would like to thank all the participants in the study, the TILDA
   research, the team of interviewers and the study nurses and
   administrators.
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NR 37
TC 1
Z9 1
U1 0
U2 7
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 MAY
PY 2019
VL 119
BP 14
EP 24
DI 10.1016/j.exger.2019.01.009
PG 11
WC Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology
GA HN2FH
UT WOS:000460000600003
PM 30677467
DA 2022-11-30
ER

PT J
AU Kim, SY
   Kundu, J
   Williams, A
   Yandulskaya, AS
   Monaghan, JR
   Carrier, RL
   Linhardt, RJ
AF Kim, So Young
   Kundu, Joydip
   Williams, Asher
   Yandulskaya, Anastasia S.
   Monaghan, James R.
   Carrier, Rebecca L.
   Linhardt, Robert J.
TI Glycosaminoglycans compositional analysis of Urodele axolotl (Ambystoma
   mexicanum) and Porcine Retina
SO GLYCOCONJUGATE JOURNAL
LA English
DT Article
DE Amphibian; Axolotl; Glycosaminoglycans; Regeneration; Retina
ID FIBROBLAST-GROWTH-FACTOR; CHONDROITIN SULFATE PROTEOGLYCANS; COMPLEMENT
   FACTOR-H; HEPARAN-SULFATE; HYALURONIC-ACID; MACULAR DEGENERATION; BRUCHS
   MEMBRANE; CHICK-EMBRYO; INTERPHOTORECEPTOR MATRIX; EXTRACELLULAR-MATRIX
AB Retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are major causes of blindness worldwide. Humans cannot regenerate retina, however, axolotl (Ambystoma mexicanum), a laboratory-bred salamander, can regenerate retinal tissue throughout adulthood. Classic signaling pathways, including fibroblast growth factor (FGF), are involved in axolotl regeneration. Glycosaminoglycan (GAG) interaction with FGF is required for signal transduction in this pathway. GAGs are anionic polysaccharides in extracellular matrix (ECM) that have been implicated in limb and lens regeneration of amphibians, however, GAGs have not been investigated in the context of retinal regeneration. GAG composition is characterized native and decellularized axolotl and porcine retina using liquid chromatography mass spectrometry. Pig was used as a mammalian vertebrate model without the ability to regenerate retina. Chondroitin sulfate (CS) was the main retinal GAG, followed by heparan sulfate (HS), hyaluronic acid, and keratan sulfate in both native and decellularized axolotl and porcine retina. Axolotl retina exhibited a distinctive GAG composition pattern in comparison with porcine retina, including a higher content of hyaluronic acid. In CS, higher levels of 4- and 6- O-sulfation were observed in axolotl retina. The HS composition was greater in decellularized tissues in both axolotl and porcine retina by 7.1% and 15.4%, respectively, and different sulfation patterns were detected in axolotl. Our findings suggest a distinctive GAG composition profile of the axolotl retina set foundation for role of GAGs in homeostatic and regenerative conditions of the axolotl retina and may further our understanding of retinal regenerative models.
C1 [Kim, So Young; Linhardt, Robert J.] Rensselaer Polytech Inst, Biochem & Biophys Grad Program, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
   [Kundu, Joydip; Carrier, Rebecca L.] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA.
   [Williams, Asher; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
   [Yandulskaya, Anastasia S.; Monaghan, James R.] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
   [Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biol Sci, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
   [Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
   [Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biomed Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
C3 Rensselaer Polytechnic Institute; Northeastern University; Rensselaer
   Polytechnic Institute; Northeastern University; Rensselaer Polytechnic
   Institute; Rensselaer Polytechnic Institute; Rensselaer Polytechnic
   Institute
RP Linhardt, RJ (通讯作者)，Rensselaer Polytech Inst, Biochem & Biophys Grad Program, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.; Carrier, RL (通讯作者)，Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA.; Linhardt, RJ (通讯作者)，Rensselaer Polytech Inst, Dept Chem & Biol Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.; Linhardt, RJ (通讯作者)，Rensselaer Polytech Inst, Dept Biol Sci, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.; Linhardt, RJ (通讯作者)，Rensselaer Polytech Inst, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.; Linhardt, RJ (通讯作者)，Rensselaer Polytech Inst, Dept Biomed Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
EM rebecca@coe.neu.edu; linhar@rpi.edu
RI Carrier, Rebecca/AAK-2315-2020
FU NIH [DK111958, CA231074, HL125371]; NSF-CBET [1606128]
FX This research was funded by the NIH in the form of grants DK111958,
   CA231074, HL125371 (to RJL) and by grant NSF-CBET #1606128 (to RLC).
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NR 63
TC 6
Z9 6
U1 0
U2 21
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0282-0080
EI 1573-4986
J9 GLYCOCONJUGATE J
JI Glycoconjugate J.
PD APR
PY 2019
VL 36
IS 2
BP 165
EP 174
DI 10.1007/s10719-019-09863-5
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA HV7VX
UT WOS:000466190200007
PM 30963354
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bennis, A
   Jacobs, JG
   Catsburg, LAE
   ten Brink, JB
   Koster, C
   Schlingemann, RO
   van Meurs, J
   Gorgels, TGMF
   Moerland, PD
   Heine, VM
   Bergen, AA
AF Bennis, A.
   Jacobs, J. G.
   Catsburg, L. A. E.
   ten Brink, J. B.
   Koster, C.
   Schlingemann, R. O.
   van Meurs, J.
   Gorgels, T. G. M. F.
   Moerland, P. D.
   Heine, V. M.
   Bergen, A. A.
TI Stem Cell Derived Retinal Pigment Epithelium: The Role of Pigmentation
   as Maturation Marker and Gene Expression Profile Comparison with Human
   Endogenous Retinal Pigment Epithelium
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE Human embryonic stem cells; Retinal pigment epithelium; Pigmentation;
   Age related macular degeneration; Cell replacement therapy;
   Transcriptomics
ID INTEGRIN-LINKED KINASE; RPE CELLS; AGE; MELATONIN; DIFFERENTIATION;
   PHAGOCYTOSIS; JUNCTIONS; PROTECTS; THERAPY
AB In age-related macular degeneration (AMD) the retinal pigment epithelium (RPE) deteriorates, leading to photoreceptor decay and severe vision loss. New therapeutic strategies aim at RPE replacement by transplantation of pluripotent stem cell (PSC)-derived RPE. Several protocols to generate RPE have been developed where appearance of pigmentation is commonly used as indicator of RPE differentiation and maturation. It is, however, unclear how different pigmentation stages reflect developmental stages and functionality of PSC-derived RPE cells. We generated human embryonic stem cell-derived RPE (hESC-RPE) cells and investigated their gene expression profiles at early pigmentation (EP) and late pigmentation (LP) stages. In addition, we compared the hESC-RPE samples with human endogenous RPE. We used a common reference design microarray (44 K). Our analysis showed that maturing hESC-RPE, upon acquiring pigmentation, expresses markers specific for human RPE. Interestingly, our analysis revealed that EP and LP hESC-RPE do not differ much in gene expression. Our data further showed that pigmented hESC-RPE has a significant lower expression than human endogenous RPE in the visual cycle and oxidative stress pathways. In contrast, we observed a significantly higher expression of pathways related to the process adhesion-to-polarity model that is typical of developing epithelial cells. We conclude that, in vitro, the first appearance of pigmentation hallmarks differentiated RPE. However, further increase in pigmentation does not result in much significant gene expression changes and does not add important RPE functionalities. Consequently, our results suggest that the time span for obtaining differentiated hESC-RPE cells, that are suitable for transplantation, may be greatly reduced.
C1 [Bennis, A.; Catsburg, L. A. E.; ten Brink, J. B.; Koster, C.; Bergen, A. A.] AMC, Dept Clin Genet, Amsterdam, Netherlands.
   [Bennis, A.; ten Brink, J. B.; Gorgels, T. G. M. F.; Bergen, A. A.] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci NIN KNAW, Amsterdam, Netherlands.
   [Jacobs, J. G.; Heine, V. M.] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Child Neurol, Amsterdam, Netherlands.
   [Schlingemann, R. O.] AMC, Ocular Angiogenesis Grp, Amsterdam, Netherlands.
   [Schlingemann, R. O.; Bergen, A. A.] AMC, Dept Ophthalmol, Amsterdam, Netherlands.
   [Schlingemann, R. O.] AMC, Dept Cell Biol & Histol, Amsterdam, Netherlands.
   [van Meurs, J.] Rotterdam Eye Hosp, Amsterdam, Netherlands.
   [Gorgels, T. G. M. F.] MUMC, Univ Eye Clin Maastricht, Amsterdam, Netherlands.
   [Moerland, P. D.] AMC, Dept Clin Epidemiol Biostat & Bioinformat, Bioinformat Lab, Amsterdam, Netherlands.
   [Heine, V. M.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
C3 University of Amsterdam; Academic Medical Center Amsterdam; Royal
   Netherlands Academy of Arts & Sciences; Netherlands Institute for
   Neuroscience (NIN-KNAW); Vrije Universiteit Amsterdam; University of
   Amsterdam; Academic Medical Center Amsterdam; University of Amsterdam;
   Academic Medical Center Amsterdam; University of Amsterdam; Academic
   Medical Center Amsterdam; Rotterdam Eye Hospital; Maastricht University;
   University of Amsterdam; Academic Medical Center Amsterdam; Vrije
   Universiteit Amsterdam
RP Bergen, AA (通讯作者)，AMC, Dept Clin Genet, Amsterdam, Netherlands.; Bergen, AA (通讯作者)，Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci NIN KNAW, Amsterdam, Netherlands.; Heine, VM (通讯作者)，Vrije Univ Amsterdam, Med Ctr, Dept Pediat Child Neurol, Amsterdam, Netherlands.; Bergen, AA (通讯作者)，AMC, Dept Ophthalmol, Amsterdam, Netherlands.; Heine, VM (通讯作者)，Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
EM vm.heine@vumc.nl; a.bergen@amc.uva.nl
RI Moerland, Perry/AAG-1425-2020; Heine, Vivi M/F-1741-2011
OI Moerland, Perry/0000-0002-2357-3659; Heine, Vivi M/0000-0003-4416-3875;
   Koster, Celine/0000-0002-0936-3970; Bergen, Arthur/0000-0002-6333-9576
FU General Dutch Foundation Preventing Blindness; Foundation
   Blinden-Penning; National Foundation for Blindness and Low Vision
   (LSBS); National Foundation of Macular Degeneration (MD); Netherlands
   Eye Foundation; Gelderse Foundation for the Blind; Retina Netherlands
   Foundation; Foundation Winckel-Sweep; Rotterdam Foundation for the Blind
   (RvB) [2011-6]; Hague Foundation
FX This study was supported by grants from the General Dutch Foundation
   Preventing Blindness, the Foundation Blinden-Penning, the National
   Foundation for Blindness and Low Vision (LSBS); The National Foundation
   of Macular Degeneration (MD); The Netherlands Eye Foundation
   (Oogvereniging); The Gelderse Foundation for the Blind; Retina
   Netherlands Foundation; The Foundation Winckel-Sweep; all coordinated
   through the UitZicht platform, project 2011-6, as well as the Rotterdam
   Foundation for the Blind (RvB); and The Hague Foundation "Care for the
   Blind". 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 14
Z9 16
U1 3
U2 13
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 2629-3269
EI 2629-3277
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD OCT
PY 2017
VL 13
IS 5
BP 659
EP 669
DI 10.1007/s12015-017-9754-0
PG 11
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA FH0IQ
UT WOS:000410823500009
PM 28730556
OA Green Published
DA 2022-11-30
ER

PT J
AU Merrigan, SL
   Kennedy, BN
AF Merrigan, Stephanie L.
   Kennedy, Breandan N.
TI Vitamin D receptor agonists regulate ocular developmental angiogenesis
   and modulate expression of dre-miR-21 and VEGF
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; RETINAL VASCULATURE;
   IN-VIVO; COLORECTAL-CANCER; GENE-EXPRESSION; CONCISE GUIDE; ZEBRAFISH;
   NEOVASCULARIZATION; PHARMACOLOGY
AB BACKGROUND AND PURPOSE
   Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype-based screening in zebrafish.
   EXPERIMENTAL APPROACH
   A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae. Selectivity was assessed by evaluation of non-ocular intersegmental vasculature development. Safety pharmacology examined visual behaviour and retinal histology in larvae. Molecular mechanisms of action were scrutinized using expression profiling of target mRNAs and miRNAs in larval eyes.
   KEY RESULTS
   Library screening identified 10 compounds which significantly inhibited HV developmental angiogenesis. The validated hit calcitriol selectively demonstrated dose-dependent attenuation of HV development. In agreement, vitamin D receptor (VDR) agonists paricalcitol, doxercalciferol, maxacalcitol, calcipotriol, seocalcitol, calcifediol and tacalcitol significantly and selectively attenuated HV development. VDR agonists induced minor ocular morphology abnormalities and affected normal visual function. Calcitriol induced a three to sevenfold increase in ocular dre-miR-21 expression. Consistently, all-trans-retinoic acid attenuated HV development and increased ocular dre-miR-21 expression. Interestingly, zebrafish ocular vegfaa and vegfab expression was significantly increased while, vegfc, flt1 and kdrl expression was unchanged by calcitriol.
   CONCLUSION AND IMPLICATIONS
   These studies identified VDR agonists as significant and selective anti-angiogenics in the developing vertebrate eye andmiR21 as a key downstream regulated miRNA. These targets should be further evaluated as molecular hallmarks of, and therapeutic targets for pathological ocular neovascularization.
C1 [Merrigan, Stephanie L.; Kennedy, Breandan N.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin D04 V1W8, Ireland.
C3 University College Dublin
RP Kennedy, BN (通讯作者)，Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin D04 V1W8, Ireland.
EM brendan.kennedy@ucd.ie
RI kennedy, Breandan/H-5643-2019
OI kennedy, Breandan/0000-0001-7991-4689
FU Health Research Board [HRB-POR-2013-390]; Irish Research Council
   [GOIPG/2015/2061]
FX We thank Catherine Moss of the UCD Conway Institute genomics facility
   for assistance with QRT-PCR data analyses and use of facility. We thank
   the staff of the UCD Conway Institute imaging facility for technical
   support. We thank Dr Yolanda Alvarez and Dr Alison Reynolds
   formanuscript proof reading. This work was supported by the Health
   Research Board, HRB-POR-2013-390, and the Irish Research Council,
   GOIPG/2015/2061.
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NR 65
TC 27
Z9 27
U1 5
U2 34
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2017
VL 174
IS 16
BP 2636
EP 2651
DI 10.1111/bph.13875
PG 16
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA FB4WC
UT WOS:000406141700003
PM 28547797
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Schaal, KB
   Gregori, G
   Rosenfeld, PJ
AF Schaal, Karen B.
   Gregori, Giovanni
   Rosenfeld, Philip J.
TI En Face Optical Coherence Tomography Imaging for the Detection of
   Nascent Geographic Atrophy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SCANNING LASER OPHTHALMOSCOPE; DRUSEN-ASSOCIATED ATROPHY; MACULAR
   DEGENERATION; FUNDUS AUTOFLUORESCENCE; COMPLEMENT INHIBITION;
   NATURAL-HISTORY; SEVERITY SCALE; GROWTH-RATES; EYE DISEASE; PROGRESSION
AB PURPOSE: To determine if en face optical coherence tomography (OCT) imaging can identify nascent geographic atrophy (nGA) in eyes with intermediate age-related macular degeneration (iAMD).
   DESIGN: Retrospective observational case series.
   METHODS: Patients with iAMD from the COMPLETE study at the Bascom Palmer Eye Institute were evaluated to determine if nGA was present at baseline and at follow-up using high-density Spectralis OCT B-scans and en face OCT images from the Cirrus OCT instrument. If available, additional en face OCT images and B-scans were analyzed at follow-up times beyond the 52-week period.
   RESULTS: A total of 37 eyes (27 patients) were evaluated for at least 1 year using both B-scans and en face images. Two drusen suspicious for nGA at baseline were identified, but neither druse developed GA after 24 and 62 months of follow-up, respectively. Another druse displayed hypertransmission into the choroid at week 52 on B-scan imaging and was classified as nGA. En face OCT imaging identified this druse as a focal bright area. Drusen breakdown occurred during a follow-up of 39 months.
   CONCLUSIONS: En face OCT imaging appeared to be as useful as routine B-scan imaging for identifying areas suspicious for nGA in this population from the COMPLETE Study. Additional longitudinal follow-up of eyes with drusen is needed to determine if en face OCT imaging can replace the evaluation of individual B-scans for the detection of nGA. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Schaal, Karen B.; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Schaal, Karen B.] Univ Bern, Univ Hosp Bern, Inselspital, Dept Ophthalmol, CH-3012 Bern, Switzerland.
C3 Bascom Palmer Eye Institute; University of Miami; University of Bern;
   University Hospital of Bern
RP Rosenfeld, PJ (通讯作者)，Bascom Palmer Eye Inst, Ophthalmol, 900 NW 17th St, Miami, FL 33136 USA.
EM prosenfeld@miami.edu
FU CARL ZEISS MEDITEC INC (DUBLIN, CALIFORNIA); MACULA Vision Research
   Foundation; National Eye Institute Center Core Grant [P30EY014801]; Feig
   Family Foundation; Emma Clyde Hodge Memorial Foundation; German Research
   Foundation (DFG), Bonn, Germany [SCHA 1869/1-1]; Research to Prevent
   Blindness
FX RESEARCH SUPPORTED BY A GRANT FROM CARL ZEISS MEDITEC INC (DUBLIN,
   CALIFORNIA), THE MACULA Vision Research Foundation, the National Eye
   Institute Center Core Grant (P30EY014801), an unrestricted grant from
   Research to Prevent Blindness, the Feig Family Foundation, and the Emma
   Clyde Hodge Memorial Foundation. Karen B. Schaal receives funding from a
   grant from the German Research Foundation (DFG), Bonn, Germany, (SCHA
   1869/1-1).
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NR 37
TC 22
Z9 22
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
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD FEB
PY 2017
VL 174
BP 145
EP 154
DI 10.1016/j.ajo.2016.11.002
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EJ3YN
UT WOS:000393148800017
PM 27864062
DA 2022-11-30
ER

PT J
AU Hollborn, M
   Reichmuth, K
   Prager, P
   Wiedemann, P
   Bringmann, A
   Kohen, L
AF Hollborn, Margrit
   Reichmuth, Konrad
   Prager, Philipp
   Wiedemann, Peter
   Bringmann, Andreas
   Kohen, Leon
TI Osmotic induction of placental growth factor in retinal pigment
   epithelial cells in vitro: contribution of NFAT5 activity
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE Retinal pigment epithelium; Osmolarity; Hypoxia; PlGF; VEGF; NFAT5
ID PATHOGENIC T(H)17 CELLS; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; DIABETIC-RETINOPATHY; RISK-FACTORS; VEGF-C; AGE;
   EXPRESSION; HYPOXIA; DISEASE
AB One risk factor of neovascular age-related macular degeneration is systemic hypertension; hypertension is mainly caused by extracellular hyperosmolarity after consumption of dietary salt. In retinal pigment epithelial (RPE) cells, high extracellular osmolarity induces vascular endothelial growth factor (VEGF)-A (Hollborn et al. in Mol Vis 21:360-377, 2015). The aim of the present study was to determine whether extracellular hyperosmolarity and chemical hypoxia trigger the expression of further VEGF family members including placental growth factor (PlGF) in human RPE cells. Hyperosmotic media were made up by addition of 100 mM NaCl or sucrose. Chemical hypoxia was induced by CoCl2. Gene expression was quantified by real-time RT-PCR, and secretion of PlGF-2 was investigated with ELISA. Nuclear factor of activated T cell 5 (NFAT5) was depleted using siRNA. Extracellular hyperosmolarity triggered expression of VEGF-A, VEGF-D, and PlGF genes, and secretion of PlGF-2. Hypoosmolarity decreased PlGF gene expression. Hypoxia induced expression of VEGF-A, VEGF-B, VEGF-D, and PlGF genes. Extracellular hyperosmolarity and hypoxia produced additive PlGF gene expression. Both hyperosmolarity and hypoxia induced expression of KDR and FLT-4 receptor genes, while hyperosmolarity caused neuropilin-2 and hypoxia neuropilin-1 gene expression. The hyperosmotic, but not the hypoxic, PlGF gene expression was in part mediated by NFAT5. The expression of PlGF in RPE cells depends on the extracellular osmolarity. The data suggest that high consumption of dietary salt may exacerbate the angiogenic response of RPE cells in the hypoxic retina via transcriptional activation of various VEGF family member genes.
C1 [Hollborn, Margrit; Reichmuth, Konrad; Prager, Philipp; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon] Univ Leipzig, Fac Med, Dept Ophthalmol, Liebigstr 10-14, D-04103 Leipzig, Germany.
   [Hollborn, Margrit; Reichmuth, Konrad; Prager, Philipp; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon] Univ Leipzig, Fac Med, Hosp Eye, Liebigstr 10-14, D-04103 Leipzig, Germany.
   [Kohen, Leon] Helios Klinikum Aue, Aue, Germany.
C3 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.; Hollborn, M (通讯作者)，Univ Leipzig, Fac Med, Hosp Eye, Liebigstr 10-14, D-04103 Leipzig, Germany.
EM hollbm@medizin.uni-leipzig.de
FU Deutsche Forschungsgemeinschaft [KO 1547/7-1]; Geschwister Freter
   Stiftung (Hannover, Germany)
FX The authors thank Ute Weinbrecht for excellent technical assistance.
   This work was supported by grants from the Deutsche
   Forschungsgemeinschaft (KO 1547/7-1 to L.K.) and the Geschwister Freter
   Stiftung (Hannover, Germany).
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NR 51
TC 9
Z9 9
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
EI 1573-4978
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD AUG
PY 2016
VL 43
IS 8
BP 803
EP 814
DI 10.1007/s11033-016-4016-9
PG 12
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DR4GY
UT WOS:000379860800007
PM 27230578
DA 2022-11-30
ER

PT J
AU Gliem, M
   Muller, PL
   Mangold, E
   Bolz, HJ
   Stohr, H
   Weber, BHF
   Holz, FG
   Issa, PC
AF Gliem, Martin
   Mueller, Philipp L.
   Mangold, Elisabeth
   Bolz, Hanno J.
   Stoehr, Heidi
   Weber, Bernhard H. F.
   Holz, Frank G.
   Issa, Peter Charbel
TI Reticular Pseudodrusen in Sorsby Fundus Dystrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; BRUCHS MEMBRANE; GEOGRAPHIC-ATROPHY; PSEUDOXANTHOMA
   ELASTICUM; MORPHOMETRIC-ANALYSIS; CHOROIDAL THICKNESS; TISSUE INHIBITOR;
   TIMP3 GENE
AB Purpose: To investigate the association of reticular pseudodrusen (RPD) with Sorsby fundus dystrophy (SFD).
   Design: Prospective, monocenter, cross-sectional case series.
   Subjects: Sixteen patients of 4 unrelated families with SFD caused by mutations in TIMP3.
   Methods: All subjects underwent multimodal imaging including near-infrared (NIR) reflectance and fundus autofluorescence with a confocal scanning laser ophthalmoscope and spectral-domain optical coherence tomography (SD OCT).
   Main Outcome Measures: Prevalence, topographic distribution, and phenotype of RPD.
   Results: Mean age of the investigated patients was 56.8 years (range, 23-78 years). Reticular pseudodrusen were identified frequently in SFD patients in the sixth decade of life (5 of 7 [71%]) and were absent in younger (n = 3) or older (n = 6) patients. They were most abundant in the superior quadrant and spared the foveal region. Reticular pseudodrusen appeared as yellowish round to oval (dot subtype; n = 5) or confluent, wriggled (ribbon subtype; n = 3) lesions, sometimes forming irregular networks. Reticular pseudodrusen were hyporeflective on NIR reflectance and hypofluorescent on fundus autofluorescence imaging. They appeared as subretinal deposits on SD OCT imaging. Other lesions, such as peripheral pseudodrusen and soft drusen, were present less frequently.
   Conclusions: Reticular pseudodrusen are a frequent finding in patients with SFD. Although SFD patients with RPD are younger, distribution and phenotype of RPD are similar to those observed in patients with age-related macular degeneration. The association of RPD with SFD implicates a role of Bruch's membrane, the Bruch's membraneeretinal pigment epithelium interface, or both in the pathogenesis of RPD. (C) 2015 by the American Academy of Ophthalmology.
C1 [Gliem, Martin; Mueller, Philipp L.; Holz, Frank G.; Issa, Peter Charbel] Univ Hosp Bonn, Dept Ophthalmol, Bonn, Germany.
   [Mangold, Elisabeth] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
   [Bolz, Hanno J.] Bioscientia, Ctr Human Genet, Ingelheim, Germany.
   [Bolz, Hanno J.] Univ Hosp Cologne, Inst Human Genet, Cologne, Germany.
   [Stoehr, Heidi; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
C3 University of Bonn; University of Bonn; University of Cologne;
   University of Regensburg
RP Issa, PC (通讯作者)，Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM peter.issa@ukb.uni-bonn.de
RI Müller, Philipp L./P-3350-2019; Issa, Peter Charbel/E-8935-2018; Issa,
   Peter Charbel/O-2580-2019
OI Issa, Peter Charbel/0000-0002-0351-6673; Issa, Peter
   Charbel/0000-0002-0351-6673; Weber, Bernhard H.F./0000-0002-8808-7723
FU ProRetina Deutschland, Aachen, Germany; BONFOR research program of the
   University of Bonn, Bonn, Germany
FX Supported by the ProRetina Deutschland, Aachen, Germany (Charbel Issa);
   and the BONFOR research program of the University of Bonn, Bonn, Germany
   (Gliem). The Department of Ophthalmology, University of Bonn, receives
   imaging devices from Heidelberg Engineering, Heidelberg, Germany. The
   sponsor or funding organization had no role in the design or conduct of
   this research.
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NR 45
TC 40
Z9 42
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 AUG
PY 2015
VL 122
IS 8
BP 1555
EP 1562
DI 10.1016/j.ophtha.2015.04.035
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CN3JV
UT WOS:000358322900012
PM 26077580
DA 2022-11-30
ER

PT J
AU Liu, RZT
   Wang, AK
   To, E
   Gao, JY
   Cao, SJ
   Cui, JZ
   Matsubara, JA
AF Liu, Ruozhou Tom
   Wang, Aikun
   To, Eleanor
   Gao, Jiangyuan
   Cao, Sijia
   Cui, Jing Z.
   Matsubara, Joanne A.
TI Vinpocetine inhibits amyloid-beta induced activation of NF-kappa B,
   NLRP3 inflammasome and cytokine production in retinal pigment epithelial
   cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE AMD; amyloid-beta; NF-kappa B; vinpocetine; RPE; inflammasome; cytokine
ID MACULAR DEGENERATION; GENE-EXPRESSION; DRUSEN; MODEL; STIMULATION;
   RECOGNITION; MEDIATORS; PROTEINS; PATHWAYS; PEPTIDE
AB Chronic inflammation is a key pathogenic process in age-related macular degeneration (AMD). Amyloid-beta (A beta) is a constituent of AMD drusen and promotes the activation of NLRP3 inflammasome which facilitates the production of cytokines. We investigated the role of transcription factor NF-kappa B in the activation of inflammasome in the RPE and the effect of vinpocetine, a dietary supplement with inhibitory effect on NF-kappa B. ARPE19/NF-kappa B-luciferase reporter cells treated with All demonstrated enhanced NF-kappa B activation that was significantly suppressed by vinpocetine. Intraperitoneal injection of vinpocetine (15 mg/kg) inhibited NF-kappa B nuclear translocation and reduced the expression and activation of NLRP3, caspase-1, IL-1 beta, IL-18, and TNF-alpha in the RPE of adult rats that received intraocular A beta, as measured by retinal immunohistochemistry and Western blot. Cytokine level in the vitreous was assayed using multiplex suspension arrays and revealed significantly lower concentration of MIP-3 alpha, IL-6, IL-1 alpha, IL-1 beta, IL-18, and TNF-alpha in vinpocetine treated animals. These results suggest that the NF-kappa B pathway is activated by A beta in the RPE and signals the priming of NLRP3 inflammasome and the expression of pro-inflammatory cytokines including the inflammasome substrates IL-1 beta and IL-18. NF-kappa B inhibition may be an effective approach to stem the chronic inflammatory milieu that underlies the development of AMD. Vinpocetine is a potentially useful anti-inflammatory agent that is well-tolerated in long term use. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Liu, Ruozhou Tom; Wang, Aikun; To, Eleanor; Gao, Jiangyuan; Cao, Sijia; Cui, Jing Z.; Matsubara, Joanne A.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Fac Med, Vancouver, BC V5Z 3N9, Canada.
C3 University of British Columbia
RP Matsubara, JA (通讯作者)，Univ British Columbia, Dept Ophthalmol & Visual Sci, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
FU Vancouver Hospital + UBC Foundation; Faculty of Medicine (UBC); Canadian
   Institutes of Health Research [CIHR MOP-97806]
FX The authors would like to acknowledge Meysam Abbasi for technical
   assistance, and support by Vancouver Hospital + UBC Foundation, Faculty
   of Medicine (UBC). This study was funded by Canadian Institutes of
   Health Research Grant (CIHR MOP-97806) to JAM.
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NR 51
TC 60
Z9 65
U1 0
U2 21
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2014
VL 127
BP 49
EP 58
DI 10.1016/j.exer.2014.07.003
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ1KI
UT WOS:000342539900008
PM 25041941
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Tabor, HK
   Auer, PL
   Jamal, SM
   Chong, JX
   Yu, JH
   Gordon, AS
   Graubert, TA
   O'Donnell, CJ
   Rich, SS
   Nickerson, DA
   Bamshad, MJ
AF Tabor, Holly K.
   Auer, Paul L.
   Jamal, Seema M.
   Chong, Jessica X.
   Yu, Joon-Ho
   Gordon, Adam S.
   Graubert, Timothy A.
   O'Donnell, Christopher J.
   Rich, Stephen S.
   Nickerson, Deborah A.
   Bamshad, Michael J.
CA NHLBI Exome Sequencing Project
TI Pathogenic Variants for Mendelian and Complex Traits in Exomes of 6,517
   European and African Americans: Implications for the Return of
   Incidental Results
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME; PHARMACOGENOMICS; FRAMEWORK; RECOMMENDATIONS; INDIVIDUALS;
   PREVALENCE; MUTATIONS; TOOL; ERA
AB Exome sequencing (ES) is rapidly being deployed for use in clinical settings despite limited empirical data about the number and types of. incidental results (with potential clinical utility) that could be offered for return to an individual. We analyzed deidentified ES data from 6,517 participants (2,204 African Americans and 4,313 European Americans) from the National Heart, Lung, and Blood Institute Exome Sequencing Project. We characterized the frequencies of pathogenic alleles in genes underlying Mendelian conditions commonly assessed by newborn-screening (NBS, n = 39) programs, genes associated with age-related macular degeneration (ARMD, n = 17), and genes known to influence drug response (PGx, n = 14). From these 70 genes, we identified 10,789 variants and curated them by manual review of OMIM, HGMD, locus-specific databases, or primary literature to a total of 399 validated pathogenic variants. The mean number of risk alleles per individual was 15.3. Every individual had at least five known PGx alleles, 99% of individuals had at least one ARMD risk allele, and 45% of individuals were carriers for at least one pathogenic NBS allele. The carrier burden for severe recessive childhood disorders was 0.57. Our results demonstrate that risk alleles of potential clinical utility for both Mendelian and complex traits are detectable in every individual. These findings highlight the necessity of developing guidelines and policies that consider the return of results to all individuals and underscore the need to develop innovative approaches and tools that enable individuals to exercise their choice about the return of incidental results.
C1 [Tabor, Holly K.] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Seattle, WA 98101 USA.
   [Tabor, Holly K.; Jamal, Seema M.; Chong, Jessica X.; Yu, Joon-Ho; Bamshad, Michael J.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Auer, Paul L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA.
   [Gordon, Adam S.; Nickerson, Deborah A.; Bamshad, Michael J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Graubert, Timothy A.] Harvard Univ, Dept Med, Boston, MA 02114 USA.
   [O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Div Intramural Res, Framingham, MA 01702 USA.
   [Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
C3 Seattle Children's Hospital; University of Washington; University of
   Washington Seattle; Fred Hutchinson Cancer Center; University of
   Wisconsin System; University of Wisconsin Milwaukee; University of
   Washington; University of Washington Seattle; Harvard University;
   National Institutes of Health (NIH) - USA; NIH National Heart Lung &
   Blood Institute (NHLBI); University of Virginia
RP Bamshad, MJ (通讯作者)，Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
EM mbamshad@u.washington.edu
RI Hardy, John/C-2451-2009; Auer, Paul/AAC-5060-2019; Singleton, Andrew
   B/C-3010-2009; Chong, Jessica/GZH-1625-2022; Johnson, Andrew
   D/G-6520-2013; Barbalić, Maja/E-2161-2017; de Bakker, Paul
   IW/B-8730-2009; Assimes, Themistocles/D-9696-2015
OI Hardy, John/0000-0002-3122-0423; Johnson, Andrew D/0000-0001-6369-5178;
   Barbalić, Maja/0000-0001-8914-1691; de Bakker, Paul
   IW/0000-0001-7735-7858; Caan, Bette/0000-0002-5803-310X; Ballantyne,
   Christie/0000-0002-6432-1730; Rich, Stephen/0000-0003-3872-7793; Akey,
   Joshua/0000-0002-4411-1330; O'Connor, Timothy/0000-0002-0276-1896;
   Turner, Emily/0000-0001-9040-9229; Seshadri, Sudha/0000-0001-6135-2622;
   Gordon, Adam/0000-0002-2058-7289; Quinlan, Aaron/0000-0003-1756-0859;
   Assimes, Themistocles/0000-0003-2349-0009; Chong,
   Jessica/0000-0002-1616-2448; Shendure, Jay/0000-0002-1516-1865;
   Graubert, Timothy/0000-0002-7710-1171; Bustamante, Carlos
   D./0000-0002-4187-7920
FU National Heart, Lung, and Blood Institute (NHLBI) [RC2 HL-103010, RC2
   HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]; NATIONAL HEART,
   LUNG, AND BLOOD INSTITUTE [ZIAHL006175, ZIAHL006173, ZIAHL006002,
   T32HL007208, RC2HL102925, RC2HL102924, RC2HL103010, RC2HL102926,
   RC2HL102923] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING
   [U01AG049505] Funding Source: NIH RePORTER; National Institute on
   Minority Health and Health Disparities [P20MD006899] Funding Source: NIH
   RePORTER
FX We acknowledge the support of the National Heart, Lung, and Blood
   Institute (NHLBI), the contributions of the many research institutions
   that participated in this study, the study investigators, field staff,
   and the study participants who created the Exome Sequencing Project
   (ESP) resource for biomedical research. Funding for the NHLBI Grand
   Opportunity (GO) ESP was provided by NHLBI grants RC2 HL-103010 (Heart
   GO), RC2 HL-102923 (Lung GO), and RC2 HL-102924 (Women's Health
   Initiative Sequencing Project). Exome sequencing was supported by NHLBI
   grants RC2 HL-102925 (Broad GO) and RC2 HL-102926 (Seattle GO). The
   content is solely the responsibility of the authors and does not
   necessarily represent the official views of the NIH.
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NR 47
TC 64
Z9 67
U1 0
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD AUG 7
PY 2014
VL 95
IS 2
BP 183
EP 193
DI 10.1016/j.ajhg.2014.07.006
PG 11
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA AM7VE
UT WOS:000340076000005
PM 25087612
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Cameron, MA
   Suaning, GJ
   Lovell, NH
   Morley, JW
AF Cameron, Morven A.
   Suaning, Gregg J.
   Lovell, Nigel H.
   Morley, John W.
TI Electrical Stimulation of Inner Retinal Neurons in Wild-Type and
   Retinally Degenerate (rd/rd) Mice
SO PLOS ONE
LA English
DT Article
ID CONE BIPOLAR CELLS; GANGLION-CELLS; RABBIT RETINA; AMACRINE CELLS;
   RESPONSE PROPERTIES; MOUSE RETINA; RAT RETINA; ACTIVATION; CHANNELS;
   CURRENTS
AB Electrical stimulation of the retina following photoreceptor degeneration in diseases such as retinitis pigmentosa and age-related macular degeneration has become a promising therapeutic strategy for the restoration of vision. Many retinal neurons remain functional following photoreceptor degeneration; however, the responses of the different classes of cells to electrical stimuli have not been fully investigated. Using whole-cell patch clamp electrophysiology in retinal slices we investigated the response to electrical stimulation of cells of the inner nuclear layer (INL), pre-synaptic to retinal ganglion cells, in wild-type and retinally degenerate (rd/rd) mice. The responses of these cells to electrical stimulation were extremely varied, with both extrinsic and intrinsic evoked responses observed. Further examination of the intrinsically evoked responses revealed direct activation of both voltage-gated Na+ channels and K+ channels. The expression of these channels, which is particularly varied between INL cells, and the stimulus intensity, appears to dictate the polarity of the eventual response. Retinally degenerate animals showed similar responses to electrical stimulation of the retina to those of the wild-type, but the relative representation of each response type differed. The most striking difference between genotypes was the existence of a large amplitude oscillation in the majority of INL cells in rd/rd mice (as previously reported) that impacted on the signal to noise ratio following electrical stimulation. This confounding oscillation may significantly reduce the efficacy of electrical stimulation of the degenerate retina, and a greater understanding of its origin will potentially enable it to be dampened or eliminated.
C1 [Cameron, Morven A.; Morley, John W.] Univ Western Sydney, Sch Med, Campbelltown, NSW, Australia.
   [Suaning, Gregg J.; Lovell, Nigel H.] Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia.
C3 Western Sydney University; University of New South Wales Sydney
RP Cameron, MA (通讯作者)，Univ Western Sydney, Sch Med, Campbelltown, NSW, Australia.
EM m.cameron@uws.edu.au
RI Lovell, Nigel H/AGF-6679-2022
OI Lovell, Nigel H/0000-0003-1637-1079; Cameron,
   Morven/0000-0002-2277-7035; Suaning, Gregg/0000-0003-1918-3313; Morley,
   John/0000-0001-9246-853X
FU Australian Research Council (ARC) through its Special Research
   Initiative (SRI) in Bionic Vision Science and Technology grant
FX This research was supported by the Australian Research Council (ARC)
   through its Special Research Initiative (SRI) in Bionic Vision Science
   and Technology grant to Bionic Vision Australia (BVA). The 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 15
Z9 15
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 JUL 11
PY 2013
VL 8
IS 7
AR e68882
DI 10.1371/journal.pone.0068882
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 188UA
UT WOS:000322218800050
PM 23874798
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Giani, A
   Cigada, M
   Choudhry, N
   Deiro, AP
   Oldani, M
   Pellegrini, M
   Invernizzi, A
   Duca, P
   Miller, JW
   Staurenghi, G
AF Giani, Andrea
   Cigada, Mario
   Choudhry, Netan
   Deiro, Antonio Peroglio
   Oldani, Marta
   Pellegrini, Marco
   Invernizzi, Alessandro
   Duca, Piergiorgio
   Miller, Joan W.
   Staurenghi, Giovanni
TI Reproducibility of Retinal Thickness Measurements on Normal and
   Pathologic Eyes by Different Optical Coherence Tomography Instruments
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DIABETIC MACULAR EDEMA; TIME-DOMAIN; QUANTITATIVE ASSESSMENT; FOVEAL
   THICKNESS; REPEATABILITY; HEALTHY; DEGENERATION; DIAGNOSIS; ANALYZER;
   OCT
AB PURPOSE: To compare retinal thickness measurements produced by different time-domain and spectral-domain optical coherence tomography (TD-OCT and SD-OCT) devices when imaging normal and pathologic eyes.
   DESIGN: Prospective, observational study in an academic institutional setting.
   METHODS: A total of 110 eyes were imaged by 6 different OCT devices: Stratus and Cirrus (Carl Zeiss Meditec Inc), Spectra lis HRA+OCT (Heidelberg Engineering), RTVue-100 (Optovue Inc), SDOCT Copernicus HR (Optopol Technology S.A.), and 3D OCT-1000 (Topcon Corporation). Eyes were normal or affected by different pathologies of the retina, including exudative and nonexudative age-related macular degeneration, epiretinal membrane, cystoid macular edema, and macular hole. For each instrument we used standard analysis protocols for macular thickness evaluation. Mean retinal thickness values between the instruments in the ETDRS central circular 1000-mu m-diameter areas and in the ETDRS midperipheral circular 3000-mu m-diameter areas were compared.
   RESULTS: The 6 different devices produced measurements that differ in variance (Bartlett test, P = .006), and mean values (Friedman test, P < .001). Bland-Altman analysis revealed that the limits of agreement for all the comparisons were not acceptable. Regression was calculated and it was elaborated into a conversion table, despite a high standard error for both intercepts and slope conversion values.
   CONCLUSIONS: This study suggests that retinal thickness measurements obtained with various OCT devices are different beyond clinical practice tolerance, according to Bland-Altman analysis. Furthermore, regression analysis reveals high standard error values. These differences appear to be primarily attributable to the analysis algorithms used to set retinal inner and
C1 [Duca, Piergiorgio] Univ Milan, Dept Clin Sci Luigi Sacco, Luigi Sacco Hosp, Unita Satist Med & Biometria, I-20100 Milan, Italy.
   [Giani, Andrea; Choudhry, Netan; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA.
   [Giani, Andrea; Cigada, Mario; Deiro, Antonio Peroglio; Oldani, Marta; Pellegrini, Marco; Invernizzi, Alessandro; Staurenghi, Giovanni] Univ Milan, Eye Clin Luigi Sacco Hosp, I-20100 Milan, Italy.
C3 University of Milan; Luigi Sacco Hospital; Harvard University; Harvard
   Medical School; Massachusetts Eye & Ear Infirmary; University of Milan;
   Luigi Sacco Hospital
RP Staurenghi, G (通讯作者)，Univ Milan, Dept Clin Sci Luigi Sacco, Sacco Hosp, Via GB Grassi 74, I-20100 Milan, Italy.
EM giovanni.staurenghi@unimi.it
RI Invernizzi, Alessandro/K-8605-2016; Giani, Andrea/L-5926-2017; Duca,
   Piergiorgio/S-7525-2017; Staurenghi, Giovanni/K-4388-2017
OI Invernizzi, Alessandro/0000-0003-3400-1987; Miller,
   Joan/0000-0003-2046-3996; Giani, Andrea/0000-0003-0682-1945; Duca,
   Piergiorgio/0000-0003-4499-8805; Staurenghi,
   Giovanni/0000-0002-2299-5251; pellegrini, marco/0000-0002-3550-591X
FU Heidelberg Engineering, Heidelberg, Germany; Zeiss Meditec, Dublin,
   California, USA
FX THE AUTHORS INDICATE NO FINANCIAL SUPPORT FOR THIS STUDY. ANDREA GIANI
   RECEIVED TRAVEL FEES FOR ATTENDING a meeting from Heidelberg
   Engineering, Heidelberg, Germany. Giovanni Staurenghi received fees for
   service on an advisory board from Heidelberg Engineering, Heidelberg,
   Germany, and also received fees for attending a meeting from Zeiss
   Meditec, Dublin, California, USA. The Massachusetts Eye and Ear
   Infirmary has an ownership interest in 3 US patents directed to the use
   of verteporfin. In addition, the Massachusetts Eye and Ear Infirmary has
   an ownership interest in, certain patent applications directed to the
   selective destruction of subretinal choroidal neovasculature for the
   treatment of macular degeneration and other disorders. The Massachusetts
   Eye and Ear Infirmary receives royalties as a result of these patents
   and patent applications, and Joan W. Miller receives a share of the same
   in accordance with the Massachusetts Eye and Ear Infirmary's
   institutional Patent Policy and Procedures, which includes
   royalty-sharing provisions. Joan W. Miller is also currently on the
   Alcon Laboratory Board of Directors and is an ad hoc consultant for
   Bausch & Lomb and Genentech. Involved in design of the study (A.G., MC.,
   G.S.); conduct of the study (A.G., A.O., M.O., M.P., A.I.); collection
   and management of the data (A.G., MC.); analysis and interpretation of
   the data (A.G., MC., P.D.); preparation of the manuscript (A.G., MC.,
   N.C., J.W.M., G.S.); and review and approval of the manuscript (A.G.,
   N.C., J.W.M., G.S.). This study was conducted in accordance with the
   ethical standards stated in the Declaration of Helsinki and was approved
   by the Sacco Hospital IRB. At the time of follow-up examination,
   eligible patients were asked to participate in the study and informed
   consent for participation in this research was obtained.
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NR 39
TC 126
Z9 128
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2010
VL 150
IS 6
BP 815
EP 824
DI 10.1016/j.ajo.2010.06.025
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 695KB
UT WOS:000285367900008
PM 20965494
DA 2022-11-30
ER

PT J
AU Parapuram, SK
   Cojocaru, RI
   Chang, JR
   Khanna, R
   Brooks, M
   Othman, M
   Zareparsi, S
   Khan, NW
   Gotoh, N
   Cogliati, T
   Swaroop, A
AF Parapuram, Sunil K.
   Cojocaru, Radu I.
   Chang, Jessica R.
   Khanna, Ritu
   Brooks, Matthew
   Othman, Mohammad
   Zareparsi, Sepideh
   Khan, Naheed W.
   Gotoh, Norimoto
   Cogliati, Tiziana
   Swaroop, Anand
TI Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors:
   Implications for Retinal Diseases
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION PROFILE; FATTY-ACIDS; RECEPTOR-ALPHA; LIFE-SPAN;
   IN-VITRO; MECHANISMS; MICE; IDENTIFICATION; INFLAMMATION; ACTIVATION
AB Background: Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown.
   Methodology/Principal Findings: To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response).
   Conclusions/Significance: Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases.
C1 [Parapuram, Sunil K.; Cojocaru, Radu I.; Khanna, Ritu; Brooks, Matthew; Othman, Mohammad; Zareparsi, Sepideh; Khan, Naheed W.; Swaroop, Anand] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [Cojocaru, Radu I.; Chang, Jessica R.; Brooks, Matthew; Gotoh, Norimoto; Cogliati, Tiziana; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Chang, Jessica R.] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA.
C3 University of Michigan System; University of Michigan; National
   Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI);
   Howard Hughes Medical Institute; National Institutes of Health (NIH) -
   USA
RP Parapuram, SK (通讯作者)，Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
EM swaroopa@nei.nih.gov
OI Chang, Jessica/0000-0001-6663-2519; Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute; National Institutes of Health [EY11115, EY07003,
   DK20572]; Foundation Fighting Blindness; Elmer and Sylvia Sramek
   Foundation; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [P30EY007003, F31EY007003, ZIAEY000475, R01EY011115, ZIAEY000451]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [P30DK020572, P60DK020572] Funding Source:
   NIH RePORTER
FX This research was supported by intramural funds of the National Eye
   Institute and by grants (EY11115, EY07003, DK20572) from the National
   Institutes of Health, http://grants.nih.gov/grants/oer.htm, the
   Foundation Fighting Blindness, http://www.blindness.org/, the Elmer and
   Sylvia Sramek Foundation, and Research to Prevent Blindness,
   http://www.rpbusa.org/rpb/. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 76
TC 24
Z9 24
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 NOV 8
PY 2010
VL 5
IS 11
AR e13885
DI 10.1371/journal.pone.0013885
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 676NU
UT WOS:000283920000016
PM 21079736
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Khurana, RN
   Sun, XF
   Pearson, E
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   Goldberg, MF
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AF Khurana, Rahul N.
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   Pearson, Eric
   Yang, Zhenglin
   Harmon, Jennifer
   Goldberg, Morton F.
   Zhang, Kang
TI A Reappraisal of the Clinical Spectrum of North Carolina Macular
   Dystrophy
SO OPHTHALMOLOGY
LA English
DT Article
ID PIGMENT EPITHELIAL DYSTROPHY; PROGRESSIVE FOVEAL DYSTROPHY; FAMILY;
   TEARS; DEGENERATION; PHENOTYPE; MCDR1; MAPS
AB Purpose: To characterize the clinical phenotypes and genotype of a large family with North Carolina macular dystrophy (NCMD).
   Design: Observational, retrospective case series.
   Participants: Thirteen participants who were at risk of inheriting a dominantly transmitted disease gene from a 4-generation family from Baltimore were examined.
   Methods: Thirteen participants underwent ophthalmic examination and genomic linkage analysis. Fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, ultrasonography, full-field electroretinography, and electro-oculography were performed on some patients.
   Main Outcome Measures: Description of clinical phenotypes with genomic linkage to the MCDR1 locus.
   Results: Nine of 13 participants were affected with NCMD. There are variable and previously unreported clinical manifestations among affected individuals with NCMD, including drusen, macular staphyloma, choroidal neovascularization, a retinal pigment epithelial tear, and geographic atrophy. The distinctive and virtually pathognomonic grade 3 lesions in NCMD are neither staphylomas nor colobomas, as previously thought. As shown by ultrasonography and SD-OCT, they are deep chorioretinal excavations not involving the sclera, for which the authors propose a new term: macular caldera. Linkage analysis was performed, and the disease-causing gene in this family was mapped to the MCDR1 locus.
   Conclusions: North Carolina macular dystrophy has a wide spectrum of clinical phenotypes that resemble age-related macular degeneration except for their early age of onset.
   Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:1976-1983 (C) 2009 by the American Academy of Ophthalmology.
C1 [Khurana, Rahul N.; Goldberg, Morton F.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Sun, Xufang; Yang, Zhenglin; Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, San Diego, CA 92093 USA.
   [Sun, Xufang; Pearson, Eric; Yang, Zhenglin; Harmon, Jennifer; Zhang, Kang] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; University of
   California System; University of California San Diego; Utah System of
   Higher Education; University of Utah
RP Goldberg, MF (通讯作者)，Johns Hopkins Univ, Wilmer Eye Inst, 733 N Broadway St, Baltimore, MD 21205 USA.
EM mgoldbrg@jhmi.edu
RI Zhang, Kang/Y-2740-2019
OI Zhang, Kang/0000-0002-4549-1697; Khurana, Rahul/0000-0001-5198-1353
FU Wilmer Eye Institute, Baltimore, Maryland; Research to Prevent
   Blindness, Inc., New York, New York; National Eye Institute, Bethesda,
   Maryland [90709]; National Institutes of Health, Bethesda, Maryland
   [R01EY14428, R01EY14448, R01EY18660, P30EY014800]; Foundation Fighting
   Blindness, Owings Mills, Maryland; Macular Vision Research Foundation,
   West Conshohocken, Pennsylvania; Ruth and Milton Steinbach Fund, New
   York, New York; Burroughs Wellcome Fund; NATIONAL EYE INSTITUTE
   [R01EY018660, P30EY014800, R01EY014428, R01EY014448] Funding Source: NIH
   RePORTER
FX RNK is a Ronald G. Michels Fellow and is supported by the Ronald G.
   Michels Foundation, Riderwood, Maryland; MFG is supported in part by the
   Guerrieri Retinal Research Fund at the Wilmer Eye Institute, Baltimore,
   Maryland; an unrestricted grant from Research to Prevent Blindness,
   Inc., New York, New York; and by the National Eye Institute, Bethesda,
   Maryland (core grant no.: 90709). KZ is supported by the National
   Institutes of Health, Bethesda, Maryland (grant nos.: R01EY14428,
   R01EY14448, R01EY18660, and P30EY014800) Foundation Fighting Blindness,
   Owings Mills, Maryland; the Macular Vision Research Foundation, West
   Conshohocken, Pennsylvania; Research to Prevent Blindness. Inc., New
   York, New York; the Ruth and Milton Steinbach Fund, New York, New York;
   and the Burroughs Wellcome Fund Clinical Scientist Award in
   Translational Research, Research Triangle Park, North Carolina.
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NR 26
TC 18
Z9 18
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD OCT
PY 2009
VL 116
IS 10
BP 1976
EP 1983
DI 10.1016/j.ophtha.2009.03.028
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 506RX
UT WOS:000270794600021
PM 19616854
DA 2022-11-30
ER

PT J
AU Majumdar, S
   Srirangam, R
AF Majumdar, Soumyajit
   Srirangam, Ramesh
TI Solubility, Stability, Physicochemical Characteristics and In Vitro
   Ocular Tissue Permeability of Hesperidin: A Natural Bioflavonoid
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE hesperetin; hesperidin; ocular; permeability; solubility
ID MONOESTER GANCICLOVIR PRODRUGS; DRUG-DELIVERY; ACID-HYDROLASES; RABBIT
   CORNEA; ORANGE JUICE; FLAVONOIDS; RAT; TRANSPORT; HESPERETIN; EPITHELIUM
AB Hesperidin holds potential in treating age-related macular degeneration, cataract and diabetic retinopathy. The aim of this study, constituting the first step towards efficient ocular delivery of hesperidin, was to determine its physicochemical properties and in vitro ocular tissue permeability.
   pH dependent aqueous solubility and stability were investigated following standard protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi-side diffusion apparatus.
   Hesperidin demonstrated poor, pH independent, aqueous solubility. Solubility improved dramatically in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the results supported 1:1 complex formation. Solutions were stable in the pH and temperature (25, 40A degrees C) conditions tested, except for samples stored at pH 9. Transcorneal permeability in the apical-basal and basal-apical directions was 1.11 A +/- 0.86 x 10(-6) and 1.16 A +/- 0.05 x 10(-6) cm/s, respectively. The scleral tissue was more permeable (10.2 A +/- 2.1 x 10(-6) cm/s). However, permeability across sclera/choroid/RPE in the sclera to retina and retina to sclera direction was 0.82 A +/- 0.69 x 10(-6), 1.52 A +/- 0.78 x 10(-6) cm/s, respectively, demonstrating the barrier properties of the RPE.
   Our results suggest that stable ophthalmic solutions of hesperidin can be prepared and that hesperidin can efficiently permeate across the corneal tissue. Further investigation into its penetration into the back-of-the eye ocular tissues is warranted.
C1 [Majumdar, Soumyajit; Srirangam, Ramesh] Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA.
   [Majumdar, Soumyajit] Univ Mississippi, Pharmaceut Sci Res Inst, University, MS 38677 USA.
C3 University of Mississippi; University of Mississippi
RP Majumdar, S (通讯作者)，Univ Mississippi, Sch Pharm, Dept Pharmaceut, 111 Faser Hall, University, MS 38677 USA.
EM majumso@olemiss.edu
FU NIH [P20RR021929]; National Center for Research Resources; National Eye
   Institute [EY018426-01]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [P20RR021929] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R21EY018426] Funding Source: NIH RePORTER
FX This project was supported by NIH grant numbers P20RR021929, from the
   National Center for Research Resources, and EY018426-01 from the
   National Eye Institute. The content is solely the responsibility of the
   authors and does not necessarily represent the of. cial views of the
   National Center for Research Resources or the National Eye Institute,
   National Institutes of Health.
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NR 37
TC 81
Z9 86
U1 5
U2 44
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD MAY
PY 2009
VL 26
IS 5
BP 1217
EP 1225
DI 10.1007/s11095-008-9729-6
PG 9
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA 428IS
UT WOS:000264841800019
PM 18810327
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zareba, M
   Szewczyk, G
   Sarna, T
   Hong, L
   Simon, JD
   Henry, MM
   Burke, JM
AF Zareba, Mariusz
   Szewczyk, Grzegorz
   Sarna, Tadeusz
   Hong, Lian
   Simon, John D.
   Henry, Michele M.
   Burke, Janice M.
TI Effects of photodegradation on the physical and antioxidant properties
   of melanosomes isolated from retinal pigment epithelium
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID ELECTRON-SPIN-RESONANCE; CHEMICAL-PROPERTIES; OXIDATIVE STRESS;
   SUBSTANTIA-NIGRA; SYNTHETIC DOPA; FREE-RADICALS; HUMAN RPE; MELANIN;
   LIGHT; IRON
AB Melanosomes of the retinal pigment epithelium (RPE) are relatively long-lived organelles that are theoretically susceptible to changes induced by exposure to visible light. Here melanosomes were isolated from porcine RPE cells and subjected to high intensity visible light to determine the effects of illumination on melanosome structure and on the content and antioxidant properties of melanin. As compared to untreated melanosomes, illuminated granules showed morphologic changes consistent with photo degradation, which included variable reductions in electron density demonstrated by transmission electron microscopy (TEM), and particle fragmentation and surface disruption revealed by scanning electron microscopy (SEM) and atomic force microscopy. Illuminated melanosomes had lower melanin content, indicated by measures of absorbance and electron spin resonance (ESR) signal intensity, and reduced ability to bind iron, shown by chemical and ESR analyses. Compared to untreated melanosomes, ESR-spin trapping analyses further indicated that illuminated melanosomes show increased photogeneration of superoxide anion and reduced ability to inhibit the iron ioncatalyzed free radical decomposition of hydrogen peroxide. It appears therefore that visible light irradiation can disrupt: the structure of RPE melanosomes and reduce the amount and antioxidant properties of melanin. Some of these changes occur in human RPE melanosomes with aging and the results obtained here suggest that visible light irradiation is at least partly responsible. The consequence of light-induced changes in RPE melanosomes may be a diminished capacity of melanin to help protect aged cells from oxidative damage, perhaps increasing the risk of diseases with an oxidative stress component such as age-related macular degeneration.
C1 Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
   Jagiellonian Univ, Dept Biophys, Krakow, Poland.
   Duke Univ, Dept Chem, Durham, NC 27706 USA.
C3 Medical College of Wisconsin; Jagiellonian University; Duke University
RP Burke, JM (通讯作者)，Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
EM jburke@mcw.edu
RI Szewczyk, Grzegorz/AAL-7326-2020
OI Szewczyk, Grzegorz/0000-0003-0834-1080
FU NEI NIH HHS [P30 EY01931, R01 EY013722] Funding Source: Medline;
   NATIONAL EYE INSTITUTE [R01EY013722, P30EY001931] Funding Source: NIH
   RePORTER
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NR 45
TC 67
Z9 69
U1 0
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD JUL-AUG
PY 2006
VL 82
IS 4
BP 1024
EP 1029
DI 10.1562/2006-03-08-RA-836
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 078FR
UT WOS:000240088300021
PM 17205626
DA 2022-11-30
ER

PT J
AU Yamada, Y
   Ishibashi, K
   Ishibashi, K
   Bhutto, IA
   Tian, J
   Lutty, GB
   Handa, JT
AF Yamada, Yuko
   Ishibashi, Kazuko
   Ishibashi, Kazuki
   Bhutto, Imran A.
   Tian, Jane
   Lutty, Gerard B.
   Handa, James T.
TI The expression of advanced glycation endproduct receptors in rpe cells
   associated with basal deposits in human maculas
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; advanced glycation endproducts;
   advanced glycation endproduct receptor complex; aging; basal deposits;
   Bruch's membrane; receptor for advanced glycation endproducts; retinal
   pigment epithelium
ID RETINAL-PIGMENT EPITHELIUM; END-PRODUCTS; BRUCHS MEMBRANE;
   ENDOTHELIAL-CELLS; GROWTH-FACTOR; FACTOR-H; AGE; DEGENERATION; DRUSEN;
   RAGE
AB Basal deposits within Bruch's membrane are associated with aging and age-related macular degeneration (AMD) although the factors causing their formation are incompletely understood. Advanced glycation endproducts (AGEs) accumulate in Bruch's membrane including basal deposits and drusen with aging. One mechanism by which AGEs alter a cell's phenotype is via AGE receptors. The purpose of this study was to immunolocalize and quantify the expression of AGE receptors by RPE cells associated with basal deposits or normal Bruch's membrane that were microdissected from human maculas. Postmortem eyes from 14 aged control donors and five donors with non-neovascular AMD were cryopreserved. RPE cells associated with normal Bruch's membrane or basal deposits were laser capture microdissected. The RNA was extracted and used for RT-qPCR to quantify the expression of RAGE, AGE R1, AGE R2, and AGE R3. Streptavidin alkaline phosphatase immunohistochemistry for these receptors was also performed and sections were bleached from 14 normal and nine AMD donors. RT-qPCR showed significant upregulation of RAGE, AGE R1, and AGE R3 in RPE cells overlying basal deposits compared to cells attached to morphologically normal Bruch's membrane. Immunohistochemical analysis for RAGE, AGER1, R2, and R3 showed diffuse, light staining of RPE cells and strong choriocapillaris staining in areas of normal Bruch's membrane. In areas of basal deposits, the RPE had more intense staining for RAGE and AGER1 compared to regions of normal Bruch's membrane. These results suggest that AGE receptors could influence the formation of basal deposits during aging and AMD. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Johns Hopkins Med Inst, Michael Panitch Macular Degenerat Res Lab, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins
   University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，3-109 Jefferson St Bldg,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
FU NEI NIH HHS [R01 EY016151-05, R01 EY016151, R01 EY014005, EY 14055]
   Funding Source: Medline; NATIONAL EYE INSTITUTE [R01EY016151,
   R01EY014005] Funding Source: NIH RePORTER
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NR 43
TC 80
Z9 85
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 2006
VL 82
IS 5
BP 840
EP 848
DI 10.1016/j.exer.2005.10.005
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 041FU
UT WOS:000237440300012
PM 16364296
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Grunweller, A
   Hartmann, RK
AF Grunweller, A
   Hartmann, RK
TI RNA interference as a gene-specific approach for molecular medicine
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE RNA interference; RNAi; RNA silencing; siRNA; miRNA; shRNA; RISC;
   therapeutic application
ID RETRACTED ARTICLE. SEE; DOUBLE-STRANDED-RNA; TARGETED MESSENGER-RNAS;
   GROWTH-FACTOR RECEPTOR; SHORT HAIRPIN RNAS; MAMMALIAN-CELLS; NUCLEAR
   EXPORT; DEPENDENT STIMULATION; EFFICIENT DELIVERY; LENTIVIRAL VECTORS
AB The discovery of RNA interference (RNAi) in eukaryotic cells has been the major recent breakthrough in molecular and cell biology. RNAi machineries exert biological functions in gene regulation, genome defense and chromatin architecture and dynamics. The potential of RNAi to silence any gene of interest in a highly specific and efficient manner via double-stranded RNA (dsRNA) has literally revolutionized modern genetics. RNAi-based functional genomics now permits, for the first time, to evaluate the cellular role of individual gene products on a genome-wide scale in higher organisms like mammals, presenting an alternative to the generation of animal knockouts often doomed to failure because of a lethal phenotypes. RNAi has had an enormous impact on the development of novel disease models in animals, and it is likely that small interfering RNAs (siRNAs), which are the trigger molecules for RNA silencing, will become an invaluable tool for the treatment of genetic diseases. First clinical trials, using siRNAs directed against the vascular endothelial growth factor (VEGF) or one of its receptors, have been initiated recently for the treatment of age-related macular degeneration. Improving guidelines for the rational design of siRNAs, based on recent progress in understanding the mechanisms underlying RNAi, as well as the introduction of chemical modifications into siRNAs are expected to improve their pharmacokinetic and pharmacodynamic properties for in vivo applications. Finally, successful therapeutic application of RNAi will depend on the development of improved siRNA delivery strategies that combine high specificity and efficiency with a low immunostimulatory and tumorigenic potential.
C1 Univ Marburg, Inst Pharmaceut Chem, D-35037 Marburg, Germany.
C3 Philipps University Marburg
RP Grunweller, A (通讯作者)，Univ Marburg, Inst Pharmaceut Chem, Marbacher Weg 6, D-35037 Marburg, Germany.
EM gruenwel@staff.uni-marburg.de; roland.hartmann@staff.uni-marburg.de
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NR 223
TC 52
Z9 62
U1 0
U2 18
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PY 2005
VL 12
IS 26
BP 3143
EP 3161
DI 10.2174/092986705774933489
PG 19
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 990VF
UT WOS:000233770600009
PM 16375707
DA 2022-11-30
ER

PT J
AU Bora, PS
   Hu, ZW
   Tezel, TH
   Sohn, JH
   Kang, SG
   Cruz, JMC
   Bora, NS
   Garen, A
   Kaplan, HJ
AF Bora, PS
   Hu, ZW
   Tezel, TH
   Sohn, JH
   Kang, SG
   Cruz, JMC
   Bora, NS
   Garen, A
   Kaplan, HJ
TI Immunotherapy for choroidal neovascularization in a laser-induced mouse
   model simulating exudative (wet) macular degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID VASCULAR ENDOTHELIAL-CELLS; TISSUE FACTOR; ANTIBODY FRAGMENT;
   TUMOR-CELLS; TRANSLOCATION; ANGIOGENESIS; EXPERIENCE; EXPRESSION;
   MEMBRANES; THERAPY
AB Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.
C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40202 USA.
C3 Yale University; University of Louisville
RP Garen, A (通讯作者)，Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
RI Hu, Zhiwei/L-3727-2013
OI Hu, Zhiwei/0000-0002-0023-1170; Bora, Puran/0000-0003-4781-1217
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NR 27
TC 71
Z9 92
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2003
VL 100
IS 5
BP 2679
EP 2684
DI 10.1073/pnas.0438014100
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 652DR
UT WOS:000181365000092
PM 12589025
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Efferth, T
AF Efferth, T
TI Adenosine triphosphate-binding cassette transporter genes in ageing and
   age-related diseases
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE ABC transporter genes; age-related macular degeneration;
   atherosclerosis; non-insulin-dependent diabetes mellitus; T-cell ageing
ID P-GLYCOPROTEIN EXPRESSION; MULTIDRUG-RESISTANCE GENE; SULFONYLUREA
   RECEPTOR GENE; T-CELL SUBSETS; STARGARDT-DISEASE; TANGIER-DISEASE; ABCR
   GENE; RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; CHOLESTEROL EFFLUX
AB The family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters is the largest gene family known. While some ABC transporters translocate single substances across membranes with high specificity, others transport a wide variety of different lipophilic compounds. They are responsible for many physiological processes and are also implicated in a number of diseases. The present review focuses on ABC transporter genes which are involved in ageing and age-related diseases. Expression of ABCB1 (MDR1, P-glycoprotein) increases with age in CD4(+) and CD8(+) T-lymphocytes indicating that P-glycoprotein may be involved in the secretion of cytokines, growth factors, and cytotoxic molecules. As T cells in aged individuals are hyporesponsive leading to a reduced immunodefence capability, a role of ABCB1 in age-related immunological processes is presumed. The ABCA1 (ABC1) gene product translocates intracellular cholesterol and phospholipids out of macrophages. Genetic aberrations in ABCA1 cause perturbations in lipoprotein metabolism and contribute to atherosclerosis. ABCA4 (ABCR) represents a retina-specific ABC transporter expressed in rod photoreceptor cells. The ABCA4 gene product translocates retinyl-derivatives. Mutations in the ABCA4 gene contribute to age-related macular degeneration. Polymorphisms in the sulfonylurea receptor gene (ABCC8, SUR1) are associated with non-insulin-dependent diabetes mellitus (NIDDM). Sulfonylureas inhibit potassium conductance and are used to treat NIDDM by stimulation of insulin secretion across ATP-sensitive potassium channels in pancreatic P-cell membranes. Possible diagnostic and therapeutic implications of ABC transporters for age-related diseases are discussed. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
RP Efferth, T (通讯作者)，Virtual Campus Rhineland Palatinate,Rodeneck Pl 2, D-55126 Mainz, Germany.
EM efferth@vcrp.de
OI Efferth, Thomas/0000-0002-3096-3292
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NR 119
TC 35
Z9 36
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD JAN
PY 2003
VL 2
IS 1
BP 11
EP 24
AR PII S1568-1637(02)00046-6
DI 10.1016/S1568-1637(02)00046-6
PG 14
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Cell Biology; Geriatrics & Gerontology
GA 622ZL
UT WOS:000179678200002
PM 12437993
DA 2022-11-30
ER

PT J
AU Escandon, P
   Vasini, B
   Whelchel, AE
   Nicholas, SE
   Matlock, HG
   Ma, JX
   Karamichos, D
AF Escandon, Paulina
   Vasini, Brenda
   Whelchel, Amy E.
   Nicholas, Sarah E.
   Matlock, H. Greg
   Ma, Jian-Xing
   Karamichos, Dimitrios
TI The role of peroxisome proliferator-activated receptors in healthy and
   diseased eyes
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Eye; Peroxisome proliferator-activated receptors; Diabetic retinopathy;
   Diabetic keratopathy; Ocular neuropathy; Fibrates; Thiazolidinedione;
   Ocular disease
ID ENDOTHELIAL GROWTH-FACTOR; TYPE-2 DIABETES-MELLITUS; PPAR-GAMMA LIGANDS;
   ALPHA DOWN-REGULATION; RETINOID-X-RECEPTOR; LIPID-METABOLISM;
   GENE-EXPRESSION; TISSUE DISTRIBUTION; PATHOGENIC ROLE; NITRIC-OXIDE
AB Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors that play essential roles in modulating cell differentiation, inflammation, and metabolism. Three subtypes of PPARs are known: PPAR-alpha (PPAR alpha), PPAR-gamma (PPAR gamma), and PPAR-beta/delta (PPAR beta/delta). PPAR alpha activation reduces lipid levels and regulates energy homeostasis, activation of PPAR gamma results in regulation of adipogenesis, and PPAR beta/delta activation increases fatty acid metabolism and lipolysis. PPARs are linked to various diseases, including but not limited to diabetes, non-alcoholic fatty liver disease, glaucoma and atherosclerosis.
   In the past decade, numerous studies have assessed the functional properties of PPARs in the eye and key PPAR mechanisms have been discovered, particularly regarding the retina and cornea. PPAR gamma and PPAR alpha are well established in their functions in ocular homeostasis regarding neuroprotection, neovascularization, and inflammation, whereas PPAR beta/delta isoform function remains understudied. Naturally, studies on PPAR agonists and antagonists, associated with ocular pathology, have also gained traction with the development of PPAR synthetic ligands.
   Studies on PPARs has significantly influenced novel therapeutics for diabetic eye disease, ocular neuropathy, dry eye, and age-related macular degeneration (AMD). In this review, therapeutic potentials and implications will be highlighted, as well as reported adverse effects.
   Further investigations are necessary before any of the PPARs ligands can be utilized, in the clinics, to treat eye diseases. Future research on the prominent role of PPARs will help unravel the complex mechanisms involved in order to prevent and treat ocular diseases.
C1 [Escandon, Paulina; Vasini, Brenda; Nicholas, Sarah E.; Karamichos, Dimitrios] Univ North Texas, North Texas Eye Res Inst, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
   [Escandon, Paulina; Vasini, Brenda; Nicholas, Sarah E.; Karamichos, Dimitrios] Univ North Texas, Dept Pharmaceut Sci, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
   [Whelchel, Amy E.; Matlock, H. Greg; Ma, Jian-Xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, 940 Stanton L Young, Oklahoma City, OK USA.
   [Ma, Jian-Xing] Harold Hamm Oklahoma Diabet Ctr, 1000 N Lincoln Blvd, Oklahoma City, OK USA.
   [Karamichos, Dimitrios] Univ North Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
C3 University of North Texas System; University of North Texas Denton;
   University of North Texas Health Science Center; University of North
   Texas System; University of North Texas Denton; University of North
   Texas Health Science Center; University of Oklahoma System; University
   of Oklahoma Health Sciences Center; University of Oklahoma System;
   University of Oklahoma Health Sciences Center; University of North Texas
   System; University of North Texas Denton; University of North Texas
   Health Science Center
RP Karamichos, D (通讯作者)，Univ North Texas, North Texas Eye Res Inst, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
EM Dimitrios.Karamichos@unthsc.edu
OI karamichos, dimitrios/0000-0002-8761-3824; Vasini Rosell,
   Brenda/0000-0002-5271-3120
FU National Eye Institute [EY028949]
FX The authors would like to thank the National Eye Institute for providing
   research support (EY028949).
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NR 226
TC 6
Z9 6
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 JUL
PY 2021
VL 208
AR 108617
DI 10.1016/j.exer.2021.108617
EA MAY 2021
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SV3VG
UT WOS:000663749400007
PM 34010603
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wong, EKS
   Hallam, TM
   Brocklebank, V
   Walsh, PR
   Smith-Jackson, K
   Shuttleworth, VG
   Cox, TE
   Anderson, HE
   Barlow, PN
   Marchbank, KJ
   Harris, CL
   Kavanagh, D
AF Wong, Edwin K. S.
   Hallam, Thomas M.
   Brocklebank, Vicky
   Walsh, Patrick R.
   Smith-Jackson, Kate
   Shuttleworth, Victoria G.
   Cox, Thomas E.
   Anderson, Holly E.
   Barlow, Paul Nigel
   Marchbank, Kevin James
   Harris, Claire L.
   Kavanagh, David
TI Functional Characterization of Rare Genetic Variants in the N-Terminus
   of Complement Factor H in aHUS, C3G, and AMD
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE complement factor H; age-related macular degeneration; aHUS; C3G; MPGN
ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; MUTATIONS; BINDING;
   CFH; POLYMORPHISM; MECHANISMS; RISK
AB Membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), atypical haemolytic uraemic syndrome (aHUS) and age-related macular degeneration (AMD) have all been strongly linked with dysfunction of the alternative pathway (AP) of complement. A significant proportion of individuals with MPGN, C3G, aHUS and AMD carry rare genetic variants in the CFH gene that cause functional or quantitative deficiencies in the factor H (FH) protein, an important regulator of the AP. In silico analysis of the deleteriousness of rare genetic variants in CFH is not reliable and careful biochemical assessment remains the gold standard. Six N-terminal variants of uncertain significance in CFH were identified in patients with these diseases of the AP and selected for analysis. The variants were produced in Pichia Pastoris in the setting of FH CCPs 1-4, purified by nickel affinity chromatography and size exclusion and characterized by surface plasmon resonance and haemolytic assays as well as by cofactor assays in the fluid phase. A single variant, Q81P demonstrated a profound loss of binding to C3b with consequent loss of cofactor and decay accelerating activity. A further 2 variants, G69E and D130N, demonstrated only subtle defects which could conceivably over time lead to disease progression of more chronic AP diseases such as C3G and AMD. In the variants S159N, A161S, and M162V any functional defect was below the capacity of the experimental assays to reliably detect. This study further underlines the importance of careful biochemical assessment when assigning functional consequences to rare genetic variants that may alter clinical decisions for patients.
C1 [Wong, Edwin K. S.; Hallam, Thomas M.; Brocklebank, Vicky; Walsh, Patrick R.; Smith-Jackson, Kate; Shuttleworth, Victoria G.; Cox, Thomas E.; Anderson, Holly E.; Marchbank, Kevin James; Harris, Claire L.; Kavanagh, David] Newcastle Univ, Translat & Clin Res Inst, Complement Therapeut Res Grp, Newcastle Upon Tyne, Tyne & Wear, England.
   [Wong, Edwin K. S.; Hallam, Thomas M.; Brocklebank, Vicky; Walsh, Patrick R.; Smith-Jackson, Kate; Shuttleworth, Victoria G.; Cox, Thomas E.; Anderson, Holly E.; Marchbank, Kevin James; Harris, Claire L.; Kavanagh, David] Royal Victoria Infirm, Natl Renal Complement Therapeut Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
   [Barlow, Paul Nigel] Univ Edinburgh, Sch Chem, Joseph Black Bldg,David Brewster Rd, Edinburgh, Midlothian, Scotland.
   [Kavanagh, David] NIHR Newcastle Biomed Res Ctr, Biomed Res Bldg,Campus Ageing & Vital, Newcastle Upon Tyne, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle University - UK; University of
   Edinburgh; Newcastle University - UK
RP Kavanagh, D (通讯作者)，Newcastle Univ, Translat & Clin Res Inst, Complement Therapeut Res Grp, Newcastle Upon Tyne, Tyne & Wear, England.; Kavanagh, D (通讯作者)，Royal Victoria Infirm, Natl Renal Complement Therapeut Ctr, Newcastle Upon Tyne, Tyne & Wear, England.; Kavanagh, D (通讯作者)，NIHR Newcastle Biomed Res Ctr, Biomed Res Bldg,Campus Ageing & Vital, Newcastle Upon Tyne, Tyne & Wear, England.
EM david.kavanagh@ncl.ac.uk
OI Hallam, Thomas/0000-0002-4632-9640; Wong, Edwin/0000-0003-4867-6117;
   marchbank, kevin james/0000-0003-1312-5411
FU NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne
   Hospitals NHS Foundation Trust; Fight for Sight; Wellcome Trust; Medical
   Research Council; Kidney Research UK; Complement UK; Northern Counties
   Kidney Research Fund; Medical Research Council/Kidney Research UK
   [MR/R000913/1]; Medical Research Council (MRC) [MR/R001359/1]; MRC
   Discovery Medicine North; Newcastle Healthcare Charites; Kidney Research
   UK [RP7/2015]; MRC [1786288, MR/K023519/1, MR/R000913/1] Funding Source:
   UKRI
FX The research was supported/funded by NIHR Newcastle Biomedical Research
   Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust. DK was
   funded by Fight for Sight, the Wellcome Trust, the Medical Research
   Council, Kidney Research UK and Complement UK. CLH was funded by the
   Medical Research Council. EKSW was funded by Northern Counties Kidney
   Research Fund and was an MRC clinical research fellow and an NIHR
   Academic Clinical Lecturer. TMH is funded by Complement UK. VB is a
   Medical Research Council/Kidney Research UK Clinical Research Training
   Fellow (MR/R000913/1. PW is funded by the Wellcome trust. KSJ is a
   Medical Research Council (MRC) clinical research fellow (MR/R001359/1).
   TEC is funded by MRC Discovery Medicine North. KJM was funded by the
   Northern Counties Kidney Research Fund, the Newcastle Healthcare
   Charites and a Kidney Research UK project grant (RP7/2015).
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NR 40
TC 6
Z9 6
U1 0
U2 0
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 JAN 14
PY 2021
VL 11
AR 602284
DI 10.3389/fimmu.2020.602284
PG 10
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA PY8XS
UT WOS:000612325200001
PM 33519811
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Boyd, MJ
   Scott, DAR
   Squirrell, DM
   Wilson, GA
AF Boyd, Matt J.
   Scott, Daniel A. R.
   Squirrell, David M.
   Wilson, Graham A.
TI Proof-of-concept calculations to determine the health-adjusted life-year
   trade-off between intravitrealanti-VEGFinjections and transmission
   ofCOVID-19
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE age-related macular degeneration; anti-VEGF; COVID-19; health-adjusted
   life-years; mathematical model
ID MACULAR DEGENERATION
AB Background Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. Method We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. Results Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). Conclusion Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.
C1 [Boyd, Matt J.] Adapt Res Ltd, Reefton, New Zealand.
   [Scott, Daniel A. R.; Wilson, Graham A.] Hauora Tairawhiti, Gisborne Hosp, Dept Ophthalmol, Gisborne, New Zealand.
   [Squirrell, David M.] Auckland Dist Hlth Board, Greenlane Clin Ctr, Dept Ophthalmol, Auckland, New Zealand.
   [Wilson, Graham A.] Matai Lab, Gisborne, New Zealand.
C3 Auckland District Health Board
RP Boyd, MJ (通讯作者)，14 Broadway, Reefton 7830, New Zealand.
EM mattjamesboyd@gmail.com
RI Scott, Daniel/AAM-9983-2021
OI Scott, Daniel/0000-0002-0954-582X
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NR 32
TC 5
Z9 5
U1 0
U2 0
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 DEC
PY 2020
VL 48
IS 9
BP 1276
EP 1285
DI 10.1111/ceo.13855
EA SEP 2020
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PF6IB
UT WOS:000569391200001
PM 32902023
DA 2022-11-30
ER

PT J
AU Voigt, AP
   Whitmore, SS
   Flamme-Wiese, MJ
   Riker, MJ
   Wiley, LA
   Tucker, BA
   Stone, EM
   Mullins, RF
   Scheetz, TE
AF Voigt, A. P.
   Whitmore, S. S.
   Flamme-Wiese, M. J.
   Riker, M. J.
   Wiley, L. A.
   Tucker, B. A.
   Stone, E. M.
   Mullins, R. F.
   Scheetz, T. E.
TI Molecular characterization of foveal versus peripheral human retina by
   single-cell RNA sequencing
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Retina; Cones; Fovea; Single-cell; Transferrin
ID GENE-EXPRESSION; TRANSFERRIN
AB The human retina is a complex tissue responsible for detecting photons of light and converting information from these photons into the neurochemical signals interpreted as vision. Such visual signaling not only requires sophisticated interactions between multiple classes of neurons, but also spatially-dependent molecular specialization of individual cell types. In this study, we performed single-cell RNA sequencing on neural retina isolated from both the fovea and peripheral retina in three human donors. We recovered a total of 8,217 cells, with 3,578 cells originating from the fovea and 4,639 cells originating from the periphery. Expression profiles for all major retinal cell types were compiled, and differential expression analysis was performed between cells of foveal versus peripheral origin. Globally, mRNA for the serum iron binding protein transferrin (TF), which has been associated with age-related macular degeneration pathogenesis, was enriched in peripheral samples. Cone photoreceptor cells were of particular interest and formed two predominant clusters based on gene expression. One cone cluster had 96% of cells originating from foveal samples, while the second cone cluster consisted exclusively of peripherally isolated cells. A total of 148 genes were differentially expressed between cones from the fovea versus periphery. Interestingly, peripheral cones were enriched for the gene encoding Beta-Carotene Oxygenase 2 (BCO2). A relative deficiency of this enzyme may account for the accumulation of carotenoids responsible for yellow pigment deposition within the macula. Overall, this data set provides rich expression profiles of the major human retinal cell types and highlights transcriptomic features that distinguish foveal and peripheral cells.
C1 [Voigt, A. P.; Whitmore, S. S.; Flamme-Wiese, M. J.; Riker, M. J.; Wiley, L. A.; Tucker, B. A.; Stone, E. M.; Mullins, R. F.; Scheetz, T. E.] Univ Iowa, Carver Coll Med, Dept Ophthalmol, Iowa City, IA USA.
   [Voigt, A. P.; Whitmore, S. S.; Flamme-Wiese, M. J.; Riker, M. J.; Wiley, L. A.; Tucker, B. A.; Stone, E. M.; Mullins, R. F.; Scheetz, T. E.] Univ Iowa, Carver Coll Med, Dept Visual Sci, Iowa City, IA USA.
   [Voigt, A. P.; Whitmore, S. S.; Flamme-Wiese, M. J.; Riker, M. J.; Wiley, L. A.; Tucker, B. A.; Stone, E. M.; Mullins, R. F.; Scheetz, T. E.] Univ Iowa, Inst Vis Res, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa; University of Iowa
RP Scheetz, TE (通讯作者)，Univ Iowa, 375 Newton Rd, Iowa City, IA 52242 USA.
EM todd-scheetz@uiowa.edu
RI Mullins, Robert F/I-6717-2013
OI Mullins, Robert/0000-0002-5006-0891; Stone, Edwin
   M./0000-0003-3343-4414; Voigt, Andrew/0000-0001-8107-8317; Whitmore, S.
   Scott/0000-0003-0161-9625; Wiley, Luke/0000-0003-0136-2364; Scheetz,
   Todd/0000-0002-1965-5811; Tucker, Budd/0000-0003-2178-1742
FU National Institutes of Health [EY027038, EY025580]; Roy J. Carver, Jr.
   Chair in Bioinformatics and Computational Biology (TES); Research to
   Prevent Blindness; MSTP training grant [T32 GM007337]; NATIONAL EYE
   INSTITUTE [R21EY027038, P30EY025580, R01EY024605] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007337]
   Funding Source: NIH RePORTER
FX We thank the donors, their families, and the Iowa Lions Eye Bank for
   their generous and essential role in this research. This work was
   supported by National Institutes of Health grants EY027038 and EY025580,
   MSTP training grant T32 GM007337, the Roy J. Carver, Jr. Chair in
   Bioinformatics and Computational Biology (TES), and support from
   Research to Prevent Blindness.
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NR 31
TC 61
Z9 62
U1 1
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2019
VL 184
BP 234
EP 242
DI 10.1016/j.exer.2019.05.001
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IF3ND
UT WOS:000472986600027
PM 31075224
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Menghini, M
   Prunte, C
   Krayenbuehl, PA
   Nowak, A
AF Menghini, Moreno
   Prunte, Christian
   Krayenbuehl, Pierre A.
   Nowak, Albina
TI ASSESSMENT OF DRUSEN AND OTHER RETINAL DEGENERATIVE CHANGES IN PATIENTS
   WITH HEREDITARY HEMOCHROMATOSIS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; AMD; iron accumulation; hereditary
   hemochromatosis; oxidative damage; retinal pigment epithelium; RPE;
   human hemochromatosis protein; HFE
ID HALLERVORDEN-SPATZ SYNDROME; MACULAR DEGENERATION; PARKINSONS-DISEASE;
   PIGMENT EPITHELIUM; IRON ACCUMULATION; POTENTIAL FACTOR; BRUCHS
   MEMBRANE; GENE-MUTATIONS; HFE; AGE
AB Purpose: Iron can exert oxidative damage, and increased accumulation is believed to play a role in age-related macular degeneration. Hereditary hemochromatosis leads to an increase in total body iron. Patients with HH were assessed for drusen and other retinal changes.
   Methods: Descriptive uncontrolled study of spectral-domain optical coherence tomography, short-wavelength autofluorescence, and color fundus images from patients with HH were used. Diagnosis of HH was established by measuring ferritin and transferrin saturation, and confirmed by genetic testing. Classification of the patients according to initial ferritin level was: Group A > 1,032 mu g/L; Group B below.
   Results: Twenty-five percent of the invited participants were enrolled. Mean age at diagnosis was 46 +/- 15 years in Group A, and 38 +/- 13 years in Group B, P = 0.07, whereas mean age at imaging was 60 +/- 13 years in Group A, and 48 +/- 15 years in Group B (P = 0.003). The median of the initial ferritin level was 1,869 (1,262-3,256) ng/mL in Group A, and 534 (439-679) ng/mL in Group B. No subject in either group revealed multiple drusen, unambiguous changes of the retinal pigment epithelium, or increased lipofuscin in any of the images.
   Conclusion: The study results did not show an increased prevalence of drusen or other retinal degenerative changes in patients with HH. Thus, it was concluded that increased intestinal iron absorption as well as increased blood iron concentration are not risk factors for the early development of retinal degenerative changes in this study population.
C1 [Menghini, Moreno] Vista Diagnost, Limmatquai 4, CH-8001 Zurich, Switzerland.
   [Prunte, Christian] Kantonsspital Basel Land, Eye Clin, Liestal, Switzerland.
   [Krayenbuehl, Pierre A.] Linth Hosp, Div Internal Med, Uznach, Switzerland.
   [Nowak, Albina] Univ Hosp Zurich, Dept Internal Med, Zurich, Switzerland.
C3 Kantonsspital Baselland; University of Zurich; University Zurich
   Hospital
RP Menghini, M (通讯作者)，Vista Diagnost, Limmatquai 4, CH-8001 Zurich, Switzerland.
EM moreno@menghini.biz
OI Menghini, Moreno/0000-0002-1432-2524
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NR 33
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2018
VL 38
IS 3
BP 594
EP 599
DI 10.1097/IAE.0000000000001577
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GP2AB
UT WOS:000440619200022
PM 28291154
DA 2022-11-30
ER

PT J
AU Wu, WY
   Duan, YJ
   Ma, GE
   Zhou, GH
   Park-Windhol, C
   D'Amore, PA
   Lei, HT
AF Wu, Wenyi
   Duan, Yajian
   Ma, Gaoen
   Zhou, Guohong
   Park-Windhol, Cindy
   D'Amore, Patricia A.
   Lei, Hetian
TI AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In
   Vitro
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AAV5; CRISPR/Cas9; VEGFR2; angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; LEBERS CONGENITAL AMAUROSIS; AKT
   PROTOONCOGENE; FAMILY KINASES; RECEPTOR; TRANSDUCTION; ACTIVATION;
   VECTORS; PROTEIN; CELLS
AB PURPOSE. Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adenoassociated viral (AAV)-mediated CRISPR (clustered regularly interspaced short palindromic repeats)-associated endonuclease (Cas) 9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events.
   METHODS. The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined.
   RESULTS. AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs.
   CONCLUSIONS. AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis.
C1 [Wu, Wenyi; Duan, Yajian; Ma, Gaoen; Zhou, Guohong; Park-Windhol, Cindy; D'Amore, Patricia A.; Lei, Hetian] Harvard Med Sch, Schepens Eye Res Inst Massachusetts Eye & Ear, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA.
   [Wu, Wenyi] Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
   [Duan, Yajian; Zhou, Guohong] Shanxi Eye Hosp, Taiyuan, Shanxi, Peoples R China.
   [Ma, Gaoen] Xinxiang Med Univ, Eye Hosp, Affiliated Hosp 3, Dept Ophthalmol, Xinxiang, Henan, Peoples R China.
C3 Harvard University; Harvard Medical School; Central South University;
   Shanxi Medical University; Xinxiang Medical University
RP Lei, HT (通讯作者)，Harvard Med Sch, Schepens Eye Res Inst Massachusetts Eye & Ear, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA.
EM Hetian_lei@meei.harvard.edu
FU National Eye Institute of the National Institutes of Health
   [R01EY012509]; China Scholarship Council; Central South University
   Student Innovation Project [2016zzts148]; NATIONAL EYE INSTITUTE
   [R01EY012509] Funding Source: NIH RePORTER
FX Supported by the National Eye Institute of the National Institutes of
   Health under Award No. R01EY012509 (HL), China Scholarship Council (WW),
   and Central South University Student Innovation Project 2016zzts148
   (WW).
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NR 54
TC 20
Z9 21
U1 3
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 DEC
PY 2017
VL 58
IS 14
BP 6082
EP 6090
DI 10.1167/iovs.17-21902
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FY4GV
UT WOS:000426781300011
PM 29204648
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Seo, S
   Suh, W
AF Seo, Songyi
   Suh, Wonhee
TI Antiangiogenic effect of dasatinib in murine models of oxygen-induced
   retinopathy and laser-induced choroidal neovascularization
SO MOLECULAR VISION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL NEOVASCULARIZATION;
   DIABETIC-RETINOPATHY; MACULAR DEGENERATION; TUMOR PROGRESSION; KINASE
   INHIBITOR; CANCER CELLS; SRC KINASES; METASTASIS; ACTIVATION
AB Purpose: Vascular endothelial growth factor (VEGF) is a principal mediator of pathological ocular neovascularization, which is the leading cause of blindness in various ocular diseases. As Src, a non-receptor tyrosine kinase, has been implicated as one of the major signaling molecules in VEGF-mediated neovascularization, the present study aimed to investigate whether dasatinib, a potent Src kinase inhibitor, could suppress pathological ocular neovascularization in murine models of oxygen-induced retinopathy (OIR) and choroidal neovascularization (CNV).
   Methods: Tube formation, scratch wounding migration, and cell proliferation assays were performed to measure the inhibitory effect of dasatinib on VEGF-induced angiogenesis in human retinal microvascular endothelial cells. Murine models of OIR and laser-induced CNV were used to assess the preventive effect of an intravitreal injection of dasatinib on pathological neovascularization in the retina and choroid. Neovascularization and Src phosphorylation were evaluated with immunofluorescence staining.
   Results: Dasatinib efficiently inhibited VEGF-induced endothelial proliferation, wounding migration, and tube formation. In mice with OIR and laser injury-induced CNV, eyes treated with a single intravitreal injection of dasatinib exhibited significant decreases in pathological neovascularization compared with that of controls injected with vehicle. The dasatinib-treated OIR mice also showed a decrease in Src phosphorylation in the periretinal tufts. The intravitreal injection of dasatinib did not cause ocular toxicity at the treatment dose administered.
   Conclusions: These results demonstrated that dasatinib suppressed pathological neovascularization in the mouse retina and choroid. Therefore, dasatinib may be indicated for the treatment of ischemia-induced proliferative retinopathy and neovascular age-related macular degeneration.
C1 [Seo, Songyi; Suh, Wonhee] Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea.
C3 Chung Ang University
RP Suh, W (通讯作者)，Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea.
EM wsuh@cau.ac.kr
FU National Research Foundation of Korea grant - Korea government
   [2015R1D1A1A02061724, 2016M3A9A8918381]
FX This research was supported by National Research Foundation of Korea
   grant funded by the Korea government [2015R1D1A1A02061724;
   2016M3A9A8918381].
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NR 20
TC 9
Z9 9
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,
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SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD NOV 24
PY 2017
VL 23
BP 823
EP 831
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA FQ1BK
UT WOS:000418090900001
PM 29225458
DA 2022-11-30
ER

PT J
AU Miller, JW
AF Miller, Joan W.
TI VEGF: From Discovery to Therapy: The Champalimaud Award Lecture
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration (AMD); angiogenesis; Antonio
   Champalimaud Vision Award; Factor X; vascular endothelial growth factor
   (VEGF)
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; RETINAL VEIN
   OCCLUSION; MACULAR EDEMA SECONDARY; RANIBIZUMAB PLUS PROMPT; CHOROIDAL
   NEOVASCULARIZATION; INTRAVITREAL AFLIBERCEPT; IRIS NEOVASCULARIZATION;
   ANGIOGENIC ACTIVITY; HYPOXIC INDUCTION
AB Purpose: Intraocular vascular diseases are leading causes of adult vision loss, and in the mid-1900s, I. C. Michaelson postulated that the retina releases a soluble, diffusible factor that causes abnormal vascular growth and leakage. What became known as "Factor X'' eluded investigators for decades.
   Methods: The field of cancer research, where Judah Folkman pioneered the concept of angiogenesis, provided the inspiration for the work honored by the 2014 Champalimaud Vision Award. Recognizing that tumors recruit their own blood supply to achieve critical mass, Dr Folkman proposed that angiogenic factors could be therapeutic targets in cancer. Napoleone Ferrara identified vascular endothelial growth factor (VEGF) as such an angiogenic agent: stimulated by hypoxic tumor tissue, secreted, and able to induce neovascularization. VEGF also was a candidate for Factor X, and the 2014 Champalimaud Laureates and colleagues worked individually and collaboratively to identify the role of VEGF in ocular disease.
   Results: The Champalimaud Laureates correlated VEGF with ocular neovascularization in animal models and in patients. Moreover, they showed that VEGF not only was sufficient, but it also was required to induce neovascularization in normal animal eyes, as VEGF inhibition abolished ocular neovascularization in key animal models.
   Conclusions: The identification of VEGF as Factor X altered the therapeutic paradigms for age-related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, and other retinal disorders.
   Translational Relevance: The translation of VEGF from discovery to therapy resulted in the most successful applications of antiangiogenic therapy to date. Annually, over one million patients with eye disease are treated with anti-VEGF agents.
C1 [Miller, Joan W.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear, Massachusetts Gen Hosp, 243 Charles St, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Massachusetts General Hospital
RP Miller, JW (通讯作者)，Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear, Massachusetts Gen Hosp, 243 Charles St, Boston, MA 02114 USA.
EM Joan_Miller@meei.harvard.edu
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NR 47
TC 33
Z9 34
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD MAR
PY 2016
VL 5
IS 2
AR 9
DI 10.1167/tvst.5.2.9
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ED2JD
UT WOS:000388669300009
PM 26981331
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Shu, WT
   Mao, K
   Gu, Q
   Yin, LL
   Wu, XW
AF Shu, Wanting
   Mao, Ke
   Gu, Qing
   Yin, Lili
   Wu, Xingwei
TI Inflammatory cytokine secretion and toll-like receptor 4 activation in
   retinal pigment epithelium induced by oxidized low-density lipoprotein
SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
LA English
DT Article
DE Age-related macular degeneration; oxidized low-density lipoprotein;
   retinal pigment epithelium; inflammation; toll-like receptor 4
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; APOLIPOPROTEIN-B; BRUCHS
   MEMBRANE; BASAL DEPOSITS; RISK-FACTORS; CELLS; CHOLESTEROL; DRUSEN; EYES
AB Native and oxidized (OX) low-density lipoprotein (LDL) may contribute to the pathogenesis of age-related macular degeneration (AMD). In this study, we investigated the effects of lipoproteins, including n-LDL and OX-LDL, on the expression of inflammation factors, interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta), in vivo and in cultured retinal pigment epithelial (RPE) cells. The potential role of Toll-like receptor 4 (TLR4) was preliminarily explored. Fifteen male Sprague-Dawley rats were randomized into three groups and injected intravenously with PBS, low n-LDL (1 mg/kg), and high n-LDL (4 mg/kg) for 14 days. Immunohistochemistry analysis of retina sections was conducted to detect IL-6 and IL-1 beta. ARPE-19 cells were incubated with 10-100 mg/mL n-LDL or OX-LDL for 24 h. Reverse transcription polymerase chain reaction was used to detect IL-6, IL-1 beta and TLR4 mRNA levels in ARPE-19. IL-6 and IL-1 beta protein expression was measured by enzyme-linked immune sorbent assay. Activation of TLR4 and extracellular signal-regulated kinase (ERK) protein were evaluated by western blot analysis. One-way analysis of variance was used to compare differences. As a result, circulating LDL increased both IL-6 and IL-1 beta expression in rat retina tissue. OX-LDL treatment increased IL-6 and IL-1 beta expression in ARPE-19 cells, and activated TLR4-ERK signaling pathway. In conclusion, LDL activates inflammation cytokines in rat retina. OX-LDL induces inflammation promotion and TLR4-ERK signaling pathway upregulation in cultured RPE cells.
C1 [Shu, Wanting; Mao, Ke; Gu, Qing; Yin, Lili; Wu, Xingwei] Shanghai Jiao Tong Univ, Dept Ophthalmol, Shanghai Gen Hosp, Sch Med, 100 Haining Rd, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University
RP Yin, LL; Wu, XW (通讯作者)，Shanghai Jiao Tong Univ, Dept Ophthalmol, Shanghai Gen Hosp, Sch Med, 100 Haining Rd, Shanghai, Peoples R China.
EM yll144@aliyun.com; wxweye@sina.com
FU National Natural Science Foundation of China [81200702]
FX This project was supported by the National Natural Science Foundation of
   China (No. 81200702).
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NR 40
TC 0
Z9 0
U1 0
U2 4
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 2016
VL 9
IS 8
BP 8223
EP 8230
PG 8
WC Oncology; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Pathology
GA EA5IR
UT WOS:000386653400048
DA 2022-11-30
ER

PT J
AU Day, AC
   Donachie, PHJ
   Sparrow, JM
   Johnston, RL
AF Day, A. C.
   Donachie, P. H. J.
   Sparrow, J. M.
   Johnston, R. L.
CA Royal Coll Ophthalmologists Natl
TI The Royal College of Ophthalmologists' National Ophthalmology Database
   Study of cataract surgery: report 2, relationships of axial length with
   ocular copathology, preoperative visual acuity, and posterior capsule
   rupture
SO EYE
LA English
DT Article
ID ELECTRONIC MULTICENTER AUDIT; 55 567 OPERATIONS; AGE-RELATED
   MACULOPATHY; INTRAOCULAR-LENS IMPLANTATION; SINGAPORE-MALAY-EYE;
   UNITED-KINGDOM; HIGH MYOPIA; MACULAR DEGENERATION; RETINAL-DETACHMENT;
   REFRACTIVE ERRORS
AB Purpose To describe the relationships of axial length with ocular copathology, preoperative visual acuity, and posterior capsule rupture rates in patients undergoing cataract surgery.
   Design The Royal College of Ophthalmologists' National Ophthalmology Database (NOD) study.
   Methods Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Data parameters included: demographics, biometry, ocular copathology, visual acuity measurements, and surgical complications including posterior capsule rupture, or vitreous loss or both (PCR).
   Results Consultant surgeons performed a higher proportion of operations on eyes whose axial length were at the extremes. Glaucoma and age related macular degeneration were more common in eyes with shorter axial lengths, whilst previous vitrectomy was associated with longer axial lengths. Eyes with brunescent or white cataracts or amblyopia were more common at both axial length extremes. Preoperative visual acuities were similar for eyes with axial length measurements up to approximately 28 mm and worse for eyes with longer axial length measurements. PCR rates showed little change with axial length (overall mean 1.95%, 95% CI: 1.89 to 2.01%), except for a borderline increase in eyes with axial length <20.0mm where rates were 3.6% (95% CI: 2.0 to 6.3%). The likelihood of PCR in eyes with axial length <20.0mm was 1.88 times higher than those of >= 20.0mm (P=0.0373).
   Conclusion Rates of ocular comorbidities vary by axial length. PCR rates in eyes with very short or long axial lengths were lower than expected.
C1 [Day, A. C.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Day, A. C.] UCL Inst Ophthalmol, London, England.
   [Donachie, P. H. J.; Sparrow, J. M.; Johnston, R. L.] Royal Coll Ophthalmologists Natl Ophthalmol Datab, London, England.
   [Donachie, P. H. J.; Johnston, R. L.] Gloucestershire Hosp NHS Fdn Trust, Cheltenham, Glos, England.
   [Sparrow, J. M.] Bristol Eye Hosp, Bristol BS1 2LX, Avon, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Gloucestershire Hospitals NHS Foundation Trust; Bristol Eye Hospital
RP Johnston, RL (通讯作者)，Royal Coll Ophthalmologists, Royal Coll Ophthalmologists Natl Ophthalmol Datab, 18 Stephenson Way, London NW1 2HD, England.
EM robert.johnston3@nhs.net
FU Special Trustees of Moorfields Eye Hospital [ST1307A]; National
   Institute for Health Research (NIHR) Biomedical Research Centre based at
   Moorfields Eye Hospital NHS Foundation Trust; National Institute for
   Health Research (NIHR) Biomedical Research Centre based at UCL Institute
   of Ophthalmology
FX The Special Trustees of Moorfields Eye Hospital provided an unrestricted
   grant to fund the analysis (grant number ST1307A). Alex Day was
   supported by the National Institute for Health Research (NIHR)
   Biomedical Research Centre based at Moorfields Eye Hospital NHS
   Foundation Trust and UCL Institute of Ophthalmology. The views expressed
   are those of the author(s) and not necessarily those of the NHS, the
   NIHR or the Department of Health. The authors acknowledge the clinicians
   who contributed data to the National Ophthalmology Database. The
   contributing centres are listed in parenthesis. Aintree University
   Hospital NHS Foundation Trust; Airedale NHS Foundation Trust; Barking,
   Havering and Redbridge University Hospitals NHS Trust; Bedford Hospital
   NHS Trust; Bradford Teaching Hospitals NHS Foundation Trust; Calderdale
   and Huddersfield NHS Foundation Trust; Cambridge University Hospitals
   NHS Foundation Trust; Epsom and St Helier University Hospital NHS Trust;
   Frimley park Hospital NHS Foundation Trust; Gloucestershire Hospitals
   NHS Foundation Trust; Hampshire Hospitals NHS Foundation Trust; King's
   College Hospital NHS Foundation Trust; Leeds Teaching Hospitals NHS
   Trust; Mid Cheshire Hospitals NHS Foundation Trust; Mid Yorkshire
   Hospitals NHS Trust; NHS Dumfries and Galloway; Norfolk and Norwich
   University Hospitals NHS Foundation Trust; North Devon Healthcare NHS
   Trust; Peterborough and Stamford Hospitals NHS Foundation Trust;
   Portsmouth Hospitals NHS Trust; Royal Berkshire NHS Foundation Trust;
   Royal United Hospital Bath NHS Trust; South London Healthcare NHS Trust;
   The Hillingdon Hospital NHS Trust; University Hospitals Bristol NHS
   Foundation Trust; University Hospital Birmingham NHS Foundation Trust;
   Wirral University Teaching Hospital NHS Foundation Trust.
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NR 32
TC 14
Z9 14
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD DEC
PY 2015
VL 29
IS 12
BP 1529
EP 1536
DI 10.1038/eye.2015.198
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CY7UC
UT WOS:000366613800004
PM 26493034
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Scholler, A
   Richter-Mueksch, S
   Weingessel, B
   Vecsei-Marlovits, PV
AF Scholler, Andreas
   Richter-Mueksch, Sibylla
   Weingessel, Birgit
   Vecsei-Marlovits, Pia-Veronika
TI Differences of frequency in administration of ranibizumab and
   bevacizumab in patients with neovascular AMD
SO WIENER KLINISCHE WOCHENSCHRIFT
LA English
DT Article
DE Ranibizumab; Bevacizumab; Neovascular AMD; Number of treatment
ID MACULAR DEGENERATION; DOSING REGIMEN
AB Intravitreal ranibizumab or bevacizumab are the most used drugs for treatment of neovascular age-related macular degeneration (nAMD). Repeated intravitreal injections represent an economic burden and may be associated with serious complications. The aim of this study is to evaluate the number of needed injections within 1 year of treatment.
   55 patients over 50 years of age with nAMD and visual acuity (VA) between 20/40 and 20/320 were included. Scheduled visits and treatment were performed monthly for 1 year. After a loading dose of three intravitreal injections (either ranibizumab = group 1 or bevacizumab = group 2), an "as needed" regimen was performed. Primary endpoint was a difference in the injection frequencies of ranibizumab and bevacizumab. Secondary endpoints were best corrected visual acuity (BCVA) and central retinal thickness (CRT).
   Difference in number of injections was not significant (5.00 +/- 1.67 (ranibizumab group) vs. 5.80 +/- 2.28 (bevacizumab group), p = 0.084). Mean BCVA was 59.12 +/- 16.64 letters after 12 months if patients received ranibizumab (p = 0.001) and 64.75 +/- 17.03 letters if patients received bevacizumab (p = 0.037). There was no statistical significance between the two groups (p = 0.631). The mean CRT did not differ significantly between groups after 12 months (315.67 +/- 65.86 A mu m for ranibizumab, 350.47 A +/- 102.84 A mu m for bevacizumab, p = 0.088).
   There was no difference in number of treatment, BCVA and CRT after 1 year between ranibizumab and bevacizumab in patients with nAMD.
C1 [Scholler, Andreas; Richter-Mueksch, Sibylla; Weingessel, Birgit; Vecsei-Marlovits, Pia-Veronika] Hietzing Hosp, Dept Ophthalmol, Vienna, Austria.
   [Scholler, Andreas; Richter-Mueksch, Sibylla; Weingessel, Birgit; Vecsei-Marlovits, Pia-Veronika] Karl Landsteiner Inst Proc Optimizat & Qual Manag, Vienna, Austria.
C3 Hietzing Hospital
RP Vecsei-Marlovits, PV (通讯作者)，Hietzing Hosp, Dept Ophthalmol, Vienna, Austria.
EM veronika.vecsei-marlovits@wienkav.at
RI Weingessel, Birgit/AAM-6617-2021; Weingessel, Birgit/ABD-5201-2021
OI Weingessel, Birgit/0000-0002-1110-0432
FU Novartis Austria
FX Andreas Scholler and Sibylla Richter-Muksch didn't receive any
   unrestricted grants during the last 5 years. Birgit Weingessel and Pia
   Veronika Vecsei-Marlovits received unrestricted grants from Novartis
   Austria during the last 5 years.
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NR 14
TC 7
Z9 7
U1 0
U2 4
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0043-5325
EI 1613-7671
J9 WIEN KLIN WOCHENSCHR
JI Wien. Klin. Wochen.
PD JUN
PY 2014
VL 126
IS 11-12
BP 355
EP 359
DI 10.1007/s00508-014-0539-z
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA AK6IR
UT WOS:000338531800006
PM 24696051
DA 2022-11-30
ER

PT J
AU Klaassen, I
   Van Noorden, CJF
   Schlingemann, RO
AF Klaassen, Ingeborg
   Van Noorden, Cornelis J. F.
   Schlingemann, Reinier O.
TI Molecular basis of the inner blood-retinal barrier and its breakdown in
   diabetic macular edema and other pathological conditions
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Blood-retinal barrier; Capillary permeability; Retina; Diabetic
   retinopathy; Diabetic macular edema; Tight junctions; Transcytosis;
   Caveolae; Endothelium; Pericytes; Vascular endothelial growth factor
   A/antagonists & inhibitors
ID ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE-C; TIGHT JUNCTION PROTEINS;
   GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; EXPERIMENTAL AUTOIMMUNE
   ENCEPHALOMYELITIS; MESSENGER-RNA LEVELS; CELL-CELL JUNCTIONS; IN-VITRO
   MODEL; ANTIGEN PAL-E
AB Breakdown of the inner endothelial blood-retinal barrier (BRB), as occurs in diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, uveitis and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing loss of vision. The central mechanism of altered BRB function is a change in the permeability characteristics of retinal endothelial cells caused by elevated levels of growth factors, cytokines, advanced glycation end products, inflammation, hyperglycemia and loss of pericytes. Subsequently, paracellular but also transcellular transport across the retinal vascular wall increases via opening of endothelial intercellular junctions and qualitative and quantitative changes in endothelial caveolar transcellular transport, respectively. Functional changes in pericytes and astrocytes, as well as structural changes in the composition of the endothelial glycocalyx and the basal lamina around BRB endothelium further facilitate BRB leakage. As Starling's rules apply, active transcellular transport of plasma proteins by the BRB endothelial cells causing increased interstitial osmotic pressure is probably the main factor in the formation of macular edema. The understanding of the complex cellular and molecular processes involved in BRB leakage has grown rapidly in recent years. Although appropriate animal models for human conditions like diabetic macular edema are lacking, these insights have provided tools for rational design of drugs aimed at restoring the BRB as well as for design of effective transport of drugs across the BRB, to treat the chronic retinal diseases such as diabetic macular edema that affect the quality-of-life of millions of patients. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Klaassen, Ingeborg; Schlingemann, Reinier O.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Ocular Angiogenesis Grp, NL-1105 AZ Amsterdam, Netherlands.
   [Van Noorden, Cornelis J. F.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Ocular Angiogenesis Grp, NL-1105 AZ Amsterdam, Netherlands.
   [Schlingemann, Reinier O.] Netherlands Inst Neurosci, Amsterdam, Netherlands.
C3 University of Amsterdam; Academic Medical Center Amsterdam; University
   of Amsterdam; Academic Medical Center Amsterdam; Royal Netherlands
   Academy of Arts & Sciences; Netherlands Institute for Neuroscience
   (NIN-KNAW)
RP Schlingemann, RO (通讯作者)，Acad Med Ctr, Dept Ophthalmol, Med Retina Unit, Room A2-122,POB 22660, NL-1100 DD Amsterdam, Netherlands.
EM r.schlingemann@amc.uva.nl
RI Klaassen, Ingeborg/F-7333-2015
OI Klaassen, Ingeborg/0000-0003-1695-9403
FU Diabetes Fonds Nederland [1999.050]; Landelijke Stichting voor Blinden
   en Slechtzienden (LSBS); Stichting Blinden-Penning; Stichting Oogfonds
   Nederland; Vereniging Blindenbelangen Rotterdam; Stichting Blindenhulp;
   Prof. Hoppenbrouwers Fonds, Stichting Nederlands Oogheelkundig Onderzoek
   (SNOO)
FX We thank Kees Hoeben for his help with electron microscopy work and
   Monique Arendse for help with preparing the manuscript. This study was
   supported by grants of the Diabetes Fonds Nederland (Grant 1999.050) and
   by grants of the Landelijke Stichting voor Blinden en Slechtzienden
   (LSBS); Stichting Blinden-Penning; Stichting Oogfonds Nederland;
   Vereniging Blindenbelangen Rotterdam; Stichting Blindenhulp; Prof.
   Hoppenbrouwers Fonds, Stichting Nederlands Oogheelkundig Onderzoek
   (SNOO). Fig. 7 is reproduced with permission of the Informa Healthcare
   Publishing Group in respect of earlier publication in Current Eye
   Research.
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NR 434
TC 402
Z9 415
U1 7
U2 88
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAY
PY 2013
VL 34
BP 19
EP 48
DI 10.1016/j.preteyeres.2013.02.001
PG 30
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 141RT
UT WOS:000318744900002
PM 23416119
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Tran, K
   Mendel, TA
   Holbrook, KL
   Yates, PA
AF Tran, Kenneth
   Mendel, Thomas A.
   Holbrook, Kristina L.
   Yates, Paul A.
TI Construction of an Inexpensive, Hand-Held Fundus Camera through
   Modification of a Consumer "Point-and-Shoot" Camera
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID DIABETIC-RETINOPATHY; POLARIZED-LIGHT; SAFETY
AB PURPOSE. To construct a low-cost, easy-to-use, high-imagequality mydriatic fundus camera with "point-and-shoot" operation, and to evaluate the efficacy of this camera to accurately document retinal disease.
   METHODS. A prototype portable fundus camera was designed by interfacing a novel optical module with a Panasonic Lumix G2 consumer camera. Low-cost, commercially available optics were used to create even illumination of the fundus, providing a 508 retinal field of view. A comparative study assessing the image quality of the prototype camera against a traditional tabletop fundus camera was conducted under an Institutional Review Board (IRB)-approved study.
   RESULTS. A stand-alone, mydriatic camera prototype was successfully developed at a parts cost of less than $1000. The prototype camera was capable of operating in a point-and-shoot manner with automated image focusing and exposure, and the image quality of fundus photos was comparable to that of existing commercial cameras. Pathology related to both nonproliferative and proliferative diabetic retinopathy and age-related macular degeneration was easily identified from fundus images obtained from the low-cost camera.
   CONCLUSIONS. Early prototype development and clinical testing have shown that a consumer digital camera can be inexpensively modified to image the fundus with professional diagnostic quality. The combination of low cost, portability, point-and-shoot operation, and high image quality provides a foundational platform on which one can design an accessible fundus camera to screen for eye disease. (Invest Ophthalmol Vis Sci. 2012; 53: 7600-7607) DOI:10.1167/iovs.12-10449
C1 [Mendel, Thomas A.; Holbrook, Kristina L.; Yates, Paul A.] Univ Virginia, Dept Ophthalmol, Charlottesville, VA 22908 USA.
   [Tran, Kenneth; Yates, Paul A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
   [Mendel, Thomas A.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia
RP Yates, PA (通讯作者)，Univ Virginia, Dept Ophthalmol, POB 801375, Charlottesville, VA 22908 USA.
EM pyates@virginia.edu
FU UVa-Coulter Translational Partnership Grant [GF11938]; Ivy Foundation of
   Charlottesville Research Grant [DR-02314]; National Institutes of Health
   (NIH) [T32 GM08715, K08 GC11897]; NATIONAL EYE INSTITUTE [K08EY019533]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL
   SCIENCES [T32GM008715, T32GM007267] Funding Source: NIH RePORTER
FX Supported by the UVa-Coulter Translational Partnership Grant (GF11938),
   Ivy Foundation of Charlottesville Research Grant (DR-02314), and
   National Institutes of Health (NIH) Grants T32 GM08715 (TAM) and K08
   GC11897 (PAY).
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NR 24
TC 41
Z9 43
U1 1
U2 20
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2012
VL 53
IS 12
BP 7600
EP 7607
DI 10.1167/iovs.12-10449
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064EE
UT WOS:000313053500023
PM 23049089
OA Green Published
DA 2022-11-30
ER

PT J
AU Parravano, M
   Pilotto, E
   Musicco, I
   Varano, M
   Introini, U
   Staurenghi, G
   Menchini, U
   Virgili, G
AF Parravano, Mariacristina
   Pilotto, Elisabetta
   Musicco, Ilenia
   Varano, Monica
   Introini, Ugo
   Staurenghi, Giovanni
   Menchini, Ugo
   Virgili, Gianni
TI Reproducibility of fluorescein and indocyanine green angiographic
   assessment for RAP diagnosis: a multicenter study
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Fluorescein angiography; Indocyanine green angiography; RAP;
   Reproducibility; Retinal angiomatous proliferation
ID RETINAL ANGIOMATOUS PROLIFERATION; OCCULT CHOROIDAL NEOVASCULARIZATION;
   MACULAR DEGENERATION; ANASTOMOSES; VIDEOANGIOGRAPHY; DETACHMENTS;
   PREVALENCE; FEATURES
AB PURPOSE. To explore the interobserver agreement in the diagnosis of retinal angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green angiographies (ICGA) and to detect which morphologic features of the neovascular lesion are associated with RAP diagnosis.
   METHODS. In this cross-sectional study, consecutive patients with newly diagnosed neovascular age-related macular degeneration (AMD) evaluated in 8 retina centers were considered. The FA and ICGA were obtained in all centers according to a standard protocol, both performed either as a static or as a dynamic examination. All images were graded by 2 observers from different institutions.
   RESULTS. A total of 201 eyes with neovascular AMD of 155 consecutive patients (mean age 76 +/- 8 years) were considered. Overall RAP prevalence was 30% using FA and 26% using ICGA. Patients studied with dynamic angiography were twice as likely to be diagnosed with RAP as those using static angiography. Interobserver agreement for the overall detection of RAP was high using FA (kappa: 0.868; 95% confidence interval [CI]: 0.793-0.944) and very high using ICGA (kappa: 0.905; 95% CI 0.836-0.974). The agreement between the 2 observers tended to be higher for the truncated vessel than for the anastomosis in FA as well as in ICGA, but no comparison yielded statistical significance (p=0.258 and p=0.584, respectively).
   CONCLUSIONS. The interobserver agreement for RAP detection was very good both using FA and ICGA, but the overall detection of RAP was higher for dynamic strategy compared with static one.
C1 [Parravano, Mariacristina; Varano, Monica] GB Bietti Eye Fdn IRCCS, Rome, Italy.
   [Pilotto, Elisabetta] Univ Padua, Inst Ophthalmol, Padua, Italy.
   [Musicco, Ilenia] Eye Clin, Dept Surg Specialties Radiol & Med Legal Sci Bres, Brescia, Italy.
   [Introini, Ugo] Univ Vita Salute, San Raffaele Sci Inst, Dept Ophthalmol, Milan, Italy.
   [Staurenghi, Giovanni] Univ Milan, Dept Clin Sci Luigi Sacco, Sacco Hosp, Eye Clin, Milan, Italy.
   [Menchini, Ugo; Virgili, Gianni] Univ Florence, Dept Otoneuroophthalmol Sci, Florence, Italy.
C3 IRCCS - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in
   Oftalmologia; University of Padua; Vita-Salute San Raffaele University;
   IRCCS Ospedale San Raffaele; University of Milan; Luigi Sacco Hospital;
   University of Florence
RP Parravano, M (通讯作者)，Fdn GB Bietti IRCCS, Via Livenza 3, I-00198 Rome, Italy.
EM criparra@tin.it
RI Varano, Monica/K-8573-2016; Staurenghi, Giovanni/K-4388-2017; Virgili,
   Gianni/P-6607-2014
OI Staurenghi, Giovanni/0000-0002-2299-5251; Virgili,
   Gianni/0000-0002-9960-2989; Varano, Monica/0000-0002-6530-1563
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NR 20
TC 6
Z9 6
U1 0
U2 2
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-AUG
PY 2012
VL 22
IS 4
BP 598
EP 606
DI 10.5301/ejo.5000087
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 026HY
UT WOS:000310266900009
PM 22139618
DA 2022-11-30
ER

PT J
AU Bolz, M
   Michels, S
   Geitzenauer, W
   Prager, F
   Schmidt-Erfurth, U
AF Bolz, Matthias
   Michels, Stephan
   Geitzenauer, Wolfgang
   Prager, Franz
   Schmidt-Erfurth, Ursula
TI Effect of systemic bevacizumab therapy on retinal pigment epithelial
   detachment
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION SECONDARY;
   OPTICAL COHERENCE TOMOGRAPHY; METASTATIC COLORECTAL-CANCER; MACULAR
   DEGENERATION; MEMBRANES; FLUOROURACIL; LEUCOVORIN; EXPRESSION; INJECTION
AB Background: To evaluate the effect of systemic bevacizumab (Avastin (R)) therapy on pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) and to identify prognostic factors for PED regression and improvement in best corrected visual acuity (BCVA).
   Study design: Prospective uncontrolled pilot study.
   Methods: Nine patients ( nine eyes) received three systemic bevacizumab treatments at 2 week intervals and were examined at baseline, weeks 1, 2, 4, 6 and month 3 by using optical coherence tomography ( Stratus OCT (TM), Carl Zeiss (R) Meditec, Dublin, California, USA). Changes in maximum PED height and greatest linear diameter (GLD) were planimetrically analysed by using Adobe Photoshop CS and correlated with retinal morphological changes and changes in BCVA.
   Results: Systemic bevacizumab therapy was well tolerated. Mean maximum PED height decreased significantly by 21% as early as 1 week (-96 mu m (SD 48.8), p < 0.01). At 3 months follow-up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (-179 mu m (SD 178), p=0.02) and mean PED GLD by 24% (-714 mu m (SD 1010), p = 0.07). Mean BCVA improved significantly by week 2 (+8.7 letters (SD 5.7), p < 0.01) and at 3 months with 12.7 letters (SD 6.4) (p < 0.01).
   Conclusion: In the examined nine patients, systemic bevacizumab therapy showed evidence for an effect on PED secondary to neovascular AMD in terms of a decrease in lesion height and diameter. A high PED at baseline was found to be a negative predictive factor for visual outcome.
C1 Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Michels, S (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM michels@meduniwien.ac.at
RI Bolz, Matthias/HCI-0622-2022
OI Bolz, Matthias/0000-0001-8691-5276
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NR 24
TC 25
Z9 27
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUN
PY 2007
VL 91
IS 6
BP 785
EP 789
DI 10.1136/bjo.2006.102467
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 169BA
UT WOS:000246566500021
PM 17050580
OA Green Published
DA 2022-11-30
ER

PT J
AU Fisher, SA
   Rivera, A
   Fritsche, LG
   Babadjanova, G
   Petrov, S
   Weber, BHF
AF Fisher, Sheila A.
   Rivera, Andrea
   Fritsche, Lars G.
   Babadjanova, Gulja
   Petrov, Sergey
   Weber, Bernhard H. F.
TI Assessment of the contribution of CFH and chromosome 10q26 AMD
   susceptibility loci in a Russian population isolate
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   POLYMORPHISM; ASSOCIATION; PREVALENCE; LOC387715; JAPANESE; SMOKING;
   DISEASE
AB Background/aims: A strong association has been confirmed between age-related macular degeneration (AMD) and variants at two independent loci including Tyr402His in the complement factor H (CFH) on 1q32 and Ser69Ala at LOC387715, a hypothetical gene on chromosome 10q26. The contribution of both loci to AMD was investigated in an isolated north-west Russian population.
   Methods: Together with a PLEKHA1 variant at 10q26, the CFH Tyr402His and LOC387715 Ser69Ala polymorphisms were genotyped in 155 patients with AMD and 151 age-matched controls. chi(2) and Mantel Haenszel (M-H) score tests were used to test for association. Sex-adjusted ORs were calculated.
   Results: The frequency of the Tyr402His C allele was significantly higher in patients with AMD compared with controls (p(M-H) = 0.0035). The increased risk observed in patients homozygous for the C allele (ORHOM = 2.71, 95% CI 1.25 to 5.90) in this indigenous Russian population was considerably lower than that observed in previous western Caucasian populations. A significant increase in the frequency of the LOC387715 variant was observed in patients with late-stage AMD compared with controls (p(M-H) = 0.007), with a homozygous OR of 3.47 (95% CI 1.01 to 11.9), although this association was not seen with early-stage AMD.
   Conclusion: The CFH gene contributes to AMD in this Russian population, although the risk conferred is considerably lower in this population than that found in other Western populations. A contribution of LOC387715 to disease in this population is also likely to be of weak effect.
C1 Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   Kings Coll London, Dept Med & Mol Genet, Guys Kings & St Thomas Sch Med, London WC2R 2LS, England.
   Russian State Med Univ, Inst Pulmonol, Moscow 117437, Russia.
   Inst Ophthalmol Dis, Moscow, Russia.
C3 University of Regensburg; University of London; King's College London;
   Pirogov Russian National Research Medical University
RP Weber, BHF (通讯作者)，Univ Regensburg, Inst Human Genet, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany.
EM bweb@klinik.uniregensburg.de
RI Fritsche, Lars G/AAF-9387-2019
OI Fritsche, Lars G/0000-0002-2110-1690; Weber, Bernhard
   H.F./0000-0002-8808-7723
CR Barrett JC, 2005, BIOINFORMATICS, V21, P263, DOI 10.1093/bioinformatics/bth457
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NR 19
TC 31
Z9 31
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAY
PY 2007
VL 91
IS 5
BP 576
EP 578
DI 10.1136/bjo.2006.105577
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 158XW
UT WOS:000245829900007
PM 17050575
OA Green Published
DA 2022-11-30
ER

PT J
AU Saunders, RE
   Garrido, CA
   Fremeaux-Bacchi, V
   de Jorge, EG
   Goodship, THJ
   Trascasa, ML
   Noris, M
   Castro, IMP
   Remuzzi, G
   de Cordoba, SR
   Corral, PS
   Skerka, C
   Zipfel, PF
   Perkins, SJ
AF Saunders, Rebecca E.
   Abarrategui Garrido, Cynthia
   Fremeaux-Bacchi, Veronique
   Goicoechea de Jorge, Elena
   Goodship, Timothy H. J.
   Lopez Trascasa, Margarita
   Noris, Marina
   Ponce Castro, Isabel Maria
   Remuzzi, Giuseppe
   Rodriguez de Cordoba, Santiago
   Corral, Pilar Sanchez
   Skerka, Christine
   Zipfel, Peter F.
   Perkins, Stephen J.
TI The interactive factor H-atyplical hemolytic uremic syndrome mutation
   database and website: Update and integration of membrane cofactor
   protein and factor I mutations with structural models
SO HUMAN MUTATION
LA English
DT Article
DE factor H; CFH; hemolytic uremic syndrome; Factor 1; IF; membrane
   cofactor protein; MCP; complement; mutation database; immunodeficiency
   diseases
ID COMPLEMENT FACTOR-H; CRYSTAL-STRUCTURE; X-RAY; NEUTRON-SCATTERING;
   MOLECULAR-BASIS; BINDING-SITES; ANALYTICAL ULTRACENTRIFUGATION; DOMAIN;
   REVEALS; CD46
AB Atypical hemolytic uremic syndrome (aHUS) is a disease of hemolytic anemia, thrombocytopenia, and renal failure associated with defective alternative pathway (AP) complement control. Previously, we presented a database (www.FH-HUS.org) focusing on aHUS mutations in the Factor H gene (CFH). Here, new aHUS mutations are reported for the complement regulatory proteins Factor H (FH), Factor I (FI), and membrane cofactor protein (MCP). Additional mutations or polymorphisms within CFH have been associated with membranoproliferative glomerulonephritis (MPGN) and age,related macular degeneration (AMD). Accordingly, the database now includes substitutions that predispose to aHUS, MPGN, and AMD. For this, structural models for the domains in MCP and FI were developed using homology modeling. With this new database, patients with mutations in more than one gene can be displayed and interpreted in a coherent manner. The database also includes SNP polymorphisms in CFH, MCP, and IF There are now a total of 167 genetic alterations, including 100 in CFH, 43 in MCP, and 24 in IF. The mutations characterize clinical outcomes that vary from several AMD-associated polymorphisms to those associated with aHUS, MPGN, or FI deficiency. A consensus short complement regulator (SCR) domain structure facilitated the interpretations of aHUS mutations. Specific locations within this consensus domain often correlate with the occurrence of clinical phenotypes. The AMD Tyr402His polymorphism is structurally located at a hotspot for several aHUS mutations. The database emphasizes the causative role of the alternative pathway of complement in disease and provides a repository of knowledge to assist future diagnosis and novel therapeutic approaches.
C1 UCL, Dept Biochem & Mol Biol, Royal Free & Univ Coll, Sch Med, London WC1E 6BT, England.
   Hosp Univ La Paz, Unidad Invest, Madrid, Spain.
   Hop Europeen Georges Pompidou, AP HP, Serv Immunol Biol, Paris, France.
   CSIC, Dept Inmunol, Ctr Invest Biol, Madrid, Spain.
   Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   Hosp Univ La Paz, Unidad Inmunol, Madrid, Spain.
   Mario Negri Inst Pharmacol Res, I-24100 Bergamo, BG, Italy.
   Hans Knoll Inst Nat Prod Res, Dept Infect Biol, Jena, Germany.
C3 University of London; University College London; UCL Medical School;
   Hospital Universitario La Paz; Assistance Publique Hopitaux Paris
   (APHP); Hopital Universitaire Europeen Georges-Pompidou - APHP;
   UDICE-French Research Universities; Universite Paris Cite; Consejo
   Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de
   Investigaciones Biologicas (CIB); Newcastle University - UK; Hospital
   Universitario La Paz; Istituto di Ricerche Farmacologiche Mario Negri
   IRCCS; Hans Knoll Institute (HKI)
RP Perkins, SJ (通讯作者)，UCL, Dept Biochem & Mol Biol, Royal Free & Univ Coll, Sch Med, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM s.perkins@medsch.ucl.ac.uk
RI de Jorge, Elena Goicoechea/L-4580-2016; de Cordoba, Santiago
   Rodriguez/K-6727-2014; NORIS, MARINA/ABG-2219-2020; López-Trascasa,
   Margarita/L-2699-2014; Remuzzi, Giuseppe/V-9766-2017
OI de Jorge, Elena Goicoechea/0000-0002-4978-2483; de Cordoba, Santiago
   Rodriguez/0000-0001-6401-1874; NORIS, MARINA/0000-0001-7651-5033;
   López-Trascasa, Margarita/0000-0001-8594-282X; Remuzzi,
   Giuseppe/0000-0002-6194-3446
FU Wellcome Trust Funding Source: Medline
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NR 46
TC 132
Z9 138
U1 0
U2 10
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 MAR
PY 2007
VL 28
IS 3
BP 222
EP 234
DI 10.1002/humu.20435
PG 13
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 134QT
UT WOS:000244099500002
PM 17089378
OA Bronze
DA 2022-11-30
ER

PT J
AU Chu, RY
   Zheng, XF
   Chen, DH
   Hu, DN
AF Chu, Rengyuan
   Zheng, Xiaofen
   Chen, Donghong
   Hu, Dan-Ning
TI Blue light irradiation inhibits the production of HGF by human retinal
   pigment epithelium cells in vitro
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; INDUCED DAMAGE; PROLIFERATIVE
   VITREORETINOPATHY; UVEAL MELANOCYTES; FACTOR RECEPTOR; VISIBLE-LIGHT;
   RPE CELLS; SENSITIVITY; APOPTOSIS; ISCHEMIA
AB Blue visible light damage to retinal pigment epithelial cells occurs through a photooxidative mechanism and the resultant damage is hypothesized to induce or exacerbate age-related macular degeneration. The purpose of the present study was to identify changes in the cell growth and the expression of hepatocyte growth factor (HGF) in cultured human retinal pigment epithelium (RPE) cells as a result of both blue and red light irradiation. HGF is a growth factor and neurotrophic factor that stimulates growth of various ocular cells and promotes the survival of RPE and retinal neurons. Early passages of human RPE cells were exposed to blue light (460 nm) and red light (640 nm). Nonirradiated cells were used as controls. After 24 and 48 h, conditioned medium was collected and the amount of HGF was measured by ELISA. Cells were detached from the well and counted. Cell viability was evaluated by trypan-blue exclusion study. Blue light at dosage of 63 J/cm(2) significantly inhibited the growth of RPE cells without affecting of cell viability. Amounts of HGF in the culture medium were significantly inhibited by blue-light irradiation at the dosage from 32 to 63 J/cm(2). Red light at a dose of 174 J/cm(2) causes a nonsignificant inhibition of growth of RPE cells and a slight decrease of secretion of HGF. As HGF promotes survival of RPE cells and retinal neurons, the inhibition of production of HGF by visible light, especially by blue light, may enhance the phototoxic effects of visible light on the RPE and retinal neurons.
C1 New York Eye & Ear Infirm, Tissue Culture Ctr, New York Med Coll, New York, NY USA.
   Fudan Univ, Dept Ophthalmol, Eye Ear Nose & Throat Hosp, Shanghai 200433, Peoples R China.
C3 New York Eye & Ear Infirmary of Mount Sinai; New York Medical College;
   Fudan University
RP Hu, DN (通讯作者)，New York Eye & Ear Infirm, Tissue Culture Ctr, New York Med Coll, New York, NY USA.
EM hu2095@yahoo.com
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NR 47
TC 11
Z9 13
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD SEP-OCT
PY 2006
VL 82
IS 5
BP 1247
EP 1250
DI 10.1562/2006-04-19-RA-880
PG 4
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 097DK
UT WOS:000241426600012
PM 16740060
DA 2022-11-30
ER

PT J
AU Jones, ST
   Aryana, KJ
   Losso, JN
AF Jones, ST
   Aryana, KJ
   Losso, JN
TI Storage stability of lutein during ripening of cheddar cheese
SO JOURNAL OF DAIRY SCIENCE
LA English
DT Article
DE lutein; fermented; dairy; age-related macular degeneration
ID MACULAR DEGENERATION; CAROTENOIDS; ZEAXANTHIN; BITTERNESS; FOOD; PH
AB Lutein (3,3'-dihydroxy-alpha-carotene) has been identified as a dietary factor that can delay the onset of age-related macular degeneration (AMD). However, available food sources of lutein contain only modest amounts of the carotenoid. Food fortification with lutein extract has been identified as a low-budget approach to prevent the onset or progression of AMD. The objectives of this study were to 1) incorporate various amounts of lutein into Cheddar cheese; 2) examine the color, pH, microbiological, and sensory characteristics of the Cheddar cheese during storage; and 3) analyze the stability of lutein during the cheese maturation process. Lutein extracted from corn was added to Cheddar cheese in quantities of 1, 3, and 6 mg per serving size. Measurements of the lutein stability were carried out by HPLC using a YMC C-30 carotenoid column. Microbiological analyses of cheese samples included aerobic plate count, coliform, and yeast/mold counts. The color attributes a* and b* were significantly different between the treatment and control groups; however, no significant difference was observed in L* value and pH. Significant differences among 1, 3, and 6 mg lutein-enriched cheeses were observed in the aerobic plate count and yeast/mold compared with the control. Cheese samples contained no detectable levels of coliforms (< 10 cfu/g). The HPLC data showed quantitative recovery of lutein during the storage period, and no lutein degradation products were identified. These results indicate that lutein, a functional additive with purported ability to prevent or reduce the onset of AMD, can be incorporated into cheese adding value to this product.
C1 Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA.
   Louisiana State Univ, Ctr Agr, Dept Dairy Sci, Baton Rouge, LA 70803 USA.
C3 Louisiana State University System; Louisiana State University; Louisiana
   State University System; Louisiana State University
RP Losso, JN (通讯作者)，Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA.
EM jlosso@agctr.lsu.edu
CR Banavara DS, 2003, J DAIRY SCI, V86, P3866, DOI 10.3168/jds.S0022-0302(03)73994-0
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NR 40
TC 19
Z9 21
U1 0
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0022-0302
EI 1525-3198
J9 J DAIRY SCI
JI J. Dairy Sci.
PD MAY
PY 2005
VL 88
IS 5
BP 1661
EP 1670
DI 10.3168/jds.S0022-0302(05)72838-1
PG 10
WC Agriculture, Dairy & Animal Science; Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Food Science & Technology
GA 916BK
UT WOS:000228358800007
PM 15829657
OA Bronze
DA 2022-11-30
ER

PT J
AU Bamashmus, MA
   Matlhaga, B
   Dutton, GN
AF Bamashmus, MA
   Matlhaga, B
   Dutton, GN
TI Causes of blindness and visual impairment in the West of Scotland
SO EYE
LA English
DT Article
DE registration; blind; partial sight; age-related macular degeneration
AB Aims To determine the overall reported incidence and causes of registrable blindness and visual impairment in the West of Scotland and any trends that have occurred in the previous 16 years since data from the same area were published.
   Methods Data for analysis were obtained from BP1 registration forms returned to the Resource Centre for the Blind serving the Strathclyde region in the West of Scotland between 1 April 1996 and 31 March 1997.
   Results A total of 1595 visually handicapped people were registered during the study year. Of these, 99 forms ( 6.2%) were excluded from further analysis because of insufficient information. The remaining 1496 completed BP1 Forms were in respect of 530 males and 966 females. Of these, 253 males and 450 females were legally blind ( total 703 or 47.0%) and 277 males and 516 females were partially sighted ( total 793 or 53.0%). The five leading causes of blindness, in decreasing frequency, were age-related macular degeneration (ARMD), glaucoma, diabetic retinopathy, myopic degeneration, and optic atrophy. ARMD and diabetic retinopathy were the most common causes of blindness in those over 65 years and persons of working age, respectively.
   Conclusions In adults, cataract is no longer a significant cause of registrable visual impairment. The proportions of registrations owing to glaucoma, diabetic retinopathy, and myopia have not significantly changed since 1983 and the proportion owing to macular degeneration has increased. In children, congenital glaucoma, cataract, and corneal infection were no longer causes of registration, but impairment of vision caused by brain damage is now a significant contributor.
C1 Gartnavel Royal Hosp, Tennent Inst Ophthalmol, Glasgow G12 0YN, Lanark, Scotland.
   Univ Sci & Technol, Ibn Al Haitham Eye Clin, Sanaa, Yemen.
   Gaberone Private Hosp, Broadhurst, Botswana.
C3 Gartnavel Royal Hospital
RP Dutton, GN (通讯作者)，Gartnavel Royal Hosp, Tennent Inst Ophthalmol, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
EM Sheena.MacKay.WG@NorthGlasgow.Scot.NHS.UK
OI BAMASHMUS, MAHFOUTH/0000-0002-2219-5983
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NR 12
TC 55
Z9 56
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAR
PY 2004
VL 18
IS 3
BP 257
EP 261
DI 10.1038/sj.eye.6700606
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 801FD
UT WOS:000220080900006
PM 15004574
OA Bronze
DA 2022-11-30
ER

PT J
AU Ribeiro, M
   Pasini, S
   Baratta, RO
   Del Buono, BJ
   Schlumpf, E
   Calkins, DJ
AF Ribeiro, Marcio
   Pasini, Silvia
   Baratta, Robert O.
   Del Buono, Brian J.
   Schlumpf, Eric
   Calkins, David J.
TI Collagen Mimetic Peptides Promote Adherence and Migration of ARPE-19
   Cells While Reducing Inflammatory and Oxidative Stress
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE ocular collagen; collagen mimetic peptides; retinal pigment epithelium;
   macular degeneration; extracellular matrix; ocular inflammation; Bruch's
   membrane; cytokines; oxidative stress
ID PIGMENT EPITHELIAL-CELLS; MATRIX-METALLOPROTEINASE ACTIVITY; MACULAR
   DEGENERATION; GENE-EXPRESSION; BRUCHS; RPE; PHAGOCYTOSIS; ACTIVATION;
   IL-8
AB Epithelial cells of multiple types produce and interact with the extracellular matrix to maintain structural integrity and promote healthy function within diverse endogenous tissues. Collagen is a critical component of the matrix, and challenges to collagen's stability in aging, disease, and injury influence survival of adherent epithelial cells. The retinal pigment epithelium (RPE) is important for maintaining proper function of the light-sensitive photoreceptors in the neural retina, in part through synergy with the collagen-rich Bruch's membrane that promotes RPE adherence. Degradation of Bruch's is associated with RPE degeneration, which is implicated early in age-related macular degeneration, a leading cause of irreversible vision loss worldwide. Collagen mimetic peptides (CMPs) effectively repair damage to collagen helices, which are present in all collagens. Our previous work indicates that in doing so, CMPs promote survival and integrity of affected cells and tissues in models of ocular injury and disease, including wounding of corneal epithelial cells. Here, we show that CMPs increase adherence and migration of the ARPE-19 line of human RPE cells challenged by digestion of their collagen substrate. Application of CMPs also reduced both ARPE-19 secretion of pro-inflammatory cytokines (interleukins 6 and 8) and production of reactive oxygen species. Taken together, these results suggest that repairing collagen damaged by aging or other pathogenic processes in the posterior eye could improve RPE adherence and survival and, in doing so, reduce the inflammatory and oxidative stress that perpetuates the cycle of destruction at the root of age-related diseases of the outer retina.
C1 [Ribeiro, Marcio; Pasini, Silvia; Calkins, David J.] Vanderbilt Univ, Dept Ophthalmol & Visual Sci, Vanderbilt Eye Inst, Med Ctr, AA7103 MCN,1161 21st Ave S, Nashville, TN 37232 USA.
   [Baratta, Robert O.; Del Buono, Brian J.; Schlumpf, Eric] Stuart Therapeut Inc, 411 SE Osceola St,Suite 203, Stuart, FL 34994 USA.
C3 Vanderbilt University
RP Calkins, DJ (通讯作者)，Vanderbilt Univ, Dept Ophthalmol & Visual Sci, Vanderbilt Eye Inst, Med Ctr, AA7103 MCN,1161 21st Ave S, Nashville, TN 37232 USA.
EM marcio.ribeiro@vumc.org; silvia.pasini@vumc.org;
   bob@stuarttherapeutics.com; brian@stuarttherapeutics.com;
   eric@stuarttherapeutics.com; david.j.calkins@vumc.org
OI Calkins, David/0000-0002-8475-9959
FU Stuart Therapeutics, Inc.
FX Support provided by an unrestricted endowment (D.J.C) and internal
   funding from Stuart Therapeutics, Inc. (R.O.B., B.J.D.B., E.S.).
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NR 43
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUL
PY 2022
VL 23
IS 13
AR 7004
DI 10.3390/ijms23137004
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 2S9XN
UT WOS:000822138200001
PM 35806007
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Herranz-Cabarcos, A
   Vega-Lopez, Z
   Salas-Fandos, O
   Quiroz-Quiroga, MJ
   Burgos-Fernandez, P
   Marti-Rodrigo, P
   Castilla-Marti, M
   Poposki, V
   Martinez-Palmer, AR
AF Herranz-Cabarcos, A.
   Vega-Lopez, Z.
   Salas-Fandos, O.
   Quiroz-Quiroga, M. J.
   Burgos-Fernandez, P.
   Marti-Rodrigo, P.
   Castilla-Marti, M.
   Poposki, V
   Martinez-Palmer, A. R.
TI Macular optical coherence tomography for screening of pathology prior to
   cataract surgery: An approach based on tele-evaluation
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
AB Background To assess the benefit of macular spectral-domain optical coherence tomography (SD-OCT) as a part of the routinary preoperative study of patients undergoing cataract surgery. Methods A prospective single-center study study was performed. Consecutive patients with normal biomicroscopic funduscopy, moderate cataract and no history of ophthalmological pathologies were enrolled. All patients underwent macular SD-OCT. The obtained images were analysed by a general ophthalmologist and two retina specialists. Incidence of macular pathology and its relation to age and comorbidities were assessed. Results Eight-hundred and thirty-six eyes of 419 patients were enrolled in this study. All images were analysed telematically by a general ophthalmologist. Forty-nine eyes were excluded due to insufficient quality of the obtained images. Abnormal images were observed in 156 eyes (18.6%), including age-related macular degeneration in 68 (8.2%), epiretinal membrane (ERM) in 67 (8.0%), cystoid macular edema in 3 eyes (0.4%), among others. Diagnostics with severe impact on patient visual prognosis were observed in 16 eyes (3.82%) from 12 patients. The relationship between incidence of macular pathologies and age or comorbidities was not statistically significant. To assess accuracy of the first observer, images were subsequently analysed by two retinologists. The kappa index of concordance was 0.80 and 0.85. Conclusions Implementing a systematic macular SD-OCT as a preoperative test prior to cataract surgery would improve quality of postoperative visual prognosis information. A general ophthalmologist would be suitable to screen for pathology through macular OCT images.
C1 [Herranz-Cabarcos, A.] Complex Hosp Moises Broggi, Vallirana St 28 1-2, Barcelona, Spain.
   [Vega-Lopez, Z.; Salas-Fandos, O.; Quiroz-Quiroga, M. J.; Burgos-Fernandez, P.; Marti-Rodrigo, P.; Castilla-Marti, M.; Poposki, V; Martinez-Palmer, A. R.] Hosp Esperanca Parc Salut Mar, Barcelona, Spain.
RP Herranz-Cabarcos, A (通讯作者)，Complex Hosp Moises Broggi, Vallirana St 28 1-2, Barcelona, Spain.
EM alejandra.herranz.cabarcos@gmail.com
RI Herranz-Cabarcos, Alejandra/AFV-2795-2022
OI Quiroz Quiroga, Maria Jesus/0000-0001-8336-0607; Herranz Cabarcos,
   Alejandra/0000-0002-9407-454X
CR Abdelmassih Y, 2018, J CATARACT REFR SURG, V44, P610, DOI 10.1016/j.jcrs.2018.02.020
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   Gibbons A, 2016, CLIN OPHTHALMOL, V10, P1965, DOI 10.2147/OPTH.S114890
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   Meuer SM, 2015, OPHTHALMOLOGY, V122, P787, DOI 10.1016/j.ophtha.2014.10.014
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   Saleem SM, 2020, AM J OPHTHALMOL, V216, P237, DOI 10.1016/j.ajo.2020.04.029
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   Zafar S, 2017, J CATARACT REFR SURG, V43, P324, DOI 10.1016/j.jcrs.2016.12.022
NR 15
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 NOV
PY 2022
VL 32
IS 6
BP 3433
EP 3437
AR 11206721221080818
DI 10.1177/11206721221080818
EA FEB 2022
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4Z0VS
UT WOS:000762786000001
PM 35187961
DA 2022-11-30
ER

PT J
AU Hamid, MA
   Moustafa, MT
   Nashine, S
   Costa, RD
   Schneider, K
   Atilano, SR
   Kuppermann, BD
   Kenney, MC
AF Hamid, Mohamed A.
   Moustafa, M. Tarek
   Nashine, Sonali
   Costa, Rodrigo Donato
   Schneider, Kevin
   Atilano, Shari R.
   Kuppermann, Baruch D.
   Kenney, M. Cristina
TI Anti-VEGF Drugs Influence Epigenetic Regulation and AMD-Specific
   Molecular Markers in ARPE-19 Cells
SO CELLS
LA English
DT Article
DE AMD; age-related macular degeneration; trichostatin A (TSA); HDAC;
   histone deacetylase; vascular endothelial growth factor (VEGF)
AB Our study assesses the effects of anti-VEGF (Vascular Endothelial Growth Factor) drugs and Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) activity, on cultured ARPE-19 (Adult Retinal Pigment Epithelial-19) cells that are immortalized human retinal pigment epithelial cells. ARPE-19 cells were treated with the following anti-VEGF drugs: aflibercept, ranibizumab, or bevacizumab at 1x and 2x concentrations of the clinical intravitreal dose (12.5 mu L/mL and 25 mu L/mL, respectively) and analyzed for transcription profiles of genes associated with the pathogenesis age-related macular degeneration (AMD). HDAC activity was measured using the Fluorometric Histone Deacetylase assay. TSA downregulated HIF-1 alpha and IL-1 beta genes, and upregulated BCL2L13, CASPASE-9, and IL-18 genes. TSA alone or bevacizumab plus TSA showed a significant reduction of HDAC activity compared to untreated ARPE-19 cells. Bevacizumab alone did not significantly alter HDAC activity, but increased gene expression of SOD2, BCL2L13, CASPASE-3, and IL-18 and caused downregulation of HIF-1 alpha and IL-18. Combination of bevacizumab plus TSA increased gene expression of SOD2, HIF-1 alpha, GPX3A, BCL2L13, and CASPASE-3, and reduced CASPASE-9 and IL-beta. In conclusion, we demonstrated that anti-VEGF drugs can: (1) alter expression of genes involved in oxidative stress (GPX3A and SOD2), inflammation (IL-18 and IL-1 beta) and apoptosis (BCL2L13, CASPASE-3, and CASPASE-9), and (2) TSA-induced deacetylation altered transcription for angiogenesis (HIF-1 alpha), apoptosis, and inflammation genes.
C1 [Hamid, Mohamed A.; Moustafa, M. Tarek; Nashine, Sonali; Costa, Rodrigo Donato; Schneider, Kevin; Atilano, Shari R.; Kuppermann, Baruch D.; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
   [Hamid, Mohamed A.; Moustafa, M. Tarek] Menia Univ, Dept Ophthalmol, Fac Med, Al Minya 61111, Egypt.
   [Costa, Rodrigo Donato] Inst Donato Oftalmol, BR-37701528 Pocos De Caldas, MG, Brazil.
   [Kuppermann, Baruch D.] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA.
   [Kenney, M. Cristina] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine;
   Egyptian Knowledge Bank (EKB); Minia University; University of
   California System; University of California Irvine; University of
   California System; University of California Irvine
RP Kenney, MC (通讯作者)，Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.; Kenney, MC (通讯作者)，Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
EM drmohamedhamid83@mu.edu.eg; mohamedtarek@mu.edu.eg; snashine@uci.edu;
   rodrigodonato@yahoo.com.br; kschneid@hs.uci.edu; satilano@hs.uci.edu;
   bdkupper@uci.edu; mkenney@hs.uci.edu
RI Hamid, Mohamed/GRO-7342-2022
OI Moustafa, M. Tarek/0000-0003-4545-6012; Donato Costa,
   Rodrigo/0000-0002-2064-8539; Atilano, Shari/0000-0002-7729-7864; Hamid,
   Mohamed/0000-0003-2494-4578
FU Discovery Eye Foundation; Polly and Michael Smith Foundation; Iris and
   B. Gerald Cantor Foundation; Beckman Initiative for Macular Research;
   Max Factor Family Foundation; Guenther Foundation; Research to Prevent
   Blindness, Inc.; Institute for Clinical and Translational Science at
   University of California, Irvine [ICTS (ULI TR001414/TR/NCATS)]
FX This research was funded by Discovery Eye Foundation, Polly and Michael
   Smith Foundation, Iris and B. Gerald Cantor Foundation, Beckman
   Initiative for Macular Research, Max Factor Family Foundation, and
   Guenther Foundation. This study was also supported in part by an
   unrestricted grant from Research to Prevent Blindness, Inc. The authors
   acknowledge the support of the Institute for Clinical and Translational
   Science grant number: ICTS (ULI TR001414/TR/NCATS) at University of
   California, Irvine.
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NR 87
TC 3
Z9 3
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD APR
PY 2021
VL 10
IS 4
AR 878
DI 10.3390/cells10040878
PG 18
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA RR1OK
UT WOS:000642875900001
PM 33921543
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kataoka, K
   Horiguchi, E
   Kawano, K
   Ushida, H
   Nakano, Y
   Ito, Y
   Terasaki, H
AF Kataoka, Keiko
   Horiguchi, Etsuyo
   Kawano, Kenichi
   Ushida, Hiroaki
   Nakano, Yuyako
   Ito, Yasuki
   Terasaki, Hiroko
TI Three cases of brolucizumab-associated retinal vasculitis treated with
   systemic and local steroid therapy
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Brolucizumab; Retinal vasculitis; Retinal vascular occlusion;
   Intraocular inflammation; Age-related macular degeneration
AB Purpose To describe three Japanese cases of retinal vasculitis that occurred following intravitreal brolucizumab injections and the systemic and local steroid treatment administered. Cases Three patients developed intraocular inflammation (IOI) and retinal vasculitis following the first injection of brolucizumab for age-related macular degeneration. For two eyes, monthly aflibercept injections did not control exudation, and therapy was changed to brolucizumab; one eye was treatment-naive. All three patients noticed blurry vision and floaters 11-18 days after brolucizumab injections, and the treated eyes exhibited anterior chamber cells, fine keratic precipitates, vitreous cells, and vitreous haze. Ultra-widefield color images of the fundus showed retinal hemorrhage in the peripheral retina and, in two cases vascular sheathing. Ultra-widefield fluorescein angiography (FA) showed segmental vascular leakage in all eyes and leakage from the optic disc in two eyes. Vascular filling defects were noted in the peripheral retinae of two eyes. Brolucizumab-associated retinal vasculitis was diagnosed, and treated with 30 mg/day of oral prednisolone, subtenon triamcinolone acetonide injection (20 mg/0.5 ml), and 0.1% betamethasone sodium phosphate solution. After 1 week, color fundus images and FA showed improvements in vascular sheathing, leakage from retinal vessels, and optic disc leakage, but the vascular filling defects remained. Visual acuity was restored in all three eyes 6 weeks after the onset. Conclusion Brolucizumab-associated IOI, including retinal vasculitis and retinal occlusion, is a rare but important adverse event that can cause severe vision loss. Prompt diagnosis with FA and treatment with systemic or local steroids should be considered.
C1 [Kataoka, Keiko; Horiguchi, Etsuyo; Ushida, Hiroaki; Nakano, Yuyako; Ito, Yasuki; Terasaki, Hiroko] Nagoya Univ, Grad Sch Med, Dept Ophthalmol, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan.
   [Kawano, Kenichi] Yokkaichi Municipal Hosp, Dept Ophthalmol, Yokaichi, Mie, Japan.
C3 Nagoya University
RP Kataoka, K (通讯作者)，Nagoya Univ, Grad Sch Med, Dept Ophthalmol, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan.
EM kkeiko@med.nagoya-u.ac.jp
CR Baumal CR, 2020, OPHTHALMOLOGY, V127, P1345, DOI 10.1016/j.ophtha.2020.04.017
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NR 14
TC 11
Z9 11
U1 0
U2 1
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAR
PY 2021
VL 65
IS 2
BP 199
EP 207
DI 10.1007/s10384-021-00818-8
EA FEB 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA QZ0AH
UT WOS:000614709300002
PM 33543352
DA 2022-11-30
ER

PT J
AU Foreman, J
   Keel, S
   McGuinness, MB
   Crowston, JG
   Taylor, HR
   Dirani, M
AF Foreman, Joshua
   Keel, Stuart
   McGuinness, Myra B.
   Crowston, Jonathan G.
   Taylor, Hugh R.
   Dirani, Mohamed
TI Prevalence and associations of non-retinopathy ocular conditions among
   older Australians with self-reported diabetes: The National Eye Health
   Survey
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE retinopathy; diabetes; prevalence; public health; national survey;
   cataract
ID AGE-RELATED MACULOPATHY; RETINAL VEIN OCCLUSION; OPEN-ANGLE GLAUCOMA;
   BLUE MOUNTAINS EYE; MAJOR RISK-FACTORS; EPIRETINAL MEMBRANES; INDIGENOUS
   AUSTRALIANS; INTRAOCULAR-PRESSURE; GLOBAL PREVALENCE; POPULATION
AB AIM: To determine the prevalence and associations of non-retinopathy ocular conditions among older Australian adults with diabetes.
   METHODS: Multistage random-cluster sampling was used to select 3098 non-indigenous Australians aged 50y or older (46.4% male) and 1738 indigenous Australians aged 40y or older (41.1% male) from all levels of geographic remoteness in Australia. Participants underwent a standardised questionnaire to ascertain diabetes history, and a clinical examination to identify eye disease. We determined the prevalence of uncorrected refractive error, visually significant cataract, cataract surgery, age-related macular degeneration, glaucoma, ocular hypertension, retinal vein occlusion and epiretinal membrane among those with and without self-reported diabetes.
   RESULTS: Participants with self-reported diabetes had a higher prevalence of cataract surgery than those without diabetes (28.8% vs 16.9%, OR 1.78, 95%CI: 1.35-2.34 among non-indigenous Australians, and 11.3% vs 5.2%, OR 1.62, 95%CI: 1.22-2.14 among indigenous Australians). Diabetic retinopathy (DR) increased the odds of cataract surgery among self-reported diabetic indigenous and non-indigenous Australians (OR 1.89, P=0.004 and OR 2.33, P<0.001 respectively). Having diabetes for >= 20y and having vision-threatening DR increased the odds of cataract surgery among indigenous Australians with diabetes (OR 3.73, P=0.001 and 7.58, P<0.001, respectively).
   CONCLUSION: Most non-retinopathy ocular conditions are not associated with self-reported diabetes. However, to account for Australia's worsening diabetes epidemic, interventions to reduce the impact of diabetes-related
C1 [Foreman, Joshua; Keel, Stuart; McGuinness, Myra B.; Crowston, Jonathan G.; Dirani, Mohamed] Royal Victorian Eye & Far Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
   [Foreman, Joshua; Keel, Stuart; McGuinness, Myra B.; Crowston, Jonathan G.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic 3010, Australia.
   [Taylor, Hugh R.] Univ Melbourne, Indigenous Eye Hlth Unit, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
   [Dirani, Mohamed] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore.
C3 Centre for Eye Research Australia; University of Melbourne; University
   of Melbourne; National University of Singapore; Singapore National Eye
   Center
RP Foreman, J (通讯作者)，Univ Melbourne, Dept Ophthalmol, Level 7,32 Gisborne St, Melbourne, Vic 3002, Australia.
EM foremanj@unimelb.edu.au
RI McGuinness, Myra/G-4900-2017
OI McGuinness, Myra/0000-0002-5422-040X
FU Department of Health of the Australian Government; Novartis Australia;
   Peggy and Leslie Cranbourne Foundation; NHMRC [1090466]; Australian
   Postgraduate Award scholarship
FX Supported by Department of Health of the Australian Government, Novartis
   Australia and the Peggy and Leslie Cranbourne Foundation. In-kind
   support from our industry and sector partners, OPSM, Carl Zeiss, Designs
   for Vision, the Royal Flying Doctor Service, Optometry Australia and the
   Brien Holden Vision Institute. The Centre for Eye Research Australia
   receives Operational Infrastructure Support from the Victorian
   Government. The Principal Investigator, Dr Mohamed Dirani, is supported
   by an NHMRC Career Development Fellowship (No.1090466). The PhD student,
   Joshua Foreman is supported by an Australian Postgraduate Award
   scholarship.
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PU IJO PRESS
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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 OCT 18
PY 2020
VL 13
IS 10
BP 1642
EP 1651
DI 10.18240/ijo.2020.10.20
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA NX2EZ
UT WOS:000575529300020
PM 33078117
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Boutzen, J
   Valet, M
   Alviset, A
   Fradot, V
   Rousseau, L
   Francais, O
   Picaud, S
   Lissorgues, G
AF Boutzen, Jocelyn
   Valet, Manon
   Alviset, Agathe
   Fradot, Valerie
   Rousseau, Lionel
   Francais, Olivier
   Picaud, Serge
   Lissorgues, Gaelle
TI Impedance spectroscopy study of the retinal pigment epithelium:
   Application to the monitoring of blue light exposure effect on
   A2E-loaded in-vitro cell cultures
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Impedance spectroscopy; Retinal pigment epithelium; Constant phase
   element; Blue light; A2E
ID LIPOFUSCIN ACCUMULATION; MACULAR DEGENERATION; ELECTROPORATION;
   ELECTRODES; MODEL
AB In age-related macular degeneration, the retinal pigment epithelium can be damaged by light acting on photosensitizers like N-retinylidene-N-retinylethanolamine (A2E). In this paper, the underlying cellular mechanism of lesion at the cell layer scale is analyzed by impedance spectroscopy. Retinal pigment epithelium (RPE) cells are cultured on top of custom-made electrodes capable of taking impedance measurements, with the help of a custom-made electronic setup but without the use of any chemical markers. An incubator is used to house the cells growing on the electrodes. An electrical model circuit is presented and linked to the constituents of the cell layer in which various electrical elements have been defined including a constant phase element (CPE) associated to the interface between the cell layer and the electrolyte. Their values are extracted from the fitted model of the measured impedance spectra. In this paper, we first investigate which parameters of the model can be analyzed independently. In that way, the parameter's evolution is examined with respect to two different targeted changes of the epithelium: 1. degradation of tight junctions between cells by extracellular calcium sequestration with Ethylenediaminetetraacetic acid (EDTA); 2. application of high amplitude short length electric field pulses. Based on the results obtained showing a clear relation between the model and the physiological state of the cell layer, the same procedure is applied to blue light exposure experiment. When A2E-loaded cells are exposed to blue light, the model parameters indicate, as expected, a clear degradation of the cell layer opposed to a relative stability of the not loaded ones.
C1 [Boutzen, Jocelyn; Rousseau, Lionel; Francais, Olivier; Lissorgues, Gaelle] Univ Paris Est, ESIEE Paris, ESYCOM UMR 9007, F-93160 Noisy Le Grand, France.
   [Valet, Manon; Alviset, Agathe; Fradot, Valerie; Picaud, Serge] Sorbonne Univ, Inst Vis, CNRS, INSERM, F-75012 Paris, France.
C3 Universite Gustave-Eiffel; ESIEE Paris; Centre National de la Recherche
   Scientifique (CNRS); Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; Universite Paris Cite
RP Boutzen, J (通讯作者)，Univ Paris Est, ESIEE Paris, ESYCOM UMR 9007, F-93160 Noisy Le Grand, France.
EM jocelyn.boutzen@gmail.com
RI Picaud, Serge/H-4012-2014
OI Picaud, Serge/0000-0002-0548-5145
FU Ecole Normale Superieure Paris-Saclay scholarship; French state
   [ANR-10-LABX-65, ANR-18-IAHU-0001]; ESIEE Paris (Noisy-le-Grand)
FX Jocelyn Boutzen acknowledges support from Ecole Normale Superieure
   Paris-Saclay scholarship.This work was supported by French state funds
   managed by the Agence Nationale de la Recherche within the
   Investissements d'Avenir program, LABEX LIFESENSES [ANR-10-LABX-65], IHU
   FOReSIGHT [ANR-18-IAHU-0001]. The authors acknowledge support from ESIEE
   Paris (Noisy-le-Grand) for clean room fabrication and instrumentation on
   internal funds. The authors also thank Diep Nguyen for English
   proofreading.
CR Ando Y, 2014, J FOOD ENG, V121, P24, DOI 10.1016/j.jfoodeng.2013.08.008
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NR 32
TC 5
Z9 5
U1 0
U2 20
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 AUG 1
PY 2020
VL 161
AR 112180
DI 10.1016/j.bios.2020.112180
PG 8
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 LP8ON
UT WOS:000534577000001
PM 32365009
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU de Jong, S
   Volokhina, EB
   de Breuk, A
   Nilsson, SC
   de Jong, EK
   van der Kar, NCAJ
   Bakker, B
   Hoyng, CB
   van den Heuvel, LP
   Blom, AM
   den Hollander, AI
AF de Jong, Sarah
   Volokhina, Elena B.
   de Breuk, Anita
   Nilsson, Sara C.
   de Jong, Eiko K.
   van der Kar, Nicole C. A. J.
   Bakker, Bjorn
   Hoyng, Carel B.
   van den Heuvel, Lambert P.
   Blom, Anna M.
   den Hollander, Anneke, I
TI Effect of rare coding variants in the CFI gene on Factor I expression
   levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID COMPLEMENT FACTOR-I; HEMOLYTIC-UREMIC SYNDROME; MACULAR DEGENERATION;
   MOLECULAR-BASIS; BINDING-SITES; MUTATIONS; DISEASE; DYSREGULATION;
   INSIGHTS; RISK
AB Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level analysis of rare coding variants in CFI to date. More than half of CFI variants lead to reduced FI expression, which might impair complement regulation in vivo. Our study will aid the interpretation of rare coding CFI variants identified in clinical practice, which is in particular important in light of patient inclusion in ongoing clinical trials for CFI gene supplementation in AMD.
C1 [de Jong, Sarah; de Breuk, Anita; de Jong, Eiko K.; Bakker, Bjorn; Hoyng, Carel B.; den Hollander, Anneke, I] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
   [Volokhina, Elena B.; van der Kar, Nicole C. A. J.; van den Heuvel, Lambert P.] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
   [Volokhina, Elena B.; van der Kar, Nicole C. A. J.] Radboud Univ Nijmegen, Amalia Childrens Hosp, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
   [Volokhina, Elena B.; van den Heuvel, Lambert P.] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
   [Nilsson, Sara C.; Blom, Anna M.] Lund Univ, Dept Translat Med, S-21428 Malmo, Sweden.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud
   University Nijmegen; Radboud University Nijmegen; Lund University
RP den Hollander, AI (通讯作者)，Radboud Univ Nijmegen, Dept Ophthalmol, Med Ctr, NL-6525 GA Nijmegen, Netherlands.; den Hollander, AI (通讯作者)，Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
EM anneke.denhollander@radboudumc.nl
RI Volokhina, Elena/L-4725-2015; Blom, Anna/B-9607-2009; Blom,
   Anna/AFS-7343-2022; Blom, Anna/AFS-7369-2022
OI Volokhina, Elena/0000-0002-4294-8460; Blom, Anna/0000-0002-1348-1734; de
   Jong, Sarah/0000-0002-3705-3371
FU European Research Council under the European Union's Horizon 2020
   Research and Innovation Programme/ERC [737607 (MACULA2)]; Netherlands
   Organization for Scientific Research [016.Vici.170.024]
FX The research leading to these results has received funding from the
   European Research Council under the European Union's Horizon 2020
   Research and Innovation Programme/ERC Grant Agreement n. 737607
   (MACULA2) and from the Netherlands Organization for Scientific Research
   (016.Vici.170.024).
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NR 40
TC 20
Z9 21
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2020
VL 29
IS 14
BP 2313
EP 2324
DI 10.1093/hmg/ddaa114
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA OH6JJ
UT WOS:000582695800003
PM 32510551
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Wright, C
   Mazzucco, AE
   Becker, SM
   Sieving, PA
   Tumminia, SJ
AF Wright, Charles
   Mazzucco, Anna E.
   Becker, Steven M.
   Sieving, Paul A.
   Tumminia, Santa J.
TI NEI-Supported Age-RelatedMacular Degeneration Research: Past, Present,
   and Future
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE age-related macular degeneration; clinical trial; genetic diseases
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; EYE
   DISEASE; NATURAL-HISTORY; SUSCEPTIBILITY; RISK; GENE; VARIANT; DRUSEN
AB Purpose: To review past and current National Eye Institute (NEI)-supported age-related macular degeneration (AMD) activities and initiatives and preview upcoming coordinated efforts for studying AMD.
   Methods: We conducted and summarized a portfolio analysis and literature review of NEI intramural and extramural AMD activities.
   Results: The NEI supports a broad range of AMD research, both by individual independent investigators as well as through networks and consortia. The International AMD Genomics Consortium, Age-Related Eye Disease Study, Age-Related Eye Disease Study 2 (AREDS2), and Comparison of AMD Treatments Trial legacy work probed the complex genetics, clinical presentation, and standards of patient care, respectively. The NEI AMD Pathobiology Working Group identified gaps and opportunities for future research efforts. The AMD Ryan Initiative Study and clinical trials testing the efficacies of minocycline to modulate retinal microglia activity and induced pluripotent stem cells-derived retinal pigmented epithelium (RPE) patch implants to rescue photoreceptor cell death are among the future directions for NEI-supported AMD research. Finally, NEI commissioned the creation of AREDS2 participant-derived induced pluripotent stem cell (iPSC) lines linked to their associated genomic and phenotypic datasets. These datasets will also be linked to the data obtained using their associated iPSC-derived cells (RPE, retina, choroid) and made publicly available.
   Conclusions: Investments by NEI for AMD research will continue to provide invaluable resources to investigators committed to addressing this complex blinding disease and other retinal degenerative diseases.
   Translational Relevance: NEI now stands poised to expand the resources available to clinical investigators to uncover disease mechanisms and move experimental therapies into clinical trials.
C1 [Wright, Charles] NEI, Div Extramural Sci Programs, Bethesda, MD 20892 USA.
   [Mazzucco, Anna E.] NIH, Immediate Off Director, Bldg 10, Bethesda, MD 20892 USA.
   [Becker, Steven M.; Tumminia, Santa J.] NEI, Off Director, Bethesda, MD 20892 USA.
   [Sieving, Paul A.] NEI, 31 Ctr Dr,Rm 6A03, Bethesda, MD 20892 USA.
   [Sieving, Paul A.] Univ Calif Davis, Ophthalmol & Vis Sci, Davis, CA 95616 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; National Institutes of
   Health (NIH) - USA; NIH National Eye Institute (NEI); National
   Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI);
   University of California System; University of California Davis
RP Tumminia, SJ (通讯作者)，NEI, 31 Ctr Dr,Rm 6A03, Bethesda, MD 20892 USA.
EM charles.wright@nih.gov
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NR 59
TC 5
Z9 5
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUN
PY 2020
VL 9
IS 7
AR 49
DI 10.1167/tvst.9.7.49
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA MJ6TQ
UT WOS:000548221000014
PM 32832254
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Brautigam, J
   Bischoff, I
   Schurmann, C
   Buchmann, G
   Epah, J
   Fuchs, S
   Heiss, E
   Brandes, RP
   Furst, R
AF Braeutigam, Jacqueline
   Bischoff, Iris
   Schuermann, Christoph
   Buchmann, Giulia
   Epah, Jeremy
   Fuchs, Simone
   Heiss, Elke
   Brandes, Ralf P.
   Fuerst, Robert
TI Narciclasine inhibits angiogenic processes by activation of Rho kinase
   and by downregulation of the VEGF receptor 2
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Narciclasine; Angiogenesis; Endothelial cells; VEGF receptor 2; Protein
   biosynthesis
ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE; AMARYLLIDACEAE ISOCARBOSTYRILS;
   ENDOTHELIAL-CELLS; STRESS FIBERS; PHOSPHORYLATION; CALCIUM; PERSPECTIVE;
   MECHANISM; ANTITUMOR
AB The process of angiogenesis is involved in several pathological conditions, such as tumor growth or age-related macular degeneration. Although the available anti-angiogenic drugs have improved the therapy of these diseases, major drawbacks, such as unwanted side effects and resistances, still exist. Consequently, the search for new anti-angiogenic substances is still ongoing. Narciclasine, a plant alkaloid from different members of the Amaryllidaceae family, has extensively been characterized as anti-tumor compound. Beyond the field of cancer, the compound has recently been shown to possess anti-inflammatory properties. Surprisingly, potential actions of narciclasine on endothelial cells in the context of angiogenesis have been neglected so far. Thus, we aimed to analyze the effects of narciclasine on angiogenic processes in vitro and in vivo and to elucidate the underlying mechanism. Narciclasine (100-300 nM) effectively inhibited the proliferation, undirected and directed migration, network formation and angiogenic sprouting of human primary endothelial cells. Moreover, narciclasine (1 mg/kg/day) strongly reduced the VEGF-triggered angiogenesis in vivo (Matrigel plug assay in mice). Narciclasine mediated its anti-angiogenic effects in part by a RhoA-independent activation of the Rho kinase ROCK. Most importantly, however, the compound reduced the de novo protein synthesis in endothelial cells by approx. 50% without exhibiting considerable cytotoxic effects. As a consequence, narciclasine diminished the presence of proteins with a short half-life, such as the VEGF receptor 2, which is the basis for its anti-angiogenic effects. Taken together, our study highlights narciclasine as an interesting anti-angiogenic compound that is worth to be further evaluated in preclinical studies.
C1 [Braeutigam, Jacqueline; Bischoff, Iris; Fuchs, Simone; Fuerst, Robert] Goethe Univ, Inst Pharmaceut Biol, Fac Biochem Chem & Pharm, Frankfurt, Germany.
   [Schuermann, Christoph; Buchmann, Giulia; Epah, Jeremy; Brandes, Ralf P.] Goethe Univ, Inst Cardiovasc Physiol, Fac Med, Frankfurt, Germany.
   [Schuermann, Christoph; Brandes, Ralf P.] German Ctr Cardiovasc Res DZHK, Partner Site Rhine Main, Frankfurt, Germany.
   [Heiss, Elke] Univ Vienna, Dept Pharmacognosy, Vienna, Austria.
C3 Goethe University Frankfurt; Goethe University Frankfurt; German Centre
   for Cardiovascular Research; University of Vienna
RP Furst, R (通讯作者)，Goethe Univ Frankfurt, Inst Pharmaceut Biol, Max von Laue Str 9, D-60438 Frankfurt, Germany.
EM fuerst@em.uni-frankfurt.de
RI ; Heiss, Elke/B-6086-2015
OI Furst, Robert/0000-0002-9926-7578; Buchmann, Giulia/0000-0002-7266-5613;
   Schurmann, Christoph/0000-0003-1530-1378; Heiss,
   Elke/0000-0001-7618-5505
FU DFG (Deutsche Forschungsgemeinschaft/German Research Foundation)
   Excellence Cluster Cardio-Pulmonary System (ECCPS) [SFB 834 (TPA2)];
   Faculty of Medicine, Goethe University, Frankfurt, Germany; German
   Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main,
   Frankfurt, Germany
FX The study was supported by the DFG (Deutsche
   Forschungsgemeinschaft/German Research Foundation) Excellence Cluster
   Cardio-Pulmonary System (ECCPS), SFB 834 (TPA2 to RPB), the Faculty of
   Medicine, Goethe University, Frankfurt, Germany and the German Center
   for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Frankfurt,
   Germany. The authors thank Mareike Lang for her excellent technical
   support.
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NR 48
TC 12
Z9 12
U1 2
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD OCT
PY 2019
VL 135
BP 97
EP 108
DI 10.1016/j.yjmcc.2019.08.001
PG 12
WC Cardiac & Cardiovascular Systems; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology; Cell Biology
GA JA1KE
UT WOS:000487575100010
PM 31381906
DA 2022-11-30
ER

PT J
AU Hu, TT
   Vanhove, M
   Porcu, M
   Van Hove, I
   Van Bergen, T
   Jonckx, B
   Barbeaux, P
   Vermassen, E
   Feyen, JHM
AF Hu, Tjing-Tjing
   Vanhove, Marc
   Porcu, Michael
   Van Hove, Inge
   Van Bergen, Tine
   Jonckx, Bart
   Barbeaux, Philippe
   Vermassen, Elke
   Feyen, Jean H. M.
TI The potent small molecule integrin antagonist THR-687 is a promising
   next-generation therapy for retinal vascular disorders
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID DIABETIC-RETINOPATHY; ANGIOGENESIS; VASCULOPATHY; PERMEABILITY; ANTIBODY
AB Integrins are associated with various eye diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) and implicated in main pathologic disease hallmarks like neovascularization, inflammation, fibrosis and vascular leakage. Targeting integrins has the potential to attenuate these vision-threatening processes, independent of anti-vascular endothelial growth factor (VEGF) responsiveness. The current investigation characterized THR-687 as a novel pan RGD (arginylglycylaspartic acid) integrin receptor antagonist able to compete for binding with the natural ligand with nanomolar potency (e.g. alpha(v)beta(3) (IC50 of 4.4 +/- 2.7 nM), alpha(v)beta(5) (IC50 of 1.3 +/- 0.5 nM) and alpha(5)beta(1) (IC50 of 6.8 +/- 3.2 nM)). THR-687 prevented the migration of human umbilical vein endothelial cells (HUVECs) into a cell-free area (IC50 of 258 +/- 113 nM) as well as vessel sprouting in an ex vivo mouse choroidal explant model (IC50 of 236 +/- 173 nM), and was able to induce the regression of pre-existing vascular sprouts. Moreover, combined intravitreal and intraperitoneal administration of THR-687 potently inhibited VEGF-induced leakage in the mouse retina. In addition, THR-687 injected intravitreally at 3 different dose levels (0.45 mg, 2.25 mg or 4.5 mg/eye) potently inhibited neovascularization-induced leakage in the cynomolgus laser-induced choroidal neovascularization (CNV) model.
   These data suggest that THR-687 is a promising drug candidate for the treatment of vision-threatening retinal vascular eye diseases such as DR and wet AMD.
C1 [Hu, Tjing-Tjing; Vanhove, Marc; Porcu, Michael; Van Hove, Inge; Van Bergen, Tine; Jonckx, Bart; Barbeaux, Philippe; Vermassen, Elke; Feyen, Jean H. M.] Oxurion NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
RP Hu, TT (通讯作者)，Oxurion NV, Gaston Geenslaan 1, B-3001 Heverlee, Belgium.
EM tjing-tjing.hu@oxurion.com; marc.vanhove@oxurion.com;
   michael.porcu@oxurion.com; inge.varthove@oxurion.com;
   tine.vanbergen@oxurion.com; bart.joncicx@oxurion.com;
   philippe.barbeaux@oxurion.com; elke.vermassen@oxurion.com;
   jean.feyen@oxurion.com
OI Porcu, Michael/0000-0002-9369-5547; Van Hove, Inge/0000-0002-3125-0438
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NR 72
TC 18
Z9 18
U1 0
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2019
VL 180
BP 43
EP 52
DI 10.1016/j.exer.2018.11.022
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN7KO
UT WOS:000460368500007
PM 30472075
DA 2022-11-30
ER

PT J
AU Sivaprasad, S
   Tschosik, EA
   Guymer, RH
   Kapre, A
   Suner, IJ
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   Lanzetta, P
   Ferrara, D
AF Sivaprasad, Sobha
   Tschosik, Elizabeth A.
   Guymer, Robyn H.
   Kapre, Audrey
   Suner, Ivan J.
   Joussen, Antonia M.
   Lanzetta, Paolo
   Ferrara, Daniela
TI Living with Geographic Atrophy: An Ethnographic Study
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Article
DE Activities of daily living; Age-related macular degeneration;
   Ethnography; Geographic atrophy; Quality of life; Visual acuity
ID MACULAR DEGENERATION; LIVED EXPERIENCE; PEOPLE
AB IntroductionThe specific impact from the patient's perspective of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), is not well understood.MethodsAn ethnographic study was conducted to understand the impact of bilateral GA secondary to AMD on daily functioning by observing regular activities performed at home and through semi-structured interviews. Eligible subjects had a definitive GA diagnosis, including presence of drusen, GA lesion size of at least one disc area in the better-seeing eye, and no other confounding ophthalmologic diagnosis. Data were collected via video recordings and field notes, and analyzed by coding video transcripts.ResultsFunctional impact domains affecting more than two of the 16 subjects from the United Kingdom, United States, or Germany were activities of daily living (difficulty reading, n=16; driving, n=12; and watching movies, television, or theater, n=11), emotional (frustration, and fear of blindness, n=7 each), social/leisure (interference with hobbies, n=8, and diminished social activities, n=4), physical (n=4), and financial (n=10). Subjects with a best-corrected visual acuity (BCVA) of 20/100 or better in the better-seeing eye (n=10) reported similar functional impacts to those with a BCVA of worse than 20/100 in their better-seeing eye (n=5).ConclusionThis study helps address gaps in patient-focused research into GA, which negatively impacts the day-to-day functioning of patients. Larger qualitative and quantitative studies are needed to quantify patient experiences and assess the correlation between BCVA score and impact of GA.
C1 [Sivaprasad, Sobha] NIHR Moorfields Biomed Res Ctr, London, England.
   [Tschosik, Elizabeth A.; Kapre, Audrey] Genentech Inc, Dept Patient Ctr Outcomes Res, San Francisco, CA 94080 USA.
   [Ferrara, Daniela] Genentech Inc, Clin Sci Ophthalmol, San Francisco, CA 94080 USA.
   [Guymer, Robyn H.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Guymer, Robyn H.] Univ Melbourne, Dept Surg Ophthalmol, Melbourne, Vic, Australia.
   [Suner, Ivan J.] Retina Associates Florida, Tampa, FL USA.
   [Joussen, Antonia M.] Charite Univ Med Berlin, Dept Ophthalmol, Berlin, Germany.
   [Lanzetta, Paolo] Univ Udine, Dept Med Ophthalmol, Udine, Italy.
   [Lanzetta, Paolo] IEMO, Udine, Italy.
C3 Roche Holding; Genentech; Roche Holding; Genentech; Centre for Eye
   Research Australia; Royal Victorian Eye & Ear Hospital; University of
   Melbourne; Free University of Berlin; Humboldt University of Berlin;
   Charite Universitatsmedizin Berlin; University of Udine
RP Tschosik, EA (通讯作者)，Genentech Inc, Dept Patient Ctr Outcomes Res, San Francisco, CA 94080 USA.
EM tschosik.elizabeth@gene.com
RI Joussen, Antonia/AAA-6901-2022; Sivaprasad, S./D-6876-2015
OI Sivaprasad, S./0000-0001-8952-0659; Guymer, Robyn/0000-0002-9441-4356
FU F. Hoffmann-La Roche Ltd.
FX F. Hoffmann-La Roche Ltd. supported and contributed to all aspects of
   the study, including the study design; financial support to Edelman for
   assistance with conducting the study; Endpoint Outcomes for assistance
   with analyses, data interpretation, and report writing; and funding of
   publication fees. All authors had full access to all of the data in this
   study and take complete responsibility for the integrity of the data and
   accuracy of the data analysis.
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NR 21
TC 14
Z9 14
U1 0
U2 1
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 MAR
PY 2019
VL 8
IS 1
BP 115
EP 124
DI 10.1007/s40123-019-0160-3
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN6FO
UT WOS:000460281000011
PM 30706242
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Qu, YQ
   He, YM
   Zhang, Y
   Ma, T
   Zhu, J
   Miao, YS
   Dai, CX
   Humayun, M
   Zhou, QF
   Chen, ZP
AF Qu, Yueqiao
   He, Youmin
   Zhang, Yi
   Ma, Teng
   Zhu, Jiang
   Miao, Yusi
   Dai, Cuixia
   Humayun, Mark
   Zhou, Qifa
   Chen, Zhongping
TI Quantified elasticity mapping of retinal layers using synchronized
   acoustic radiation force optical coherence elastography
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID MACULAR DEGENERATION; SHEAR-WAVE; MODULUS; SEGMENTATION; TOMOGRAPHY;
   ULTRASOUND
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly (over the age of 60 years) in western countries. In the early stages of the disease, structural changes may be subtle and cannot be detected. Recently it has been postulated that the mechanical properties of the retina may change with the onset of AMD. In this manuscript, we present a novel, non-invasive means that utilizes synchronized acoustic radiation force optical coherence elastography (ARF-OCE) to measure and estimate the elasticity of cadaver porcine retina. Both regions near the optic nerve and in the peripheral retina were studied. An acoustic force is exerted on the tissue for excitation and the resulting tissue vibrations, often in the nanometer scale, are detected with high-resolution optical methods. Segmentation has been performed to isolate individual layers and the Young's modulus has been estimated for each. The results have been successfully compared and mapped to corresponding histological results using H&E staining. Finally, 64 elastograms of the retina were analyzed, as well as the elastic properties, with stiffness ranging from 1.3 to 25.9 kPa in the ganglion to the photoreceptor sides respectively. ARF-OCE allows for the elasticity mapping of anatomical retinal layers. This imaging approach needs further evaluation but has the potential to allow physicians to gain a better understanding of the elasticity of retinal layers in retinal diseases such as AMD. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Qu, Yueqiao; He, Youmin; Zhu, Jiang; Miao, Yusi; Dai, Cuixia; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd East, Irvine, CA 92612 USA.
   [Zhang, Yi; Humayun, Mark; Zhou, Qifa] Univ Southern Calif, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
   [Zhang, Yi; Humayun, Mark; Zhou, Qifa] Univ Southern Calif, Inst Biomed Therapeut, Los Angeles, CA 90033 USA.
   [Ma, Teng; Zhou, Qifa] Univ Southern Calif, Dept Biomed Engn, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA.
C3 University of California System; University of California Irvine;
   University of Southern California; University of Southern California;
   National Institutes of Health (NIH) - USA; University of Southern
   California
RP Zhou, QF (通讯作者)，Univ Southern Calif, USC Roski Eye Inst, Los Angeles, CA 90033 USA.; Zhou, QF (通讯作者)，Univ Southern Calif, Inst Biomed Therapeut, Los Angeles, CA 90033 USA.; Zhou, QF (通讯作者)，Univ Southern Calif, Dept Biomed Engn, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM qifazhou@usc.edu; z2chen@uci.edu
RI Zhu, Jiang/O-4869-2016
OI Zhu, Jiang/0000-0002-2601-4967
FU National Institutes of Health (NIH) [R01HL-125084, R01HL-127271,
   R01EY-026091, R01EY-028662, P41EB-015890, T32HL116270, F31EY027666]; Air
   Force Office of Scientific Research [FA9550-17-1-0193]; NATIONAL EYE
   INSTITUTE [F31EY027666, R01EY026091] Funding Source: NIH RePORTER;
   NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL125084, R01HL127271]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING
   AND BIOENGINEERING [P41EB015890] Funding Source: NIH RePORTER
FX National Institutes of Health (NIH) (R01HL-125084, R01HL-127271,
   R01EY-026091, R01EY-028662, P41EB-015890, T32HL116270, F31EY027666); Air
   Force Office of Scientific Research (FA9550-17-1-0193).
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NR 24
TC 24
Z9 24
U1 2
U2 8
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD SEP 1
PY 2018
VL 9
IS 9
BP 4054
EP 4063
DI 10.1364/BOE.9.004054
PG 10
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA GS1SZ
UT WOS:000443313700005
PM 30615733
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Tetikoglu, M
   Kurt, MM
   Sagdik, HM
   Aktas, S
   Yildirim, MA
   Ozcura, F
AF Tetikoglu, Mehmet
   Kurt, Muhammed Mustafa
   Sagdik, Haci Murat
   Aktas, Serdar
   Yildirim, Medine Asli
   Ozcura, Fatih
TI Retrospective analysis of the effect of aflibercept loading dose on the
   retinal vessel diameters in patients with treatment-naive neovascular
   AMD
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Aflibercept; retinal vessel diameter; choroidal thickness; retinal blood
   flow; macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; BEAVER DAM EYE; VEGF TRAP-EYE; MACULAR
   DEGENERATION; INTRAVITREAL INJECTION; BLOOD-FLOW; CHOROIDAL THICKNESS;
   VISUAL IMPAIRMENT; RANIBIZUMAB; BEVACIZUMAB
AB Background: To evaluate the effects of intravitreal aflibercept (IVA) on retinal vessel diameters in patients with neovascular age-related macular degeneration (AMD).Design, setting, and participants: A retrospective study conducted at the Kutahya Dumlupinar University Faculty of Medicine included 15 eyes of 15 patients with treatment naive neovascular AMD.Methods: All eyes received IVA injections once per month for 3months; untreated contralateral eyes were used as controls. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery-vein ratio (AVR) values were measured using a computer-based program before the first IVA injection and 30days after the first, second, and third injections. The main outcome measurements were the central macular thickness (CMT), best-corrected visual acuity (BCVA), choroidal thickness, CRAE, CRVE, and AVR.Results: Significant vasoconstriction of the retinal arterioles was observed in all eyes treated with IVA when compared to baseline (p=0.009). However, no significant differences were found for CRVE or AVR throughout the study period in treated eyes. In the control group, all parameters measured during each visit were similar to baseline measurements (p>0.05). The mean BCVA significantly improved at the end of the loading dose of IVA, when compared to baseline (p=0.006). After the IVA injections, the mean CMT and choroidal thickness were significantly reduced at all visits, compared to baseline (p<0.001).Conclusions: The current study showed that IVA led to significant retinal arteriolar vasoconstriction and choroidal thinning, which may cause reduced retinal blood flow.
C1 [Tetikoglu, Mehmet; Sagdik, Haci Murat; Aktas, Serdar; Ozcura, Fatih] Dumlupinar Univ, Dept Ophthalmol, Sch Med, TR-43270 Kutahya, Turkey.
   [Kurt, Muhammed Mustafa] Samsun Gazi State Hosp, Dept Ophthalmol, Samsun, Turkey.
   [Yildirim, Medine Asli] Bahcelievler State Hosp, Istanbul, Turkey.
C3 Dumlupinar University; Samsun Gazi State Hospital; Bahcelievler State
   Hospital
RP Tetikoglu, M (通讯作者)，Dumlupinar Univ, Dept Ophthalmol, Sch Med, TR-43270 Kutahya, Turkey.
EM drtetikoglu@yahoo.com.tr
RI Ozcura, Fatih/F-8640-2011; kurt, muhammed mustafa/AAI-6225-2020
OI Ozcura, Fatih/0000-0001-6482-180X; 
CR Ameri H, 2007, INVEST OPHTH VIS SCI, V48, P5708, DOI 10.1167/iovs.07-0731
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NR 37
TC 5
Z9 5
U1 0
U2 2
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 1
BP 84
EP 89
DI 10.1080/15569527.2017.1354217
PG 6
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA FZ8DJ
UT WOS:000427835700013
PM 28697703
DA 2022-11-30
ER

PT J
AU Shen, CL
   Ma, W
   Zheng, WB
   Huang, H
   Xia, RC
   Li, C
   Zhu, XB
AF Shen, Chaolan
   Ma, Wei
   Zheng, Wenbin
   Huang, Hao
   Xia, Renchun
   Li, Chu
   Zhu, Xiaobo
TI The antioxidant effects of riluzole on the APRE-19 celll model
   injury-induced by t-BHP
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Riluzole; TRAAK K2P channel; ARPE-19 cells; AMD; apoptosis
ID DOMAIN K+ CHANNELS; OXIDATIVE STRESS; RAT; APOPTOSIS
AB Background: Age-related macular degeneration (AMD) causes the dysfunction of the retinal pigment epithelial (RPE) cells. In this study, we examined the effects of riluzole, a sustained activator of the TRAAK potassium channel, on human RPE (ARPE-19) cells in an oxidant-induced cell-injury model and elucidate the mechanism of riluzole on RPE cell apoptosis.
   Methods: The follow four groups of ARPE-19 cells were treated with riluzole and/or tert-butyl hydroperoxide (t-BHP) for 24.0 h: control, t-BHP, riluzole, and t-BHP + riluzole. Cell apoptosis was measured by flow cytometry, and Western blotting was performed to analyze the expression of the weakly inward rectifying potassium (TRAAK) channel. Finally, the mitochondrial membrane potential (Delta psi m) was detected by flow cytometry, and cytochrome C (Cyt-c) release was assessed by Western blotting.
   Results: The viability of the cells in the cotreated group was significantly higher (85.6 +/- 3.1%) than that in the t-BHP group (66.2 +/- 2.5%). In addition, the cells in the cotreated group had a higher effect on increasing the expression of TRAAK than the t-BHP group. The results also showed that Cyt-c translocation significantly decreased and..m increased in the cotreated group.
   Conclusions: These results demonstrate that riluzole protects RPE cells from apoptosis. The protection mechanism of riluzole could be from stabilizing mitochondrial Delta psi m and preventing the release of Cyt-c. Changes in TRAAK expression might also contribute to the protection of RPE cells.
C1 [Shen, Chaolan; Ma, Wei; Huang, Hao; Li, Chu; Zhu, Xiaobo] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Shen, Chaolan] Peoples Hosp Guangxi Zhuang Autonomous Reg, Nanning, Guangxi, Peoples R China.
   [Zheng, Wenbin] Gannan Med Univ, Affiliated Hosp 1, Ganzhou, Jiangxi, Peoples R China.
   [Xia, Renchun] Peoples Hosp Deyang City, Deyang, Sichuan, Peoples R China.
C3 Sun Yat Sen University; Gannan Medical University
RP Zhu, XB (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
EM zhuxbo@mail.sysu.edu.cn
OI Zheng, Wenbin/0000-0002-2256-4865
FU National Natural Science Foundation of China [81,271,012]; Specialized
   Research Fund for the Doctoral Program of Higher Education of China
   [20100171120097]
FX This work is supported in part by National Natural Science Foundation of
   China (Grant 81,271,012) and Specialized Research Fund for the Doctoral
   Program of Higher Education of China (20100171120097).
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NR 21
TC 7
Z9 8
U1 1
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 NOV 23
PY 2017
VL 17
AR 210
DI 10.1186/s12886-017-0614-0
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FN4TK
UT WOS:000415999400001
PM 29169345
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kim, BZ
   Patel, DV
   McGhee, CNJ
AF Kim, Bia Z.
   Patel, Dipika V.
   McGhee, Charles N. J.
TI Auckland cataract study 2: clinical outcomes of phacoemulsification
   cataract surgery in a public teaching hospital
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE cataract surgery; complication rate; observational study; visual outcome
ID POSTERIOR CAPSULE RUPTURE; ELECTRONIC MULTICENTER AUDIT; VISUAL-ACUITY;
   RISK-FACTORS; COMPLICATIONS; MORBIDITY
AB ImportanceA contemporary benchmark for the most common ophthalmic surgery.
   BackgroundTo assess patient characteristics and outcomes of contemporary phacoemulsification cataract surgery in a New Zealand public teaching hospital setting.
   DesignProspective observational study.
   ParticipantsConsecutive cases (n=500) of phacoemulsification surgery between April and June 2015.
   MethodsAn independent observer assessed clinical and surgical data preoperatively and 4-6weeks postoperatively.
   Main Outcome MeasuresVisual acuity, intraoperative and postoperative complications.
   ResultsMean age was 72.311.9years and 57% female. Mean preoperative best-measured visual acuity was 6/30. Ocular comorbidity was present in 45.8% of eyes, most commonly glaucoma (10%), age-related macular degeneration (8%) and diabetic retinopathy (8%). Systemically, hypertension (59%) and diabetes mellitus (31%) were prevalent. Mean contralateral best-measured visual acuity was 6/12 (n=495) with 62% being phakic. The rate of posterior capsular tear was 2.6% and cystoid macular oedema 3.5%. Intraoperative complication rates were not significantly different between surgeon levels (P=0.234). However, registrars had fewer postoperative complications than fellows (2.2% vs. 11.9%, P=0.012). Postoperatively, mean unaided and best-measured visual acuity were 6/12 and 6/9.
   Conclusions and RelevanceThis study reports current phacoemulsification surgery outcomes in a major public teaching institution. A large proportion of patients exhibited systemic and ocular comorbidities, relatively dense cataracts and poor presenting visual acuity. However, visual outcomes and intraoperative complication rates were not statistically different between trainees and senior surgeons. Generally, outcomes reflect international standards and have improved since the last comparable study in this region.
C1 [Kim, Bia Z.; Patel, Dipika V.; McGhee, Charles N. J.] Univ Auckland, Dept Ophthalmol, New Zealand Natl Eye Ctr, Fac Med & Hlth Sci, Private Bag 92019, Auckland, New Zealand.
   [Kim, Bia Z.; Patel, Dipika V.; McGhee, Charles N. J.] Auckland Dist Hlth Board, Greenlane Clin Ctr, Dept Ophthalmol, Auckland, New Zealand.
C3 University of Auckland; Auckland District Health Board
RP McGhee, CNJ (通讯作者)，Univ Auckland, Dept Ophthalmol, New Zealand Natl Eye Ctr, Fac Med & Hlth Sci, Private Bag 92019, Auckland, New Zealand.
EM c.mcghee@auckland.ac.nz
OI McGhee, Charles NJ/0000-0001-7048-0706
FU University of Auckland
FX Dr Bia Z Kim was funded by an unrestricted Senior Health Research
   Scholarship, University of Auckland.
CR Davis P, 1997, NEW ZEAL MED J, V110, P390
   Day AC, 2015, EYE, V29, P552, DOI 10.1038/eye.2015.3
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NR 22
TC 11
Z9 11
U1 1
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD AUG
PY 2017
VL 45
IS 6
BP 584
EP 591
DI 10.1111/ceo.12922
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FE6MO
UT WOS:000408323800004
PM 28168827
DA 2022-11-30
ER

PT J
AU Ilim, O
   Akkin, C
   Oztas, Z
   Nalcaci, S
   Afrashi, F
   Degirmenci, C
   Mentes, J
AF Ilim, Orhan
   Akkin, Cezmi
   Oztas, Zafer
   Nalcaci, Serhad
   Afrashi, Filiz
   Degirmenci, Cumali
   Mentes, Jale
TI The Role of Posterior Vitreous Detachment and Vitreomacular Adhesion in
   Patients With AgeRelated Macular Degeneration
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTERFACE; THERAPY
AB BACKGROUND AND OBJECTIVE: The aim of this study was to assess the prevalence of posterior vitreous detachment (PVD) and vitreoretinal interface in patients with age-related macular degeneration (AMD).
   PATIENTS AND METHODS: This clinical trial included 206 eyes of 138 patients who presented to the authors' clinic between January 2012 and November 2014. Patients were divided into three groups: 98 eyes of 67 patients with exudative AMD, 55 eyes of 36 patients with nonexudative AMD, and 53 eyes of 35 patients having no vitreoretinal disease. All patients underwent complete ocular examination, including best-corrected visual acuity, Goldmann applanation tonometry, fundus photography, spectral-domain optical coherence tomography, and B-mode ultrasonography at 6 months and 12 months after the initial examination.
   RESULTS: Total and partial PVD rates were significantly higher at baseline, 6 months, and 12 months in both exudative and nonexudative AMD groups when compared to the control group (Chi-square test, P = .006, P = .001, and P = .009, respectively). The prevalence of total PVD was significantly higher in nonexudative AMD, whereas partial PVD was higher in exudative AMD. The exudative AMD group reported significantly more VMA than the other two groups at baseline, 6 months, and 12 months (Chi-square test, P =. 005, P = .003, and P = .019, respectively).
   CONCLUSION: This study indicates that the incidence of vitreoretinal interface abnormalities such as partial PVD and vitreomacular adhesion were higher in the exudative AMD group. It can be concluded that abnormal adhesive and tractional forces due to PVD may play a role in the progression of AMD.
C1 [Ilim, Orhan; Akkin, Cezmi; Oztas, Zafer; Nalcaci, Serhad; Afrashi, Filiz; Degirmenci, Cumali; Mentes, Jale] Ege Univ, Fac Med, Dept Ophthalmol, Izmir, Turkey.
C3 Ege University
RP Ilim, O (通讯作者)，Hakkari State Hosp, TR-30000 Hakkari, Turkey.
EM orhanilim@gmail.com
RI afrashi, filiz/ABB-6647-2020; akkın, cezmi/ABG-4054-2021; MENTES,
   JALE/AFO-2110-2022; degirmenci, cumali/AAF-1815-2021
OI afrashi, filiz/0000-0001-6359-1600; degirmenci,
   cumali/0000-0002-8268-536X
CR Houston SK, 2015, RETINA-J RET VIT DIS, V35, P1757, DOI 10.1097/IAE.0000000000000663
   Jackson TL, 2013, RETINA-J RET VIT DIS, V33, P1099, DOI 10.1097/IAE.0b013e31828991d6
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NR 17
TC 3
Z9 3
U1 0
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 MAR
PY 2017
VL 48
IS 3
BP 223
EP 229
DI 10.3928/23258160-20170301-05
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA EQ6VG
UT WOS:000398221300005
PM 28297034
DA 2022-11-30
ER

PT J
AU Miller, CG
   Budoff, G
   Jeng-Miller, KW
   Fine, HF
   Roth, DB
   Prenner, JL
AF Miller, Charles G.
   Budoff, Greg
   Jeng-Miller, Karen W.
   Fine, Howard F.
   Roth, Daniel B.
   Prenner, Jonathan L.
TI Retina Specialists Treating Diabetic Macular Edema Recommend Different
   Approaches for Patients Than They Would Choose for Themselves
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID PREVALENCE
AB BACKGROUND AND OBJECTIVE: Prior investigation shows retina specialists may select different treatment for age-related macular degeneration for themselves than for a hypothetical patient. The authors sought to investigate whether a similar bias exists for treatment decisions by retina specialists with regard to diabetic macular edema (DME).
   PATIENTS AND METHODS: Two surveys asked retina specialists to select treatment for hypothetical patients with DME or for themselves. In Survey 2, a distinction was drawn between a visual acuity (VA) of 20/40 or better and 20/50 or worse.
   RESULTS: In Survey 1, 54% to 61% of respondents selected bevacizumab (Avastin; Genentech, South San Francisco, CA) for patients and 36% to 40% selected the drug for themselves (P <.0004). It was found that 14% to 17% selected aflibercept (Eylea; Regeneron, Tarrytown, NY) for patients versus 31% to 38% who selected it for themselves (P <.0001). For a VA of 20/40 or better, 42% to 50% selected bevacizumab for their patients versus 32% to 39% (P <.0005) for themselves, and 20% to 23% selected aflibercept for patients versus 39% to 48% (P <.0007) for themselves. For a VA of 20/50 or worse, 24% to 28% chose bevacizumab for patients versus 17% to 20% for themselves (P value was not significant), and 59% to 66% selected aflibercept for their patients versus 66% to 78% for themselves (P <.05).
   CONCLUSION: Physicians recommend different treatment for their patients than for themselves, though not for a VA of 20/50 or worse, where data support the use of aflibercept over bevacizumab.
C1 [Miller, Charles G.; Budoff, Greg; Jeng-Miller, Karen W.; Fine, Howard F.; Prenner, Jonathan L.] Rutgers Robert Wood Johnson Med Sch, Piscataway, NJ USA.
   [Fine, Howard F.; Roth, Daniel B.; Prenner, Jonathan L.] NJ Retina, New Brunswick, NJ USA.
C3 Rutgers State University New Brunswick; Rutgers State University Medical
   Center
RP Prenner, JL (通讯作者)，Rutgers Robert Wood Johnson Med Sch, NJ Retina, 10 Plum St,6th Floor, New Brunswick, NJ 08901 USA.
EM jonathanprenner@gmail.com
CR Agarwal A, 2015, CURR DIABETES REP, V15, P652
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NR 15
TC 2
Z9 3
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 JUN
PY 2016
VL 47
IS 6
BP 544
EP 554
DI 10.3928/23258160-20160601-06
PG 11
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA EJ3ER
UT WOS:000393095900007
PM 27327284
DA 2022-11-30
ER

PT J
AU Genewsky, A
   Jost, I
   Busch, C
   Huber, C
   Stindl, J
   Skerka, C
   Zipfel, PF
   Rohrer, B
   Strauss, O
AF Genewsky, Andreas
   Jost, Ingmar
   Busch, Catharina
   Huber, Christian
   Stindl, Julia
   Skerka, Christine
   Zipfel, Peter F.
   Rohrer, Baerbel
   Strauss, Olaf
TI Activation of endogenously expressed ion channels by active complement
   in the retinal pigment epithelium
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE (4-6): complement system; Retinal pigment epithelium; RPE; L-type
   channels; BK channels
ID MEMBRANE-ATTACK-COMPLEX; VEGF SECRETION; CA2+ CHANNELS; FACTOR-H; CELLS;
   INCREASE; PATHWAY; C5A; RPE; PERMEABILITY
AB Defective regulation of the alternative pathway of the complement system is believed to contribute to damage of retinal pigment epithelial (RPE) cells in age-related macular degeneration. Thus we investigated the effect of complement activation on the RPE cell membrane by analyzing changes in membrane conductance via patch-clamp techniques and Ca2+ imaging. Exposure of human ARPE-19 cells to complement-sufficient normal human serum (NHS) (25 %) resulted in a biphasic increase in intracellular free Ca2+ ([Ca2+](i)); an initial peak followed by sustained Ca2+ increase. C5- or C7-depleted sera did not fully reproduce the signal generated by NHS. The initial peak of the Ca2+ response was reduced by sarcoplasmic Ca2+-ATPase inhibitor thapsigargin, L-type channel blockers (R)-(+)-BayK8644 and isradipine, transient-receptor-potential (TRP) channel blocker ruthenium-red and ryanodine receptor blocker dantrolene. The sustained phase was carried by Ca(V)1.3 L-type channels via tyrosine-phosphorylation. Changes in [Ca2+](I) were accompanied by an abrupt hyperpolarization, resulting from a transient increase in membrane conductance, which was absent under extracellular Ca2+- or K+-free conditions and blocked by (R)-(+)-BayK8644 or paxilline, a maxiK channel inhibitor. Single-channel recordings confirmed the contribution of maxiK channels. Primary porcine RPE cells responded to NHS in a comparable manner. Pre-incubation with NHS reduced H2O2-induced cell death. In summary, in a concerted manner, C3a, C5a and sC5b-9 increased [Ca2+](i) by ryanodine-receptor-dependent activation of L-type channels in addition to maxi-K channels and TRP channels absent from any insertion of a lytic pore.
C1 [Genewsky, Andreas] Max Planck Inst Psychiat, D-80804 Munich, Germany.
   [Genewsky, Andreas; Jost, Ingmar; Stindl, Julia; Strauss, Olaf] Univ Med Ctr Regensburg, Eye Clin, Expt Ophthalmol, Regensburg, Germany.
   [Skerka, Christine; Zipfel, Peter F.] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
   [Zipfel, Peter F.] Univ Jena, Jena, Germany.
   [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA.
   [Busch, Catharina; Huber, Christian; Strauss, Olaf] Charite, Dept Ophthalmol, Expt Ophthalmol, Campus Virchow Klinikum, D-13353 Berlin, Germany.
C3 Max Planck Society; University of Regensburg; Hans Knoll Institute
   (HKI); Friedrich Schiller University of Jena; Medical University of
   South Carolina; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center; Free University
   of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin
   Berlin
RP Strauss, O (通讯作者)，Charite, Dept Ophthalmol, Expt Ophthalmol, Campus Virchow Klinikum, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM olaf.strauss@charite.de
RI Strauss, Olaf/AAA-6485-2019
OI Strauss, Olaf/0000-0002-6272-8596; Genewsky, Andreas
   J./0000-0002-6017-2862
FU National Institutes of Health (NIH) [R01EY019320]; Department for
   Veterans Affairs [RX000444]; Research to Prevent Blindness (RPB), New
   York, NY; Deutsche Forschungsgemeinschaft (DFG) [SK46/2-1, SK46/2-2];
   NATIONAL EYE INSTITUTE [R01EY019320, R01EY024581] Funding Source: NIH
   RePORTER; Veterans Affairs [I01RX000444, I01BX003050] Funding Source:
   NIH RePORTER
FX The authors thank Andrea Dannullis, Elfriede Eckert and Renate Fockler
   for expert technical assistance. Financial support: OS: Novartis
   Professorship; BR: in part by the National Institutes of Health (NIH)
   (R01EY019320), a Department for Veterans Affairs merit award RX000444
   and an unrestricted grant to MUSC from Research to Prevent Blindness
   (RPB), New York, NY; CS: Deutsche Forschungsgemeinschaft (DFG) SK46/2-1,
   SK46/2-2.
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NR 44
TC 9
Z9 9
U1 0
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0031-6768
EI 1432-2013
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD OCT
PY 2015
VL 467
IS 10
BP 2179
EP 2191
DI 10.1007/s00424-014-1656-2
PG 13
WC Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Physiology
GA CR0IB
UT WOS:000361000800011
PM 25427445
DA 2022-11-30
ER

PT J
AU Kim, JH
   Lee, TG
   Kim, JW
   Kim, CG
   Cho, SW
   Han, JI
AF Kim, Jae Hui
   Lee, Tae Gon
   Kim, Jong Woo
   Kim, Chul Gu
   Cho, Sung Won
   Han, Jung Il
TI Small retinal haemorrhages accompanied by macular soft drusen:
   prevalence, and funduscopic and angiographic characteristics
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OCCULT CHOROIDAL NEOVASCULARIZATION; ANGIOMATOUS PROLIFERATION;
   RETICULAR PSEUDODRUSEN; DEGENERATION; ASSOCIATION; ANASTOMOSIS;
   THICKNESS; LESIONS; EXTENT; EYE
AB Purpose To investigate the prevalence and clinical significance of small retinal haemorrhages accompanied by macular soft drusen in exudative age-related macular degeneration (AMD).
   Methods This observational case series included patients who had first been diagnosed with exudative AMD. Small retinal haemorrhages were defined as preretinal or intraretinal haemorrhages, no larger than half the disc diameter in size and located within 3000 m of the fovea centre. If there was more than one haemorrhage, the entire affected area was less than two-thirds of the disc diameter. Macular soft drusen was defined as the presence of soft drusen (=125 m in diameter) within the macular area. The presence of retinal angiomatous proliferation (RAP) was estimated based on the results of indocyanine green angiography (ICGA). The prevalence of reticular pseudodrusen was also estimated.
   Results Among the 1921 eyes from 1604 patients who were newly diagnosed with exudative AMD during the 40 months prior to the study, 101 eyes (5.3%) from 79 patients presented with the fundus characteristics described above. ICGA images were available for 69 eyes. Among these eyes, 28 eyes (43.1%) and 25 eyes (38.5%) were found to have type 1 and 2 RAP, respectively. A chorioretinal anastomosis (type 3 RAP) was identified in 12 (18.5%) eyes. Reticular pseudodrusen were noted in 78 eyes (77.2%).
   Conclusions The presence of small retinal haemorrhages accompanied by macular soft drusen was highly predictive of RAP. The high prevalence of both soft drusen and reticular pseudodrusen in these eyes may suggest a profound decrease in choroidal perfusion in these eyes.
C1 [Kim, Jae Hui; Lee, Tae Gon; Kim, Jong Woo; Kim, Chul Gu; Cho, Sung Won; Han, Jung Il] Konyang Univ, Kims Eye Hosp, Dept Ophthalmol, Coll Med, Seoul, South Korea.
C3 Konyang University; Konyang University Hospital
RP Lee, TG (通讯作者)，Kims Eye Hosp, Dept Ophthalmol, 156 Youngdeungpo Dong 4Ga, Seoul 150034, South Korea.
EM idoc@kimeye.com
FU Kim's Eye Hospital Research Center
FX This study is supported by Kim's Eye Hospital Research Center.
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NR 26
TC 11
Z9 11
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD AUG
PY 2014
VL 98
IS 8
BP 1066
EP 1072
DI 10.1136/bjophthalmol-2013-304405
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AN3OG
UT WOS:000340497200015
PM 24659351
DA 2022-11-30
ER

PT J
AU Lee, HS
   Jun, JH
   Jung, EH
   Koo, BA
   Kim, YS
AF Lee, Hak Sung
   Jun, Jae-Hyun
   Jung, Eun-Ha
   Koo, Bon Am
   Kim, Yeong Shik
TI Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and
   Vascular Permeability in Human Retinal Pigment Epithelial and Human
   Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and
   VEGF Activation
SO MOLECULES
LA English
DT Article
DE EGCG; ARPE-19; HRMEC; ocular neovascularization; vascular permeability;
   MMP-9; VEGF
ID ANGIOGENESIS IN-VITRO; GROWTH-FACTOR; GREEN-TEA; CORNEAL
   NEOVASCULARIZATION; MATRIX METALLOPROTEINASE-2; DIABETIC-RETINOPATHY;
   BARRIER BREAKDOWN; OXIDATIVE STRESS; EPIGALLOCATECHIN-3-GALLATE;
   EXPRESSION
AB Epigalloccatechin-3-gallate (EGCG) is the main polyphenol component of green tea (leaves of Camellia sinensis). EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a key role in the processes of extracellular matrix (ECM) remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF-alpha) in human retinal pigment epithelial cells (HRPECs). EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2) by inhibiting generation of reactive oxygen species (ROS). EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs). Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31) on corneal neovascularization (CNV) induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.
C1 [Lee, Hak Sung; Kim, Yeong Shik] Seoul Natl Univ, Coll Pharm, Inst Nat Prod Res, Seoul 151742, South Korea.
   [Lee, Hak Sung; Jun, Jae-Hyun; Jung, Eun-Ha; Koo, Bon Am] Samil Pharmaceut Co Ltd, Res Ctr, Ansan 425852, South Korea.
C3 Seoul National University (SNU)
RP Koo, BA (通讯作者)，Samil Pharmaceut Co Ltd, Res Ctr, 216 Sandan Ro, Ansan 425852, South Korea.
EM mildpeople@snu.ac.kr; wogustodrkr@nate.com; eunha.jung@samil-pharm.com;
   bakoo9@samil-pharm.com; kims@snu.ac.kr
FU Samil Pharmaceuticals, Korea
FX This study was supported by a grant from Samil Pharmaceuticals, Korea.
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NR 47
TC 62
Z9 62
U1 0
U2 17
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD AUG
PY 2014
VL 19
IS 8
BP 12150
EP 12172
DI 10.3390/molecules190812150
PG 23
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA AO6ZW
UT WOS:000341502600081
PM 25123184
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Nolan, JM
   Loskutova, E
   Howard, AN
   Moran, R
   Mulcahy, R
   Stack, J
   Bolger, M
   Dennison, J
   Akuffo, KO
   Owens, N
   Thurnham, DI
   Beatty, S
AF Nolan, John M.
   Loskutova, Ekaterina
   Howard, Alan N.
   Moran, Rachel
   Mulcahy, Riona
   Stack, Jim
   Bolger, Maggie
   Dennison, Jessica
   Akuffo, Kwadwo Owusu
   Owens, Niamh
   Thurnham, David I.
   Beatty, Stephen
TI Macular Pigment, Visual Function, and Macular Disease among Subjects
   with Alzheimer's Disease: An Exploratory Study
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Article
DE Age-related macular degeneration; Alzheimer's disease; cognitive
   function; contrast sensitivity; lutein; meso-zeaxanthin; visual
   function; zeaxanthin
ID AGE-RELATED MACULOPATHY; OPTICAL-DENSITY; RISK-FACTORS; LUTEIN
   SUPPLEMENTATION; COGNITIVE PERFORMANCE; WORKING-MEMORY; HUMAN PLASMA;
   EYE DISEASE; CAROTENOIDS; ZEAXANTHIN
AB Background: The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MP's constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MP's constituent carotenoids are also important for cognitive function.
   Objective: To investigate if patients with Alzheimer's disease (AD) are comparable to controls in terms of MP and visual function.
   Methods: 36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis (R)); cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed.
   Results: In the AD group, central MP (i.e., at 0.23 degrees) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all).
   Conclusion: AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited.
C1 [Nolan, John M.; Loskutova, Ekaterina; Moran, Rachel; Stack, Jim; Dennison, Jessica; Akuffo, Kwadwo Owusu; Owens, Niamh; Beatty, Stephen] Waterford Inst Technol, Dept Chem & Life Sci, Macular Pigment Res Grp, Waterford, Ireland.
   [Howard, Alan N.] Howard Fdn, Cambridge, England.
   [Howard, Alan N.] Univ Cambridge, Downing Coll, Cambridge, England.
   [Mulcahy, Riona; Bolger, Maggie] Waterford Reg Hosp, Age Related Care Unit, Waterford, Ireland.
   [Thurnham, David I.] Univ Ulster, NICHE, Coleraine BT52 1SA, Londonderry, North Ireland.
C3 South East Technological University (SETU); University of Cambridge;
   Ulster University
RP Nolan, JM (通讯作者)，Waterford Inst Technol, Vis Res Ctr, Macular Pigment Res Grp, Carriganore House,West Campus, Waterford, Ireland.
EM jmnolan@wit.ie
RI Dennison, Jessica/AAG-1199-2020; Akuffo, Kwadwo Owusu/J-2036-2019;
   Nolan, John/N-4921-2014
OI Akuffo, Kwadwo Owusu/0000-0001-6683-249X; Loskutova,
   Ekaterina/0000-0002-2438-9036; Nolan, John/0000-0002-5503-7084; Moran,
   Rachel/0000-0003-0501-5431; Dennison, Jessica/0000-0001-8793-9237
FU Howard Foundation, Cambridge, CB22 5LA, United Kingdom
FX We would like to thank the Howard Foundation, Cambridge, CB22 5LA,
   United Kingdom for supporting this research. We would like to
   acknowledge Dr. Robert Coen from the Mercer's Institute for Successful
   Ageing, St. James's Hospital, Dublin, Ireland for his assistance and
   advice with the measurements of cognitive function. We would like to
   acknowledge Cambridge Cognition, UK for guidance with respect to the
   assessment of cognitive function. Also, we would like to thank all the
   staff at the Waterford Regional Hospital, Age-Related Care Unit and at
   the Vision Research Centre, Waterford Institute of Technology for
   assisting this study.
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NR 61
TC 76
Z9 79
U1 0
U2 22
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 2014
VL 42
IS 4
BP 1191
EP 1202
DI 10.3233/JAD-140507
PG 12
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA AR7ME
UT WOS:000343763000008
PM 25024317
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Sparrow, JR
   Gregory-Roberts, E
   Yamamoto, K
   Blonska, A
   Ghosh, SK
   Ueda, K
   Zhou, JL
AF Sparrow, Janet R.
   Gregory-Roberts, Emily
   Yamamoto, Kazunori
   Blonska, Anna
   Ghosh, Shanti Kaligotla
   Ueda, Keiko
   Zhou, Jilin
TI The bisretinoids of retinal pigment epithelium
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE A2E; All-trans-retinal; Bisretinoid; Retinal pigment epithelium; Macular
   degeneration; Retina
ID RECESSIVE STARGARDT-DISEASE; AGE-RELATED-CHANGES; PHOTORECEPTOR OUTER
   SEGMENTS; SINGLET-OXYGEN GENERATION; DYSTROPHY PROTEIN ELOVL4; ABC
   TRANSPORTER ABCA4; FACTOR-H POLYMORPHISM; LIGHT-INDUCED DAMAGE; CONE-ROD
   DYSTROPHY; MACULAR DEGENERATION
AB The retina exhibits an inherent autofluorescence that is imaged ophthalmoscopically as fundus autofluorescence. In clinical settings, fundus autofluorescence examination aids in the diagnosis and follow-up of many retinal disorders. Fundus autofluorescence originates from the complex mixture of bisretinoid fluorophores that are amassed by retinal pigment epithelial (RPE) cells as lipofuscin. Unlike the lipofuscin found in other cell-types, this material does not form as a result of oxidative stress. Rather, the formation is attributable to non-enzymatic reactions of vitamin A aldehyde in photoreceptor cells: transfer to RPE occurs upon phagocytosis of photoreceptor outer segments. These fluorescent pigments accumulate even in healthy photoreceptor cells and are generated as a consequence of the light capturing function of the cells. Nevertheless, the formation of this material is accelerated in some retinal disorders including recessive Stargardt disease and ELOVL4-related retinal degeneration. As such, these bisretinoid side-products are implicated in the disease processes that threaten vision. In this article, we review our current understanding of the composition of RPE lipofuscin, the structural characteristics of the various bisretinoids, their related spectroscopic features and the biosynthetic pathways by which they form. We will revisit factors known to influence the extent of the accumulation and therapeutic strategies being used to limit bisretinoid formation. Given their origin from vitamin A aldehyde, an isomer of the visual pigment chromophore, it is not surprising that the bisretinoids of retina are light sensitive molecules. Accordingly, we will discuss recent findings that implicate the photodegradation of bisretinoid in the etiology of age-related macular degeneration. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Sparrow, Janet R.; Gregory-Roberts, Emily; Yamamoto, Kazunori; Blonska, Anna; Ghosh, Shanti Kaligotla; Ueda, Keiko; Zhou, Jilin] 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
FU National Institutes of Health [EY12951, P30EY019007]; Research to
   Prevent Blindness; Carl Marshall Reeves and Mildred Almen Reeves
   Foundation; Endeavour Australia Research Fellowship; Lucy Falkiner
   Fellowship; NATIONAL EYE INSTITUTE [P30EY019007, R01EY012951] Funding
   Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants EY12951
   (JRS) and P30EY019007 and a grant from Research to Prevent Blindness to
   the Department of Ophthalmology. The Carl Marshall Reeves and Mildred
   Almen Reeves Foundation provided funds for equipment. EGR was supported
   by an Endeavour Australia Research Fellowship and Lucy Falkiner
   Fellowship. Drs. Yalin Wu, Emiko Yanase, Chul Young Kim and Kee Dong
   Yoon are acknowledged for contributions.
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NR 134
TC 259
Z9 263
U1 3
U2 35
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAR
PY 2012
VL 31
IS 2
BP 121
EP 135
DI 10.1016/j.preteyeres.2011.12.001
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 910GC
UT WOS:000301624200001
PM 22209824
OA Green Accepted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Bittencourt, ZZLD
   Montilha, RDL
   Gasparetto, MERF
   Temporini, ER
   de Carvalho, KMM
AF Lourenco de Camargo Bittencourt, Zelia Zilda
   Letto Montilha, Rita de Cassia
   Rodrigues Freire Gasparetto, Maria Elisabete
   Temporini, Edmea Rita
   Monteiro de Carvalho, Keila Miriam
TI Diabetic retinopathy and visual disabilities among patients in a
   rehabilitation program
SO REVISTA BRASILEIRA DE OFTALMOLOGIA
LA English
DT Article
DE Diabetes mellitus; Blindness; Vision, low; Vision
   disorders/rehabilitation; Quality of life
ID PREVALENCE; MELLITUS
AB Objective: To assess the prevalence of diabetic retinopathy and to evaluate the management of patients with visual disabilities attending at the CEPRE Rehabilitation Program of University of Campinas. Methods: A retrospective study was carried out based on medical records of patients with visual disabilities attending a vision rehabilitation program. The following variables were studied: gender, age, marital status, level of schooling, social security status, origin, type and cause of visual disability and vision rehabilitation actions. Results: The sample consisted of 155 patients, 55.5% males, aged between 12 and 88 years, mean age 41 years old, 34.8% were blind and 65.2% with low vision disability. Of those blind patients, 81.8% reported acquired blindness, and the leading cause was diabetic retinopathy (33.3%), followed by glaucoma (16.6%), and retinal detachment (15.0%). Of those patients with low vision disability, 14.9% had diabetic retinopathy, 14.9% hereditary syndromes, and 10.9% age-related macular degeneration. Vision rehabilitation therapy included interdisciplinary team consultations helping patients go through the mourning process for the loss or impairment of vision, and promoting the enhancement of their skills for performing activities of daily living independently. The management of patients with low vision was also focused on vision rehabilitation. Conclusion: The health of the eyes of patients with chronic diseases such as diabetes is at risk. The prevalence of diabetic retinopathy was found to be a cause for visual disability, suggesting the need to assess these patients' access to health care and rehabilitation and promote health education for changing habits and improving quality of life.
C1 [Lourenco de Camargo Bittencourt, Zelia Zilda; Letto Montilha, Rita de Cassia; Rodrigues Freire Gasparetto, Maria Elisabete; Temporini, Edmea Rita; Monteiro de Carvalho, Keila Miriam] Univ Estadual Campinas, UNICAMP, Fac Ciencias Med, Ctr Rehabil Studies CEPRE, Campinas, SP, Brazil.
C3 Universidade Estadual de Campinas
RP Bittencourt, ZZLD (通讯作者)，Rua Tessalia Vieira de Camargo 126, BR-13083887 Campinas, SP, Brazil.
EM zeliaz@fcm.unicamp.br
OI Montilha, Rita/0000-0003-3741-0006
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   World Health Organization, 1994, WHO TECHN REP SER, V844
   World Health Organization, DIAB MELL FACT SHEET
NR 27
TC 3
Z9 7
U1 0
U2 2
PU SOC BRASILEIRA OFTALMOLOGIA
PI RIO DE JANEIRO
PA RUA SAO SALVADOR 107, RIO DE JANEIRO, 22231-170, BRAZIL
SN 0034-7280
J9 REV BRAS OFTALMOL
JI Rev. Bras. Oftalmol.
PD NOV-DEC
PY 2011
VL 70
IS 6
BP 342
EP 348
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 889FT
UT WOS:000300059700002
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Peng, XJ
   Su, LP
AF Peng Xi-jia
   Su Lan-ping
TI Characteristics of fundus autofluorescence in cystoid macular edema
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE cystoid macular edema; fundus autofluorescence; lipofuscin; retinal
   pigment epithelium; fundus fluorescein angiography
ID SCANNING LASER OPHTHALMOSCOPE; RETINAL-PIGMENT EPITHELIUM; GEOGRAPHIC
   ATROPHY; DEGENERATION; LIPOFUSCIN; PATTERNS; EYES
AB Background Fundus autofluorescence (FAF) imaging is a fast and noninvasive technique developed over the last decade.. The authors utilized fluorescent properties of lipofuscin to study the health and viability of the retinal pigment epithelium (RPE)-photoreceptor complex. Observing the intensity and distribution of FAF of various retinal diseases is helpful for ascertaining diagnosis and evaluating prognosis. In this study, we described the FAF characteristics of cystoid macular edema (CME).
   Methods Sixty-two patients (70 eyes) with CME were subjected to FAF and fundus fluorescein angiography (FFA) by a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2 (HRA2)). Characteristics of FAF images were compared with FFA images.
   Results FAF intensity in normal subjects was highest at the posterior pole and dipped at the fovea. All cases of CME showed fluorescein dye accumulated into honeycomb-like spaces in macular and formated a typical petaloid pattern or atypical petaloid pattern in the late phases of the angiography. Sixty-one eyes with CME on FAF images showed mild or moderate hyperautofluorescence petaloid pattern in fovea, the FAF patterns of these CME was perfectly corresponding with shape in their FFA images; nine eyes with CME secondary to exudative age related macular degeneration (AMD) showed expansion of the hypoautofluorescence without petaloid pattern in macula.
   Conclusion FAF imaging can be used as a new rapid, non-invasive and ancillary technique in the diagnosis of the majority of CME, except for AMD and small part of other fundus diseases. Chin Med J 2011;124(2):253-257
C1 [Peng Xi-jia; Su Lan-ping] Rehabil Ctr Hosp Gansu, Dept Ophthalmol, Lanzhou 730000, Gansu, Peoples R China.
RP Peng, XJ (通讯作者)，Rehabil Ctr Hosp Gansu, Dept Ophthalmol, Lanzhou 730000, Gansu, Peoples R China.
EM xijiapeng480@sohu.com
FU Science and Technology Support Project of Gansu Province [090NKCA093]
FX This study was supported by a grant from the Science and Technology
   Support Project of Gansu Province (No. 090NKCA093).
CR Bessho K, 2009, GRAEF ARCH CLIN EXP, V247, P729, DOI 10.1007/s00417-008-1033-y
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NR 20
TC 5
Z9 5
U1 0
U2 1
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD JAN 20
PY 2011
VL 124
IS 2
BP 253
EP 257
DI 10.3760/cma.j.issn.0366-6999.2011.02.019
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 714DI
UT WOS:000286787300021
PM 21362376
DA 2022-11-30
ER

PT J
AU Costagliola, C
   Semeraro, F
   Cipollone, U
   Rinaldi, M
   della Corte, M
   Romano, MR
AF Costagliola, Ciro
   Semeraro, Francesco
   Cipollone, Ugo
   Rinaldi, Michele
   della Corte, Michele
   Romano, Mario R.
TI Changes in neovascular choroidal morphology after intravitreal
   bevacizumab injection: prospective trial on 156 eyes throughout 12-month
   follow-up
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Choroidal neovascularization; Bevacizumab; Age-related macular
   degeneration; Anti-VEGF
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; SUBGROUP ANALYSIS;
   AVASTIN; RANIBIZUMAB; SECONDARY; MECHANISMS; THERAPY; MARINA
AB To report 12-month follow-up results of 156 eyes treated with anti-VEGF for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration, and to verify the efficacy of this treatment in terms of functional results and changes of morphology of choroidal membrane for the different types of choroidal neovascularization analyzed.
   This prospective case series study included subjects with different forms of subfoveal CNV. After the first intravitreal injection of 1.25 mg bevacizumab at baseline, re-injections of bevacizumab were scheduled at least 4 weeks after initial treatment following standardized criteria.
   One hundred and fifty six patients were divided into two study groups: 60 eyes with classic CNV (group C) and 96 eyes with occult CNV (group O). The improvement in BCVA was greater in group C than group O, although the difference was not statistically significant (P = 0.26). The area of CNV and subretinal fibrous tissue/disciform scar remained stable over time in both groups. The macular thickness significantly decreased through the follow-up period in both groups. The hyper-reflective area of the neovascular complex remained stable in both groups during the first 6 months of follow-up, whereas a slight increase of hyper-reflective lesion size occurred throughout the second 6 months of follow-up.
   The CNV lesion treated with IVB didn't disappear in neither group, but showed less exudation, demonstrated by a decrease in the area of leakage from CNV, subretinal fluid area, and centre point retinal thickness on OCT.
C1 [Semeraro, Francesco] Univ Brescia, Clin Oculist, Brescia, Italy.
   [Cipollone, Ugo] Osped G Vietri, Dipartimento Oftalmol, Campobasso, Italy.
   [Rinaldi, Michele; della Corte, Michele] Univ Naples 2, Dipartimento Oftalmol, Naples, Italy.
   [Costagliola, Ciro; Romano, Mario R.] Univ Molise, Dipartimento Sci Salute, I-86100 Campobasso, Italy.
C3 University of Brescia; Universita della Campania Vanvitelli; University
   of Molise
RP Romano, MR (通讯作者)，Univ Molise, Dipartimento Sci Salute, Via F De Sanctis, I-86100 Campobasso, Italy.
EM romanomario@email.it
RI Costagliola, Ciro/G-5707-2012; Romano, Mario R/I-8320-2012; Semeraro,
   Francesco fs/K-8667-2016
OI Costagliola, Ciro/0000-0001-8477-6188; Semeraro, Francesco
   fs/0000-0002-2275-4917
CR Aisenbrey S, 2007, GRAEF ARCH CLIN EXP, V245, P941, DOI 10.1007/s00417-006-0471-7
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NR 26
TC 13
Z9 13
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 AUG
PY 2009
VL 247
IS 8
BP 1031
EP 1037
DI 10.1007/s00417-009-1081-y
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 469KK
UT WOS:000267896700004
PM 19404665
DA 2022-11-30
ER

PT J
AU Rudolf, M
   Curcio, CA
AF Rudolf, Martin
   Curcio, Christine A.
TI Esterified Cholesterol Is Highly Localized to Bruch's Membrane, as
   Revealed by Lipid Histochemistry in Wholemounts of Human Choroid
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE Bruch's membrane; wholemount; lipids; cholesterol; aging; age-related
   maculopathy
ID POLYENE ANTIBIOTICS; NILE RED; AGE; DEPOSITS; DRUSEN; ACCUMULATION;
   FLUORESCENCE; PARTICLES; FILIPIN; AMD
AB Accumulation of neutral lipids in Bruch's membrane (BrM) is a major a e g change in human retina and contributes to the formation of extracellular lesions associated with age-related macular degeneration. We developed a BrM-choroid wholemounting technique suitable for reliable staining and evaluated different fluorescent lipid dyes for topographic semiquantitative analysis of BrM lipids. Thin BrM-choroid complexes with partially stripped choroid from 10 aged donor eyes were prepared with an optimized wholemounting technique. Preparation quality was monitored by examining 1-mu m-thick sections of representative samples. The staining patterns of Nile Red, BODIPY 493/503, filipin for unesterified cholesterol (UC-F), filipin for esterified cholesterol (EC-F), and Oil Red 0 in wholemounts were compared with their staining patterns in chorioretinal sections, using wide-field epi-fluorescence microscopy. Wholemounts exhibited optimal flatness on the BrM side. Reduced tissue thickness-allowed reliable dye penetration and staining of BrM. Only EC-F was with high specificity localized to BrM and demonstrated an intense and distinct granular staining pattern not previously appreciated in chorioretinal sections. All other lipid dyes also stained choroidal or retinal tissue intensely. No dye provided perfect characteristics in regard to representing all neutral lipid classes present in BrM or to fluorescence intensity. Nevertheless, only EC-F was highly localized to BrM with a specific granular pattern. Because direct assays indicate that esterified cholesterol is abundantly present in BrM, we consider EC-F the most valuable choice for analyzing neutral lipid deposits inhuman BrM. (J Histochem Cytochem 57:731-739, 2009)
C1 [Rudolf, Martin] Univ Klinikum Schleswig Holstein, Univ Eye Hosp Lubeck, D-23538 Lubeck, Germany.
   Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Alabama System; University of Alabama Birmingham
RP Rudolf, M (通讯作者)，Univ Klinikum Schleswig Holstein, Univ Eye Hosp Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM martin.rudolf@uk-sh.de
FU Macula Vision Research Foundation; Deutsche Forschungsgemeinschaft [DFG
   13942]; Research to Prevent Blindness
FX This project was supported by the Macula Vision Research Foundation,
   Deutsche Forschungsgemeinschaft (DFG 13942), and Research to Prevent
   Blindness.; We thank Susan Vogt, M.Sc., and Melissa Chimento, B.Sc., for
   technical assistance. We also thank the Alabama Eye Bank for timely
   retrieval of donor eyes.
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NR 34
TC 58
Z9 59
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
EI 1551-5044
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD AUG
PY 2009
VL 57
IS 8
BP 731
EP 739
DI 10.1369/jhc.2009.953448
PG 9
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 472HU
UT WOS:000268122000003
PM 19365091
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Hu, WZ
   Criswell, MH
   Ottlecz, A
   Cornell, TL
   Danis, RP
   Lambrou, GN
   Ciulla, TA
AF Hu, WZ
   Criswell, MH
   Ottlecz, A
   Cornell, TL
   Danis, RP
   Lambrou, GN
   Ciulla, TA
TI Oral administration of lumiracoxib reduces choroidal neovascular
   membrane development in the rat laser-trauma model
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 GENE-EXPRESSION;
   RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; THERAPEUTIC
   ARTHRITIS RESEARCH; RANDOMIZED CONTROLLED-TRIAL; MACULAR DEGENERATION;
   TUMOR ANGIOGENESIS; MESSENGER-RNA; MOLECULAR PATHOLOGY
AB Purpose: To determine whether lumiracoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that exhibits anti-inflammatory and antiangiogenic properties, can inhibit experimental choroidal neovascular membrane (CNVM) development induced by focal laser trauma in a well-characterized Brown Norway rat CNVM model.
   Methods: Over a 35-day period, 24 rats received daily oral gavage dosages of 20 mg/kg lumiracoxib in a 0.5% (w/v) suspension of sodium carboxymethylcellulose (CMC), while a control group received the 0.5% CMC suspension only. After 7 days, eight laser photocoagulation sites were placed concentrically around the optic disk to induce CNVMs. Thirty-five days later, fundus photography and fluorescein angiography (FA) were performed and eyes were processed for histopathologic analysis.
   Results: Masked FA grading of lesion sites revealed a small, but statistically significant difference (P < 0.0001) in late stage staining intensity and leakage between the mean group scores of treated (1.4) and control (1.7) eyes. Histopathologic analysis demonstrated that the mean CNVM thickness +/- SD of 38 +/- 19 mu m (n = 24 eyes, 175 photocoagulation sites) in the lumiracoxib-treated animals was reduced by 30% (P < 0.001) compared to the CNVM mean thickness +/- SD of 54 +/- 20 mu m (n = 24 eyes, 171 photocoagulation sites) in the control animals.
   Conclusion: Systemic administration of the selective COX-2 inhibitor lumiracoxib results in a partial but significant reduction in CNVM development in the rat laser-trauma model and thus may be clinically beneficial as a potential inhibitor of CNVM formation in exudative age-related macular degeneration.
C1 Indiana Univ, Sch Med, Dept Ophthalmol, Retinal Serv Res Labs, Indianapolis, IN 46202 USA.
   Novartis, Inst Biomed Res, Basel, Switzerland.
C3 Indiana University System; Indiana University-Purdue University
   Indianapolis; Novartis; Universita della Svizzera Italiana
RP Criswell, MH (通讯作者)，Indiana Univ, Sch Med, Dept Ophthalmol, Retinal Serv Res Labs, 702 Rotary Circle, Indianapolis, IN 46202 USA.
EM mcriswel@iupui.edu
RI Ciulla, Thomas/AAA-1299-2020
OI Ciulla, Thomas/0000-0001-5557-6777
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NR 83
TC 23
Z9 28
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 2005
VL 25
IS 8
BP 1054
EP 1064
DI 10.1097/00006982-200512000-00015
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 008AQ
UT WOS:000235013000015
PM 16340537
DA 2022-11-30
ER

PT J
AU Yu, XR
   Tang, YH
   Li, F
   Frank, MB
   Huang, H
   Dozmorov, I
   Zhu, YP
   Centola, M
   Cao, W
AF Yu, XR
   Tang, YH
   Li, F
   Frank, MB
   Huang, H
   Dozmorov, I
   Zhu, YP
   Centola, M
   Cao, W
TI Protection against hydrogen peroxide-induced cell death in cultured
   human retinal pigment epithelial cells by 17 beta-estradiol: A
   differential gene expression profile
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE estrogen; retina; gene
ID MITOCHONDRIAL-DNA DAMAGE; ESTROGEN-RECEPTOR; MACULAR DEGENERATION;
   KINASE-A; AGE; APOPTOSIS; GENDER
AB It has been demonstrated that estrogen receptors are present in the retinal pigment epithelium (RPE)-choroids complex regardless of sex. This suggests that estrogen could play a functional role in the outer retina, especially the RPE. To gain further insights on the molecular mechanisms differentially activated by 17 beta-estradiol (beta E2) in RPE cells, we investigated gene expression changes in response to beta E2 in cultured RPE cells using cDNA microarray technology. A total of 47 genes among 21,329 human genes are significantly altered in response to beta E2 treatment in RPE cells. Among these 47 altered genes, 34 are up-regulated and 13 are down-regulated by beta E2. The products of 34 genes have a known or suspected function. These functions belong to various categories, including caspases; extracellular matrix proteins; metabolism pathway components; GTP/GDP exchangers and G-protein GTPase activity modulators; transcription activators and repressors. Six genes which may contribute to the unique functions of the RPE cells have been validated by both quantitative real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR. In addition, we also demonstrated that beta E2 quenches H2O2-induced up-regulation of apoptosis-related protein, and protects RPE cell degeneration. These results indicate that estrogen regulates functions of RPE cells and is involved in the maintaining and survival of RPE cells during oxidative stress, and its deficiency during menopause period may be a factor contributing to the development of age-related macular degeneration in elderly women. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA.
   Xi An Jiao Tong Univ, Sch Med, Dept Biochem & Mol Biol, Key Lab Environm & Genes Related Dis,Minist Educ, Xian 710061, Peoples R China.
   Oklahoma Med Res Fdn, Microarray Res Facil, Oklahoma City, OK 73104 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; Xi'an Jiaotong University; Oklahoma Medical Research Foundation
RP Cao, W (通讯作者)，Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Dean A McGee Eye Inst, 608 Stanton L Young Blvd, Oklahoma City, OK 73104 USA.
EM wei-cao@ouhsc.edu
FU NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017703, P20RR015577,
   P20RR020143, P20RR016478] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [P30EY012190, R03EY014427] Funding Source: NIH RePORTER; NCRR
   NIH HHS [P20 RR16478-04, P20 RR15577, P20 RR020143, P20 RR17703] Funding
   Source: Medline; NEI NIH HHS [EY014427, EY12190] Funding Source:
   Medline; PHS HHS [01700172] Funding Source: Medline
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NR 37
TC 31
Z9 36
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0047-6374
EI 1872-6216
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD NOV
PY 2005
VL 126
IS 11
BP 1135
EP 1145
DI 10.1016/j.mad.2005.05.005
PG 11
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA 978BI
UT WOS:000232846800001
PM 16029884
DA 2022-11-30
ER

PT J
AU Silva, RM
   de Abreu, JRF
   Travassos, A
   Cunha-Vaz, JG
AF Silva, RM
   de Abreu, JRF
   Travassos, A
   Cunha-Vaz, JG
TI Stabilization of visual acuity with photodynamic therapy in eyes with
   chorioretinal anastomoses
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RANDOMIZED CLINICAL-TRIALS;
   MACULAR DEGENERATION; OCCULT; VERTEPORFIN; DETACHMENTS
AB Purpose. (1) To evaluate, in a non-randomized, institutional, prospective study, the efficacy of photodynamic therapy with Visudyne (PDT) in neovascular age-related macular degeneration (AMD) eyes with chorioretinal anastomoses (CRA). (2) To review, in a retrospective study and for comparison, the natural evolution of neovascular AMD eyes with CRA. Methods. Prospective clinical and angiographic study of 17 consecutive eyes with CRA, treated with PDT. Retrospective clinical and angiographic study of the natural course of 17 consecutive patients with CRA. Masked best-corrected visual acuity (VA) and angiographic features at baseline and during the period of one year were evaluated. Results. The two groups presented similar characteristics at baseline regarding age, sex, initial VA, duration of follow-up and angiographic features. PDT-treated eyes showed, at 1-year follow-up, VA stabilization or improvement in 73.3% of the eyes, no cases with very severe VA loss, and no fluorescein leakage in 46.6% of the eyes. In contrast, at 1-year follow-up the natural evolution of CRA was characterized by severe or very severe VA loss in 69% of the eyes and statistically significant mean VA loss (P=0.001) with persistence of fluorescein leakage in all cases. Conclusion. The natural history of AMD eyes with CRA leads to progressive and dramatic VA loss, which is associated with blindness in most of the cases. PDT with verteporfin can offer some benefit to these patients, allowing VA stabilization or improvement in more than two thirds of the cases, at one year.
C1 Univ Hosp Coimbra, Dept Ophthalmol, P-3000 Coimbra, Portugal.
   Surg Ctr Coimbra, Coimbra, Portugal.
   AIBILI, Coimbra, Portugal.
   Univ Coimbra, Fac Med, Inst Biomed Res Light & Image, Ctr Ophthalmol, Coimbra, Portugal.
C3 Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra
   (CHUC); Universidade de Coimbra; Universidade de Coimbra
RP Silva, RM (通讯作者)，Univ Hosp Coimbra, Dept Ophthalmol, Praceta Mota Pinto, P-3000 Coimbra, Portugal.
EM rufino.silva@oftalmologia.co.pt
RI Silva, Rufino M/J-2817-2012
OI Silva, Rufino M/0000-0001-8676-0833; Cunha-Vaz, Jose/0000-0002-0947-9850
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NR 10
TC 20
Z9 20
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 MAY
PY 2004
VL 242
IS 5
BP 368
EP 376
DI 10.1007/s00417-003-0844-0
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 820OE
UT WOS:000221398300002
PM 14758484
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Bressler, NM
   Bressler, SB
   Congdon, NG
   Ferris, FL
   Friedman, DS
   Klein, R
   Lindblad, AS
   Milton, RC
   Seddon, JM
AF Bressler, NM
   Bressler, SB
   Congdon, NG
   Ferris, FL
   Friedman, DS
   Klein, R
   Lindblad, AS
   Milton, RC
   Seddon, JM
CA Age Related Eye Dis Study Res Grp
TI Potential public health impact of Age-Related Eye Disease Study results
   - AREDS Report No. 11
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PREVALENCE
AB Objective: To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States.
   Methods: The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS.
   Results: An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300 000 (95% confidence interval, 158000-487000) of them would avoid advanced AMD and any associated vision loss during the next 5 years.
   Conclusion: If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.
OI Friedman, David/0000-0002-2055-5797; Ferris,
   Frederick/0000-0002-4933-0639
FU NATIONAL EYE INSTITUTE [Z01EY000394] Funding Source: NIH RePORTER; NEI
   NIH HHS [Z01 EY000394-03] Funding Source: Medline
CR Friedman DS, 1999, OPHTHALMOLOGY, V106, P1049, DOI 10.1016/S0161-6420(99)90267-1
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   KLEIN R, 1992, OPHTHALMOLOGY, V99, P933
NR 3
TC 285
Z9 289
U1 0
U2 12
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 NOV
PY 2003
VL 121
IS 11
BP 1621
EP 1624
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 741QC
UT WOS:000186467900016
PM 14609922
DA 2022-11-30
ER

PT J
AU Gensler, G
   Gore-Langton, R
   Kurinij, N
   Lindblad, AS
   Sowell, A
AF Gensler, G
   Gore-Langton, R
   Kurinij, N
   Lindblad, AS
   Sowell, A
CA Age Related Eye Dis Study Res Grp
TI The effect of five-year zinc supplementation on serum zinc, serum
   cholesterol and hematocrit in persons randomly assigned to treatment
   group in the Age-Related Eye Disease Study: AREDS report no. 7
SO JOURNAL OF NUTRITION
LA English
DT Article
DE AREDS; zinc oxide; cupric oxide; serum cholesterol; randomized trial;
   humans
ID COPPER LEVELS; DEFICIENCY; METABOLISM; MAGNESIUM; CALCIUM; RISK
AB The effects of long-term supplementation with pharmacologic doses of zinc oxide on serum levels of zinc, lipids and hematocrit have not been studied systematically to date. Eleven Clinical Centers enrolled 4757 participants from 1992 to 1998 as part of the Age-Related Eye Disease Study (AREDS). Of these, 3640 participants, aged 55-80 y, who had early-to-late age-related macular degeneration (AMD) were randomly assigned to daily supplementation with or without 80 mg of zinc as zinc oxide plus 2 mg of copper as cupric oxide to study the effects of zinc supplementation on the progression to late AMD. This paper reports on the effect of a 5-y supplementation with zinc oxide and cupric oxide on serum zinc, copper, lipids, and hematocrit for 717 participants from three clinical centers. At the 5-y exam, the median increase in serum zinc levels for participants assigned to zinc formulations was 17% compared with a 2% increase for participants not assigned to zinc (P < 0.001). The differential effect on serum zinc was observed at 1 y and remained fairly constant over the 5-y period. After 5 y, no significant differences in changes in serum hematocrit, copper or lipids were found between participants assigned to formulations containing zinc and copper, and those assigned to formulations without zinc and copper. Estimates from a modified Block Food-Frequency Questionnaire suggest the AREDS population at baseline had a zinc intake from diet similar to that of the general population.
C1 EMMES Corp, Rockville, MD 20850 USA.
C3 Emmes Corporation
RP Gensler, G (通讯作者)，EMMES Corp, 401 N Washington St,Suite 700, Rockville, MD 20850 USA.
RI SanGiovanni, John Paul/AAU-3895-2020
FU NATIONAL EYE INSTITUTE [Z01EY000394] Funding Source: NIH RePORTER; NEI
   NIH HHS [Z01 EY000394-03] Funding Source: Medline
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NR 28
TC 53
Z9 55
U1 0
U2 2
PU AMER INST NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD APR
PY 2002
VL 132
IS 4
BP 697
EP 702
PG 6
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 538ZG
UT WOS:000174844500012
PM 11925463
DA 2022-11-30
ER

PT J
AU Shin, CY
   Jeong, KW
AF Shin, Chae Young
   Jeong, Kwang Won
TI Photooxidation of A2E by Blue Light Regulates Heme Oxygenase 1
   Expression via NF-kappa B and Lysine Methyltransferase 2A in ARPE-19
   Cells
SO LIFE-BASEL
LA English
DT Article
DE retinal pigment epithelium; N-retinylidene-N-retinylethanolamine; blue
   light; NF-kappa B; heme oxygenase 1; lysine methyltransferase 2A
ID MACULAR DEGENERATION; OXIDATIVE STRESS; INDUCED SENESCENCE; INDUCED
   DAMAGE; DNA-DAMAGE; ACTIVATION; TRANSCRIPTION; APOPTOSIS; ROLES; RPE
AB Background: N-retinylidene-N-retinylethanolamine (A2E) is a component of drusen that accumulates in retinal cells and induces oxidative stress through photooxidation, such as blue light (BL). We found that the heme oxygenase 1 (HMOX1) gene responds sensitively to photooxidation by the BL of A2E in retinal pigment epithelial (RPE) cells, and we sought to identify the transcription factors and coactivators involved in the upregulation of HMOX1 by A2E and BL. Methods: A2E-laden human RPE cells (ARPE-19) were exposed to BL (430 nm). RNA sequencing was performed to identify genes responsive to BL exposure. Chromatin immunoprecipitation and RT-qPCR were performed to determine the regulation of HMOX1 transcription. Clinical transcriptome data were used to evaluate HMOX1 expression in patients with age-related macular degeneration (AMD). Results: In ARPE-19 cells, the expression of HMOX1, one of the NF-kappa B target genes, was significantly increased by A2E and BL. The binding of RELA and RNA polymerase II to the promoter region of HMOX1 was significantly increased by A2E and BL. Lysine methyltransferase 2A (MLL1) plays an important role in H3K4me3 methylation, NF-kappa B recruitment, chromatin remodeling at the HMOX1 promoter, and, subsequently, HMOX1 expression. The retinal tissues of patients with late-stage AMD showed significantly increased expression of HMOX1 compared to normal retinal tissues. In addition, the expression levels of MLL1 and HMOX1 in retinal tissues were correlated. Conclusions: Taken together, our results suggest that BL induces HMOX1 expression by activating NF-kappa B and MLL1 in RPE cells.
C1 [Shin, Chae Young; Jeong, Kwang Won] Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
C3 Gachon University
RP Jeong, KW (通讯作者)，Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, 191 Hambakmoero, Incheon 21936, South Korea.
EM kwjeong@gachon.ac.kr
FU Basic Science Research Program of the National Research Foundation of
   Korea (NRF) - Ministry of Education [NRF-2021R1A2C1011132]; Gachon
   University [GCU-202008420011]
FX This research was supported by the Basic Science Research Program of the
   National Research Foundation of Korea (NRF) funded by the Ministry of
   Education (NRF-2021R1A2C1011132) and by the Gachon University Research
   Fund of 2020 (GCU-202008420011).
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NR 63
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-1729
J9 LIFE-BASEL
JI Life-Basel
PD NOV
PY 2022
VL 12
IS 11
AR 1698
DI 10.3390/life12111698
PG 12
WC Biology; Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Microbiology
GA 6E5VR
UT WOS:000883447900001
PM 36362853
OA Green Accepted, gold
DA 2022-11-30
ER

PT J
AU Yusuf, IH
   Garrett, AM
   MacLaren, RE
   Issa, PC
AF Yusuf, Imran H.
   Garrett, Andrew M.
   MacLaren, Robert E.
   Issa, Peter Charbel
TI Retinal cadherins and the retinal cadherinopathies: Current concepts and
   future directions
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Cadherin; Protocadherin; Retina; CDHR1; CDH23; PCDH15; CDH3; Retinitis
   pigmentosa; Usher syndrome; Cone-rod dystrophy; Macular dystrophy;
   Photoreceptor; Retinal pigment epithelium; Outer segment disc; Cilium;
   Outer segment
ID CELL-ADHESION MOLECULES; AUTOSOMAL RECESSIVE DEAFNESS; JUVENILE MACULAR
   DYSTROPHY; NONSYNDROMIC HEARING-LOSS; USHER-SYNDROME; N-CADHERIN;
   GAMMA-PROTOCADHERINS; MUTANT ALLELES; PCDH15 GENE; MYOSIN VIIA
AB Cadherins are a superfamily of calcium-dependent intercellular adhesion molecules that are widely expressed in living tissues. Within the retina and retinal pigment epithelium (RPE), cadherins contribute to tissue morphogenesis, neural circuit formation, adherens junctions of the outer blood-retinal barrier, photoreceptor disc morphogenesis, maintenance and survival. Four monogenic disorders involving genes which encode cadherins have been identified as causes of inherited retinal degeneration: the retinal cadherinopathies (CDHR1, CDH23, PCDH15, CDH3). Biallelic variants in CDHR1 result in cone-rod dystrophy, rod-cone dystrophy or late-onset macular dystrophy which may be misclassified as dry age-related macular degeneration. Biallelic variants in CDH23 and PCDH15 underlie Usher Syndrome type 1D and 1F. Hypotrichosis with juvenile macular dystrophy results from biallelic variants in CDH3, which contributes to adherens tight junctions between RPE cells. In this review, we summarise the classification of cadherins, and the role of cadherins in the physiology and morphogenesis of the inner and outer retina. Cadherins expressed in primate photoreceptors (CDHR1, CDH23 and PCDH15) have evolved complex roles in outer segment disc morphogenesis and maintenance involving intracellular heterophilic interactions which are as yet incompletely characterised. We highlight what is currently unknown about the molecular function of these cadherins, and review the pathogenesis, clinical phenotype and molecular genetics of each monogenic retinal cadherinopathy. Genes regulating the expression and posttranslational modification of retinal cadherins, or those coding for as yet unidentified interacting partners, are candidates for unsolved cases of retinal degeneration. This group of disorders is potentially treatable; we summarise the likely molecular therapeutic approaches and future directions for each retinal cadherinopathy.
C1 [Yusuf, Imran H.; MacLaren, Robert E.; Issa, Peter Charbel] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
   [Yusuf, Imran H.; MacLaren, Robert E.; Issa, Peter Charbel] Oxford Eye Hosp, Oxford OX3 9DU, England.
   [Yusuf, Imran H.; MacLaren, Robert E.; Issa, Peter Charbel] John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 9DU, England.
   [Garrett, Andrew M.] Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI USA.
   [Garrett, Andrew M.] Wayne State Univ, Sch Med, Dept Ophthalmol Visual & Anat Sci, Detroit, MI USA.
C3 University of Oxford; University of Oxford; Wayne State University;
   Wayne State University
RP Issa, PC (通讯作者)，Univ Oxford, John Radcliffe Hosp, Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
EM study-enquiry@outlook.com
RI Charbel Issa, Peter/E-8935-2018
OI Charbel Issa, Peter/0000-0002-0351-6673; Garrett,
   Andrew/0000-0001-5765-2585
FU Medical Research Council, UK [MR/R000735/1]; NIHR Oxford Biomedical
   Research Centre
FX IHY: Medical Research Council, UK (MR/R000735/1) .REM & PCI: NIHR Oxford
   Biomedical Research Centre.
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NR 234
TC 2
Z9 2
U1 6
U2 10
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 2022
VL 90
AR 101038
DI 10.1016/j.preteyeres.2021.101038
PG 26
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4R5EQ
UT WOS:000856787600001
PM 35066146
DA 2022-11-30
ER

PT J
AU Limnios, IJ
   Chau, YQ
   Skabo, SJ
   Surrao, DC
   O'Neill, HC
AF Limnios, Ioannis J.
   Chau, Yu-Qian
   Skabo, Stuart J.
   Surrao, Denver C.
   O'Neill, Helen C.
TI Efficient differentiation of human embryonic stem cells to retinal
   pigment epithelium under defined conditions
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Retinal pigment epithelium; Pluripotent stem cells; Differentiation;
   Small molecules; Age-related macular degeneration
ID DIRECTING DIFFERENTIATION; MACULAR DEGENERATION; HUMAN RPE; GENERATION;
   MITF; TRANSPLANTATION; MECHANISMS; BETA; BMP
AB Age-related macular degeneration (AMD) is a highly prevalent form of blindness caused by loss death of cells of the retinal pigment epithelium (RPE). Transplantation of pluripotent stem cell (PSC)-derived RPE cells is considered a promising therapy to regenerate cell function and vision.
   Objective: The objective of this study is to develop a rapid directed differentiation method for production of RPE cells from PSC which is rapid, efficient, and fully defined and produces cells suitable for clinical use.
   Design: A protocol for cell growth and differentiation from hESCs was developed to induce differentiation through screening small molecules which regulated a primary stage of differentiation to the eyefield progenitor, and then, a subsequent set of molecules to drive differentiation to RPE cells. Methods for cell plating and maintenance have been optimized to give a homogeneous population of cells in a short 14-day period, followed by a procedure to support maturation of cell function.
   Results: We show here the efficient production of RPE cells from human embryonic stem cells (hESCs) using small molecules in a feeder-free system using xeno-free/defined medium. Flow cytometry at day 14 showed similar to 90% of cells expressed the RPE markers MITF and PMEL17. Temporal gene analysis confirmed differentiation through defined cell intermediates. Mature hESC-RPE cell monolayers exhibited key morphological, molecular, and functional characteristics of the endogenous RPE.
   Conclusion: This study identifies a novel cell differentiation process for rapid and efficient production of retinal RPE cells directly from hESCs. The described protocol has utility for clinical-grade cell production for human therapy to treat AMD.
C1 [Limnios, Ioannis J.; Chau, Yu-Qian; Skabo, Stuart J.; Surrao, Denver C.; O'Neill, Helen C.] Bond Univ, Clem Jones Ctr Regenerat Med, Gold Coast, Qld 4229, Australia.
C3 Bond University
RP Limnios, IJ; O'Neill, HC (通讯作者)，Bond Univ, Clem Jones Ctr Regenerat Med, Gold Coast, Qld 4229, Australia.
EM ilimnios@bond.edu.au; honeill@bond.edu.au
RI O'NEILL, Helen/AAW-8921-2021
OI O'NEILL, Helen/0000-0002-9506-284X
FU Clem Jones Foundation (Brisbane, Queensland, Australia); Cutmore Bequest
   to Bond University (Robina, Queensland, Australia)
FX This work was supported by philanthropic funding from the Clem Jones
   Foundation (Brisbane, Queensland, Australia) and the Cutmore Bequest to
   Bond University (Robina, Queensland, Australia).
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IS 1
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PG 14
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WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA RS6TG
UT WOS:000643908500001
PM 33883023
OA gold, Green Published
DA 2022-11-30
ER

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   Workman, Michael
   Yang, Wenxin
   Daza, Paula
   Ruano, Diego
   Dominguez-Martin, Helena
   Antonio Rodriguez-Navarro, Jose
   Du, Xue-Liang
   Brownlee, Michael A.
   Bejarano, Eloy
   Taylor, Allen
TI Autophagic receptor p62 protects against glycation-derived toxicity and
   enhances viability
SO AGING CELL
LA English
DT Article
DE aging; autophagy; glycative stress; p62; proteotoxicity
ID END-PRODUCTS; LIFE-SPAN; PHOSPHORYLATION; DEGRADATION; CONNEXINS;
   CROSSTALK; INTERPLAY; DISEASES; STRESS; SYSTEM
AB Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age-related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62-dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age-related diseases, including age-related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62-dependent autophagy offers novel potential therapeutic targets to treat AGEs-related pathologies.
C1 [Aragones, Gemma; Dasuri, Kalavathi; Olukorede, Opeoluwa; Francisco, Sarah G.; Renneburg, Carol; Rowan, Sheldon; Volkin, Jonathan; Workman, Michael; Yang, Wenxin; Bejarano, Eloy; Taylor, Allen] Tufts Univ, USDA Human Nutr Res Ctr Aging, Lab Nutr & Vis Res, Boston, MA 02111 USA.
   [Kumsta, Caroline; Hansen, Malene] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA.
   [Kageyama, Shun; Komatsu, Masaaki] Juntendo Univ, Dept Physiol, Sch Med, Bunkyo Ku, Tokyo, Japan.
   [Daza, Paula] Univ Seville, Fac Biol, Dept Biol Celular, Seville, Spain.
   [Ruano, Diego; Dominguez-Martin, Helena] Univ Seville, Fac Farm, Dept Bioquim & Biol Mol, Seville, Spain.
   [Ruano, Diego; Dominguez-Martin, Helena] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, Seville, Spain.
   [Antonio Rodriguez-Navarro, Jose] Hosp Ramon & Cajal, Inst Ramon y Cajal Invest Sanitarias, Serv Neurobiol, Dept Invest, Carretera Colmenar, Madrid, Spain.
   [Du, Xue-Liang; Brownlee, Michael A.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Bejarano, Eloy] Univ CEU Cardenal Herrera, Sch Hlth Sci, Valencia, Spain.
C3 Tufts University; United States Department of Agriculture (USDA);
   Sanford Burnham Prebys Medical Discovery Institute; Juntendo University;
   University of Sevilla; University of Sevilla; Consejo Superior de
   Investigaciones Cientificas (CSIC); University of Sevilla; CSIC-JA-USE -
   Instituto de Biomedicina de Sevilla (IBIS); Virgen del Rocio University
   Hospital; Hospital Universitario Ramon y Cajal; Yeshiva University;
   Albert Einstein College of Medicine; Universidad CEU Cardenal Herrera
RP Bejarano, E; Taylor, A (通讯作者)，Tufts Univ, USDA Human Nutr Res Ctr Aging, Lab Nutr & Vis Res, Boston, MA 02111 USA.
EM eloy.bejarano@tufts.edu; allen.taylor@tufts.edu
RI Komatsu, Masaaki/B-8321-2011; Bejarano, Eloy/AAJ-4708-2021; Aragones,
   Gemma/A-9693-2013
OI Komatsu, Masaaki/0000-0001-7672-7722; Bejarano,
   Eloy/0000-0001-8390-1581; Francisco, Sarah/0000-0001-9794-1533;
   Aragones, Gemma/0000-0002-1924-9231
FU NIH [R01AG028664, R21AG058038, R01EY021212, R01EY026979, R01EY028559];
   Thome Memorial Foundation; USDA [8050-51000-089-01S]; BrightFocus
   Foundation; Human Nutrition Research Center on Aging; USDA NIFA
   [2016-08885]; MINECO SAF [2016 78666-R]
FX NIH, Grant/Award Number: R01AG028664, R21AG058038, R01EY021212,
   R01EY026979 and R01EY028559; Thome Memorial Foundation; USDA,
   Grant/Award Number: 8050-51000-089-01S; BrightFocus Foundation; Human
   Nutrition Research Center on Aging; USDA NIFA, Grant/Award Number:
   2016-08885; MINECO SAF, Grant/Award Number: 2016 78666-R
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NR 46
TC 14
Z9 14
U1 1
U2 12
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD NOV
PY 2020
VL 19
IS 11
AR e13257
DI 10.1111/acel.13257
EA NOV 2020
PG 17
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA PA5EA
UT WOS:000584687700001
PM 33146912
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Herranz-Heras, JC
   de-Pablo-Cabrera, A
   Alonso-Martin, B
   de-Lucas-Viejo, B
   de-Castro-Liebana, M
   Mencia-Gutierrez, E
   Ferro-Osuna, MJ
   Romero, C
   Sambricio, J
AF Herranz-Heras, Juan-Carlos
   de-Pablo-Cabrera, Almudena
   Alonso-Martin, Beatriz
   de-Lucas-Viejo, Beatriz
   de-Castro-Liebana, Marta
   Mencia-Gutierrez, Enrique
   Ferro-Osuna, Manuel-Jesus
   Romero, Carmen
   Sambricio, Javier
TI Evaluation of Anxiety Levels in Patients Undergoing Intravitreal
   Injections and Associated Risk Factors Related to the Disease
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VISUAL ANALOG SCALE; QUALITY-OF-LIFE; PREOPERATIVE ANXIETY; DEPRESSION;
   SURGERY
AB Purpose. To analyze patients' anxiety levels using the Visual Analog Scale for Anxiety (VASA), in regard to intravitreal injection treatment and to determine possible associated risk factors related to the disease and treatment characteristics. Methods. Cross-sectional observational study with consecutive sampling of patients who were going to receive an intravitreal injection. Subjects completed the VASA prior to the procedure, and afterwards, their data were collected from the electronic medical history. Analysis was performed through a linear regression model. Results. Fifty-five men and forty-seven women were enrolled. The mean age was 73.9 +/- 12.4 years (mean +/- standard deviation (SD)), and the mean +/- SD of previous injections was 12.8 +/- 12. The most frequent pathologies found were age-related macular degeneration with 46.1% and diabetic macular edema with 36.3%. The median of anxiety levels measured in millimeters (mm) was 16 (interquartile range: 0-48). In univariate models, women presented a mean of 10.8 mm of anxiety more than men (p=0.03). The adjusted multivariate analysis demonstrated that younger patients declared higher anxiety levels (p=0.036). No significant association was found between the best corrected visual acuity (BCVA) on the day of the injection, the change in BCVA since the beginning of the treatment or the number of injections received, and the registered anxiety levels. Conclusions. Sex and age may have an influence on anxiety levels. BCVA and the number ofinjections received did not seem to have an influence on our patients anxiety levels.
C1 [Herranz-Heras, Juan-Carlos; de-Pablo-Cabrera, Almudena; Alonso-Martin, Beatriz; de-Lucas-Viejo, Beatriz; de-Castro-Liebana, Marta; Mencia-Gutierrez, Enrique; Ferro-Osuna, Manuel-Jesus; Sambricio, Javier] Univ Complutense Madrid, 12 Octubre Hosp, Ophthalmol Dept, Madrid 28041, Spain.
   [Romero, Carmen] Univ Complutense Madrid, 12 Octubre Hosp, Biostat Res Inst I 12, Madrid 28041, Spain.
C3 Complutense University of Madrid; Hospital Universitario 12 de Octubre;
   Complutense University of Madrid; Hospital Universitario 12 de Octubre
RP Mencia-Gutierrez, E (通讯作者)，Univ Complutense Madrid, 12 Octubre Hosp, Ophthalmol Dept, Madrid 28041, Spain.
EM emencia.hdoc@salud.madrid.org
OI ROMERO, CARMEN/0000-0002-9125-2275; de-Pablo-Cabrera,
   Almudena/0000-0003-4591-0860; Alonso Martin,
   Beatriz/0000-0003-2478-1051; Mencia-Gutierrez,
   Enrique/0000-0001-5314-6976; Herranz-Heras, Juan
   Carlos/0000-0002-3358-5880
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NR 24
TC 1
Z9 1
U1 0
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2090-004X
EI 2090-0058
J9 J OPHTHALMOL
JI J. Ophthalmol.
PD OCT 21
PY 2020
VL 2020
AR 4375390
DI 10.1155/2020/4375390
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OU6WD
UT WOS:000591666100001
PM 33145102
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Thiele, S
   Isselmann, B
   Pfau, M
   Holz, FG
   Schmitz-Valckenberg, S
   Wu, ZC
   Guymer, RH
   Luu, CD
AF Thiele, Sarah
   Isselmann, Ben
   Pfau, Maximilian
   Holz, Frank G.
   Schmitz-Valckenberg, Steffen
   Wu, Zhichao
   Guymer, Robyn H.
   Luu, Chi D.
TI Validation of an Automated Quantification of Relative Ellipsoid Zone
   Reflectivity on Spectral Domain-Optical Coherence Tomography Images
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Article
DE reflectivity; imaging; biomarker
ID MACULAR DEGENERATION; LIGHT-SCATTERING; PROGRESSION; INTENSITY; RETINA;
   BANDS
AB Purpose: Relative ellipsoid zone reflectivity (rEZR) represents a potential biomarker of photoreceptor health on spectral-domain optical coherence tomography (SD-OCT). Because manual quantification of rEZR is laborious and lacks of spatial resolution, automated quantification of the rEZR would be beneficial. The purpose of this study was to evaluate the reliability and reproducibility of an automated rEZR quantification method.
   Methods: The rEZR was acquired using a manual and an automated approach in eyes with age-related macular degeneration (AMD) and healthy controls. The rEZR obtained from both methods was compared and the agreement between the methods and their reproducibility assessed.
   Results: Forty eyes of 40 participants with a mean (+/- standard deviation) age of 65.2 +/- 7.8 years were included. Both the manual and automated method showed that control eyes exhibit a greater rEZR than AMD eyes (P < 0.001). Overall, the limits of agreement between the manual and automated method were -7.5 to 7.3 arbitrary units (AU) and 95% of the data points had a difference in the rEZR between the methods of +/- 8.2%. An expected perfect reproducibility was observed for the automated method, whereas the manual method had a coefficient of repeatability of 6.3 arbitrary units.
   Conclusions:The automated quantification of rEZR method is reliable and reproducible. Further studies of the rEZR as a novel biomarker for AMD severity and progression are warranted.
   Translational Relevance: Automated quantification of SD-OCT-based rEZR allows for its comprehensive and longitudinal characterization evaluating its relevance as an in vivo biomarker of photoreceptor function and its prognostic value for AMD progression.
C1 [Thiele, Sarah; Isselmann, Ben; Pfau, Maximilian; Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, Dept Ophthalmol, Bonn, Germany.
   [Thiele, Sarah; Pfau, Maximilian; Holz, Frank G.; Schmitz-Valckenberg, Steffen] Univ Bonn, GRADE Reading Ctr, Bonn, Germany.
   [Pfau, Maximilian] Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA.
   [Wu, Zhichao; Guymer, Robyn H.; Luu, Chi D.] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Australia.
   [Wu, Zhichao; Guymer, Robyn H.; Luu, Chi D.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia.
C3 University of Bonn; University of Bonn; Stanford University; Centre for
   Eye Research Australia; Royal Victorian Eye & Ear Hospital; University
   of Melbourne
RP Thiele, S (通讯作者)，Univ Bonn, Dept Ophthalmol, FEBO, Venusberg Campus 1,Gebaude 04, D-53127 Bonn, Germany.
EM sarah.thiele@ukbonn.de
FU National Health & Medical Research Council of Australia [APP1027624,
   GNT1103013]; Bupa Health Foundation, Australia; BONFOR GEROK Program,
   Faculty of Medicine, University of Bonn [O-137.0026]; Maria-von-Linden
   Program, University of Bonn; Werner Jackstadt Nachwuchspreis of the
   German Retina Society; BM-AXIS program of the University of Bonn;
   University of Melbourne
FX Supported by the National Health & Medical Research Council of Australia
   (Project Grant no.: APP1027624 [RHG, CDL]; and fellowship grant nos.:
   GNT1103013 [RHG], Bupa Health Foundation, Australia (RHG, CDL), BONFOR
   GEROK Program, Faculty of Medicine, University of Bonn, Grant No
   O-137.0026 to ST; by the Maria-von-Linden Program, University of Bonn to
   ST; by the Werner Jackstadt Nachwuchspreis of the German Retina Society
   to ST and by the BM-AXIS program of the University of Bonn and
   University of Melbourne to ST. The Centre for Eye Research Australia
   receives operational infrastructure support from the Victorian
   Government.
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NR 24
TC 4
Z9 4
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD OCT
PY 2020
VL 9
IS 11
AR 17
DI 10.1167/tvst.9.11.17
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA OO8KU
UT WOS:000587624500009
PM 33133775
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Namburi, P
   Khateb, S
   Meyer, S
   Bentovim, T
   Ratnapriya, R
   Khramushin, A
   Swaroop, A
   Schueler-Furman, O
   Banin, E
   Sharon, D
AF Namburi, Prasanthi
   Khateb, Samer
   Meyer, Segev
   Bentovim, Tom
   Ratnapriya, Rinki
   Khramushin, Alisa
   Swaroop, Anand
   Schueler-Furman, Ora
   Banin, Eyal
   Sharon, Dror
TI A unique PRDM13-associated variant in a Georgian Jewish family with
   probable North Carolina macular dystrophy and the possible contribution
   of a unique CFH variant
SO MOLECULAR VISION
LA English
DT Article
ID COMPLEMENT FACTOR-H; TRANSLATIONAL MINIREVIEW SERIES; MCDR1; PHENOTYPE;
   PROTEINS; GENETICS; MUTATION; RISK; MAPS
AB Purpose: North Carolina macular dystrophy (NCMD) is an autosomal dominant maculopathy that is considered a nonprogressive developmental disorder with variable expressivity. Our study aimed to clinically and genetically characterize macular dystrophy in a family (MOL1154) consisting of six affected subjects with a highly variable maculopathy phenotype in which no correlation between age and severity exists.
   Methods: Clinical characterization included visual acuity testing and electroretinography. Genetic analysis included Sanger sequencing and whole exome sequencing (WES).
   Results: WES analysis performed on DNA samples from two individuals revealed a heterozygous deletion of six nucleotides [c.2247_2252del; p.(Leu750_Lys751del)] in the CFH gene. Co-segregation analysis revealed that five of the six NCMD affected subjects carried this deletion, while one individual who had a relatively mild phenotype compatible with dry age-related macular degeneration (AMD) did not carry it. We subsequently analyzed the upstream region of PRDM13 that has previously been reported to be associated with NCMD and identified a unique heterozygous transversion (chr6:100040974A>C) located within the previously described suspected control region in all six affected individuals. This transversion is likely to cause NCMD.
   Conclusions: NCMD has a wide spectrum of clinical phenotypes that can overlap with AMD, making it challenging to correctly diagnose affected individuals and family members. The DNA sequence variant we found in the CFH gene of some of the affected family members may suggest some role as a modifier gene. However, this variant still does not explain the huge phenotypic variability of NCMD and needs to be studied in other and larger populations.
C1 [Namburi, Prasanthi; Khateb, Samer; Meyer, Segev; Bentovim, Tom; Banin, Eyal; Sharon, Dror] Hebrew Univ Jerusalem, Fac Med, Hadassah Med Ctr, Dept Ophthalmol, Jerusalem, Israel.
   [Ratnapriya, Rinki; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [Khramushin, Alisa; Schueler-Furman, Ora] Hebrew Univ Jerusalem, Fac Med, Dept Microbiol & Mol Genet, IMRIC, Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Hadassah University Medical Center;
   National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); Hebrew University of Jerusalem
RP Sharon, D (通讯作者)，Hadassah Med Ctr, POB 12000, Jerusalem 91120, Israel.
EM dror.sharon1@mail.huji.ac.il
RI Sharon, Dror/P-4539-2015
OI Sharon, Dror/0000-0002-1789-5811; Schueler-Furman,
   Ora/0000-0002-1624-0362
FU United States-Israel Binational Science Foundation [2011202]
FX The authors thank all affected individuals and family members for their
   participation in this study. We would like also to thank Nina Schnaider
   for language editing. The study was financially supported by the United
   States-Israel Binational Science Foundation (no. 2011202, to D.S. and
   A.S.). Dr. Eyal Banin (banine@ml.huji.ac.il) and Dror
   Sharon(dror.sharon1@mail.huji.ac.il) are co-corresponding authors for
   this study.
CR Beit-Ya'acov A, 2007, INVEST OPHTH VIS SCI, V48, P4308, DOI 10.1167/iovs.07-0244
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NR 30
TC 5
Z9 5
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 16
PY 2020
VL 26
BP 299
EP 310
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA LL5CE
UT WOS:000531574000001
PM 32476814
DA 2022-11-30
ER

PT J
AU Unlu, M
   Sevim, DG
   Karaca, C
   Duzgun, B
   Oner, AO
   Mirza, E
AF Unlu, Metin
   Sevim, Duygu Gulmez
   Karaca, Cagatay
   Duzgun, Bahadir
   Oner, Ayse Ozturk
   Mirza, Ertugrul
TI Evaluation of the effect of fluorescein angiography on retinal vessel
   diameter: an optical coherence tomography study
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Article
DE Fluorescein angiography; Optical coherence tomography; Retinal vessel
   diameter
ID DIABETIC MACULAR EDEMA; INTRAVITREAL RANIBIZUMAB; BLOOD-VESSELS; AGE;
   HYPERTENSION; RETINOPATHY; PRESSURE
AB Purpose To evaluate the effect of fluorescein angiography on retinal vessel diameter with Optical Coherence Tomography (OCT).
   Methods In this cross-sectional study, a total of 81 eyes of 81 patients who were performed fluorescein angiography (FA) procedure were included. Retinal vessels were examined with the Spectral-domain OCT at baseline and immediately after FA procedure. A cube scan consisting of seven horizontal scans were placed at the inferior border of the disk to include the inferior temporal retinal vessels. Vessels diameters were measured at five measurement points (480-1440 mu m inferiorly from the optic disk border).
   Results The mean age of the study subjects was 58.02 +/- 14.1 years. At baseline, the mean diameter of the retinal artery was 120.16 +/- 24.56 lm and of the vein 157.94 +/- 32.34 lm at the measurement point of 480 lm, with a gradual decrease to 114.91 +/- 25.59 and 152.17 +/- 28.17 lm, respectively, at 1440 lm. After FA procedure, the mean diameter of the retinal artery was 122.85 +/- 26.35 and of the vein 158.30 +/- 32.21 lmat the measurement point of 480 lm, with a gradual decrease to 115.22 +/- 22.91 and 151.94 +/- 28.93 lm, respectively, at 1440 lm. There were no statistical differences for either of these comparisons at any of the points of both artery and vein measurements.
   Conclusion There was not any clinically significant change in retinal artery diameter such as a dilatatory response after FA procedure in patients with hypertension, diabetes, and age-related macular degeneration (AMD).
C1 [Unlu, Metin; Sevim, Duygu Gulmez; Karaca, Cagatay; Duzgun, Bahadir; Oner, Ayse Ozturk; Mirza, Ertugrul] Erciyes Univ, Ophthalmol Dept, Sch Med, TR-38039 Kayseri, Turkey.
C3 Erciyes University
RP Unlu, M (通讯作者)，Erciyes Univ, Ophthalmol Dept, Sch Med, TR-38039 Kayseri, Turkey.
EM drunlumetin@hotmail.com
RI Sevim, Duygu Gülmez/AAB-7286-2019
OI Sevim, Duygu Gülmez/0000-0002-1413-2528
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NR 24
TC 0
Z9 1
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0165-5701
EI 1573-2630
J9 INT OPHTHALMOL
JI Int. Ophthalmol.
PD FEB
PY 2018
VL 38
IS 1
BP 75
EP 82
DI 10.1007/s10792-016-0425-y
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GB0TQ
UT WOS:000428760800012
PM 28039673
DA 2022-11-30
ER

PT J
AU Jurisic, D
   Sesar, I
   Cavar, I
   Sesar, A
   Zivkovic, M
   Curkovic, M
AF Jurisic, Darija
   Sesar, Irena
   Cavar, Ivan
   Sesar, Antonio
   Zivkovic, Maja
   Curkovic, Marko
TI HALLUCINATORY EXPERIENCES IN VISUALLY IMPAIRED INDIVIDUALS: CHARLES
   BONNET SYNDROME - IMPLICATIONS FOR RESEARCH AND CLINICAL PRACTICE
SO PSYCHIATRIA DANUBINA
LA English
DT Review
DE visual hallucinations; Charles Bonnet syndrome; low vision; mental
   health in elderly
ID MACULAR DEGENERATION; LOW-VISION; PREVALENCE; POPULATION; PSYCHOSIS;
   DISEASE; BRAIN
AB Background: Charles Bonnet syndrome (CBS) refers to visual hallucinations that occur in individuals with preserved cognitive functions associated with visual impairment.
   Methods: This article reviews occurence of visual hallucinations in subjects with CBS by journals published in English in the Pubmed database in the period 1992-2018. Criteria for selection of appropriate papers were sufficient information and perspicuous view on pathogenesis, epidemiology, clinical presentation and treatment possibilities of CBS.
   Results: Most commonly, visual hallucinations in patients with CBS are complex, repetitive and stereotyped. Such individuals have preserved insight that those percepts are not real, and there is an absence of secondary explanatory delusions and hallucinations within other modalities. Seeing as the aforementioned percepts do not share all the characteristics of hallucinations, it remains unresolved how they should be referred to. Terms as release hallucinations, one that is reflecting its underlying pathogenesis, or confabulatory hallucinatory experiences have been proposed. Moreover, CBS has also been referred to as phantom vision syndrome and may occur in any ophthalmological disease. It is not particularly connected with loss of function along any level of the visual pathway. Although this syndrome is mostly associated with age-related macular degeneration, glaucoma and cataract, it could be related to almost any other ophthalmological conditions. The incidence of CBS alongside with mostly other ocular pathology is rising as population is ageing.
   Conclusions: Nonetheless, CBS remains commonly underreported, under recognized and/or misrecognized. Albeit the treatment recommendations and guidelines are not yet fully established, it is important to raise awareness of this specific and distinct condition, which inevitably implicates many differential diagnostic deliberations.
C1 [Jurisic, Darija; Sesar, Irena; Cavar, Ivan; Sesar, Antonio] Univ Clin Hosp Mostar, Dept Ophthalmol, Mostar, Bosnia & Herceg.
   [Zivkovic, Maja] Univ Hosp Ctr Zagreb, Dept Psychiat, Zagreb, Croatia.
   [Curkovic, Marko] Univ Psychiat Hosp Vrapce, Zagreb, Croatia.
C3 University of Mostar; University of Zagreb
RP Jurisic, D (通讯作者)，Univ Clin Hosp Mostar, Bijeli Brijeg Bb, Mostar 88000, Bosnia & Herceg.
EM jurisicd2@gmail.com
RI Cavar, Ivan/HCI-4973-2022
OI Cavar, Ivan/0000-0002-0685-3982
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NR 49
TC 11
Z9 11
U1 0
U2 7
PU MEDICINSKA NAKLADA
PI ZAGREB
PA VLASKA 69, HR-10000 ZAGREB, CROATIA
SN 0353-5053
J9 PSYCHIAT DANUB
JI Psychiatr. Danub.
PY 2018
VL 30
IS 2
BP 122
EP 128
DI 10.24869/psyd.2018.122
PG 7
WC Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Psychiatry
GA GJ8QJ
UT WOS:000435654600001
PM 29930220
DA 2022-11-30
ER

PT J
AU Schnabolk, G
   Beon, MK
   Tomlinson, S
   Rohrer, B
AF Schnabolk, Gloriane
   Beon, Mee Keong
   Tomlinson, Stephen
   Rohrer, Baerbel
TI New Insights on Complement Inhibitor CD59 in Mouse Laser-Induced
   Choroidal Neovascularization: Mislocalization After Injury and Targeted
   Delivery for Protein Replacement
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE terminal complement pathway; membrane attack complex; CD59; CR2-CD59;
   choroidal neovascularization; wound healing
ID MEMBRANE-ATTACK-COMPLEX; PIGMENT EPITHELIAL-CELLS; MACULAR-DEGENERATION;
   ALTERNATIVE PATHWAY; OXIDATIVE STRESS; VEGF SECRETION; GROWTH-FACTOR;
   ACTIVATION; MODEL; MODULATION
AB Purpose: The membrane attack complex (MAC) in choriocapillaris (CC) and retinal pigment epithelium (RPE) increase with age and disease (age-related macular degeneration). MAC assembly can be inhibited by CD59, a membrane-bound regulator. Here we further investigated the role of CD59 in murine choroidal neovascularization (CNV), a model involving both CC and RPE, and tested whether CR2-CD59, a soluble targeted form of CD59, provides protection. Methods: Laser-induced CNV was generated in wild type and CD59a-deficient mice (CD59(-/-)). CNV size was measured by optical coherence tomography, and CR2-CD59 was injected intraperitoneally. Endogenous CD59 localization and MAC deposition were identified by immunohistochemistry and quantified by confocal microscopy. Cell-type-specific responses to MAC were examined in retinal pigment epithelial cells (ARPE-19) and microvascular endothelial cells (HMEC-1). Results: CD59 levels were severely reduced and protein was mislocalized in the RPE surrounding the lesion. CNV lesion size and subretinal fluid accumulation were exacerbated in CD59(-/-) when compared with those in WT mice, and an increase in MAC deposition was noted. In contrast, CR2-CD59 significantly reduced both structural features of CNV severity. In vitro, MAC inhibition in ARPE-19 cells prevented barrier function loss and accelerated wound healing and cell adhesion, whereas in HMEC-1 cells, CR2-CD59 decelerated wound healing and cell adhesion. Conclusion: These data further support the importance of CD59 in controlling ocular injury responses and indicate that pharmacological inhibition of the MAC with CR2-CD59 may be a viable therapeutic approach for reducing complement-mediated ocular pathology.
C1 [Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC USA.
   [Schnabolk, Gloriane; Beon, Mee Keong; Rohrer, Baerbel] Med Univ South Carolina, Dept Opthalmol, Div Res, Charleston, SC USA.
   [Tomlinson, Stephen] Med Univ South Carolina, Dept Microbiol & Immunol, Div Res, Charleston, SC USA.
   [Rohrer, Baerbel] Med Univ South Carolina, Dept Neurosci, Div Res, Charleston, SC USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Ralph H Johnson VA Medical Center; Medical University of South Carolina;
   Medical University of South Carolina; Medical University of South
   Carolina
RP Schnabolk, G; Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM faith@musc.edu; rohrer@musc.edu
FU Department of Veterans Affairs merit award [RX000444]; National
   Institutes of Health [EY019320]; Research to Prevent Blindness, New
   York, NY; NIH [C06 RR015455]; NATIONAL CENTER FOR RESEARCH RESOURCES
   [C06RR015455] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY019320, R01EY024581] Funding Source: NIH RePORTER; Veterans
   Affairs [I01BX003050, I01RX000444] Funding Source: NIH RePORTER
FX The authors would like to thank Mausumi Bandyopadhyay, Balasubramaniam
   Annamalai, Elizabeth Obert, and Kannan Kunchithapautham for their
   technical assistance, as well as Luanna Bartholomew for critical review.
   This work was sponsored, in part, by a Department of Veterans Affairs
   merit award RX000444 (B.R.), a National Institutes of Health grant
   EY019320 (B.R.), (B.R.), as well as an unrestricted grant to MUSC from
   Research to Prevent Blindness, New York, NY. Animal studies were
   conducted in a facility constructed with support from the NIH (C06
   RR015455).
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NR 50
TC 7
Z9 8
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN
PY 2017
VL 33
IS 5
BP 400
EP 411
DI 10.1089/jop.2016.0101
PG 12
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA EX2KB
UT WOS:000403054100011
PM 28333572
OA Green Published
DA 2022-11-30
ER

PT J
AU Kvanta, A
   De Salles, MC
   Amren, U
   Bartuma, H
AF Kvanta, Anders
   De Salles, Manuel Casselholm
   Amren, Urban
   Bartuma, Hammurabi
TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEAL MICROVASCULATURE
   IN GEOGRAPHIC ATROPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; non-invasive imaging; retina; choroid
ID MACULAR DEGENERATION; CHORIOCAPILLARIS; FLUORESCEIN; COMPLEX
AB Purpose: To examine the retinal and choroidal foveal and parafoveal vasculature in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration using optical coherence tomography angiography (OCTA).
   Methods: Fourteen eyes from 7 patients with and without fovea-sparing bilateral GA at St. Erik Eye Hospital. All patients were examined by optical coherence tomography angiography, en face OCT and fundus autofluorescence (FAF). Segmented optical coherence tomography angiography flow scans were obtained from the superficial retinal vascular layer (SL) and the choriocapillaris (CC) and correlated with areas of retinal pigment epithelial (RPE) loss on fundus autofluorescence. The foveal avascular zone (FAZ) was measured on superficial retinal vascular layer scans and compared to the GA area of each patient.
   Results: No significant correlation (r = -0.17, P = 0.58) was found between superficial retinal vascular layer foveal avascular zone (0.49 mm(2) +/- 0.23 mm(2)) and GA area (7.36 mm(2) +/- 4.36 mm(2)). Absent or severely impaired CC flow was observed inside all GA lesions and to varied extent outside the GA margins including areas of fovea sparing. A high level of symmetry was observed in CC flow between fellow eyes.
   Conclusion: In this cross-sectional study, no relation was found between superficial retinal vascular layer foveal avascular zone and GA area. CC flow inside the GA was severely impaired, whereas CC flow outside the GA correlated poorly with both RPE integrity and visual acuity. Fellow eye symmetry suggests that CC monitoring may be a relevant clinical end point in interventional GA studies.
C1 [Kvanta, Anders; De Salles, Manuel Casselholm; Amren, Urban; Bartuma, Hammurabi] Karolinska Inst, St Erik Eye Hosp, Sect Ophthalmol & Vis, Dept Clin Neurosci, Stockholm, Sweden.
C3 Karolinska Institutet
RP Bartuma, H (通讯作者)，Karolinska Inst, St Erik Eye Hosp, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
EM hammurabi.bartuma@ki.se
CR An L, 2008, OPT EXPRESS, V16, P11438, DOI 10.1364/OE.16.011438
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NR 22
TC 32
Z9 33
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2017
VL 37
IS 5
BP 936
EP 942
DI 10.1097/IAE.0000000000001248
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EW0IO
UT WOS:000402173400035
PM 27533772
DA 2022-11-30
ER

PT J
AU Nesper, PL
   Soetikno, BT
   Fawzi, AA
AF Nesper, Peter L.
   Soetikno, Brian T.
   Fawzi, Amani A.
TI Choriocapillaris Nonperfusion is Associated With Poor Visual Acuity in
   Eyes With Reticular Pseudodrusen
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SUBRETINAL DRUSENOID DEPOSITS; MACULAR CHOROIDAL THICKNESS; FELLOW-EYES;
   GEOGRAPHIC-ATROPHY; RISK-FACTOR; DEGENERATION; PREVALENCE; IMPACT;
   MICROPERIMETRY; ANGIOGRAPHY
AB PURPOSE: To study choriocapillaris blood flow in age related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and study its correlation to visual acuity (VA) in eyes with reticular pseudodrusen (RPD) vs those with drusen without RPD (drusen).
   DESIGN: Cross-sectional study.
   METHODS: Patients with either drusen or RPD in early AMD underwent OCTA imaging of the superior, inferior, and/or nasal macula. We quantified "percent choriocapillaris area of nonperfusion" (PCAN) in eyes with RPD vs those with drusen. We assessed the repeatability of PCAN and its correlations with VA.
   RESULTS: Twenty-nine eyes of 26 patients with RPD and 21 eyes of 16 age-matched AMD patients with drusen were included. Qualitatively, the choriocapillaris in areas with RPD showed focal dark regions without flow signal on OCTA. (nonperfusion). The repeatability coefficient of PCAN was 0.49%. Eyes with RPD had significantly greater PCAN compared with eyes with drusen (7.31% and 3.88%, respectively; P < .001). We found a significant correlation between PCAN and VA for the entire dataset (r = 0.394, P = .005). When considering eyes with RPD separately, this correlation was stronger (r = 0.474, P = .009) but lost significance when considering eyes with drusen separately. (r = 0.175, P = .45).
   CONCLUSIONS: Eyes with RPD have significantly larger areas of choriocapillaris nonperfusion compared with eyes with drusen and no RPD. The correlation between PCAN and VA in this RPD population provides a potential mechanistic explanation for vision compromise in RPD compared with other forms of drusen in AMD. (C) 2016 Elsevier Inc. All rights reserved.)
C1 [Nesper, Peter L.; Soetikno, Brian T.; Fawzi, Amani A.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
   [Soetikno, Brian T.] Northwestern Univ, Feinberg Sch Med, Med Scientist Training Program, Chicago, IL 60611 USA.
   [Soetikno, Brian T.] Northwestern Univ, Dept Biomed Engn, Funct Opt Imaging Lab, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern
   University; Feinberg School of Medicine; Northwestern University
RP Fawzi, AA (通讯作者)，Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA.
EM afawzimd@gmail.com
RI fawzi, amani/AAA-9199-2021
OI fawzi, amani/0000-0002-9568-3558
FU NIH [DP3DK108248, F30EY026472]; NATIONAL EYE INSTITUTE [F30EY026472]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [DP3DK108248] Funding Source: NIH RePORTER
FX THIS WORK WAS FUNDED IN PART BY NIH DP3DK108248 (A.A.F.), NIH
   F30EY026472 (B.T.S.), AND RESEARCH instrument support by Optovue, Inc,
   Fremont, California, USA. The funders had no role in study design, data
   collection and analysis, data interpretation, decision to publish, or
   preparation of the manuscript.
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NR 49
TC 85
Z9 88
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD FEB
PY 2017
VL 174
BP 42
EP 55
DI 10.1016/j.ajo.2016.10.005
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EJ3YN
UT WOS:000393148800006
PM 27794427
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Li, J
   Zhang, YL
   Cai, XH
   Xia, QQ
   Chen, JM
   Liao, Y
   Liu, ZG
   Wu, YL
AF Li, Jie
   Zhang, Yanli
   Cai, Xianhui
   Xia, Qingqing
   Chen, Jingmeng
   Liao, Yi
   Liu, Zuguo
   Wu, Yalin
TI All-trans-retinal dimer formation alleviates the cytotoxicity of
   all-trans-retinal in human retinal pigment epithelial cells
SO TOXICOLOGY
LA English
DT Article
DE All-trans-retinal; Metabolism; All-trans-retinal dimer; Human retinal
   pigment epithelial cells; Cytotoxicity
ID ENDOPLASMIC-RETICULUM STRESS; MACULAR DEGENERATION; ROD PHOTORECEPTORS;
   STARGARDT-DISEASE; VISUAL CYCLE; INVOLVEMENT; ACTIVATION; EXPRESSION;
   CLEARANCE; A2E
AB Effective clearance of all-trans-retinal (atRAL) from retinal pigment epithelial (RPE) cells is important for avoiding its cytotoxicity. However, the metabolism of atRAL in RPE cells is poorly clarified. The present study was designed to analyze metabolic products of atRAL and to compare the cytotoxicity of atRAL versus its derivative all-trans-retinal dimer (atRAL-dimer) in human RPE cells. We found that all-transretinol (atROL) and a mixture of atRAL condensation metabolites including atRAL-dimer and A2E were generated after incubating RPE cells with atRAL for 6 h, and the amount of atRAL-dimer was significantly higher than that of A2E. In the eyes of Rdh8(-/-) Abca4(-/-) mice, a mouse model with defects in retinoid cycle that displays some symbolic characteristics of age-related macular degeneration (AMD), the level of atRAL-dimer was increased compared to wild-type mice, and was even much greater than that of A2E & isomers. The cytotoxicity of atRAL-dimer was reduced compared with its precursor atRAL. The latter could provoke intracellular reactive oxygen species (ROS) overproduction, increase the mRNA expression of several oxidative stress related genes (Nrf2, HO-1, and gamma-GCSh), and induce Delta psi m loss in RPE cells. By contrast, the abilities of atRAL-dimer to induce intracellular ROS and oxidative stress were much weaker versus that of concentration-matched atRAL, and atRAL-dimer exhibited no toxic effect on mitochondrial function at higher concentrations. In conclusion, the formation of atRAL-dimer during atRAL metabolic process ameliorates the cytotoxicity of atRAL by reducing oxidative stress. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Li, Jie; Liao, Yi; Liu, Zuguo; Wu, Yalin] Xiamen Univ, Coll Med, Inst Eye, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiangan South Rd, Xiamen 361102, Fujian Province, Peoples R China.
   [Li, Jie; Xia, Qingqing] Taizhou First Peoples Hosp, Taizhou, Zhejiang, Peoples R China.
   [Zhang, Yanli; Cai, Xianhui] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China.
   [Chen, Jingmeng] Xiamen Univ, Coll Med, Xiamen, Fujian Province, Peoples R China.
C3 Xiamen University; Zhejiang University; Xiamen University
RP Wu, YL (通讯作者)，Xiamen Univ, Coll Med, Inst Eye, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiangan South Rd, Xiamen 361102, Fujian Province, Peoples R China.
EM yalinw@xmu.edu.cn
OI Li, Jie/0000-0001-5463-3995
FU China National Natural Science Foundation [81570857, 81271018];
   Fundamental Research Funds for the Central Universities grant; Medical
   Science and Technology Program of Zhejiang Province [2016KYA195]
FX The present study was supported by China National Natural Science
   Foundation Grants 81570857 (Yalin Wu) and 81271018 (Yalin Wu); the
   Fundamental Research Funds for the Central Universities grant (Yalin
   Wu); and Medical Science and Technology Program of Zhejiang Province
   2016KYA195 (Jie Li).
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NR 40
TC 9
Z9 9
U1 0
U2 12
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 SEP 14
PY 2016
VL 371
BP 41
EP 48
DI 10.1016/j.tox.2016.10.005
PG 8
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA EF7NU
UT WOS:000390517100006
PM 27751755
DA 2022-11-30
ER

PT J
AU Brown, HDH
   Woodall, RL
   Kitching, RE
   Baseler, HA
   Morland, AB
AF Brown, Holly D. H.
   Woodall, Rachel L.
   Kitching, Rebecca E.
   Baseler, Heidi A.
   Morland, Antony B.
TI Using magnetic resonance imaging to assess visual deficits: a review
SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS
LA English
DT Review
DE albinism; amblyopia; anophthalmia; functional magnetic resonance
   imaging; glaucoma; macular degeneration; magnetic resonance imaging;
   magnetic resonance spectroscopy; ophthalmology; visual deficit
ID VOXEL-BASED MORPHOMETRY; LATERAL GENICULATE-NUCLEUS; OCULAR DOMINANCE
   COLUMNS; SPECTROSCOPY H-1-MRS REVEALS; CRITICAL PERIOD PLASTICITY;
   RETINAL GANGLION-CELLS; OPEN-ANGLE GLAUCOMA; MACULAR DEGENERATION;
   WHITE-MATTER; RETINOTOPIC ORGANIZATION
AB Purpose: Over the last two decades, magnetic resonance imaging (MRI) has been widely used in neuroscience research to assess both structure and function in the brain in health and disease. With regard to vision research, prior to the advent of MRI, researchers relied on animal physiology and human post-mortem work to assess the impact of eye disease on visual cortex and connecting structures. Using MRI, researchers can non-invasively examine the effects of eye disease on the whole visual pathway, including the lateral geniculate nucleus, striate and extrastriate cortex. This review aims to summarise research using MRI to investigate structural, chemical and functional effects of eye diseases, including: macular degeneration, retinitis pigmentosa, glaucoma, albinism, and amblyopia.
   Recent Findings: Structural MRI has demonstrated significant abnormalities within both grey and white matter densities across both visual and non-visual areas. Functional MRI studies have also provided extensive evidence of functional changes throughout the whole of the visual pathway following visual loss, particularly in amblyopia. MR spectroscopy techniques have also revealed several abnormalities in metabolite concentrations in both glaucoma and age-related macular degeneration. GABA-edited MR spectroscopy on the other hand has identified possible evidence of plasticity within visual cortex.
   Summary: Collectively, using MRI to investigate the effects on the visual pathway following disease and dysfunction has revealed a rich pattern of results allowing for better characterisation of disease. In the future MRI will likely play an important role in assessing the impact of eye disease on the visual pathway and how it progresses over time.
C1 [Brown, Holly D. H.; Woodall, Rachel L.; Kitching, Rebecca E.; Baseler, Heidi A.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
   [Morland, Antony B.] Univ York, Dept Psychol, Visual Neurosci, York YO10 5DD, N Yorkshire, England.
   [Baseler, Heidi A.] Univ York, Hull York Med Sch, Imaging Sci, Ctr Neurosci, York YO10 5DD, N Yorkshire, England.
   [Morland, Antony B.] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
C3 University of York - UK; University of York - UK; University of Hull;
   University of York - UK; University of Hull; University of York - UK
RP Morland, AB (通讯作者)，Univ York, Dept Psychol, Visual Neurosci, York YO10 5DD, N Yorkshire, England.; Morland, AB (通讯作者)，Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
EM antony.morland@york.ac.uk
RI Hanson, Rachel/AAF-3784-2020; Baseler, Heidi/AAI-7387-2020
OI Baseler, Heidi/0000-0003-0995-8453; Morland, Antony/0000-0002-6754-5545;
   Hanson, Rachel/0000-0002-2569-9810; Brown, Holly/0000-0001-5128-9172
FU Fight for Sight project grant [1523/1524]; Wellcome Trust; Medical
   Research Council [G0401339]; MRC [G0401339] Funding Source: UKRI; Fight
   for Sight [1523/24] Funding Source: researchfish
FX The authors acknowledge with thanks Fight for Sight project grant
   (1523/1524), the Wellcome Trust for its Institutional Strategic Support
   Fund, awarded to the University of York, and the Medical Research
   Council (G0401339).
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NR 188
TC 50
Z9 54
U1 2
U2 40
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 MAY
PY 2016
VL 36
IS 3
SI SI
BP 240
EP 265
DI 10.1111/opo.12293
PG 26
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DP2RC
UT WOS:000378336600003
PM 27112223
OA Green Accepted, Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Kachi, I
   Yasukawa, T
   Kato, A
   Takase, N
   Morita, H
   Kubota, A
   Hirano, Y
   Uemura, A
   Ogura, Y
AF Kachi, Ikuko
   Yasukawa, Tsutomu
   Kato, Aki
   Takase, Noriaki
   Morita, Hiroshi
   Kubota, Ayae
   Hirano, Yoshio
   Uemura, Akiyoshi
   Ogura, Yuichiro
TI Combination therapy with intravitreal tissue plasminogen activator and
   ranibizumab for subfoveal type 2 choroidal neovascularization
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; Intravitreal ranibizumab; Tissue
   plasminogen activator; Type 2 choroidal neovascularization
ID VISUAL-ACUITY LOSS; MACULAR DEGENERATION; PNEUMATIC DISPLACEMENT;
   SUBMACULAR HEMORRHAGE; AFLIBERCEPT; PREVALENCE; RISK
AB Purpose Fibrovascular scar formation related to subfoveal type 2 choroidal neovascularization (CNV) often causes severe vision loss in eyes with age-related macular degeneration. The authors assessed additional impacts of intravitreal tissue plasminogen activator (tPA), a fibrinolytic compound, combined with intravitreal ranibizumab (IVR) on subfoveal type 2 CNV.
   Methods Eight eyes of eight patients with type 2 CNV underwent intravitreal injections of ranibizumab and tPA (IVR/tPA) (40 kIU). Twelve eyes of 12 patients with type 2 CNV were treated with only IVR injections, as the control group. For retreatment, IVR was performed as needed. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) and macular volume (MV) on optical coherence tomography were recorded periodically for 6 months.
   Results The subretinal fibrinous and fibrovascular tissue complex regressed or contracted immediately after administration of IVR/tPA in contrast to IVR monotherapy. The total numbers of IVR injections did not differ significantly between the two groups. The mean logarithm of the minimum angle of resolution BCVA in the combination therapy group improved significantly from 0.72 at baseline to 0.51 at month 6 and was superior to that in the monotherapy group (0.70-0.79). The improvements of the mean CRT and MV in the combination therapy group were superior to the monotherapy group. No tPA-related complications developed.
   Conclusions tPA may have a specific ability to regress already formed subretinal fibrinous and fibrovascular tissue complexes in eyes with type 2 CNV, potentially increasing the chances of visual improvement through a synergistic relationship with anti-VEGF therapies.
C1 [Kachi, Ikuko; Yasukawa, Tsutomu; Kato, Aki; Takase, Noriaki; Morita, Hiroshi; Kubota, Ayae; Hirano, Yoshio; Uemura, Akiyoshi; Ogura, Yuichiro] Nagoya City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
C3 Nagoya City University
RP Yasukawa, T (通讯作者)，Nagoya City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med Sci, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
EM yasukawa@med.nagoya-cu.ac.jp
RI Uemura, Akiyoshi/I-7510-2017
OI Uemura, Akiyoshi/0000-0001-5574-5470; Hirano, Yoshio/0000-0002-9173-0839
FU Japan Society for the Promotion of Science; Ministry of Health, Labour
   and Welfare of Japan; Grants-in-Aid for Scientific Research [25462758]
   Funding Source: KAKEN
FX The Research Committee on Chorioretinal Degenerations and Optic Atrophy,
   the Ministry of Health, Labour and Welfare of Japan (Tsutomu Yasukawa,
   Yuichiro Ogura), and a Grant-in-Aid for Scientific Research (C) from the
   Japan Society for the Promotion of Science, and a Grant-in-Aid for
   Scientific Research from the Ministry of Health, Labour and Welfare of
   Japan (Tsutomu Yasukawa, Yuichiro Ogura). We thank Ms. Lynda Charters
   (Medical International, Framingham, MA) for English proofreading.
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NR 21
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER JAPAN KK
PI TOKYO
PA SHIROYAMA TRUST TOWER 5F, 4-3-1 TORANOMON, MINATO-KU, TOKYO, 105-6005,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAY
PY 2016
VL 60
IS 3
BP 179
EP 186
DI 10.1007/s10384-016-0434-4
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DK5IK
UT WOS:000374953400008
PM 26919844
DA 2022-11-30
ER

PT J
AU Kwong, TQ
   Mohamed, M
AF Kwong, Tsong Qiang
   Mohamed, Moin
TI Anti-vascular endothelial growth factor therapies in ophthalmology:
   current use, controversies and the future
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE eye; retina; vascular endothelial growth factor
ID MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; CANCER-PATIENTS; CHOROIDAL
   NEOVASCULARIZATION; VEGF; ANGIOGENESIS; RANIBIZUMAB; AFLIBERCEPT;
   RETINOPATHY; INHIBITION
AB Use of anti-vascular endothelial growth factor (VEGF) therapies was introduced for the treatment of ocular disorders in 2005. In the UK, the current licensed and NICE approved indications are for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO), macular oedema secondary to a retinal vein occlusion (RVO) and choroidal neovascularization in pathological myopia. These diagnoses alone account for two-thirds of the main causes of legally registrable visual impairment and blindness. Ranibizumab (Lucentis (R); Genentech/Novartis), a drug specifically designed for intraocular use, is the primary licensed medication. Controversially however, clinicians have been using an unlicensed cheaper drug, bevacizumab (Avastin (R); Genentech/Roche), originally designed for systemic administration, with a similar mode of action and shown to have a similar efficacy. However, there are fears of greater side effects with bevacizumab though studies have not been sufficiently powered to show statistical difference. In the current global economic climate, anti-VEGF treatment places huge financial and logistical pressure on already strained health care systems. Bevacizumab is considerably more cost effective than ranibizumab, and thus using bevacizumab would widen access to treatment particularly in developing countries. This licensing issue also places clinicians in a difficult medico-legal position especially in Europe, where doctors are duty bound to use a licensed drug for a particular indication if this is available. As the indications of anti-VEGF therapies expand and the cost of health care provision becomes more expensive, the controversies surrounding their use will inevitably become more important.
C1 [Kwong, Tsong Qiang] Eastbourne Dist Gen Hosp, Dept Ophthalmol, Eastbourne BN21 2UD, E Sussex, England.
   [Mohamed, Moin] St Thomas Hosp, London SE1 7HY, England.
C3 Guy's & St Thomas' NHS Foundation Trust
RP Kwong, TQ (通讯作者)，Eastbourne Dist Gen Hosp, Dept Ophthalmol, Eastbourne BN21 2UD, E Sussex, England.
EM qiangk@gmail.com
FU Alcon; Alimera Sciences; Bausch and Lomb; Allergan; Bayer; Novartis
FX All authors have completed the Unified Competing Interest form at
   www.icmje.org/coi_disclosure.pdf (available on request from the
   corresponding author) and declare: no support from any organization for
   the submitted work; MM has received personal fees from Alcon, Alimera
   Sciences, Bausch and Lomb, Allergan, Bayer and Novartis in the previous
   3 years; TQK has no financial relationships with any organizations that
   may have an interest in the submitted work; no other relationships or
   activities that could appear to have influenced the submitted work.
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NR 62
TC 29
Z9 31
U1 0
U2 17
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 OCT
PY 2014
VL 78
IS 4
BP 699
EP 706
DI 10.1111/bcp.12371
PG 8
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AQ2NC
UT WOS:000342622500003
PM 24602183
OA Green Published
DA 2022-11-30
ER

PT J
AU Kobayashi, H
   Okamoto, H
   Murakami, A
   Iwata, T
AF Kobayashi, Hiroaki
   Okamoto, Haru
   Murakami, Akira
   Iwata, Takeshi
TI Plasma Proteome Analysis on Cynomolgus Monkey (Macaca Fascicularis)
   Pedigrees with Early Onset Drusen Formation
SO EXPERIMENTAL ANIMALS
LA English
DT Article
DE age-related macular degeneration; drusen; mass spectrometry; plasma;
   proteome
ID MACULAR DEGENERATION; APOLIPOPROTEIN-E; PROTEINS; ABUNDANCE; RETINA;
   MODEL
AB The central region of the primate retina is called macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create neural network adapted for high visual acuity. Damage to the fovea by macular dystrophies and age-related macular degeneration (AMD) can reduce the central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in macula differ from that in peripheral retina in expression level. Previously, we reported an early onset macular degeneration with drusen in cynomolgus monkey pedigrees. These monkeys show similar fundus findings of early stage of AMD at 2 years after birth. To elucidate mechanism of drusen formation and to find disease biomarkers for early stage of AMD, we performed plasma proteome analysis. Plasma samples were collected from four affected and control monkeys within the same pedigree. Successful fractionation of the plasma proteins by ProteoMiner and Gelfree8100 were confirmed by SDS-PAGE. Total of 245 proteins were identified from eight samples. From the results of spectral counting, we selected some proteins, Apolipoprotein E, Histidine-rich glycoprotein, and Retinol-binding protein 4 as candidate proteins that would be related with drusen formation. Candidate proteins would be potentially beneficial as biomarkers for human AMD. One of the identified proteins, Apolipoprotein E (ApoE), is structural component of drusen and also related with other neurodegenerative disease like Alzheimer disease. In this plasma proteome analysis, ApoE would be one of the possible factors of early drusen formation in these cynomolgus monkey pedigrees.
C1 [Kobayashi, Hiroaki; Okamoto, Haru; Iwata, Takeshi] Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol,Meguro Ku, Tokyo 1528902, Japan.
   [Kobayashi, Hiroaki; Murakami, Akira] Juntendo Univ, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138421, Japan.
C3 Juntendo University
RP Iwata, T (通讯作者)，Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol,Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan.
FU Ministry of Health, Labour, and Welfare of Japan
FX This study was funded in part by a grant to TI from the Ministry of
   Health, Labour, and Welfare of Japan.
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   Witkowski C., 2009, JOVE-J VIS EXP, V34, P1842
   Xiaoyun F., 2007, J PROTEOME, V7, P845
NR 23
TC 4
Z9 4
U1 0
U2 7
PU INT PRESS EDITING CENTRE INC
PI TOKYO
PA 1-2-3 SUGAMO, TOSHIMA-KU, TOKYO, 170 0002, JAPAN
SN 1341-1357
EI 1881-7122
J9 EXP ANIM TOKYO
JI Exp. Anim.
PD JUL
PY 2014
VL 63
IS 3
BP 305
EP 310
DI 10.1538/expanim.63.305
PG 6
WC Veterinary Sciences; Zoology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Veterinary Sciences; Zoology
GA AM2US
UT WOS:000339706900005
PM 25077760
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Mayer, WJ
   Hakim, I
   Haritoglou, C
   Gandorfer, A
   Ulbig, M
   Kampik, A
   Wolf, A
AF Mayer, Wolfgang J.
   Hakim, Imad
   Haritoglou, Christos
   Gandorfer, Arnd
   Ulbig, Michael
   Kampik, Anselm
   Wolf, Armin
TI Efficacy and safety of recombinant tissue plasminogen activator and gas
   versus bevacizumab and gas for subretinal haemorrhage
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE AMD; avastin; bevacizumab; rtPA; subretinal haemorrhage
ID MACULAR DEGENERATION; INTRAVITREAL INJECTION; NATURAL-HISTORY;
   SECONDARY; RABBITS
AB Purpose: To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD).
   Methods: Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 mu g/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS).
   Results: There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups).
   Conclusion: Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA + gas is important for all cases.
C1 [Mayer, Wolfgang J.; Hakim, Imad; Haritoglou, Christos; Gandorfer, Arnd; Ulbig, Michael; Kampik, Anselm; Wolf, Armin] Univ Munich, Dept Ophthalmol, Munich, Germany.
C3 University of Munich
RP Wolf, A (通讯作者)，Klinikum Univ Munchen, Augenklin, Campus Innenstadt,Mathildenstr 8, D-80336 Munich, Germany.
EM armin.wolf@med.uni-muenchen.de
RI Mayer, Wolfgang/AAJ-1407-2020
OI Mayer, Wolfgang/0000-0001-8891-4875
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NR 18
TC 22
Z9 23
U1 0
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAY
PY 2013
VL 91
IS 3
BP 274
EP 278
DI 10.1111/j.1755-3768.2011.02264.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 131HH
UT WOS:000317983000034
PM 21952010
DA 2022-11-30
ER

PT J
AU Amaral, J
   Lee, JW
   Chou, J
   Campos, MM
   Rodriguez, IR
AF Amaral, Juan
   Lee, Jung Wha
   Chou, Joshua
   Campos, Maria M.
   Rodriguez, Ignacio R.
TI 7-Ketocholesterol Induces Inflammation and Angiogenesis In Vivo: A Novel
   Rat Model
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; LOW-DENSITY-LIPOPROTEIN;
   MACULAR DEGENERATION; CELLS; OXYSTEROLS; VEGF; CHOLESTEROL; MACROPHAGES;
   OXIDATION; MEMBRANE
AB Accumulation of 7-Ketocholesterol (7KCh) in lipid deposits has been implicated in a variety of chronic diseases including atherosclerosis, Alzheimer's disease and age-related macular degeneration. 7KCh is known to be pro-inflammatory and cytotoxic to various types of cultured cells but little is known about its effects in vivo. In this study we have investigated the effects of 7KCh in vivo by implanting biodegradable wafers into the anterior chamber of the rat eye. The wafers were prepared using a mixture of two biodegradable polymers with different amounts of 7KCh. The 7KCh-containing implants induced massive angiogenesis and inflammation. By contrast, no angiogenesis and very little inflammation were observed with cholesterol-containing implants. The neovessel growth was monitored by fluorescein angiography. Neovessels were observed 4 days post implantation and peaked between 7 to 10 days. The angiography and isolectin IB4 labeling demonstrated that the neovessels originated from the limbus and grew through the cornea. Immunolabeling with anti-CD68 suggested that the 7KCh-containing implants had extensive macrophage infiltration as well as other cell types. A significant increase in VEGF was also observed in 7KCh-containing implants by fluorescent immunolabeling and by immunoblot of the aqueous humor (AH). Direct measurement of VEGF, IL-1 beta and GRO/KC demonstrated a marked elevation of these factors in the AH of the 7KCh-implants. In summary this study demonstrates two important things: 1) 7KCh is pro-angiogenic and pro-inflammatory in vivo and 2) implants containing 7KCh may be used to create a novel angiogenesis model in rats.
C1 [Amaral, Juan; Lee, Jung Wha; Chou, Joshua; Rodriguez, Ignacio R.] NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
   [Campos, Maria M.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI); National Institutes of Health (NIH) - USA; NIH National Eye
   Institute (NEI)
RP Rodriguez, IR (通讯作者)，NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
OI Amaral, Juan/0000-0001-8755-9170
FU National Eye Institute; NATIONAL EYE INSTITUTE [ZIAEY000307] Funding
   Source: NIH RePORTER
FX National Eye Institute intramural research program (IRR). 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 25
TC 38
Z9 38
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 8
PY 2013
VL 8
IS 2
AR e56099
DI 10.1371/journal.pone.0056099
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 086CJ
UT WOS:000314660300058
PM 23409131
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Tan, J
   Xu, YP
   Liu, GP
   Ye, XH
AF Tan, Jian
   Xu, Yi-pin
   Liu, Guang-peng
   Ye, Xin-hai
TI Involvement of acid-sensing ion channel 1a in functions of cultured
   human retinal pigment epithelial cells
SO JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL
   SCIENCES
LA English
DT Article
DE acid-sensing ion channel 1a; retinal pigment epithelium; amiloride;
   PCTx1; hydrogen peroxide
ID SODIUM-CHANNEL; REDOX REAGENTS; DEGENERATION; FAMILY; METABOLISM;
   MODULATION; MECHANISMS; EXPRESSION; SUBUNITS; CALCIUM
AB In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space (SRS) under pathological conditions such as age-related macular degeneration (AMD). Although it is well known that many transporters in the retinal pigment epithelium (RPE) cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels (ASICs). In this study, we investigated whether ASIC1a was expressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASIC1a expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide (H2O2). Furthermore, inhibition or over-expression of ASIC1a in RPE cells was obtained using inhibitors (amiloride and PCTx1) or by the transfection of cDNA encoding hASIC1a. Cell viability was determined by using the MTT assay. The real-time RT-PCR and Western blotting results showed that both the mRNA and protein of ASIC1a were expressed in RPE cells. Inhibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASIC1a in RPE cells prolonged cell survival under oxidative stress induced by H2O2. In conclusion, ASIC1a is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by protecting them from oxidative stress.
C1 [Tan, Jian; Xu, Yi-pin; Liu, Guang-peng; Ye, Xin-hai] Tongji Univ, Shanghai Peoples Hosp 10, Dept Plast Surg, Shanghai 200072, Peoples R China.
C3 Tongji University
RP Ye, XH (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 10, Dept Plast Surg, Shanghai 200072, Peoples R China.
EM j-tan@163.com; dryxh@189.cn
FU National Natural Science Foundation of China [81200681]
FX This project was supported by the National Natural Science Foundation of
   China (No. 81200681).
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NR 31
TC 4
Z9 4
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1672-0733
EI 1993-1352
J9 J HUAZHONG U SCI-MED
JI J. Huazhong Univ. Sci. Tech.-Med.
PD FEB
PY 2013
VL 33
IS 1
BP 137
EP 141
DI 10.1007/s11596-013-1086-y
PG 5
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 086OS
UT WOS:000314695600024
PM 23392723
DA 2022-11-30
ER

PT J
AU Zhu, L
   Liu, ZB
   Feng, ZH
   Hao, JJ
   Shen, WL
   Li, XS
   Sun, LJ
   Sharman, E
   Wang, Y
   Wertz, K
   Weber, P
   Shi, XL
   Liu, JK
AF Zhu, Lu
   Liu, Zhongbo
   Feng, Zhihui
   Hao, Jiejie
   Shen, Weili
   Li, Xuesen
   Sun, Lijuan
   Sharman, Edward
   Wang, Ying
   Wertz, Karin
   Weber, Peter
   Shi, Xianglin
   Liu, Jiankang
TI Hydroxytyrosol protects against oxidative damage by simultaneous
   activation of mitochondrial biogenesis and phase II detoxifying enzyme
   systems in retinal pigment epithelial cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Hydroxytyrosol; RPE cells; Acrolein; AMD; Mitochondrial biogenesis;
   Phase II enzymes
ID ALPHA-LIPOIC ACID; OLIVE OIL; CARDIOVASCULAR-DISEASE; MACULAR
   DEGENERATION; ANTIOXIDANT ACTIVITY; DYSFUNCTION; ACROLEIN; STRESS;
   MECHANISMS; INDUCTION
AB Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1 alpha) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including gamma-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1 alpha led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Liu, Jiankang] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mitochondrial Biol & Med, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China.
   [Zhu, Lu; Liu, Zhongbo; Feng, Zhihui; Hao, Jiejie; Shen, Weili; Li, Xuesen] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
   [Zhu, Lu; Liu, Zhongbo; Feng, Zhihui; Hao, Jiejie; Li, Xuesen] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China.
   [Sun, Lijuan] E China Normal Univ, Coll Phys Educ & Hlth, Shanghai 200062, Peoples R China.
   [Sharman, Edward] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA.
   [Wang, Ying; Wertz, Karin; Weber, Peter] DSM Nutr Prod R&D Human Nutr & Hlth, CH-4303 Basel, Switzerland.
   [Shi, Xianglin; Liu, Jiankang] Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY 40536 USA.
C3 Xi'an Jiaotong University; Chinese Academy of Sciences; Shanghai
   Institutes for Biological Sciences, CAS; Chinese Academy of Sciences;
   University of Chinese Academy of Sciences, CAS; East China Normal
   University; University of California System; University of California
   Irvine; DSM NV; University of Kentucky
RP Liu, JK (通讯作者)，Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mitochondrial Biol & Med, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China.
EM j.liu@mail.xjtu.edu.cn
RI Liu, Jiankang/A-1610-2011; Zhu, Lu/N-1073-2017; Feng,
   Zhihui/E-7408-2011; surname, name s/A-2183-2010; Liu,
   Zhongbo/U-3004-2017
OI Zhu, Lu/0000-0003-2716-4649; Feng, Zhihui/0000-0002-2448-6565; 
FU National Eye Institute; NIH [EY0160101, 5R01 CA119028-05, R01 CA116697,
   R01 ES015518, R01 ES015375]; UC Davis Center for Human and Nutrition
   [CHNR08-318]; DSM; NATIONAL CANCER INSTITUTE [R01CA119028, R01CA116697]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH
   SCIENCES [R01ES015518, R01ES015375] Funding Source: NIH RePORTER
FX Supported by National Eye Institute, NIH grant EY0160101, 5R01
   CA119028-05, R01 CA116697, R01 ES015518, R01 ES015375, a UC Davis Center
   for Human and Nutrition Pilot Award (CHNR08-318), and DSM Nutritional
   Products.
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NR 58
TC 123
Z9 136
U1 1
U2 35
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD NOV
PY 2010
VL 21
IS 11
BP 1089
EP 1098
DI 10.1016/j.jnutbio.2009.09.006
PG 10
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 675JE
UT WOS:000283825600009
PM 20149621
DA 2022-11-30
ER

PT J
AU Chang, B
   Mandal, MNA
   Chavali, VRM
   Hawes, NL
   Khan, NW
   Hurd, RE
   Smith, RS
   Davisson, ML
   Kopplin, L
   Klein, BEK
   Klein, R
   Iyengar, SK
   Heckenlively, JR
   Ayyagari, R
AF Chang, Bo
   Mandal, Md Nawajes A.
   Chavali, Venkata R. M.
   Hawes, Norman L.
   Khan, Naheed W.
   Hurd, Ronald E.
   Smith, Richard S.
   Davisson, Muriel L.
   Kopplin, Laura
   Klein, Barbara E. K.
   Klein, Ronald
   Iyengar, Sudha K.
   Heckenlively, John R.
   Ayyagari, Radha
TI Age-related retinal degeneration (arrd2) in a novel mouse model due to a
   nonsense mutation in the Mdm1 gene
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PROTEIN; PROGRESS; ELOVL4; RPE; DNA
AB We observed that a naturally occurring mouse strain developed age-related retinal degeneration (arrd2). These mice had normal fundi, electroretinograms (ERGs) and retinal histology at 6 months of age; vessel attenuation, RPE atrophy and pigmentary abnormalities at 14 months, which progressed to complete loss of photoreceptors and extinguished ERG by 22 months. Genetic analysis revealed that the retinal degeneration in arrd2 segregates in an autosomal recessive manner and the disease gene localizes to mouse chromosome 10. A positional candidate cloning approach detected a nonsense mutation in the mouse double minute-1 gene (Mdm1), which results in the truncation of the putative protein from 718 amino acids to 398. We have identified a novel transcript of the Mdm1 gene, which is the predominant transcript in the retina. The Mdm1 transcript is localized to the nuclear layers of neural retina. Expression of Mdm1 in the retina increases steadily from post-natal day 30 to 1 year, and a high level of Mdm1 are subsequently maintained. The Mdm1 transcript was found to be significantly depleted in the retina of arrd2 mice and the transcript was observed to degrade by nonsense-mediated decay. These results indicate that the depletion of the Mdm1 transcript may underlie the mechanism leading to late-onset progressive retinal degeneration in arrd2 mice. Analysis of a cohort of patients with age-related macular degeneration (AMD) wherein the susceptibility locus maps to chromosome 12q, a region bearing the human ortholog to MDM1, did not reveal association between human MDM1 and AMD.
C1 [Chang, Bo; Hawes, Norman L.; Hurd, Ronald E.; Smith, Richard S.; Davisson, Muriel L.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Mandal, Md Nawajes A.; Chavali, Venkata R. M.; Khan, Naheed W.; Heckenlively, John R.; Ayyagari, Radha] Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48105 USA.
   [Kopplin, Laura; Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.
C3 Jackson Laboratory; University of Michigan System; University of
   Michigan; Case Western Reserve University; University of Wisconsin
   System; University of Wisconsin Madison
RP Ayyagari, R (通讯作者)，Univ Calif San Diego, Jacobs Retina Ctr, Shiley Eye Ctr, Rm 206,9415 Campus Point Dr, La Jolla, CA 92093 USA.
EM rayyagari@ucsd.edu
RI /S-1190-2019
OI /0000-0001-7488-250X; Klein, Ronald/0000-0002-4428-6237; Chang,
   Bo/0000-0001-8259-7290
FU National Institutes of Health [EY13198, U10EY06594, EY015286, EY13438,
   EY10605, EY015810, NIH T32-EY07157, T32 GM007250, EY07758, RR01183];
   Research to Prevent Blindness, Inc., New York, NY; Foundation Fighting
   Blindness; Retina Research foundation; National Cancer Institute; Cancer
   Center [CA34196]; Comprehensive Cancer Center of Case Western Reserve
   University; University Hospitals of Cleveland [P30CA43703]; NATIONAL
   CANCER INSTITUTE [P30CA034196, P30CA043703] Funding Source: NIH
   RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCES [P40RR001183,
   P41RR003655] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY007758, T32EY007157, U10EY006594, R03EY013438, R01EY013198,
   R01EY015286, R01EY010605, R01EY015810] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007250] Funding
   Source: NIH RePORTER
FX This study was supported by the grants from the National Institutes of
   Health grants EY13198, U10EY06594, EY015286, EY13438, EY10605, EY015810,
   NIH T32-EY07157, T32 GM007250, EY07758, RR01183, Research to Prevent
   Blindness, Inc., New York, NY (R.A.) and EY07758 (B.C.). Foundation
   Fighting Blindness (R.A., J.R. H., B.C.), Retina Research foundation.
   Institutional shared services are supported by National Cancer
   Institute, Cancer Center grant CA34196. The results of this paper were
   obtained by using the software package S. A. G. E., which is supported
   by a US Public Health Service Resource Grant (RR03655) from the National
   Center for Research Resources. This research was supported by the Gene
   Expression and Genotyping Facility of the Comprehensive Cancer Center of
   Case Western Reserve University and University Hospitals of Cleveland
   (P30CA43703).
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NR 38
TC 23
Z9 26
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD DEC 15
PY 2008
VL 17
IS 24
BP 3929
EP 3941
DI 10.1093/hmg/ddn295
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 377VQ
UT WOS:000261280300010
PM 18805803
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Fujikado, T
   Asonuma, S
   Ohji, M
   Kusaka, S
   Hayashi, A
   Ikuno, Y
   Kamei, M
   Oda, K
   Tano, Y
AF Fujikado, T
   Asonuma, S
   Ohji, M
   Kusaka, S
   Hayashi, A
   Ikuno, Y
   Kamei, M
   Oda, K
   Tano, Y
TI Reading ability after macular translocation surgery with 360-degree
   retinotomy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID FOVEAL TRANSLOCATION; VISUAL FUNCTION; PSYCHOPHYSICS; SCOTOMA
AB PURPOSE: To report reading ability using a standardized reading chart after macular translocation with 360-degree retinotomy in eyes with age-related macular degeneration (AMD) or with myopic choroidal neovascularization (mCNV).
   DESIGN: Interventional case series.
   METHODS: In 34 eyes of 34 patients with subfoveal choroidal neovascular membrane (AMD, 23; mCNV, 11), macular translocation surgery with 360,degree retinotomy and simultaneous extraocular muscle surgery were performed. The average age was 67.4 +/- 7.9 years, and the average follow-up period was 7.6 +/- 3.3 months. The best-corrected far visual acuity (FVA) was measured with a standardized visual acuity chart using Landolt Cs, and the critical print size (CPS) was determined with the Japanese version of the Minnesota reading chart (MN- READ-J Chart) preoperatively and postoperatively. Preoperative and postoperative change in the CPS was compared with the subjective visual improvement as assessed by a questionnaire.
   RESULTS: The postoperative improvement of FVA was statistically significant in eyes with mCNV (P =.010) but not significant in eyes with AMD (P =.495). The postoperative improvement of CPS was statistically significant both in eyes with AMD (P =.027) and in eyes with mCNV (P =.004). The subjective visual improvement was significantly correlated with the change of CPS in patients after a second better eye surgery.
   CONCLUSIONS: After macular translocation with 360-degree retinotomy, the improvement of reading ability was significant in eyes with both AMD and mCNV. We conclude that this surgical method is well suited to improve reading ability of patients with AMD or mCNV.
C1 Osaka Univ, Sch Med, Dept Visual Sci, Suita, Osaka 5650871, Japan.
   Osaka Univ, Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan.
   Tokyo Womans Christian Univ, Dept Commun, Tokyo, Japan.
C3 Osaka University; Osaka University
RP Fujikado, T (通讯作者)，Osaka Univ, Sch Med, Dept Visual Sci, Rm G4,2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM fujikado@ophthal.med.osaka-u.ac.jp
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NR 14
TC 34
Z9 35
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2002
VL 134
IS 6
BP 849
EP 856
AR PII S0002-9394(02)01756-7
DI 10.1016/S0002-9394(02)01756-7
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 624BA
UT WOS:000179738600008
PM 12470753
DA 2022-11-30
ER

PT J
AU Steinle, JJ
   Pierce, JD
   Clancy, RL
   Smith, PG
AF Steinle, JJ
   Pierce, JD
   Clancy, RL
   Smith, PG
TI Increased ocular blood vessel numbers and sizes following chronic
   sympathectomy in rat
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE choroid; denervation; vascular; sympathetic nervous system; angiogenesis
ID SPONTANEOUSLY HYPERTENSIVE RATS; SMOOTH-MUSCLE; NEONATAL GANGLIONECTOMY;
   DENERVATION; FLOW; ARTERIES; MORPHOMETRY; HYPERTROPHY; CATS
AB Disease states characterized by ocular vascular pathology are often associated with impaired sympathetic function. This study examined the effect of sympathetic denervation on ocular vasculature of the adult rat. Uveal perfusion and choroidal and retinal blood vessel sizes and numbers were assessed in rats with intact innervation and after short- (2 days) or long-term (6 weeks) sympathetic denervation induced by ipsilateral superior cervical ganglion excision. In rats with intact innervation and after short-term sympathectomy, blood flow in both eyes was comparable. However, after long-term sympathectomy, blood flow was four-fold greater in the denervated than in the innervated eye, but was unaltered in lacrimal gland, cerebral cortex, and masseter muscle. Choroid surface area was not affected by long-term sympathectomy, but choroidal thickness was increased and choroidal cross-sectional area occupied by vascular lumina was greater. Arteriolar number per unit cross-sectional area of choroid was not altered although arteriolar diameters were enlarged. Choroidal venules were larger and more abundant. Choroidal capillary numbers were unchanged, but retinal capillaries of the outer plexiform layer were increased. To determine if these changes result from loss of sympathetic activity, sympathetic preganglionic innervation was excised chronically. This produced significant increases in choroidal thickness and vascular luminal area, and in numbers of arterioles, small venules, and capillaries in the outer plexiform layer. These findings show that sympathetic innervation is critical in regulating choroidal and retinal vascularity, and that chronic loss of sympathetic activity may contribute to abnormal vascular proliferation in diseases such as age-related macular degeneration and diabetic retinopathy. (C) 2002 Elsevier Science Ltd.
C1 Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA.
   Univ Kansas, Med Ctr, RL Smith Mental Retardat Res Ctr, Kansas City, KS 66160 USA.
C3 University of Kansas; University of Kansas Medical Center; University of
   Kansas; University of Kansas Medical Center
RP Smith, PG (通讯作者)，Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
RI Smith, Peter G/G-9172-2014
OI Smith, Peter G/0000-0002-1931-7660; Steinle, Jena/0000-0002-7539-2892
FU NICHD NIH HHS [HD 02528, HD 33025] Funding Source: Medline; EUNICE
   KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
   [P30HD002528] Funding Source: NIH RePORTER; EUNICE KENNEDY SHRIVER
   NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD033025]
   Funding Source: NIH RePORTER
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NR 29
TC 36
Z9 36
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
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2002
VL 74
IS 6
BP 761
EP 768
DI 10.1006/exer.2002.1182
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 597NW
UT WOS:000178228500010
PM 12126949
DA 2022-11-30
ER

PT J
AU Pai, HL
   Hsieh, SMT
   Su, YS
   Sue, XY
   Chang, HH
   Lin, DPC
AF Pai, Hung-Liang
   Hsieh, Sophie Meng-Tien
   Su, Yu-Shan
   Sue, Xin-Yuan
   Chang, Han-Hsin
   Lin, David Pei-Cheng
TI Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be
   Reversed by Serum Uric Acid Lowering Agents in Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE metabolic disorders; hyperuricemia; retinal injuries; allopurinol;
   benzbromarone
ID METABOLIC SYNDROME; OPTIC-NERVE; DIABETIC-RETINOPATHY; PROTEIN
   EXPRESSION; PREVALENCE; OUTGROWTH; CATARACT; CHANNELS; PATHWAY; ALPHA
AB PURPOSE. Metabolic disorders have been implicated in ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Recently, hyperuricemia (HUA) has been proposed as another risk factor for AMD, although no cause-and-effect experimental data have been published. In this study, we investigated whether HUA would initiate AMD or related retinal damages in hyperuricemic mice.
   METHODS. HUA was induced in male ICR mice by dietary supplements of uric acid and oxonic acid potassium salt, with or without treatments by allopurinol or benzbromarone for various durations. Serum uric acid and angiotensin II concentrations were measured by enzyme-linked immunosorbent assay (ELISA) at regular intervals. The retinal damages were assessed by hematoxylin and eosin staining, immunostaining, and TUNEL assay. The cause-and-effect of HUA was compared among the study groups.
   RESULTS. The results showed that the total thickness of photoreceptor inner and outer segments, as well as the thickness of the photoreceptor outer segment alone, were reduced under HUA. Furthermore, HUA elevated serum angiotensin II, which indicated activation of the renin-angiotensin system (RAS), leading to higher matrix metalloproteinase-2 (MMP-2) expression, and glial activation in the ganglion cell layer. HUA also led to the reduction of retinal pigment epithelium gap junction protein connexin-43 and apoptosis. Uric acid lowering agents, allopurinol or benzbromarone, were effective in ameliorating the impairments.
   CONCLUSIONS. HUA may pose as a causative factor of retinal injuries. The reduction of serum uric acid may reduce the detrimental effects caused by HUA.
C1 [Pai, Hung-Liang] Chung Shan Med Univ, Dept Med, Taichung, Taiwan.
   [Hsieh, Sophie Meng-Tien; Sue, Xin-Yuan; Lin, David Pei-Cheng] Chung Shan Med Univ, Dept Med Lab & Biotechnol, Taichung, Taiwan.
   [Su, Yu-Shan; Chang, Han-Hsin] Chung Shan Med Univ, Dept Nutr, Taichung, Taiwan.
   [Lin, David Pei-Cheng] Chung Shan Med Univ Hosp, Dept Ophthalmol, Taichung, Taiwan.
C3 Chung Shan Medical University; Chung Shan Medical University; Chung Shan
   Medical University; Chung Shan Medical University; Chung Shan Medical
   University Hospital
RP Chang, HH; Lin, DPC (通讯作者)，LinSec 1,Jianguo North Rd, Taichung 40201, Taiwan.
EM jhhc@csmu.edu.tw; pcl@csmu.edu.tw
OI Pai, Hung-Liang/0000-0002-4326-1855
FU Ministry of Science and Technology, Taiwan (ROC) [CSMU-INT-102-07, MOST
   110-2320-B-040-022, MOST 110-2813-C-040-020-B]
FX Supported by a research grant (CSMU-INT-102-07) to H.H.C.from Chung Shan
   Medical University, a research grant (MOST 110-2320-B-040-022) to
   D.P.-C.L., and a studentship (MOST 110-2813-C-040-020-B) to H.-L.P. from
   the Ministry of Science and Technology, Taiwan (ROC).
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NR 59
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 8
DI 10.1167/iovs.63.10.8
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5U4DV
UT WOS:000876500500002
PM 36098977
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Shor, R
   Segal, O
   Mimouni, M
   Greenbaum, E
   Zur, D
   Trivizki, O
   Schwartz, S
   Loewenstein, A
   Goldstein, M
   Rabina, G
AF Shor, Reut
   Segal, Ori
   Mimouni, Michael
   Greenbaum, Eran
   Zur, Dinah
   Trivizki, Omer
   Schwartz, Shulamit
   Loewenstein, Anat
   Goldstein, Michaella
   Rabina, Gilad
TI IMPACT OF COVID-19 PANDEMIC LOCKDOWNS ON VISUAL ACUITY OF PATIENTS WITH
   NEOVASCULAR AMD A Large Cohort
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; anti-VEGF; COVID-19; lockdown; neovascular AMD
ID MACULAR DEGENERATION; RANIBIZUMAB; OUTCOMES; MARINA
AB Purpose: Evaluating the impact of delayed care, secondary to coronavirus disease 2019 (COVID-19) pandemic lockdowns, on visual acuity in previously treated neovascular age-related macular degeneration (nAMD) patients. Methods: This was a multicenter, retrospective, study of patients with nAMD previously treated with anti-VEGF injections who were followed up during 2019 (pre-COVID-19) and compared with patients with nAMD during 2020 (COVID-19). Results: A total of 1,192 patients with nAMD with a mean age of 81.5 years met the inclusion criteria. Of these, 850 patients were assessed in 2019 (pre-COVID-19) and 630 patients were assessed in 2020 (COVID-19). Three hundred eight patients were assessed through both 2019 and 2020 and thus were included in both cohorts. There was no significant difference between 2020 and 2019 in baseline and change in best-corrected visual acuity (BCVA; P = 0.342 and P = 0.911, respectively). The mean number of anti-VEGF injections was significantly lower (5.55 vs. 6.13, P < 0.01), with constant lower ratio of injections per patient in the COVID-19 period. Baseline BCVA (0.859, P < 0.01), number of injections (-0.006, P = 0.01), and age (0.003, P < 0.01) were predictors of final BCVA. Conclusion: In patients with nAMD, delayed care secondary to COVID-19 pandemic lockdowns has no statistically significant impact on BCVA. Best-corrected visual acuity, older age, and lower number of yearly anti-VEGF injections are predictors for decrease BCVA.
C1 [Shor, Reut; Zur, Dinah; Trivizki, Omer; Schwartz, Shulamit; Loewenstein, Anat; Goldstein, Michaella; Rabina, Gilad] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Ophthalmol, Tel Aviv, Israel.
   [Segal, Ori; Greenbaum, Eran] Tel Aviv Univ, Sackler Fac Med, Meir Med Ctr, Dept Ophthalmol, Kefar Sava, Israel.
   [Mimouni, Michael] Rambam Hlth Care Campus, Dept Ophthalmol, Haifa, Israel.
   [Mimouni, Michael] Technion Israel Inst Technol, Haifa, Israel.
C3 Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky
   Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Rambam
   Health Care Campus; Technion Israel Institute of Technology
RP Rabina, G (通讯作者)，Tel Aviv Sourasky Med Ctr, Dept Ophthalmol, 6 Weizmann St, IL-64239 Tel Aviv, Israel.
EM giladrabina@hotmail.com
CR [Anonymous], NEOVASCULAR AGE RELA
   [Anonymous], PROPOSED STRATEGIES
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NR 30
TC 0
Z9 0
U1 2
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 2022
VL 42
IS 8
BP 1529
EP 1535
DI 10.1097/IAE.0000000000003497
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 3D9GA
UT WOS:000829601100023
PM 35502974
DA 2022-11-30
ER

PT J
AU Shu, DY
   Frank, SI
   Fitch, TC
   Karg, MM
   Butcher, ER
   Nnuji-John, E
   Kim, LA
   Saint-Geniez, M
AF Shu, Daisy Y.
   Frank, Scott, I
   Fitch, Tessa C.
   Karg, Margarete M.
   Butcher, Erik R.
   Nnuji-John, Emmanuella
   Kim, Leo A.
   Saint-Geniez, Magali
TI Dimethyl Fumarate Blocks Tumor Necrosis Factor-Alpha-Driven Inflammation
   and Metabolic Rewiring in the Retinal Pigment Epithelium
SO FRONTIERS IN MOLECULAR NEUROSCIENCE
LA English
DT Article
DE inflammation; metabolism; mitochondria; retinal pigment epithelium;
   tumor necrosis factor-alpha; oxidative phosphorylation; glycolysis;
   age-related macular degeneration
ID OXIDATIVE-METABOLISM; MACULAR DEGENERATION; GENE POLYMORPHISMS;
   TNF-ALPHA; AGE; EXPRESSION; CELLS; ACTIVATION; SECRETION; PROMOTES
AB The retinal pigment epithelium (RPE) acts as a metabolic gatekeeper between photoreceptors and the choroidal vasculature to maintain retinal function. RPE dysfunction is a key feature of age-related macular degeneration (AMD), the leading cause of blindness in developed countries. Inflammation is a key pathogenic mechanism in AMD and tumor necrosis factor-alpha (TNF alpha) has been implicated as a pro-inflammatory cytokine involved in AMD. While mitochondrial dysfunction has been implicated in AMD pathogenesis, the interplay between inflammation and cellular metabolism remains elusive. The present study explores how the pro-inflammatory cytokine, TNF alpha, impacts mitochondrial morphology and metabolic function in RPE. Matured human primary RPE (H-RPE) were treated with TNF alpha (10 ng/ml) for up to 5 days. TNF alpha-induced upregulation of IL-6 secretion and inflammatory genes (IL-6, IL-8, MCP-1) was accompanied by increased oxidative phosphorylation (OXPHOS) and reduced glycolysis, leading to an increase in cellular adenosine triphosphate (ATP) content. Transmission electron microscopy (TEM) revealed defects in mitochondrial morphology with engorged mitochondria and loss of cristae integrity following TNF alpha treatment. Pre-treatment with the anti-inflammatory drug, 80 mu M dimethyl fumarate (DMFu), blocked TNF alpha-induced inflammatory activation of RPE (IL-6, IL-8, MCP-1, CFH, CFB, C3) and normalized their bioenergetic profile to control levels by regulating PFKFB3 and PKM2 gene expression. Furthermore, DMFu prevented TNF alpha-induced mitochondrial dysfunction and morphological anomalies. Thus, our results indicate that DMFu serves as a novel therapeutic avenue for combating inflammatory activation and metabolic dysfunction of RPE in AMD.
C1 [Shu, Daisy Y.; Frank, Scott, I; Fitch, Tessa C.; Karg, Margarete M.; Butcher, Erik R.; Nnuji-John, Emmanuella; Kim, Leo A.; Saint-Geniez, Magali] Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Shu, Daisy Y.; Karg, Margarete M.; Kim, Leo A.; Saint-Geniez, Magali] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
   [Nnuji-John, Emmanuella] Cold Spring Harbor Lab, Sch Biol Sci, POB 100, Cold Spring Harbor, NY 11724 USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Schepens Eye
   Research Institute; Harvard University; Harvard Medical School; Cold
   Spring Harbor Laboratory
RP Saint-Geniez, M (通讯作者)，Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA 02114 USA.; Saint-Geniez, M (通讯作者)，Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
EM msaintgeniez@gmail.com
OI Butcher, Erik/0000-0001-5595-589X; Frank, Scott/0000-0002-8203-7127
FU Fight for Sight Leonard & Robert Weintraub Postdoctoral Fellowship;
   BrightFocus Foundation Postdoctoral Fellowship Program in Macular
   Degeneration Research [M2021010F]; Department of Defense, Spinal Vision
   Research Program [VR180132]; National Eye Institute of the National
   Institutes of Health [R01EY027739]; Grimshaw-Gudewicz Charitable
   Foundation; Iraty Award; NEI [P30EYE003790]
FX This study was supported in part by grants from the Fight for Sight
   Leonard & Robert Weintraub Postdoctoral Fellowship (DYS); BrightFocus
   Foundation Postdoctoral Fellowship Program in Macular Degeneration
   Research (M2021010F, DYS); Department of Defense, Spinal Vision Research
   Program under Award no. VR180132 (MS-G and LAK); National Eye Institute
   of the National Institutes of Health under Award no. R01EY027739 (LAK);
   the Grimshaw-Gudewicz Charitable Foundation (MS-G); The Iraty Award
   (MS-G); and the NEI Core Grant P30EYE003790.
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NR 47
TC 0
Z9 0
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1662-5099
J9 FRONT MOL NEUROSCI
JI Front. Molec. Neurosci.
PD JUN 23
PY 2022
VL 15
AR 896786
DI 10.3389/fnmol.2022.896786
PG 13
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 3B1FT
UT WOS:000827694700001
PM 35813071
OA Green Accepted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Cunha, LP
   Pires, LA
   Cruzeiro, MM
   Almeida, ALM
   Martins, LC
   Martins, PN
   Shigaeff, N
   Vale, TC
AF Cunha, Leonardo Provetti
   Pires, Leopoldo Antonio
   Cruzeiro, Marcelo Maroco
   Maciel Almeida, Ana Laura
   Martins, Luiza Cunha
   Martins, Pedro Nascimento
   Shigaeff, Nadia
   Vale, Thiago Cardoso
TI Optical coherence tomography in neurodegenerative disorders
SO ARQUIVOS DE NEURO-PSIQUIATRIA
LA English
DT Review
DE Tomography; Optical Coherence; Alzheimer Disease; Parkinson Disease;
   Multiple Sclerosis; Neurodegenerative Diseases; Amyotrophic Lateral
   Sclerosis; Retina
ID NERVE-FIBER LAYER; MILD COGNITIVE IMPAIRMENT;
   AMYOTROPHIC-LATERAL-SCLEROSIS; FUNCTIONAL RETINAL IMPAIRMENT;
   ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; POTENTIAL BIOMARKER; VISUAL
   DYSFUNCTION; THICKNESS; ABNORMALITIES
AB Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.
C1 [Cunha, Leonardo Provetti] Univ Fed Juiz de Fora, Fac Med, Div Oftalmol, Juiz De Fora, MG, Brazil.
   [Cunha, Leonardo Provetti] Univ Sao Paulo, Fac Med, Div Oftatmol, Sao Paulo, SP, Brazil.
   [Cunha, Leonardo Provetti; Pires, Leopoldo Antonio; Cruzeiro, Marcelo Maroco; Maciel Almeida, Ana Laura; Martins, Luiza Cunha; Martins, Pedro Nascimento; Shigaeff, Nadia; Vale, Thiago Cardoso] Univ Fed Juiz de Fora, Fac Med, Posgrad Saude, Nucleo Pesquisa Neurol, Juiz De Fora, MG, Brazil.
   [Pires, Leopoldo Antonio; Cruzeiro, Marcelo Maroco; Maciel Almeida, Ana Laura; Vale, Thiago Cardoso] Univ Fed Juiz de Fora, Hosp Univ, Serv Neurol, Juiz De Fora, MG, Brazil.
   [Pires, Leopoldo Antonio; Cruzeiro, Marcelo Maroco; Maciel Almeida, Ana Laura; Martins, Luiza Cunha; Martins, Pedro Nascimento; Vale, Thiago Cardoso] Univ Fed Juiz de Fora, Fac Med, Dept Clin Mod, Juiz De Fora, MG, Brazil.
   [Shigaeff, Nadia] Univ Fed Juiz de Fora, Dept Psicol, Inst Ciencias Humanas, Juiz De Fora, MG, Brazil.
C3 Universidade Federal de Juiz de Fora; Universidade de Sao Paulo;
   Universidade Federal de Juiz de Fora; Universidade Federal de Juiz de
   Fora; Universidade Federal de Juiz de Fora; Universidade Federal de Juiz
   de Fora
RP Vale, TC (通讯作者)，Univ Fed Juiz de Fora, Fac Med, Posgrad Saude, Nucleo Pesquisa Neurol, Juiz De Fora, MG, Brazil.; Vale, TC (通讯作者)，Univ Fed Juiz de Fora, Hosp Univ, Serv Neurol, Juiz De Fora, MG, Brazil.; Vale, TC (通讯作者)，Univ Fed Juiz de Fora, Fac Med, Dept Clin Mod, Juiz De Fora, MG, Brazil.
EM thiago.vale@ufjf.edu.br
RI Martins, Pedro/GWC-7702-2022; Cruzeiro, Marcelo/S-3094-2018
OI Pires, Leopoldo Antonio/0000-0002-8636-3931; CUNHA, LEONARDO
   PROVETTI/0000-0001-7984-1790; Cruzeiro, Marcelo/0000-0001-6898-2790;
   Vale, Thiago/0000-0001-6145-9868; Shigaeff, Nadia/0000-0003-1549-6240
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NR 92
TC 1
Z9 1
U1 2
U2 2
PU ASSOC ARQUIVOS NEURO- PSIQUIATRIA
PI SAO PAULO SP
PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL
SN 0004-282X
EI 1678-4227
J9 ARQ NEURO-PSIQUIAT
JI Arq. Neuro-Psiquiatr.
PD FEB
PY 2022
VL 80
IS 2
BP 180
EP 191
DI 10.1590/0004-282X-ANP-2021-0134
PG 12
WC Neurosciences; Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Psychiatry
GA 1P6MS
UT WOS:000802121300013
PM 35352756
OA gold
DA 2022-11-30
ER

PT J
AU Jin, HL
   Jeong, KW
AF Jin, Hong Lan
   Jeong, Kwang Won
TI Transcriptome Analysis of Long-Term Exposure to Blue Light in Retinal
   Pigment Epithelial Cells
SO BIOMOLECULES & THERAPEUTICS
LA English
DT Article
DE Dry age-related macular degeneration; Retinal pigment epithelium;
   Lipofuscin; A2E; Blue light; Transcriptome
ID VACCINIUM-ULIGINOSUM L.; GEOGRAPHIC ATROPHY
AB Dry age-related macular degeneration (AMD) is a type of progressive blindness that is primarily due to dysfunction and the loss of retinal pigment epithelium (RPE). The accumulation of N-retinylidene-N-retinylethanolamine (A2E), a by-product of the visual cycle, causes RPE and photoreceptor degeneration that impairs vision. Genes associated with dry AMD have been identified using a blue light model of A2E accumulation in the retinal pigment epithelium and transcriptomic studies of retinal tissue from patients with AMD. However, dry macular degeneration progresses slowly, and current approaches cannot reveal changes in gene transcription according to stages of AMD progression. Thus, they are limited in terms of identifying genes responsible for pathogenesis. Here, we created a model of long-term exposure to identify temporally-dependent changes in gene expression induced in human retinal pigment epithelial cells (ARPE-19) exposed to blue light and a non-cytotoxic dose of A2E for 120 days. We identified stage-specific genes at 40, 100, and 120 days, respectively. The expression of genes corresponding to epithelial-mesenchymal transition (EMT) during the early stage, glycolysis and angiogenesis during the middle stage, and apoptosis and inflammation pathways during the late stage was significantly altered by A2E and blue light. Changes in the expression of genes at the late stages of the EMT were similar to those found in human eyes with late-stage AMD. Our results provide further insight into the pathogenesis of dry AMD induced by blue light and a novel model in vitro with which relevant genes can be identified in the future.
C1 [Jin, Hong Lan] Yanbian Univ, Key Lab Nat Med Changbai Mt, Coll Pharm, Mol Med Res Ctr,Minist Educ, Yanji 133002, Peoples R China.
   [Jeong, Kwang Won] Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, Incheon 21936, South Korea.
C3 Yanbian University; Gachon University
RP Jeong, KW (通讯作者)，Gachon Univ, Coll Pharm, Gachon Res Inst Pharmaceut Sci, Incheon 21936, South Korea.
EM kwjeong@gachon.ac.kr
FU National Research Foundation of Korea (NRF) - Ministry of Education
   [NRF-2021R1A2C1011132]; National Natural Science Foundation of China
   [81960667]
FX This research was supported by the Basic Science Research Program
   through the National Research Foundation of Korea (NRF) funded by the
   Ministry of Education (NRF-2021R1A2C1011132) to K.W.J. and National
   Natural Science Foundation of China (No. 81960667) to H.L.J.
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NR 25
TC 3
Z9 3
U1 1
U2 3
PU KOREAN SOC APPLIED PHARMACOLOGY
PI SEOUL
PA RM 805, KOREAN FEDERATION SCIENCE & TECHNOLOGY B/D, 635-4 YEOKSAM-DONG,
   KANGNAM-GU, SEOUL, 135-703, SOUTH KOREA
SN 1976-9148
EI 2005-4483
J9 BIOMOL THER
JI Biomol. Ther.
PY 2022
VL 30
IS 3
BP 291
EP 297
DI 10.4062/biomolther.2021.155
EA JAN 2022
PG 7
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 3K3YU
UT WOS:000752189300001
PM 35074938
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Stemplewitz, B
   Luethy, J
   Eddy, MT
   Spitzer, M
   Brocks, U
   Kieckhoefel, J
   Schneemann, C
   Schaudig, U
   Schargus, M
AF Stemplewitz, Birthe
   Luethy, Joel
   Eddy, Mau-Thek
   Spitzer, Martin
   Brocks, Ulrike
   Kieckhoefel, Julie
   Schneemann, Christa
   Schaudig, Ulrich
   Schargus, Marc
TI Impact of the COVID-19 pandemic's first wave on the care and treatment
   situation of intravitreal injections in a German metropolitan region
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Intravitreal injections; COVID-19; Pandemic; Adherence
ID DIABETIC MACULAR EDEMA; DEGENERATION; RANIBIZUMAB; THERAPY
AB Purpose This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region. Methods We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data. Results A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME). Conclusion A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.
C1 [Stemplewitz, Birthe; Kieckhoefel, Julie; Schneemann, Christa; Schaudig, Ulrich] Asklepios Hosp Barmbek, Dept Ophthalmol, Hamburg, Germany.
   [Luethy, Joel; Schargus, Marc] Asklepios Hosp Nord Heidberg, Dept Ophthalmol, Hamburg, Germany.
   [Eddy, Mau-Thek] Asklepios Hosp Altona, Dept Ophthalmol, Hamburg, Germany.
   [Spitzer, Martin; Brocks, Ulrike] Univ Med Ctr Hamburg Eppendorf, Dept Ophthalmol, Hamburg, Germany.
C3 Asklepios Klinik Altona; University of Hamburg; University Medical
   Center Hamburg-Eppendorf
RP Schargus, M (通讯作者)，Asklepios Hosp Nord Heidberg, Dept Ophthalmol, Hamburg, Germany.
EM m.schargus@asklepios.com
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NR 29
TC 2
Z9 2
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 JUN
PY 2022
VL 260
IS 6
BP 1877
EP 1886
DI 10.1007/s00417-021-05521-5
EA JAN 2022
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 0X7EL
UT WOS:000741596100001
PM 35006330
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Wang, Y
   Xiu, XY
   Wu, SZ
AF Wang, Yan
   Xiu, Xiaoyu
   Wu, Shengzhou
TI Amyloid peptide exerts a rapid induction of Dicer1 protein in neuron via
   reducing phosphorylation
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Article
DE Dicer1; Amyloid peptide; JNK; ERK; Synapse; TRBP; Synaptophysin; PSD95
ID ALZHEIMERS-DISEASE; CORTICAL-NEURONS; BETA; ACTIVATION; KINASE; ERK;
   PATHWAYS; ROLES; TRIAL; TRBP
AB A growing number of evidence suggests that altered microRNA network in the brain contributes to the risk of Alzheimer's disease(AD). Dicer1 is a type III riboendonuclease which cleaves pre-microRNA into functional microRNA. Reduction of Dicer1 or Dicer1 mutation has been involved in cancer, aging or age-related macular degeneration. Recently, we found a possible link between Dicer1 and AD. In particular, Dicer1 protein and Dicer1 mRNA is reduced in the hippocampus and the cortex of an animal model of AD and exposure to A1342 oligomer (A13O) longer than 6 h reduces the transcription of Dicer1 gene in neuron, via depletion of NF-E2-related factor-2. In this study, exposure to A13O at shorter time increased Dicer1 protein in neuron in a dose-dependent mode; but the mRNA level remained unaltered. Under this treatment regime,A13O reduced phosphorylation level of Dicer1 and of its binding partner, transactivation response element RNA-binding protein(TRBP). Addition of a JNK inhibitor,SP600125, or an ERK inhibitor,U0126, further increased Dicer1 protein compared to A13o treatment alone, with simultaneaous reduction of phospho-Dicer1, but with different effects on phospho-TRBP. Finally, an inhibitor of calcineurin,FK506, further increased Dicer1 protein compared to A13o treatment alone. Thus, phosphorylation of Dicer1 and TRBP was determined by mitogen activated protein kinases JNK,ERK, and protein phosphatase 2B(calcineurin) which together determined Dicer1 stability. In summary, reduced phosphorylation of Dicer1 accounted for the rapid induction of Dicer1 by A13O. This study highlights a novel way by which A13O regulates Dicer1.
C1 [Wang, Yan; Xiu, Xiaoyu; Wu, Shengzhou] Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou, Peoples R China.
   [Wang, Yan; Xiu, Xiaoyu; Wu, Shengzhou] Wenzhou Med Univ, Hosp Eye, Wenzhou, Peoples R China.
   [Wang, Yan; Xiu, Xiaoyu; Wu, Shengzhou] State Key Lab Optometry Ophthalmol & Visual Sci, 270 Xueyuan Rd, Wenzhou 325003, Zhejiang, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University
RP Wu, SZ (通讯作者)，Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou, Peoples R China.
EM wszlab@wmu.edu.cn
RI wu, shengzhou/ABG-8579-2021
OI wu, shengzhou/0000-0003-1154-2369
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NR 55
TC 1
Z9 1
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
EI 1872-9754
J9 NEUROCHEM INT
JI Neurochem. Int.
PD DEC
PY 2021
VL 151
AR 105210
DI 10.1016/j.neuint.2021.105210
EA OCT 2021
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA WN9HI
UT WOS:000712076000002
PM 34695450
DA 2022-11-30
ER

PT J
AU Franco, PJ
   Suwezda, A
   Schlottmann, P
   Destefanis, MP
   Rosenstein, RE
   Iribarren, R
   Grzybowski, A
AF Franco, Pablo J.
   Suwezda, Alejandro
   Schlottmann, Patricio
   Pia Destefanis, Maria
   Rosenstein, Ruth E.
   Iribarren, Rafael
   Grzybowski, Andrzej
TI ANALYSIS OF VISUAL DISABILITY IN BUENOS AIRES, ARGENTINA. PATHOLOGIC
   MYOPIA IS THE LEADING CAUSE IN WORKING AGE
SO MEDICINA-BUENOS AIRES
LA English
DT Article
DE visual disability; degenerative myopia; glaucoma; macular degeneration
ID ADULT-POPULATION; TIME TRENDS; VISION LOSS; BLINDNESS; IMPAIRMENT;
   PREVALENCE; IMI; URBAN
AB This study assessed the causes of visual impairment over a decade in Buenos Aires City. This is a retrospective case series where we reviewed the database of visual disability certificates issued by the Buenos Aires City Ministry of Health between 2009 and 2017. In Argentina, visual disability is defined as a visual acuity <= 20/200 in the better eye, or a corresponding visual field of less than 20 degrees in the less impaired eye. The database included the following variables: year of issue, age, gender, and cause of visual disability. Between 2009 and 2017 a total of 7656 subjects were certified as legally blind. The mean age of the sample was 57 +/- 21 years and 52.1% were females. The emission was near 700 certificates per year. The age distribution showed that 62.8% of certificates were from patients older than 50 years and that only 6.6% were given to subjects under 20. The leading causes of visual disability in Buenos Aires City were age-related macular degeneration (ARMD) with a rate of 15.5%, degenerative myopia (14.4%), primary open-angle glaucoma (11.3%) and diabetic retinopathy (6.6%). In subjects younger than 50, degenerative myopia was the first cause of visual disability. Interestingly in Argentina, where the prevalence of myopia is low, degenerative myopia is found to be the major cause of visual disability in middle-aged adult subjects. Population and clinical methods to avoid this preventable disease should need to be implemented as a matter of urgency.
C1 [Franco, Pablo J.; Pia Destefanis, Maria] Hosp Santa Lucia, Buenos Aires, DF, Argentina.
   [Suwezda, Alejandro] Fdn Hosp, Buenos Aires, DF, Argentina.
   [Schlottmann, Patricio] Org Med Invest OMI, Buenos Aires, DF, Argentina.
   [Rosenstein, Ruth E.] Univ Buenos Aires, CONICET, Lab Neuroquim Retinal & Oftalmol Expt, Dept Bioquim Humana,Fac Med CEFyBO, Buenos Aires, DF, Argentina.
   [Iribarren, Rafael] Consultorio Dres Iribarren, Buenos Aires, DF, Argentina.
   [Grzybowski, Andrzej] Univ Warmia & Mazuty, Dept Ophthalmol, Olsztyn, Poland.
   [Grzybowski, Andrzej] Fdn Ophthalmol Dev, Inst Res Ophthalmol, Poznan, Poland.
C3 University of Buenos Aires; Consejo Nacional de Investigaciones
   Cientificas y Tecnicas (CONICET); University of Buenos Aires
RP Iribarren, R (通讯作者)，Arenales 981, RA-1061 Buenos Aires, DF, Argentina.
EM rafairibarren@gmail.com
OI Schlottmann, Patricio/0000-0003-0196-0452
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NR 29
TC 0
Z9 0
U1 0
U2 0
PU MEDICINA (BUENOS AIRES)
PI BUENOS AIRES
PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA
SN 0025-7680
EI 1669-9106
J9 MEDICINA-BUENOS AIRE
JI Med.-Buenos Aires
PD SEP-OCT
PY 2021
VL 81
IS 5
BP 735
EP 741
PG 7
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA XU8KQ
UT WOS:000734507300008
PM 34633945
DA 2022-11-30
ER

PT J
AU Mackey, DA
AF Mackey, David A.
TI What colour are your eyes? Teaching the genetics of eye colour & colour
   vision. Edridge Green Lecture RCOphth Annual Congress Glasgow May 2019
SO EYE
LA English
DT Review
ID INDIVIDUAL-DIFFERENCES; DRESS; PERCEPTION; DROSOPHILA; MUTATIONS; BLUE
AB Eye colour and colour perception are excellent examples to use when teaching genetics as they encompass not simply the basic Mendelian genetics of dominant, recessive and X-linked disorders, but also many of the new concepts such as non-allelic diseases, polygenic disease, phenocopies, genome-wide association study (GWAS), founder effects, gene-environment interaction, evolutionary drivers for variations, copy number variation, insertions deletions, methylation and gene inactivation. Beyond genetics, colour perception touches on concepts involving optics, physics, physiology and psychology and can capture the imagination of the population, as we saw with social media trend of "#the dress". Television shows such as Game of Thrones focused attention on the eye colour of characters, as well as their Dire-wolves and Dragons. These themes in popular culture can be leveraged as tools to teach and engage everyone in genetics, which is now a key component in all eye diseases. As the explosion of data from genomics, big data and artificial intelligence transforms medicine, ophthalmologists need to be genetically literate. Genetics is relevant, not just for Inherited Retinal Diseases and congenital abnormalities but also for the leading causes of blindness: age-related macular degeneration, glaucoma, myopia, diabetic retinopathy and cataract. Genetics should be part of the armamentarium of every practicing ophthalmologist. We need to ask every patient about their family history. In the near future, patients will attend eye clinics with genetic results showing they are at high risk of certain eye diseases and ophthalmologists will need to know how to screen, follow and treat these patients.
C1 [Mackey, David A.] Univ Western Australia, Lions Eye Inst, Perth, WA, Australia.
   [Mackey, David A.] Univ Tasmania, Sch Med, Hobart, Tas, Australia.
C3 Lions Eye Institute; University of Western Australia; University of
   Tasmania
RP Mackey, DA (通讯作者)，Univ Western Australia, Lions Eye Inst, Perth, WA, Australia.; Mackey, DA (通讯作者)，Univ Tasmania, Sch Med, Hobart, Tas, Australia.
EM D.Mackey@utas.edu.au
RI Mackey AO, David/H-5340-2014
OI Mackey AO, David/0000-0001-7914-4709
FU NHMRC practitioner fellowship
FX DAM is funded by an NHMRC practitioner fellowship.
CR 23andme, GEN STRIP DRESS
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NR 64
TC 1
Z9 1
U1 2
U2 10
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD APR
PY 2022
VL 36
IS 4
BP 704
EP 715
DI 10.1038/s41433-021-01749-x
EA AUG 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ZZ4YG
UT WOS:000687551200001
PM 34426658
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Charles-Messance, H
   Blot, G
   Couturier, A
   Vignaud, L
   Touhami, S
   Beguier, F
   Siqueiros, L
   Forster, V
   Barmo, N
   Augustin, S
   Picaud, S
   Sahel, JA
   Rendon, A
   Grosche, A
   Tadayoni, R
   Sennlaub, F
   Guillonneau, X
AF Charles-Messance, Hugo
   Blot, Guillaume
   Couturier, Aude
   Vignaud, Lucile
   Touhami, Sara
   Beguier, Fanny
   Siqueiros, Lourdes
   Forster, Valerie
   Barmo, Nour
   Augustin, Sebastien
   Picaud, Serge
   Sahel, Jose-Alain
   Rendon, Alvaro
   Grosche, Antje
   Tadayoni, Ramin
   Sennlaub, Florian
   Guillonneau, Xavier
TI IL-1 beta induces rod degeneration through the disruption of retinal
   glutamate homeostasis
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Age-related macular degeneration; Monocyte; Macrophage; Photoreceptor;
   Glutamate
ID SYSTEM X(C)(-); PHOTORECEPTOR DEGENERATION; INTERLEUKIN-1-BETA;
   RECEPTORS; MICROGLIA; MODEL; NEUROTOXICITY; LOCALIZATION; ASTROCYTES;
   MECHANISMS
AB Background Age-related macular degeneration is characterized by the accumulation of subretinal macrophages and the degeneration of cones, but mainly of rods. We have previously shown that Mononuclear Phagocytes-derived IL-1 beta induces rod photoreceptor cell death during experimental subretinal inflammation and in retinal explants exposed to IL-1 beta but the mechanism is unknown. Methods Retinal explants were culture in the presence of human monocytes or IL-1 beta and photoreceptor cell survival was analyzed by TUNEL labeling. Glutamate concentration and transcription levels of gene involved in the homeostasis of glutamate were analyzed in cell fractions of explant cultured or not in the presence of IL-1 beta. Glutamate receptor antagonists were evaluated for their ability to reduce photoreceptor cell death in the presence of IL1-beta or monocytes. Results We here show that IL-1 beta does not induce death in isolated photoreceptors, suggesting an indirect effect. We demonstrate that IL-1 beta leads to glutamate-induced rod photoreceptor cell death as it increases the extracellular glutamate concentrations in the retina through the inhibition of its conversion to glutamine in Muller cells, increased release from Muller cells, and diminished reuptake. The inhibition of non-NMDA receptors completely and efficiently prevented rod apoptosis in retinal explants cultured in the presence of IL-1 beta or, more importantly, in vivo, in a model of subretinal inflammation. Conclusions Our study emphasizes the importance of inflammation in the deregulation of glutamate homeostasis and provides a comprehensive mechanism of action for IL-1 beta-induced rod degeneration.
C1 [Charles-Messance, Hugo; Blot, Guillaume; Couturier, Aude; Vignaud, Lucile; Touhami, Sara; Beguier, Fanny; Siqueiros, Lourdes; Forster, Valerie; Barmo, Nour; Augustin, Sebastien; Picaud, Serge; Sahel, Jose-Alain; Rendon, Alvaro; Tadayoni, Ramin; Sennlaub, Florian; Guillonneau, Xavier] Sorbonne Univ, Inst Vis, CNRS, INSERM, 17 Rue Moreau, F-75012 Paris, France.
   [Couturier, Aude; Touhami, Sara; Tadayoni, Ramin] Hop Lariboisiere, Dept Ophthalmol, Paris, France.
   [Sahel, Jose-Alain] CHNO Quinze Vingts, DHU Sight Restore, INSERM DGOS CIC 1423, 28 Rue Charenton, F-75012 Paris, France.
   [Sahel, Jose-Alain] Univ Pittsburgh, Dept Ophthalmol, Sch Med, Pittsburgh, PA 15213 USA.
   [Grosche, Antje] Ludwig Maximilians Univ Munchen, Dept Physiol Genom, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire
   Lariboisiere-Fernand-Widal - APHP; UDICE-French Research Universities;
   Universite Paris Cite; CHNO des Quinze-Vingts; UDICE-French Research
   Universities; Sorbonne Universite; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh; University of Munich
RP Guillonneau, X (通讯作者)，Sorbonne Univ, Inst Vis, CNRS, INSERM, 17 Rue Moreau, F-75012 Paris, France.
EM xavier.guillonneau@inserm.fr
RI Guillonneau, xavier/E-3995-2017; Beguier, Fanny/AAY-8581-2020;
   couturier, aude/AAP-7901-2021; Couturier, Aude/AAQ-4387-2021; Blot,
   Guillaume/AAK-5849-2021; Grosche, Antje/N-1978-2014; guillonneau,
   xavier/AAF-9495-2021; Sennlaub, Florian/F-2756-2017; Touhami,
   Sara/AAF-7836-2021
OI Guillonneau, xavier/0000-0001-7379-3935; Beguier,
   Fanny/0000-0002-6123-2978; couturier, aude/0000-0001-8549-7455; Blot,
   Guillaume/0000-0002-8955-6704; Grosche, Antje/0000-0003-0338-7530;
   guillonneau, xavier/0000-0001-7379-3935; Sennlaub,
   Florian/0000-0003-4412-1341; CHARLES-MESSANCE, Hugo/0000-0002-6627-2098;
   Siqueiros-Marquez, Lourdes/0000-0001-9528-8489
FU INSERM; LABEX LIFESENSES [ANR-10-LABEX-65]; ANR MACLEAR
   [ANR-15-CE14-0015-01]; INSERM -UNADEV [17UU113-00, 19UU159-00]; Retina
   France; Promex Stiftung fur die Forschung, Vaduz
FX This work was supported by grants from INSERM, LABEX LIFESENSES
   (ANR-10-LABEX-65), ANR MACLEAR (ANR-15-CE14-0015-01), INSERM -UNADEV
   17UU113-00 and 19UU159-00, Retina France and Promex Stiftung fur die
   Forschung, Vaduz.
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NR 42
TC 12
Z9 12
U1 1
U2 4
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JAN 3
PY 2020
VL 17
IS 1
AR 1
DI 10.1186/s12974-019-1655-5
PG 12
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA KK3SD
UT WOS:000512665200002
PM 31900165
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Dorschmann, P
   Kopplin, G
   Roider, J
   Klettner, A
AF Doerschmann, Philipp
   Kopplin, Georg
   Roider, Johann
   Klettner, Alexa
TI Effects of Sulfated Fucans from Laminaria hyperborea Regarding VEGF
   Secretion, Cell Viability, and Oxidative Stress and Correlation with
   Molecular Weight
SO MARINE DRUGS
LA English
DT Article
DE fucoidan; fucan; age-related macular degeneration; VEGF; oxidative
   stress; Laminaria hyperborea; brown seaweed extracts; proliferation;
   molecular weight; retinal pigment epithelium
ID MACULAR DEGENERATION; IN-VITRO; FACTOR-H; FUCOIDAN; GROWTH;
   ANGIOGENESIS; PATHWAY; ARPE-19; BINDING
AB Background: Sulfated fucans show interesting effects in the treatment of ocular diseases (e.g., age-related macular degeneration), depending on their chemical structure. Here, we compared three purified sulfated fucans from Laminaria hyperborea (LH) regarding cell viability, oxidative stress protection, and vascular endothelial growth factor (VEGF) secretion in ocular cells. Methods: High-molecular-weight sulfated fucan (M-w = 1548.6 kDa, Fuc1) was extracted with warm water and purified through ultrafiltration. Lower-molecular-weight samples (M-w = 499 kDa, Fuc2; 26.9 kDa, Fuc3) were obtained by mild acid hydrolysis of ultrapurified sulfated fucan and analyzed (SEC-MALS (Size-exclusion chromatography-Multi-Angle Light Scattering), ICP-MS, and GC). Concentrations between 1 and 100 mu g/mL were tested. Cell viability was measured after 24 h (uveal melanoma cell line (OMM-1), retinal pigment epithelium (RPE) cell line ARPE-19, primary RPE cells) via MTT/MTS (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide/3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Oxidative stress protection was determined after 24 h (OMM-1, ARPE-19). VEGF secretion was analyzed via ELISA after three days (ARPE-19, RPE). Results: Fuc2 and Fuc3 were antiproliferative for OMM-1, but not for ARPE. Fuc1 protected OMM-1. VEGF secretion was lowered with all fucans except Fuc3 in ARPE-19 and RPE. The results suggest a correlation between molecular weight and biological activity, with efficiency increasing with size. Conclusion: The LH sulfated fucan Fuc1 showed promising results regarding VEGF inhibition and protection, encouraging further medical research.
C1 [Doerschmann, Philipp; Roider, Johann; Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
   [Kopplin, Georg] Alginor ASA, Haraldsgata 162, N-5525 Haugesund, Norway.
   [Kopplin, Georg] NTNU, Dept Biotechnol & Food Sci, Norwegian Biopolymer Lab NOBIPOL, N-7491 Trondheim, Norway.
C3 University of Kiel; Schleswig Holstein University Hospital; Norwegian
   University of Science & Technology (NTNU)
RP Dorschmann, P (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
EM philipp.doerschmann@uksh.de; Georg.Kopplin@ntnu.no;
   Johann.Roider@uksh.de; Alexa.Klettner@uksh.de
RI Kopplin, Georg/AAL-3211-2020
OI Kopplin, Georg/0000-0001-5002-1465; Klettner, Alexa/0000-0002-2709-1059
FU EU InterReg-Deutschland-Denmark; European Fund of Regional Development
FX This study is part of the FucoSan-Health from the Sea Project and is
   supported by EU InterReg-Deutschland-Denmark and the European Fund of
   Regional Development.
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PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
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JI Mar. Drugs
PD OCT
PY 2019
VL 17
IS 10
AR 548
DI 10.3390/md17100548
PG 14
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA JP1XI
UT WOS:000498064500008
PM 31557816
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schultz, H
   Song, Y
   Baumann, BH
   Kapphahn, RJ
   Montezuma, SR
   Ferrington, DA
   Dunaief, JL
AF Schultz, Hannah
   Song, Ying
   Baumann, Bailey H.
   Kapphahn, Rebecca J.
   Montezuma, Sandra R.
   Ferrington, Deborah A.
   Dunaief, Joshua L.
TI Increased serum proteins in non-exudative AMD retinas
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration (AMD); Blood retinal barrier (BRB);
   Albumin; Fibrinogen; IgG; Complement factor 9 (C9); Iron; Retina
ID MACULAR-DEGENERATION; PIGMENT EPITHELIUM; BARRIER BREAKDOWN;
   ACTIVE-TRANSPORT; UP-REGULATION; BLOOD; COMPLEMENT; POLYMORPHISM;
   FLUORESCEIN; TRANSFERRIN
AB The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing potentially harmful plasma components. While eyes with non-exudative age-related macular degeneration (AMD) were previously felt to have an intact BRB, we propose that the BRB in non-exudative AMD eyes may be subclinically compromised, allowing entry of retina-toxic plasma proteins. We test this hypothesis by measuring retinal levels of abundant plasma proteins that should not cross the intact BRB. Two cohorts of frozen, post mortem neurosensory retinas were studied by Western analysis. One cohort from Alabama had 4 normal controls and 4 eyes with various forms of AMD. Another cohort from Minnesota had 5 intermediate AMD eyes and 5 normals. Both cohorts were age/post mortem interval (PMI) matched. The non exudative AMD retinas in the Alabama cohort had significantly higher levels of albumin and complement component 9 (C9) than normal controls. The positive control exudative AMD donor retina had higher levels of all but one serum protein. In both macular and peripheral neurosensory retina samples, intermediate AMD retinas in the Minnesota cohort had significantly higher levels of albumin, fibrinogen, IgG, and C9 than controls. Our results suggest that there may be moderate subclinical BRB leakage in non-exudative AMD. Potentially harmful plasma components including complement or iron could enter the neurosensory retina in AMD patients prior to advanced disease. Thus, therapies aiming to stabilize the BRB might have a role in the management of non exudative AMD.
C1 [Schultz, Hannah; Song, Ying; Baumann, Bailey H.; Dunaief, Joshua L.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.
   [Kapphahn, Rebecca J.; Montezuma, Sandra R.; Ferrington, Deborah A.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Minnesota System; University of Minnesota Twin Cities
RP Dunaief, JL (通讯作者)，Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Perelman Sch Med, 305 Stellar Chance Lab,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@pennmedicine.upenn.edu
OI Ferrington, Deborah/0000-0003-2561-7464; Baumann,
   Bailey/0000-0002-9595-5795
FU NIH/NEI [EY015240]; Research to Prevent Blindness Medical Student
   Research Award; F. M. Kirby Foundation; Paul and Evanina Bell Mackall
   Foundation Trust [EY026012]; Anonymous Donor for AMD Research; NATIONAL
   EYE INSTITUTE [R01EY026012, R01EY015240] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI070077]
   Funding Source: NIH RePORTER
FX This work was funded in the lab of JLD by: NIH/NEI EY015240, Research to
   Prevent Blindness Medical Student Research Award and unrestricted funds,
   the Jeffrey W. Berger, MD, PhD Foundation, the F. M. Kirby Foundation, a
   gift in memory of Lee F. Mauger, MD, and the Paul and Evanina Bell
   Mackall Foundation Trust. Funding for DAF: NIH/NEI EY026012, Helen
   Lindsay Foundation, Larson Endowed Vision Research Chair, and an
   Anonymous Donor for AMD Research. All funding sources are based in the
   USA.
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NR 45
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 SEP
PY 2019
VL 186
AR 107686
DI 10.1016/j.exer.2019.05.026
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IU6FY
UT WOS:000483683100031
PM 31158383
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Raza, S
   Ergun, SB
   Toklu, Y
   Cakmak, HB
   Ipek, A
   Cagil, N
AF Raza, Sabri
   Ergun, Sule Berk
   Toklu, Yasin
   Cakmak, Hasan Basri
   Ipek, Ali
   Cagil, Nurullah
TI Evaluating the Effect of Intravitreal Ranibizumab on Retrobulbar
   Hemodynamics by Color Doppler Ultrasonography in Neovascular AMD
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID AGE-RELATED MACULOPATHY; GROWTH-FACTOR THERAPY; BLOOD-FLOW-VELOCITY;
   MACULAR DEGENERATION; BEVACIZUMAB AVASTIN(R); INTRAOCULAR
   PHARMACOKINETICS; INJECTION; CHORIOCAPILLARIS; REPRODUCIBILITY
AB BACKGROUND AND OBJECTIVE: To evaluate changes in retrobulbar blood flow by using color Doppler ultrasonography (CDUS) after intravitreal ranibizumab injection in patients with neovascular age-related macular degeneration (AMD).
   PATIENTS AND METHODS: Eighteen patients who had undergone intravitreal ranibizumab (0.05 mg/0.05 mL) injection due to choroidal neovascular membrane (CNVM) were included in the study. Contralateral eyes of the patients were also analyzed. Peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) were measured from the ophthalmic artery (OA), central retinal artery (CRA), lateral posterior ciliary artery (LPCA), and medial posterior ciliary artery (MPCA) for all patients pre-injection, and at 1 day, 1 week, and 1 month after ranibizumab injection.
   RESULTS: The mean age of the 18 patients included in the study was 66.94 years (+/- 8.3 years). Of these 10 patients, eight were female and 10 were male. After Bonferroni's correction for multiple comparisons was carried out, there were significant differences only in some values of LPCA; these included the decrease in EDV and an increase in PI values of LPCA between the pre-injection and post-injection of the first month measurements in uninjected eyes (P = .002, P = .002), and a decrease in PI value of LPCA between post-injection first day and first week measurements in injected eyes (P = .004). There were no statistically significant differences in other parameters.
   CONCLUSION: Ocular blood flow velocities may change after intravitreal ranibizumab injection in patients with CNVM.
C1 [Raza, Sabri] Ataturk Training & Res Hosp, Dept Ophthalmol, Ankara, Turkey.
   [Ergun, Sule Berk] Ankara Numune Training & Res Hosp, Dept Ophthalmol, Ankara, Turkey.
   [Toklu, Yasin; Cagil, Nurullah] Yildirim Beyazit Univ, Fac Med, Dept Ophthalmol, Ankara, Turkey.
   [Cakmak, Hasan Basri] Hitit Univ, Fac Med, Dept Ophthalmol, Corum, Turkey.
   [Ipek, Ali] Ataturk Training & Res Hosp, Dept Radiol, Ankara, Turkey.
C3 Ankara Ataturk Training & Research Hospital; Ankara Numune Training &
   Research Hospital; Yildirim Beyazit University; Hitit University; Ankara
   Ataturk Training & Research Hospital
RP Ergun, SB (通讯作者)，Numune Egitim & Arastirma Hastanesi, Goz Hastaliklari Klin, Ankara, Turkey.
EM suleberk@yahoo.com
RI Cagil, Nurullah/AAG-1401-2019
OI Berk Ergun, Sule/0000-0002-6698-8440; CAKMAK, HASAN
   BASRI/0000-0001-6877-8773
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NR 41
TC 0
Z9 0
U1 0
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 JUL
PY 2019
VL 50
IS 7
BP 437
EP 443
DI 10.3928/23258160-20190703-05
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA IM1IU
UT WOS:000477743100006
PM 31344243
DA 2022-11-30
ER

PT J
AU Lucas, RM
   Yazar, S
   Young, AR
   Norval, M
   de Gruijl, FR
   Takizawa, Y
   Rhodes, LE
   Sinclair, CA
   Neale, RE
AF Lucas, R. M.
   Yazar, S.
   Young, A. R.
   Norval, M.
   de Gruijl, F. R.
   Takizawa, Y.
   Rhodes, L. E.
   Sinclair, C. A.
   Neale, R. E.
TI Human health in relation to exposure to solar ultraviolet radiation
   under changing stratospheric ozone and climate
SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
LA English
DT Article
ID VITAMIN-D SUPPLEMENTATION; NONMELANOMA SKIN-CANCER; SQUAMOUS-CELL
   CARCINOMA; CUTANEOUS MALIGNANT-MELANOMA; POLYMORPHIC LIGHT ERUPTION;
   SUN-PROTECTION POLICIES; ADJUSTED LIFE-YEARS; BASAL-CELL;
   MULTIPLE-SCLEROSIS; UNITED-STATES
AB The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.
C1 [Lucas, R. M.] Australian Natl Univ, Res Sch Populat Hlth, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.
   [Lucas, R. M.; Yazar, S.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia.
   [Yazar, S.] Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
   [Young, A. R.] Kings Coll London, London, England.
   [Norval, M.] Univ Edinburgh, Sch Med, Biomed Sci, Edinburgh, Midlothian, Scotland.
   [de Gruijl, F. R.] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands.
   [Takizawa, Y.] Akita Univ, Sch Med, Natl Inst Minamata Dis, Itabashi Ku, Tokyo, Japan.
   [Rhodes, L. E.] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Ctr Dermatol Res, Manchester, Lancs, England.
   [Rhodes, L. E.] Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
   [Sinclair, C. A.] Canc Council Victoria, Melbourne, Vic, Australia.
   [Neale, R. E.] QIMR Berghofer Inst Med Res, Brisbane, Qld, Australia.
   [Neale, R. E.] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.
C3 Australian National University; University of Western Australia;
   University of Edinburgh; University of London; King's College London;
   University of Edinburgh; Leiden University; Leiden University Medical
   Center (LUMC); Leiden University - Excl LUMC; University of Manchester;
   Salford Royal NHS Foundation Trust; University of Manchester; Cancer
   Council Victoria; QIMR Berghofer Medical Research Institute; University
   of Queensland
RP Lucas, RM (通讯作者)，Australian Natl Univ, Res Sch Populat Hlth, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.; Lucas, RM (通讯作者)，Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia.
EM robyn.lucas@anu.edu.au
RI Yazar, Seyhan/U-4032-2018; Rhodes, Lesley/H-5324-2015; Neale,
   Rachel/I-4427-2018
OI Yazar, Seyhan/0000-0003-0994-6196; Young, Antony/0000-0002-4163-6772;
   Rhodes, Lesley/0000-0002-9107-6654; Lucas, Robyn/0000-0003-2736-3541;
   Neale, Rachel/0000-0001-7162-0854; Sinclair, Craig/0000-0002-6467-1191;
   Neale, Patrick/0000-0002-4047-8098
FU National Health and Medical Research Council of Australia; National
   Institute for Health Research (NIHR) Manchester Biomedical Research
   Centre; CJ Martin Biomedical Fellowship from the National Health and
   Medical Research Council of Australia
FX RML and REN are funded by Senior Research Fellowships from the National
   Health and Medical Research Council of Australia. LER is supported by
   the National Institute for Health Research (NIHR) Manchester Biomedical
   Research Centre. SY is funded by a CJ Martin Biomedical Fellowship from
   the National Health and Medical Research Council of Australia. Travel
   support for CAS was provided by the World Meteorological Organization.
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NR 394
TC 95
Z9 101
U1 6
U2 134
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 1474-905X
EI 1474-9092
J9 PHOTOCH PHOTOBIO SCI
JI Photochem. Photobiol. Sci.
PD MAR 1
PY 2019
VL 18
IS 3
BP 641
EP 680
DI 10.1039/c8pp90060d
PG 40
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA HO6OL
UT WOS:000461049300002
PM 30810559
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Shanmuganathan, S
   Angayarkanni, N
AF Shanmuganathan, Sivasankar
   Angayarkanni, Narayanasamy
TI Chebulagic acid Chebulinic acid and Gallic acid, the active principles
   of Triphala, inhibit TNF alpha induced pro-angiogenic and
   pro-inflammatory activities in retinal capillary endothelial cells by
   inhibiting p38, ERK and NFkB phosphorylation
SO VASCULAR PHARMACOLOGY
LA English
DT Article
DE Diabetic retinopathy; Triphala; Chebulagic acid; Chebulinic acid;
   Anti-angiogenic; Anti-inflammatory; TNF alpha; Age related macular
   degeneration
ID TUMOR-NECROSIS-FACTOR; LPS-INDUCED INFLAMMATION; GLYCATION END-PRODUCTS;
   DIABETIC MACULAR EDEMA; KAPPA-B; GROWTH-FACTOR; IN-VIVO; EXPRESSION;
   INTERLEUKIN-8; RETINOPATHY
AB Tumor necrosis factor-alpha (TNF alpha) a pleiotropic cytokine induces pro-inflammatory and pro-angiogenic changes in conditions such as diabetic retinopathy (DR) and neovascular age related macular degeneration (NV-AMD). Hence, inhibition of TNF alpha mediated changes can benefit the management of DR and NV-AMD. Triphala, an ayurvedic herbal preparation is known to have immunomodulatry functions. In this study we evaluated the alcoholic extract of triphala (AlE) and its compounds Chebulagic acid (CA), Chebulinic acid (CI) and Gallic acid (GA) for their anti-TNF alpha activity. TNF alpha induced pro-inflammatory and pro-angiogenic changes in the retinal-choroid microvascular endothelial cells (RF/6A). Treatment with CA/Cl/GA and the whole Triphala extract showed characteristic inhibition of MMP-9, cell proliferation/migration and tube formation as well the expression of IL-6, IL-8 and MCP-1 without affecting cell viability. This was mediated by inhibition of p38, ERK and NF kappa B phosphorylation. Ex vivo angiogenesis assay using chick chorioallantoic membrane (CAM) model also showed that TNF alpha-induced angiogenesis and it was inhibited by AlE and its active principles. Further, in silico studies revealed that CA, CI and GA are capable of binding the TNF alpha-receptor-1 to mediate anti-TNF alpha activity. This study explains the immunomodulatory function of Triphala, evaluated in the context of retinal and choroid vasculopathies in vitro and ex vivo; which showed that CA, CI and GA can be a potential pharmacological agents in the management of DR and NV-AMD.
C1 [Shanmuganathan, Sivasankar; Angayarkanni, Narayanasamy] Sankara Nethralaya, Vis Res Fdn, RS Mehta Jain Dept Biochem & Cell Biol, 41 Coll Rd, Madras 600006, Tamil Nadu, India.
   [Shanmuganathan, Sivasankar] SASTRA Univ, Sch Chem & Biotechnol, Thanjavur 613401, India.
C3 Shanmugha Arts, Science, Technology & Research Academy (SASTRA)
RP Angayarkanni, N (通讯作者)，Sankara Nethralaya, Vis Res Fdn, RS Mehta Jain Dept Biochem & Cell Biol, 41 Coll Rd, Madras 600006, Tamil Nadu, India.
EM drak@snmail.org
RI Narayanasamy, Angayarkanni/ABD-8584-2020
FU Council of Scientific and Industrial Research, Extramural Research
   Division-II [CSIR-27/029/13-EMRII]
FX This project is funded by Council of Scientific and Industrial Research,
   Extramural Research Division-II, through grant number
   CSIR-27/029/13-EMRII.
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NR 59
TC 40
Z9 41
U1 2
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 1537-1891
EI 1879-3649
J9 VASC PHARMACOL
JI Vasc. Pharmacol.
PD SEP
PY 2018
VL 108
BP 23
EP 35
DI 10.1016/j.vph.2018.04.005
PG 13
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GQ1EE
UT WOS:000441368500004
PM 29678603
DA 2022-11-30
ER

PT J
AU Dorr, M
   Elze, T
   Wang, H
   Lu, ZL
   Bex, PJ
   Lesmes, LA
AF Dorr, Michael
   Elze, Tobias
   Wang, Hui
   Lu, Zhong-Lin
   Bex, Peter J.
   Lesmes, Luis A.
TI New Precision Metrics for Contrast Sensitivity Testing
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Biomarkers; psychometric testing; reproducibility of results
ID VISUAL-ACUITY; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; CHARTS;
   MYOPIA; IPAD; WORLDWIDE; VISION
AB Visual sensitivity is comprehensively described by the contrast sensitivity function (CSF), but current routine clinical care does not include its assessment because of the time-consuming need to estimate thresholds for a large number of spatial frequencies. The quick CSF method, however, dramatically reduces testing times by using a Bayesian information maximization rule. We evaluate the test-retest variability of a tablet-based quick CSF implementation in a study with 100 subjects who repeatedly assessed their vision with and without optical correction. We first discuss two commonly used measures of repeatability, intraclass correlation and the Bland-Altman Coefficient of Repeatability, and show that they are vulnerable to artifacts. Instead, we propose to formulate precision as an information retrieval task: from all repeat test scores, can we retrieve a certain individual based on their first test score? We then use rank-based analyses such as mean average precision as a better measure to compare different test metrics, and show that the highest test-retest precision is achieved using a summary statistic, the area under the log CSF (AULCSF). This demonstrates the benefit of assessment of the whole CSF compared to sensitivity at individual spatial frequencies only. AULCSF also yields best discrimination performance (99.2%) between measurements that were taken with and without glasses, respectively, even better than CSF Acuity. The tablet-based quick CSF thus enables the rapid and reliable home monitoring of visual function, which has the potential to improve early diagnosis and treatment of ophthalmic pathologies such as diabetic retinopathy or age-related macular degeneration.
C1 [Dorr, Michael] Tech Univ Munich, Inst Human Machine Commun, D-80333 Munich, Germany.
   [Elze, Tobias] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Wang, Hui] Jilin Univ Finance & Econ, Changchun 3699, Jilin, Peoples R China.
   [Lu, Zhong-Lin] Ohio State Univ, Ctr Cognit & Behav Brain Imaging Arts & Sci, Columbus, OH 43210 USA.
   [Bex, Peter J.] Northeastern Univ, Coll Sci, Boston, MA 02115 USA.
   [Lesmes, Luis A.] Adapt Sensory Technol, San Diego, CA 92121 USA.
C3 Technical University of Munich; Harvard University; Massachusetts Eye &
   Ear Infirmary; Schepens Eye Research Institute; Jilin University of
   Finance & Economics; University System of Ohio; Ohio State University;
   Northeastern University
RP Dorr, M (通讯作者)，Tech Univ Munich, Inst Human Machine Commun, D-80333 Munich, Germany.
EM michael.dorr@tum.de; tobias-elze@tobias-elze.de; huiwangedu@163.com;
   lu.535@osu.edu; p.bex@northeastern.edu;
   luis.lesmes@adaptivesensorytech.com
OI Dorr, Michael/0000-0002-7879-7908; Elze, Tobias/0000-0002-2032-0496; Lu,
   Zhong-Lin/0000-0002-7295-727X
FU NIH [EY018664, EY021553-01, EY023902]; Bavarian State Ministry for
   Research and Education's Elite Network Bavaria; China Scholarship
   Council Grant; NATIONAL EYE INSTITUTE [R01EY021553, R01EY029713] Funding
   Source: NIH RePORTER
FX This work was supported by the NIH under Grants EY018664, EY021553-01,
   and EY023902. The work of M. Dorr was supported by the Bavarian State
   Ministry for Research and Education's Elite Network Bavaria. The work of
   H. Wang was supported by a China Scholarship Council Grant.
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NR 42
TC 16
Z9 16
U1 2
U2 14
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD MAY
PY 2018
VL 22
IS 3
BP 919
EP 925
DI 10.1109/JBHI.2017.2708745
PG 7
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Mathematical & Computational Biology;
   Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematical & Computational Biology; Medical
   Informatics
GA GE6XN
UT WOS:000431374500031
PM 28650831
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Zimmermann, T
   Hochel, J
   Becka, M
   Boettger, MK
   Rohde, B
   Schug, B
   Kunert, KS
   Donath, F
AF Zimmermann, Torsten
   Hoechel, Joachim
   Becka, Michael
   Boettger, Michael K.
   Rohde, Beate
   Schug, Barbara
   Kunert, Kathleen S.
   Donath, Frank
TI Topical administration of regorafenib eye drops: phase I dose-escalation
   study in healthy volunteers
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE convenience; eye drops; neovascular age-related macular degeneration;
   pharmacokinetics; regorafenib; safety
ID MELANIN
AB AimRegorafenib is a multikinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure.
   MethodsThis was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30mg ml(-1), 25l) as a 0.75mg single dose (Cohort 1), 0.75mg twice daily (bid) or thrice daily (tid) over 14days (Cohorts 2 and 3, respectively), 1.5mg tid unilaterally for 3days, then bilaterally for up to 14days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study.
   ResultsThirty-six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75mg was 600-700-fold lower than after multiple oral administration of 160mg day(-1), the dose approved in cancer indications.
   ConclusionThese results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30mg ml(-1) tid for use in clinical studies.
C1 [Zimmermann, Torsten; Hoechel, Joachim; Becka, Michael; Boettger, Michael K.; Rohde, Beate] Bayer AG, Pharmaceut, Berlin, Germany.
   [Zimmermann, Torsten; Hoechel, Joachim; Becka, Michael; Boettger, Michael K.; Rohde, Beate] Bayer AG, Pharmaceut, Wuppertal, Germany.
   [Schug, Barbara; Donath, Frank] SocraTec R&D GmbH, Erfurt, Germany.
   [Kunert, Kathleen S.] HELIOS Klinikum Erfurt, Dept Ophthalmol, Erfurt, Germany.
C3 Bayer AG; Bayer AG; Helios Kliniken
RP Zimmermann, T (通讯作者)，Bayer AG, Pharmaceut, Berlin, Germany.; Zimmermann, T (通讯作者)，Bayer AG, Pharmaceut, Wuppertal, Germany.
EM torsten.zimmermann@bayer.com
FU Bayer AG, Germany; Bayer AG
FX F.D. is an employee of SocraTec R&D GmbH. B.S. is an owner and Managing
   Director of SocraTec R&D GmbH. This research and publication were funded
   by Bayer AG, Germany (sponsor of the studies and owner of the compound).
   T.Z., J.H., M.B., M.K.B. and B.R. are employees of Bayer AG. All authors
   have approved the manuscript as written. The authors declare that they
   have no other real or potential conflicts of interest.; The authors
   would like to acknowledge the following individuals: Christin Gruhn,
   Sabine Ley, Monique Nennstiel from SocraTec, for their contributions to
   the study conduct, and Antonia Kohnke from Bayer, for her contributions
   to the pharmacokinetic evaluation. They would also like to thank Georg
   Mathis from Appletree, Mario Fsadni from International Pharm-Med and
   Samantha Phillips from Parexel International for their contributions to
   the study preparation (G.M., M.F.), to the safety evaluation (M.F.) and
   for their assistance in the writing and editing of this publication
   (S.P.). This research and publication were funded by Bayer AG.
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NR 23
TC 7
Z9 7
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 MAY
PY 2018
VL 84
IS 5
BP 865
EP 875
DI 10.1111/bcp.13502
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GD0CQ
UT WOS:000430167400005
PM 29315699
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Parmar, T
   Parmar, VM
   Arai, E
   Sahu, B
   Perusek, L
   Maeda, A
AF Parmar, Tanu
   Parmar, Vipul M.
   Arai, Eisuke
   Sahu, Bhubanananda
   Perusek, Lindsay
   Maeda, Akiko
TI Acute Stress Responses Are Early Molecular Events of Retinal
   Degeneration in Abca4(-/-)Rdh8(-/-) Mice After Light Exposure
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE visual cycle; early stress response; RPE; Abca4(-/-)Rdh8(-/-) mice
ID GELATINASE-ASSOCIATED LIPOCALIN; MACULAR DEGENERATION; EPITHELIAL-CELLS;
   GENE-EXPRESSION; RENAL INJURY; STEM-CELLS; DISEASE; ACTIVATION; IRON;
   IDENTIFICATION
AB PURPOSE. Mice lacking ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8) mimic features of human Stargardt disease and age-related macular degeneration. RNA-sequencing of whole eyes was done to study early gene expression changes in Abca4(-/-)Rdh8(-/-) mice.
   MTHODS. Abca4(-/-)Rdh8(-/-) mice at 4 weeks of age were exposed to intense light. Total RNA was extracted from whole eyes and used to generate RNA libraries that were paired-end sequenced on the Illumina HiSeq 2500 device. Differentially expressed genes were annotated using Gene set enrichment analysis (GSEA). Selected genes in enriched pathways exhibiting differential expression were validated using quantitative qRT-PCR and ELISA.
   RESULTS. Transcriptome analysis of the whole eye identified 200 genes that were differentially expressed 24 hours after light exposure compared to no light in Abca4(-/-)Rdh8(-/-) mice. Expression of several visual cycle and photoreceptor genes were decreased, indicative of photoreceptor/RPE cell death. Gene categories of early stress response genes, inflammatory cytokines, immune factors, and JAK STAT components were upregulated. Lipocalin 2 (Lcn2) was the most upregulated early stress response gene identified. Protein LCN2 was produced by RPE cells and the neural retina after intense light exposure as well as in cultured RPE cells from mice and humans incubated with lipopolysaccharide or photoreceptor outer segments.
   CONCLUSIONS. Identification of important mediators involved in the crosstalk between the acute stress response and immune activation in RPE cells and the neural retina, such as LCN2, provide novel molecular targets for reducing cellular stress during retinal degeneration.
C1 [Parmar, Tanu; Parmar, Vipul M.; Arai, Eisuke; Sahu, Bhubanananda; Perusek, Lindsay; Maeda, Akiko] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 10900 Euclid Ave, Cleveland, OH 44106 USA.
   [Maeda, Akiko] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA.
C3 Case Western Reserve University; Case Western Reserve University
RP Maeda, A (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM aam19@case.edu
FU National Institutes of Health (NIH; Bethesda, MD, USA) [EY022658,
   EY11373]; Research to Prevent Blindness Foundation; Foundation Fighting
   Blindness; Ohio Lions Eye Research Foundation; NATIONAL EYE INSTITUTE
   [P30EY011373, R01EY022658] Funding Source: NIH RePORTER
FX Supported by funding from the National Institutes of Health (NIH;
   Bethesda, MD, USA; EY022658 and EY11373), Research to Prevent Blindness
   Foundation, Foundation Fighting Blindness, and Ohio Lions Eye Research
   Foundation.
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TC 20
Z9 20
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2016
VL 57
IS 7
BP 3257
EP 3267
DI 10.1167/iovs.15-18993
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DT8GA
UT WOS:000381726600041
PM 27315541
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Perusek, L
   Sahu, B
   Parmar, T
   Maeno, H
   Arai, E
   Le, YZ
   Subauste, CS
   Chen, Y
   Palczewski, K
   Maeda, A
AF Perusek, Lindsay
   Sahu, Bhubanananda
   Parmar, Tanu
   Maeno, Hiroshi
   Arai, Eisuke
   Le, Yun-Zheng
   Subauste, Carlos S.
   Chen, Yu
   Palczewski, Krzysztof
   Maeda, Akiko
TI Di-retinoid-pyridinium-ethanolamine (A2E) Accumulation and the
   Maintenance of the Visual Cycle Are Independent of Atg7-mediated
   Autophagy in the Retinal Pigmented Epithelium
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE aging; autophagy; autophagy-related protein 7 (ATG7); retina; retinal
   degeneration; A2E; ABCA4; Stargardt disease
ID CHAPERONE-MEDIATED AUTOPHAGY; LIPOFUSCIN FLUOROPHORE A2E; PLURIPOTENT
   STEM-CELLS; HUMAN RPE CELLS; MACULAR DEGENERATION; OUTER SEGMENTS;
   MICROGLIAL ACTIVATION; OXIDATIVE STRESS; IN-VIVO; MICE
AB Autophagy is an evolutionarily conserved catabolic mechanism that relieves cellular stress by removing/recycling damaged organelles and debris through the action of lysosomes. Compromised autophagy has been implicated in many neurodegenerative diseases, including retinal degeneration. Here we examined retinal phenotypes resulting from RPE-specific deletion of the autophagy regulatory gene Atg7 by generating Atg7(flox/flox);VMD2-rtTA-cre+ mice to determine whether autophagy is essential for RPE functions including retinoid recycling. Atg7-deficient RPE displayed abnormal morphology with increased RPE thickness, cellular debris and vacuole formation indicating that autophagy is important in maintaining RPE homeostasis. In contrast, 11-cis-retinal content, ERGs and retinal histology were normal in mice with Atg7-deficient RPE in both fasted and fed states. Because A2E accumulation in the RPE is associated with pathogenesis of both Stargardt disease and age-related macular degeneration (AMD) in humans, deletion of Abca4 was introduced into Atg7(flox/flox);VMD2-rtTA-cre+ mice to investigate the role of autophagy during A2E accumulation. Comparable A2E concentrations were detected in the eyes of 6-month-old mice with and without Atg7 from both Abca4(-/-) and Abca4(+/+) backgrounds. To identify other autophagy-related molecules involved in A2E accumulation, we performed gene expression array analysis on A2E-treated human RPE cells and found up-regulation of four autophagy related genes; DRAM1, NPC1, CASP3, and EIF2AK3/PERK. These observations indicate that Atg7-mediated autophagy is dispensable for retinoid recycling and A2E deposition; however, autophagy plays a role in coping with stress caused by A2E accumulation.
C1 [Perusek, Lindsay; Sahu, Bhubanananda; Parmar, Tanu; Maeno, Hiroshi; Arai, Eisuke; Maeda, Akiko] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Chen, Yu; Palczewski, Krzysztof; Maeda, Akiko] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Chen, Yu; Palczewski, Krzysztof; Maeda, Akiko] Case Western Reserve Univ, Cleveland Ctr Membrane & Struct Biol, Cleveland, OH 44106 USA.
   [Subauste, Carlos S.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Med Endocrinol, Dept Cell Biol, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
   [Le, Yun-Zheng] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Diabet Ctr, Oklahoma City, OK 73104 USA.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; Case Western Reserve University; University
   of Oklahoma System; University of Oklahoma Health Sciences Center;
   University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center
RP Maeda, A (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM aam19@case.edu
RI Regan, Clinton/E-6250-2012
FU National Institutes of Health [5P30AR039750]; Ohio Department of
   Development - Center for Innovative Immunosuppressive Therapeutics [TECH
   09-023];  [P30 EY11373]; NATIONAL EYE INSTITUTE [R01EY022658,
   P30EY011373, R24EY021126] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
   [P30AR039750] Funding Source: NIH RePORTER
FX We thank Dr. Leslie T. Webster, Jr, Vipulkumar Parmar (Case Western
   Reserve University) for helpful comments on the manuscript, the Visual
   Sciences Research Center Core Facility (supported by P30 EY11373), in
   particular Scott Howell and Sarah Lindstrom for their help with
   microscopy, and the flow cytometry facility in the Department of
   Dermatology's Skin Diseases Research Center (SDRC) for assistance with
   confocal microscopy. The Department of Dermatology's Skin Diseases
   Research Center (SDRC) is supported in part by the National Institutes
   of Health Grant (5P30AR039750) and the Ohio Department of Development -
   Center for Innovative Immunosuppressive Therapeutics (TECH 09-023).
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NR 61
TC 24
Z9 24
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 27
PY 2015
VL 290
IS 48
BP 29035
EP 29044
DI 10.1074/jbc.M115.682310
PG 10
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CX5SH
UT WOS:000365762300041
PM 26468292
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Falkner-Radler, CI
   Krebs, I
   Glittenberg, C
   Povazay, B
   Drexler, W
   Graf, A
   Binder, S
AF Falkner-Radler, Christiane I.
   Krebs, Ilse
   Glittenberg, Carl
   Povazay, Boris
   Drexler, Wolfgang
   Graf, Alexandra
   Binder, Susanne
TI Human retinal pigment epithelium (RPE) transplantation: outcome after
   autologous RPE-choroid sheet and RPE cell-suspension in a randomised
   clinical study
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; BRUCHS MEMBRANE; TRANSLOCATION
AB Aims To evaluate the outcome after two types of retinal pigment epithelium (RPE) transplantation techniques.
   Methods Fourteen consecutive patients with advanced exudative age-related macular degeneration (AMD) were randomly assigned to RPE-choroid sheet transplantation (group 1) or RPE cell-suspension transplantation (group 2). Outcome measures included best corrected distance and near visual acuity (BCVA), complication and recurrence rates, autofluorescence (AF), angiography, and time-domain and spectral-domain optical coherence tomography (TD- and SD-OCT).
   Results A gain of three or more lines in BCVA at 24 months was found in two patients in group 1 and in one patient in group 2, whereas a loss of vision of three or more lines occurred in one patient in each group. Revision surgery for proliferative vitreoretinopathy was required in one patient in group 1. Epiretinal membranes developed in two patients in group 1 and in one patient in group 2. No recurrence occurred in this series. AF showed hyperfluorescence coincident with the graft in group 1, and hyper- and hypofluorescence in irregular patterns in group 2. Revascularisation of the graft was present in all patients in group 1, and a normal choroidal vasculature in the area of RPE atrophy in all patients in group 2. OCT showed a decrease in retinal thickness in all patients, with an improved visualisation of inter- and intralaminar structures with SD-OCT.
   Conclusion The anatomical and functional outcome after both RPE transplantation techniques was comparable. Intrastructural irregularities of the sheet assessed using SD-OCT might explain the rather limited visual gain in otherwise successful sheet transplants.
C1 [Falkner-Radler, Christiane I.; Krebs, Ilse; Glittenberg, Carl; Binder, Susanne] Rudolf Fdn Clin, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Dept Ophthalmol, A-1030 Vienna, Austria.
   [Povazay, Boris; Drexler, Wolfgang] Cardiff Univ, Biomed Imaging Grp, Dept Optometry & Vis Sci, Cardiff, S Glam, Wales.
   [Graf, Alexandra] Med Univ Vienna, Dept Med Stat, Core Unit Med Stat & Informat, Vienna, Austria.
C3 Ludwig Boltzmann Institute; Cardiff University; Medical University of
   Vienna
RP Falkner-Radler, CI (通讯作者)，Rudolf Fdn Clin, Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, Dept Ophthalmol, Juchgasse 25, A-1030 Vienna, Austria.
EM christiane.falkner-radler@wienkav.at
RI Považay, Boris/F-6258-2012
OI Povazay, Boris/0000-0001-5571-5116; Graf, Alexandra/0000-0003-0035-2658;
   Drexler, Wolfgang/0000-0002-3557-6398
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NR 24
TC 97
Z9 105
U1 1
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2011
VL 95
IS 3
BP 370
EP 375
DI 10.1136/bjo.2009.176305
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 722NY
UT WOS:000287440400014
PM 20610478
OA Bronze
DA 2022-11-30
ER

PT J
AU Yeh, B
   Ferrucci, S
AF Yeh, Brenda
   Ferrucci, Steven
TI Retinal pigment epithelium tears after bevacizumab injection
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Article
DE Age-related macular degeneration; Bevacizumab; Avastin; Choroidal
   neovascularization (CNV); Vascular endothelial growth factor; Pigment
   epithelial detachment; Retinal pigment epithelial tear
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; INTRAVITREAL BEVACIZUMAB;
   AVASTIN; PATHOGENESIS; DETACHMENTS; PREDICTORS; THERAPY; RISK
AB BACKGROUND: The advent of anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization has become the standard of care for wet age-related macular degeneration (AMD). Among the choices, intravitreal bevacizumab, for off-label use, has gained popularity. Recent attention has been on the complications of anti-VEGF treatment, one of them being a retinal pigment epithelial (RPE) tear. A tear in the RPE is a visually devastating complication, most commonly associated with fibrovascular pigment epithelial detachments (PED) in AMD, and may develop during the course of intravitreal bevacizumab treatment.
   CASE REPORT: We report a case of an 85-year-old white man with decreased visual acuities of 20/70 in the right eye (O.D.) and 20/150 in the left eye (O.S.) secondary to dry AMD O.D. and wet AMD with a fibrovascular PED O.S. The patient underwent treatment with an intravitreal bevacizumab injection O.S. Six weeks after the initial injection, the patient returned with further declining vision in the left eye secondary to an RPE tear.
   CONCLUSION: Intravitreal bevacizumab has proven to be an effective treatment for choroidal neovascularization and shows a significant improvement of vision for wet AMD patients. However, there are risks associated with the procedure. One of the most visually significant is an RPE tear, which can occur at an incidence rate as high as 17%. Optometrists should be aware of this rare, but serious, complication associated with anti-VEGF treatment for wet AMD. Optometry 2011;82:152-157
C1 [Yeh, Brenda; Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
   [Yeh, Brenda; Ferrucci, Steven] Sepulveda Vet Affairs Ambulatory Care Ctr Nursing, Sepulveda, CA USA.
   [Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   VA Greater Los Angeles Healthcare System
RP Ferrucci, S (通讯作者)，Sepulveda Vet Affairs Ambulatory Care Ctr, 16111 Plummer St 112E, Sepulveda, CA 91343 USA.
EM Steven.Ferrucci@va.gov
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NR 44
TC 4
Z9 4
U1 0
U2 1
PU AMER OPTOMETRIC ASSN INC
PI ST LOUIS
PA 243 N LINDBERGH BLVD, ST LOUIS, MO 63141 USA
SN 1529-1839
EI 1558-1527
J9 OPTOMETRY
JI Optometry
PD MAR
PY 2011
VL 82
IS 3
BP 152
EP 157
DI 10.1016/j.optm.2010.09.010
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 778MO
UT WOS:000291708600006
PM 21130699
DA 2022-11-30
ER

PT J
AU Miyaoka, T
   Furuya, M
   Kristian, L
   Wake, R
   Kawakami, K
   Nagahama, M
   Kawano, K
   Ieda, M
   Tsuchie, K
   Horiguchi, J
AF Miyaoka, Tsuyoshi
   Furuya, Motohide
   Kristian, Liaury
   Wake, Rei
   Kawakami, Kazunori
   Nagahama, Michiharu
   Kawano, Kiminori
   Ieda, Masa
   Tsuchie, Keiko
   Horiguchi, Jun
TI Yi-Gan San for Treatment of Charles Bonnet Syndrome (Visual
   Hallucination Due to Vision Loss): An Open-Label Study
SO CLINICAL NEUROPHARMACOLOGY
LA English
DT Review
DE Charles Bonnet syndrome; hallucinations; yi-gan san; open-label study;
   GABA; NMDA; 5-HT
ID DEMENTIA; SCHIZOPHRENIA; THERAPY
AB Background: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful for treating behavioral and psychological symptoms in dementia, borderline personality disorder, neuroleptic-induced tardive dyskinesia, and treatment-resistant schizophrenia. Visual hallucinations are common and often distressing consequences of vision loss, particularly in age-related macular degeneration. Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration, and preserved cognitive status. We aimed at evaluating both the efficacy and safety of YGS in patients with CBS.
   Methods: Twenty patients diagnosed with CBS were investigated, according to the diagnostic criteria established by Gold and Rabins and Teunisse. Participants were treated in a 4-week open-label study with YGS at an average daily dose of 5.8 +/- 2.6 g (2.5-7.5 g). Psychometric instruments used to assess efficacy included the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression. No cases of serious adverse events were attributed to the study's drug therapy.
   Results: A significant decrease in visual hallucination was observed at 2 and 4 weeks in the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression scores.
   Conclusions: Yi-gan san may be an effective and safe therapy to control visual hallucination in patients with CBS and should be further tested in double-blind, placebo-controlled trials. Given the design characteristics of this trial, the present findings should be taken cautiously.
C1 [Miyaoka, Tsuyoshi; Furuya, Motohide; Kristian, Liaury; Wake, Rei; Kawakami, Kazunori; Nagahama, Michiharu; Kawano, Kiminori; Ieda, Masa; Tsuchie, Keiko; Horiguchi, Jun] Shimane Univ, Dept Psychiat, Sch Med, Izumo, Shimane 6938501, Japan.
C3 Shimane University
RP Miyaoka, T (通讯作者)，Shimane Univ, Dept Psychiat, Sch Med, 89-1 Enyacho, Izumo, Shimane 6938501, Japan.
EM miyanyan@med.shimane-u.ac.jp
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NR 34
TC 16
Z9 16
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0362-5664
EI 1537-162X
J9 CLIN NEUROPHARMACOL
JI Clin. Neuropharmacol.
PD JAN-FEB
PY 2011
VL 34
IS 1
BP 24
EP 27
DI 10.1097/WNF.0b013e318206785a
PG 4
WC Clinical Neurology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 707UA
UT WOS:000286312700006
PM 21164340
DA 2022-11-30
ER

PT J
AU Gendron, RL
   Laver, NV
   Good, WV
   Grossniklaus, HE
   Miskiewicz, E
   Whelan, MA
   Walker, J
   Paradis, H
AF Gendron, Robert L.
   Laver, Nora V.
   Good, William V.
   Grossniklaus, Hans E.
   Miskiewicz, Ewa
   Whelan, Maria A.
   Walker, Jacqueline
   Paradis, Helene
TI Loss of Tubedown Expression as a Contributing Factor in the Development
   of Age-Related Retinopathy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BLOOD-RETINAL BARRIER; N-TERMINAL ACETYLTRANSFERASES; MACULAR
   DEGENERATION; ENDOTHELIAL-CELLS; SEQUENCE REQUIREMENTS;
   VASCULAR-PERMEABILITY; DIABETIC-RETINOPATHY; OXIDATIVE STRESS; IN-VITRO;
   CORTACTIN
AB PURPOSE. Tubedown (Tbdn), a cortactin-binding acetyltransferase subunit, regulates retinal vascular permeability and homeostasis in adulthood. Here the authors explore whether Tbdn loss during aging might contribute to the mechanisms underlying age-related neovascular retinopathy.
   METHODS. A conditional endothelial-specific transgenic model of Tbdn loss was compared with aged mouse and human specimens from 5- to 93-year-old individuals. Specimens were analyzed by morphometric measurements and for functional markers using immunohistochemistry and Western blot analysis.
   RESULTS. An age-dependent decrease in Tbdn expression in endothelial cells of the posterior pole of the eye correlated with pathologic changes in choroidal and retinal tissues of aged mice. In humans, aged specimens without eye disease exhibited a moderate decrease in retinal and choroidal endothelial Tbdn expression compared with younger persons, whereas a greater decrease in choroid vascular Tbdn expression was observed in patients with age-related macular degeneration. In mice, Tbdn loss resulting from old age or conditional Tbdn knockdown was associated with retinal lesions showing significant extravascularly localized albumin and correlated with increased activity of senescence-associated beta-galactosidase in the retinal pigment epithelium. A range of abnormalities in RPE, Bruch's membrane, and choriocapillaris observable at the ultrastructural level in Tbdn-knockdown eyes recapitulate those present in human AMD.
   CONCLUSIONS. This work provides evidence that the marked decrease in the level of expression of Tbdn in the retinal and choroidal vasculature during aging contributes to the multifactorial process that leads to the development of age-related retinopathy and choroidopathy. (Invest Ophthalmol Vis Sci. 2010;51:5267-5277) DOI:10.1167/iovs.09-4527
C1 [Gendron, Robert L.; Miskiewicz, Ewa; Whelan, Maria A.; Walker, Jacqueline; Paradis, Helene] Mem Univ Newfoundland, Dept Med, Div Basic Med Sci, St John, NF A1B 3V6, Canada.
   [Laver, Nora V.] New England Eye Ctr, Ocular Pathol Lab, Boston, MA USA.
   [Good, William V.] Smith Kettlewell Eye Res Inst, San Francisco, CA 94115 USA.
   [Grossniklaus, Hans E.] Emory Eye Ctr, Dept Ophthalmol, LF Montgomery Pathol Lab, Atlanta, GA USA.
C3 Memorial University Newfoundland; The Smith-Kettlewell Eye Research
   Institute
RP Gendron, RL (通讯作者)，Mem Univ Newfoundland, Dept Med, Div Basic Med Sci, St John, NF A1B 3V6, Canada.
EM rgendron@mun.ca; hparadis@mun.ca
FU Canadian Institutes for Health Research [IAP-7337, ROP, MOP-78948];
   Newfoundland and Labrador Innovation and Rural Development
   Infrastructure Fund; Canadian Foundation for Innovation [7411]; Atlantic
   Canada Opportunities Agency
FX Supported by operating grants from Canadian Institutes for Health
   Research (IAP-7337, ROP, and MOP-78948), Newfoundland and Labrador
   Innovation and Rural Development Infrastructure Fund, an Infrastructure
   grant from Canadian Foundation for Innovation (7411) (HP, RLG), and an
   Atlantic Canada Opportunities Agency grant to Memorial University in
   support of the specific pathogen-free barrier animal housing
   infrastructure.
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NR 62
TC 8
Z9 8
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 OCT
PY 2010
VL 51
IS 10
BP 5267
EP 5277
DI 10.1167/iovs.09-4527
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 655UI
UT WOS:000282275500054
PM 20463314
DA 2022-11-30
ER

PT J
AU Adelman, RA
   Zheng, Q
   Mayer, HR
AF Adelman, Ron A.
   Zheng, Qi
   Mayer, Hylton R.
TI Persistent Ocular Hypertension Following Intravitreal Bevacizumab and
   Ranibizumab Injections
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID INTRAOCULAR-PRESSURE CHANGES; LASER POSTERIOR CAPSULOTOMY; MACULAR
   DEGENERATION; PEGAPTANIB; ELEVATION; AVASTIN(R); NEODYMIUM
AB Purpose: To study ocular hypertension (OHT) following intravitreal injections of bevacizumab and/or ranibizumab in patients with age-related macular degeneration (AMD).
   Methods: Retrospective case series. Patients with AMD who were treated at a tertiary referral center with intravitreal bevacizumab and/or ranibizumab injections from January 1, 2006 to December 31, 2008 were studied. The development of OHT following these injections was investigated.
   Results: Four out of 116 patients with AMD (3.45%) developed sustained elevated intraocular pressure (IOP) after multiple intravitreal injections of bevacizumab 1.5 mg/0.06 mL and/or ranibizumab 0.5 mg/0.05 mL. An analysis of 4 cases revealed: None of the patients had a previous diagnosis or family history of glaucoma/OHT. Two patients had both bevacizumab and ranibizumab injections. Two patients developed OHT after recent intravitreal ranibizumab and 2 patients after recent intravitreal bevacizumab injection. Two patients were pseudophakic with a history of YAG capsulotomy. The range of preinjection IOP was 8-15 mmHg (mean, 13 mmHg). The range of postinjection IOP was 28-36 mmHg (mean, 31.75 mmHg). The range of IOP increase was 17-21 mmHg (mean, 18.75 mmHg). Mean number of pan-anti-VEGF injections prior to OHT was 13.3 (range, 3-19). A disrupted posterior capsule might predispose patients to the development of OHT.
   Conclusions: Persistent OHT may occur after intravitreal anti-VEGF injection in patients with no previous diagnosis of glaucoma or OHT. OHT may persist across several visits and patients may require IOP-lowering therapy. Sustained elevation in IOP usually occurs after multiple injections.
C1 [Adelman, Ron A.; Zheng, Qi; Mayer, Hylton R.] Yale Univ, Sch Med, Yale Eye Ctr, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
C3 Yale University
RP Adelman, RA (通讯作者)，Yale Univ, Sch Med, Yale Eye Ctr, Dept Ophthalmol & Visual Sci, 40 Temple St,Suite 3D, New Haven, CT 06510 USA.
EM ron.adelman@yale.edu
FU Leir Foundation (New York, NY); Newman's Own Foundation (Westport, CT);
   Research to Prevent Blindness (New York, NY)
FX Funding/Support: This study was supported by the Leir Foundation (New
   York, NY), Newman's Own Foundation (Westport, CT), and Research to
   Prevent Blindness (New York, NY). The sponsors or funding organizations
   had no role in the design or conduct of this research.
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NR 18
TC 121
Z9 127
U1 0
U2 6
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 FEB
PY 2010
VL 26
IS 1
BP 105
EP 110
DI 10.1089/jop.2009.0076
PG 6
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 562JT
UT WOS:000275047000014
PM 20187807
DA 2022-11-30
ER

PT J
AU Sabbieti, MG
   Marchegiani, A
   Sufianov, AA
   Gabai, VL
   Shneider, A
   Agas, D
AF Sabbieti, Maria Giovanna
   Marchegiani, Andrea
   Sufianov, Albert A.
   Gabai, Vladimir L.
   Shneider, Alexander
   Agas, Dimitrios
TI P62/SQSTM1 beyond Autophagy: Physiological Role and Therapeutic
   Applications in Laboratory and Domestic Animals
SO LIFE-BASEL
LA English
DT Review
DE p62; SQSTM1; inflammation; aging; inflammatory diseases; degenerative
   diseases
ID CANINE MAMMARY-TUMORS; POOR-PROGNOSIS; DNA VACCINE; PROTEIN P62;
   DISEASE; DOGS; OSTEOARTHRITIS; DEGENERATION; INFLAMMATION; MUTATION
AB Inflammation is the preceding condition for the development of mild and severe pathological conditions, including various forms of osteopenia, cancer, metabolic syndromes, neurological disorders, atherosclerosis, cardiovascular, lung diseases, etc., in human and animals. The inflammatory status is induced by multifarious intracellular signaling cascades, where cytokines, chemokines, arachidonic acid metabolites, adhesion molecules, immune cells and other components foster a "slow burn" at a local or systemic level. Assuming that countering inflammation limits the development of inflammation-based diseases, a series of new side-effects-free therapies was assessed in experimental and domestic animals. Within the targets of the drug candidates for quenching inflammation, an archetypal autophagic gear, the p62/sqstm1 protein, has currently earned attention from researchers. Intracellular p62 has been recently coined as a multi-task tool associated with autophagy, bone remodeling, bone marrow integrity, cancer progression, and the maintenance of systemic homeostasis. Accordingly, p62 can act as an effective suppressor of inflamm-aging, reducing oxidative stress and proinflammatory signals. Such an operational schedule renders this protein an effective watchdog for degenerative diseases and cancer development in laboratory and pet animals. This review summarizes the current findings concerning p62 activities as a molecular hub for cell and tissues metabolism and in a variety of inflammatory diseases and other pathological conditions. It also specifically addresses the applications of exogenous p62 (DNA plasmid) as an anti-inflammatory and homeostatic regulator in the treatment of osteoporosis, metabolic syndrome, age-related macular degeneration and cancer in animals, and the possible application of p62 plasmid in other inflammation-associated diseases.
C1 [Sabbieti, Maria Giovanna; Marchegiani, Andrea; Agas, Dimitrios] Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy.
   [Sufianov, Albert A.] Fed Ctr Neurosurg, Tyumen 625032, Russia.
   [Sufianov, Albert A.] Sechenov First Moscow State Med Univ, Moscow 119991, Russia.
   [Gabai, Vladimir L.; Shneider, Alexander] CureLab Oncol Inc, Dedham, MA 02026 USA.
   [Shneider, Alexander] Ariel Univ, Dept Mol Biol, IL-40700 Ariel, Israel.
   [Shneider, Alexander] Peter Great St Petersburg Polytech Univ, Inst Biomed Syst & Biotechnol, St Petersburg 195251, Russia.
C3 University of Camerino; Sechenov First Moscow State Medical University;
   Ariel University; Peter the Great St. Petersburg Polytechnic University
RP Agas, D (通讯作者)，Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy.
EM giovanna.sabbieti@unicam.it; andrea.marchegiani@unicam.it;
   sufianov@gmail.com; vgabai@curelab.com; ashneider@curelab.com;
   dimitrios.agas@unicam.it
RI Marchegiani, Andrea/L-3533-2019
OI Marchegiani, Andrea/0000-0002-3629-0391; Agas,
   Dimitrios/0000-0002-7809-3601
FU UNICAM Noemi Avicolli funds
FX This work was financially supported by the UNICAM Noemi Avicolli funds.
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NR 81
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-1729
J9 LIFE-BASEL
JI Life-Basel
PD APR
PY 2022
VL 12
IS 4
AR 539
DI 10.3390/life12040539
PG 12
WC Biology; Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Microbiology
GA 0S1NR
UT WOS:000786048900001
PM 35455030
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Altinisik, M
   Kurt, E
   Kayikcioglu, O
   Yildirim, A
AF Altinisik, Muhammed
   Kurt, Emin
   Kayikcioglu, Ozcan
   Yildirim, Abdulmutalip
TI Quantitative Analysis of the Activity in Choroidal Neovascularizations
   after a Single Anti-VEGF injection: OCT Versus OCT Angiography
SO SEMINARS IN OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF; biomarker; choroidal neovascularization; CNV area; optical
   coherence tomography angiography
AB Purpose: To analyze early quantitative changes in the choroidal neovascularization (CNV) area observed with optical coherence tomography angiography (OCTA) after single anti-vascular endothelial growth factor (anti-VEGF) injection.
   Materials and Methods: Treatment-naive patients with CNV secondary to neovascular age-related macular degeneration were analyzed immediately before and -4 weeks after anti-VEGF injection. The primary endpoints of the study included changes in CNV total and vascular area. Secondary endpoints were best-corrected visual acuity (BCVA), central macular thickness (cMT), central total macular thickness (cTMT), and subfoveal choroidal thickness (SFCT).
   Results: A total of 27 patients (69.19 +/- 5.91 years, 21 men/6 women, 14 type 1 NV, 11 type 2 NV, and 2 type 3 NV) were included in the study. There was a significant increase in BCVA and decreases in cMT, cTMT, and SFCT after treatment (p<0.05 for all). CNV total and vascular area changed by -11.55 +/- 44.26% (95% confidence interval [CI]: -29.06 and 5.95; p=0.269) and -21.06 +/- 41.2% (95% CI: -36.45/-5.67; p=0.786), respectively. The cases with decreased cTMT were accompanied by a decrease in CNV area only in 37% of the cases. No significant correlation was detected between cTMT and CNV total and vascular area percentage changes (r = -0.06, p=0.74; r = 0.02, p=0.9, respectively).
   Conclusions: Changes in CNV total and vascular area seem to have limited sensitivity as a biomarker in terms of activation, as wide variability was observed in CNV area after anti-VEGF injection.
C1 [Altinisik, Muhammed; Kurt, Emin; Kayikcioglu, Ozcan; Yildirim, Abdulmutalip] Manisa Celal Bayar Univ, Ophthalmol Dept, Manisa, Turkey.
C3 Celal Bayar University
RP Altinisik, M (通讯作者)，Manisa Celal Bayar Univ, Ophthalmol Dept, Manisa, Turkey.
EM dr.maltinisik@gmail.com
OI Altinisik, Muhammed/0000-0003-0239-0180
FU Scientific Research Project Office of Manisa Celal Bayar University
   [2018-130]
FX This project was funded by the Scientific Research Project Office of
   Manisa Celal Bayar University under project no: 2018-130.
CR Al-Sheikh M, 2018, RETINA-J RET VIT DIS, V38, P220, DOI 10.1097/IAE.0000000000001628
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NR 30
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0882-0538
EI 1744-5205
J9 SEMIN OPHTHALMOL
JI Semin. Ophthalmol.
PD OCT 3
PY 2021
VL 36
IS 7
BP 573
EP 581
DI 10.1080/08820538.2021.1903944
EA APR 2021
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UN2DV
UT WOS:000635009700001
PM 33784223
DA 2022-11-30
ER

PT J
AU Nicholson, C
   Ishii, M
   Annamalai, B
   Chandler, K
   Chwa, M
   Kenney, MC
   Shah, N
   Rohrer, B
AF Nicholson, Crystal
   Ishii, Masaaki
   Annamalai, Balasubramaniam
   Chandler, Kyrie
   Chwa, Marilyn
   Kenney, M. Cristina
   Shah, Navjot
   Rohrer, Barbel
TI J or H mtDNA haplogroups in retinal pigment epithelial cells: Effects on
   cell physiology, cargo in extracellular vesicles, and differential
   uptake of such vesicles by naive recipient cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Retinal pigment epithelium; Extracellular vesicles; mtDNA cybrids;
   OXPHOS; Ligands; Age-related macular degeneration
AB Purpose: Extracellular vesicles (EVs) are predicted to represent the internal state of cells. In polarized RPE monolayers, EVs can mediate long-distance communication, requiring endocytosis via protein-protein interactions. EV uptake from oxidatively stressed donor cells triggers loss in transepithelial resistance (TER) in recipient monolayers mediated by HDAC6. Here, we examine EVs released from RPE cells with identical nuclear genes but different mitochondrial (mt)DNA haplogroups (H, J). J-cybrids produce less ATP, and the J-haplogroup is associated with a higher risk for age-related macular degeneration.
   Methods: Cells were grown as mature monolayers to either collect EVs from apical surfaces or to serve as naive recipient cells. Transfer assays, transferring EVs to a recipient monolayer were performed, monitoring TER and EV-uptake. The presence of known EV surface proteins was quantified by protein chemistry.
   Results: H- and J-cybrids were confirmed to exhibit different levels of TER and energy metabolism. EVs from J-cybrids reduced TER in recipient ARPE-19 cells, whereas EVs from H-cybrids were ineffective. TER reduction was mediated by HDAC6 activity, and EV uptake required interaction between integrin and its ligands and surface proteoglycans. Protein quantifications confirmed elevated levels of fibronectin and annexin A2 on J-cybrid EVs.
   Conclusions: We speculate that RPE EVs have a finite set of ligands (membrane proteoglycans and integrins and/or annexin A2) that are elevated in EVs from stressed cells; and that if EVs released by the RPE could be captured from serum, that they might provide a disease biomarker of RPE-dependent diseases.
C1 [Nicholson, Crystal; Ishii, Masaaki; Annamalai, Balasubramaniam; Chandler, Kyrie; Shah, Navjot; Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
   [Chwa, Marilyn; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Dept Ophthalmol, Irvine, CA 92697 USA.
   [Rohrer, Barbel] Univ South Carolina, Dept Neurosci Med, Charleston, SC 29425 USA.
   [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
C3 Medical University of South Carolina; University of California System;
   University of California Irvine; US Department of Veterans Affairs;
   Veterans Health Administration (VHA); Ralph H Johnson VA Medical Center
RP Rohrer, B (通讯作者)，Med Univ South Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
OI Ishii, Masaaki/0000-0002-0775-5401
FU Department of Veterans Affairs [I01RX000444, I01BX003050, IK6BX004858];
   National Institutes of Health [R01EY024581]; South Carolina SmartState
   Endowment; NIH [R01EY0127363]; Research to Prevent Blindness, New York,
   NY; Discovery Eye Foundation, Los Angeles, CA
FX In the Rohrer laboratory, the study was supported in part by the
   Department of Veterans Affairs (I01RX000444, I01BX003050 and
   IK6BX004858), the National Institutes of Health (R01EY024581), and the
   South Carolina SmartState Endowment; Cris Kenney is supported by NIH
   R01EY0127363 and Unrestricted grants to the Department of Ophthalmology
   from Research to Prevent Blindness, New York, NY and the Discovery Eye
   Foundation, Los Angeles, CA. The authors would like to thank James Chao
   for help with the HDAC6 assay.
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NR 55
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD APR
PY 2021
VL 1865
IS 4
SI SI
AR 129798
DI 10.1016/j.bbagen.2020.129798
EA FEB 2021
PG 10
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA RJ1AD
UT WOS:000637333900013
PM 33217521
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Romo-Bucheli, D
   Erfurth, US
   Bogunovic, H
AF Romo-Bucheli, David
   Erfurth, Ursula Schmidt
   Bogunovic, Hrvoje
TI End-to-End Deep Learning Model for Predicting Treatment Requirements in
   Neovascular AMD From Longitudinal Retinal OCT Imaging
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Retina; Predictive models; Task analysis; Deep learning; Biomedical
   imaging; Visualization; Age-related macular degeneration; deep learning;
   longitudinal imaging; optical coherence tomography
ID OPTICAL COHERENCE TOMOGRAPHY; QUANTIFICATION; RANIBIZUMAB
AB Neovascular age-related macular degeneration (nAMD) is nowadays successfully treated with anti-VEGF substances, but inter-individual treatment requirements are vastly heterogeneous and currently poorly plannable resulting in suboptimal treatment frequency. Optical coherence tomography (OCT) with its 3D high-resolution imaging serves as a companion diagnostic to anti-VEGF therapy. This creates a need for building predictive models using automated image analysis of OCT scans acquired during the treatment initiation phase. We propose such a model based on deep learning (DL) architecture, comprised of a densely connected neural network (DenseNet) and a recurrent neural network (RNN), trainable end-to-end. The method starts by sampling several 2D-images from an OCT volume to obtain a lower-dimensional OCT representation. At the core of the predictive model, the DenseNet learns useful retinal spatial features while the RNN integrates information from different time points. The introduced model was evaluated on the prediction of anti-VEGF treatment requirements in nAMD patients treated under a pro-re-nata (PRN) regimen. The DL model was trained on 281 patients and evaluated on a hold-out test set of 69 patient. The predictive model achieved a concordance index of 0.7 in regressing the number of received treatments, while in a classification task it obtained an 0.85 (0.81) AUC in detecting the patients with low (high) treatment requirements. The proposed model outperformed previous machine learning strategies that relied on a set of spatio-temporal image features, showing that the proposed DL architecture successfully learned to extract the relevant spatio-temporal patterns directly from raw longitudinal OCT images.
C1 [Romo-Bucheli, David; Erfurth, Ursula Schmidt; Bogunovic, Hrvoje] Med Univ Vienna, Dept Ophthalmol & Optometry, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Erfurth, US (通讯作者)，Med Univ Vienna, Dept Ophthalmol & Optometry, A-1090 Vienna, Austria.
EM romobucheli@meduniwien.ac.at; midt-erfurth@meduniwien.ac.at;
   hrvoje.bogunovic@meduniwien.ac.at
RI Bogunovic, Hrvoje/J-3445-2014
OI Bogunovic, Hrvoje/0000-0002-9168-0894; Schmidt-Erfurth,
   Ursula/0000-0002-7788-7311
FU Christian Doppler Research Association; Austrian Federal Ministry for
   Digital and Economic Affairs; National Foundation for Research,
   Technology and Development
FX This work was supported in part by the Christian Doppler Research
   Association, in part by the Austrian Federal Ministry for Digital and
   Economic Affairs, and in part by the National Foundation for Research,
   Technology and Development.
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NR 35
TC 15
Z9 15
U1 5
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
EI 2168-2208
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD DEC
PY 2020
VL 24
IS 12
BP 3456
EP 3465
DI 10.1109/JBHI.2020.3000136
PG 10
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Mathematical & Computational Biology;
   Medical Informatics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Mathematical & Computational Biology; Medical
   Informatics
GA PC7JM
UT WOS:000597173000012
PM 32750929
DA 2022-11-30
ER

PT J
AU Cheng, YS
   Linetsky, M
   Li, HT
   Ayyash, N
   Gardella, A
   Salomon, RG
AF Cheng, Yu-Shiuan
   Linetsky, Mikhail
   Li, Haoting
   Ayyash, Naji
   Gardella, Anthony
   Salomon, Robert G.
TI 4-Hydroxy-7-oxo-5-heptenoic acid lactone can induce mitochondrial
   dysfunction in retinal pigmented epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Oxidative stress; Reactive oxygen species (ROS); Age related macular
   degeneration; Retinal pigment epithelium cells;
   4-Hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone; Carboxyethylpyrrole;
   Mitochondria
ID HISTIDINE-CONTAINING PEPTIDES; PERMEABILITY TRANSITION PORE; TRAUMATIC
   BRAIN-INJURY; OXIDATIVE STRESS; HOHA LACTONE; ANTIOXIDANT ACTIVITY;
   PROGRESSIVE STAGES; CARNOSINE REACTS; MICHAEL ADDUCTS; PROTECTION
AB Oxidation of docosahexaenoate (DHA)-containing phospholipids in the cell plasma membrane leads to release of the alpha, beta-unsaturated aldehyde 4-hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone which is capable of inducing retinal pigmented epithelial (RPE) cell dysfunction. Previously, HOHA lactone was shown to induce apoptosis and angiogenesis, and to activate the alternative complement pathway. RPE cells metabolize HOHA lactone through enzymatic conjugation with glutathione (GSH). Competing with this process is the adduction of HOHA lactone to protein lysyl residues generating 2-(omega-carboxyethyl)pyrrole (CEP) derivatives that have pathological relevance to age-related macular degeneration (AMD). We now find that HOHA lactone induces mitochondrial dysfunction. It decreases ATP levels, mitochondrial membrane potentials, enzymatic activities of mitochondrial complexes, depletes GSH and induces oxidative stress in RPE cells. The present study confirmed that pyridoxamine and other primary amines, which have been shown to scavenge gamma-ketoaldehydes formed by carbohydrate or lipid peroxidation, are ineffective for scavenging the alpha, beta-unsaturated aldehydes. Histidyl hydrazide (HH), that has both hydrazide and imidazole nucleophile functionalities, is an effective scavenger of HOHA lactone and it protects ARPE-19 cells against HOHA lactone-induced cytotoxicity. The HH alpha-amino group is not essential for this electrophile trapping activity. The N-6-acyl L-histidyl hydrazide derivatives with 2- to 7-carbon acyl groups with increasing lipophilicities are capable of maintaining the effectiveness of HH in protecting ARPE-19 cells against HOHA lactone toxicity, which potentially has therapeutic utility for treatment of age related eye diseases.
C1 [Cheng, Yu-Shiuan; Linetsky, Mikhail; Li, Haoting; Ayyash, Naji; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Linetsky, Mikhail; 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 NIH [R01-EY016813, P30 EY011373]
FX This work was supported by NIH Grant R01-EY016813 (to RGS) and Core
   Grant P30 EY011373 (to Case Visual Sciences Research Center).
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NR 68
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 20
PY 2020
VL 160
BP 719
EP 733
DI 10.1016/j.freeradbiomed.2020.09.009
PG 15
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA OZ3VZ
UT WOS:000594859300001
PM 32920040
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Martel, A
   Nahon-Esteve, S
   Martini, K
   Almairac, F
   Baillif, S
AF Martel, A.
   Nahon-Esteve, S.
   Martini, K.
   Almairac, F.
   Baillif, S.
TI Feelings, preoperative anxiety, and need for information in patients
   undergoing intravitreal injections
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Intravitreal injection; Anxiety; APAIS score; Age-related macular
   degeneration
ID QUALITY-OF-LIFE; GROWTH-FACTOR TREATMENT; RETINAL VEIN OCCLUSION;
   ANTI-VEGF TREATMENT; MACULAR DEGENERATION; PAIN INTENSITY; BEVACIZUMAB;
   EXPERIENCES; DEPRESSION; OUTCOMES
AB Purpose To assess feelings, preoperative anxiety, and need for information in patients undergoing intravitreal injections (IVI). Methods An observational cross-sectional study was conducted in our tertiary university care center between December 2017 and December 2018. Consecutive patients undergoing IVI were included. A paper survey was completed before and after IVI to assess patient experience. Preoperative anxiety and need for information were assessed using the Amsterdam Preoperative Anxiety Information Scale (APAIS) score. Results Hundred patients with a median age of 76.5 years (42-95, SD = 10.1) were included. Median best-corrected visual acuity (BCVA) in both eyes was 0.4 logMAR. Main IVI indications were wet age-related macular degeneration (n = 58), diabetic macular edema (n = 19), and venous occlusion (n = 16). The IVI most unpleasant steps were as follows: using an eyelid retractor, needle entry, changing of physician from one IVI to another, the pre-IVI waiting time, and the high number of IVI required for disease control. Preoperative anxiety (APAIS score >= 11) was correlated in the multivariate analysis with the need for information (p = 0.004), changing of ophthalmologist between different IVI sessions (p = 0.006), and pain expected before the IVI (p = 0.010). The need for information (APAIS score >= 5) was only associated with the preoperative anxiety in the multivariate analysis (p = 0.001). Conclusion Preoperative anxiety and need for information are common in patients undergoing IVI even after many IVI. Being injected by different practitioners was strongly correlated with preoperative anxiety and should be avoided as much as possible. Better educational and information programs are needed.
C1 [Martel, A.; Nahon-Esteve, S.; Martini, K.; Baillif, S.] Univ Hosp Nice, Ophthalmol Dept, Nice, France.
   [Almairac, F.] Univ Hosp Nice, Neurosurg Dept, Nice, France.
C3 CHU Nice; CHU Nice
RP Martel, A (通讯作者)，Univ Hosp Nice, Ophthalmol Dept, Nice, France.
EM martel.a@chu-nice.fr
RI baillif, stephanie/AAX-9883-2020; Nahon-Esteve, Sacha/AAZ-7074-2020
OI baillif, stephanie/0000-0003-1700-8570; NAHON-ESTEVE,
   Sacha/0000-0003-2274-0256
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NR 39
TC 5
Z9 5
U1 0
U2 7
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 2020
VL 258
IS 7
BP 1395
EP 1403
DI 10.1007/s00417-020-04699-4
EA APR 2020
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LZ6OV
UT WOS:000529498300001
PM 32346786
DA 2022-11-30
ER

PT J
AU Cho, MJ
   Yoon, SJ
   Kim, W
   Park, J
   Lee, J
   Park, JG
   Cho, YL
   Kim, JH
   Jang, H
   Park, YJ
   Lee, SH
   Min, JK
AF Cho, Min Ji
   Yoon, Sung-Jin
   Kim, Wooil
   Park, Jongjin
   Lee, Jangwook
   Park, Jong-Gil
   Cho, Young-Lai
   Kim, Jeong Hun
   Jang, Hyejin
   Park, Young-Jun
   Lee, Sang-Hyun
   Min, Jeong-Ki
TI Oxidative stress-mediated TXNIP loss causes RPE dysfunction
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
ID THIOREDOXIN-INTERACTING PROTEIN; MACULAR DEGENERATION; NUCLEAR EXPORT;
   NADPH OXIDASE; GROWTH-FACTORS; P53; AUTOPHAGY; CELLS; PATHOGENESIS;
   EXPRESSION
AB The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood-retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1 alpha, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.
C1 [Cho, Min Ji; Kim, Wooil; Park, Jongjin; Lee, Jangwook; Park, Jong-Gil; Lee, Sang-Hyun; Min, Jeong-Ki] KRIBB, Biotherapeut Translat Res Ctr, 125 Gwahak Ro, Daejeon 34141, South Korea.
   [Cho, Min Ji; Kim, Wooil; Jang, Hyejin; Park, Young-Jun; Min, Jeong-Ki] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Biomol Sci, 217 Gajeong Ro, Daejeon 34141, South Korea.
   [Yoon, Sung-Jin; Jang, Hyejin; Park, Young-Jun] KRIBB, Environm Dis Res Ctr, 125 Gwahak Ro, Daejeon 34141, South Korea.
   [Cho, Young-Lai] KRIBB, Metab Regulat Res Ctr, 125 Gwahak Ro, Daejeon 34141, South Korea.
   [Kim, Jeong Hun] Seoul Natl Univ Hosp, Clin Res Inst, Fight Angiogenesis Related Blindness FARB Lab, 101 Daehak Ro, Seoul 03080, South Korea.
C3 Korea Research Institute of Bioscience & Biotechnology (KRIBB);
   University of Science & Technology (UST); Korea Research Institute of
   Bioscience & Biotechnology (KRIBB); Korea Research Institute of
   Bioscience & Biotechnology (KRIBB); Seoul National University (SNU);
   Seoul National University Hospital
RP Lee, SH; Min, JK (通讯作者)，KRIBB, Biotherapeut Translat Res Ctr, 125 Gwahak Ro, Daejeon 34141, South Korea.; Min, JK (通讯作者)，Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Biomol Sci, 217 Gajeong Ro, Daejeon 34141, South Korea.
EM leesh@kribb.re.kr; jekmin@kribb.re.kr
OI Yoon, Sung-Jin/0000-0002-7372-0231; Min, Jeong-Ki/0000-0003-4924-8739;
   Kim, Jeong Hun/0000-0003-2957-1766; Lee, Sang-Hyun/0000-0002-9682-1473
FU Korea Research Institute of Bioscience and Biotechnology; National
   Research Foundation of Korea - Ministry of Science, Information and
   Communication Technology and Future Planning [NRF-2018R1A2B2006724,
   2015M3A9D7029882, NRF-2015M3A9E6028953]
FX This study was supported by a grant from the Korea Research Institute of
   Bioscience and Biotechnology and by grants from the National Research
   Foundation of Korea, which was funded by the Ministry of Science,
   Information and Communication Technology and Future Planning
   (NRF-2018R1A2B2006724, 2015M3A9D7029882, and NRF-2015M3A9E6028953).
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NR 57
TC 23
Z9 24
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1226-3613
EI 2092-6413
J9 EXP MOL MED
JI Exp. Mol. Med.
PD OCT 15
PY 2019
VL 51
AR 121
DI 10.1038/s12276-019-0327-y
PG 13
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA JE1KE
UT WOS:000490450900001
PM 31615975
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sung, IS
   Park, SY
   Jeong, KY
   Kim, HM
AF Sung, In Sung
   Park, Seon Young
   Jeong, Keun-Yeong
   Kim, Hwan Mook
TI Investigation of the preventive effect of calcium on
   inflammation-mediated choroidal neovascularization
SO LIFE SCIENCES
LA English
DT Article
DE Age-related macular degeneration; Calcium supplementation; Inflammation;
   Angiogenesis
ID TOLL-LIKE RECEPTORS; TISSUE-REPAIR; CELLS
AB Aims: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in elderly people. The pathogenesis of neovascular AMD is known but is closely related to inflammation and choroidal neovascularization (CNV). The aim of this study was to investigate the anti-inflammatory and anti-angiogenic effects of calcium on neovascular AMD.
   Main methods: Human retinal pigment epithelial cells (ARPE-19) were used to identify protein markers of inflammation induced by differentiated macrophages. Choroidal neovascularization (CNV) mouse model was established by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. Mice were divided into the following groups: untreated control and calcium supplemented. The expression levels of toll-like receptor isotype (TLR) 4, nuclear factor kappa B (NF-kappa B), hypoxia-inducible factor-1 alpha (Hif-1 alpha), and vascular endothelial growth factor (VEGF) were investigated to check whether calcium supplementation results in suppression of inflammation and has an anti-angiogenic effect. CNV was evaluated by immunofluorescence staining on choroidal flat mounts.
   Key finding: The inflammation-induced expression of TLR4, NF-kappa B, and Hif-1 alpha was decreased in ARPE-19 cells after calcium supplementation. Inhibition of the transcriptional activation of ARPE-19 cells by Hif-1 alpha suppression resulted in decreased VEGF expression. In the laser-induced CNV mouse model, calcium supplementation inhibited inflammatory mediators and neovascularization in the retinal tissue.
   Significance: Supplementation with calcium seems to constrain inveterate symptoms of neovascular AMD by inhibiting inflammation and angiogenesis in the laser-induced CNV mouse model.
C1 [Sung, In Sung; Park, Seon Young; Kim, Hwan Mook] Gachon Univ, Gachon Inst Pharmaceut Sci, 191 Hambangmoe Ro, Incheon 21936, South Korea.
   [Jeong, Keun-Yeong] MetiMedi Pharmaceut Co, Res Ctr, 263 Cent Ro, Incheon 22006, South Korea.
C3 Gachon University
RP Kim, HM (通讯作者)，Gachon Univ, Gachon Inst Pharmaceut Sci, 191 Hambangmoe Ro, Incheon 21936, South Korea.; Jeong, KY (通讯作者)，MetiMedi Pharmaceut Co, Res Ctr, 263 Cent Ro, Incheon 22006, South Korea.
EM alvirus@naver.com; hwanmook@gachon.ac.kr
RI Jeong, Keun-Yeong/B-8845-2015
OI Jeong, Keun-Yeong/0000-0002-4933-3493
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NR 24
TC 4
Z9 4
U1 1
U2 4
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 SEP 15
PY 2019
VL 233
AR 116727
DI 10.1016/j.lfs.2019.116727
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA IV1KG
UT WOS:000484035300040
PM 31381895
DA 2022-11-30
ER

PT J
AU Sun, ZY
   Sun, YK
AF Sun, Zhongyang
   Sun, Yankui
TI Automatic detection of retinal regions using fully convolutional
   networks for diagnosis of abnormal maculae in optical coherence
   tomography images
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE image segmentation; image classification; fully convolutional networks;
   retina optical coherence tomography
ID OCT IMAGES; LAYER SEGMENTATION; THICKNESS; EDEMA; AMD; CLASSIFICATION;
   DEGENERATION
AB In conventional retinal region detection methods for optical coherence tomography (OCT) images, many parameters need to be set manually, which is often detrimental to their generalizability. We present a scheme to detect retinal regions based on fully convolutional networks (FCN) for automatic diagnosis of abnormal maculae in OCT images. The FCN model is trained on 900 labeled age-related macular degeneration (AMD), diabetic macular edema (DME) and normal (NOR) OCT images. Its segmentation accuracy is validated and its effectiveness in recognizing abnormal maculae in OCT images is tested and compared with traditional methods, by using the spatial pyramid matching based on sparse coding (ScSPM) classifier and Inception V3 classifier on two datasets: Duke dataset and our clinic dataset. In our clinic dataset, we randomly selected half of the B-scans of each class (300 AMD, 300 DME, and 300 NOR) for training classifier and the rest (300 AMD, 300 DME, and 300 NOR) for testing with 10 repetitions. Average accuracy, sensitivity, and specificity of 98.69%, 98.03%, and 99.01% are obtained by using ScSPM classifier, and those of 99.69%, 99.53%, and 99.77% are obtained by using Inception V3 classifier. These two classification algorithms achieve 100% classification accuracy when directly applied to Duke dataset, where all the 45 OCT volumes are used as test set. Finally, FCN model with or without flattening and cropping and its influence on classification performance are discussed. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
C1 [Sun, Zhongyang; Sun, Yankui] Tsinghua Univ, Dept Comp Sci & Technol, Beijing, Peoples R China.
   [Sun, Zhongyang] Northeastern Univ, Coll Engn, Boston, MA 02115 USA.
   [Sun, Zhongyang; Sun, Yankui] Sun Yat Sen Univ, Guangzhou Higher Educ Mega Ctr, Guangdong Key Lab Big Data Anal & Proc, Guangzhou, Guangdong, Peoples R China.
C3 Tsinghua University; Northeastern University; Sun Yat Sen University
RP Sun, YK (通讯作者)，Tsinghua Univ, Dept Comp Sci & Technol, Beijing, Peoples R China.; Sun, YK (通讯作者)，Sun Yat Sen Univ, Guangzhou Higher Educ Mega Ctr, Guangdong Key Lab Big Data Anal & Proc, Guangzhou, Guangdong, Peoples R China.
EM syk@mail.tsinghua.edu.cn
RI Sun, Yankui/AAD-2524-2019
FU National Natural Science Foundation of China [61671272]; Opening Project
   of Guangdong Province Key Laboratory of Big Data Analysis and Processing
   [201803]; National Key Research Program of China [2016YFB1000600]
FX This work was supported by the National Natural Science Foundation of
   China (Award No. 61671272), the Opening Project of Guangdong Province
   Key Laboratory of Big Data Analysis and Processing (Grant No. 201803),
   and the National Key Research Program of China (Grant No.
   2016YFB1000600). The authors would like to thank the anonymous reviewers
   for their careful reading of our paper and their many insightful
   comments and suggestions that greatly improve the paper.
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NR 44
TC 6
Z9 7
U1 0
U2 4
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAY
PY 2019
VL 24
IS 5
AR 056003
DI 10.1117/1.JBO.24.5.056003
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 IS0ZB
UT WOS:000481880600019
PM 31111697
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Oishi, M
   Oishi, A
   Lindner, M
   Pfau, M
   Schmitz-Valckenberg, S
   Holz, FG
   Fleckenstein, M
AF Oishi, Maho
   Oishi, Akio
   Lindner, Moritz
   Pfau, Maximillian
   Schmitz-Valckenberg, Steffen
   Holz, Frank G.
   Fleckenstein, Monika
TI Structural Changes in Optical Coherence Tomography Underlying Spots of
   Increased Autofluorescence in the Perilesional Zone of Geographic
   Atrophy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE geographic atrophy; fundus autofluorescence; age-related macular
   degeneration; optical coherence tomography; retinal pigment epithelium
ID RETINAL-PIGMENT EPITHELIUM; INCREASED FUNDUS AUTOFLUORESCENCE; MACULAR
   DEGENERATION; DONOR EYES; PROGRESSION; PATTERNS; IMAGES
AB PURPOSE. To investigate structural correlates corresponding to the appearance of increased fundus autofluorescence (FAF) in the perilesional area of geographic atrophy (GA) secondary to age-related macular degeneration.
   METHODS. Serial FAF images of 181 eyes with GA of 134 patients participating in the Directional Spread in Geographic Atrophy study (NCT02051998) were screened for increased FAF spots that had developed during the review period. Thickness and reflectivity of the retinal pigment epithelium (RPE)-basal lamina complex, as well as the integrity of the external limiting membrane (ELM) and the ellipsoid zone (EZ), respectively, in corresponding optical coherence tomography (OCT) scans were compared between the time points before and after the appearance of increased FAF. Adjacent areas without development of abnormal FAF were assessed as internal control.
   RESULTS. A total of 36 areas (15 eyes) with de novo developed increased FAF spots and 54 control areas were included. Analysis of the corresponding OCT images revealed an increase in RPE-basal lamina complex thickness (31.8 +/- 6 7.3 to 42.1 6 11.9 lm [ P < 0.001]) and reflectivity (reflectivity ratio: 1.42 +/- 6 0.11 to 1.54 +/- 6 0.27 [ P = 0.009]) corresponding to an increased FAF signal while there was no significant change in control areas. Development of increased FAF spots was associated with disruption of the ELM and the EZ.
   CONCLUSIONS. Increase of RPE-basal lamina complex thickness and reflectivity was spatially and temporally associated with the development of increased FAF spots in eyes with GA. In addition, outer retinal disruption may contribute to the corresponding increased FAF signal.
C1 [Oishi, Maho; Oishi, Akio; Lindner, Moritz; Pfau, Maximillian; Schmitz-Valckenberg, Steffen; Holz, Frank G.; Fleckenstein, Monika] Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
C3 University of Bonn
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 Oishi, Akio/AAE-9996-2020; Lindner, Moritz/AAC-8639-2021; Pfau,
   Maximilian/N-1888-2019
OI Oishi, Akio/0000-0002-0977-9458; Lindner, Moritz/0000-0002-4416-3421;
   Pfau, Maximilian/0000-0001-9761-9640; Fleckenstein,
   Monika/0000-0001-8321-8037
FU German Research Foundation [FL658/4-1, FL658/4-2]; Alexander von
   Humboldt Foundation (Bonn, Germany); Alcon Japan (Tokyo, Japan); BONFOR
   GEROK Program of the Faculty of Medicine, University of Bonn
   [O-137.0020, O- 137.0022]
FX Supported by German Research Foundation Grant No. FL658/4-1 and
   FL658/4-2 to MF for the DSGA study. AO was supported by Alexander von
   Humboldt Foundation (Bonn, Germany) and Alcon Japan (Tokyo, Japan). ML,
   BONFOR GEROK Program of the Faculty of Medicine, University of Bonn,
   Grant No. O-137.0020. MP, BONFOR GEROK Program of the Faculty of
   Medicine, University of Bonn, Grant No. O- 137.0022.
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NR 32
TC 8
Z9 8
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2017
VL 58
IS 7
BP 3303
EP 3310
DI 10.1167/iovs.17-21498
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EZ8FE
UT WOS:000404959300053
PM 28666281
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lee, BL
   Kang, JH
   Kim, HM
   Jeong, SH
   Jang, DS
   Jang, YP
   Choung, SY
AF Lee, Bom-Lee
   Kang, Jung-Hwan
   Kim, Hye-Mi
   Jeong, Se-Hee
   Jang, Dae-Sik
   Jang, Young-Pyo
   Choung, Se-Young
TI Polyphenol-enriched Vaccinium uliginosum L. fractions reduce retinal
   damage induced by blue light in A2E-laden ARPE19 cell cultures and mice
SO NUTRITION RESEARCH
LA English
DT Article
DE Vaccinium uliginosum L.; Age-related macular degeneration; A2E; Blue
   light exposure; HP20 resin
ID PIGMENT EPITHELIAL-CELLS; BETA-CAROTENE; VITAMIN-E; A2E; ANTHOCYANINS;
   RPE; ANTIOXIDANTS; FLAVONOIDS; PROTECTION; RHODOPSIN
AB Polyphenols exert beneficial effects on vision. We hypothesized that polyphenol components of Vaccinium uliginosum L. (V.U.) extract protect retinal pigment epithelial (RPE) cells against blue light-induced damage. Our aim was to test extracts containing polyphenol components to ascertain effects to reduce damage against blue light in RPEs. We measured the activity in fractions eluted from water, ethanol, and HP20 resin (FH), and found that the FH fraction had the highest beneficial activity. We isolated the individual active compounds from the FH fraction using chromatographic techniques, and found that FH contained flavonoids, anthocyanins, phenyl propanoids, and iridoids. Cell cultures of A2E-laden ARPE-19 exposed to blue light after treatment with V.U. extract fractions and their individual constituents indicated improvement. V uliginosum L extract fractions and constituent compounds significantly reduced A2E photo-oxidation-induced RPE cell death and inhibited intracellular A2E accumulation. Furthermore, Balb/c male mice were exposed to blue light at 10000 lux for 1 h/d for 2 weeks to induce retinal damage. One week after the final blue light exposure, retinal damage evaluated revealed that the outer nuclear layer thickness and nuclei count were improved. Histologic examination of murine photoreceptor cells demonstrated that FH, rich in polyphenols, inhibited the loss of outer nuclear layer thickness and nuclei. Our findings suggest that V.U. extract and eluted fractions are a potential source of bioactive compounds that potentially serve a therapeutic approach for age-related macular degeneration. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lee, Bom-Lee; Kang, Jung-Hwan; Jang, Dae-Sik; Jang, Young-Pyo; Choung, Se-Young] Kyung Hee Univ, Grad Sch, Dept Life & Nanopharmaceut Sci Pharm, Seoul, South Korea.
   [Kim, Hye-Mi; Choung, Se-Young] Kyung Hee Univ, Dept Prevent Pharm & Toxicol, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea.
   [Jeong, Se-Hee; Jang, Young-Pyo] Kyung Hee Univ, Dept Oriental Pharmaceut Sci, Coll Pharm, Seoul, South Korea.
   [Jang, Dae-Sik] Kyung Hee Univ, Dept Prevent Pharm Sci, Coll Pharm, Seoul, South Korea.
C3 Kyung Hee University; Kyung Hee University; Kyung Hee University; Kyung
   Hee University
RP Choung, SY (通讯作者)，Kyung Hee Univ, Dept Prevent Pharm & Toxicol, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea.
EM sychoung@khu.ac.kr
RI Jang, Dae Sik/AAI-4526-2020; Choung, Young/AAH-9208-2020; Jang, Young
   Pyo/AAJ-8782-2020
OI Jang, Young Pyo/0000-0001-5865-9228
FU Technology Innovation Industrial Program - Ministry of Trade, Industry
   and Energy (Korea) [10048028]; Korea Evaluation Institute of Industrial
   Technology
FX This work was supported by the Technology Innovation Industrial Program
   (10048028, development of functional food products for improving AMD and
   extending the global market) funded by the Ministry of Trade, Industry
   and Energy (Korea) and the Korea Evaluation Institute of Industrial
   Technology.
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   Zhou Z, 2015, CELL DEATH DIFFER, V22, P488, DOI 10.1038/cdd.2014.229
NR 58
TC 22
Z9 23
U1 2
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD DEC
PY 2016
VL 36
IS 12
BP 1402
EP 1414
DI 10.1016/j.nutres.2016.11.008
PG 13
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA EG5KN
UT WOS:000391082800011
PM 27993192
DA 2022-11-30
ER

PT J
AU Luna, G
   Keeley, PW
   Reese, BE
   Linberg, KA
   Lewis, GP
   Fisher, SK
AF Luna, Gabriel
   Keeley, Patrick W.
   Reese, Benjamin E.
   Linberg, Kenneth A.
   Lewis, Geoffrey P.
   Fisher, Steven K.
TI Astrocyte structural reactivity and plasticity in models of retinal
   detachment
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Review
DE Glia; Astrocyte; Retinal astrocytes; Astrocyte reactivity; Astrocyte
   hypertrophy astrocyte remodeling; Astrocyte structural plasticity;
   Retinal detachment
ID FIBRILLARY ACIDIC PROTEIN; GLAUCOMATOUS OPTIC-NERVE;
   RETINITIS-PIGMENTOSA; MULLER CELLS; PROLIFERATIVE VITREORETINOPATHY;
   MICE DEFICIENT; CAT RETINA; EPIRETINAL MEMBRANES; NEURITE OUTGROWTH;
   MAMMALIAN RETINA
AB Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and pathological characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Muller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Miller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina's overall response to injury and disease. (C) 2016 The Authors. Published by Elsevier Ltd.
C1 [Luna, Gabriel; Keeley, Patrick W.; Reese, Benjamin E.; Linberg, Kenneth A.; Lewis, Geoffrey P.; Fisher, Steven K.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Luna, Gabriel; Lewis, Geoffrey P.; Fisher, Steven K.] Univ Calif Santa Barbara, Ctr Bioimage Informat, Santa Barbara, CA 93106 USA.
   [Fisher, Steven K.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Reese, Benjamin E.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara;
   University of California System; University of California Santa Barbara
RP Fisher, SK (通讯作者)，Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
EM steven.k.fisher@lifesci.ucsb.edu
FU National Science Foundation [IIS-0808772, ITR-0331697]; Macula Vision
   Research Foundation [SB090054]; Santa Barbara Cottage Hospital Research
   Grant [253]; International Retinal Research Foundation [SB100067];
   National Eye Institute [EY019968]; NATIONAL EYE INSTITUTE [R01EY019968]
   Funding Source: NIH RePORTER
FX National Science Foundation (IIS-0808772 and ITR-0331697). Macula Vision
   Research Foundation (SB090054). Santa Barbara Cottage Hospital Research
   Grant (253). International Retinal Research Foundation (SB100067).
   National Eye Institute (EY019968).
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NR 82
TC 30
Z9 30
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 SEP
PY 2016
VL 150
SI SI
BP 4
EP 21
DI 10.1016/j.exer.2016.03.027
PG 18
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DX5BR
UT WOS:000384395300002
PM 27060374
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Lorach, H
   Lei, X
   Galambos, L
   Kamins, T
   Mathieson, K
   Dalal, R
   Huie, P
   Harris, J
   Palanker, D
AF Lorach, Henri
   Lei, Xin
   Galambos, Ludwig
   Kamins, Theodore
   Mathieson, Keith
   Dalal, Roopa
   Huie, Philip
   Harris, James
   Palanker, Daniel
TI Interactions of Prosthetic and Natural Vision in Animals With Local
   Retinal Degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE prosthetics; VEP; AMD; rehabilitation
ID STIMULATION; HEARING; TRIAL
AB PURPOSE. Prosthetic restoration of partial sensory loss leads to interactions between artificial and natural inputs. Ideally, the rehabilitation should allow perceptual fusion of the two modalities. Here we studied the interactions between normal and prosthetic vision in a rodent model of local retinal degeneration.
   METHODS. Implantation of a photovoltaic array in the subretinal space of normally sighted rats induced local degeneration of the photoreceptors above the chip, and the inner retinal neurons in this area were electrically stimulated by the photovoltaic implant powered by near-infrared (NIR) light. We studied prosthetic and natural visually evoked potentials (VEP) in response to simultaneous stimulation by NIR and visible light patterns.
   RESULTS. We demonstrate that electrical and natural VEPs summed linearly in the visual cortex, and both responses decreased under brighter ambient light. Responses to visible light flashes increased over 3 orders of magnitude of contrast (flash/background), while for electrical stimulation the contrast range was limited to 1 order of magnitude. The maximum amplitude of the prosthetic VEP was three times lower than the maximum response to a visible flash over the same area on the retina.
   CONCLUSIONS. Ambient light affects prosthetic responses, albeit much less than responses to visible stimuli. Prosthetic representation of contrast in the visual scene can be encoded, to a limited extent, by the appropriately calibrated stimulus intensity, which also depends on the ambient light conditions. Such calibration will be important for patients combining central prosthetic vision with natural peripheral sight, such as in age-related macular degeneration.
C1 [Lorach, Henri; Huie, Philip; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Lorach, Henri; Dalal, Roopa; Huie, Philip; Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
   [Lei, Xin; Galambos, Ludwig; Kamins, Theodore; Harris, James] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Mathieson, Keith] Univ Strathclyde, Inst Photon, Glasgow, Lanark, Scotland.
C3 Stanford University; Stanford University; Stanford University;
   University of Strathclyde
RP Lorach, H (通讯作者)，HEPL, 452 Lomita Mall, Stanford, CA 94305 USA.
EM henri.lorach@gmail.com
RI Mathieson, Keith/G-6308-2011
OI Mathieson, Keith/0000-0002-9517-8076; Palanker,
   Daniel/0000-0002-0480-3025; LORACH, HENRI/0000-0003-4337-2798
FU NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025744] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY018608] Funding Source: NIH
   RePORTER; NCRR NIH HHS [UL1RR025744, UL1 RR025744] Funding Source:
   Medline; NEI NIH HHS [R01 EY018608, R01-EY-018608] Funding Source:
   Medline
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NR 23
TC 12
Z9 12
U1 0
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2015
VL 56
IS 12
BP 7444
EP 7450
DI 10.1167/iovs.15-17521
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DB0ZS
UT WOS:000368238200056
PM 26618643
OA Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Korthagen, NM
   van Bilsen, K
   Swagemakers, SMA
   van de Peppel, J
   Bastiaans, J
   van der Spek, PJ
   van Hagen, PM
   Dik, WA
AF Korthagen, Nicoline M.
   van Bilsen, Kiki
   Swagemakers, Sigrid M. A.
   van de Peppel, Jeroen
   Bastiaans, Jeroen
   van der Spek, Peter J.
   van Hagen, P. Martin
   Dik, Willem A.
TI Retinal pigment epithelial cells display specific transcriptional
   responses upon TNF-alpha stimulation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GENE-EXPRESSION; BARRIER; NEOVASCULARIZATION
AB Background/aims Tumour necrosis factor-alpha (TNF-alpha) is a key mediator of ocular inflammation and its interaction with the retinal pigment epithelium (RPE) may be a driving force in vitreoretinal disorders such as age-related macular degeneration, proliferative vitreoretinopathy (PVR) and diabetic retinopathy. Under inflammatory conditions, the ability of RPE cells to maintain the blood-retinal barrier and immune privilege may be lost and proliferation of RPE cells is facilitated. To gain insight into the effects of TNF-alpha on RPE cells, a gene expression study was performed.
   Methods ARPE-19 and HT-29 cells were stimulated with 50 ng/mL TNF-alpha for 6 h. Gene expression patterns were compared between stimulated and control cells using whole genome gene expression arrays. Data were analysed using Partek and OmniViz and validated using quantitative RT-PCR. Functional annotation analysis was performed using Ingenuity and DAVID.
   Results A total of 97 genes were uniquely modulated by TNF-alpha in ARPE-19 cells compared with HT-29 cells (86 upregulated and 11 downregulated). Most commonly affected biological processes were apoptosis, cell motility and cell signalling. The highest upregulated gene was EFNA1. Among the downregulated genes were transcription factors implicated in ocular development (SIX3, PAX6) and modulation of p53-mediated apoptosis (CITED2).
   Conclusions This study provides insight into the unique responses of RPE cells to TNF-alpha stimulation and suggests a role for genes involved in apoptosis and retinal epithelial development. These findings contribute to our understanding of the behaviour of RPE cells under inflammatory conditions and the crucial role of RPE cells in vitreoretinal diseases.
C1 [Korthagen, Nicoline M.; Bastiaans, Jeroen; van Hagen, P. Martin; Dik, Willem A.] Univ Med Ctr Rotterdam, Dept Immunol, Lab Med Immunol, Erasmus MC, NL-3015 CN Rotterdam, Netherlands.
   [van Bilsen, Kiki; van de Peppel, Jeroen; van Hagen, P. Martin] Univ Med Ctr Rotterdam, Dept Internal Med, Clin Immunol Sect, Erasmus MC, NL-3015 CN Rotterdam, Netherlands.
   [Swagemakers, Sigrid M. A.; van der Spek, Peter J.] Univ Med Ctr Rotterdam, Dept Bioinformat, Erasmus MC, NL-3015 CN Rotterdam, Netherlands.
C3 Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC; Erasmus University Rotterdam; Erasmus MC
RP Dik, WA (通讯作者)，Univ Med Ctr Rotterdam, Dept Immunol, Lab Med Immunol, Erasmus MC, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands.
EM w.dik@erasmusmc.nl
RI van de Peppel, Jeroen/K-6683-2019; Korthagen, Nicoline M./AAA-4338-2021
OI van de Peppel, Jeroen/0000-0002-6524-727X; Korthagen, Nicoline
   M./0000-0002-9277-0795; Bastiaans, Jeroen/0000-0003-4407-0329
FU SWOO-Flieringa [OZR-2008-05]; International Retinal Research Foundation
   (IRRF); Stichting MD Fonds [Uitzicht 2011-2]
FX This work was supported by SWOO-Flieringa (OZR-2008-05), International
   Retinal Research Foundation (IRRF) and Stichting MD Fonds (Uitzicht
   2011-2).
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NR 27
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 2015
VL 99
IS 5
BP 700
EP 704
DI 10.1136/bjophthalmol-2014-306309
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CG5BR
UT WOS:000353305800026
PM 25680620
DA 2022-11-30
ER

PT J
AU Sturrock, BA
   Xie, J
   Holloway, EE
   Lamoureux, EL
   Keeffe, JE
   Fenwick, EK
   Rees, G
AF Sturrock, Bonnie A.
   Xie, Jing
   Holloway, Edith E.
   Lamoureux, Ecosse L.
   Keeffe, Jill E.
   Fenwick, Eva K.
   Rees, Gwyneth
TI The Influence of Coping on Vision-Related Quality of Life in Patients
   With Low Vision: A Prospective Longitudinal Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE coping strategies; vision-related quality of life; longitudinal
ID VISUAL IMPAIRMENT; DEPRESSIVE SYMPTOMS; RASCH ANALYSIS; OLDER-ADULTS;
   IMPACT; PREVALENCE; STRATEGIES; SEVERITY; PEOPLE; QUESTIONNAIRE
AB PURPOSE. To determine the longitudinal impact of specific coping strategies on vision-related quality of life (VRQoL) in patients with low vision.
   METHODS. This was a single-group, longitudinal study utilizing telephone-administered interviews conducted at baseline and at 3 and 6 months with patients (visual acuity < 6/12 in the better eye) recruited from low vision services. The Coping Strategy Indicator (CSI) assessed three strategies used specifically in relation to vision-related problems: avoidant coping, problem-solving coping, and seeking social support. Vision-related quality of life was assessed using the Impact of Vision Impairment (IVI) questionnaire, which comprises two domains: vision-related functioning and vision-related emotional well-being. We used multivariable mixed linear regression including time as an independent variable to assess change in VRQoL.
   RESULTS. The study comprised 162 patients (mean age = 69.8 years, 66% female), most with age-related macular degeneration (42%) and moderate vision impairment (41%; <6/18-6/60). Multivariable mixed linear regression showed that avoidant coping was a significant determinant of decline in vision-related functioning (beta = -0.11, 95% confidence interval [CI] -0.22 to -0.01, P = 0.036) and emotional well-being (beta = -0.29, 95% CI -0.45 to -0.13, P < 0.001) over a 6-month period.
   CONCLUSIONS. Our findings showed that avoidant coping has a detrimental impact on VRQoL over time. Low vision specialists should be aware of their patients' coping strategies and encourage them to engage in active rather than avoidant coping to deal with the impact of their vision impairment.
C1 [Sturrock, Bonnie A.; Xie, Jing; Holloway, Edith E.; Lamoureux, Ecosse L.; Fenwick, Eva K.; Rees, Gwyneth] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic 8002, Australia.
   [Lamoureux, Ecosse L.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
   [Lamoureux, Ecosse L.] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
   [Keeffe, Jill E.] LV Prasad Eye Inst, Hyderabad, Andhra Pradesh, India.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; National University of Singapore; Singapore
   National Eye Center; National University of Singapore; L. V. Prasad Eye
   Institute
RP Rees, G (通讯作者)，Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Gwyneth Rees Behav Res Ophthalmol, Locked Bag 8, East Melbourne, Vic 8002, Australia.
EM grees@unimelb.edu.au
RI Lamoureux, Ecosse/Z-5482-2019; xie, jing/GRY-1689-2022
OI /0000-0001-6694-3587
FU beyondblue: the national depression and anxiety initiative; NHMRC
   [1072987, 1045280, 1061801]; National Health and Medical Research
   Council (NHMRC) Centre for Clinical Research Excellence in Eye Disease
   [529923]
FX Supported by a grant from beyondblue: the national depression and
   anxiety initiative. Centre for Eye Research Australia receives
   Operational Infrastructure Support from the Victorian Government and
   National Health and Medical Research Council (NHMRC) Centre for Clinical
   Research Excellence in Eye Disease (529923). Supported also by NHMRC
   Early Career Fellowship (no. 1072987, EKF), NHMRC Research Fellowship
   (no. 1045280, ELL), and NHMRC Career Development Fellowship (no.
   1061801, GR). None of the authors have any proprietary interests or
   conflicts of interest related to this submission. This submission has
   not been published anywhere previously and it is not simultaneously
   being considered for any other publication.
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NR 45
TC 19
Z9 22
U1 0
U2 15
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2015
VL 56
IS 4
BP 2416
EP 2422
DI 10.1167/iovs.14-16223
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA CJ1NP
UT WOS:000355250700033
PM 26066595
DA 2022-11-30
ER

PT J
AU Yip, W
   Siantar, R
   Perera, SA
   Milastuti, N
   Ho, KK
   Tan, B
   Wong, TY
   Cheung, CY
AF Yip, WanFen
   Siantar, Rosalynn
   Perera, Shamira A.
   Milastuti, Nia
   Ho, Kee Ka
   Tan, Bernard
   Wong, Tien Yin
   Cheung, Carol Y.
TI Reliability and Determinants of Retinal Vessel Oximetry Measurements in
   Healthy Eyes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinal oxygen saturation; functional imaging; retinal oximetry
ID OXYGEN-SATURATION; GLAUCOMA
AB PURPOSE. To assess the reliability and determinants of retinal vessel oximetry measurements with the Oxymap T1 Retinal Oximeter in normal Asian eyes.
   METHODS. Subjects older than 40 years without a history of stroke and heart disease were recruited from a community-based clinic. Subjects underwent standardized systemic and ocular examinations. Normal eyes were defined as eyes without major eye diseases such as age-related macular degeneration, glaucoma, or retinopathy. Retinal vessel oximetry levels were measured by using the Oxymap T1 Retinal Oximeter. Intra-and intergrader reliability of retinal vessel oximetry measurements were assessed by using 50 images. Intravisit repeatability of retinal vessel oximetry measurements was assessed by using 20 paired images. Univariable linear regression was performed to examine the associations between retinal vessel oximetry measurements and systemic determinants.
   RESULTS. A total of 118 retinal oximetry images were included in the final analysis. Intra( intraclass correlation coefficient [ICC] values: 0.89-0.99) and intergrader (ICC values: 0.77-0.94) reliability, and intravisit (ICC values: 0.85-0.96) repeatability were both high. In the linear regression analysis, older age was associated with reduced overall retinal venular oximetry levels (beta: -2.61%; 95% confidence interval [CI]: -4.92 to -0.29) and reduced inferior-nasal retinal venular oximetry levels (b: -3.53%; 95% CI: -6.07 to -0.99).
   CONCLUSIONS. The Oxymap Retinal Oximeter allows reliable and repeatable retinal vessel oximetry measurements. Age is the main factor that influences retinal venular oximetry levels and should be taken into account when retinal oximetry measurements are interpreted.
C1 [Yip, WanFen; Siantar, Rosalynn; Perera, Shamira A.; Milastuti, Nia; Ho, Kee Ka; Tan, Bernard; Wong, Tien Yin; Cheung, Carol Y.] Singapore Eye Res Inst, Singapore Eye Res Inst, Singapore 169856, Singapore.
   [Yip, WanFen; Wong, Tien Yin; Cheung, Carol Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
   [Wong, Tien Yin; Cheung, Carol Y.] Natl Univ Hlth Syst, Singapore, Singapore.
   Duke NUS Grad Med Sch, Singapore, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; National University of Singapore;
   National University of Singapore
RP Cheung, CY (通讯作者)，Singapore Eye Res Inst, 20 Coll Rd,Discovery Tower Level 6, Singapore 169856, Singapore.
EM carol.cheung.y.1@seri.com.sg
RI Cheung, Carol Y./G-7895-2016; Wong, Tien Yin/AAC-9724-2020; Cheung,
   Carol/AAF-1101-2020
OI Wong, Tien Yin/0000-0002-8448-1264; Cheung, Carol/0000-0002-9672-1819;
   Cheung, Carol/0000-0003-0869-859X; Perera, Shamira/0000-0002-1404-5096
FU SingHealth Foundation [SHF/FG522S/2011]
FX Supported by the SingHealth Foundation Grant No. SHF/FG522S/2011. The
   authors alone are responsible for the content and writing of the paper.
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NR 28
TC 38
Z9 40
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 NOV
PY 2014
VL 55
IS 11
BP 7104
EP 7110
DI 10.1167/iovs.13-13854
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AX9IR
UT WOS:000347217300010
PM 25301879
DA 2022-11-30
ER

PT J
AU Bastiaans, J
   van Meurs, JC
   van Holten-Neelen, C
   Smits-te Nijenhuis, M
   Kolijn-Couwenberg, MJ
   van Hagen, PM
   Kuijpers, RWAM
   Hooijkaas, H
   Dik, WA
AF Bastiaans, Jeroen
   van Meurs, Jan C.
   van Holten-Neelen, Conny
   Smits-te Nijenhuis, Marja
   Kolijn-Couwenberg, Marion J.
   van Hagen, P. Martin
   Kuijpers, Robert W. A. M.
   Hooijkaas, Herbert
   Dik, Willem A.
TI Factor Xa and thrombin stimulate proinflammatory and profibrotic
   mediator production by retinal pigment epithelial cells: a role in
   vitreoretinal disorders?
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Factor Xa; Thrombin; Retinal pigment epithelium; Vitreoretinal fibrotic
   disorders; Cytokine antibody array; Inflammation; Fibrosis
ID PROLIFERATIVE DIABETIC-RETINOPATHY; TRACTIONAL FORCE GENERATION;
   GROWTH-FACTOR EXPRESSION; SIGNAL-TRANSDUCTION; GRAVES OPHTHALMOPATHY;
   SUBRETINAL FLUID; FACTOR RECEPTORS; GENE-EXPRESSION; LUNG INJURY;
   ACTIVATION
AB Vitreoretinal disorders, including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and exudative age-related macular degeneration (AMD), are a major cause of visual impairment worldwide and can lead to blindness when untreated. Loss of blood-retinal barrier (BRB) integrity associated with vitreoretinal fibrin deposition, inflammation, fibrosis and neovascularization contribute to the pathophysiological processes in these disorders. Retinal pigment epithelial (RPE) cells are well recognized to contribute to vitreoretinal inflammation/fibrosis and are likely to encounter contact with coagulation factor upon loss of BRB integrity.
   An extensive study was performed in which we examined the effect of factor Xa and thrombin on the production of a broad panel of cytokines/chemokines and growth factors by RPE cells. For this purpose we used the ARPE-19 cell line as well as primary RPE cells, a glass slide based array that allows simultaneous detection of 120 cytokines/chemokines and growth factors, ELISA and real-time-quantitative PCR. The involved signaling cascade was examined using specific inhibitors for protease activated receptor (PAR)1, PAR2 and nuclear factor kappa-B (NF-kappa B).
   Factor Xa and thrombin regulated the production of cytokines and growth factors (including GM-CSF, IL-6, IL-8, MCP-3, PDGF-AA, PDGF-BB, TIMP-1 and TGF-alpha) that fit well in the pathobiology of vitreoretinal disease. Blocking studies revealed that the effects were mediated via PAR1 induced NF-kappa B activation.
   Our findings suggest that factor Xa and thrombin can drive vitreoretinal inflammation and fibrosis and should be considered as treatment targets in vitreoretinal disorders such as PVR, PDR and AMD.
C1 [Bastiaans, Jeroen; van Meurs, Jan C.] Rotterdam Eye Hosp, Rotterdam, Netherlands.
   [Bastiaans, Jeroen; van Holten-Neelen, Conny; Smits-te Nijenhuis, Marja; Kolijn-Couwenberg, Marion J.; van Hagen, P. Martin; Hooijkaas, Herbert; Dik, Willem A.] Erasmus MC, Dept Immunol, NL-3015 GE Rotterdam, Netherlands.
   [van Hagen, P. Martin] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [van Meurs, Jan C.; Kuijpers, Robert W. A. M.] Erasmus MC, Dept Ophthalmol, NL-3015 GE Rotterdam, Netherlands.
C3 Rotterdam Eye Hospital; Erasmus University Rotterdam; Erasmus MC;
   Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC
RP Bastiaans, J (通讯作者)，Erasmus MC, Dept Immunol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM j.bastiaans@erasmusmc.nl; w.dik@erasmusmc.nl
RI kuijpers, robert/AAD-5194-2019
OI Bastiaans, Jeroen/0000-0003-4407-0329
FU Combined Ophthalmic Research Rotterdam (CORR- Project) [3.1.0]
FX This study is financially supported by: Combined Ophthalmic Research
   Rotterdam (CORR- Project code: 3.1.0)
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NR 54
TC 28
Z9 28
U1 0
U2 9
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 JUL
PY 2013
VL 251
IS 7
BP 1723
EP 1733
DI 10.1007/s00417-013-2335-2
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 164CP
UT WOS:000320386700010
PM 23604512
DA 2022-11-30
ER

PT J
AU Ioannidis, JPA
   Yu, Y
   Seddon, JM
AF Ioannidis, John P. A.
   Yu, Yi
   Seddon, Johanna M.
TI Correction of Phenotype Misclassification Based on High-Discrimination
   Genetic Predictive Risk Models
SO EPIDEMIOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION; EMPIRICAL-EVALUATION;
   RELATIVE RISK; DEFINITION; BIAS; POLYMORPHISM; VARIANTS; SIGNALS; IMPACT
AB Misclassification of phenotype status can seriously affect accuracy in association studies, including studies of genetic risk factors. A common problem is the classification of participants as nondiseased because of insufficient diagnostic workup or because participants have not been followed up long enough to develop disease. Some validated predictive models may have high discrimination in predicting disease. We suggest that information from such models can be used to predict the risk that a nondiseased participant will eventually develop disease and to recode the status of participants predicted to be at highest risk. We evaluate conditions under which recoding results in a maximal net improvement in the accuracy of phenotype classification. Net improvement is expected only when the positive likelihood ratio of the predictive model is larger than the inverse of the odds of disease among apparently nondiseased controls. We conducted simulations to probe the impact of reclassification on the power to detect new risk factors under several scenarios of classification accuracy of the previously developed models. We also apply this framework to a validated model of progression to advanced age-related macular degeneration that uses genetic and nongenetic variables (area under the curve = 0.915). In the training cohort (n = 2,937) and a separate validation cohort (n = 1,227), 195-272 and 78-91 nonprogressor participants, respectively, were reclassified as progressors. Correction of phenotype misclassification based on highly informative predictive models may be helpful in identifying additional genetic and other risk factors, when there are validated risk factors that provide strong discriminating ability.
C1 [Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Med, Stanford, CA 94305 USA.
   [Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
   [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA.
   [Yu, Yi; Seddon, Johanna M.] Tufts Univ, Sch Med, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv,New England Eye C, Boston, MA 02111 USA.
   [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Stanford University; Stanford University; Stanford University; Tufts
   Medical Center; Tufts University; Tufts University
RP Ioannidis, JPA (通讯作者)，Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Med, 1265 Welch Rd,Med Sch Off Bldg X306, Stanford, CA 94305 USA.
EM jioannid@stanford.edu
RI Ioannidis, John P. A./G-9836-2011
FU Massachusetts Lions Eye Research Fund, Inc. [RO1-EY11309]; Foundation
   Fighting Blindness; Research to Prevent Blindness Challenge Grant to the
   New England Eye Center, Department of Ophthalmology, Tufts University
   School of Medicine; Macular Degeneration Research Fund of the Ophthalmic
   Epidemiology and Genetics Service, New England Eye Center, Tufts Medical
   Center, Tufts University School of Medicine; NATIONAL EYE INSTITUTE
   [R01EY011309] Funding Source: NIH RePORTER
FX Supported by grants RO1-EY11309 (JMS), Massachusetts Lions Eye Research
   Fund, Inc.; the Foundation Fighting Blindness; Research to Prevent
   Blindness Challenge Grant to the New England Eye Center, Department of
   Ophthalmology, Tufts University School of Medicine; and the Macular
   Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics
   Service, New England Eye Center, Tufts Medical Center, Tufts University
   School of Medicine. We appreciate the contribution of an anonymous donor
   to the research of J.M.S.
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NR 38
TC 4
Z9 4
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2012
VL 23
IS 6
BP 902
EP 909
DI 10.1097/EDE.0b013e31826c3129
PG 8
WC Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health
GA 022NJ
UT WOS:000309965800022
PM 23023008
OA Bronze
DA 2022-11-30
ER

PT J
AU Finger, RP
   Fenwick, E
   Chiang, PPC
   Petrak, M
   Holz, FG
   Marella, M
   Lamoureux, EL
AF Finger, Robert P.
   Fenwick, Eva
   Chiang, Peggy Pei-Chia
   Petrak, Michael
   Holz, Frank G.
   Marella, Manjula
   Lamoureux, Ecosse L.
TI The impact of the severity of vision loss on vision-specific functioning
   in a German outpatient population - an observational study
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Visual functioning; VF-14; Severity of vision loss; Rasch analysis;
   Germany
ID QUALITY-OF-LIFE; FUNCTION INDEX VF-14; SINGAPORE MALAY EYE; MACULAR
   DEGENERATION; VISUAL FUNCTION; CATARACT-SURGERY; SEE PROJECT;
   IMPAIRMENT; OUTCOMES; DISEASE
AB To validate the German-translated VF-14, a vision-specific scale, and determine the relationship between the severity of vision impairment, ocular conditions, and visual functioning.
   This was a clinic-based, cross-sectional study with 184 patients with low vision and 90 normal-sighted controls recruited from a German eye hospital. Participants underwent a clinical examination and completed the German VF-14 scale. The validity of the VF-14 scale was assessed using Rasch analysis. The main outcome measure was the visual functioning overall score.
   The participants' mean +/- A SD [standard deviation] age was 59.4 A +/- 21.8 years ,and there were more female (58.4%) than male participants. The main cause of vision loss was age-related macular degeneration [AMD] (n = 54, 19.7%). Rasch analysis substantiated the German VF-14 to be a valid scale to assess visual functioning in the sample. Visual functioning consistently declined with worsening vision. In adjusted-multivariate analysis models, compared to control participants, those with mild, or moderate/severe vision impairment recorded significantly poorer visual functioning scores (p < 0.05). The independent association was clinically significant for those with moderate/severe vision impairment. The main ocular conditions were also found to be independently associated with worse visual functioning, with clinical significance found for AMD, diabetic retinopathy, and other retinal diseases.
   Using a psychometrically valid German-translated VF-14, even mild vision impairment was independently associated with poor visual functioning. These findings reinforce the importance of early preventative and rehabilitative efforts to prevent longitudinal deterioration in vision loss.
C1 [Finger, Robert P.; Fenwick, Eva; Chiang, Peggy Pei-Chia; Marella, Manjula; Lamoureux, Ecosse L.] Univ Melbourne, Ctr Eye Res Australia, Dept Ophthalmol, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia.
   [Finger, Robert P.; Petrak, Michael; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-5300 Bonn, Germany.
   [Lamoureux, Ecosse L.] Singapore Eye Res Inst, Singapore, Singapore.
C3 Centre for Eye Research Australia; Royal Victorian Eye & Ear Hospital;
   University of Melbourne; University of Bonn; National University of
   Singapore; Singapore National Eye Center
RP Finger, RP (通讯作者)，Univ Melbourne, Ctr Eye Res Australia, Dept Ophthalmol, Royal Victorian Eye & Ear Hosp, Level 1,32 Gisborne St, Melbourne, Vic 3002, Australia.
EM robertfinger@gmx.net
RI Marella, Majula/AAN-2488-2021; Lamoureux, Ecosse/Z-5482-2019
OI Marella, Majula/0000-0002-1877-7956; Finger, Robert
   P/0000-0003-4253-7597
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NR 38
TC 13
Z9 13
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2011
VL 249
IS 8
BP 1245
EP 1253
DI 10.1007/s00417-011-1646-4
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 804GM
UT WOS:000293642300018
PM 21465288
DA 2022-11-30
ER

PT J
AU Pons, M
   Cousins, SW
   Alcazar, O
   Striker, GE
   Marin-Castano, ME
AF Pons, Marianne
   Cousins, Scott W.
   Alcazar, Oscar
   Striker, Gary E.
   Marin-Castano, Maria E.
TI Angiotensin II Induced MMP-2 Activity and MMP-14 and Basigin Protein
   Expression Are Mediated via the Angiotensin II Receptor Type 1
   Mitogen-Activated Protein Kinase 1 Pathway in Retinal Pigment Epithelium
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MATRIX-METALLOPROTEINASE INDUCER; SMOOTH-MUSCLE-CELLS; P38 MAPK;
   SIGNAL-TRANSDUCTION; CONVERTING ENZYME; GELATINASE-A;
   CARDIOVASCULAR-DISEASE; CARDIAC-HYPERTROPHY; GENE-EXPRESSION;
   GROWTH-FACTORS
AB Accumulation of various lipid-rich extracellular matrix (ECM) deposits under the retinal pigment epithelium (RPE) has been observed in eyes with age-related macular degeneration (AMD). RPE-derived matrix metalloproteinase (MMP)-2, MMP-14, and basigin (BSG) are major enzymes involved in the maintenance of ECM turnover. Hypertension (HTN) is a systemic risk factor for AMD. It has previously been reported that angiotensin H (Ang II), one of the most important hormones associated with HTN, increases MMP-2 activity and its key regulator, MMP-14, in RPE, inducing breakdown of the RPE basement membrane, which may lead to progression of sub-RPE deposits. Ang II exerts most of its actions by activating the mitogen-activated protein kinase (MAPK) signaling pathway. Herein is explored the MAPK signaling pathway as a potential key intracellular modulator of Ang II induced increase in MMP-2 activity and MMP-14 and BSG protein expression. It was observed that Ang II stimulates phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in RPE cells and ERK/p38 and Jun N-terminal kinase (JNK) in mice. These effects were mediated by Ang H type 1 receptors. Blockade of ERK or p38 MAPK abrogated the increase in MMP-2 activity and MMP-14 and BSG proteins in ARPE-19 cells. A better understanding of the molecular events by which Ang II induces ECM dysregulation is of critical importance to further define its contribution to the progression of sub-RPE deposits in AMD patients with HTN. (Am J Pathol 2011, 178:2665-2681; DOI: 10.1016/j.ajpath.2011.02.006)
C1 [Marin-Castano, Maria E.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Cousins, Scott W.] Duke Univ, Ctr Eye, Durham, NC USA.
   [Striker, Gary E.] Sch Med, Div Expt Diabet & Aging, New York, NY USA.
C3 Bascom Palmer Eye Institute; University of Miami; Duke University
RP Marin-Castano, ME (通讯作者)，Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW,10th Ave, Miami, FL 33136 USA.
EM mcastano@med.miami.edu
FU National Eye Institute [R01 EY015249-01A1, EY015249-01A1S1]; Research to
   Prevent Blindness [P30-EY14801]; NATIONAL EYE INSTITUTE [P30EY014801,
   R01EY015249, P30EY005722] Funding Source: NIH RePORTER
FX Supported by grants R01 EY015249-01A1 and EY015249-01A1S1 from the
   National Eye Institute (M.E.M.-C.) and unrestricted grant P30-EY14801
   from Research to Prevent Blindness (M.E M.-C., O.A., and M.P.).
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NR 81
TC 54
Z9 55
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2011
VL 178
IS 6
BP 2665
EP 2681
DI 10.1016/j.ajpath.2011.02.006
PG 17
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 865JJ
UT WOS:000298306900022
PM 21641389
OA Green Published
DA 2022-11-30
ER

PT J
AU Cashman, SM
   Desai, A
   Ramo, K
   Kumar-Singh, R
AF Cashman, Siobhan M.
   Desai, Akshata
   Ramo, Kasmir
   Kumar-Singh, Rajendra
TI Expression of Complement Component 3 (C3) from an Adenovirus Leads to
   Pathology in the Murine Retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MEMBRANE ATTACK COMPLEX; CHOROIDAL
   NEOVASCULARIZATION; MACULAR DEGENERATION; FACTOR-H; PIGMENT EPITHELIUM;
   MEDIATED EXPRESSION; POTENTIAL THERAPY; MULLER CELLS; MOUSE MODEL
AB PURPOSE. Activation of complement has been implicated as one of the major causes of age-related macular degeneration (AMD). Evidence is accumulating for a role of complement in other retinal diseases, such as diabetic retinopathy and proliferative vitreoretinopathy. Because of the paucity of animal models that directly investigate the role of complement in retinal pathology, the authors sought to develop a model of increased complement expression and activation, specifically in the murine retina.
   METHODS. The authors constructed a recombinant adenovirus-expressing murine complement component 3 (C3, AdcmvC3). Adult mice were injected in the subretinal space with either AdcmvC3 or a control virus, AdcmvGFP. After 1 to 2 weeks of exogenous C3 expression, mice were analyzed by scotopic electroretinography and fluorescein angiography. Eyes were harvested for histologic, immunohistochemical, and quantitative RT-PCR analyses.
   RESULTS. Mice injected with C3-expressing adenovirus exhibited significantly increased vascular permeability, endothelial cell proliferation and migration, RPE atrophy, loss of photoreceptor outer segments, reactive gliosis, retinal detachment, and reduced retinal function relative to those injected with a control adenovirus. Deposition of the membrane attack complex was observed on endothelial cells and photoreceptor outer segments.
   CONCLUSIONS. Adenovirus-mediated delivery of C3 to murine RPE induces significant functional and anatomic changes that reproduce many of the features of AMD as well as those of other retinal diseases. This novel model may be useful in assessing the role of complement in retinal pathology and in developing anti-complement therapies for retinal diseases associated with complement activation. (Invest Ophthalmol Vis Sci. 2011;52:3436-3445) DOI:10.1167/iovs.10-6002
C1 [Cashman, Siobhan M.; Desai, Akshata; Ramo, Kasmir; Kumar-Singh, Rajendra] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts University
RP Kumar-Singh, R (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, 136 Harrison Ave, Boston, MA 02111 USA.
EM rajendra.kumar-singh@tufts.edu
OI Kumar-Singh, Rajendra/0000-0002-7754-0713
FU Ellison Foundation; Virginia B. Smith Trust; Lions Eye Foundation;
   Research to Prevent Blindness
FX Supported by The Ellison Foundation (RK-S), The Virginia B. Smith Trust
   (RK-S), the Lions Eye Foundation (departmental grant), and Research to
   Prevent Blindness (departmental grant).
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NR 60
TC 35
Z9 39
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 MAY
PY 2011
VL 52
IS 6
BP 3436
EP 3445
DI 10.1167/iovs.10-6002
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 770PN
UT WOS:000291100800074
PM 21357400
DA 2022-11-30
ER

PT J
AU Bruban, J
   Maoui, A
   Chalour, N
   An, N
   Jonet, L
   Feumi, C
   Treton, J
   Sennlaub, F
   Behar-Cohen, F
   Mascarelli, F
   Dinet, V
AF Bruban, Julien
   Maoui, Agathe
   Chalour, Naima
   An, Na
   Jonet, Laurent
   Feumi, Charles
   Treton, Jacques
   Sennlaub, Florian
   Behar-Cohen, Francine
   Mascarelli, Frederic
   Dinet, Virginie
TI CCR2/CCL2-mediated inflammation protects photoreceptor cells from
   amyloid-beta-induced apoptosis
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Retina; Microglial cells; Inflammation; Oxidative stress; Age-related
   macular degeneration; Alzheimer's disease
ID COMPLEMENT COMPONENT C1Q; AGE-RELATED MACULOPATHY; FACTOR-H
   POLYMORPHISM; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; PRECURSOR
   PROTEIN; CYTOCHROME-C; MOUSE MODEL; RETINAL DEGENERATION; OXIDATIVE
   DAMAGE
AB Age-related macular degeneration is characterized by the formation of drusen containing amyloid-beta (A beta) and the degeneration of photoreceptors. To explore the largely unknown role of A beta in the retina, we investigated the effects on photoreceptors of the oligomeric form of A beta(1-42). Subretinal injection of the A beta peptide induced misplaced expression of recoverin and synaptophysin in the photoreceptors, oxidative stress in their inner and outer segments, and finally apoptosis. A beta did not induce cell death in purified photoreceptor cell cultures, but did so in retinal cell cultures, thereby suggesting that the cellular environment plays a role in A beta-induced photoreceptor photoreceptor apoptosis. Subretinal injection of A beta was followed by activation and migration of microglial cells and then by photoreceptor apoptosis. Microglial cells phagocytosed rhodopsin-containing debris and A beta in the subretinal space. Quantitative RT-PCR allowed us to identify a specific gene expression profile associated with the A beta-induced progression of retinal degeneration and consistent with oxidative stress, inflammation, and an apoptotic program. The gene most highly upregulated in A beta-injected retinas was that for the chemokine CCL2, and its absence or that of its cognate receptor CCR2 greatly reduced migration of activated microglial cells to the site of retinal injury and profoundly worsened photoreceptor degeneration and disorganization of the retinal pigment epithelium in A beta-injected retinas. Our study pinpoints the roles of A beta and of CCL2/CCR2 axis-dependent inflammation in photoreceptor apoptosis. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Mascarelli, Frederic] Univ Paris 06, Ctr Rech Cordeliers, UMRS 872, F-75006 Paris, France.
   Univ Paris 05, UMR S 872, F-75006 Paris, France.
   NSERM, U872, F-75006 Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; UDICE-French Research Universities; Universite Paris Cite;
   Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Universite Paris Cite
RP Mascarelli, F (通讯作者)，Univ Paris 06, Ctr Rech Cordeliers, UMRS 872, 15 Rue Ecole Med, F-75006 Paris, France.
EM frederic.mascarelli@inserm.fr
RI Sennlaub, Florian/F-2756-2017; Mascarelli, Frederic/L-8916-2018
OI Sennlaub, Florian/0000-0003-4412-1341; Dinet,
   virginie/0000-0002-5458-0253
FU Ministere de la Recherche; EVI-GenoRET [LSHG-CT-2005-512036]; Agence
   Nationale de la Recherche
FX Grant support: Supported by grant from the Ministere de la Recherche.;
   Grant support: Supported by grant LSHG-CT-2005-512036 from EVI-GenoRET.;
   Grant support: Supported by grant from the Agence Nationale de la
   Recherche.
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NR 82
TC 23
Z9 23
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD APR
PY 2011
VL 42
IS 1
BP 55
EP 72
DI 10.1016/j.nbd.2011.01.004
PG 18
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 726MS
UT WOS:000287727000006
PM 21220018
DA 2022-11-30
ER

PT J
AU Mabry, R
   Gilbertson, DG
   Frank, A
   Vu, T
   Ardourel, D
   Ostrander, C
   Stevens, B
   Julien, S
   Franke, S
   Meengs, B
   Brody, J
   Presnell, S
   Hamacher, NB
   Lantry, M
   Wolf, A
   Bukowski, T
   Rosler, R
   Yen, C
   Anderson-Haley, M
   Brasel, K
   Pan, Q
   Franklin, H
   Thompson, P
   Dodds, M
   Underwood, S
   Peterson, S
   Sivakumar, PV
   Snavely, M
AF Mabry, Robert
   Gilbertson, Debra G.
   Frank, Amanda
   Vu, Tuyen
   Ardourel, Dan
   Ostrander, Craig
   Stevens, Brenda
   Julien, Susan
   Franke, Secil
   Meengs, Brent
   Brody, Jennifer
   Presnell, Scott
   Hamacher, Nels B.
   Lantry, Megan
   Wolf, Anitra
   Bukowski, Tom
   Rosler, Robert
   Yen, Cindy
   Anderson-Haley, Monica
   Brasel, Kenneth
   Pan, Qi
   Franklin, Hank
   Thompson, Penny
   Dodds, Mike
   Underwood, Sara
   Peterson, Scott
   Sivakumar, Pallavur V.
   Snavely, Mark
TI A dual-targeting PDGFR beta/VEGF-A molecule assembled from stable
   antibody fragments demonstrates anti-angiogenic activity in vitro and in
   vivo
SO MABS
LA English
DT Article
DE bispecific; antibody; PDGFR beta; VEGF-A; stability; angiogenesis
ID BISPECIFIC ANTIBODIES; GROWTH-FACTOR; KINASE INHIBITORS;
   ENDOTHELIAL-CELLS; PROTEIN STABILITY; ESCHERICHIA-COLI; FV FRAGMENTS;
   AFFINITY; TUMORS; THERAPY
AB Targeting angiogenesis is a promising approach to the treatment of solid tumors and age-related macular degeneration (AMD). Inhibition of vascularization has been validated by the successful marketing of monoclonal antibodies (mAbs) that target specific growth factors or their receptors, but there is considerable room for improvement in existing therapies. Combination of mAbs targeting both the VEGF and PDGF pathways has the potential to increase the efficacy of anti-angiogenic therapy without the accompanying toxicities of tyrosine kinase inhibitors and the inability to combine efficiently with traditional chemotherapeutics. However, development costs and regulatory issues have limited the use of combinatorial approaches for the generation of more efficacious treatments. The concept of mediating disease pathology by targeting two antigens with one therapeutic was proposed over two decades ago. While mAbs are particularly suitable candidates for a dual-targeting approach, engineering bispecificity into one molecule can be difficult due to issues with expression and stability, which play a significant role in manufacturability. Here, we address these issues upstream in the process of developing a bispecific antibody (bsAb). Single-chain antibody fragments (scFvs) targeting PDGFR beta and VEGF-A were selected for superior stability. The scFvs were fused to both termini of human Fc to generate a bispecific, tetravalent molecule. The resulting molecule displays potent activity, binds both targets simultaneously, and is stable in serum. The assembly of a bsAb using stable monomeric units allowed development of an anti-PDGFRB/VEGF-A antibody capable of attenuating angiogenesis through two distinct pathways and represents an efficient method for rapid engineering of dual-targeting molecules.
C1 [Mabry, Robert; Gilbertson, Debra G.; Frank, Amanda; Vu, Tuyen; Ardourel, Dan; Franke, Secil; Franklin, Hank; Thompson, Penny; Snavely, Mark] Zymogenet Inc, Antibody Discovery & Assay Technol, Seattle, WA 98105 USA.
   [Ostrander, Craig; Stevens, Brenda; Julien, Susan; Meengs, Brent; Hamacher, Nels B.; Lantry, Megan; Wolf, Anitra; Bukowski, Tom] Zymogenet Inc, Prot Biochem, Seattle, WA 98105 USA.
   [Rosler, Robert; Yen, Cindy; Anderson-Haley, Monica; Brasel, Kenneth; Pan, Qi; Peterson, Scott; Sivakumar, Pallavur V.] Zymogenet Inc, Oncol, Seattle, WA 98105 USA.
   [Brody, Jennifer; Presnell, Scott] Zymogenet Inc, Sci Comp, Seattle, WA 98105 USA.
   [Dodds, Mike; Underwood, Sara] Zymogenet Inc, Preclin Dev, Seattle, WA 98105 USA.
C3 Zymogenet Inc.; Zymogenet Inc.; Zymogenet Inc.; Zymogenet Inc.;
   Zymogenet Inc.
RP Mabry, R (通讯作者)，Zymogenet Inc, Antibody Discovery & Assay Technol, Seattle, WA 98105 USA.
EM mabryr@zgi.com
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NR 46
TC 43
Z9 56
U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PD JAN-FEB
PY 2010
VL 2
IS 1
BP 20
EP 34
DI 10.4161/mabs.2.1.10498
PG 15
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 644OH
UT WOS:000281387700004
PM 20065654
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kammer, R
   Sell, C
   Jamara, RJ
   Kollbaum, E
AF Kammer, Rebecca
   Sell, Christy
   Jamara, Richard J.
   Kollbaum, Elti
TI Survey of optometric low vision rehabilitation training methods for the
   moderately visually impaired
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Article
DE Low vision rehabilitation; Age-related macular degeneration; Training;
   Visual impairment; Low vision
AB PURPOSE: The goal of this survey study is to determine the low vision rehabilitation training practices of optometrists who prescribe near magnifying devices for low vision patients who have moderate visual impairment from age-related macular degeneration.
   METHODS: A total of 2,028 surveys were sent electronically or by mail. A total of 136 optometrists reporting a special interest in low vision rehabilitation responded to an 18-item survey about practice mode, educational background, affiliations, and other demographic information. They were queried on methodology, frequency, and specific strategic content of rehabilitation training.
   RESULTS: Sixty-eight percent of the 136 respondents were private practitioners. Fifty-four percent of all respondents agreed that they train patients for 1 hour or less. Nine percent provided 3 or more training visits and were more likely to utilize an occupational therapist. Forty-six percent of respondents reported using various other personnel to perform the training. The majority of respondents spend 25% of their time examining low vision patients. Eighteen percent of all respondents were low vision residency trained.
   CONCLUSIONS: Descriptions of current practice patterns are difficult to ascertain without consensus on terminology and management criteria among low vision practitioners. This survey and accompanying literature review support the need for clinical research and education that will establish an efficacious and cost-effective model for private outpatient low vision rehabilitation for individuals with various levels of vision impairment to determine the true availability of low vision rehabilitation care in the United States. Optometry 2009;80:185-192
C1 [Kammer, Rebecca] So Calif Coll Optometry, Fullerton, CA 92831 USA.
   [Sell, Christy] SUNY Coll Optometry, New York, NY 10010 USA.
   [Jamara, Richard J.] New England Coll Optometry, Boston, MA USA.
   [Kollbaum, Elti] Indiana Univ, Sch Optometry, Bloomington, IN USA.
C3 State University of New York (SUNY) System; SUNY Optometry; Indiana
   University System; Indiana University Bloomington
RP Kammer, R (通讯作者)，So Calif Coll Optometry, 2575 Yorba Linda Blvd, Fullerton, CA 92831 USA.
EM rkammer@scco.edu
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NR 25
TC 3
Z9 4
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-1839
J9 OPTOMETRY
JI Optometry
PD APR
PY 2009
VL 80
IS 4
BP 185
EP 192
DI 10.1016/j.optm.2008.10.015
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V18QE
UT WOS:000208018500006
PM 19329062
DA 2022-11-30
ER

PT J
AU Murata, N
   Yamaji, T
   Uchida, M
   Tsuboi, H
   Suzuki, H
   Yamada, M
   Oikawa, T
   Nobuhiro, J
   Choshi, T
   Hibino, S
AF Murata, Natsuko
   Yamaji, Taketo
   Uchida, Masayuki
   Tsuboi, Hiroshi
   Suzuki, Hiroto
   Yamada, Masashi
   Oikawa, Tsutomu
   Nobuhiro, Junko
   Choshi, Tominari
   Hibino, Satoshi
TI Suppression of laser-induced choroidal neovascularization by
   subconjunctival injection of 9 alpha-fluoromedroxyprogesterone acetate
   (FMPA), an anti-angiogenic agent, in rats
SO BIOLOGICAL & PHARMACEUTICAL BULLETIN
LA English
DT Article
DE choroidal neovascularization; age-related macular degeneration;
   anti-angiogenesis agent; 9 alpha-fluoromedroxyprogesterone acetate
   (FMPA); electro retinogram
ID MEDROXYPROGESTERONE ACETATE; TUMOR-GROWTH; PLASMINOGEN-ACTIVATOR; FOVEAL
   TRANSLOCATION; ANGIOSTATIC STEROIDS; RABBIT CORNEA; INHIBITION; CAM;
   BETAMETHASONE; IRSOGLADINE
AB 9 alpha-Fluoromedroxyprogesterone acetate (FMPA) is a synthetic analog of medroxyprogesterone acetate (MPA). FMPA exhibited more potent anti-tumor and anti-angiogenic activities in some assay systems than the parent agent, MPA. Exudative age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Anecortave acetate, an angiostatic steroid, is clinically efficacious in patients with exudative AMD. Betamethasone is an anti-angiogenic steroid. Therefore, we examined the effects of FMPA, anecortave acetate and betamethasone on laser-induced CNV in rats. Anecortave acetate and betamethasone were included as positive controls. Crypton laser was applied to the fundus in Brown Norway rats. Laser photocoagulations were performed in each eye between the major retinal vessels of the superior retina. Subconjunctival injection of FMPA, anecortave acetate or betamethasone was performed once just after the photocoagulation (on day 0). The incidence of CNV formation was evaluated by fluorescein angiography (FAG) on day 14. On the next day, examination of the retinal function was performed by electro retinogram (ERG). Subconjunctival injection of FMPA at doses of 300, 1000 and 3000 mu g/eye dose-dependently inhibited the incidence of CNV formation. Significant differences were observed at doses of 1000 and 3000 mu g/eye of FMPA as compared with the control group. Anecortave acetate and betamethasone significantly inhibited the incidence of CNV formation. FMPA at the doses used in this study did not affect the retinal function in rats, as determined by ERG. FMPA appeared to be effective in a rat model of CNV, so it was demonstrated that FMPA might be useful in the treatment of AMD.
C1 Meiji Dairies Corp, Pharmaceut Dev Dept, Koto Ku, Tokyo 1368908, Japan.
   Meiji Dairies Corp, Div Res & Dev, Odawara, Kanagawa 2500862, Japan.
   Kanagawa Univ Human Serv, Fac Hlth & Social Work, Yokosuka, Kanagawa 2388522, Japan.
   Fukuyama Univ, Fac Pharm & Pharmaceut Sci, Fukuyama, Hiroshima 7290292, Japan.
C3 Meiji Holdings Co., Ltd.; Meiji Holdings Co., Ltd.; Fukuyama University
RP Murata, N (通讯作者)，Meiji Dairies Corp, Pharmaceut Dev Dept, Koto Ku, 1-2-10 Shinsuna, Tokyo 1368908, Japan.
EM natsuko_murata@meiji-milk.com
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NR 40
TC 2
Z9 3
U1 0
U2 2
PU PHARMACEUTICAL SOC JAPAN
PI TOKYO
PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN
SN 0918-6158
J9 BIOL PHARM BULL
JI Biol. Pharm. Bull.
PD DEC
PY 2006
VL 29
IS 12
BP 2410
EP 2414
DI 10.1248/bpb.29.2410
PG 5
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 121GP
UT WOS:000243146400015
PM 17142973
OA Bronze
DA 2022-11-30
ER

PT J
AU Thompson, DA
   Gal, A
AF Thompson, DA
   Gal, A
TI Vitamin A metabolism in the retinal pigment epithelium: genes,
   mutations, and diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
ID LEBER CONGENITAL AMAUROSIS; ALL-TRANS-RETINOL; AGE-RELATED MACULOPATHY;
   SHORT-CHAIN DEHYDROGENASE/REDUCTASE; RECESSIVE RETINITIS-PIGMENTOSA;
   DELAYED DARK-ADAPTATION; BINDING PROTEIN CRALBP; COUPLED RECEPTOR OPSIN;
   ROD-CONE DYSTROPHY; FUNDUS-ALBIPUNCTATUS
AB Mutations in the genes necessary for the metabolism of vitamin A (all-trans retinol) and cycling of retinoids between the photoreceptors and retinal pigment epithelium (RPE) (the visual cycle) have recently emerged as an important class of genetic defects responsible for retinal dystrophies and dysfunctions. Research into the causes and treatment of diseases resulting from defects in retinal vitamin A metabolism is currently the subject of intense interest, since disorders affecting the RPE are, in principle, more accessible to therapeutic intervention than those affecting the proteins of photoreceptor cells. This chapter presents an overview of the visual cycle, as well as the function of the RPE genes involved in the conversion of vitamin A to 11-cis retinal, the chromophore of the visual pigments. The identification of disease-causing mutations in this group of genes is described as well as the associated phenotypes that range from stationary night blindness to childhood-onset severe visual handicap. Consideration is also given to alternative genetic paradigms potentially relevant to defects in vitamin A metabolism, including a discussion of the relationship of this pathway to age-related macular degeneration, a non-Mendelian disease of late onset. Finally, progress and prospects for targeted therapeutic intervention in vitamin A metabolism are presented, including retinoid and gene replacement therapy. On the basis of early successes in animal models, and plans underway for Phase I/II clinical trials, it is hoped that the near future will bring effective therapies for many retinal dystrophy patients with defects in vitamin A metabolism. (C) 2003 Elsevier Ltd. All rights reserved.
C1 Univ Michigan, Sch Med, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48105 USA.
   Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan; University of Hamburg;
   University Medical Center Hamburg-Eppendorf
RP Thompson, DA (通讯作者)，Univ Michigan, Sch Med, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM dathom@umich.edu
OI Thompson, Debra/0000-0003-3485-0794
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NR 171
TC 145
Z9 149
U1 0
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 SEP
PY 2003
VL 22
IS 5
BP 683
EP 703
DI 10.1016/S1350-9462(03)00051-X
PG 21
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 711EF
UT WOS:000184726100005
PM 12892646
DA 2022-11-30
ER

PT J
AU Lorenzo-Soler, L
   Praphanwittaya, P
   Olafsdottir, OB
   Kristinsdottir, IM
   Asgrimsdottir, GM
   Loftsson, T
   Stefansson, E
AF Lorenzo-Soler, Laura
   Praphanwittaya, Pitsiree
   Olafsdottir, Olof Birna
   Kristinsdottir, Iris Myrdal
   Asgrimsdottir, Gudrun Marta
   Loftsson, Thorsteinn
   Stefansson, Einar
TI Topical noninvasive retinal drug delivery of a tyrosine kinase
   inhibitor: 3% cediranib maleate cyclodextrin nanoparticle eye drops in
   the rabbit eye
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE cediranib; cyclodextrins; drug delivery; in vivo; neovascularization;
   pharmacokinetics; topical administration
ID POSTERIOR SEGMENT; PHYSICOCHEMICAL CHARACTERIZATION; COMPLEXES; VEGF
AB Purpose Tyrosine kinase inhibitors inhibit VEGF receptors. If delivered to the retina, they might inhibit oedema and neovascularization such as in age-related macular degeneration and diabetic retinopathy. The aim of this study was to formulate cediranib maleate, a potent VEGF inhibitor, as gamma-cyclodextrin nanoparticle eye drops and measure the retinal delivery and overall ocular pharmacokinetics after a single-dose administration in rabbits. Methods A novel formulation technology with 3% cediranib maleate as gamma-cyclodextrin micro-suspension was prepared by autoclaving method. Suitable stabilizers were tested for heat-stable eye drops. The ophthalmic formulation was topically applied to one eye in rabbits. The pharmacokinetics in ocular tissues, tear film and blood samples were studied at 1, 3 and 6 hr after administration. Results gamma-cyclodextrin formed complex with cediranib maleate. The formation of gamma-cyclodextrin nanoparticles occurred in concentrated complexing media. Combined stabilizers prevented the degradation of drug during the autoclaving process. Three hours after administration of the eye drops, treated eyes showed cediranib levels of 737 +/- 460 nM (mean +/- SD) in the retina and 10 +/- 6 nM in the vitreous humour. Conclusions Cediranib maleate in gamma-cyclodextrin nanoparticles were stable to heat in presence of stabilizers. The drug as eye drops reached the retina in concentrations that are more than 100 times higher than the 0.4 nM IC50 value reported for the VEGF type-II receptor and thus, presumably, above therapeutic level. These results suggest that gamma-cyclodextrin-based cediranib maleate eye drops deliver effective drug concentrations to the retina in rabbits after a single-dose administration.
C1 [Lorenzo-Soler, Laura; Olafsdottir, Olof Birna; Stefansson, Einar] Univ Iceland, Fac Med, Reykjavik, Iceland.
   [Praphanwittaya, Pitsiree; Loftsson, Thorsteinn] Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland.
   [Olafsdottir, Olof Birna; Stefansson, Einar] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
   [Olafsdottir, Olof Birna; Kristinsdottir, Iris Myrdal; Asgrimsdottir, Gudrun Marta; Loftsson, Thorsteinn; Stefansson, Einar] Oculis Ehf, Reykjavik, Iceland.
C3 University of Iceland; University of Iceland; Landspitali National
   University Hospital
RP Lorenzo-Soler, L (通讯作者)，Univ Iceland, Fac Med, Reykjavik, Iceland.
EM lauralrnzs@gmail.com
OI Lorenzo-Soler, Laura/0000-0002-2514-1323
FU Oculis ehf, Reykjavik, Iceland
FX This work was supported by Oculis ehf, Reykjavik, Iceland.
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NR 35
TC 0
Z9 0
U1 8
U2 14
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD NOV
PY 2022
VL 100
IS 7
BP 788
EP 796
DI 10.1111/aos.15101
EA JAN 2022
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 5E2FF
UT WOS:000746864000001
PM 35080812
DA 2022-11-30
ER

PT J
AU Khodamoradi, M
   Eskandari, M
   Keshvari, H
   Zarei, R
AF Khodamoradi, Maedeh
   Eskandari, Mahnaz
   Keshvari, Hamid
   Zarei, Reza
TI An electro-conductive hybrid scaffold as an artificial Bruch's membrane
SO MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
LA English
DT Article
DE hydrogel; fiber scaffold; electro-conductivity; polyaniline; Age-related
   macular degeneration (AMD); Bruch&apos; s membrane
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; SUBSTRATE; MATRIX
AB Many research groups have investigated the various kinds of scaffolds to mimic the natural Bruch's membrane (BM) and support the retinal pigmented epithelial cells to form an organized cellular monolayer. While using prosthetic BM is identified as a promising treatment of age-related macular degeneration (AMD), a degenerative and progressive retinal disease, the effects of different signals such as electrical and morphological cues on the retinal pigmented epithelial (RPE) cells are still unknown. In this study, a laminated and conductive hydrogel/ fiber composite scaffold by adding conductive polyaniline (PANi) to the scaffold's nanofibrous phase was prepared. This hybrid scaffold offers the closest morphology to the native structure of the human Bruch's membrane by imitating the inner and outer collagenous layer and induces the electrical signal to the scaffold to assess the electrical cue on behaviors of polarized retinal pigmented epithelial cells in the retina. The electrospun nanofibrous phase consisted of gelatin-Polyaniline in different ratios incorporated into the hydrogel precursor, a blend of gelatin and 4-armed PEG. We used a novel dual crosslinking process by incorporating the exposure of gamma irradiation and glutaraldehyde vapor treatment to construct the scaffold's hydrogel phase. The results showed the best composition was the sample which included the 40/60, Polyaniline/gelatin nanofiber sheets ratio because this scaffold revealed a 2.66 +/- 0.33 MPa, Young's modulus and 1.84 +/- 0.21 S/cm, electrochemical conductivity, which are close to the main features of native Bruch's membrane. In addition, this scaffold showed good biocompatibility by reaching 83.47% cell viability.
C1 [Khodamoradi, Maedeh; Eskandari, Mahnaz; Keshvari, Hamid] Amirkabir Univ Technol, Biomed Engn Fac, Tehran, Iran.
   [Zarei, Reza] Univ Tehran Med Sci, Farabi Eye Hosp, Eye Res Ctr, Tehran, Iran.
C3 Amirkabir University of Technology; Tehran University of Medical
   Sciences
RP Eskandari, M (通讯作者)，Amirkabir Univ Technol, Biomed Engn Fac, Tehran, Iran.
EM eskandarim@aut.ac.ir
RI Zarei, Reza/GRF-6080-2022; Eskandari, Mahnaz/S-3331-2018
OI Eskandari, Mahnaz/0000-0002-8141-7814
CR [Anonymous], 2020, BLINDNESS VISION IMP
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NR 47
TC 3
Z9 3
U1 6
U2 21
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0928-4931
EI 1873-0191
J9 MAT SCI ENG C-MATER
JI Mater. Sci. Eng. C-Mater. Biol. Appl.
PD JUL
PY 2021
VL 126
AR 112180
DI 10.1016/j.msec.2021.112180
EA MAY 2021
PG 14
WC Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science
GA SU9LX
UT WOS:000663452600005
PM 34082980
OA Bronze
DA 2022-11-30
ER

PT J
AU Chandra, S
   Sivaprasad, S
   Ursell, PG
   Naderi, K
   O'Brart, D
   Alwitry, A
   Ashena, Z
   Nanavaty, MA
AF Chandra, Shruti
   Sivaprasad, Sobha
   Ursell, Paul G.
   Naderi, Khayam
   O'Brart, David
   Alwitry, Amar
   Ashena, Zahra
   Nanavaty, Mayank A.
TI Recurring themes during cataract assessment and surgery
SO EYE
LA English
DT Review
ID INTRAOCULAR-LENS POWER; ANTERIOR-CHAMBER DEPTH; BILATERAL
   ENDOPHTHALMITIS; CALCULATION FORMULAS; MACULAR DEGENERATION; HOFFER-Q;
   REFRACTIVE OUTCOMES; BARRETT UNIVERSAL; SHORT EYES; 1ST EYE
AB The aim of this review was to discuss frequently encountered themes such as cataract surgery in presence of age-related macular degeneration (AMD), dementia, Immediate Sequential Bilateral Cataract Surgery (ISBCS), discussing non-standard intraocular lens (IOL) options during consultation in the National Health Services (NHS) and the choice of the biometric formulae based on axial length. Individual groups of authors worked independently on each topic. We found that cataract surgery does improve visual acuity in AMD patients but the need for cataract surgery should be individualised. In patients with dementia, cataract surgery should be considered 'sooner rather than later' as progression may prevent individuals presenting for surgery. This should be planned after discussion of patients' best interests with any carers; multifocal IOLs are not proven to be the best option in these patients. ISBCS gives comparable outcomes to delayed sequential surgeries with a low risk of bilateral endophthalmitis and it can be cost-saving and efficient. Patients are entitled to know all suitable IOL options that can improve their quality of life. Deliberately withholding this information or pressuring patients to choose a non-standard IOL is inappropriate. However, one should be mindful of the not spending inappropriate amounts of time discussing these in the NHS setting which may affect care of other NHS patients. Evidence suggests Hoffer Q, Haigis, Hill-RBF and Kane formulae for shorter eyes; Barrett Universal II (BU II), Holladay II, Haigis and Kane formulae for longer eyes and BU II, Hill-RBF and Kane formulae for medium axial length eyes.
C1 [Chandra, Shruti; Sivaprasad, Sobha] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Chandra, Shruti; Sivaprasad, Sobha] UCL, Inst Ophthalmol, London, England.
   [Ursell, Paul G.] Epsom & St Helier Univ Hosp NHS Trust, Epsom, Surrey, England.
   [Naderi, Khayam; O'Brart, David] Guys & St Thomas NHS Fdn Trust, Dept Ophthalmol, London, England.
   [Naderi, Khayam; O'Brart, David] Kings Coll London, London, England.
   [Alwitry, Amar] Loughborough Hosp, Epinal Way, Loughborough, Leics, England.
   [Ashena, Zahra; Nanavaty, Mayank A.] Brighton & Sussex Univ Hosp NHS Trust, Sussex Eye Hosp, Brighton, E Sussex, England.
   [Nanavaty, Mayank A.] Univ Sussex, Brighton & Sussex Med Sch, Brighton, E Sussex, England.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Guy's & St Thomas' NHS Foundation Trust; University of London; King's
   College London; Brighton and Sussex University Hospitals NHS Trust;
   University of Brighton; University of Brighton; University of Sussex
RP Nanavaty, MA (通讯作者)，Brighton & Sussex Univ Hosp NHS Trust, Sussex Eye Hosp, Brighton, E Sussex, England.; Nanavaty, MA (通讯作者)，Univ Sussex, Brighton & Sussex Med Sch, Brighton, E Sussex, England.
EM mayank.nanavaty@nhs.net
OI Nanavaty, Mayank/0000-0003-0667-3700; Sivaprasad,
   Sobha/0000-0001-8952-0659; Chandra, Shruti/0000-0002-2634-9775
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NR 110
TC 0
Z9 0
U1 3
U2 5
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD SEP
PY 2021
VL 35
IS 9
BP 2482
EP 2498
DI 10.1038/s41433-021-01548-4
EA APR 2021
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UC8OV
UT WOS:000645477300004
PM 33927353
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Huang, XN
   Chau, Y
AF Huang, Xiaonan
   Chau, Ying
TI Enhanced Delivery of siRNA to Retinal Ganglion Cells by Intravitreal
   Lipid Nanoparticles of Positive Charge
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE positive lipid nanoparticles for retinal siRNA therapy; ocular delivery;
   siRNA delivery; ganglion cells; neuron targeting
ID CELLULAR UPTAKE; GENE-THERAPY; EXPRESSION; DIFFUSION; MOVEMENT; PROTEIN;
   MARKER
AB RNAi therapy has been developed and explored for treating retinal conditions since last decades. The progression of retinal diseases including the age-related macular degeneration and glaucoma is associated with the malfunction of specific retinal cells. Therefore, to deliver therapeutic RNAi to selective retinal tissues with desired gene downregulation is crucial for the treatment of retinal diseases via RNAi therapy. Lipid-based nanoparticles are potent delivery vectors for RNAi therapeutics to achieve high gene silencing efficiency. The surface charge has been demonstrated to affect the intraocular behaviors and retinal distribution of intravitreally administered lipid nanoparticles (LNPs), which could subsequently affect the gene knockdown efficiency in specific retinal layers. Here, we evaluated three charged LNPs for their ability to deliver siRNA and facilitate gene downregulation both in vitro and in vivo. LNPs with different surface charges ranging from neutral to positive (5-34 mV) were successfully formulated. All types of charged LNPs managed gene knockdown in both mammalian cell line and primary neurons. At 48 h post intravitreal injection, neutral LNPs (6.2 mV) and mildly positive LNPs (15.9 mV) mediated limited retinal gene suppression (<10%) and the more positive LNPs (31.2 mV) led to similar to 25% gene suppression in the retinal ganglion cell (RGC) layer. No gene silencing in the retinal pigmented epithelium layer was facilitated by any LNPs independent of the charges. In summary, this study has shown that positive LNPs with an optimized charge managed specific gene downregulation in the RGC layer. These RNAi carriers hold potential for the treatment of RGC-associated retinal diseases.
C1 [Huang, Xiaonan; Chau, Ying] Hong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Kowloon, Hong Kong 999077, Peoples R China.
C3 Hong Kong University of Science & Technology
RP Chau, Y (通讯作者)，Hong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Kowloon, Hong Kong 999077, Peoples R China.
EM keychau@ust.hk
FU Hong Kong Research Grants Council [GRF 16100014]; Science and Technology
   Plan of Shenzhen [JCY20170818114038319]
FX This work was supported by the Hong Kong Research Grants Council (GRF
   16100014) and Science and Technology Plan of Shenzhen
   (JCY20170818114038319).
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NR 44
TC 5
Z9 5
U1 3
U2 31
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JAN 4
PY 2021
VL 18
IS 1
BP 377
EP 385
DI 10.1021/acs.molpharmaceut.0c00992
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA PQ8OX
UT WOS:000606803900030
PM 33295773
DA 2022-11-30
ER

PT J
AU Tanaka, M
   Inoue, Y
   Imai, T
   Tanida, N
   Takahashi, K
   Hara, H
AF Tanaka, Miruto
   Inoue, Yuki
   Imai, Takahiko
   Tanida, Norifumi
   Takahashi, Koichi
   Hara, Hideaki
TI Guanabenz and Clonidine, alpha 2-Adrenergic Receptor Agonists, Inhibit
   Choroidal Neovascularization
SO CURRENT NEUROVASCULAR RESEARCH
LA English
DT Article
DE Age-related macular degeneration; alpha 2-adrenergic receptor agonist;
   choroidal neovascularization; guanabenz; clonidine; retinal endothelial
   cells; vascular endothelial growth factor
ID GROWTH-FACTOR; EXPRESSION; PROTECTS; SUBTYPES
AB Background: Neovascular age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of blindness in elderly people. Anti-vascular endothelial growth factor (anti-VEGF)-drugs are used to treat AMD patients; however, some patients are resistant to these therapies.
   Objective: The purpose of this study was to investigate the anti-angiogenic effects of alpha 2-adrenergic agonists, including guanabenz and clonidine.
   Methods: We evaluated the anti-angiogenic effects of alpha 2-adrenergic agonists in human retinal microvascular endothelial cells (HRMECs). A proliferation assay was conducted, and the migration ratio was evaluated. In a laser-induced CNV model, guanabenz and clonidine were delivered via intraperitoneal injection or implantation of an osmotic pump device. Fourteen days following CNV induction, CNV lesion size and fundus fluorescein angiography (FFA) were evaluated.
   Results: Guanabenz and clonidine inhibited VEGF-induced retinal endothelial cell growth and migration. In the CNV model mice, CNV lesion sizes were reduced by intraperitoneal administration of guanabenz or clonidine. Data, including body weight, systolic blood pressure, and heart rate showed that guanabenz (0.5 and 2.0 mg/kg/day) had little effect on these parameters; conversely, a high dose of clonidine (1.0 mg/kg/day) did affect these parameters. Additionally, clonidine did not affect CNV size, but continuous administration of guanabenz attenuated both CNV size and leakage from neovessels.
   Conclusion: Our study suggests a key role for alpha 2-adrenergic receptors during CNV formation. Therefore, we suggest that alpha 2-adrenergic receptor agonists may represent novel therapeutic drugs for patients with neovascular AMD.
C1 [Tanaka, Miruto; Inoue, Yuki; Imai, Takahiko; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
   [Tanida, Norifumi; Takahashi, Koichi] Hisamitsu Pharmaceut Co Inc, Res & Dev Div, Basic Res Labs, Ibaraki, Japan.
C3 Gifu Pharmaceutical University; Hisamitsu Pharmaceutical Co Ltd
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
RI Imai, Takahiko/ABF-6143-2020
OI Imai, Takahiko/0000-0002-4422-2946; Hara, Hideaki/0000-0003-2046-9001
FU Hisamitsu Pharmaceutical Co., Inc.
FX HH received a research Grant from Hisamitsu Pharmaceutical Co., Inc.
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NR 19
TC 1
Z9 1
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1567-2026
EI 1875-5739
J9 CURR NEUROVASC RES
JI Curr. Neurovasc. Res.
PY 2021
VL 18
IS 1
BP 85
EP 92
DI 10.2174/1567202618666210518133634
PG 8
WC Clinical Neurology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA UE4UJ
UT WOS:000687885000006
PM 34011258
DA 2022-11-30
ER

PT J
AU Wang, HB
   Ramshekar, A
   Kunz, E
   Sacks, DB
   Hartnett, ME
AF Wang, Haibo
   Ramshekar, Aniket
   Kunz, Eric
   Sacks, David B.
   Hartnett, M. Elizabeth
TI IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated
   Rac1 activation
SO ANGIOGENESIS
LA English
DT Article
DE Age-related macular degeneration; choroidal neovascularization; IQGAP1;
   Vascular endothelial growth factor; Vascular endothelial growth factor
   receptor 2; Rac1
ID CELL-MIGRATION; NADPH OXIDASE; ENDOTHELIAL-CELLS; IN-VIVO; VEGF;
   PROTEINS; TRANSMIGRATION; TUMORIGENESIS; POLYMORPHISMS; CROSSTALK
AB Loss of visual acuity in neovascular age-related macular degeneration (nAMD) occurs when factors activate choroidal endothelial cells (CECs) to transmigrate the retinal pigment epithelium into the sensory retina and develop into choroidal neovascularization (CNV). Active Rac1 (Rac1GTP) is required for CEC migration and is induced by different AMD-related stresses, including vascular endothelial growth factor (VEGF). Besides its role in pathologic events, Rac1 also plays a role in physiologic functions. Therefore, we were interested in a method to inhibit pathologic activation of Rac1. We addressed the hypothesis that IQGAP1, a scaffold protein with a Rac1 binding domain, regulates pathologic Rac1GTP in CEC migration and CNV. Compared to littermateIqgap1(+/+),Iqgap1(-/-)mice had reduced volumes of laser-induced CNV and decreased Rac1GTP and phosphorylated VEGFR2 (p-VEGFR2) within lectin-stained CNV. Knockdown of IQGAP1 in CECs significantly reduced VEGF-induced Rac1GTP, mediated through p-VEGFR2, which was necessary for CEC migration. Moreover, sustained activation of Rac1GTP induced by VEGF was eliminated when CECs were transfected with an IQGAP1 construct that is unable to bind Rac1. IQGAP1-mediated Src activation was involved in initiating Rac1 activation, CEC migration, and tube formation. Our findings indicate that CEC IQGAP1 interacts with VEGFR2 to mediate Src activation and subsequent Rac1 activation and CEC migration. In addition, IQGAP1 binding to Rac1GTP results in sustained activation of Rac1, leading to CEC migration toward VEGF. Our study supports a role of IQGAP1 and the interaction between IQGAP1 and Rac1GTP to restore CECs quiescence and, therefore, prevent vision-threatening CNV in nAMD.
C1 [Wang, Haibo; Ramshekar, Aniket; Kunz, Eric; Hartnett, M. Elizabeth] Univ Utah, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
   [Sacks, David B.] NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
C3 Utah System of Higher Education; University of Utah; National Institutes
   of Health (NIH) - USA
RP Hartnett, ME (通讯作者)，Univ Utah, John A Moran Eye Ctr, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM ME.Hartnett@hsc.utah.edu
OI Hartnett, Mary Elizabeth/0000-0002-7270-5670
FU National Institutes of Health [R01EY015130, R01EY017011, EY014800];
   Research to Prevent Blindness, Inc., New York, NY; Intramural Research
   Program of the National Institutes of Health;  [T32 EY024234]
FX This work was supported by the National Institutes of Health EY014800
   and an Unrestricted Grant from Research to Prevent Blindness, Inc., New
   York, NY, to the Department of Ophthalmology & Visual Sciences,
   University of Utah; and the National Institutes of Health R01EY015130
   and R01EY017011 to M.E.H and by T32 EY024234 to A. R. D.B.S. is
   supported by the Intramural Research Program of the National Institutes
   of Health. We thank Dr. William A. Muller for providing
   adenovirus-IQGAP1shRNA constructs.
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NR 57
TC 18
Z9 18
U1 1
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD NOV
PY 2020
VL 23
IS 4
BP 685
EP 698
DI 10.1007/s10456-020-09740-y
EA AUG 2020
PG 14
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA NV3WP
UT WOS:000558606000001
PM 32783108
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Dorschmann, P
   Mikkelsen, MD
   Thi, TN
   Roider, J
   Meyer, AS
   Klettner, A
AF Dorschmann, Philipp
   Mikkelsen, Maria Dalgaard
   Thi, Thuan Nguyen
   Roider, Johann
   Meyer, Anne S.
   Klettner, Alexa
TI Effects of a Newly Developed Enzyme-Assisted Extraction Method on the
   Biological Activities of Fucoidans in Ocular Cells
SO MARINE DRUGS
LA English
DT Article
DE fucoidan; fucose; enzymatic purification; age-related macular
   degeneration; VEGF; oxidative stress; Laminaria digitata; Fucus
   distichussubsp; evanescens; Saccharina latissima; retinal pigment
   epithelium
ID MACULAR DEGENERATION; BROWN SEAWEEDS; ARPE-19 CELLS; SACCHARIFICATION
AB Fucoidans from brown seaweeds are promising substances as potential drugs against age-related macular degeneration (AMD). The heterogeneity of fucoidans requires intensive research in order to find suitable species and extraction methods. Ten different fucoidan samples extracted enzymatically fromLaminaria digitata(LD),Saccharina latissima(SL) andFucus distichussubsp.evanescens(FE) were tested for toxicity, oxidative stress protection and VEGF (vascular endothelial growth factor) inhibition. For this study crude fucoidans were extracted from seaweeds using different enzymes and SL fucoidans were further separated into three fractions (SL_F1-F3) by ion-exchange chromatography (IEX). Fucoidan composition was analyzed by high performance anion exchange chromatography (HPAEC) after acid hydrolysis. The crude extracts contained alginate, while two of the fractionated SL fucoidans SL_F2 and SL_F3 were highly pure. Cell viability was assessed with an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay in OMM-1 and ARPE-19. Protective effects were investigated after 24 h of stress insult in OMM-1 and ARPE-19. Secreted VEGF was analyzed via ELISA (enzyme-linked immunosorbent assay) in ARPE-19 cells. Fucoidans showed no toxic effects. In OMM-1 SL_F2 and several FE fucoidans were protective. LD_SiAT2 (Cellic(R)CTec2 + Sigma-Aldrich alginate lyase), FE_SiAT3 (Cellic(R)CTec3 + Sigma-Aldrich alginate lyase), SL_F2 and SL_F3 inhibited VEGF with the latter two as the most effective. We could show that enzyme treated fucoidans in general and the fractionated SL fucoidans SL_F2 and SL_F3 are very promising for beneficial AMD relevant biological activities.
C1 [Dorschmann, Philipp; Roider, Johann; Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
   [Mikkelsen, Maria Dalgaard; Thi, Thuan Nguyen; Meyer, Anne S.] Tech Univ Denmark, Dept Biotechnol & Biomed, Soltofts Plads, DK-2800 Lyngby, Denmark.
C3 University of Kiel; Schleswig Holstein University Hospital; Technical
   University of Denmark
RP Dorschmann, P (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
EM philipp.doerschmann@uksh.de; mdami@dtu.dk; thuthi@dtu.dk;
   johann.roider@uksh.de; asme@dtu.dk; alexakarina.klettner@uksh.de
RI Meyer, Anne S/AAN-2157-2020; Mikkelsen, Maria Dalgaard/AAP-3139-2021
OI Meyer, Anne S/0000-0001-8910-9931; Mikkelsen, Maria
   Dalgaard/0000-0003-4297-6119; Klettner, Alexa/0000-0002-2709-1059;
   Nguyen, Thuan Thi/0000-0003-2423-4461
FU EU InterReg-Deutschland-Denmark; European Fund of Regional Development;
   Innovation Fund Denmark [0603-00522B]
FX This study is part of the FucoSan-Health from the Sea Project and is
   supported by EU InterReg-Deutschland-Denmark and the European Fund of
   Regional Development. This work was part of the BioValue SPIR Platform
   funded by Innovation Fund Denmark, case no. 0603-00522B.
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NR 40
TC 14
Z9 15
U1 2
U2 16
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1660-3397
J9 MAR DRUGS
JI Mar. Drugs
PD JUN
PY 2020
VL 18
IS 6
AR 282
DI 10.3390/md18060282
PG 16
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA MN9TB
UT WOS:000551180900050
PM 32466624
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Garweg, JG
AF Garweg, Justus G.
TI A Randomized, Double-Masked, Multicenter, Phase III Study Assessing the
   Efficacy and Safety of Brolucizumab versus Aflibercept in Patients with
   Visual Impairment due to Diabetic Macular Edema (KITE)
SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE
LA English
DT Article
DE diabetic macular edema; DME; Brolucizumab; Aflibercept; intravitreal
   therapy; randomized clinical trial
ID RANIBIZUMAB PLUS PROMPT; DEFERRED LASER; INTRAVITREAL AFLIBERCEPT;
   INTRAOCULAR-PRESSURE; RETINOPATHY SEVERITY; ANTIBODY FRAGMENT; 0.5 MG;
   RESTORE; DEGENERATION; INJECTIONS
AB Background Brolucizumab is a single-chain variable antibody fragment (scVF) that specifically binds to VEGF-A. The results of two large phase III, multicentre, randomized clinical trials comparing intravitreal treatment with Brolucizumab and Aflibercept in neovascular age-related degeneration demonstrated its potency in the treatment of neovascular age-related macular degeneration (nAMD).
   Methods The currently tested injected dose of 6mg Brolucizumab results in a 11.2-13.3 times higher equivalent molar dose compared to Aflibercept 2 mg. Thus, it is conceivable that the effect of Brolucizumab in DME exceeds that of other currently used anti-VEGF agents with regards to effect durability; this was confirmed for nAMD in a phase I/II study.
   Results Approved anti-VEGF drugs have shown unprecedented success compared to laser treatment with regards to restoration of visual acuity and improvement of diabetic retinopathy severity scores for up to 5 years. The visual gains were sustained after the loading phase and a reduced number of injections were required after the first year independent of the treatment strategy. Compared to pan-retinal laser photocoagulation, the time to progression of DRP was markedly extended and was proven by better preservation of the visual field, prevention of severe vision loss, hemorrhagic complications, and the need for intraocular surgery.
   Conclusions The ongoing prospective, randomized, phase III clinical studies in DME, KITE, and KESTREL aim to confirm the non-inferiority of Brolucizumab 6mg compared to Aflibercept 2mg on a functional and morphological level as well as durability effect over 2 years.
C1 [Garweg, Justus G.] Swiss Eye Inst, Clin Vitreoretinal Dis, Bremgartenstr 119, CH-3012 Bern, Switzerland.
RP Garweg, JG (通讯作者)，Swiss Eye Inst, Clin Vitreoretinal Dis, Bremgartenstr 119, CH-3012 Bern, Switzerland.
EM justus.garweg@swiss-eye-institute.com
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NR 32
TC 7
Z9 8
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 2020
VL 237
IS 4
BP 450
EP 453
DI 10.1055/a-1101-9126
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LJ6UT
UT WOS:000530298700025
PM 32131127
DA 2022-11-30
ER

PT J
AU Sun, JR
   Chen, JQ
   Li, T
   Huang, PR
   Li, J
   Shen, MX
   Gao, M
   Sun, Y
   Liang, J
   Li, XM
   Wang, YM
   Xiao, YS
   Shi, X
   Hu, YF
   Feng, JY
   Jia, HX
   Liu, T
   Sun, XD
AF Sun, Junran
   Chen, Jieqiong
   Li, Tong
   Huang, Peirong
   Li, Jie
   Shen, Mengxi
   Gao, Min
   Sun, Yang
   Liang, Jian
   Li, Xiaomeng
   Wang, Yimin
   Xiao, Yushu
   Shi, Xiang
   Hu, Yifan
   Feng, Jingyang
   Jia, Huixun
   Liu, Te
   Sun, Xiaodong
TI ROS production and mitochondrial dysfunction driven by PU.1-regulated
   NOX4-p22(phox) activation in A beta-induced retinal pigment epithelial
   cell injury
SO THERANOSTICS
LA English
DT Article
DE retinal pigment epithelial cells; amyloid beta; age-related macular
   degeneration; PU.1; NADPH oxidases
ID NLRP3 INFLAMMASOME ACTIVATION; AMYLOID-BETA; OXIDATIVE STRESS; NADPH
   OXIDASE; RPE CELLS; NOX4; EXPRESSION; CYTOSCAPE; PEPTIDE;
   CHORIOCAPILLARIS
AB Rationale: Amyloid beta (A beta) deposition, an essential pathological process in age-related macular degeneration (AMD), causes retinal pigment epithelium (RPE) degeneration driven mostly by oxidative stress. However, despite intense investigations, the extent to which overoxidation contributes to A beta-mediated RPE damage and its potential mechanism has not been fully elucidated.
   Methods: We performed tandem mass-tagged (TMT) mass spectrometry (MS) and bioinformatic analysis of the RPE-choroid complex in an A beta(1-40)-induced mouse model of retinal degeneration to obtain a comprehensive proteomic profile. Key regulators in this model were confirmed by reactive oxygen species (ROS) detection, mitochondrial ROS assay, oxygen consumption rate (OCR) measurement, gene knockout experiment, chromatin immunoprecipitation (ChIP), and luciferase assay.
   Results: A total of 4243 proteins were identified, 1069 of which were significantly affected by A beta(1-40) and found to be enriched in oxidation-related pathways by bioinformatic analysis. Moreover, NADPH oxidases were identified as hub proteins in A beta(1-40)-mediated oxidative stress, as evidenced by mitochondrial dysfunction and reactive oxygen species overproduction. By motif and binding site analyses, we found that the transcription factor PU.1/Spi1 acted as a master regulator of the activation of NADPH oxidases, especially the NOX4-p22(phox) complex. Also, PU.1 silencing impeded RPE oxidative stress and mitochondrial dysfunction and rescued the retinal structure and function.
   Conclusion: Our study suggests that PU.1 is a novel therapeutic target for AMD, and the regulation of PU.1 expression represents a potentially novel approach against excessive oxidative stress in A beta-driven RPE injury.
C1 [Sun, Junran; Chen, Jieqiong; Li, Tong; Huang, Peirong; Gao, Min; Liang, Jian; Li, Xiaomeng; Wang, Yimin; Xiao, Yushu; Shi, Xiang; Hu, Yifan; Feng, Jingyang; Jia, Huixun; Sun, Xiaodong] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Sch Med,Shanghai Peoples Hosp 1, Shanghai, Peoples R China.
   [Sun, Junran; Chen, Jieqiong; Li, Tong; Huang, Peirong; Gao, Min; Li, Xiaomeng; Wang, Yimin; Xiao, Yushu; Shi, Xiang; Hu, Yifan; Feng, Jingyang; Jia, Huixun; Sun, Xiaodong] Natl Clin Res Ctr Ophthalm Dis, Shanghai, Peoples R China.
   [Sun, Junran; Chen, Jieqiong; Li, Tong; Huang, Peirong; Gao, Min; Liang, Jian; Li, Xiaomeng; Wang, Yimin; Xiao, Yushu; Shi, Xiang; Hu, Yifan; Feng, Jingyang; Jia, Huixun; Sun, Xiaodong] Shanghai Engn Ctr Visual Sci & Photomed, 100 Haining Rd, Shanghai 200080, Peoples R China.
   [Huang, Peirong] Univ Virginia, Sch Med, Ctr Adv Vis Sci, Charlottesville, VA 22908 USA.
   [Li, Jie] Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Dept Ophthalmol, Shanghai, Peoples R China.
   [Shen, Mengxi] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Sun, Yang] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Dermatol, Sch Med, Shanghai, Peoples R China.
   [Liang, Jian; Sun, Xiaodong] Shanghai Key Lab Fundus Dis, 100 Haining Rd, Shanghai 200080, Peoples R China.
   [Jia, Huixun; Sun, Xiaodong] Shanghai Engn Ctr Precise Diag & Treatment Eye Di, Shanghai, Peoples R China.
   [Liu, Te] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Geriatr Inst Chinese Med, Shanghai, Peoples R China.
   [Liu, Te] Yale Univ, Sch Med, Dept Pathol, 10 Amistad St, New Haven, CT 06510 USA.
C3 Shanghai Jiao Tong University; University of Virginia; Shanghai
   University of Traditional Chinese Medicine; Bascom Palmer Eye Institute;
   University of Miami; Shanghai Jiao Tong University; Shanghai University
   of Traditional Chinese Medicine; Yale University
RP Sun, XD (通讯作者)，Shanghai Engn Ctr Visual Sci & Photomed, 100 Haining Rd, Shanghai 200080, Peoples R China.; Sun, XD (通讯作者)，Shanghai Key Lab Fundus Dis, 100 Haining Rd, Shanghai 200080, Peoples R China.; Liu, T (通讯作者)，Yale Univ, Sch Med, Dept Pathol, 10 Amistad St, New Haven, CT 06510 USA.; Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Natl Clin Res Ctr Ophthalm Dis,Dept Ophthalmol,Sh, 100 Haining Rd, Shanghai 200080, Peoples R China.; Liu, T (通讯作者)，Shanghai Univ Tradit Chinese Med, Shanghai Geriatr Inst Chinese Med, Shanghai 201031, Peoples R China.
EM 0721160004@mail.tongji.edu.cn; xdsun@sjtu.edu.cn
RI Shen, Mengxi/ABC-6941-2021
OI Shen, Mengxi/0000-0002-1336-1695
FU National Natural Science Foundation of China [81730026, 81900871,
   81700843]; Shanghai Sailing Plan for the Young Scientific Talents
   [19YF1439600, 19YF1439800]; National Major Scientific and Technological
   Special Project for "Significant New Drugs Development" during the
   Thirtieth Five-year Plan Period [2019ZX09301113]; National Key RD
   Program [2017YFA0105301]; Science and Technology Commission of Shanghai
   Municipality [17411953000, 19495800700]; Frontier Project of Hospital
   Development Center [SHDC12016105]; National Key R&D Program of China
   [2016YFC0904800, 2019YFC0840607]; National Science and Technology Major
   Project of China [2017ZX09304010]
FX This work was supported by the National Natural Science Foundation of
   China (81730026), National Natural Science Foundation of China
   (81900871), Shanghai Sailing Plan for the Young Scientific Talents
   (19YF1439600), National Major Scientific and Technological Special
   Project for "Significant New Drugs Development" during the Thirtieth
   Five-year Plan Period (2019ZX09301113), National Key R&D Program
   (2017YFA0105301), Science and Technology Commission of Shanghai
   Municipality (17411953000), Frontier Project of Hospital Development
   Center (SHDC12016105), Science and Technology Commission of Shanghai
   Municipality (19495800700), Shanghai Sailing Plan for the Young
   Scientific Talents (19YF1439800), National Natural Science Foundation of
   China (81700843), National Key R&D Program of China (2016YFC0904800,
   2019YFC0840607), National Science and Technology Major Project of China
   (2017ZX09304010). Special thanks for Xiaoxiong Gong in supporting and
   healing us psychologically through the whole period of conducting this
   research.
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NR 67
TC 12
Z9 14
U1 4
U2 11
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2020
VL 10
IS 25
BP 11637
EP 11655
DI 10.7150/thno.48064
PG 19
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA OE4XO
UT WOS:000580535400019
PM 33052238
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Uji, A
   Nittala, MG
   Hariri, A
   Velaga, SB
   Sadda, SR
AF Uji, Akihito
   Nittala, Muneeswar Gupta
   Hariri, Amirhossein
   Velaga, Swetha Bindu
   Sadda, SriniVas R.
TI Directional kinetics analysis of the progression of geographic atrophy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Geographic atrophy; Fundus autofluorescence; Progression rate; Euclidean
   distance map
ID EYE DISEASE; MACULAR DEGENERATION; ENLARGEMENT; AREA
AB Purpose To investigate the influence of baseline geographic atrophy (GA) size on the rate of GA progression by using both distance and area measurements.
   Methods Thirty-five eyes from 24 patients with GA due to age-related macular degeneration were obtained from anonymized datasets available at the Doheny Image Reading Center. Baseline and month 12 fundus autofluorescence (FAF) images were used for this analysis. Borders of GA lesions were semiautomatically segmented by certified reading center graders to create masks of the GA lesion. The masks from the two visits were registered and overlaid to allow the differences in area as well as the differences in the position of GA border between the visits to be computed. Distance measurements were performed using a Euclidean distance map. Sectoral (clock hour)/directional GA progression rates with respect to the foveal center were also calculated.
   Results GA progressed 1.6 +/- 0.9mm(2) in area and 92.9 +/- 64.9 mu m in distance over the 12 months. Smaller GA lesions were associated with more rapid progression when measured using distance (P=0.0004, R=-0.554). In contrast, there was no significant correlation in this cohort between baseline GA area and the progression measured in area (P=0.406). In the sectoral/directional GA progression analysis, progression speed differed among clockwise directions, when progression was evaluated by using area measurements. However, this difference was not found, when evaluated by using distance measurements.
   Conclusions Use of linear distance-based measurements enables evaluation of GA progression which is not confounded by baseline lesion size.
C1 [Uji, Akihito; Nittala, Muneeswar Gupta; Hariri, Amirhossein; Velaga, Swetha Bindu; Sadda, SriniVas R.] Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St,Suite 211, Los Angeles, CA 90033 USA.
   [Uji, Akihito; Nittala, Muneeswar Gupta; Hariri, Amirhossein; Velaga, Swetha Bindu; Sadda, SriniVas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA
RP Sadda, SR (通讯作者)，Doheny Eye Inst, Doheny Image Reading Ctr, 1355 San Pablo St,Suite 211, 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 Nittala, Muneeswar/AAT-7533-2020
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NR 26
TC 7
Z9 7
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD AUG
PY 2019
VL 257
IS 8
BP 1679
EP 1685
DI 10.1007/s00417-019-04368-1
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IJ3MX
UT WOS:000475809900012
PM 31147841
DA 2022-11-30
ER

PT J
AU Kumar, D
   Batra, J
   Komives, C
   Rathore, AS
AF Kumar, Deepak
   Batra, Jyoti
   Komives, Claire
   Rathore, Anurag S.
TI QbD Based Media Development for the Production of Fab Fragments in E.
   coli
SO BIOENGINEERING-BASEL
LA English
DT Article
DE quality by design; Ranibizumab; design of experiments; media development
AB Ranibizumab is a biotherapeutic Fab fragment used for the treatment of age-related macular degeneration and macular oedema. It is currently expressed in the gram-negative bacterium, Escherichia coli. However, low expression levels result in a high manufacturing cost. The protein expression can be increased by manipulating nutritional requirements (carbon source, nitrogen source, buffering agent), process parameters (pH, inducer concentration, agitation, temperature), and the genetic make-up of the producing strain. Further, understanding the impact of these factors on product quality is a requirement as per the principles of Quality by Design (QbD). In this paper, we examine the effect of various media components and process parameters on the expression level and quality of the biotherapeutic. First, risk analysis was performed to shortlist different media components based on the literature. Next, experiments were performed to screen these components. Eight components were identified for further investigation and were examined for their effect and interactions using a Fractional Factorial experimental design. Sucrose, biotin, and pantothenate were found to have the maximum effect during Fab production. Furthermore, cyanocobalamin glutathione and biotin-glutathione were the most significant interactions observed. Product identification was performed with Liquid Chromatography-Mass Spectrometry (LC-MS), the expression level was quantified using Bio-layer Interferometry, Reverse Phase-HPLC, and SDS-PAGE, and product quality were measured by RP-HPLC. Overall, a five-fold enhancement of the target protein titer was obtained (from 5 mg/L to 25 mg/L) using the screened medium components vis-a-vis the basal medium, thereby demonstrating the efficacy of the systematic approach purported by QbD.
C1 [Kumar, Deepak; Batra, Jyoti; Rathore, Anurag S.] Indian Inst Technol, Dept Chem Engn, Hauz Khas 110016, India.
   [Komives, Claire] San Jose State Univ, Dept Biomed Chem & Mat Engn, San Jose, CA 95192 USA.
C3 Indian Institute of Technology System (IIT System); Indian Institute of
   Technology (IIT) - Delhi; California State University System; San Jose
   State University
RP Rathore, AS (通讯作者)，Indian Inst Technol, Dept Chem Engn, Hauz Khas 110016, India.
EM dpakk10@gmail.com; batrajyoti123@gmail.com; claire.komives@sjsu.edu;
   asrathore@biotechcmz.com
OI Kumar, Deepak/0000-0003-1154-0179
FU Department of Biotechnology, Government of India
   [BT/COE/34/SP15097/2015]
FX This work was funded by the Department of Biotechnology, Government of
   India (number BT/COE/34/SP15097/2015).
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NR 47
TC 8
Z9 9
U1 1
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2306-5354
J9 BIOENGINEERING-BASEL
JI Bioengineering-Basel
PD JUN
PY 2019
VL 6
IS 2
DI 10.3390/bioengineering6020029
PG 17
WC Biotechnology & Applied Microbiology; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Engineering
GA II6IW
UT WOS:000475298500002
PM 30925730
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Jiang, Z
   Yu, ZK
   Feng, SX
   Huang, ZY
   Peng, YH
   Guo, JX
   Ren, QS
   Lu, YY
AF Jiang, Zhe
   Yu, Zekuan
   Feng, Shouxin
   Huang, Zhiyu
   Peng, Yahui
   Guo, Jianxin
   Ren, Qiushi
   Lu, Yanye
TI A super-resolution method-based pipeline for fundus fluorescein
   angiography imaging
SO BIOMEDICAL ENGINEERING ONLINE
LA English
DT Article
DE Fundus fluorescein angiography imaging; Super-resolution; Machine
   learning; Random forest; Convolutional network
ID COHERENCE TOMOGRAPHY ANGIOGRAPHY; ALGORITHM; DISEASE; IMAGES
AB Background: Fundus fluorescein angiography (FFA) imaging is a standard diagnostic tool for many retinal diseases such as age-related macular degeneration and diabetic retinopathy. High-resolution FFA images facilitate the detection of small lesions such as microaneurysms, and other landmark changes, in the early stages; this can help an ophthalmologist improve a patient's cure rate. However, only low-resolution images are available in most clinical cases. Super-resolution (SR), which is a method to improve the resolution of an image, has been successfully employed for natural and remote sensing images. To the best of our knowledge, no one has applied SR techniques to FFA imaging so far.
   Methods: In this work, we propose a SR method-based pipeline for FFA imaging. The aim of this pipeline is to enhance the image quality of FFA by using SR techniques. Several SR frameworks including neighborhood embedding, sparsity-based, locally-linear regression and deep learning-based approaches are investigated. Based on a clinical FFA dataset collected from Second Affiliated Hospital to Xuzhou Medical University, each SR method is implemented and evaluated for the pipeline to improve the resolution of FFA images.
   Results and conclusion: As shown in our results, most SR algorithms have a positive impact on the enhancement of FFA images. Super-resolution forests (SRF), a random forest-based SR method has displayed remarkable high effectiveness and outperformed other methods. Hence, SRF should be one potential way to benefit ophthalmologists by obtaining high-resolution FFA images in a clinical setting.
C1 [Jiang, Zhe; Yu, Zekuan; Huang, Zhiyu; Ren, Qiushi] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China.
   [Feng, Shouxin; Guo, Jianxin] Xuzhou Med Univ, Xuzhou 221006, Jiangsu, Peoples R China.
   [Peng, Yahui] Beijing Jiaotong Univ, Sch Elect & Informat Engn, Beijing 100044, Peoples R China.
   [Lu, Yanye] Friedrich Alexander Univ Erlangen Nuremberg, Pattern Recognit Lab, D-91058 Erlangen, Germany.
C3 Peking University; Xuzhou Medical University; Beijing Jiaotong
   University; University of Erlangen Nuremberg
RP Guo, JX (通讯作者)，Xuzhou Med Univ, Xuzhou 221006, Jiangsu, Peoples R China.; Lu, YY (通讯作者)，Friedrich Alexander Univ Erlangen Nuremberg, Pattern Recognit Lab, D-91058 Erlangen, Germany.
EM guojianxin_724@126.com; yanye.lu@pku.edu.cn
RI Peng, Yahui/O-5290-2018; Lu, Yanye/ABF-8769-2020
OI Peng, Yahui/0000-0002-2520-1170; Lu, Yanye/0000-0002-3063-8051; Yu,
   Zekuan/0000-0003-3655-872X
FU National Key Research and Development Program of China [2017YFE0104200];
   National Natural Science Foundation of China [81421004]; National Key
   Instrumentation Development Project of China [2013YQ030651]
FX This work was funded by the National Key Research and Development
   Program of China (2017YFE0104200); the National Natural Science
   Foundation of China (81421004); the National Key Instrumentation
   Development Project of China (2013YQ030651).
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NR 60
TC 8
Z9 8
U1 4
U2 21
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1475-925X
J9 BIOMED ENG ONLINE
JI Biomed. Eng. Online
PD SEP 19
PY 2018
VL 17
AR 125
DI 10.1186/s12938-018-0556-7
PG 19
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA GU2VI
UT WOS:000445128700001
PM 30231879
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zambrowski, O
   Tavernier, E
   Souied, EH
   Desmidt, T
   Le Gouge, A
   Bellicaud, D
   Cochener, B
   Limousin, N
   Hommet, C
   Autret-Leca, E
   Pisella, PJ
   Camus, V
AF Zambrowski, Olivia
   Tavernier, Elsa
   Souied, Eric H.
   Desmidt, Thomas
   Le Gouge, Amelie
   Bellicaud, David
   Cochener, Beatrice
   Limousin, Nadege
   Hommet, Caroline
   Autret-Leca, Elisabeth
   Pisella, Pierre-Jean
   Camus, Vincent
TI Sleep and mood changes in advanced age after blue-blocking (yellow)
   intra ocular lens (IOLs) implantation during cataract surgical
   treatment: a randomized controlled trial
SO AGING & MENTAL HEALTH
LA English
DT Article
DE Blue-blocking intra ocular lens (IOL); sleep; depression; aging;
   cataract surgery; circadian rhythms
ID FILTERING INTRAOCULAR LENSES; PRIMARY-CARE PATIENTS; RISK-FACTORS;
   LIGHT; DEPRESSION; QUALITY; PREVALENCE; SURGERY; IMPAIRMENT; MECHANISMS
AB Objectives: Both advanced age and depression are characterized by changes in sleep patterns. Light exposure is one of the main synchronizers of circadian cycles and influences sleep by inhibiting melatonin secretion, which is mostly sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract surgery to prevent age-related macular degeneration, however, the impact of yellow IOLs on sleep and mood is unclear. The purpose of this study was to compare the effects of yellow and clear IOLs on sleep and mood in aged patients undergoing bilateral cataract surgery.Methods: A randomized controlled superiority study was conducted within three ophthalmic surgical wards in France. A total of 204 subjects (mean age 76.27.5 years) were randomized into yellow or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness scale and the Beck Depression Inventory (BDI) one week before and eight weeks after the last surgical procedure.Results: According to an Intent To Treat (ITT) analysis, no significant difference was found between yellow and clear IOLs groups regarding sleep time, sleep latency, total sleep duration, quality of sleep and BDI scores. The rate of patients whose BDI score increased at the cutoff score of 5 after surgery was significantly higher in the yellow IOL group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02.Conclusions: Using yellow IOLs for cataract surgery doesn't significantly impact sleep but may induce mood changes in aging.
C1 [Zambrowski, Olivia; Desmidt, Thomas; Bellicaud, David; Limousin, Nadege; Hommet, Caroline; Autret-Leca, Elisabeth; Pisella, Pierre-Jean; Camus, Vincent] CHRU Tours, Tours, France.
   [Zambrowski, Olivia; Souied, Eric H.] Ctr Hosp Intercommunal Creteil, Creteil, France.
   [Tavernier, Elsa; Le Gouge, Amelie; Camus, Vincent] INSERM, CIC 1415, Tours, France.
   [Hommet, Caroline; Autret-Leca, Elisabeth; Pisella, Pierre-Jean; Camus, Vincent] Univ Francois Rabelais Tours, Tours, France.
   [Cochener, Beatrice] CHU Brest, Brest, France.
   [Hommet, Caroline; Camus, Vincent] INSERM, U930, Tours, France.
C3 CHU Tours; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI
   Creteil; Institut National de la Sante et de la Recherche Medicale
   (Inserm); CHU Brest; Institut National de la Sante et de la Recherche
   Medicale (Inserm)
RP Camus, V (通讯作者)，CHRU Tours, Tours, France.; Camus, V (通讯作者)，INSERM, CIC 1415, Tours, France.; Camus, V (通讯作者)，Univ Francois Rabelais Tours, Tours, France.; Camus, V (通讯作者)，INSERM, U930, Tours, France.
EM vincent.camus@univ-tours.fr
RI Camus, Vincent/ABC-4021-2020
OI Tavernier, Elsa/0000-0003-0798-1182; Desmidt, Thomas/0000-0003-0949-8389
FU Ministere des Affaires Sociales et de la Sante (French Ministry of
   Health) [PHRC-IR-2009-A00719-48]
FX This work was supported by Ministere des Affaires Sociales et de la
   Sante (French Ministry of Health) [grant number PHRC-IR-2009-A00719-48].
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NR 42
TC 6
Z9 8
U1 0
U2 4
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1360-7863
EI 1364-6915
J9 AGING MENT HEALTH
JI Aging Ment. Health
PY 2018
VL 22
IS 10
BP 1351
EP 1356
DI 10.1080/13607863.2017.1348482
PG 6
WC Geriatrics & Gerontology; Gerontology; Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Geriatrics & Gerontology; Psychiatry
GA HH1PG
UT WOS:000455491500015
PM 28691893
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ramtin, A
   Seyfoddin, A
   Coutinho, FP
   Waterhouse, GIN
   Rupenthal, ID
   Svirskis, D
AF Ramtin, A.
   Seyfoddin, A.
   Coutinho, F. P.
   Waterhouse, G. I. N.
   Rupenthal, I. D.
   Svirskis, D.
TI 0 Cytotoxicity considerations and electrically tunable release of
   dexamethasone from polypyrrole for the treatment of back-of-the-eye
   conditions
SO DRUG DELIVERY AND TRANSLATIONAL RESEARCH
LA English
DT Article
DE Electrically triggered release; Solvent washing; Conducting polymer;
   Smart materials; Ocular implant; Sequential polymerization
ID POLYMERIZATION; CONDUCTIVITY; SCAFFOLDS; PYRROLE
AB Age-related macular degeneration (AMD) and diabetic macular edema (DME) are common causes of blindness in people aged over 55 years. Current treatment involves frequent intravitreal administration of corticosteroids such as dexamethasone. The aim of this research was to formulate an electrically controlled delivery system for dexamethasone. Polypyrrole (PPy) was polymerized with dexamethasone sodium phosphate (Dex-P) through two approaches. Firstly, conventional films (CFs) of PPy were electropolymerized by applying a constant current density of 2 mA/cm(2) for 4 min. Secondly, for the first time, we report drug-loaded ethanol-washed films (EWFs). EWFs were prepared in the same manner as CFs, except ethanol washing steps were introduced in the middle and at the end of PPy electropolymerization. The ethanol washing removed unbound PPy oligomers resulting in the formation of smooth surfaces with two distinct layers when viewed in cross-section. The EWFs showed superior electrochemical activity compared to CFs. Sustained release was observed from both CFs and EWFs with bursts of release triggered by electrical stimulation. The EWFs were initially more responsive to the electrical trigger, offering future opportunities to fine tune release. The cytotoxicity of aqueous extracts collected from both films was evaluated on human adult retinal pigment epithelium (ARPE-19) cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with negligible toxicity observed. The results suggest PPy-Dex-P films are highly suitable for the development of electro-responsive implants for the treatment of AMD and DME.
C1 [Ramtin, A.; Seyfoddin, A.; Svirskis, D.] Univ Auckland, Sch Pharm, Auckland, New Zealand.
   [Ramtin, A.] Univ Appl Sci Fresenius, Dept Biol & Chem, Idstein, Germany.
   [Seyfoddin, A.] Auckland Univ Technol, Fac Hlth & Environm Sci, Sch Appl Sci, Auckland, New Zealand.
   [Coutinho, F. P.; Rupenthal, I. D.] Univ Auckland, New Zealand Natl Eye Ctr, Dept Ophthalmol, Buchanan Ocular Therapeut Unit, Auckland, New Zealand.
   [Waterhouse, G. I. N.] Univ Auckland, Sch Chem Sci, Auckland, New Zealand.
   [Waterhouse, G. I. N.] MacDiarmid Inst Adv Mat & Nanotechnol, Wellington, New Zealand.
C3 University of Auckland; Auckland University of Technology; University of
   Auckland; University of Auckland; Victoria University Wellington
RP Svirskis, D (通讯作者)，Univ Auckland, Sch Pharm, Auckland, New Zealand.
EM d.svirskis@auckland.ac.nz
RI Rupenthal, Ilva D/M-5340-2016; Waterhouse, Geoffrey/G-1688-2011
OI Rupenthal, Ilva D/0000-0001-5997-5994; Waterhouse,
   Geoffrey/0000-0002-3296-3093
FU University of Auckland's Faculty of Medical and Health Science Research
   Development Fund; Health Research Council of New Zealand; MacDiarmid
   Institute for Advanced Materials and Nanotechnology
FX We would like to thank the University of Auckland's Faculty of Medical
   and Health Science Research Development Fund, the Health Research
   Council of New Zealand, and the MacDiarmid Institute for Advanced
   Materials and Nanotechnology for funding this research.
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NR 26
TC 12
Z9 12
U1 0
U2 35
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 2190-393X
EI 2190-3948
J9 DRUG DELIV TRANSL RE
JI Drug Deliv. Transl. Res.
PD DEC
PY 2016
VL 6
IS 6
BP 793
EP 799
DI 10.1007/s13346-016-0284-0
PG 7
WC Instruments & Instrumentation; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Instruments & Instrumentation; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA ED2MD
UT WOS:000388679000014
PM 26887593
DA 2022-11-30
ER

PT J
AU Giocanti-Auregan, A
   Tadayoni, R
   Grenet, T
   Fajnkuchen, F
   Nghiem-Buffet, S
   Delahaye-Mazza, C
   Quentel, G
   Cohen, SY
AF Giocanti-Auregan, Audrey
   Tadayoni, Ramin
   Grenet, Typhaine
   Fajnkuchen, Franck
   Nghiem-Buffet, Sylvia
   Delahaye-Mazza, Corinne
   Quentel, Gabriel
   Cohen, Salomon Y.
TI Estimation of the need for bilateral intravitreal anti-VEGF injections
   in clinical practice
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Intravitreal injection; Age-related macular degeneration; Anti-VEGF;
   Diabetic macular edema; Retinal diseases
ID RETINAL VEIN OCCLUSION; DIABETIC MACULAR EDEMA; CHOROIDAL
   NEOVASCULARIZATION; RANIBIZUMAB; AFLIBERCEPT; SECONDARY; EYES
AB Background: To estimate the need for bilateral intravitreal anti-VEGF injections in patients treated for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion, choroidal neovascularization (CNV) in high myopia, and other causes of CNV.
   Methods: All consecutive patients treated with intravitreal anti-VEGF injection over a 1-month period were included in a prospective multicenter survey. The reason for intravitreal anti-VEGF injection and the involvement of the fellow eye in the pathology requiring a treatment with intravitreal anti-VEGF were recorded. A time interval between bilateral injections longer than 1 month, within a 1-month period, and same-day bilateral injections were recorded.
   Results: A total of 1335 patients were included, corresponding to 1024 (76.7 %) patients treated for nAMD, 167 (12. 5 %) for DME, and 144 (10.8 %) for other reasons. Four hundred and fifty-nine (34.4 %) patients were treated bilaterally with a time interval between injections longer than 1 month, 170 (12.7 %) were treated bilaterally within a 1-month interval, and 87 (6.6 %) had same-day bilateral injections. Bilateral injections were more frequent in diabetic patients than in nAMD patients (respectively 48 % vs. 36 %, p = 0.0033).
   Conclusions: Patients with DME are more likely to be treated bilaterally with anti-VEGF injections. As the rate of second eye involvement requiring treatment increases progressively over time, a same-day bilateral injection strategy will become more common as it decreases the administrative burden on the healthcare system and treatment burden experienced by patients.
C1 [Giocanti-Auregan, Audrey; Grenet, Typhaine; Fajnkuchen, Franck; Nghiem-Buffet, Sylvia] Hop Avicenne, AP HP, Dept Ophthalmol, Seine St Denis, France.
   [Giocanti-Auregan, Audrey; Grenet, Typhaine; Fajnkuchen, Franck; Nghiem-Buffet, Sylvia] Univ Paris 13 Bobigny, Seine St Denis, France.
   [Giocanti-Auregan, Audrey; Tadayoni, Ramin; Grenet, Typhaine; Fajnkuchen, Franck; Nghiem-Buffet, Sylvia] Dept Hosp Univ Vis & Handicaps, Paris, France.
   [Tadayoni, Ramin] Hop Lariboisiere, AP HP, Dept Ophthalmol, Paris, France.
   [Tadayoni, Ramin] Univ Paris 07, Paris, France.
   [Grenet, Typhaine; Fajnkuchen, Franck; Nghiem-Buffet, Sylvia; Delahaye-Mazza, Corinne; Quentel, Gabriel; Cohen, Salomon Y.] Ctr Ophtalmol Imagerie & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
   [Cohen, Salomon Y.] Hop Intercommunal Creteil, Creteil, France.
   [Cohen, Salomon Y.] Univ Paris Est Creteil, Creteil, France.
C3 Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Avicenne - APHP; 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)，Ctr Ophtalmol Imagerie & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.; Cohen, SY (通讯作者)，Hop Intercommunal Creteil, Creteil, France.; Cohen, SY (通讯作者)，Univ Paris Est Creteil, Creteil, France.
EM sycsyc75@gmail.com
FU CIL-ASSOC (association for research in vision and ophthalmology)
FX CIL-ASSOC (association for research in vision and ophthalmology). No
   other funding was obtained for this study.
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NR 29
TC 11
Z9 13
U1 0
U2 5
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD AUG 9
PY 2016
VL 16
AR 142
DI 10.1186/s12886-016-0317-y
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DT2YQ
UT WOS:000381348100003
PM 27507298
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Jacobson, SG
   Matsui, R
   Sumaroka, A
   Cideciyan, AV
AF Jacobson, Samuel G.
   Matsui, Rodrigo
   Sumaroka, Alexander
   Cideciyan, Artur V.
TI Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based
   Therapies of Retinal Degenerations
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinitis pigmentosa; Usher syndrome; Stargardt disease; age-related
   macular degeneration
ID OPTICAL COHERENCE TOMOGRAPHY; LEBER CONGENITAL AMAUROSIS; FIBER LAYER
   ANALYSIS; HUMAN GENE-THERAPY; RETINITIS-PIGMENTOSA; MACULAR
   DEGENERATION; LAMINAR ARCHITECTURE; MOUSE MODEL; MUTATIONS; RECEPTOR
AB PURPOSE. We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials.
   METHODS. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified.
   RESULTS. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented.
   CONCLUSIONS. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.
C1 [Jacobson, Samuel G.; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V.] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine
RP Jacobson, SG (通讯作者)，Univ Penn, Scheie Eye Inst, 51 N 39th St, Philadelphia, PA 19104 USA.
EM jacobsos@mail.med.upenn.edu
RI Matsui, Rodrigo/AAH-6883-2020; Cideciyan, Artur V/A-1075-2007
OI Matsui, Rodrigo/0000-0002-4492-7006; Cideciyan, Artur
   V/0000-0002-2018-0905; Jacobson, Samuel/0000-0003-2122-169X
FU Ocular Research Symposia Foundation, Inc.
FX Supported by The Ocular Research Symposia Foundation, Inc. The authors
   alone are responsible for the content and writing of the paper.
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NR 59
TC 15
Z9 15
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2016
VL 57
IS 5
SI SI
DI 10.1167/iovs.15-17654
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DO8NC
UT WOS:000378039300013
PM 27116670
OA gold
DA 2022-11-30
ER

PT J
AU Zhan, J
   He, J
   Zhou, Y
   Wu, M
   Liu, Y
   Shang, F
   Zhang, X
AF Zhan, J.
   He, J.
   Zhou, Y.
   Wu, M.
   Liu, Y.
   Shang, F.
   Zhang, X.
TI Crosstalk Between the Autophagy-Lysosome Pathway and the
   Ubiquitin-Proteasome Pathway in Retinal Pigment Epithelial Cells
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Ubiquitin; proteasome; autophagy; lysosome; protein aggregates
ID MACULAR DEGENERATION; MOLECULAR-MECHANISMS; SELECTIVE AUTOPHAGY;
   OXIDATIVE STRESS; DRUSEN FORMATION; BETA-PEPTIDE; AMYLOID-BETA; RPE
   CELLS; DEGRADATION; SYSTEM
AB Background: The accumulation of damaged or misfolded proteins in retinal pigment epithelial (RPE) cells was considered a contributing factor for RPE dysfunction in age-related macular degeneration (AMD). The ubiquitinprotea-some pathway (UPP) and the autophagy-lysosome pathway (ALP) are the two major proteolytic systems for clearance of misfolded or damaged proteins.
   Objective: The aim is to investigate how these two systems communicate and coordinate with each other in RPE cells for eliminating intracellular misfolded and damaged proteins.
   Methods: Cultured ARPE-19 cells were treated with proteasome inhibitor MG132 and lysosomotropic agent chloroquine (CQ), respectively. The levels and cellular distributions of ubiquitinated proteins, LC3-I, LC3-II, LAMP1 and p62 were analyzed by Western blotting and immunofluorescence. Proteasome activity was determined using Suc-LLVY-AMC as a substrate.
   Results: The level of ubiquitinated protein aggregations was significantly increased after the treatment of MG132 in RPE cells. The levels of LC3-I, LC3-II and LAMP1 increased in MG132 treated cells. The levels of gamma-tubulin and p62 also increased in MG132 treated cells, suggesting that inhibition of the UPP up-regulates autophagy-lysosome pathway. Inhibition of lysosomal activity with CQ also increased the levels of high mass ubiquitin conjugates, LC3-II and p62. In addition, proteasome activity was compromised upon prolonged lysosomal inhibition.
   Conclusions: These data indicate that the UPP and the ALP are interrelated and that dysfunction of the ALP would also result in dysfunction of the UPP and severely compromise the capacity of eliminating misfolded and other forms of damaged proteins.
C1 [Zhan, J.; He, J.; Zhou, Y.; Wu, M.; Liu, Y.; Shang, F.; Zhang, X.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xanlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University
RP Shang, F; Zhang, X (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 South Xanlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM shangf3@sysu.edu.cn; zhangxinyu0294@163.com
FU National Natural Science Foundation of China [81200670]; Science and
   Technology Project of Guangdong Province [2011B050400022]
FX Supported by National Natural Science Foundation of China (No.
   81200670), and the Science and Technology Project of Guangdong Province
   (No. 2011B050400022).
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NR 58
TC 21
Z9 22
U1 0
U2 11
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1566-5240
EI 1875-5666
J9 CURR MOL MED
JI Curr. Mol. Med.
PY 2016
VL 16
IS 5
BP 487
EP 495
DI 10.2174/1566524016666160429121606
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA DV0VW
UT WOS:000382639700006
PM 27132793
DA 2022-11-30
ER

PT J
AU McKibbin, M
   Devonport, H
   Gale, R
   Gavin, M
   Lotery, A
   Mahmood, S
   Patel, PJ
   Ross, A
   Sivaprasad, S
   Talks, J
   Walters, G
AF McKibbin, M.
   Devonport, H.
   Gale, R.
   Gavin, M.
   Lotery, A.
   Mahmood, S.
   Patel, P. J.
   Ross, A.
   Sivaprasad, S.
   Talks, J.
   Walters, G.
TI Aflibercept in wet AMD beyond the first year of treatment:
   recommendations by an expert roundtable panel
SO EYE
LA English
DT Review
ID MACULAR DEGENERATION; RANIBIZUMAB
AB This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for >= 3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the retreatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.
C1 [McKibbin, M.] St James Univ Hosp, Dept Ophthalmol, Leeds, W Yorkshire, England.
   [Devonport, H.] Bradford Royal Infirm, Dept Ophthalmol, Bradford BD9 6RJ, W Yorkshire, England.
   [Gale, R.] York Hosp, Dept Ophthalmol, York, N Yorkshire, England.
   [Gavin, M.] NHS Greater Glasgow & Clyde, Dept Ophthalmol, Glasgow, Lanark, Scotland.
   [Lotery, A.] Southampton Gen Hosp, Southampton SO9 4XY, Hants, England.
   [Mahmood, S.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Royal Eye Hosp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
   [Mahmood, S.] Univ Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester, Lancs, England.
   [Patel, P. J.; Sivaprasad, S.] Moorfields Eye Hosp, NIHR Biomed Res Ctr, London, England.
   [Patel, P. J.; Sivaprasad, S.] UCL Inst Ophthalmol, London, England.
   [Ross, A.] Bristol Eye Hosp, Bristol BS1 2LX, Avon, England.
   [Talks, J.] Royal Victoria Infirm, Newcastle Eye Ctr, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Walters, G.] Harrogate Dist Hosp, Dept Ophthalmol, Harrogate, England.
C3 Saint James's University Hospital; Bradford Royal Infirmary; University
   of Southampton; Manchester Royal Eye Hospital; University of Manchester;
   University of Manchester; University of London; University College
   London; Moorfields Eye Hospital NHS Foundation Trust; University of
   London; University College London; Bristol Eye Hospital; Newcastle
   University - UK
RP McKibbin, M (通讯作者)，Leeds Teaching Hosp NHS Trust, St Jamess Univ Hosp, Dept Ophthalmol, Beckett St, Leeds LS9 7TF, W Yorkshire, England.
EM Martin.McKibbin@nhs.net
RI Mahmood, Sajjad/AAK-7645-2021; Sivaprasad, S./D-6876-2015
OI Sivaprasad, S./0000-0001-8952-0659; Lotery, Andrew/0000-0001-5541-4305
FU Bayer HealthCare; AS&K Communications Ltd; NIHR Biomedical Research
   Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology,
   London, UK
FX This supplement, and the meeting on which it is based, were sponsored by
   Bayer HealthCare. All authors received honoraria, contributed to the
   development of the manuscript, and retained final control of the content
   and editorial decisions. Medical writing assistance was funded by Bayer
   HealthCare and provided by AS&K Communications Ltd. Bayer HealthCare
   checked that the content was factually accurate, balanced, and compliant
   with the Association of the British Pharmaceutical Industry Code of
   Practice. PP and SS received support from the NIHR Biomedical Research
   Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology,
   London, UK. The views expressed are those of the author (s) and not
   necessarily those of the NHS, the NIHR or the Department of Health.
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NR 19
TC 19
Z9 19
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 JUL
PY 2015
VL 29
SU 1
BP S1
EP S11
DI 10.1038/eye.2015.77
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL6ZB
UT WOS:000375787500001
PM 26156564
OA Green Accepted, Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Segal, O
   Mimouni, M
   Nemet, AY
   Segev, F
   Geffen, N
   Nesher, R
AF Segal, Ori
   Mimouni, Michael
   Nemet, Arie Y.
   Segev, Fani
   Geffen, Noa
   Nesher, Ronit
TI The Effects of the Frequency of the Initial Treatment with Intravitreal
   Bevacizumab on Macular Volume and Visual Acuity
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID AGE-RELATED MACULOPATHY; CLINICAL-PRACTICE; SUBGROUP ANALYSIS; AVASTIN
   TREATMENT; UNITED-STATES; DEGENERATION; RANIBIZUMAB; TRIAL; RETINOPATHY;
   MANAGEMENT
AB Purpose: The ideal notion of monthly intravitreal injections is difficult to achieve when it comes to real-life scenarios. In reality, patients often are treated with larger intervals due to circumstances. The purpose of this study was to compare the results of intravitreal bevacizumab injections with shorter intervals versus longer intervals for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a real-life clinic. Methods: A retrospective, consecutive cohort study of naive eyes of patients with CNV secondary to AMD treated with intravitreal bevacizumab. Patients included underwent at least 3 consecutive injections with intervals <45 days in between them (Group A) or >45 days (Group B). Best corrected visual acuity (BCVA) and optical coherence tomography were performed before the initial intravitreal injections and after the last injection. Results: Group A consisted of 24 eyes of 18 patients and Group B 30 eyes of 25 patients. There was a significantly larger mean of consecutive (5.0 vs. 3.78, P=0.013) and total (9.44 vs. 7.2, P=0.021) injections in Group B. There was a significant improvement in average BCVA in Group A only (0.65-0.52, P=0.006). However, a significant and similar improvement in retinal volume was found in both groups (P<0.05). Conclusion: This study emphasizes the importance of achieving consecutive injections with short intervals. Practitioners and decision makers should be mindful that providing additional resources to accomplish proper frequency may be more effective (visual outcome), cost effective (less injections), and safer (less exposure) for the patient.
C1 [Segal, Ori; Nemet, Arie Y.; Segev, Fani; Geffen, Noa; Nesher, Ronit] Meir Med Ctr, Dept Ophthalmol, IL-44281 Kefar Sava, Israel.
   [Segal, Ori; Nemet, Arie Y.; Segev, Fani; Geffen, Noa; Nesher, Ronit] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Mimouni, Michael] Rambam Med Ctr, Dept Ophthalmol, Haifa, Israel.
C3 Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv University;
   Sackler Faculty of Medicine; Rambam Health Care Campus; Technion Israel
   Institute of Technology
RP Segal, O (通讯作者)，Meir Med Ctr, Dept Ophthalmol, IL-44281 Kefar Sava, Israel.
EM orisegal@gmail.com
RI Mimouni, Michael/S-2916-2018
OI Mimouni, Michael/0000-0002-4661-0993; Segev, Fani/0000-0003-3879-8831
CR Axer-Siegel R, 2012, CURR EYE RES, V37, P818, DOI 10.3109/02713683.2012.678543
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NR 30
TC 2
Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN 1
PY 2015
VL 31
IS 5
BP 277
EP 281
DI 10.1089/jop.2014.0079
PG 5
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA CV0ZW
UT WOS:000363983600004
PM 25853291
DA 2022-11-30
ER

PT J
AU Ahn, KN
   Ahn, JY
   Kim, JH
   Cho, K
   Koo, KI
   Senok, SS
   Goo, YS
AF Ahn, Kun No
   Ahn, Jeong Yeol
   Kim, Jae-hyung
   Cho, Kyoungrok
   Koo, Kyo-in
   Senok, Solomon S.
   Goo, Yong Sook
TI Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal
   Ganglion Cell Responses in Retinal Degeneration (rd1) mice
SO KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
LA English
DT Article
DE Anodic phase-1st stimulus; Cathodic phase-1st stimulus; Multi-electrode
   array (MEA); Retinal ganglion cell (RGC); Retinal prosthesis
ID ELECTRICAL-STIMULATION; ROD PHOSPHODIESTERASE; NERVOUS-SYSTEM;
   BETA-SUBUNIT; TISSUE; COMPONENT; ELEMENTS; BRAIN; MODEL
AB A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an 8x8 multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than 10 mu A and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to 500 mu s (30 mu A), changing the intensities (or duration) from 2 to 60 mu A (60 to 1000 mu s). RGCs were classified as response-positive when PSTH showed multiple (3 similar to 4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.
C1 [Ahn, Kun No; Ahn, Jeong Yeol; Goo, Yong Sook] Chungbuk Natl Univ, Dept Physiol, Sch Med, Cheongju 362763, South Korea.
   [Kim, Jae-hyung] Chungbuk Natl Univ, Dept Ophthalmol, Sch Med, Cheongju 362763, South Korea.
   [Cho, Kyoungrok] Chungbuk Natl Univ, Coll Elect & Comp Engn, Dept Informat & Commun Engn, Cheongju 362763, South Korea.
   [Koo, Kyo-in] Univ Ulsan, Dept Elect Engn, Ulsan 680749, South Korea.
   [Senok, Solomon S.] Alfaisal Univ, Coll Med, Neurosci, Riyadh 11533, Saudi Arabia.
C3 Chungbuk National University; Chungbuk National University; Chungbuk
   National University; University of Ulsan
RP Goo, YS (通讯作者)，Chungbuk Natl Univ, Dept Physiol, Sch Med, 410 Sungbong Ro, Cheongju 362763, South Korea.
EM ysgoo@chungbuk.ac.kr
RI Koo, Kyo-in/E-4611-2017
OI Koo, Kyo-in/0000-0003-4173-9218; Senok, Solomon/0000-0002-9041-5845
FU Chungbuk National University;  [NRF-2010-0020852]; 
   [NRF-2013R1A1A3009574]
FX This work was supported by grants of NRF-2010-0020852,
   NRF-2013R1A1A3009574, and research grant of the Chungbuk National
   University in 2011.
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   Ye JH, 2008, KOREAN J PHYSIOL PHA, V12, P307, DOI 10.4196/kjpp.2008.12.6.307
   Zrenner E, 2011, P ROY SOC B-BIOL SCI, V278, P1489, DOI 10.1098/rspb.2010.1747
NR 46
TC 14
Z9 15
U1 0
U2 7
PU KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
PI SEOUL
PA C/O EDITORIAL OFFICE, 448-13 SEOKYO-DONG, SEOUL, SOUTH KOREA
SN 1226-4512
EI 2093-3827
J9 KOREAN J PHYSIOL PHA
JI KOREAN J. PHYSIOL. PHARMACOL.
PD MAR
PY 2015
VL 19
IS 2
BP 167
EP 175
DI 10.4196/kjpp.2015.19.2.167
PG 9
WC Pharmacology & Pharmacy; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Physiology
GA CC8JD
UT WOS:000350613600012
PM 25729279
OA hybrid, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Owsley, C
   Huisingh, C
   Jackson, GR
   Curcio, CA
   Szalai, AJ
   Dashti, N
   Clark, M
   Rookard, K
   McCrory, MA
   Wright, TT
   Callahan, MA
   Kline, LB
   Witherspoon, CD
   McGwin, G
AF Owsley, Cynthia
   Huisingh, Carrie
   Jackson, Gregory R.
   Curcio, Christine A.
   Szalai, Alexander J.
   Dashti, Nassrin
   Clark, Mark
   Rookard, Kia
   McCrory, Mark A.
   Wright, Tyler T.
   Callahan, Michael A.
   Kline, Lanning B.
   Witherspoon, C. Douglas
   McGwin, Gerald, Jr.
TI Associations Between Abnormal Rod-Mediated Dark Adaptation and Health
   and Functioning in Older Adults With Normal Macular Health
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aging; dark adaptation; rod function; age-related macular degeneration
ID C-REACTIVE PROTEIN; AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H;
   CHEMISTRY STANDARDIZATION PROJECT; VITAMIN-A; ALCOHOL-CONSUMPTION;
   VISUAL FUNCTION; INTERNATIONAL-FEDERATION; CARDIOVASCULAR-DISEASE;
   RHODOPSIN LEVELS
AB PURPOSE. Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health.
   METHODS. The sample consisted of adults aged >= 60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5 degrees on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept >= 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history).
   RESULTS. Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions.
   CONCLUSIONS. Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP.
C1 [Owsley, Cynthia; Huisingh, Carrie; Curcio, Christine A.; Clark, Mark; Rookard, Kia; Callahan, Michael A.; Kline, Lanning B.; Witherspoon, C. Douglas; McGwin, Gerald, Jr.] Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA.
   [Jackson, Gregory R.] Penn State Coll Med, Dept Ophthalmol, Hershey, PA USA.
   [Szalai, Alexander J.; McCrory, Mark A.; Wright, Tyler T.] Univ Alabama Birmingham, Sch Med, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
   [Dashti, Nassrin] Univ Alabama Birmingham, Sch Med, Dept Med, Div Gerontol & Geriatr, Birmingham, AL 35294 USA.
   [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
C3 University of Alabama System; University of Alabama Birmingham;
   Pennsylvania Commonwealth System of Higher Education (PCSHE);
   Pennsylvania State University; Penn State Health; University of Alabama
   System; University of Alabama Birmingham; University of Alabama System;
   University of Alabama Birmingham; University of Alabama System;
   University of Alabama Birmingham
RP Owsley, C (通讯作者)，Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, 700 S 18th St,Suite 609, Birmingham, AL 35294 USA.
EM owsley@uab.edu
OI Huisingh, Carrie/0000-0002-7010-2024; Witherspoon,
   Clark/0000-0003-4456-9437; Szalai, Alexander J/0000-0001-6638-579X
FU National Institute on Aging [R01AG04212]; Research to Prevent Blindness;
   EyeSight Foundation of Alabama; Alfreda J. Schueler Trust; NATIONAL
   INSTITUTE ON AGING [R01AG004212] Funding Source: NIH RePORTER
FX Supported by the National Institute on Aging (R01AG04212 and R01AG04212
   Supplement), Research to Prevent Blindness, the EyeSight Foundation of
   Alabama, and the Alfreda J. Schueler Trust.
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NR 88
TC 54
Z9 55
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2014
VL 55
IS 8
BP 4776
EP 4789
DI 10.1167/iovs.14-14502
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AQ9DV
UT WOS:000343145500012
PM 24854857
OA Green Published
DA 2022-11-30
ER

PT J
AU Kunchithapautham, K
   Atkinson, C
   Rohrer, B
AF Kunchithapautham, Kannan
   Atkinson, Carl
   Rohrer, Baerbel
TI Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid
   Accumulation in Retinal Pigment Epithelium through Oxidative Stress and
   Complement Activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
   CIGARETTE-SMOKE; BRUCHS MEMBRANE; CHOROIDAL NEOVASCULARIZATION;
   REGULATORY PROTEINS; ALTERNATIVE PATHWAY; GEOGRAPHIC ATROPHY;
   APOLIPOPROTEIN-E
AB Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD.
C1 [Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
   [Rohrer, Baerbel] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA.
C3 Medical University of South Carolina; Medical University of South
   Carolina; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Ralph H Johnson VA Medical Center
RP Rohrer, B (通讯作者)，167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU National Institutes of Health [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 Animal studies were conducted in a facility constructed with support
   from the National Institutes of Health Grant C06RR015455.
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NR 78
TC 104
Z9 105
U1 1
U2 10
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 MAY 23
PY 2014
VL 289
IS 21
BP 14534
EP 14546
DI 10.1074/jbc.M114.564674
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AI9JE
UT WOS:000337248100012
PM 24711457
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Sachdeva, MM
   Cano, M
   Handa, JT
AF Sachdeva, Mira M.
   Cano, Marisol
   Handa, James T.
TI Nrf2 signaling is impaired in the aging RPE given an oxidative insult
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; aging; Nrf2; oxidative stress; retinal
   pigment epithelium
ID MACULAR DEGENERATION; CIGARETTE-SMOKING; POOLED FINDINGS; RISK-FACTORS;
   PREVALENCE
AB Age-related macular degeneration (AMD) represents the leading cause of blindness in the elderly, yet no definitive therapy exists for early, dry disease. Several lines of evidence have implicated oxidative stressinduced damage to the retinal pigment epithelium (RPE) in the pathogenesis of AMD, suggesting that the aging RPE may exhibit increased susceptibility to cell damage induced by exogenous stressors. The transcription factor Nrf2 serves as the master regulator of a highly coordinated antioxidant response in virtually all cell types. We compared Nrf2 signaling in the RPE of young (2 months) and old (15 months) mice under unstressed and stressed (sodium iodate) conditions. The aging RPE expressed higher levels of the Nrf2 target genes NQ01, GCLM, and H01 compared with the RPE of younger mice under unstressed conditions, suggesting an age-related increase in basal oxidative stress. Moreover, the RPE of older mice demonstrated impaired induction of the protective Nrf2 pathway following oxidative stress induced with sodium iodate. The RPE of old mice exposed to sodium iodate also exhibited higher levels of superoxide anion and malondialdehyde than young mice, suggesting inadequate protection against oxidative damage. Induction of Nrf2 signaling in response to sodium iodate was partially restored in the RPE of aging mice with genetic rescue, using conditional knockdown of the Nrf2 negative regulator Keapl (TamCre; KeaplloxP) compared to Keapl loxP mice. These data indicate that the aging RPE is vulnerable to oxidative damage due to impaired Nrf2 signaling, and that Nrf2 signaling is a promising target for novel pharmacologic or genetic therapeutic strategies. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Sachdeva, Mira M.; Cano, Marisol; Handa, James T.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，Wilmer Ophthalmol Inst, John Hopkins Med Inst, Smith Bldg,Room 3015,400 N Broadway, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
FU Thome Foundation Award; RPB Senior Scientist Award; Wilmer Core Grant
   [EY001765]; Unrestricted RPB grant; NATIONAL EYE INSTITUTE [P30EY001765,
   R01EY014005, R01EY019904] Funding Source: NIH RePORTER
FX NEI EY019904 (JTH), EY14005 (JTH), Thome Foundation Award in AMD (JTH),
   RPB Senior Scientist Award (JTH), Wilmer Core Grant, EY001765,
   Unrestricted RPB grant to Wilmer Eye Institute, generous donations by
   the Merlau Family. JTH is the Robert Bond Welch Professor. We thank Hong
   Wei, Sonny Dike, and Brad Barnett for their technical assistance.
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NR 18
TC 128
Z9 132
U1 4
U2 16
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 2014
VL 119
BP 111
EP 114
DI 10.1016/j.exer.2013.10.024
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 304LH
UT WOS:000330747900014
PM 24216314
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kozhevnikova, OS
   Korbolina, EE
   Ershov, NI
   Kolosova, NG
AF Kozhevnikova, Oyuna S.
   Korbolina, Elena E.
   Ershov, Nikita I.
   Kolosova, Natalia G.
TI Rat retinal transcriptome Effects of aging and AMD-like retinopathy
SO CELL CYCLE
LA English
DT Article
DE aging; age-related macular degeneration; retinal transcriptome; RNA-Seq;
   OXYS rats
ID ALPHA-B-CRYSTALLIN; MITOCHONDRIAL COMPLEX-I; AGE-RELATED DISEASES;
   MACULAR DEGENERATION; PIGMENT EPITHELIUM; OXIDATIVE STRESS;
   GENE-EXPRESSION; FACTOR-H; SENESCENCE; INFLAMMATION
AB Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. to identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We Identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. the majority of them are related to the immune system and extracellular matrix turnover. only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. over 600 genes showed significant differences in expression between the two strains. these genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. the altered expression for selected genes was confirmed by qRt-pCR analysis. to our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy.
C1 [Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Natalia G.] Russian Acad Sci SB RAS, Siberian Branch, Inst Cytol & Genet, Novosibirsk, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS
RP Kolosova, NG (通讯作者)，Russian Acad Sci SB RAS, Siberian Branch, Inst Cytol & Genet, Novosibirsk, Russia.
EM kolosova@bionet.nsc.ru
RI Kolosova, Nataliya G/AAR-7409-2020; Kolosova, Nataliya G/P-3178-2015;
   Ershov, Nikita/F-7484-2017; Kozhevnikova, Oyuna S./H-3588-2016
OI Kolosova, Nataliya G/0000-0003-2398-8544; Kolosova, Nataliya
   G/0000-0003-2398-8544; Ershov, Nikita/0000-0003-3423-3497; Kozhevnikova,
   Oyuna S./0000-0001-6475-4061
FU Russian Foundation for Basic Research [11-04-00666-a, 12-04-00091-a,
   12-04-31975]; Presidium of RAS "Fundamental Sciences for Medicine"
FX This work has been supported by Russian Foundation for Basic Research
   (project 11-04-00666-a, 12-04-00091-a and 12-04-31975) and Presidium of
   RAS "Fundamental Sciences for Medicine."
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NR 117
TC 45
Z9 55
U1 1
U2 6
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD JUN 1
PY 2013
VL 12
IS 11
BP 1745
EP 1761
DI 10.4161/cc.24825
PG 17
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 301IL
UT WOS:000330525900022
PM 23656783
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Rostron, E
   McKibbin, M
AF Rostron, E.
   McKibbin, M.
TI Visual impairment certification secondary to ARMD in Leeds, 2005-2010:
   is the incidence falling?
SO EYE
LA English
DT Article
DE age-related macular degeneration; ARMD; visual impairment certification
ID MACULAR DEGENERATION; PARTIAL SIGHT; BLINDNESS; ENGLAND; WALES
AB Aim The aim of this study was to evaluate trends in visual impairment certification due to age-related macular degeneration (ARMD) in the Leeds metropolitan area between 2005 and 2010.
   Methods In this retrospective study, the primary causes of visual impairment certification in the Leeds metropolitan area between 2005 and 2010 were reviewed. ARMD was considered to be the cause of certification when recorded as the primary factor contributing to visual impairment in one or both eyes. The incidence of visual impairment certification due to ARMD was calculated using population estimates from the Office of National Statistics.
   Results ARMD was the primary cause of visual impairment certification in all study years, accounting for 58.7 and 50.8% of certifications in 2005 and 2010, respectively. For the same period, the incidence of certification due to ARMD fell from 364 to 248 per million population per year. This was largely the result of a fall in the incidence of visual impairment certification due to neovascular ARMD from 225 to 137 per million population per year, beginning in 2008 after the introduction of a local commissioning policy on the use of intra-vitreal ranibizumab.
   Conclusion The incidence of visual impairment certification due to ARMD in the Leeds metropolitan area appears to be falling. This is largely the result of a decrease in certification secondary to neovascular ARMD. This represents a change in the previously described trend for ARMD visual impairment certification. Eye (2012) 26, 933-936; doi:10.1038/eye.2012.61; published online 13 April 2012
C1 [Rostron, E.; McKibbin, M.] St James Univ Hosp, Dept Ophthalmol, Leeds LS9 7TF, W Yorkshire, England.
C3 Saint James's University Hospital
RP McKibbin, M (通讯作者)，St James Univ Hosp, Dept Ophthalmol, Beckett St, Leeds LS9 7TF, W Yorkshire, England.
EM Martin.McKibbin@leedsth.nhs.uk
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NR 15
TC 20
Z9 21
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD JUL
PY 2012
VL 26
IS 7
BP 933
EP 936
DI 10.1038/eye.2012.61
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 973LE
UT WOS:000306360800005
PM 22498793
OA Green Published, Bronze
DA 2022-11-30
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